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Demaerel R, Decraene B, Masrori P, Marcelis L, Sciot R, Demaerel P, Van Calenbergh F. Exploring perivascular epithelioid cell tumors (PEComas) in the CNS: insights from two case reports and a comprehensive literature review. Childs Nerv Syst 2025; 41:190. [PMID: 40423698 DOI: 10.1007/s00381-025-06845-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 05/08/2025] [Indexed: 05/28/2025]
Abstract
Perivascular epithelioid cell tumors (PEComas) represent a rare and intriguing subset of neoplasms within the central nervous system (CNS). This report describes two unique cases that highlight distinct origins and clinical behaviors, offering valuable contributions to the limited body of knowledge regarding CNS PEComas. Despite their rarity, PEComas should be considered in the differential diagnosis of mesenchymal tumors that display an atypical combination of clinical, radiological, and histomolecular features, especially when melanocytic and/or myoid markers are present. Treatment with mTOR inhibitors can potentially stabilize the disease in a significant number of more aggressive PEComas, even those located in the CNS.
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Affiliation(s)
- Rik Demaerel
- Department of Neurosurgery, University Hospitals Leuven, Louvain, Belgium
| | - Brecht Decraene
- Department of Neurosurgery, University Hospitals Leuven, Louvain, Belgium.
- Experimental Neurosurgery and Neuroanatomy Research Group, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Louvain, Belgium.
| | - Pegah Masrori
- Department of Neurology, University Hospitals Leuven, Louvain, Belgium
- Experimental Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Louvain, Belgium
| | - Lukas Marcelis
- Department of Pathology, University Hospitals Leuven, Louvain, Belgium
| | - Raf Sciot
- Department of Pathology, University Hospitals Leuven, Louvain, Belgium
| | - Philippe Demaerel
- Department of Radiology, University Hospitals Leuven, Louvain, Belgium
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Izubuchi Y, Tanaka T. PEComa-its clinical features, histopathology, and current therapy. Jpn J Clin Oncol 2025:hyaf056. [PMID: 40336169 DOI: 10.1093/jjco/hyaf056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 03/22/2025] [Indexed: 05/09/2025] Open
Abstract
Perivascular epithelioid cell tumors (PEComas) are a rare family of mesenchymal tumors that includes angiomyolipoma, lymphangioleiomyomatosis, pulmonary clear cell "sugar" tumors, and PEComa-not otherwise specified. This study aimed to provide a comprehensive review of the clinical features, molecular biology, and current status of PEComa treatment. It reportedly occurs at several sites, including the uterus, kidney, liver, lung, abdominopelvic soft tissue, gastrointestinal organs, retroperitoneum, soft tissue, bone, and skin. More common in women, it occurs in young to middle-aged people. Although the disease generally follows a benign course, cases of malignant PEComa have been reported. Malignant PEComa is characterized by a large tumor size, a high mitotic rate, and the presence of necrosis and nuclear atypia. Immunohistochemically, PEComas typically express melanocytic markers such as human melanoma black 45 (HMB45) and melanoma antigen (melan-A) and muscle markers such as smooth muscle actin (α-SMA), desmin, and caldesmon. More recently, a subtype of PEComa harboring TFE3 gene rearrangement that is mutually exclusive with tuberous sclerosis complex (TSC) mutations has been identified. The identification of TFE3 gene rearrangement can help confirm the diagnosis. The distinctive features of these TFE3-rearranged PEComas include a young-age tendency, the absence of an association with tuberous sclerosis, predominant alveolar architecture and epithelioid cytology, minimal immunoreactivity for muscle markers, and strong (3+) TFE3 immunoreactivity. Surgery is the curative treatment of choice; however, there are reports of cases and randomized controlled trials showing the efficacy of mTOR inhibitors. To the best of our knowledge, there are no reports of radiation therapy's efficacy.
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Affiliation(s)
- Yuya Izubuchi
- Department of Orthopaedics and Rehabilitaion Medicine, Unit of Surgery, Division of Medicine, Faculty of Medical Sciences, University of Fukui 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan
| | - Takaaki Tanaka
- Department of Orthopaedics and Rehabilitaion Medicine, Unit of Surgery, Division of Medicine, Faculty of Medical Sciences, University of Fukui 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan
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MacDonald W, Avenarius MR, Aziz J, Guo A, D'Souza DM, Satturwar S, Shilo K. Perivascular Epithelioid Cell Tumor of the Lung With a Novel YAP1::TFE3 Fusion. Int J Surg Pathol 2025:10668969251323936. [PMID: 40080865 DOI: 10.1177/10668969251323936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/15/2025]
Abstract
Perivascular epithelioid cell tumor (PEComa) belongs to a family of rare mesenchymal neoplasms that share characteristic morphologic, immunohistochemical and molecular findings. In this report, we provide a detailed clinicopathological characterization of a PEComa incidentally discovered in the right lung of a 53-year-old woman. This tumor with epithelioid cell morphology and myomelanocytic differentiation demonstrated a TFE3::YAP1 fusion by targeted RNA sequencing. While a subset of PEComas shows TFE3 rearrangements, fusion with YAP1 has not been systematically documented in this entity. Clear cell stromal tumor of the lung and epithelioid hemangioendothelioma characteristically display the TFE3::YAP1 fusion; however, as currently defined, both lack myomelanocytic features. Here, we describe a novel TFE3 fusion partner that further expands the spectrum of molecular alterations seen in PEComa.
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Affiliation(s)
- William MacDonald
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Matthew R Avenarius
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jenna Aziz
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Aaron Guo
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Desmond M D'Souza
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Swati Satturwar
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Konstantin Shilo
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Choi JH, Thung SN. Mesenchymal Tumors of the Liver: An Update Review. Biomedicines 2025; 13:479. [PMID: 40002892 PMCID: PMC11852400 DOI: 10.3390/biomedicines13020479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Hepatic mesenchymal tumors (HMTs) are non-epithelial benign and malignant tumors with or without specific mesenchymal cell differentiation. They are relatively uncommon. Except for mesenchymal hamartoma, calcified nested stromal-epithelial tumor, and embryonal sarcoma, most mesenchymal lesions are not specific to the liver. Pathologists face challenges in diagnosing HMTs due to their diverse morphologies and phenotypic variations. Accurate diagnosis is critical for directing appropriate patient care and predicting outcomes. This review focuses on mesenchymal tumors with a relative predilection for the liver, including vascular and non-vascular mesenchymal neoplasms. It provides a thorough and up-to-date overview, concentrating on clinical and pathological features, differential diagnosis, and diagnostic approaches.
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Affiliation(s)
- Joon Hyuk Choi
- Department of Pathology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Namgu, Daegu 42415, Republic of Korea
| | - Swan N. Thung
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA;
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Kojima N, Nishino S, Sasahara Y, Taki T, Imada H, Miyoshi T, Watanabe SI, Ishii G, Yatabe Y, Mori T, Yoshida A. Inflammatory spindle cell PEComa of the lung with YAP1::TFE3 fusion: a report of two cases and a potential relationship with clear cell stromal tumour. Histopathology 2025; 86:365-372. [PMID: 39327855 DOI: 10.1111/his.15328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 08/25/2024] [Accepted: 09/12/2024] [Indexed: 09/28/2024]
Abstract
AIMS The PEComa family of tumours is defined by spindle/epithelioid cells with myomelanocytic differentiation. A small subset harbours TFE3 fusion; however, YAP1::TEE3 has not been reported. Clear cell stromal tumour of the lung (CCST-L) is an emerging entity characterized by spindle to epithelioid cells with focal cytoplasmic clearing, inflammatory infiltrates, no myomelanocytic differentiation, and YAP1::TFE3 fusion. Herein, we report two cases of lung tumours with myomelanocytic differentiation that showed inflammatory spindle cell histology, focal epithelioid clear cells, as well as YAP1::TFE3 fusion. METHODS AND RESULTS The patients were both men, aged 61 and 68 years. The tumours in both cases presented as well-circumscribed solid masses involving the lung hilum. After lobectomy, no recurrence was observed at 7 and 32 months. Both tumours shared storiform to short fascicular growth of long spindle cells, with a minor component of epithelioid cells showing clear cytoplasm in the background of substantial intratumoral chronic inflammation and dilated blood vessels. One tumour showed focal melanin deposition. Both tumours were immunohistochemically positive for HMB45, Melan A, and h-caldesmon. Fluorescence in situ hybridization assays indicated the presence of YAP1::TFE3 fusions, which was confirmed by RNA sequencing in one case tested, and by immunohistochemical TFE3 expression and loss of YAP1 C-terminus staining. CONCLUSION We present two cases of inflammatory spindle to epithelioid cell tumours of the lungs with myomelanocytic differentiation and YAP1::TFE3 fusion. This unique morphology and gene fusion suggest that these tumours may constitute a distinct subset of lung PEComa. Furthermore, morphological and molecular overlap with CCST-L gives rise to a hypothesis of a potential inherent relationship between PEComa and CCST-L.
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Affiliation(s)
- Naoki Kojima
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
| | - Shogo Nishino
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yukiko Sasahara
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Chiba, Japan
| | - Tetsuro Taki
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Chiba, Japan
| | - Hiroki Imada
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Chiba, Japan
- Department of Pathology, Saitama Medical University Saitama Medical Center, Saitama, Japan
| | - Tomohiro Miyoshi
- Department of Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Shun-Ichi Watanabe
- Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Genichiro Ishii
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Chiba, Japan
- Division of Innovative Pathology and Laboratory Medicine, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan
| | - Yasushi Yatabe
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Taisuke Mori
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
| | - Akihiko Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
- Rare Cancer Center, National Cancer Center, Tokyo, Japan
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Takahashi Y, Yoshida A, Yoshimoto S, Suzuki S, Kishikawa S, Mitsui A, Ryo E, Kojima Y, Yonemori K, Yatabe Y, Mori T. TFE3-rearranged perivascular epithelioid cell tumors of the head and neck with rare fusion partners: clues to the differential diagnosis between benign and malignant tumors. Diagn Pathol 2025; 20:7. [PMID: 39815310 PMCID: PMC11734225 DOI: 10.1186/s13000-025-01602-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/07/2025] [Indexed: 01/30/2025] Open
Abstract
BACKGROUND Perivascular epithelioid cell tumors (PEComas) rarely appear in the head and neck region. This case report describes two transcription factor E3 (TFE3)-rearranged PEComa cases, consisting of one in the orbit and one in the nasal cavity. CASE PRESENTATION Both cases demonstrated sheet-like or focal nested architecture and comprised epithelioid cells with abundant clear to eosinophilic cytoplasm and vascular stroma. The first case exhibited partial pleomorphism, a small necrosis area, and slightly increased mitosis and was classified as malignant. The second case demonstrated mild atypia and no mitosis or necrosis and was categorized as benign. The nasal tumor was initially considered a TFE3-rearranged renal cell carcinoma metastasis. However, a subsequent renal tumor biopsy revealed angiomyolipoma. The RNA sequence revealed ZC3H4::TFE3 and PRCC::TFE3 fusions in the first and second cases, respectively. CONCLUSION The fusion partner gene ZC3H4 is uncommon, and this is the third reported PEComa case. The fusion partner gene PRCC is often reported in TFE3-rearranged renal cell carcinoma, and this PEComa case is the second reported in the head and neck region. The initially reported cases with the fusion partner genes ZC3H4 and PRCC were categorized as malignant. These cases were discussed with a literature review.
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Affiliation(s)
- Yuka Takahashi
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Akihiko Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Seiichi Yoshimoto
- Department of Head and Neck Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Shigenobu Suzuki
- Department of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Satsuki Kishikawa
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Ayaka Mitsui
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Eijitsu Ryo
- Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan
| | - Yuki Kojima
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kan Yonemori
- Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yasushi Yatabe
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
- Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan
| | - Taisuke Mori
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
- Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
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Radaelli S, Merlini A, Khan M, Gronchi A. Progress in histology specific treatments in soft tissue sarcoma. Expert Rev Anticancer Ther 2024; 24:845-868. [PMID: 39099398 DOI: 10.1080/14737140.2024.2384584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 07/22/2024] [Indexed: 08/06/2024]
Abstract
INTRODUCTION Soft tissue sarcomas (STS) represent a heterogenous group of rare tumors, primarily treated with surgery. Preoperative radiotherapy is often recommended for extremity high-risk STS. Neoadjuvant chemotherapy, typically based on doxorubicin with ifosfamide, has shown efficacy in limbs and trunk wall STS. Second-line chemotherapy, commonly utilized in the metastatic setting, is mostly histology-driven. Molecular targeted agents are used across various histologies, and although the use of immunotherapy in STS is still in its early stages, there is increasing interest in exploring its potential. AREAS COVERED This article involved an extensive recent search on PubMed. It explored the current treatment landscape for localized and metastatic STS, focusing on the combined use of radiotherapy and chemotherapy for both extremity and retroperitoneal tumors, and with a particular emphasis on the most innovative histopathology driven therapeutic approaches. Additionally, ongoing clinical trials identified via clinicaltrials.gov are included. EXPERT OPINION Recently there have been advancements in the treatment of STS, largely driven by the outcomes of clinical trials. However further research is imperative to comprehend the effect of chemotherapy, targeted therapy and immunotherapy in various STS, as well as to identify biomarkers able to predict which patients are most likely to benefit from these treatments.
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Affiliation(s)
- Stefano Radaelli
- Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alessandra Merlini
- Department of Oncology, University of Turin, Orbassano, Italy
- Department of Oncology, San Luigi Gonzaga University Hospital, Orbassano, Italy
| | - Misbah Khan
- Surgery, East Sussex NHS Healthcare, East Sussex, UK
| | - Alessandro Gronchi
- Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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8
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Alruwaii ZI, Williamson SR, Al-Obaidy KI. Mechanistic Target of Rapamycin Kinase is a Common Convergent Pathway to Renal Neoplasia: A Contemporary Review. Int J Surg Pathol 2024; 32:1095-1108. [PMID: 38258297 DOI: 10.1177/10668969231219653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2024]
Abstract
Mechanistic target of rapamycin kinase (mTOR) is a member of the phosphatidylinositol-3-hydroxide kinase (PI3 K)-related protein kinase family that functions as a central regulator of cell growth, metabolism, proliferation, and survival. The role of the TSC-mTOR signaling pathway in kidney tumors has been implicated in some hamartoma syndromes; however, with the advent and wide utilization of molecular studies, a growing number of kidney tumors have been linked to somatic or germline mutations involving genes that encode for this pathway, including eosinophilic solid and cystic renal cell carcinoma, low-grade oncocytic tumor, eosinophilic vacuolated tumor, renal cell carcinoma with fibromyomatous stroma and angiomyolipoma, among others. Herein, we review the contemporary developments of mTOR pathway-related renal neoplasia, focusing on the clinicopathologic features of the tumor entities.
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Affiliation(s)
- Zainab I Alruwaii
- Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital, Dammam, KSA
| | - Sean R Williamson
- Pathology and Laboratory Medicine Institute, The Cleveland Clinic, Cleveland, OH, USA
| | - Khaleel I Al-Obaidy
- Department of Pathology and Laboratory Medicine, Henry Ford Health, Detroit, MI, USA
- Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, USA
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Alodaini AA. Uterine Mesenchymal Tumors: Updates on Pathology, Molecular Landscape, and Therapeutics. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1085. [PMID: 39064514 PMCID: PMC11278911 DOI: 10.3390/medicina60071085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 06/22/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024]
Abstract
Background: Mesenchymal uterine tumors are a diverse group of neoplasms with varying biological potential. Many of these neoplasms can have overlapping morphologic similarities, which, in some instances, render their diagnosis and categorization thorough histomorphologic examination inconclusive. In the last decade, an exponential amount of molecular data aiming to more accurately characterize and, consequently, treat these tumors have accumulated. Objective: The goal of this narrative review is to provide a pathologic review, a genetic update, and to know the new therapeutic avenues of primary uterine mesenchymal neoplasms.
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Affiliation(s)
- Amal A Alodaini
- Pathology Department, King Fahd University Hospital, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
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Dong BN, Zhan H, Luan T, Wang JS. Comprehensive Insights Into Renal Perivascular Epithelioid Cell Neoplasms: From Molecular Mechanisms to Clinical Practice. World J Oncol 2024; 15:372-381. [PMID: 38751707 PMCID: PMC11092404 DOI: 10.14740/wjon1794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 03/16/2024] [Indexed: 05/18/2024] Open
Abstract
Perivascular epithelioid cell neoplasms (PEComas) are a rare category of mesenchymal tissue tumors, manifesting across various tissues and organs such as the kidneys, liver, lungs, pancreas, uterus, ovaries, and gastrointestinal tract. They predominantly affect females more than males. PEComas characteristically express both melanocytic and smooth muscle markers, making immunohistochemistry vital for their diagnosis. Renal angiomyolipoma (AML) represents a common variant of PEComas, typically marked by favorable prognoses. Nonetheless, only a small fraction of subtypes, especially epithelioid AML, possess the capacity to be malignant. Renal PEComas usually appear as asymptomatic masses accompanied by vague imaging characteristics. The main methods for diagnosis are histopathological analysis and the application of immunohistochemical stains. Presently, a uniform treatment plan for renal PEComas is absent. Strategies for management include active surveillance, selective arterial embolization, surgical procedures, and drug-based treatments. The focus of this review is on renal PEComas, shedding light on their pathogenesis, pathological characteristics, clinical presentations, diagnosis, and treatment modalities, and incorporating a clinical case study.
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Affiliation(s)
- Bao Nan Dong
- Urology Surgery Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Hui Zhan
- Urology Surgery Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Ting Luan
- Urology Surgery Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Jian Song Wang
- Urology Surgery Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
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Katsakhyan L, Shahi M, Eugene HC, Nonogaki H, Gross JM, Nucci MR, Vang R, Xing D. Uterine Leiomyosarcoma Associated With Perivascular Epithelioid Cell Tumor: A Phenomenon of Differentiation/Dedifferentiation and Evidence Suggesting Cell-of-Origin. Am J Surg Pathol 2024; 48:761-772. [PMID: 38497360 DOI: 10.1097/pas.0000000000002208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
Perivascular epithelioid cell tumor (PEComa) is a mesenchymal tumor thought to originate from perivascular epithelioid cells (PECs). The normal counterpart to PEC, however, has not been identified in any human organ, and the debate as to whether PEComa is related to smooth muscle tumors has persisted for many years. The current series characterizes 4 cases of uterine leiomyosarcoma (LMS) coexisting with PEComas. All cases exhibited an abrupt transition from the LMS to PEComa components. The LMS component displayed typical spindled morphology and fascicular growth pattern and was diffusely positive for desmin and smooth muscle myosin heavy chain, completely negative for HMB-45 and Melan A, and either negative or had focal/weak expression of cathepsin K and GPNMB. In contrast, the PEComa tumor cells in case 1 contained glycogen or lipid-distended cytoplasm with a foamy appearance (low grade), and in cases 2, 3, and 4, they displayed a similar morphology characterized by epithelioid cells with eosinophilic and granular cytoplasm and high-grade nuclear atypia. Different from the LMS component, the epithelioid PEComa cells in all cases were focally positive for HMB-45, and diffusely immunoreactive for cathepsin K and GPNMB. Melan A was focally positive in cases 1 and 3. Loss of fumarate hydratase expression (case 1) and RB1 expression (cases 2, 3, 4) was identified in both LMS and PEComa components, indicating that they are clonally related. In addition, both components showed an identical TP53 p.R196* somatic mutation and complete loss of p53 and ATRX expression in case 2 and complete loss of p53 expression in case 3. We hypothesize that LMSs containing smooth muscle progenitor cells may give rise to divergent, lineage-specific PEComatous lesions through differentiation or dedifferentiation. While we do not dispute the recognition of PEComas as a distinct entity, we advocate the hypothesis that modified smooth muscle cells represent the origin of a subset of PEComas, and our case series provides evidence to suggest this theory.
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Affiliation(s)
| | | | | | | | | | - Marisa R Nucci
- Department of Pathology, Brigham and Women's Hospital/Harvard Medical School, Boston, MA
| | - Russell Vang
- Departments of Pathology
- Gynecology and Obstetrics
| | - Deyin Xing
- Departments of Pathology
- Gynecology and Obstetrics
- Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD
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12
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Wangsiricharoen S, Ingram DR, Morey RR, Wani K, Lazar AJ, Wang WL. Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Immunohistochemistry Can Be a Useful Ancillary Tool to Identify Perivascular Epithelioid Cell Tumor. Mod Pathol 2024; 37:100426. [PMID: 38219952 DOI: 10.1016/j.modpat.2024.100426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 12/13/2023] [Accepted: 01/07/2024] [Indexed: 01/16/2024]
Abstract
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that express smooth muscle and melanocytic makers. Diagnosis of PEComas can be challenging due to focal or lost expression of traditional immunohistochemical markers, limited availability of molecular testing, and morphological overlap with much more common smooth muscle tumors. This study evaluates the use of glycoprotein nonmetastatic melanoma protein B (GPNMB) immunohistochemical staining as a surrogate marker for TSC1/2/MTOR alteration or TFE3 rearrangement to differentiate PEComas from other mesenchymal tumors. Cathepsin K was also assessed for comparison. A total of 399 tumors, including PEComas, alveolar soft part sarcomas, and other histologic PEComa mimics, were analyzed using GPNMB and cathepsin K immunohistochemistry. GPNMB expression was seen in all PEComas and alveolar soft part sarcomas with the majority showing diffuse and moderate-to-strong labeling, whereas other sarcomas were negative or showed focal labeling. When a cutoff of diffuse and at least moderate staining was used, GPNMB demonstrated 95% sensitivity and 97% specificity in distinguishing PEComas from leiomyosarcoma, well-differentiated/dedifferentiated liposarcomas, and undifferentiated pleomorphic sarcomas. Cathepsin K with a cutoff of any labeling had lower sensitivity (78%) and similar specificity (94%) to GPNMB. This study highlights GPNMB as a highly sensitive marker for PEComas and suggests its potential use as an ancillary tool within a panel of markers for accurate classification of these tumors.
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Affiliation(s)
- Sintawat Wangsiricharoen
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland, Oregon
| | - Davis R Ingram
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Rohini R Morey
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Khalida Wani
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Alexander J Lazar
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Wei-Lien Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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13
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Chang HY, Dermawan J, Sharma A, Dickson B, Turashvili G, Torrence D, Nucci M, Chiang S, Oliva E, Kirchner M, Stenzinger A, Mechtersheimer G, Antonescu C. Sarcomas With RAD51B Fusions Are Associated With a Heterogeneous Phenotype. Mod Pathol 2024; 37:100402. [PMID: 38141829 PMCID: PMC11251009 DOI: 10.1016/j.modpat.2023.100402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 10/27/2023] [Accepted: 12/05/2023] [Indexed: 12/25/2023]
Abstract
RAD51B-rearranged sarcomas are rare neoplasms that exhibit a heterogeneous morphology. To date, 6 cases have been reported, all involving the uterus, including 4 perivascular epithelioid cell tumors (PEComas) and 2 leiomyosarcomas (LMS). In this study, we describe the morphologic, immunohistochemical, and molecular features of 8 additional sarcomas with RAD51B rearrangement, including the first extrauterine example. All patients were women with a median age of 57 years at presentation. Seven tumors originated in the uterus, and one in the lower extremity soft tissue, with a median tumor size of 12 cm. Histologically, 4 tumors showed predominantly spindle cell morphology with eosinophilic fibrillary cytoplasm, with or without nuclear pleomorphism, whereas 2 tumors exhibited pleomorphic epithelioid cells, featuring clear to eosinophilic, granular cytoplasm. Two neoplasms exhibited undifferentiated cytomorphology, including one with uniform small blue round cells. All tumors showed high-grade cytologic atypia and high mitotic activity (median: 30/10 high-power fields), whereas coagulative necrosis was noted in 6 cases and lymphovascular invasion in 2. By immunohistochemistry, 2 showed myoid and melanocytic markers in keeping with PEComa, whereas 4 cases were only positive for smooth muscle markers consistent with LMS (including 3 myxoid). The remaining 2 cases had a nonspecific immunoprofile. Five cases tested by targeted RNA sequencing (Archer FusionPlex, Illumina TruSight) showed different fusion partners (HMGA2, PDDC1, and CEP170). RAD51B rearrangements were identified by FISH in the remaining 3 cases. Targeted DNA sequencing in 2 cases was negative for TSC gene alterations. Clinical outcome, available in 5 patients (median follow-up, 19 months), revealed 3 local recurrences, 2 lung metastases, and 4 deaths due to disease. Our results expand the spectrum of sarcomas with RAD51B fusions, demonstrating variable clinical presentations, morphologic spectrum, and fusion partners. These tumors have a predilection for a uterine location, with either LMS, PEComa, or undifferentiated phenotypes, and are associated with an aggressive clinical course.
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Affiliation(s)
- Hsin-Yi Chang
- Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Josephine Dermawan
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio
| | - Aarti Sharma
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Brendan Dickson
- Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Gulisa Turashvili
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia
| | - Dianne Torrence
- Department of Pathology, Northwell Health, New York, New York
| | - Marisa Nucci
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Sarah Chiang
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Esther Oliva
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
| | - Martina Kirchner
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | | | | | - Cristina Antonescu
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
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14
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Pervaiz J, Zaman S, Khalid S, Rafique Z, Noor R. Hepatic Angiomyolipoma With Predominant Lipomatous Component: A Rare Entity. Cureus 2024; 16:e54357. [PMID: 38510893 PMCID: PMC10951131 DOI: 10.7759/cureus.54357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2024] [Indexed: 03/22/2024] Open
Abstract
Hepatic angiomyolipoma (HAML) is a rare benign mesenchymal tumor with varying amounts of mature adipose tissue, smooth muscle cells, and thick-walled blood vessels. We present a rare case of hepatic angiomyolipoma (AML) with predominant lipomatous components. A 42-year-old female presented to the hospital with pain in the right lumbar region. On imaging, there was a large fat-predominant mass attached to the surface of the liver extending down to the lumbar region. On small biopsy, it was reported as a well-differentiated adipocytic neoplasm, and fluorescence in situ hybridization (FISH) studies performed for MDM2 were negative. On excision, histopathological examination showed predominantly fat components, but there were few epithelioid cells between adipocytes and thick-walled blood vessels. These cells were positive for Melan-A, HMB45, and smooth muscle actin (SMA) and negative for hepatocyte paraffin-1 (Hep Par1). Angiomyolipoma is a benign tumor and has a good prognosis with surgical excision. Few cases are associated with tuberous sclerosis.
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Affiliation(s)
- Jaweria Pervaiz
- Department of Histopathology, Chughtai Institute of Pathology, Lahore, PAK
| | - Samina Zaman
- Department of Histopathology, Children's Hospital and Institute of Child Health, Lahore, PAK
| | - Sohaib Khalid
- Department of Histopathology, Chughtai Institute of Pathology, Lahore, PAK
| | - Zubaria Rafique
- Department of Histopathology, Chughtai Institute of Pathology, Lahore, PAK
| | - Rida Noor
- Department of Pathology, Faisalabad Medical University, Faisalabad, PAK
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15
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Giannikou K, Klonowska K, Tsuji J, Wu S, Zhu Z, Probst CK, Kao KZ, Wu CL, Rodig S, Marino-Enriquez A, Zen Y, Schaefer IM, Kwiatkowski DJ. TSC2 inactivation, low mutation burden and high macrophage infiltration characterise hepatic angiomyolipomas. Histopathology 2023; 83:569-581. [PMID: 37679051 DOI: 10.1111/his.15005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/30/2023] [Accepted: 06/26/2023] [Indexed: 09/09/2023]
Abstract
AIMS Although TSC1 or TSC2 inactivating mutations that lead to mTORC1 hyperactivation have been reported in hepatic angiomyolipomas (hAML), the role of other somatic genetic events that may contribute to hAML development is unknown. There are also limited data regarding the tumour microenvironment (TME) of hAML. The aim of the present study was to identify other somatic events in genomic level and changes in TME that contribute to tumorigenesis in hAML. METHODS AND RESULTS In this study, we performed exome sequencing in nine sporadic hAML tumours and deep-coverage targeted sequencing for TSC2 in three additional hAML. Immunohistochemistry and multiplex immunofluorescence were carried out for 15 proteins to characterise the tumour microenvironment and assess immune cell infiltration. Inactivating somatic variants in TSC2 were identified in 10 of 12 (83%) cases, with a median allele frequency of 13.6%. Five to 18 somatic variants (median number: nine, median allele frequency 21%) not in TSC1 or TSC2 were also identified, mostly of uncertain clinical significance. Copy number changes were rare, but detection was impaired by low tumour purity. Immunohistochemistry demonstrated numerous CD68+ macrophages of distinct appearance from Küpffer cells. Multiplex immunofluorescence revealed low numbers of exhausted PD-1+/PD-L1+, FOXP3+ and CD8+ T cells. CONCLUSION hAML tumours have consistent inactivating mutations in TSC2 and have a low somatic mutation rate, similar to other TSC-associated tumours. Careful histological review, standard IHC and multiplex immunofluorescence demonstrated marked infiltration by non-neoplastic inflammatory cells, mostly macrophages.
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Affiliation(s)
- Krinio Giannikou
- Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Cancer Genome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Division of Hematology and Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Katarzyna Klonowska
- Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Cancer Genome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Junko Tsuji
- Genomics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Shulin Wu
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Zachary Zhu
- Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Clemens K Probst
- Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Neurological Sciences, Larner College of Medicine, University of Vermont, Burlighton, VT, USA
| | - Katrina Z Kao
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Chin-Lee Wu
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Scott Rodig
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Adrian Marino-Enriquez
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Yoh Zen
- Department of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Inga-Marie Schaefer
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - David J Kwiatkowski
- Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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16
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Previtali R, Prontera G, Alfei E, Nespoli L, Masnada S, Veggiotti P, Mannarino S. Paradigm shift in the treatment of tuberous sclerosis: Effectiveness of everolimus. Pharmacol Res 2023; 195:106884. [PMID: 37549757 DOI: 10.1016/j.phrs.2023.106884] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 08/03/2023] [Accepted: 08/03/2023] [Indexed: 08/09/2023]
Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by abnormal cell proliferation and differentiation that affects multiple organs and can lead to the growth of hamartomas. Tuberous sclerosis complex is caused by the disinhibition of the protein mTOR (mammalian target of rapamycin). In the past, various therapeutic approaches, even if only symptomatic, have been attempted to improve the clinical effects of this disease. While all of these therapeutic strategies are useful and are still used and indicated, they are symptomatic therapies based on the individual symptoms of the disease and therefore not fully effective in modifying long-term outcomes. A new therapeutic approach is the introduction of allosteric inhibitors of mTORC1, which allow restoration of metabolic homeostasis in mutant cells, potentially eliminating most of the clinical manifestations associated with Tuberous sclerosis complex. Everolimus, a mammalian target of the rapamycin inhibitor, is able to reduce hamartomas, correcting the specific molecular defect that causes Tuberous sclerosis complex. In this review, we report the findings from the literature on the use of everolimus as an effective and safe drug in the treatment of TSC manifestations affecting various organs, from the central nervous system to the heart.
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Affiliation(s)
- Roberto Previtali
- Pediatric Neurology Unit, Buzzi Children's Hospital, Milan, Italy; Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Giorgia Prontera
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Enrico Alfei
- Pediatric Neurology Unit, Buzzi Children's Hospital, Milan, Italy
| | - Luisa Nespoli
- Pediatric Cardiology Unit, Department of Pediatric, Buzzi Children's Hospital, Milan, Italy
| | - Silvia Masnada
- Pediatric Neurology Unit, Buzzi Children's Hospital, Milan, Italy
| | - Pierangelo Veggiotti
- Pediatric Neurology Unit, Buzzi Children's Hospital, Milan, Italy; Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Savina Mannarino
- Pediatric Cardiology Unit, Department of Pediatric, Buzzi Children's Hospital, Milan, Italy.
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17
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Anderson WJ, Dong F, Fletcher CDM, Hirsch MS, Nucci MR. A Clinicopathologic and Molecular Characterization of Uterine Sarcomas Classified as Malignant PEComa. Am J Surg Pathol 2023; 47:535-546. [PMID: 36856023 DOI: 10.1097/pas.0000000000002028] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
Perivascular epithelioid cell tumors (PEComas) are a distinctive group of mesenchymal neoplasms that demonstrate features of smooth muscle and melanocytic differentiation. Here, we present the clinicopathologic, immunohistochemical, and molecular features of 15 uterine sarcomas diagnosed as malignant PEComa. The median patient age was 56 years (range: 27 to 86 y). The median tumor size was 8.0 cm (range: 5.0 to 14.0 cm). All tumors were classified as malignant based on the presence of mitoses (15/15; 100%), necrosis (15/15; 100%), lymphovascular invasion (8/15; 53%), and high nuclear grade (13/15; 87%). Molecular analysis revealed the mammalian target of rapamycin pathway gene mutations in 7 cases (47%), including mutually exclusive variants in TSC1 (27%) and TSC2 (20%). Recurrent alterations were also identified in TP53 (53%), RB1 (30%), ATRX (33%), and BRCA2 (13%). Tumors with inactivating ATRX mutations all demonstrated loss of ATRX expression by immunohistochemistry. Loss of expression was also observed in 2 tumors without demonstrable ATRX alterations. Clinical follow-up was available for 14 patients (range: 5 to 92 mo; median: 15 mo). Five patients developed local recurrence and 9 developed metastases; 2 patients died of their disease. Our series expands the spectrum of molecular events in tumors diagnosed as malignant PEComa and further highlights the important role of targeted sequencing in tumors with focal melanocytic marker expression.
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Affiliation(s)
- William J Anderson
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
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18
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Meredith L, Chao T, Nevler A, Basu Mallick A, Singla RK, McCue PA, Bowne WB, Jiang W. A rare metastatic mesenteric malignant PEComa with TSC2 mutation treated with palliative surgical resection and nab-sirolimus: a case report. Diagn Pathol 2023; 18:45. [PMID: 37041531 PMCID: PMC10088294 DOI: 10.1186/s13000-023-01323-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 03/05/2023] [Indexed: 04/13/2023] Open
Abstract
BACKGROUND Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of and predicting response to mTOR inhibitors in cases of malignant PEComas. CASE PRESENTATION Here, we report a case of an aggressive, 23 cm mesenteric malignant PEComa with multiple peritoneal metastases in a young male patient. Pathological examination of the initial biopsy showed a malignant epithelioid neoplasm with high-grade morphology and atypical immunoprofile, which precluded a definitive diagnosis. Because of the patient's excessive transfusion requirements due to intra-tumoral hemorrhage, a palliative R2 resection was performed. Histopathological examination of the tumor revealed focal immunoreactivity for Melan-A, HMB-45, desmin, and CD117. Although a diagnosis of malignant PEComa was favored, other entities such as epithelioid gastrointestinal stromal tumor (GIST) or melanoma could not be definitively ruled out. Given the favored diagnosis, the patient was started on sirolimus, an mTOR inhibitor, rather than chemotherapy. Molecular analyses were performed and the tumor was found to harbor mutations in TP53 and TSC2, supporting a definitive diagnosis of malignant PEComa. The patient was then switched to nab-sirolimus, with initial stabilization of the disease. CONCLUSIONS This report details a multidisciplinary approach for the diagnosis and management of a highly aggressive, metastatic malignant PEComa in a young male patient. The basis for the treatment of malignant PEComas with the recently FDA-approved mTOR inhibitor, nab-sirolimus, is also reviewed. In summary, this case highlights the importance of molecular analysis, particularly TSC1/2 alterations, for both the definitive diagnosis of malignant PEComas and predicting their response to nab-sirolimus.
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Affiliation(s)
- Luke Meredith
- Department of Surgery, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA
| | - Timothy Chao
- Department of Pathology and Genomic Medicine, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA
| | - Avinoam Nevler
- Department of Surgery, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA
| | - Atrayee Basu Mallick
- Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA
| | - Rajan K Singla
- Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA
| | - Peter A McCue
- Department of Pathology and Genomic Medicine, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA
| | - Wilbur B Bowne
- Department of Surgery, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA
| | - Wei Jiang
- Department of Pathology and Genomic Medicine, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA.
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19
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Zhang Y, Wei X, Teng X, Chen G. p53 aberration and TFE3 gene amplification may be predictors of adverse prognosis in epithelioid angiomyolipoma of the kidney. Diagn Pathol 2023; 18:14. [PMID: 36740682 PMCID: PMC9901144 DOI: 10.1186/s13000-023-01298-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 01/19/2023] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Although epithelioid angiomyolipoma of the kidney has been studied by several groups, the reported prevalence of malignant behavior remains uncertain and there are not yet definitive predictive biomarkers. We evaluated the behavior of renal epithelioid angiomyolipoma in a consecutive series in a single institution and investigated the prognostic value of aberrant p53 expression and TFE3 gene abnormality. METHODS We retrospectively reviewed 14 epithelioid angiomyolipomas, most with pure or close to pure epithelioid components, comprising 12 consecutive cases who had attended our institution and two consultation cases. Fluorescence in situ hybridization with TFE3 break-apart probe was performed on 14 cases. The 14 cases were also labeled for p53 and TFE3 by immunohistochemistry. All cases were followed up. RESULTS Three of the epithelioid angiomyolipomas were strongly positive for TFE3 and two had a mutant expression of p53. Although no TFE3 gene rearrangement was found, the two tumors with strong TFE3 expression showed TFE3 gene amplification. Follow-up details were available for seven of the 12 consecutive cases: two of them had developed metastases and died (29%), their mean overall survival was 41 months, and both had mutant p53 expression. The two consultation cases with TFE3 gene amplification developed recurrence/metastasis within 1 year after surgery. CONCLUSIONS Our series study from a single institution presented the prevalence of malignant behavior in pure epithelioid angiomyolipomas, although the small number of cases with follow-up data greatly reduced the accuracy. p53 may be a prognostic marker for epithelioid angiomyolipoma. Cases with TFE3 gene amplification had poor prognoses.
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Affiliation(s)
- Yanning Zhang
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xicheng District, Beijing, 100050, China.
| | - Xuejing Wei
- grid.411610.30000 0004 1764 2878Department of Pathology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xicheng District, Beijing, 100050 China
| | - Xiaojing Teng
- grid.411610.30000 0004 1764 2878Department of Pathology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xicheng District, Beijing, 100050 China
| | - Guangyong Chen
- grid.411610.30000 0004 1764 2878Department of Pathology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xicheng District, Beijing, 100050 China
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20
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Djerroudi L, Masliah-Planchon J, Brisse HJ, El Zein S, Helfre S, Tzanis D, Hamzaoui N, Bonnet C, Laurence V, Bonvalot S, Watson S. Metastatic Malignant Perivascular Epithelioid Cell Tumors With Microsatellite Instability Within Lynch Syndrome Successfully Treated With Anti-PD1 Pembrolizumab. JCO Precis Oncol 2023; 7:e2200627. [PMID: 36716416 PMCID: PMC9928971 DOI: 10.1200/po.22.00627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Sarcoma developed within Lynch Syndrome are rare but must be recognized. They can show complete response to anti-PD1
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Affiliation(s)
- Lounes Djerroudi
- Department of Diagnostic and Theranostic Medicine, Institut Curie Hospital, Paris, France
| | | | - Hervé J. Brisse
- Department of Radiology, Institut Curie Hospital, Paris, France
| | - Sophie El Zein
- Department of Diagnostic and Theranostic Medicine, Institut Curie Hospital, Paris, France
| | - Sylvie Helfre
- Department of Radiotherapy, Institut Curie Hospital, Paris, France
| | - Dimitri Tzanis
- Department of Surgical Oncology, Institut Curie Hospital, Paris, France
| | - Nadim Hamzaoui
- INSERM U1016, CNRS UMR8104, Université de Paris, CARPEM, Institut Cochin, Paris, France,Fédération de Génétique et Médecine Génomique, Hôpital Cochin, AP-HP Centre-Université de Paris, Paris, France
| | - Clément Bonnet
- Department of Medical Oncology, Institut Curie Hospital, Paris, France
| | - Valérie Laurence
- Department of Medical Oncology, Institut Curie Hospital, Paris, France
| | - Sylvie Bonvalot
- Department of Surgical Oncology, Institut Curie Hospital, Paris, France
| | - Sarah Watson
- Department of Medical Oncology, Institut Curie Hospital, Paris, France,INSERM U830, Équipe Labellisée Ligue Nationale Contre le Cancer, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Center, Paris, France,Sarah Watson, MD, PhD, Department of Medical Oncology, Institut Curie Hospital, 26 rue d'Ulm, Paris 75005, France; Twitter: @SarahWatson1985; e-mail:
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21
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Natsume T, Yoshida H, Nishikawa T, Kikkawa N, Naka T, Kobayashi-Kato M, Tanase Y, Uno M, Ishikawa M, Kato T. Uterine Leiomyosarcoma Masquerading as a Malignant Perivascular Epithelioid Cell Tumor: A Diagnostic Challenge. Int J Surg Pathol 2022:10668969221133348. [DOI: 10.1177/10668969221133348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Uterine sarcomas with myomelanocytic differentiation have been reported to be diagnostically challenging. We report a case of uterine leiomyosarcoma with extensive perivascular epithelioid cell tumor (PEComa)-like areas and extrauterine metastases. The patient was a 49-year-old gravida 3 para 2 Japanese woman with no relevant medical history. She noticed a vaginal mass with bleeding. Imaging examination revealed a uterine tumor and multiple liver and lung metastases. The vaginal tumor (3.5 cm) was resected and diagnosed as a malignant PEComa based on morphology and myomelanocytic marker expression. Clinically used targeted sequencing (FoundationOneCDx™) revealed gene alterations in RB1, TP53, and ATRX but not TSC1/2. Despite administration of an mTOR inhibitor, the tumor size increased, and subsequently, hysterectomy was performed to relieve the symptoms. The uterine tumor was composed of conventional leiomyosarcoma showing RB1 loss, wild-type TP53 staining, and retained ATRX expression, as well as adjacent predominant PEComa-like components with RB1 loss, TP53 overexpression, and ATRX loss, identical to the characteristics of the vaginal tumor. In the uterine tumor, both HMB-45 and MITF were weak to moderately positive for approximately 40% of tumor cells while Melan-A was negative. The tumor was finally diagnosed as leiomyosarcoma with PEComa-like features. This case exemplifies the tumorigenesis of diagnostically challenging tumors with myomelanocytic differentiation and demonstrates the importance of integrating multiple types of information, including genomic profiling, in making a correct diagnosis leading to appropriate treatment.
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Affiliation(s)
- Takashi Natsume
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Hiroshi Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Tadaaki Nishikawa
- Department of Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Nao Kikkawa
- Department of Diagnostic Radiology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Tomoaki Naka
- Department of Diagnostic Pathology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | | | - Yasuhito Tanase
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Masaya Uno
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Mitsuya Ishikawa
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
| | - Tomoyasu Kato
- Department of Gynecology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
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22
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Yang JW, Liang C, Yang L. Advancements in the diagnosis and treatment of renal epithelioid angiomyolipoma: A narrative review. Kaohsiung J Med Sci 2022; 38:925-932. [PMID: 36056704 DOI: 10.1002/kjm2.12586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 06/19/2022] [Accepted: 07/31/2022] [Indexed: 11/12/2022] Open
Abstract
Renal epithelioid angiomyolipoma (EAML) is a unique subtype of angiomyolipoma that contains a variety of cytoplasmic-rich, eosinophilic cytoplasm epithelioid cells in addition to mature adipocytes, hyaline thick-walled vessels, and smooth muscle-like spindle cells. In recent years, increasing evidence has shown that EAML is a potentially malignant tumor. Due to the lack of typical clinical manifestations and imaging features, it is difficult to diagnose before surgery, and the diagnosis mainly depends on postoperative histopathological examination. With the advancement of pathological diagnostic techniques, more EAML cases has been discovered, but clinicians still lack a comprehensive understanding of EAML. This review comprehensively describes some pathological and clinical features of EAML, with special attention to the pathogenesis and treatment of malignant EAML in order to assist with clinical diagnosis and treatment.
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Affiliation(s)
- Jian-Wei Yang
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China.,Clinical Center of Gansu Province for Nephron-urology, Lanzhou, China
| | - Cheng Liang
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China.,Clinical Center of Gansu Province for Nephron-urology, Lanzhou, China
| | - Li Yang
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China.,Clinical Center of Gansu Province for Nephron-urology, Lanzhou, China
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23
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Zhang X, Zhong X, Lin X, Li X, Tian H, Chang B, Wang Y, Tong J, Wang N, Li D, Jin X, Huang D, Wang Y, Cui H, Guan L, Li Y. Tuberous Sclerosis Complex With Multiple Organ Tumors: Case Report and Literature Review. Front Oncol 2022; 12:916016. [PMID: 35928867 PMCID: PMC9343591 DOI: 10.3389/fonc.2022.916016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 06/21/2022] [Indexed: 11/13/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (PNEN) are tumors that originate from neuroendocrine cells. Only about 1% patients are related to mutation of tuberous sclerosis complex gene. Here, we reported a rare case with involvement of multiple organs and space-occupying lesions. Initially, the patient was thought to have metastasis of a pancreatic tumor. However, the patient was diagnosed as pancreatic neuroendocrine tumors, liver perivascular epithelioid tumors, splenic hamartoma, and renal angiomyolipoma by pathological examination after surgery. We performed genetic mutation detection to identify that tuberous sclerosis complex 2 gene presented with a heterozygous variant. Tuberous sclerosis often presents with widespread tumors, but it is less common to present with pancreatic neuroendocrine tumors and liver perivascular tumors as highlighted in the case. So we analyzed the relationship between TSC gene mutations and related tumors. And we also reviewed the current molecular mechanisms and treatments for tuberous sclerosis complex.
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Affiliation(s)
- Xinhe Zhang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xinping Zhong
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xuyong Lin
- Department of Pathology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xuedan Li
- Radiology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Haoyu Tian
- The 3rd Clinical Department, China Medical University, Shenyang, China
| | - Bing Chang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Ying Wang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jing Tong
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Ningning Wang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Dan Li
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xiuli Jin
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Die Huang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yanmeng Wang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Huipeng Cui
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Lin Guan
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Yiling Li, ; Lin Guan,
| | - Yiling Li
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Yiling Li, ; Lin Guan,
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Abstract
This review focuses on recent advances in epithelioid and myxoid uterine mesenchymal neoplasms, a category of tumors whereby diagnostic criteria have been rapidly evolving due to advances in molecular testing. Pertinent clinicopathological and molecular features are highlighted for perivascular epithelioid cell tumors, uterine tumors resembling ovarian sex cord tumors, BCOR/BCORL1-altered high-grade endometrial stromal sarcomas, and inflammatory myofibroblastic tumors. Novel developments in epithelioid and myxoid leiomyosarcomas are briefly discussed, and differential diagnoses with key diagnostic criteria are provided for morphologic mimickers.
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Affiliation(s)
- Elizabeth C Kertowidjojo
- Department of Pathology, University of Chicago Medicine, 5837 South Maryland Avenue, MC 6101, Chicago, IL 60637, USA
| | - Jennifer A Bennett
- Department of Pathology, University of Chicago Medicine, 5837 South Maryland Avenue, MC 6101, Chicago, IL 60637, USA.
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Vibert J, Watson S. The Molecular Biology of Soft Tissue Sarcomas: Current Knowledge and Future Perspectives. Cancers (Basel) 2022; 14:2548. [PMID: 35626152 PMCID: PMC9139698 DOI: 10.3390/cancers14102548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 05/15/2022] [Accepted: 05/21/2022] [Indexed: 02/04/2023] Open
Abstract
Soft tissue sarcomas are malignant tumors of mesenchymal origin, encompassing a large spectrum of entities that were historically classified according to their histological characteristics. Over the last decades, molecular biology has allowed a better characterization of these tumors, leading to the incorporation of multiple molecular features in the latest classification of sarcomas as well as to molecularly-guided therapeutic strategies. This review discusses the main uses of molecular biology in current practice for the diagnosis and treatment of soft tissue sarcomas, in addition to perspectives for this rapidly evolving field of research.
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Affiliation(s)
- Julien Vibert
- INSERM U830, Équipe Labellisée Ligue Nationale Contre le Cancer, Diversity and Plasticity of Childhood Tumors Lab, Institut Curie Research Center, PSL Research University, 75005 Paris, France;
| | - Sarah Watson
- INSERM U830, Équipe Labellisée Ligue Nationale Contre le Cancer, Diversity and Plasticity of Childhood Tumors Lab, Institut Curie Research Center, PSL Research University, 75005 Paris, France;
- Department of Medical Oncology, Institut Curie Hospital, 75005 Paris, France
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26
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Merhe A, Horodyski L, Ritch CR, Kryvenko ON, Gonzalgo ML. Robotic partial nephrectomy with inferior vena cava thrombectomy. UROLOGY VIDEO JOURNAL 2022. [DOI: 10.1016/j.urolvj.2021.100108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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27
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Chung NKX, Metherall P, McCormick JA, Simms RJ, Ong ACM. OUP accepted manuscript. Clin Kidney J 2022; 15:1160-1168. [PMID: 35754971 PMCID: PMC9214570 DOI: 10.1093/ckj/sfac037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Indexed: 12/05/2022] Open
Abstract
Background Everolimus is a potential alternative to embolization and nephrectomy for managing tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML). In 2016, National Health Service England approved its use through regional centres for renal AML ≥30 mm showing interval growth. Evidence of lesion stabilization or reduction after 6 months is mandated for continuation of long-term treatment. Methods From November 2016 to June 2021, all potentially eligible adult TSC patients with AML across Yorkshire and Humber were referred for assessment and monitoring. Eligible patients underwent baseline renal magnetic resonance imaging (MRI) assessment and a follow-up MRI scan after 6 months on everolimus. Dose titration was guided by trough levels and lesion responsiveness using a new 3D MRI volumetric protocol. Results Of 28 patients commencing treatment, 19 tolerated everolimus for >3 months. Overall, 11 patients (40%) discontinued treatment, mostly due to recurrent infections (42%) and allergic reactions (25%). Sixty-eight percent required dose adjustments from the initiating dose (10 mg) due to sub-optimal trough levels (38%), minimal AML response (15%) or adverse events (47%). 3D volumetric assessment confirmed a reduction in AML volume of a pre-selected index lesion in all treatment-naïve cases (n = 14), showing superiority over 2D measurements of lesion diameter. Conclusion In this cohort, everolimus promoted AML regression in all patients who tolerated the drug for >6 months with stabilization observed over 3 years. Trough levels enabled individual dose titration to maximize responsiveness and minimize side effects. The use of 3D MRI assessment of lesion volume was superior to 2D measurements of lesion diameter in monitoring treatment response.
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Affiliation(s)
- Noelle K X Chung
- The Medical School, University of Sheffield, Sheffield, UK
- Sheffield Kidney Institute, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Peter Metherall
- 3D Lab, Medical Imaging and Medical Physics, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Janet A McCormick
- Sheffield Kidney Institute, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Roslyn J Simms
- Sheffield Kidney Institute, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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28
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Saoud R, Kristof TW, Judge C, Chumbalkar V, Antic T, Eggener S, Modi P. Clinical and pathological features of renal epithelioid angiomyolipoma (PEComa): A single institution series. Urol Oncol 2021; 40:18-24. [PMID: 34815169 DOI: 10.1016/j.urolonc.2021.09.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 07/20/2021] [Accepted: 09/20/2021] [Indexed: 10/19/2022]
Abstract
Renal angiomyolipomas are benign tumors of the kidney that belong to the 'PEComa: perivascular epithelioid cell' family. Epithelioid AMLs (eAML) are a rare monotypic subtype with malignant potential, that can occur sporadically or be associated with tuberous sclerosis (TSC). Due to their epithelioid nature, eAMLs can closely resemble high-grade renal cell carcinoma (RCC), which may result in misdiagnosis. Multiple clinicopathologic parameters are predictive of worse outcomes for patients with eAML. Those can be used to stratify patients into groups with low, intermediate and high risk for disease progression. A high index of suspicion and a thorough immunohistochemical study are required to correctly diagnose eAML. Radiographically, eAMLs are also a diagnostic challenge as they share features with RCC on CT and MR imaging. Due to this close mimicry, the true incidence of eAML is thought to be much higher than 200 cases as reported in the literature. We report a series of four patients diagnosed with eAML and compare their clinical courses. We also report on the successful treatment of a patient with pulmonary metastasis from eAML using the mTOR inhibitor, everolimus. By identifying eAML and recognizing its high-risk features, it is possible mTOR inhibitors may have a meaningful role in the adjuvant treatment of these patients.
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Affiliation(s)
- Ragheed Saoud
- Section of Urology, Department of Surgery, The University of Chicago Medicine, Chicago, IIllinois.
| | - Tanya W Kristof
- Section of Urology, Department of Surgery, The University of Chicago Medicine, Chicago, IIllinois
| | - Clark Judge
- Section of Urology, Department of Surgery, The University of Chicago Medicine, Chicago, IIllinois
| | - Vaibhav Chumbalkar
- Department of Pathology, The University of Chicago Medicine, Chicago, IIllinois
| | - Tatjana Antic
- Department of Pathology, The University of Chicago Medicine, Chicago, IIllinois
| | - Scott Eggener
- Section of Urology, Department of Surgery, The University of Chicago Medicine, Chicago, IIllinois
| | - Parth Modi
- Section of Urology, Department of Surgery, The University of Chicago Medicine, Chicago, IIllinois
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29
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Choi JH, Ro JY. Mesenchymal Tumors of the Mediastinum: An Update on Diagnostic Approach. Adv Anat Pathol 2021; 28:351-381. [PMID: 34050062 DOI: 10.1097/pap.0000000000000306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Mesenchymal tumors of the mediastinum are a heterogenous group of rare tumors with divergent lineages. Mediastinal mesenchymal tumors are diagnostically challenging due to their diversity and morphologic overlap with nonmesenchymal lesions arising in the mediastinum. Accurate histologic diagnosis is critical for appropriate patient management and prognostication. Many mediastinal mesenchymal tumors affect distinct age groups or occur at specific mediastinal compartments. Neurogenic tumors, liposarcoma, solitary fibrous tumor, and synovial sarcoma are common mesenchymal tumors in the mediastinum. Herein, we provide an update on the diagnostic approach to mediastinal mesenchymal tumors and a review of the histologic features and differential diagnosis of common benign and malignant mesenchymal tumors of the mediastinum.
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Affiliation(s)
- Joon Hyuk Choi
- Department of Pathology, Yeungnam University College of Medicine, Daegu, South Korea
| | - Jae Y Ro
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX
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30
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Świtaj T, Sobiborowicz A, Teterycz P, Klimczak A, Makuła D, Wągrodzki M, Szumera-Ciećkiewicz A, Rutkowski P, Czarnecka AM. Efficacy of Sirolimus Treatment in PEComa-10 Years of Practice Perspective. J Clin Med 2021; 10:3705. [PMID: 34442003 PMCID: PMC8396894 DOI: 10.3390/jcm10163705] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/06/2021] [Accepted: 08/17/2021] [Indexed: 11/17/2022] Open
Abstract
Perivascular epithelioid cell tumors (PEComa) represent a family of rare mesenchymal tumors resultant from deregulation in mTOR pathway activity. The aim of this study is to evaluate the long-term efficacy of targeted PEComa treatment. We reviewed all consecutive patients with PEComa who started systemic treatment with sirolimus in our reference sarcoma center between January 2011 and August 2020. Histopathology of PEComa was reviewed and confirmed in all cases by a designated sarcoma pathologist. Any surviving progression-free patients were censored at the last follow-up (31 March 2021). Survival curves were calculated according to Kaplan-Meier method and compared with the log-rank test or a Cox proportional hazard model. Fifteen (12 females and 3 males) consecutive PEComa patients were treated. The median age of patients treated systemically was 50 years. Median progression-free survival (PFS) was 4.9 months (95% CI: 3.8-NA) for first-line chemotherapy and was not reached (95% CI: 42.0-NA) for sirolimus as first-line therapy. There was one objective response (OR) in the chemotherapy group. The OR rate reached 73% (11/15 cases) for sirolimus regardless of the treatment line. All patients archived disease control. Three patients died due to disease progression after 55, 32, and 32 months since metastatic disease diagnosis. After a median follow-up of 55.7 (range: 3.2-220) months, the 5 yr OS was 65% (CI 95% 39-100). Our study is the largest single-institution report on PEComa systemic targeted therapy and fills the gap in the field of advanced PEComa care since the FDA/EMEA approval of sirolimus.
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Affiliation(s)
- Tomasz Świtaj
- Department of Soft Tissue/Bone, Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (T.Ś.); (A.S.); (P.T.); (A.K.); (P.R.)
| | - Aleksandra Sobiborowicz
- Department of Soft Tissue/Bone, Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (T.Ś.); (A.S.); (P.T.); (A.K.); (P.R.)
- Medical Faculty, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Paweł Teterycz
- Department of Soft Tissue/Bone, Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (T.Ś.); (A.S.); (P.T.); (A.K.); (P.R.)
- Department of Computational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Anna Klimczak
- Department of Soft Tissue/Bone, Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (T.Ś.); (A.S.); (P.T.); (A.K.); (P.R.)
| | - Donata Makuła
- Department of Radiology I, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland;
| | - Michał Wągrodzki
- Department of Pathology and Laboratory Diagnostics, Maria Skłodowska-Curie Institute-Oncology Center, 02-781 Warsaw, Poland; (M.W.); (A.S.-C.)
| | - Anna Szumera-Ciećkiewicz
- Department of Pathology and Laboratory Diagnostics, Maria Skłodowska-Curie Institute-Oncology Center, 02-781 Warsaw, Poland; (M.W.); (A.S.-C.)
- Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, 00-791 Warsaw, Poland
| | - Piotr Rutkowski
- Department of Soft Tissue/Bone, Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (T.Ś.); (A.S.); (P.T.); (A.K.); (P.R.)
| | - Anna M. Czarnecka
- Department of Soft Tissue/Bone, Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (T.Ś.); (A.S.); (P.T.); (A.K.); (P.R.)
- Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences Warsaw, 02-106 Warsaw, Poland
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31
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Abstract
Herein, we wanted to explore the molecular landscape of mucosal melanoma from different sites and identify potential molecular targets for future therapy. Mucosal melanomas (N = 40) from different sites (conjunctiva, sinonasal cavity, rectum, and vagina) were investigated. Targeted next-generation sequencing along with Nanostring gene expression profiling was performed. Genetically, conjunctival melanoma was characterized by BRAF-V600E (30%) and NF1 mutations (17%). Mucosal melanomas at nonsun-exposed sites harbored alterations in NRAS, KIT, NF1, along with atypical BRAF mutations. When comparing the gene expression profile of conjunctival melanoma and nonsun-exposed mucosal melanoma, 41 genes were found to be significantly deregulated. Programmed death-ligand 1 (PD-L1) presented a significant sixfold upregulation in conjunctival melanoma compared to the other mucosal melanomas. While melanomas of the sinonasal cavity, vagina, and rectum are molecularly similar, conjunctival melanoma is characterized by a higher frequency of BRAF-V600E mutations and differential expression of several genes involved in the immune response.
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32
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McBride A, Garcia AJ, Sanders LJ, Yiu K, Cranmer LD, Kuo PH, Kay M, Kraft AS. Sustained response to pembrolizumab in recurrent perivascular epithelioid cell tumor with elevated expression of programmed death ligand: a case report. J Med Case Rep 2021; 15:400. [PMID: 34301321 PMCID: PMC8305520 DOI: 10.1186/s13256-021-02997-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 06/02/2021] [Indexed: 12/30/2022] Open
Abstract
Background Perivascular epithelioid cell tumors are defined by the World Health Organization as “a collection of rare mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells.” Whereas localized perivascular epithelioid cell tumor is typically benign and treated successfully with surgical resection, prognosis for patients with advanced or metastatic perivascular epithelioid cell tumor is unfavorable, and there is no standard curative treatment. Case presentation We report a Caucasian case of metastatic perivascular epithelioid cell tumor previously treated with chemotherapy and surgery with elevated surface expression of programmed cell death ligand 1. Based on this result, treatment via immune checkpoint inhibition with the monoclonal antibody pembrolizumab was pursued. After 21 cycles, the patient sustained a complete response. Therapy was stopped after the 40th cycle, and she was moved to surveillance. She remained disease free 19 months off treatment. Conclusions This case report of a patient with perivascular epithelioid cell tumor treated successfully with programmed cell death protein-1 targeted therapy suggests that programmed cell death ligand-1 levels should be measured in patients with perivascular epithelioid cell tumor and immunotherapy considered for recurrent or metastatic patients. Future phase II/III studies in this disease should focus on sequencing of surgery and immunotherapy with a design of curative intent.
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Affiliation(s)
- Ali McBride
- University of Arizona Cancer Center, 1515 N. Campbell Ave., Tucson, AZ, 85718, USA
| | - Andrew J Garcia
- College of Pharmacy, University of Arizona, Tucson, AZ, USA.,College of Medicine, George Washington University, Washington, DC, USA
| | - Lauren J Sanders
- University of Arizona Cancer Center, 1515 N. Campbell Ave., Tucson, AZ, 85718, USA
| | - Kelly Yiu
- College of Pharmacy, University of Arizona, Tucson, AZ, USA
| | - Lee D Cranmer
- University of Arizona Cancer Center, 1515 N. Campbell Ave., Tucson, AZ, 85718, USA.,Seattle Cancer Care Alliance, Seattle, WA, USA
| | - Phillip H Kuo
- Department of Medical Imaging, Medicine and Biomedical Engineering, University of Arizona College of Medicine, Tucson, AZ, USA
| | - Matthew Kay
- Department of Medical Imaging, Medicine and Biomedical Engineering, University of Arizona College of Medicine, Tucson, AZ, USA
| | - Andrew S Kraft
- University of Arizona Cancer Center, 1515 N. Campbell Ave., Tucson, AZ, 85718, USA.
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Primary soft tissue angiomyolipoma in a dog with unusual clinical features. ACTA VET BRNO 2021. [DOI: 10.2754/avb202190020179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Angiomyolipoma is an extremely rare neoplasm in animals. It belongs to a group of perivascular epithelioid cell tumours (so-called PEComas). This study reports a case of primary soft tissue angiomyolipoma in a dog with some unusual clinical features. A 4-year old female Labrador dog with a rapidly growing pelvic tumour measuring 30 × 20 cm with a short history of 12 weeks was presented. The tumour was well-circumscribed and pushed into the right vaginal wall and into the perineum. The tumour was completely surgically excised. An extensive histological examination was performed, including immunohistochemical analysis. Histology revealed a mesenchymal neoplasm consisting of three tissue components – mature adipose tissue (which dominated), vessels, and smooth muscle (spindle) cells. The lesion showed positive immunohistochemical staining with smooth muscle actin and desmin in mature-appearing smooth muscle cells and S-100 protein positivity in adipocytes. The diagnosis of angiomyolipoma must be considered in different types of benign and malignant tumours of various lineages. The diagnostic approach to soft tissue tumours, including angiomyolipoma, requires optimal processing and sectioning of resected specimens. This paper is believed to be the first case of primary soft tissue angiomyolipoma reported in the veterinary literature.
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Shukla PS, Xia R, Lin LH, Schwartz CJ. Gynaecological perivascular epithelioid cell tumour (PEComa): comparative analysis of proposed algorithms for prediction of clinical outcome. Histopathology 2021; 79:847-860. [PMID: 34157139 DOI: 10.1111/his.14434] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/09/2021] [Accepted: 06/18/2021] [Indexed: 01/31/2023]
Abstract
AIMS Perivascular epithelioid cell tumours (PEComas) are rare mesenchymal tumours that coexpress smooth muscle and melanocytic markers. They have a predilection for gynaecological organs, where they present a unique diagnostic challenge, because of morphological and immunohistochemical overlap with more common smooth muscle and stromal tumours. Limited information regarding the natural history, owing to the rarity of this tumour, makes accurate risk stratification difficult. We aimed to review clinicopathological features of gynaecological PEComa and compare accuracy of five different classification systems for prediction of prognosis. METHODS AND RESULTS We have described the clinicopathological features of 13 new cases and tested five prognostic algorithms in a total of 67 cases of gynaecological PEComa. Receiver operating characteristic curves were constructed and areas under the curve (AUCs) were calculated to evaluate predictive accuracy. The modified gynaecological-specific algorithm showed high sensitivity and specificity and yielded the highest AUC (0.864). It's earlier version, the gynaecological-specific algorithm, suffered from lower specificity (AUC = 0.843). The post-hoc McNemar test confirmed significant differences between the performances of the modified gynaecological-specific algorithm and the gynaecological-specific algorithm (P = 0.008). The original Folpe algorithm for PEComas of all sites showed low specificity, had a lower AUC (0.591), and was inapplicable in 18% of cases. Its two later versions (the revised Folpe algorithm and the modified Folpe algorithm) also yielded lower AUCs (0.690 and 0.591, respectively). CONCLUSION We have shown that the modified gynaecological-specific algorithm predicts the clinical outcome of gynaecological PEComa with high accuracy, and have validated its use for prognostic stratification of gynaecological PEComa.
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Affiliation(s)
| | - Rong Xia
- NYU Langone Medical Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Lawrence Hsu Lin
- NYU Langone Medical Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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35
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Kopparthy P, Murphy M. Rapid and Durable Response With Nab-Sirolimus After Everolimus Failure in a Patient With Perivascular Epithelioid Cell Tumors (PEComas) of the Uterus. Cureus 2021; 13:e14951. [PMID: 34123648 PMCID: PMC8190830 DOI: 10.7759/cureus.14951] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors with a natural history ranging from indolent benign lesions to ones with an aggressive clinical course including distant metastases. Recent reports have suggested that mTOR inhibitor sirolimus and related drugs show some benefit in non-tuberous sclerosis complex PEComas. However, therapeutic options for patients who progress on sirolimus are very limited. We describe a patient with metastatic uterine PEComa, who progressed on mTOR inhibitor everolimus but had a rapid and durable response to nab-sirolimus.
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Affiliation(s)
| | - Martina Murphy
- Hematology and Oncology, University of Florida Health, Gainesville, USA
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36
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Ruiz Guerrero E, Ledo Cepero MJ, Ojeda Claro AV, Soto Delgado M, Álvarez-Ossorio Fernández JL. Renal angiomyolipoma and tuberous sclerosis complex: long-term safety and efficacy outcomes of Everolimus therapy. Actas Urol Esp 2021; 45:264-272. [PMID: 33637375 DOI: 10.1016/j.acuro.2020.11.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 10/25/2020] [Accepted: 11/10/2020] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Renal angiomyolipoma is a frequent manifestation of Tuberous Sclerosis Complex (TSC), for which everolimus therapy has been recently established as a novel non-invasive therapeutic option. As there are limited real life and long-term data, the analysis of our experience provides added value in terms of safety and efficacy. MATERIAL AND METHODS Descriptive analysis of our experience in patients with giant bilateral renal angiomyolipomas, in the context of TSC, treated with 10 mg oral everolimus daily, during a median of 71.5 months. We evaluated the following parameters: response rate and duration, reduction of kidney size and lesions, prevention of complications and presentation of toxicity and its cause. RESULTS We confirm the effectiveness of treatment in 4 young patients, with multiple, bilateral angiomyolipomas of a median of 12 (5-19) cm maximum diameter, from June 2013 to date, after continuous reduction in lesion size, a decrease of 30% of the volume in 75% at six months and 50% in half of the subjects at two years, still showing drug response. Absence of complications such as bleeding or glomerular filtration rate decline in the long term, with a favorable safety profile, without interruptions and with mild-moderate, non-cumulative adverse effects, mostly within the first year of treatment. CONCLUSION Everolimus is a safe and effective therapeutic option for renal angiomyolipoma and various manifestations of TSC, which has been reproduced in real life with six years of follow-up.
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Affiliation(s)
- E Ruiz Guerrero
- Unidad de Uro-Oncología, Servicio Urología, Hospital Universitario Puerta del Mar, INIBICA (Instituto de Investigación e Innovación Biomédica), Cádiz, España.
| | - M J Ledo Cepero
- Unidad de Uro-Oncología, Servicio Urología, Hospital Universitario Puerta del Mar, INIBICA (Instituto de Investigación e Innovación Biomédica), Cádiz, España
| | - A V Ojeda Claro
- Unidad de Uro-Oncología, Servicio Urología, Hospital Universitario Puerta del Mar, INIBICA (Instituto de Investigación e Innovación Biomédica), Cádiz, España
| | - M Soto Delgado
- Unidad de Uro-Oncología, Servicio Urología, Hospital Universitario Puerta del Mar, INIBICA (Instituto de Investigación e Innovación Biomédica), Cádiz, España
| | - J L Álvarez-Ossorio Fernández
- Unidad de Uro-Oncología, Servicio Urología, Hospital Universitario Puerta del Mar, INIBICA (Instituto de Investigación e Innovación Biomédica), Cádiz, España
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Ramezanpour S, Horvai AE, Zimel M, Bucknor M, Link TM. Fibroma-like perivascular epithelioid cell tumor: a rare case in a long bone. Skeletal Radiol 2021; 50:821-825. [PMID: 32944815 DOI: 10.1007/s00256-020-03610-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/02/2020] [Accepted: 09/10/2020] [Indexed: 02/02/2023]
Abstract
Fibroma-like perivascular epithelioid cell (PEComa) tumor is an extremely rare family of mesenchymal tumors composed of cells co-expressing melanocytic and myogenic markers. To date, 13 cases of primary bone PEComa have been reported in the literature and five reported fibroma-like PEComas were found in the soft tissues of patients with tuberous sclerosis (TSC). However, no fibroma-like PEComa has been reported in bone, either sporadic or TSC-associated. Here we report the case of a 22-year-old man with known TSC, who presented for evaluation of an asymptomatic mass in his left fibula diaphysis that had been present for 5 years. He had no activity-related pain, numbness, weakness, or limitations in range of motion. Both 3-T MRI and CT demonstrated a tumor originating from the midshaft middiaphyseal fibula. Axial T1-weighted and fat-saturated T2-weighted fast spin echo images showed a well-defined lesion in the fibula with extension into the surrounding soft tissues. Whole body bone scan was negative for metastasis using technetium-99m. Renal ultrasound was unremarkable with no evidence of angiomyolipoma. Histopathology demonstrated isolated spindle cells in a dense collagenous matrix. By immunohistochemical staining, tumor cells were positive for HMB-45 and MiTF and partially positive for alpha-smooth muscle actin supporting a diagnosis of fibroma-like PEComa of the midshaft fibula. Although fibroma-like PEComa of bone is very rare, a bone tumor in the setting of TSC should raise suspicion for the diagnosis, in particular if histology demonstrates rare epithelioid cells in a densely fibrotic stroma.
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Affiliation(s)
- Sara Ramezanpour
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, 400 Parnassus Ave, A-367, San Francisco, CA, 94143, USA.
| | - Andrew E Horvai
- Department of Pathology, University of California, San Francisco, San Francisco, CA, USA
| | - Melissa Zimel
- Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA, USA
| | - Matthew Bucknor
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, 400 Parnassus Ave, A-367, San Francisco, CA, 94143, USA
| | - Thomas M Link
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, 400 Parnassus Ave, A-367, San Francisco, CA, 94143, USA.
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Liapi A, Mathevet P, Herrera FG, Hastir D, Sarivalasis A. VEGFR Inhibitors for Uterine Metastatic Perivascular Epithelioid Tumors (PEComa) Resistant to mTOR Inhibitors. A Case Report and Review of Literature. Front Oncol 2021; 11:641376. [PMID: 33842348 PMCID: PMC8032946 DOI: 10.3389/fonc.2021.641376] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 02/19/2021] [Indexed: 12/20/2022] Open
Abstract
Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms. PI3K/AKT/mTOR pathway upregulation is critical for their pathogenesis and is often associated with TSC1/TSC2 inactivation. Although first line mTOR inhibitors are an effective treatment, metastatic PEComas eventually progress. A 53-year-old woman presented a 4-month history of post-menopausal vaginal bleeding. Clinical and radiological examination detected a uterine mass and a single S1 bone lesion. The patient underwent a radical hysterectomy and bone biopsy. The anatomopathological evaluation concluded to an oligo-metastatic uterine PEComa. The tumor harbored a heterozygous deletion of 9q34 that contains the TSC1 gene. Concerning the primary lesion, the resection was complete and the single bone metastasis was treated with radiotherapy. Three months later, the patient presented bone, lung and subcutaneous metastatic progression. An everolimus and denosumab treatment was initiated. After 2 years of treatment, a clinically significant bone, lung and subcutaneous progression was detected. Following a literature review of the possible therapeutic options, we initiated a second line treatment by pazopanib. This treatment resulted in regression of the subcutaneous lesions and stability of lung and bone metastases. In this challenging, rare setting, our report suggests single agent, anti-angiogenic, tyrosine kinase inhibitor to be effective as second line treatment of metastatic uterine PEComa progressing on mTOR inhibitors.
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Affiliation(s)
- Aikaterini Liapi
- Département d'oncologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Patrice Mathevet
- Département de Gynécologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Fernanda G Herrera
- Département d'oncologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Delfyne Hastir
- Institut Universitaire de Pathologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Apostolos Sarivalasis
- Département d'oncologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
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Mimickers of Urothelial Carcinoma and the Approach to Differential Diagnosis. Clin Pract 2021; 11:110-123. [PMID: 33668963 PMCID: PMC7931042 DOI: 10.3390/clinpract11010017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 02/09/2021] [Accepted: 02/18/2021] [Indexed: 01/03/2023] Open
Abstract
A broad spectrum of lesions, including hyperplastic, metaplastic, inflammatory, infectious, and reactive, may mimic cancer all along the urinary tract. This narrative collects most of them from a clinical and pathologic perspective, offering urologists and general pathologists their most salient definitory features. Together with classical, well-known, entities such as urothelial papillomas (conventional (UP) and inverted (IUP)), nephrogenic adenoma (NA), polypoid cystitis (PC), fibroepithelial polyp (FP), prostatic-type polyp (PP), verumontanum cyst (VC), xanthogranulomatous inflammation (XI), reactive changes secondary to BCG instillations (BCGitis), schistosomiasis (SC), keratinizing desquamative squamous metaplasia (KSM), post-radiation changes (PRC), vaginal-type metaplasia (VM), endocervicosis (EC)/endometriosis (EM) (müllerianosis), malakoplakia (MK), florid von Brunn nest proliferation (VB), cystitis/ureteritis cystica (CC), and glandularis (CG), among others, still other cellular proliferations with concerning histological features and poorly understood etiopathogenesis like IgG4-related disease (IGG4), PEComa (PEC), and pseudosarcomatous myofibroblastic proliferations (post-operative spindle cell nodule (POS), inflammatory myofibroblastic tumor (IMT)), are reviewed. Some of these diagnoses are problematic for urologists, other for pathologists, and still others for both. Interestingly, the right identification of their definitory features will allow their correct diagnoses, thus, avoiding overtreatment. The literature selected for this review also focuses on the immunohistochemical and/or molecular data useful to delineate prognosis.
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40
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Caliò A, Brunelli M, Gobbo S, Pedron S, Segala D, Argani P, Martignoni G. Stimulator of interferon genes (STING) immunohistochemical expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney. Pathology 2021; 53:579-585. [PMID: 33461798 DOI: 10.1016/j.pathol.2020.09.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 09/20/2020] [Indexed: 01/13/2023]
Abstract
Angiomyolipoma is the prototype of renal perivascular epithelioid cell (PEC) lesions whose pathogenesis is determined by mutations affecting TSC genes, with eventual deregulation of the mTOR pathway. It is well known that mTOR complex protein is involved in autophagy, and recently the role of STING in this process has been demonstrated. Based on this background, we sought to investigate STING immunohistochemical expression in a series of PEC lesions of the kidney. Fifty classic angiomyolipomas, 14 epithelioid angiomyolipomas/pure epithelioid PEComas, two angiomyolipomas with epithelial cysts (AMLEC), and two intraglomerular PEC lesions were collected. Immunostaining for STING was carried out in all cases and FISH analysis using dual colour break apart TFE3 and TFEB probes was performed in all pure epithelioid PEComas and AMLEC. Control cases including 20 normal adult kidneys, five fetal kidneys, and 30 MiT family translocation renal cell carcinomas (the main differential diagnosis with epithelioid angiomyolipoma/pure epithelioid PEComa) were also immunohistochemically stained with STING. Strong and diffuse cytoplasmic expression of STING was observed in 100% of classic angiomyolipomas, AMLEC, and intraglomerular lesions, and in 79% (11/14) of epithelioid angiomyolipomas/pure epithelioid PEComas. TFE3 gene rearrangement was demonstrated in two epithelioid angiomyolipomas/pure epithelioid PEComas, both completely negative for STING. None of the MiT family translocation renal cell carcinomas expressed STING. In conclusion, we demonstrate the expression of STING in almost all PEC lesions of the kidney. This result provides novel insights into the possible role of autophagy in PEC lesions of the kidney. Moreover, this finding may be useful for diagnostic purposes, particularly in distinguishing epithelioid angiomyolipoma/pure epithelioid PEComa from MiT family translocation renal cell carcinoma and detecting intraglomerular PEC lesions.
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Affiliation(s)
- Anna Caliò
- Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - Matteo Brunelli
- Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - Stefano Gobbo
- Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy
| | - Serena Pedron
- Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy
| | - Diego Segala
- Department of Molecular and Translational Medicine, Section of Pathology, University-Spedali Civili of Brescia, Italy
| | - Pedram Argani
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Guido Martignoni
- Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy; Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy.
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Selenica P, Conlon N, Gonzalez C, Frosina D, Jungbluth AA, Beets-Tan RGH, Rao MK, Zhang Y, Benayed R, Ladanyi M, Solit DB, Chiang S, Hyman DM, Hensley ML, Soslow RA, Weigelt B, Murali R. Genomic Profiling Aids Classification of Diagnostically Challenging Uterine Mesenchymal Tumors With Myomelanocytic Differentiation. Am J Surg Pathol 2021; 45:77-92. [PMID: 32889887 PMCID: PMC8276853 DOI: 10.1097/pas.0000000000001572] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Although diagnosis of high-grade uterine mesenchymal tumors (UMTs) exhibiting classic morphologic features is straightforward, diagnosis is more challenging in tumors in which prototypical features are poorly developed, focal, and/or coexist with features seen in other neoplasms. Here, we sought to define the repertoire of somatic genetic alterations in diagnostically challenging UMTs with myomelanocytic differentiation, including some reported as perivascular epithelioid cell tumors (PEComas). In 17 samples from 15 women, the tumors were histologically heterogenous. Immunohistochemical expression of at least 1 melanocytic marker (HMB45, Melan-A, or MiTF) was identified in all tumors, and of myogenic markers (desmin or smooth muscle actin) in most tumors. Targeted massively parallel sequencing revealed several genetic alterations, most commonly in TP53 (41% mutation, 12% deletion), TSC2 (29% mutation, 6% deletion), RB1 (18% deletion), ATRX (24% mutation), MED12 (12% mutation), BRCA2 (12% deletion), CDKN2A (6% deletion) as well as FGFR3, NTRK1, and ERBB3 amplification (each 6%). Gene rearrangements (JAZF1-SUZ12; DNAJB6-PLAG1; and SFPQ-TFE3) were identified in 3 tumors. Integrating histopathologic, immunohistochemical, and genetic findings, tumors from 4 patients were consistent with malignant PEComa (1 TFE3-rearranged); 6 were classified as leiomyosarcomas; 3 showed overlapping features of PEComa and other sarcoma types (leiomyosarcoma or low-grade endometrial stromal sarcoma); and 2 were classified as sarcoma, not otherwise specified. Our findings suggest that diagnostically challenging UMTs with myomelanocytic differentiation represent a heterogenous group of neoplasms which harbor a diverse repertoire of somatic genetic alterations; these genetic alterations can aid classification.
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Affiliation(s)
- Pier Selenica
- Departments of Pathology
- GROW School for Oncology and Developmental Biology
| | - Niamh Conlon
- Departments of Pathology
- Department of Pathology, Cork University Hospital, Cork, Ireland
| | | | | | | | - Regina G. H. Beets-Tan
- GROW School for Oncology and Developmental Biology
- Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | | | - David B. Solit
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Medicine
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Bennett JA, Oliva E. Undifferentiated and dedifferentiated neoplasms of the female genital tract. Semin Diagn Pathol 2020; 38:137-151. [PMID: 33323288 DOI: 10.1053/j.semdp.2020.11.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 11/07/2020] [Accepted: 11/25/2020] [Indexed: 12/25/2022]
Abstract
Undifferentiated neoplasms in the female gynecologic tract comprise two main groups-undifferentiated carcinoma, most common in the endometrium and ovary, and undifferentiated uterine sarcoma, although tumors with an undifferentiated appearance may occur in all gynecologic organs. Their differential diagnosis is broad and generous sampling, careful morphological evaluation, judicious use of immunohistochemistry, and in many cases, molecular testing is often essential in the diagnostic work-up. As some of these neoplasms fail to respond to conventional chemotherapy regimens and/or radiation therapy, targeted therapy may be valuable in treating these highly aggressive tumors, thus the importance of precise diagnosis. In this review we discuss the clinicopathological features of undifferentiated carcinoma, dedifferentiated carcinoma, and undifferentiated uterine sarcoma, followed by a comprehensive analysis of morphological mimickers. Finally, we briefly review ovarian and lower genital tract tumors with an undifferentiated histological appearance.
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Affiliation(s)
- Jennifer A Bennett
- Department of Pathology, University of Chicago Medicine, 5841 S. Maryland Ave, Chicago, IL, 60637, USA.
| | - Esther Oliva
- Department of Pathology, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
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43
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Schmiester M, Dolnik A, Kornak U, Pfitzner B, Hummel M, Treue D, Hartmann A, Agaimy A, Weyerer V, Lekaj A, Brakemeier S, Peters R, Öllinger R, Märdian S, Bullinger L, Striefler JK, Flörcken A. TFE3 activation in a TSC1-altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms. JOURNAL OF PATHOLOGY CLINICAL RESEARCH 2020; 7:3-9. [PMID: 33180365 PMCID: PMC7737753 DOI: 10.1002/cjp2.187] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 09/25/2020] [Accepted: 09/30/2020] [Indexed: 02/06/2023]
Abstract
Perivascular epithelioid cell tumors (PEComas) form a family of rare mesenchymal neoplasms that typically display myomelanocytic differentiation. Upregulation of mTOR signaling due the inactivation of TSC1/2 (Tuberous Sclerosis 1 and 2) is believed to be a key oncogenic driver in this disease. Recently, a subgroup of PEComas harboring TFE3 (Transcription Factor E3) rearrangements and presenting with a distinctive morphology has been identified. TSC1/2 and TFE3 aberrations are deemed to be mutually exclusive in PEComa, with two different pathogenic mechanisms assumed to lead to tumorigenesis. Here, we challenge this dichotomy by presenting a case of a clinically aggressive TCS1‐mutated PEComa displaying a TFE3‐altered phenotype. FISH analysis was suggestive of a TFE3 inversion; however, RNA and whole genome sequencing was ultimately unable to identify a fusion involving the gene. However, a copy number increase of the chromosomal region encompassing TFE3 was detected and transcriptome analysis confirmed upregulation of TFE3, which was also seen at the protein level. Therefore, we believe that the TSC1/2‐mTOR pathway and TFE3 overexpression can simultaneously contribute to tumorigenesis in PEComa. Our comprehensive genetic analyses add to the understanding of the complex pathogenic mechanisms underlying PEComa and harbor insights for clinical treatment options.
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Affiliation(s)
- Maren Schmiester
- Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany
| | - Anna Dolnik
- Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Uwe Kornak
- Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany
| | - Berit Pfitzner
- Institute of Pathology, DRK Kliniken Berlin Westend, Berlin, Germany
| | - Michael Hummel
- Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Denise Treue
- Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Arndt Hartmann
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany
| | - Abbas Agaimy
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany
| | - Veronika Weyerer
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany
| | - Anja Lekaj
- Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Susanne Brakemeier
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Robert Peters
- Department of Urology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Robert Öllinger
- Department of Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Sven Märdian
- Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Lars Bullinger
- Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jana Käthe Striefler
- Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Anne Flörcken
- Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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44
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Bennett JA, Oliva E. Perivascular epithelioid cell tumors (PEComa) of the gynecologic tract. Genes Chromosomes Cancer 2020; 60:168-179. [PMID: 33099813 DOI: 10.1002/gcc.22908] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 10/21/2020] [Indexed: 12/13/2022] Open
Abstract
PEComas of the female genital tract are rare mesenchymal neoplasms that are most common in the uterus, but also may occur in other gynecologic locations. As they morphologically and immunohistochemically resemble smooth muscle tumors, distinction between the two entities is often challenging, and may be aided by molecular analysis. Thus far, two distinct molecular groups-classic PEComas with TSC mutations and TFE3-translocation associated PEComas with TFE3 fusions have been described. Recognition of the first group is imperative as these patients may benefit from targeted therapy with mTOR inhibitors, if malignant. This review will focus on recognition of the morphologic and immunophenotypic features of PEComas, as well as the role of molecular testing in their diagnosis and treatment, analysis of the different algorithms to predict behavior, and differential diagnosis.
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Affiliation(s)
- Jennifer A Bennett
- Department of Pathology, University of Chicago Medicine, Chicago, Illinois, USA
| | - Esther Oliva
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
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45
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Andión Catalán M, Buendía López S, Camarena Pavón N, Rubio San Simón A, Cañas Maciá T, Azorín Cuadrillero D. Composite sarcoma of bone with focal rhabdomyosarcoma and lymph node metastasis in an adolescent. Pediatr Blood Cancer 2020; 67:e28679. [PMID: 32860659 DOI: 10.1002/pbc.28679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 08/12/2020] [Accepted: 08/17/2020] [Indexed: 11/10/2022]
Abstract
Composite sarcoma of bone is a very rare entity that primarily affects adolescent and young adult patients. It usually combines areas of liposarcoma and osteosarcoma, and up to 60% of cases have metastatic disease at diagnosis. It is a highly aggressive pathology with intrinsic resistance to bone sarcoma conventional treatments. The prognosis is poor, with long-term survival rates not exceeding 30%. We present the case of an adolescent female diagnosed with an aggressive composite sarcoma of bone with rhabdomyosarcoma foci and loco-regional lymph node involvement.
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Affiliation(s)
- Maitane Andión Catalán
- Pediatric Hematology-Oncology and Hematopoietic Stem Cell Transplantation Unit, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Susana Buendía López
- Pediatric Hematology-Oncology and Hematopoietic Stem Cell Transplantation Unit, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Natalia Camarena Pavón
- Pediatric Hematology-Oncology and Hematopoietic Stem Cell Transplantation Unit, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Alba Rubio San Simón
- Pediatric Hematology-Oncology and Hematopoietic Stem Cell Transplantation Unit, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Teresa Cañas Maciá
- Pediatric Radiology Unit, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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46
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Eosinophilic Renal Cell Tumors With a TSC and MTOR Gene Mutations Are Morphologically and Immunohistochemically Heterogenous: Clinicopathologic and Molecular Study. Am J Surg Pathol 2020; 44:943-954. [PMID: 32091432 DOI: 10.1097/pas.0000000000001457] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Eosinophilic renal neoplasms have a wide spectrum of histologic presentations, and several studies have demonstrated a subtype of renal cell carcinomas (RCCs) associated with the tuberous sclerosis complex (TSC)/mammalian target of rapamycin pathway. A review of our institutional archives led to the identification of 18 cases of renal eosinophilic tumors with unusual morphology. Immunohistochemical analysis demonstrated that these could be separated into 3 groups: group 1 had solid architecture and morphology similar to chromophobe RCC but was negative for CK20 and vimentin, and had weak focal staining for CK7 and P504S; group 2 had solid architecture and morphology similar to either renal oncocytoma or chromophobe RCC, eosinophilic variant and had diffuse staining of CK7 and P504S, absent to weak staining of CK20, and negative staining for vimentin; and group 3 had solid, cystic and papillary architecture and was negative for CK7, except for 1 case, along with moderate to strong staining of CK20, P504S, and vimentin. The cases were then sent for next-generation sequencing to determine whether molecular pathogenic variants were present. In group 1, all 3 cases had mutations in TSC2. In group 2, pathogenic variants were identified in 3 genes: TSC1, TSC2, and MTOR. In group 3, genetic alterations and pathogenic variants were identified in TSC1 and TSC2. Our results support TSC/MTOR-associated neoplasms as a distinct group that exhibits heterogenous morphology and immunohistochemical staining.
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47
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Wangsiricharoen S, Larman TC, Wakely PE, Siddiqui MT, Ali SZ. Cytopathology of extra-renal perivascular epithelioid cell tumor (PEComa): a series of 7 cases and review of the literature. J Am Soc Cytopathol 2020; 10:175-186. [PMID: 33162379 DOI: 10.1016/j.jasc.2020.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/16/2020] [Accepted: 09/16/2020] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Perivascular epithelioid cell tumor (PEComa) is a family of rare mesenchymal tumors consisting of histologically and immunohistochemically distinctive perivascular epithelioid cells. Relatively little is known about the cytopathology of extra-renal PEComas. Because of a considerable range of morphology and their rarity, accurate cytologic classification can be challenging. We evaluated cytologic characteristics and diagnostic pitfalls of extra-renal PEComas on fine-needle aspiration (FNA). MATERIALS AND METHODS We performed a retrospective search in our cytopathology and surgical pathology database for cases diagnosed as PEComa that had corresponding cytology specimens from 3 medical institutions. All available cytopathology specimens were reviewed. We evaluated cytologic characteristics and recorded histologic diagnoses and immunohistochemical stains. RESULTS Seven FNA specimens from 6 patients were identified, and cytologic diagnoses were made in all cases as follows: PEComa (4 cases), most consistent with PEComa (1 case), malignant neoplasm (1 case), and hepatocellular carcinoma (1 case). Most specimens were moderately to highly cellular. Cell distribution occurred as tissue fragments with background proliferating capillaries. Most smears were composed of epithelioid cells showing mild to moderate anisonucleosis, abundant eosinophilic cytoplasm, well-defined borders, intranuclear pseudoinclusions, and prominent nucleoli. A combination of myoid and melanocytic markers was expressed in 6 cases except 1 case, which was called hepatocellular carcinoma. CONCLUSIONS This was the largest FNA series for extra-renal PEComas to date. Our study highlights some common cytomorphologic characteristics of PEComa with which cytopathologists should be familiar. In the right clinical and radiologic context, and with the aid of immunohistochemistry, a definitive diagnosis can be achieved.
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Affiliation(s)
| | - Tatianna C Larman
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Paul E Wakely
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Momin T Siddiqui
- Department of Pathology and Laboratory Medicine, Weil Cornell Medicine, New York Presbyterian Hospital, New York, New York
| | - Syed Z Ali
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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Retroperitoneal Sarcomas: An Update on the Diagnostic Pathology Approach. Diagnostics (Basel) 2020; 10:diagnostics10090642. [PMID: 32867125 PMCID: PMC7555595 DOI: 10.3390/diagnostics10090642] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/24/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023] Open
Abstract
Retroperitoneal sarcomas are a heterogenous group of rare tumors arising in the retroperitoneum. Retroperitoneal sarcomas comprise approximately 10% of all soft tissue sarcomas. Though any soft tissue sarcoma histologic types may arise in the retroperitoneal space, liposarcoma (especially well-differentiated and dedifferentiated types) and leiomyosarcoma do so most commonly. Retroperitoneal sarcomas are diagnostically challenging, owing to their diversity and morphological overlap with other tumors arising in the retroperitoneum. An accurate diagnosis is necessary for correct management and prognostication. Herein, we provide an update on the diagnostic approach to retroperitoneal sarcomas and review their key histologic findings and differential diagnoses.
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Lee G, Nabavizadeh R, Osunkoya AO, Master VA. A Rare Case of Vena Cava Tumor Thrombus Associated With Epithelioid Angiomyolipoma. Urology 2020; 142:e4-e7. [PMID: 32445769 DOI: 10.1016/j.urology.2020.05.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 04/18/2020] [Accepted: 05/10/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Grace Lee
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Reza Nabavizadeh
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Adeboye O Osunkoya
- Department of Urology, Emory University School of Medicine, Atlanta, GA; Department of Pathology, Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute, Emory University, Atlanta, GA
| | - Viraj A Master
- Department of Urology, Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute, Emory University, Atlanta, GA.
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50
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Penel N, Lebellec L, Blay JY, Robin YM. Overview of « druggable » alterations by histological subtypes of sarcomas and connective tissue intermediate malignancies. Crit Rev Oncol Hematol 2020; 150:102960. [PMID: 32320927 DOI: 10.1016/j.critrevonc.2020.102960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 04/07/2020] [Accepted: 04/08/2020] [Indexed: 10/24/2022] Open
Abstract
We summarize herein the literature data about molecular targeted therapies in sarcomas and conjunctive tissue intermediate malignancies. For each clinical setting, the level of evidence, the mechanism of action and the target are described. The two major axes include (i) identification of subgroups of tumors with druggable alteration irrespective of the histological diagnosis (e.g. NTRK), and (ii) druggable target of pathway related to the physiopathology of the tumor: denosumab and bone giant cell tumor, imatinib and soft tissue giant cell tumor, mTOR inhibitor and PECOMA.
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Affiliation(s)
- Nicolas Penel
- Department of Medical Oncology, Centre Oscar Lambret, Lille, France; Lille University, Medical School, Lille, France.
| | - Loïc Lebellec
- Lille University, Medical School, Lille, France; Medical Oncology Unit, Dron Hospital, Tourcoing, France
| | - Jean-Yves Blay
- Department of Medicine, Centre Leon Bérard, Lyon, France; Claude Bernard University, Medical School Lyon, France
| | - Yves-Marie Robin
- Biopathology department, Centre Oscar Lambret, Lille, France; Lille University, Inserm U1192, Laboratoire « Protéomique, Réponse Inflammatoire et Spectrométrie de Masse » (PRISM), Villeneuve d'Ascq, France
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