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1
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Sidorov IV, Sharlai AS, Konovalov DM. [Gastric tumors with GLI1 gene alterations (plexiform fibromyxoma and gastroblastoma). Case report and literature review]. Arkh Patol 2025; 87:37-40. [PMID: 39943727 DOI: 10.17116/patol20258701137] [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: 05/09/2025]
Abstract
Plexiform fibromyxoma (PFM) and gastroblastoma (GB) are rare gastric tumors with a specific MALAT1::GLI1 rearrangement, included in the conditional spectrum of neoplasms with alterations of the GLI1 gene. The article presents a clinical case of PFM in a 6-year-old girl and a literature review highlighting current data on the morphology, immunophenotype and molecular genetic characteristics of PFM and GB. Despite the common genetic anomaly, differences in the morphology and clinical course of these tumors indicate the need for further research to clarify their relationship and potential reclassification in the light of new data on tumors with GLI1 gene abnormalities. Integrating the accumulated knowledge about tumors with GLI1 gene alterations into diagnostic algorithms and therapeutic approaches will help improve the treatment outcomes of patients with these rare neoplasms.
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Affiliation(s)
- I V Sidorov
- Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - A S Sharlai
- Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - D M Konovalov
- Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- Russian Medical Academy of Continuous Professional Education, Moscow, Russia
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2
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He YF. Malignant melanoma: An important differential diagnosis for clear cell sarcoma of the gastrointestinal tract. World J Clin Cases 2024; 12:6664-6668. [PMID: 39650811 PMCID: PMC11514356 DOI: 10.12998/wjcc.v12.i34.6664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 08/13/2024] [Accepted: 08/23/2024] [Indexed: 10/12/2024] Open
Abstract
A case report by Liu et al describes the characteristics of metastatic clear cell sarcoma (CCS) of the pancreas and provides valuable therapeutic insights for this rare malignancy. This case is interesting because of its rarity, suggesting that the pancreas may be a potential target organ for CCS, either primary or metastatic. At the same time, the authors also emphasize the importance of regular postoperative follow-up for timely detection of recurrent lesions, as CCS is characterized by a high degree of malignancy and a high rate of recurrent metastases. Considering that CCS of the gastrointestinal tract is easily confused with malignant melanoma (MM) of the gastrointestinal tract, here we compare the clinical features, histopathological and immunohistochemical characteristics, diagnosis, treatment, and prognosis of CCS and MM of the gastrointestinal tract, hoping to provide a reference for clinical work.
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Affiliation(s)
- Yan-Fei He
- Health Management Center, The Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, China
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3
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Gebbia V, Carnaghi C. Metastatic clear cell sarcoma of the pancreas: A sporadic cancer. World J Clin Cases 2024; 12:3291-3294. [PMID: 38983428 PMCID: PMC11229925 DOI: 10.12998/wjcc.v12.i18.3291] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 04/14/2024] [Accepted: 04/25/2024] [Indexed: 06/13/2024] Open
Abstract
Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease. In addition to pathology, molecular analysis is pivotal in differential diagnosis, especially with malignant melanoma. A key aspect in identifying clear cell sarcoma is specific genetic alterations, notably the translocation of t(12;22) (q13;q13), a diagnostic hallmark of this sarcoma subtype, which is absent in malignant melanoma. Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.
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Affiliation(s)
- Vittorio Gebbia
- Department of Medical Oncology, Faculty of Medicine, University of Enna “Kore”, Enna 94100, Italy
- Medical Oncology Unit, Cdc Torina, Palermo 90145, Italy
| | - Carlo Carnaghi
- Medical Oncology Unit, Humanitas Istituto Clinico Catanese, Misterbianco, Catania 95045, Italy
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4
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Dashti NK, Schukow CP, Kilpatrick SE. Back to the future! Selected bone and soft tissue neoplasms with shared genetic alterations but differing morphological and immunohistochemical phenotypes. Hum Pathol 2024; 147:129-138. [PMID: 38521373 DOI: 10.1016/j.humpath.2024.03.005] [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: 03/07/2024] [Accepted: 03/13/2024] [Indexed: 03/25/2024]
Abstract
Bone and soft tissue tumors (BST) are a highly heterogeneous group largely classified by their line of differentiation, based on their resemblance to their normal counterpart in adult tissue. Yet, rendering a specific diagnosis can be challenging, primarily due to their rarity and overlapping histopathologic features or clinical presentations. Over the past few decades, seemingly histogenetic-specific gene fusions/translocations and amplifications have been discovered, aiding in a more nuanced classification, leading to well-established objective diagnostic criteria and the development of specific surrogate ancillary tests targeting these genetic aberrations (e.g., immunohistochemistry). Ironically, the same research also has revealed that some specific tumor subtypes may be the result of differing and often multiple gene fusions/translocations, but, more interestingly, identical gene fusions may be present in more than one phenotypically and biologically distinct neoplasm, sometimes with entirely different clinical behavior. Prime examples include, EWSR1::ATF1 and, less commonly, EWSR1::CREB1 gene fusions present in both clear cell sarcoma, a malignant high-grade tumor with melanocytic differentiation, and angiomatoid fibrous histiocytoma, a mesenchymal neoplasm of intermediate malignancy with a generally indolent course. Similarly, MDM2 amplification, once deemed to be pathognomonic for atypical lipomatous tumor/well differentiated and dedifferentiated liposarcoma, has been documented in a range of additional distinct tumors, including low grade osteosarcomas (e.g. low grade central and surface parosteal) and high-grade intimal sarcomas, amongst others. Such findings reinforce the importance of careful attention to morphological and clinicoradiological features and correlation with molecular testing before rendering a specific diagnosis. Future classification systems in BST neoplasms cannot be solely based on molecular events and ideally will balance morphologic features with molecular analysis. Herein, we provide a narrative literature review of the more common BST neoplasms with shared genetic events but differing demographics, morphology, immunophenotype, and clinical behavior, re-emphasizing the importance of the hematoxylin and eosin slide and the "eye" of the practicing pathologist.
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Affiliation(s)
- Nooshin K Dashti
- Department of Pathology and Laboratory Medicine Dartmouth Health, Lebanon, 03766, NH, USA; Geisel School of Medicine at Dartmouth, Lebanon, 03766, NH, USA
| | - Casey P Schukow
- Corewell Health's Beaumont Hospital, Department of Pathology, Royal Oak, MI, 48073, USA
| | - Scott E Kilpatrick
- Department of Pathology & Laboratory Medicine, Cleveland Clinic, L25, 9500 Euclid Ave, Cleveland, OH, 44195, USA.
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5
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Fujiwara T, Kunisada T, Nakata E, Mitsuhashi T, Ozaki T, Kawai A. Factors associated with survival in patients with clear cell sarcoma. Bone Joint J 2023; 105-B:1216-1225. [PMID: 37907082 DOI: 10.1302/0301-620x.105b11.bjj-2022-0743.r3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/02/2023]
Abstract
Aims Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. Methods The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. Results The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). Conclusion Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents.
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Affiliation(s)
- Tomohiro Fujiwara
- Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Toshiyuki Kunisada
- Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Eiji Nakata
- Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Toshiharu Mitsuhashi
- Centre for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | - Toshifumi Ozaki
- Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Akira Kawai
- Department of Musculoskeletal Oncology, National Cancer Centre Hospital, Tokyo, Japan
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Epithelioid and Clear Cell Solitary Fibrous Tumors: Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 13 Cases. Am J Surg Pathol 2023; 47:259-269. [PMID: 36253890 DOI: 10.1097/pas.0000000000001983] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Solitary fibrous tumors (SFTs) are ubiquitous soft tissue neoplasms known for their protean histology and potentially aggressive behavior. Although most cases are composed of a monotonous proliferation of spindle cells, some tumors show unusual cytologic features. We have studied 13 SFTs that were characterized by a predominant population of round epithelioid cells with abundant eosinophilic cytoplasm and clear cell changes. The tumors occurred in 8 women and 5 men, aged 36 to 80 years (mean=63 y), and were located within the orbit (3), lower extremity (3), retroperitoneum (2), abdominal cavity (2), and superficial soft tissues of the neck, pelvis, and pubis (1 each). The tumors measured from 3.5 to 24.5 cm. Using a risk assessment system, 6 cases were stratified as low-risk tumors; 3 of these showed no evidence of recurrence or metastases from 6 to 18 years, and 1 tumor in the orbit recurred and led to the patient's demise. Five cases were of intermediate risk; clinical follow-up showed no evidence of recurrence or metastases from 3 to 4 years in 3 patients, and 1 patient suffered a recurrence 4 years after diagnosis. Two cases were high risk; 1 patient died after 1 year and the second patient experienced local recurrence at 4 years. Immunohistochemical studies showed nuclear positivity for STAT6 in 10 cases. CD34 immunohistochemistry was positive in 11 cases. A NAB2::STAT6 rearrangement was present in all cases. Epithelioid and clear cell SFT should be considered in the differential diagnosis of soft tissue neoplasms with epithelioid and clear cell morphology.
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7
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Kataria B, Sharma A, Biswas B, Bakhshi S, Pushpam D. Pazopanib in rare histologies of metastatic soft tissue sarcoma. Ecancermedicalscience 2021; 15:1281. [PMID: 34824604 PMCID: PMC8580588 DOI: 10.3332/ecancer.2021.1281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Indexed: 01/20/2023] Open
Abstract
Background Uncommon histopathological subtypes account for less than 5% cases of soft tissue sarcoma (STS) and unclassified STSs comprise another 16%, these are often chemotherapy-resistant, with a dismal outcome in unresectable/metastatic disease. Prospective studies on the use of pazopanib in this cohort of patients are lacking in the literature. Here, we describe the safety and efficacy of pazopanib in rare histologies of advanced STS. Materials and methods We conducted a retrospective study at two tertiary cancer centres in India, evaluating 33 cases of rare subtypes of STS, who received pazopanib as per institutional protocol between January 2013 and December 2019. Patients who received pazopanib for unresectable/metastatic disease were enrolled in this study for clinicopathologic features, treatment outcome and evaluation of prognostic factors. Results Out of 33 patients, there were seven cases of undifferentiated pleomorphic sarcoma, four cases each of myxofibrosarcoma, epithelioid sarcoma and malignant peripheral nerve sheath tumour, three cases each of haemangiopericytoma and spindle cell sarcoma, two cases of haemangioendothelioma and a case each of clear cell sarcoma, retroperitoneal sarcoma, angiosarcoma and pleomorphic rhabdomyosarcoma-adult type. The objective response rate was 27%. Most of the patients (67%) received pazopanib in second or subsequent lines of therapy. The majority (70%) were started at a lower dose of 400/600 mg and only 43% of these (10/23) could be escalated to a full dose of 800 mg based on tolerance. On univariate analysis, pazopanib’s starting dose didn’t predict progression-free survival (PFS)/overall survival (OS)/response rate. At a median duration of follow-up of 18.8 months (range 1.9–150.4 months), the median PFS and median OS were 10.3 months (95% confidence interval (CI): 5.9–14.8) and 17.8 months (95% CI: 10.7–29.3), respectively. 27% of the patients experienced grade ¾ toxicities, 12% required dose modification of pazopanib and 21% needed permanent discontinuation due to toxicity. Conclusion Our study shows that pazopanib is active in rare subtypes of STS.
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Affiliation(s)
- Babita Kataria
- Department of Medical Oncology, National Cancer Institute, Badsa, Jhajjar, Haryana, 124105, India
| | - Aparna Sharma
- Department of Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar East, New Delhi, 110029, India.,Equally contributed to this work
| | - Bivas Biswas
- Department of Medical Oncology, Tata Medical Center, DH Block(Newtown),Action area I, Kolkata, West Bengal, 700160, India
| | - Sameer Bakhshi
- Department of Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar East, New Delhi, 110029, India
| | - Deepam Pushpam
- Department of Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar East, New Delhi, 110029, India
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8
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A Smooth, Round Nodule on the Right Foot: Answer. Am J Dermatopathol 2021; 43:533-535. [PMID: 34140443 DOI: 10.1097/dad.0000000000001753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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9
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Leckey BD, John I, Reyes-Múgica M, Naous R. EWSR1-ATF1 Fusion in a Myoepithelial Carcinoma of Soft Tissue With Small Round Cell Morphology: A Potential Diagnostic Pitfall. Pediatr Dev Pathol 2021; 24:258-263. [PMID: 33683984 DOI: 10.1177/1093526621998869] [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] [Indexed: 11/17/2022]
Abstract
Myoepithelial tumors of soft tissue are rare mesenchymal neoplasms that overlap with their salivary gland and skin counterparts at both the histopathologic and molecular levels. EWSR1 gene rearrangements with various fusion partners represent a common genetic event in myoepithelial tumors of soft tissue, whether benign or malignant, and may prove useful as a diagnostic tool in difficult cases. However, the number of diagnostic entities with EWSR1 gene rearrangements has grown considerably in recent years, and there is significant morphologic and immunophenotypic overlap amongst this group, underscoring the importance of fusion testing to detect fusion partners that are characteristic of discrete diagnostic entities. Herein, we report a malignant myoepithelial tumor of soft tissue/myoepithelial carcinoma with an undifferentiated round cell morphology arising in a pediatric patient with a EWSR1-ATF1 gene fusion.
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Affiliation(s)
- Bruce D Leckey
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Ivy John
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Miguel Reyes-Múgica
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.,Department of Pathology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
| | - Rana Naous
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
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10
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Preclinical In Vivo Modeling of Pediatric Sarcoma-Promises and Limitations. J Clin Med 2021; 10:jcm10081578. [PMID: 33918045 PMCID: PMC8069549 DOI: 10.3390/jcm10081578] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/05/2021] [Accepted: 04/06/2021] [Indexed: 02/07/2023] Open
Abstract
Pediatric sarcomas are an extremely heterogeneous group of genetically distinct diseases. Despite the increasing knowledge on their molecular makeup in recent years, true therapeutic advancements are largely lacking and prognosis often remains dim, particularly for relapsed and metastasized patients. Since this is largely due to the lack of suitable model systems as a prerequisite to develop and assess novel therapeutics, we here review the available approaches to model sarcoma in vivo. We focused on genetically engineered and patient-derived mouse models, compared strengths and weaknesses, and finally explored possibilities and limitations to utilize these models to advance both biological understanding as well as clinical diagnosis and therapy.
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Abou Chaar MK, Jaber OI, Asha W, Abdel Al S. Novel Double Central Ray Amputation of the Third and Fourth Digits: Case Report and Literature Review. Case Rep Oncol 2020; 13:91-99. [PMID: 32110226 PMCID: PMC7036542 DOI: 10.1159/000504934] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Accepted: 11/20/2019] [Indexed: 12/16/2022] Open
Abstract
Whenever partial hand amputations for soft tissue sarcomas are attempted, special consideration should be given to achieve a balance between complete resection associated with negative margins and preservation of functionality to the patient so that the hand can support the contralateral intact hand for bimanual activities. This difficult decision is even more challenging within the limited anatomical confines of the hand. Based on our literature review, this is the first case of double central 3rd and 4th ray amputation, as far as we know with good hand function, evaluated by the Musculoskeletal Tumor Rating Scale.
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Affiliation(s)
| | - Omar I Jaber
- Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman, Jordan
| | - Wafa Asha
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Samer Abdel Al
- Department of Orthopedic Oncology, King Hussein Cancer Center, Amman, Jordan
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12
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Evert M, Schildhaus HU. [Epithelioid, biphasic and mixed tumors of soft tissue]. DER PATHOLOGE 2019; 40:393-411. [PMID: 31243551 DOI: 10.1007/s00292-019-0627-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Epithelioid soft tissue tumors consist exclusively of epithelioid tumor cells. Biphasic tumors are composed of both a spindle-cell and an epithelioid component. The rare mixed tumors of soft tissue show a broader variety of cellular and stromal differentiation but also include at least one, possibly several, epithelioid portions.The close morphological similarity of some of these entities with each other, as well as with the more frequent soft tissue metastases of carcinomas, carcinosarcomas, and melanomas, to malignant mesothelioma and certain lymphomas, can often make the correct diagnosis extremely difficult. Recent advances in the detection of certain molecular alterations (mostly chromosomal translocations) have contributed to changes in tumor classification but also to improved pathological diagnostics (e.g. through the development of potent diagnostic antibodies) and biological understanding.The present overview should help the pathologist in the diagnosis of these rare tumors through the classical approach of morphological pattern recognition. The most important entities are discussed and illustrated in more detail, with the incorporation of the latest immunohistochemical and molecular aspects and the differential diagnosis of similar tumors.
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Affiliation(s)
- M Evert
- Institut für Pathologie, Universität Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Deutschland.
| | - H-U Schildhaus
- Institut für Pathologie, Universitätsklinikum Essen, Hufelandstraße 55, 45147, Essen, Deutschland
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Chen G, Sun S, Du Z, Sun Y, Pan Z, Che X, Xie R. Intra-Extracranial Primary Clear Cell Sarcoma: The First Report and Review of the Literature. World Neurosurg 2019; 126:e1140-e1146. [PMID: 30880192 DOI: 10.1016/j.wneu.2019.02.216] [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: 12/27/2018] [Revised: 02/21/2019] [Accepted: 02/22/2019] [Indexed: 10/27/2022]
Abstract
BACKGROUND Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor with poor prognosis owing to metastasis and insensitive response to chemotherapy and radiotherapy. METHODS We first searched PubMed and Embase using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," "head," and "neck." In the 15 articles selected for literature review, only 27% (4/15) of patients were diagnosed with primary CCS of the head. Pathologically, those tumors arose from either the scalp or the superficial temporal fascia, but none invaded the skull and brain. Next, the search was performed in the same database using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," and "bone," and only 24 articles were selected. RESULTS In the case reported here, a 36-year-old woman was found to have a palpable mass located at the left temporal-occipital region, and surgical finding confirmed the invasion into the skull and the brain. The diagnosis of primary CCS was made because of the detection of t(12;22)(q13;q12) in >50% of tumor cells by fluorescence in situ hybridization, and metastasis to the lymph nodes and lungs was discovered by postoperative positron emission tomography-computed tomography. CONCLUSIONS To the best of our knowledge, this is the first case of primary central nervous system CCS. Primary CCS may involve the skull and should be one of the differential diagnoses for intra-extracranial communicating tumors. Further research on biological characteristics and molecular targeted therapy of CCS are needed to improve its poor prognosis.
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Affiliation(s)
- Gong Chen
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Shifeng Sun
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Zunguo Du
- Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yirui Sun
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhiguang Pan
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiaoming Che
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Rong Xie
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
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14
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Nakai T, Imura Y, Tamiya H, Yamada S, Nakai S, Yasuda N, Kaneko K, Outani H, Takenaka S, Hamada K, Myoui A, Araki N, Ueda T, Itoh K, Yoshikawa H, Naka N. Trabectedin is a promising antitumor agent potentially inducing melanocytic differentiation for clear cell sarcoma. Cancer Med 2017; 6:2121-2130. [PMID: 28745431 PMCID: PMC5603837 DOI: 10.1002/cam4.1130] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 04/28/2017] [Accepted: 05/24/2017] [Indexed: 12/19/2022] Open
Abstract
Clear cell sarcoma is an aggressive soft tissue sarcoma and highly resistant to conventional chemotherapy and radiation therapy. This devastating disease is defined by EWSR1-ATF1 fusion gene resulting from chromosomal translocation t(12;22)(q13;q12) and characterized by melanocytic differentiation. A marine-derived antineoplastic agent, trabectedin, inhibits the growth of myxoid liposarcoma and Ewing sarcoma by causing adipogenic differentiation and neural differentiation, respectively. In this study, we examined the antitumor effects and mechanism of action of trabectedin on human clear cell sarcoma cell lines. We showed that trabectedin decreased the cell proliferation of five clear cell sarcoma cell lines in a dose-dependent manner in vitro and reduced tumor growth of two mouse xenograft models. Flow cytometry and immunoblot analyses in vitro and immunohistochemical analysis in vivo revealed that trabectedin-induced G2/M cell cycle arrest and apoptosis. Furthermore, trabectedin increased the expression of melanocytic differentiation markers along with downregulation of ERK activity in vitro and the rate of melanin-positive cells in vivo. These results suggest that trabectedin has potent antitumor activity against clear cell sarcoma cells by inducing cell cycle arrest, apoptosis, and, in part, by promoting melanocytic differentiation through inactivation of ERK signaling. Our present study indicates that trabectedin is a promising differentiation-inducing agent for clear cell sarcoma.
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Affiliation(s)
- Takaaki Nakai
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
| | - Yoshinori Imura
- Musculoskeletal Oncology ServiceOsaka International Cancer Institute3‐1‐69, OtemaeChuo‐kuOsaka541‐8567Japan
| | - Hironari Tamiya
- Musculoskeletal Oncology ServiceOsaka International Cancer Institute3‐1‐69, OtemaeChuo‐kuOsaka541‐8567Japan
| | - Shutaro Yamada
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
| | - Sho Nakai
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
| | - Naohiro Yasuda
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
| | - Keiko Kaneko
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
| | - Hidetatsu Outani
- Musculoskeletal Oncology ServiceOsaka International Cancer Institute3‐1‐69, OtemaeChuo‐kuOsaka541‐8567Japan
| | - Satoshi Takenaka
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
| | - Kenichiro Hamada
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
| | - Akira Myoui
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
| | - Nobuhito Araki
- Musculoskeletal Oncology ServiceOsaka International Cancer Institute3‐1‐69, OtemaeChuo‐kuOsaka541‐8567Japan
| | - Takafumi Ueda
- Department of Orthopaedic SurgeryOsaka National Hospital2‐1‐14 HoenzakaChuo‐kuOsaka540‐0006Japan
| | - Kazuyuki Itoh
- Research InstituteNozaki Tokushukai2‐10‐50 TanigawaDaitoOsaka574‐0074Japan
| | - Hideki Yoshikawa
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
| | - Norifumi Naka
- Department of Orthopaedic SurgeryOsaka University Graduate School of Medicine2‐2 YamadaokaSuitaOsaka565‐0871Japan
- Musculoskeletal Oncology ServiceOsaka International Cancer Institute3‐1‐69, OtemaeChuo‐kuOsaka541‐8567Japan
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15
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Montgomery EA, Meis JM, Ramos AG, Frisman DM, Martz KL. Clear Cell Sarcoma of Tendons and Aponeuroses. Int J Surg Pathol 2016. [DOI: 10.1177/106689699300100201] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Fifty-eight previously unreported cases of clear cell sarcoma of tendons and apo neuroses occurring in 29 males and 29 females with a median age of 31 years are presented. The distal extremities were most frequently involved (58%), followed by the limbs and limb girdles (33%), and trunk (9%). Median tumor size was 2.5 cm (range, 0.6-9 cm). Kaplan-Meier estimates revealed a 5-year survival rate of 63%. Eleven of 43 patients (26%) had local recurrences at a median interval of 33 months. Metastases occurred in 20 of 45 cases (44%) at a median interval of 26 months; 19 of 20 patients with metastases died of the disease. The most common metastatic site was the lungs (11 cases), followed by bone (9 cases), and lymph nodes (8 cases). Clear cell sarcoma had a stereotypic morphology consisting of packeted arrangements of uniform, round to fusiform cells with eosinophilic to clear glycogen-rich cytoplasm, and prominent nucleoli, as well as multinucleated tumor cells with a wreath-like arrangement of nuclei. S100 protein was detected in all 44 cases studied, vimentin in 36, and HMB45 stained 36. Twenty-six cases were studied with antibodies directed against proliferating cell nuclear antigen. Neither the intensity of proliferating cell nuclear antigen staining, percentage of positive cells, nor the combined score of these two variables corresponded with mitotic rate or survival. Increasing size (as a continu ous variable) and necrosis were found to be independent adverse prognostic factors by multivariate analysis. Int J Surg Pathol 1 (2):89-100, 1993
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16
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Cornillie J, van Cann T, Wozniak A, Hompes D, Schöffski P. Biology and management of clear cell sarcoma: state of the art and future perspectives. Expert Rev Anticancer Ther 2016; 16:839-45. [PMID: 27253849 DOI: 10.1080/14737140.2016.1197122] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
INTRODUCTION Clear cell sarcoma (CCS) is an aggressive tumor, typically developing in tendons or aponeuroses. The outcome of this orphan disease is poor, with 5-year and 10-year survival rates of localized CCS around 60-70% and 40-50%. Once the disease has metastasized, it is usually fatal due to its chemotherapy-resistant nature. Systemic treatment options are poorly standardized and the use of chemotherapy is based on weak scientific evidence. AREAS COVERED In this review, we systematically discuss the current scientific evidence for the systemic treatment of CCS, including tyrosine kinase inhibitors, immunotherapy and MET inhibitors. Expert commentary: Recent insights in the biology of CCS have identified new potential therapeutic targets, which should be tested in prospective clinical trials. Whenever possible, patients with metastatic CCS should be included in clinical trials with good biological rationale. Innovative trial methodology and new regulatory mechanisms are required to provide patients with uncommon cancers with active drugs.
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Affiliation(s)
- Jasmien Cornillie
- a Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute , Leuven , Belgium
| | - Thomas van Cann
- a Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute , Leuven , Belgium
| | - Agnieszka Wozniak
- a Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute , Leuven , Belgium
| | - Daphne Hompes
- b Department of Surgical Oncology , KU Leuven and University Hospitals Leuven , Leuven , Belgium
| | - Patrick Schöffski
- a Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology , University Hospitals Leuven, Leuven Cancer Institute , Leuven , Belgium
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Abstract
A variety of different non-mesenchymal neoplasms may mimic sarcoma, in particular sarcomatoid carcinoma and melanoma, but also mesothelioma and rarely some lymphomas. This article reviews the key clinical and histologic features of such neoplasms in different settings, along with the use of ancillary studies to help identify the tumor types most frequently misdiagnosed as sarcoma.
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Affiliation(s)
- Leona A Doyle
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
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18
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Abstract
Mesenchymal tumors involve the gastrointestinal (GI) tract more frequently than other visceral organs. Many such tumors are small, and are benign and increasingly being detected incidentally during colonoscopic screening. Some tumors show distinctive features at this site, such as schwannoma and clear cell sarcoma-like tumor of the GI tract. Without knowledge of these features, recognition of these tumor types can be difficult. This reviews addresses recent developments and diagnostic features of mesenchymal tumors of the GI tract other than gastrointestinal stromal tumor (GIST).
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19
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Sidiropoulos M, Busam K, Guitart J, Laskin WB, Wagner AM, Gerami P. Superficial paramucosal clear cell sarcoma of the soft parts resembling melanoma in a 13-year-old boy. J Cutan Pathol 2012; 40:265-8. [DOI: 10.1111/cup.12058] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Revised: 11/01/2012] [Accepted: 11/03/2012] [Indexed: 01/09/2023]
Affiliation(s)
- Michael Sidiropoulos
- Department of Dermatology, Feinberg School of Medicine; Northwestern University; Chicago; IL; USA
| | - Klaus Busam
- Department of Pathology; Memorial Sloan-Kettering Cancer Center; New York; NY; USA
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20
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Jones RL, Constantinidou A, Thway K, Ashley S, Scurr M, Al-Muderis O, Fisher C, Antonescu CR, D'Adamo DR, Keohan ML, Maki RG, Judson IR. Chemotherapy in clear cell sarcoma. Med Oncol 2012; 28:859-63. [PMID: 20390470 DOI: 10.1007/s12032-010-9502-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2010] [Accepted: 03/15/2010] [Indexed: 10/19/2022]
Abstract
Clear cell sarcoma is a rare translocation-related sarcoma. There have been few studies documenting the response rate and progression-free survival in clear cell sarcoma patients treated with palliative chemotherapy. The prospectively maintained databases of two referral centres were searched to identify clear cell sarcoma patients treated with chemotherapy. Twenty-four patients were treated with palliative first-line chemotherapy with a median age of 30 years at diagnosis. There were 18 men and 6 women. One (4%) achieved a partial response and 9 (38%) had stable disease. Fourteen patients (58%) progressed on therapy. The median progression-free survival was 11 weeks (95% CI, 3–20 weeks). The median overall survival from commencing first-line chemotherapy was 39 weeks (95% CI, 34–45 weeks). Second-line chemotherapy was administered to 12 patients, 11 (92%) of these progressed and one (8%) had stable disease. Of the 5 patients treated with third-line chemotherapy, 4 (80%) progressed and one (20%) had stable disease. One patient received fourth-line chemotherapy and maintained stable disease for 4 months. Conventional chemotherapy has minimal activity in clear cell sarcoma as documented by the response rate of 4% and median progression-free survival of 11 weeks in this retrospective series. These data provide a reference for response and outcome in the assessment of novel agents in this histological subtype.
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Goletz TJ, Mackall CL, Berzofsky JA, Helman LJ. Molecular alterations in pediatric sarcomas: potential targets for immunotherapy. Sarcoma 2011; 2:77-87. [PMID: 18521238 PMCID: PMC2395387 DOI: 10.1080/13577149878037] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Purpose/results/discussion. Recurrent chromosomal translocations are common features of many human malignancies. While such translocations often serve as diagnostic markers, molecular analysis of these breakpoint regions and the characterization of the affected genes is leading to a greater understanding of the causal role such translocations play in
malignant transformation. A common theme that is emerging from the study of tumor-associated translocations is the generation of chimeric genes that, when expressed, frequently retain many of the functional properties of the wild-type genes from which they originated. Sarcomas, in particular, harbor chimeric genes that are often derived from transcription factors, suggesting that the resulting chimeric transcription factors contribute to tumorigenesis. The tumor-specific expression of the fusion proteins make them likely candidates for tumor-associated antigens (TAA) and are thus of interest in the development of new therapies. The focus of this review will be on the translocation events associated with Ewing's sarcomas/PNETs (ES), alveolar rhabdomyosarcoma (ARMS), malignant melanoma of soft parts (MMSP) (clear cell sarcoma), desmoplastic small round cell tumor (DSRCT), synovial sarcoma (SS), and liposarcoma (LS), and the potential for targeting the resulting chimeric proteins in novel immunotherapies.
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Affiliation(s)
- T J Goletz
- Molecular Immunogenetics and Vaccine Research Section Metabolism Branch National Cancer Institute National Institutes of Health Bethesda MD 20892 USA
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22
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Cutaneous clear cell sarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of 12 cases emphasizing its distinction from dermal melanoma. Am J Surg Pathol 2010; 34:216-22. [PMID: 20087159 DOI: 10.1097/pas.0b013e3181c7d8b2] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Clear cell sarcoma (CCS) of tendons and aponeuroses/malignant melanoma (MM) of soft parts is a rare tumor and in the majority of cases presents a characteristic reciprocal translocation t(12;22)(q13;q12) that results in fusion of the EWS and ATF1 genes. Although the melanocytic differentiation of CCS is indisputable, its precise lineage remains unclear. Typically, the slowly growing tumor affects the extremities of adolescents or young adults, especially around the ankle and foot. CCS is classically regarded as a deep soft tissue tumor associated with tendons or aponeuroses. This traditional view is put into perspective by the description of primary CCS of the gastrointestinal tract that may have a variant fusion gene EWSR1-CREB1. We describe 12 cases of cutaneous CCS and discuss the differential diagnoses. These 12 cases share an identical immunohistochemical profile with MM and thus can easily be confused with a dermal variant of spindle cell MM or metastasis of MM. The patients' ages ranged from 6 to 74 years (median: 25 y), and there was a female predominance (10 females, 2 males). Most tumors (n = 9) were located on the extremities, 2 tumors arose on the back, and 1 on the abdomen. The mean tumor size was 0.97 cm (range, 0.4 to 1.7 cm). Six cases showed invasion of the subcutis, the other 6 cases were entirely dermal. Tumor necrosis was evident in 2 cases, melanin pigment in 2 cases, and ulceration in 1 tumor. All cases showed uniform nests and fascicles of pale spindled or slightly epitheloid cells with finely granular eosinophilic or clear cytoplasm. There was fair pleomorphism with plump spindled nuclei and significantly prominent nucleoli. Multinucleated wreath-like tumor giant cells were observed in two-thirds of cases, but were usually present only focally. The dense cellular aggregates were encased by delicate fibrous septa. The stroma showed a sclerotic reticulated pattern. Partly, the nests of spindle cells bordered the epidermis, prima vista mimicking junctional nests of melanocytes. The specific translocation pattern was confirmed in all cases by fluorescence in situ hybridization. Local recurrences and metastases developed in 2 and 3 patients, respectively, and 1 patient died of the disease.
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23
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Davis IJ, McFadden AW, Zhang Y, Coxon A, Burgess TL, Wagner AJ, Fisher DE. Identification of the receptor tyrosine kinase c-Met and its ligand, hepatocyte growth factor, as therapeutic targets in clear cell sarcoma. Cancer Res 2010; 70:639-45. [PMID: 20068147 DOI: 10.1158/0008-5472.can-09-1121] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Clear cell sarcoma (CCS), a childhood tumor of the tendons and aponeuroses, is uniformly fatal once it has metastasized because of its profound therapeutic resistance. CCS is characterized by production of a chimeric transcription factor, EWS-ATF1, which is formed as the result of a disease-specific chromosomal translocation. EWS-ATF1 activates the melanocyte transcription factor MITF, which in turn activates transcription of c-Met, an oncogenic receptor tyrosine kinase recently shown to be activated in CCS. Based on this connection, we hypothesized that c-Met inhibition may offer a strategy to treat CCS, as an indirect tactic to defeat a transforming pathway downstream of EWS-ATF1. Here, we show that primary CCS and CCS-derived cell lines express c-Met, which is activated in an autocrine fashion by its ligand hepatocyte growth factor (HGF)/scatter factor in some CCS cell lines. c-Met expression is critical for CCS invasion, chemotaxis, and survival. Blocking c-Met activity with a small-molecule inhibitor (SU11274) or a neutralizing antibody to its ligand HGF (AMG 102) significantly reduced CCS cell growth in culture. Similarly, AMG 102 significantly suppressed in vivo tumor growth in an autocrine xenograft model of CCS. Collectively, these findings suggest the HGF:c-Met signaling axis as a candidate therapeutic target to improve clinical management of CCS.
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Affiliation(s)
- Ian J Davis
- Department of Pediatric Oncology, Ludwig Center for Cancer Research, Dana-Farber Cancer Institute, Children's Hospital Boston, Boston, Massachusetts, USA.
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24
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Wang WL, Mayordomo E, Zhang W, Hernandez VS, Tuvin D, Garcia L, Lev DC, Lazar AJ, López-Terrada D. Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). Mod Pathol 2009; 22:1201-9. [PMID: 19561568 DOI: 10.1038/modpathol.2009.85] [Citation(s) in RCA: 161] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Unlike melanoma, clear cell sarcoma harbors either a t(12;22)(q13;q12) recurrent translocation, resulting in an EWSR1/ATF1 chimeric gene, or less commonly a t(2;22)(q34;q12) translocation fusing EWSR1 and CREB1. Few studies have examined the prevalence of all chimeric types and variants to assess the usage of ancillary genetic testing in routine diagnosis. We investigated rearrangement prevalence in 17 clear cell sarcomas, two positive control cell lines, and two melanomas (negative controls). Fluorescence in situ hybridization (FISH) analysis using the LSI EWSR1 break-apart probe and a reverse transcription polymerase chain reaction (RT-PCR) assay optimized for formalin-fixed paraffin-embedded tissue to detect all four reported EWSR1/ATF1 clear cell sarcoma chimeric types and the EWSR1/CREB1 variant was performed. All 15 cases available for testing by FISH were positive for EWSR1 rearrangement including two cases with insufficient RNA for RT-PCR. Thirteen of 15 cases successfully tested by RT-PCR harbored a type 1 chimeric transcript (EWSR1 exon 8/ATF1 exon 4), of which five tumors simultaneously carried a type 2 chimeric transcript (EWSR1 exon 7/ATF1 exon 5). One case carried a type 2 transcript alone and one case contained an EWSR1/CREB1 transcript. Both control cases were positive by both techniques with one case carrying both types 1 and 2 chimeric transcripts and the other types 2 and 3 (EWSR1 exon 10/ATF1 exon 5). Consequently, both techniques are equally effective in assessing for an EWSR1 rearrangement and are useful ancillary diagnostic tests for clear cell sarcoma. They also reinforce the prevalence of this translocation in these tumors. In addition, EWSR1-CREB1 was identified in a clear cell sarcoma of soft tissue providing further evidence that this chimeric variant is not exclusive to gastrointestinal clear cell sarcomas and should be included in RT-PCR assays of soft tissue clear cell sarcomas.
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Affiliation(s)
- Wei-Lien Wang
- Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-2313, USA
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25
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Gollard R, Hussong J, Bledsoe J, Rosen L, Anson J. Clear cell sarcoma originating in a paraspinous tendon: case report and literature review. Acta Oncol 2008; 47:1593-5. [PMID: 18607869 DOI: 10.1080/02841860701843068] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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26
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Gastrointestinal melanoma or clear cell sarcoma? Molecular evaluation of 7 cases previously diagnosed as malignant melanoma. Am J Surg Pathol 2008; 32:858-66. [PMID: 18408594 DOI: 10.1097/pas.0b013e31815b8288] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Clear cell sarcoma (CCS) is a rare tumor classically associated with the tendons and aponeuroses of distal extremities of young adults. CCS and malignant melanoma (MM) share immunohistochemical profiles and ultrastructural features, but classic CCS has characteristic morphology with low mitotic activity and minimal pleomorphism. Occasional cases show pleomorphism, high mitotic index, and/or melanin pigmentation, making CCS indistinguishable from MM based on morphology. However, CCS is genetically distinct owing to its consistent association with a t(12;22)(q13;q12) chromosomal translocation, leading to the formation of the EWS/ATF1 fusion transcript. This translocation has never been documented in cutaneous melanoma, and thus is regarded as specific for CCS. Recent evidence suggests that primary "malignant melanomas" in unusual anatomic sites, most notably the gastrointestinal (GI) tract, may be CCS. This is supported by 11 cases of primary GI CCS with the t(12;22) translocation. We used reverse-transcription polymerase chain reaction and fluorescence in situ hybridization to examine whether a proportion of cases diagnosed as MM of the GI tract in patients without a history of cutaneous MM actually represent primary GI CCS. In total, we examined 7 cases: Four with no prior history of MM, 2 with histories of cutaneous MM, and 1 with an anal MM. All 4 cases for which there was no history of cutaneous/mucosal MM harbored the EWS/ATF1 fusion transcript. We report the largest series of GI CCS and have shown that molecular studies may be warranted in cases that otherwise seem to represent MM of unusual primary locations.
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27
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Bron JL, Mooi WJ, Saouti R, Wuisman PIJM. A slow-growing prepatellar mass in a 31-year-old woman. Clin Orthop Relat Res 2008; 466:1511-5. [PMID: 18259832 PMCID: PMC2384042 DOI: 10.1007/s11999-008-0137-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2007] [Accepted: 01/16/2008] [Indexed: 01/31/2023]
Affiliation(s)
- J. L. Bron
- />Department of Orthopaedic Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands
| | - W. J. Mooi
- />Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
| | - R. Saouti
- />Department of Orthopaedic Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands
| | - P. I. J. M. Wuisman
- />Department of Orthopaedic Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands
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28
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Curry CV, Dishop MK, Hicks MJ, Naeem R, Reed JA, López-Terrada DH. Clear cell sarcoma of soft tissue: diagnostic utility of fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction. J Cutan Pathol 2008; 35:411-7. [DOI: 10.1111/j.1600-0560.2007.00821.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Clark MA, Johnson MB, Thway K, Fisher C, Thomas JM, Hayes AJ. Clear cell sarcoma (melanoma of soft parts): The Royal Marsden Hospital experience. Eur J Surg Oncol 2007; 34:800-4. [PMID: 18042498 DOI: 10.1016/j.ejso.2007.10.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2007] [Accepted: 10/12/2007] [Indexed: 10/22/2022] Open
Abstract
INTRODUCTION Clear cell sarcoma (CCS) is a rare tumour with a propensity for local recurrence and nodal metastasis. About 300 cases have been reported, thus further clarification regarding the course and outcome of the disease is required. METHODS Patients with a histopathologic diagnosis of CCS were identified from prospective histopathology and sarcoma databases and supplemented with a retrospective analysis of the patients' hospital records. RESULTS Between 1990 and 2005, a total of 72 patients with a diagnosis of CCS were identified, 35 having been referred for management and 37 having been referred for histopathologic opinion. The median age was 39 years (range 5-90 years). Of the 35 patients referred to the Royal Marsden Hospital for management, 23% developed local recurrence or in-transit metastases at a median of 9 months (2-79 months) after resection of the primary, and nodal or distant metastatic disease was seen in 63% after 14 months (range 0-177 months). Five- and 10-year survival were 52% and 25%, respectively. CONCLUSIONS CCS has a number of similarities with melanoma, particularly in its peripheral distribution and propensity for nodal disease. Wide excision with clear margins offers the best chance of cure. Local recurrence and regional metastases are common, and are almost always followed by distant metastases and death.
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Affiliation(s)
- M A Clark
- Sarcoma and Melanoma Unit, Royal Marsden Hospital, Fulham Road, London SW36JJ, UK
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30
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Dim DC, Cooley LD, Miranda RN. Clear Cell Sarcoma of Tendons and Aponeuroses: A Review. Arch Pathol Lab Med 2007; 131:152-6. [PMID: 17227118 DOI: 10.5858/2007-131-152-ccsota] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/03/2006] [Indexed: 12/18/2022]
Abstract
Abstract
Clear cell sarcoma of tendons and aponeuroses, also referred to as malignant melanoma of soft parts, is a rare malignancy derived from neural crest cells. It usually presents in the distal lower extremities of young adults, frequently attached to tendons or aponeuroses. It behaves like a high-grade soft tissue sarcoma and is associated with poor overall survival. Magnetic resonance imaging studies of the lesion reveal T1 hypointensity, T2 hyperintensity, and gadolinium uptake. Grossly, the tumor is usually circumscribed with a histologic pattern of uniform polygonal to fusiform cells with clear to pale eosinophilic cytoplasm divided into variably sized clusters by fibrous septa. Immunohistochemical studies in most cases show that the neoplastic cells are positive with HMB-45 and react with antibody against S100 protein. Most cases show a reciprocal cytogenetic translocation t(12;22)(q13;q12) that creates a unique chimeric fusion EWSR1/ATF1 gene transcript. Metastasis occurs mainly to regional lymph nodes and lungs. Poor prognostic indicators include a tumor size equal to or more than 5 cm, presence of metastasis, and necrosis. The mainstay of treatment is wide excision of the tumor. The use of sentinel lymph node biopsy may become an important procedure in detecting occult regional metastasis and guiding the extent of surgery. The beneficial effects of adjuvant chemotherapy and radiotherapy have not been fully evaluated. This article provides a short overview of the current knowledge of clear cell sarcoma of tendons and aponeuroses.
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MESH Headings
- Activating Transcription Factor 1
- Antigens, Neoplasm
- Calmodulin-Binding Proteins/genetics
- DNA-Binding Proteins/genetics
- Diagnosis, Differential
- Humans
- Melanoma-Specific Antigens
- Neoplasm Proteins/metabolism
- Neoplasms, Connective Tissue/diagnosis
- Neoplasms, Connective Tissue/genetics
- Neoplasms, Connective Tissue/metabolism
- Neoplasms, Connective Tissue/pathology
- Neoplasms, Connective Tissue/therapy
- Nuclear Proteins/genetics
- Prognosis
- RNA-Binding Protein EWS
- RNA-Binding Proteins/genetics
- Regulatory Factor X Transcription Factors
- S100 Proteins/metabolism
- Sarcoma, Clear Cell/diagnosis
- Sarcoma, Clear Cell/genetics
- Sarcoma, Clear Cell/metabolism
- Sarcoma, Clear Cell/pathology
- Sarcoma, Clear Cell/therapy
- Tendons/pathology
- Transcription Factors
- Translocation, Genetic
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Affiliation(s)
- Daniel C Dim
- Department of Pathology, University of Missouri at Kansas City School of Medicine/Truman Medical Center, 2301 Holmes St, Kansas City, MO 64108-2677, USA
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31
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Meis-Kindblom JM. Clear cell sarcoma of tendons and aponeuroses: a historical perspective and tribute to the man behind the entity. Adv Anat Pathol 2006; 13:286-92. [PMID: 17075294 DOI: 10.1097/01.pap.0000213052.92435.1f] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Clear cell sarcoma of tendons and aponeuroses is a unique sarcoma initially described by Dr Franz M. Enzinger. The tumor has a proclivity to involve the tendons and aponeuroses of distal extremities of relatively young individuals and is characterized by multiple local recurrences with late metastases and a high rate of tumor deaths. Since its seminal description in 1965, there have been many studies verifying the uniqueness of this entity and probing its differentiation. Ultrastructural and immunohistochemical studies have shown melanocytic differentiation, whereas molecular genetic studies have shown cytogenetic rearrangements resulting in a EWSR1-ATF1 fusion gene that is characteristic but not entirely unique for clear cell sarcoma (similar fusion genes are also seen in angiomatoid fibrous histiocytoma). Detection of this fusion gene and the absence of BRAF gene mutations clearly distinguish clear cell sarcoma from cutaneous melanoma. Adverse prognostic factors identified to date include larger tumor size and any microscopic tumor necrosis. Surgery is the mainstay of treatment for this high grade sarcoma, with chemotherapy having little effect. Although the melanocytic differentiation of clear cell sarcoma is indisputable, its precise lineage remains unclear. Thus, clear cell sarcoma maintains the status of a unique yet enigmatic clinicopathologic entity of ever increasing complexity 40 years after its original description by an extraordinarily gifted man.
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Affiliation(s)
- Jeanne M Meis-Kindblom
- Royal Orthopaedic Hospital NHS Trust, Department of Musculoskeletal Pathology, Division of Cancer Studies, Department of Pathology, University of Birmingham Medical School, Birmingham, United Kingdom.
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32
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Patel RM, Downs-Kelly E, Weiss SW, Folpe AL, Tubbs RR, Tuthill RJ, Goldblum JR, Skacel M. Dual-color, break-apart fluorescence in situ hybridization for EWS gene rearrangement distinguishes clear cell sarcoma of soft tissue from malignant melanoma. Mod Pathol 2005; 18:1585-90. [PMID: 16258500 DOI: 10.1038/modpathol.3800503] [Citation(s) in RCA: 84] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Clear cell sarcoma of soft tissue (malignant melanoma of soft parts) is a soft tissue sarcoma with melanocytic differentiation that typically occurs in the tendons and aponeuroses of young adults. As demonstrated by cytogenetics and reverse-transcriptase polymerase chain reaction, between 70% and over 90% of clear cell sarcomas have a t(12;22) translocation, fusing the EWS and ATF1 genes on chromosomes 22q12 and 12q13, respectively. Identification of this translocation distinguishes clear cell sarcoma from histologic mimics, most importantly conventional malignant melanoma. We report our experience with a commercially available, dual-color, break-apart fluorescence in situ hybridization (FISH) probe, which allows detection of EWS (22q12) gene rearrangement in formalin-fixed, paraffin-embedded tissues. Histologically and immunophenotypically well-characterized cases of clear cell sarcoma (n = 10) and malignant melanoma (n = 32) were evaluated with a 22q12 dual-color, break-apart probe (Vysis, Downer's Grove, IL, USA), which spans the known common breakpoints in the EWS gene on chromosome 22 (introns 7-10). Signals from tumor cell nuclei were counted under a fluorescence microscope and the presence of red-green break-apart signals was recorded. Of the clear cell sarcoma cases, seven of 10 showed evidence of an EWS gene rearrangement with a mean of 81.6% positive cells per sample (range: 60-95%). All cases of malignant melanoma (n = 32) showed virtually absent break-apart signals in the EWS gene (less than 4% cells per case). FISH detects EWS gene rearrangement in a substantial proportion of clear cell sarcomas, with excellent specificity. Importantly, EWS FISH is negative in malignant melanoma, a clinically dissimilar tumor, which may closely mimic clear cell sarcoma histologically and immunohistochemically. As the studied probe can be utilized in routinely processed tissue, FISH provides an excellent alternative to reverse-transcriptase polymerase chain reaction in cases where fresh tissue is unavailable.
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Affiliation(s)
- Rajiv M Patel
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30355, USA.
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Covinsky M, Gong S, Rajaram V, Perry A, Pfeifer J. EWS-ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma. Hum Pathol 2005; 36:74-81. [PMID: 15712185 DOI: 10.1016/j.humpath.2004.10.015] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Clear cell sarcoma (CCS) is classically a deep soft tissue tumor associated with tendons or aponeuroses, although cases of primary CCS of the gastrointestinal (GI) tract have recently been reported. Because it is difficult to distinguish CCS from metastatic melanoma based on morphology, immunohistochemical profile, and ultrastructural features, it is possible that some GI tumors diagnosed as metastatic melanoma actually represent primary GI CCS. Because the EWS-ATF1 fusion transcript and the associated t(12;22)(q13;q12) translocation occur in CCS but not cutaneous melanoma, we investigated the use of molecular-based testing for discriminating CCS from metastatic melanoma (MM) in GI tumors. METHODS Patients with GI tumors diagnosed as MM were identified from departmental files. The tumors were tested for the EWS-ATF1 fusion transcript by RT-PCR and for t(12;22)(q13;q12) by fluorescence in situ hybridization. RESULTS Detailed review of medical records revealed that 16 (80%) of the 20 had a documented history of cutaneous melanoma. Two cases (10%) harbored the EWS-ATF1 fusion transcript, and fluorescence in situ hybridization confirmed the presence of t(12;22) in both cases. Of the 2 positive tumors, 1 developed in a patient who had no history of cutaneous melanoma, and the other developed in a patient with a remote history of vulvar melanoma. CONCLUSION Based on molecular genetic findings, a subset of GI tumors diagnosed as MM by routine histopathologic evaluation represents CCS.
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Affiliation(s)
- Michael Covinsky
- Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA
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Zelger BG, Debiec-Rychter M, Sciot R, Zelger B. Cytogenetic comparison between clear cell sarcoma and a case of acral clear cell melanoma. J Dtsch Dermatol Ges 2003; 1:363-8. [PMID: 16285301 DOI: 10.1046/j.1610-0387.2003.02043.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Clear cell melanoma is a recently described variant of melanoma characterized by prominent clear cell features similar to clear cell sarcoma. PATIENTS AND METHODS The present report describes a deeply invasive case of clear cell melanoma clinically, histologically, immunohistochemically, ultrastructurally and with the FISH technique and compares these findings with those in clear cell sarcoma. RESULTS A 68-year-old male presented with an ulcerated, deeply invasive melanoma on the heel, corresponding to Clark level V, with a maximum tumour thickness of more than 14 mm; follow-up revealed inguinal lymph-node and lung metastases. Apart from characteristic histological features of melanoma with intraepidermal involvement, the lesion was immunohistochemically positive for 5100 protein, with HMB45 and A103 (anti-human Melan-A/MART-1), and ultrastructurally showed melanosomes. In deeply invasive parts, the lesion was indistinguishable from clear cell sarcoma, exhibiting nests, fascicles and sheets of pale-staining epithelioid to spindle-shaped cells ('clear cells') with scattered Touton-like multinucleated giant cells. Cytogenetic analysis using the FISH technique revealed a 12q13 chromosomal break in the vicinity of the ATFI gene but without ATF1 disruption. CONCLUSION These findings may indicate the possible involvement of the ATF1 gene in clear cell melanoma tumorigenesis, similar to clear cell sarcoma with classical t(12;22) translocation.
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Affiliation(s)
- Bettina G Zelger
- Department of Human Genetics, Catholic University of Leuven, Belgium.
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35
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Ferrari A, Casanova M, Bisogno G, Mattke A, Meazza C, Gandola L, Sotti G, Cecchetto G, Harms D, Koscielniak E, Treuner J, Carli M. Clear cell sarcoma of tendons and aponeuroses in pediatric patients: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 2002; 94:3269-76. [PMID: 12115360 DOI: 10.1002/cncr.10597] [Citation(s) in RCA: 83] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Clear cell sarcoma (CCS) of tendons and aponeuroses is extremely rare in childhood and little information is available on its clinical management. Originally believed to be a type of melanoma of soft tissue origin, CCS is now considered a distinct clinicopathologic entity that behaves like a high-grade soft tissue sarcoma. We report on a series of 28 pediatric patients treated from 1980 to 2000 by the Soft Tissue Sarcoma Italian Cooperative Group and the German Cooperative Group. METHODS Patients were treated with a multimodality therapeutic approach. Surgical resection was complete in 17 patients (mutilating in 3), radiotherapy was administered to 8 patients, and 20 patients received chemotherapy. RESULTS After a median follow-up of 102 months (range, 19-238 months), the 5-year and event-free survival rates were 66.4% and 63.3%, respectively. Seventeen patients were alive in first remission, two were alive in second remission, and nine had died of disease. The response to chemotherapy in the 7 evaluable patients included one partial remission, one minor response, and five no responses. Radiotherapy contributed to achieving local control in four of six Intergroup Rhabdomyosarcoma Study (IRS) Group II patients. Statistically significant differences in outcome were evident according to IRS group, tumor size, and site. CONCLUSIONS Our study confirms the aggressive behavior of CCS. Complete surgical resection represents the mainstay of treatment, and even the only treatment for patients with small tumors. Radiotherapy may control microscopic residual disease after surgery. Chemotherapy is ineffective and the prognosis is unfavorable for patients with unresectable and large tumors.
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Affiliation(s)
- Andrea Ferrari
- Pediatric Oncology Unit, Istituto Nazionale Tumori, Milan, Italy.
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36
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Folpe AL, McKenney JK, Li Z, Smith SJ, Weiss SW. Clear cell myomelanocytic tumor of the thigh: report of a unique case. Am J Surg Pathol 2002; 26:809-12. [PMID: 12023589 DOI: 10.1097/00000478-200206000-00018] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
The clear cell myomelanocytic tumor (CCMMT) is a recently reported and very rare member of the perivascular epithelioid cell family of tumors (PEComa). All CCMMTs reported to date have occurred in or immediately adjacent to the falciform ligament/ligamentum teres. We report a case of CCMMT that occurred in the right thigh of a 43-year-old woman. Histologic examination showed the classic features of CCMMT, and immunohistochemical studies confirmed co-expression of smooth muscle actin, HMB-45, and microphthalmia transcription factor.
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Affiliation(s)
- Andrew L Folpe
- Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
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37
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Antonescu CR, Tschernyavsky SJ, Woodruff JM, Jungbluth AA, Brennan MF, Ladanyi M. Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. J Mol Diagn 2002; 4:44-52. [PMID: 11826187 PMCID: PMC1906974 DOI: 10.1016/s1525-1578(10)60679-4] [Citation(s) in RCA: 135] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Clear cell sarcoma (CCS), also known as melanoma of soft parts, is an uncommon deep soft tissue tumor presenting typically in the lower extremities of young adults. Previous cytogenetic studies have established the specificity of the recurrent t(12;22)(q13;q12), resulting in a EWS-ATF1 fusion, for CCS. The prevalence of the EWS-ATF1 fusion in CCS remains unclear, since most genetically confirmed CCS have been reported as isolated cytogenetic or molecular diagnostic case reports. We therefore studied histologically confirmed CCS from 12 patients for the presence of EWS-ATF1 by reverse-transcriptase polymerase chain reaction (RT-PCR), using RNA extracted from either frozen (four cases) or formalin-fixed paraffin-embedded (eight cases) material. All primary tumors were located in the deep soft tissues of the extremities. Histologically, 10 cases had a typical epithelioid nested appearance. Most or all cases showed immunostaining for HMB45 (12 of 12), S-100 protein (10 of 12), and MITF (12 of 12). Ultrastructural analysis showed melanosomes in six of seven cases. The presence of an EWS-ATF1 fusion transcript was identified by RT-PCR in 11 of 12 cases (91%), all of which showed the same fusion transcript structure, namely the previously described in-frame fusion of EWS exon 8 to ATF1 codon 65. RT-PCR analysis for the melanocyte-specific splice form of the MITF transcript was positive in all cases tested (4 of 4). These data confirm that EWS-ATF1 detection can be used as a highly sensitive diagnostic test for CCS and that CCS expresses the melanocyte-specific form of the MITF transcript, further supporting its genuine melanocytic differentiation.
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MESH Headings
- Adult
- Aged
- Antigens, Neoplasm
- Cell Differentiation
- Chromosomes, Human, Pair 12
- Chromosomes, Human, Pair 22
- DNA Primers
- DNA-Binding Proteins/genetics
- Female
- Humans
- Male
- Melanocytes/metabolism
- Melanoma-Specific Antigens
- Microphthalmia-Associated Transcription Factor
- Middle Aged
- Neoplasm Proteins/genetics
- Oncogene Proteins, Fusion/genetics
- Prospective Studies
- RNA, Neoplasm/analysis
- Reverse Transcriptase Polymerase Chain Reaction
- S100 Proteins/genetics
- Sarcoma/genetics
- Sarcoma/pathology
- Sarcoma/ultrastructure
- Sarcoma, Clear Cell/genetics
- Sarcoma, Clear Cell/pathology
- Sarcoma, Clear Cell/ultrastructure
- Transcription Factors/genetics
- Translocation, Genetic
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Affiliation(s)
- Cristina R Antonescu
- Department of Patholog, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
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38
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Katabuchi H, Honda R, Tajima T, Ohtake H, Kageshita T, Ono T, Okamura H. Clear cell sarcoma arising in the retroperitoneum. Int J Gynecol Cancer 2002; 12:124-7. [PMID: 11860547 DOI: 10.1046/j.1525-1438.2002.01052.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Clear cell sarcoma is a rare soft-tissue neoplasm, arising most commonly in the tendons and aponeuroses of young adults. We report here the first female case of clear cell sarcoma arising in the retroperitoneum with clinical features similar to those of malignant ovarian tumors. Aspects of clinical presentation, histopathologic evaluation, and treatment are described.
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Affiliation(s)
- H Katabuchi
- Department of Obstetrics and Gynecology, Kumamoto University School of Medicine, Honjo 1-1-1, Kumamoto City, Kumamoto 860-8556, Japan.
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39
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Reichert B, Hoch J, Plötz W, Mailänder P, Moubayed P. Metastatic clear-cell sarcoma of the capitate. A case report. J Bone Joint Surg Am 2001; 83:1713-7. [PMID: 11701796 DOI: 10.2106/00004623-200111000-00016] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- B Reichert
- Division of Plastic Surgery, Medical University of Lübeck, Germany
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40
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Finley JW, Hanypsiak B, McGrath B, Kraybill W, Gibbs JF. Clear cell sarcoma: the Roswell Park experience. J Surg Oncol 2001; 77:16-20. [PMID: 11344475 DOI: 10.1002/jso.1057] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND AND OBJECTIVES Clear cell sarcoma of the tendons and aponeuroses (CCSTA) is an aggressive, rare soft-tissue tumor with approximately 300 reported cases. Although it appears to be histogenetically related to melanoma, its clinical behavior resembles soft tissue sarcoma with a propensity for lymph node metastases. We report our experience at a tertiary cancer center. METHODS Eight cases of CCSTA evaluated at Roswell Park Cancer Institute between 1970 and 1998 were reviewed retrospectively. Patient data analyzed included patient age, gender, anatomic location, size of tumor, development of local, regional and distant recurrence, and patient status at last follow up. RESULTS Six of eight patients were alive at 2 years, while three of seven patients were alive at 5 years. Of the patients alive with no evidence of recurrence, two had tumors of less than 2 cm, and the remaining patient had incomplete information regarding tumor size. Five patients recurred within 2 years of definitive surgical management. Four had tumors > 5 cm. All five patients progressed to metastatic disease at a median follow up of 20 months (range 1-108 months) following definitive surgical management and all eventually died of their disease at a median of 3 months (range 0-24 months) from presentation with metastatic disease. Four of five patients with lesions > 5 cm received adjuvant chemotherapy with intent to cure, but all eventually died of disease at 4, 22, 34, and 41 months from initial presentation. CONCLUSIONS CCSTA is an aggressive tumor of the soft tissues. Early recognition and management are associated with an excellent long-term prognosis. Tumors greater than 5 cm warrant aggressive surgical management and treatment, and are at high risk of the development of distant disease. Aggressive multiagent chemotherapy appeared to have no impact on outcome. Other adjuvant therapeutic options including immunotherapy should be investigated.
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Affiliation(s)
- J W Finley
- Division of General Surgery, Geisinger Medical Center, Penn State Geisinger Health System, Danville, Pennsylvania, USA
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41
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Langezaal SM, Graadt van Roggen JF, Cleton-Jansen AM, Baelde JJ, Hogendoorn PC. Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts). Br J Cancer 2001; 84:535-8. [PMID: 11207050 PMCID: PMC2363762 DOI: 10.1054/bjoc.2000.1628] [Citation(s) in RCA: 102] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) and conventional malignant melanoma may demonstrate significant morphologic overlap at the light microscopic and ultrastructural level. Consequently, the clinically relevant distinction between primary clear cell sarcoma and metastatic melanoma in the absence of a known primary cutaneous, mucosal or ocular tumour may occasionally cause diagnostic problems. A balanced translocation, t(12;22)(q13;q13), which can be detected, amongst others, using the reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH), has been identified in a high percentage (50-75%) of clear cell sarcomas and is presumed to be tumour specific. Whether this chromosomal rearrangement is present in malignant melanoma has, to date, not as yet been studied by molecular genetic or molecular cytogenetic techniques. Using RT-PCR and FISH, a series of metastases from 25 known cutaneous melanomas and 8 melanoma cell lines (5 uveal and 3 cutaneous) were screened for the t(12;22)(q13;q13) translocation. Primers for RT-PCR were chosen based upon published breakpoint sequences. The Cosmids G9 and CCS2.2, corresponding to the 5' region of EWS and 3' region of ATF-1 respectively, were used as probes. The translocation was not identified in any of the melanomas or melanoma cell lines analysed in this study; in contrast this translocation was identified in 3 out of 5 clear cell sarcomas using these techniques. This allows distinction between translocation positive cases of clear cell sarcoma and malignant melanoma at a molecular genetic level. Consequently, in diagnostically challenging cases, this represents a valuable tool for the clinicopathologic differentiation between these two entities, with an important impact on patient management and prognosis.
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MESH Headings
- Chromosomes, Human, Pair 12/genetics
- Chromosomes, Human, Pair 13/genetics
- Chromosomes, Human, Pair 22/genetics
- Cosmids
- Diagnosis, Differential
- Humans
- In Situ Hybridization, Fluorescence
- Melanoma/diagnosis
- Melanoma/genetics
- Melanoma/pathology
- Reverse Transcriptase Polymerase Chain Reaction
- Sarcoma, Clear Cell/diagnosis
- Sarcoma, Clear Cell/genetics
- Sarcoma, Clear Cell/pathology
- Skin Neoplasms/diagnosis
- Skin Neoplasms/genetics
- Skin Neoplasms/pathology
- Soft Tissue Neoplasms/diagnosis
- Soft Tissue Neoplasms/genetics
- Soft Tissue Neoplasms/pathology
- Translocation, Genetic
- Tumor Cells, Cultured
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Affiliation(s)
- S M Langezaal
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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42
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Rubin BP, Pins MR, Nielsen GP, Rosen S, Hsi BL, Fletcher JA, Renshaw AA. Isochromosome 7q in adult Wilms' tumors: diagnostic and pathogenetic implications. Am J Surg Pathol 2000; 24:1663-9. [PMID: 11117788 DOI: 10.1097/00000478-200012000-00011] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Wilms' tumors affecting adults are rare and are thought to have a worse prognosis than similar stage tumors in the pediatric population. To understand these tumors better, the authors reviewed their multi-institutional experience in a series of nine lesions diagnosed as Wilms' tumors in adults. In addition to histologic and immunohistochemical examination, they performed cytogenetic analysis and fluorescence in situ hybridization. On review, four cases were reclassified: two "blastema only" as Ewing's sarcoma/primitive neuroectodermal tumor and the other two as clear cell sarcoma of soft parts and sarcoma not otherwise specified (NOS). Of the remaining five cases, three exhibited biphasic histology and two were triphasic. In this group, there were three women and two men, and patient age ranged from 17 to 37 years (median age, 26 years). Tumor size was large and ranged from 10 to 31 cm (median tumor size, 12.5 cm). Histologically, the tumors showed the typical features of Wilms' tumors with varying amounts of blastema (n = 5), epithelium (n = 5), and stroma (n = 2). No tumors contained anaplasia, and persistent renal blastema was not identified in the non-neoplastic kidney in any specimen. All tumors were positive for cytokeratins (CK7, n = 3; pankeratin, n = 5), and one tumor was weakly positive for CD99 (0-13). Molecular analysis including dual color fluorescence in situ hybridization (all tumors), and cytogenetic analysis (n = 2) disclosed the presence of isochromosome 7q in three of five tumors whereas all tumors were diploid with respect to chromosome 12. Follow-up data ranged from 6 to 133 months (median follow-up, 82 months) with progression in only one patient who had stage IV disease with lymph node and lung metastases at presentation. The authors conclude that adult Wilms' tumor has been overdiagnosed. Most "blastema-only" tumors in adults are not Wilms' tumors, and in an adult, biphasic morphology should be the minimum criteria for their diagnosis. Using strict diagnostic criteria, adult Wilms' tumors have a relatively favorable prognosis. The characteristic findings of isochromosome 7q, lack of trisomy or tetrasomy for chromosome 12, and absence of persistent renal blastema suggest that the pathogenesis of Wilms' tumors in adults may be different than in the pediatric population. These genetic features may be helpful in distinguishing adult Wilms' tumors from other primary renal tumors.
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Affiliation(s)
- B P Rubin
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
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43
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Folpe AL, Goodman ZD, Ishak KG, Paulino AF, Taboada EM, Meehan SA, Weiss SW. Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults. Am J Surg Pathol 2000; 24:1239-46. [PMID: 10976698 DOI: 10.1097/00000478-200009000-00007] [Citation(s) in RCA: 173] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The perivascular epithelioid cell family of tumors (PEComas), defined by their co-expression of melanocytic and muscle markers, includes angiomyolipoma, lymphangioleiomyoma, and clear cell "sugar" tumors of the lung, pancreas, and uterus. We present seven cases of a unique and previously unrecognized tumor of children and young adults, which represents a new addition to the PEComa group of tumors. Culled from three institutions over a 50-year period, all cases occurred in or immediately adjacent to the ligamentum teres and falciform ligament. Six patients were female and one male; their ages ranged from 3 to 21 years (median, 11 yrs). Tumor sizes ranged from 5 to 20 cm (median, 8 cm). All cases consisted of clear to faintly eosinophilic spindled cells arranged in fascicular and nested patterns. The cells had small but distinct nucleoli and low mitotic activity. Immunohistochemically, all cases were positive with antibodies to gp100 protein (HMB-45) and negative for S-100 protein. In three of the seven cases studied immunohistochemically, the tumors expressed smooth muscle actin, melan-A, microphthalmia transcription factor (MiTF), and myosin, but not desmin. No expression of the TSC2 gene product, tuberin, was seen in three cases. One case studied cytogenetically disclosed a t(3;10). Follow-up data, available in six of seven cases (median duration, 18 mos), showed five patients to be free of disease and one to have a radiographically presumed lung metastasis. We think these tumors comprise a new entity for which we propose the term "clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres." The differential diagnosis of these tumors includes clear cell sarcoma of tendons and aponeuroses, leiomyosarcoma, and angiomyolipoma.
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Affiliation(s)
- A L Folpe
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
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44
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Hombal SM. Fine needle aspiration cytology of malignant melanoma of soft parts: a case report and literature review. Cytopathology 2000; 11:61-6. [PMID: 10714378 DOI: 10.1046/j.1365-2303.2000.00203.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Affiliation(s)
- S M Hombal
- Department of Pathology, Armed Forces Hospital, Kuwait
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45
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Affiliation(s)
- S Hazra
- Northeastern Ohio Universities College of Medicine, USA
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46
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Sato H, Hasegawa T, Abe Y, Sakai H, Hirohashi S. Expression of E-cadherin in bone and soft tissue sarcomas: a possible role in epithelial differentiation. Hum Pathol 1999; 30:1344-9. [PMID: 10571515 DOI: 10.1016/s0046-8177(99)90066-7] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
The cadherin-mediated cell-cell adhesion system is now known to play a critical role in both the morphogenesis of cancer cells and suppression of their invasion. However, the pattern of expression of E-cadherin, the major cadherin of epithelial cells in bone and soft tissue sarcomas, remains unclear. This prompted us to study E-cadherin expression in a variety of bone and soft tissue sarcomas. Using the monoclonal antibody HECD-1, raised against the extracellular domain of E-cadherin, we observed immunoreactivity in 1 pleomorphic rhabdomyosarcoma, 2 of 5 diffuse mesotheliomas, 4 of 5 clear cell sarcomas, 1 of 5 epithelioid sarcomas, and 10 synovial sarcomas. Other types of bone and soft tissue sarcoma (4 osteosarcomas, 4 chondrosarcomas, 3 primitive neuroectodermal tumors, 1 fibrosarcoma, 4 malignant fibrous histiocytomas, 5 liposarcomas, 4 leiomyosarcomas, 6 alveolar and 5 embryonal rhabdomyosarcomas, 4 angiosarcomas, 4 malignant peripheral nerve sheath tumors, 2 extraskeletal myxoid chondrosarcomas, 2 extraskeletal osteosarcomas, and 3 alveolar soft part sarcomas) were completely negative for E-cadherin. Our findings indicate that E-cadherin is expressed in certain kinds of soft tissue sarcomas, especially those with epithelioid features, suggesting that E-cadherin plays a role in the constitution of their architecture.
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Affiliation(s)
- H Sato
- Pathology Division, National Cancer Center Research Institute, Tokyo, Japan
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47
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Ohba Y, Suzuki H, Hiraga H, Ito T, Sawa H, Nagai M, Satoh SI, Iwaki H, Nagashima K. Melanotic peritoneal sarcomatosis originating from clear cell sarcoma. Pathol Int 1999; 49:653-7. [PMID: 10504528 DOI: 10.1046/j.1440-1827.1999.00916.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Peritoneal sarcomatosis was found in a 53-year-old male who had a history of resection of clear cell sarcoma (CCS) of the right wrist 7 years previously. Both the previous wrist tumor and the peritoneal disseminants consisted of small, spindle-shaped cells occasionally containing melanophages. Histologic features, histochemical demonstration of argentaffin granules, immunohistochemical reaction with HMB 45, and the demonstration of a chimeric transcript of EWS-ATF-1 established the diagnosis of CCS in the peritoneal tumors. As far as we are aware, this is the first case of a peritoneal sarcomatosis associated with CCS.
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Affiliation(s)
- Y Ohba
- Laboratory of Molecular and Cellular Pathology, Hokkaido University School of Medicine, Sapporo, Japan
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48
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Rubin BP, Fletcher JA, Renshaw AA. Clear cell sarcoma of soft parts: report of a case primary in the kidney with cytogenetic confirmation. Am J Surg Pathol 1999; 23:589-94. [PMID: 10328092 DOI: 10.1097/00000478-199905000-00014] [Citation(s) in RCA: 50] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Clear cell sarcoma of soft parts (CCSSP), also known as malignant melanoma of soft parts, is an aggressive tumor that usually presents in soft tissue and very rarely in small bowel. We report a case arising in the kidney of a 20-year-old man which was difficult to distinguish from Wilms' tumor. The tumor metastasized to the liver and lungs, and the patient died of disseminated disease 5 years after his initial presentation. Both the primary and metastatic tumors were composed predominantly of spindle cells with occasional more epithelioid areas that were inconsistently arranged in nests. In both primary and metastatic sites, the tumor surrounded and entrapped normal epithelial elements, mimicking the biphasic appearance of Wilms' tumor. The tumor cells, however, were positive for S-100 protein and HMB45 and negative for keratin and CD99, and cytogenetic analysis revealed a clonal abnormality, translocation t(12;22)(q13;q12), characteristic of CCSSP. This result was verified by fluorescence in situ hybridization on paraffin-embedded tissue, which demonstrated EWS gene-region rearrangement. CCSSP joins a growing list of tumors that typically arise in soft tissue (PNET, solitary fibrous tumor, and infantile/congenital fibrosarcoma), but can also present in the kidney and may be confused with primary renal tumors. Awareness of this possibility and the use of ancillary studies. including immunohistochemistry, cytogenetic analysis, and fluorescence in situ hybridization, are important for accurate diagnosis.
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Affiliation(s)
- B P Rubin
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
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49
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Sonobe H, Takeuchi T, Taguchi T, Shimizu K, Iwata J, Furihata M, Ohtsuki Y. Further characterization of the human clear cell sarcoma cell line HS-MM demonstrating a specific t(12;22)(q13;q12) translocation and hybrid EWS/ATF-1 transcript. J Pathol 1999; 187:594-7. [PMID: 10398127 DOI: 10.1002/(sici)1096-9896(199904)187:5<594::aid-path277>3.0.co;2-h] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Only a small number of clear cell sarcoma (CCS) cell lines have been reported, including the cell line HS-MM. In the present study, this cell line, maintained for more than 4 years since establishment, was further characterized by cytogenetic studies, fluorescence in situ hybridization (FISH) analysis, and reverse transcriptase-polymerase chain reaction (RT-PCR). HS-MM cells both in vitro and in vivo exhibited pseudodiploid karyotypes with the specific t(12;22)(q13;q12) translocation. The translocation between chromosomes 12 and 22 was confirmed by FISH analysis and the hybrid EWS/ATF-1 transcript induced by this translocation was detected by RT-PCR. The HS-MM cell line will be useful for further studies of CCS.
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MESH Headings
- Chromosome Aberrations
- Chromosomes, Human, Pair 12
- Chromosomes, Human, Pair 22
- Humans
- In Situ Hybridization, Fluorescence
- Karyotyping
- Oncogene Proteins, Fusion/genetics
- Reverse Transcriptase Polymerase Chain Reaction
- Sarcoma, Clear Cell/genetics
- Sarcoma, Clear Cell/pathology
- Transcription Factors/genetics
- Translocation, Genetic
- Tumor Cells, Cultured
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Affiliation(s)
- H Sonobe
- Department of Pathology, Kochi Medical School, Nankoku, Kochi, Japan
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Campanacci M. Clear Cell Sarcoma of Tendons and Aponeuroses. BONE AND SOFT TISSUE TUMORS 1999:1161-1165. [DOI: 10.1007/978-3-7091-3846-5_84] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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