1
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Garg P, Ali M, Alomari M, Schoolmeester JK, Edgar M, Landolfo CK, Attia S, Landolfo KP. Cardiac benign metastatic leiomyoma- a comprehensive review. CARDIO-ONCOLOGY (LONDON, ENGLAND) 2025; 11:41. [PMID: 40317090 PMCID: PMC12046675 DOI: 10.1186/s40959-025-00336-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 04/10/2025] [Indexed: 05/04/2025]
Abstract
Cardiac benign metastatic leiomyoma (BML) is a rare cardiac tumor that is usually asymptomatic, frequently misdiagnosed and may result in serious complications, including embolization, heart failure and death. This review highlights the importance of considering cardiac BML in the differential diagnosis of cardiac masses, especially in women with a history of uterine leiomyomas. This review summarizes the current knowledge about cardiac BML, including its demographics, clinical presentation, etio-pathogenesis, diagnosis, and management. The authors discuss the challenges associated with diagnosing cardiac BML and emphasize the importance of a thorough history, physical examination, and imaging studies. They also review the different treatment options for cardiac BML, including surgical resection and role of medical and surgical castration. Early diagnosis and management of cardiac BML is crucial to prevent complications. This review provides valuable insights for clinicians who may encounter this rare condition. By raising awareness of cardiac BML and its management strategies, this review can improve patient care and outcomes.
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Affiliation(s)
- Pankaj Garg
- Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, FL, USA
| | - Mostafa Ali
- Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, FL, USA
| | - Mohammad Alomari
- Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, FL, USA.
| | | | - Mark Edgar
- Laboratory Medicine and Pathology Department, Mayo Clinic, Jacksonville, FL, USA
| | | | - Steven Attia
- Hematology and Oncology Department, Mayo Clinic, Jacksonville, FL, USA
| | - Kevin P Landolfo
- Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, FL, USA.
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2
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Ginetti MB, Oyhamburu P, Bosio M, Di Tullio F. [Long-term Titanium mesh cage implant failure after total en bloc spondylectomy due to spinal chondrosarcoma: case report and literature review]. REVISTA DE LA FACULTAD DE CIENCIAS MÉDICAS 2025; 82:154-164. [PMID: 40163833 PMCID: PMC12057708 DOI: 10.31053/1853.0605.v82.n1.44999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 09/27/2024] [Indexed: 04/02/2025] Open
Abstract
Objective To report an unusual titanium mesh cage failure after ten years of follow-up. Clinical case A 40-year-old woman diagnosed with low-grade spinal chondrosarcoma underwent a total en-bloc spondylenctomy (TES) surgery. This technique required a wide resection, anterior reconstruction with a titanium mesh cage (TMC), and posterior stabilization. For several years a favorable clinical outcome was achieved. After 10 years of follow-up, the patient developed acute non-traumatic low back pain without neurological repercussions. The images confirmed a rupture of the titanium cage. After ruling out tumor recurrence, the patient went through spinal instrumentation revision. Conclusion Isolated TMC rupture is a rare event scarcely reported in the literature. There is a strong recommendation to instrument two levels proximal and distal to the bone defect in 360° reconstructions after a TES. Stability had likely been lost over the years due to the slow resorption of the bone graft. We consider necessary studies with a higher casuistry and level of evidence to analyze the contributing factors for the event of TMC rupture.
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Affiliation(s)
- María Belén Ginetti
- Hospital Británico de Buenos AiresCentro de Medicina RespiratoriaBuenos AiresArgentina
| | - Pablo Oyhamburu
- Hospital Británico de Buenos AiresCentro de Medicina RespiratoriaBuenos AiresArgentina
| | - Martín Bosio
- Hospital Británico de Buenos AiresCentro de Medicina RespiratoriaBuenos AiresArgentina
| | - Fernando Di Tullio
- Hospital Británico de Buenos AiresCentro de Medicina RespiratoriaBuenos AiresArgentina
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3
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Lau HY, Huang M, Chang KTE, Kuick CH, Takano A. Metastatic Leiomyoma With Malignant Transformation Harboring RAB2A-PLAG1 Fusion: A Case Report and Review With Molecular Analysis. Int J Gynecol Pathol 2025; 44:160-166. [PMID: 39230504 DOI: 10.1097/pgp.0000000000001058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2024]
Abstract
Metastasizing leiomyoma is a rare condition characterized by the development of benign-appearing smooth muscle neoplasms at extrauterine sites in patients with a history of uterine leiomyoma. These lesions occur most commonly in the lung, with the abdominopelvic and mediastinal lymph nodes being other reported sites. Malignant transformation of metastasizing leiomyoma is extremely rare, with only a few cases described in the literature. We describe a case of metastasizing leiomyoma with malignant transformation in a middle-aged Asian lady, who developed pulmonary metastatic foci 12 years after surgical excision of the original uterine leiomyomata. Molecular analysis showed a common RAB2A-PLAG1 fusion gene and identical single nucleotide variants in both tumor foci, with significantly more pronounced segmental chromosomal copy number variations in one focus showing high-grade features. A comprehensive review of the literature lends support to the hypothesis that the original leiomyomata and the metastatic foci are clonally related, with high-grade features being associated with more complex genomic signatures.
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Affiliation(s)
- Hiu Yeung Lau
- Department of Anatomical Pathology, Singapore General Hospital, Singapore
- Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore
- Pathology Academic Clinical Program, SingHealth Duke-NUS Academic Medical Centre, Singapore
| | - Mingjie Huang
- Department of Cardiothoracic Surgery, National Heart Centre Singapore, Singapore
| | - Kenneth Tou En Chang
- Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore
- Pathology Academic Clinical Program, SingHealth Duke-NUS Academic Medical Centre, Singapore
| | - Chik Hong Kuick
- Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore
- Pathology Academic Clinical Program, SingHealth Duke-NUS Academic Medical Centre, Singapore
| | - Angela Takano
- Department of Anatomical Pathology, Singapore General Hospital, Singapore
- Pathology Academic Clinical Program, SingHealth Duke-NUS Academic Medical Centre, Singapore
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4
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Momeni-Boroujeni A, Nucci MR, Chapel DB. Risk Stratification of Uterine Smooth Muscle Tumors: The Role of Morphology, Immunohistochemistry, and Molecular Testing. Adv Anat Pathol 2025; 32:44-56. [PMID: 39711162 DOI: 10.1097/pap.0000000000000478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
Uterine smooth muscle neoplasms are a biologically and clinically heterogeneous group of tumors. Morphology is the cornerstone of pathologic diagnosis of these tumors, and most are readily classified as benign or malignant on the basis of routine histologic examination. However, rare subsets-including intravenous leiomyomatosis, benign metastasizing leiomyoma, and disseminated peritoneal leiomyomatosis-have a capacity for extrauterine spread despite benign cytomorphology. A further subset of uterine smooth muscle neoplasms, termed "smooth muscle tumor of uncertain malignant potential (STUMP)," are not readily classified as benign or malignant and carry an intermediate prognosis. STUMP is a protean category, whose precise definition is subject to disagreement among experts. The risk profiles of different STUMP morphotypes remain largely unresolved. Finally, multiple morphology-based systems for risk stratification of uterine leiomyosarcoma have been proposed, though none is widely adopted. Immunohistochemical and molecular prognostic markers for both STUMP and leiomyosarcoma remain in the early phases of adoption in routine diagnostic practice.
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Affiliation(s)
| | - Marisa R Nucci
- Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, MA
| | - David B Chapel
- Department of Pathology, University of Michigan-Michigan Medicine, Ann Arbor, MI
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5
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Piórek A, Płużański A, Wiśniewski P, Tabor S, Winiarczyk K, Knetki-Wróblewska M, Kowalski DM, Krzakowski M. Pulmonary Benign Metastasizing Leiomyoma in a Postmenopausal Woman: A Case Report and Review of the Literature. Diseases 2024; 12:181. [PMID: 39195180 DOI: 10.3390/diseases12080181] [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: 05/31/2024] [Revised: 08/02/2024] [Accepted: 08/09/2024] [Indexed: 08/29/2024] Open
Abstract
Pulmonary benign metastasizing leiomyoma (PBML) is a rare condition characterized by the spread of uterine leiomyomas to the lungs, typically observed in premenopausal women with a history of hysterectomy or myomectomy. This report presents a unique case of a postmenopausal woman, aged 65, that emphasizes the clinical, radiological, histologic, and immunohistochemical aspects of the disease. On presentation, the patient suffered from severe pain. On imaging, a sizable lung tumor was found. Histopathological examination and immunoprofiling confirmed PBML. The patient underwent various treatments, including surgery, radiation therapy, and hormonal therapy, illustrating the challenges in managing PBML. A literature review underscores the rarity of PBML and its diverse clinical manifestations. This study provides valuable insights into the complexities of PBML.
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Affiliation(s)
- Aleksandra Piórek
- Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Adam Płużański
- Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Piotr Wiśniewski
- Department of Pathology, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, Poland
| | - Sylwia Tabor
- Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Kinga Winiarczyk
- Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Magdalena Knetki-Wróblewska
- Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Dariusz M Kowalski
- Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Maciej Krzakowski
- Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
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6
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Hu Z, Liu K, Liu Q, Zhu H. Whole exon capture sequencing for identifying mutations associated with pulmonary benign metastasising leiomyoma. BMJ Case Rep 2023; 16:e251072. [PMID: 36948524 PMCID: PMC10040003 DOI: 10.1136/bcr-2022-251072] [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] [Accepted: 02/04/2023] [Indexed: 03/24/2023] Open
Abstract
A woman in her early 20s presented with cough and fever. She had undergone an abdominal myomectomy 3 years ago for uterine leiomyoma. Chest CT and positron emission tomography-CT revealed multiple round nodules in both lungs, suggesting metastatic lesions. A CT-guided lung biopsy was performed, and the tumour was diagnosed as pulmonary benign metastasising leiomyoma (PBML) based on pathological analyses. Whole exon capture sequencing of uterine leiomyoma and PBML sections revealed that 13 genes (MCM10, SLC16A9, RAG1, BAZ1A, NLRP2, TRMT61B, CPXM1, NGLY1, SUCLG2, FAM13A, CAGE1, PHTF2 and ZDHHC2) were concurrently present in the two tumours. The patient was prescribed goserelin injections every 4 weeks. The symptoms improved 2 weeks after starting the treatment. The lung nodules considerably decreased in size after three courses of goserelin treatment. The nodular size continues to decrease with the treatment.
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Affiliation(s)
- Zhijun Hu
- Department of Gynecologic Oncology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
| | - Kaijiang Liu
- Department of Gynecologic Oncology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
| | - Qing Liu
- Department of Gynecologic Oncology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
| | - Hong Zhu
- Department of Gynecologic Oncology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
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7
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A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity. Int J Mol Sci 2023; 24:ijms24065752. [PMID: 36982825 PMCID: PMC10056617 DOI: 10.3390/ijms24065752] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 03/07/2023] [Accepted: 03/15/2023] [Indexed: 03/19/2023] Open
Abstract
Uterine leiomyomas (ULs), frequent benign tumours of the female reproductive tract, are associated with a range of symptoms and significant morbidity. Despite extensive research, there is no consensus on essential points of UL initiation and development. The main reason for this is a pronounced inter- and intratumoral heterogeneity resulting from diverse and complicated mechanisms underlying UL pathobiology. In this review, we comprehensively analyse risk and protective factors for UL development, UL cellular composition, hormonal and paracrine signalling, epigenetic regulation and genetic abnormalities. We conclude the need to carefully update the concept of UL genesis in light of the current data. Staying within the framework of the existing hypotheses, we introduce a possible timeline for UL development and the associated key events—from potential prerequisites to the beginning of UL formation and the onset of driver and passenger changes.
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8
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Mehine M, Ahvenainen T, Khamaiseh S, Härkönen J, Reinikka S, Heikkinen T, Äyräväinen A, Pakarinen P, Härkki P, Pasanen A, Levonen AL, Bützow R, Vahteristo P. A novel uterine leiomyoma subtype exhibits NRF2 activation and mutations in genes associated with neddylation of the Cullin 3-RING E3 ligase. Oncogenesis 2022; 11:52. [PMID: 36068196 PMCID: PMC9448808 DOI: 10.1038/s41389-022-00425-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 08/02/2022] [Accepted: 08/05/2022] [Indexed: 11/11/2022] Open
Abstract
Uterine leiomyomas, or fibroids, are the most common tumors in women of reproductive age. Uterine leiomyomas can be classified into at least three main molecular subtypes according to mutations affecting MED12, HMGA2, or FH. FH-deficient leiomyomas are characterized by activation of the NRF2 pathway, including upregulation of the NRF2 target gene AKR1B10. Here, we have identified a novel leiomyoma subtype showing AKR1B10 expression but no alterations in FH or other known driver genes. Whole-exome and whole-genome sequencing revealed biallelic mutations in key genes involved in neddylation of the Cullin 3-RING E3 ligase, including UBE2M, NEDD8, CUL3, and NAE1. 3′RNA sequencing confirmed a distinct molecular subtype with activation of the NRF2 pathway. Most tumors displayed cellular histopathology, perivascular hypercellularity, and characteristics typically seen in FH-deficient leiomyomas. These results suggest a novel leiomyoma subtype that is characterized by distinct morphological features, genetic alterations disrupting neddylation of the Cullin 3-RING E3 ligase, and oncogenic NRF2 activation. They also present defective neddylation as a novel mechanism leading to aberrant NRF2 signaling. Molecular characterization of uterine leiomyomas provides novel opportunities for targeted treatment options.
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Affiliation(s)
- Miika Mehine
- Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland.,Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland
| | - Terhi Ahvenainen
- Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland.,Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.,iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland
| | - Sara Khamaiseh
- Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland.,Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.,iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland
| | - Jouni Härkönen
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Siiri Reinikka
- Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland.,Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland
| | - Tuomas Heikkinen
- Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland.,Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland
| | - Anna Äyräväinen
- Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland.,Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.,Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland
| | - Päivi Pakarinen
- Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland
| | - Päivi Härkki
- Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland
| | - Annukka Pasanen
- Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland.,Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland
| | - Anna-Liisa Levonen
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Ralf Bützow
- Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland.,Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland
| | - Pia Vahteristo
- Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland. .,Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland. .,iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland.
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9
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Li M, Lee AX, Wong WL, Tan KT. Benign metastasising leiomyoma: a rare disease and a diagnostic challenge. BMJ Case Rep 2022; 15:e248575. [PMID: 35835485 PMCID: PMC9289031 DOI: 10.1136/bcr-2021-248575] [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: 12/24/2022] Open
Abstract
Benign metastasising leiomyoma (BML) is a rare tumour characterised by extrauterine metastasis of histologically benign leiomyomas. We present a case of BML with pulmonary involvement. A 49-year-old woman presented with large pelviabdominal masses complicated by gross abdominal and lower limb swelling 6 years following open myomectomy. Preoperative CT imaging showed pelviabdominal masses and multiple bilateral pulmonary nodules. Initial impression was that of a stage 4 gynaecological malignancy. Palliative total hysterectomy bilateral salpingo-oophorectomy was performed. Histopathology confirmed benign uterine leiomyomas. Biopsy of pulmonary nodules showed benign leiomyomas, strongly positive for oestrogen and progesterone receptors. Definitive diagnosis of BML was made on histopathology and immunohistochemistry. The patient declined letrozole treatment as she had just undergone bilateral oophorectomy. She opted for conservative monitoring of her lung nodules. CT imaging 7 months postsurgery showed disease regression. She will require long-term surveillance scans to detect disease progression.
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Affiliation(s)
- Mingyue Li
- Obstetrics and Gynaecology, KK Women's and Children's Hospital, Singapore
| | - Ai Xin Lee
- Ministry of Health Holdings Pte Ltd, Singapore
| | - Wai Loong Wong
- Obstetrics and Gynaecology, KK Women's and Children's Hospital, Singapore
| | - Kim Teng Tan
- O&G, KK Women's and Children's Hospital, Singapore
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10
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Lung metastases and subsequent malignant transformation of a fumarate hydratase -deficient uterine leiomyoma. Exp Mol Pathol 2022; 126:104760. [DOI: 10.1016/j.yexmp.2022.104760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/21/2022] [Accepted: 03/28/2022] [Indexed: 11/17/2022]
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11
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Boavida Ferreira J, Cabrera R, Santos F, Relva A, Vasques H, Gomes A, Guimarães A, Moreira A. Benign Metastasizing Leiomyomatosis to the Skin and Lungs, Intravenous Leiomyomatosis, and Leiomyomatosis Peritonealis Disseminata: A Series of Five Cases. Oncologist 2022; 27:e89-e98. [PMID: 35305104 PMCID: PMC8842467 DOI: 10.1093/oncolo/oyab019] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 09/09/2021] [Indexed: 11/14/2022] Open
Abstract
Abstract
Benign metastasizing leiomyomatosis (BML) is a rare disease that typically occurs in women with a history of uterine leiomyomatosis. Benign metastasizing leiomyomatosis occurs more frequently in the lungs but may also develop in other organs and tissues. Other unusual variants of extra-uterine leiomyomatosis include intravenous leiomyomatosis (IVL) and leiomyomatosis peritonealis disseminata (LPD). In this article, three cases of BML are presented. One case, in a premenopausal woman, presented cutaneous metastases. We also present a case of IVL and a case of LPD, which occurred in postmenopausal women. Given the rarity of BML, IVL, and LPD, the authors reviewed the literature and herein discuss the implications for treatment in all five cases. Evidence for treating BML, IVL, and LPD is still scarce, and data available from our series and other small series seem to point to the patient’s hormonal status playing a fundamental part in the treatment plan. Furthermore, a collecting bag when performing excision of uterine leiomyomas may help avoid the potential spreading of leiomyomatosis. Hysterectomized patients with chronic cough, frequent respiratory infections, abdominal discomfort, right heart failure, or non-specific symptoms should be actively screened for BML, IVL, and LPD. Treatment should be individualized according to each patient’s hormonal status and desires.
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Affiliation(s)
- João Boavida Ferreira
- Serviço de Oncologia Médica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
| | - Rafael Cabrera
- Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
| | - Filipa Santos
- Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
| | - Andreia Relva
- Serviço de Ginecologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
| | - Hugo Vasques
- Serviço de Cirurgia Geral, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
| | - António Gomes
- Serviço de Ginecologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
| | - António Guimarães
- Serviço de Oncologia Médica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
| | - António Moreira
- Serviço de Oncologia Médica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
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12
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[18F]-FDG PET/CT of the Pulmonary Benign Metastasizing Leiomyoma in a Breast Cancer Patient: A Case Report. SURGERIES 2021. [DOI: 10.3390/surgeries2030023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
18F-fluorodeoxyglucose ([18F]-FDG) positron emission tomography/computed tomography (PET/CT) is a useful functional image technique to evaluate the disease extent in many cancers, as well as differentiate benign disease from malignant metastasis. We report the case of a 49-year-old woman with breast cancer and suspected lung metastasis by conventional images. After FDG-PET/CT demonstrating faint, or even no FDG uptake in bilateral pulmonary nodules, accompanied with obvious uterine fibroids, benign metastasizing leiomyoma (BML) of the lung was included in a differential diagnosis and finally confirmed by surgical pathology. FDG PET/CT showed its value in the diagnosis of BML in the breast cancer patient who was misleading as lung metastasis during outpatient follow-up.
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13
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Benign Metastasizing Leiomyoma of the Uterus with Pulmonary and Bone Metastases. Case Rep Obstet Gynecol 2021; 2021:5536675. [PMID: 34211791 PMCID: PMC8205596 DOI: 10.1155/2021/5536675] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 05/22/2021] [Indexed: 11/17/2022] Open
Abstract
Benign metastasizing leiomyoma (BML) is a rare spindle cell neoplasm seen in middle-aged women who have a history of leiomyoma of the uterus. The most common sites of metastases are the lungs; however, other sites of spread have been documented. These tumors by definition have no malignant features on histology and tend to be estrogen and progesterone positive. We present a middle-aged woman who was incidentally found to have multiple pulmonary nodules and a mass on her sternum after she was involved in a motor vehicle accident. She had a history of uterine leiomyoma and had undergone a hysterectomy ten years prior to the accident. Biopsies were performed of the lung nodules and sternum mass and compared to her hysterectomy specimen, and they were identical, and hence, she was diagnosed with BML. Due to the growing tumor of her sternum, she was started on tamoxifen with stability of her tumors. These tumors, since they are benign, tend to have an indolent course. However, in the instances that treatment is warranted, options include surgery or antiestrogen therapy. We will be discussing the pathogenesis, histological findings, and treatment options of this rare condition. Our case is unique because BML in general do not tend to spread to multiple organs and tend to be limited to one site of disease.
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14
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Ventura L, Gnetti L, Rossi M, Tiseo M, Giordano G, Corradi M, Silva M, Milanese G, Minari R, Leonetti A, Cattadori S, Ampollini L, Carbognani P, Mozzoni P. The role of miRNA-221 and miRNA-126 in patients with benign metastasizing leiomyoma of the lung: an overview with new interesting scenarios. Mol Biol Rep 2021; 48:3485-3494. [PMID: 33856606 DOI: 10.1007/s11033-021-06322-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 03/27/2021] [Indexed: 01/03/2023]
Abstract
Benign metastasizing leiomyoma (BML) is a rare disease characterized by extrauterine benign leiomyomatosis in patients with a previous or concomitant history of uterine leiomyoma. Currently, there are no specific criteria to predict the metastasizing ability of the uterine leiomyoma and the risk of malignant degeneration of pulmonary BML, and these are the aims of this study. We analyzed 10 uterine (three leiomyomas, four leiomyomas that gave rise to lung BML, three healthy tissues) and 11 pulmonary tissue samples (eight lung BML, three healthy tissues). Interestingly, one of the BML lesions exceptionally evolved into a leiomyosarcoma (case 2). Uterine leiomyoma microvascular density (MVD) was higher in the patients with uterine leiomyomas that gave rise to lung BML, reaching a peak in case 2. Strong positivity for the estrogen (ER) and progesterone (PR) receptors and a low proliferation index (Ki67 < 1%) were discovered both in patients with uterine leiomyoma and in patients with BML. Interestingly, in case 2, the last dedifferentiated leiomyosarcoma showed a weaker ER and PR positivity with a higher proliferation index (Ki67:30%). Regarding the uterine miRNA-126, a trend toward a hypo-expression between uterine leiomyoma and uterine leiomyoma that gave rise to lung BML was discovered, reaching the lowest level in case 2. Considering the pulmonary samples, we observed a higher miRNA-221 and a lower miRNA-126 expression in the leiomyosarcoma. We tried to better elucidate the biological behaviour of this rare disease. The analysis of the miRNA-221 and miRNA-126 could offer new diagnostic, prognostic and therapeutic perspectives.
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Affiliation(s)
- Luigi Ventura
- Thoracic Surgery, Department of Medicine and Surgery, University Hospital of Parma, Viale Gramsci 14, 43126, Parma, Italy.
| | - Letizia Gnetti
- Pathology Unit, Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy
| | - Maurizio Rossi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Marcello Tiseo
- Medical Oncology, Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy
| | - Giovanna Giordano
- Pathology Unit, Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy
| | - Massimo Corradi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Mario Silva
- Section of Radiology, Diagnostic Department, University Hospital of Parma, Parma, Italy
| | - Gianluca Milanese
- Section of Radiology, Diagnostic Department, University Hospital of Parma, Parma, Italy
| | - Roberta Minari
- Medical Oncology, Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy
| | - Alessandro Leonetti
- Medical Oncology, Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy
| | - Sara Cattadori
- Thoracic Surgery, Department of Medicine and Surgery, University Hospital of Parma, Viale Gramsci 14, 43126, Parma, Italy
| | - Luca Ampollini
- Thoracic Surgery, Department of Medicine and Surgery, University Hospital of Parma, Viale Gramsci 14, 43126, Parma, Italy
| | - Paolo Carbognani
- Thoracic Surgery, Department of Medicine and Surgery, University Hospital of Parma, Viale Gramsci 14, 43126, Parma, Italy
| | - Paola Mozzoni
- Department of Medicine and Surgery, University of Parma, Parma, Italy
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15
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Fan R, Feng F, Yang H, Xu K, Li S, You Y, Wan X, Zhu L. Pulmonary benign metastasizing leiomyomas: a case series of 23 patients at a single facility. BMC Pulm Med 2020; 20:292. [PMID: 33172427 PMCID: PMC7653756 DOI: 10.1186/s12890-020-01330-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 10/30/2020] [Indexed: 11/10/2022] Open
Abstract
Background Pulmonary benign metastasizing leiomyoma (PBML) is a rare disease characterized by leiomyoma of benign histopathology existing in the lungs. Because of its rarity, limited literature with a single case or small number of cases has been regarding to the clinical course, pathology or management of PBML. Methods A retrospective study was performed of all PBML cases diagnosed and managed at Peking Union Medical College Hospital (PUMCH) from 2001 to 2019. The clinical characteristics, pathology, treatment and outcomes of each case were studied. Results There were 25 PBML patients identified in the 19-year period in PUMCH, and 23 patients’ data was analyzed. The median age at diagnosis was 46 years. There were 7 patients (30.4%) diagnosed with postmenopausal status. Two patients (8.7%) had no uterine leiomyoma, and 3 patients (13.0%) had no gynecologic surgery history. Immunohistochemistry of most lesions demonstrated positive for desmin, SMA and Estrogen/Progesterone Receptors; and negative for S-100 were shown in 7 cases. After curative or diagnostic surgeries for the PBML, several treatments from observation to medical or surgical castration were performed. Nine premenopausal patients preserved their ovaries at first. At a median follow-up of 8 years, 3 patients finally had oophorectomy. Conclusions PBML is a rare disease and should be treated by individualization according to the patients’ age, symptoms and extent of lesion. Curative surgery for patients with limited lesions can achieve the complete response. For patients that are young and asymptomatic, close observation is recommended as the first choice. All patients should undergo long-term surveillance.
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Affiliation(s)
- Rong Fan
- Department of Obstetrics & Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), No. 1, Shuai Fu Yuan, Dong Cheng District, Beijing, China
| | - Fengzhi Feng
- Department of Obstetrics & Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), No. 1, Shuai Fu Yuan, Dong Cheng District, Beijing, China.
| | - Hua Yang
- Department of Obstetrics & Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), No. 1, Shuai Fu Yuan, Dong Cheng District, Beijing, China
| | - Kaifeng Xu
- Department of Pulmonary and Critical Care Medicine, PUMCH, CAMS & PUMC, Beijing, China
| | - Shanqing Li
- Department of Thoracic Surgery, PUMCH, CAMS & PUMC, Beijing, China
| | - Yan You
- Department of Pathology, PUMCH, CAMS & PUMC, Beijing, China
| | - Xirun Wan
- Department of Obstetrics & Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), No. 1, Shuai Fu Yuan, Dong Cheng District, Beijing, China
| | - Lan Zhu
- Department of Obstetrics & Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), No. 1, Shuai Fu Yuan, Dong Cheng District, Beijing, China
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16
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Williams EA, Sharaf R, Decker B, Werth AJ, Toma H, Montesion M, Sokol ES, Pavlick DC, Shah N, Williams KJ, Venstrom JM, Alexander BM, Ross JS, Albacker LA, Lin DI, Ramkissoon SH, Elvin JA. CDKN2C-Null Leiomyosarcoma: A Novel, Genomically Distinct Class of TP53/ RB1-Wild-Type Tumor With Frequent CIC Genomic Alterations and 1p/19q-Codeletion. JCO Precis Oncol 2020; 4:PO.20.00040. [PMID: 33015533 PMCID: PMC7529542 DOI: 10.1200/po.20.00040] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/24/2020] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Leiomyosarcoma (LMS) harbors frequent mutations in TP53 and RB1 but few actionable genomic alterations. Here, we searched for recurrent actionable genomic alterations in LMS that occur in the absence of common untreatable oncogenic drivers. METHODS Tissues from 276,645 unique advanced cancers, including 2,570 uterine and soft tissue LMS, were sequenced by hybrid-capture-based next-generation DNA and RNA sequencing/comprehensive genomic profiling of up to 406 genes. We characterized clinicopathologic features of relevant patient cases. RESULTS Overall, 77 LMS exhibited homozygous copy loss of CDKN2C at chromosome 1p32.3 (3.0% of LMS). Genomic alterations (GAs) in TP53, RB1, and ATRX were rare compared with the remainder of the LMS cohort (11.7% v 73.4%, 0% v 54.5%, 2.6% v 24.5%, respectively; all P < .0001). CDKN2C-null LMS patient cases were significantly enriched for GAs in CIC (40.3% v 1.4%) at 19q13.2, CDKN2A (46.8% v 7.0%), and RAD51B (16.9% v 1.7%; all P < .0001). Chromosome arm-level aneuploidy analysis of available LMS patient cases (n = 1,284) found that 81% (58 of 72) of CDKN2C-null LMS exhibited 1p/19q-codeletion, a significant enrichment compared with 5.1% in the remainder of the LMS cohort (P < .0001). In total, 99% of CDKN2C-null LMS were in women; the median age was 61 years at surgery (range, 36-81 years). Fifty-five patient cases were uterine primary, four were nonuterine, and the remaining 18 were of uncertain primary site. Sixty percent of cases showed at least focal epithelioid variant histology. Most patients had advanced-stage disease, with 62% of confirmed uterine primary LMS at International Federation of Gynecology and Obstetrics stage IVB. We further validated our findings in two publicly available datasets: The Cancer Genome Atlas and the Project GENIE initiative. CONCLUSION CDKN2C-null LMS defines a genomically distinct tumor that may have prognostic and/or therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.
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Affiliation(s)
| | | | - Brennan Decker
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Adrienne J. Werth
- Christiana Hospital, Department of Obstetrics and Gynecology, Newark, DE
| | - Helen Toma
- Christiana Hospital, Department of Obstetrics and Gynecology, Newark, DE
| | | | | | | | | | - Kevin Jon Williams
- Department of Physiology, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA
| | | | | | - Jeffrey S. Ross
- Foundation Medicine, Cambridge, MA
- Department of Pathology, State University of New York Upstate Medical University, Syracuse, NY
| | | | | | - Shakti H. Ramkissoon
- Foundation Medicine, Cambridge, MA
- Wake Forest Comprehensive Cancer Center and Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC
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17
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Ordulu Z, Chai H, Peng G, McDonald AG, De Nictolis M, Garcia-Fernandez E, Hardisson D, Prat J, Li P, Hui P, Oliva E, Buza N. Molecular and clinicopathologic characterization of intravenous leiomyomatosis. Mod Pathol 2020; 33:1844-1860. [PMID: 32341498 PMCID: PMC7483566 DOI: 10.1038/s41379-020-0546-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Revised: 04/06/2020] [Accepted: 04/06/2020] [Indexed: 12/14/2022]
Abstract
Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n = 15), usual (n = 11), and vascular (n = 5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding nonneoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH, and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%), and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed three molecular groups: Groups 1 (29%) and 2 (18%) with associated del(22q), and Group 3 (18%) with del(10q). The remaining IVL had nonspecific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features.
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Affiliation(s)
- Zehra Ordulu
- Department of Pathology, Massachusetts General Hospital, Boston, MA, United States
| | - Hongyan Chai
- Department of Genetics, Yale University School of Medicine; New Haven, CT
| | - Gang Peng
- Department of Biostatistics, Yale School of Public Health, New Haven, CT
| | - Anna G McDonald
- Department of Pathology, Wake Forest Baptist Medical Center, Winston Salem, NC
| | | | - Eugenia Garcia-Fernandez
- Department of Pathology, Hospital Universitario La Paz, IdiPAZ, and Faculty of Medicine, Universidad Autónoma de Madrid, Spain
| | - David Hardisson
- Department of Pathology, Hospital Universitario La Paz, IdiPAZ, and Faculty of Medicine, Universidad Autónoma de Madrid, Spain
| | - Jaime Prat
- Department of Pathology, Hospital de la Sta Creu i Sant Pau, Barcelona, Spain
| | - Peining Li
- Department of Genetics, Yale University School of Medicine; New Haven, CT
| | - Pei Hui
- Department of Pathology, Yale University School of Medicine; New Haven, CT
| | - Esther Oliva
- Department of Pathology, Massachusetts General Hospital, Boston, MA, United States
| | - Natalia Buza
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
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18
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Uncommon thoracic manifestations from extrapulmonary tumors: Computed tomography evaluation - Pictorial review. Respir Med 2020; 168:105986. [PMID: 32469707 DOI: 10.1016/j.rmed.2020.105986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 04/04/2020] [Accepted: 04/19/2020] [Indexed: 11/23/2022]
Abstract
Although metastasis can occur at a variety of sites, pulmonary involvement is common in patients with cancer. Depending on the source and type of tumor, pulmonary metastases present with a wide range of radiologic appearances. Hematogenous dissemination through the pulmonary arteries to the pulmonary capillary network is the most common form of spread in pulmonary metastases. However, they may also reach the lung via lymphatic dissemination, secondary airway involvement, vessel tumor embolism, and direct chest invasion. In the evaluation of patients with known extrathoracic tumors, CT is the state-of-the-art imaging modality for detecting and characterize pulmonary metastases as well as to predict resectability. Although CT limitations are well known, knowledge of growth rates of various tumors and understanding the pattern of spread may be helpful clues in suggesting and even establish the specific diagnosis. The purpose of this pictorial review is to discuss the imaging appearances of different patterns of intrathoracic tumoral dissemination.
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19
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Abstract
RATIONALE Pulmonary benign metastasizing leiomyoma (PBML) is rare, usually occurs in women who underwent hysterectomy during the reproductive years, and has no obvious clinical symptoms. A full understanding of the characteristics of PBML is important for its sequential treatment and prognosis. PATIENT CONCERNS In this report, a 36-year-old female patient with previous uterine leiomyoma who underwent 3 surgical resections of the uterus, bilateral fallopian tubes, and partial omentum was investigated. The physical examination revealed a tumor in the right lower lobe and mediastinum and a solid nodule in the right middle lobe. DIAGNOSES Chest computed tomography (CT) confirmed a tumor in the right lower lobe and mediastinum and a solid nodule in the right middle lobe. Further positron-emission tomography computed tomography (PET-CT) with 18F-fluorodeoxyglucose (FDG) of the whole body showed mildly intense accumulation of 18F-FDG in the tumor (maximum standardized uptake value [SUV max], 2.6). A pathological examination then confirmed the presence of fibrous and vascular tissue after CT-guided percutaneous biopsy of the tumor in the right lower lobe. Additionally, surgical resection of the tumor and nodule was performed for histological analysis and immunohistochemical assays for estrogen receptor (ER) and progesterone receptor (PR). INTERVENTIONS The patient underwent complete tumor surgical resection and nodule wedge resection. OUTCOMES No postoperative complications occurred. No recurrence or other signs of metastasis were found during an 18-month follow-up observation period. CONCLUSION In this case, lung and mediastinal metastasis of uterine fibroids was observed. However, depending on only a postoperative histological analysis is insufficient for the diagnosis of PBML. Histological analysis combined with an evaluation of the expression levels of ER and PR is crucial for the diagnosis and treatment of PBML.
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Affiliation(s)
| | | | | | - Yuwei Guo
- Department of pathology, Hebei Medical University Fourth Hospital
| | - Mengdi Cong
- Department of pathology, Children's hospital of Hebei Province, Shijiazhuang, China
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20
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Yuan X, Sun Y, Jin Y, Xu L, Dai H, Wang J, Zhang Z, Chen X. Multiple organ benign metastasizing leiomyoma: A case report and literature review. J Obstet Gynaecol Res 2019; 45:2132-2136. [PMID: 31381225 DOI: 10.1111/jog.14066] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 06/30/2019] [Indexed: 11/29/2022]
Affiliation(s)
- Xiong Yuan
- Department of Gynecologythe First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Ying Sun
- Department of Gynecologythe First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Yichao Jin
- Department of Gynecologythe First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Lei Xu
- Department of Gynecologythe First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Huihua Dai
- Department of Gynecologythe First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Jun Wang
- Department of Radiologythe First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Zhihong Zhang
- Department of Pathologythe First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Xing Chen
- Department of Gynecologythe First Affiliated Hospital of Nanjing Medical University Nanjing China
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21
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Devereaux KA, Schoolmeester JK. Smooth Muscle Tumors of the Female Genital Tract. Surg Pathol Clin 2019; 12:397-455. [DOI: 10.1016/j.path.2019.02.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2023]
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22
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Ofori K, Fernandes H, Cummings M, Colby T, Saqi A. Benign metastasizing leiomyoma presenting with miliary pattern and fatal outcome: Case report with molecular analysis & review of the literature. Respir Med Case Rep 2019; 27:100831. [PMID: 30989050 PMCID: PMC6446132 DOI: 10.1016/j.rmcr.2019.100831] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 03/25/2019] [Accepted: 03/25/2019] [Indexed: 11/17/2022] Open
Abstract
Benign metastasizing leiomyoma (BML) is a rare benign smooth muscle neoplasm that originates in the uterus and metastasizes to distant sites—most commonly the lungs. BMLs are often found incidentally in patients with a history of uterine leiomyoma(s) and tend to be indolent. Occasionally they may be symptomatic and rarely follow an aggressive clinical course. We report an unusual case of BML presenting in a 46-year-old woman as a miliary nodular pattern bilaterally in the lungs and progressive respiratory failure. Her past medical history was significant for uterine “leiomyomas” of at least 9 years' duration. Post mortem histologic evaluation of the uterine and lung lesions revealed benign smooth muscle neoplasms (leiomyomas and BMLs, respectively), and molecular analyses demonstrated identical clonal MED12 mutation, though with greater mutant allelic frequency in the uterus. We document a rare aggressive clinical course in a patient with BML, which presented as a miliary radiologic pattern mimicking an infectious etiology or interstitial lung disease.
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Affiliation(s)
- Kenneth Ofori
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, USA
| | - Helen Fernandes
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, USA
| | - Matthew Cummings
- Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia, University Medical Center, New York, USA
| | | | - Anjali Saqi
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, USA
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23
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Hernández-Plata E, Velázquez-Wong AC, Jiménez-Ramírez C, Fernández-Ramírez F, Galicia-Sánchez LM, Flores-García CA, Hernández-Hernández JM, Rosas-Vargas H, Huicochea-Montiel JC, Espinosa-Poblano E. Identification of genomic copy number variations in lung benign metastasizing leiomyomatosis. CLINICAL RESPIRATORY JOURNAL 2019; 13:105-113. [PMID: 30597752 DOI: 10.1111/crj.12987] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 12/01/2018] [Accepted: 12/14/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Lung metastasizing leiomyomatosis (LML) is an infrequently diagnosed pathology developed after sexual maturation, commonly preceded by uterine myomas. Symptoms can include difficulties to breathe, cough, dyspnea and pain, because of mechanical obstruction exerted by expanding local growing leiomyomas. Lung leiomyomas are normally detected by imaging studies, but nowadays the precise diagnosis demands histological characterization of biopsies obtained from the affected tissues. The purpose of the present study was to determine the presence of genomic alterations in circulating cells of LML. METHODS Immunohistochemical characterization of a lung biopsy extracted by thoracoscopy was performed. Pathologic proliferative smooth muscle cells were observed in a major lung metastasizing nodule, with a growing pattern similar to a uterine myoma. The presence of cellular linages different to smooth muscle cells was discarded by testing the presence of a battery of molecular markers. Also, a normal karyotype was determine by GTG-banding cytogenetic study, but a high density microarray analysis revealed six submicroscopic chromosomal regions displaying genomic abnormalities: microduplications were detected on chromosomes 4, 14, 17 and 22; and microdeletions on chromosomes 8 and 10. CONCLUSION This study remarks the relevance of submicroscopic chromosomal analysis of unusual pathologic conditions such as Benign Metastasizing Leiomyomatosis. This propitiate a better understanding of the molecular basis on the development of the pathology, in order to reckon on minimally invasive diagnostic methods, and to design appropriate treatments.
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Affiliation(s)
- Everardo Hernández-Plata
- Unidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social IMSS, Ciudad de México, México.,Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, UNAM, Ciudad de México, México
| | - Ana Claudia Velázquez-Wong
- Unidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social IMSS, Ciudad de México, México
| | - Carmina Jiménez-Ramírez
- Unidad Médica de Alta Especialidad, Hospital de traumatología, Dr. Victorio de la Fuente Narváez Instituto Mexicano del Seguro Social IMSS, Ciudad de México, México
| | | | - Luz María Galicia-Sánchez
- Servicio de Neumología, Hospital de Cardiología, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - César Antonio Flores-García
- Departamento de Patología, Unidad Médica de Alta Especialidad, Hospital de Cardiología del Centro Médico Nacional, Siglo XXI, IMSS, Ciudad de México, México
| | - José Manuel Hernández-Hernández
- Unidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social IMSS, Ciudad de México, México
| | - Haydeé Rosas-Vargas
- Unidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social IMSS, Ciudad de México, México
| | - Juan Carlos Huicochea-Montiel
- Departamento Clínico de Genética Médica, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Eliseo Espinosa-Poblano
- Servicio de Neumología, Unidad Médica de Alta Especialidad, Hospital de Especialidades del Centro Médico Nacional, Siglo XXI, IMSS, Ciudad de México, México
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24
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Benign Metastasizing Leiomyoma of the Uterus: Rare Manifestation of a Frequent Pathology. Case Rep Obstet Gynecol 2018; 2018:5067276. [PMID: 30510824 PMCID: PMC6232788 DOI: 10.1155/2018/5067276] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 10/14/2018] [Accepted: 10/16/2018] [Indexed: 12/22/2022] Open
Abstract
Benign Metastasizing Leiomyoma (BML) is a rare condition with few cases reported in the literature. It is usually incidentally diagnosed several years after a primary gynecological surgery for uterine leiomyoma. Differential diagnosis of BML is complex requiring an extensive work-up and exclusion of malignancy. Here, we report two cases of BML based on similarity of histopathological, immunohistochemical, and genetic patterns between lung nodules and uterine leiomyoma previously resected, evidencing the variability of clinical and radiological features of BML. We highlight the importance of 19q and 22q deletions as highly suggestive of BML. These findings are particularly relevant when there is no uterine sample for review.
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25
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Post-menopausal pulmonary leiomyoma metastasis: an unexpected finding. Indian J Thorac Cardiovasc Surg 2018; 34:513-515. [PMID: 33060928 DOI: 10.1007/s12055-018-0676-5] [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: 02/13/2018] [Revised: 03/17/2018] [Accepted: 03/27/2018] [Indexed: 10/17/2022] Open
Abstract
Benign metastasizing leiomyoma (BML) is a rare entity characterized by proliferation of extra-uterine smooth muscle tumors. BML has both malignant behavior and benign characteristics. Here, we present a case of pulmonary BML occurring in a 70-year-old woman treated by surgery.
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26
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Jo HC, Baek JC. Case of pulmonary benign metastasizing leiomyoma from synchronous uterine leiomyoma in a postmenopausal woman. Gynecol Oncol Rep 2018; 26:33-36. [PMID: 30225333 PMCID: PMC6138877 DOI: 10.1016/j.gore.2018.08.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 08/19/2018] [Accepted: 08/27/2018] [Indexed: 12/11/2022] Open
Abstract
Benign metastasizing leiomyoma (BML) is a rare tumor comprising histologically benign smooth muscle cells and exhibits the same histological findings as a uterine myoma although in an extra-uterine location. Most BMLs occur several years after surgery for uterine myoma in women of reproductive age. Here, we report a case of pulmonary BML in a 54-year-old postmenopausal woman with no previous history of myomectomy or hysterectomy. The patient presented with a rapid increase in abdominal girth over the past 3 months and a cough lasting for 2 months. Chest computed tomography (CT) revealed multiple pulmonary nodules, ranging in diameter from a few millimeters to 1.5 cm. Abdominal CT revealed a well-defined heterogeneous hypervascular uterine mass measuring 25 cm at the widest diameter. In addition to the uterine mass, imaging studies identified no other origin of the metastatic lung nodules. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed followed by video-assisted thoracoscopy. The histological findings of the lungs and uterus suggested myoma. The patient remains asymptomatic and disease-free at 7 years after surgery without adjuvant treatment.
Benign metastasizing leiomyoma (BML) can occur in postmenopausal woman without uterine surgery. BMLs in postmenopausal woman can cause respiratory and gynecologic symptoms. Total abdominal hysterectomy and bilateral salpingo-oophorectomy could reduce lung BML in postmenopausal woman.
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Affiliation(s)
- H C Jo
- Department of Obstetrics and Gynecology, College of Medicine, Gyeongsang National University, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - J C Baek
- Department of Obstetrics and Gynecology, College of Medicine, Gyeongsang National University, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
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27
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Pulmonary benign metastasizing leiomyoma: A case report. Respir Med Case Rep 2018; 24:117-121. [PMID: 29977777 PMCID: PMC6010632 DOI: 10.1016/j.rmcr.2018.04.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 04/28/2018] [Indexed: 11/24/2022] Open
Abstract
Uterine leiomyoma is the most common benign gynecological tumor. Rarely, it has benign extra-uterine growth patterns, including benign metastasizing leiomyoma (BML), with lungs being the most common metastatic site. We present a case of a 47-year-old female who, 3 years prior to presentation, underwent abdominal supra-cervical hysterectomy for benign leiomyoma. Approximately 6 months prior to presentation, she was seen for shortness of breath and chest pain. A CT of the chest revealed multiple new non-calcified pulmonary nodules bilaterally. PET/CT demonstrated mild FDG uptake in multiple lung nodules, with no significant extra-thoracic sites of abnormal FDG uptake. A CT guided lung biopsy showed a low grade, smooth muscle tumor. Immunohistochemical staining was positive for smooth-muscle actin and desmin, estrogen and progesterone receptor and was negative for CD117, HMB-45, CD34, pan cytokeratin and EMA. She underwent wedge resection of one of the nodules which confirmed the above findings. A cytogenetic analysis was also performed, which was consistent with pulmonary BML. She ultimately underwent left lower lobe resection and was started on a daily aromatase inhibitor. BML is a rare disease usually seen in women of reproductive age. The pathogenesis and treatment remain controversial. BML mostly tends to have an indolent course and a favorable outcome.
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Fukui K, Takase N, Miyake T, Hisano K, Maeda E, Nishimura T, Abe K, Kozuki A, Tanaka T, Harada N, Takamatsu M, Kaneda K. Review of the literature laparoscopic surgery for metastatic hepatic leiomyosarcoma associated with smooth muscle tumor of uncertain malignant potential: Case report. World J Hepatol 2018; 10:402-408. [PMID: 29713398 PMCID: PMC5924371 DOI: 10.4254/wjh.v10.i4.402] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 03/10/2018] [Accepted: 04/03/2018] [Indexed: 02/06/2023] Open
Abstract
Metastatic hepatic leiomyosarcoma is a rare malignant smooth muscle tumor. We report a case of metastatic hepatic leiomyosarcoma associated with smooth muscle tumor of uncertain malignant potential (STUMP). A 68-year-old female presented with a liver mass (60 mm × 40 mm, Segment 4). She underwent left salpingo-oophorectomy for an ovary tumor with STUMP in a broad ligament 6 years ago. Though FDG-PET showed obvious metabolically active foci, abnormal metabolically active foci other than the lesion were not detected. A malignant liver tumor was strongly suspected and laparoscopic partial liver resection was performed with vessel-sealing devices using the crush clamping method and Pringle maneuver. Immunohistochemical findings revealed metastatic liver leiomyosarcoma associated with STUMP in a broad ligament. This case is an extremely rare case of malignant transformation from primary STUMP to metastatic hepatic leiomyosarcoma. It provides important evidence regarding the treatment for metastatic hepatic leiomyosarcoma associated with STUMP.
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Affiliation(s)
- Keisuke Fukui
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Nobuhisa Takase
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Taiichiro Miyake
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Koji Hisano
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Eri Maeda
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Tohru Nishimura
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Koichiro Abe
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Akihito Kozuki
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Tomohiro Tanaka
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Naoki Harada
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Manabu Takamatsu
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
| | - Kunihiko Kaneda
- Department of Surgery, Kakogawa Central City Hospital, Kakogawa 675-8611, Japan
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29
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Wu RC, Chao AS, Lee LY, Lin G, Chen SJ, Lu YJ, Huang HJ, Yen CF, Han CM, Lee YS, Wang TH, Chao A. Massively parallel sequencing and genome-wide copy number analysis revealed a clonal relationship in benign metastasizing leiomyoma. Oncotarget 2018; 8:47547-47554. [PMID: 28533481 PMCID: PMC5564585 DOI: 10.18632/oncotarget.17708] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 04/26/2017] [Indexed: 01/08/2023] Open
Abstract
Benign metastasizing leiomyoma (BML) is a rare disease entity typically presenting as multiple extrauterine leiomyomas associated with a uterine leiomyoma. It has been hypothesized that the extrauterine leiomyomata represent distant metastasis of the uterine leiomyoma. To date, the only molecular evidence supporting this hypothesis was derived from clonality analyses based on X-chromosome inactivation assays. Here, we sought to address this issue by examining paired specimens of synchronous pulmonary and uterine leiomyomata from three patients using targeted massively parallel sequencing and molecular inversion probe array analysis for detecting somatic mutations and copy number aberrations. We detected identical non-hot-spot somatic mutations and similar patterns of copy number aberrations (CNAs) in paired pulmonary and uterine leiomyomata from two patients, indicating the clonal relationship between pulmonary and uterine leiomyomata. In addition to loss of chromosome 22q found in the literature, we identified additional recurrent CNAs including losses of chromosome 3q and 11q. In conclusion, our findings of the clonal relationship between synchronous pulmonary and uterine leiomyomas support the hypothesis that BML represents a condition wherein a uterine leiomyoma disseminates to distant extrauterine locations.
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Affiliation(s)
- Ren-Chin Wu
- Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan
| | - An-Shine Chao
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan
| | - Li-Yu Lee
- Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan
| | - Gigin Lin
- Department of Medical Imaging and Intervention, Clinical Phenome Center, Chang Gung Memorial Hospital and Institute for Radiological Research, Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan
| | | | | | - Huei-Jean Huang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan.,Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chi-Feng Yen
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan
| | - Chien Min Han
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan
| | - Yun-Shien Lee
- Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan
| | - Tzu-Hao Wang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan.,Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Angel Chao
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan.,Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
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Jiang J, He M, Hu X, Ni C, Yang L. Deep sequencing reveals the molecular pathology characteristics between primary uterine leiomyoma and pulmonary benign metastasizing leiomyoma. Clin Transl Oncol 2018; 20:1080-1086. [PMID: 29484624 DOI: 10.1007/s12094-018-1847-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 02/15/2018] [Indexed: 12/31/2022]
Abstract
PURPOSE Pulmonary benign metastasizing leiomyoma (PBML), a rare condition of smooth muscle tumor, originates from women with a history of uterine leiomyoma (LM). Numerous genetic studies of uterine LM have been reported; however, there are few cytogenetic and molecular descriptions of PBML. Therefore, molecular subtyping is necessary to understand the pathogenesis of metastasizing sites. METHODS Driver gene exon-capture sequencing was performed on one patient's peripheral blood, paraffin samples from primary uterine LM, and lung metastasizing leiomyoma 8 years later. RESULTS The results showed that the same missense mutations of BLMH, LRP2, MED12, SMAD2, and UGT1A8 were concurrently mutated in the primary uterine LM and the PBML. Moreover, a splice mutation of PTEN (c.492+1G>A) was uniquely identified in the lung metastasis of the patient. CONCLUSION This study indicates that the metastatic lung lesions were derived from the same malignant cell clone of uterine LMs and later acquired the novel driver mutations in the evolution of the tumor. In addition, driver gene sequencing can discriminate somatic driver mutations as biological indicators of potential malignant leiomyoma and can identify pathogenic variation driver mutations, which could be used for individualized therapy.
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Affiliation(s)
- J Jiang
- Department of Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, People's Republic of China
| | - M He
- Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310014, Zhejiang, People's Republic of China
| | - X Hu
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Shang Tang Road 158, Hangzhou, 310014, Zhejiang, People's Republic of China.
| | - C Ni
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Shang Tang Road 158, Hangzhou, 310014, Zhejiang, People's Republic of China. .,Department of Thyroid and Breast Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, Zhejiang, People's Republic of China.
| | - L Yang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Shang Tang Road 158, Hangzhou, 310014, Zhejiang, People's Republic of China.
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Sõritsa D, Teder H, Roosipuu R, Tamm H, Laisk-Podar T, Soplepmann P, Altraja A, Salumets A, Peters M. Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene. BMC MEDICAL GENETICS 2018; 19:20. [PMID: 29386003 PMCID: PMC5793349 DOI: 10.1186/s12881-018-0537-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Accepted: 01/24/2018] [Indexed: 02/06/2023]
Abstract
Background Benign metastasizing leiomyoma (BML) is an orphan neoplasm commonly characterized by pulmonary metastases consisting of smooth muscle cells. Patients with BML have usually a current or previous uterine leiomyoma, which is therefore suggested to be the most probable source of this tumour. The purpose of this case report was to determine the possible genetic grounds for pulmonary BML. Case presentation We present a case report in an asymptomatic 44-year-old female patient, who has developed uterine leiomyoma with subsequent pulmonary BML. Whole exome sequencing (WES) was used to detect somatic mutations in BML lesion. Somatic single nucleotide mutations were identified by comparing the WES data between the pulmonary metastasis and blood sample of the same BML patient. One heterozygous somatic mutation was selected for validation by Sanger sequencing. Clonality of the pulmonary metastasis and uterine leiomyoma was assessed by X-chromosome inactivation assay. Conclusions We describe a potentially deleterious somatic heterozygous mutation in bone morphogenetic protein 8B (BMP8B) gene (c.1139A > G, Tyr380Cys) that was identified in the pulmonary metastasis and was absent from blood and uterine leiomyoma, and may play a facilitating role in the metastasizing of BML. The clonality assay confirmed a skewed pattern of X-chromosome inactivation, suggesting monoclonal origin of the pulmonary metastases. Electronic supplementary material The online version of this article (10.1186/s12881-018-0537-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Deniss Sõritsa
- Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia. .,Elite Clinic, Sangla 63, 50407, Tartu, Estonia. .,Competence Centre on Health Technologies, Tartu, Estonia.
| | - Hindrek Teder
- Competence Centre on Health Technologies, Tartu, Estonia.,Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia
| | - Retlav Roosipuu
- Department of Pathology, Tartu University Hospital, Tartu, Estonia
| | - Hannes Tamm
- Department of Pathology, Tartu University Hospital, Tartu, Estonia
| | - Triin Laisk-Podar
- Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia.,Competence Centre on Health Technologies, Tartu, Estonia
| | - Pille Soplepmann
- Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia.,Elite Clinic, Sangla 63, 50407, Tartu, Estonia.,Tartu University Hospital's Women's Clinic, Tartu, Estonia
| | - Alan Altraja
- Department of Pulmonary Medicine, University of Tartu, Tartu, Estonia.,Lung Clinic, Tartu University Hospital, Tartu, Estonia
| | - Andres Salumets
- Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia.,Competence Centre on Health Technologies, Tartu, Estonia.,Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia.,Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Maire Peters
- Institute of Clinical Medicine, Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia.,Competence Centre on Health Technologies, Tartu, Estonia
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Choe YH, Jeon SY, Lee YC, Chung MJ, Park SY, Lee YC, Kim SR. Benign metastasizing leiomyoma presenting as multiple cystic pulmonary nodules: a case report. BMC WOMENS HEALTH 2017; 17:81. [PMID: 28899426 PMCID: PMC5596933 DOI: 10.1186/s12905-017-0435-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Accepted: 08/29/2017] [Indexed: 11/10/2022]
Abstract
BACKGROUND Benign metastatic leiomyoma (BML) is an extremely rare disease. Although uterine leiomyomas are benign histologically, they can metastasize to distant sites. While the incidence is very low, the lung is the organ most frequently affected by BML. Pulmonary BML usually presents as numerous well-defined nodules of various sizes, while the cavitary or cystic features in the nodules are rarely observed on radiologic images. CASE PRESENTATION A 52-year-old woman complained of cough and dyspnea for one month. She had been previously diagnosed with uterine leiomyoma and had undergone total hysterectomy about 14 years prior. High-resolution computed tomography (CT) images showed that there were multiple cystic nodules of various sizes in both lungs. Pathologic examination revealed that the pulmonary nodule had complex branching glandular structures lined by a single layer of simple cuboidal to columnar epithelium that was surrounded by abundant spindle cells. Additional immunohistochemistry data suggested that pulmonary nodule diagnosis was BML-associated uterine leiomyoma. CONCLUSION In this report, we introduce an interesting case of pulmonary BML that presented as a combination of various kinds of nodules including simple round nodules, simple cysts, and cysts with a solid portion, which are very rare radiologic features of BML in lung. In addition, when the patient is a woman of reproductive age, physicians should meticulously review the gynecological history and suspect BML when there are various cystic pulmonary lesions.
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Affiliation(s)
- Yeong Hun Choe
- Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-180, South Korea.,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, South Korea
| | - So Yeon Jeon
- Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-180, South Korea
| | - Yoon Chae Lee
- Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-180, South Korea
| | - Myung Ja Chung
- Department of Pathology, Chonbuk National University Medical School, Jeonju, South Korea.,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, South Korea
| | - Seung Yong Park
- Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-180, South Korea.,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, South Korea
| | - Yong Chul Lee
- Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-180, South Korea. .,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, South Korea.
| | - So Ri Kim
- Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-180, South Korea. .,Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, South Korea.
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Barnaś E, Książek M, Raś R, Skręt A, Skręt- Magierło J, Dmoch- Gajzlerska E. Benign metastasizing leiomyoma: A review of current literature in respect to the time and type of previous gynecological surgery. PLoS One 2017; 12:e0175875. [PMID: 28426767 PMCID: PMC5398563 DOI: 10.1371/journal.pone.0175875] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2016] [Accepted: 03/31/2017] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Benign metastasizing leiomyoma (BML) is a rare disorder that affects women with a history of uterine leiomyoma, which is found to metastasise within extrauterine sites. The aetiology of BML remains unexplained. Because BML is rare, and most publications contain descriptions of single cases, no statistically determined time relations were found between the primary and secondary surgeries, which may have aetiological implications. OBJECTIVES To determine age before BML surgery, age during diagnosis of BML, type of prior surgery, and location of metastasis based on the literature. METHODS A systematic review of four databases (Medline/PubMed, Embase, Web of Science, and Cochrane) covering articles published from 1 January 1965 to 10 April 2016. The inclusion criteria were full-text articles in English and articles containing case reports. Articles in languages other than English (39), articles containing incomplete data (14), i.e. no information regarding the time of surgery and/or the site of metastasis, articles bereft of case studies (25), and articles with access only to summaries, without access to the complete text (10) were excluded. Of 321 titles identified, only 126 articles met the aforementioned criteria. RESULTS AND CONCLUSIONS The mean age during primary surgery and BML diagnosis was 38.5 years and 47.3 years, respectively. The most common surgery was total hysterectomy. The most frequent site of metastasis was the lungs; other organs were affected less frequently.The site of metastases and their number were not related to the longer time span between the patient's initial surgery and occurrence of metastasis. The analysed data, such as the age during primary surgery, age during BML diagnosis, site and type of metastasis, do not provide us a clear answer. Thus, BML pathogenesis is most probably complex in nature and requires further multidirectional research.
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Affiliation(s)
- Edyta Barnaś
- Institute of Obstetrics and Emergency Medicine, Medical Faculty, University of Rzeszow, Rzeszow, Poland
- * E-mail:
| | - Mariusz Książek
- Clinical Department of Pathology, Frederick Chopin Clinical Provincial Hospital No 1, Rzeszow, Poland
| | - Renata Raś
- Obstetrics and Gynecology Clinic, Frederick Chopin Clinical Provincial Hospital No 1 Rzeszow, University of Rzeszow, Rzeszow, Poland
| | - Andrzej Skręt
- Obstetrics and Gynecology Clinic, Frederick Chopin Clinical Provincial Hospital No 1 Rzeszow, University of Rzeszow, Rzeszow, Poland
| | - Joanna Skręt- Magierło
- Obstetrics and Gynecology Clinic, Frederick Chopin Clinical Provincial Hospital No 1 Rzeszow, University of Rzeszow, Rzeszow, Poland
| | - Ewa Dmoch- Gajzlerska
- Faculty of Health Sciences, Gynaecological and Obstetrics Department, Medical University of Warsaw, Warsaw, Poland
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Liegl-Atzwanger B, Heitzer E, Flicker K, Müller S, Ulz P, Saglam O, Tavassoli F, Devouassoux-Shisheboran M, Geigl J, Moinfar F. Exploring chromosomal abnormalities and genetic changes in uterine smooth muscle tumors. Mod Pathol 2016; 29:1262-77. [PMID: 27363490 DOI: 10.1038/modpathol.2016.107] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 04/25/2016] [Accepted: 04/25/2016] [Indexed: 01/18/2023]
Abstract
Smooth muscle tumors of the uterus are a diagnostically challenging group of tumors. Molecular surrogate markers reliably distinguishing between benign and malignant tumors are not available. Therefore, the diagnosis is based on morphologic criteria. The aim was to investigate a well-characterized group of challenging uterine smooth muscle tumors consisting of 20 leiomyomas, 13 leiomyomas with bizarre nuclei, and 14 leiomyosarcomas for copy number alterations, MED12 mutations and FH deletions to search for potential diagnostically useful surrogate markers. MED12 mutations were detected in 47, 15, and 25% of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas, respectively. MED12 mutations in leiomyomas with bizarre nuclei were detected outside the hotspot region. FH-deletions were seen in 27, 30.8, and 25% of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas, respectively. By using copy number alteration profiling a clear separation of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas could not be observed. Copy number alterations revealed clear genetic similarities between leiomyomas with bizarre nuclei and leiomyosarcomas. Leiomyosarcomas showed a similar pattern of gains and losses as leiomyomas with bizarre nuclei, with additional copy number alterations and more homozygous losses and high-level amplifications compared to leiomyomas with bizarre nuclei. In conclusion, this study demonstrates that known FH-deletions, a recurrent molecular change in leiomyomas, occur in morphologically challenging variants of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas. Although MED12 mutations are common in leiomyomas, they infrequently occur in leiomyomas with bizarre nuclei and leiomyosarcomas. The genetic similarities between leiomyomas with bizarre nuclei and leiomyosarcomas raise the intriguing possibility that uterine leiomyomas with bizarre nuclei and leiomyosarcomas are closely related and challenge the traditional concept that leiomyoma with bizarre nuclei is a tumor with just marked 'degenerative' cellular changes. These findings support the hypothesis that tumor progression within uterine smooth muscle tumors might occur.
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Affiliation(s)
| | - Ellen Heitzer
- Department of Human Genetics, Medical University of Graz, Graz, Austria
| | - Karin Flicker
- Department of Human Genetics, Medical University of Graz, Graz, Austria
| | - Stephanie Müller
- Department of Human Genetics, Medical University of Graz, Graz, Austria
| | - Peter Ulz
- Department of Human Genetics, Medical University of Graz, Graz, Austria
| | - Ozlen Saglam
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Fattaneh Tavassoli
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | | | - Jochen Geigl
- Department of Human Genetics, Medical University of Graz, Graz, Austria
| | - Farid Moinfar
- Department of Pathology, Hospital of the Sisters of Charity, Linz, Austria
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Abstract
Benign metastasizing leiomyoma (BML) is a rare and poorly characterized disease affecting primarily premenopausal women. Asymptomatic patients are often diagnosed incidentally by radiographs or other lung-imaging procedures performed for other indications, and the diagnosis is eventually confirmed by biopsy. Patients with BML are usually treated pharmacologically with antiestrogen therapies or surgically with oophorectomy or hysterectomy. Antiestrogen therapy is typically efficacious and, in general, most patients have a favorable prognosis. Asymptomatic patients with a confirmed diagnosis of BML, may be followed conservatively without treatment.
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Affiliation(s)
- Gustavo Pacheco-Rodriguez
- Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 5N307, 9000 Rockville Pike, Bethesda, MD 20892-1434, USA
| | - Angelo M Taveira-DaSilva
- Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 6D05, MSC-1590, 9000 Rockville Pike, Bethesda, MD 20892-1590, USA
| | - Joel Moss
- Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 6D05, MSC-1590, 9000 Rockville Pike, Bethesda, MD 20892-1590, USA.
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A Rare Concurrence of Leiomyomatosis Peritonealis Disseminata, Leiomyosarcoma of the Pelvis and Leiomyomatous Nodule of the Liver. Case Rep Oncol Med 2016; 2016:3025432. [PMID: 26998373 PMCID: PMC4779833 DOI: 10.1155/2016/3025432] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 02/01/2016] [Accepted: 02/08/2016] [Indexed: 11/17/2022] Open
Abstract
Leiomyomatosis peritonealis disseminata (LPD) is a rare entity that is characterized by the presence of multiple subperitoneal or peritoneal smooth muscle nodules throughout the peritoneal surface mimicking a malignant process. LPD follows a benign course in general, and it is often found incidentally during abdominal surgery. There have been reported cases of LPD with malignant degeneration although the association is uncertain. Concurrent finding of LPD and leiomyosarcoma of the pelvis is very rare that could be coincidental, malignant transformation of LPD to leiomyosarcoma, or progression of undetected primary leiomyosarcoma. There are only a few previously reported cases in the literature. Herein, we report a case of 56-year-old woman with a history of leiomyoma of uterus who presented with progressive abdominal swelling secondary to mass lesions in the pelvis. The patient underwent exploratory laparotomy and debulking of the tumors, and the histologic examination of the tumors revealed coexistence of LPD and leiomyosarcoma. After recovery from the operation, core needle biopsy of the superficial, residual liver mass was obtained to investigate potential liver metastasis, and the histopathologic findings are consistent with leiomyoma which represents the first simultaneous occurrence of LPD, leiomyosarcoma, and leiomyomatous nodule of the liver.
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38
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de Graaff MA, de Jong D, Briaire-de Bruijn IH, Hogendoorn PC, Bovée JV, Szuhai K. A translocation t(6;14) in two cases of leiomyosarcoma: Molecular cytogenetic and array-based comparative genomic hybridization characterization. Cancer Genet 2015; 208:537-44. [DOI: 10.1016/j.cancergen.2015.07.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 06/29/2015] [Accepted: 07/27/2015] [Indexed: 11/17/2022]
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Miller J, Shoni M, Siegert C, Lebenthal A, Godleski J, McNamee C. Benign Metastasizing Leiomyomas to the Lungs: An Institutional Case Series and a Review of the Recent Literature. Ann Thorac Surg 2015; 101:253-8. [PMID: 26321441 DOI: 10.1016/j.athoracsur.2015.05.107] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Revised: 04/16/2015] [Accepted: 05/18/2015] [Indexed: 02/03/2023]
Abstract
BACKGROUND Benign metastasizing leiomyomas (BMLs) represent the extrauterine spread of a benign uterine process. Pulmonary BMLs are the most common example of distant spread of uterine leiomyomas and are usually found incidentally in premenopausal women. The rarity of BMLs accounts for the limited literature that currently exists regarding their underlying pathophysiology, disease course, and management. METHODS A retrospective analysis was performed of all BML cases diagnosed and managed at Brigham and Women's Hospital during a 22-year period. The demographic and clinical characteristics of these patients were compared with a PubMed-derived cohort of BML cases reported since 2006. RESULTS Benign metastasizing leiomyoma tumors were identified in 10 Brigham and Women's Hospital patients, whereas 57 cases were reported in the literature. The average age at diagnosis was 54.1 and 46.7 years, respectively. Mean interval time from a pertinent gynecologic procedure to BML diagnosis was 23 years at Brigham and Women's Hospital. All patients demonstrated positivity for actin, desmin, and estrogen/progesterone receptors, confirming the diagnosis of uterine leiomyomas. Management primarily consisted of diagnostic resection with subsequent observation with or without hormonal suppression for residual pulmonary nodules. Progression of residual BMLs was noticed in 30% and 8.3% of Brigham and Women's Hospital and literature patients, respectively, when follow-up was reported. One patient in our series required further surgical management. CONCLUSIONS Benign metastasizing leiomyomas are a rare cause of pulmonary nodules. They likely represent a clonal spread of uterine leiomyomas to the lungs. Management includes pathologic diagnosis with long-term surveillance with or without hormonal manipulation.
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Affiliation(s)
- Jordan Miller
- Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Melina Shoni
- Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Thoracic Surgery, West Roxbury Veterans Affairs Medical Center, West Roxbury, Massachusetts
| | - Charles Siegert
- Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Thoracic Surgery, West Roxbury Veterans Affairs Medical Center, West Roxbury, Massachusetts
| | - Abraham Lebenthal
- Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Thoracic Surgery, West Roxbury Veterans Affairs Medical Center, West Roxbury, Massachusetts
| | - John Godleski
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Ciaran McNamee
- Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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An unusual cause of pulmonary nodules in the emergency department. Case Rep Emerg Med 2015; 2015:278020. [PMID: 25802769 PMCID: PMC4352908 DOI: 10.1155/2015/278020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2014] [Revised: 02/03/2015] [Accepted: 02/03/2015] [Indexed: 11/17/2022] Open
Abstract
We report a 51-year-old woman who presented to the emergency department with left-sided pleuritic chest pain 2 weeks after subtotal hysterectomy and bilateral salpingo-oophorectomy for a leiomyomatous uterus. Computed tomography scan of the chest revealed bilateral pulmonary nodules. Biopsy showed cytologically bland spindle cells without overt malignant features. Immunohistochemistry confirmed smooth muscle phenotype, in keeping with a clinicopathologic diagnosis of benign metastasizing leiomyoma (BML). BML does not frequently come to the attention of the emergency physician because it is rare and usually asymptomatic. When symptomatic, its clinical presentation depends on the site(s) of metastasis, number, and size of the smooth muscle tumors. Emergent presentations of BML are reviewed.
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Chen S, Liu RM, Li T. Pulmonary benign metastasizing leiomyoma: a case report and literature review. J Thorac Dis 2014; 6:E92-8. [PMID: 24977035 DOI: 10.3978/j.issn.2072-1439.2014.04.37] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 04/15/2014] [Indexed: 11/14/2022]
Abstract
Benign metastasizing leiomyoma (BML) is a rare condition that occurs in all age groups and that is particularly prevalent among women of late childbearing age. All patients have a history of uterine leiomyoma and/or myomectomy, often associated with distant metastases from the uterus, which commonly occurs in the lung. We report the case of a 32-year-old young woman suffering from chest stuffiness, labored respiration and weakness after a myomectomy performed one month earlier. The chest CT showed a diffuse miliary shadow in both sides of her lungs, but serum tumor markers such as CA125, CA199, carcinoembryonic antigen (CEA), neuron specific enolase (NSE), and CYFRA21-1 were normal. The patient underwent a lung biopsy by thoracoscopic surgery after four weeks of anti-TB treatment; there were no significant changes in the chest CT. H&E staining showed that the tumor cells had characteristics of smooth muscle cell differentiation. Immunohistochemical staining showed a low tumor cell proliferation index, which indicated that the likelihood of a malignancy was not high. There was no expression of CD10, indicating a diagnosis of pulmonary benign metastasizing leiomyoma (PBML). Smooth muscle actin (SMA) and desmin as specific markers of smooth muscle and the estrogen receptor (ER) and progesterone receptor (PR) were all strongly positive, which is characteristic of PBML. The patient was given the anti-estrogen tamoxifen for 3 months. With no radiological evidence of disease development and further distant metastasis, the patient will continue to be followed.
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Affiliation(s)
- Shi Chen
- 1 Department of Respiratory Medicine, Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China ; 2 Department of Internal Medicine, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China ; 3 Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, China
| | - Rui-Ming Liu
- 1 Department of Respiratory Medicine, Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China ; 2 Department of Internal Medicine, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China ; 3 Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, China
| | - Tian Li
- 1 Department of Respiratory Medicine, Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China ; 2 Department of Internal Medicine, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China ; 3 Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, China
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Buza N, Xu F, Wu W, Carr RJ, Li P, Hui P. Recurrent chromosomal aberrations in intravenous leiomyomatosis of the uterus: high-resolution array comparative genomic hybridization study. Hum Pathol 2014; 45:1885-92. [PMID: 25033729 DOI: 10.1016/j.humpath.2014.05.010] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2014] [Revised: 05/15/2014] [Accepted: 05/21/2014] [Indexed: 12/17/2022]
Abstract
Uterine intravenous leiomyomatosis (IVL) is a distinct smooth muscle neoplasm with a potential of clinical aggressiveness due to its ability to extend into intrauterine and extrauterine vasculature. In this study, chromosomal alterations analyzed by oligonucleotide array comparative genomic hybridization were performed in 9 cases of IVL. The analysis was informative in all cases with multiple copy number losses and/or gains observed in each tumor. The most frequent recurrent loss of 22q12.3-q13.1 was observed in 6 tumors (66.7%), followed by losses of 22q11.23-q13.31, 1p36.13-p33, 2p25.3-p23.3, and 2q24.2-q32.2 and gains of 6p22.2, 2q37.3 and 10q22.2-q22.3, in decreasing order of frequency. Copy number variants were identified at 14q11.2, 15q11.1-q11.2, and 15q26.2. Genes mapping to the regions of loss include CHEK2, EWS, NF2, PDGFB, and MAP3K7IP1 on chromosome 22q, HEI10 on chromosome 14q, and succinate dehydrogenase subunit B, E2F2, ARID1A KPNA6, EIF3S2 , PTCH2, and PIK3R3 on chromosome 1p. Regional losses on chromosomes 22q and 1p and gains on chromosomes 12q showed overlaps with those previously observed in uterine leiomyosarcomas. In addition, presence of multiple chromosomal aberrations implies a higher level of genetic instability. Follow-up polymerase chain reaction (PCR) sequencing analysis of MED12 gene revealed absence of G> A transition at nucleotides c.130 or c.131 in all 9 cases, a frequent mutation found in uterine leiomyoma and its variants. In conclusion, this is the first report of high-resolution, genome-wide investigation of IVL by oligonucleotide array comparative genomic hybridization. The presence of high frequencies of recurrent regional loss involving several chromosomes is an important finding and likely related to the pathogenesis of the disease.
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Affiliation(s)
- Natalia Buza
- Department of Pathology, Yale University, School of Medicine, New Haven, CT 06520-8023
| | - Fang Xu
- Department of Genetics, Yale University, School of Medicine, New Haven, CT 06520-8023
| | - Weiqing Wu
- Department of Genetics, Yale University, School of Medicine, New Haven, CT 06520-8023
| | - Ryan J Carr
- Department of Pathology, Yale University, School of Medicine, New Haven, CT 06520-8023
| | - Peining Li
- Department of Genetics, Yale University, School of Medicine, New Haven, CT 06520-8023
| | - Pei Hui
- Department of Pathology, Yale University, School of Medicine, New Haven, CT 06520-8023
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Pulmonary leiomyomas in a patient with bilateral renal cell cancer mimicking pulmonary metastases. Clin Imaging 2014; 38:330-2. [PMID: 24636136 DOI: 10.1016/j.clinimag.2014.01.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2013] [Revised: 01/10/2014] [Accepted: 01/15/2014] [Indexed: 12/18/2022]
Abstract
Pulmonary benign metastasizing leiomyoma (PBML) characterized by uterine leiomyoma in the lung is very rare. Here we report the case of a 55-year-old woman with a history of surgically resected multiple uterine leiomyomas who was histopathologically diagnosed with PBML associated with bilateral primary renal cell carcinoma (RCC). Clinicians should be aware of this unusual entity and consider pulmonary leiomyoma as a differential diagnosis in asymptomatic women with primary RCC and a history of hysterectomy for leiomyoma.
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Benign metastasizing leiomyoma: a rare type of lung metastases-two case reports and review of the literature. Case Rep Oncol Med 2014; 2014:842801. [PMID: 24716049 PMCID: PMC3970365 DOI: 10.1155/2014/842801] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 12/23/2013] [Indexed: 11/17/2022] Open
Abstract
Benign metastasizing leiomyoma (BML) is a rare disease that usually occurs in women of reproductive age. They typically have history of uterine leiomyoma treated with hysterectomy. BML can metastasize to distant organs, with the lung being the most common organ. We report two patients who presented with benign metastasizing leiomyoma to the lung. Our first case was a fifty-two-year-old female who presented with multiple lung masses, with a past medical history of uterine leiomyoma who underwent hysterectomy 17 years ago. A CT-guided biopsy showed benign appearing spindle cells and pathology confirmed her diagnosis with additional positive estrogen/progesterone receptor stains. Our second case was a fifty-six-year-old female who presented with multiple cavitary pulmonary nodules. She subsequently underwent a video-assisted thoracoscopic surgery (VATS) with wedge resection of one of the nodules. Pathology confirmed the diagnosis based on morphology and immunohistochemical staining strongly positive for estrogen/progesterone receptors. Benign metastasizing leiomyoma is a rare condition which may affect women of reproductive age. This should be considered in the differential in patients who present with multiple pulmonary nodules, especially with a history of uterine leiomyoma. Additional stains, such as estrogen/progesterone receptors, may need to be done to confirm the diagnosis.
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Ki EY, Hwang SJ, Lee KH, Park JS, Hur SY. Benign metastasizing leiomyoma of the lung. World J Surg Oncol 2013; 11:279. [PMID: 24134076 PMCID: PMC3842688 DOI: 10.1186/1477-7819-11-279] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 10/01/2013] [Indexed: 11/30/2022] Open
Abstract
Benign leiomyomas of the uterus are uncommonly found in association with benign smooth muscle tumors beyond the confines of the uterus. Benign metastasizing leiomyoma (BML) is a rare disease in which the lung is described to be the most afflicted extrauterine organ. We present a brief review of the literature, along with case reports for four patients who were followed up after resection of a pulmonary lesion or after pathological confirmation by biopsy. The clinical course of BML varies from chronic asymptomatic appearance to rapid progression, leading to respiratory failure and death. Our BML patients did not complain of pulmonary symptoms, such as cough, dyspnea, or chest tightness. Pathology revealed benign leiomyomas with no atypia and mitotic activity <5 per 10 high-power field. Immunohistochemical staining was positive for actin and desmin. A standard treatment for BML has not yet been established. Because of the hormone-sensitive characteristics of BML, treatments are based on hormonal manipulation along with either surgical or medical oophorectomy. Benign metastasizing leiomyoma can be observed in postmenopausal women. We observed four patients who did not receive adjuvant hormonal therapy because they were postmenopausal or perimenopausal. All patients are still healthy and show no evidence of recurrence or progression of the disease.
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Affiliation(s)
| | | | | | | | - Soo Young Hur
- Department of Obstetrics and Gynecology, Seoul St, Mary's Hospital, The Catholic University of Korea, #505 Banpo-Dong, Seocho-Gu, Seoul, South Korea.
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Rothmund R, Kurth RR, Lukasinski NM, Huebner M, Hartkopf A, Wallwiener M, Staebler A, Brucker SY, Taran FA. Clinical and pathological characteristics, pathological reevaluation and recurrence patterns of cellular leiomyomas: a retrospective study in 76 patients. Eur J Obstet Gynecol Reprod Biol 2013; 171:358-61. [PMID: 24176540 DOI: 10.1016/j.ejogrb.2013.10.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Revised: 08/08/2013] [Accepted: 10/02/2013] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To analyze clinical and pathologic features as well as recurrence patterns of cellular leiomyomas (CL) in women who underwent surgical therapy for symptomatic disease. STUDY DESIGN This retrospective study was conducted at the Department of Obstetrics and Gynecology, University Women's Clinic, Tuebingen, Germany. We identified all women who had CL on final diagnosis after surgery between January 1, 2000, and December 31, 2010. RESULTS Our study sample comprised 76 women with a diagnosis of CL. A single uterine mass was present in 51.3% of the cases; in uteri with both CL and uterine leiomyomas (UL), the CL constituted the largest uterine mass in 20 of 21 (95.2%) cases. Additionally, in 98% of the uteri, CL were either the largest or the only uterine mass. Five women (6.6%; 5/76) had reported surgical procedures for symptomatic leiomyoma before the index surgery in our analysis. Three women underwent hysteroscopic resection of the leiomyomas and 2 women underwent abdominal myomectomy. Mean time to recurrence was 14.0 months (median 6.0; range, 4.0-52.0). Over the follow-up period, 6 women who underwent uterus-conserving surgery (12.0%; 6/50) with CL had leiomyoma recurrence. Five women underwent abdominal myomectomy and one underwent hysteroscopic resection of the CL. One patient had recurrence of a CL 43 months after abdominal myomectomy and underwent vaginal hysterectomy; the other five women had recurrences of UL. Mean time to recurrence was 28.6 months (median 12.5; range, 4.0-83.0). CONCLUSIONS Recurrence rates of CL in our study group resemble recurrence rates of UL.
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Affiliation(s)
- Ralf Rothmund
- Department of Obstetrics and Gynecology, University Women's Clinic, Tuebingen, Germany
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Alraiyes AH, Kheir F, Hirsh S, Salerno D, Bernal-Green L, Daroca P. A 40-year-old woman with multiple lung nodules. Chest 2013; 143:1826-1829. [PMID: 23732596 DOI: 10.1378/chest.12-1795] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Affiliation(s)
- Abdul Hamid Alraiyes
- Department of Pulmonary, Critical Care and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, LA.
| | - Fayez Kheir
- Department of Pulmonary, Critical Care and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, LA
| | - Sharon Hirsh
- Department of Pulmonary, Critical Care and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, LA
| | - Daniel Salerno
- Department of Pulmonary, Critical Care and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, LA
| | - Lynn Bernal-Green
- Department of Pulmonary, Critical Care and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, LA
| | - Philip Daroca
- Department of Pulmonary, Critical Care and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, LA
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Benign metastatic leiomyoma presenting as a hemothorax. Case Rep Oncol Med 2013; 2013:504589. [PMID: 23956897 PMCID: PMC3730183 DOI: 10.1155/2013/504589] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 06/28/2013] [Indexed: 11/18/2022] Open
Abstract
Uterine leiomyomas have been reported to metastasize to various organs including the lungs, skeletal muscles, bone marrow, peritoneum, and heart. They may present with symptoms related to the metastases several years after hysterectomy. These tumors regress after menopause, and it is rare to detect active tumors in postmenopausal women. Despite their ability to metastasize, they are considered to be benign due to the lack of anaplasia. Pulmonary benign metastasizing leiomyoma is usually detected in the form of pulmonary nodules incidentally on imaging. Tissue biopsy of these nodules is required to identify them as benign metastasizing leiomyomas. Immunohistochemical analysis and molecular profiling may further help detect any malignant transformation in it. Untreated pulmonary benign metastasizing leiomyoma may result in the formation of cystic structures, destruction of lung parenchyma, and hemothorax and may cause respiratory failure. Surgical resection and hormonal therapy help prevent progression of this disease and provide an avenue for a cure.
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Lewis EI, Chason RJ, DeCherney AH, Armstrong A, Elkas J, Venkatesan AM. Novel hormone treatment of benign metastasizing leiomyoma: an analysis of five cases and literature review. Fertil Steril 2013; 99:2017-24. [PMID: 23465706 PMCID: PMC3672263 DOI: 10.1016/j.fertnstert.2013.01.147] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2011] [Revised: 01/30/2013] [Accepted: 01/30/2013] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To evaluate novel hormonal therapies in patients with unresectable benign metastasizing leiomyoma (BML) disease. DESIGN Case series. SETTING National Institutes of Health (NIH). PATIENT(S) Five subjects with the diagnosis of BML based on imaging and/or histopathologic diagnosis. INTERVENTION(S) Four patients were treated with single or combination therapy of leuprolide acetate and/or an aromatase inhibitor. One patient was treated with an antiprogestin (CDB-2914). MAIN OUTCOME MEASURE(S) Response to therapy was measured by tumor burden on cross-sectional imaging employing RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 guidelines. RESULT(S) Four patients treated with single or combination therapy of leuprolide acetate and/or an aromatase inhibitor demonstrated stable disease with reduction in tumor burden. The fifth patient treated with antiprogestin (CDB-2914) had degeneration of her tumor, progression of its size, and an improvement in symptoms. CONCLUSION(S) Hormone treatment with GnRH agonist and/or aromatase inhibition may be a therapeutic option to reduce tumor burden in unresectable BML disease or for those patients who wish to avoid surgical intervention. RECIST 1.1 guidelines, while traditionally used to evaluate tumor response to cancer therapeutics, may be useful in evaluating BML tumor burden response to hormone therapy.
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Affiliation(s)
- Erin I Lewis
- Department of Obstetrics and Gynecology, UCLA Medical Center, Los Angeles, California 90095, USA.
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