Uterine leiomyosarcoma with HMB45+ clear cell areas: report of two cases

Hurrell, Daniel; McCluggage, W. Glenn

doi:10.1111/j.1365-2559.2005.02147.x

Cited by 33 publications

(12 citation statements)

References 15 publications

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“…Hyperplasia of the epidermis with hyperpigmentation of basal layer overlying the LMS has been previously described and was consistent with our patient's dermatofibroma‐like features . However, the peculiar observation of the presence of clear‐cell features to the best of our knowledge has never been described in cutaneous LMS, although a few cases of clear‐cell LMS have been reported in the uterus . Interestingly, our patient's mother died from a uterine LMS with clear‐cell changes, a malignancy in which germline RB1 mutations are recognized to be a risk factor .…”

Section: Discussionsupporting

confidence: 90%

Clear‐cell variant of superficial cutaneous leiomyosarcoma associated with RB1 mutation: Clinical, dermoscopic, and histopathological characteristics

et al. 2020

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Leiomyosarcoma is a relatively rare soft tissue tumor whose clear-cell variant has only been reported in leiomyosarcomas of the uterus. We report here for the first time a primary cutaneous clear-cell leiomyosarcoma in the trunk skin of a 49-yearold man, characterized by a very indolent clinical and dermoscopic presentation, mimicking a dermatofibroma. Genetic analysis of the otherwise healthy patient revealed a germline mutation in the retinoblastoma 1 gene (RB1); the same mutation was found in his son, who had previously developed retinoblastoma. Moreover, the mother of the patient had died of uterine leiomyosarcoma with clear-cell changes. Mutations in the RB1 gene occur commonly in human neoplasms. In this patient, we were able to link his clear-cell variant of cutaneous leiomyosarcoma with the loss of retinoblastoma protein expression, as revealed by immunohistochemical staining analysis. K E Y W O R D S clear-cell leiomyosarcoma, dermoscopy, RB1 gene mutation, superficial cutaneous leiomyosarcoma

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Section: Discussionsupporting

confidence: 90%

Clear‐cell variant of superficial cutaneous leiomyosarcoma associated with RB1 mutation: Clinical, dermoscopic, and histopathological characteristics

et al. 2020

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“…‘leiomyosarcomas with HMB45 positivity’). 37, 38 In our study, one of the three tumors with RAD51B fusion also showed TSC2 and TP53 mutations, further supporting the classification of these tumors as PEComas. Further studies are needed in order to investigate if these observations point to a common disease spectrum or merely overlapping immunophenotype of two genetically distinct pathologic entities.…”

Section: Discussionsupporting

confidence: 82%

Dichotomy of Genetic Abnormalities in PEComas With Therapeutic Implications

Agaram

Sung

Zhang

et al. 2015

American Journal of Surgical Pathology

195

180

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Perivascular epithelioid cell neoplasms (PEComa) are a family of rare mesenchymal tumors with hybrid myo-melanocytic differentiation. Although most PEComas harbor loss of function TSC1/TSC2 mutations, a small subset were reported to carry TFE3 gene rearrangements. As no comprehensive genomic study has addressed the molecular classification of PEComa, we sought to investigate by multiple methodologies the incidence and spectrum of genetic abnormalities and their potential genotype-phenotype correlations in a large group of 38 PEComas. The tumors were located in soft tissue (11 cases) and visceral sites (27) including uterus, kidney, liver, lung and urinary bladder. Combined RNA sequencing and Fluorescence In Situ Hybridization (FISH) analysis identified 9 (23%) TFE3 gene rearranged tumors, with 3 cases showing a SFPQ/PSF-TFE3 fusion and one case a novel DVL2-TFE3 gene fusion. The TFE3-positive lesions showed a distinctive nested/alveolar morphology and were equally distributed between soft tissue and visceral sites. Additionally, novel RAD51B gene rearrangements were identified in 3 (8%) uterine PEComas, which showed a complex fusion pattern and were fused to RRAGB/OPHN1 genes in two cases. Other non-recurrent gene fusions, HTR4-ST3GAL1 and RASSF1-PDZRN3, were identified in 2 cases. Targeted exome sequencing using the IMPACT assay was used to address if the presence of gene fusions are mutually exclusive from TSC gene abnormalities. TSC2 mutations were identified in 80% of the TFE3 fusion-negative cases tested. Co-existent TP53 mutations were identified in 63% of the TSC2 mutated PEComas. Our results showed that TFE3-rearranged PEComas lacked co-existing TSC2 mutations, indicating alternative pathways of tumorigenesis. In summary, this comprehensive genetic analysis significantly expands our understanding of molecular alterations in PEComas and brings forth the genetic heterogeneity of these tumors.

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“…45 Another trial evaluated the efficacy of sirolimus in cases of LAM and reported stabilization of pulmonary function as well as reduction of symptoms and improved quality of life. 20,[47][48][49] However, there are histologic and IHC features that distinguish PEComa from ESMTs. By distinguishing it from ESMTs, the most effective chemotherapeutic agent is made available to patients.…”

Section: Pecoma Of the Female Genital Tract: Its Controversial Relatimentioning

confidence: 99%

Perivascular Epithelioid Cell Neoplasm (PEComa) of the Gynecologic Tract

Schoolmeester

Howitt

Hirsch

et al. 2014

American Journal of Surgical Pathology

164

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Perivascular epithelioid cell tumor (PEComa) belongs to a family of tumors characterized by coexpression of melanocytic and muscle markers. Recent studies have shown that sporadic and tuberous sclerosis complex-associated PEComa may respond to mTOR inhibitors underscoring the importance of recognizing this tumor. However, its occurrence in the gynecologic tract continues to be disputed owing to its common misclassification as other types of uterine sarcoma and its controversial relationship with epithelioid smooth muscle tumors. To more fully characterize PEComa of the female genital tract, 16 cases of gynecologic PEComa were identified (1990 to 2012) and formed the basis of this study. Each case was analyzed for conventional morphologic and immunohistochemical characteristics established for PEComa of extrauterine sites; clinical outcome data were obtained for all cases. The 16 patients were aged 28 to 60 (mean 49; median 50) years, and 1 had a history of tuberous sclerosis complex. Thirteen cases were primary of the uterus, 2 of the adnexa, and 1 of the vagina. Tumor size ranged from 0.3 to 25.0 (mean 8.7) cm. Three patients died of disease, 6 were alive with disease, and 7 were alive without evidence of disease at last follow-up (1 mo to 13 y follow-up; mean 26 mo). All patients with an adverse outcome met established criteria for malignancy as proposed for extrauterine sites (ie, 2 or more features present: size ≥5 cm, high-grade nuclear features, infiltration, necrosis, lymphovascular invasion, or a mitotic rate ≥1/50 high-power fields). Of the melanocytic markers, HMB45 was most commonly expressed (16/16 positive, 100%), followed by microphthalmia transcription factor (11/12 positive, 92%), MelanA (14/16 positive, 88%), and S100 protein (2/10 positive, 20%). Of the smooth muscle markers, desmin was most commonly expressed (15/15 cases, 100%), followed by SMA (14/15 cases, 93%) and h-caldesmon (11/12 cases, 92%). TFE3 immunopositivity was identified in 5 of 13 cases; however, 3 tested cases were negative for a TFE3 rearrangement by fluorescence in situ hybridization. Current criteria for malignancy appear to be valid in the female genital tract, although modified criteria, as described herein, may be more specific. Awareness of the characteristic features of PEComa is important to help distinguish it from epithelioid smooth muscle tumors and other mimics as PEComa may respond to unique chemotherapeutic regimens.

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Uterine leiomyosarcoma with HMB45+ clear cell areas: report of two cases

Cited by 33 publications

References 15 publications

Clear‐cell variant of superficial cutaneous leiomyosarcoma associated with RB1 mutation: Clinical, dermoscopic, and histopathological characteristics

Clear‐cell variant of superficial cutaneous leiomyosarcoma associated with RB1 mutation: Clinical, dermoscopic, and histopathological characteristics

Dichotomy of Genetic Abnormalities in PEComas With Therapeutic Implications

Perivascular Epithelioid Cell Neoplasm (PEComa) of the Gynecologic Tract

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