Malignant uterine perivascular epithelioid cell tumor: histopathologic and immunohistochemical characterization of a rare tumor in a post-menopausal woman

Background: Perivascular epithelioid cell tumors (PEComas) are rare, mesenchymal neoplasms composed of epithelioid cells exhibiting myogenic and melanocytic differentiation. The uterus is an infrequent site of involvement. The most common histopathologic mimics include leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, and malignant melanoma. Rendering an accurate histopathologic diagnosis is essential, owing to the prognostic and therapeutic implications. Case: A 65-years-old post-menopausal woman presented with post-menopausal bleeding, abdominal pain, and heaviness for the last four months. Ultrasound abdomen revealed a large uterine mass replacing the endometrial cavity. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Result: Microscopically, a circumscribed tumor with tumor cells arranged in sheets and interlacing fascicles, with interspersed fine capillary network, was seen. The individual tumor cells were epithelioid to spindle with moderate pleomorphism, round nuclei, vesicular chromatin, prominent macronucleoli, and moderate cytoplasm. Mitosis was 2-3/50 HPFs. On immunohistochemistry, tumor cells were positive for HMB-45, Melan-A, and smooth muscle actin and were negative for h-caldesmon, TFE3, S-100, CD10, and pan-cytokeratin. Based on the histopathologic and immunohistochemical features, a final diagnosis of malignant uterine PEComa was rendered. Conclusions: This index report describes the characteristic histopathologic and immunohistochemical features of malignant uterine PEComa and highlights the salient features that distinguish it from other commonly encountered histopathologic mimics.     

An immunohistochemical analysis of stathmin 1 expression in uterine smooth muscle tumors: differential expression in leiomyosarcomas and leiomyomas

The oncogenic phosphatidylinositol 3-kinase-AKT-mammlian target of rapamycin pathway (PI3K-AKT-mTOR) pathway is known to be activated in uterine smooth muscle tumors, and Stathmin 1 (STMN1) expression has been identified as a marker of PI3K-AKT-mTOR pathway activation. We hypothesized that STMN1 may have some diagnostic utility and explored how well STMN1 expression correlated with histologic classifications of uterine smooth muscle tumors into benign and malignant groupings. 84 smooth muscle tumors were assessed for STMN1 expression by immunohistochemistry. These included spindle cell leiomyosarcoma (n = 32), conventional spindle cell leiomyomas (n = 30), atypical (symplastic) leiomyoma (n = 5), cellular leiomyoma (n = 7), smooth muscle tumor of uncertain malignant potential (n = 4), mitotically active leiomyomas (n = 2), benign metastasizing leiomyoma (n = 3), and cotyledonoid dissecting leiomyoma (n = 1). All spindle cell leiomyosarcomas were positive (32/32 positive; 100%) as compared with conventional leiomyomata (11/30; 37%) (P < 0.0001). The average immunohistochemical score (0-12+, reflective of intensity and extent) for leiomyosarcomas was 8.7 (± 1.43) whereas the conventional leiomyomata average score was 1.6 (± 1.07) (P < 0.0001). This difference in scores was reflected in the patterns of expression: leiomyosarcomas were predominantly strongly and diffusely positive whereas leiomyomata were predominantly weakly, albeit diffusely positive when expression was present. The sensitivity of STMN1 expression for leiomyosarcomas was 100%. However, the specificity was found to be only 55% (CI = 43-68%). The negative and positive predictive values for leiomyosarcomas were 100% and 52% respectively. The odds ratio (OR) for any STMN1 expression in predicting a spindle cell leiomyosarcoma diagnosis from this dataset was highly significant (OR = 144, P = 0.0006). Thirteen non-smooth muscle tumors that involved the uterus all showed at least focal STMN1 immunoreactivity. In summary, STMN1 is a highly sensitive marker for leiomyosarcoma but is suboptimally specific for diagnostic purposes. The 100% negative predictive value for leiomyosarcoma may offer some diagnostic utility in a small sample, since the absence of STMN1 immunoreactivity in a putative leiomyosarcoma is a strong argument against this diagnostic possibility.     

Malignant perivascular epithelioid cell tumour of the fibula: a report and a short review of bone perivascular epithelioid cell tumour

Perivascular epithelioid cell tumour (PEComa) is a term applied to a family of mesenchymal tumours composed of varying proportions of spindle and epithelioid cell components associated with HMB-45 expression. PEComa rarely arises in the soft tissue, visceral organs, skin and bone. This report details an instance when a purely epithelioid PEComa arose from the right fibula of a 52-year-old Chinese woman without features of tuberous sclerosis complex. The excision specimen disclosed an epithelioid tumour with a nested pattern associated with areas of nuclear pleomorphism, mitotic activity, necrosis and vascular invasion in addition to HMB-45 expression on immunohistochemistry. To the best of the authors' knowledge, this represents the first case of a histologically malignant PEComa of the bone. A short review of primary bone PEComas and potential problems in diagnosis is presented.     

Utility of CD10 in distinguishing between endometrial stromal sarcoma and uterine smooth muscle tumors: an immunohistochemical comparison of 34 cases.

Endometrial stromal sarcoma (ESS), uterine cellular leiomyoma (UCL), and uterine leiomyosarcoma (ULS) are composed mainly of spindle cells that express similar antigens such as desmin, smooth muscle actin (SMA), and muscle-specific actin (MSA). The differential diagnosis of an ESS versus a uterine smooth muscle tumor or an extrauterine spindle cell sarcoma can be problematic based solely on clinical presentation, histologic assessment, or routine immunohistochemistry. Recently, we reported that normal endometrium, but not myometrium, as well as five cases of ESS, were positive for CD10. We now report the results of CD10 immunohistochemistry in an additional 11 cases of ESS (total 16 cases), 10 cases of UCL, and nine cases of ULS. CD10 immunoreactivity was detected in 16 of 16 cases of ESS (100%) as compared to only 2 of 10 cases of UCL (20%) and none of nine cases of ULS (0%). We compared the utility of CD10 immunoreactivity with that of desmin, SMA, MSA, estrogen receptor (ER), and inhibin in these tumors. Although the majority of cases of UCL and ULS were positive for SMA, MSA, and desmin, a substantial portion of cases of ESS were also positive for SMA, MSA, and desmin. We conclude that in combination with SMA, MSA, and desmin, CD10 is a useful immunohistochemical marker in the differential diagnosis of ESS versus UCL or ULS.     

Perivascular epithelioid cell tumor of the uterus: immunohistochemical, ultrastructural and molecular study

A case of perivascular epithelioid cell tumor of the uterus is reported, occurring in a 32-year-old woman. The tumor (8.0 cm in dimension) showed exophytic growth from the outer half of the myometrium. Histopathologically, the tumor was composed of thick blood vessels and perivascular epithelioid cells. The neoplastic cells were strongly immunoreactive for HMB45 antigen, CD117 (c-kit), vimentin and the progesterone receptor, but completely negative for S-100 protein, smooth muscle actin, desmin, CD34, the estrogen receptor and p16. The Ki-67 labeling index was low (1.25%). Ultrastructurally, the neoplastic cells had numerous premelanosomes with some glycogen deposits. Single-stranded DNA conformational polymorphism of p53 and methylation-specific polymerase chain reaction of p16 revealed negative results. Definite melanosomes on electron microscopic analysis and coexpression of HMB45 antigen and stem cell factor receptor (CD117) may provide the clue to understanding perivascular epithelioid cell tumor because angiomyolipoma also coexpresses HMB45 antigen and CD117.     

Leiomyoblastoma of the uterus: an immunohistochemical and electron microscopic study of distinctive tumours with immature smooth muscle cell differentiation mimicking fetal uterine myocytes

AIMS: We present three distinctive uterine tumours which exhibited immature smooth muscle differentiation mimicking smooth muscle cells of the fetal uterus. METHODS AND RESULTS: The patients were 45, 46 and 49 years old, and all of them had simple hysterectomies. Grossly, all tumours were present in the uterine body, and two of the three tumours were well demarcated 60-mm and 85-mm lesions, and the other tumour was a small 25-mm incidental lesion within multiple conventional leiomyomas. The tumours had varied histological features and were composed of round epithelioid, rhabdoid and large vacuolated cells intermingled with spindle-shaped cells to various degrees. Although their round vesicular nuclei showed mild to moderate variation in size, prominent nuclear atypia was not seen. Necrosis and mitotic figures suggesting biological aggressiveness were not present in any of the tumours. Immunohistochemically, tumour cells were intensely positive for desmin and alpha-smooth muscle actin, whereas positivity for heavy molecular weight caldesmon was restricted. In addition, two cases were positive for non-muscle myosin heavy chain (SMemb). Ultrastructurally, most tumour cells contained various amounts of intermediate filaments which were occasionally abundant and aggregated as in rhabdoid cells. Well-developed myofilaments with focal densities were observed in only a few tumour cells. Intermediate filaments and bundles of thin filaments without dense bodies were often intermingled and they occasionally formed distinctive complexes with many irregular dense body-like structures and crystalloid bodies. Other cytoplasmic organelles including rather rich mitochondria, some rough endoplasmic reticulum and free ribosomes were also common. CONCLUSIONS: These findings support their immature smooth muscle cell differentiation which mimics the mesenchymal cells of fetal uterus during 14-26 weeks of gestation. The term 'uterine leiomyoblastoma' is thought to be appropriate for describing these distinctive immature smooth muscle tumours.     

Epithelioid trophoblastic tumor of the uterus: cytological and immunohistochemical observation of a case

Epithelioid trophoblastic tumor (ETT) is a new entity of trophoblastic tumor and 14 such cases were reported by Shih and Kurman in 1998. However, only three subsequent cases supporting ETT have been reported. Recently, we experienced a case of ETT in a 37-year-old woman whose preoperative endometrial brushings showed atypical mononucleate giant cells and who underwent hysterectomy with the diagnosis of a uterine fibroid. The specimens revealed a 2.5 x 3.0 cm yellow-tan intramural nodule located in the lower uterine segment, which was composed of a neoplastic proliferation of intermediate trophoblasts in epithelioid arrangements. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin and inhibin-alpha, and focally positive for human chorionic gonadotropin and human placental lactogen. She presented an uneventful clinical course as of September 2001.     

Perivascular epithelioid cell tumor of the uterus: a case report

A case of a perivascular epithelioid cell tumor (PEComa) arising in the uterus of a 35-year-old woman is presented. Imaging studies revealed a 5 cm well circumscribed mass in the uterine fundus. The tumor was composed of clear to faintly eosinophilic, epithelioid and spindled cells. Immunohistochemically, most tumour cells were strongly positive for HMB-45, smooth muscle actin and desmine, but negative for epithelial markers, S-100 Protein and neuroendocrine markers. Reevaluation of the patient for signs of tuberous sclerosis complex after the diagnosis gave negative results. At the most recent follow-up 4 months later there was no evidence of recurrence.     

Syndecan-1 (CD138): an immunohistochemical marker of plasma cell tumors

The immunohistochemical detection of syndecan-1 (belonging to the cluster CD138) is a sensitive and reliable method for identifying normal and neoplastic plasma cells. It may be used in paraffin-embedded bone marrow specimens, as well as in extramedullary tumours of unknown origin. The three anaplastic tumours reported by us in the lymph node, the gingiva, and pleura were negative for other markers, but the syndecan-1 positivity elucidated their plasmocytic histogenesis.     

Leiomyoma of the uterus with multiple extrauterine smooth muscle tumors: a case report suggesting multifocal origin

A 17-year-old woman underwent hysterectomy for removal of a "mitotically active" (six to seven mitoses per 10 high-power fields) yet otherwise benign-appearing cellular smooth muscle tumor. Eleven years later, she developed multiple histologically benign smooth muscle tumors in the posterior mediastinum, deep soft tissues of the neck, paravertebral region, incisional scar, and mesentery. The distribution and histologic appearance of the tumors, as well as the protracted clinical course, suggest multifocal origin rather than widespread metastases from a low-grade uterine leiomyosarcoma. This case raises the possibility that some similar cases reported as so-called benign metastasizing leiomyoma may be more satisfactorily explained by the concept of multifocality.     

Smooth muscle tumors of the uterus: a practical approach

Smooth muscle tumors (SMTs) are the most frequent mesenchymal tumors of the uterus. The majority of the uterine SMTs are readily classificable as benign or malignant based on their gross and microscopic appearances. However, when unusual features are seen in some leiomyoma variants, the differential diagnosis with a leiomyosarcoma may become challenging. Moreover, diagnostic criteria for the different subtypes of leiomyosarcoma are not uniform. Finally, non-smooth muscle tumors that originate in the uterus may show overlapping histologic and even immunohistochemical features with uterine SMTs, more commonly with the spindle and epithelioid variants, complicating their correct classification. The diagnosis of malignant uterine SMTs has important prognostic and therapeutic implications. This review provides a practical approach to the diagnosis of uterine leiomyosarcoma based on a systematic assessment of histologic parameters as well as a systematic approach to its differential diagnosis based on histologic and immunohistochemical features.     

非特殊性血管周上皮样细胞肿瘤31例的病理学观察

目的 探讨非特殊性血管周上皮样细胞肿瘤(PEComa-NOS)的临床病理学特征,评价恶性血管周上皮样细胞肿瘤(PEComa)的诊断标准.方法 回顾性复习31例PEComa-NOS的临床表现、影像学资料、光镜形态和免疫学表型,分析预后资料.2例为空芯针穿刺活检标本,2例为剖腹探查活检标本,其余27例为手术切除标本.结果 ...     

Reproducibility of the mitosis count in the histologic diagnosis of smooth muscle tumors of the uterus

In order to ascertain the reproducibility of the mitosis count in histologic tumor diagnosis a reference set of 10 microscopic slides from smooth muscle tumors of the uterus was shown to six different pathologists, who were asked to record the number of mitotic figures per 10 high power fields in the most active region of each slide. The results, when tabulated., revealed considerable observer variation in this supposedly objective and quantitative diagnostic criterion. The diagnoses of benignity or malignancy, based on this criterion alone, were unanimous in only four of the 10 cases, whereas the diagnoses based on a constellation of histologic criteria were unanimous in all cases and correlated well with the subsequent clinical evolution of those cases with follow-up data. Possible reasons for the lack of reproducibility of the mitosis count are discussed. We conclude that a qualitative estimation of mitotic activity is helpful as one of the diagnostic and prognostic criteria in the assessment of uterine and other smooth muscle tumors, but that it cannot be used as the sole criterion for distinguishing benign from malignant tumors.     

Cytoskeletal filaments in the smooth muscle cells of uterine leiomyomata and myometrium: An ultrastructural and immunohistochemical analysis

Summary The filamentous components of the cytoskeleton in smooth muscle cells of leiomyomata and normal myometrium were studied by immunohistochemistry and electron microscopy. Fourteen patients hysterectomised for non-malignant disease provided leiomyomata of conventional histological type and histologically normal myometrium: four samples of fetal myometrium were studied by immunohistochemistry alone. All samples of leiomyoma and myometrium were strongly positive for -smooth muscle actin and desmin, the latter often as paranuclear columns or granules. Vimentin was also stained in most samples but less intensely, while cytokeratin stained in about half the samples with an intensity comparable to that of vimentin. By electron microscopy, myofilaments with focal densities were abundant in both normal myometrium and leiomyomata. Intermediate filaments corresponding to the desmin and vimentin demonstrated by immunohistochemistry were also recognised in a variety of architectural arrangements. At one extreme, comparatively small numbers of filaments were loosely distributed around membranous organelles; at the other, filaments formed conspicuous aggregates, largely excluding other organelles and corresponding to the paranuclear granules seen by immunohistochemistry. A comparison of these findings with those of the literature and comments on the possible significance and origin of these aggregates are provided.     

Malignant perivascular epithelioid cell tumor of the colon: report of a case with molecular analysis

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm, and malignant cases are extremely rare. A case of malignant PEComa arising in the colon is described herein. The patient was a 43-year-old Japanese woman without a history of tuberous sclerosis complex. The tumor occurred in the abdominal cavity attached to the serosal side of the descending colon. Histologically, the tumor consisted of sheets or closely packed nests of epithelioid cells with clear or eosinophilic cytoplasms. The tumor cells were positive for HMB-45 but negative for S-100 protein and cytokeratins by immunohistochemical staining. Ki-67 labeling index was 2.9%. Peritoneal dissemination of tumor occurred at 20 months and the patient died of tumor at 38 months after the initial operation. This was considered to be a case of malignant PEComa, based on the histological and clinical features. Tumor cells showed overexpression of cyclin D1 but lacked the loss of heterozygosity of the TSC1 and TSC2 genes. The result suggests that the overexpression of cyclin D1 may play an important role in the tumorigenesis of PEComa. Because PEComas can behave in an aggressive manner, careful follow up is warranted.