PEComas, occasionally associated with the tuberous sclerosis complex, are defined by the presence of perivascular epithelioid cells that coexpress muscle and melanocytic markers. This family of tumors includes angiomyolipoma (AML), clear cell sugar tumor of the lung (CCST), lymphangioleiomyomatosis (LAM), and very rare tumors in other locations. Because non-AML/non-LAM PEComas are extremely rare and their natural history and prognostic features undefined, we present our experience with 26 PEComas of soft tissue and the gynecologic tract, the largest series to date. We also performed a detailed review of the literature, with special attention to features predictive of clinical behavior. All PEComas exclusive of AML and LAM were retrieved from our consultation files. Immunohistochemistry for pan-cytokeratin (CK), S-100 protein, smooth muscle actins (SMA), desmin, vimentin, HMB45, Melan-A, microphthalmia transcription factor (MiTF), TFE3, CD117, and CD34 was performed. Clinical follow-up information was obtained. Fisher's exact test was performed. The median patient age was 46 years (range, 15-97 years); there was a marked female predominance (22 females, 4 males). Sites of involvement included the omentum or mesentery (6 cases), uterus (4 cases), pelvic soft tissues (3 cases), abdominal wall (2 cases), uterine cervix (2 cases), and vagina, retroperitoneum, thigh, falciform ligament, scalp, broad ligament, forearm, shoulder, and neck (1 case each). The tumors ranged from 1.6 to 29 cm in size (median, 7.8 cm). Tumors were epithelioid (N = 9), spindled (N = 7), or mixed (N = 10). Multinucleated giant cells were present in 18 cases. High nuclear grade was noted in 10 cases, high cellularity in 7 cases, necrosis in 8 cases, and vascular invasion in 3 cases. Mitotic activity was 0 to 50 mitotic figures (MF)/50 high power fields (HPF) (median, 0 MF/50 HPF) with atypical MF in 6 cases. IHC results were: SMA (20/25), desmin (8/22), HMB45 (22/24), Melan-A (13/18), MITF (9/18), S-100 protein (8/24), CK (3/23), vimentin (12/14), TFE3 (5/17), c-kit (1/20), and CD34 (0/7). Clinical follow-up (24 of 26 patients, 92%; median, 30 months; range, 10-84 months) showed 3 local recurrences and 5 distant metastases. At last available clinical follow-up, 2 patients (8%) were dead of disease, 4 patients (17%) were alive with metastatic or unresectable local disease, and 18 patients (75%) were alive with no evidence of disease. No patient in our series had a history of tuberous sclerosis complex. Recurrence and/or metastasis was strongly associated tumor size > median size (8 cm), mitotic activity greater than 1/50 HPF, and necrosis. We conclude that PEComas of soft tissue and gynecologic origin may be classified as "benign," "of uncertain malignant potential," or "malignant." Small PEComas without any worrisome histologic features are most likely benign. PEComas with nuclear pleomorphism alone ("symplastic") and large PEComas without other worrisome features have uncertain malignant potential. PEComas with two or more worrisome histologic features should be considered malignant. Occasional PEComas express unusual markers, such as S-100 protein, desmin, and rarely CK. The role of TFE3 in PEComas should be further studied.

Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature.

https://www.gynecologiconcology-online.net/article/S0090-8258(09)00722-7/pdf

Uterine sarcomas: A review

https://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1016/j.ijgo.2008.12.008

FIGO staging for uterine sarcomas

Aims: To determine the frequency and survival of the various types of uterine sarcoma in the total population of Norway and evaluate histopathological prognostic factors in order to identify risk groups.



Methods and results:  Histopathological review of all uterine sarcoma cases reported to the Norwegian Cancer Registry during 1970–2000 was undertaken. Survival dates were provided by The Cancer Registry. Kaplan–Meier survival curves were generated. The log rank test was used for univariate analysis and a Cox proportional hazards regression model for multivariate evaluation of survival. Stage of disease was the most important prognostic factor for all tumour types. Tumour size and the mitotic index (MI) were significant prognostic factors (P < 0.0001) in leiomyosarcomas confined to the uterus and allowed for separation into three risk groups with marked differences in prognosis. The prognosis of endometrial stromal sarcomas confined to the uterus was related to MI (P < 0.0001) and tumour cell necrosis (P < 0.004). Combining these parameters allowed for separation into three risk groups with marked difference in prognosis. In adenosarcomas, tumour cell necrosis was the only significant prognostic factor.



Conclusions:  There are marked differences in survival between uterine sarcoma types. Leiomyosarcomas and endometrial stromal sarcomas can be divided into different groups.

Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients

Summary Malignant pure mesenchymal uterine tumours encompass endometrial stromal sarcoma (ESS), uterine leiomyosarcoma, and undifferentiated sarcomas. This Review discusses pathology, preoperative diagnosis, and standard treatment of uterine leiomyosarcoma and low-grade ESS (distinct from undifferentiated uterine sarcomas), with an emphasis on targeted treatment. We show that several features on ultrasonography and MRI can raise suspicion of a uterine sarcoma; however, there are no pathognomonic features on any imaging technique. For both ESS and uterine leiomyosarcoma, hysterectomy with bilateral salpingo-oophorectomy, but without lymphadenectomy, is the standard surgical treatment for early stage disease. The clinical benefit of chemotherapy is limited, which underscores the importance of targeted therapy. ESS and uterine leiomyosarcoma are driven by different pathways, resulting in a different clinical behaviour. ESS typically is a hormone-sensitive tumour with indolent growth. Uterine leiomyosarcoma is notorious for its aggressive growth and poor outcome. Individualisation of treatment is mandatory, because randomised trials are almost non-existent. The progesterone and oestrogen receptors are clinically important targets for most primarily advanced or recurrent ESS and a subset of recurrent uterine leiomyosarcomas. Potential future targets and targeted treatments that are under investigation are presented for both entities.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(09)70226-8.pdf

Clinical management of uterine sarcomas

A recent trend in the classification of uterine smooth muscle neoplasms (USMNs) into clinically benign and clinically malignant groups has been to move from exclusive reliance upon mitotic index (MI) to an approach that incorporates additional histopathologic characteristics. In furtherance of this goal, we assessed a variety of histopathologic features of 213 problematic smooth muscle neoplasms for which we had > or = 2 years of clinical follow-up data or for which there was an unfavorable outcome. One hundred and thirteen of these patients have had a minimum follow-up of 5 years, and 48 have been followed for > or = 10 years. Cases eliminated from the study group included USMNs with a significant myxoid or epithelioid component and cases of intravenous leiomyomatosis. USMNs, whether cellular or not, with no cytologic atypia and with a mitotic index (MI = number of mitotic figures [mf]/10 high-power fields [hpf]) of or = 10 mf/10 hpf, four of 10 failed.(ABSTRACT TRUNCATED AT 400 WORDS)

Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases.

We report two cases of microvillous inclusion disease (MID) occurring in a set of siblings. Although it is a rare disorder, MID appears to be a common cause of familial intractable secretory diarrhea. Diagnosis rests on the ultrastructural finding of intracytoplasmic inclusions that are lined by intact microvilli. These inclusions are present in the absorptive surface epithelial cells of the small and large intestine and are associated with poorly developed surface brush border microvilli. The prognosis of MID is poor and curative therapy is not currently available. Because MID appears to be a hereditary disorder, genetic counseling of affected families is essential.

Stephen W. Bell

Papers

Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases.

Microvillous inclusion disease. The importance of electron microscopy for diagnosis

Problematic Uterine Smooth Muscle Neoplasms: Authors' Response