Micronodular PEComas of the appendix.

AIMS: Perivascular epithelioid cell tumours (PEComas) of the appendix have been reported very rarely. In this study, we describe three cases of a distinctive micronodular proliferation in the appendix consistent with a variant of PEComa. Although known as 'granular degeneration of smooth muscle' in prior reports, we reappraise its clinicopathological, immunohistochemical and ultrastructural features which support a change in classification. METHODS AND RESULTS: Patients were two females (aged 33 and 41 years) and one male (aged 41). None had a history of tuberous sclerosis. Histologically, each case demonstrated a multifocal nodular proliferation towards the distal tip of the appendix, composed of epithelioid cells with abundant granular eosinophilic to clear cytoplasm. By immunohistochemistry, the lesional cells were positive for muscle markers [smooth muscle actin (SMA) and desmin], melanocytic markers (HMB45, melan A), cathepsin K and the lysosomal marker NKI-C3 in each case. MITF was positive in two of three cases. None expressed S100 protein. Electron microscopy in one case revealed striated electron-dense structures consistent with pre-melanosomes. Follow-up, available in one case, showed no recurrence at 5 years. CONCLUSIONS: We propose the term 'micronodular PEComa' for this appendiceal lesion to reflect more accurately its histological and immunohistochemical characteristics, which include consistent positivity for both muscle and melanocytic markers. Micronodular PEComa seems to follow an indolent course, consistent with its uniformly low-grade histological features, and appears to be unassociated with tuberous sclerosis.

Fibroma-like PEComa: A Tuberous Sclerosis Complex-related Lesion.

Perivascular epithelioid cell tumor (PEComa), mesenchymal tumors morphologically characterized by epithelioid cells, coexpress melanocytic and muscle markers. Herein, we describe a heretofore-undescribed tuberous sclerosis complex (TSC)-related neoplasm, morphologically resembling a soft tissue fibroma-like lesion, but showing an immunophenotype resembling PEComa. We identified 3 soft tissue fibroma-like lesions in individuals with TSC. We also evaluated 6 TSC-related periungual fibroma as well as a range of non-TSC fibroma-like lesions (n=19). Immunohistochemistry for HMB-45, desmin, smooth muscle actin, TFE3, and S100 was performed on the TSC-related fibromas. Periungual fibromas and non-TSC fibroma-like lesions were also stained for HMB-45. All 3 TSC patients were female, ranging in age from 4 to 51 years (mean, 26.7 y). Two tumors were located in extremities and 1 on the chest wall. The tumors showed elongated to stellate spindle-shape cells, prominent collagenous background, and lacked mitotic activity and cytologic atypia. Immunohistochemically, all 3 tumors were positive for HMB-45; smooth muscle actin or desmin was positive in both tumors tested. TFE3 was negative. All patients were alive with no evidence of disease with median follow-up of 55 months (range, 6 to 131 mo). Non-TSC fibroma-like lesions and oral and periungual fibromas were negative for HMB-45. Fibroma-like PEComa, a newly recognized soft tissue tumor with a strong association with TSC, mimics soft tissue fibroma but shows reactivity with melanocytic markers.

PEComa: morphology and genetics of a complex tumor family.

Perivascular epithelioid cell tumors, or PEComas, are mesenchymal neoplasms composed of histologically and immunohistochemically distinctive epithelioid or spindle cells, which are immunoreactive for both smooth muscle and melanocytic markers. The cells in PEComas are typically arranged around blood vessels and appear to form the vessel wall, often infiltrating the smooth muscle of small- to medium-sized vessels. Periluminal cells are usually epithelioid and the more peripheral cells are spindle shaped. The cells have small, round to oval nuclei, sometimes with focal nuclear atypia, and clear to eosinophilic cytoplasm, and no counterpart normal cell has been identified. The PEComa "family" now includes angiomyolipoma, pulmonary clear cell "sugar" tumor and lymphangioleiomyomatosis, primary extrapulmonary sugar tumor, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, abdominopelvic sarcoma of perivascular epithelioid cells, and other tumors with similar features at various sites that are simply termed PEComa. Some PEComas occur in patients with tuberous sclerosis complex and share the genetic abnormalities. There is a behavioral spectrum from benign to frankly malignant, and histologic criteria have been proposed for assessing malignant potential. The differential diagnosis can include carcinomas, smooth muscle tumors, other clear cell neoplasms, and adipocytic tumors. PEComas constitute a genetically diverse group that includes neoplasms harboring TFE3 gene rearrangements and those with TSC2 mutations, indicating alternative tumorigenic pathways. Recent advances in therapy of malignant PEComas relate to increased knowledge of specific genetic changes and their effects on metabolic pathways that are susceptible to specific interventions. We review PEComas, emphasizing the diagnostic spectrum and recent immunohistochemical and genetic findings.

PEComa of the nose: report of a case with immunohistochemical and ultrustructural studies and a review of the literature.

PEComas are a family of mesenchymal neoplasms that have in common the presence of a unique cell type, the perivascular epithelioid cell (PEC). PECs uniquely exhibit a distinct immunophenotype with expression of both melanocytic, particularly HMB-45, and myogenic markers. Nasal PEComas are exceedingly rare. To date, 14 cases have been described in the literature and with the exception of 6 cases, the rest consistently lack epithelioid cells and HMB-45 expression and are best classified as nasal hamartomas or angioleiomyomas with an adipocytic component. Nasal PEComas may closely resemble malignant melanomas since both entities share many morphologic, immunohistochemical, ultrastructural and clinical features. The distinction is of paramount importance as melanomas tend to display an aggressive behaviour with associated poor outcome. Herein, we report a case of nasal PEComa in a 19 year girl, focusing on the importance of light microscopic, immunohistochemical and ultrastructural features in accurately establishing the diagnosis.

Primary perivascular epithelioid cell tumor in the rectum: a case report and review of the literature.

Perivascular epithelioid cell tumor (PEComa) is a rare collection of tumors arising in a wide array of anatomic locations. It is characterized by the presence of a peculiar population of myomelanocytic marker-positive perivascular epithelioid cells, and is commonly detected in the uterus. The colorectal area is an uncommon site for primary PEComa. In this study, we describe a 17-year-old patient presenting with a rectal polyp. Histologically, the tumor consisted of sheets of round to polygonal epithelioid cells with clear and granular cytoplasm, and a prominent capillary network. Some of the tumor cells were positive for Fontana-Masson staining. Immunohistochemically, the tumor cells were positive for HMB-45, and were negative for cytokeratin, vimentin, S-100 protein, actin, desmin, EMA, CD34, and c-kit. After finding melanosomes or premelanosomes at the ultrastructural level, the diagnosis of PEComa was made. Although PEComa arising within the intestinal tract is unusual and clinically unexpected, PEComa should be considered in the differential diagnosis of rectal polypoid lesions.

Evidence on the neural crest origin of PEComas.

The perivascular epithelioid cell (PEC) has been proposed to be the proliferating cell type in a group of tumors known as PEComas. The histogenesis of PEComas is one of the most mysterious aspects of pathology. Hypothesis on its precursor are many, including a cell from blood vessel walls or the myoblast. In the current report, we review many morphologic, clinical, ultrastructural, molecular and genetic aspects that support the hypothesis of an origin of PEComas from the neural crest.

Perivascular epithelioid cell tumor (PEComa) of the pancreas: immunoelectron microscopy and review of the literature.

A perivascular epithelioid tumor (PEComa) is a rare tumor probably arising from the perivascular epithelioid cells. Only three cases of pancreatic PEComa have been reported in the English-language literature. The present report describes an extremely rare case of pancreatic PEComa. A 47-year-old Japanese woman complained of lower abdominal pain and a well-demarcated solid tumor was found in the pancreatic head. There was no history of tuberous sclerosis complexes. Pylorus-preserving pancreaticoduodenectomy was thus performed. There was a well-demarcated, solid tumor measuring 17 mm in the pancreatic head. The tumor was composed of a diffuse proliferation of epithelioid tumor cells with many blood vessels but no adipose tissue. The tumor cells expressed HMB45 and alpha-smooth muscle actin. Ultrastructurally, the tumor cells possessed many membrane-bound granules that were positive for HMB45 on immunoelectron microscopy. The results of immunoelectron microscopy show that some PEComas possess not only typical melanosomes or premelanosomes but also aberrant melanosomes.