PEComa: what do we know so far?

PEComas (tumours showing perivascular epithelioid cell differentiation) are a family of related mesenchymal neoplasms that include angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumour of the lung, and a group of rare, morphologically and immunophenotypically similar lesions arising at a variety of visceral and soft tissue sites. These tumours all share a distinctive cell type, the perivascular epithelioid cell or "PEC' (which has no known normal tissue counterpart). PEComas show a marked female predominance and are composed of nests and sheets of usually epithelioid but occasionally spindled cells with clear to granular eosinophilic cytoplasm and a focal association with blood vessel walls. PEComas appear to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites, with a subset occurring in somatic soft tissue and skin. Nearly all PEComas show immunoreactivity for both melanocytic (HMB-45 and/or melan-A) and smooth muscle (actin and/or desmin) markers. A subset of PEComas behave in a malignant fashion. This review examines the members of the PEComa family, with an emphasis on lesions arising outside of the kidney, lung and liver, and discusses preliminary evidence for pathological features that might predict malignant behaviour.     

Perivascular epithelioid cell tumor in the duodenum: challenge in differential diagnosis

Defined as a family of scarce mesenchymal neoplasm which distinctively co-express melanocytic markers and muscle markers, perivascular epithelioid cell tumors (PEComas) have been reported almost everybody site. Perivascular epithelioid cell tumors-not otherwise specified (PEComas-NOS) arising in the gastrointestinal (GI) tract are still restricted into sporadic case reports. Herein we present a case of GI PEComas-NOS which occurs in the duodenum of a 27-year-old male. Our initial diagnosis tended to gastrointestinal stromal tumor or smooth muscle tumor till the correct diagnosis of perivascular epithelioid cell tumor (PEComa) was established by postoperative pathological examination. We also make a literature review of GI PEComas-NOS and highlight the challenge it brings to the differential diagnosis.     

Malignant neoplasm of perivascular epithelioid cells of the liver

Neoplasms of perivascular epithelioid cells (PEComas) have in common the coexpression of muscle and melanocytic immunohistochemical markers. Although this group includes entities with distinct clinical features, such as angiomyolipoma, clear cell sugar tumor of the lung, and lymphangioleiomyomatosis, similar tumors have been documented in an increasing diversity of locations. The term PEComa is now generally used in reference to these lesions that are not angiomyolipomas, clear cell sugar tumors, or lymphangioleiomyomatoses. While most reported PEComas have behaved in a benign fashion, malignant PEComas have occasionally been documented. We present a case of hepatic PEComa with benign histologic features, which nonetheless presented with metastases to multiple sites nearly 9 years later. This case represents the second documented malignant PEComa of the liver, as well as the longest follow-up of a surviving patient with a malignant PEComa, emphasizing both the need for criteria that more accurately predict the behavior of PEComas and the necessity of long-term follow-up of patients with PEComas.     

Heterologous and rare homologous sarcomas of the uterine corpus: a clinicopathologic review

Pure sarcomas of the uterine corpus are uncommon, constituting less than 3% of all malignancies at this site, and most of them are leiomyosarcomas and endometrial stromal sarcomas. Rare histotypes of homologous sarcomas and heterologous sarcomas are occasionally encountered, and the absence of significant accumulated experience with these histotypes at this location may potentially raise diagnostic and patient management difficulties. In this article, the clinicopathologic attributes of all earlier reported sarcomas of the uterine corpus other than leiomyosarcomas and endometrial stromal sarcomas are summarized. Included are embryonal rhabdomyosarcoma, pleomorphic rhabdomyosarcoma, angiosarcoma, alveolar soft part sarcoma, malignant perivascular epithelioid cell tumors (PEComas), osteosarcoma, chondrosarcoma, liposarcomatous tumors, malignant extrarenal rhabdoid tumors, Ewing sarcoma/primitive neuroectodermal tumor, and other rare histotypes. Embryonal rhabdomyosarcoma (20%), Ewing sarcoma/primitive neuroectodermal tumor (17%), angiosarcoma (14%), and pleomorphic rhabdomyosarcoma (13%) appeared to be more common than the others, although there was no single overwhelmingly prevalent histotype in the group. A subset, including embryonal rhabdomyosarcoma, alveolar soft part sarcoma, and PEComas, peak in the premenopausal years, but most of the others were observed in postmenopausal women. Favorable outcomes have been reported for the patients diagnosed with alveolar soft part sarcoma, and the prognosis for their counterparts with PEComa remains a matter of debate. Multimodal therapeutic approaches to contemporary patients with embryonal rhabdomyosarcomas have resulted in significantly improved outcomes. Unfortunately, most of the other sarcomas have been associated with rapid tumor progression and unfavorable patient outcomes. The differential diagnosis for these sarcomas is often extensive and varies by histotype, but their accurate diagnosis fundamentally requires the careful exclusion of biphasic malignancies.     

Pancreatic perivascular epithelioid cell tumor (PEComa)

Neoplasms with perivascular épithelioid-cell differentiation (PEComas) are rare tumors with a distinctive immunoreactivity for melanocytic markers. They have been described in various organs. We report an intrapancreatic PEComa discovered in a 46-year-old woman during a workup for diarrhea. CT scan showed a 1.7cm nodule in the body of the pancreas with slight-contrast enhancement at arterial time and isodense at portal time. The aspect was suggestive of an endocrine tumor despite negative somatostatin-receptor scintigraphy. Enucleation was performed. Pathologic evaluation showed a well-circumscribed intrapancreatic tumor consisting of a population of clear to eosinophilic spindle cells and a less abundant population of epithelioid cells arranged around blood vessels. Tumor cells expressed vimentin, HMB45 and actin and only focally S-100 protein, KL1, CD117 and CD34. These features were consistent with a PEComa. Pancreatic PEComas are rare, but should be included in the differential diagnostic of pancreatic clear cells tumors or pancreatic spindle- and epithelioid-cells tumors.     

Abdominopelvic sarcoma of perivascular epithelioid cells. Report of four cases in young women, one with tuberous sclerosis.

The perivascular epithelioid cell has been proposed to be the unifying proliferating cell type in a number of lesions such as angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumor and renal capsuloma. With the exception of rare examples of angiomyolipoma, they are non-metastasizing. We report four examples of a new member of this family of perivascular epithelioid cell neoplasms that occur in abdominopelvic location and show metastatic properties. The patients, all women, were aged 19 to 41 years (mean, 32), and presented with a tumor mass involving the serosa of the ileum, uterus or pelvic cavity. Morphologically, the tumors were composed of sheets of large polygonal cells with glycogen-rich clear or eosinophilic cytoplasm and moderately pleomorphic nuclei, traversed by a delicate vasculature, mimicking clear cell carcinoma. There were areas of coagulative necrosis and occasional mitotic figures. Intracytoplasmic brown pigment was present in two cases. Spindly cells, smooth muscle and fat were absent. Lymphovascular invasion was present in all, lymph node metastasis was documented in two and metastasis to the ovary was present in one case. Two patients developed widespread metastatic disease after 10 and 28 months from diagnosis. One patient showed the clinical signs of tuberous sclerosis. In spite of the epithelial-like appearance, the tumor cells were negative for epithelial markers but were strongly positive with the melanogenesis-related marker HMB45. Another melanogenesis marker (MART-1) was positive in two cases. Other markers including S-100 protein, vimentin, muscle-specific actin, desmin and chromogranin A were negative. Thus, these tumors are not readily classifiable in the existing schema of known entities, and show overlapping morpho-phenotypic features of clear cell "sugar" tumor of the lung and epithelioid angiomyolipoma. We consider them as sarcomas composed of a pure population of uncommitted perivascular epithelioid cell, that lack modulation toward smooth muscle or adipose cells.     

PEComas: report of five abdominopelvic cases

We report five cases of abdomino-pelvic PEComas diagnosed in the last 10 years in the Rouen University Hospital. Four are hepatic and one is in a pelvic location which is unusual due to its strongly pigmented aspect. The tumors derived from "perivascular epithelioid cells" are rare. They are characterized by spindle or epithelioid cells in an immediate perivascular location. The immunochemistry is positive for HMB45, MelanA and smooth muscle Actin. The criteria for malignancy are infiltrative growth pattern, necrosis, high cellularity, high nuclear grade and mitotic activity. There are 8% of recurrence and 20% of metastasis (lung, bones, liver). This study presents the clinical, pathologic, immunohistochemical and molecular aspects of these PEComas and discusses the main differential diagnosis of the pigmented one.     

Pancreatic PEComa: A Case Report with Ultrastructural Localization of HMB-45 within Melanosomes

PEComas (perivascular epithelioid cell tumors) represent a group of mesenchymal neoplasms showing characteristic morphologic, immunohistochemical, ultrastructural, and genetic features. These neoplasms are usually considered benign, being often well circumscribed by a thin capsule and showing scarce atypia. However, in some cases, they show local invasion and multiple metastases and cause the patient’s death. PEComas have been found in many locations, but only 7 cases have been described in the pancreas to date. Here, the authors report an additional case of this rare neoplasm and demonstrate the HMB-45 immunoreactivity of melanosomes or premelanosomes at the ultrastructural level.     

Pancreatic PEComa: a case report with ultrastructural localization of HMB-45 within melanosomes

PEComas (perivascular epithelioid cell tumors) represent a group of mesenchymal neoplasms showing characteristic morphologic, immunohistochemical, ultrastructural, and genetic features. These neoplasms are usually considered benign, being often well circumscribed by a thin capsule and showing scarce atypia. However, in some cases, they show local invasion and multiple metastases and cause the patient's death. PEComas have been found in many locations, but only 7 cases have been described in the pancreas to date. Here, the authors report an additional case of this rare neoplasm and demonstrate the HMB-45 immunoreactivity of melanosomes or premelanosomes at the ultrastructural level.     

A case of a pleomorphic hyalinizing angiectatic tumor of soft parts with intracytoplasmic hemosiderin pigment apparent upon fine‐needle aspiration cytology

Pleomorphic hyalinizing angiectatic tumors of soft parts are extremely rare low‐grade mesenchymal lesions that frequently occur subcutaneously, especially in the lower extremity. The tumor is histologically characterized by sheets of plump, spindled or rounded cells, and clusters of ectatic blood vessels. It also has a number of previously characterized cytological features such as pleomorphic cells, intranuclear pseudoinclusion, and intracytoplasmic hemosiderin pigments. However, intracytoplasmic hemosiderin has not been carefully evaluated in cytology specimens. Here, we report the case of a 56‐year‐old Japanese man with an encapsulated pleomorphic hyalinizing angiectatic tumor of soft parts that included fine and coarse hemosiderin‐laden tumor cells. The tumor was clinically followed up as a hematoma, but malignant tumors, including malignant melanoma, were suspected because aspiration cytology specimens contained pleomorphic cells with intracytoplasmic brown pigments. The tumor was closely associated with an intratumoral hematoma and a few microscopic satellite lesions. Pleomorphic hyalinizing angiectatic tumor of soft parts should be included in the differential cytological diagnosis of soft tissue tumors if the three cytological features described earlier are present. Enucleation therapy could facilitate local recurrence, as the tumor may have the potential to infiltrate surrounding soft tissue or form satellite lesions. Diagn. Cytopathol. 2015;43:407–411. © 2014 The Authors. Diagnostic Cytopathology Published by Wiley Periodicals, Inc.     

Application of biomarkers in the diagnosis and differential diagnosis of uterine and vulval mesenchymal tumours

The gold standard for pathologica1 diagnosis is microscopic examination of tissue stained by the haematoxylin and eosin method. Nevertheless, there have been recent advances, particularly in the subspecialty of gynaecological pathology, with regard to the diagnostic usefulness of novel and established biomarkers. This review will focus upon those biomarkers that may be useful in the diagnosis and differential diagnosis of uterine and vulvovaginal mesenchymal neoplasia. In particular, a practical approach to the use of desmin, h-caldesmon and CD10 will be discussed in reference to commonly encountered scenarios in the distinction between uterine endometrial stromal and smooth muscle neoplasia. The histological and immunophenotypic characteristics of tumours of perivascular epithelioid cells (so-called PEComas), relatively recently described to occur in the uterus, will also be addressed. Finally, the usefulness of a newly developed antibody against the high mobility group protein A2 (formerly HMGIC) as well as established markers will be discussed in the differential diagnosis of vulvar mesenchymal neoplasia, particularly the distinction of aggressive angiomyxoma from other vulva1 soft tissue tumours.     

PEComas: the past,the present and the future

The perivascular epithelioid cell (PEC) is a cell type constantly present in a group of tumors called PEComas. PEC expresses myogenic and melanocytic markers, such as HMB45 and actin. Recently, recurrent chromosomal alterations have been demonstrated in PEC. At present, PEComa is a widely accepted entity. In the past 10 years, the use of this term has allowed to report and describe numerous cases permitting to start highlighting the biology of this group of lesions. PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway. There are some open questions about PEComas regarding its histogenesis, the definition of epithelioid angiomyolipoma and the identification of the histological criteria of malignancy. An innovative therapeutic trial using rapamycin is under way for tumors occurring in TSC such as renal angiomyolipoma and lymphangioleiomyomatosis. Its success could provide the rationale for the use of the same drug in other lesions composed of PECs, especially in the malignant ones.     

Pleomorphic hyalinizing angiectatic tumor: cytomorphologic features on fine-needle aspiration

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare low-grade neoplasm occurring predominantly in the subcutaneous tissue of the lower extremity, which is characterized histologically by intermixed bland spindle cells and larger pleomorphic cells, ectatic blood vessels with fibrin, and prominent hyalinization. Here we describe the cytologic features of PHAT seen on fine-needle aspiration of a right calf mass in a 46-year-old man. The smears were cellular, composed predominantly of bland spindle cells dispersed singly as well as in tissue fragments and characterized by open chromatin and small nucleoli. A second population of pleomorphic spindle cells with coarse chromatin, prominent nucleoli, and occasional intranuclear pseudoinclusions was also present. Many of the pleomorphic cells surrounded hyalizined vessels. No mitotic figures were identified. The cytologic diagnosis was a "spindle cell lesion, NOS" with the differential diagnosis including benign lesions and low-grade neoplasms, including PHAT and schwannoma.     

Malignant perivascular epithelioid tumor of the vagina: Report of a rare case with brief review of literature

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors with immunohistochemical co‐expression of melanocytic and myoid markers. Vaginal PEComas have been described in only nine cases so far. We describe the case of a 65‐year‐old female with a large growth in the left lateral vaginal wall. Biopsy imprint smears showed dispersed tumor cells with anisonucleosis, multinucleation, and bizarre forms, suggestive of a malignant tumor. Histopathology, however, showed perivascular arrangement of clear epithelioid cells, focal necrosis, intracellular brown pigment in few cells, and mitotic activity at 2 to 3 per 50 high power fields. Immunohistochemical positivity for vimentin, HMB‐45, S‐100 protein, desmin, and MyoD1 assisted in rendering a final pathological diagnosis of malignant PEComa of the vagina. Further work‐up revealed metastatic deposits in liver and retroperitoneal lymph nodes. PEComa arising in vagina is an unusual phenomenon with the malignant variant being an extremely rare tumor. Awareness of the characteristic morphology and utilization of a panel of immunohistochemical stains are mandatory to be able to make a precise diagnosis and appropriate prognostication.     

Two unusual benign lesions of the neck masquerading as malignancy on fine-needle aspiration cytology

Two cases of unusual benign tumors of the neck are described, both of which were initially misdiagnosed on cytology as carcinomas. Fine-needle aspiration findings in each case demonstrated a pleomorphic population of cells including bizarre multi-nucleated giant cells, the latter raising the false impression of malignancy. However, on review the cytological appearances of the tumors, a pleomorphic lipoma and a carotid body tumor, were characteristic. the correct diagnosis in each case would have been made or suggested if the pathologist had been familiar with the cytologic features characteristic of the lesion and the differential diagnosis of the head and neck tumors. in addition, the point is made that adequate clinical information is essential for the pathologist if all relevant conditions are not to be missed in the differential diagnosis.     

Malignant PEComa of the adrenal gland

Perivascular epithelioid cell neoplasms, also known as PEComas, are unique mesenchymal tumors exhibiting perivascular epithelioid cell differentiation, characterized by a mixed myogenic and melanocytic phenotype. PEComas arising in visceral organs outside of the kidney, liver, and lung are rare, and often pose problems in diagnosis. Examples of this neoplasm originating in the adrenal gland are limited. The present report details the clinical and pathologic features of an unusual case of a pure epithelioid PEComa (epithelioid angiomyolipoma) of the adrenal gland exhibiting clinically malignant behavior in the form of pulmonary metastases, a feature not previously described in tumors of this site. The diagnosis was supported by immunohistochemical studies demonstrating expression of myoid and melanocytic antigens. The present case serves to emphasize the potential of PEComa for clinically aggressive behavior and the importance of distinguishing this tumor from other epithelioid neoplasms that are more commonly encountered in the adrenal gland.     

Nodular fasciitis of parotid region: a pitfall in the diagnosis of pleomorphic adenomas on fine-needle aspiration cytology

Fine-needle aspiration cytology (FNAC) is routinely employed for the preoperative diagnosis of salivary gland lesions. Although most cases show morphologic features characteristic of specific entities, some lesions can be diagnostically challenging. We report two parotid aspirates, initially diagnosed as pleomorphic adenoma on FNA. The patients, a 33-yr-old white man, and a 24-yr-old white woman, presented with indurated lesions arising in the parotid gland region. The aspirates from both patients were markedly hypercellular. Smears showed a mixture of spindle cells with a well-demarcated cytoplasm showing occasional long cytoplasmic process; and cells with abundant cytoplasm with round to oval eccentric nuclei, giving the impression of plasmacytoid cells of pleomorphic adenoma. The nuclear chromatin was evenly distributed and finely granular with one or two occasional small nucleoli. Intermingled with the tumor cells were scattered neutrophils, eosinophils, and macrophages. Aggregates of spindle cells were also seen embedded in a mucoid background with occasional small tufts of a fibrillar mucoid stroma. These fibrillar tufts were magenta red in the Diff-Quik stain, giving the impression of matrix of pleomorphic adenoma. Both cases were later diagnosed on histologic examination as nodular fasciitis. Nodular fasciitis should be considered in the differential diagnosis of a mass arising in association with the parotid gland.     

Perivaskuläre Tumoren der Haut und des Weichgewebes

Perivascular neoplasms of skin and soft tissues comprise a group of benign and malignant mesenchymal neoplasms showing a perivascular myogenic differentiation. Whereas glomus tumour including its variants represents a clearly defined clinicopathological entity, the whole concept of haemangiopericytoma has been questioned in the last years, and no clear diagnostic criteria are established at the moment. Myopericytomas and myofibromas represent a morphological spectrum of perivascular spindle-shaped lesions. Infantile myofibroma/infantile myofibromatosis and solitary myofibroma of adults are characterized by a biphasic growth of mature, spindled, myofibroblastic cells and smaller, immature, mesenchymal cells associated with numerous haemangiopericytoma-like vessels. Benign and rare malignant myopericytomas of skin and soft tissues are characterized by a concentric, perivascular growth of plump spindled and round tumour cells staining positively for muscle actin, alpha-smooth muscle actin and more rarely for desmin. PEComas represent an enigmatic family of neoplasms composed of perivascular epithelioid, clear, and spindled tumour cells characterized by a coexpression of melanocytic and myogenic markers.