Coexistence of Conventional Leiomyoma, Fumarate Hydratase-deficient Atypical Leiomyoma, and Perivascular Epithelioid Cell Tumor in a Uterus: A Case Study.

A 44-yr-old woman with menorrhagia and uterine fibroids underwent total laparoscopic hysterectomy, revealing several submucosal, intramural, and subserosal tan-white nodules in the uterus. Microscopic examination revealed tumors displaying 3 distinct morphologies: 1 tumor with features of conventional leiomyoma; 1 tumor with increased cellularity, staghorn/hemangiopericytoma-like vasculature, and occasional atypical cells with prominent red nucleoli and some perinucleolar halos suggesting a fumarate hydratase (FH)-deficient atypical leiomyoma; and 1 tumor with an admixture of epithelioid and spindled cells with the former arranged around blood vessels suggesting a perivascular epithelioid cell tumor (PEComa). Immunohistochemical studies confirmed these diagnoses by demonstrating loss of FH expression in the atypical leiomyoma and diffuse expression of HMB45 and cathepsin K in the tumor with epithelioid features. Sanger sequencing analysis revealed that the FH-deficient atypical leiomyoma harbored a c.181A>G (p.Lys61Glu) mutation in exon 2 of the FH gene. As this mutation was not present in either the other tumors or peripheral blood, the mutation is somatic and hereditary leiomyomatosis and renal cell cancer syndrome is excluded. This case highlights the importance of thorough examination of uterine mesenchymal tumors with atypical and epithelioid features so that tumors with some potential for recurrence (PEComas) and those that might indicate a hereditary cancer syndrome (FH-deficient atypical leiomyoma) are identified and can trigger appropriate clinical investigation and follow-up.

Rupture of perivascular epithelioid cell neoplasm at 34 weeks' gestation: A nonendometriosis case of spontaneous hemoperitoneum in pregnancy.

Spontaneous hemoperitoneum in pregnancy (SHiP) has mainly been discussed in the context of endometriosis. With hormonal changes and enlargement of the uterus during pregnancy, tumors can also increase the chance of rupture and consequent SHiP. We report a case of a 30-year-old primiparous woman presented with sudden-onset intraabdominal hemorrhage at 34 weeks' gestation. The source of bleeding was rupture of a perivascular epithelioid cell neoplasm on the left round ligament of the uterus. The pregnancy ended with an uncomplicated, full-term, vaginal delivery. We performed an additional post-partum surgery to resect the left round ligament and transposition of the right ovary. In cases of SHiP, the possibility of a nonendometriosis origin should be considered. Preoperative imaging and histologic examinations of bleeding lesions are crucial for managing SHiP.

Perivascular Epithelioid Cell Tumor (PEComa) of the Uterine Cervix: A Case Report of a 43-Yr-Old Woman With Abnormal Uterine Bleeding Treated With Hysterectomy.

Perivascular epithelioid cell tumor (PEComas) are a group of ubiquitous neoplasms described in different organs that share distinctive morphologic, immunohistochemical, ultrastructural, and genetic features. They have been reported in several organs such as the uterus, lung, kidney, liver, small and large bowel, and prostate. To the best of our knowledge, only 8 cervical PEComa cases have been described. We report the case of a 43-yr-old woman who presented with abnormal uterine bleeding. Clinical diagnosis of a malignant cervical lesion followed an excision, histopathologically evaluated as PEComa. The hysterectomy specimen confirmed the diagnosis by strong HMB-45 positivity, weak S100 positivity, and focal, moderate cytoplasmic TTF-1 positivity, and negative melan A, SMA, desmin, vimentin, cytokeratins, CD1a and other markers. The patient was negative for tuberous sclerosis complex, did not receive additional therapy, and 3 yr later is disease free. Cervical PEComas are very rare tumors but have to be considered in the differential diagnosis of cervical lesions exhibiting unusual cytologic and immunohistochemical characteristics.

Malignant Pigmented Mass "Sequestrated" in the Lung: A Unique Case Report.

Primary lung tumors arising in pulmonary sequestration is an exceptional event, usually consisting of common histologic types. On the other hand, malignant perivascular epithelioid cell (PEComatous) tumors with deposition of melanin pigment have never been reported in the lung so far. In this study, we report a challenging case of a 34-year-old man presented with recurrent hemoptysis and CT scan detection of a pulmonary mass at the left lower lobe, vascularized by aberrant communication with the left diaphragmatic artery. After surgical resection, we documented a malignant PEComatous tumor (characterized by TFE3 expression and high mitotic rate) that had arisen in the context of an extralobar sequestration.

A Rare Cause of Chronic Hip Pain From PEComa: An Aggressive Mesenchymal Sarcoma.

Perivascular epithelioid cell tumors (PEComas) are related to the tuberous sclerosis complex (TSC) and are commonly benign. When malignant, they can be aggressive with local invasion and metastatic spread. Conventional PEComas do not have TFE3 gene rearrangement and are associated with TSC with a preference for an occurrence at a younger age. We report a case of a young male who had progressive chronic hip pain and was found to have a TFE3-associated PEComa in his pelvic region.

Acute and repeated haemoperitoneum: a challenging case of lymphangioleiomyomatosis with uterine PEComa.

A 39-year-old woman presented in the emergency ward for abdominal pain and acute anemiation. Abdominal-thoracic CT scan showed haemoperitoneum, with a parauterine mass and a pathological pulmonary pattern suspicious for lymphangioleiomyomatosis (LAM), a systemic disease belonging to perivascular epithelioid cell tumours (PEComas). Gynaecological ultrasound showed a hypoechoic irregular solid mass of the uterine right wall. Ultrasonographic virtual organ computer-aided analysis showed the mass completely formed by arteriovenous vessels, and that allowed distinction from leiomyosarcoma. Repeated haemoperitoneum required uterine artery embolisation. Mass revascularisation occurred in the following 7 days. A laparotomic hysterectomy with removal of the uterus and right parametrium was performed in epidural analgesia. Histological features were consistent with the diagnosis of uterine PEComa of uncertain malignant features, in the presence of coexisting pulmonary LAM. In women with LAM, acute haemoperitoneum may indicate the presence of a uterine PEComa whose diagnosis can be challenging.

Perivascular Epithelioid Cell Tumor of the Urinary Bladder: A Systematic Review.

Perivascular epithelioid cell tumor (PEComa) of the urinary bladder is a rare neoplasm showing distinct melanocytic and smooth muscle differentiation. We aimed to review the clinicopathologic features of bladder PEComa using all the available cases in the literature, along with 2 new cases from our database. The patients included 15 females and 15 males with a mean age of 39.2 ± 15.3 years. Painless hematuria was the most common clinical presentation. The tumors were usually well circumscribed with a mean tumor size of 4.4 ± 2.7 cm. Bladder PEComas demonstrated nests, trabeculae, or sheets of epithelioid cells with intermixed spindled cells and numerous thin-walled vessels. Immunohistochemical studies showed that the tumors were positive for HMB45 (27/27), cathepsin (4/4), SMA (20/22), and caldesmon (3/3) and were negative for pan cytokeratin (0/18) and EMA (0/4). Molecular studies revealed that PEComa was associated with the TFE3 (n = 3) and EWSR1 (n = 1) gene rearrangements. Treatment included partial cystectomy (n = 18), transurethral resection (n = 8), and radical cystectomy (n = 4). Twenty patients had no evidence of disease during a mean follow-up time of 19.4 ± 17.2 months. Two patients had recurrence, and 1 patient died of metastatic disease. In conclusion, bladder PEComas demonstrate distinct morphologic and immunohistochemical features. Although most tumors follow a benign course, a small subset may develop metastasis and cause death.

Malignant variant of sclerosing perivascular epithelioid cell tumor arising in the adnexa.

The perivascular epithelioid cell family of tumors (PEComas) includes angiomyolipoma, lymphangioleiomyomatosis, clear-cell "sugar" tumor of the lung and a variety of extrapulmonary epithelioid and spindle-cell tumors referred to by various names. PEComas are now widely recognized histologically, and have been reported to occur at most anatomical sites, including the female genital tract. However, a distinctive variant of PEComa, designated "sclerosing PEComa," has only recently been described in the literature. All 13 of the cases of sclerosing PEComa reported thus far have been in women (mean age of 49 y), with a predilection for the retroperitoneum. Only one of the reported cases showed transition to a high-grade malignant phenotype. We report the first case of sclerosing PEComa arising in the uterine adnexa, with high-grade malignant transformation.

Acute abdomen as an unusual presentation of hepatic PEComa. A case report.

Perivascular epithelioid cell (PEC) tumors (or PEComas) are myomelanocytic lesions defined by coexpression of melanocytic and muscle markers, suggesting dual differentiation. They are rare mesenchymal tumors and include subtypes with distinct clinical features: angiomyolipoma, lymphangioleiomyomatosis, and clear cell "sugar" tumors of the lung, pancreas and uterus. Consequent upon the World Health Organization's recognition of PEC-derived tumors as a distinct entity, an increasing number of reports has documented PEComas arising at various anatomical locations. Clear cell myomelanocytic tumors of the falciform ligament/ligamentum teres (CCMTs) represent a rare variant of the PEComas. These hepatic PEComas, different from angiomyolipoma of the liver, pose a clinical, radiological and morphological diagnostic challenge. Because of their rarity, the clinical features and biological behavior of these tumors have yet to be established. We experienced our first case of CCMT in a 36-year-old woman who presented to our emergency department with a 3-day history of abdominal discomfort and progressive growth of an epigastric bulk. Intralesional hemorrhage was causing abdominal distension, which progressed to acute abdomen soon after. The hemoglobin concentration was 9.9 g/dL. Liver laboratory tests showed slight elevation of AST, ALT and gamma-GT. The alpha-fetoprotein level was not elevated. The radiological images showed a hemorrhagic mass with some bizarre features in left hepatic lobe, immediately adjacent to the ligamentum teres and falciform ligament. The patient underwent a left hepatic lobectomy. The diagnosis of CCMT was based on histological and immunohistochemical staining. The postoperative course was uneventful. The patient received no adjuvant treatment and is currently, 34 months after surgery, alive and disease free. In this report we describe a peculiar and hitherto undescribed clinical presentation of this tumor and its further course. Moreover, we discuss previously undescribed diagnostic imaging. We recommend that all unusual carcinomas and mesenchymal tumors of the liver should be tested for HMB-45: when positive, there is a high likelihood of PEComa.

Acute lymphoblastic leukemia secondary to chemoradiotherapy for perivascular epithelioid cell tumor of uterus.

Acute lymphoblastic leukemia (ALL), a primary hematologic malignancy that is especially common in childhood, occurs relatively rarely as a secondary malignant neoplasm. Available data indicate that ALL often follows chemoradiotherapy for soft tissue sarcoma. Perivascular epithelioid tumor (PEComa), a primitive mesenchymal tissue origin, can be classified as a soft tissue sarcoma. An 11-year-old girl was diagnosed with ALL secondary to chemoradiotherapy (vincristine, ifosfamide, and anthracycline) and radiotherapy comprising 45 Gy to the whole pelvis for PEComa. ALL, FAB L2, and immunophenotypically pro-B developed 16 months after the final chemotherapy treatment. Moreover, a cytogenetic study of lymphoblasts showed t(1;11)(p32;q23). Herein, the authors report a case of secondary ALL that might be related to a previously used intercalating DNA topoisomerase II inhibitor (anthracycline) for a very rare sarcoma, PEComa.

MR findings of uterine PEComa in patients with tuberous sclerosis: report of two cases.

Tuberous sclerosis complex (TSC), a rare autosomal dominant neurocutaneous disorder, is characterized by the presence of benign congenital tumors in multiple organs. Neoplasms with perivascular epithelioid cell differentiation (PEComas), including angiomyolipoma (AML) and lymphangioleiomyomatosis (LAM), can occur in association with TSC. This report describes two cases of uterine PEComas presenting characteristic MR imaging features reflecting pathological findings. From MR images, both cases showed single or multiple large, irregularly shaped or lobulated hemorrhagic lesions within the myometrium. They differed from typical adenomyotic cysts in their large size and irregular margins. Histopathologic analysis revealed that the hemorrhage was caused by adenomyosis and tumor cells that proliferated in surrounding stroma of the hemorrhagic lesions, compatible with PEComas. Microscopic observation revealed an infiltrative growth pattern of PEComas, with small nodules formed. The tumor lesions, however, were difficult to detect on MR images. The myometrium showed normal appearance on both T1-weighted and T2-weighted images in both cases. We speculate that PEComas may infiltrate extensively into the myometrium even when the myometrium shows almost normal radiologic appearance.

Hepatic perivascular epithelioid cell tumor (PEComa): a case report with a review of literatures.

Hepatic perivascular epithelioid cell tumors (PEComas) are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45) and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA).

Ruptured pericardial perivascular epithelioid cell tumor (PEComa) leading to sudden death: an autopsy case report and review of the literature.

A 30-year-old man with past medical history of atrial fibrillation/flutter passed away after presenting with sudden-onset cardiac dysfunction. The postmortem examination revealed cardiac tamponade secondary to rupture of a 7.2-cm pericardial perivascular epithelioid cell tumor (PEComa). The tumor grossly appeared to arise from the transverse pericardial sinus and focally penetrated the epicardium of the right atrium. Microscopically, it was composed of predominately spindle cells with low nuclear grade, no pleomorphism, or readily apparent mitoses. Immunohistochemistry revealed cytoplasmic reactivity for HMB-45, desmin, and smooth muscle actin. Electron microscopic findings were characterized by melanosome-like structures intermixed with intermediate filaments and abundant stacked endoplasmic reticulum. The present case is unique among previously reported pericardial/myocardial PEComas as a first example resulting in unexpected cardiac tamponade and sudden cardiac death.

PEComa of the uterus with coexistence of situs inversus totalis, a case report and literature review.

PEComas are a group of very rare mesenchymal neoplasms, which express myogenic and melanocytic markers, such as HMB-45 and actin. Situs inversus totalis represents a complete left to right side transposition of the asymmetrical thoracic and abdominal organs and incorporates dextrocardia. The presence of uterus PEComa in the setting of situs inversus totalis is extremely rare. Here, we report a case of PEComa of uterus with coexistence of situs inversus totalis and review the literatures. To the best of our knowledge this is the fist report of a uterus PEComa patient with situs inversus totalis.

Coincidence between malignant perivascular epithelioid cell tumor arising in the gastric serosa and lung adenocarcinoma.

A 4-mo history of both epigastralgia and back pain was presented in a 39-year-old male. Computed tomography showed right lung nodule and abdominal mass attached to the gastric wall, measuring approximately 30 mm and 70 mm in diameter. Since biopsy samples from the lung and abdomen revealed poorly differentiated adenocarcinoma and malignant tumor, clinicians first interpreted the abdominal mass as metastatic carcinoma, and a right lower lobectomy with following resection of the mass was performed. Gross examination of both lesions displayed gray-whitish to yellow-whitish cut surfaces with hemorrhagic and necrotic foci, and the mass attached to the serosa of the lesser curvature on the gastric body. On microscopic examination, the lung tumor was composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, predominantly arranged in an acinar or solid growth pattern with vessel permeation, while the abdominal tumor consisted of sheets or nests with markedly atypical epithelioid cells having pleomorphic nuclei and abundant eosinophilic to clear cytoplasm focally in a radial perivascular or infiltrative growth pattern. Immunohistochemically, the latter cells were positive for HMB45 or α-smooth muscle actin, but the former ones not. Therefore, we finally made a diagnosis of malignant perivascular epithelioid cell tumor (PEComa) arising in the gastric serosa, combined with primary lung adenocarcinoma. Furthermore, small papillary carcinoma of the thyroid gland was identified. The current case describes the coincidence of malignant PEComa with other carcinomas, posing a challenge in distinction from metastatic tumor disease.

Ectopic prolactin secretion from a perivascular epithelioid cell tumor (PEComa).

BACKGROUND: The diagnosis of ectopic pituitary hormone secretion requires abnormally high circulating hormone levels, absence of a pituitary tumor, and localization of the hormone in question to the extrapituitary malignant neoplasm. No case of a malignant solid tumor producing prolactin has been documented thus far. CASE REPORT: A 47-year-old woman presented with amenorrhea and galactorrhea of 3-year duration. Serum prolactin ranged from 300 to > 900 ng/mL, and other pituitary and thyroid indices were normal, including testing for macroprolactinemia. Pituitary magnetic resonance imaging revealed a partially empty sella but no tumor. Cabergoline 0.5 mg twice weekly did not affect her prolactinemia (1700 to 1900 ng/mL), and the medication was stopped. In the meantime, she developed abdominal pain, and a computed tomography scan showed a 17 × 13 × 8-cm mass abutting the distal stomach, proximal duodenum, and right colon. After the tumor was excised, her galactorrhea resolved, menstrual periodicity resumed within the first month, and serum prolactin fell to 5 ng/mL. Pathological examination of the excised tumor was consistent with perivascular epithelioid cell tumor. Between 5 and 10% of the tumor cells were strongly positive for prolactin on immunohistochemistry. RT-PCR detected prolactin mRNA in the tumor cell extract, confirming the diagnosis of ectopic prolactin synthesis and secretion. CONCLUSION: We present the first example of massive and symptomatic hyperprolactinemia due to ectopic prolactin production by a solid extrapituitary mesenchymal tumor confirmed with both mRNA analysis and immunohistochemistry. Ectopic prolactin secretion should be suspected in patients with a prolactin >200 ng/mL and negative sellar MRI.

Incidental perivascular epithelioid cell tumor in an inguinal hernia sac.

Perivascular epithelioid tumors (PEComa) are uncommon mesenchymal neoplasms demonstrating positivity for muscular and melanocytic immuno-markers. Included in this category are angiomyolipoma, lymphangioleiomyomatosis, and clear cell sugar tumors. Lesions which do not fit into these categories are classified as "not otherwise specified". We present a case of an incidentally discovered PEComa within inguinal hernia sac contents in a 70-year-old woman. It consisted of spindled and epithelioid cells with bland oval nuclei, small nucleoli and clear to light eosinophilic cytoplasm. There was no atypia or mitoses. The lesion was strongly positive for HMB45 and smooth muscle actin. Pelvic soft tissue and peritoneal PEComas are rarely reported in literature and very little is known about their prognosis. We discuss the immunohistochemistry, differential diagnosis, and pathogenesis of PEComas.