肝脏单形性上皮样血管平滑肌脂肪瘤

目的：探讨肝脏单形性上皮样血管平滑肌脂肪瘤的临床病理学特征及诊断、鉴别诊断要点。方法：对1例单形性上皮样血管平滑肌脂肪瘤进行临床病理学分析及免疫组织化学研究。结果：肝脏单形性上皮样血管平滑肌脂肪瘤临床多无症状,光镜下单形性上皮样血管平滑肌脂肪瘤由形态多样的上皮样细胞构成,胞质透明或嗜酸,无脂肪组织及异常血管;免疫表型;HMB45阳性,SMA及vimentin部分阳性,desmin少数阳性,S－100蛋白弱阳性,cytokeratin及AFP阴性,CD34血管内皮细胞阳性。结论：肝脏单形性上皮样血管平滑肌脂肪瘤是极为罕见的间叶性肿瘤,组织起源至今不明,其诊断及鉴别诊断主要依靠病理组织学及免疫组织化学。     

Perivascular epithelioid cell tumor of the pancreas: case report and literature review

Neoplasms with perivascular epithelioid cell differentiation (PEComas) of the pancreas are rare, and only 22 cases have been reported globally. Therefore, clinician and pathologist knowledge of this tumor’s biologic behavior and molecular genetics has been limited. A 40-year-old female patient presented with a space-occupying mass in the pancreas found by abdominal B-mode ultrasonography upon physical examination. Laparoscopic resection of the pancreatic body and tail was performed, and a cystic-solid tumor of about 2 × 2 cm was identified. PEComa is a type of mesenchymal tumor with uncertain biologic behavior, more frequently found in females. PEComa features a unique histomorphology and immunophenotype. We summarize the characteristics and research progress of the pancreatic PEComa, which will be convenient for physicians and pathologists to fully understand the disease to avoid misdiagnosis and to provide a reference for treatment and prognosis.     

4例胃肠道血管周上皮样细胞肿瘤临床病理学分析

目的 探讨胃肠道血管周上皮样细胞肿瘤(perivasculaRepithelioid cell tumor,PEComa)的临床及病理学特点.方法 回顾性复习4例胃肠道原发血管周上皮样细胞肿瘤的病理切片及临床资料,选取典型蜡块做相关的免疫组化染色,抗体包括黑色素相关抗原HMB45、melan-A、肌源性标记抗原SMA、desmin,以及vimentin、CgA、CK、S-100、CD117、CD34.结果 4例PEComas中男性3例,女性1例,年龄分别为36、38、42及45岁.其中2例位于升结肠,1例位于降结肠,1例位于乙状结肠.肿瘤大小4.5～10 cm,境界清楚,切面灰白色,质地均匀,局部可见出血.镜检:肿瘤细胞呈上皮样排列,细胞质丰富,透亮或嗜酸性颗粒状,细胞核空泡状,有明显的核仁,间质富于毛细血管、血窦以及厚壁血管.细胞异型性小,个别病例局部可见轻～中度异型性,分裂象0～3个/10 HPF.免疫组化结果 :肿瘤弥漫表达HMB45(4/4),弥漫或片状表达vimentin(4/4)、SMA(4/4)以及desmin(3/4).CgA、Syn、CK、S-100、CD117、CD10及CD34均阴性.4例患者行局部肠管及肿瘤切除,术后随访8、15、32及36个月均无复发和肿瘤转移.结论 胃肠道PEComa少见,为低度恶性潜能肿瘤,形态类似于软组织和其他部位的同类肿瘤,手术切除为首选治疗.     

Perivascular epithelioid cell tumor of the uterine cervix identified on a conventional cervical smear

Perivascular epithelioid cell tumors (PEComas) most frequently involve the uterus, particularly the uterine corpus and very occasionally the cervix. One case of PEComa identified using a conventional cervical smear has previously been documented. Herein, we present the second such case. The patient was a 51‐year‐old woman with abnormal genital tract bleeding. Samples collected for conventional cervical smears were submitted for cytopathological examination, which revealed discohesive monotonous tumor cells showing epithelioid morphology, ample cytoplasm that was pale to weakly eosinophilic, and mildly enlarged nuclei. The cytopathological features were well correlated with histopathological findings. Upon immunohistochemistry, the tumor cells were positive for both melanocytic and smooth muscle markers. Based on these findings, PEComa was diagnosed. Subsequently, a total hysterectomy with bilateral salpingo‐oophorectomy was performed, revealing that the tumor (28 × 22 × 12 mm) was located at the superficial part of the endocervix. We propose that the cytopathological findings described herein can guide the diagnosis of PEComa, even though this tumor is rare. Diagn. Cytopathol. 2015;43:1011–1016. © 2015 Wiley Periodicals, Inc.     

Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum

BACKGROUND: Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. OBJECTIVE: To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). DESIGN: Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. RESULTS: All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. CONCLUSION: In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.     

Monotypic epithelioid angiomyolipoma of the liver

AIMS: Monotypic epithelioid angiomyolipoma is a recently recognized renal tumour, which is composed purely of epithelioid cells coexpressing markers of both smooth muscle differentiation and melanogenesis (HMB45). We report here the first case of monotypic epithelioid angiomyolipoma arising in the liver. CASE DETAILS: A 30-year-old woman without tuberous sclerosis complex (TSC) was incidentally found to have a hepatic mass by ultrasonography. Grossly, the resected tumour showed a nodule-in-nodule appearance, with large areas of haemorrhagic necrosis. Microscopically, the tumour was composed of pleomorphic epithelioid cells with clear, eosinophilic cytoplasm. Neither adipocytes nor abnormal vessels were recognized in the tumour. Immunohistochemically, the tumour cells were strongly positive for HMB45 and S100 protein, focally positive for desmin, vimentin and smooth muscle actin, and negative for epithelial markers (cytokeratins, EMA). Ultrastructural analysis showed numerous dense granules with some striated ones resembling melanosomes, myofilaments and pinocytic vesicles in the cytoplasm. Molecular analysis showed no allelic loss of the TSC2 region or 12 other chromosomal regions. The patient is free of disease over 1 year after the operation. CONCLUSION: We consider that this hepatic tumour is closely related to angiomyolipoma, and a counterpart of renal monotypic epithelioid angiomyolipoma.     

Malignant perivascular epithelioid cell tumor of the retroperitoneum

Perivascular epithelioid cell tumors (PEComas) are a rare type of mesenchymal neoplasms characterized by a proliferation of perivascular cells with an epithelioid phenotype and expression of myo-melanocytic markers. The majority of PEComas seem to be benign and usually their prognosis is good. Malignant cases are extremely rare, exhibiting a malignant course with local recurrences and distant metastases. We herein report a case of a malignant PEComa arising in the retroperitoneum. The patient was a 55-year-old woman experiencing abdominal discomfort for approximately one month. Ultrasound and computer tomography (CT) scans of the abdomen revealed a solid mass arising from the retroperitoneum. Microscopically, the tumor was composed of epithelioid cells mixed with spindled cells. The nucleus had significant atypia, and the mitoses were obvious. The focal intravascular tumor embolus was visible. Immunohistochemically, the epithelioid tumor cells were positive for HMB45 and Melan-A, and the spindled tumor celLs were positive for SMA and desmin. Seven months after a surgical resection, an ultrasound revealed liver metastases. In conclusion, the malignant PEComas of the retroperitoneum is a very rare neoplasm with unique morphological and immunohistochemical characteristics. It should be differentiated from other epithelioid cell tumors of the retroperitoneum.     

Hepatic angiomyolipoma resembling an inflammatory pseudotumor of the liver. A case report

Hepatic angiomyolipoma (AML) may demonstrate a marked histologic diversity and is frequently misdiagnosed. HMB45 is a promising marker for this tumor and is expected to facilitate the recognition of some AMLs with unusual morphology. We report on a case of hepatic AML exhibiting histologic features that were similar to inflammatory pseudotumor (IPT) or to IPT-like follicular dendritic cell (FDC) tumor of the liver. The patient was a 21-year-old Japanese woman with a mass in the left lobe of the liver (70 x 73 mm). There were no clinical features of tuberous sclerosis. Histologically, numerous inflammatory cells, including small lymphocytes, plasma cells, and histiocytes, showed diffuse infiltration throughout the lesion. However, the present case also shared some of the morphologic findings of hepatic AML, including clusters of smooth muscle cells with clear cytoplasm, a few scattered adipose cells, and thick-walled blood vessels. Moreover, the smooth muscle cells consisted of spindle-shaped cells or larger, more rounded cells with either clear cytoplasm or eosinophilic epithelioid cell features positive for vimentin, muscle-specific actin, and smooth muscle actin. HMB45 immunostaining confirmed the diagnosis of AML. The present case indicates that IPT or IPT-like FDC tumor should be added to the list of differential diagnoses for AML of the liver.     

Hepatic epithelioid angiomyolipoma with trabecular growth pattern: a mimic of hepatocellular carcinoma on fine needle aspiration cytology

Epithelioid angiomyolipomas (AMLs) of the liver are rare tumors with imaging and cytologic features overlapping with those of hepatocellular carcinomas. We report the fine needle aspiration and core biopsy findings of an epithelioid AML in the right hepatic lobe of a 32-year-old female with tuberous sclerosis. She had undergone renal transplantation 8 years previously after bilateral nephrectomy for renal AMLs and a 3-cm chromophobe renal cell carcinoma. Hepatocellular carcinoma was suspected during the initial cytologic and histologic examination based on the presence of numerous large polygonal cells with ample finely vacuolated or granular cytoplasm, low nucleocytoplasmic ratio, and mild nuclear pleomorphism in the smears, as well as a distinctive trabecular histologic pattern in the core biopsies. Immunoperoxidase stains showed that the neoplastic cells were negative for cytokeratins and positive for HMB45, Melan-A, and smooth muscle actin, establishing the diagnosis of epithelioid AML. To determine the distinguishing cytomorphologic features between epithelioid AML and HCC, we have compared the cytologic features of 15 cases of hepatic AML reported in the literature, including the present case, to the FNA cytologic findings of 38 consecutive cases of HCC diagnosed at out institution.     

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 α-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.     

Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma

Perivascular epithelioid cell tumours (PEComas) are a family of tumours including classic angiomyolipoma, lymphangioleiomyomatosis, and clear epithelioid cell tumours reported under a variety of names such as epithelioid angiomyolipoma, pulmonary and extrapulmonary clear cell sugar tumour, and PEComa. Our previous comparative genomic hybridization study of PEComas demonstrated recurrent chromosomal aberrations including deletions on chromosome 16p, where the TSC2 gene is located. In this study, we focused on the alteration of chromosome 16p, including TSC2. We collected ten sporadic and two tuberous sclerosis complex-associated PEComas, as well as 14 sporadic classic hepatic and renal angiomyolipomas (AMLs) as controls. We used 16 microsatellite markers distributed along chromosome 16p to test for allelic imbalances on chromosome 16p and at TSC2, and two markers for TSC1. Furthermore, we carried out immunohistochemical staining for phospho-p706K, phospho-AKT, and phospho-S6 to evaluate the effect of TSC2 alterations on the mTOR signalling pathway. Loss of heterozygosity (LOH) was found in 11 PEComas and involved the region of the TSC2 locus in seven. Six classic angiomyolipomas had allelic changes at chromosome 16p. Microsatellite instability was detected in two PEComas. The incidence of genetic aberrations was significantly higher in the PEComa group. Only one PEComa showed LOH at the TSC1 locus. Eleven PEComas and 13 AMLs revealed elevated phospho-p70S6K accompanied by reduced phospho-AKT. Five PEComas and eight classic angiomyolipomas were positive for phospho-S6. The phosphorylation profile indicates functional activation of the mTOR pathway through a disrupted TSC1/2 complex. Our observations of frequent deletion of TSC2 and the mTOR signalling pathway provide evidence that the oncogenetic lineage of PEComa, as a distinct TSC2-linked neoplasm, is similar to that of angiomyolipoma.     

Primary hepatic clear cell myomelanocytic tumor. Case report and review of the literature

A case of hepatic clear cell myomelanocytic tumor in a 31-year-old woman presenting clinically with abdominal pain is reported. Histopathologic examination showed a lesion characterized by a population of large epithelioid cells with clear or eosinophilic granular cytoplasm, rich in glycogen. Immunohistochemically, the tumor cells were positive for HMB-45, Melan-A and muscle-specific actin, but negative for epithelial markers, desmin, S-100 protein, and neuroendocrine markers. Ultrastructurally, the tumor cells had abundant glycogen, well-developed rough endoplasmic reticulum, microtubules and aberrant melanosomes. Clinical and pathologic features with a brief review of the relevant literature for hepatic CCMMT as a variant of perivascular epithelioid cell tumor (PEComa) are discussed.     

Hepatic angiomyolipoma: a series of six cases with emphasis on pathological-radiological correlations and unusual variants diagnosed by core needle biopsy

Hepatic angiomyolipoma is rare and may pose differential diagnostic difficulty, particularly if encountered in core needle biopsy. We studied 6 cases from 5 males and one female (median age, 48.6 yrs). All presented with non-specific symptoms or an incidentally discovered tumor mass. Two patients had a remote history of chemotherapy for hematological neoplasms (acute lymphoblastic leukemia and Hodgkin lymphoma respectively) and another had clear cell renal cell carcinoma and anaplastic pancreatic carcinoma diagnosed at autopsy without definable syndrome. None of the patients had evidence of the tuberous sclerosis complex or renal or other extra-renal angiomyolipoma. Three tumors were resected completely and three have been only biopsied and followed up. None of the resected cases recurred at a mean follow-up of 35 months. Histologically, tumors were classified as classical triphasic (1), lipomatous (2), epithelioid/oncocytoid (1), epithelioid trabecular (1) and myelolipoma-like (1). The adjacent liver parenchyma was normal in 3 cases, showed pigment cirrhosis in one case and mild fatty change in another case. One case had clinically diagnosed but histologically unverified cirrhosis. The initial diagnostic impression/frozen section was misleading in 5 of the cases and included vascular lesion, focal fatty change, myelolipoma, hepatocellular tumor and oncocytic neoplasm. All tumors expressed HMB45 and variably desmin. One epithelioid lesion expressed HMB45 and TFE3, but lacked desmin expression. In conclusion, hepatic angiomyolipomas are increasingly recognized as incidental findings during surveillance for cirrhosis or investigations for unrelated conditions. Awareness of their diverse morphological spectrum in liver biopsy is necessary to avoid misdiagnosis as hepatocellular carcinoma, metastatic melanoma or other malignant neoplasms.     

Comparative genomic hybridization study of perivascular epithelioid cell tumor: molecular genetic evidence of perivascular epithelioid cell tumor as a distinctive neoplasm

Perivascular epithelioid cell tumor (PEComa) is a neoplasm composed chiefly of HMB-45-positive epithelioid cells with clear to granular cytoplasm and a perivascular distribution. Such tumors have been reported in different organs under a variety of designations. The cytogenetic features of these neoplasms have not been well studied. We collected 9 tumors (5 of kidney, 1 of prostate, 1 of urinary bladder, 1 of the pelvic cavity soft tissue, and 1 of uterus) from 8 patients, including one patient with tuberous sclerosis complex. The paraffin blocks of tumor tissue were submitted for comparative genomic hybridization analyses. Gross chromosomal aberrances were observed in all cases. The frequent imbalances were losses on chromosome 19 (8 cases), 16p (6 cases), 17p (6 cases), 1p (5 cases), and 18p (4 cases) and gains on chromosome X (6 cases), 12q (6 cases), 3q (5 cases), 5 (4 cases), and 2q (4 cases). The frequent deletion of 16p in which TSC2 gene is located indicates the oncogenetic relationship of PEComas with angiomyolipoma as a TSC2-linked neoplasm. From a molecular genetic perspective, the recurrent chromosomal alterations in both renal and extrarenal tumors further support the concept of PEComa as a distinctive tumor entity regardless of anatomic location.     

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.     

Minute perivascular epithelioid cell (PEC) nests in the abdominal lymph nodes—a putative precursor of PEComa

A perivascular epithelioid cell tumor (PEComa) is a peculiar growth defined as a mesenchymal tumor composed of histologically and immunohistochemically distinct perivascular epithelioid cells (PECs). Because neither normal counterparts nor precursor lesions of PEComa have been identified, we examined minute PEC nests, ranged from 0.8 mm to 10 mm, to investigate the possible origin of the PEComa. We examined a total of 80 677 para‐aortic and pelvic lymph nodes that were systematically dissected from 1656 patients for gynecological malignancies. The identified lesions were confirmed immunohistochemically with multiple PEC markers, including smooth muscle actin, HMB45, melan‐A, MiTF, ER and PgR. A total of 66 minute PEC nests were found in 21 patients (1.3% of the total population) with an average frequency of 3.1 lesions per patient. In cases of multiple involvement, 11 of 13 nests were located at the same level of multiple lymph node or on continuous levels. The lesions were preferentially distributed at the level of para‐aortic and high pelvic lymph nodes. All nests were positive for actin and HMB45, whereas the other markers were positive with varying frequencies. The minute PEC nests may be associated with the possible normal counterpart of PEComas.     

Sclerosing variant of perivascular epithelioid cell tumor in the female genital organs

Perivascular epithelioid cell tumor (PEComas), other than angiomyolipoma, clear cell 'sugar' tumor of the lung, and lymphangioleiomyomatosis, is an uncommon mesenchymal neoplasm that arises in the soft tissue and visceral organs. We report herein two cases of sclerosing PEComa; a distinctive variant of PEComa, which is characterized by extensive stromal hyalinization, occurring in the uterus and broad ligament. The patients were 34- and 51-year-old females with no family history of tuberous sclerosis complex. Macroscopically, the tumors had white to gray cut surfaces and were microscopically composed of predominantly spindle- to polygon-shaped cells with clear to slightly eosinophilic cytoplasm and pleomorphic nuclei focally arranged in a perivascular pattern, accompanied by marked stromal hyalinization. These tumor cells were immunohistochemically positive for HMB45 and α-smooth muscle actin. Although this variant of PEComa is very rare, this entity should be considered as a potential primary neoplasm of the female genital organs.     

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.