Gastrointestinal stromal tumours can express CD10 and epithelial membrane antigen but not oestrogen receptor or HMB45

Wong N A C S & Melegh Z
(2011) Histopathology 59 , 781–785 Gastrointestinal stromal tumours can express CD10 and epithelial membrane antigen but not oestrogen receptor or HMB45 Aims: Gastrointestinal stromal tumour (GIST) may share morphological and/or immunohistochemical features with various intra‐abdominal neoplasms, including endometrial stromal sarcoma, perivascular epithelioid cell tumour (PEComa), melanoma and synovial sarcoma. Each of these various neoplasms has characteristic immunohistochemical markers, including epithelial membrane antigen (EMA), CD10, oestrogen receptor alpha (ERa) and/or HMB45, and therefore the primary aim of this study was to determine whether these markers are also expressed by GISTs. Methods and results: Standard size sections of 52 GISTs were immunostained for EMA, CD10, ERa and a melanoma marker cocktail (targeting HMB45 and melan‐A). Ten GISTs (19%) showed CD10 immunopositivity. This positivity was confined almost completely to small intestinal GISTs, and was seen among spindle cell GISTs but not epithelioid or mixed cell‐type GISTs. Five of the 52 GISTs (9.6%) showed EMA immunopositivity. This positivity was always focal and usually seen in a perivascular location. None of the GISTs showed immunopositivity for ERa or the melanoma marker cocktail. Conclusions: GISTs occasionally show CD10 immunopositivity (especially small intestinal spindle cell GISTs), and infrequently show focal EMA positivity. GISTs do not show immunopositivity for ERa or HMB45.     

Retroperitoneal PEcoma (angiomyolipoma) composed exclusively of epithelioid lipoblastic-like cells: a diagnostic conundrum on needle biopsy

Angiomyolipomas are one of several distinct entities that belong to the “PEComa” (perivascular epithelioid cell tumour) family that comprise varying degrees of fatty, smooth muscle and vascular components. Angiomyolipomas occurring in the retroperitoneum are relatively uncommon; however, when all of the three components are represented, the diagnosis can be readily made. Herein, we report the first case of a retroperitoneal angiomyolipoma composed exclusively of epithelioid and lipoblast-like cells. An extra-renal retroperitoneal mass was biopsied and revealed a relatively uniform population of epithelioid cells arranged in sheets separated by both a delicate vascular network and vessels of larger calibre. The tumour cells were small to medium in size with mild nuclear pleomorphism and cytoplasmic vacuolization ranging from multiple large vacuoles to larger vacuoles, resembling lipoblasts. Occasional nuclei were seen to have prominent clear nuclear pseudo-inclusions. Immunohistochemistry revealed the cells to be strongly positive for SMA and focally positive for HMB45, MiTF and S100. The tumour cells were negative for AE1/AE3, CAM5.2, CD45, Pax8, SF-1 and TFE3. Angiomyolipomas in the retroperitoneum share morphological similarities with a wide variety of tumours, chiefly liposarcoma. Awareness of angiomyolipomas composed purely of epithelioid and lipoblast-like cells is essential to avoid misdiagnoses.     

Kba.62 and S100 protein expression in cytologic samples of metastatic malignant melanoma

The diagnosis of melanoma can be challenging, especially in metastatic lesions, due to the ability of melanoma cells to morphologically mimic carcinoma, sarcoma and even lymphoma cells. Moreover, melanomas can exhibit negative immunostaining for the melanoma markers HMB‐45 and MART‐1/Melan‐A, often used in the diagnosis of this tumor. KBA.62 is a recently described antibody that reacts with benign and malignant melanocytic proliferations. In this study, we report our experience with KBA.62 and S100 protein immunostaining in the diagnosis of metastatic melanoma on fine‐needle aspiration and effusion samples. We reviewed 60 cytology samples from 58 patients with metastatic melanoma. Our results showed that KBA.62 stained 75% of the cases and S100 protein 87% of the cases. KBA.62 and S100 protein stained the majority of metastatic melanomas that were negative for HMB‐45 and MART‐1; KBA.62 stained 73% of the cases and S100 protein 73% of the cases. The majority (85%) of the cases negative for HMB‐45 and MART‐1 were positive for KBA.62 and/or S100 protein. Additionally, we also observed that KBA.62 staining was positive in the majority of epithelioid and spindle cell type melanoma cells. In conclusion, the performances of KBA.62 and S100 protein were similar and both markers are useful in the diagnosis of metastatic melanoma in cytology material, especially when the tumor cells lack expression of HMB‐45 and MART‐1. Diagn. Cytopathol. 2013;41:847‐851. © 2013 Wiley Periodicals, Inc.     

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.     

Perivascular epithelioid cell tumor of the rib

We present a rare case of perivascular epithelioid cell tumor (PEComa) in the right 6th rib of a 28-year-old man. A plain computed tomography scan showed a round osteolytic lesion in the right 6th rib. The resected tissue contained a globular-shaped, soft tumor. Histologically, the tumor was rich in vasculature and exclusively composed of perivascular epithelioid cells with clear cytoplasm. Immunohistochemically, the tumor expressed diffusely a melanocyte marker, human melanoma black-45, and focally a myogenic marker, alpha-smooth muscle actin, but not an epithelial marker, AE1/AE3. Fontana-Masson-positive melanin pigments were present and c-kit receptor tyrosine kinase (CD117), involved in the development of melanocytes but not myogenic cells, was expressed in tumor cells. These findings indicate that the tumor is PEComa with some differentiation into melanocytes. Notably, owing to the unique location of the occurrence, the tumor occupied bone marrow tissues of the rib, resulting that the tumor has the potential for hematogenous metastasis. In spite of the lack of cells with severe atypia, necrosis, and numerous mitoses, tumor cells invaded into surrounding tissues and overexpressed cyclin D1. To the best of our knowledge, this is the first case report of PEComa arising from the rib with the signs of malignant potential.     

硬化性上皮样纤维肉瘤的临床病理学观察

目的探讨硬化性上皮样纤维肉瘤的临床病理学特征、免疫表型及鉴别诊断.方法应用光镜和免疫组织化学LSAB法对8例硬化性上皮样纤维肉瘤进行临床病理学分析和免疫表型检测.结果患者均为成年人,男性5例,女性3例,年龄35～54岁(平均45岁).临床上表现为深部软组织内缓慢性生长的肿块,其中大腿/臀部3例,右上臂/肩部2例,胸壁和背部2例,小腿1例.大体上,肿块呈结节状,境界相对清楚,直径2.0～10.5 cm(平均6 em),切面呈灰白色,质地坚韧或有弹性.组织学上,肿瘤由形态一致、小至中等大的圆形或多边形上皮样细胞组成,多呈单个或狭窄的条索状排列,夹杂于大量嗜伊红色、玻璃样变的胶原纤维之间.部分区域中也可排列成巢状、片状或腺泡状.高倍镜下,瘤细胞的胞质透亮或嗜伊红色,核异型性不明显,核分裂象也少见(＜1/10HPF).另在2例肿瘤的局部区域,细胞密度明显增加,核有显著的异型性,核分裂象也易见,类似经典的纤维肉瘤.免疫组织化学标记显示,瘤细胞弥漫强阳性表达波形蛋白,灶性或弱阳性表达上皮膜抗原,不表达细胞角蛋白、S-100蛋白、HMB45、肌动蛋白、结蛋白、CD34、bcl-2、CD30和白细胞共同抗原(LCA)等标记.随访6例,3例复发,1例发生肺部转移.结论硬化性上皮样纤维肉瘤是纤维肉瘤的一种少见亚型,尽管瘤细胞异型性不明显,核分裂象也少见,但肿瘤可发生局部复发及远处转移,临床上应视为一种低至中度恶性的软组织肉瘤处理,组织学上则应注意与一些具有上皮样形态和硬化性间质的肿瘤相鉴别.     

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.     

High-grade extraskeletal myxoid chondrosarcoma: a high-grade epithelioid malignancy

AIMS: Extraskeletal myxoid chondrosarcoma is typically a low-to-intermediate grade sarcoma that is associated with a prolonged clinical course. High-grade forms are rare and not well characterized. In this series we report the clinicopathological, immunohistochemical and ultrastructural findings in four cases of high-grade extraskeletal myxoid chondrosarcoma. METHODS AND RESULTS: The patients were three men and one woman (ages 34-73 years) with tumours located in the thigh (two cases), paraspinal soft tissue and perineum. Three patients had metastases, one at 12 weeks, one at 10 months, and one at presentation of recurrent tumour. In the latter case the original tumour was low grade and became high grade when it recurred 3.5 years later. All three patients died of disease. One patient was lost to follow-up. The most striking histological feature in all four tumours was the presence of numerous large epithelioid cells. These cells were arranged in cords within myxoid matrix and in sheets devoid of matrix. Two tumours had areas of conventional extraskeletal myxoid chondrosarcoma intermixed with the high-grade areas. One tumour showed transition to high-grade spindle cell sarcoma. One tumour had cells with rhabdoid features. Immunohistochemically, two tumours focally expressed S100 protein, and one focally expressed EMA. All were negative with cytokeratin, desmin, smooth muscle actin, HMB45, CD31 and CD34. Ultrastructural features in three cases were compatible with chondrosarcoma; one tumour had aggregates of microtubules within rough endoplasmic reticulum, a characteristic feature of this tumour. CONCLUSIONS: High-grade extraskeletal myxoid chondrosaroma is a rare and aggressive soft tissue sarcoma, and should be included in the differential diagnosis of other epithelioid malignancies.     

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.     

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.     

Digestive PEComas: a solution when the diagnosis fails to "fit"

We report two cases of digestive/intra-abdominal PEComa. The first lesion developed in the caecum of a 36-year-old woman, the second in the pararectal region of a 35-year-old woman. The first tumor was formed from spindle cells arranged in fascicles, the second contained predominantly epithelioid cells with prominent nucleoli. Immunohistochemically, tumor cells expressed smooth muscle actin and melanocyte markers (HMB45), S-100 protein and CD117 were negative. Based on the morphologic aspect and, above all, on the immunohistochemical study the diagnosis of PEComa was retained for both lesions. In the gastrointestinal tract, the principal differential diagnoses of PEComas are gastrointestinal stromal tumors, particularly the round cell/epithelioid subtype, and metastases of carcinoma and melanoma. Other differential diagnoses include rhabdomyosarcoma, paraganglioma, leiomyosarcoma, and clear cell sarcoma.     

Perivascular epithelioid cell tumor (PEComa) of the liver: a case report and review of the literature

Perivascular epithelioid cell tumor (PEComa) is rare entity and has been described only recently. By immunohistochemistry and genetics it belongs to the family of tumours which comprises angiomyolipoma, clear cell "sugar" tumor of lung, lymphangioleiomyomatosis and clear cell myomelanotic tumor of ligamentum falciforme/teres hepatis. We describe an unusual case of hepatic PEComa arising in a 55-year-old woman with previous history of glioblastoma. Histologically the tumor grew in expansive way, and was composed of clear and eosinophilic epithelioid cels, without vascular or lipomatous component characteristic of angiomyolipoma. There was mild nuclear pleomorphism, sporadic mitotic activity and haemorrhage without necrosis. On immunohistochemistry, the tumor was HMB-45+50, Melan-A and smooth muscle actin positive. Tyrosinase, S-100 protein, cytokeratin coctail, EMA, vimentin, muscle specific actin, CD10, TTF-1, hepatocyte, desmin and cyclin D1 were negative. Sporadic nuclear p53 positivity was seen. The main differential diagnosis of hepatic PEComa includes clear cell variant of liver cell adenoma and hepatocellular carcinoma, metastases of various clear cell carcinomas and metastasis of malignant melanoma. In respect of uncertain biologic potential of PEComa, long term follow up is indicated.     

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.     

Malignant perivascular epithelioid cell tumour of the fibula: a report and a short review of bone perivascular epithelioid cell tumour

Perivascular epithelioid cell tumour (PEComa) is a term applied to a family of mesenchymal tumours composed of varying proportions of spindle and epithelioid cell components associated with HMB-45 expression. PEComa rarely arises in the soft tissue, visceral organs, skin and bone. This report details an instance when a purely epithelioid PEComa arose from the right fibula of a 52-year-old Chinese woman without features of tuberous sclerosis complex. The excision specimen disclosed an epithelioid tumour with a nested pattern associated with areas of nuclear pleomorphism, mitotic activity, necrosis and vascular invasion in addition to HMB-45 expression on immunohistochemistry. To the best of the authors' knowledge, this represents the first case of a histologically malignant PEComa of the bone. A short review of primary bone PEComas and potential problems in diagnosis is presented.     

Epithelioid angiosarcoma of the kidney: a diagnostic dilemma in fine-needle aspiration cytology

Epithelioid angiosarcomas (EAS) of kidney are rare and aggressive tumors with noncharacteristic imaging features that overlap with those of inflammatory conditions and renal cell carcinoma (RCC). We report the fine-needle aspiration (FNA) cytology findings of a case of EAS that involved the left kidney of an 83-year-old male. The smears and cell block sections showed pleomorphic epithelioid cells with ample cytoplasm, eccentric nuclei, occasional cytoplasmic hyaline globules, and rare intracytoplasmic lumina. Immunohistochemical stains performed on cellblock sections showed that the tumor cells were positive for vimentin, CD31, CD34, Factor VIII, and CD10, but showed no staining for cytokeratins AE1/AE3 and 8/18, HMB45, CD45, smooth muscle actin, and S100. The morphological and immunohistochemical distinction between EAS, primary tumors of the kidney, and other epithelioid and rhabdoid neoplasms is discussed.     

Hemangioblastoma of pelvic cavity: report of a case and review of literature

Hemangioblastoma of soft tissue is a very rare tumor of uncertain histological type. Herein, we reported a 51-year-old woman was found to have a solid and cystic mass measuring 31×30 mm in the right adnexa area on a computed tomography scan. The tumor showed the typical histology of hemangioblastoma. Tumor was composed of numerous capillaries and stromal cells with cytoplasmic vacuolization. Immunohistochemical study revealed that the tumor stromal cells were positive for CD56, S-100 protein, NSE, Syn, CgA, and inhibin-α. Focal EMA positivity was present. Ki-67 expression was found in approximately 1% of tumor cells. The tumor cells were negative for CK, HMB-45, Melan-A, SMA, and CD68. The differential diagnosis of Hemangioblastoma arising in pelvic cavity includes hemangioma, hemangioendothelioma, liposarcoma, renal cell carcinoma, fat-forming solitary fibrous tumor, paraganglioma, and perivascular epithelioid cell tumor (PEComa).     

Epithelioid smooth muscle tumors of the uterus do not express CD1a: a potential immunohistochemical adjunct in their distinction from uterine perivascular epithelioid cell tumors

Uterine epithelioid smooth muscle tumors and uterine perivascular epithelioid cell tumors (PEComas) are known to display such a substantial overlap in morphologic and immunophenotypic characteristics that the existence of the latter as a distinct clinicopathologic entity at this location has been called into question. Recent research suggests that the constituent entities of the PEComa family at all anatomical locations, including lymphangioleiomyomatosis of the uterus, uniformly display immunoreactivity for CD1a. The purpose of this study is to determine the proportion of uterine epithelioid smooth muscle tumors that may similarly be CD1a-positive. Representative sections from 18 archived epithelioid smooth muscle tumors of the uterine corpus (6 epithelioid leiomyosarcomas and 12 epithelioid leiomyomas), diagnosed and classified as such based on World Health Organization criteria, were subjected to immunohistochemical stains for CD1a and HMB-45. The epithelioid component of the tissue sections evaluated ranged from 10% to 100% (mean, 70%). Two cases were composed predominantly of cells with overtly clear cytoplasm. All cases were entirely negative for CD1a. Of 18 cases, 1 (5.5%) (an epithelioid leiomyosarcoma) displayed immunoreactivity for HMB-45 in scattered lesional cells that constituted approximately 5% of the overall tumoral volume for the case. All others were HMB-45-negative. Given their rarity, future studies are required to confirm that all PEComas of the uterus are indeed uniformly positive for CD1a. However, if the latter staining pattern is confirmed, our findings herein suggest that CD1a may be a useful immunohistochemical adjunct in distinguishing uterine epithelioid smooth muscle tumors from uterine PEComas.     

Adenomatoid tumour of the liver

An unusual primary adenomatoid tumour arising in the normal liver is described. Hepatectomy was performed, and the patient is alive and free of disease 1 year postsurgery. Grossly, the tumour showed a haemorrhagic cut surface with numerous microcystic structures. Histological examination revealed cystic or angiomatoid spaces of various sizes lined by cuboidal, low-columnar, or flattened epithelioid cells with vacuolated cytoplasm and round to oval nuclei. The epithelioid cells were entirely supported by proliferated capillaries and arteries together with collagenous stroma. Immunohistochemical studies showed that the epithelioid cells were strongly positive for a broad spectrum of cytokeratins (AE1/AE3, CAM5.2, epithelial membrane antigen and cytokeratin 7) and mesothelial markers (calretinin, Wilms' tumour 1 and D2-40). These cells were negative for Hep par-1, carcinoembryonic antigen, neural cell adhesion molecule, CD34, CD31 and HMB45. Atypically, abundant capillaries were observed; however, the cystic proliferation of epithelioid cells with vacuoles and immunohistochemical profile of the epithelioid element were consistent with hepatic adenomatoid tumour.     

Clear cell sarcoma of soft tissue in right parapharyngeal region: report of a rare case

Clear cell sarcoma (CCS), initially named malignant melanoma of soft parts, is a rare malignant neoplasm typically involving deep soft tissue of the extremities, in close proximity to tendons and aponeuroses. Here we describe a case of clear cell sarcoma of the right parapharyngeal region in a young female aged 20 years. MRI detected a mass about 4.4 cm×3.4 cm×3.0 cm, located in the right parapharyngeal area and between the external pterygoid and the medial pterygoid. Microscopically, most of the tumor cells were epithelioid with palely eocinophilic cytoplasm arranged in sheets. Pleophorism of tumor cells were not marked. Immunohistochemical analysis shows that the tumor cells were positive for vimentin, S-100, HMB45 and MelanA, and negative for AE1/AE3, actin-sm, desmin, CD117, TFE-3, and P63. Ki67 index was about 5%.