Epithelioid sarcoma--immunohistochemical and ultrastructural study

Five cases of epithelioid sarcoma are reported, of which four were studied by immunohistochemistry and one by electron microscopy. Immunohistochemically, the results of cytokeratin showed that these four cases were positive to different degrees by polyclonal cytokeratin and three out of four revealed positive results with low molecular weight cytokeratin monoclonal antibody. Two cases were positive with carcinoembryonic antigen and the other two were negative. The immunohistochemical stain was helpful for differential diagnosis from other sarcomas, such as malignant fibrous histiocytoma and rhabdomyosarcoma. By electron microscopy, tumor cells could be divided into light and dark cells which possessed more or less cell organelles, intermediate microfilaments in the cytoplasm and numerous pinocytic vesicles lying along the cell membrane. The occasional presence of poorly developed desmosomes or the absence of tonofibril bundles and glandular structures can rule out the diagnosis of carcinoma. One of these cases was originally diagnosed as metastatic carcinoma to the skin by light microscopy, which was refuted by electron microscopy, and the keratin positive reaction by immunohistochemistry was helpful for the diagnosis of epithelioid sarcoma. Therefore, the authors suggest that immunohistochemical and electron microscopic studies be used for diagnosing difficult cases of epithelioid sarcoma. From our observation, we consider that the cells of epithelioid sarcoma may derive from undifferentiated mesenchymal cells possessing the potentials of differentiating into synovioblasts, histiocytes or fibroblasts.     

Va-es-bj - an epithelioid sarcoma cell-line

A tumor cell line was derived and established from a bone marrow aspirate of a 41-year-old male who presented with motor symptoms of cord compression and an epidural tumor with osseous, pulmonary and hepatic metastases. The epidural tumor was an epithelioid sarcoma staining positive for cytokeratin markers of epithelial differentiation AE-1 and AE-3. This cell line was composed of lowly refractile, multinucleated giant or mononuclear round or elongated cells with monopolar or bipolar short processes. When permitted to grow beyond confluence these cells clumped up and formed mounds progressing to free floating spheroids. The cells were characterized by chromosomal triploidy with marker chromosomes, rapid growth in nude mice and secretion of immunoreactive and biologically functional granulocyte macrophage colony stimulating factor. This epithelioid sarcoma cell line stained positive for AE-1, AE-3, vimentin, epithelial membrane antigen and was designated VA-ES-BJ.     

附睾腺瘤样瘤5例组织学和免疫组化观察

本文对5例附睾腺瘤样瘤的组织学和免疫组化特征进行了观察。结果表明，肿瘤对细胞角蛋白（cytokeratin）、上皮膜抗原（EMA）和波形蛋白（vementin）均呈阳性反应，对第八因子相关抗原（FvlllRAg）均呈阴性表达。这些结果明确揭示了肿瘤细胞的双向分化特征，进一步支持该瘤间皮起源的观点。在病理诊断中，该瘤须与上皮样血管瘤和腺癌进行鉴别。     

骨原发性上皮样血管肉瘤3例临床病理分析

目的:探讨3例骨原发性上皮样血管肉瘤的临床病理特点、诊断和鉴别诊断。方法:对3例发生于骨的上皮样血管肉瘤进行光镜、组织化学和免疫组化观察,并结合文献讨论。结果:3例肿瘤分别发生在颅骨、肋骨和骨盆,镜下肿瘤由具有上皮样特征的瘤细胞构成,细胞体积大,胞质丰富带有细小空泡,细胞核大,呈空泡状或受挤压呈印戒样,有明显核仁,核分裂象多见。瘤细胞在骨小梁间呈弥漫片状、腺管状、乳头状或单排条索状排列,有散在完整的红细胞或红细胞碎片的背景,可见形状不规则、大小不一互相交织的血管腔,其内衬上皮样瘤细胞,有的呈乳头状生长。网织纤维染色可清晰的显示瘤性血管结构,并见网织纤维围绕瘤细胞巢分布。免疫组化染色,肿瘤细胞呈上皮性标记物CKpan、高分子量角蛋白、低分子量角蛋白、EMA、间质标记物vimentin以及血管内皮细胞标记物vWF阳性,CD34、CD31弱阳性(考虑因脱钙导致该抗原严重丢失)。结论:骨原发性血管肉瘤是一种罕见的高度恶性肿瘤,诊断和鉴别诊断主要依赖其病理形态学特点结合免疫表型。     

Proximal-Type Epithelioid Sarcoma in the Groin Presenting as a Diagnostic Dilemma

Epithelioid sarcoma is an uncommon soft-tissue sarcoma typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Lately, a ‘proximal’ subtype has been described, which occurs in the pelvic and genital areas of somewhat older individuals and tends to behave more aggressively than the conventional subtype. The correct diagnosis of this subtype is essential, since this tumor can be easily mistaken for other malignant tumors that exhibit epithelioid morphology. We report a case of proximal-type epithelioid sarcoma that presented as an inguinal mass in a 47-year-old man. Histologically, the tumor consisted of diffuse sheets of epithelioid cells with scattered rhabdoid morphology. By immunohistochemistry, the neoplastic cells expressed cytokeratin, epithelial membrane antigen, vimentin, CD34, CD99 and showed complete loss of nuclear INI1 protein expression. Fluorescence in situ hybridization was considered borderline for 22q deletion. We present this case to emphasize the importance of diagnosing this uncommon tumor and the role of INI1 immunohistochemistry in establishing the diagnosis.     

Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations

The authors report three cases of sarcomatoid carcinoma arising in the stomach. This uncommon tumor is characterized by a mixture of malignant epithelial and spindle cell elements. All three tumors were large (average diameter, 5 cm) and infiltrated deep into the stomach wall. Two of the tumors had a polypoid configuration; the third was ulcerated and endophytic. Intestinal metaplasia was present adjacent to the tumor in all cases, with dysplasia in two. Immunohistochemical studies showed positivity for cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen in the epithelial component of all tumors, and Leu-M1 was positive in the epithelial component of one. The spindle cell components contained vimentin, and in tumor 2, the spindle cell component was also positive for desmin. Two tumors showed focal positivity for cytokeratin in the spindle cells immediately adjacent to the epithelial component. Ultrastructurally, the spindle cell component of two tumors was composed of undifferentiated cells without specific epithelial or mesenchymal features. The third tumor contained occasional cells with features of myofibroblasts.     

外阴上皮样肉瘤的临床分析

目的 探讨外阴上皮样肉瘤的临床特点、诊断治疗方法及预后.方法 对我院收治的4例和文献报道资料完整的16例外阴上皮样肉瘤患者进行回顾性分析.结果 20例外阴上皮样肉瘤患者年龄23～80岁,中位年龄36岁.肿物直径为1～10 cm,中位数为5.1 cm.免疫组化检测结果显示,20例外阴上皮样肉瘤患者vimentin阳性,19例CK阳性,16例EMA阳性.10例患者行双侧或同侧腹股沟淋巴结清扫,3例未行腹股沟淋巴结清扫.术后7例患者未补充治疗,13例患者行术后放疗和(或)化疗.20例外阴上皮样肉瘤患者中,无复发及转移11例(55.0%),腹股沟淋巴结转移治疗后存活2例(10.0%),死亡7例(35.0%).早期患者(Ⅰ～Ⅱ期)的中位生存时间(21个月)高于晚期患者(6个月,P＜0.05).10例行双侧或同侧腹股沟淋巴结清扫患者的中位生存时间为11.5个月,3例未行腹股沟淋巴结清扫患者的中位生存时间为6个月,差异无统计学意义(P=0.086).结论 外阴上皮样肉瘤误诊率较高,确诊时需要结合免疫组化检查,诊断上皮样肉瘤的标记性蛋白为vimentin、EMA和CK.外阴上皮样肉瘤的有效治疗方法为局部广泛切除加双侧腹股沟淋巴结清扫,手术切缘至少2 cm,化疗和放疗的疗效尚不确切.     

Sclerosing Epithelioid Fibrosarcoma–A Report of Two Cases with Cytogenetic Analysis of FUS Gene Rearrangement by FISH Technique

Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue sarcoma. Recently, a link has been suggested between SEF and low-grade fibromyxoid sarcoma (LGFMS) on the basis of the finding of the characteristic translocation t(7;16) (FUS-CREB3L2) of LGFMS in a small number of studied cases of SEF. The frequency of this translocation in SEF is still unknown. We present 2 cases of SEF with cytogenetic analysis for FUS rearrangement. The tumors occurred in 12 and 58 year old patients, respectively and consisted of a well to partially circumscribed, non-encapsulated mass, comprising monomorphic, polygonal cells arranged in aggregates, cords and single file arrays in a variably sclerotic stroma. The cells exhibited minimal nuclear atypia with moderate amount of clear to eosinophilic cytoplasm and rare mitotic figures. One case also showed bland spindle cell areas with myxoid change, as seen in LGFMS. By immunohistochemistry (IHC), the tumor cells were diffusely positive for vimentin, focally for S-100 in 1 case and negative for cytokeratin (CK), epithelial membrane antigen (EMA), HMB-45, desmin, smooth muscle actin (SMA), H-caldesmon, Myo D-1, CD34 and CD 168. By fluorescent in-situ hybridization (FISH) technique, the case with mixed SEF and LGFMS histology was positive for FUS rearrangement. Our study reinforces the previously reported relationship between SEF and LGFMS, and suggests that SEF may represent a variant of LGFMS in at least some cases, rather than an entirely distinct fibrosarcoma variant.     

Multidirectional differentiation in a newly established human epithelioid sarcoma cell line (GRU-1) with co-expression of vimentin, cytokeratins and neurofilament proteins.

A new permanent cell line (GRU-1) derived from the lymph-node metastasis of a human epithelioid sarcoma was established in tissue culture. Immunohistochemically, the original tumor had exhibited an intriguing potential for multidirectional differentiation with features of mesenchymal, epithelial and neural differentiation, evidenced by the co-expression of vimentin, cytokeratins and neurofilament proteins, respectively. This capability for multidirectional differentiation was fully preserved in the cultured cells. GRU-1 tumor cells proved to be uniformly positive for vimentin and a considerable proportion of the tumor cells exhibited a positive reaction for cytokeratins and neurofilament proteins. The neural markers neuron-specific enolase (NSE) and synaptophysin were observed in a small proportion of GRU-1 cells. Ultrastructurally, GRU-1 cells showed desmoplastic activity in vitro, being enmeshed by collagen fibrils. DNA distribution, as studied by flow cytophotometry, revealed DNA-diploidy (DNA index = 1) and a G0/G1-proportion of 70.5%. After heterotransplantation in nude mice, GRU-1 tumor cells expressed vimentin and cytokeratin only, whereas the neural markers could not be further demonstrated.     

骨外黏液样软骨肉瘤研究进展

骨外黏液样软骨肉瘤（ex-traske-letal myxoid chondrosarcoma,EMC）是一类罕见的软组织恶性肿瘤,主要发生于四肢深部。其组织病理学为分叶状结构,肿瘤细胞排列成丝带状由小叶周边向中心放射状分布;电镜下部分肿瘤细胞质内可见神经内分泌颗粒;免疫组化显示肿瘤细胞表达波形蛋白（vi mentin）,部分表达NSE、Syn、CgA及S-100,CK和EMA可灶性表达于上皮样分化区。其粘液样基质奥新兰染色阳性,并抗透明质酸酶。由于该肿瘤生长缓慢,局部复发率高,使肿瘤细胞发生退变或间变,从而形成复杂的病理组织学图像,极易造成病理诊断错误,须与骨黏液样软骨肉瘤、脊索瘤及软组织多种黏液性肿瘤鉴别。由于该肿瘤有特异性的细胞遗传学改变,因此,目前主要研究方向为筛选出最为特异性的肿瘤融合基因作为病理诊断指标,并找出基因治疗的有效途径。     

Carcinosarcoma of the colon. Report of a unique case with light and immunohistochemical studies

A unique case of carcinosarcoma of the colon is reported. The tumor invaded the bowel wall deeply, metastasized widely, resisted multi-agent chemotherapy, and caused the patient's death 4 years later. The tumor was composed of adenosquamous carcinoma admixed with sarcoma showing osseous, cartilaginous, and nonspecific spindle-cell differentiation. Although carcinoembryonic antigen appeared limited to carcinoma cells, cytokeratin immunoreactivity was observed in both carcinoma and sarcoma cells. Like carcinosarcomas at other body sites, the finding of cytokeratin in sarcoma cells supports partial epithelial differentiation in this component, likely retained from carcinoma precursor cells.     

上皮样肉瘤的病理诊断与鉴别诊断

目的探讨上皮样肉瘤的病理特点及鉴别诊断。方法13例上皮样肉瘤,男9例,女4例,年龄10～45岁。病变主要位于前臂、手掌和手指。行显微镜下观察组织形态特点并结合免疫组化染色结果进行分析。结果组织学表现为肿瘤细胞由恶性上皮样细胞和梭形细胞组成,呈结节样排列并伴有中心坏死。所有瘤组织CK、EMA和Vimentin均为阳性表达。结论上皮样肉瘤无特异性症状和体征,病理学特点及鉴别诊断应紧密结合临床表现和免疫组化结果。     

Primary epithelioid angiosarcoma of the adrenal gland case report and review of the literature.

Primary angiosarcoma of the adrenal gland is extremely rare. Here, we report on a 70-year-old man with an angiosarcoma of the right adrenal gland who died 3 weeks after tumor resection due to intestinal infarction and acute renal failure. No metastases were found at autopsy. Histologically, the tumor showed a predominantly epithelioid differentiation. Immunohistochemical examination revealed positive reactivity for cytokeratin, epithelial membrane antigen, vimentin, factor VIII-related antigen, CD31, CD34 and Ulex europaeus agglutinin-I. Features of endothelial origin were also demonstrable by electron microscopy. The differential diagnosis of this uncommon neoplasm is discussed. The present case emphasizes problems in differential diagnosis that arise from its epithelioid differentiation. A review of the literature underlines the poor clinical outcome of adrenal angiosarcoma.     

CA125 expression in epithelioid sarcoma

OBJECTIVE: There has been no report on useful immunohistological markers for epithelioid sarcoma (ES) so far. The purpose of this study is to evaluate the positivity and specificity of CA125 as a marker for the correct diagnosis of ES. METHODS: This study was performed in 11 patients with ES (nine men and two women; distal type: 10 cases; proximal type: one case), 78 patients with other soft tissue tumors and nine with benign granulomas. The other soft tissue tumors consisted of six synovial sarcomas, six clear cell sarcomas, eight leiomyosarcomas, six rhabdomyosarcomas, five malignant peripheral nerve sheath tumors, ten malignant fibrous histiocytomas, 17 desmoid tumors, 14 liposarcomas, six squamous cell carcinomas (cutaneous SCC of the distal extremities), two rheumatoid nodules and seven foreign body granulomas. Immunohistochemical analysis for CA125 was performed for these 89 soft tissue tumors and nine granulomas using a labeled streptavidin biotin method. Immunohistochemical analysis of epithelial membrane antigen, cytokeratin, carcinoembrionic antigen, vimentin and CD34 was performed only for the 11 ES patients. RESULTS: CA125 was strongly expressed in 10 out of the 11 ES patients. EMA, cytokeratin and vimentin were also positive in all the cases. CEA was positive in two of the 11 patients. Immunohistochemical study in six ES patients showed expression of CD 34. The other 78 soft tissue tumors and nine granulomas did not express CA125. CONCLUSION: This study clearly revealed the specificity and positivity of CA125 in ES. These data indicate that CA125 may be a useful tumor marker for diagnosing ES.     

Adenomatoid tumor of the ovary: an immunohistochemical and ultrastructural study

A rare case of adenomatoid tumor arising in the ovary is presented. At autopsy on a 61-year-old woman, a soft, solid and cystic tumor, measuring 0.8 X 0.7 cm, was detected in the hilus of the left ovary. Light microscopic study showed characteristic features of adenomatoid tumor. Alcian blue stain, with and without hyaluronidase pretreatment, revealed the presence of hyaluronic acid on the luminal surface and in the vacuoles of the tumor cells. Immunohistochemical stains of tumor cells were positive for low-molecular-weight cytokeratin (PKKL), vimentin, and carbohydrate antigen (CA) 125, whereas they were focally positive for high-molecular-weight cytokeratin (34 beta E12). They were negative for factor VIII-related antigen (FVIII-RAG), Ulex europaeus I lectin (UEA I), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Ultrastructural studies disclosed surface microvilli and bundles of tonofilaments. These observations strongly support the idea of this tumor being of mesothelial origin.     

Carcinosarcoma of the stomach

In the gastrointestinal tract, carcinosarcomas are most frequently seen in the esophagus. Carcinosarcoma in the stomach is a rare tumor. We report a carcinosarcoma of the antrum of stomach. The tumor was polypoid and exophytic in appearance and located in the antrum. Immunohistochemical studies showed positivity for cytokeratin, epithelial membrane antigen and cytoplasmic carcinoembryonic antigen in the epithelial component. Positive staining with vimentin, desmin and focal smooth muscle actin and negative staining with chromogranin were observed in spindle cells. Nuclear positive staining was observed with p53 and Ki-67 in both glandular and spindle atypical cells.     

Kaposiform hemangioendothelioma of the spleen in an adult: an initial case report

Kaposiform hemangioendothelioma (KHE) is a rare locally aggressive vascular neoplasm characterized by infiltrating nodules and sheets of spindle cells, and unmistakable resemblance to Kaposi's sarcoma. KHE occurs mainly in newborns and infants and presents most commonly in the skin, deep soft tissue, and bone. We report a case of KHE in a 36-year-old female who presented with a spleen mass and underwent splenectomy. Macroscopic examination revealed a large, dark-red, firm mass in the spleen. Histologically, the tumor consisted of irregular, infiltrating nodules of densely packed spindle-shaped tumor cells closely associated with small slit-like and sieve-like blood vessels, which were separated with hyalinized hypocellular fibrous stroma. Immunohistochemically, both spindle and epithelioid cells were positive for CD34, CD31, and vimentin, but negative for EMA, cytokeratin, CD21, CD35, CD1a, and S-100 protein. The well-formed capillaries and mature vessels but not spindle tumor cell showed reactivity for factor VIII- related antigen. Alpha-Smooth muscle actin was detected in pericytes surrounding small round or slit-like capillaries. The final histologic diagnosis was KHE. Follow-up 6 month after operation revealed no sign of recurrence or metastasis.To the best of our knowledge, this is the first report of KHE arising in the spleen.     

Epithelioid angiosarcoma of the adrenal gland with cytokeratin expression. Report of a case with accompanying mesenteric fibromatosis.

A case report of epithelioid adrenal angiosarcoma is presented. Tumor cells showed expression of cytokeratin, Factor VIII-related antigen, Ulex europaeus agglutinin-I, and vimentin. The patient also was found to have mesenteric fibromatosis (abdominal desmoid tumor) and an elevated serum level of estradiol. The authors discuss the unique appearance of these rare tumors, their relationship to hyperestrinism, and review the recent data in the literature showing cytokeratin expression by malignant epithelioid vascular tumors.     

Interclonal heterogeneity in a human epithelioid-sarcoma cell line (Gru-1)

Three clonal sub-populations, GRU-IA, GRU-IB, and GRU-IC, isolated from the human epithelioid sarcoma cell line GRU-I, were characterized morphologically, cytogenetically and with regard to proliferation kinetics. Immunocytochemically, major differences became evident in the expression of cytokeratin 18 and neurofilament proteins, which are indicative for epithelial and neural differentiation respectively. Vimentin, a mesenchymal differentiation marker, however, could be detected in all tumor cells of each sub-population. Laminin, a major compound of basement membranes, formed abundant intercellular network-like patterns in GRU-IB and GRU-IC, whereas GRU-IA was characterized by a diffuse intracellular reaction, suggesting a disorder in laminin secretion. Cytogenetically, all sub-populations proved to be DNA-aneuploid, the DNA index ranging from 1.4 to 1.5. Proliferation analysis revealed doubling times ranging from 13 (GRU-IC) to 19 hr (GRU-IA). These strictly defined clonal sub-populations provide a valuable tool for further investigations of the biological behavior of human epithelioid sarcoma with special regard to tumor heterogeneity. © 1994 Wiley-Liss, Inc.