A case of pulmonary malignant epithelioid hemangioendothelioma misdiagnosed as adenocarcinoma by fine needle aspiration cytology

Malignant epithelioid hemangioendothelioma (MEHE) is a rare vascular tumor with a biological behavior that lies between those of classical epithelioid hemangioendothelioma and angiosarcoma. Furthermore, MEHE is rarely diagnosed by fine needle aspiration cytology. The authors describe the cytological features of MEHE in a 41-year-old man who presented with increasing dyspnea over a period of 1 month before admission. Computed tomography of the chest showed a 3 cm poorly defined mass in the right lower lobe. Fine needle aspiration cytology demonstrated cellular smears of loosely cohesive clusters of epithelioid cells with numerous intracytoplasmic lumens in a necrotic background. Cellular features included fine chromatin and vesicular or slightly hyperchromatic nuclei with inconspicuous nucleoli and intranuclear inclusions. Nuclear membranes were relatively irregular with indentation. Mean N/C ratio was not increased, presumably due to a moderate amount of cytoplasm. The histologic examination displayed epithelioid and spindle cell proliferation with necrosis accompanying a classical epithelioid hemangioendotheliomatous area. The immunohistochemical evaluation was confirmatory and showed immunoreactivity for vascular markers. The authors also reviewed FNAB findings of epithelioid angiosarcoma, primary adenocarcinoma, and bronchioloalveolar carcinoma of the lung to identify cytomorphologic differences by literature bases. MEHE of the lung is difficult to diagnose cytologically because of its rarity and its cytomorphologic similarities with other malignant epithelial and mesenchymal tumors. However, it may be possible to distinguish it from other entities when the possibility of this unusual vascular neoplasm is suspected and ancillary studies are supportive.     

Fine‐needle aspiration of metastatic radiation‐induced cutaneous epithelioid angiosarcoma of the breast to the liver: A diagnostic dilemma

Radiation therapy is a significant risk factor for the development of angiosarcoma. With the increase in breast conservation treatment, the incidence of cutaneous radiation‐induced angiosarcoma of the breast is rising. If the angiosarcoma demonstrates epithelioid features, the tumor cells may present a diagnostic dilemma on fine‐needle aspiration cytology. We present a case of metastatic radiation‐induced cutaneous epithelioid angiosarcoma of the breast to the liver and a review of the literature. Diagn. Cytopathol. 2010;38:768–771. © 2010 Wiley‐Liss, Inc.     

Cytopathologic features of hepatic epithelioid hemangioendothelioma

We present the cytological features of hepatic epithelioid hemangioendothelioma (EH), which is considered to be a vascular proliferation of intermediate malignant potential. The case report concerns a 52-yr-old previously healthy man discovered to have multiple hepatic masses upon evaluation for abnormal liver function tests. Fine-needle aspiration demonstrated a neoplasm composed of interanastomosing epithelioid cells that contained intracytoplasmic lumens. Histologic sections, immunohistochemistry, and ultrastructural evaluation were confirmatory. Although hepatic EH is a rare tumor, its characteristic cytological, histological, and ultrastructural features permit a straightforward diagnosis. It is important to distinguish this entity from adenocarcinoma and angiosarcoma because long-term disease-free survival is possible, especially in the setting of orthotopic liver transplantation. Diagn. Cytopathol. 17:50–53, 1997. © 1997 Wiley-Liss, Inc.     

Epithelioid angiosarcoma: A neoplasm with potential diagnostic challenges

Epithelioid angiosarcomas are extremely rare tumors associated with poor prognosis and early metastases. Its epithelioid cytomorphology and limited vasoformation make it difficult to distinguish from more common malignancies, such as, carcinoma. This can be a potential diagnostic pitfall for the cytopathologist. In this report, the patient is a 24‐year‐old man presenting with testicular pain, a pelvic mass, and innumerable liver nodules. Immediate interpretation of the needle core biopsies of the pelvic mass and liver lesions initially favored a poorly differentiated adenocarcinoma. Unusual positive immunohistochemical stains for CD30 and CK7 ultimately led the investigation toward a tumor of mesenchymal origin. Further, immunohistochemical evaluation demonstrated positive CD31 and Factor VIII staining and established the final diagnosis of epithelioid angiosarcoma. The tumor cells were negative for CD34, CK20, alpha‐fetoprotein, placental‐like alkaline phosphatase, hepatocyte paraffin 1, polyclonal carcinoembryonic antigen, CD10, CA‐125, prostate‐specific antigen, and prostatic acid phosphatase. This case is reported to illustrate the importance of considering the diagnosis of epithelioid angiosarcoma when encountering an “epithelioid” neoplasm particularly with unusual immunoreactivity for CK7 and CD30. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Fine needle aspiration biopsy of epithelioid hemangioendothelioma of the oral cavity: report of one case and review of literature

Epithelioid hemangioendothelioma (EHE) is an uncommon vascular tumor with biological behavior intermediate between hemangioma and angiosarcoma. It rarely occurs in the oral cavity. We report a case of an 81-yr-old woman with a 2-mo history of a 2 x 2 cm2 submucosal buccal mass. Fine needle aspiration (FNA) smears were paucicellular and showed mainly single atypical large epithelioid cells in a bloody background. The atypical cells had abundant dense cytoplasm, some with fine vacuoles. Occasionally, cells with large cytoplasmic lumina were seen. Cytology preparations from fresh tissue received for frozen section revealed numerous neoplastic cells with large intracytoplasmic lumina, some of which contained red blood cells. In addition, cells with distinct intranuclear inclusions were present. Histologic sections and immunohistochemical stains confirmed the diagnosis of EHE. Although the histologic features of EHE are well recognized, reports of FNA cytology findings are sparsely existent in the literature as several case reports. The characteristic cytological features of EHE are reviewed in this report. We believe that the diagnosis of this rare tumor can be suggested when an adequate FNA specimen is obtained.     

Epithelioid angiomyolipoma of kidney with atypical nuclear features and intranuclear inclusions on cytology

Described herein are the cytological findings of epithelioid angiomyolipoma (EAML) of the kidney with atypical nuclear features mistaken for renal cell carcinoma (RCC) in a 61‐year‐old male patient. Aspirates from this large renal mass were cellular and showed epithelioid cell clusters with focally crowded nuclei showing moderate anisonucleosis, small nucleoli, and prominent eosinophilic intranuclear inclusions. Failure to recognize the scanty adipose tissue component and preponderance of epithelioid cells with nuclear pleomorphism lead to a diagnosis of RCC on cytology. On histology, the tumor was essentially composed of epithelioid and spindle cells that showed the typical immunoprofile of an angiomyolipoma and only occasional foci of typical AML were seen. The hilar lymph node was involved in contiguity. However, in view of lack of obvious features of malignancy, the tumor was labeled as EAML with atypical features. Immunocytochemistry on the destained cytology aspirates revealed strong smooth muscle actin staining of all cells. To conclude, EAML can mimic a RCC. In such instances, lack of arborizing vasculature, absence of cytoplasmic fatty vacoulation, crowded nuclei with intranuclear inclusions, and lack of prominent nucleoli along with typical immunophenotype of EAML may assist in the cytology diagnosis. Diagn. Cytopathol. 2011;39:278–282. © 2010 Wiley‐Liss, Inc.     

骨原发性上皮样血管肉瘤2例报道并文献复习

目的提高对骨原发性上皮样血管肉瘤(epithelioid angiosarcoma,EA)的认识,避免误诊。方法对2例原发于骨的EA进行临床病理、组织学及免疫组化分析,并进行文献复习。结果 2例均为男性,为骨组织内的多灶性、溶骨性病变,组织学上肿瘤主要由实性片状排列的上皮样细胞组成,瘤细胞核大,空泡状,含有明显核仁,可见细胞内空泡和血管腔样结构形成。免疫组化标记显示瘤细胞表达CD31、FⅧRAg、CK、vimentin。分别进行单纯化疗和手术治疗。1例失访,1例2个月后死亡。结论骨原发性EA是一种具有上皮样特征的高度恶性血管源性肿瘤,必须与转移癌等鉴别,CD31、CK等血管标记物对鉴别诊断具有重要的意义。     

Sclerosing epithelioid fibrosarcoma

A case of sclerosing epithelioid fibrosarcoma arising in the thigh of a 40-year-old man is reported. This recently described sarcoma has a distinctive histological appearance which may cause confusion with a variety of other sarcomas with an epithelioid pattern, and indeed with benign soft tissue tumours showing hyalinization. Despite its bland cytology, sclerosing epithelioid fibrosarcoma is capable of metastases, often several years after surgical removal. The patient described here developed lung metastases five years after excision and remains alive a further three years later. The differential diagnosis and possible histogenesis are discussed.     

Vaginal epithelioid angiosarcoma

A case of epithelioid angiosarcoma of the vagina is described. Only five cases of angiosarcoma at this site have been reported, three of which followed radiotherapy for other gynaecological malignancies. None is described as an epithelioid angiosarcoma, an unusual and recently described variant which is readily confused with carcinoma. This is thought to be the first reported epithelioid angiosarcoma at this site and highlights the difficulties in diagnosis.     

Primary pulmonary epithelioid angiosarcoma presenting as a solitary pulmonary nodule on image

Primary angiosarcoma of lung is a rare condition. Only about 20 cases have appeared in English published reports so far. Its rarity and consequent low index of suspicion makes clinical diagnosis difficult. Pathological diagnosis of the epithelioid variant of pulmonary angiosarcoma is particularly challenging. We report a case of primary pulmonary epithelioid angiosarcoma as a solitary pulmonary nodule in image study in a 41-year-old man with a brief review, to contribute it to the sparse literature on this disease.     

Characteristic cytologic findings of epithelioid hemangioendothelioma: A case report and review of literature

Epithelioid hemangioendothelioma is a rare vascular neoplasm of low-grade malignancy. We observed a case of epithelioid hemangioendothelioma arising in a cervical lymph node. Fine needle aspiration cytology showed several characteristic findings of epithelioid hemangioendothelioma, that is, nuclear inclusion bodies, nuclear grooves, and amorphous material, in addition to physaliform chromatin pattern of a new clue. By reviewing the reports, the prevalence of these is clarified. Complex appearance of these findings is useful in the diagnosis.     

Update on cutaneous epithelioid vascular tumours

Cutaneous epitheiloid vascular tumours are heterogeneous groups of vascular proliferations sharing in common the epithelioid morphology of tumour cells. Based on the WHO classification epithelioid vascular tumours are classified on the basis of their biological behavior into benign tumours (epithelioid haemangioma, epithelioid angiomatous nodule) and malignant tumours (epithelioid haemangioendothelioma and epithelioid angiosarcoma). While cutaneous epithelioid haemangioendothelioma affecting only the skin usually but not always follows an indolent clinical course, cutaneous epithelioid angiosarcoma is generally a highly aggressive tumour with dismal prognosis. Also included in this review is pseudomyogenic haemangioendothelioma, a vascular tumour of intermediate (rarely metastasizing) malignancy. It is not traditionally grouped under vascular tumours with epithelioid morphology. Nevertheless, pseudomyogenic haemangioendothelioma is discussed herein because it often contains a proportion of cells with epithelioid morphology, mimicking other epithelioid tumours of different lineage. Correct recognition of cutaneous epithelioid vascular tumours can be difficult due to their overlapping histological features and often absent or limited formation of open vascular spaces, but is crucial for correct management of the patients. In this paper, we review the main clinicopathological and immunohistochemical features of cutaneous epithelioid vascular tumours, including pseudomyogenic haemangioendothelioma, discuss their crucial differential diagnosis, analyze treatment options and prognosis, and give an update on molecular genetic features of this distinctive group of vascular proliferations.     

Cutaneous epithelioid angiosarcoma: A potential diagnostic trap for cytopathologists

We report on the cytologic features of a rare case of cutaneous epithelioid angiosarcoma of the scalp occurring in a 65-yr-old Chinese male. The prominent epithelioid features may cytologically mimic poorly-differentiated carcinoma, malignant melanoma, and even epithelioid sarcoma. Recognition of subtle cytologic features of vasoproliferation, immunohistochemical demonstration of endothelial markers, and ultrastructural examination are necessary before a final conclusion may be drawn. Diagn. Cytopathol. 16:160–167, 1997. © 1997 Wiley-Liss, Inc.     

Cytology of angiosarcoma. Findings in fourteen fine-needle aspiration biopsy specimens and one pleural fluid specimen

We report the cytologic features of 15 cases of angiosarcoma from various sites and include 14 fine-needle aspiration (FNA) biopsy specimens and 1 pleural fluid specimen. Six were initial diagnoses with histologic confirmation; an additional case in the liver was an initial diagnosis without tissue confirmation. One case represented lymph node metastasis from a primary prostatic epithelioid angiosarcoma. In 10 cases, immunohistochemical staining for factor VIII-related antigen, CD34, CD31, or Ulex europaeus agglutinin I was performed on the cytology or histology specimen. The aspirates varied in cellularity, and the degree of nuclear atypia ranged from relatively bland in a case of low-grade angiosarcoma of the prostate to highly pleomorphic in a lymph node metastasis from a facial cutaneous angiosarcoma. Vasoformative features such as intracellular RBCs, well-formed vessels, attempts at microacinar/lumen formation, and intracytoplasmic lumens were variably present. The background was bloody in all specimens, with necrosis in rare cases. This cytologic series emphasizes that the cytologic features are heterogeneous but that the diagnosis can be suggested by fine-needle aspiration (FNA) when vasoformative features are present. The diagnosis can be made conclusively by FNA with immunocytochemical confirmation of endothelial differentiation.     

Gastric epithelioid angiosarcoma, a biopsy diagnostic pitfall

We report the case of a 70-year-old man who presented a bulky gastric mass. The diagnosis of poorly differenciated adenocarcinoma was made on the biopsy. On surgical specimen, the final diagnosis of gastric angiosarcoma with secondary intestinal involvement was established. The patient did not respond to chemotherapy and died 8 months later. The diagnosis was difficult because of epithelioid areas which expressed both cytokeratin and vascular antigens. Human herpesvirus 8 previously detected in some soft tissue angiosarcoma was not found by polymerase chain reaction.     

Epithelioid hemangioendothelioma with extensive cystic change and CAMTA1 rearrangement

Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm that has the ability to recur locally and metastasize. Thus, it is important to distinguish this tumor from other epithelioid vascular neoplasms. A 47‐year‐old man presented to our hospital with a pelvic mass with severe ischialgia and weight loss. Surgical resection was performed, and the mass was found to have dark red multiloculated cysts with hemorrhage and calcification. The histopathologic examination showed a central sclerotic, hypocellular zone and a peripheral cellular zone. Only the peripheral portion of the wall revealed nested tumor cells in light blue myxoid stroma. These tumors are typically composed of short strands or cords of bland epithelioid cells with occasional intracytoplasmic lumens embedded in a myxohyalinized stroma. The tumor cells were positive for CD31 and CD34 and negative for factor VIII‐related antigen, CK (AE1/AE3) and S‐100. The tumor nuclei showed distinct break‐apart signals with individual green and/or red signals, indicating the presence of CAMTA1 rearrangement. In this study, we report a case of EHE that was difficult to diagnose based on histology alone. Therefore, we also performed fluorescence in situ hybridization, and found that the tumor harbored a CAMTA1 gene rearrangement, which confirmed the diagnosis.     

Sclerosing Epithelioid Fibrosarcoma of the Pituitary

Primary pituitary sarcoma in the absence of previous radiation therapy is very rare, only eight cases having been reported. We present the first reported case of sclerosing epithelioid fibrosarcoma of the pituitary, a 56-year-old woman presenting with diplopia and panhypopituitarism. Magnetic resonance imaging showed a 1.2 × 0.4 × 0.5-cm sellar mass invading the right cavernous sinus. Despite surgery and radiation therapy, our patient developed intracranial metastases and died 2 years after the initial diagnosis. Sclerosing epithelioid fibrosarcoma is an infrequently occurring, distinct variant of soft tissue fibrosarcoma. Its immunophenotype includes vimentin and occasionally CD-34, B cell lymphoma-2, S-100 protein, or keratin expression. Although initially thought to be a low-grade lesion, sclerosing epithelioid fibrosarcomas may also behave in a high-grade manner.     

Periosteal Epithelioid Hemangioendothelioma with Leptomeric Fibrils

A case of recurrent periosteal epithelioid hemangioendothelioma of the right femur in a 66-year-old woman is reported. Microscopic examination showed epithelioid tumor cells with frequent intracytoplasmic vacuoles arranged in small nests or cords in hyalinized stroma. Immuno- and lectinhistochemical studies for factor VIII-related antigen and ulex europaeus I lectin indicated the endothelial nature of the tumor cells. Ultrastructurally, a few tumor cells contained leptomeric fibrils and crystalline filamentous aggregates in addition to showing certain features of endothelial cells. There seems to be no previous report of a vascular tumor containing leptomeric fibrils, which are often noted in normal striated muscle cells and their tumors. The bland appearance of the epithelioid tumor cells, poor vasoformative nature and prolonged clinical course differentiated this tumor from conventional angiosarcoma and so-called hemangioendothelioma of bone.     

Periosteal Epithelioid Hemangioendothelioma with Leptomeric Fibrils

A case of recurrent periosteal epithelioid hemangioendothelioma of the right femur in a 66-year-old woman is reported. Microscopic examination showed epithelioid tumor cells with frequent intracytoplasmic vacuoles arranged in small nests or cords in hyalinized stroma. Immuno- and lectinhistochemical studies for factor VIII-related antigen and ulex europaeus I lectin indicated the endothelial nature of the tumor cells. Ultrastructurally, a few tumor cells contained leptomeric fibrils and crystalline filamentous aggregates in addition to showing certain features of endothelial cells. There seems to be no previous report of a vascular tumor containing leptomeric fibrils, which are often noted in normal striated muscle cells and their tumors. The bland appearance of the epithelioid tumor cells, poor vasoformative nature and prolonged clinical course differentiated this tumor from conventional angiosarcoma and so-called hemangioendothelioma of bone.