bromochloroacetic-acid and Hemangiosarcoma

Angiosarcoma may rarely arise near an inert foreign body material including vascular grafts and metal joint prostheses. Sixteen such cases have been reported since 1972 but mostly in the radiologic or surgical literature without detailed histologic or molecular analyses. We herein describe the clinicopathologic and molecular features of 2 new cases and reanalyzed 3 previously reported cases of angiosarcoma that developed in association with Dacron grafts for vascular repair (n=3) or related to orthopedic metal prostheses for joint replacement (n=2). All patients were men aged 50 to 84 years (median, 71 years). Mean time to development of angiosarcoma was 9 years (range, 4.6-17 years). Symptoms were recurrent bleeding/loosening of prosthesis for suspected infection (in the joint prosthesis cases) and fatigue, weight loss, and abdominal symptoms in the Dacron-associated cases. Four patients died of disease within 1 to 24 months (mean, 8 months). One patient was alive after radical surgery, radiochemotherapy, and embolization of pulmonary metastases (17 months). Histologically, all tumors were high-grade epithelioid neoplasms with a predominant solid growth pattern and variable vasoformation. All tumors expressed CD31, ERG, FLI-1, and variably pancytokeratin (diffuse in 3 cases), but none expressed D2-40, MDM2, or CDK4. Fluorescence in situ hybridization analysis revealed no MDM2 or CDK4 alterations. MYC was expressed in all cases, but only 1 case was MYC amplified by fluorescence in situ hybridization. Angiosarcomas are exceedingly rare fatal complications of long-standing metal and Dacron prostheses. Awareness of their morphology and frequent cytokeratin expression is necessary to avoid misdiagnosis as metastatic carcinoma. Limited awareness of their existence explains delayed clinical diagnosis in most of cases. Absence of MDM2/CDK4 alterations underlines their distinction from intimal-type sarcomas.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Blood Vessel Prosthesis; Blood Vessels; Carcinoma; Diagnosis, Differential; Hemangiosarcoma; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Joint Prosthesis; Joints; Keratins; Male; Middle Aged; Polyethylene Terephthalates

There is a great deal of confusion in the literature as to whether or not true angiosarcomas of the thyroid exist or whether these are all anaplastic carcinomas of the thyroid which have an angiosarcomatoid appearance. Due to the fact that undifferentiated carcinomas of this organ can strikingly resemble various sarcomas it is recommended that great care should be taken prior to qualify as an angiosarcoma a malignant thyroid tumor. A lot of viewpoints have been expressed so far in literature concerning this theme, and they can be summarized as follows. On one side and not admitting the existence of angiosarcoma in this location there are opinions which think of it as a "variant" of undifferentiated carcinoma (a pure carcinoma with a pseudovascular pattern or a carcinoma with an intermingled non-neoplastic reactive vascular component), or as a neoplasm in transition from epithelial to endothelial differentiation ("mesenchymal neometaplasia"), or as a carcinoma with aberrant expression of endothelial markers, or as a carcinoma with a non-specific uptake of endothelial antigens(e.g. from serum in case of F-VIII R-Ag positivity). On the other side there are opinions in favor of the existence of such an entity, based upon light microscopy features coupled with immunocytochemical results (endothelial antigens expression without or with cytokeratins expression) and with the possible support of electron microscopy. Anyway ultrastructural findings of specific markers (Weibel-Palade bodies, pericellular basal lamina, tight junctions, subplasmalemmal pinocytotic vesicles) according to some authors are not a prerequisite: so poorly differentiated neoplasma can fail to show those histogenetic markers.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma; Cell Adhesion Molecules; Cell Differentiation; Endothelium; Hemangiosarcoma; Humans; Keratins; Lectins; Male; Neoplasm Proteins; Plant Lectins; Platelet Endothelial Cell Adhesion Molecule-1; Thyroid Neoplasms; Vimentin; von Willebrand Factor

Malignant vascular neoplasms such as epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS) can arise within the liver. The aim of this study was to study the expression of keratins CK7, AE1/AE3 and OSCAR in primary hepatic EHE and AS. 9 cases of hepatic EHE and 13 cases of hepatic AS were stained with ERG, CK7, keratin AE1/AE3 and keratin OSCAR. Their expression was graded as 1+ (1-25% of tumor cells positive), 2+ (26-50%), 3+ (51-75%) or 4+ (>75%). ERG was positive in all 9 (100%) EHEs and all 13 (100%) ASs. CK7 was positive in 5/9 (56%) EHEs (2, 1+; 1, 2+; 1, 3+; 1, 4+) and 1/13 (8%) AS (2+). Keratin OSCAR was positive in 6/9 (67%) EHEs (5, 1+; 1, 2+) and 4/13 (31%) ASs (2, 1+; 1, 2+; 1, 4+). Keratin AE1/AE3 was positive in 6/9 (67%) EHEs (3, 1+; 3; 2+) and 4/13 (31%) ASs (2, 1+; 1, 2+; 1, 4+). Overall, 6/ 9 (67%) EHEs were positive for at least one keratin marker, of which 5 were positive for all 3 keratins (AE1/AE3, OSCAR and CK7) while 1 was positive only for 2 keratins (OSCAR and AE1/AE3). 4/13 (31%) of ASs were positive for both keratins OSCAR and AE1/AE3, of which 1 case was also positive for CK7. Aberrant keratin expression is common in primary hepatic EHEs (67%) and ASs (31%). Awareness of this diagnostic pitfall is important for avoiding misdiagnosis of these primary hepatic malignant vascular tumors as carcinomas.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Hemangioendothelioma, Epithelioid; Hemangiosarcoma; Humans; Keratins; Liver Neoplasms; Male; Middle Aged; Young Adult

We report the case of a 94-year-old man with a rapidly growing nodule on the preauricular area, which on histology showed a poorly differentiated spindle cell tumor with negative p63 and p40 antibody immunostains, negative high- and low-molecular-weight cytokeratins albeit for a focal expression of cytokeratin AE1/AE3. Spindle cell melanoma, angiosarcoma, and leiomyosarcoma were excluded. We explore the diagnostic approach to this challenging conundrum. Certain authors have suggested that sarcomatoid carcinoma and atypical fibroxanthoma (AFX) may lie within a spectrum of "sarcoma-like tumors of the head and neck" and that they may all run a similarly indolent clinical course. However, AFX appears to remain a diagnosis of exclusion, and expert consensus is that by definition AFX cannot express any cytokeratin antigens.

Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Face; Hemangiosarcoma; Humans; Keratins; Leiomyosarcoma; Male; Melanoma; Mohs Surgery; Skin; Skin Neoplasms

Primary angiosarcoma of the breast is extremely rare. Radiologic findings are often non specific and may appear completely normal in one-third of cases with primary angiosarcoma. The prognosis is usually poor because of the high rates of local recurrence and early development of metastasis. Surgical removal followed by adjuvant chemotherapy seems improve the prognosis. We report a case of a 33- year-old woman with a highly vascular mass in her right breast which is suggestive of malignancy at radiology. Initial core needle biopsy showed a benign hemangioma. The patient underwent a mastectomy. The tumor histology showed papillary formations and vascular structures lined by atypical cells with hyperchromatic nucleus and eosinophilic cytoplasm with solid areas. The tumor cells expressed CD34 and CD31 but were negative for cytokeratin. The diagnosis of angiosarcoma grade III was made. The patient is now receiving chemotherapy. She is still alive.. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1530481200889780.

Topics: Adult; Biopsy; Breast Neoplasms; Female; Hemangiosarcoma; Humans; Keratins; Neoplasm Recurrence, Local; Prognosis

Angiosarcoma (AS) is a rare soft tissue sarcoma showing endothelial differentiation as indicated by morphology and expression of CD31 (blood), D2-40 (lymphatic), factor VIII, and CD34 (both). We sought to examine the pattern of immunohistochemical markers of differentiation in AS and correlate these with outcome.. An AS tissue microarray (n = 70 specimens) was constructed for immunohistochemical analysis of CD31, CD34, factor VIII, D2-40, and pan-cytokeratin. Samples on this array were linked to clinicopathologic and outcome data for these patients. Univariate analyses were used to explore disease-specific survival (DSS) factors.. Nine metastatic, 23 localized, and 4 recurrent cases were included. Information about the tissue status (ie, primary or metastasis) was unavailable in 4 patients. Primary sites for the tumor included bone (n = 1), breast parenchyma (n = 11), breast skin (n = 4), heart (n = 5), skin (n = 8), soft tissue (n = 7), and unknown (n = 3). Three patients presented with multifocal disease (primary sites in these patients included breast, skin, and soft tissue). Metastatic sites included lung, bone, lymph nodes, brain, liver, and parotid. Of the 40 cases, 8 (20%) showed a pure or predominant epithelioid histology. Of the biomarkers evaluated by tissue microarray, 92% of tumors expressed at least one endothelial marker (factor VIII = 83%, CD31 = 80%, CD34 = 63%, and D2-40 = 43%) with 88% expressing 2 or more markers. Eighty-eight percent of tumors expressing D2-40 coexpressed CD31, an unusual combination in normal vessels. No endothelial marker clearly associated with disease-specific survival. Fifty percent (4/8) of epithelioid cases and 9% (3/32) of nonepithelioid cases showed keratin expression.. Unusual patterns and loss of endothelial markers are common in AS, suggesting use of multiple markers in challenging cases and perhaps indicating important biologic characteristics.

Topics: Antibodies, Monoclonal, Murine-Derived; Antigens, CD34; Biomarkers, Tumor; Biopsy; Disease-Free Survival; Endothelial Cells; Epithelial Cells; Factor VIII; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Lymphatic Metastasis; Male; Multivariate Analysis; Neoplasm Recurrence, Local; Platelet Endothelial Cell Adhesion Molecule-1; Predictive Value of Tests; Soft Tissue Neoplasms; Time Factors; Tissue Array Analysis; Treatment Outcome

Squamous cell carcinoma, a malignant proliferation of keratinocytes, can be found in many regions of the body covered by stratified squamous epithelium and in areas covered by other epithelia but which had undergone squamous metaplasia. Squamous cell carcinoma has many variants.. We, retrospectively, reviewed the case file and histological features of a 75 year old trader with a rare variant of squamous cell carcinoma arising from an old surgical scar.. The 75-year-old African female trader presented to the hospital with three and a-half month history of a swelling in the anterior aspect of the left leg arising from an old surgical scar. Clinical examination showed an irregularly shaped ulcer measuring 14 x 16 cm with an everted edge and a hyperpigmented floor. Histologic sections of the specimen showed the infiltration of the papillary and reticular dermis of the skin by sheets of atypical spindle cells with areas of squamous differentiation. There was a contiguous area of capillary-like structures constituting about 30% of the sections examined. The neoplastic cells were positive for vimentin and cytokeratin but were negative for CD34. The diagnosis was pseudoangiosarcomatous squamous cell carcinoma.. This tumour can be found in Africans and in an old surgical scar. It can coexist with other variants of squamous cell carcinoma. There may be need in the future to add a new mixed variant to the current classification scheme.

Topics: Aged; Carcinoma, Squamous Cell; Cicatrix; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Retrospective Studies; Skin Neoplasms; Vimentin

Primary oral cavity sarcomas are exceedingly rare and may pose a great diagnostic challenge. A 71-year-old woman without history of malignancy or radiation to the head and neck presented with an antibiotic-refractory diffuse painful swelling of the right tonsil necessitating tonsillectomy. Histologic evaluation revealed subtotal replacement of the right tonsil by a high-grade epithelioid neoplasm displaying extensive ulceration, necrosis, and primitive vasoformation. Immunohistochemistry showed strong/diffuse expression of pancytokeratin antibodies KL-1 and Lu5, cytokeratin 8, cytokeratin 18, cytokeratin 19, vimentin, CD31, ERG, and Freund leukemia integration site 1 (FLI-1). High-molecular-weight cytokeratins (cytokeratin 5, 34β12), cytokeratin 7, cytokeratin 13, and cytokeratin 20 were not expressed. Within months, the patient underwent surgical resection of multiple bleeding intraoral and gastrointestinal metastases. She is currently alive with disease 9 months from diagnosis. To our knowledge, this case represents the first well-documented primary epithelioid angiosarcoma of the tonsil. The strong cytokeratin expression in epithelioid angiosarcomas represents a diagnostic pitfall. Thus, awareness of this rare and highly aggressive neoplasm is necessary for distinguishing it from poorly differentiated and acantholytic squamous cell carcinoma and diffuse large cell lymphoma.

Topics: Aged; Female; Hemangiosarcoma; Humans; Keratins; Tonsillar Neoplasms

Epithelioid angiosarcoma of the parotid gland is rare, and may pose a great diagnostic challenge. We report a case of primary epithelioid angiosarcoma in a 64-year-old male without history of radiation. The histopathological findings demonstrated a high grade epithelioid neoplasm. Immunostaining showed that the tumor was positive for the pan-cytokeratin, p63, cytokeratin18, Vimentin and vascular markers CD31, and was negative for CD34, cytokeratin5/6, cytokeratin7, cytokeratin20, CD68, CD30, S-100, HMB45, desmin, α-SMA and CD45. The tumor was diagnosed as an epithelioid angiosarcoma. To our knowledge, this is the first reported case of angiosarcoma which showed common positivity for cytokeratin and p63. In addition to cytokeratin, p63 is considered a useful marker for carcinoma. The co-expression of cytokeratin and p63 in epithelioid angiosarcoma represents a diagnostic pitfall. Thus, using a panel of antibodies is essential for distinguishing this tumor from poorly differentiated carcinoma. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6548916707504750.

Topics: Biomarkers, Tumor; Biopsy; Carcinoma; Diagnosis, Differential; Epithelioid Cells; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Parotid Neoplasms; Predictive Value of Tests; Transcription Factors; Tumor Suppressor Proteins

Epithelioid angiosarcomas are rare aggressive neoplasms that occur most frequently in deep soft tissues. Primary cutaneous lesions are rare, and there are discrepant findings in the literature regarding their behavior. In this study, we report a series of 13 cases of primary cutaneous epithelioid angiosarcoma and analyze their clinicopathologic features. The tumors arising in the conventional settings for cutaneous angiosarcoma (ie, in the head and neck region of elderly patients, and those occurring postradiation or associated with lymphedema) were excluded. Primary cutaneous epithelioid angiosarcoma occurred in adults (mean age, 66 y) with an equal sex distribution, and presented as solitary (n=10) or multiple (n=3) nodules ranging in size from 8 to 80 mm, with a predilection for the limbs (n=10). Histopathologically, the tumors comprised infiltrative sheets of atypical epithelioid cells within the dermis with or without the involvement of the subcutis. Vascular channel formation and intracytoplasmic lumina were seen, at least focally, in most cases. Mitoses were readily identified and necrosis was seen in 40% of the cases. The tumors were immunoreactive for vascular markers, with CD31 and FLI-1 offering the highest sensitivity. Pancytokeratin was positive in two thirds of the cases, and epithelial membrane antigen was positive in one-quarter of the cases. There was rare focal expression of Melan-A (n=2) and smooth muscle actin (n=3). Follow-up information was available for 11 patients. Six patients died of metastatic disease after a median follow-up of 12 months (range, 3 to 36 mo), and 1 patient died of unrelated causes. These findings suggest that primary cutaneous epithelioid angiosarcoma occurring outside the conventional settings of angiosarcoma is a highly aggressive malignant tumor with mortality rates in excess of 55% after 3 years.

Topics: Actins; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Epithelioid Cells; Extremities; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; MART-1 Antigen; Microfilament Proteins; Middle Aged; Mitosis; Mucin-1; Neoplasm Invasiveness; Neoplasm Staging; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Cytoplasmic and Nuclear; Skin Neoplasms; Time Factors; Trans-Activators; Treatment Outcome

Primary pleural angiosarcoma is a rare and clinically aggressive tumor. Patients usually present with chest pain, dyspnea, hemoptysis and/or cough. Radiologic studies reveal diffuse pleural thickening and pleural effusion with or without mass lesion. The clinical and radiological features both resemble those of mesothelioma, and its definite diagnosis requires careful histologic examination. However, frequent epithelioid feature and immunoreactivity to cytokeratin in primary pleural angiosarcoma further complicate the pathologic diagnosis. The use of proper immunohistochemical stains is often needed to support endothelial differentiation in the tumor cells and to exclude metastatic carcinoma and mesothelioma. We report the case of a 49-year-old male patient with primary pleural angiosarcoma, who presented with initial hemothorax, followed by a rapid progress to an inoperable status.

Topics: Antineoplastic Agents; Biomarkers, Tumor; Chemoradiotherapy; Diagnosis, Differential; Hemangiosarcoma; Hemothorax; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Pleura; Pleural Neoplasms

Topics: Actins; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinosarcoma; Diagnosis, Differential; ErbB Receptors; Female; Hemangiosarcoma; Humans; Keratins; Membrane Proteins; Metaplasia; Neoplasm Proteins; Phyllodes Tumor; Stromal Cells; Syringoma

Thyroid gland angiomatoid tumors are an extremely aggressive neoplasms with varied histological patterns and features of endothelial differentiation. The histogenesis of thyroid angiomatoid tumors has been controversial for many years: these tumors may be either a variant of anaplastic carcinoma, or an angiosarcoma. We report a case of thyroid angiomatoid tumor in a 68-year-old woman. We also discuss, through a review of the literature, the pathologic criteria that could be used to distinguish between angiosarcoma and anaplastic carcinoma of the thyroid.

Topics: Aged; Carcinoma; Diagnosis, Differential; Epithelial Cells; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

In general, it has been stated that keratin (K) molecules are glycosylated. During biochemical studies of K subunits, we encountered a glycoprotein that does not judge K subunits.. This study was intended to elucidate how the above glycoprotein co-exists in the K fraction prepared from ISO-HAS (cultured angiosarcoma cell line).. We analyzed and sequenced a remarkable spot, which was shown as a glycoprotein by periodic acid Sciff's (PAS) staining, in the K fraction prepared from ISO-HAS.. The glycoprotein was identified as an N-terminal amino acid sequence covering 10 residues of the spot. A homology search showed that it was identical to that of Hsp47 (matured type), except for one amino acid (seventh amino acid: Val 7 Leu). Similar results were confirmed for four other tumorigenic cell line types. Subsequent PAS staining using the same samples after 2D-PAGE revealed no glycosylated Ks.. No glycosylated Ks were found by PAS staining in the K fraction prepared from four tumorigenic cell line types. During K preparation from cultured human tumor cell lines, Hsps might be associated with K expression in tumor cells.

Topics: Amino Acid Sequence; Amino Acid Substitution; Carcinoma, Squamous Cell; Cell Line, Transformed; Fibrosarcoma; Gene Expression Regulation, Neoplastic; Glycosylation; HeLa Cells; Hemangiosarcoma; HSP47 Heat-Shock Proteins; Humans; Keratinocytes; Keratins; Melanoma; Molecular Sequence Data; Periodic Acid-Schiff Reaction; Skin Neoplasms

Expression of epithelial cell markers can occur in mesenchymal tumors and has been reported in angiosarcomas with variable frequency. In these situations, establishing the diagnosis becomes problematic.. To determine the expression of cytokeratin and epithelial membrane antigen in angiosarcoma.. To address this issue, 33 well-documented cases of angiosarcomas were retrieved from the archival material of Shands Hospital at the University of Florida, Gainesville, and Jackson Memorial Hospital at the University of Miami, Miami, Florida. These cases were all reviewed and studied using a cytokeratin cocktail (CAM 5.2 and AE1/AE3) and epithelial membrane antigen using standard immunohistochemical techniques. All 33 cases had available material for cytokeratin analysis; however, only 20 cases had enough material for epithelial membrane antigen staining.. In the 33 cases studied, the age range of the patients was 2 to 88 years (mean, 63 years). There were 23 (70%) men and 10 (30%) women. One (3%) of 33 was cytokeratin-immunoreactive and 2 (10%) of 20 were epithelial membrane antigen-immunoreactive.. Cytokeratin and epithelial membrane antigen immunoreactivity in angiosarcomas is infrequent but may be encountered. Interpretation of such expression should be done with caution and in conjunction with the characteristic clinical and morphologic features of the tumor as well as the expression of endothelial cell antigens.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child, Preschool; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Retrospective Studies

This case report discusses the clinical presentation, imaging, surgery and further treatment and course of a primary angiosarcoma of a non-irradiated parotid gland.

Topics: Aged; Aged, 80 and over; Hemangiosarcoma; Humans; Keratins; Leukocyte Common Antigens; Magnetic Resonance Imaging; Male; Neoplasm Staging; Neoplasms, Second Primary; Parotid Neoplasms; Skin Neoplasms; Tomography, X-Ray Computed

Epithelioid angiosarcoma of the bone is a rare tumor and is a diagnostic challenge. Here we present an autopsy case of a 62-year-old man with multifocal osteolytic lesions in the extremities and the pelvis. The initial diagnosis of a tibial biopsy was poorly differentiated adenocarcinoma. On the occasion of autopsy, a fungating thrombotic nodule was found at the anterior wall of the right atrium, and small hemorrhagic infarcts with tumor thrombi were found in the lung. Histologically, the above lesions were identical to the former tibial biopsy and they showed large eosinophilic epithelioid cells with irregular ovoid nuclei and prominent eosinophilic nucleoli. Rare intracytoplasmic lumina were identified. Immunohistochemically, the tumor cells were positive for cytokeratins (CAM5.2 and AE1/AE3), CD31, factor VIII-related antigen, and vimentin. This case showed angiotropic spread of the tumor only to the right atrium and the lung, with no solid mass in other organs. Multicentric epithelioid angiosarcoma of the bone is a pitfall in pathological diagnoses, especially if a strong radiological impression of metastatic carcinoma is provided. Therefore, pathologists should be aware of this rare variant.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Bone Neoplasms; Diagnosis, Differential; Epithelioid Cells; Fatal Outcome; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasms, Multiple Primary; Platelet Endothelial Cell Adhesion Molecule-1; Tibia; Vimentin; von Willebrand Factor

The expression of cytokeratins in gastrointestinal stromal tumours (GISTs) is rare and may lead to diagnostic confusion when it occurs. This report describes a metastatic GIST that stained strongly for cytokeratins, CD117, and CD34 in a patient who was previously diagnosed with gastric epithelioid angiosarcoma. A review of both tumours showed the same histological and immunohistochemical profiles, and c-kit molecular analysis revealed an insertional mutation at codon 558 of exon 11 in both tumours. Thus, pathologists should be aware that GISTs can occasionally express cytokeratins, and that c-kit mutational investigations may have a key diagnostic role and may prevent diagnostic mistakes that could have important clinical implications.

Topics: Adult; Biomarkers, Tumor; Diagnosis, Differential; Female; Gastrointestinal Stromal Tumors; Hemangiosarcoma; Humans; Keratins; Mutation; Pelvic Neoplasms; Proto-Oncogene Proteins c-kit; Stomach Neoplasms

We investigated keratin (K) expression in cultured fibroblasts, endothelial cells and their sarcomas by using two-dimensional gel electrophoresis and electron microscopy techniques. Although the fibroblast and endothelial cell lines were derived from mesenchyme, we confirmed Ks in both cell lines. The K in two cultured cell lines consisted of K14 and K16, together with vimentin. In addition to the above Ks, K5 and K8/K17 were comprised in each cell line, respectively. On the other hand, the cultured fibrosarcomas contained K8 and K18 in addition to the Ks present in the cultured fibroblasts, except K17. Moreover, cultured angiosarcomas showed the same Ks expression as those of the cultured fibrosarcomas, except vimentin. However, electron microscopy showed that the extremely thin fiber-like substances existed or at least did not form filamentous structures in four cultured cell types.

Topics: Blotting, Western; Cell Line; Electrophoresis, Gel, Two-Dimensional; Endothelium, Vascular; Fibroblasts; Fibrosarcoma; Hemangiosarcoma; Humans; Keratins; Protein Isoforms; Tumor Cells, Cultured

Chronic pyothorax associated with pulmonary tuberculosis was recently proposed to be one of the predisposing factors of angiosarcoma arising in the chest wall. Separately, several authors have reported pleural angiosarcoma that has a close resemblance to mesothelioma, the latter having no apparent association with a history of pyothorax. I present a detailed pathologic description of an autopsy case of thoracic angiosarcoma arising after long-standing tuberculous pyothorax, for the purpose of better illustrating this condition. In this case, the main tumor mass was situated on the soft tissue of the chest wall outside the rib girdle. On the pleuropulmonary tissue, tumor infiltration was grossly observable as a dark patch, 2 cm in diameter, on the outer surface of the wall of the pyothorax (pleural peel). Infiltration of the tumor was found in the soft tissue just outside of the peel and in the attached rib. However, the tumor was not found in the peel itself, nor was it found in the necrotic content of the pyothorax. This case suggests that angiosarcoma associated with pyothorax is not similar to primary pleural angiosarcoma and shows the rather ordinary feature of the tumor's arising in the soft tissue.

Topics: Antigens, CD34; Biomarkers; Empyema, Tuberculous; Factor VIII; Fatal Outcome; Hemangiosarcoma; Hemoptysis; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; Pleural Neoplasms; Tomography, X-Ray Computed

A 67-year-old man presented with weight loss, intermittent severe abdominal pain and melaena. Initial radiology (including abdominal ultrasonography), gastroscopy and colonoscopy did not demonstrate any lesions that could explain the complaints. Three weeks later, upper gastrointestinal and small-bowel barium studies revealed two areas in the small intestine with an abnormal mucosal pattern. Explorative laparotomy revealed three tumoral lesions. Three partial enterectomies were performed. Gross examination showed centrally depressed dark reddish tumoral lesions extending from the mucosa throughout the full thickness of the bowel wall (diameter varying between 1.6 cm and 2.2 cm). The tumours, composed of large, plump, polygonal cells showing little architectural differentiation, were mainly situated in submucosa and muscularis propria. The growth pattern appeared rather solid. The epithelioid cells showed pronounced nuclear pleomorphism and atypia with central large nucleoli. There were several small blood vessels with occasional anaplastic endothelial cells. Immunohistochemical staining demonstrated an intense expression of CD 31, CD 34, factor VIII related antigen and keratin. This supported the diagnosis of an epithelioid angiosarcoma. The patient died 3 months after diagnosis. Tumours of the small intestine are very rare, and angiosarcomas of the small intestine are even more rare. Epithelioid variants have only been described in two patients and only one of these had a multifocal presentation. The prognosis is very poor. Because of the epithelioid growth pattern and the cytokeratin expression, these tumours may erroneously be diagnosed as a carcinoma.

Topics: Abdominal Pain; Aged; Antigens, CD34; Colonoscopy; Factor VIII; Fatal Outcome; Gastroscopy; Hemangiosarcoma; Humans; Immunohistochemistry; Intestinal Neoplasms; Intestine, Small; Keratins; Male; Melena; Platelet Endothelial Cell Adhesion Molecule-1; Tomography, X-Ray Computed; Ultrasonography; Weight Loss

The histogenesis of thyroid gland angiomatoid tumors, probably as a primary angiosarcoma, has been a controversy for many years. These tumors may be variants of undifferentiated (anaplastic) carcinomas. We report a thyroid gland angiomatoid carcinoma in a 61-year-old African American male. The tumor had a heterogeneous pattern with both sarcomatous and epithelioid areas. Tumor cells lined some vascular-like spaces and others had intracytoplasmic lumens containing red blood cells. The tumor cells were found to express multiple endothelial (factor VIII-related antigen, CD31, CD34, and Ulex europaeus I lectin) and epithelial (cytokeratin and epithelial membrane antigen) markers as well as thyroglobulin by immunohistochemistry. This rare presentation demonstrates the heterogeneous nature of thyroid gland angiomatoid carcinoma with both epithelial and endothelial differentiation.

Topics: Antigens, CD34; Carcinoma; Cell Differentiation; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Lectins; Male; Middle Aged; Mucin-1; Plant Lectins; Platelet Endothelial Cell Adhesion Molecule-1; Thyroglobulin; Thyroid Neoplasms; von Willebrand Factor

Vascular endothelial cells are specialized mesenchyme-derived epithelial-like lining cells which are the essential participants in benign and malignant vascular tumors. Although endothelia in lower animals often express keratins (K), human endothelia are generally K negative and vimentin-positive. However, K expression has been noted in some endothelia and in some epithelioid vascular tumors. In this study, we systematically examined normal human vascular endothelia and a spectrum of human vascular tumors (n = minimum of 137 tumors with each marker) for simple epithelial keratin polypeptides of the Moll catalogue (K7, K8, K18, and K19). Selected vascular tumors were also evaluated with antibodies to K14 and the monoclonal antibody 34betaE12 that recognizes several keratins of stratified epithelia. Endothelia of normal veins, venules, and lymphatics commonly exhibited focal positivity for K7 and K18, whereas K8, K14, and K19 were not seen in non-neoplastic endothelia with the antibodies used. Lymphangiomas (6 of 7) and venous hemangiomas (6 of 13) often showed K7-positive endothelial cells; K18 was detected less commonly, whereas K8 and K19 were not detected. Epithelioid hemangioendotheliomas (EHEs) showed K7 and K18 expression in the majority of cases (50% and 100%, respectively), while K8 was seen in 10% cases and K14 and K19 in none. In contrast, epithelioid angiosarcomas (EAs) were often positive for K8 and K18 (approximately 50%), whereas they less commonly showed K7 and only occasionally K19; all tumors were negative for K14 and with the antibody 34betaE12. Nonepithelioid angiosarcomas (AS) less commonly showed keratin expression with K7, K8, and K18 being positive in 20% of cases, and K14 and K19 in none of the cases. Epithelial membrane antigen (EMA) was occasionally detectable in EHE (2/19) but was present in 4 of 16 (25%) EAs and 17 of 48 (35%) nonepithelioid AS. These findings document the common presence of focal reactivity for K7 and K18 in subsets of normal endothelia and also the frequent presence of simple epithelial keratins in malignant vascular tumors, while such expression is uncommon in nonepithelioid angiosarcomas. K- and EMA-positivity in neoplastic endothelia needs to be considered in the evaluation of human tumors. K antibodies such as those specific to K19 or AE1 that do not react with K8 and K18 should be used in the differential diagnosis of epithelioid vascular tumors and carcinomas.

Topics: Biomarkers, Tumor; Diagnosis, Differential; Endothelium, Vascular; Hemangioendothelioma, Epithelioid; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Keratins; Lymphangioma; Soft Tissue Neoplasms

Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Diagnosis, Differential; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Prognosis

The existence of angiosarcoma (AS) of the thyroid has been a matter of debate for many years, because some authors believe that most if not all ASs are in fact "angiomatoid" anaplastic carcinomas (ACs). Immunohistochemistry alone was not successful in solving the problem, since cytokeratin expression is a known occurrence in AS. Therefore, we wanted to compare nine cases of AS with ten cases of AC, assessing whether thyroglobulin (TG) mRNA was still transcribed in undifferentiated tumors and could be helpful to distinguish AC from AS. The cases were analyzed for TG mRNA expression by means of radioactive in situ hybridization. The silver grains were counted using an automated device, and their amount was compared with that of stroma, background, and peritumoral thyroid. A weak signal was present in all AC but not in AS (mean counts 35.7 and 9.6 arbitrary units, respectively: P<0.01). In two cases of AC, residual areas of poorly differentiated insular carcinoma had a strong signal (similar to that of peritumoral thyroid). These findings further confirm that AC and AS of the thyroid are unrelated malignant tumors.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD34; Carcinoma; Diagnosis, Differential; Endothelium, Vascular; Factor VIII; Female; Gene Expression; Hemangiosarcoma; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Male; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; RNA, Messenger; Thyroglobulin; Thyroid Neoplasms; Vimentin

A cell line, designated ISOS-1, was established from a tumor formed by transplantation of a human angiosarcoma into mice with severe combined immunodeficiency (SCID). The cells showed endothelial properties, based on the uptake of Dil-Ac-LDL and binding of UEA-I/GSA-I lectins, but were negative for CD11b and Pan Cytokeratin. However, the cells lost differentiated characteristics such as expression of von Willebrand factor, contact inhibition growth and tube formation activity. These findings indicate that ISOS-1 is a poorly-differentiated endothelial cell line. At the 81st passage, all of the cells were positive for H-2Dd in various intensity, but not HLA-ABC. The metaphase chromosomes consistently showed a characteristic mouse, but not human, telocentric form. Furthermore, this cell line produced fatal tumor growth in SCID mice and also in BALB/c mice. These results suggest that ISOS-1 is a murine-phenotypic angiosarcoma cell line.

Topics: Animals; CD11 Antigens; Cell Division; Cell Transformation, Neoplastic; Chromosomes; Female; H-2 Antigens; Hemangiosarcoma; Histocompatibility Antigens Class I; Humans; Immunohistochemistry; Keratins; Lectins; Lipoproteins, LDL; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mice, Inbred Strains; Mice, SCID; Neoplasm Transplantation; Phenotype; Skin Neoplasms; Tumor Cells, Cultured; von Willebrand Factor

The present report of a 25 year old woman with a primary ovarian angiosarcoma is supplemented by histochemical and ultrastructural studies and reviews the literature of this extremely rare neoplasm. Since this ovarian tumor, especially in young women, may constitute a diagnostic pitfall, problems relating to differential diagnosis are emphasized. Although the origin of this neoplasm appears to occur most likely from the rich ovarian vasculature, other less conventional histogenetic theories such as a possible origin in mixed mullerian tumor, in teratoma or in other ovarian germ cell tumors have also been proposed and are considered in this paper.

Topics: Actins; Adult; Carcinoma, Embryonal; Cytoplasmic Granules; Diagnosis, Differential; Factor VIII; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Ovarian Neoplasms; Platelet Endothelial Cell Adhesion Molecule-1; Sertoli-Leydig Cell Tumor; Vimentin

The clinicopathologic, immunohistochemical, and ultrastructural features of soft tissue angiosarcomas are not well defined. Eighty cases of angiosarcoma that involved the deep subcutis, skeletal muscle, retroperitoneum, mesentery, and mediastinum are reported. The lesions occurred in 50 male and 30 female patients who were 5-97 years of age; the peak incidence was in the seventh decade of life. A variety of associated conditions were documented in 20 of these cases, including a history of other neoplasms (some irradiated), synthetic vessel grafts, heritable conditions, and prior trauma or surgery. The angiosarcomas occurred in the extremities (n = 43 cases), trunk (n = 28), and the head and neck (n = 9) regions, with the thigh and the retroperitoneum being the most common sites. They often were characterized as enlarging, painful masses of several weeks' duration and were occasionally associated with acute hemorrhage, anemia, or a coagulopathy. The tumors measured 1-15 cm in diameter (median 5 cm) and frequently were hemorrhagic and multinodular. There was a wide morphologic spectrum within and between cases, including areas similar to cavernous and capillary hemangioma, Dabska tumor, spindle cell and epithelioid hemangioendothelioma, various spindle cell sarcomas, or carcinoma. Histologically, epithelioid angiosarcoma was the most frequently observed pattern; 70% of cases had epithelioid cells that were arranged in nests, clusters, papillae, and gaping vascular channels. Hemorrhage tended to obscure the diagnosis in several cases and often was associated with papillary endothelial hyperplasia-like areas. All 42 cases studied immunohistochemically stained at least focally for Factor VIII-related antigen, and nearly all stained strongly for vimentin, which accentuated the endothelial cells and vessel lumen formation. CD34 antigen was detected in 74% of cases, BNH9 in 72%, and cytokeratins in 35%. Epithelial membrane antigen, S-100 protein, and HMB45 were not detected. Fifty-five percent of the tumors had intracytoplasmic aggregates of laminin. Immunostains for alpha-smooth muscle actin demonstrated a prominent pericytic component in several tumors (24%). Ki67 immunostains with MIB1 indicated high proliferative activity (> or =10%) in 72% of cases. p53 immunoreactivity (>20% nuclear staining) was observed in 20% of cases. Ultrastructural studies performed on poorly differentiated areas of 12 cases showed groups of cells, which were frequently epithelioid, s

Topics: Actins; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Child, Preschool; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Prognosis; Soft Tissue Neoplasms; von Willebrand Factor

Angiosarcoma of bone is a rare, high-grade sarcoma of vascular origin. This article describes an epithelioid angiosarcoma in the humerus of a 48-year-old man. A multilocular osteolytic lesion with undefined margins and destroyed cortical and medullary bone, associated with a large soft tissue mass was demonstrated radiologically in the proximal metaphysis of the right humerus. The tumor, resected by amputation, was composed mostly of proliferating malignant cells with an epithelioid morphology. It had a predominantly sheet-like growth pattern, and an occasional pseudoglandular or alveolar arrangement, mimicking an adenocarcinoma. The dilated anastomotic vascular spaces lined by epithelioid endothelial cells and the intracytoplasmic lumina/vacuoles that sometimes contained erythrocytes suggested focal endothelial differentiation. On immunohistochemical investigation, many neoplastic cells expressed cytokeratin and endothelial markers: factor-VIII related antigen, CD31, and UEA-I. The ultrastructure of the tumor was consistent with that of an angiosarcoma. Our patient died of disease shortly after the diagnosis, implying an aggressive clinical course. Awareness of the existence of skeletal epithelioid angiosarcoma, combined with the identification of intracytoplasmic lumina, or at least small vasoformative foci, and immunohistochemical positivity for endothelial markers provide the best guide for distinguishing this tumor from metastatic carcinomas.

Topics: Biomarkers, Tumor; Bone Neoplasms; Epithelioid Cells; Fatal Outcome; Hemangiosarcoma; Humans; Humerus; Immunohistochemistry; Keratins; Lectins; Male; Middle Aged; Plant Lectins; Platelet Endothelial Cell Adhesion Molecule-1; von Willebrand Factor

Although vascular invasion is common in many malignant tumors, disseminated intravascular anaplastic neoplasms with occult primary tumor are rare occurrences. Intravascular malignant lymphoma, also called angiotropic lymphoma, is a rare variant of large cell lymphoma predominantly involving vessels in multiple organs, and usually without significant nodal involvement. Although initially misinterpreted as an endothelial neoplasm-angioendotheliomatosis-immunohistochemical studies subsequently proved it to represent a peculiar form of malignant lymphoma. In this report, we describe two patients with extensive intravascular dissemination of angiosarcoma initially without clinically obvious primary tumor. These may be interpreted as examples of true angioendotheliomatosis. In each case the immunohistochemical studies ruled out the most common intravascular malignant neoplasms. The diagnosis of intravascular angiosarcoma was confirmed by the immunoreactivity of the tumor cells to several markers of endothelial lineage in both cases. Thus, angiosarcoma may present with intravascular dissemination and occult primary tumor and closely resemble metastatic carcinoma, melanoma, or angiotropic lymphoma. Immunohistochemical studies are crucial in ruling out these possibilities and in confirming the endothelial origin of the neoplastic cells.

Topics: Adult; Aged; Biomarkers; Biopsy; Diagnosis, Differential; Fatal Outcome; Female; Gallbladder Neoplasms; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Liver Neoplasms; Lung Neoplasms; Platelet Endothelial Cell Adhesion Molecule-1; Vascular Neoplasms; von Willebrand Factor

A 39-year-old male presented with an exceedingly rare primary intracranial epithelioid angiosarcoma in the right parietal lobe manifesting as weakness of the left hand. Neuroimaging revealed a well-defined intensely enhanced lesion in the right parietal lobe with peripheral cerebral edema. The tumor was grossly totally removed. Light microscopy of the surgical specimens revealed features typical of an epithelioid vascular tumor. The tumor cells showed intense positive immunohistochemical staining for cytokeratin and vimentin and focally positive staining for both Ulex europaeus agglutinin and anti-human endothelial cells, CD31. Tumor regrowth required two further operations. This progressive growth was consistent with an angiosarcoma. The tumor was diagnosed as an epithelioid angiosarcoma based on the histological and clinical characteristics. He became progressively obtunded and finally died. This is the first intracranial epithelioid angiosarcoma which expressed epithelial markers detectable by immunohistochemical methods.

Topics: Adult; Biomarkers, Tumor; Brain Neoplasms; Fatal Outcome; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Keratins; Magnetic Resonance Imaging; Male; Neoplasm Recurrence, Local; Parietal Lobe; Reoperation; Vimentin

Pulmonary artery angiosarcoma is a rare entity. We report a case of an epithelioid angiosarcoma developing from the right pulmonary artery with pulmonary parenchymal invasion. The patient was a 69-year-old man who presented with massive hemoptysis and shortness of breath. Right middle and lower lobectomies were performed because of uncontrollable bleeding. An angiosarcoma was observed developing from the right pulmonary artery with contiguous spread down smaller artery branches with invasion of the pulmonary parenchyma. Although typical angiosarcomatous areas were observed, the neoplasm was dominated by cells with an epithelioid morphology. Immunohistochemically, the majority of cells stained for endothelial markers factor VIII-related antigen and CD34, but in addition, the cells with an epithelioid morphology stained intensely for cytokeratin. Knowledge of cytokeratin positivity in epithelioid vascular neoplasms is critical to avoid a misdiagnosis of carcinoma, particularly at sites where carcinoma is a much more likely diagnosis.

Topics: Aged; Antigens, CD34; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Pulmonary Artery; Vascular Neoplasms; von Willebrand Factor

Topics: Buttocks; Epithelium; Hemangiosarcoma; Humans; Keratins; Male; Middle Aged; Skin Neoplasms

Cytological, biopsy and autopsy findings in a patients suffering from massively metastasizing adrenal angiosarcoma are reported. Histogenetic typing of the tumour initially manifestating itself by osseous and liver metastases was problematic with regard to its partially epithelioid structure and its positivity upon cytokeratin immunostaining. Of relevance for the correct typing was the finding that the tumour cells in addition exhibited positivity for vascular markers. This case confirms literature data according to which cytokeratin expression not infrequently may be encountered in endothelial neoplasms and which by no means should lead to exclude such a tentative diagnosis.

Topics: Adrenal Gland Neoplasms; Adrenal Glands; Adult; Antibodies, Monoclonal; Antigens; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Cell Adhesion Molecules; Factor VII; Femoral Neoplasms; Femur Head; Hemangiosarcoma; Humans; Keratins; Liver; Liver Neoplasms; Male; Platelet Endothelial Cell Adhesion Molecule-1

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.

Topics: Adrenal Gland Neoplasms; Adult; Estradiol; Fibroma; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Mesentery; Peritoneal Neoplasms

Six cases of primary hepatic carcinomas with a significant amount of sarcomatoid elements were examined by using immunohistochemical stainings. Four of the six cases were associated with ordinary hepatocellular carcinoma (HCC), one with cholangiocellular carcinoma (CCC), and one with mixed HCC and CCC. Alpha-fetoprotein and alpha-1-antitrypsin were negative in sarcomatoid cells of all cases; vimentin stained positively in sarcomatoid tumor cells in two of the six cases; and cytokeratin (CK8) was detected in five cases. The CK8 was not detected in tumor cells of two cases of hepatic angiosarcoma, two of metastatic leiomyosarcomas, and one of metastatic fibrosarcoma, although vimentin stained positively in all these true sarcomas. It was concluded that sarcomatoid dedifferentiation of liver carcinomas might derive from both HCC and CCC. In addition CK8 might be an excellent marker to make a differential diagnosis of sarcomatoid cancers from true metastatic or primary sarcomas of the liver.

Topics: Aged; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; Fibrosarcoma; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Leiomyosarcoma; Liver Neoplasms; Male; Middle Aged; Sarcoma; Vimentin

Nineteen primary intracranial sarcomas out of a total of about 25,000 brain tumour biopsies are reported. Subtypes included malignant fibrous histiocytoma (6 cases), leiomyosarcoma (3), rhabdomyosarcoma (2), angiosarcoma (2), and one case each of fibrosarcoma, low-grade fibromyxoid sarcoma, malignant ectomesenchymoma, mesenchymal chondrosarcoma, differentiated chondrosarcoma and Ewing's sarcoma. Histological and immunohistochemical features corresponded to those of extracranial sarcomas. Nests of pleomorphic astrocytes mimicking glioma were detected in the five storiform-pleomorphic malignant fibrous histiocytomas. Our results indicate that intracranial sarcomas can be classified like their extracranial counterparts. The low incidence compared with earlier series is related to changes in classification and progress in histogenetic clarification.

Topics: Adult; Aged; Biomarkers, Tumor; Brain Neoplasms; Child; Child, Preschool; Desmin; Female; Glial Fibrillary Acidic Protein; Hemangiosarcoma; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Infant; Keratins; Leiomyosarcoma; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Rhabdomyosarcoma; Sarcoma; Vimentin

We report eight cases of epithelioid angiosarcoma arising in deep, usually intramuscular soft tissue. All the patients were men (mean age, 58). All the lesions arose in a limb or limb girdle. Cardinal morphologic features were the diffuse, sheetlike growth pattern, with only focally apparent vascular differentiation, and epithelioid tumor cells with a degree of intracytoplasmic vacuolation/lumen formation. Immunohistochemically, all eight cases coexpressed keratin as well as endothelial markers. In three cases, endothelial differentiation was confirmed ultrastructurally. Clinically, deep-seated epithelioid angiosarcomas are high-grade neoplasms that rapidly develop metastases. These findings expand the range of recognized epithelioid endothelial tumors and provide further evidence of keratin expression by such lesions. The presence of intracytoplasmic lumina/vacuoles (sometimes containing red blood cells) combined with the characteristic reticulin pattern and striking positivity for Factor VIII-RAg provide the clearest means of distinction from an epithelial metastasis.

Topics: Adult; Aged; Diagnosis, Differential; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Soft Tissue Neoplasms; von Willebrand Factor

Seven epithelioid and eight non-epithelioid vascular tumors were studied by the avidin-biotin-peroxidase method for the presence of endothelial- and epithelial-associated markers, using Ulex europaeus agglutinin-1 (UEA-1) lectin, and antibodies directed against factor VIII-related antigen, (FVIII-RA), vimentin, keratin, carcinoembryonic antigen, and epithelial membrane antigen. The cases included four epithelioid hemangiomas, two epithelioid hemangioendotheliomas (EHE), one epithelioid angiosarcoma (EAS), four common non-epithelioid capillary hemangiomas, and four non-epithelioid angiosarcomas. Staining for FVIII-RA, UEA-1, and vimentin were observed in all cases. The EAS showed staining for keratin in formalin-fixed, paraffin-embedded sections and in frozen sections. Staining for keratin was also observed in frozen sections of one EHE. Both keratin-positive vascular tumors were confirmed with electron microscopy. Carcinoembryonic antigen and epithelial membrane antigen stains were negative in all cases. Our results show that the epithelioid vascular tumors EHE and EAS, in addition to staining for the endothelial markers and vimentin, may also express the epithelial marker keratin. This is important since these tumors may closely resemble carcinomas by routine light microscopy. This study further underscores the importance of using a broad panel of immunohistochemical markers in the diagnostic workup of soft-tissue neoplasms.

Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Epithelium; Hemangioendothelioma; Hemangioma; Hemangiosarcoma; Humans; Keratins; Lectins; Leg; Membrane Glycoproteins; Mucin-1; Plant Lectins; Skin; Vimentin; von Willebrand Factor

We present four cases of a malignant thyroid tumor showing morphologic, immunocytochemical, and ultrastructural features of endothelial cell differentiation. The tumor cells had epithelioid features and displayed strong immunoreactivity for keratin. There was no evidence of follicular or C-cell differentiation in any instance. We interpreted these cases as keratin-positive epithelioid angiosarcomas. The findings presented here support the existence of primary malignant vascular tumors in the thyroid even in the presence of keratin positivity, a marker traditionally regarded as indicative of epithelial differentiation.

Topics: Aged; Aged, 80 and over; Cell Transformation, Neoplastic; Endothelium; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Lectins; Male; Microscopy, Electron; Middle Aged; Plant Lectins; Thyroid Neoplasms; Vimentin; von Willebrand Factor

We used a battery of antigens to determine whether immunohistochemistry can (a) contribute to resolving the histogenesis of the stromal component of the capillary hemangioblastoma, and (b) answer cases of difficult pathologic differential diagnosis with metastatic clear cell carcinoma. The stromal cells of the capillary hemangioblastoma are antigenically polymorphous and may express immunoreactive erythropoietin, renin, keratin, Leu M1, Leu 7, actin, neuron-specific enolase, S100 protein, and glial fibrillary acidic protein. However, the use of epithelial membrane antigen allows certain histopathologic distinction between capillary hemangioblastoma and metastatic clear cell carcinoma.

Topics: Adenocarcinoma; Aged; Antigens, Differentiation; Antigens, Neoplasm; Carcinoma, Renal Cell; Cerebellar Neoplasms; Diagnosis, Differential; Erythropoietin; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Male; Membrane Glycoproteins; Mucin-1; Renin

Two cases of von Hippel-Lindau's disease with special reference to the occurrence of renal carcinoma are presented. The first case demonstrates the difficulty of differentiating cerebellar haemangioblastoma from metastatic renal carcinoma affecting the cerebellum. The valuable differentiating histological features were positive staining of metastatic renal carcinoma by antiepithelial membrane antigen (anti-EMA) and the demonstration of a distinct pattern of packeting of cells by staining reticulin fibres. Staining with periodic acid Schiff and cytokeratin antibody (anti-CK) were not found to be useful. The second case exhibits the wide variety of neoplasms which may be present in von Hippel-Lindau's disease. Special stains support the findings of the first case.

Topics: Adult; Angiomatosis; Biomarkers, Tumor; Carcinoma, Renal Cell; Cerebellar Neoplasms; Cerebellum; Cerebral Angiography; Diagnosis, Differential; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Magnetic Resonance Imaging; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Tomography, X-Ray Computed; von Hippel-Lindau Disease

Immunoperoxidase techniques for S-100 protein, keratin, cytokeratin, vimentin and desmin were applied to 65 canine skin tumours. These included eight squamous cell carcinomas, eight fibrosarcomas, eight melanomas, eight mastocytomas, eight haemangiosarcomas, eight leiomyosarcomas, five liposarcomas and 12 poorly differentiated tumours. Consistent results were obtained within each group. Cytokeratin and keratin immunoreactivity was detected only in squamous cell carcinomas. Vimentin was present in fibrosarcomas, melanomas, haemangiosarcomas, mastocytomas, leiomyosarcomas and liposarcomas. S-100 protein immunoreactivity was detected in melanomas, haemangiosarcomas, liposarcomas and leiomyosarcomas. Only leiomyosarcomas were positive for desmin. According to these results the 12 anaplastic tumours were diagnosed either as carcinomas, fibrosarcomas or malignant melanomas.

Topics: Animals; Carcinoma, Squamous Cell; Desmin; Dog Diseases; Dogs; Fibrosarcoma; Hemangiosarcoma; Immunoenzyme Techniques; Keratins; Leiomyosarcoma; Liposarcoma; Mast-Cell Sarcoma; Melanoma; S100 Proteins; Skin Neoplasms; Vimentin

Postirradiation sarcomas are an unusual but well-recognized late effect of cancer therapy. In this article, a fine-needle aspiration (FNA) series of four cases is presented. There were three female patients and one male patient, with an age range of 28-55 yr (mean, 41). Two of the patients were irradiated for uterine cervical carcinoma while the other two received irradiation for malignant lymphoma. The time interval to the development of the postirradiation sarcoma ranged from 10 to greater than 20 yr. There were a postirradiation synovial sarcoma of the buttock region, malignant fibrous histiocytoma of the bone (femur), and rhabdomyosarcoma and angiosarcoma of the retroperitoneum. A spectrum of cytologic findings was encountered, reflecting the specific types of sarcomas. Immunocytochemical studies performed on the aspirated material from the angiosarcoma demonstrated the utility of immunoperoxidase stains for ULEX europaeus agglutinin-1 (UEA-1) and, to a lesser degree, factor VIII-related antigen antibody, confirming the vascular nature of this malignancy. The FNA findings from all four cases demonstrated cytologic features that allowed recognition of this unusual complication of irradiation treatment. This article confirms the utility of FNA cytology in following patients with previous malignancies and differentiating a postirradiation sarcoma from recurrent carcinoma.

Topics: Adult; Aged; Biopsy, Needle; Female; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neoplasms; Neoplasms, Radiation-Induced; Radiotherapy; Vimentin

We studied 23 cases of capillary hemangioblastoma (CHB) of the cerebellum with 17 immunohistochemical cell markers in an attempt to define the nature of the so-called "stromal" cells. These cases were compared to four cases of intracranial metastatic renal cell carcinoma (RCC), which may mimic CHB histologically. The 17 markers studied included vimentin (VIM), Factor VIII-related antigen (FVIIIR:Ag), blood group antigens A, B, and H, Ulex I lectin (Ulex), Alkaline Phosphatase (Alk P), neurofilament protein (NF), glial fibrillary acidic protein (GFAP), S-100 protein (S-100), nerve growth factor receptor (NGFR), muscle-specific actin (MSA), desmin (Des), monoclonal keratin (MKER, including Cam 5.2 and AE1/3), epithelial membrane antigen (EMA), and chromogranin (Chrom). No significant stromal cell staining was seen by markers for endothelial, epithelial, chromaffin, or smooth muscle origin. In some cases individual cells demonstrated positivity for GFAP (4/22) and S-100 protein (13/23); these cells were generally stellate and located near the periphery, and we conclude that these were the result of entrapment of surrounding cerebellum. No case demonstrated NF in stromal cells. However, nearly all cases of CHB showed stromal cell staining with VIM (19/22). In contrast, all of the cases of RCC showed significant staining for at least one marker of epithelial origin (3/4 for MKER and 4/4 for EMA). We conclude that the stromal cell of CHB is neither endothelial, neural, epithelial, pericytic, nor neuroendocrine in origin, and is instead of undifferentiated mesenchymal origin. The designation of this tumor as an "hemangioblastoma," although a misnomer, is firmly established in the literature and should probably be retained.

Topics: Actins; Alkaline Phosphatase; Cell Transformation, Neoplastic; Cerebellar Neoplasms; Chromogranins; Desmin; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Hemangiosarcoma; Humans; Immunohistochemistry; Intermediate Filament Proteins; Isoantigens; Keratins; Lectins; Membrane Glycoproteins; Mesenchymoma; Mucin-1; Neoplasm Metastasis; Plant Lectins; Receptors, Cell Surface; Receptors, Nerve Growth Factor; S100 Proteins; Vimentin; von Hippel-Lindau Disease; von Willebrand Factor

Immunohistochemical techniques were used to determine the intermediate filament content of normal arachnoidal cells, meningiomas (including the so-called hemangiopericytoma of the meninges), soft tissue hemangiopericytoma, and the normal pericyte. Arachnoid granulations and all types of meningioma stained similarly: positive for vimentin and variably positive for keratin. Soft tissue hemangiopericytomas and normal pericytes were negative for both vimentin and keratin. This suggests that the "hemangiopericytoma" of the meninges is a variant of meningioma and not of pericytic origin.

Topics: Arachnoid; Hemangiopericytoma; Hemangiosarcoma; Histocytochemistry; Humans; Keratins; Meningeal Neoplasms; Vimentin

A chronic brawny edema developed in the shoulder and arm ipsilateral to the site of a previous mastectomy in a 68-year-old woman. Bluish nodules and telangiectasia admixed with more superficial papules and plaques developed subsequently. Histologically, many of these lesions showed angiocentric clusters of large hyperchromatic tumor cells, often with lumina in the center. It was difficult to differentiate two possibilities, ie, postmastectomy angiosarcoma in lymphedema (Stewart-Treves syndrome) and nodulotelangiectatic metastasis of the original breast carcinoma. Monoclonal anti-keratin antibody and anti-desmosome antibody identified keratin and desmosomes in the tumor cells, whereas staining with factor VIII-related antigen yielded negative results. Electron microscopy revealed, in addition to keratin filaments and desmosomes, typical secretory cells and lumen formation. A combined use of specific monoclonal and polyclonal antibodies is helpful in the determination of tumor origins.

Topics: Aged; Antibodies, Monoclonal; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Desmosomes; Diagnosis, Differential; Factor VIII; Female; Hemangiosarcoma; Histocytochemistry; Humans; Immunochemistry; Keratins; Lymphatic Metastasis; Mastectomy

The origin of spindle-shaped cells in Kaposi's sarcoma (KS) remains controversial. Non-specific histochemical reactions, electron microscopic examinations and immunostainings using antibody against factor VIII-related antigen (F VIII-RAG) and Ulex europaeus agglutinin I (UEAI) lectin as endothelial markers have given contradictory results. Immunohistochemical techniques were applied to 7 frozen skin biopsy specimen of KS from 5 elderly Mediterranean people and 1 renal allograft recipient, and a group of 27 other frozen cutaneous tumours including haemangio and lymphangiosarcomas, benign vascular lesions and various epithelial, melanocytic, fibrohistiocytic, fibrosarcomatous and muscular tumours. Using UEAI and antibodies against F VIII-RAG, HLA-DR and vimentin, a large proportion of positive KS spindle cells was found in all cases whereas cells were negative for keratin. Among the various immunoreactivity patterns observed in this study, a unique immunohistochemical profile was demonstrated for KS, angiosarcoma and endothelial cell, which strongly supports the endothelial origin of spindle cells in KS. Whereas F VIII-RAG, HLA-DR, vimentin and UEAI were sensitive endothelial markers, only F VIII-RAG appeared specific for endothelial cells since UEAI stained 2 squamous cell carcinomas and HLA-DR and vimentin were present in various mesenchymal and melanocytic tumours.

Topics: Adult; Aged; Antigens; Endothelium; Factor VIII; Hemangiosarcoma; Histocompatibility Antigens Class II; Histocytochemistry; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Lectins; Middle Aged; Plant Lectins; Sarcoma, Kaposi; Skin Neoplasms; Vimentin; von Willebrand Factor

Two cases of postmastectomy angiosarcoma were characterized morphologically and immunohistologically using markers for epithelial (anti-keratin antibodies) and endothelial cells (anti-vimentin antibodies, anti-Factor VIII-related antigen antibodies and Ulex europaeus I lectin). In both cases, the angiosarcoma had developed in a lymphedematous arm, 10 and 16 years after the mastectomy, and both patients died with metastatic angiosarcoma within 1 year. Both mammary tumors were adenocarcinomas, showing keratin-positive tumor cells, whereas the angiosarcomas cells were keratin-negative but vimentin-positive. The best-differentiated vascular lumina in the angiosarcomas were positive for Factor VIII-related antigen (FVIIIR:Ag), whereas most of the tumor cells reacted with Ulex europaeus I-lectin (UEA I), a recently introduced marker for endothelial cells. The carcinomas, on the other hand, were negative for FVIII R:Ag and did not bind UEA I, except the non-neoplastic vessels of the tumors. Ultrastructurally, the tumor cells showed prominent pinocytic vesicles and cell-cell junctions, but no Weibel-Palade bodies. The results corroborate the conclusions of endothelial origin of these tumors and rule out their derivation from the primary mammary carcinomas. The results also suggest that immunohistochemical markers for epithelial and endothelial cells can be used as diagnostic aids in distinguishing these neoplasms.

Topics: Adenocarcinoma; Aged; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Hemangiosarcoma; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Mastectomy; Microscopy, Electron; Neoplasms, Multiple Primary; Staining and Labeling; Vimentin

Antibodies against constitutive proteins of different types of intermediate-sized filaments were used in immunofluorescence microscopy on frozen sections of normal rat liver and various rat liver tumors induced by treatment with nitrosamines. Antibodies to tonofilament prekeratin stained bile duct epithelia and hepatocytes of normal liver and hepatocellular carcinoma cells and ductal cells of cholangiofibromas. These cells were not significantly stained by antibodies to vimentin. By contrast, antibodies to vimentin stained mesenchymal cells of normal liver and cells of early and advanced angiosarcomas and of undifferentiated spindle cell sarcoma. These mesenchymal tumor cells were not stained with antibodies to prekeratin. The presence of intermediate-sized filaments in these tumors, often in large whorl-like aggregates, was also demonstrated by electron microscopy. The results show that immunofluorescence microscopy with antibodies to cytoskeletal proteins is a powerful tool for the classification and differential diagnosis of mesenchymal and epithelial liver tumors. We propose that staining with antibodies to proteins of different types of intermediate filaments can be used to improve the identification of tumors of other organs, including metastases, as well as non-neoplastic proliferative lesions.

Topics: Adenoma, Bile Duct; Animals; Cytoskeleton; Hemangiosarcoma; Keratins; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Muscle Proteins; Rats; Sarcoma; Vimentin