Angiomyofibroblastoma of the vulva: Case report with immunohistochemical, ultrastructural and DNA ploidy studies and a review of the literature

A case of anglomyofibroblastoma of the vulva in a 49-year-old woman was examined. The tumor measured 3×2.5×2 cm and appeared light gray to tan In color on the cut surface. Light microscopic examinations revealed that spindle or oval shaped tumor cells were arranged in loose edematous stroma with numerous thin-walled vessels. Ultrastructurally, cell organellae were not well developed but intracytoplasmic filaments of intermediate size were abundant in the tumor cells. Desmin, CD34 and vimentin immunoreactivity were detected in almost all of the tumor cells. Both estrogen and progesterone receptors were diffusely expressed In the tumor, suggestive of the sex sterold-dependency of this tumor. The Ki-67 labeling index was less than 1% and the DNA content of the tumor cells, which was examined by image cytometry, demonstrated diploidy (DNA index=0.97). These findings may reflect the quiescent or slow growing features of angiomyofibroblastoma.     

Malignant rhabdoid tumor of the vulva: Case report with cytological, immunohistochemical, ultrastructural and DNA ploidy studies and a review of the literature

A case of malignant rhabdoid tumor of the vulva in a 25-year-old female was examined. The patient presented with a subcutaneous nodule in the lefl labium majus. Smears of the material obtained by percutaneus fineneedle asplratlon demonstrated clusters of atypical cells with prominent nucleoli. The tumor measured 6 × 5 × 5 cm and appeared tan to brown on the cut surface and partly cystlc. Pathological findings obtalned from intraoperative frozen tlssue sections had been originally interpreted as rhabdomyosar-coma. Light microscopic examination revealed that polyge nal tumor cells having vesicular nuclei with prominent nucleoli were arranged in sheets and the great majority of the tumor cells contained an eosinophillc globular paranu-clear cytoplasmic Inclusion. Ultrastructurally, this cytoplas-mic inclusion corresponds to whirls of intermediate filaments. Vlmentln immunoreactlvity was detected in both the cytoplasm and cytoplamic inclusion of almost all the tumor cells. No cytokeratin and desmin immunoreactivlty were detected In the tumor cells. The Ki-67 labeling index was 36% and the DNA content of the tumor cells, which was examined by image cytometry, demonstrated diploidy (DNA Index = 0.95).     

Characterization of the binucleated giant cells generated in the autologous mixed leucocyte reaction from patients with rheumatoid arthritis.

Binucleated giant cells several times larger than lymphocytes or monocytes were generated in an autologous mixed leucocyte reaction (AMLR) independent of DNA synthesis in patients with rheumatoid arthritis (RA). The AMLR giant cells with multiple cytoplasmic granules were non-specific esterase-staining positive, phagocytic, non-adherent, HLA-DR+, CD11b+, CD14+, 4F2+, CDW29+, and anti-transferrin receptor positive, but negative for T, B, or NK markers. RA patients aged less than 60 years from more giant cells: 12.6 +/- 13.5% (n = 33) as compared with 0.4 +/- 1.5% in age- and sex-matched normals (n = 38, (P less than 0.001). More giant cells were seen over age 60 in both groups: RA 20.1 +/- 15.5% (n = 5) and healthy controls 3.0 +/- 3.2% (n = 8) (P less than 0.01). Neither disease activity nor treatment appear to influence the result in RA. The giant cells that are probably derived from monocytes in AMLR may explain the formation of the giant cells in rheumatoid granulation tissues.     

Polypoid tumor of the esophagus

Five cases of an uncommon esophageal tumor consisting of a mucosal squamous cell carcinoma that surrounds a polypoid mass of spindle cells were examined. The spindle cell component was composed of elongated cells with blunt nuclei, admixed with multinucleated giant cells. Reticulin fibers enveloped individual cells, and abundant collagen was present. Thirteen to 69 mitotic figures occurred per 10 high-power fields. Electron microscopy showed dilated cisternae of rough endoplasmic reticulum and peripheral intermediate filaments within the cytoplasm. Intermediate-type junctions (zonulae adherens) and subplasmalemmal linear densities connected some cells. No tonofibrillar bundles or desmosomes (maculae adherens) were present. Immunoperoxidase stains detected no keratin in the spindle cells. Alpha-1-antichymotrypsin and alpha-1-antitrypsin were in the spindle cells in five of five and three of five cases, respectively. The absence of desmosomes, tonofibrillar bundles, and keratin and the presence of alpha-1-antitrypsin and alpha-1-antichymotrypsin favor fibrohistiocytic differentiation of the spindle cell component.     

Spindle cell carcinoma of head and neck: an immunohistochemical and molecular approach to its pathogenesis

BACKGROUND: Spindle cell carcinoma (SpCC) is a rare microscopic type of cancer of the mouth and oropharynx. Although SpCC is thought to arise from squamous cell carcinoma (SCC), it carries a worse prognosis. AIM: To find out the difference in immunohistochemical expression of cytokeratin, vimentin and smooth-muscle actin, and mutational alterations in the K-ras oncogene between the two tumours, in an attempt to characterise SpCC. METHODS: Immunohistochemical analysis was performed by standard avidin-biotin complex method in 35 cases each of SpCCs and SCCs. DNA extracted from paraffin wax-embedded tumours was used for PCR followed by single-strand conformation polymorphism for mutational analysis of K-ras exon 1 and exon 2. RESULTS: In the SpCC group, cytokeratin positivity was significantly higher in epithelial areas (52.2%) than in spindle cell areas (16.1%), whereas vimentin was more positive in spindle cell areas (18.7%) than epithelial areas (2.7%). Cells intermediate between epithelial and spindle cell areas were consistently positive for both cytokeratin and vimentin. Cytokeratin was found to be significantly more positive in SCC (72.6%) than the squamous component and spindle cell component of SpCC. In this study, no mutation was detected in the K-ras gene of either the SpCC or SCC group. CONCLUSIONS: The spindle cell component of SpCC is intermixed with cells that are morphologically mesenchymal but express dual antigen-positivity characteristic of epithelial (cytokeratin) and mesenchymal (vimentin) cells. These, possibly, are cells in transition suggesting that SpCC may be a sarcomatous metaplasia of SCC.     

Detection of centromeres in vinblastine- and radiation-induced micronuclei of human lymphocytes using FISH with an α satellite pancentromeric DNA probe

Fluorescence in situ hybridisation (FISH) with a human alphoid satellite pancentromeric DNA probe was used to detect centromeres in micronuclei of human lymphocytes induced by γ-irradiation and by Vinblastine sulfate. In a cytokinesis-block micronucleus assay a dose-dependent increase of micronuclei was detected for both agents. 72–89% of Vinblastine-induced micronuclei, but only 7–48% of radiation-induced micronuclei showed centromere-positive fluorescence signals. Vinblastine treatment frequencies of centromere-negative micronuclei did not increase compared to control values, nor did frequencies of centromere-positive micronuclei in irradiated lymphocytes. Since FISH with an α satellite DNA probe allows the direct detection of centromeric DNA sequences the spindle damaging or clastogenic effectiveness of a compound can be easily and reliably examined in a cytokinesis-block micronucleus assay in human lymphocytes. © 1996 Wiley-Liss, Inc.     

Transitional cell carcinoma of the urinary bladder with osteoclast-type giant cells: a report of two cases and review of the literature

We report two transitional cell carcinomas of the urinary bladder containing numerous osteoclast-type giant cells that stained for vimentin and acid phosphatase (with and without tartrate) and were negative for cytokeratin and lysozyme. One tumour, in a 65-year-old man, was composed of papillary transitional cell carcinoma, invasive poorly differentiated carcinoma with a prominent spindle cell component and numerous osteoclast-type giant cells; repeat curettage 2 months later showed no residual tumour. The second tumour occurred in a 75-year-old woman who underwent a radical cystectomy for a deeply invasive transitional cell carcinoma with a spindle and anaplastic giant cell component and areas containing numerous osteoclast-type giant cells. Osteoclast-type giant cells, which appear to be reactive, should be distinguished from the neoplastic giant cells of giant cell carcinoma.     

Infection of a human retinal pigment epithelial cell line with human herpesvirus 6 variant A

A retinal pigment epithelial (RPE) cell line (K-1034) was examined for its susceptibility to human herpesvirus 6 variant A (HHV-6A). Exposure of K-1034 cells to HHV-6A induced the formation of multinucleated giant cells, which was suppressed by an inhibitor of viral DNA synthesis. In the giant cells, herpesvirus nucleocapsids were demonstrated by electron microscopy and the viral glycoprotein B was detected by immunofluorescence assay. These results indicate that K-1034 cells are susceptible to HHV-6A and suggest that HHV-6A has an ability to directly destroy epithelial cells. J. Med. Virol. 53:105–110, 1997. © 1997 Wiley-Liss, Inc.     

Low mitochondrial DNA and ATP contents contribute to the absence of birefringent spindle imaged with PolScope in in vitro matured human oocytes

BACKGROUND: Birefrigent meiotic spindle in live human oocytes can be visualized by the PolScope. This study investigated the relationship between birefrigent meiotic spindle and cytoplasmic mitochondrial DNA (mtDNA) and ATP contents in in vitro matured human oocytes. METHODS: Oocytes at germinal vesicle stage were collected and cultured for 24-48 h with or without the metabolic inhibitor, carbonyl cyanide p-(tri-fluromethoxy) phenyl-hydrazone (FCCP). All in vitro matured oocytes were examined by PolScope for the presence of meiotic spindle, then the oocytes were used for either intracytoplasmic sperm injection or the measurement of mitochondrial quantity and ATP content. RESULTS: Meiotic spindles were observed in 51.3% (60/117) of the in vitro matured oocytes. Oocytes with detectable meiotic spindle contained significantly higher mtDNA copies (637 250 +/- 237 606 versus 491 454 +/- 153 406, P = 0.027) and ATP content (1.97 +/- 0.38 versus 1.65 +/- 0.32 pmol, P = 0.028) when compared with those without detectable meiotic spindle. However, in vitro matured oocytes showed a significantly reduced rate of positive meiotic spindle and a lower ATP content when cultured with FCCP. A lower incidence of normal fertilization and good quality embryos were observed if meiotic spindles were not detected. CONCLUSIONS: Low mtDNA and ATP content might contribute to the absence of birefringent spindle imaged with the PolScope in human in vitro matured oocytes.     

Postmenopausal intra-abdominal desmoplastic small cell tumor

Intra-abdomlnal desmoplastic small cell tumor (DSCT) usually occurs In infants and young male adults. A case of DSCT occurring in a 60 year old female Is described. No other apparent primary origin was detected. A mesocolon tumor, measuring 23times12times10cm, was composed predominantly of round to spindle cells which showed epithelioid- and focally sarcomatous arrangements. Irnmunohlstochemically, the tumor cells showed perinuclear dot-like staining of CAM5.2, many cells expressed HHF35, and some cells contained vimentin, epithelial membrane antigen, desmln, alpha-smooth muscle actin, neuron-specific enolase, or Leu 7. Electron microscopic examination showed that the tumor cells had mesenchymal-fibroblastic features. The tumor had an aneuploid DNA content with high S-phase fraction. The patient, who was treated with adjuvant chemotherapy, was alive, having had three recurrences in 36 months. In the second and third recurrent lesions, increased cellular atypla and fascicular arrangements of spindle cells were observed. DSCT should be included in differential diagnoses of postmenopausal pelvic tumors which show light-microscopically and immunohistochemically divergent phenotypes.     

Synovial sarcoma. Inter-relationship of the biphasic and monophasic subtypes.

In order to assess minimum diagnostic criteria for synovial sarcoma, particularly the monophasic variety, and the inter-relationship between the monophasic and biphasic types, 32 examples were studied histologically, immunohistochemically (26 cases), and ultrastructurally (13 cases). Of the six biphasic synovial sarcomas examined by electron microscopy, the spindle cell component did not show evidence of epithelial differentiation or resemble the epithelial phase, but did appear fibroblastic; no tumor cells transitional between the spindle and epithelial component were evident. In contrast, all of the seven monophasic lesions had ultrastructural growth patterns and some cellular features approximating the epithelial cells of the biphasic variant. In 11 biphasic synovial sarcomas, epithelial membrane antigen was detected in the glandular epithelium of all cases and cytokeratins in eight cases; in no case were these antigens detected in the spindle cell regions of biphasic lesions. Of the 15 monophasic synovial sarcomas, two were positive for cytokeratins and four for epithelial membrane antigen. Thus, the detection of epithelial markers either immunohistochemically or by electron microscopy (or both) should be the minimal diagnostic criteria for monophasic synovial sarcomas. Based on these findings, it is suggested that monophasic synovial sarcomas do not represent the spindle cell or "stromal" phase of biphasic synovial sarcomas, but are a poorly differentiated variant of the latter. As others have suggested, these tumors are, in fact, carcinosarcomas and carcinomas of the soft tissues and the designation synovial sarcoma is inappropriate for this tumor class.     

Spindle cell carcinoma of the breast: A case report and an immunohistochemical study including p53 and Ki-67 expression

A rare case of spindle cell carcinoma (SpCC) of the breast occurring In a 51-yearold Japanese woman Is reported. A firm and well-circumscribed tumor, measuring 9times8.5times8.5 cm, was located on the upper lateral region of the right breast. Microscopically, the tumor consisted of sheets of both malignant spindle cells and poorly differentiated ductal carcinoma containing squamold islands with gradual transition to the spindle cell component. The Immunocyto chemical expression of epithelial markers was recognized in the spindle cells, as well as in the carcinomatous cells. Moreover, the spindle cell component expressed vimentin, α-smooth muscle actln and S-100 protein. Ultrastructurally, in addition to the features of adenocarcinoma, squamous or rnyoeptthelial differentiation was confirmed in the spindle cell component. These findings thus suggest an epithelial origin with squamous differentiations and myoepithellal participation In the genesis of SpCC. In a comparative study, the expression of p53 protein and KI-67 as a proliferation marker In each component of this tumor was also Investigated. The mean p53 labeling index (LI) in both the carcinomatous and spindle cell area was similar, however the mean MIB-1 LI in the spindle cell area was significantly higher than that in the carcinomatous area. The results indicate that p53 over-expression is Involved In the tumorigenesis of both components in the SpCC, and the spindle cell component shows a higher degree of proliferative activity than the carcinomatous component.     

DNA aberrations in the epithelial cell component of adamantinoma of long bones.

Adamantinoma of long bones is a rare malignant tumor composed of cells with epithelial characteristics in various differentiation patterns surrounded by fibrous cells. Evidence as to whether this neoplasm should be designated as an epithelial bone tumor or a biphasic sarcoma with both epithelial and mesenchymal features is lacking. In this study the nature of the mesenchymal and epithelial components of adamantinoma was investigated by DNA flow cytometry, DNA image cytometry, p53 immunohistochemistry, and polymerase chain reaction-based loss of heterozygosity detection at the p53 locus. Specimens from 6 of 15 patients (40%) analyzed by flow cytometry had an aneuploid DNA index. Image cytometry analysis of Feulgen-stained paraffin sections of 6 aneuploid and 2 diploid tumors revealed that aneuploid nuclei were detected in cells with an epithelial phenotype only, whereas all fibrous cells were diploid. Immunohistochemistry for p53 on specimens from 25 patients revealed moderate or strong immunoreactivity in 12 tumors (48%) restricted to the epithelial cells. Loss of heterozygosity at the p53 locus could be confirmed in the epithelial component of an immunohistochemically p53-positive tumor. Additionally, sections of 7 lung metastases were studied histologically. Only keratin-positive epithelial cells, predominantly in the spindle cell pattern, were present in these metastases, whereas the osteofibrous tissue present in the primary tumors was not detected. These results suggest that either adamantinoma consists of a malignant epithelial part with a reactive osteofibrous stroma or that the malignant epithelial cells develop next to a proliferating benign fibrous component. Additional analysis of common genetic abnormalities in the fibrous and epithelial cells of adamantinoma is therefore indicated.     

Localization of simian immunodeficiency virus in the central nervous system of rhesus monkeys.

Simian immunodeficiency virus (SIV), like the human immunodeficiency virus (HIV), is a lentivirus that is both immunosuppressive and neurovirulent. Rhesus macaques (Macaca mulatta) inoculated with SIV often develop a giant cell encephalitis similar to that seen in humans infected with HIV. The authors examined SIV expression by immunohistochemistry and RNA in situ hybridization in the cerebrum, cerebellum, choroid plexus, and spinal cord from five macaques with and two macaques without giant cell encephalitis. Selected portions of the central nervous system (CNS) also were examined by electron microscopy. Simian immunodeficiency virus was detected in the CNS of all seven monkeys whether or not they had giant cell encephalitis. Both SIV antigen and RNA were present in all levels of the CNS examined. Macrophage/giant cell lesions always contained viral RNA and antigen and were the only sites where viral particles were detected by electron microscopy. However, SIV antigen and RNA also were commonly associated with small vessels, the choroid plexus, and meninges; these were the only locations where virus was detected in animals without giant cell encephalitis. Immunophenotyping showed that the cellular infiltrates consisted primarily of monocyte/macrophages and occasional CD8-positive T cells. Macrophages and T cells also were present in the stroma of the choroid plexus and were intimately associated with vessels in the CNS of SIV-infected but not uninfected macaques. Simian immunodeficiency virus infection of the macaque CNS provides an excellent model for studying the pathogenesis, treatment, and prevention of HIV-1-encephalitis.     

Effect of hypercholesterolemia on the in vitro production of granulocytes and monocytes in the chick

Normal and hypercholesterolemic sera were not different with regard to the number of granulocyte-monocyte clones supported or to the percentage of granulocytic clones supported. However, 97% of the mononuclear cell clones induced by hypercholesterolemic serum contained cells which had differentiated into very large, highly vacuolated macrophages (= giant cell) of very low replicative potential (clone size = 3–9 cells). When low-density lipoproteins isolated from hypercholesterolemic plasma (LDL-H) were added to cultures stimulated with normal serum, most (74%) of the resulting clones were giant-cell ones. Other classes of lipoproteins had this effect but the magnitude was lower (53% maximum). Even LDL from normal animals was ineffective. Approximately 70% of the mononuclear cell clones induced by normal serum contained cells which had differentiated into monocytes and small macrophages (three to four times smaller than giant cells) of very high replicative potential (clones ? 50 cells). The number of granulocytic clones was not affected by any lipoprotein class. Dilution, heat inactivation, and lipoprotein depletion of hypercholesterolemic serum eliminated its ability to induce giant cells and, following these treatments, it was as active (or more in the case of lipoprotein depletion) as normal serum at inducing regular macrophage clones. These treatments showed that a decrease in a serum's ability to induce giant cells was correlated in degree and kinetics with an increase in its ability to produce regular macrophages, suggesting that the two cell types derive from a common progenitor.     

Acute and Chronic Effects of Intraperitoneal Injection of Two Types of Asbestos in Rats with a Study of the Histopathogenesis and Ultrastructure of Resulting Mesotheliomas

Malignant mesotheliomas were induced in the rat peritoneum by a single injection of chrysotile or crocidolite asbestos fibers. The immediate toxicity of the fibers was noted in both groups of animals, producing approximately 40% mortality, within 8 days after the injection associated with acute peritonities. Tissue reactions to these two types of asbestos were significantly different. Crocidolite fibers were easily seen by light microscopy, in the tissue sections throughout the period of study, and they produced foreign-body giant cell granulomas. However, giant cells were not seen in chrysotile granulomas, and the asbestos fibers were only seen by electron microscopic study. They appeared to be coated by a protein-like substance. During earlier stages of tumorigenesis, the epithelioid and/or mixed cell type mesotheliomas seemed to have no specific relationship to granulomas, but pure spindle cell tumors were seen to develop in close relationship to granulomas, and they appear to be fibrosarcomas. Electron microscopic and histochemical methods were used to define the morphologic characteristics of the tumor cells. The formation of hyaluronic acid was found in cells of the epithelioid type, contrasted with extracellular accumulation in the spindle cell tumors.     

Uterine leiomyosarcoma with osteoclast-like giant cells: Histopathological and cytological observations

A 56 year old woman presented with abnormal uterine bleeding. Except for a myomatous uterus, no other abnormalities were noted on physical examination and in radiographic and serologic studies. The hysterectomy specimen revealed an 8 cm uterine fundic tumor composed of two histologically different patterns that merged with one another; one was a well differentiated leiomyosarcoma and the other a mixture of osteoclast-like giant cells (OGC) and plump spindle cells whose cell borders blended, resembling the histology of giant cell tumor of bone. lmmunohistochemical studies showed positive staining for muscle actin, α-smooth muscle actin, and KP-1 (CD68) in both the spindle cells and OGC. The latter also stained for α-1-antitrypsin and α-1-antichy-motrypsln. These findings suggested that OGC may be formed by the fusion of spindle cells of leiomyosarcoma and also express histiocytic markers.     

Primary spindle-cell sarcomas of the breast: diagnosis by fine-needle aspiration

Primary breast sarcomas (excluding cytosarcoma phyllodes and its sarcomatous recurrences) are rare neoplasms. Few have been described in the aspiration cytology literature. We report the cytologic features of two cases of stromal sarcoma (both with the pattern of malignant fibrous histiocytoma) and two cases of angiosarcoma. The dominant cytologic features included individual atypical spindle cells and fragments of collagenous stroma. Tumor giant cells were present in one stromal sarcoma. Features of possible significance in the diagnosis of angiosarcoma include obvious vessel formation by atypical spindle cells, bridging of adjacent tumor fragments by spindle cells, and microacinar structures lined by atypical spindle cells. The differential diagnostic considerations in spindle-cell breast aspirations are discussed.