Virchows Archiv

Thiele, Juergen; Fischer, Robert

doi: 10.1007/BF01606907pmid: 1455689

Löhr, M.; Bergstrome, B.; Maekawa, R.; Oldstone, M.; Klöppel, G.

doi: 10.1007/BF01606908pmid: 1360719

Human cytomegalovirus (HCMV) was recently demonstrated in the pancreas of about half the patients with type 2 diabetes mellitus in the absence of mumps, rubella or Coxsackie B virus. The present study addresses the question as to whether type 2 diabetes with an HCMV-positive pancreas differs from those with HCMV-negative pancreases with respect to age, sex, treatment, duration of disease, volume densities of B-cells and D-cells, mRNA levels of insulin and somatostatin, islet amyloid peptide deposits and major histocompatibility complex (MHC) class I and class II gene transcription, and protein expression. HCMV-positive type 2 diabetic patients showed a tendency towards a shorter duration of disease and significantly increased levels of MHC class II on RNA. In addition, expression of MHC class II product (HLA-DR) was identified in duct epithelial cells and/or islet cells in 9 diabetic pancreases and in 2 non-diabetic glands. No MHC class I expression could be detected. No other clinical differences between HCMV-positive and HCMV-negative glands were found. All 10 HCMV-positive diabetics showed a strong expression of MHC class II mRN in the pancreas. By immunocytochemistry, 4 of 10 demonstrated expression on the islets; three of ten also expressed MHC DRβ on ductal cells. This finding might be related to the viral infection, as only 2 of the 9 HCMV-negative patients were HLA-DRβ positive and none of the non-diabetic controls showed increased levels of MHC class II mRNA. These data suggest that HCMV infection in the pancreas is associated with type 2 diabetes. However, no conclusions as to a role of this virus in the aetiopathology of type 2 diabetes can be drawn at present.

Rosa, G.; Donofrio, V.; Boscaino, A.; Zeppa, P.; Staibano, S.

doi: 10.1007/BF01606909pmid: 1280880

We investigated the clinicopathological findings in five cases of multicystic mesothelial proliferation (MMP). All masses consisted of multiloculated cysts attached to pelvic organs and sometimes growing into the upper abdominal cavity. The cystic spaces were lined by flattened or cuboidal cells. The stroma showed fibrosis, oedema and chronic inflammation. Immunohistochemistry revealed strong positive staining for cytokeratin and epithelial membrane antigen, and focal positivity for vimentin and carcinoembryonic antigen. The endothelial markers were negative. Electron microscopy showed abundant surface microvilli and well-developed basal lamina. DNA analysis identified euploid cell populations in all cases. All but one case had a previous history of abdominal surgery. Despite the worrying appearance the clinical outcome was favourable in all cases; there was one recurrence. Clinical and pathological data support the hypothesis that MMP represent a reactive mesothelial proliferation and not a neoplastic process.

Niwa, Kanji; Yokoyama, Yasuhiro; Furui, Tatsuro; Tanaka, Takuji; Mori, Hideki; Mori, Hidehiro; Tamaya, Teruhiko

doi: 10.1007/BF01606910pmid: 1455690

A high incidence of endometrial adenocarcinoma and pre-neoplastic lesions was induced in ICR mice treated withN-methyl-N-nitrosourea and 17β-oestradiol within 23 weeks. The endometrial lesions were histopathologically similar to those of human subjects. To assess the cell proliferative activity of these lesions, a one-step silver colloid staining for nucleolar organizer regions was applied and the numbers of silver-stained nucleolar organizer regions (AgNORs) were counted. The mean numbers±SD of AgNORs in each lesion were as follows: simple hyperplasia, 2.07±0.36; complex hyperplasia without cytological atypia, 2.79±0.39; complex hyperplasia with cytological atypia, 3.43±0.38; and well-differentiated adenocarcinoma, 4.17±0.40. Significant differences were observed in each lesion (P<0.001). These findings suggest that the mean numbers of AgNORs are increased in the progression of neoplastic changes in the mouse endometrium, as in human endometrial lesions. This rapid induction model of endometrial carcinoma in mice is useful in the understanding of the histogenesis of endometrial carcinoma in human subjects.

Wang, Da-peng; Konishi, Ikuo; Koshiyama, Masafumi; Nanbu, Yoshihiko; Iwai, Toshiko; Nonogaki, Hirofumi; Mori, Takahide; Fujii, Shingo

doi: 10.1007/BF01606911pmid: 1360720

The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor showing molecular homology with the epidermal growth factor receptor (EGFR). We examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary. The ovarian tumours were classified as benign (16), borderline malignant (2), and malignant (19). Normal surface ovarian epithelium was weakly positve for both c-erbB-2 protein and EGFR. In surface inclusion cysts, however, the epithelial cells lining the lumen exhibited stronger staining for c-erbB-2 protein, but no staining for EGFR. All 16 benign ovarian tumours and the 2 borderline malignant ovarian tumours were positive for c-erbB-2 protein and negative for EGFR. Of the ovarian carcinomas, 13 of the 19 (68.4%) were positive for c-erbB-2 protein and negative for EGFR, while 4 showed positivity for both c-erbB-2 protein and EGFR. Two cases were negative for both proteins. Expression of both c-erbB-2 protein and EGFR was found in endometrioid carcinoma with squamous differentiation and in clinically advanced poorly differentiated serous carcinomas. Expression of c-erbB-2 protein appears to be increased and that of EGFR is reduced in the early stage of epithelial ovarian oncogenesis. The expression of EGFR with c-erbB-2 protein in ovarian carcinoma is related both to histological differentiation and/or advanced clinical stage.

Ishida, Tsuyoshi; Oka, Teruaki; Matsushita, Hiroshi; Machinami, Rikuo

doi: 10.1007/BF01606912pmid: 1280881

Eight epithelioid sarcomas (ES) were studied by electron microscopy, immunohistochemistry, and DNA flow cytometry. Ultrastructurally, the tumour cells showed desmosome-like intercellular junctions and numerous microvilli, in addition to whorled arrangements of intermediate filaments. Tumour cells were positive for epithelial membrane antigen, cytokeratin, and vimentin, and negative for carcinoembryonic antigen and desmin. All seven cases examined by flow cytometry showed diploid or hyperploid (near diploid) DNA content. This seems to correspond to the relatively long clinical course and low-grade malignant nature of ES. Although the histogenesis of ES is still uncertain, the results of this study suggest that it is a tumour of primitive mesenchymal cells with the capacity to show epithelial differentiation.

Nakanoma, Takashi; Nakamura, Kaoru; Deguchi, Nobuhiro; Fujimoto, Junichiro; Tazaki, Hiroshi; Hata, Jun-ichi

doi: 10.1007/BF01606913pmid: 1455691

Immunological characterization of tumour infiltrating lymphocytes (TIL) by immunohistological techniques was carried out in 20 cases of stage I seminoma. Routine pathological examination of these surgical specimens showed typical seminoma in 20 cases. Eighteen cases showed obvious TIL and immunohistological staining on frozen specimens was performed in 12. TIL in seminomas were predominantly T-cells but B-cells were also identified. T-cells were distributed diffusely with predominance of the CD 8+ phenotype judged semiquantitatively. In contrast to the distribution of T-cells, B-cells tended to accumulate and occasionally formed lymphoid follicles. In such follicles the phenotypic pattern of B-cell antigens was comparable with secondary lymphoid follicles in lymphoid organs. There is an immunologically complex response to seminoma by the host with a predominant infiltration of cytotoxic/ suppressor T-cells and functional maturation of B-cells.

Soini, Ylermi; Kamel, Dia; Nuorva, Kyösti; Lane, David; Vähäkangas, Kirsi; Pääkkö, Paavo

doi: 10.1007/BF01606914pmid: 1333678

Fifty-one salivary gland tumours (23 pleomorphic adenomas, 5 Warthin's tumours, 12 mucoepidermoid carcinomas, 7 adenoid cystic carcinomas, 3 undifferentiated carcinomas and 1 acinic cell tumour) and 27 lung carcinomas (18 squamous cell carcinomas, 6 adenocarcinomas and 3 small cell carcinomas) were analysed immunohistochemically for the expression ofp53 nuclear phosphoprotein. Eight out of 51 (16%) salivary gland tumours werep53 positive. Three of these were benign and 5 malignant. All 3 benign salivary gland tumours were pleomorphic adenomas and expressed only occasional nuclear positivity with less than 1% of tumour cells positive. Of the 5p53-positive malignant tumours, 3 were mucoepidermoid carcinomas and 2 undifferentiated carcinomas. The malignant salivary gland tumours expressed more than 1% of positive nuclei in every case. Seventeen lung carcinomas werep53 positive (63%). Thirteen of these were squamous cell carcinomas, 3 were adenocarcinomas and 1 small cell lung carcinoma. The results show that mutations of thep53 gene may be infrequent in salivary gland tumours when compared with lung carcinomas. The relatively indolent course of some histological types of malignant salivary gland tumours could be associated with the preservation of the non-mutatedp53 gene in most of these tumours. The presence ofp53 positivity in some pleomorphic adenomas might, on one hand, suggest thatp53 gene alterations are also present in these tumours; on the other hand, the accumulation of thep53 protein in these tumours might also be due to some unknown mechanism, not necessarily related top53 gene mutation.

Ohtsuki, Yuji; Furihata, Mutsuo; Inoue, Keiji; Iwata, Jun; Manabe, Yuiko; Sonobe, Hiroshi; Ochi, Kenji; Seike, Hiroshi; Hashimoto, Hirofumi; Terao, Naotami

doi: 10.1007/BF01606915pmid: 1280882

Intraluminal crystalloids (ICr) observed in 19 cases of incidental or invasive human prostatic carcinoma (PCa) and in a case of benign prostatic hyperplasia were examined extensively by immunohistochemistry and electron microscopy. They were brilliantly eosinophilic with haematoxylin and eosin, manifesting needlelike, triangular, rectangular, hexagonal and irregular lump-like in shape. They were strongly positive, dark blue, with phosphotungstic acid -haematoxylin (PTAH) stain in all cases examined. Among the human antibodies tested, epithelial membrane antigen (EMA) gave specifically positive immunostainability with ICr in all cases. Annual ring-like lamellar or concentric structures were detected by electron microscopy. Positive staining of ICr with PTAH and anti-EMA antibody is very useful as a diagnostic marker for PCa in human prostatic tissues.

Bianco, Paolo; Silvestrini, Giuliana; Ballanti, Paola; Bonucci, Ermanno

doi: 10.1007/BF01606916pmid: 1455692

Nuclear inclusions, identical to those characteristic of Paget's disease of bone, were observed in giant cells in four of eight cases of primary oxalosis. The giant cells containing nuclear inclusions were directly involved in phagocytosis of large oxalate crystals in the context of typical foreign body granulomas in the bone marrow. Cytochemically, all of them exhibited strong tartrateresistant acid phosphatase activity, and a proportion of them also tartrate-resistant acid ATPase. The inclusions consisted of typical arrays of filamentous material as described in Paget's disease, admixed with variable proportions of electron-dense material closely reminiscent of nucleolar pars fibrillaris and fibrillary centres. These data indicate: (a) the occurrence of Paget-like inclusions in a bone disease unrelated to Paget's disease, not causally related to viral infection, and resulting from an inborn metabolic derangement; and (b) the occurrence of Paget-like inclusions in foreign body giant cells as opposed to osteoclasts. We suggest that the occurrence of paramyxovirus-like nuclear inclusions in either osteoclasts or giant cells may represent an epiphenomenon of cell fusion and giant cell formation whenever appropriate stimuli act on latently infected precursor cells. Further-more, our data suggest that nucleoli may represent the specific site of virus-like inclusion formation.