Takeaki Fukuda

Preferential localization of c-kit product in tissue mast cells, basal cells of skin, epithelial cells of breast, small cell lung carcinoma and seminoma/dysgerminoma in human: immunohistochemical study on formalin-fixed, paraffin-embedded tissues

Eighteen hundred and eighty-four cases of human solid tumours and 833 samples of normal human tissues, formalin-fixed and paraffin-embedded, were examined immunohistochemically for expression of c-kit oncogene product using polyclonal antibody against synthesized c-kit peptide. Seminoma/dysgerminoma and small cell lung carcinoma (SCLC) show preferential c-kit expression at 92% and 36% frequency, respectively, whereas only sporadic cases of cervical carcinoma and non-SCLC lung carcinoma show c-kit positivity. A normal tissue counterpart positive for c-kit product is detected in the testis (spermatocyte) and ovary (oocyte) but not in the lung or the cervix. In contrast, normal epithelial cells of the breast, skin basal cells and tissue mast cells harbour c-kit product, but transformed cells of the former two are largely deficient in the c-kit protein. One hundred and thirty-nine neuroendocrine tumours and 39 non-pulmonary small cell carcinomas were all negative, except for two cases of neuroblastoma. This indicates a distinct character for SCLC in c-kit expression. The c-kit product may be a useful marker in diagnostic pathology of seminoma/dysgermona and SCLC among human solid tumours, and in distinction of SCLC from non-pulmonary small cell carcinoma.

Expression of Deoxycytidine Kinase (dCK) Gene in Leukemic Cells in Childhood: Decreased Expression of dCK Gene in Relapsed Leukemia

Competitive RT-PCR was used to determine the quantitative variation in the expression of deoxycytidine kinase (dCK) gene in childhood leukemic cells. The degree of dCK gene expression varied over a 50-fold range. In two cases in which both primary and relapsed leukemic cells were analysed, decreased expression of dCK gene was found in relapsed leukemic cells. The sequence variation analysis using bisbenzimide/polyethylene glycol electrophoresis demonstrated no sequence alteration of dCK cDNA in all cases. These results indicate that the expression of dCK gene varies in patients and suggests decreased expression of the dCK gene as one of the mechanisms responsible for clinical resistance to ara-C.

Both acute phase and constitutive serum amyloid A are present in atherosclerotic lesions

The polymorphic protein, serum amyloid A (SAA), consists of acute phase Isotypes and a constitutive Isotype. Both are associated mostly with high density lipoproteins (HDL) In the circulation. In the present study, both SAA isotypes were detected by Immunohistochemistry and Immunoblotting using monocional antlbodies In atherosclerotic lesions. As the distribution of SAA was identical with that of apolipoprotein B and SAA is known to be associated also with low density lipoproteins (LDL), SAA may also be delivered to the artery wall by LDL.

Pigmented renal cell carcinoma

A rare case of pigmented renal cell carcinoma is presented. The tumor was yellow, somewhat elastic, and soft with focal gray and tan areas. Microscopically, the tumor was a typical renal cell carcinoma of the clear-cell type. Tumor cells containing brown pigment in the cytoplasm were scattered throughout the tumor. Ultrastructurally, the electron-dense granules consistent with the brown pigment noted at the microscopic level showed a coarse or fine granular matrix with or without homogeneous high electron-dense areas, resembling lipofuscin. However, the nature of the pigment was different from that of lipofuscin by the Masson-Fontana method after bleaching and rather similar to neuromelanin. The current case is a rare renal cell carcinoma with pigmentation attributed to abnormally excessive accumulation of neuromelanin pigment.

Carcinosarcoma of the urinary bladder: Expression of epithelial markers and different expression of heat shock proteins between epithelial and sarcomatous elements

A case of carcinosarcoma composed of both adenocarcinoma and saarcomataus elements in the non‐trigone region of the urinary bladder is presented. The epithelial element was a well to pooriy differentiated adenocarcinome with focal squamous metaplasia. The sarcomatous elements disclosed spindle cell sarcoma with focal epltheliold pattern and myxold change In the stroma, together with chondrosarcomatous and rhabdomyosarcomatous elements. By Immunohistochemical examination, not onty the carcinoma element but also the sarcomatous elements showed a positive lmmunoreaction for cytokeratin (CK), epithelial membrane antigen (EMA) and carcinoembryonic antigen. Some population of sarcomatous elements expressed smooth muscle actin and muscle specific actin (MSA) and a limited portion of epitheliold area showed a positive Immunoreaction for desmin, MSA and myoglobin, Indicating leiomyosarcomatous and rhabdomyosarcomatous differentiation, respectively. Unexpectedly, tumor cells In the chondrosarcomatws element revealed a simultaneous positvity of CK and EMA as well as S‐100 protein. Both epithelial and sarcomatous elements showed an Intensive positive Immunoreaction for p53 and heat shock protein (HSP) 70. However, HSP27 and HSPGO were detected in most epitheilal elements and only in a small number of tumor cells in the sarcomatous area. These findings indicate that sarcomatous elements, Including heterologous elements, may derive from epithelial elements with partial or complete loss of epithelial features, and different factors other than p53 and HSP7O may associate wtth the morphological alteration of carcinoma.

Amyopathic dermatomyositis associated with transformed malignant lymphoma

Amyopathic dermatomyositis is a disease of unknown origin characterized by the specific skin lesions of dermatomyositis but without clinical or laboratory evidence of myopathy. During the past 15 years, a great controversy between the different reports concerning a possible association of dermatomyositis with malignancy has been noted. In this report, the authors describe a patient with amyopathic dermatomyositis who presented first with a benign hyperplasia of the lymph node, which finally transformed into frank malignant lymphoma. In addition to follow-up care, screening tests to search for occult malignancy in patients with amyopathic dermatomyositis (or dermatomyositis) are recommended.

Low Expression of the Deoxycytidine Kinase (dCK) Gene in a 1-β-D- Arabinofuranosylcytosine-Resistant Human Leukemic Cell Line KY-Ra

Molecular change of the deoxycytidine kinase (dCK) gene in a 1-beta-D-arabinofuranosylcytosine-resistant human leukemic cell line (KY-Ra) was investigated. KY-Ra showed the same restriction pattern of genomic DNA and the same nucleotide sequences of the dCK gene as the parental cell line. However, the amount of deoxycytidine kinase mRNA was markedly decreased in KY-Ra compared to the parental cell line. This is the first report showing that the down regulation of dCK gene expression may be affected by a different mechanism than mutation.

Primary small cell carcinoma of the esophagus with ectopic gastrin production. Report of a case and review of the literature.

SummaryA case of primary small cell carcinoma of the esophagus in which extensive hormonal studies could be performed is reported. The tumor was considered as a neuroendocrine tumor because the tumor cells showed intracytoplasmic argyrophilia, neurosecretory granules, and positive stain for neuron-specific enolase with Grimelius stain, electron microscopy, and immunohistochemistry, respectively. Furthermore, the tumor was regarded as a gastrin-producing tumor because of positive stain for gastrin in the tumor cells. The present case is the esophagus with ectopic gastrin production.

Sarcomatoid carcinoma of the small intestine: Histologic, immunohistochemical and ultrastructural features of three cases and its differential diagnosis

Three cases of sarcomatoid carcinoma of the small intestine are presented. One of them was found accidentally in the duodenum of a patient with a well differentiated adenocarcinoma and a malignant lymphoma that were limited to the stomach. The other two cases arose from the lleum. All of the tumors were whitish, soft and ulcerated with focal hemorrhage and necrosis and showed expansive growth. Each tumor consisted of a mixture of polygonal and spindle shaped anaplastic neoplastic cells arranged in sheet, short fas‐cicular or haphazard fashion, with no finding suggesting epithelial differentiation. Special stains demonstrated intra‐cellular mucin in only a small number of tumor cells in two cases, but not in the other case. Immunohistochemically, the tumor cells of two cases at both primary and metastatic sites showed a positive immunoreaction for cytokeratin and epithelial membrane antigen. In the other case, only a few tumor cells at the metastatic site, but not at the primary site, showed cytokeratin positivity. Various numbers of tumor cells positive for vimentin, α‐1‐antitrypsin (AAT), α‐1‐antichy‐motrypsin (ACT) and KP‐1 were detected in each case. Ultrastructurally, some populations of tumor cells possessed various amounts of tonofilaments with a few Intercellular connections between adjacent tumor cells. These cases should be classified as sarcomatoid carcinoma of the small intestine, despite partial or complete loss of epithelial features, and distinguished from the various sarcomas.

Peripheral carcinoid tumor of the lung with focal melanin production

A case of carcinoid tumor of the lung with focal melanin production was encountered in a 56 year old Japanese woman. The tumor was found 16 years previously by mass survey chest X‐ray and had enlarged two‐fold in the intervening period. The tumor consisted of a variety of tumor cells showing a spindle, polygonal and pleomorphic appearance with abundant vasculature in the stroma. All tumor cells showed argyrophilia, together with a few showing argent‐affinity. Melanin‐containing tumor cells were also present in parts. Ultrastructurally, most tumor cells possessed various numbers of neurosecretory granules and a few of them contained granular type rnelanosomes. Tumor cells were connected with desmosomes and a few of them contained tonofilament‐like microfilaments. Only a few contained both neurosecretory granules and melanin. By immunohistochemistry, serotonin, metenkephalin and β‐endorphin positive cells were observed scattered throughout the tumor. A few tumor cells positive for tyrosine hydroxylase were also detected. Additionally, most tumor cells were positive for keratin. On the basis of these findings, the tumor of the current case is a pulmonary carcinoid tumor with focal melanin production.