A Case Report of Inflammatory Pseudosarcoma of the Urinary Bladder

A case of inflammatory pseudosarcoma of the urinary bladder in a 35 year-old Japanese male is presented. This benign lesion can easily be mistaken for spindle cell sarcoma since it consists of rhabdomyoblast like elongated strap cells showing infiltrative growth, and whether it is benign or malignant is difficult to determine by microscopic examination. In this case, spindle cell proliferation extended among bundles of the superficial muscle layer. However, no abnormal mitoses, severe nuclear atypia or cellular pleomorphism could be seen, thus indicating inflammatory pseudosarcoma. Although the lesion was not completely resected, no recurrent disease has been clinically observed for two years following transurethral resection. Urologists and surgical pathologists must be able to detect this lesion in order to avoid unnecessary surgical procedures. Acta Pathol Jpn 42: 760 765,1992.     

Immunohistochemical examination of lung cancers using monoclonal antibodies reacting with sialosylated Lewisx and sialosylated Lewisa

Summary In order to explore the relationship between the expression of cancer-associated glycolipids such as sialylated Le^x (SLEX) and sialylated Le^a (SLEA) and the histological subtypes of lung cancers, 30 cases of small cell carcinoma (SCC) and 47 cases of non-small cell carcinoma (non-SCC) were examined immunohistochemically using monoclonal antibodies reacting with SLEX and SLEA. The forty-seven cases of non-SCC included 20 cases of adenocarcinoma, 20 of squamous cell carcinoma and 7 of large cell carcinoma. Tumour cells of most non-SCCs expressed SLEX and SLEA. In adenocarcinomas, the number of tumour cells having SLEX and SLEA was more than that of squamous cell carcinomas, large cell carcinomas and SCC. In SCC, 14 of the 30 cases were found to be positive for both antigens. Although the cancer cells of 11 cases of 17 intermediate cell type SCC had both antigens, the cells of only 3 of 13 oat cell tumours expressed SLEX and SLEA. The present study shows that SLEX and SLEA are useful markers for lung adenocarcinomas, that most cases of intermediate cell type of SCCs have characteristics similar to non-SCC but that many oat cell tumours lack them.     

Active Cyclin A-CDK2 Complex, a Possible Critical Factor for Cell Proliferation in Human Primary Lung Carcinomas

Expression of cyclins A and E and cyclin-dependent kinase 2 (CDK2) was examined immunohistochemically in 190 cases of human lung carcinoma. Cyclin A and CDK2 were expressed in the majority of squamous cell carcinomas, small cell carcinomas, and large cell carcinomas, but in significantly fewer cases of adenocarcinomas. Cyclin E was expressed in a minority of all subtypes. In particular, well differentiated cells in squamous cell carcinoma stained positively for cyclin E; in contrast, cyclin A was expressed in the nonkeratinized proliferating areas of the tumor nests. Immunoblotting revealed that all these proteins were expressed at higher levels in tumor tissues than in adjacent normal tissues. Immunoprecipitation also revealed higher levels of cyclin A and cyclin E associated with CDK2 in tumor tissues. Furthermore, tumor tissues which exhibited higher cyclin A and CDK2 expression also had higher CDK2 kinase activity. However, cyclin E-associated kinase activity was barely detectable even in tumor samples exhibiting higher cyclin E expression. Consistent with these data, elevated expression of cyclin A correlated to shorter survival periods in contrast to expression of cyclin E, which correlated to longer survival periods. These results suggest that in human lung carcinomas, elevated expression of active cyclin A-CDK2 complexes with associated higher CDK2 kinase activity is critical for promoting cell cycle progression and unrestrained proliferation of tumor cells and can be a predictive marker for patients’ prognosis. On the other hand, immunohistochemical detection of cyclin E-CDK2 reflects accumulation of inactive forms of protein complexes, implying differentiation or senescence of the tumor and the better prognosis.     

Pituitary choristoma composed of corticotrophs and adrenocortical cells in the sella turcica

A pituitary tumour composed of well-differentiated corticotrophs and adrenocortical cells is reported. Sections of the tumour revealed a mixture of small round cells with amphophilic or basophilic periodic acid-Schiff (PAS)-positive cytoplasm and large spherical and oval cells with abundant, granular, partly vacuolated PAS-negative cytoplasm. The small cells contained type 1 cytokeratin-positive microfilaments, numerous 250–500 nm endocrine-type secretory granules immunoreactive for adenocorticotropic hormone (ACTH) and -lipotropin. The large cells possessed ample cytoplasm filled with abundant vesicular smooth endoplasmic reticulum, numerous mitochondria possessing tubulovesicular cristae and frequent dense bodies. They lacked the features of pituitary endocrine cells or folliculostellate cells and were found to contain a panel of steroidogenic dehydrogenases and hydroxylases. The tumour was classified as a choristoma, in which two distinct cells types, corticotrophs and adrenocortical cells, were mixed. We suggest that, under continued ACTH stimulation, uncommitted stem cells may differentiate into adrenocortical cells. Alternatively, the presence of adrenocortical cells may be the result of heterotopia.     

Human cytomegalovirus infection in foci of Langerhans cell histiocytosis

 Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection and expression of TNFα. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated with HCMV infection. Received: 24 November 1998 / Accepted: 24 April 1998     

Mixed growth hormone cell- prolactin cell pituitary adenoma with acromegaly: α-subunit most growth hormone cells

A 51 -year-old woman with mixed growth hormone (GH) cell-prolactin (PRL) cell pituitary adenoma is presented. She had clinical signs due to hypersecretion of GH and PRL. Resected tissue was studied immunohistochemically and morphologically. The serial sections revealed that GH and α-subunit were co-localized in most cells, while GH and PRL were localized in different cells.     

Pulmonary blastoma. Comparison between its epithelial components and fetal bronchial epithelium.

Three cases of pulmonary blastoma exhibiting biphasic epithelial and stromal patterns, and a case of fetal lung-type adenocarcinoma, were examined by immunohistochemistry and electron microscopy (EM) and compared with fetal bronchial epithelium in order to explore the multidirectional differentiation of their epithelial components. The glandular cells of all four tumors resembled fetal bronchial epithelial cells in the pseudoglandular stage. Neuroendocrine (NE) cells were also present; they were argyrophilic and expressed pan-NE markers, neurosecretory granules and peptide hormones. The neural cell adhesion molecule (NCAM) was strongly expressed on the cell membranes of glandular cells, as in the case of proximal bronchial epithelial cells at the pseudoglandular stage in fetal lung. Sialosylated Lewis X was also expressed, indicating that the epithelial cells were possibly of endodermal origin. Two of the four cases showed considerable immunoreactivity for alpha-fetoprotein (AFP). The epithelial cells of pulmonary blastomas may occasionally de-differentiate into cells functionally resembling fetal hepatic, foregut and yolk sac cells expressing AFP. Tumor examination by immunohistochemistry and EM suggested that the glandular cells of the tumors may differentiate to some extent like those of fetal large bronchi at the pseudoglandular stage, but there was concordance and discordance in the expression of neuroendocrine and oncofetal markers between blastomatous tumors and fetal bronchial epithelium.     

Pancreatic endocrine tumours associated with WDHA syndrome

Summary Nine pancreatic endocrine tumours of patients with watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome were examined by immunohistochemistry and electron microscopy. All cases revealed neoplastic proliferation of VIP (vasoactive intestinal peptide)-immunoreactive (IR) cells. Immunoreactivity to a novel peptide hormone PHM-27, which is processed from a common big precursor peptide of VIP (prepro VIP/PHM-27), was identified in VIP-IR cells of 8 tumours. VIP-PHM-IR cells had secretory granules measuring about 130 to 220 nm in diameter. Radioimmunoassay of tumour tissue extracts showed high VIP and PHM contents in proportional amounts in most cases. According to the results of immunostaining, the 8 tumours fell into two large groups; 5 with PP (pancreatic polypeptide)-IR cells and 3 with CT (calcitonin)-IR cells. The former group demonstrated VIP cells and PP cells intermingled in various proportions, including one tumour in which coexistence of PP-IR and VIP-IR in the same cells was demonstrated. Cell heterogeneity of the tumours and possible relationships of VIP, PP and CT cells were discussed.This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare and from the Ministry of Education, Science and Culture, Japan     

Studies on plasma immunoreactive human brain natriuretic peptide (hBNP) levels in patients with congestive heart failure and present forms of hBNP in human cardiac ventricle

By using a specific radioimmunoassay (RIA) for human brain natriuretic peptide (hBNP), we measured immunoreactive hBNP (ir-hBNP) in plasma from patients with congestive heart failure (CHF). There appeared to be relationship between the enhanced ir-hBNP secretory activity and the severity of the failing heart as well as that of immunoreactive human atrial natriuretic peptide (ir-hANP). However, the secretion of ir-hBNP was augmented much more than that of ir-hANP in sever CHF patients. Gel permeation chromatography coupled with the RIA revealed that ir-hBNP in human ventricle is composed with gamma-hBNP and hBNP (1-32) as well as that of human atrium. However, we found differences of the gamma-hBNP/hBNP (1-32) ratio in atrial and ventricular tissues. These findings suggest that the hBNP secretion mechanism differ in the two areas of human heart.