Shigeo Aizawa

Early colorectal carcinoma with special reference to its development de novo

The growth type of early colorectal carcinoma was classified into two types. The first type is intramucosal polypoid growth (PG‐Ca) and the second type nonpolypoid growth (NPG‐Ca) which shows mainly massive infiltration of tumor cells below the submucosal layer. The incidence of adenoma‐carcinoma sequence was 72 of 75 lesions (96.0%) in pedunculated polypoid carcinoma, and 61 of 71 lesions (85.9%) in sessile and broad‐based polypoid carcinomas. Their average sizes were 15.0 and 18.7 mm, respectively. Submucosal invasive carcinoma (SM‐Ca) showed a low incidence. They were detected as microscopical or scattered lesions with a few lymphatic and venous permeation. The NPG‐Ca contained 32 lesions. Intramucosal carcinoma without adenoma showing slight depression consisted of ten lesions of which the average size was 5.1 mm. The other 22 lesions showed massive submucosal invasion with marked lymphatic and venous permeation. The average size was 10.3 mm being smaller than PG‐Ca. Histologically, NPG‐Ca was not accompanied with adenoma. The NPG‐Ca arose from de novo carcinoma less than 10 mm in diameter and invaded into the submucosal layer. In advanced carcinoma, the PG‐Ca showed a low incidence (21.8%), and almost all cases were of the NPG type (78.2%). The NPG advanced carcinomas increased in those over the size of 20 mm. It is concluded that nonpolypoid early colorectal carcinomas easily progress to advanced carcinoma, and de novo carcinoma occupied about 80% of colorectal carcinoma.

Clinical Characterization of Drug-Induced Allergic Nephritis

To elucidate the clinical characterization of drug-induced allergic nephritis (DIAN), we analyzed the cases attending our department. We now report on the 14 cases of DIAN due to administration of penicillin in 2 cases, cephem antibiotics in 6 cases, nonsteroidal anti-inflammatory drugs in 4 cases and new quinolone anticidal drugs in 2 cases. With 1 exception, all these cases reached the stage of acute renal failure after taking these drugs for 2-13 days, followed by characteristic allergic symptoms such as fever, skin eruptions and serum IgE elevation in 5 of the 14 cases. A lymphocyte stimulation test (LST) with the suspected drugs proved to be positive in 10 of the 12 cases examined, and the uptake of 67Ga in the kidneys was extremely positive in all 6 cases examined, reflecting the natural course of this disease. Furthermore, there were some cases where 67Ga accumulated in the kidneys in spite of the negative result of LST examination. In all of these cases, a needle or open renal biopsy was performed, and acute tubulointerstitial nephritis (AIN) was diagnosed. Almost all cases were treated with glucocorticoid for AIN or dialysis for acute uremic symptoms several times. However, 4 of the 14 cases could not return to normal condition in spite of these forms of treatment. We would therefore like to suggest that LST and 67Ga scintigram are useful diagnostic tools for DIAN as an alternative to renal biopsy.

Carcinosarcoma of the uterus with extensive neuroectodermal differentiation

A case of uterine carcinosarcoma with extensive neuroectodermal differentiation occurring in a 54‐year‐old woman is described. Microscopically, the endometrial tumour was predominantly composed of a sheet‐like proliferation of small‐ and medium‐sized cells. These cells were characterized by fibrillary cytoplasmic processes, rosette‐like formations, perivascular palisading patterns, and immunoreactivity for glial fibrillary acidic protein, synaptophysin, leu 7 and neuron‐specific enolase. In limited areas, features of conventional carcinosarcoma, including squamous cell carcinoma, leiomyosarcoma and islands of the above mentioned small‐to medium‐sized cells that were intermingled, were observed. The tumour was aneuploid by flow cytometry. The patient is alive with tumour for three months. It is suggested that at least some cases of uterine primitive neuroectodermal tumour may be explained by one‐sided neuroectodermal development within a carcinosarcoma.

RENAL CELL CARCINOMA OF LOWER NEPHRON ORIGIN

Thirty‐four renal cell carcinomas, including 4 small tumors localized in the medulla were studied by means of histochemical and immunohistochemical methods using the markers for the lower nephron. Seven tumors had binding sites for soybean and peanut agglutinins and showed positive reactions to monoclonal antibodies to epithelial membrane antigen and cytokeratin. All these markers normally exist in the epithelial cells of distal and collecting tubules. There was no tumor from the thick ascending limb in our materials because of negative reaction to the monoclonal antibody against Tamm‐Horsfall protein. Also negative was to CEA, which means there was no adenocarcinoma of colonic metaplastic origin from the renal pelvic mucosa. There were two histologically different types of cancers derived from the lower nephron, papillotubular adenocarcinoma with partial transitional differentiation, and papillary adenocarcinoma. All seven patients were males, aged between 30 and 84 years. The prognosis was quite poor since all six patients with known follow‐up died of tumor.

Drug-induced hypersensitivity nephritis: lymphocyte stimulation testing and renal biopsy in 10 cases

The pathomorphological and clinical findings were investigated in 10 cases of drug-induced hypersensitivity nephritis. Hypersensitivity due to drugs was strongly suggested by the lymphocyte stimulation test in all patients. The offending drugs included penicillin, cephem derivatives, nonsteroidal anti-inflammatory drugs, and minocycline. All patients developed acute renal failure shortly after administration of regular doses of the drugs. Allergic symptoms plus a raised level of serum IgE or eosinophilia were seen in 7 patients. The remaining 3 patients receiving nonsteroidal anti-inflammatory drugs had no allergic symptoms, but developed severe proteinuria. Eight patients without severe glomerular damage recovered after withdrawal of the offending drugs and temporal dialysis and/or steroid therapy. Renal biopsies revealed tubulitis and tubular epithelial degeneration with interstitial edema as the common characteristic findings. Granulomatous lesions were occasionally observed. Multinucleated giant cells found in the granulomas were positive for LN-3 which is compatible with HLA-DR antigen. The glomeruli appeared normal, except in 2 cases in whom crescentic glomerulonephritis and thrombotic microangiopathy were seen. Our study suggests that the lymphocyte stimulation test and renal biopsy are the most useful means to confirm the diagnosis and provides further evidence for the participation of cell-mediated immunity in the pathogenesis of drug-induced hypersensitivity nephritis.

Clear cell carcinoma of the ovary: light and electron microscopic studies.

Twelve cases of ovarian clear cell carcinoma were studied histologically. Four cases were examined electron microscopically and compared with other conditions. Five tumors were directly connected with ovarian endometriosis. They were histologically classified into a tubular type with hobnail cells and a solid type without tubular pattern or hobnail cells. Electron microscopic figures of the tumor cells are identical having large nuclei, abundant glycogen, lamellated RER, few lipid droplets, and sparse but well‐developed microvilli. The basophilic dark cells frequently encountered in the tubular type are morphologically quite similar to clear cells excepting for sparsity of glycogen and lipid droplets. Alveolar arrangement of 6 to 10 tubular structures (honeycomb structure) resembling alveolate structure seen in late secretory endometrium was found in tumor cells of one case. Ultrastructural feature of clear cell carcinoma closely resemble those of Arias‐Stella endometrium and clear cell carcinoma of endocervix suggesting their Muellerian origin. Cancer 40:3019‐3029, 1977.

Clinicopathologic and mucin histochemical analyses of 90 cases of ovarian mucinous borderline tumors of intestinal and müllerian types

Clinicopathologlc and mucin histochemical characteristics of 90 cases of ovarian mucinous borderline tumors (MBT) of Intestinal (IMET) and müllerian types (MMBT) were studied to determine whether IMBT and MMBT constitute distinct tumor subtypes. The IMBT (77 cases, 78 lesions) contained goblet cells, absorptive cells and endocrine cells, which represented Intestinal differentiation. The average diameter of IMBT was 13.4 cm. Five patients (6.5%) had stage III disease wtth pseudomyxoma perltonel and one of them died from tumor. Approximately 50% of IMBT demonstrated gastrointestinal characteistics on mucin histochemistry. The MMBT (13 cases, 14 lesions) consisted of mumus columnar cells and eosinophilic cells, with no Intestinal differentiation. MMBT accounted for 15.2% of MBT. MMBT averaged 8.4 cm in diameter, and 29% were associated with endometriosls of the ipsilateral ovary. All patients with MMBT had stage I disease, and none suffered from pseudomyxoma peritonel. All patients whose follow‐up data were available were alive and well, without evidence of tumor recurrence. The mucin histochemical findings in MMBT resembled those of noml endocervix. Results of the present study suggest that IMBT and MMBT have different characteristics and constitute distinct subtypes of MBT.

Crystalline inclusions in the glomerular podocytes in a patient with benign monoclonal gammopathy and focal segmental glomerulosclerosis.

We report a case of a 40-year-old woman with benign monoclonal gammopathy who developed focal segmental glomerulosclerosis associated with widespread deposition of large crystalline inclusions in the glomerular podocytes. Electron microscopy showed that the crystalline structures were electron dense and needle shaped or polygonal. At a higher magnification, they were seen to be surrounded by unit membranes and to feature a longitudinal filamentous substructure. These inclusions showed positive immunohistochemical staining for kappa light chain. Clinically, the patient had shown nephrotic syndrome on the first medical examination, and later revealed chronic renal failure and monoclonal gammopathy of the immunoglobulin G kappa type, but no evidence of multiple myeloma or other lymphoproliferative diseases. This patient seems to have had a rare form of glomerular involvement associated with benign monoclonal gammopathy.

Testicular sex cord-stromal lesions: immunohistochemical analysis of cytokeratin, vimentin and steroidogenic enzymes.

We have studied immunolocalization of all steroidogenic enzyme involved in sex steroids biosynthesis, P-450 side chain cleavage (P-450scc), 3β hydroxy steroid dehydrogenase (3β-HSD),P-450 17α hydroxylase (P-45014α) andP-450 aromatase (P-450arom) and that of vimentin and cytokeratin in 14 cases of testicular sex cord-stromal tumours (6 Leydig cell tumours, 5 Sertoli cell tumours, 2 fibromas and 1 granulosa cell tumour) as well as 4 cases of hyperplasia (2 Leydig and 2 Sertoli). Leydig cell tumour expressed all four steroidogenic enzymes examined, indicating that this tumour can synthesize oestrogen from cholesterol. In 2 cases of Sertoli cell tumour, the tumour cells with clear cytoplasm and without Reinkes crystals expressedP-450ssc, 3β-HSD andP-45017α, suggesting the capability of androgen production in these tumour cells. Fibromas and granulosa cell tumour were negative for the enzymes examined. In immunohistochemistry of intermediate filaments, Leydig cell tumours demonstrated only vimentin. Sertoli cells in hyperplasia and non-neoplastic testis expressed only vimentin but Sertoli cell tumours expressed both cytokeratin and vimentin. Cytokeratin immunoreactivity was correlated with morphological epithelial differentiation in Sertoli cell tumour. These findings in testicular Sertoli cell tumour are considered to represent the multiple differentiation capacity of this neoplasm. Immunohisto-chemical study of steroidogenic enzymes and intermediate filaments provided new insight into neoplastic steroidogenesis and the differentiation capacity of testicular sex cordstromal neoplasms.

Carcinosarcoma of the Liver Report of an Autopsy Case With Review of the Literature and Histogenetic Consideration

An autopsy case of carcinosarcoma of the liver in an 84-year-old man is described. The 14 x 6-cm solid tumor was located in the hilus to the left lobe and was grayish-white with some translucent areas. Histologically, the tumor consisted of an intimate mixture of adenocarcinomatous and chondrosarcomatous elements with transitional areas in between. Immunohistochemically, cells of the adenocarcinomatous elements were positive for cytokeratin but negative for S100 protein, whereas cells of the chondrosarcomatous elements showed the reverse staining pattern. Cells of transitional areas were positive for both cytokeratin and S100 protein. Most previously reported cases of carcinosarcoma of the liver have involved elderly men and have had a poor prognosis. The findings of the present case support the view that carcinosarcomas represent carcinomas that develop a sarcomatous element via metaplasia of the epithelial element.