Immunohistochemical study of testicular sex cord-stromal tumors, including staining with anti-inhibin antibody.

Inhibin is a peptide hormone produced by ovarian granulosa cells and testicular Sertoli cells. Ovarian granulosa cell and other sex cord-stromal tumors usually exhibit positive immunohistochemical staining with antiinhibin antibodies, and this may be valuable in differentiating these neoplasms from histologic mimics. In the present study, we investigated the immunohistochemical staining of testicular sex cord-stromal tumors using antiinhibin. Immunostaining with CAM5.2, vimentin, S-100 protein, desmin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) also was performed because few studies have investigated in detail the immunophenotype of testicular sex cord-stromal tumors. Fifteen of 16 Leydig cell tumors exhibited strong positive staining with antiinhibin. A proportion of Leydig cell tumors also stained positively with CAM5.2 (7 of 16), vimentin (14 of 16), S-100 protein (10 of 16), desmin (2 of 16) and epithelial membrane antigen (4 of 16). Four of six testicular sex cord-stromal tumors with varying degrees of Sertoli or granulosa cell differentiation were positive with antiinhibin, as were two of three sex cord-stromal tumors that were unclassified. Some of these tumors were positive with CAM 5.2, vimentin, S-100 protein, desmin, and epithelial membrane antigen. All tumors were negative with carcinoembryonic antigen and placental alkaline phosphatase. The immunohistochemical findings show that, analogous to their ovarian counterparts, most testicular sex cord-stromal tumors are immunoreactive with antiinhibin. Immunohistochemistry using this antibody as part of a panel may be valuable in confirming a diagnosis of testicular sex cord-stromal tumor and in differentiating these neoplasms from others that may mimic them.

Primary synovial chondromatosis: a clinicopathologic review and assessment of malignant potential.

This is a clinicopathologic review of 53 cases of primary synovial chondromatosis covering a period of 30 years. The average age at presentation was 41 years (range, 17 to 64 years) with a male/female preponderance of 1.8:1. The condition was always monarticular, the most common site being the knee joint (70%) followed by the hip (20%). Degenerative joint disease was well established in three patients (5%), all occurring in the hip. Nine patients suffered recurrences (15%), including three that became malignant. There was no relationship between the age and site of the lesion, nor between the degree of cellularity of the cartilage and age or site. However, there was an association between cellularity of the cartilage and the extent of calcification and ossification--highly cellular lesions were poorly calcified and ossified, but heavily calcified lesions were usually of relatively low cellularity. There was no relationship between extent of calcification and ossification and the age of the patient. Three patients suffered malignant change representing a relative risk of 5%, much higher than that quoted in other series. This suggests that primary synovial chondromatosis has a significant potential for malignant change.

Granulomatous disease in the vermiform appendix.

In a twenty-year period 19 appendicectomy specimens were diagnosed as primary Crohn's disease. This represents 4.9% of the total number of both resection specimens and mucosal biopsies diagnosed as Crohn's disease during that time. This is a review of the main histopathological features found in these appendices and their subsequent clinical outcome. The predominant feature is transmural inflammation characterised by fibrosis and giant cell epithelioid granulomata. An accompanying spectrum of acute inflammatory changes is also seen. One patient progressed to more widespread ileal and caecal disease 17 months later. One patient developed perianal fistulae and chronic non-specific proctitis 24 months later. This represents a proven recurrence of one case in a study population of 19. The conclusion is that primary Crohn's disease of the appendix is usually an isolated phenomenon but rarely it may forewarn of more widespread bowel disease in the future. A discussion regarding the differential diagnosis of granulomatous appendiceal lesions is included.

Primary adenocarcinoma of the jejunum and ileum: clinicopathological review of 25 cases.

Between 1954 and 1988 only a total of twenty five cases of primary adenocarcinoma of the small bowel (excluding periampillary tumours) were recorded at the Department of Histopathology, Belfast City Hospital. Of these, 14 tumours were located in the jejunum: the remainder arose in the ileum. The average age at presentation was 61.3 years and a slight female to male preponderance of 1:7:1 was noted. The adenocarcinoma arose from a preexisting villous adenoma in six cases. The overall prognosis was poor, with a five year survival of 15.7%. All the survivors had tumours located in the jejunum. The single most important prognostic indicator was the depth of tumour invasion or stage at the time of diagnosis. Tumour size and grade did not seem to correlate well with survival. It is concluded that the rarity of these tumours and their inaccessibility hinder detection and treatment and that surgical resection is more effective than chemotherapy.

Immunohistochemical staining of colorectal tissues with monoclonal antibodies to ras oncogene p21 product and carbohydrate determinant antigen 19-9.

Two monoclonal antibodies were applied to benign, dysplastic, and malignant human colorectal tissues using immunohistochemical techniques on formalin fixed paraffin embedded material. RAP-5 antibody is directed against a synthetic peptide, reflecting an amino acid sequence of the ras oncogene p21 protein product. Despite using several different techniques and antibody dilutions differential staining between the various epithelial populations was not obtained. RAP-5 also showed other tissue components such as plasma cells, histiocytes, fibroblasts, smooth muscle and vascular endothelium. CA19-9 antibody recognizes an epithelial surface carbohydrate antigen originally derived from a human colorectal carcinoma cell line: it did not stain normal colorectal mucosa or adenomatous polyps, but showed focal expression of variable strength in regenerative, dysplastic, and cancerous mucosa in ulcerative colitis, and in non-colitic colorectal carcinoma. Neither antibody was found to be a reliable marker of the evolution of malignant mucosal changes, although CA19-9 may be of limited use in confirming adenocarcinoma of gastrointestinal origin.

c-erbB-2 overexpression and histological type of in situ and invasive breast carcinoma.

AIMS: To assess c-erbB-2 immunostaining in relation to morphological type of in situ and invasive breast carcinoma. METHODS: Formalin fixed, wax embedded archival tissue was used. Invasive carcinomas comprised 50 infiltrating ductal (NOS); seven medullary, 10 tubular, 15 mucinous and 24 classic invasive lobular. In situ carcinomas comprised 48 ductal (DCIS) and 10 cases of lobular (LCIS). The antibodies used were pAB1 (polyclonal) which stains cell lines that over express the c-erbB-2 oncogene, and ICR 12 (monoclonal) which stains sections of breast carcinoma known to show c-erbB-2 amplification. RESULTS: Immunostaining consistent with c-erbB-2 overexpression was found in 10 out of 50 cases of infiltrating ductal carcinoma (NOS), one of 24 infiltrating lobular carcinomas and one of seven medullary carcinomas only. Seventy per cent of ICR 12 positive cases of infiltrating ductal carcinoma also had extratumoral DCIS. Forty six per cent of pure DCIS lesions also showed strong membrane staining for c-erbB-2 protein, confined to large cell types. CONCLUSIONS: Immunostaining for c-erb B-2 oncoprotein occurs mainly in large cell DCIS and infiltrating ductal carcinoma NOS, especially those with an extratumoral DCIS component. There is a low incidence in other types of breast cancer, including those associated with a better prognosis. Different biological mechanisms may be responsible for histologically distinct types of breast carcinoma.

Large bowel mucosal dysplasia and carcinoma in ulcerative colitis.

The clinicopathological details of eight cases of ulcerative colitis complicated by carcinoma of the colon are described. There was a total of 14 primary colonic cancers, six of which were not detected before pathological examination of the resection specimens. The reason for this may be related to atypical tumour growth patterns. Three occurred in flat mucosa, one in a mucosal plaque lesion, and another in polypoidal mucosa. The occurrence, distribution, and morphology of mucosal dysplasia were noted in both resection specimens and biopsies taken at varying stages before resection. Tumour was associated with normal and adjacent dysplastic mucosa of varying grades. The extent and grade of dysplasia were not reliable indicators of tumour differentiation or subsequent clinical outcome. Only two cancers were poorly differentiated. In five cases a total of 23 mucosal biopsies were taken, all less than 12 months before resection. Three rectal biopsies were graded positive for dysplasia and three colonic biopsies indefinite for dysplasia. The subsequent resection specimens showed both dysplastic and carcinomatous changes. Three rectal and 14 colonic biopsies were graded negative for dysplasia despite positive findings in the subsequent resection specimens. This anomaly is partly attributed to the patchy nature of dysplasia in colitic mucosa. Two cases illustrate the possibility of dysplasia pursuing a rapidly progressive course. The mucosal changes of ulcerative colitis were assessed using a recently introduced and standardised international classification.

An immunoperoxidase study of epithelial marker antigens in ulcerative colitis with dysplasia and carcinoma.

An immunoperoxidase technique was applied to formalin and Helly fixed paraffin wax sections from cases of ulcerative colitis complicated by dysplasia and carcinoma for carcinoembryonic antigen and components of the colonic secretory immunoglobulin system--namely, secretory component, IgA, and J chain. Sections from both resection specimens and mucosal biopsies were available. Intensity of immunostaining was assessed qualitatively. There was appreciable variation in expression of carcinoembryonic antigen and secretory component antigens. Carcinoembryonic antigen stained heavily in dysplasia and carcinoma while these tissues showed only focal light staining for secretory component. Normal tissue stained heavily for secretory component. The variation in staining intensity for both carcinoembryonic antigen and secretory component in inflamed and regenerative mucosa precluded their use as a reliable diagnostic aid in discriminating these tissues from true dysplasia. Loss of secretory component production or transport or both may be incurred during malignant change, but it should not be assessed as an isolated index of epithelial maturity. The relation with mucosal plasma cells warrants further study to determine more fully the factors affecting tissue secretory component expression.

Chronic sclerosing osteomyelitis. An unusual case.

An unusual case of bilateral chronic sclerosing osteomyelitis of the clavicles is reported. A culture of resistant Staphylococcus aureus was obtained. Curettage of the lesions resulted in healing and symptomatic relief. There has been no recurrence on follow-up at one year.

Predictive value for coeliac disease of antibodies to gliadin, endomysium, and jejunum in patients attending for jejunal biopsy.

OBJECTIVE: To investigate the extent to which the detection of antibodies to gliadin, endomysium, and jejunum predicts the eventual diagnosis of coeliac disease according to the revised ESPGAN diagnostic criteria in a group of patients in whom there is a high suspicion of coeliac disease. DESIGN: Clinical assessment and laboratory analysis of patients with suspected coeliac disease. SETTING: Gastroenterology department of teaching hospital. PATIENTS: 96 adults with suspected coeliac disease attending for jejunal biopsy. MAIN OUTCOME MEASURES: Diagnosis of coeliac disease with the revised criteria of the European Society of Paediatric Gastroenterology and Nutrition in patients with and without antibodies associated with coeliac disease. RESULTS: 28 patients had a clinical diagnosis of coeliac disease, seven of other gastrointestinal diseases, and 12 of miscellaneous diseases; 49 had no diagnosis. Gliadin IgA detected by ELISA was found in all patients with coeliac disease and none of those without, giving a sensitivity, specificity, positive and negative predictive values, and predictive efficiency of 100% for diagnosing coeliac disease within the group. Endomysial IgA was found in 25 (89%) patients with coeliac disease and jejunal IgA in 21 (75%); neither IgA was found in patients without coeliac disease. CONCLUSION: Detection of gliadin IgA by ELISA and to a lesser extent the endomysial IgA should allow better selection of patients for jejunal biopsy and thus make diagnosing coeliac disease simpler and more efficient.