Vinblastine, bleomycin and cis-diamminedichloroplatinum in the treatment of advanced testicular carcinoma. Possible importance of longer induction and shorter maintenance schedules.

Twenty-eight patients with stage III or recurrent stage I or II testicular cancer were treated with four to six cycles of vinblastine, bleomycin and cis-diamminedichloroplatinum, and then with vinblastine maintenance for one year. With a median follow-up of more than 20.5 months for all patients, complete remission has been achieved with chemotherapy and operation in 23 (82 per cent). One of these 23 patients has had a relapse, and only three are still receiving maintenance therapy. The toxicity incurred by the extra cycles of chemotherapy in patients with extensive disease was no greater than that experienced by patients receiving smaller doses of drugs. These results confirm the high response rate reported for this combination of drugs and strongly suggest that some relapses after complete remission can be prevented by longer remission induction schedules. The value of maintenance therapy is questionable and needs further study.

Inflammatory pseudotumor of the urinary bladder--possible relationship to nodular fasciitis. Two case reports, cytologic observations, and ultrastructural observations.

An inflammatory pseudotumor of the urinary bladder might cause a large, pedunculated intraluminal mass that clinically and radiologically simulates a malignant tumor. This benign lesion can easily be mistaken for a sarcoma because by light microscopy it consists of clon-gated strap cells that resemble rhabdomyoblasts. The loose texture, the myxoid background, the relative paucity of mitoses, and the absence of nuclear hyperchromasia are important histologic determinants of benignity. Smears and imprints yield voluminous tapering cells in an inflammatory background. There are no cytoplasmic cross-striations or Z-bands and the tumor cells have the ultrastructural characteristics of myofibroblasts. It is important to recognize this lesion as benign to avoid the potentially serious consequences of misdiagnosis.

Adenocarcinoma of the rete testis. Case report, ultrastructural observations, and clinicopathologic correlates.

Adenocarcinoma of the rete testis is a rare tumor that tends to occur in men over the age of 60 and is usually associated with a poor prognosis. We report such a tumor occurring in a 63-year-old male 2 years after he underwent a scrotal exploration in the management of a hydrocele, varicocele, and inguinal hernia. The postorchidectomy course was characterized by slowly advancing, painful scrotal and perineal skin recurrences, lymph node metastases, and the absence of response to Adriamycin and electron-beam therapy. We are confident that the lesion is a carcinoma of the rete testis because: 1) the tumor is situated mainly in the testicular mediastinum, 2) primary germinal and nongerminal testicular tumors and spread from distant sources have been excluded, 3) a transition from normal rete testis to atypical and neoplastic rete epithelium is demonstrable, and 4) the transmission electron-microscopic findings support our conclusion. The distinction between carcinoma of the rete testis and malignant mesothelioma may be difficult and requires consideration of the gross, light-microscopic, and ultrastructural tumor characteristics in optimally fixed tissue.

Cancer associated antigen CA19-9 in colonic effluent of patients with neoplasia of the colon and inflammatory bowel disease.

We measured colonic effluent samples from 10 patients with colorectal cancer, 13 with adenomatous polyps, 14 with normal colons and compared them to 10 patients with inflammatory bowel disease by measuring this CA19-9 content. Results showed considerable overlap between the different pathologic categories, making differentiation impossible. A lower level of CA19-9 in the effluent samples from patients with adenomas was noted. These differences were reproducible for assays performed several months apart. CA19-9 may originate from the upper gastrointestinal tract since large amounts are present in pancreatico-biliary secretions. This antigen is therefore not useful in the diagnosis of neoplasia or inflammatory bowel disease using colonic effluent samples as the test material.

Detection of carcinoembryonic antigen in colonic effluent by specific anti-CEA monoclonal antibodies.

To characterize the CEA in colonic effluent, anti-CEA monoclonal antibody COL-4 was used in a qualitative radioimmunoassay in both fractionated and unfractionated colonic effluent. Both effluent samples and tissue extracts, were subjected to Western blotting and tissue sections to immunohistochemistry. Quantitative levels of colonic effluent CEA were determined by a kit (Abbott-EIA). Higher mean values of COL-4 binding activity were seen only in patients with a past history of polyps (P < 0.01). Quantitated CEA correlated with the presence of colorectal cancer (CRC) as compared to normal subjects, (1133 +/- 875 vs. 459 ng/ml +/- 602, P < 0.05) but not when standardized for protein content. COL-4 reacted with an 180,000 M(r) CEA in the effluent and activity was associated with membrane fraction of the effluent, but bore no relation to the immunohistological staining. We conclude that CEA is detectable in colonic effluent and is membrane associated, but the overlapping values in effluent samples do not make this a useful test in the diagnosis of CRC.

Adenoma-derived antibody, Adnab-9 recognizes a membrane-bound glycoprotein in colonic tissue and effluent material from patients with colorectal neoplasia.

The binding in pre-colonoscopic effluent of Adnab-9, a monoclonal antibody raised against colonic adenomas, was evaluated for specificity in the diagnosis of colorectal cancer. A heterogeneous group of 58 patients was evaluated by ELISA. Effluent samples and tissue extracts were subjected to Western blotting or ELISA to confirm specificity. Immunohistochemistry was performed on the cancer tissue sections. The proportion of positive effluent binding was higher in the cancer when compared to the normal group (P = 0.036). A dominant 87 M(r) band was found in adenoma extracts and some effluent samples. Adnab-9 binding in effluent samples predominated in membrane-bound fractions. Immunohistochemistry showed no specific staining in the cancer cells. The antigen recognised is a glycoprotein shown by effects of N-glycanase digestion and not cross-reactive with carcinoembryonic antigen. Non-gastro-intestinal tissue extracts did not bind Adnab-9. The major 87 M(r) adenoma-derived antigen may be found in effluent material, particularly in the membrane-bound fraction.

Increased expression of a putative adenoma-associated antigen in pre-colonoscopic effluent of patients with colorectal cancer.

A monoclonal antibody Adnab-9, was raised against antigens derived from benign polyps of the colon. Adnab-9 was tested against pre-colonoscopic effluent material obtained from groups of patients with a macroscopically normal colonscopic examination, histologically confirmed adenomatous polyps and patients with colorectal cancer (CRC). The resultant binding levels displayed little overlap between the CRC group and the normal, and the difference was statistically significant. Since this putative early neoplasia associated antigen is essentially not expressed in CRC extracts, it may originate from a region of the colon predisposed to neoplasia, increasing in expression as the tendency to malignancy progresses, useful in the diagnosis of early stage malignancy.

The rhabdomyoblast in mixed Müllerian tumors of the uterus and ovary. An immunohistochemical study of myoglobin in 25 cases.

Forty per cent of 25 uterine and ovarian mixed müllerian tumors contained stainable myoglobin that was present in the abundant cytoplasm of large rounded tumor cells. Intracytoplasmic cross striations identified rhabdomyoblasts in 32% of the cases, but were difficult to find. The authors believe that the immunoperoxidase technic successfully demonstrates skeletal muscle differentiation in a high proportion of mixed müllerian tumors and may be employed as a suitable diagnostic aid. However, the nonspecific staining of benign and malignant squamous elements should be interpreted with caution.

Scrotal carcinoid. Presenting manifestation of multiple lesions in the small intestine.

A middle-aged man presented with a paratesticular carcinoid tumor, his first manifestation of multiple carcinoid tumors of the small bowel. Of the nine carcinoids reported in the English-language literature as metastatic to the scrotum, five simulated a primary lesion. Although the bulk of scrotal carcinoids arise in the testis, the differential diagnosis always should include metastasis from an extrascrotal source.

Recommendations for the reporting of resected neoplasms of the kidney. Association of Directors of Anatomical and Surgical Pathology.

The Association of Directors of Anatomic and Surgical Pathology has developed recommendations for the surgical pathology reporting of common malignant tumors. The recommendations for renal cell neoplasms are reported here.

Cerulein induces hyperplasia of the pancreas in a rat model of chronic pancreatic insufficiency.

Chronic pancreatic insufficiency (CPI) was induced in male Wistar rats by the injection of a zein-oleic acid-linoleic acid solution into their pancreaticobiliary ducts. Animals injected developed severe pancreatic atrophy with fibrosis and greater than 90% loss of pancreatic enzyme content. The animals also developed malabsorption of fat and bentiromide. Three weeks after the CPI lesion was induced, animals were randomized to receive cerulein 2 micrograms/kg twice daily subcutaneously or saline twice daily subcutaneously for 2 weeks. Cerulein significantly increased pancreatic trypsinogen (p less than 0.03), amylase (p less than 0.01), lipase (p less than 0.02), DNA (p less than 0.02), and RNA (p less than 0.01) content and improved fat and bentiromide malabsorption as compared to saline (p less than 0.05). We conclude that cerulein therapy can cause significant hyperplasia of pancreatic acinar parenchyma in an animal model of CPI and that this therapy can partially reverse malabsorption.

Pathology of germ cell tumors of the testis.

Testicular germ cell tumors form a complex group of interrelated entities. Problems of nomenclature remain, but there does appear to be a close agreement between the major classifications in use. The identification of clinically useful markers for certain germ cell testicular tumors has provided a major impetus in this field. Information gained from the study of these markers has promoted an understanding of the histogenesis of germ cell tumors, has improved standard nomenclature, and has stimulated progress in patient care. Radioimmunoassay techniques are now frequently used to measure beta-human chorionic gonadotrophin and alpha-fetoprotein levels in evaluating the clinical course of patients with nonseminomatous germ cell tumors of the testis. It is hoped that the use of these markers will permit earlier detection of tumor recurrence, prompt treatment, and an improved survival rate. The knowledge of the production of alpha-fetoprotein by the human yolk sac has further refined tumor classification. It is against this general background that we have outlined the standard pathology of germ cell tumors of the testis.

Lymphocytic hypophysitis: occurrence in two men.

Two men undergoing transsphenoidal exploration for pituitary adenoma were found to have lymphocytic hypophysitis. Both presented with frontal headaches, lethargy, and diminished libido. Laboratory investigations showed markedly depressed serum testosterone, and magnetic resonance imaging demonstrated pituitary enlargement, with optic chiasm involvement. Intraoperatively, the dura was adherent to the pituitary in each case. The resected glands were effaced by a dense lymphoplasmacytic infiltrate and fibrosis, without granulomas. Nonspecific peripheral enhancement on imaging suggested a diagnosis other than adenoma, but more experience with peripheral enhancement in lymphocytic hypophysitis is needed. The diagnosis was histological and required surgical intervention. Long-term pituitary replacement therapy is usually required.

The diagnostic challenge of metastatic linitis plastica. Two cases and a consideration of the problem.

Linitis plastica of the stomach is usually difficult to diagnose preoperatively and can extend locally and metastasize widely before recognition. This insidious manner of spread may cause unusual presentations in organs distant from the stomach. The authors recently treated two patients who were initially found to have radiologic abnormalities of the colon and bladder, respectively. One patient was surgically explored with a view towards the resection of a primary colonic tumor, the other to determine the nature of a bladder tumor. Intraoperative histologic interpretation of frozen tissue samples from the gastric wall in each case radically altered the surgical approach and the prognosis. The clinical presentations illustrate that it may be difficult to obtain preoperative diagnostic tissue samples in such cases and that it is important for the surgeon to inspect and palpate the stomach wall during all abdominal explorations for cancer.

Gastroduodenal polyps in familial polyposis coli.

This endoscopic evaluation of 25 patients with familial polyposis coli (FPC) further establishes gastro-duodenal polyps as a significant extracolonic manifestation of the condition. Ten patients had polyps, distributed as follows: stomach (2), duodenum (4), stomach and duodenum (4). Altogether, there were six gastric and seven duodenal lesions. Half of the gastric tumors were hyperplastic and half were adenomatous. All the duodenal tumors were adenomatous, four being ampullary. The one symptomatic patient had intra-polypoid adenocarcinoma. There were no significant correlations between the endoscopic findings and patient age, sex, presence of colon cancer, or other extracolonic abnormalities. The authors affirm that gastroduodenal polyps are an important component of FPC and recommend that all patients with this condition undergo initial and follow-up gastroduodenoscopy. Multiple small lesions may be carefully monitored, but larger ones, particularly those in the region of the ampulla, must be excised.

Immunocytochemical localization of lingual lipase in serous cells of the developing rat tongue.

The ontogeny of the rat lingual serous and mucous glands was explored by light and electron immune microscopy using the peroxidase-antiperoxidase and streptavidin-gold techniques. Tissues from fetal and neonatal rats from day 18 of gestation through 4 wk after birth were fixed and embedded in paraffin or Epon for light and transmission electron microscopy, respectively. Electron microscopy revealed that the only cells containing lingual lipase were the developing serous cells; secretory granules containing lingual lipase of varying degrees of maturity were seen. Mucous cells did not show immunospecific staining in rats of any age. The neonatal "mixed" lingual glands secrete lingual lipase from serous components immediately after birth to aid in fat digestion.

Meningioma of the scalp. Light and electron microscopic observations.

Meningiomas occurring in the skin are rare and may be difficult to recognize on frozen section. We found intraoperative cytologic smears helpful in identifying the characteristically bland nuclei, cellular whorls, and psammoma bodies that are typical of the light microscopy of meningiomas in the CNS. This case (a scalp lesion) was also examined ultrastructurally. Cutaneous meningiomas are histologically and ultrastructurally identical to their meningeal counterparts and must be approached with caution surgically.

Pseudoangiomatous stromal hyperplasia: presentation as a mass in the female nipple.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign, localized fibroblastic and myofibroblastic overgrowth that occurs almost exclusively in premenopausal women as a painless, palpable intramammary mass. The lesion has a pale, fibrous, and homogeneous cut surface, is typically well circumscribed, and may have a diameter of 2.0-15 cm. Its ramifying slits lined by flattened myofibroblastic cells are apt to be mistaken for vascular spaces, leading to an erroneous diagnosis of angiosarcoma. The etiology of the condition is unknown, but a relationship to myofibroblastoma has been postulated. Hormonal factors, too, are thought to play a developmental role. The potential for PASH to create a palpable breast mass has been only quite recently advanced in the medical literature, and it has evidently not been reported in the nipple.