Histology of the normal testis.

The gross and microscopic features of the normal adult, prepubertal, and aging testis are described. Qualitative and quantitative parameters of spermatogenic activity are presented in practical terms. Emphasis is placed on these findings, which are important to the pathologist in interpretation of diagnostic biopsy specimens other than neoplasms.

Intratubular germ cell neoplasia (ITGCN) with p53 and PCNA expression and adjacent mature teratoma in an infant testis. An immunohistochemical and morphologic study with a review of the literature.

Intratubular germ cell neoplasia (ITGCN) and mature teratoma of the testis are uncommon findings in children. We report a case of a 3-year-old boy with both ITGCN and mature teratoma--a unique finding in our experience. Immunohistochemical markers, including placental alkaline phosphatase (PLAP), 43-9F, p53, and proliferating cell nuclear antigen (PCNA), as well as the periodic acid-Schiff (PAS) stain, were applied to the ITGCN. PLAP and 43-9F were not detected, whereas p53 and PCNA nuclear expression was detected in approximately 5% of atypical germ cells. Abundant clumped intracytoplasmic glycogen deposits were identified within atypical germ cells. Our findings indicate that both PCNA and p53, in addition to a PAS stain, may be useful markers in detecting malignant intratubular germ cells.

Diagnostic accuracy of a rural live video telepathology system.

Accuracy of diagnoses rendered using a live video telepathology network was assessed for permanent sections of surgical pathology specimens. To determine accuracy, telepathology diagnoses were compared with those obtained by directly viewing the glass slide using a standard microscope. A total of 294 cases were read via both telepathology and glass slide by attending pathologists at a tertiary care medical center. Overall accuracy was defined as exact concordance between diagnoses. Clinically insignificant differences in diagnoses were excluded to determine clinically significant accuracy. For the 285 cases with complete data, the overall accuracy for telepathology was 0.912 (95% confidence interval [CI], 0.872-0.941), whereas the overall accuracy for glass slide readings was 0.968 (95% CI, 0.939-0.985). This difference is statistically significant (p = 0.009). When focusing on clinically significant discrepancies, where the difference in diagnosis might affect therapeutic decisions, the video accuracy was only slightly less than the glass slide accuracy (0.965 [95% CI, 0.934-0.982] vs. 0.982 [95% CI, 0.957-0.994], respectively), but this difference is not statistically significant (p = 0.302). Most of the cases with clinically significant differences involved lesions with inherently high interobserver variation. Certainty of diagnosis did not differ between video and glass slide readings (p = 0.911), but there was an association between certainty of diagnosis and diagnostic accuracy for video (p = 0.003 for clinically significant accuracies). Based on these findings, we recommend when using this telepathology system that only preliminary diagnoses should be given in the following situations: for diagnostic areas with known high interobserver variability; when the consultant has any degree of uncertainty about the presence or absence of the lesion in question; and when there is insufficient experience using telepathology as a diagnostic medium.

Systemic amyloidosis involving two renal transplants.

Two patients with primary amyloidosis, each of whom had received a renal transplant for chronic renal failure, developed amyloid in their allografts. In one patient amyloid was present primarily in glomeruli and to a lesser extent in the interstitial tissue. This patient developed renal failure necessitating retransplantation. In the second patient amyloid was seen in the interstitium and interlobular blood vessels. Minimal amyloid was present in the glomeruli. This patient died of cardiac amyloidosis with good graft function at the time of death. Of the several patients recorded in the literature with amyloid in renal allografts, our first patient is the only one to exhibit glomerular amyloid and failure of the graft. Amyloid in areas other than the glomerulus does not appear to be incompatible with satisfactory graft function.

Diagnosis of pneumonia due to Pneumocystis by subsegmental pulmonary lavage via the fiberoptic bronchoscope.

To assess the accuracy of pulmonary lavage in diagnosing pneumonia due to Pneumocystis, we used animals as a model and then prospectively studied 33 immunosuppressed adults with diffuse pulmonary infiltrates. In rats treated with cortisone, Pneumocystis organisms could be found in the effluent from lavage as early as in sections of pulmonary tissue, and the effluent from lavage remained diagnostic throughout the ten weeks of observation. Subsegmental lavage in adult patients was performed through the wedged fiberoptic bronchoscope. Pneumocystis organisms were demonstrated in seven patients by lavage, and no false-negative results were recorded. Pneumocystis organisms were readily identified among the sheets of alveolar macrophages seen in smears of the effluent from lavage that were stained with methenamine silver. Subsegmental lavage via the fiberoptic bronchoscope is an accurate and safe technique for establishing the diagnosis of pneumonia due to Pneumocystis in patients whose respiratory embarrassment or thrombocytopenia makes biopsy of the lung hazardous.

Comparison of an automated radioimmunoassay method and a competitive protein-binding method for evaluation of serum cortisol.

A competitive protein-binding method (CPB) for serum cortisol determination has been compared with a newly developed automated radioimmunoassay (RIA) technic with respect to reproducibility and correlation of patient results. The RIA method uses an immobilized anti-cortisol antibody covalently coupled to the inner surface of a plastic cartridge. A mixture of 3H-labeled and unlabeled cortisol is passed through the cartridge to achieve separation of free and bound cortisol. The bound cortisol is later eluted to regenerate the antibody for the next sample. The RIA procedure had a day-to-day coefficient of variation (CV) of 7% at three cortisol levels. The CPB method had a day-to-day CV of 10% at a concentration of 8 microgram/dl. A comparison of 67 patient samples showed no statistically significant difference between the methods. The regression equation was RIA = 0.96 CPB + 0.14 microgram/dl, with a correlation of 0.92.

The adolescent varicocele. A histopathologic study of 13 testicular biopsies.

Testicular varicocele, the most common cause of male infertility, frequently presents in early adolescence. To determine whether testicular damage occurs early in the natural history of varicocele, testicular biopsy specimens from 13 patients, 13 to 18 years of age (mean age, 15.5 years), were studied. The biopsies were compared with testicular tissue from six normal control subjects 15 to 28 years of age (mean age, 23.2 years). Nine of the patients with varicoceles (69.2%) demonstrated some degree of tubular sclerosis. Ultrastructural study demonstrated that the tubular sclerosis was due to collagen deposition by fibromyocytes in the peritubular sheath. Premature germ cell sloughing was present in greater than 50% of tubules examined in all but one biopsy. Six patients (46%) demonstrated small vessel sclerosis. Quantitation of the germinal epithelium revealed that the mean germ cell/Sertoli cell ratio and the percentage of germ cells present as late stage forms (secondary spermatocytes, spermatids and spermatozoa) were significantly reduced in the varicocele group. The testes of two patients exhibited severe hypospermatogenesis approaching germ cell aplasia. None of these changes were seen in the control group. The authors conclude that pathologic changes in the testes of patients with varicoceles are found at or soon after puberty. The histopathologic features include peritubular sclerosis, small vessel sclerosis, premature germ cell sloughing, and variable degrees of hypospermatogenesis.

Collagenous gastritis: a long-term follow-up with the development of endocrine cell hyperplasia, intestinal metaplasia, and epithelial changes indeterminate for dysplasia.

This report reviews the literature pertaining to collagenous gastritis and describes the clinicopathologic evolution of this disease in a patient during a 12-year period. We examined 109 biopsy specimens of gastric mucosa from 19 different endoscopic procedures for the severity and distribution of collagenous gastritis in a single patient. Assessments were undertaken for the presence of endocrine and gastrin cell hyperplasias and dysplastic epithelial changes. Relative to biopsy specimens from age- and sex-matched control subjects, the patient's biopsy specimens showed a significantly lower number of antral gastrin cells, along with a significant corpus endocrine cell hyperplasia, suggesting an increased risk of endocrine neoplasia. Gastric corpus biopsy specimens revealed an active, chronic gastritis, subepithelial collagen deposition, smooth muscle hyperplasia, and mild to moderate glandular atrophy. Additional findings of intestinal metaplasia and reactive epithelial changes indeterminate for dysplasia raise concerns about the potential for adenocarcinoma.

Localization of anti-Leu-M1 (CD15) binding sites in Hodgkin's disease by immunoelectron microscopic examination.

Anti-Leu-M1 (CD15) is a monoclonal antibody used in surgical pathology to diagnoses Hodgkin's disease. By light microscopic immunohistochemistry, anti-Leu-M1 reacts with Reed-Sternberg cells and their variants, notably lacunar cells in nodular sclerosing Hodgkin's disease, as well as granulocytes in Hodgkin's disease. The immunostaining of Reed-Sternberg cells has been characteristically described as a diffuse cytoplasmic pattern with a prominent perinuclear globular component. In addition, irregular plasma membrane reactivity has been observed. To define the intracellular localization of Leu-M1 precisely, the authors performed postembedding immunoelectron microscopy with the protein A-gold technique on sections embedded in Lowicryl K4M from a patient with nodular-sclerosing-type Hodgkin's disease. At the electron microscopic level, gold particle staining indicative of Leu-M1 binding was found within cytoplasmic granules and the Golgi apparatus, as well as focally at the plasma membrane. The cytoplasmic granules were located in a perinuclear region and in the cell periphery. Although the morphology of the granules was suggested of lysosomal structures, immunolabel was not detected on serial sections of these granules with three different antibodies directed against lysosomal antigens.

Immunohistochemical demonstration of Toxoplasma gondii.

A peroxidase-antiperoxidase method that demonstrates both free and encysted toxoplasmata in routinely prepared histologic sections is described. This technic and ultrastructural study were employed to confirm the presence of Toxoplasma gondii in the infected tissues of an immunosuppressed patient who had postmortem examination. An immunohistochemical method may be an aid in the diagnosis of toxoplasmosis.

DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer.

BACKGROUND: Recent studies have shown that minichromosome maintenance (MCM) proteins (Mcm2-7) may be useful proliferation markers in dysplasia and cancer in various tissues. AIMS: To investigate the use of Mcm7 as a proliferation marker in 79 lymph node negative prostate cancers and compare it with Ki-67, a commonly used cell proliferation marker. METHODS: The percentage of proliferating cells (proliferation index; PI) was calculated for basal and luminal epithelial cells in benign prostate tissue, prostatic intraepithelial neoplasia (PIN), and epithelial cells in adenocarcinoma. The PI for each biomarker was correlated with the preoperative prostate specific antigen concentration, the Gleason score, surgical resection margin status, and the AJCC pT stage for each patient. RESULTS: The mean PIs for Ki-67 and Mcm7 were: benign luminal epithelium 0.7 and 1.2 and benign basal epithelium 0.8 and 8.2; PIN non-basal epithelium 4.9 and 10.6 and PIN basal epithelium 0.7 and 3.1; adenocarcinoma 9.8 and 22.7, respectively. Mcm7 had a significantly higher mean PI (p<0.0001) than Ki-67 for all cell categories except benign luminal epithelial cells. Mcm7 was a better discriminatory marker of proliferation between benign epithelium, PIN, and invasive adenocarcinoma (p<0.0001) than Ki-67. The drop in Mcm7 mean basal cell PI from benign epithelium to PIN epithelium was significantly larger than for Ki-67 (p<0.0001). Mcm7 had a significantly higher PI than Ki-67 at each risk level. CONCLUSION: Mcm7 may be a useful proliferation marker in prostatic neoplasia and warrants further evaluation as a complementary tool in the diagnosis of PIN and prostate carcinoma.

Atypical germ cells preceding metachronous bilateral testicular tumors.

This is the sixth reported case of metachronous testicular neoplasia in which a seminoma has preceded an embryonal carcinoma. Of particular note is the presence of atypical germ cells in the biopsy specimen of the gonad from which the embryonal carcinoma arose. There has developed recently an increasing awareness of germ cell atypia and carcinoma in situ. Pathologists examining testicular biopsies in the infertile patient should be alerted to this process.

Error in histologic dating of secretory endometrium: variance component analysis.

OBJECTIVE: To characterize the extent and sources of imprecision in histologic dating of the endometrial biopsy. DESIGN: Duplicate endometrial biopsies from 25 women were dated by five evaluators on two separate occasions to evaluate the overall precision of the measure. Using variance component analysis, estimates of intrauterine, intraevaluator, and interevaluator variability were determined. SETTING: Samples were obtained during outpatient fertility testing. Evaluators were colleagues at the same institution. PATIENTS, PARTICIPANTS: Women presenting with infertility undergoing routine evaluation. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Variability in histologic dating of the endometrium. RESULTS: Inconsistencies between evaluators accounted for 65% of the observed variability, whereas 27% was because of inconsistencies in duplicate readings by the same evaluator. Regional differences in the uterus accounted for only 8% of the total variability. CONCLUSIONS: The overall error from these sources have the potential to result in a substantial false-positive rate for diagnosis of luteal phase defect.

Creatine phosphokinase isoenzymes: a comparison of a kinetic and electrophoretic method in the diagnosis of myocardial infarction.

A comparison has been made of the results of the levels of the MB isoenzyme of creatine phosphokinase by a kinetic and an electrophoretic method performed on patients suspected of having myocardial infarction. Reviewed in depth are those cases in which discrepant results have occurred. On the basis of the combined clinical and laboratory data, the kinetic method is a more sensitive but less specific indicator of myocardial necrosis. Thus, the kinetic method may be used as a screening test, with confirmation of positive results by electrophoresis.

Orbital paraganglioma: case report and review of the literature.

Paragangliomas of the orbit are extremely rare. A case of an orbital paraganglioma, including the first magnetic resonance imaging description of this tumour is described here. The patient underwent surgery with gross total removal of the tumour and relief of his initial chief complaint of visual blurring. The differential diagnosis and therapeutic options for the management of this tumour are discussed.

Intervertebral chondrocalcinosis: A coincidental finding possibly related to previous surgery.

Chondrocalcinosis of the intervertebral discs is a common finding in patients who have had prior surgical procedures involving the same or adjacent disc space. The crystals in the tissues have the characteristic morphologic and spectrophotometric features of calcium pyrophosphate dihydrate. None of the patients described herein had clinical or radiographic evidence of crystal accumulation in sites remote from the surgical procedure. We propose that the surgical trauma may have played a role in the induction of the crystal deposits.

Adenocarcinoma of the uterine cervix of small intestinal type containing numerous Paneth cells.

A case of invasive adenocarcinoma of the uterine cervix with small intestinal differentiation to include numerous Paneth cells is presented. The light microscopic findings are confirmed by immunohistochemical and electron microscopic study. To our knowledge, this is only the second reported case of small intestinal cervical adenocarcinoma that contained Paneth cells and the first with ultrastructural and immunohistochemical confirmation. A small focus of in situ adenocarcinoma with similar features is seen adjacent to the invasive area.

CAP survey of parathyroid hormone assays.

Parathyroid hormone (PTH) analysis was recently added to the College of American Pathologists ligand assay survey. Synthetic whole-molecule PTH was used as the test hormone. This material was found to be stable in lyophilized serum for at least 10.7 days at 35 degrees C and 3.9 days at 45 degrees C. The survey results showed wide ranges of answers yielding within-assay coefficients of variation from 12% to 93%. The median percentage of the spiked hormone that was recovered by the various assay methods ranged from 24% to 390%. Separation of the spiked and endogenous measured PTH concentrations ranged from a twofold separation to an approximate 50% overlap of results. The survey may not be a valid indicator of PTH assay efficacy since whole-molecule human PTH may not be the most clinically important form of circulating PTH; however, the survey shows that there is a large heterogeneity in commercial PTH assays.

Juvenile polyp with intramucosal carcinoma.

Intramucosal carcinoma arising in an otherwise typical juvenile polyp is reported. Adenomatous change and carcinoma in situ have been previously documented in patients with the multiple juvenile polyposis syndrome. The syndrome was not present in this case. Although rare, juvenile polyps (both in solitary and multiple forms) are a potential site of malignant change.

The pathologist's role in the use of human tissues in research--legal, ethical, and other issues.

Because of their central role in examining and storing samples of human tissues obtained for diagnosis or therapy of diseases, pathologists frequently are involved in providing human tissues for a wide range of research. This is an important role for the pathologist that leads to increased understanding of disease, to potential methods of prevention, and to improved therapy. Recent conferences concerning uses of human tissues in research have indicated that there is confusion with respect to legal issues and requirements of pathologists who are involved in research with human tissues. This paper discusses current federal regulations concerning the use of human tissues and medical information in research as specified in Title 45, Part 46 of the Code of Federal Regulations (45 CFR 46) "Protection of Human Subjects." The authors also recommend approaches that pathologists can utilize to ensure that they are meeting all federal regulations with respect to the use of human tissues in research.