The use of post-embedding immunoelectron microscopy in the diagnosis of glomerular diseases. Comparison of immunoelectron microscopic and immunofluorescence studies.

Fifty renal biopsies were studied by immunoelectron microscopy after embedding in a partly hydrophilic polyacrylic resin (LR White). Immunofluorescence studies were carried out on frozen sections of parallel tissue samples. Polyacrylic embedding gave good preservation of the renal ultrastructure and precise localization of immunoglobulin and C3c antibodies within glomerular electron-dense deposits. Non-specific staining of plasma proteins within vascular lumina could easily be detected. There was good correlation between immunoelectron and immunofluorescence microscopy. Immunoelectron microscopy is a very sensitive method, which can detect small amounts of antigen. More cases were, however, positive by immunofluorescence than by immunoelectron microscopy. This discrepancy may be explained by difference in sample size, and by difference in resolution of morphological details (electron microscopy versus fluorescence microscopy).

The histopathology of non-palpable breast lesions detected by clinical mammography.

An histological study of 227 non-palpable breast lesions detected by clinical mammography revealed 64 invasive carcinomas at a mean patient age of 60.5 years. There were 10 carcinomas in situ, mean age 57.2 years. Fibrocystic disease with intraductal epithelial hyperplasia was found in 41 specimens, mean age 54.3 years. Fibrocystic disease without intraductal hyperplasia was found in 57 biopsies, mean age 50.7 years. Histological microcalcifications were found in 113 biopsies, and were considered to be a marker for epithelial proliferation of both benign and malignant kinds. Microcalcifications detectable in histological sections and by mammography differ in size by a factor of 10 or more. This difference has to be considered when comparing histological and mammographic findings.

The reliability of frozen section diagnosis.

We undertook a retrospective study of 594 consecutive diagnosis by frozen section. Clinically important discrepancies were found between the frozen section and final diagnoses in 18 (3%), and unimportant discrepancies in 35 (6%). The reasons for the discrepancies were misinterpretation in 22 (41%), the presence of focal lesions in 29 (55%), and technical errors in 2 (4%). There were 4 false positive and 18 false negative diagnoses, giving a sensitivity of 93% and a specificity of 99%. Diagnoses from frozen sections were deferred in 40 cases (7%). These results are in accordance with those of similar studies, and confirm that frozen section is a highly accurate, but not infallible, method of rapid histological diagnosis.

Follow-up of prostatic intraepithelial neoplasia.

Biopsy or fine-needle aspiration cytology are the only appropriate methods for detection of prostatic intraepithelial neoplasia (PIN). PIN has been suggested to be a principal precursor of invasive carcinoma of the prostate. Most reports on an association of PIN and invasive prostatic cancer have a follow-up of less than 1 year, indicating that the successively diagnosed cancer most probably was present at the time of diagnosis of PIN. The natural history of PIN is unknown and detection of PIN should therefore not influence therapeutic decisions. If coexistent carcinoma is not found, close surveillance is recommended to identify a possible subsequent cancer at an early stage. Follow-up examinations should be performed at 6-month intervals for 2 years and thereafter annually.

[Undiagnosed microinvasive carcinomas of the prostate]. / Ikke-diagnostiserte mikroinvasive karsinomer i prostata.

Quality assurance is becoming increasingly important in all aspects of health care, but a growing workload in recent years may delay the introduction of new quality assurance procedures. In 1994-95, in order to evaluate the standard of quality in executing routine histopathological procedures, a total of 1,135 prostatic specimens representing all surgical material taken from the prostate during 1974-75 were reviewed. The patients were followed up for to 20 years by comparing with the files of The Norwegian Cancer Registry. Only a few registration errors were found. Microscopic examination in 1994-95 revealed 311 carcinomas, 83 of which were not recorded in 1974-75. 73 of the patients had not received treatment. The histology reports revealed suspected malignancy, with irregular or atypical epithelium, or both, in 42% of the 83 carcinomas not reported in 1994-95, whereas for 45 carcinomas the histology reports did not describe changes suggestive of malignancy. Only 3% of the patients not treated died of prostate cancer during the follow-up time, compared with 78 (54%) cancer deaths in the group that had received treatment. Most undiagnosed cancers were well differentiated and in the pT1a category. It is important that the clinician is aware of the fairly benign outcome of these borderline tumors in order to avoid overtreatment.

Follow-up of localized prostate cancer, with emphasis on previous undiagnosed incidental cancer.

OBJECTIVE: To determine the natural course of incidental untreated transition zone prostate cancer and thus help to identify criteria to predict the prognosis and to determine treatment for individual patients. MATERIALS AND METHODS: A total of 1135 unselected surgical specimens of the prostate, examined during 1974 and 1975, were reviewed while unaware of case by two experienced pathologists. The patients from which the samples were obtained were followed for up to 20 years or death by The Cancer Registry of Norway and the outcome compared with the histological review. RESULTS: The histology review revealed a total of 311 cancers, of which 73 had not been initially recorded; these patients had received no treatment. The kappa coefficient for interobserver reproducibility was 0.86 for carcinoma. The follow-up showed that patient age was the strongest predictor of survival, followed by histological grade and percentage of tumour involvement. Only two of the 73 patients with untreated transition zone cancer died from prostate cancer during the follow-up, compared with 78 of 144 patients with standard management of transition zone tumours. The 5- and 10-year relative survival rates for the 144 patients with standard management of transitional zone tumours and for the 53 patients with peripheral zone tumours were 56% and 26%, and 45% and 33%, respectively. Metastasis (+ or -) was the only individual prognostic factor in the multivariate analysis. CONCLUSION: This study shows that patients with incidental low-grade tumours have a low probability of dying from prostate cancer and may thus be followed expectantly. The biological distinction between atypical hyperplasia and stage T1a cancer is unclear. The survival of men with prostate cancer is significantly reduced with loss of differentiation and with increasing tumour volvement.

Prostatic intraepithelial neoplasia in surgical resections: relationship to coexistent adenocarcinoma and atypical adenomatous hyperplasia of the prostate.

BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is associated with coincident prostate carcinoma, and has been considered to be a precursor of prostate carcinoma. Most studies on PIN have been performed on total prostatectomy or core needle biopsy specimens. Few reports deal with the occurrence of PIN in consecutive surgical resections, which is the objective of the current study. METHODS: A total of 1135 nonselected surgical specimens from the prostate, examined during 1974 and 1975, underwent blind review by 2 experienced pathologists. There were 79 core needle biopsies, 731 transurethral resections of the prostate and 325 transvesical prostatic enucleations. The kappa coefficient for interobserver reproducibility was 0.66 for PIN and 0.86 for carcinoma. RESULTS: Grade 1 PIN was found in 9%, Grade 2 PIN in 32%, and Grade 3 PIN in 20% of the total cases. Atypical adenomatous hyperplasia (AAH) was found in 11% and adenocarcinoma in 27% of the cases. Grade 3 PIN was associated with coincident adenocarcinoma in 39% of the cases. The prevalence of carcinoma for cases with Grade 1 and 2 PIN did not exceed that of those with Grade 0 PIN. PIN was most commonly found in association with small carcinomas. The mean age of the entire group of patients was 70.0 years, and was 69.4 years for patients with PIN without coincident carcinoma. Patients with PIN and coincident carcinoma had a mean age of 71.7 years, similar to all PIN grades, but patients with carcinoma without PIN had the highest mean age, 73.3 years. CONCLUSIONS: PIN is a common histologic finding in tissues from prostatic resections. In this study, Grade 3 PIN was strongly associated with coincident carcinoma, but lower grade PIN was not. There was no association between PIN and AAH. Patients with PIN did not appear to have a higher mean age than corresponding patients without PIN.

Is prostatic intraepithelial neoplasia in the transition/central zone a true precursor of cancer? A long-term retrospective study in Norway.

Prostatic intraepithelial neoplasia (PIN) has been considered as a precursor of prostatic cancer. Few reports have dealt with the long-term follow-up of PIN lesions, and there is still a lack of proof that PIN is a true premalignant lesion. The objective of this study was to evaluate PIN in the transition/central zone as a marker for subsequent development of prostatic cancer. The PIN status of tissue specimens from 789 men without prostate cancer was determined in 508 transurethral resections and 281 transvesical prostatic enucleations. All slides were reviewed blind and independently by two pathologists. The patients were followed for an average of 11 years, and the incidence of subsequent cancer and cause-specific survival were analysed. Thirty-six cases of clinical prostatic cancer occurred among the cohort of 789 men through follow-up. No association between the presence of PIN in the transition/central zone and subsequent cancer development was found. There was also no difference in survival related to PIN status among the subsequent cancer patients.