Report of the Committee on Staging and Pathology.
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Biomedical subjects
Publications and source records attributed to F K Mostofi.
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Carcinoma is found unexpectedly in approximately 10% or more of the 400,000 prostatectomies performed annually in the United States. Patients with Stage A2 carcinoma die of their disease in only 35% of the cases. To alter the course of disease in these patients, 65% of Stage A2 patients may be treated unnecessarily by radical prostatectomy, radiation therapy, or hormonal therapy. An accurate method to predict the outcome of patients with Stage A2 carcinoma is needed. Histologic sections from 18 patients with Stage A2 prostatic carcinoma followed without further treatment until progression, or followed without progression, were evaluated by several investigators who did not have knowledge of patient outcomes and who employed standard pathologic grading systems as well as morphometric, cytophotometric, flow cytometric, and immunohistochemical techniques. Outcome was predicted correctly by random sampled absolute (17 of 18 cases) and relative (16 of 18) nuclear roundness factor (NRF), tumor volume expressed as percent of specimen (13 of 16), primary (13 of 18), secondary (14 of 18), sum (15 of 18), and worse (14 of 18) Gleason grades and prostate-specific antigen immunohistochemical findings (13 of 18) that produced statistically significant separation of the two groups. Significant separation was not obtained with Mostofi's pattern, nuclear, sum, and worse grades, Johns Hopkins' grade, absolute tumor volume, nuclear DNA content measured by image cytophotometric study of Feulgen-stained histologic sections and flow cytometric study of propidium iodide-labeled suspensions of nuclei obtained from paraffin blocks, nonrandom sampled NRF of worse and most prevalent neoplastic areas, and prostatic acid phosphatase and peanut agglutinin immunohistochemical study. NRF measured by a random technique best predicted outcome in these patients with A2 prostatic carcinoma and should be evaluated prospectively as a means for selecting patients who require therapy.
In patients with biopsy proven prostate cancer, preoperative transrectal magnetic resonance imaging (MRI) and ultrasound were performed, followed by total prostatectomy. Generally, the findings with MRI correlated well with the histopathologic findings, including infiltration of and extension through the capsule into periprostatic tissue and the seminal vesicles. False negative results with MRI included centrally located tumors and small tumors. False positive results with MRI included lobular atrophy, cystic hyperplasia, cystic atrophy, florid glandular hyperplasia and scars with chronic inflammation.
Premalignant lesions of the prostate fall into two categories. The first category includes formation of new, usually small, glands which are either abnormally distributed or show minimal nuclear atypia or both. Morphologically, this lesion presents the differential diagnostic alternatives of micro-acinar hyperplasia on the one hand and a low grade micro-acinar cancer on the other. If the presence or absence of nuclear anaplasia or acinar dispersion (i.e., stromal invasion) raises any degree of doubt, atypical glands are diagnosed. This is the category that is considered by some to be the precursor of well differentiated prostate cancer. The second category is prostatic intraepithelial neoplasia (PIN). We have defined PIN as an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. We consider PIN as essentially carcinoma in situ. The lesion designated by some as PIN 1 is classified by us as atypical hyperplasia.
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We have endeavored to identify problems the pathologist may face in dealing with prostatic carcinoma (PCa). We have covered criteria for diagnosis and have discussed lesions that simulate PCa and the distinguishing features, treatment effects, and specific types of PCa. In many of these areas there is a need for developing objective, reproducible, and measurable criteria. The need for research is obvious.
PURPOSE: The Testicular Cancer Intergroup Study (TCIS) was undertaken to evaluate the pathologic findings in early-stage testicular cancer as determined by central pathology review, to compare these findings with the interpretation by the contributing pathologists, and to make correlations with various clinical parameters and outcomes. PATIENTS AND METHODS: The prospective study of non-seminomatous germ cell testicular cancer staged surgically involved 459 eligible patients with stage I (node-negative) or stage II (node-positive) disease. Pathologic materials from both the orchiectomy and lymphadenectomy specimens were submitted to a central laboratory for evaluation. RESULTS: Central and local pathologists differed significantly in their identification of certain cellular histologies (primarily yolk sac tumors [YST]) and recognition of invasion into vascular structures. In contrast to our prior findings with local pathologic assessment, venous/lymphatic invasion as determined by central review predicted relapse in both stages. In pathologic stage I disease, the relapse rate was 19.4% (12 of 62 cases) for those with invasion versus 6.0% (10 of 168 cases) for those without invasion. In pathologic stage II disease, the respective relapse rates were 63.5% (40 of 63 cases) and 24.0% (six of 25 cases). Vascular invasion was jointly predictive with nodal stage for risk of relapse. The percentage of embryonal carcinoma (EC) in the primary tumor was predictive of nodal stage and relapse in a univariate, but not a multivariate, analysis. In a large substudy, immunohistochemical staining identified a correlation between stain intensity in YST and serum alpha-fetoprotein (AFP) levels. In a similar fashion human chorionic gonadotropin (HCG) staining reactivity occurred exclusively in patients with syncytiotrophoblasts and correlated with serum levels of beta-HCG. CONCLUSIONS: A number of tumor histology correlates with clinical parameters have been identified or confirmed. Careful pathologic scrutiny of the primary testicular tumor, especially for vascular invasion, provides important prognostic information.
About 600 cases of urethral carcinoma have been reported. Such tumors may arise from the surface epithelium or any of the glands, and four histologic patterns--squamous, transitional, glandular, and undifferentiated--have been recognized. Metastases from other sites are possible, as are melanomas and various types of sarcoma.
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The first case of primary Wilms' tumor of the prostatic gland is described. It occurred in a 32-year-old man. Histologically, it consisted of a triphasic tumor; tubular and glomeruloid structures were identified, among prominent blastematous sheets and in an edematous stroma. No teratomatous components were encountered. We propose that this prostatic primary, nonteratomatous Wilms' tumor can arise from persistent, nephrogenic, blastematous rests in the prostate, in relation to the Wolffian duct system.
In the course of a Medical Research Council trial of intravesical chemotherapy, biopsies were taken from apparently normal bladder urothelium near to newly diagnosed superficial bladder cancers in 417 patients. Differences were noted in the rates at which histological features were described in different centres. To gain more information about the reproducibility of the pathological findings, a group of 6 pathologists (5 from the UK and 1 from the USA), all having a special interest in urological pathology, were asked to examine a representative sample of 92 slides. They were then asked to re-examine 30 of them after an interval of at least 6 months. At first examination and at re-examination the slides were assessed using a standard proforma. However, the definitions of the categories were left unspecified for the pathologists to use their own criteria. The 5 UK pathologists then met to establish a consensus view of each slide. The results indicated that: (1) The reporting of non-dysplastic changes varied so much between pathologists as to render it of little value to clinical practice. (2) There were wide variations between different pathologists in the reported incidence of dysplastic change. (3) On a second review the pathologists reproduced their own assessment on only 62% of occasions. (4) Even after discussion between pathologists there was no consensus on the diagnosis of mild as opposed to moderate dysplasia. Consensus was reached on all biopsies which showed either severe dysplasia or carcinoma in situ. (5) In adopting a policy of taking urothelial biopsies, urologists should be aware of the imprecision and lack of reproducibility in the interpretation of such biopsies. (6) Biopsies of cystoscopically normal urothelium may not be a useful guide in defining therapy.
A modification of the silver colloid technique for staining nucleoar organizer regions in paraffin embedded tissues is described. This modification involves the application of a gold toning step with subsequent gold reduction, if necessary, following incubation of sections in the standard silver colloid solution. Silver stained nucleolar organizer regions (AgNORs) in toned sections are more sharply delineated when compared to untoned controls. In high grade tumors the addition of the toning step results in significantly higher AgNOR counts due to the ability to discriminate more easily individual AgNORs in argyrophilic aggregates within the nucleus. It is recommended, because of enhanced visualization, that this modification of the silver colloid technique be used in studies involving quantification of AgNORs in tissue sections.
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We report on 5 patients 14 months to 6 1/2 years old with prepubertal teratoma of the testis treated by testicular sparing tumor enucleation. All 5 patients had no evidence of recurrence at a mean followup of 96 months. Recognizing that this is not accepted therapy for testis tumors, 17 orchiectomy specimens containing teratoma from children were histologically analyzed in cooperation with the Armed Forces Institute of Pathology Tumor Registry. All patients were prepubertal at orchiectomy (3 months to 8 years old) and all are well with a mean followup of 174 months. Histological examination revealed no foci of teratoma separate from the main tumor in any specimens. Immunohistochemical studies with placental alkaline phosphatase, a marker for malignant germ cells, were done to detect carcinoma in situ in the seminiferous tubules of these testes. This test did not reveal any intratubular malignant germ cells (carcinoma in situ). Based on our clinical experience with testicular sparing tumor enucleation, the histological findings on Armed Forces Institute of Pathology review demonstrating no associated carcinoma in situ and the universally benign behavior of prepubertal testicular teratomas, we recommend a testicular sparing operation rather than orchiectomy for testicular teratoma in prepubertal patients.
Urinary bladder is an easily accessible organ and its histology is simple, but there exists considerable controversy in the interpretation of pathological findings; in fact, even in the criteria for diagnosis of malignancy. These controversies must be resolved to provide us with proper management of patients with cancer of the bladder.
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