Testicular regression syndrome: a clinical and pathologic study of 11 cases.

CONTEXT: The vanishing or regressed testis is an entity well known to urologists and pediatric surgeons, affecting approximately 5% of patients with cryptorchidism. However, there is little review and discussion of this entity among pathologists with only 2 of 40 published reviews of testicular regression syndrome (TRS) found in the pathologic literature. OBJECTIVES: To assess recognition of TRS among a subset of pathologists and to determine the applicability of histologic criteria for TRS as published. DESIGN: An 8-year retrospective review of cases submitted as atrophic or regressed testis was performed. Original diagnosis and diagnosis after review were compared to assess pathologic recognition of TRS. Pathologic assessment included identification of vas deferens, epididymis, dystrophic calcification, hemosiderin, dominant vein, pampiniform plexus-like vessels, and vascularized fibrous nodule formation. At minimum, the presence of a vascularized fibrous nodule (VFN) with calcification or hemosiderin or VFN with cord element(s) was required for diagnosis. SETTING AND PARTICIPANTS: Medical records and pathologic specimens of patients undergoing surgery for cryptorchidism or with specimens reviewed at a medium-sized university hospital were analyzed. RESULTS: The original diagnosis in 3 (23%) of 13 cases was that of TRS. On secondary review, 11 (85%) of 13 cases showed features consistent with TRS. The diagnoses both before and after review showed a concurrence of 23% (3/13 cases). Two (15%) of 13 cases were correctly recognized and diagnosed as TRS at primary review; 1 case originally thought to represent TRS was not confirmed. Pathologic features correlated well with those reported in the literature. Among all 13 cases, the 11 confirmed TRS cases showed VFN in 11 (85%), intranodular calcification in 8 (62%), intranodular hemosiderin in 9 (69%), vas deferens in 9 (69%), epididymal structures in 5 (38%), and a dominant venous structure in 11 (85%). The average size of the VFN was 1.1 cm. CONCLUSION: A urologic and pediatric surgical problem, TRS may be unrecognized by many practicing pathologists. In the typical situation in which a blind ending spermatic cord is submitted for tissue analysis, characterization of such cases as consistent with regressed testis is desirable and achievable in a high percentage of cases. Pathologists may play a pivotal role in management of these patients since histologic confirmation of the testis as regressed reassures the surgeon and the family of the correctness of diagnosis and can eliminate the necessity for further intervention.

Neuroendocrine signet ring cell adenocarcinoma of the endocervix.

Signet ring cell morphology in mixed carcinoma of the uterine cervix is not uncommon. It is rare for such morphology to predominate, however, and there are no reported cases of a signet ring cell adenocarcinoma (SRCA) of the endocervix with neuroendocrine differentiation. A 53-year-old woman presented with abnormal perimenopausal bleeding, and uterine curettings revealed a signet ring cell carcinoma. After clinical evaluation to eliminate a metastasis from an extra-uterine primary, the patient underwent surgical therapy and staging, and was treated with postoperative adjuvant chemoradiation. Pathologic evaluation found the tumor to arise from the endocervix and to be of predominant signet ring cell morphology. Immunohistochemical staining revealed that the tumor exhibited neuroendocrine differentiation and helped confirm its endocervical origin. The patient remains without evidence of disease 6 months after primary therapy. This is the first case report of endocervical SRCA with neuroendocrine differentiation (SRCA with features of carcinoid tumor). Discussion of this entity is provided.

Etiologies for non-correlating cervical cytologies and biopsies.

To investigate the etiologies for discrepancies between cervicovaginal smear and corresponding cervical biopsy results, 615 patients with cytologic diagnoses of dysplasia or malignancy during 1 year were reviewed. Sixty-nine patients (11%) were identified in which the cytologic and histologic diagnoses differed. Utilizing an algorithm developed for the study, these cases were assigned an etiologic category for discrepancy: colposcopic biopsy or cytologic sampling, cytologic screening, histotechnical processing, histologic or cytologic interpretation. The most common cause for a discrepancy was colposcopic biopsy sampling (36 cases, 51%). There were nine errors (13%) in biopsy interpretation, with seven underdiagnoses and two overdiagnoses. Eight errors (11%) in cytologic interpretation occurred with half of these representing underdiagnoses. The other causes for discrepancy were less common--cytologic sampling (6 cases), histotechnical processing (3 cases), cytologic screening (2 cases), and a combination of factors (5 cases). Use of this algorithm allows laboratories to identify problem areas and design specific corrective protocols to improve diagnostic accuracy and patient care.

Assessment of cervicovaginal smear adequacy. The Bethesda System guidelines and reproducibility.

Criteria for assessing adequacy of cervicovaginal smears according to the Bethesda System include cellular composition and quantity, specimen preservation, fixation, and absence of obscuring elements. The reproducibility of adequacy assessment using these parameters was the focus of this study. Specimens were chosen to include a wide spectrum of clinical history and adequacy interpretations, but excluded cases with epithelial abnormalities and those judged "limited" because of insufficient transformation zone component. The 114 specimens were independently evaluated twice by five reviewers, with interceding randomization. Full interobserver concordance was obtained in 50.4% of cases, with consensus reached by three or more observers in 97.4% of cases. Of 2280 paired interpretations, 74% (1692) concurred. Pairwise kappa values for interobserver agreement ranged from .71 to .54 (very good to fair), with overall kappa = .61. Interobserver agreement for each category was near excellent for "satisfactory" (kappa = .73), good for "unsatisfactory" (kappa = .63), and only fair for "satisfactory but limited" (kappa = .48). Paired intraobserver reproducibility (agreement for two separate readings by the same observer) ranged from 69% to 77% (average, 74%), with good to fair kappa values (.66-.51). These findings indicate that the specimen adequacy guidelines of the Bethesda System provide good inter- and intraobserver reproducibility. The "satisfactory but limited" category appears to show the lowest concordance. Problem areas include evaluation of adequate minimum cellularity and estimation of number of cells obscured.

Gleason histologic grading in prostatic carcinoma. Correlation of 18-gauge core biopsy with prostatectomy.

Histologic grading of adenocarcinoma of the prostate gland is a reliable predictor of extension and metastasis. Studies involving correlation of grade between biopsy and prostatectomy specimens have traditionally involved biopsies using a large-bore (14-gauge) cutting needle. However, common practice has shifted to the use of biopsy cores with a smaller caliber (18 gauge). This study was undertaken to determine the degree of correlation of tumor grade between 18-gauge core biopsy samples and excised glands. Sixty-seven patients with stage A or B adenocarcinoma of the prostate gland who had previously undergone 18-gauge core biopsy, who underwent radical prostatectomies, were studied. The Gleason score was determined by referred consensus among three pathologists. There was exact agreement between biopsy and excision in 39 cases (58%), whereas 24 cases (36%) differed by one digit. Three cases (4.5%) were undergraded, and one case (1.5%) was overgraded by two or more points. Only six tumors (8.9%) would have been incorrectly specified by the degree of differentiation. Discrepancies in grade of two points or more were not more frequent in cases with a small tumor volume (< or = 10%) in the biopsy specimens. We concluded that with careful histologic evaluation, the grade of tumor identified in these smaller biopsy cores correlates well with that seen at prostatectomy.

Proliferating cell nuclear antigen in prostatic adenocarcinoma: correlation with established prognostic indicators.

OBJECTIVE: The utility of an antibody to proliferating cell nuclear antigen (PCNA), a growth-specific nuclear protein, was assessed as a prognostic variable for prostatic adenocarcinoma. Its expression was correlated with established prognostic indicators, including tumor grade, stage, prostatic-specific antigen (PSA), and percent of tumor in the gland at excision. METHODS: Forty archival needle biopsies containing a minimum of four hundred tumor cells were analyzed. Immunoperoxidase staining of paraffin sections was performed for PCNA (PC10) after pretreatment in antigen retrieval solution. A proliferative index (PI) for each case was derived using image analysis with measurement of at least four hundred twenty-five nuclei. RESULTS: PI values ranged from 2.4 to 31.3 percent. Mean PI values varied significantly (ANOVA, p = 0.005) among cases with dominant Gleason grade (DGG) of 3 (mean PI = 9.3%), 4 (mean PI = 13.7%), and 5 (mean PI = 18.8%). By t test, significant differences were noted for PI in cases with DGG 2 and 3 versus those with DGG 4 and 5 (p = 0.0065). PI for cases with DGG 3 versus 5 showed significant difference (p = 0.0017). Tumors of Gleason scores 5 to 7 differed significantly from those with scores 8 to 10 (p = 0.014). A statistical relationship for PI and PSA, clinical stage, and percent tumor at resection could not be established by linear regression. CONCLUSIONS: These findings suggest that additional study of the PI, as determined by PCNA immunohistochemistry and image analysis, may be warranted to determine its usefulness as an adjunctive parameter in prostate adenocarcinoma. This technique may be particularly useful in needle biopsies where limited tumor may render assessment of grade difficult.

Adenocarcinoma of renal pelvis.

Adenocarcinoma accounts for a small percentage of neoplasms arising within the renal pelvis. We describe a mucinous adenocarcinoma of the renal pelvis that occurred in a 57-year-old woman. Investigation of the recent literature reveals an additional 12 cases of adenocarcinoma of the renal pelvis reported since 1980. These 13 cases are summarized in detail, for a total of 59 cases of adenocarcinoma of the renal pelvis documented in the English-language literature. These tumors can be subdivided into three major histologic types: tubulovillous, mucinous, and papillary non-intestinal. The tubulovillous and mucinous tumors are morphologically similar to intestinal tumors accounting for 71.5% and 21.5% of cases, respectively. They are believed to arise in foci of intestinal metaplasia. Only three cases (7%) were of the nonintestinal, nonmucinous, papillary subtype. These rare tumors are notable for their morphologic similarity to Bellini or collecting duct carcinoma, but a specific morphologic precursor has not been identified. Of the three subtypes, tumors of tubulovillous morphology confer the worst prognosis with 70% of patients dying within 5 years. Thirty-three percent of mucinous tumors and none of the papillary nonintestinal tumors were fatal.