Epididymal rhabdomyoma: report of a case, including histologic and immunohistochemical findings.

Genital rhabdomyoma is a rare tumor of skeletal muscle origin that is usually found in the vulvar area of young women. The English literature contains only 2 previous case reports involving men, both of whom were 19 years old. One of these lesions originated in the tunica vaginalis of the testis, and the other originated in the prostate gland. We present the clinical, histologic, and immunohistochemical findings of an epididymal rhabdomyoma in a 20-year-old man. To our knowledge, this is the first such case reported in this location.

Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guérin.

OBJECTIVES: Bropirimine is an oral immunomodulator that has demonstrated anticancer activity in transitional cell carcinoma in situ (CIS) in both the bladder and upper urinary tract. Activity also has been documented in patients after prior therapy with bacille Calmette-Guérin (BCG). To more accurately estimate bropirimine's efficacy in BCG-resistant bladder CIS, a Phase II trial was performed. A separate analysis was performed in additional patients intolerant of BCG toxicity. METHODS: Patients received bropirimine 3.0 g/day by mouth for 3 consecutive days, weekly, for up to 1 year. Bladder biopsies and cytologic examination were performed quarterly. Complete response (CR) required negative biopsy and cytology results. RESULTS: Twenty-one of 86 patients entered were not evaluable. CR was seen in 21 (32%; 95th percentile confidence interval [CI], 21% to 44%) of 65 evaluable patients, including 14 (30%, CI 17% to 43%) of 47 BCG-resistant, and 7 (39%, CI 16% to 61%) of 18 BCG-intolerant patients. Overall, by intent-to-treat analysis, CR was thus seen in 21 (24%) of 86 subjects. Most BCG-resistant patients were failures to BCG without relapse, and had received 12 to 36 (median 12) BCG treatments; intolerant patients had received 4 to 11 treatments (median 6). Response duration ranged from 65 to 810 days, with median not yet reached (but greater than 12 months). Thirteen (15%) of 86 stopped bropirimine due to toxicity. Progression to invasive or metastatic disease during or immediately after therapy was documented in only 4 patients (6%), all nonresponders. CONCLUSIONS: Bropirimine may be an alternative to cystectomy for some patients with bladder CIS who have failed or have not tolerated BCG. Further evaluation to improve responses and durability is warranted.

Terminal nerve distribution to the urethra and bladder neck: considerations in the management of stress urinary incontinence.

PURPOSE: Recent reports have suggested an increased incidence of intrinsic sphincter dysfunction, most of which seems to appear following the failure of a previous, usually vaginal, surgical repair. Our studies attempt to define more precisely the neuroanatomical relationships that exist in the region of the bladder neck and proximal urethra, and between the urethra and anterior vaginal wall. MATERIALS AND METHODS: We dissected the pelves of adult female cadavers and step sectioned them at 4 mm. intervals. Several staining methods were used on each section to identify and document the position of the nerves and vascular structures between the vaginal wall and urethra. RESULTS: A rich plexus of blood vessels and nerves with ganglia is located between the vaginal wall, and the proximal urethra and bladder neck. The greatest concentrations of nerves are in the 4 o'clock and 8 o'clock positions but nerve fibers are identified throughout the loose areolar tissue planes through which vaginal surgery for stress urinary incontinence is often performed. CONCLUSIONS: When performing surgical procedures for the correction of stress urinary incontinence, the possibility that denervation and devascularization of the terminal urethra and bladder neck secondary to surgical dissection could contribute to the subsequent development of intrinsic sphincter dysfunction should be considered.

The significance of central pathology review in clinical studies of transitional cell carcinoma in situ.

PURPOSE: The causes of interobserver variation in the pathological diagnosis of urothelial neoplasia were studied. MATERIALS AND METHODS: A central review was performed on pathological specimens in a multi-institutional clinical study of patients with in situ transitional cell carcinoma of the bladder. RESULTS: A significant discrepancy in pathological diagnosis was noted between the original report and the central review in 60 of 159 biopsies (38%) and in 73 of 217 cytology specimens (34%). Biopsy discrepancies were almost equally divided between upgrades and downgrades, whereas 89% of cytology discrepancies involved an upgrade in diagnosis by the central reviewer. The most significant factor causing variability in biopsy diagnoses was the multiplicity of classifications used by the originating pathologists. Other factors included fixation and biopsy artifacts. Cell degeneration secondary to treatment was the most important factor resulting in cytology under grading. At originating institutions the correlation of diagnoses between concurrent biopsy and cytology specimens was poor. CONCLUSIONS: The lack of a well accepted standard for the histopathological diagnosis of transitional cell carcinoma in situ poses a major problem for multi-institutional studies of this disease. Organizers must include a histopathological standard in the study plan and publicize it to all participants, particularly pathologists. Central review of pathological specimens is essential to maintain data integrity.

Effects of preoperative chemotherapy on the morphology of resectable breast carcinoma.

We examined pathologic specimens from 43 patients with Stage T1-T3 lesions who were treated preoperatively with four cycles of doxorubicin/cyclophosphamide, followed by segmentectomy/mastectomy and axillary node dissection (the National Surgical Adjuvant Breast and Bowel Project B-18 protocol). Specimens from 46 patients treated post-operatively with the same regimen served as histologic controls. The initial diagnosis was made by core needle biopsy (28%) or by fine-needle aspiration (72%). Six changes were noted in 36 patients (84%), with complete regression in 10, but histologic evidence of regression and characteristic cytologic changes occurred in only one-half of the 43 patients, and there was poor correlation between histologic regression and clinical response; (2) an increased nuclear grade occurred in 32% of the cases; (3) unusually prominent intraductal and/or intralymphatic tumor was observed in 40%; (4) histologic evidence of tumor regression in axillary lymph nodes was noted in nine cases; (5) regressive changes also occurred in non-neoplastic breast tissue and in lymphoid populations of lymph nodes; and (6) difficulty was noted in evaluating residual atypical intraductal proliferations. These findings add a quantitative dimension to previously published descriptions and emphasize the need for pathologic staging in these patients. In addition, they provide histopathologic evidence of downstaging in axillary lymph nodes and of relative treatment resistance by intraductal and intralymphatic tumor.

Recruitment of a pathology course director.

The process of choosing a course director rarely involves a rigorous examination of the duties to be assumed, primarily because the selection is from among existing faculty rather than as a result of formal recruitment. The selectee tends to be surprised (and often disheartened) by the amount of time the job requires. This report was developed from workshops conducted at recent meetings of both the Group for Research in Pathology Education and the Association of Pathology Chairmen. It describes the overall scope of a course director's activities, including the percentage of time devoted to various functions, and identifies issues to be addressed at the time of the course director's selection. Although the appointment may still be from within the department, the recruitment process does allow for a more full and open discussion of the job to be accomplished.

Morphology of the uvula in obstructive sleep apnea.

Alterations in pharyngeal structure and function are considered fundamental in the pathogenesis of obstructive sleep apnea (OSA). However, little is known about morphologic features of the pharynx in patients with OSA. We therefore studied the tissue composition of the uvula (midsagittal section) in patients with OSA, using a quantitative, morphometric point-counting technique. Uvula tissue was obtained by uvulopalatopharyngoplasty (UPPP) in 33 patients (mean number of apneas per hour of sleep = 32.7 +/- 5.2) and by autopsy in 22 normal subjects not known to have OSA. All statistical comparisons were controlled for differences caused by age and body mass index. Patients with OSA had a significantly greater percentage of muscle in the uvula (18.1 +/- 1.9% versus 9.3 +/- 2.1%, p = 0.02) than did normal subjects. A significant difference in fat content was also found (9.5 +/- 1.4% in patients versus 4.0 +/- 1.0% in normal subjects, p less than 0.02). These differences between patients with OSA and control subjects could not be accounted for by anthropometric or sex differences. The percentage of uvula fat tissue was significantly related to the frequency of apneas and hypopneas in sleep (r = 0.43, p less than 0.01). Uvula morphology in 6 nonapneic snorers undergoing UPPP was similar to that of patients with OSA. We conclude that the uvula in patients with OSA contains more muscle and fat than the uvula in control subjects, possibly contributing to pharyngeal narrowing in OSA.

Correlation of aromatase activity with histological differentiation of breast cancer--a morphometric analysis.

Differentiation is a term that indicates the degree to which a tumor resembles histologically the tissue or cell of origin. A system to quantitate the proportion of breast cancer cells participating in glandular differentiation or remaining within ducts was employed. The degree of tumor differentiation of 58 primary breast cancers was correlated with estrogen (ER) and progesterone receptors (PR) and tumor aromatase activity. There was a significant association between tumor differentiation (greater than or equal to 2% cancer cells exhibiting glandular differentiation) and the presence of ER or PR in tumors. Conversely, there was no correlation between tumor differentiation and measurable tumor aromatase activity.

Tumor-associated antigens in breast carcinomas. Prognostic significance.

In an attempt to identify biologic markers that might predict prognosis in breast cancer patients, the presence or absence of seven tumor-associated antigens in 54 infiltrating breast carcinomas was correlated with tumor recurrence rates (minimum five-year follow-up), axillary lymph node metastases and tumor volume. Immunohistochemical kappa-casein was present in 30 (56%) tumors, alpha-lactalbumin in 39 (72%) tumors, secretory component of IgA in 26 (48%) tumors, carcinoembryonic antigen in 34 (63%) tumors, pregnancy-specific beta-1-glycoprotein in 7 (13%) tumors, beta subunit of human chorionic gonadotrophin in 1 (2%) tumor and human placental lactogen in 0 (0%) tumors. There was no significant correlation between the presence or absence in tumor of any of the antigens, and prognosis as assessed either by 5-year recurrence rates (P greater than 0.18) or by the presence of axillary lymph node metastases (P greater than 0.20). No significant difference was noted in mean tumor volume (cm3) +/- SEM, between tumors with or without antigen immunoreactivity (P greater than 0.05).

Synovial sarcoma of the jaw in a dog.

A case of synovial sarcoma of the jaw with pulmonary metastasis is described in a dog. It appears to be a rare or underdiagnosed neoplasm in animals and not previously reported in the jaw. Its diagnostic microscopic features are the biphasic cellular pattern and cleft formations. It may otherwise resemble haemangiopericytoma, malignant fibrous histiocytoma, reticulum cell sarcoma, fibrosarcoma, or giant-cell tumour of soft tissue.

Purkinje cell inclusions and 'atelencephaly' in 13q-chromosomal syndrome.

Severe microcephaly was present from birth in a child with a 13q-chromosomal syndrome [46,XY,del(13)(q22q31)]. He died at 20 months of age. Neuropathologic findings included atelencephaly and eosinophilic cytoplasmic inclusions in cerebellar Purkinje cells. Ultrastructurally, the inclusions consisted of stacks of parallel cisternae separated by electron-dense granular material. The relationship between these inclusions and the smaller cytoplasmic inclusions known as "lamellar bodies" is discussed, and the central nervous system malformations in this syndrome are reviewed.

Morphometric analysis of endometrial adenocarcinoma: 1. Does architectural dedifferentiation accompany deep invasion by endometrial adenocarcinoma?

Important prognostic factors for endometrial adenocarcinoma include histologic differentiation, depth of myometrial invasion, and clinical stage. Deep myometrial penetration is more commonly observed with poorly differentiated carcinomas, but it is unknown if these tumors are poorly differentiated de novo, or if selection toward more aggressive, less differentiated cells occurs during invasion. To study this question, we performed a morphometric analysis to quantitate the amount of glandular differentiation in superficial portions of 22 endometrial carcinomas for comparison with deep portions of the same neoplasm. Point counting of randomly selected fields was performed on histologic sections of hysterectomy specimens of 22 women with stage I endometrial adenocarcinoma. The components enumerated were tumor cells participating in gland formation (DI), non-gland-forming tumor cells (UI), tumor gland lumens (LUM), inflammatory cells (IC), and stroma (endometrium or myometrium) (ST). Slides of tumors were divided into superficial, middle, and deep thirds. No statistically significant differences were seen between superficial and deep thirds (UI: 45% vs. 43%; DI: 33% vs. 32%; LUM: 22% vs. 24%; IC: 3% vs. 3% of points counted, p greater than .1, paired t-test). The density of tumor cells relative to stroma was greater in the superficial region (55% vs. 41%, p less than .001, paired t-test). Additionally, field-to-field heterogeneity was examined by four methods. No relationship between increased heterogeneity and poor prognosis was identified. These findings do not support the concept that invasion by endometrial adenocarcinoma is accompanied by architectural dedifferentiation.

Morphometric analysis of endometrial adenocarcinoma: 2. A comparison of architectural differentiation determined morphometrically with subjective grading.

Architectural differentiation is the primary criterion used in the grading of endometrial adenocarcinomas. However, there is little evidence supporting the accuracy of pathologists' assignment of histologic grade, and few studies on the value of architectural morphometry in predicting prognosis for endometrial adenocarcinoma. We have thus investigated whether a pathologist's estimate of percentage of tumor in solid array correlated with the volume fraction of tumors composed of cells not participating in gland formation determined morphometrically. Additionally, we conducted this morphometric study of 31 cases of Stage I endometrial cancer to determine the relationship between a variety of objective measurements of architectural arrangement and prognosis. We found that a pathologist can accurately estimate the proportion of endometrial tumors arranged in solid or glandular fashion. In this limited study, morphometric assessment of the proportion of differentiated or undifferentiated cells or lumens did not improve the accuracy of prediction of outcome beyond conventional architectural grading. Further, we reaffirm that estimation of architectural arrangement coupled with measurement of the depth of penetration provides a good index of the probability of survival.

Urogenital tract carcinoma metastatic to the head and neck.

A 9-year review of our experience with head and neck metastases from 845 urogenital tract tumors of the kidney, prostate, bladder, testicle, spermatic cord, penis, urethra, and ureter was performed. Thirty-one (3.7%) of these tumors developed metastases to the cervical and supraclavicular lymph nodes, scalp, thyroid gland, thyroid cartilage, parotid gland, retroorbit, mandible, nasal cavity, and paranasal sinuses. Unusual cases and a review of the literature are presented. The frequency of such metastases to the head and neck from various primaries, diagnostic application of current immunohistochemical methodology, and therapeutic alternatives are emphasized.

Morphometric grading of squamous cell carcinoma.

Histological grading of squamous cell carcinoma is subjective and suffers from poor observer reproducibility. We investigated the feasibility of quantifying histological differentiation via point counting, using both the degree of keratinization and a novel definition of differentiation that was based on architectural features of the tumour. Multiple recounts of 20 cases of human oral squamous cell carcinoma were performed at several magnifications (X100, X160 and X250). Six lines of human squamous cell carcinoma tumour lines were examined for changes in differentiation following transplantation to athymic nude mice. Observer reproducibility was extremely high for all recounts except at the highest magnification, where the tumour architecture may have been obscured. Of the human squamous cell carcinomas transplanted to nude mice, five of six tumour lines showed significant histological changes, most commonly toward decreased differentiation. The changes were usually present in the initial transplant and were similar to those we have reported for transplants of adenocarcinomas. We conclude that histological differentiation can be quantified in squamous cell carcinomas with a high degree of observer reproducibility, even in the absence of keratinization; the method employed is sufficiently sensitive to be applied to practical problems of biological significance.

Cystic hygroma of the breast.

Cystic hygroma is a common benign lymphatic tumor that presents at birth or during infancy. We report an unusual case of a cystic hygroma of the breast, which was discovered in a 49-year-old woman on screening mammography.

Observer reproducibility during computer-assisted planimetric measurements of nuclear features.

To evaluate observer variance during microprocessor-assisted planimetry, nuclear features (area, perimeter, and form factor) were studied in a series of mammary ductal carcinomas. Fragments of formalin-fixed, paraffin-embedded tissue were re-embedded in plastic, sectioned at 1 micron, stained with methylene blue, and studied with a Zeiss-Kontron MOP-3 microprocessor-assisted planimeter. Both interobserver and intraobserver reproducibility were evaluated, the former among three different observers and the latter by two observers repeating their own measurements. Reproducibility was good for measurement of area, but deteriorated progressively for measurement of perimeter and form factor. Not only was observer correlation poor (identified via linear regression), but paired t-tests also showed consistent variation among observers. The major difficulty was in following the irregular nuclear contours that are characteristic of cancer cells. It is concluded that adequate demonstration of observer reproducibility remains an essential part of tissue investigation, even when the objective methods typical of morphometry are used.

Morphologic identity of primary tumor and axillary metastases in breast carcinoma. A quantitative study.

The amount of glandular differentiation was quantitated in 64 cases of primary human mammary ductal carcinoma (PR) and their axillary lymph node metastases (LNMs) to identify differences between the two groups and their effect on patient prognosis. A significant difference between a PR and any of its LNMs was uncommon (less than 5% of the cases), and variation between each PR and its LNMs was directly proportional to the amount of differentiation within the PR itself. Variance among the LNMs was proportional to that found within the PR. Each LNM usually varied as much within itself as it did from the other LNMs. Prognosis was not affected by the LNMs being less differentiated than the PR, nor vice versa. This study has provided no evidence for selection of a morphologically more aggressive tumor clone during this phase of the metastatic process, but selection by other morphologic or functional parameters is not excluded.