Eva M. Wojcik

T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer

Manipulations capable of breaking host tolerance to induce tissue-specific T cell-mediated inflammation are of central importance to tumor immunotherapy and our understanding of autoimmunity. We demonstrate that androgen ablative therapy induces profuse T cell infiltration of benign glands and tumors in human prostates. T cell infiltration is readily apparent after 7–28 days of therapy and is comprised predominantly of a response by CD4+ T cells and comparatively fewer CD8+ T cells. Also, T cells within the treated prostate exhibit restricted TCR Vβ gene usage, consistent with a local oligoclonal response. Recruitment/activation of antigen-presenting cells in treated prostate tissues may contribute to local T cell activation. The induction of T cell infiltration in prostate tissues treated with androgen ablation may have implications for the immunotherapeutic treatment of prostate cancer as well as other hormone-sensitive malignancies, including breast carcinoma.

Immunohistochemical Expression of Galectin-3 in Benign and Malignant Thyroid Lesions

CONTEXT The expression of galectin-3, a human lectin, has been shown to be highly associated with malignant behavior of thyroid lesions. DESIGN We studied the immunohistochemical expression pattern of galectin-3 in a variety of follicular-derived thyroid lesions (13 benign and 62 malignant), including Hürthle cell and follicular carcinoma, papillary carcinomas and variants, and anaplastic and poorly differentiated carcinomas. RESULTS Immunoreactivity was strongest in papillary thyroid carcinomas, whereas staining was less intense in Hürthle cell and anaplastic carcinomas, and even weaker in the follicular variant of papillary thyroid carcinoma. Staining was absent or weak in the 3 follicular thyroid carcinomas and was negative in both insular carcinomas. In several tumors, staining was stronger at the advancing invasive edge of the lesion than in the central portion of the tumor. Galectin-3 was also expressed focally and weakly in reactive follicular epithelium and entrapped follicles in chronic lymphocytic thyroiditis. A variety of thyroid lesions showed prominent endogenous, biotin-like activity, which could cause flaws in interpretation if a biotin-detection system were used. CONCLUSION We conclude that galectin-3 immunostaining, when used in biotin-free detection systems, may be useful as an adjunct to distinguish benign from malignant thyroid lesions.

Effects of vaginal distension on urethral anatomy and function

Objective  To determine the effect of repeated and prolonged vaginal distension on the leak‐point pressure (LPP) and urethral anatomy in the female rat, as prolonged vaginal distension has been clinically correlated with signs of stress urinary incontinence (SUI).

PROSTATIC LEVELS OF FATTY ACIDS AND THE HISTOPATHOLOGY OF LOCALIZED PROSTATE CANCER

PURPOSE The consumption of various fatty acids has been associated with advanced stage and fatal prostate cancer. While numerous mechanisms have been postulated, to our knowledge there physiological data linking exposure and prognosis in humans are lacking. We examined prostatic levels of individual fatty acids in relation to the prevalence of histopathological characteristics associated with invasiveness and the risk of progression in 49 men undergoing radical prostatectomy for localized prostate cancer. MATERIALS AND METHODS Fatty acids were measured using capillary gas chromatography in fresh nonmalignant prostate tissue collected at surgery. Markers of invasiveness and increased risk of progression (Gleason sum 7 or greater, perineural invasion, anatomical or surgical margin involvement, extracapsular extension, seminal vesical involvement and stage T3 tumor) were evaluated separately. Each marker was dichotomized into a yes (case) and no (control) level with patients grouped accordingly. Mean concentrations were compared using the Wilcoxon rank sum test. RESULTS The percent of total prostatic polyunsaturated fat and polyunsaturated-to-saturated fat ratios were significantly lower in the presence of perineural invasion, seminal vesical involvement and stage T3 tumor (p = 0.02 to 0.049). alpha-Linolenic acid was significantly lower when tumor extended to an anatomical or surgical margin (p = 0.008). The omega-3 and omega-3-to-omega-6 fatty acid ratios were 1.5 to 3.3-fold lower in cases than in controls, reaching borderline significance in nearly all comparisons (p = 0.052 to 0.097). Saturated and monounsaturated fatty acids were not associated with the traits examined. CONCLUSIONS These data suggest that polyunsaturated fatty acids and perhaps essential fatty acids in particular help to regulate prostate carcinogenesis in humans.

Diagnostic significance of ‘atypia’ in instrumented versus voided urine specimens

Urine cytology plays an important role in monitoring patients with a history of urothelial carcinoma. Because it is difficult to reliably discriminate artifacts induced by instrumentation, inflammation, or therapy those of from malignant cells, many of these specimens are categorized as atypical. The objective of the current study was to study the prevalence and significance of atypical urine cytology with regard to the effect of instrumentation and prior biopsy.

Further characterization of the muscle layers and lamina propria of the urinary bladder by systematic histologic mapping: Implications for pathologic staging of invasive urothelial carcinoma

The muscularis mucosae (MM) and muscularis propria (MP) are important landmarks for pathologic tumor (pT) staging of urinary bladder cancer, which is the quintessential prognostic factor. In our routine practice, we have occasionally noted patterns of MM, which do not always conform to the originally described configuration of thin slender bundles arranged in a single layer of interrupted, dispersed, or continuous muscle. We evaluated the lamina propria (LP), MM, and MP characteristics in 35 urinary bladder resection specimens with systematic sampling from the dome, trigone, anterior, posterior, right, and left lateral walls. Among the subsites, the trigone had a relatively flatter surface and attenuated LP depth (0.46 to 1.58 mm), about half of the thickest region which was the dome (0.98 to 3.07 mm). The MM was typically in individual or small groups of slender and wavy fascicles or wispy fibers. MM also had focal to rarely extensive hyperplastic appearance (53%, most common in dome) with 2 recognizable patterns: (a) aggregates of hyperplastic MM with haphazard outlines (33%) distinct from that of MP, and (b) hyperplastic compact MM with parallel muscle fibers and regular outline arranged singly or in small groups (45%) that occasionally strongly resembled MP muscle but distinguishable from it on the basis of the location in the LP. By distribution, these muscle bundles were more typically dispersed or formed a discernable layer (41%) as discontinuous or infrequently near-continuous layer. The LP vascular plexus was present in every section most often in association with the MM muscle; however, variations in the distribution were observed. The MP most commonly had a relatively regular interface with the LP. A distinctive pattern was noted in the trigone where occasionally there was gradual diminution of size of the MP muscle bundles as they extended to almost a suburothelial location. In 22%, isolated or small groups of compact regular hyperplastic MM muscle bundles were noted in deep LP situated between the more typical slender MM layer and the MP. In conclusion, there are additional patterns of MM other than previously described. Awareness of the occasionally hyperplastic appearance of MM muscle is important to prevent overstaging of invasive urothelial carcinoma. In transurethral resection specimens, lack of orientation may preclude distinction of the hyperplastic MM from true MP in these rare situations. The number and orientation of muscle bundles, relationship to urothelium and vascular plexus, and comparison with more characteristic MP, if present, would be helpful; isolated bundles immediately adjacent to the urothelium with loose haphazard fiber orientation and irregular outlines favor MM over MP muscle. The hyperplastic MM mimicking MP may be more challenging; isolated muscle bundles immediately adjacent to the urothelium would favor hyperplastic pattern of MM over MP muscle. Topographical variations exist among the subsites, the more superficial location of the MP and the rarity of MM in the trigone, relative abundance of hyperplastic MM in dome, and presence of the more superficial ureteral MP at its insertion in the bladder complicate the traditional pT stage evaluation of invasion in these regions. The inconsistency of a distinct MM layer and variations in the LP vascular plexus indicate that substaging of pT1 would be problematic and thus provides further support to the World Health Organization/International Society of Urological Pathology 1998 and World Health Organization 2004 recommendation against its implementation at the current time.

The Paris system for reporting urinary cytology

Chapter 1 Pathogenesis of Urothelial Carcinoma Eva M. Wojcik and Stefan E. Pambuccian Chapter 2 Adequacy of Urine Specimens (Adequacy) Matthew T. Olson (Chair), Guliz A. Barkan, Monique Courtade-Saidi, Z. Laura Tabatabai, Yuji Tokuda, Toyonori Tsuzuki, and Christopher J. VandenBussche Chapter 3 Negative for High Grade Urothelial Carcinoma (Negative) Dorothy L. Rosenthal (Chair), Michael B. Cohen, Hui Guan, Christopher L. Owens, Yuji Tokuda, and Eva M. Wojcik Chapter 4 Atypical Urothelial Cells (AUC) Guliz A. Barkan (Chair), Tarik M. Elsheikh, Daniel F. I. Kurtycz, Sachiko Minamiguchi, Hiroshi Ohtani, Eric Piaton, Spasenija Savic Prince, Z. Laura Tabatabai, and Christopher J. VandenBussche Chapter 5 Suspicious for High Grade Urothelial Carcinoma (Suspicious) Fadi Brimo (Chair), Manon Auger, Tarik M. Elsheikh, Hui Guan, Mitsuru Kinjo, Eric Piaton, Dorothy L. Rosenthal, Tatsuro Shimokama, and Rosemary H. Tambouret Chapter 6 High Grade Urothelial Carcinoma (HGUC) Momin T. Siddiqui (Chair), Guido Fadda, Jee-Young Han, Christopher L. Owens, Z. Laura Tabatabai, and Toyonori Tsuzuki Chapter 7 Low Grade Urothelial Neoplasia (LGUN) Eva M. Wojcik (Chair), Tatjana Antic, Ashish Chandra, Michael B. Cohen, Zulfia McCroskey, Jae Y. Ro, and Taizo Shiraish Chapter 8 Other Malignancies Primary and Metastatic and Miscellaneous Lesions Rana S. Hoda (Chair), Stefan E. Pambuccian, Jae Y. Ro, and Sun Hee Sung Chapter 9 Ancillary Studies in Urinary Cytology Lukas Bubendorf (Chair), Nancy P. Caraway, Andrew H. Fischer, Ruth L. Katz, Matthew T. Olson, Fernando Schmitt, Margareta Strojan Flezar, Theodorus H. Van Der Kwast, and Philippe Vielh Chapter 10 Cytopreparatory Techniques Gary Gill (Chair), William N. Crabtree, and Deidra P. Kelly Chapter 11 Clinical Management, Including Microscopic Hematuria Marcus L. Quek (Chair), Trinity J. Bivalacqua, Ashish M. Kamat, and Mark P. Schoenberg

Evaluation of atypical urine cytology progression to malignancy

In urine cytology, the diagnosis of atypia is subjective and clinical management based on these results can be difficult to determine. In this study, the authors determined the percentage of atypical urine diagnoses that progressed to positive cytology or surgical pathology results over an 11‐year period.

THE EXTENT OF BIOPSY INVOLVEMENT AS AN INDEPENDENT PREDICTOR OF EXTRAPROSTATIC EXTENSION AND SURGICAL MARGIN STATUS IN LOW RISK PROSTATE CANCER: : IMPLICATIONS FOR TREATMENT SELECTION

PURPOSE We identify predictors of extraprostatic extension and positive surgical margins in patients with low risk prostate cancer (prostate specific antigen [PSA] 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b). MATERIALS AND METHODS From August 1997 to January 1999, 143 previously untreated patients underwent radical retropubic prostatectomy for clinically localized prostate cancer. A total of 62 patients were low risk, with PSA 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b, and had sextant biopsy with separate pathological evaluation of each sextant cores. PSA, clinical stage, biopsy Gleason score, average percentage of cancer in the entire biopsy specimen, maximum percentage of cancer on the most involved core, number of cores involved and bilaterality were evaluated for association with extraprostatic extension, seminal vesicle involvement and positive surgical margins. RESULTS Of the 62 patients 13 (21%) had extraprostatic extension, 6 (10%) seminal vesicle involvement and 20 (32%) positive surgical margins. Average percentage greater than 10% and maximum percentage greater than 25% were associated with extraprostatic extension (p = 0.01 and 0.004, respectively). Average percentage greater than 10%, maximum percentage greater than 25%, more than 2 cores involved and bilaterality were associated with positive surgical margins (p = 0.007, 0.01, 0.002 and 0.03, respectively). On multivariate analysis maximum percentage remained the only independent predictor of extraprostatic extension (p = 0.03), and the number of cores involved remained an independent predictor of positive surgical margins (p = 0.01). Biopsy Gleason score, PSA and clinical stage did not correlate with extraprostatic extension or positive surgical margins in this patient population. CONCLUSIONS In low risk prostate cancer the extent of biopsy involvement significantly correlates with the risk of extraprostatic extension and positive surgical margins. Biopsy information should be considered when selecting and modifying treatment modalities.

Use of a new method in reaching consensus on the cause of cytologic-histologic correlation discrepancy

Pathologists exhibit very poor agreement in adjudicating the cause of cytologic-histologic correlation discrepancies, which contributes to problems in designing interventions to reduce discrepancy frequency. In this observational study, we developed a visual method of adjudicating discrepancy cause, termed the No-Blame Box method, which consisted of initially assessing specimen interpretability by separately evaluating specimen quality and the presence of tumor. Five pathologists blindly adjudicated the cause of discrepancy in pulmonary specimens from 40 patients. The kappa statistic of all pathologist pairs in adjudicating discrepancy cause using the No-Blame Box method ranged from 0.400 to 0.796, indicating acceptable to excellent agreement. Pathologists ranged in their assessment of specimen interpretability from 13% to 20%, and in no case did all 5 pathologists concur that a specimen was interpretable. Most discrepancies resulted from pathologists diagnosing noninterpretable samples. Pathologists who used the No-Blame Box showed significant agreement in the adjudication of discrepancy cause.