Urothelial Carcinomas With Trophoblastic Differentiation, Including Choriocarcinoma: Clinicopathologic Series of 16 Cases.

Trophoblastic differentiation (including choriocarcinoma) arising in urothelial carcinoma has been described in numerous case reports, but never in a single series. We present a series of these tumors, describing the morphologic spectrum, applying traditional and novel immunohistochemical stains, and characterizing clinical follow-up. We identified 16 cases, arising predominantly in the bladder (N=14), but also the ureter (N=1) and prostatic urethra (N=1). Six of our cases (38%) contained invasive urothelial carcinoma with admixed syncytiotrophoblasts, 8 cases (50%) consisted of invasive urothelial carcinoma with choriocarcinoma, 1 case (6%) showed urothelial carcinoma in situ with associated choriocarcinoma, and 1 case (6%) consisted of pure choriocarcinoma. Other subtypes of variant morphology were seen in 5 of our cases (31%) and included squamous, glandular, lipoid, chordoid/myxoid, and sarcomatoid features. Given the limited specificity of human chorionic gonadotropin immunohistochemistry, we also studied the expression of a novel specific trophoblastic marker, hydroxyl-δ-5-steroid dehydrogenase, as well as Sal-like protein 4. Human chorionic gonadotropin expression was seen in nearly all cases (93%) but was often not limited to the trophoblastic component, staining the urothelial component also in 85% of the cases. Expression of hydroxyl-δ-5-steroid dehydrogenase was more sensitive and more specific, staining 100% of the cases and limited to trophoblasts in all but 1 case. Sal-like protein 4 expression was variable, staining trophoblast in only 50% of cases and staining the urothelial carcinoma component in 43% of those positive cases. Most of our tumors presented at a high stage and were associated with poor clinical outcomes, with at least muscle-invasive disease (pT2) in 10 of the 14 bladder tumors (71%), periureteric fat invasion in the ureter tumor (pT3), distant metastases in 7 of 16 cases (44%) and death of disease in 3 of the 15 patients with follow-up (20%). Our study describes a series of urothelial carcinomas with trophoblastic differentiation, demonstrating the morphologic spectrum of this entity, its frequent association with other subtypes of variant morphology, its characteristic immunoprofile, and its aggressive clinical behavior.

Acquired Cystic Disease-associated Renal Cell Carcinoma (ACD-RCC): A Multiinstitutional Study of 40 Cases With Clinical Follow-up.

The incidence of renal cell carcinoma (RCC) is known to be higher in patients with end-stage renal disease, including those with acquired cystic kidney disease due to dialysis. Acquired cystic disease (ACD)-associated RCC was recently incorporated into the 2016 WHO Classification of Tumors of the Urinary System and Male Genital Tract as a distinct entity and is reportedly the most common RCC arising in end-stage renal disease. In this study, we sought to further describe clinicopathologic findings in a large series of ACD-RCC, emphasizing histologic features, immunophenotype, clinical outcome, and patterns of disease spread. We collected 40 previously unpublished cases of ACD-RCC with mean clinical follow-up of 27 months (median, 19 mo; range, 1 to 126 mo). Mean tumor size was 2.7 cm (median, 2.4 cm), and 32 tumors (80%) were confined to the kidney (pT stage less than pT3a). International Society of Urological Pathology grade was 3 in 37 cases (92.5%), grade 2 in 1 case (2.5%), and grade 4 in 2 cases (5%). Architectural variability among ACD-RCC was common, as 39 cases (98%) showed varying combinations of tubular, cystic, solid, and/or papillary growth. ACD-RCC frequently occurred in association with other renal tumor subtypes within the same kidney, including papillary RCC (14 patients), papillary adenomas (7 cases), clear cell papillary RCC (5 cases), clear cell RCC (1 case), and RCC, unclassified type (1 case). A previously undescribed pattern of perinephric and renal sinus adipose tissue involvement by dilated epithelial cysts with minimal or absent intervening capsule or renal parenchyma was identified in 20 cases (50%); these cysts were part of the tumor itself in 5 cases (25%) and were part of the non-neoplastic acquired cystic change in the background kidney in the remaining 15 cases (75%). Of the 24 cases (60%) with tissue available for immunohistochemical stains, 19 (79%) were positive for PAX8, 20 (83%) showed negative to patchy expression of cytokeratin 7, and 24 (100%) were both positive for AMACR and negative for CD117. Fumarate hydratase expression was retained in all tumors, including those with nuclear features resembling fumarate hydratase-deficient RCCs. Of the 36 patients (90%) with available follow-up information, 4 (11%) experienced adverse events: 2 patients developed a local recurrence, 1 patient experienced multiple visceral metastases and subsequently died of disease, and 1 patient developed metastases to regional lymph nodes only. One local recurrence and the lymph node only metastasis both had an unusual, exclusively cystic pattern of growth. In summary, we present the largest clinicopathologic series of ACD-RCC to date and describe previously unreported cystic patterns of local soft tissue involvement and recurrence/metastases.

Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer.

The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting.

A contemporary update on pathology standards for bladder cancer: transurethral resection and radical cystectomy specimens.

CONTEXT: Pathology standards for the diagnosis of bladder cancer (BCa) have recently evolved to better reflect patient diagnosis and clinical outcomes. OBJECTIVE: To update pathology reporting standards for BCa. EVIDENCE ACQUISITION: We searched the international medical literature and reviewed all articles that addressed BCa gross dissection, pathologic diagnosis, staging, and reporting as of June 6, 2012. We also reviewed the proceedings from the recent Second International Consultation on Bladder Cancer (Vienna, Austria). The literature selected for review focuses on evidence-based studies that address histopathologic factors in BCa, with emphasis placed on factors that influence patient diagnosis and clinical outcomes. EVIDENCE SYNTHESIS: We separated data into three main components for analysis based on the type of specimen obtained: (1) transurethral resection specimens, with an emphasis on pathologic staging, variants of urothelial carcinoma, angiolymphatic invasion, and relevant ancillary techniques such as immunohistochemistry in assessing these features; (2) cystectomy specimens, with an emphasis on pT0 disease, prostatic involvement by urothelial carcinoma and lymph node dissection and analysis; and (3) cytology correlates, with recommendations for the use of cytology paired with tissue-based sampling. Areas of controversy are described and recommendations based on existing guidelines are provided. The value of a multidisciplinary team is highlighted. CONCLUSIONS: Ongoing international collaborations amongst pathologists have led to emerging standards in the reporting and microscopic diagnosis of BCa specimens. Although some areas remain controversial, we present the most up-to-date data and guidelines relevant to neoplastic pathology of the urinary bladder.

Partial sampling of radical prostatectomy specimens: detection of positive margins and extraprostatic extension.

Currently there is no global agreement as to how extensively a radical prostatectomy specimen should be sectioned and histologically examined. We analyzed the ability of different methods of partial sampling in detecting positive margin (PM) and extraprostatic extension (EPE)-2 pathologic features of prostate cancer that are most easily missed by partial sampling of the prostate. Radical prostatectomy specimens from 617 patients treated with open radical prostatectomy between 1992 and 2011 were analyzed. Examination of the entirely submitted prostate detected only PM in 370 (60%), only EPE in 100 (16%), and both in 147 (24%) specimens. We determined whether these pathologic features would have been diagnosed had the examination of the specimen been limited only to alternate sections (method 1), alternate sections representing the posterior aspect of the gland in addition to one of the mid-anterior aspects (method 2), and every section representing the posterior aspect of the gland in addition to one of the mid-anterior aspects, supplemented by the remaining ipsilateral anterior sections if a sizeable tumor is seen (method 3). Methods 1 and 2 missed 13% and 21% of PMs and 28% and 47% of EPEs, respectively. Method 3 demonstrated better results missing only 5% of PMs and 7% of EPEs. Partial sampling techniques missed slightly more PMs and EPEs in patients with low-risk to intermediate-risk prostate cancer, although even in high-risk cases none of the methods detected all of the studied aggressive pathologic features.

Contralateral intramammary silicone lymphadenitis in a patient with an intact standard dual-lumen breast implant in the opposite reconstructed breast.

Silicone lymphadenopathy is a recognized complication of silicone gel implant rupture; the ipsilateral axillary lymph nodes are most commonly involved. We report imaging findings on a range of different imaging modalities and biopsy results in a case of biopsy-proven silicone lymphadenitis involving contralateral intramammary and axillary lymph nodes in a patient with an intact standard dual-lumen breast implant in the opposite reconstructed breast. This case demonstrates that in a patient with disrupted lymph drainage due to prior mastectomy and axillary node dissection for breast cancer treatment, silicone particles can migrate in a retrograde fashion via the ipsilateral internal mammary lymph nodes and reach not only the contralateral axilla but also the outer quadrants of the contralateral breast, even in the presence of an intact breast implant.

CD10+ and CK7/RON- immunophenotype distinguishes renal cell carcinoma, conventional type with eosinophilic morphology from its mimickers.

BACKGROUND: The distinction between renal cell carcinoma conventional (clear cell) type with eosinophilic morphology (ccRCC), chromophobe renal cell carcinoma eosinophilic variant (chRCC), and renal oncocytoma (RO) is a common diagnostic dilemma. We aimed to identify an immunohistochemical panel to discriminate ccRCC from its morphologic mimics. MATERIALS AND METHODS: Fifty-three renal neoplasms (19 ccRCC, 18 chRCC, and 16 RO) were selected. Immunohistochemical stains for CD10, cytokeratin 7 (CK7), c-Kit, E-cadherin, N-cadherin, kidney-specific cadherin (Ksp-cadherin), and Recepteur d'origine nantais (RON) were performed. RESULTS: Ten (53%) of 19 ccRCC were positive for CD10, 11 (58%) for E-cadherin, 8 (42%) for N-cadherin, 5 (26%) for Ksp-cadherin, 9 (47%) for RON, 6 (32%) for CK7, and 5 (26%) for c-Kit. In chRCC/RO group, 5 of 34 (15%) were positive for CD10, 32 (94%) for E-cadherin, 2 (6%) for N-cadherin, 1 (3%) for Ksp-cadherin, 22 (65%) for RON, 14 (41%) for CK7, and 25 (25/32, 76%) for c-kit. Univariately, negative c-Kit [odds ratio (OR)=8.75, P=0.001, area under the receiver operating characteristic curve (AUC)=0.747], negative E-cadherin (OR=11.64, P=0.005, AUC=0.681), positive N-cadherin (OR=11.64, P=0.005, AUC=0.681), positive Ksp-cadherin (OR=11.79, P=0.031, AUC=0.617), and positive CD10 (OR=6.44, P=0.005, AUC=0.690) detects ccRCC versus chRCC/RO. Multivariate analysis showed significant association between CD10 positivity and ccRCC (OR=16.90, P=0.007) and between RON negativity and ccRCC (OR=7.17, P=0.047) when CK7 is negative. CONCLUSIONS: The best single predictors for ccRCC are negative c-Kit, negative E-cadherin, positive N-cadherin, positive Ksp-cadherin, and positive CD10. However, considering the studied markers, a combination of positive CD10 and negative CK7 and RON is considered the best immunohistochemical panel in distinguishing ccRCC from chRCC/RO.

Glandular cells in vaginal cytology Papanicolaou tests in patients with hysterectomy for endometrial adenocarcinoma.

The vaginal apex is the most common site of recurrence in patients with endometrial cancer. Although studies demonstrate that <1% of asymptomatic vaginal recurrences are detected by routine vaginal cytology alone, many practitioners still include it as part of the routine surveillance in these patients after hysterectomy. To further evaluate the effectiveness of vaginal cytology as a surveillance tool, we assessed the subsequent findings in patients reported to have benign and atypical glandular cells on vaginal cytology after hysterectomy performed for endometrial cancer.

Treatment of Hailey-Hailey disease with tacrolimus ointment and clobetasol propionate foam.

Hailey-Hailey disease, or familial benign chronic pemphigus, is a chronic disease without a known cure. Current therapeutic strategies attempt to suppress Hailey-Hailey outbreaks and allow the patient to live comfortably with this condition. We have found that applying topical tacrolimus 0.1% ointment (Protopic) twice a day to affected areas is an excellent way to control Hailey-Hailey disease. In addition to effectively controlling Hailey-Hailey outbreaks, tacrolimus is a relatively safe and noninvasive mode of treatment, without significant side effects. We recommend intermittent therapy with clobetasol propionate 0.05% foam (Olux Foam) for patients who break through suppressive therapy with tacrolimus a few times per year. In patients with frequent outbreaks of Hailey-Hailey disease despite suppressive therapy with tacrolimus, we recommend alternating the tacrolimus with clobetasol propionate 0.05% foam every 6 weeks.