FOXA1 and CK14 as markers of luminal and basal subtypes in histologic variants of bladder cancer and their associated conventional urothelial carcinoma.

Invasive bladder cancer is diverse, and includes several named histomorphologies that differ from conventional urothelial carcinoma, termed "histologic variants." By transcriptional analysis, bladder cancers can be divided into luminal and basal subtypes. In this paper, we study associations between markers of transcriptional subtypes and variant histology in a retrospective cohort of 309 cystectomy specimens. Histology slides were methodically reviewed for all cases, and variant histology was documented. Immunohistochemistry for FOXA1 (luminal marker) and CK14 (basal maker) was performed on histologic variants and their associated conventional urothelial carcinomas. Invasive carcinoma was present in 270 of the cystectomy specimens, 35% of which contained a histologic variant. Squamous carcinomas expressed higher CK14 levels than micropapillary, nested, and plasmacytoid carcinomas (p < 0.001, Kruskal-Wallis), keeping with the basal character of squamous carcinoma. Likewise, squamous carcinomas expressed lower FOXA1 levels than micropapillary, nested, and plasmacytoid carcinomas (p < 0.001, Kruskal-Wallis), keeping with the luminal character of micropapillary carcinoma, and suggesting that nested and plasmacytoid cancers have luminal character. FOXA1 was expressed at lower levels in conventional urothelial carcinoma associated with squamous carcinoma than conventional urothelial carcinoma associated with micropapillary carcinoma (p = 0.0072, Wilcoxon rank sum). CK14 expression did not differ between conventional urothelial carcinomas associated with squamous versus micropapillary carcinoma (p = 0.89, Wilcoxon rank sum). Instead, CK14 expression was higher in squamous carcinoma than conventional urothelial carcinoma present in the same bladder (p = 0.014, Wilcoxon rank sum, paired). Overall, the findings show that squamous and micropapillary cancers have different expression patterns of CK14 and FOXA1 and suggest that they arise from distinct precursors.

Clinical significance of prominent retraction clefts in invasive urothelial carcinoma.

Micropapillary morphology in invasive urothelial carcinoma is an established predictor of aggressive disease. It is unknown, however, if prominent retraction is associated with more aggressive disease in the absence of classic micropapillary morphology. We reviewed a retrospective series of 309 radical cystectomy specimens with clinical follow-up data and documented the presence or absence of invasive urothelial carcinoma with prominent retraction clefts, defined as invasive carcinoma with retraction involving the majority of invasive tumor nests in at least one 100× field but without classic micropapillary morphology. Invasive carcinomas with plasmacytoid, sarcomatoid, nested, and small cell morphology were excluded, as were cases without lymph node sampling. In invasive conventional urothelial carcinoma, the presence of prominent retraction clefts was associated lymph node metastasis (odds ratio 4.7, P = .0015, Fisher exact test) but not pathologic tumor stage or several other oncologic parameters (all Ps > .10). Similarly, invasive urothelial carcinoma with micropapillary morphology had lymph node metastasis more frequently than conventional urothelial carcinoma without prominent retraction clefts (P < .001, Fisher exact test), but there was no difference in pathologic tumor stage or oncologic parameters (all Ps > .10). There was no statistically significant difference in rates of lymph node metastasis between invasive urothelial carcinoma with micropapillary morphology and conventional urothelial carcinoma with prominent retraction clefts (P = .54, Fisher exact test). The findings suggest that prominent retraction in invasive urothelial carcinoma may be associated with more aggressive disease, even in the absence of classic micropapillary morphology.

Squamous Dysplasia of the Urinary Bladder: A Consecutive Cystectomy Series.

Squamous dysplasia of the urinary bladder is uncommon and may represent a precursor to invasive squamous cell carcinoma. Though significant focus has been devoted to squamous differentiation in invasive bladder cancer, relatively little attention has been given to squamous dysplasia. We methodically reviewed microscopic slides from a consecutive cystectomy series at our institution (n = 303; 2001-2014), with special attention given to squamous dysplasia and squamous differentiation within association invasive carcinoma. Of these 303 cases, 3% (9 cases) had squamous dysplasia. The majority (89%; 8/9) had a similar morphological appearance to squamous dysplasia of the head and neck (ie, cytological atypia, architectural disturbances, and abnormal keratinization). Invasive carcinoma was present in 230 of the cystectomy cases. Of these 230 cases with invasive carcinoma, 4% (8 cases) also had squamous dysplasia. The invasive carcinoma had evidence of squamous differentiation in all cases with concurrent squamous dysplasia. Concurrent flat urothelial carcinoma in situ was present in 3 of the 8 cases with both invasive carcinoma and squamous dysplasia. Squamous dysplasia was not associated with clinical outcomes data, including death from bladder cancer and bladder cancer recurrence. The data from this study indicate that squamous dysplasia is uncommon in the cystectomy setting, frequently has the morphology of head and neck dysplasia, and is often associated with invasive carcinoma with squamous differentiation.

Acute Invasive Fungal Rhinosinusitis: A 15-Year Experience with 41 Patients.

OBJECTIVES: To describe a 15-year single-institution experience of 41 cases of acute invasive fungal sinusitis (AIFRS), identify clinical indicators predictive of AIFRS, and discuss our approach to these high-acuity patients. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center; The Pennsylvania State University Hershey Medical Center. SUBJECTS AND METHODS: A retrospective review was performed for AIFRS consultations between September 1999 and March 2014. Variables reviewed included underlying condition, presenting symptoms, absolute neutrophil count, disease extent on examination, radiographic findings, medical treatment, biopsy results, surgical treatment, and outcomes. Univariate analysis was performed to determine variables significantly associated with AIFRS. Outcome measures were assessed and patient assessment algorithm developed. RESULTS: Of 131 patients evaluated, 41 were diagnosed with AIFRS; 92.7% had an underlying hematologic malignancy. Disease predictive variables included absolute neutrophil count <500/µL (P < .0001; sensitivity = 78%), mucosal abnormalities of middle turbinate (P < .0001; specificity = 88%) and septum (P < .0001; specificity = 97%), and specifically, necrosis of the middle turbinate (P < .0001; specificity = 97%). Twenty-five AIFRS patients (61%) survived until discharge; 25% (n = 10) expired secondary to AIFRS infection explicitly. CONCLUSION: This series represents one of the largest single-institution experiences of AIFRS published to date. Timely diagnosis is necessary to improve patient outcomes and limit morbidity. Maintaining a high index of suspicion in at-risk patient populations, followed by prompt evaluation and management, is crucial in suspected AIFRS. The presence or absence of certain findings appear to correlate with biopsy results and may aid in appropriately gauging clinical suspicion for the presence of AIFRS.

Adherent perinephric fat at minimally invasive partial nephrectomy is associated with adverse peri-operative outcomes and malignant renal histology.

OBJECTIVES: To predict adherent perinephric fat (APF) at minimally invasive partial nephrectomy (MIPN) using the Mayo adhesive probability (MAP) score and to determine the impact of MAP score and APF on MIPN outcomes. PATIENTS AND METHODS: A total of 245 patients undergoing MIPN were included in the study. The presence of APF was determined through keywords in operating notes, and radiographic data were obtained from preoperative cross-sectional imaging. Posterior fat thickness was measured between the renal capsule and the posterior abdominal wall at the level of the renal vein. Perinephric stranding was graded on a 0-3 severity scale. RESULTS: The study included 123 men and 122 women, with a median age of 55 years, body mass index of 31.7, tumour size of 2.7 cm and nephrometry score of 6. The median posterior fat thickness was 1.79 cm and MAP score 2.63. In all, 26 patients (10.6%) had evidence of APF at the time of renal surgery. Factors predictive of APF included increasing age (P = 0.001), male gender (P = 0.045), perinephric stranding (P = 0.002), posterior fat thickness (P < 0.001) and MAP score (P < 0.001). APF was associated with adverse pathological and peri-operative outcomes including malignant renal histology (P = 0.04), longer operating time (P = 0.005) and greater estimated blood loss (EBL; P = 0.025). CONCLUSIONS: Specific clinical and radiographic factors predict APF at MIPN. The presence of APF is associated with adverse peri-operative outcomes including longer operating time and greater EBL. APF was also associated with renal malignancy on final pathology, but further studies are necessary to elucidate the precise underlying mechanism.