Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study.

The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant.

Evidence-based adequacy criteria for urinary bladder barbotage cytology.

INTRODUCTION: Adequacy criteria are well established in some areas of cytopathology to prevent false negative diagnoses. To date, no such criteria have been proposed and validated for urinary tract specimens. Our aim was to determine a cellularity cutoff point that significantly affects the sensitivity of detecting high-grade or in situ urothelial carcinoma (HGUC or UCIS) in bladder barbotage/washing specimens. MATERIALS AND METHODS: Bladder barbotage specimens collected in liquid-based media were selected. Specimens diagnosed as "positive for HGUC" (with histologic confirmation) composed the study group, with negative cases as control specimens. Samples were serially diluted and ThinPrep slides of decreasing cellularity were made and reviewed for diagnosis and cellularity. In a retrospective validation study, we identified cases with a "negative for malignancy" bladder barbotage/washing and a surgical pathology diagnosis of UCIS or HGUC (ie, false negative cytology). Cellularity was assessed. RESULTS: A distinct difference in sensitivity was noted at a cutoff point of 2644 (20 per 10 high-power fields) urothelial cells. Sensitivities increased for atypical or higher (68.3% versus 100%) and HGUC (43.3% versus 88.0%) after application of this cutoff point with high statistical significance (P = 0.001 and 0.0001, respectively). For the retrospective review, cases below the cutoff point were reclassified as unsatisfactory, and sensitivity rose from 76.3% to 84.8% (P = 0.0027). CONCLUSIONS: Our results indicate that, in the absence of atypical or malignant cells, an adequate bladder barbotage specimen should have a minimum of 2644 (20 per 10 high-power fields) well-visualized, well-preserved urothelial cells to increase the positive predictive value of this test.

Evaluation of a triple combination of cytokeratin 20, p53 and CD44 for improving detection of urothelial carcinoma in urine cytology specimens.

BACKGROUND: Atypical urine cytology results trigger cystoscopy or molecular tests, both of which are costly, complex and difficult to perform tests. Several immunostains are being investigated to improve cancer detection; however, cytology material is limited and restricts the use of multiple immunostains. This study was designed to determine the utility of a cocktail of three stains, cytokeratin (CK20), p53 and CD44 in urine cytology samples for improving the detection of urothelial carcinoma. MATERIALS AND METHODS: Urine cytology specimens with cell blocks containing adequate cytologic material between 2005 and 2010 and subsequent follow-up biopsy and/or Urovysion test (102 cases including 29 negative, 56 atypical and 17 malignant) were included in the study and evaluated with the triple stain. Results were first validated on the positive and negative cases and then applied to the atypical cases to determine the utility in the diagnosis of urothelial carcinoma. RESULTS: Based on the validation and published literature, two distinct immunoprofiles were defined - malignant, characterized by at least five CK20 and/or p53 positive atypical cells and reactive, all other staining patterns. The malignant immunoprofile showed 88% sensitivity, 78% specificity, 74% positive predictive value (PPV) and 90% negative predictive value (NPV) for detecting urothelial carcinoma. These values improved to 95% sensitivity and 96% NPV when low-grade urothelial carcinoma cases were excluded. SUMMARY: Our results indicate that the triple stain is an inexpensive, easy to perform test most useful for differentiating high-grade urothelial carcinoma from its mimics. However Inclusion of CD44 in the cocktail did not provide additional value and is best excluded.