No abstract

Sentinel lymphadenectomy is a sensitive and specific procedure that has reduced the need for complete axillary lymph node dissections in patients with negative sentinel lymph nodes (SLNs). However, numerous studies have shown that SLN may be the only positive lymph node in 40 to 70% of cases. This study was therefore undertaken to determine if the characteristics of primary breast tumor or its metastasis in the SLN could predict the presence of residual disease in the nonsentinel lymph nodes (NSLNs) and thus allow for further reduction in axillary lymph node surgery. The SLN procedure was performed on 329 patients at our institution, of which 131 had positive SLNs and underwent further axillary surgery. Fifty-four patients had additional disease in the NSLNs, while in the remaining 77 cases, no residual disease was detected. The clinical and pathologic features of these cases were reviewed and statistical analysis was performed. Multivariate analysis determined two significant independent variables for prediction of residual disease in the axilla: the size of the metastatic tumor in SLNs and the presence of its extranodal extension. The mean tumor size in SLNs without residual disease in NSLNs was 0.4 cm. It was 1.1 cm in patients with additional NSLN metastasis. The positive predictive value in both instances is about 80%. The risk of NSLN involvement in patients with SLN tumors of < or = 0.4 cm was 21%. The risk was the same (21%) for patients with micrometastatic disease (< or = 0.2 cm) in SLNs. In these cases the residual disease in the NSLNs was also small. SLNs with metastatic deposits larger than 1.0 cm were likely to contain additional metastases in the NSLNs in 81% of cases. This increased to 100% if the primary carcinoma was larger than 5 cm, if it was poorly differentiated, or if it showed HER-2/neu gene amplification. The presence of an extranodal extension of SLN metastasis was an independent predictor of residual axillary disease and was associated with NSLN metastasis in 76% of cases. Primary tumor characteristics did not correlate with the incidence of NSLN metastasis in our series.

Accurate diagnosis and grading of anal intraepithelial neoplasia (AIN) can be problematic, especially in separating AIN from anal transitional-zone epithelium. Immunohistochemistry (IHC) for p16 correlates with human papillomavirus (HPV) integration into the host genome, and HPV subtyping by in situ hybridization (ISH) is now readily available. To investigate if p16 would help in more accurately diagnosing and grading AIN, particularly when attempting to distinguish benign transitional-zone epithelium from high-grade AIN, we separately assessed these stains in a blinded manner on a large number of consecutive anal biopsies and anal tissues and correlated the findings with the diagnosis and grade of AIN. One hundred thirty-three consecutive anal tissue specimens, from 128 patients were studied. One hundred and eight were anal biopsies and 25 were hemorrhoidectomy specimens. All specimens were stained with hematoxylin and eosin, p16 (Lab Vision), and HPV-ISH (Ventana HPV-III Inform). No gold standard was chosen, rather, comparisons between the 3 tests were made and agreement between tests was tested for statistical significance using the kappa value (kappa). The comparisons included AIN grade (negative, 1, 2, 3) with nuclear intensity of p16 IHC (0 to 3+), AIN grade with IHC nuclear staining patterns (contiguous, patchy/rare), AIN grade with HPV-ISH [negative, low-risk (LR), high-risk (HR)] and, nuclear intensity of p16 IHC with HPV-ISH. One hundred percent of AIN2 and 3 cases were strongly positive for nuclear p16, whereas 80% of AIN1 were positive. Yet, 33% of AIN negative cases were positive for nuclear p16, although with less nuclear intensity than for AIN2 or 3. The kappa value for AIN/nuclear p16 intensity agreement was 0.61 (ie, substantial agreement). Seventy-nine percent of AIN3 cases were strongly positive for HR, and 9% for LR HPV; whereas 75% of AIN2 were positive for HR and 5% for LR HPV. Forty percent of AIN1 cases were positive for HR and 24% for LR HPV. Yet, 12.5% of AIN negative cases were positive for HPV for both LR and HR types. The kappa value for AIN/HPV agreement was 0.62 (ie, substantial agreement). One hundred percent of HR and 85% of LR HPV were positive for p16. Yet, 6% of negative p16 were positive for HPV (all were LR), whereas 43% of negative HPV showed some p16. Of the latter, 40% were 3+ by p16. The kappa value for HPV/nuclear p16 intensity agreement was 0.56 (ie, moderate agreement). Of interest, 30 cases were negative for AIN and p16 staining and of these, 2 (7%) were positive for HPV (both LR subtype). Three cases positive for HR HPV were negative for AIN with only patchy nuclear p16 positivity. We conclude that the correlation between AIN and p16 and HPV is strong enough to be quite useful in distinguishing true AIN from benign mimics, such as benign transitional-zone epithelium. In selected cases, p16 and HPV may be valuable in grading as well.

CytoJournal organized its first Peer-Reviewer's Retreat of 2006 during the United States and Canadian Academy of Pathology Annual Meeting at Atlanta on Feb 12, 2006. The major topics discussed were open access, peer review, and impact factors. Representative participants volunteered to join the task force to prepare an instructional guide for peer-reviewing cytopathology manuscripts. Concern about the impact factor for CytoJournal was discussed. A feedback to its readers and authors was recommended. Impact factor calculation needs at least three years of journal statistics. It is only possible after two years from the time a journal is first accepted by Thomson-ISI for citation tracking. CytoJournal is still too new for an impact factor to be calculated. However, general progress of CytoJournal suggests an encouraging pattern for high impact factor.

Background: Signifi cant variation is reported in the diagnosis of HPV-associated AIN. We previously observed that bandlike positivity for p16 in Ͼ90% of contiguous cells coupled with Ki67 positivity in Ͼ50% of lesional cells is strongly associated with high grade AIN. This study was undertaken to determine if addition of p16 and Ki67 immunostaining would reduce inter-and intraobserver variability in diagnosis and grading of AIN.