Evaluation of Single Cell Metastasis in Melanoma; Two New False Staining Patterns
Kumaran Mudaliar, Jodi Speiser, Roger Heyna, Sheela Gorordo, Kelli Hutchens. Loyola University Medical Center, Maywood, IL
Background: The American Joint Commission on Cancer (AJCC) 2010 guideline changes recommend all patients with single cell metastasis identified by immunhistochemical (IHC) staining to be classified as stage III disease. The recommendation further says that one positive cell by IHC staining with an “atypical appearance” warrants upstaging. Advancement to stage III, especially for young patients, often results in adjuvant therapies and inclusion in clinical trials with significant side effects. These guidelines place enormous confidence on IHC techniques and responsibility on the pathologist to discern whether a single chromogen covered cell truly represents a malignant melanocyte. This study aims to identify the frequency and pattern of false staining by MITF, Melan A, and HMB-45.
Design: 20 benign lymph nodes from non-melanoma patients were stained using MITF (Ventana, Tucson, AZ), Melan A (Ventana, Tucson, AZ), and HMB-45 (Leica, Newcastle, UK) with appropriate negative controls. H&E and IHC stained sections were assessed for the frequency of positive staining, pattern and number of cells stained, location of positive cells, present of pigment and perceived atypia.
Results: 17/20 (85%) of cases evaluated showed >1 cell staining with at least one IHC. 16/17 (94.1%) of the positive cases had cells located subcapsular. 14/17 (82.4%) cases showed staining on at least 2 different stains. MITF nuclear stained cells were seen in all 17 cases whereas Melan A was only seen in 6/17 cases (35.3%). HMB-45 was positive in 10/17 (58.5%) cases and correlated with Melan A staining 85% of the time (17/20). Two distinct staining patterns were noted in the MITF positive stained cases. The first pattern showed multiple nuclear and cytoplasmic positive clusters of large, atypical appearing cells in 11/17 (67.7%) cases with 9/11 (81.8%) of these having visible nodal pigment on H&E. A second pattern showed multiple, single, small, typical appearing cells with nuclear only positivity in 6/17 (35.3%) cases with only 2/6 (33.3%) of these having visible nodal pigment on H&E.
Conclusions: The new guidelines for positivity in sentinel nodes has placed much weight on the use of IHC to identify single cell metastasis in melanoma patients. False positive staining using nuclear MITF is even higher than the previous reports for Melan A and appears increased in pigmented nodes. Upstaging of melanoma patients is thus solely placed on the pathologist's ability to discern patterns of false staining as described here and the subjective identification of atypia in single stained cells.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 78, Monday Morning