Summary Successful BRAF inhibitor therapy depends on the accurate assessment of the mutation status of the BRAF V600 residue in tissue samples. In melanoma, immunohistochemical (IHC) analysis with monoclonal anti-BRAF V600E has emerged as a sensitive and specific surrogate of BRAF V600E mutation, particularly when BRAF V600E protein expression is homogeneous and strong. A subset of melanomas exhibit heterogeneous labeling for BRAF V600E, but our understanding of the significance of heterogeneous BRAF V600E IHC expression is limited. We used next-generation sequencing (NGS) to compare BRAF V600E IHC staining patterns in 154 melanomas: 79 BRAFWT and 75 BRAF (including 53 V600E) mutants. Agreement among dermatopathologists on tumor morphology, IHC expression and intensity was excellent (rho=0.99). A predominantly epithelioid cell phenotype significantly correlated with the BRAF V600E mutation (P=.0085). Tumors demonstrating either heterogeneous or homogeneous IHC expression were significantly associated with the BRAF V600E mutation (P<.0001) as was increased intensity of staining (P<.0001). The positive predictive value was 98% for homogenous IHC expression compared with 70% for heterogeneous labeling. Inclusion of both heterogeneous and homogeneous BRAF V600E IHC expression as a positive test significantly improved IHC test sensitivity from 85% to 98%. However, this reduced BRAF V600E IHC test specificity from 99% to 96%. Cautious evaluation of heterogeneous BRAF V600E IHC expression is warranted and comparison with sequencing results is critical, given its reduced test specificity and positive predictive value for detecting the BRAF V600E mutation.

RSB is a reliable method for diagnosis of IVL, especially in patients with FUO and any 1 or more of the 4 following abnormalities: (1) hematologic abnormalities; (2) high serum LDH; (3) hypoxemia; and/or, (4) unusual neurological symptoms with co-existing hematologic abnormalities and without lymphadenopathy, hepatosplenomegaly or BM abnormality.

The distinction between subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus (LE) panniculitis is remarkably challenging. Rimming by lymphocytes with an elevated Ki-67 cell proliferation index has been forwarded as a potential diagnostic finding in biopsies of SPTCL but has not been rigorously compared with biopsies from patients with LE panniculitis. Nineteen and 17 examples of SPTCL and LE panniculitis, respectively, were evaluated for periadipocytic rimming by lymphocytes expressing Ki-67, CD8, and βF1 and for attributes associated with LE, including clusters of CD123-positive cells. The identification of periadiopocytic rimming using Ki-67, CD8, and βF1 held sensitivity of 79%, 100%, and 89.5% and specificity of 100%, 52.9%, and 88.2%, respectively (P < 0.01). CD123-positive cells were in both disorders. LE-like histopathology was commonly encountered in SPTCL. In conclusion, an elevated Ki-67 cell proliferation index with rimming is useful for distinguishing SPTCL from LE panniculitis. Notably, many features of LE panniculitis can also be encountered in SPTCL.