CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma.

The diffuse variant of follicular lymphoma (dFL) is a rare variant of FL lacking t(14;18) that was first described in 2009. In this study, we use a comprehensive approach to define unifying pathologic and genetic features through gold-standard pathologic review, FISH, SNP-microarray, and next-generation sequencing of 16 cases of dFL. We found unique morphologic features, including interstitial sclerosis, microfollicle formation, and rounded nuclear cytology, confirmed absence of t(14;18) and recurrent deletion of 1p36, and showed a novel association with deletion/CN-LOH of 16p13 (inclusive of CREBBP, CIITA, and SOCS1). Mutational profiling demonstrated near-uniform mutations in CREBBP and STAT6, with clonal dominance of CREBBP, among other mutations typical of germinal-center B-cell lymphomas. Frequent CREBBP and CIITA codeletion/mutation suggested a mechanism for immune evasion, while subclonal STAT6 activating mutations with concurrent SOCS1 loss suggested a mechanism of BCL-xL/BCL2L1 upregulation in the absence of BCL2 rearrangements. A review of the literature showed significant enrichment for 16p13 and 1p36 loss/CN-LOH, STAT6 mutation, and CREBBP and STAT6 comutation in dFL, as compared with conventional FL. With this comprehensive approach, our study demonstrates confirmatory and novel genetic associations that can aid in the diagnosis and subclassification of this rare type of lymphoma.

Percentage of {gamma}{delta} T cells in panniculitis by paraffin immunohistochemical analysis.

Cutaneous T-cell lymphomas with panniculitis-like histologic features have different clinical courses depending on whether they are composed of alphabeta T cells or gammadelta T cells, necessitating their distinction for proper prognostication. However, unlike alphabeta T cells, gammadelta T cells cannot be reliably detected in formalin-fixed, paraffin-embedded sections. We demonstrated that a commercially available antibody can detect gammadelta T cells and examined 2 cases of flow cytometry-proven gammadelta T-cell lymphomas and 15 control cases of nonneoplastic panniculitis. In both lymphomas, the atypical lymphocytes were gammadelta T cells, whereas the reactive lymphocytes were alphabeta T cells. In contrast, nonneoplastic panniculitis had predominantly alphabeta T cells with many fewer and individually scattered gammadelta T cells. The detection of gammadelta T cells in paraffin sections provides a powerful new tool to characterize T cells in lymphomas and inflammation.

Flow cytometric quantitation of natural killer cells and T lymphocytes expressing T-cell receptors alpha/beta and gamma/delta is not helpful in distinguishing benign from malignant body cavity effusions.

BACKGROUND: Quantitation of natural killer (NK) cells in benign and malignant effusions has yielded conflicting results in the past. Studies have claimed higher, lower, and essentially equal percentages of NK cells for benign and malignant effusions. In addition, virtually no literature exists on the numbers and distribution of T lymphocytes expressing T-cell receptor alpha/beta (TCR alpha/beta) and T-cell receptor gamma/delta (TCR gamma/delta) in body effusions. METHODS: Using multicolor flow cytometry and sequential gating techniques, NK cells and T lymphocytes expressing TCR alpha/beta and TCR gamma/delta were identified and quantitated in 30 benign and 30 malignant effusions. RESULTS: No significant difference in percentage of NK cells was found between benign and malignant effusions. The absolute number per miroliter of CD16(+)CD56(+) NK cells was higher in malignant than in benign effusions, but only at a borderline level of statistical significance. T cells expressing TCR alpha/beta far outnumbered those expressing TCR gamma/delta in all effusions, a distribution similar to that in normal adult peripheral blood and lymphoid tissue. The percentages and absolute numbers of these T-cell subsets were the same in benign and malignant effusions. CONCLUSIONS: Enumeration of NK cells and of T lymphocytes expressing TCR alpha/beta or TCR gamma/delta in human body effusions is not helpful in attempting to distinguish between benign and malignant effusions. Values for the two T-lymphocyte subsets in human effusions are, to our knowledge, established for the first time by flow cytometric determination.