Spindle Cell Lipoma With Florid Primary Follicular Lymphocytic Hyperplasia: A Novel Association With Potential Diagnostic Pitfalls.

ABSTRACT: Spindle cell lipoma (SCL) is a benign subcutaneous lipomatous neoplasm with a heterogeneous histologic appearance that varies greatly depending on the amount of fat, collagen, and myxoid stroma, which define the multiple subtypes of SCL, such as fat poor SCL, pseudoangiomatous SCL, and dendritic fibromyxolipoma. Cutaneous lymphoid hyperplasia is a spectrum of benign conditions characterized by reactive B-cell and T-cell cutaneous lymphocytic infiltrates. Cutaneous B-cell lymphoid hyperplasia is a heterogeneous group of non-neoplastic conditions that can be observed as reactive phenomena to infections, medications, allergens, or neoplasms and must be distinguished from cutaneous B-cell lymphomas. Here, we report a novel case of spindle cell lipoma, associated with B-cell primary lymphoid follicular hyperplasia, mixed within the tumor in a peculiar pattern, while discussing potential diagnostic pitfalls with low-grade B-cell lymphomas. This is the first report of such association in the literature.

ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma.

PURPOSE: Patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Phase II studies demonstrated that adding the immunomodulatory agent lenalidomide to R-CHOP improved outcomes in ABC-type DLBCL. The goal of the global, phase III ROBUST study was to compare lenalidomide plus R-CHOP (R2-CHOP) with placebo/R-CHOP in previously untreated, ABC-type DLBCL. METHODS: Histology and cell-of-origin type were prospectively analyzed by central pathology prior to random assignment and study treatment. Patients with ABC-DLBCL received lenalidomide oral 15 mg/d, days 1-14/21 plus standard R-CHOP21 versus placebo/R-CHOP21 for six cycles. The primary end point was progression-free survival (PFS) per independent central radiology review. RESULTS: A total of 570 patients with ABC-DLBCL (n = 285 per arm) were stratified by International Prognostic Index score, age, and bulky disease, and randomly assigned to R2-CHOP or placebo/R-CHOP. Baseline demographics were similar between arms. Most patients completed six cycles of treatment: 74% R2-CHOP and 84% placebo/R-CHOP. The most common grade 3/4 adverse events for R2-CHOP versus placebo/R-CHOP were neutropenia (60% v 48%), anemia (22% v 14%), thrombocytopenia (17% v 11%), and leukopenia (14% v 15%). The primary end point of PFS was not met, with a hazard ratio of 0.85 (95% CI, 0.63 to 1.14) and P = .29; median PFS has not been reached for either arm. PFS trends favoring R2-CHOP over placebo/R-CHOP were seen in patients with higher-risk disease. CONCLUSION: ROBUST is the first DLBCL phase III study to integrate biomarker-driven identification of eligible ABC patients. Although the ROBUST trial did not meet the primary end point of PFS in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.

A Phase 2/3 Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Lenalidomide Versus Investigator's Choice in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Purpose: Randomized, multicenter, open-label, phase 2/3 trial investigating lenalidomide versus investigator's choice (IC) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Experimental Design: Patients with DLBCL who received ≥2 prior therapies were stratified by DLBCL subtype [germinal center B-cell (GCB) vs. non-GCB; determined by immunohistochemistry (IHC)] and then randomized 1:1 to lenalidomide (25 mg/day, 21 days of 28-day cycle) or IC (gemcitabine, rituximab, etoposide, or oxaliplatin). Crossover to lenalidomide was permitted for IC-treated patients with radiologically confirmed progressive disease. The primary endpoint was overall response rate (ORR). Progression-free survival (PFS), overall survival, and subtype analysis [GCB vs. activated B-cell (ABC)] using gene expression profiling (GEP) were exploratory endpoints.Results: Stage 1: 102 DLBCL patients (by IHC: non-GCB, n = 54; GCB, n = 48) received ≥1 dose of lenalidomide or IC. Hematologic treatment-emergent adverse events with lenalidomide versus IC included neutropenia (42.6%; 36.4%), anemia (33.3%; 47.3%), thrombocytopenia (24.1%; 43.6%), and leukopenia (5.6%; 12.7%), respectively. Overall, lenalidomide-treated patients had an ORR of 27.5% versus 11.8% in IC (ORRs were similar regardless of IHC-defined DLBCL subtype). Median PFS was increased in patients receiving lenalidomide (13.6 weeks) versus IC (7.9 weeks; P = 0.041), with greater improvements in non-GCB patients (15.1 vs. 7.1 weeks, respectively; P = 0.021) compared with GCB (10.1 vs. 9.0 weeks, respectively; P = 0.550).Conclusions: The clinical benefit of lenalidomide monotherapy in DLBCL patients was more evident in the non-GCB subtype. Exploratory analyses suggest that this preferential benefit was more pronounced in the GEP-defined ABC population, demonstrating a need for additional studies of lenalidomide in DLBCL using GEP subtyping. Clin Cancer Res; 23(15); 4127-37. ©2017 AACR.

New-onset psoriasis associated with adalimumab: a report of two cases.

TNF-α inhibitors, including adalimumab, are increasingly used in the management of inflammatory cutaneous, gastrointestinal, and rheumatologic diseases. An untoward class effect of these medications is the development of new-onset psoriasis, particularly in patients treated for rheumatologic diseases without any personal or family history of cutaneous psoriasis. We report two patients that developed cutaneous and histologic changes consistent with psoriasis while receiving treatment with adalimumab for inflammatory arthridities: one patient with Crohn disease and ankylosing spondylitis who tolerated adalimumab for 15 months before developing psoriasis and another patient with rheumatoid arthritis who developed psoriasis 3 years after starting adalimumab. Both patients experienced rapid resolution of their psoriasis after discontinuation of adalimumab.