Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty-three percent of patients presented with MGZL, whereas 57% had non-MGZL (NMGZL). NMGZL patients were older (50 versus 37 years, P 5 0.0001); more often had bone marrow involvement (19% versus 0%, P 5 0.001); >1 extranodal site (27% versus 8%, P 5 0.014); and advanced stage disease (81% versus 13%, P 5 0.0001); but they had less bulk (8% versus 44%, P 5 0.0001), compared with MGZL patients. Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone 1/2 rituximab (CHOP1/2R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine 1/2 rituximab (ABVD1/2R) 30%, and doseadjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, outcomes in MGZL patients seemed similar compared with that of NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival for all patients. Additionally, patients treated with ABVD1/2R had markedly inferior 2-year PFS (22% versus 52%, P 5 0.03) compared with DLBCL-directed therapy (CHOP1/2R and DA-EPOCH-R), which persisted on Cox regression (hazard ratio, 1.88; 95% confidence interval, 1.03-3.83; P 5 0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (hazard ratio, 0.35; 95% confidence interval, 0.18-0.69; P 5 0.002). Collectively, GZL is a heterogeneous and likely more common entity and often with nonmediastinal presentation, whereas outcomes seem superior when treated with a rituximab-based, DLBCL-specific regimen.

SAGN biopsies show marked variability in IgA immunofluorescence staining and low frequency of subepithelial humps compared with poststreptococcal GN. Occasional ANCA positivity is present in cases of SAGN, even in infections other than endocarditis. Therefore, biopsy diagnosis can be difficult particularly when clinical symptoms of infection are subtle. Both the pathologist and the nephrologist should be aware of these diagnostic pitfalls.

Key Points• Accurate GZL diagnosis remains challenging, with .60% of patients with presumed GZL having the diagnosis reclassified on consensus review.• Treatment with DLBCLbased therapy appears most effective for GZL (including R-CHOP); however, new therapies are needed to improve outcomes.Gray zone lymphoma (GZL) is described as sharing features with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 North American academic centers were evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL.Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20 , 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n 5 27 (including n 5 10 NS grade 2); lymphocyte predominant HL, n 5 4; DLBCL, n 5 4; EBV 1 DLBCL, n 5 3;primary mediastinal large BCL n 5 2; lymphocyte-rich cHL and BCL-not otherwise specified, n 5 1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P 5 .038) and less likely more than 1 extranodal site (0% vs 25%; P 5 .019). With a 44-month median follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39% and 95%, respectively, vs 58% and 85%, respectively, for reclassified cases (P 5 .19 and P 5 .15, respectively).Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12% vs 64%; P 5 .01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone 6 rituximab (CHOP6R) was associated with improved 3-year PFS (70% vs 20%; P 5 .03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.

Our study supports that DOG-1 is a highly sensitive and specific marker for GISTs and also highlights hitherto unrecognized and unusual patterns of expression in non-mesenchymal neoplasms.

Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n ¼ 15): myxoid and round cell (n ¼ 8); well-differentiated (n ¼ 4), and dedifferentiated (n ¼ 3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n ¼ 44): myxoid and round cell (n ¼ 18); well-differentiated (n ¼ 10); dedifferentiated (n ¼ 10); and pleomorphic (n ¼ 6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1 À 3 þ ), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2 À 3 þ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1 þ intensity in 50% of cells; 2 þ intensity in 5% of cells; and 3 þ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3 þ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this malignancy.