Morphologic Patterns and the Correlation With MYD88 L265P, CD79B Mutations in Primary Adrenal Diffuse Large B-Cell Lymphoma

Abstract

Primary adrenal diffuse large B-cell lymphoma (PA-DLBCL) is a rare subtype of extranodal DLBCL. Because of the rarity of this disease, its morphologic and genetic features are not comprehensively studied. Here, we systematically reviewed the clinicopathologic features of 42 cases of PA-DLBCL from our institution and investigated the frequency of MYD88 L265P and CD79B (exon 5) mutation in 29 eligible cases using Sanger sequencing. Clinically, PA-DLBCL was predominant in elderly male patients with advanced clinical stage and poor outcomes. Morphologically, the tumors often showed a sinusoidal and/or cohesive pattern with condensed chromatin and inconspicuous nucleolus which mimicked neuroendocrine carcinoma. Moreover, increased Reed-Sternberg–like cells were observed frequently. These confounding morphologic manifestations may lead to misdiagnosis. Genetically, PA-DLBCL harbored a high prevalence of MYD88 L265P (24%) and CD79B mutations (52%) which may be involved in lymphomagenesis. The CD79B mutation was significantly associated with a worse prognosis. A novel Histo-Molecular Classification system (4 categories) was proposed based on correlation with genetic changes. Generally, the neuroendocrine carcinoma–like type was associated with CD79B mutation, whereas the RS-like cell type indicated MYD88 L265P. The biphasic type was correlated with coexisting mutations of MYD88 and CD79B, whereas the common type implied no mutation. Furthermore, the common type showed significantly better survival. In conclusion, the proposed new category system could indicate the genetic changes as well as facilitate risk stratification to guide treatment and predict prognosis. Although this study augmented our understanding of PA-DLBCL, further analysis is required to validate our results and extend them to extranodal DLBCL at other sites.

MYD88L265Pand CD79B double mutations type (MCD type) of diffuse large B-cell lymphoma: mechanism, clinical characteristics, and targeted therapy

“…Therefore, biphasic type suggests MYD88 L265P and CD79B double mutations, which was also observed in primary breast DLBCL. 12 …”

“…Patients with RS-like cells PA-DLBCL were more likely to involve CNS and the CNS-directed prophylactic interventions should be used in conjunction with initial therapy. 12 …”

“…The concurrence of MYD88 and CD79B mutations enriched for primary extranodal diffuse large B-cell lymphomas especially in immune-privileged sites (including 48–56% primary central nervous system (CNS) and 19–27% primary testicular DLBCL) and 33% of Waldeyer’s ring and paranasal sinuses (ENT). 7 – 11 In addition, MCD type also occurs in 14% of Primary Adrenal DLBCL, 12 11–25% of primary breast DLBCL, 20% of intravascular large B-cell lymphoma, 13 and <56% of primary cutaneous DLBCL-leg type. 14 Conversely, this type is few or inexistence in other DLBCL subtypes, such as gastrointestinal DLBCL 15 , 16 and nodal lymphoma.…”

Dermatofibrosarcoma protuberans im Gesicht: Klinisch‐pathologische und molekulare Studie mit 34 Fällen

“…Antikörper gegen folgende Antigene wurden verwendet: CD34, SMA ( smooth muscle actin), EMA ( epithelial membrane antigen ), S100‐Protein, Desmin, CD10, Cytokeratin und Ki‐67 (Tabelle S1, Online‐Supplement ). Der Ki‐67‐Index wurde in drei HPF gemessen (× 400) und anschließend ein Mittelwert berechnet [15].…”

Point Mutation Specific Antibodies in B-Cell and T-Cell Lymphomas and Leukemias: Targeting IDH2, KRAS, BRAF and Other Biomarkers RHOA, IRF8, MYD88, ID3, NRAS, SF3B1 and EZH2

“…MYD88 L265P is pathogenic, occurring at significant frequencies in hematologic malignancies such as chronic lymphocytic leukemia, marginal zone lymphomas of the ocular adnexa, primary central nervous system large B-cell lymphomas and multiple myeloma amongst numerous others [46,[48][49][50][51][52][53]. In three separate studies, L265P was found in over 90% of patients with lymphoplasmacytic lymphoma (LPL) and from 86-100% of patients with related Waldenström macroglobulinemia (WM) [54][55][56].…”