Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Abstract

Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement. Management of these lymphomas should involve CNS prophylaxis, preferably using systemic high-dose methotrexate to prevent intraparenchymal recurrence. Involvement of the kidneys, adrenal glands, ovary, bone marrow, lung, or pleura usually indicates disseminated disease, conferring worse prognosis. Involvement of these sites is often associated with high CNS-International Prognostic Index (IPI), concurrent MYC and BCL2 or BCL6 rearrangements, or intravascular lymphoma-risk factors warranting CNS prophylaxis. In contrast, craniofacial, thyroid, localized bone, or gastric lymphomas have a variable prevalence of the non-GCB phenotype and lack MYD88 mutations. Their outcomes with standard immunochemotherapy are excellent, and the risk of CNS recurrence is low. We recommend individualized consideration of CNS prophylaxis based on the CNS-IPI score and anatomical proximity in cases of epidural, orbital, or skull involvement. Rituximab-containing immunochemotherapy is a standard approach for all extranodal DLBCLs. Surgery is no longer required for any primary site, but routine consolidative radiation therapy is recommended for testicular lymphoma. Radiation therapy also appears to be associated with better progression-free survival in primary bone DLBCL. Future studies should better distinguish primary from secondary sites of extranodal involvement, and investigate the association of newly identified genotypes with the risk of CNS or systemic recurrence.

Useful prognostic tools based on complete blood cell counts in diffuse large B‐cell lymphoma

“…NCCN-IPI is considered a particularly useful tool but extranodal organs used in the index are not necessarily indicators of a poor prognosis. 9 There is also evidence for a lack of reproducibility for NCCN-IPI in cases of staging by positron emission tomography (PET)-computed tomography (CT). 10 Accordingly, despite the wide use of IPI, R-IPI, and NCCN-IPI, they each have various limitations.…”

Diffuse Large B-cell Lymphoma of Testis: a Case Report and Current Literature Review

“…6 Because tumor relapses are common in the CNS, the CNS prophylaxis must be done with intrathecal chemotherapy. 9 In our case, the disease was stage 3 at the time of diagnosis and chemotherapy was inevitable. Also, since the risk of relapse to the counter-testis is high, counter-testis radiotherapy is strongly indicated in standard treatment.…”

“…Before being referred to our clinic, he was treated with various antibiotics, considering it to be chronic orchitis. The values were calculated as Hgb: 9 proliferation marker) was strongly positive in about 80% of tumors cells, bcl-6 (nuclear marker of germinal center lymphocytes) and CD 10 were negative in tumor cells. Multiple myeloma oncogene 1 (MUM1) was detected to be weakly positive (Fig.…”

Primary pancreatic lymphoma: Clinical presentation, diagnosis, treatment, and outcome

“…Almost all relapses occurred within 14 months and resulted in the early drop of PFS, which may reflect the aggressive biology of PPL.Extranodal lymphomas may have different patterns of relapse depending on the tissue/organ involved. A recent study has correlated some primitive lymphoma localization (testis, kidney, and adrenal gland) with an increased risk of CNS relapse without taking into account the pancreatic gland 25. Importantly, according to our study and literature search, patients affected by PPL may have a relatively high incidence of CNS relapse.…”