Intravascular Large B Cell Lymphoma with CNS Involvement Successfully Treated with High-Dose Methotrexate and High-Dose Ara-C Based CNS-Directed Chemoimmunotherapy Alternating with Anthracycline Based Chemoimmunotherapy.

Intravascular large B cell lymphoma (IVL) is a rare subtype of diffuse large B cell lymphoma confined to small blood vessels with a predilection for CNS involvement. The prognosis of IVL with CNS involvement (CNS-IVL) is extremely poor. The optimal treatment for CNS-IVL is not well defined. Thus, we report three patients with CNS-IVL successfully treated with a CNS-centric approach consisting of high-dose methotrexate (HDMTX) and high-dose Ara-C (HiDAC) based CNS-directed chemoimmunotherapy (CIT) alternating with anthracycline-based CIT. Our rationale for intensifying the CNS-directed therapy is the presence of intracerebral bleeding in two of our patients which would result in extravasation of lymphoma cells into the cerebral parenchyma with the development of CNS lymphoma. All three patients have achieved excellent therapeutic outcomes. Two patients with intracerebral bleeding have been in complete remission (CR) for about 11 years and 4 years. One patient was successfully induced into CR about 10 months ago and currently is in CR. This unique therapeutic approach should be further explored for CNS-IVL.

Leukemic High Grade B Cell Lymphoma is Associated With MYC Translocation, Double Hit/Triple Hit Status, Transformation, and CNS Disease Risk: The Mayo Clinic Experience.

INTRODUCTION: Leukemic involvement in high grade B cell lymphoma (L-HGBL) is rare and has been sparsely described in the literature. We report our experience in a large single institution multicenter academic setting. MATERIALS AND METHODS: Medical records of patients with HGBL who received care at Mayo Clinic between 2003 and 2020 were reviewed. L-HGBL was confirmed by peripheral blood smear and flow cytometry with corroboration from tissue and bone marrow biopsy findings. RESULTS: Twenty patients met inclusion criteria. All patients had significant bone marrow involvement by HGBL. Leukemic involvement presented in 11 of 20 (55%) in the de novo and 9 of 20 (45%) in the relapsed setting. Seven of 20 patients had DLBCL, NOS, 6 of 20 had transformation (t-DLBCL), 3 of 20 had transformed double/triple hit lymphoma (t-DHL/THL), 2 of 20 had double hit lymphoma (DHL), and 2 of 20 had HGBL with intermediate features between DLBCL and Burkitt lymphoma. Nine of 15 patients had MYC translocation. Based on Hans criteria, 11 of 20 had germinal center B-cell (GCB) cell of origin (COO) and 9/20 had non-GCB COO. Five of 11 de novo patients experienced CNS relapse/progression. All de novo patients received anthracycline-based chemoimmunotherapy. Eighteen of 20 patients died of progressive disease. Median overall survival was significantly better in the de novo compared to relapsed group (8.9 months vs. 2.8 months, P = .01). COO, MYC status, DHL/THL status, HGBL subtype, or treatment group did not demonstrate a significant effect on overall survival. CONCLUSION: L-HGBL carries a poor prognosis and is associated with MYC translocation, DHL/THL status, transformation, and high CNS risk. Novel therapeutic approaches are needed for L-HGBL.

Long-Term Survival with Ibrutinib Therapy in Elderly Patients with Newly Diagnosed Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL) carries a dismal prognosis in elderly patients above 70 years of age with a median overall survival of 6 months. Novel therapeutic agents are urgently needed to improve survival outcomes in this age group. We describe the clinical presentation, diagnostic workup, and treatment outcome in two 80-year-old patients diagnosed with PCNSL who were treated with ibrutinib therapy. Both patients remain in complete remission following treatment with ibrutinib therapy. One patient is currently 4 years and the other is 2 years and 9 months from the time of initial diagnosis. We suggest that ibrutinib therapy has significant therapeutic activity against PCNSL in the newly diagnosed setting and should be evaluated in a clinical trial as part of front-line therapy, especially in elderly patients.

Germline VHL Mutation Discovered in Association with EGFR-Positive Lung Cancer and Metachronous Hepatocellular Carcinoma: A Case Report.

VHL is a tumor suppressor gene located on chromosome 3 that is classically associated with tumors of the eye and CNS, renal cell carcinoma, and pheochromocytoma. We describe what appears to be the first report of an association between a germline VHL mutation and non-small cell lung cancer and metachronous hepatocellular carcinoma (HCC). Our case involves a 63-year-old nonsmoking male who was initially diagnosed with EGFR mutation-positive metastatic nonsquamous, non-small cell lung adenocarcinoma, who subsequently developed HCC and squamous cell carcinoma of the femur despite first-line treatment with EGFR-blocking osimertinib. Caris molecular profiling unexpectedly identified a shared underlying VHL mutation in all 3 lesions. Genetic mapping through a machine learning-based tool called Genomic Prevalence Score (GPSai™) helped determine that the femur tumor was a metastatic lesion as opposed to a separate primary and that the HCC was a distinct primary malignancy. We not only highlight the association between these tumors and a VHL mutation but also emphasize the value of next-generation sequencing and a molecular disease classifier in a patient with multiple primaries, how it helps guide therapy, and its value in guiding future studies.

Primary Cauda Equina Lymphoma Treated with CNS-Centric Approach: A Case Report and Literature Review.

Primary cauda equina lymphoma is an extremely rare entity previously documented in only 24 reported cases. Primary cauda equina lymphoma represents a subtype of neurolymphomatosis, which occurs when lymphoma cells with neurotropism infiltrate and destroy peripheral nerves, spinal nerve roots, nerve plexuses and cranial nerves. The cauda equina is an anatomic structure located in the lower part of the spinal canal consisting of multiple lumbar and sacral nerve roots. Herein, we report a unique case of primary cauda equina diffuse large B-cell lymphoma presenting as a tumor mass in the lower spinal canal, which was treated with a CNS-centric treatment approach followed by autologous hematopoietic stem cell transplantation.

Primary age-related EBV-associated effusion-based lymphoma successfully treated with rituximab and thoracentesis.

EBV-positive HHV8-negative EBL is part of the spectrum of EBV-positive diffuse large B-cell lymphoma NOS. This entity can be labeled as primary age-related EBV-associated EBL and appears to respond well to rituximab and thoracentesis.

BRAF p.V600E associated poly-neoplastic syndrome.

We report a male patient who developed eight different cancers between ages 57 and 64. BRAF p.V600E mutation was detected in Langerhans cell histiocytosis, chronic lymphocytic leukemia, histiocytic sarcoma, melanoma, and adenocarcinoma of the lung. It was not detected in multiple myeloma, basal cell carcinoma, and papillary thyroid cancer. BRAF p.V600E was not detected in normal skin tissue biopsy indicating that BRAF V600E was a somatic mutation affecting cancer cells. The presence of eight different cancers with five of them positive for BRAF p.V600E in a single patient is unprecedented. This type of BRAF p.V600E-associated poly-neoplastic syndrome has never been reported in the medical literature.

Primary peritoneal myeloid sarcoma in association with CBFB/MYH11 fusion.

Myeloid sarcoma, also known as chloroma or granulocytic sarcoma is an extramedullary disease process that typically presents in association with acute myeloid leukemia during initial presentation or at relapse. Often associated with cytogenetic mutations, including t(8;21)(q22;q22); RUNX1/RUNX1T1, and less frequently with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB/MYH11, myeloid sarcoma is most commonly discovered in skin, soft tissue, bone, and connective tissue. In rare circumstances, myeloid sarcoma can present without any evidence of bone marrow or leukemic involvement. These cases of de novo myeloid sarcoma are rare, and are commonly misdiagnosed due to similarities with other entities. We report an unusual case of a primary de novo peritoneal myeloid sarcoma, in association with inv(16)(p13;q22) and clonal heterogeneity at different sites of involvement, that has responded well to AML induction therapy and consolidation treatment with gemtuzumab ozogamicin and high dose cytarabine. Cytogenetics, immunophenotyping, and chromosomal analysis, were each critical in establishing a proper diagnosis as well as helping to develop appropriate therapeutic strategies for this rare entity.