Mantle cell lymphoma (MCL) is a rare form of malignant non-Hodgkin lymphoma affecting B lymphocytes originating in the mantle zone of lymph nodes, as characterized by Orphanet. The condition has a prevalence in the uncommon range, affecting approximately 1 to 9 per 100,000 individuals. Also referred to as mantle zone lymphoma or classical mantle cell lymphoma, MCL is an aggressive B-cell malignancy that typically involves multiple lymphoid regions and can affect extranodal sites. The disease generally presents in older adults and has a clinical course that may include initial treatment response followed by the potential for relapse. Multiple FDA-approved treatment options have been developed for MCL over recent years, reflecting sustained therapeutic investment in this disease area.

Lymphadenopathy (enlarged lymph nodes) is the most commonly documented presentation, occurring in 80–99% of cases per Orphanet HPO data, alongside a pathological finding of B-cell lymphoma as a defining feature in the same frequency range. Fatigue, splenomegaly (enlarged spleen), and anorexia (loss of appetite) each occur in 30–79% of individuals. Fever, unintentional weight loss, and abnormal bone marrow cell morphology are also documented at the same frequency. Abnormalities of the gastrointestinal tract are reported in 5–29% of cases. The total HPO phenotype catalog for MCL encompasses nine entries.

The packet does not identify specific germline disease-causing genes for mantle cell lymphoma; the known_genes field is empty and no inheritance pattern is listed. MCL is an acquired B-cell malignancy arising from molecular alterations within lymphoid cells rather than a Mendelian hereditary process. The disease definition characterizes it as affecting B lymphocytes in the mantle zone, consistent with an acquired lymphoid neoplasm. The specific molecular drivers of MCL are not enumerated in this packet.

Diagnosis is supported by the clinical presentation of lymphadenopathy and B-cell lymphoma pathology documented as defining features in the HPO data. Tissue biopsy demonstrating abnormal B-cell morphology is central to establishing the diagnosis, with bone marrow examination contributing to disease staging. Specific diagnostic criteria and protocols beyond the clinical features and phenotype data in this packet are not detailed in the available data sources.

Multiple FDA-approved therapies are identified in the packet's approved_treatments field with active market status. BTK inhibitors represented include zanubrutinib (BRUKINSA), approved by FDA/CDER in June 2025; pirtobrutinib (JAYPIRCA), approved in January 2023; ibrutinib (IMBRUVICA), with approval dating to 2022; and acalabrutinib (CALQUENCE), approved in August 2022. The proteasome inhibitor bortezomib is available in active branded formulations (BORUZU, VELCADE). Brexucabtagene autoleucel (Tecartus), a CAR-T cell therapy regulated by CBER, was approved in July 2020. Lenalidomide (REVLIMID), an immunomodulatory agent, also holds active approved status. Several additional agents in the packet's orphan drug records carry designated or withdrawn status and do not represent current approved options. A patient assistance program (Mantle Cell Lymphoma Fund via HealthWell Foundation) is listed in the packet for eligible individuals.

A dedicated natural history or prognosis field is not present in this packet. MCL is described in authoritative sources as an aggressive B-cell malignancy; the clinical trajectory and treatment response vary across individuals. Prognosis data beyond the disease definition and the clinical context provided by Orphanet and GARD is not certified in this packet.

Mantle cell lymphoma is an area of extensive active clinical investigation, with numerous trials registered on ClinicalTrials.gov. Among trials in the packet: NCT06742996 (Phase 3) evaluates sonrotoclax combined with zanubrutinib versus placebo plus zanubrutinib in relapsed or refractory MCL (CELESTIAL-RRMCL), sponsored by BeOne Medicines, recruiting since March 2025; NCT03267433 (Phase 3) examines rituximab with or without stem cell transplant in MRD-negative MCL in first complete remission, sponsored by ECOG-ACRIN; NCT07003295 (Phase 2) investigates glofitamab for MCL following CAR-T cell therapy, sponsored by the National Cancer Institute; and NCT04115631 (Phase 2) compares three chemotherapy regimens for newly diagnosed MCL. The research landscape includes publications in gene therapy, biomarker science, and recent clinical trial data, reflecting broad scientific activity in this disease.