RESUMEN
Optical genome mapping (OGM) is a new DNA-based technology which provides comprehensive examination of the entire genome. We report two patients who presented with splenomegaly and leukocytosis with lymphocytosis including villous lymphocytes. Neither patient had lymphadenopathy. Bone marrow evaluation showed involvement by small B-cell lymphoma in a sinusoidal and interstitial distribution, and immunophenotypic analysis showed that the neoplastic cells were positive for B-cell markers and cyclin D1 but were negative for SOX11 and CD5. Initially, the clinicopathologic features in both patients were thought to be suspicious for hairy cell leukemia variant or splenic marginal zone lymphoma. However, OGM detected CCND1 rearrangement: t(2;11)/IGK::CCND1 in one case and t(11;14)/IGH::CCND1 in the other case. These cases illustrate the valuable role OGM can play in establishing the diagnosis of MCL. Case 1 also contributes to the paucity of literature on the rare occurrence of IGK::CCND1 in MCL.
Asunto(s)
Leucemia Linfocítica Crónica de Células B , Linfoma de Células B , Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/patología , Leucemia Linfocítica Crónica de Células B/patología , Linfocitos/patología , Genómica , Ciclina D1/genéticaRESUMEN
OBJECTIVES: Histiocytic neoplasms demonstrate shared gene translocations and clonal immunoglobulin gene rearrangements in cases of associated B-cell lymphomas. However, the evolution of these related disease processes remains largely uncertain, especially in the setting of a prior mantle cell lymphoma. METHODS: We describe a unique case of a histiocytic sarcoma that transdifferentiated from blastoid mantle cell lymphoma after extensive therapy. Cytogenic and molecular studies were performed and provided evidence for clonal progression. RESULTS: We present the first reported case of a patient with blastoid mantle cell lymphoma harboring a CCND1 rearrangement that progressed despite multiple therapeutic regimens and ultimately transdifferentiated into histiocytic sarcoma. The histiocytic sarcoma demonstrated a CCND1 rearrangement and targeted next-generation sequencing showed a pathogenic variant in NRAS, a gene involved in the RAS/MAPK pathway, known to play a role in the pathogenesis of histiocytic sarcomas. TP53, NOTCH2, CREBBP, and NFKBIE variants were also identified, which are often seen in B-cell lymphomas, while rarely described in histiocytic sarcoma. CONCLUSIONS: To our knowledge, this is the first report to provide evidence for clonal evolution of histiocytic sarcoma from blastoid mantle cell lymphoma based on cytogenic and molecular findings. The patient's protracted therapeutic course may have acted as an evolutionary driver promoting this transdifferentiation process.
Asunto(s)
Sarcoma Histiocítico , Linfoma de Células B , Linfoma de Células del Manto , Adulto , Ciclina D1/genética , Reordenamiento Génico , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/patología , Humanos , Hibridación Fluorescente in Situ , Linfoma de Células B/patología , Linfoma de Células del Manto/genéticaRESUMEN
Anaplastic multiple myeloma (AMM) is a very rare morphologic variant of multiple myeloma with extremely poor prognosis. The anaplastic morphology of AMM may pose a diagnostic challenge. A thorough workup is critical in reaching the correct diagnosis.
Asunto(s)
Cromosomas Humanos Par 11 , Cromosomas Humanos Par 2 , Neoplasias de Células Plasmáticas/diagnóstico , Neoplasias de Células Plasmáticas/genética , Translocación Genética , Secuenciación Completa del Genoma , Biopsia , Médula Ósea/patología , Femenino , Reordenamiento Génico , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hibridación Fluorescente in Situ , Persona de Mediana EdadRESUMEN
OBJECTIVES: To demonstrate and confirm the existence of cyclin D1-positive diffuse large B-cell lymphoma (DLBCL) with IGH-CCND1 rearrangement and discuss the rationale of differentiating this entity from blastoid and pleomorphic variants of mantle cell lymphoma (MCL). METHODS: Two cyclin D1-positive lymphomas with morphologic features of DLBCL and IGH-CCND1 translocations were characterized with respect to clinical features, as well as morphologic, immunophenotypic, cytogenetic, and molecular findings. RESULTS: The large tumor cells were CD20+, CD5-, CD10-, BCL6+, MUM1+, and cyclin D1+ in both cases. SOX11 was negative. Epstein-Barr virus-encoded RNA in situ hybridization demonstrated diffuse positivity in case 1. BCL6 and IGH-CCND1 rearrangements were identified by fluorescence in situ hybridization in both cases. Specifically, the diagnosis of a relapsed DLBCL with acquisition of IGH-CCND1 was rendered for case 1, molecularly confirmed by the detection of identical monoclonal IGH rearrangements between the initial diagnostic DLBCL and relapse lymphoma. CONCLUSIONS: Our study demonstrates convincingly that IGH-CCND1 rearrangement leading to cyclin D1 overexpression can occur in DLBCL and pose a potential diagnostic pitfall, requiring thorough knowledge of the clinicopathologic findings to allow accurate discrimination from a blastoid or pleomorphic MCL. The coexistence of IGH-CCND1 and IGH-BCL6 rearrangements suggest that BCL6 and cyclin D1 may cooperate in the pathogenesis of DLBCL.