2026-08-10 | IgM Pleural Amyloidosis Diagnosed by Pleural Effusion Cell Block: A Case Report.
Immunoglobulin light chain (AL) amyloidosis is characterized by the systemic deposition of light-chain-derived amyloids. Immunoglobulin M (IgM)-associated AL amyloidosis is extremely rare and clinically distinct. A 70-year-old man presented with dyspnea, bilateral pleural effusion, and mediastinal lymphadenopathy on computed tomography (CT). Amyloid was detected in a pleural effusion cell block and confirmed via an axillary lymph node biopsy. Serum studies and bone marrow findings supported IgM-λ AL amyloidosis associated with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. First-line therapy failed, but second-line therapy reduced pleural effusion, avoiding thoracentesis for one year. A pleural effusion cell block analysis enabled rapid diagnosis with minimally invasive exploration.
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2026-08-08 | Peripheral neuropathies associated with immunoglobulin M monoclonal gammopathies and low-grade B-cell lymphomas: diagnostic and therapeutic approach.
Peripheral neuropathies associated with monoclonal gammopathies and low-grade B-cell lymphomas represent a clinically heterogeneous group of disorders encountered by both neurologists and hematologists. This review provides a practical and updated approach to their diagnosis and management, with a particular focus on IgM-associated neuropathies and anti-MAG neuropathy. IgM-related neuropathies encompass immune-mediated disorders - most commonly driven by antibodies against myelin-associated glycoprotein (MAG) - as well as infiltrative mechanisms (neurolymphomatosis, Bing-Neel syndrome) and protein deposition diseases (AL amyloidosis). Anti-MAG neuropathy remains the most common and best-characterized entity. Over the past decade, therapeutic strategies have evolved substantially with the emergence of clone-directed approaches, including anti-CD20-based regimens and covalent Bruton tyrosine kinase inhibitors (cBTKi). However, high-quality evidence remains limited. Establishing a causal relationship between neuropathy and IgM gammopathy is essential and requires a multidisciplinary approach. Treatment should be individualized and primarily reserved for progressive, functionally impairing disease. Despite therapeutic advances, many patients experience persistent disability, underscoring the need for novel strategies and prospective clinical trials using validated neurological endpoints.
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2026-07-09 | WNK2 oncogenicity revealed by the discovery and functional characterization of novel gene isoforms in MYD88 mutated Waldenström's Macroglobulinemia.
WNK2 is a known tumor suppressor in a set of solid tumors, including glioblastoma multiforme and pancreatic ductal adenocarcinoma. WNK2 functions are largely unknown beyond the kinase domain (KD)-dependent inhibition of ERK1/2 signaling. Waldenström's Macroglobulinemia (WM) is an indolent, yet incurable, B cell lymphoma characterized by highly recurrent MYD88 (MYD88MUT) and CXCR4 (CXCR4MUT) mutations that trigger sustained NF-κB and ERK1/2 signaling. Although not expressed in healthy B cells, WNK2 is a top dysregulated gene in MYD88MUT WM. To study WNK2 regulation and signaling, we performed multi-omics analyses, including bulk and PacBio Iso-Seq RNA-Seq and methylome, in 264 untreated WM and functional studies in cell lines and primary WM cells. Aberrant expression of WNK2 emerged as a near universal feature of early-stage WM and a hallmark of plasma cell-like MYD88MUT WM. We identified novel isoforms that carried a shared aberrant splicing event, either contained or lacked the KD and were highly expressed by the tumor cells, unlike the canonical full-length isoforms. Functionally, WNK2/S-NK1, the most expressed of the KD-lacking isoforms in WM, triggered a pro-inflammatory cascade that activated ERK1/2 and NF-κB signaling. We observed a similar, cancer-specific upregulation of WNK2 in a set of solid tumors, including the highly aggressive cholangiocarcinoma. Our findings reveal an undocumented oncogenic function for WNK2 driven by novel, cancer-specific isoforms and provide a framework for its further investigation as a determinant of disease progression in MYD88MUT WM and a novel therapeutic target in hematological and solid tumor oncology.
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2026-07-03 | Diagnostic challenge of occult ER-positive breast carcinoma within bone marrow indolent B-cell lymphoma and response to CDK4/6 inhibitor: a case report.
Bone marrow metastasis from hormone receptor-positive breast cancer can be challenging to detect, especially in patients with concurrent hematologic malignancies, where isolated epithelial cells may be hidden by a dominant lymphoid infiltrate. This situation requires careful histopathologic and immunophenotypic evaluation to prevent misdiagnosis. We report a 74-year-old White woman with Waldenström's macroglobulinemia carrying the MYD88 L265P mutation and bone marrow infiltration by indolent B-cell non-Hodgkin lymphoma. She was evaluated for suspected skeletal disease progression due to rising tumor markers and inconclusive PET findings. Bone marrow biopsy revealed small clusters of epithelial cells positive for estrogen receptor (ER), cytokeratin AE1/AE3, and GATA3, consistent with metastatic breast carcinoma within a lymphoid background. Notably, ER positivity was the only marker indicating epithelial origin. The patient had previously received empirical aromatase inhibitor therapy after the initial detection of scattered ER-positive epithelial cells in 2018. Following disease progression in December 2024, she was treated with palbociclib and fulvestrant, while the indolent lymphoma was managed with active surveillance. At 6-month follow-up, the patient showed clinical stability, a biochemical response, and radiologic evidence of stable disease. This case emphasizes the importance of maintaining a high level of clinical and pathological suspicion when assessing bone marrow infiltration, especially in patients with a history of malignancy. The presence of isolated ER-positive epithelial cells within a lymphoid marrow environment should raise suspicion of occult breast carcinoma metastasis. Due to the rarity of this coexistence, the underlying mechanisms and optimal management strategies are still unclear. To our knowledge, this is one of the few reported cases of occult ER-positive breast carcinoma presenting solely as bone marrow involvement in a patient with indolent B-cell lymphoma, with documented response to CDK4/6 inhibitor-based therapy. This case report was prepared in accordance with the CAse REport (CARE) guidelines.
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2026-06-10 | Combined Immunoglobulin Heavy- and Light-Chain Amyloidosis Associated With Waldenström Macroglobulinaemia: A Case Report With Diagnostic Challenges and a Favourable Treatment Outcome.
Waldenström macroglobulinaemia (WM) is a rare lymphoplasmacytic lymphoma that produces monoclonal IgM, and renal amyloidosis is an uncommon complication. Light-chain amyloidosis occurs more frequently than heavy-chain or combined heavy- and light-chain (AHL) amyloidosis. This report describes a woman with proteinuria in the nephrotic range, elevated IgM, and IgM kappa monoclonal protein in serum and urine. Kidney biopsy revealed AHL amyloidosis with IgM and kappa deposition. Laser microdissection-liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS) confirmed the presence of peptides from heavy and light chains. WM with renal amyloidosis was diagnosed, and the patient was started on bendamustine and rituximab. She had a significant hematologic response, achieving a very good partial response according to the international criteria. A renal response characterized by a reduction in proteinuria and stabilization of renal function was also observed. The patient remains asymptomatic after 43 months of follow-up. This case of WM with renal AHL amyloidosis highlights the importance of keeping renal amyloidosis in mind in patients with proteinuria. The favourable hematologic and renal response to treatment with bendamustine and rituximab in this case adds valuable data for the management of WM complicated by renal amyloidosis.
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