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Lymphoplasmacytic lymphoma (LPL) is a relatively rare form of indolent B-cell non-Hodgkin's lymphoma, termed Waldenström's macroglobulinaemia (WM) in the presence of an IgM paraprotein. Although traditionally treated with combination chemoimmunotherapy, the management is evolving in the era of targeted molecular therapies including Bruton's tyrosine kinase inhibitors (BTKi). However, intolerance and refractoriness to BTKi mean newer agents are required, and the prognosis of so-called quadruple-refractory patients is poor. BCL2 is an anti-apoptotic, pro-survival protein that promotes lymphoma cell survival. Inhibition of BCL2 using first-in-class agent venetoclax has already altered the treatment paradigm in other conditions, including chronic lymphocytic leukaemia (CLL). In-vivo inhibition of BCL2 has been shown to lead to apoptosis of LPL/WM cells. Five studies have published results on the use of BCL2 inhibitors in WM to date, including oblimersen sodium, venetoclax, and sonrotoclax. Fixed-duration venetoclax resulted in high response rates, but many patients relapsed following the completion of therapy. The combination of venetoclax with ibrutinib resulted in higher and relatively deep response rates, but unexpected deaths due to ventricular events mean this combination cannot be explored. Two pivotal trials are currently evaluating the use of fixed-duration venetoclax, either in combination with rituximab or pirtobrutinib, whereas another multi-arm study is studying the use of continuous sonrotoclax monotherapy for R/R WM or in fixed-duration combination with Zanubrutinib for treatment-naïve patients. The potential role of BCL2 inhibitors in WM/LPL remains under study, with many hopeful that they may provide an additional chemotherapy-free oral alternative for patients requiring treatment. In an indolent condition with existing effective treatment regimens, including CIT and cBTKi, cost-effectiveness and toxicity profile will be key, although an additional treatment modality for quadruple-refractory patients with limited treatment options is urgently required. [ABSTRACT FROM AUTHOR]

Lymphoplasmacytic lymphoma (LPL) is a relatively rare form of indolent B-cell non-Hodgkin’s lymphoma, termed Waldenström’s macroglobulinaemia (WM) in the presence of an IgM paraprotein. Although traditionally treated with combination chemoimmunotherapy, the management is evolving in the era of targeted molecular therapies including Bruton’s tyrosine kinase inhibitors (BTKi). However, intolerance and refractoriness to BTKi mean newer agents are required, and the prognosis of so-called quadruple-refractory patients is poor. BCL2 is an anti-apoptotic, pro-survival protein that promotes lymphoma cell survival. Inhibition of BCL2 using first-in-class agent venetoclax has already altered the treatment paradigm in other conditions, including chronic lymphocytic leukaemia (CLL). In-vivo inhibition of BCL2 has been shown to lead to apoptosis of LPL/WM cells. Five studies have published results on the use of BCL2 inhibitors in WM to date, including oblimersen sodium, venetoclax, and sonrotoclax. Fixed-duration venetoclax resulted in high response rates, but many patients relapsed following the completion of therapy. The combination of venetoclax with ibrutinib resulted in higher and relatively deep response rates, but unexpected deaths due to ventricular events mean this combination cannot be explored. Two pivotal trials are currently evaluating the use of fixed-duration venetoclax, either in combination with rituximab or pirtobrutinib, whereas another multi-arm study is studying the use of continuous sonrotoclax monotherapy for R/R WM or in fixed-duration combination with Zanubrutinib for treatment-naïve patients. The potential role of BCL2 inhibitors in WM/LPL remains under study, with many hopeful that they may provide an additional chemotherapy-free oral alternative for patients requiring treatment. In an indolent condition with existing effective treatment regimens, including CIT and cBTKi, cost-effectiveness and toxicity profile will be key, although an additional treatment modality for quadruple-refractory patients with limited treatment options is urgently required.

The B cell receptor (BCR) signaling pathway plays a crucial role in B cell development and contributes to the pathogenesis of B cell neoplasms. In B cell malignancies, the BCR is constitutively active through both ligand-dependent and ligand-independent mechanisms, resulting in continuous Bruton tyrosine kinase (BTK) signaling activation, which provides a survival and proliferation advantage to the neoplastic clone. Among B cell malignancies, those in which the most significant results were obtained by treatment with BTK inhibitors (BTKi) include chronic lymphocytic leukemia, mantle cell lymphoma, lymphoplasmacytic lymphoma, and diffuse large B cell lymphoma. Covalent BTKi (namely ibrutinib, acalabrutinib, and zanubrutinib) functions by irreversibly blocking BTK through covalent binding to the cysteine residue 481 (Cys-481) in the ATP-binding domain. Despite the high efficacy and safety of BTKi treatment, a significant fraction of patients affected by B cell malignancies who are treated with these drugs experience disease relapse. Several mechanisms of resistance to covalent BTKi, including Cys-481 mutations of BTK, have been investigated in B cell malignancies. Non-covalent BTKi, such as pirtobrutinib, have been developed and proven effective in patients carrying both Cys-481-mutated and unmutated BTK. Moreover, targeting BTK with proteolysis-targeting chimeras (PROTACs) represents a promising strategy to overcome resistance to BTKi in B cell neoplasms. [ABSTRACT FROM AUTHOR]

Background: Waldenstroms macroglobulinemia (WM) or Lymphoplasmacytic lymphoma is a rare B cell lymphoproliferative malignancy characterized by serum monoclonal immunoglobulin M (IgM) protein and lymphoplasmacytic infiltration in the bone marrow. Patients usually present in their seventh decade with symptoms related to the infiltration of the marrow or the effects of monoclonal IgM in the blood. Objective: Was to study the clinical characteristics and treatment outcome of patients diagnosed with WM. Materials and methods: This is a retrospective analysis of 26 cases of WM treated at a tertiary cancer centre. Results: WM constituted 0.68% of our nonHodgkin's lymphoma. The median age at presentation was 67 years with a male to female ratio of 2:1. Four patients had lymphadenopathy, six had splenomegaly and four patients had evidence of hyper viscosity. All patients had IgM paraproteinemia, the M band was IgM-kappa in 19 patients and IgM-lambda in seven patients. All patients had a histopathological confirmation. According to IPSS-WM, 12 patients each were in the intermediate and high risk group and 2 in the low risk group. Among the 26 patients, 20 patients received upfront treatment and four patients were kept under observation. The indications for treatment were cytopenia in ten patients, constitutional symptoms in five, hyper viscosity in four and symptomatic lymphadenopathy in one patient. Sixteen patients received rituximab-based chemotherapy. Four patients with features with hyper viscosity underwent plasmapheresis. The three year progression free survival and overall survival were 69.4% and 78 % respectively. Conclusions: WM is a low grade B cell lymphoproliferative disorder having an indolent course and do not require treatment for prolonged period. Diagnosis is challenging due to lack of distinct diagnostic features. Rituximab containing regimens are the standard of care. Newer targeted treatment options may improve the outcome of this incurable disease. [ABSTRACT FROM AUTHOR]

Introduction: Bing-Neel syndrome (BNS) is a rare and heterogenous manifestation of Waldenström macroglobulinemia (WM) involving central nervous system (CNS) infiltration by malignant lymphoplasmacytic cells. Efforts to standardize diagnostic criteria have improved in recent years, as have treatment options including the use of the Bruton tyrosine kinase inhibitor (BTKI) ibrutinib. Case Presentation: Here, we present the case of a 70-year-old male with a remote history of WM previously treated with bendamustine and rituximab, who presented to medical attention with several months of left-sided weakness, headache, and ataxia. Brain magnetic resonance imaging revealed numerous enhancing masses in the bilateral cerebral hemispheres, inferior medulla, and upper cervical spine. Laboratory studies showed serum IgM lambda monoclonal gammopathy and elevated free serum kappa and lambda light chains, while cerebrospinal fluid flow cytometry revealed CD19+ B cells. Stereotactic brain biopsy of a right frontal brain lesion was consistent with lymphoplasmacytic lymphoma, confirmed by a positive MYD88 L265P mutation. He received ibrutinib 420 mg orally daily, and this resulted in appreciable clinical and radiologic responses, which have persisted over a 31-month period. Conclusion: The advent of molecularly targeted agents and novel therapies for WM has provided patients and clinicians with additional therapeutic options. The use of BTK inhibitors with their high-level CNS penetrance, in particular, offers a novel way to treat BNS and improve patient overall survival while maintaining a high level of quality of life. We discuss the importance of MYD88 L265P testing in the context of BNS as well as the expanding role of BTKIs in treating this disease.

Waldenström macroglobulinemia (WM) rarely leads to pulmonary embolism. Due to its low incidence, the underlying pathophysiology, prognosis, and optimal treatment remain largely unexplored and uninvestigated. In this study, a patient with a double-clonal WM, a rare subtype, presented with pulmonary embolism. The patient had a small number of plasma cells without morphological abnormalities, and an effective therapeutic response was observed. Nonetheless, the clinical prognosis requires a long-term follow-up.

Waldenström macroglobulinemia (WM) is a rare, non-Hodgkin lymphoma that remains incurable. Rituximab, an anti-CD20 monoclonal antibody has been the cornerstone of treatment against WM, and its combination with an alkylator, bendamustine, achieves durable remission in treatment-naive patients with symptomatic WM. However, novel “druggable” targets that have been identified within the clonal lymphoplasmacytic cells in WM have resulted in a rapid development of targeted therapies in both the frontline and relapsed and refractory (R/R) settings. Several agents directed against the known targets have shown promising efficacy, with mostly manageable toxicities. The class of Bruton’s tyrosine kinase (BTK) inhibitors has transformed the therapeutic landscape for patients with WM, given their convenient oral dosing and strong efficacy, with high rates of attainment of very good partial response (VGPR). The tolerability of the next-generation BTK inhibitors appears to be superior to that of the first-in-class agent, ibrutinib. Targeted therapies from other classes have also demonstrated efficacy in both single-agent and combination regimens. Inhibitors of proteasome BCL-2, mTOR and PI-3 kinase have demonstrated efficacy in WM. Emerging therapies under investigation will continue to further shape the management paradigm, especially in the R/R setting. These include bispecific antibodies, radiotherapeutic agents and chimeric antigen receptor T-cell (CART) cell therapies. This review outlines the current literature and future direction of targeted therapies in WM.

The B cell receptor (BCR) signaling pathway plays a crucial role in B cell development and contributes to the pathogenesis of B cell neoplasms. In B cell malignancies, the BCR is constitutively active through both ligand-dependent and ligand-independent mechanisms, resulting in continuous Bruton tyrosine kinase (BTK) signaling activation, which provides a survival and proliferation advantage to the neoplastic clone. Among B cell malignancies, those in which the most significant results were obtained by treatment with BTK inhibitors (BTKi) include chronic lymphocytic leukemia, mantle cell lymphoma, lymphoplasmacytic lymphoma, and diffuse large B cell lymphoma. Covalent BTKi (namely ibrutinib, acalabrutinib, and zanubrutinib) functions by irreversibly blocking BTK through covalent binding to the cysteine residue 481 (Cys-481) in the ATP-binding domain. Despite the high efficacy and safety of BTKi treatment, a significant fraction of patients affected by B cell malignancies who are treated with these drugs experience disease relapse. Several mechanisms of resistance to covalent BTKi, including Cys-481 mutations of BTK, have been investigated in B cell malignancies. Non-covalent BTKi, such as pirtobrutinib, have been developed and proven effective in patients carrying both Cys-481-mutated and unmutated BTK. Moreover, targeting BTK with proteolysis-targeting chimeras (PROTACs) represents a promising strategy to overcome resistance to BTKi in B cell neoplasms.

Abstract Background Waldenström macroglobulinemia is a rare hematological malignancy and is the most common diagnosis in patients with hyperviscosity syndrome. Bilateral central retinal vein occlusion as an initial presentation of hyperviscosity syndrome in Waldenström macroglobulinemia is rare. Case presentation A 42-year-old Nepalese male presented with sudden-onset bilateral painless blurring of vision. Fundus examination revealed bilateral, diffusely dilated, tortuous retinal veins and intraretinal deep blot hemorrhages in all four quadrants of the retina in both eyes; features of bilateral central retinal vein occlusion. Serum electrophoresis showed hypoalbuminemia with an immunoglobulin M kappa monoclonal spike. Bone marrow picture and immunohistochemistry analysis were suggestive of lymphoplasmacytic lymphoma. The patient received systemic therapy for Waldenström macroglobulinemia, along with intravitreal bevacizumab. Conclusion Adequate hydration, plasmapheresis, and a combination of bortezomib, dexamethasone, and rituximab regimen as a systemic therapy may represent an ideal choice for patients with hyperviscosity in Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic disorder characterized by an IgM paraprotein. The clinical presentation of WM varies and can include common manifestations such as anemia and hyperviscosity, in addition to less common features such as cryoglobulinemia, IgM-related neuropathy, and immunoglobulin light chain (AL) amyloidosis. Amyloidosis is a protein-folding disorder in which vital organ damage occurs due to the accumulation of misfolded protein aggregates. The most common type of amyloidosis in patients with an IgM paraprotein is AL amyloidosis, although other types of amyloidosis may occur. IgM-related amyloidosis has distinct clinical features when compared with other subtypes of AL amyloidosis. This review highlights the diagnostic criteria of IgM-related AL amyloidosis, as well as the clinical characteristics and treatment options for this disorder.

Bing–Neel syndrome (BNS) is a rare neurological complication of Waldenström macroglobulinaemia. We highlight key issues in clinical presentation, diagnosis, and treatment while focusing on new and emerging therapies available for patients diagnosed with BNS. It is anticipated that further development of Bruton Tyrosine Kinase (BTK) inhibitors and less toxic chemoimmunotherapies will improve treatment delivery and response.

Abstract Lymphoplasmacytic lymphoma (LPL) and marginal zone lymphoma (MZL) frequently infiltrate the bone marrow with similar histologic and immunohistochemical characteristics posing diagnostic problems. Bone marrow biopsy specimens from 25 LPL and 16 MZL have been studied, correlating with clinical, laboratory parameters and the MYD88_p.L265P mutation. Paratrabecular and interstitial infiltration pattern, serum IgM paraprotein levels, and MYD88_p.L265P mutation were significantly more frequent in LPL. Nodular or intrasinusoidal pattern with lymphocytosis and splenomegaly were associated with MZL diagnosis. Different clinical and histological parameters should be collected when LPL or MZL is suspected in bone marrow biopsy specimens.

Abstract Waldenström macroglobulinemia (WM) is a rare, incurable low grade lymphoma following a relapsing trajectory. Management strategies have evolved with the introduction of targeted therapy including new classes of Bruton tyrosine kinase inhibitor (BTKi). Treatment may however be limited particularly at relapse by a lack of drug availability and tolerability. We assessed the real‐world efficacy and tolerability of bortezomib‐containing regimens in patients with WM at frontline and relapse including those with prior BTKi resistance. Forty‐one patients were identified with 44 bortezomib‐containing regimens administered (n = 12 frontline, n = 32 relapse). Of patients treated at relapse, the median prior lines of therapy was 3 (range 1–7). 24% (10/41) of the cohort were refractory or intolerant to BTKi prior to bortezomib delivery. The median follow‐up after bortezomib administration was 34 months (range 0‐131). Overall response rate was 88%; 2‐year overall survival and progression‐free survival were 90% (95% confidence interval [CI] 73–96) and 76% (95% CI 55–87), respectively. Median time‐to‐next‐treatment was 66 months. Neuropathy (grade 1–2) occurred in 24% (8/34) and did not result in treatment cessation in any case. Gastrointestinal disturbance occurred in 7% (3/41). Treatment discontinuations were rare (1/44; 2%), suggesting a manageable safety profile. Major response rate was comparable in those with prior BTKi compared with those without (75% [6/8] vs 84% [27/32], p = 0.61). Bortezomib should be considered as a treatment modality particularly in those who are refractory to BTKi.

Simple Summary: Waldenström's macroglobulinemia is a lymphoproliferative disorder rarely described in veterinary medicine. According to the human classification of hematopoietic tumors, this disease is defined as a subtype of lymphoplasmacytic lymphoma with bone marrow involvement and monoclonal gammopathy of IgM type. Cytopathology is a convenient and accurate diagnostic procedure to diagnose lymphoma in dogs. However, ancillary techniques, such as PCR for antigen receptor rearrangement, flow cytometry, immunohistochemistry, and histology, are usually required to fully characterize the grade and phenotype, especially in ambiguous cases. Immunosecretory lymphoproliferative disorders result from malignant clonal expansion of B-cells and are usually characterized by hyperglobulinemia, although normoglobulinemia can also occur, hypoglobulinemia being rarer. Monoclonal gammopathy can be suspected on serum protein electrophoresis as it usually migrates as a narrow peak in the γ or β fractions, but immunofixation is required for confirmation and characterization. This case report describes clinicopathologic features, diagnosis, treatment, and the outcome of Waldenström's macroglobulinemia in a 2-year-old neutered female Small Munsterlander dog with atypical bimorphic plasmacytoid differentiation and unusual M-protein migration on serum protein electrophoresis. A 2-year-old neutered female Small Munsterlander dog was presented for an insect bite. Physical examination revealed a poor body condition, a peripheral lymphadenomegaly, and suspected splenomegaly. A complete blood count (Sysmex XN-V) revealed marked leukocytosis with lymphocytosis and abnormal dot plots. An abnormal monomorphic lymphoid population and marked rouleaux formation were noted on the blood smear. Lymph node aspirates contained an atypical bimorphic population of lymphocytes, either with a plasmacytoid or a blastic appearance. This double population was also found in the spleen, liver, bone marrow, tonsils, and other tissues. Peripheral blood and lymph node clonality assays revealed clonal BCR gene rearrangement. Flow cytometry revealed a mixed population of small-sized B-cells (CD79a+ CD21+ MHCII+) and medium-sized B-cells (CD79a+ CD21− MHCII−) in lymph nodes and a dominant population of small-sized mature B-cells (CD21+ MHCII+) in peripheral blood. Though normoproteinemic, serum protein electrophoresis revealed an increased α2-globulin fraction with an atypical restricted peak, identified as monoclonal IgM by immunofixation. Urine protein immunofixation revealed a Bence-Jones proteinuria. A diagnosis of Waldenström's macroglobulinemia was made. Chemotherapy was initiated, but the dog was euthanized 12 months after the initial presentation due to marked clinical degradation. [ABSTRACT FROM AUTHOR]

Shashank Cingam,1 Surbhi Sidana2 1Division of Hematology and Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, 87102, USA; 2Division of BMT and Cell Therapy, Stanford University School of Medicine, Stanford, CA, 94305, USACorrespondence: Surbhi Sidana, Division of Blood and Marrow Transplant and Cellular Therapy, Stanford University School of Medicine, 300 Pasteur Drive, Room H0101c, Stanford, CA, 94305, USA, Tel +650 498-6000, Fax +650 725-3321, Email Surbhi.sidana@stanford.eduAbstract: Waldenström’s Macroglobulinemia (WM) is a clonal B-lymphocyte neoplasm characterized by the presence of IgM monoclonal protein and ≥ 10% bone marrow involvement with lymphoplasmacytic cells. Several mature B-cell and plasma cell disorders can potentially produce monoclonal IgM immunoglobulin and hence, careful consideration of the differential diagnosis is vital. Clinico-pathological features, immunophenotype, and MYD88 mutation status help distinguish WM from other plasma cell and lymphoproliferative disorders. Treatment is only indicated in patients symptomatic from adenopathy or organomegaly, neuropathy, hyper viscosity, cryoglobulinemia, cold agglutinin disease, cytopenia’s or amyloidosis. Alkylators (cyclophosphamide, bendamustine) in combination with anti-CD20 antibodies and novel targeted agents including Bruton tyrosine kinase (BTK) inhibitors like ibrutinib are the mainstay of frontline treatment in symptomatic WM.Keywords: Waldenström’s Macroglobulinemia, lymphoplasmacytic lymphoma, WM, LPL

Background: Waldenström macroglobulinemia is a rare hematological malignancy and is the most common diagnosis in patients with hyperviscosity syndrome. Bilateral central retinal vein occlusion as an initial presentation of hyperviscosity syndrome in Waldenström macroglobulinemia is rare. Case presentation: A 42-year-old Nepalese male presented with sudden-onset bilateral painless blurring of vision. Fundus examination revealed bilateral, diffusely dilated, tortuous retinal veins and intraretinal deep blot hemorrhages in all four quadrants of the retina in both eyes; features of bilateral central retinal vein occlusion. Serum electrophoresis showed hypoalbuminemia with an immunoglobulin M kappa monoclonal spike. Bone marrow picture and immunohistochemistry analysis were suggestive of lymphoplasmacytic lymphoma. The patient received systemic therapy for Waldenström macroglobulinemia, along with intravitreal bevacizumab. Conclusion: Adequate hydration, plasmapheresis, and a combination of bortezomib, dexamethasone, and rituximab regimen as a systemic therapy may represent an ideal choice for patients with hyperviscosity in Waldenström macroglobulinemia. [ABSTRACT FROM AUTHOR]

Introduction: Bing-Neel syndrome (BNS) is a rare and heterogenous manifestation of Waldenström macroglobulinemia (WM) involving central nervous system (CNS) infiltration by malignant lymphoplasmacytic cells. Efforts to standardize diagnostic criteria have improved in recent years, as have treatment options including the use of the Bruton tyrosine kinase inhibitor (BTKI) ibrutinib. Case Presentation: Here, we present the case of a 70-year-old male with a remote history of WM previously treated with bendamustine and rituximab, who presented to medical attention with several months of left-sided weakness, headache, and ataxia. Brain magnetic resonance imaging revealed numerous enhancing masses in the bilateral cerebral hemispheres, inferior medulla, and upper cervical spine. Laboratory studies showed serum IgM lambda monoclonal gammopathy and elevated free serum kappa and lambda light chains, while cerebrospinal fluid flow cytometry revealed CD19+ B cells. Stereotactic brain biopsy of a right frontal brain lesion was consistent with lymphoplasmacytic lymphoma, confirmed by a positive MYD88 L265P mutation. He received ibrutinib 420 mg orally daily, and this resulted in appreciable clinical and radiologic responses, which have persisted over a 31-month period. Conclusion: The advent of molecularly targeted agents and novel therapies for WM has provided patients and clinicians with additional therapeutic options. The use of BTK inhibitors with their high-level CNS penetrance, in particular, offers a novel way to treat BNS and improve patient overall survival while maintaining a high level of quality of life. We discuss the importance of MYD88 L265P testing in the context of BNS as well as the expanding role of BTKIs in treating this disease. [ABSTRACT FROM AUTHOR]

Lymphoplasmacytic lymphoma (LPL) is a low-grade B-cell neoplasm, composed of small B-lymphocytes, plasmacytoid lymphocytes, and plasma cells involving bone marrow and sometimes lymph nodes or spleen and forms 1% of all non-Hodgkin lymphomas. LPL with bone marrow involvement and an Immunoglobulin M (IgM) monoclonal gammopathy of any concentration is designated as Waldenström macroglobulinemia (WM). Due to their frequent co-occurrence, the terms LPL and WM are often used interchangeably in clinical practice. However, although the clinical diagnosis of WM is restricted to cases with an IgM monoclonal protein, the World Health Organization recognizes that LPL can rarely present with paraproteins of immunoglobulin G (IgG) or immunoglobulin A (IgA). LPL associated with non IgM gammopathies are extremely rare and form >5% of all LPLs. We hereby present the case of a 65-year-old female with no previous co morbidities who presented with nonspecific complaints of weight loss, easy fatigability, and night sweats. Examination was within the normal limits except for the presence of subcentimetric axillary lymphadenopathy. She was found to have anemia with an altered A/G ratio M spike of 2.10 g/which was IgG kappa on immunofixation electrophoresis. The bone marrow revealed a mixture of lymphocytes, lymphoplasmacytoid cells, and plasma cells along with the presence of amyloid deposits. MYD88 L265P mutation done on peripheral blood was positive, and based on these, she was diagnosed with a case of IgG Kappa LPL with associated amyloidosis.

CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature B-cell proliferations that are essential to accurately identify but can be difficult to diagnose. They comprise the majority of B-cell LPDs primary to the spleen, commonly presenting with splenomegaly and co-involvement of peripheral blood and bone marrow, but with little to no involvement of lymph nodes. Splenic marginal zone lymphoma is one of the prototypical, best studied, and most frequently encountered CD5-CD10-LPD of the spleen and typically involves white pulp. In contrast, hairy cell leukemia, another well-studied CD5-CD10-LPD of the spleen, involves red pulp, as do the two less common entities comprising so-called splenic B-cell lymphoma/leukemia unclassifiable: splenic diffuse red pulp small B-cell lymphoma and hairy cell leukemia variant. Although not always encountered in the spleen, lymphoplasmacytic lymphoma, a B-cell lymphoproliferative disorder consisting of a dual population of both clonal B-cells and plasma cells and the frequent presence of the MYD88 L265P mutation, is another CD5-CD10-LPD that can be seen in the spleen. Distinction of these different entities is possible through careful evaluation of morphologic, immunophenotypic, cytogenetic, and molecular features, as well as peripheral blood and bone marrow specimens. A firm understanding of this group of low-grade B-cell lymphoproliferative disorders is necessary for accurate diagnosis leading to optimal patient management.

Tarinee Rungjirajittranon, Yingyong Chinthammitr, Chattree Hantaweepant Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Chattree HantaweepantClinical Lecturer of Hematology, Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, ThailandTel +66 2-419-4448Email chattree.hantaweepant@gmail.comBackground: Acquired factor X deficiency is an uncommon condition, and affected individuals have severe and spontaneous bleeding. The associated conditions include malignancy, infection, burn, and inflammatory bowel disease. Many previous studies reported association between lymphoproliferative disease and factor X disappearance. Amyloid deposition causing factor X absorption was the most common mechanism. Here, we report a case of stage IV lymphoplasmacytic lymphoma (LPL) with factor X deficiency who was successfully treated with bendamustine plus rituximab (BR) regimen.Case Presentation: A 52-year-old Thai woman presented with heavy menorrhea, hoarseness, and widespread ecchymosis at her extremities. On physical examination, the patient had bilateral periorbital purpura and vocal cord hematoma. Coagulation testing showed prolonged prothrombin time (PT) and prolonged activated thromboplastin time (aPTT); however, after mixing with 1:1 normal pooled plasma, PT and aPTT were both corrected to normal levels. Factor assays demonstrated markedly decreased factor X levels, but no presence of factor X inhibitor. Bone marrow examination revealed numerous abnormal lymphoplasmacytoid lymphocytes with kappa light chain expression. Serum free light chain assay also showed kappa light chain restriction [kappa 716.16 mg/L, lambda 16.96 mg/L, ratio 42.23 (0.26– 1.65)]. The patient was diagnosed as lymphoplasmacytic lymphoma with factor X deficiency. She received chemotherapy with 6 cycles of bendamustine plus rituximab (BR) regimen. The patient responded favorably to treatment, she remains in lymphoma remission at one year after diagnosis, and her factor X level was more than 20%.Conclusion: We performed a literature review to identify previous case reports about lymphoma-associated factor X deficiency or inhibitor to determine a possible explanation in our patient. It is important to emphasize that when patients present with acquired factor deficiency, including factor X, lymphoproliferative disease is commonly one of the underlying conditions. Furthermore, the recovery of coagulation factor deficiency is possible if successful remission of lymphoma can be achieved.Keywords: factor X, lymphoproliferative disorder, lymphoplasmacytic lymphoma, amyloidosis

Abstract Background Primary malignant tumours of the retropharyngeal space are rare with only a few case reports in the literature. Lymphoplasmacytic lymphoma is a rare subtype of non-Hodgkin lymphoma and is very rarely found as a primary tumour of the retropharyngeal space. Case presentation We report the case of progressive upper airway obstruction in a 49-year-old male caused by a primary malignant tumour of the retropharyngeal space lymph nodes. He had an emergency tracheostomy to relieve the upper airway obstruction followed a week later by an elective surgical excision of the tumour via the trans-cervical route. A mixed population of lymphocytes, with a marked presence of Dutcher bodies, was noted on histopathology and positive CD20 on immunohistochemistry, confirming the lymphoplasmacytic lymphoma of the retropharyngeal space. The watchful waiting treatment method for the lymphoma was employed for him since he had no symptoms relating to lymphoma and no serum Waldenström’s macroglobulinemia. He has remained symptom-free 3 years post-surgery. Conclusion Primary malignant tumours involving the retropharyngeal space lymph nodes are very rare. They can rarely grow to a size huge enough to cause obstructive upper aerodigestive symptoms. Primary lymphoma of the retropharyngeal space should be considered in the diagnosis of the tumours involving the retropharyngeal space lymph nodes. Excisional biopsy is important to obtain tissue for histopathological diagnosis and the relief of upper aerodigestive tract obstruction when present.

Background: Anti-myelin-associated-glycoprotein (MAG) neuropathy is a distal, predominantly demyelinating, sensory or sensory-motor polyneuropathy most often developing in the context of an IgM-type monoclonal gammopathy due to monoclonal gammopathy of undetermined significance or lymphoplasmacytic lymphoma. Rituximab is considered standard therapy for treatment naïve patients, but optimal treatment methods for relapsed/refractory patients have not been established. Case presentation: We demonstrate that tirabrutinib, a second-generation Burton kinase inhibitor, led to drastic improvements of polyneuropathy that were affirmed by nerve conduction studies in a rituximab-refractory anti-MAG neuropathy patient. Tirabrutinib continues to give excellent disease control with no apparent adverse events at 11 months since initiation, and the patient remains free of plasmapheresis sessions which were originally mandatory. Conclusion: Tirabrutinib is an extremely promising treatment option for anti-MAG neuropathy.

Bing-Neel syndrome (BNS) is a rare presentation of Waldenström macroglobulinemia (WM). BNS is a consequence of the central nervous system (CNS) involvement by lymphoplasmacytic lymphoma (LPL) and, rarely, the peripheral nervous system. The data on BNS are extremely scarce. Therefore, we performed a multicenter retrospective analysis of BNS patients diagnosed and treated in centers aligned with the Polish Lymphoma Research Group. The analysis covers the years 2014–2021. Eleven patients were included, 55% females and the median age at BNS diagnosis was 61 years. The median time from WM to BNS was 3.5 years; 27% of patients did have a diagnosis of WM and BNS made simultaneously or within 30 days from each other. Isolated parenchymal involvement was the least frequent (20%). Patients were treated with different regimens, mostly able to cross the blood-brain barrier, including 18% treated with ibrutinib first line. The cumulative objective response to treatment was 73%. With the median follow-up of 20 months (95% CI, 2–32), the 36-month estimates were: overall survival (OS) 47%, progression-free survival (PFS) 33%, and cumulative incidence of BNS-associated death 41%. The performance status according to ECOG was significant for PFS (HR = 7.79) and the hemoglobin concentration below 11 g/dL was correlated with PFS. To conclude, BNS is a very rare manifestation of WM. It is associated with a poor outcome with most patients succumbing to BNS. [ABSTRACT FROM AUTHOR]

Dang Nguyen Van,1,2 Nghia Duong Van,1 Quang Le Van,1 Tung Ngo Thanh,2 To Ta Van3 1Department of Oncology, Hanoi Medical University, Hanoi, Vietnam; 2Department of Head and Neck Radiation Oncology, Vietnam National Cancer Hospital, Hanoi, Vietnam; 3Center of Pathology and Molecular Biology, Vietnam National Cancer Hospital, Hanoi, VietnamCorrespondence: Dang Nguyen VanDepartment of Oncology, Hanoi Medical University, 01 Ton That Tung Street, Dong Da District, Hanoi, 10000, VietnamTel +84 94 2727 899Email nguyenvandang@hmu.edu.vn; drdangnguyen@gmail.comBackground: Primary central nervous system (CNS) lymphoma is an uncommon non-Hodgkin disease limited to the CNS, and most cases are diffuse large B-cell lymphomas. Other pathologies, including lymphoplasmacytic lymphoma (LPL), are exceedingly rare and poorly understood. The clinical presentation of primary CNS LPL is diverse. It depends on the original site and the tumor’s extension. There is currently no consensus on a treatment strategy for this uncommon manifestation. To our knowledge, no previously published case was successfully treated with radiation therapy alone.Case Presentation: We present here a case of primary CNS LPL. A 46-year-old, previously healthy woman was presented with a worsening headache and lower extremity numbness. Multifocal enhanced masses were detected in an MRI with biopsy results consistent with LPL. A complete staging workup was performed with no evidence of systemic disease. The patient received external-beam radiotherapy alone and had a complete remission. After 2 years of follow-up, she remains disease-free.Conclusion: Radiation alone is a promising treatment option for primary CNS lymphoplasmacytic lymphoma.Keywords: lymphoplasmacytic lymphoma, primary CNS lymphoma, radiation therapy

Siriorn Sukanjanapong,1 Kumutnart Chanprapaph,1 Suthinee Rutnin,1 Paisan Boonsakan,2 Sulada Pukiat3 1Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Kumutnart ChanprapaphDivision of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, ThailandTel +66-2-2011141Fax +66-2-2011211Email kumutnartp@hotmail.comAbstract: Cutaneous macroglobulinosis is a rare manifestation of Waldenstrom macroglobulinemia when there is deposition of IgM in the dermis. The clinical presentation varies from skin colored to pink papules and ulcerative nodules on trunk, extensor surfaces of upper and lower limbs to hyperkeratotic lesions on the soles. We herein report a 78-year-old-male with Waldenstrom macroglobulinemia who presented with serpiginous purpura. The differential diagnoses included occlusion of vessel lumen by the lymphoplasmacytoid cells, high level of IgM or cryoglobulin, as well as small to medium vasculitis secondary to Waldenstrom macroglobulinemia. The histopathology revealed vasculopathy and vasculitis, while further immunohistochemistry highlighted deposition in the vessel lumen and vessel wall with IgM, suggesting the diagnosis of cutaneous macroglobulinosis. In this case report, we discuss this rare presentation and reviewed previous cases of cutaneous macroglobulinosis.Keywords: Waldenstrom macroglobulinemia, lymphoplasmacytic lymphoma, monoclonal gammopathy, vasculitis, vasculopathy

Lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) is an uncommon mature B cell lymphoma usually involving the bone marrow and, less commonly, the spleen and/or lymph nodes. This case presents a pathology-confirmed isolated extramedullary relapse of LPL, located in subcutaneous adipose tissue, 5 years after successful treatment of WM. [ABSTRACT FROM AUTHOR]

A 2-year-old neutered female Small Munsterlander dog was presented for an insect bite. Physical examination revealed a poor body condition, a peripheral lymphadenomegaly, and suspected splenomegaly. A complete blood count (Sysmex XN-V) revealed marked leukocytosis with lymphocytosis and abnormal dot plots. An abnormal monomorphic lymphoid population and marked rouleaux formation were noted on the blood smear. Lymph node aspirates contained an atypical bimorphic population of lymphocytes, either with a plasmacytoid or a blastic appearance. This double population was also found in the spleen, liver, bone marrow, tonsils, and other tissues. Peripheral blood and lymph node clonality assays revealed clonal BCR gene rearrangement. Flow cytometry revealed a mixed population of small-sized B-cells (CD79a+ CD21+ MHCII+) and medium-sized B-cells (CD79a+ CD21− MHCII−) in lymph nodes and a dominant population of small-sized mature B-cells (CD21+ MHCII+) in peripheral blood. Though normoproteinemic, serum protein electrophoresis revealed an increased α2-globulin fraction with an atypical restricted peak, identified as monoclonal IgM by immunofixation. Urine protein immunofixation revealed a Bence-Jones proteinuria. A diagnosis of Waldenström’s macroglobulinemia was made. Chemotherapy was initiated, but the dog was euthanized 12 months after the initial presentation due to marked clinical degradation.

Lymphoplasmacytic lymphoma is quite rare neoplasm of mature B lymphocytes. It accounts for less than 1% of Non Hodgkin Lymphoma in west. Its incidence is 10 times less in Asian countries.In majority of cases, patients have a circulating monoclonal IgM which is called Waldenström Macroglobulinemia. Less commonly, the tumor cells produce other immunoglobulins like gamma heavy chain or alpha heavy chain or combination of immunoglobulins (i.e. IgM and IgG). These cases are not properly defined and raises diagnostic challenges and often misdiagnosed as multiple myeloma. The purpose of this article is to report the description of an IgG lymphoplasmacytic lymphoma case which was diagnosed recently in the haematology department of Liaquat National Hospital and Medical College, Karachi.

Lymphoplasmacytic lymphoma (LPL) is a rare subtype of B cell-derived non-Hodgkin lymphoma characterized by the abnormal growth of transformed clonal lymphoplasmacytes and plasma cells. This tumor almost always displays the capability of secreting large amounts of monoclonal immunoglobulins (Ig) of the M class (Waldenström Macroglobulinemia, WM). The clinical manifestations of WM/LPL may range from an asymptomatic condition to a lymphoma-type disease or may be dominated by IgM paraprotein-related symptoms. Despite the substantial progresses achieved over the last years in the therapy of LPL/WM, this lymphoma is still almost invariably incurable and exhibits a propensity towards development of refractoriness to therapy. Patients who have progressive disease are often of difficult clinical management and novel effective treatments are eagerly awaited. In this review, we will describe the essential clinical and pathobiological features of LPL/WM. We will also analyze some key aspects about the current knowledge on the mechanisms of drug resistance in this disease, by concisely focusing on conventional drugs, monoclonal antibodies and novel agents, chiefly Bruton's Tyrosine Kinase (BTK) inhibitors. The implications of molecular lesions as predictors of response or as a warning for the development of therapy resistance will be highlighted. [ABSTRACT FROM AUTHOR]

Lymphoplasmacytic lymphoma is quite rare neoplasm of mature B lymphocytes. It accounts for less than 1% of Non Hodgkin Lymphoma in west. Its incidence is 10 times less in Asian countries. In majority of cases, patients have a circulating monoclonal IgM which is called Waldenström Macroglobulinemia. Less commonly, the tumor cells produce other immunoglobulins like gamma heavy chain or alpha heavy chain or combination of immunoglobulins (i.e. IgM and IgG). These cases are not properly defined and raises diagnostic challenges and often misdiagnosed as multiple myeloma. The purpose of this article is to report the description of an IgG lymphoplasmacytic lymphoma case which was diagnosed recently in the haematology department of Liaquat National Hospital and Medical College, Karachi. [ABSTRACT FROM AUTHOR]

CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature B-cell proliferations that are essential to accurately identify but can be difficult to diagnose. They comprise the majority of B-cell LPDs primary to the spleen, commonly presenting with splenomegaly and co-involvement of peripheral blood and bone marrow, but with little to no involvement of lymph nodes. Splenic marginal zone lymphoma is one of the prototypical, best studied, and most frequently encountered CD5-CD10-LPD of the spleen and typically involves white pulp. In contrast, hairy cell leukemia, another well-studied CD5-CD10-LPD of the spleen, involves red pulp, as do the two less common entities comprising so-called splenic B-cell lymphoma/leukemia unclassifiable: splenic diffuse red pulp small B-cell lymphoma and hairy cell leukemia variant. Although not always encountered in the spleen, lymphoplasmacytic lymphoma, a B-cell lymphoproliferative disorder consisting of a dual population of both clonal B-cells and plasma cells and the frequent presence of the MYD88 L265P mutation, is another CD5-CD10-LPD that can be seen in the spleen. Distinction of these different entities is possible through careful evaluation of morphologic, immunophenotypic, cytogenetic, and molecular features, as well as peripheral blood and bone marrow specimens. A firm understanding of this group of low-grade B-cell lymphoproliferative disorders is necessary for accurate diagnosis leading to optimal patient management. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is often differentiated from myeloma based on the presence of lytic bone lesions (LBL). However, WM/LPL can present with LBL, and management is poorly understood. We describe a case of an 81‐year‐old woman with LPL who presented with LBL and was successfully treated with chemoimmunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Lymphoplasmacytic lymphoma (LPL) is a rare low-grade B-cell neoplasm that accounts for approximately 2% of all haematological malignancies. Most patients have the clinical syndrome of Waldenstrom macroglobulinemia (WM), which is defined as LPL with an associated immunoglobulin M (IgM) serum monoclonal protein. Roughly 5% of LPL patients secrete non-IgM paraproteins (e.g., IgG, IgA, kappa, lambda) or are non-secretory. Case description: We report the case of a 41-year-old woman who was diagnosed with non-IgM LPL with lambda light chain monoclonal paraprotein production and normal serum immunoglobulin levels. The MYD88 L265P mutation was detected on fluorescence in-situ hybridization (FISH) analysis of the bone marrow. The patient underwent treatment with a combination of ibrutinib and rituximab. There was an initial response but she died 8 months after diagnosis. Discussion: Non-IgM LPL poses diagnostic and therapeutic challenges to clinicians as it is an exceptionally rare malignancy with a heterogeneous clinicopathological presentation and scarce literature. Among non-IgM LPL cases, those with lambda light chain production are even more rare. To the best of our knowledge, none have been reported to date. The addition of MYD88 L265P testing to the diagnostic armamentarium of non-IgM LPL cases is advisable for potential therapeutic reasons.

Lymphoplasmacytic lymphoma (LPL) is a rare subtype of B cell-derived non-Hodgkin lymphoma characterized by the abnormal growth of transformed clonal lymphoplasmacytes and plasma cells. This tumor almost always displays the capability of secreting large amounts of monoclonal immunoglobulins (Ig) of the M class (Waldenström Macroglobulinemia, WM). The clinical manifestations of WM/LPL may range from an asymptomatic condition to a lymphoma-type disease or may be dominated by IgM paraprotein-related symptoms. Despite the substantial progresses achieved over the last years in the therapy of LPL/WM, this lymphoma is still almost invariably incurable and exhibits a propensity towards development of refractoriness to therapy. Patients who have progressive disease are often of difficult clinical management and novel effective treatments are eagerly awaited. In this review, we will describe the essential clinical and pathobiological features of LPL/WM. We will also analyze some key aspects about the current knowledge on the mechanisms of drug resistance in this disease, by concisely focusing on conventional drugs, monoclonal antibodies and novel agents, chiefly Bruton’s Tyrosine Kinase (BTK) inhibitors. The implications of molecular lesions as predictors of response or as a warning for the development of therapy resistance will be highlighted.

Abstract Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is often differentiated from myeloma based on the presence of lytic bone lesions (LBL). However, WM/LPL can present with LBL, and management is poorly understood. We describe a case of an 81‐year‐old woman with LPL who presented with LBL and was successfully treated with chemoimmunotherapy.

Waldenström's macroglobulinemia (WM) is a B-cell non-Hodgkin's lymphoma characterized by clonal IgM-secreting lymphoplasmacytic cell proliferation. Bing-Neel syndrome (BNS) is a rare complication of WM that results in the infiltration of the central nervous system (CNS) with IgM-secreting lymphoplasmacytic cells. This case study presents a 75-year-old Caucasian male with a history of WM and Agent Orange exposure who ultimately was diagnosed with BNS. This patient posed unique diagnostic challenges as the patient experienced clinical symptoms despite the absence of MRI abnormalities and therapeutic challenges., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kotlarz et al.)

Waldenström macroglobulinemia (WM) is an infrequent variant of lymphoma, classified as a B-cell malignancy identified by the presence of IgM paraprotein, infiltration of clonal, small lymphoplasmacytic B cells in the bone marrow, and the MYD88 L265P mutation, which is observed in over 90% of cases. The direct invasion of the malignant cells into tissues like lymph nodes and spleen, along with the immune response related to IgM, can also lead to various health complications, such as cytopenias, hyperviscosity, peripheral neuropathy, amyloidosis, and Bing-Neel syndrome. Chemoimmunotherapy has historically been considered the preferred treatment for WM, wherein the combination of rituximab and nucleoside analogs, alkylating drugs, or proteasome inhibitors has exhibited notable efficacy in inhibiting tumor growth. Recent studies have provided evidence that Bruton Tyrosine Kinase inhibitors (BTKI), either used independently or in conjunction with other drugs, have been shown to be effective and safe in the treatment of WM. The disease is considered to be non-curable, with a median life expectancy of 10 to 12 years., Competing Interests: Competing interests: Michele Bibas declares no conflict of interest. Shayna Sarosiek: Research funds or honoraria from ADC Therapeutics, Beigene, and Cellectar. J.J. Castillo: Research funds and/or consulting fees from Abbvie, AstraZeneca, Beigene, Cellectar, Janssen, Loxo, Mustang Bio, and Pharmacyclics.

Background: Primary central nervous system (CNS) lymphoma is an uncommon non-Hodgkin disease limited to the CNS, and most cases are diffuse large B-cell lymphomas. Other pathologies, including lymphoplasmacytic lymphoma (LPL), are exceedingly rare and poorly understood. The clinical presentation of primary CNS LPL is diverse. It depends on the original site and the tumor's extension. There is currently no consensus on a treatment strategy for this uncommon manifestation. To our knowledge, no previously published case was successfully treated with radiation therapy alone. Case Presentation: We present here a case of primary CNS LPL. A 46-year-old, previously healthy woman was presented with a worsening headache and lower extremity numbness. Multifocal enhanced masses were detected in an MRI with biopsy results consistent with LPL. A complete staging workup was performed with no evidence of systemic disease. The patient received external-beam radiotherapy alone and had a complete remission. After 2 years of follow-up, she remains disease-free. Conclusion: Radiation alone is a promising treatment option for primary CNS lymphoplasmacytic lymphoma. [ABSTRACT FROM AUTHOR]

Primary haematological neoplasms of the larynx are uncommon; therefore, information regarding their epidemiology is limited and the diagnosis of histological types requires careful consideration. The current study describes the case of a 72-year-old male patient with primary laryngeal lymphoplasmacytic lymphoma (LPL) that was difficult to distinguish from plasmacytoma. Imaging examinations of the neck revealed a mass in the right laryngeal folds, 25×12×25 mm in size, which was surgically resected by direct laryngoscopy. Histopathologically, the mass showed diffuse proliferation of plasma cells with CD138 (+) and IgG (+) in the submucosal stroma. Flow cytometry revealed the tumour was positive for CD19 and negative for CD56. Based on these findings, the final diagnosis was confirmed as LPL, albeit similar to plasmacytoma regarding phenotypic features. There was no evidence of local or systemic recurrence following surgery, and the patient has been followed up without additional treatment. This case highlights the unique presentation of laryngeal lymphoma mimicking solitary plasmacytoma. The key factor in the diagnosis was the expression pattern of surface antigen markers. [ABSTRACT FROM AUTHOR]

Waldenstrom Macroglobulinemia (WM) is an indolent lymphoproliferative disorder characterised by Immunoglobulin M (IgM) production and neoplastic lymphoid infiltrate. The morphology of the neoplastic cells show spectrum of maturation characterised by small lymphocytes, lymphoplasmacytoid cells and plasma cells. The infiltrate is predominantly lymphoid with relatively small population of plasma cells. The plasma cell morphology is commonly of mature type with basophilic cytoplasm, eccentric nucleus with clumped chromatin and perinuclear halo (hof). But incidence of signet ring cells in WM is very rare and only one case has been reported till date. Here, authors report an interesting case of a 61-year-old man who presented with on and off chest pain and later diagnosed as WM with signet ring cells. On examination, the patient was found to have anaemia and lymphadenopathy. Bone marrow aspirate cytology showed hypercellular particles and scattered signet ring like plasma cells with large globular cytoplasmic inclusions. Flow Cytometry (FCM) established the diagnosis by demonstrating the clonal nature of plasma cells and B-lymphoid cells. Immunofixation confirmed the presence of monoclonal protein of IgM lambda type. The cytoplasmic content in these signet ring plasma cells is probably the accumulated IgM due to the defect in releasing. Clustering of these signet ring cells in marrow may raise a suspicion of metastatic adenocarcinoma and should not be misinterpreted.

Waldenstrӧm Macroglobulinemia (WM) is a rare B-cell malignancy characterized by lymphoplasmacytic lymphoma (LPL) involvement of the bone marrow with an IgM monoclonal gammopathy. We present a case of Parkinson-like symptoms, in which diagnostic workup including imaging, biopsy, and lumbar puncture revealed both an LPL manifesting as a cervical spine mass and central nervous system involvement of LPL (termed Bing Neel syndrome) as the etiologies of the patient's presenting symptoms. Ibrutinib was administered, at a lower dose of 280 mg, due to the patient's history of arrhythmias, in combination with radiation to the cervical spine mass and steroids. Four weeks later, the patient's symptoms had completely resolved. This case highlights a rare presentation of LPL as well as the efficacy of ibrutinib.

A 60-year-old man was admitted for ground glass opacity in the lower lung field and mediastinal lymphadenopathy. Blood tests revealed elevated serum IgM levels, and the urine test detected Bence-Jones protein. Surgical biopsy from the mediastinal lymph node and lung showed small lymphocytes and plasma cells between follicles, and AL kappa amyloid deposition. Genetic examination detected MYD88 L265P mutation. Our diagnosis was lymphoplasmacytic lymphoma (LPL), involving the mediastinum and the lung, followed by amyloidosis. Mutation analysis, in addition to conventional histological evaluation, was useful for a precise diagnosis.

Objectives: Lymphoplasmacytic lymphoma (LPL) is a mature B cell lymphoma that usually involves the bone marrow, spleen and lymph nodes. Extramedullary involvement, including the lung, is rarely reported. Case description: A 73-year-old female initially presented to our hospital complaining of productive cough of white-colour sputum for three weeks duration. She reported unintentional weight loss of ten pounds over the last five months. There was no history of haemoptysis, fever, night sweats, chills, recent infections or hospitalization. Chest imaging showed right lower lobe consolidation, small right pleural effusion. She was treated with oral antibiotic for pneumonia. After two months, a follow up chest imaging revealed persistent right lower lobe consolidation. Therefore, she was worked up for the possibility of malignancy. Bronchoscopy showed polypoid nodularities surrounded by black discoloured mucosa in the sub-segmental bronchi of the right lower lobe, and biopsy specimen revealed atypical B cell lymphocytic infiltrate. Polymerase chain reaction confirmed a clonal B-cell gene rearrangement supportive for a low-grade B-cell Lymphoma. Subsequently; serum immunofixation showed IgM of 1491 mg/dL (normal range 26–217 mg/dl) with normal levels of IgG and IgA. Urine contained free kappa light chains. Cytology with immunophenotyping of pleural fluid revealed lymphoplasmacytic lymphocytes. This combination of lab and bronchoscopy findings established the diagnosis of extramedullary Waldenström’s macroglobulinemia. Conclusion: Waldenström’s macroglobulinemia, a manifestation of LPL, is associated with an IgM monoclonal gammopathy in the blood. Extramedullary involvement including the lung is rarely seen in LPL. Physicians need to be aware of this rare presentation.

Waldenstrom macroglobulinemia (WM) is a variant of lymphoplasmacytic lymphoma. In WHO classification of hematolymphoid malignancy 2016, WM has been placed in between lymphoma and plasma cell myeloma under the broad heading “Neoplasms of mature lymphocytes”. This is a rare and slowly progressive disorder, which needs therapy only when symptoms appear. The average age of diagnosis is 60–70 years. WM may progress to lymphoma in 2% cases per year. Here, we are discussing a case of WM having typical findings of this rare disease, who presented with 10%–12% plasma cell in bone marrow aspirate smear, high immunoglobulin M, high beta 2 microglobulin, bilateral axillary lymphadenopathy and gastrointestinal bleeding. At present, the patient is on chlorambucil plus prednisolone therapy and is doing well. Typically, this case presented with lesions of herpes zoster, which makes this case further uncommon.

Anti-low-density lipoprotein receptor-related lipoprotein 2 (LRP2) nephropathy/anti-brush border antibody disease is rare and characterized by tubular basement membrane, Bowman's capsule and glomerular subepithelial immune deposits on kidney biopsy. No reported cases have occurred in patients with lymphoproliferative disorders or monoclonal gammopathies. We present two cases of anti-LRP2 nephropathy that occurred in patients with progressive low-grade B-cell lymphoma and had concurrent kidney infiltration by lymphoma on biopsy. We speculate that underlying immune dysregulation related to lymphoma may contribute to the development of this rare autoimmune kidney disease in some patients. [ABSTRACT FROM AUTHOR]

The development of malignant neoplasms over the site of pacemaker implantation is a rare event, with a limited number of published case reports. We report the case of a 78-year-old male who presented with discomfort and pocket mass expansion, reportedly following trauma. Due to initial presumption of a simple hematoma, dissection and drainage were performed without tissue collection for histology. Later presentation with an exophytic ulcerated mass led to biopsy and identification of a lymphoplasmacytic lymphoma. To the best of our knowledge this is the first reported case of a cutaneous lymphoplasmacytic lymphoma presenting as a pacemaker pocket mass, and underlines the importance of systematic pacemaker inspection, of adequate histological characterization and of a high degree of clinical suspicion for the identification malignancy in this context. < Learning objective: We report the first case of a lymphoplasmacytic lymphoma presenting primarily as a pacemaker pocket mass. Lymphoplasmacytic lymphoma is a rare and indolent subtype of Non-Hodgkin lymphoma that may present with cutaneous manifestations. Due to the extreme rarity of malignant neoplasms presenting as pacemaker pocket masses, a high degree is clinical suspicion is required, and tissue histology plays a key role in the diagnosis.> [ABSTRACT FROM AUTHOR]