Lymphoplasmacytic lymphoma: clinical analysis of 33 cases / 白血病·淋巴瘤

Objective:To investigate the clinicopathological characteristics and survival of patients with lymphoplasmacytic lymphoma (LPL).Methods:The data of 33 newly diagnosed LPL patients in the First Affiliated Hospital of Dalian Medical University from July 2003 to May 2021 were retrospectively analyzed. The clinical characteristics, bone marrow cell morphology, immunophenotyping, chromosomal karyotype, gene mutation, treatment response and prognosis were analyzed, and Kaplan-Meier method was used to analyze the survival of patients.Results:The median age of onset of 33 patients was 66 years old (55-84 years old). There were 26 males (78.8%) and 7 females (21.2%). The common clinical manifestations were anemia (31 cases, 93.9%), enlarged lymph nodes (16 cases, 48.5%) and B symptoms (8 cases, 24.2%). All patients had bone marrow involvement and M protein, 23 of them (69.7%) were type IgM-κ, 8 cases (24.2%) were type IgM-λ, 1 case (3.0%) was type IgG-κ, and 1 case (3.0%) was type IgA-κ. Lymphocytes, lymphoplasmacytes or plasma cells was increased in bone marrow smear; 22 patients underwent immunophenotyping of bone marrow by flow cytometry, and all patients expressed B cell surface antigens (CD19 and CD20), 16 patients (72.7%) lost the expression of CD5 and CD10, 13 patients (59.1%) expressed or weakly expressed CD138 and 5 patients (22.7%) expressed CD38. Seven out of 23 cases (30.4%) who received chromosome examination had abnormal chromosomal karyotype. Fourteen out of 16 cases (87.5%) who received MYD88 L265P mutation detection harbored the mutation. Among 21 patients with evaluable efficacy, 18 patients (85.7%) responded to treatment, achieving partial remission or stable disease, but the rate of complete remission was low (14.3%, 3/21). The median follow-up time was 34 months (2-102 months), 1 case was lost. The median overall survival time was not reached, and the 3-year and 5-year overall survival rates were 79.2% and 67.9%, respectively.Conclusions:LPL is a rare indolent small B-cell lymphoma with a long course and a variety of manifestations, which is commonly seen in elderly men.Serological examination, bone marrow cell morphology and biopsy, immunophenotyping and MYD88 L265P mutation detection are important for the diagnosis and differential diagnosis.

A Case of Lymphoplasmacytic Lymphoma/Waldenström's Macroglobulinemia with IgM-κ and IgA-λ Biclonal Gammopathy

Lymphoplasmacytic lymphoma (LPL) is a low-grade B-cell neoplasm, composed of small B lymphocytes, plasmacytoid lymphocytes, and plasma cells, usually involving bone marrow and sometimes lymph nodes or spleen. LPL with bone marrow involvement and an IgM monoclonal gammopathy of any concentration is designated as Waldenström macroglobulinemia (WM). LPL associated with non-IgM monoclonal gammopathy or biclonal gammopathy is rarely observed. LPL diagnosis was based on clinical, morphological, and immunophenotypic findings. Recently, the test for L265P mutation of the myeloid differentiation factor 88 (MYD88) gene has been helpful in the diagnosis of LPL. Here, we reported the first case of LPL/WM with IgM-κ/IgA-λ biclonal gammopathy in Korea.

Changes of blood coagulation indicators in patients with lymphoplasmacytic lymphoma and their clinical significances / 白血病·淋巴瘤

Objective To observe the alteration and clinical significances of blood coagulation indicators in patients with lymphoplasmacytic lymphoma (LPL). Methods Twenty patients who were newly diagnosed LPL in the First People's Hospital of Changzhou from January 2008 to October 2017 and twenty healthy controls were studied. The patients were treated by chemotherapy, plasma exchange, supplement of coagulation factor or other supportive therapy. The parameters of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-dimer (D-D), and platelet count (Plt) were detected in LPL group and healthy controls. Results The levels of PT and APTT in LPL group were dramatically higher than those in control group [(12.9±1.2) s vs. (11.6±0.9) s, (41.7±9.8) s vs. (24.7±2.9) s], and the level of Plt in LPL group was lower than that in control group [112×109/L (3×109/L - 379×109/L) vs. 210×109/L (170×109/L - 271×109/L)], and the differences were statistically significant (all P< 0.05). There were no significant differences in FIB, TT and D-D levels between LPL group and control group (all P ＞0.05). There were no statistical differences in PT, APTT, FIB, TT, D-D and Plt levels among LPL patients with different types of immunoglobins (all P ＞ 0.05). After treatment, all the coagulation abnormalities got relieved and no patient died of hemorrhage or thrombosis. Conclusions The LPL patients have coagulation disorders and hypercoagulability, and this is independent of the type of immunoglobulin. Clinical attention should be paid to monitoring coagulation indicators to prevent the occurrence of adverse reactions.

Progress of myeloid differentiation factor 88 L265P mutation in B-cell proliferative neoplasms / 白血病·淋巴瘤

Myeloid differentiation factor 88 (MYD88) is a key linker in the Toll-like receptor (TLR) signaling pathway, which plays an important role in the progression of the tumour. Recent studies have shown that the activating mutation of MYD88 L265P has been identified in about of 90% lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia and about of 40% diffuse large B-cell lymphoma and other subtypes of B-cell proliferative neoplasms. Different types of B-cell proliferative neoplasms have their own histology, immunohistochemistry and clinical characteristics, thus, mutation rates of MYD88 L265P are different. This review discusses the latest progress of MYD88 L265P mutation in B-cell proliferative neoplasms.

Clinical features and survival outcomes of patients with lymphoplasmacytic lymphoma, including non-IgM type, in Korea: a single-center experience

BACKGROUND: The incidence of lymphoplasmacytic lymphoma (LPL) is lower in Asian than in Western populations. Few studies have described the clinical features and treatment outcomes of patients with LPL, including non-IgM LPL, in East Asia. METHODS: We retrospectively analyzed patients diagnosed with LPL at Asan Medical Center between January 2001 and March 2016. We evaluated the clinical features and survival outcomes of patients with LPL and non-IgM LPL and compared these data with those of patients with LPL/Waldenström's macroglobulinemia (WM). RESULTS: The median age at diagnosis of patients with LPL was 61.5 years (range, 34–77 yr); most patients were male (91%). Approximately three-quarters of the 22 patients with LPL were in the low or intermediate risk groups according to the International Prognostic Scoring System for Waldenström's Macroglobulinemia classification. The median follow-up duration was 75 months [95% confidence interval (CI), 48–102 mo], and the median overall survival (OS) was 81 months (95% CI, 0–167 mo). The number of patients in the non-IgM LPL group who exhibited extramedullary involvement was higher than in the LPL/WM group. OS of the LPL/WM group was improved compared with that of the non-IgM LPL group [median not reached vs. 10.0 mo (95% CI, 0–36.7); P=0.05]. CONCLUSION: We present a single-center experience of 22 patients with LPL, including a non-IgM cohort, in Korea. The treatment of non-IgM LPL was heterogeneous, and patients with non-IgM LPL showed a higher 5-year mortality rate and more adverse prognostic factors than those with LPL/WM.

Plasmacytic or lymphoplasmacytic infiltrate in lymph nodes: Diagnostic approach and differential considerations.

Plasmacytosis is a common finding in lymph node biopsies and can be seen in diverse circumstances ranging from reactive lymphadenopathy to malignant lymphoma. Familiarity with various histopathologic features of the different entities and awareness of their typical clinical and ancillary study findings are essential for an accurate diagnosis. In this review, we present common and representative nonneoplastic entities and lymphomas that have plasmacytic differentiation or associated plasmacytosis. We focus on the histological classification with an emphasis on the diagnostic approach and areas of diagnostic challenge.

Detection of MYD88 L265P in patients with lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia and other B-cell non-Hodgkin lymphomas

BACKGROUND: Recent studies have identified a high prevalence of the MYD88 L265P mutation in lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) cases, whereas low frequencies have been observed in other B cell non-Hodgkin lymphomas (NHLs). METHODS: We evaluated the sensitivity of the mutant enrichment 3'-modified oligonucleotide (MEMO)-PCR technique, a new detection method. We examined the MYD88 L265P mutation in a series of Korean patients with LPL/WM and other B cell NHLs in bone marrow aspirates, using the MEMO-PCR technique. RESULTS: The sensitivity of MEMO-PCR was estimated to be approximately 10-16.7%. MYD88 L265P was detected in 21 of 28 LPL cases (75%) and only three of 69 B cell NHL cases (4.3%). CONCLUSION: Although MEMO-PCR had relatively low sensitivity, we confirmed the high prevalence of the MYD88 L265P mutation in Korean LPL patients. Our study suggests the diagnostic value of MYD88 L265P for differentiating B-cell NHLs.

Waldenstrom Macroglobulinemia with CD5+ Expression Presented as Cryoglobulinemic Glomerulonephropathy: A Case Report

Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.

Aspectos morfológicos da infiltração da medula óssea por condições exibindo diferenciação plasmocitária e gamopatia monoclonal / Morphological aspects of bone marrow infiltration by diseases characterized by plasma cell proliferation and monoclonal gamopathy

As doenças linfoproliferativas com diferenciação plasmocitária e pico monoclonal são causas de dificuldade diagnóstica no estudo de espécimes de medula óssea. Conhecer os aspectos clínicos, morfológicos, imunofenotípicos e citogenéticos é fundamental para o diagnóstico correto. Descrevemos os aspectos práticos mais relevantes para a interpretação de biópsias de medula óssea frente às situações mais frequentes.

Some lymphoproliferative diseases with plasma cell differentiation and monoclonal gammopathy are challenging to diagnose when dealing with bone marrow biopsies. Knowledge of clinical, morphological, phenotypic and cytogenetic aspects is crucial to establish the correct diagnosis. We describe practical relevant aspects that help in the interpretation of bone marrow biopsies in these situations.