Diagnosis Of B-cell Lymphoproliferative Disorders Research Articles

The Use of CD200 in the Differential Diagnosis of B-Cell Lymphoproliferative Disorders.

Background: B-Cell Lymphoproliferative Disorders (B-LPDs) are a group of heterogenous disorders characterised by the accumulation of B-cells in peripheral blood, bone marrow, lymph nodes and spleen. They have a variable disease course and outcome and many share similar features making differential diagnosis challenging. Therefore, accurate diagnosis is fundamental in particular for determining treatment options. Immunophenotyping by flow cytometry plays a crucial role in the diagnosis of B-LPDs. However, overlapping immunophenotyping patterns exist and the use of novel monoclonal antibodies has become increasingly important in immunophenotyping analysis. More recently differential expression of CD200 has been reported in various B-LPDs and that CD200 may improve the differentiation between chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL). In this study CD200 expression is evaluated in different B-LPDs. Methods: A total of 100 samples were collected and analysed by immunophenotyping flow cytometry over a period of 1year (2017-2018), by a panel of monoclonal antibodies including CD200. The percentage of CD200 and its expression intensity was evaluated and compared between different groups of B-LPDs. Results: All of the 50 cases of CLL expressed CD200 with moderate to bright intensity, 6 MCL cases lacked the expression of CD200. Furthermore, all 5 cases of hairy cell leukaemia (HCL) expressed CD200. Out of all B-LPDs evaluated, CD200 expression in HCL cases was noted to be the brightest. The other 39 cases were not found to be B-LPDs. Conclusion: CD200 has an important role in differentiating CLL from MCL, HCL has a consistent bright expression of CD200. By adding CD200 to the combinations of markers in routine testing panel, Immunophenotyping by flow cytometry can be an effective tool in the diagnosis of B-LPDs especially in cases with atypical immunophenotyping pattern. Our result support that CD200 can be added to routine testing panel as it is useful in differentiating them.

Low-Grade B Cell Lymphoproliferative Disorder Masquerading as Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is one of the most common persistent disorders of the developed world, requiring input from various specialists including primary care physicians, otolaryngologists, respiratory physicians, and allergologists. B-cell lymphoproliferative disorders (BLPDs) are a heterogenous group of malignant conditions defined by an accumulation of mature B lymphocytes in the bone marrow, blood, and lymphoid tissues. We present a case report of an elderly man with rhinosinusitis-like symptoms and atypical features prompting further investigations that culminated in a diagnosis of BLPD.

Consistency of the Moreau CLL score.

The Moreau score is essential for the diagnosis of B-cell lymphoproliferative disorders (B-LPD). We assessed the consistency of the Moreau score in a series of 138 patients with at least two samples involved by a B-LPD (316 samples) other than germinal center-derived malignancies, hairy cell leukemia, and mantle cell lymphomas. Patients with evidence of two distinct B-LPDs were also excluded. We found 53 inconsistencies in 44 of 138 (32%) patients. FMC7 was the most inconsistent (18 cases) and CD5 the least (5 cases). CD200 was inconsistent in 6 of 67 (9%) cases. The most important predictive factor for the finding of antigenic inconsistencies was sampling of a different anatomic site. Other factors, including number of samples, time between samples, or cytogenetic group, were not predictive. For the most part, these inconsistencies did not appear to be clinically relevant. Inconsistencies in the Moreau score are common, supporting the importance of integrated laboratory diagnosis. However, the practical implications of these antigenic inconsistencies are probably limited.

Hairy Cell Leukemia: Evaluation of Long-Term Outcomes in 487 Patients

AbstractAbstract 3921 Introduction:Hairy cell leukemia (HCL) is a rare hematologic disorder, and the place of emerging treatments, such as BRAF inhibitors, remains to be defined. We conducted a large, multi-center, retrospective survey in France to determine the frequency of malignancy in HCL patients (pts) and their families, and to analyze the long-term effects of the established purine nucleotide analogs (PNA) cladribine (C) and pentostatin (P). Methods:Physician members of the Société Française d’Hématologie were surveyed on their management of HCL pts over the past 30 years. Clinicians completed a form that collected data concerning personal and familial medical history of pts, with particular focus on hematologic malignancies, solid tumors, clinical and biological presentation at HCL diagnosis, therapeutic options, response to treatment, time to relapse, secondary malignancies and cause of death. Results:The survey included 36 French clinical centers and 487 HCL cases (mean patient age 59y; range 29–90y). In the centers surveyed, HCL diagnosis was established after examination of peripheral blood and/or bone marrow and by immunophenotyping. Solid tumors and hematologic malignancies were present before HCL diagnosis in 45 cases (9.2%). A further 38 pts (7.8%) with pre-existing cancers were diagnosed with HCL after a median time of 89mo (range 1–529mo). At diagnosis, three HCL pts presented with follicular lymphoma, monoclonal gammopathy of undetermined significance, or large cell B cell lymphoma. Four pts developed HCL within a median time of 33mo (range 30–38mo) after diagnosis of B-cell lymphoproliferative disorders. In 93 pts (19.1%), at least one family member developed neoplasia: solid tumors=75 pts (15.4%); acute or chronic hematologic malignancies=18 pts (3.7%) with one familial HCL case. Twenty-three pts (4.7%) received no treatment for a median follow-up of 32mo (1–293). Three hundred and forty-five pts (70.8%) received just one first-line treatment (C=68.1%, P=23.8%, interferon [IFN]=3.8%, other=4.3%), and 119 pts (16.6%) received two-to-seven lines of therapy. After first-line treatment, complete responses were observed in 365 pts (74.9%; P=85.1%, C=85.0%, IFN=61.1%). Median duration of response was 41 months (1–270; C=40.5mo [1–188; 234 pts], P=43.0mo [1–209; 80 pts], IFN=74mo [24–270; 13 pts], other=21mo [2–186; 15 pts]). After second line treatment, the median duration of response decreased to 33mo (1–261; 80 pts) (C=27mo [1–159; 39 pts], P=38.5mo [0–206; 24 pts]) and also tended to differ according to first-line regimen (Table).Agent used (first/second line)Median duration of response (mo)Range (mo)C/C181–97C/P331–74P/P21.53–42P/C233–71After third-line treatment, the median duration of response decreased again to 24mo (2–224; 24 pts) (C=46mo [2–92], P=20mo [2–166], other=22mo [2–224]). After 60 months follow-up (range 1–384mo), overall survival at 5 years was 95%. Twenty-nine pts (6%) had died (11 deaths were HCL-related), and a further 53 pts (10.9%) developed second malignancies (39 solid tumors and 14 hematologic malignancies). Second malignancies occurred 6 months after HCL diagnosis in 50 pts. Conclusions:This study highlights the high frequency of cancers in HCL pts and their family members, suggesting a role for genetic factors in the development of the disease. The survey also confirms the high efficacy of PNA, and we therefore need to be cautious in adopting innovative new therapies treatment such as BRAF inhibitors or immunotoxins into first-line care. Disclosures:No relevant conflicts of interest to declare.

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.