Diagnosis Of Small Lymphocytic Lymphoma Research Articles

Lymphoma presenting as the first finding in pleural fluid cytology: A rare cytologic presentation

Malignant hemato-lymphoid neoplasms presenting as the initial finding in pleural effusion cytology is one of the rare challenges a pathologist may encounter in practice among lymphocyte-rich effusions. Meanwhile, effusion cytology is an easily available, inexpensive diagnostic tool in our setting. Cytomorphological features provide crucial insights into the nature of the disease, which along with immunocytochemistry may help in solidifying the diagnosis. Here we present a rare case of a 17-year-old patient, who initially presented with pleural effusion that turned out to be lymphoma on cytological examination. Cell blocks were prepared and immunocytochemistry was performed for CD5 and CD23. Tumor cells showed positivity for both CD5 and CD23, confirming the diagnosis of small lymphocytic lymphoma.

The Role of Imaging in Predicting Time to First Treatment and Overall Survival in Individuals with CLL-like High Count Monoclonal B-Cell Lymphocytosis

Background: The 2008 International Working Group for CLL (IWCLL) criteria define MBL as a clonal B-cell disorder with a peripheral blood B-cell count of <5 x 109/L, in the absence of cytopenias(s), lymphadenopathy and/or organomegaly on physical examination, and no other concomitant lymphoproliferative disorder. In the presence of palpable lymphadenopathy and/or organomegaly, and a B-cell count of < 5 x 109/L, a diagnosis of small lymphocytic lymphoma (SLL) is established. A study by Gentile et al (Am J Hematol. 2013) reported that 29 out of 62 individuals with clinically identified MBL (42%) had lymphadenopathy identified on CT imaging. Notably, however, after a median follow-up of 35 months, the rate of progression among cases of MBL with lymphadenopathy identified on CT imaging was only 6.9% (2/29 patients), which was no different than in cases of MBL without lymphadenopathy on CT imaging (rate of progression, 9%; 3/33 patients). Our study sought to 1) determine if lymphadenopathy and/or organomegaly detected by imaging studies performed for unrelated reasons in individuals with MBL can identify a subset with shorter time to first CLL therapy (TFT) and overall survival (OS); and 2) compare outcomes of individuals with MBL who have incidentally detected lymphadenopathy/splenomegaly and SLL patients. Methods: We used the Mayo Clinic CLL Database to identify individuals with high-count MBL (absolute B-cell count: 0.5 - 4.9 x 109/L) and divided them into the following three cohorts: a) Cohort A: no imaging studies available at MBL diagnosis; b) Cohort B: imaging studies done within one year of MBL with no evidence of lymphadenopathy and/or organomegaly; and c) Cohort C: imaging studies done within one year of MBL with lymphadenopathy and/or organomegaly, attributable to MBL. All individuals with MBL were first seen at Mayo Clinic after 1/1/2002; those with a concomitant lymphoproliferative disorder within 3 months of diagnosis were excluded. Patients with SLL seen during the same time interval were identified as a comparison cohort. We compared the baseline characteristics (Kruskal Wallis for continuous and Chi-square for categorical variables) and TFT and OS across the three MBL cohorts, and patients with SLL. Cumulative incidence of TFT was adjusted for the competing risk of death. Age- and sex-adjusted OS was analyzed using inverse weights methods. Results: 657 individuals with high-count MBL with a median follow-up of 6.7 years were identified: 415 (63%) individuals were in Cohort A, 142 (22%) in Cohort B, and 100 in (15%) Cohort C. Compared to Cohort B, individuals in Cohort C were more likely to have unmutated IGHV, high expression of CD38, and higher beta-2 microglobulin level (Table 1). SLL patients were younger, had higher rate of unmutated IGHV, and had high expression of CD49d compared to MBL individuals in Cohort C (Table 1). There was suggestive evidence of a difference in TFT between Cohorts B and C (estimated 10-year treatment rate 28.3% vs. 41.6%; p=0.16; HR 1.62 95% CI 0.84-3.15). TFT was significantly shorter in SLL patients compared to those with Cohort C (estimated 10-year treatment rate 71% vs. 41.6%, respectively, P<0.001; Figure 1A). There was a trend toward shorter OS in Cohort C compared to Cohort B (estimated 10-year OS rate 53.7% vs. 64.2%, respectively, P=0.09; Figure 1B). In contrast, there was no difference in OS among MBL individuals in Cohort C compared to those with SLL (estimated 10-year OS rate 56.9% vs. 62.6%, P=0.72). Summary/Conclusion: Our findings demonstrate that individuals with MBL who have incidentally identified lymphadenopathy/splenomegaly at diagnosis are more likely to have an unfavorable risk profile, shorter TFT and OS compared to patients who did not have lymphadenopathy/splenomegaly at MBL diagnosis. Additionally, these individuals have a longer TFT but similar OS compared to SLL patients seen during the same time interval. If externally validated, these findings have significant implications for individuals with newly diagnosed MBL. Disclosures Ding: Merck: Research Funding; DTRM Biopharma: Research Funding. Kenderian:Novartis: Patents & Royalties, Research Funding; Tolero: Research Funding; Humanigen: Other: Scientific advisory board , Patents & Royalties, Research Funding; Lentigen: Research Funding; Morphosys: Research Funding; Kite/Gilead: Research Funding. Kay:MorphoSys: Other: Data Safety Monitoring Board; Infinity Pharmaceuticals: Other: DSMB; Celgene: Other: Data Safety Monitoring Board; Agios: Other: DSMB. Parikh:AstraZeneca: Honoraria, Research Funding; Janssen: Research Funding; AbbVie: Honoraria, Research Funding; Acerta Pharma: Research Funding; Ascentage Pharma: Research Funding; Genentech: Honoraria; Pharmacyclics: Honoraria, Research Funding; MorphoSys: Research Funding.

Serous retinal detachment caused by choroidal metastatic SLL: A case report

86-year-old man presented with reduced vision in his right eye corresponding to large serous detachment. Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) showed diffusely thickened choroid. Concurrent diagnosis of small lymphocytic lymphoma diagnosed from submandibular node incited suspicion of choroidal metastasis. Successful response to chemotherapy clearly documented using EDI-OCT technology.

Richter syndrome: A rare complication of chronic lymphocytic leukemia or small lymphocytic lymphoma.

Richter's syndrome (RS) is a rare complication with an unfavorable prognosis, in which chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) transform into a more aggressive type of lymphoma, most commonly into diffuse large B cell lymphoma (DLBCL) or less often into Hodgkin's lymphoma (HL). The objective of this research paper was to present a retrospective analysis of patients with CLL/SLL whose disease transformed into RS. The study included 217 patients (100 women and 107 men) with CLL/SLL diagnosed in the years 2006-2015 at the Department of Hematooncology and Bone Marrow Transplantation of the Medical University of Lublin, which transformed into RS. We analyzed clinical, laboratory, immunophenotypic (ZAP-70 and CD38 expression), histopathological, and genetic data (del(17p), del(11q)), which was collected at the time of CLL/SLL diagnosis, and some which was collected at the time of transformation. Richter's syndrome was diagnosed in 4.6% of all CLL and SLL patients. The group of patients with RS consisted of 9 patients with primary CLL and 1 patient with a diagnosis of SLL (8 patients with transformation into DLBCL and 2 patients with transformation into HL). Leukemic lymphocytes showed evidence of peripheral blood lymphocyte membrane expression of ZAP70+/CD38+ (1 patient), of ZAP-70+/CD38- (3 patients), of ZAP-70-/CD38- (1 patient), and of ZAP-70-/CD38+ (5 patients). The deletion of 11q (del(11q)) was documented in 2 patients. In 4 cases, the location of RS was extremely rare (the thyroid gland, liver, skin, bladder, and central nervous system). Richter's syndrome is a rare, but probable complication of CLL/SLL with an unfavorable prognosis, and it should be taken into account at every stage of the disease, particularly when the course of the disease is aggressive.

Dacryocystitis Caused by Lymphoproliferative Infiltration in the Course of Lymphocytic Lymphoma: Case Report

Abstract Background: Lacrimal drainage system lymphomas are rare, accounting for less than 10% of lacrimal sac tumors. They often appear as a secondary involvement within the confines of systemic lymphoproliferative disorders, therefore detailed ophthalmological examination and auxiliary testing is necessary to have an accurate diagnosis. Case report: We present the case of a 72-year-old woman with a medical history of chronic lymphocytic leukemia and small lymphocytic lymphoma. She presented to the ophthalmology clinic with a painful, discharging swelling in the right lacrimal sac area. Magnetic resonance imaging revealed a mass in the right nasolacrimal duct. A right external dacryocystorhinostomy was performed. The histological findings led to a diagnosis of small lymphocytic lymphoma. Conclusions: Special attention is required in cases of known systemic hematological disorders that associate with nasolacrimal duct obstruction or epiphora. Quick recognition and a full history with multidisciplinary clinical and diagnostic workup are fundamental to plan the treatment.

Diffuse Alveolar Hemorrhage: A Fatal Complication of Rituximab

Pulmonary toxicity is a rare but severe adverse effect of Rituximab, associated with significant morbidity and mortality. Despite increased reporting, few case reports associated with alveolar hemorrhage due to Rituximab have been published. The authors present the case of a 61 year old Caucasian male with a diagnosis of small lymphocytic lymphoma who recently completed chemotherapy with Rituximab and Bendamustine. The patient presented to the emergency room with a one week history of nonproductive cough associated with shortness of breath and low grade fevers. Differential diagnosis at the time of presentation included health care associated pneumonia, Rituximab-induced pulmonary toxicity, and Pneumocystis jiroveci infection given his history of lymphoma and treatment with Rituximab. The patient was initiated on intravenous (IV) broad-spectrum antibiotics, oral atovaquone, and IV methylprednisolone. A CT scan showed bilateral diffuse pulmonary opacities and a video-assisted thorascopic surgery guided lung biopsy revealed early diffuse alveolar hemorrhage with no evidence for infection. However, the remaining work-up consisting of blood cultures, blood tests, and bronchopulmonary lavage did not produce any suggestive findings. Despite initiating the above aggressive therapies, the patient continued to rapidly deteriorate. An autopsy revealed diffuse alveolar hemorrhage of the lungs, thought to be secondary to Rituximab toxicity. The authors recommend emphasizing the importance of early identification of worsening pulmonary symptoms in patients receiving Rituximab, with diagnostic consideration given to Rituximab-related toxicity.

Clinical Monoclonal B Lymphocytosis (cMBL), Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): Diagnostic Criteria, Features At Diagnosis and Natural History

IntroductionCLL, SLL and cMBL are considered to be part of the same spectrum of clonal expansions of CD5+ B cells. Clinically, the transition from one to another of these forms over time is a well recognized event. Diagnostic criteria to separate these disorders have been proposed (IWCLL, 2008; WHO, 2008). AimTo compare presenting and evolving features of three groups of patients with cMBL, Rai 0 CLL or SLL and to ascertain the usefulness of current diagnostic criteria for these disorders. Patients and MethodsRetrospective study of clinical, biologic and evolving characteristics of patients diagnosed with cMBL, Rai 0 CLL or SLL according to current criteria (CLL: ≥5x109 clonal B cells/L in peripheral blood; SLL <5x109/L clonal B cells with lymphadenopathy, organomegaly, cytopenia or disease-related symptoms; cMBL <5x109 clonal B cells with no signs or symptoms). ResultsBaseline characteristics of the patients are shown in the Table. Median age was 68 years (range, 24-94) and 57% of patients were males. Out of 1,093 patients, 79 had cMBL (7.2%), 522 Rai 0 CLL (48%) and 94 SLL (8.6%).CharacteristicscMBLRai 0-CLLSLLP valueAll patients (N=695)7952294Age, median (years)70 (34-90)66 (31-92)66 (24-94)NSGender, male42/79 (53%)270/522 (51%)56/94 (59%)NSWBC median (x109/L)9.4 (4-14)24 (4-170)8.1 (3-19)< 0.001Hb, median (g/dL)13.7 (10-17)13.9 (11-18)13.5 (10-18)NSPlatelets, median (x109/L)208 (11-573)211 (96-791)194 (52-390)NSLDH > 450 u/L7/78(9%)25/481 (5%)18/91 (20%)< 0.001B2M ≥ 2.4 mg/dl22/62 (36%)130/356 (37%)49/77 (64%)< 0.001ZAP70 ≥ 2011/57 (19%)104/361 (29%)34/54 (63%)< 0.001CD38≥ 3010/52 (19%)78/323(24%)36/51 (71%)< 0.001IGHV genemut.24/27 (89%)139/217 (64%)17/37 (46%)0.002NOTCH1 genemut.1/44 (2%)35/250 (14%)6/42 (14%)NSSF3B1 genemut.0/14 (0%)5/157 (3%)3/24 (12%)NSFISHNormal98/339 (29%)15/60 (25%)17/53 (33%)NS13q- (isolated)22/52 (42%)146/339 (43%)13/60 (22%)NS+ 1211/52 (23%)39/325 (12%)14/60 (34%)0.01611q-0/50 (0%)19/339 (6%)8/60 (13%)0.0117p-2/52 (4%)37/339 (11%)10/60 (17%)NSOverall, adverse biomarkers such as high LDH (p<0.001), high B2M (p<0.001), increased ZAP70 (p<0.001), high CD38 (p<0.001), unmutated IGHV status (p=0.002), +12 (p=0.02) and 11q- (p=0.01) were significantly more frequent in SLL.In subgroup analyses, the only difference between cMBL and Rai 0 CLL was a higher proportion of cases with mutated IGHV in cMBL (p=0.008). Furthermore, when SLL was compared to Rai I to IV CLL no differences were observed (data not shown). The actuarial risk for transformation from cMBL or SLL to CLL was 4.2% and 4.4 % per year (p=0.5), respectively. Median TTFT was significantly shorter in the SLL group (12 m.) than in Rai 0 CLL (174 m.) or cMBL (244 m.) (p<0.001). Median overall survival was also significantly shorter for SLL (94 m.) compared with Rai 0 CLL and cMBL (153 and 157 m., respectively) (p=0.028). Multivariate analysis of 695 patients (cMBL/Rai 0-CLL/SLL) revealed four variables independently correlated with shorter TTFT: diagnosis of SLL vs. Rai 0 CLL vs. cMBL (HR 2.28; p=0.008), high ZAP70 (HR 4.08; p<0.001), high CD38 (HR 4.68; p=0.001) and increased serum B2M levels (HR 1.54; p = 0.031). Importantly, however, when the multivariate analysis was restricted to patients with cMBL and Rai 0 CLL, variables correlated with TTFT were the clonal B-cell count (HR 3.76; p=0.01), ZAP70 (HR 3.31; p<0.001), and CD38 (HR 4.61; p=0.02). FISH cytogenetics, IGHV mutational status,NOTCH1 or SF3B1 mutations were not included in the analysis because of missing data. ConclusionsDisparities in biologic and clinical features of cMBL, CLL and SLL mainly reflect the different tumor burden in this spectrum of CD5+ monoclonal B cell disorders. In this study, the transformation rate from either cMBL or SLL to CLL was around 4% per year. As a result of differences in tumor mass, the need for therapy was shorter in SLL than in Rai 0 CLL and cMBL, and the overall survival poorer. Biologically, the only consistent difference between cMBL and Rai O CLL was a higher proportion of mutated IGHV in cMBL. Clinically, however, no differences in median survival were observed. Moreover, the clonal B cell count was the most reliable predictor of disease outcome in both cMBL and Rai 0 CLL. Therefore, the distinction between cMBL and Rai 0 CLL seems hardly justified. Disclosures:No relevant conflicts of interest to declare.

Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Fludarabine and cyclophosphamide combination in the treatment of patients with indolent non-follicular B-cell non-Hodgkin’s lymphomas. Results of a phase II trial of the Gruppo Italiano per lo Studio dei Linfomi (GISL).&gt;

6615 Background: Indolent non follicular lymphomas (INFL), comprise a rather heterogeneous subgroup of lymphomas, including small lymphocytic lymphoma (SLL), Immunocytoma (IC) and marginal zone lymphomas (MZL). In April 2002 we started a phase II trial aimed to verify the efficacy of Fludarabine and Cyclophosphamide (Flu-Cy) combination in this subset of NHL, in terms of response, survival and safety. Methods: Patients were enrolled according to the following inclusion criteria: diagnosis of SLL, IC, MZL, supported by morphologic, phenotypic and molecular data; non previous treatment; have active disease defined by the presence of anemia (Hb < 11 g/dL) or thrombocytopenia (Plt <100 x 109/l) or bulky disease or rapidly increasing lymphocytosis or enlarging masses. Treatment consisted of Fludarabine 25mg/sqm iv days 1–3 and cyclophosphamide 250mg/sqm IV days 1–3, to be repeated every 28days for 6 cycles; an intermediate evaluation of response after 3 cycles was planned and an adequate anti-infective prophyilaxis was mandatory: the use of G-CSF was not mandatory. Results: As of December 2004, 49 patients were registered into the trial; two patients were excluded from the study due to incorrect histology. Median age of the remaining 47 patients was 63 years (Range 39–74), M/F ratio was 1.7. All patients had stage IV disease; 9 patients (19%)presented with B symptoms. Anemia (Hb <11 g/dl) was present in 29%, elevated LDH in 32% elevated β2microglobulin in 63%. At the time of the present analysis 35 patients completed the treatment program achieving 50% CRs and 47% PRs. Three patients died during treatment, one after the 2nd cycle due to erosive pulmonary aspergillosis, two due to bone marrow aplasia occurred after the 4th cycle. Overall, grade III or IV neutropenia was observed in 38% of the patients and infections in 4 (12%). After a median follow up of 14 months 2years PFS was 80% while EFS was 56%. Conclusions: Flu-Cy combination is an effective treatment for patient with INFL but is also associated with a relevant toxicity profile. No significant financial relationships to disclose.

Small Lymphocytic Pulmonary Lymphoma: Diagnosis by Transthoracic Fine Needle Aspiration

A 77-year-old woman was found to have multiple densities on chest roentgenogram. Exfoliative cytology, bronchoscopy with brushings and washings, and transbronchial biopsy revealed a monomorphic population of small lymphocytes suggestive of lymphoma. Transthoracic fine-needle aspiration was performed to provide additional material for immunologic marker study. Immunocytochemistry revealed a monoclonal population of B-cells, which confirmed a diagnosis of small lymphocytic lymphoma. Chemotherapy resulted in significant clinical and roentgenographic improvement.