Central nervous system involvement in a patient with chronic lymphocytic leukemia and non-Hodgkin's lymphoma (Richter's syndrome), with concordant cell surface immunoglobulin isotypic and immunophenotypic markers

Central nervous system (CNS) involvement in Richter's syndrome has not been previously described. This report describes a 45-year-old man with the simultaneous occurrence of B-cell chronic lymphocytic leukemia (CLL), extramedullary large cell non-Hodgkin's lymphoma (NHL), and malignant lymphoid meningeal involvement. In this case, peripheral blood lymphocytes, cerebrospinal fluid (CSF) lymphoblasts, and malignant cells in surgical biopsy tissue obtained from a soft tissue mass all stained concordantly for immunoglobulin isotypes and for B-cell immunophenotypic markers, supporting the hypothesis of a clonal origin for the three malignant cell populations. These observations suggest that the different tumors in Richter's syndrome (CLL and NHL) may represent the clonal progression of a common neoplasm rather than independent neoplastic events. Richter's syndrome and other transformations of lymphoid malignancies (prolymphocytic transformation of CLL, blast crisis of CLL, and blastic transformation of NHL) may all represent possible routes of progression in the natural history of a single neoplasm. The present case also suggests that, in patients with B-cell CLL with CNS symptoms, the possibility of blastic transformation presenting as CNS lymphoma deserves consideration.     

Fine-needle aspiration biopsy findings in patients with small lymphocytic lymphoma transformed to hodgkin lymphoma

Although small lymphocytic lymphoma (SLL) is an indolent lymphoma, approximately 5% of cases can transform to a higher-grade lymphoma, rarely Hodgkin lymphoma (HL). We report the fine-needle aspiration (FNA) results of 6 cases of SLL/chronic lymphocytic leukemia (CLL) that transformed to HL. FNA findings were correlated with the histologic features and clinical follow-up. The patients included 5 men and 1 woman, ranging in age from 49 to 72 years at the time of SLL/CLL diagnosis with time for development of HL ranging from 0 to 95 months (mean, 49.3 months). The FNA diagnoses were SLL with HL transformation (2 cases), SLL with large atypical cells (1 case), and atypical lymphoid proliferation with large atypical cells (3 cases). Flow cytometry performed in 5 cases (2 FNA specimens) demonstrated a monoclonal B-cell population with CD19/CD5 coexpression.The presence of large atypical mononucleated and binucleated cells in lymph node FNA specimens from patients with SLL/CLL with progressive adenopathy should raise the possibility of transformation to HL. In these cases, histologic confirmation is always recommended, not only to differentiate HL transformation from other entities but also for subclassification of HL.     

B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma involving bone marrow with an interfollicular pattern

B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) may involve the bone marrow in nodular, interstitial, diffuse, or mixed patterns. However, B-cell CLL/SLL associated with large reactive germinal centers (the so-called interfollicular pattern) involving the bone marrow is not reported. We describe 2 examples of B-cell CLL/SLL that subtotally replaced the bone marrow with an interfollicular pattern. In both cases, the neoplasms were composed of small round lymphoid cells; proliferation centers also were present. The neoplasms surrounded large reactive germinal centers that were devoid of peripheral mantle zones. The germinal centers were paratrabecular and nonparatrabecular in case 1 and nonparatrabecular in case 2. Flow cytometry immunophenotypic studies done on bone marrow aspiration samples of both cases showed a uniform population of neoplastic cells positive for pan-B-cell antigens and the CD5 and CD23 antigens. Immunohistochemical studies done on bone marrow biopsy sections supported the flow cytometry results and demonstrated that the germinal centers were negative for BCL-2. B-cell CLL/SLL may rarely involve the bone marrow with an interfollicular pattern. Knowledge of this pattern will prevent confusion with follicle center lymphoma and large cell transformation, both of which initially were considered in the differential diagnosis of these cases.     

Epstein–Barr virus‐positive diffuse large B cell lymphoma arising from a chronic lymphocytic leukemia: Overlapping features with classical Hodgkin lymphoma

A small proportion of patients with chronic lymphocytic leukemia (CLL) may progress to large cell lymphoma, or Richter syndrome (RS). The large cells of RS may arise through transformation of the original CLL clone (clonally related) or represent a new neoplasm (clonally unrelated), which might be Epstein–Barr virus (EBV)‐associated. We present a 61‐year‐old male with 5‐year history of CLL who developed RS on bilateral adrenal glands. The tumor showed a vague nodular growth pattern separated by thick fibrous bands and the tumor cells were large and pleomorphic, with focal sheet‐like growth pattern, in a background of small B and T‐lymphocytes. The large tumor cells were positive for CD15, CD19, CD20 (intensely and diffusely), CD30, fascin, PAX5, MUM1, OCT2, and LMP‐1 by immunohistochemical stains, and EBV by in situ hybridization. The tumor was diagnosed as EBV‐positive diffuse large B cell lymphoma (DLBCL), with overlapping features of classic Hodgkin lymphoma (CHL). The patient received salvage chemotherapy and was free of disease 2 years after adrenalectomy. We speculated that our case was a clonally unrelated tumor with his underlying CLL and discussed the differential diagnoses between EBV‐positive DLBCL and CHL in the setting of RS.     

Large cell lymphoma transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma. A flow cytometric analysis of seven cases

We studied 7 cases of large cell transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) immunophenotyped by multiparameter flow cytometry. The 6 women and 1 man ranged in age from 45 to 91 years. All had previous or concurrent evidence of CLL/SLL. Morphologic features and sites of involvement of the diffuse large B-cell lymphoma (DLBCL) were heterogeneous; 2 cases had paraimmunoblastic morphologic features. Six DLBCLs had an immunophenotype consistent with CLL: CD19+, CD5+, CD23+, and FMC7 negative (3 cases) or very dim (2 cases); 1 case was not studied for FMC7. CD20 was dim in 3 of these, moderate to bright in 2, and variable in 1. Surface immunoglobulin was dim in 2 cases and moderate or bright in 4. Five of 6 expressed CD38. Comparison with the immunophenotypes of the previous or coexistent CLL/SLL (4 of 6 cases) revealed minor modulations in antigen expression but no major alterations. The seventh DLBCL lacked CD5 expression, but otherwise had immunophenotypic features similar to CLL. These findings indicate that DLBCL arising in CLL/SLL tends to retain a CLL immunophenotype, in contrast with de novo CD5+ large cell lymphomas that uncommonly express such a phenotype.     

Clonal evolution of B cells in transformation from low- to high-grade lymphoma

An outcome of low-grade B cell non-Hodgkins's lymphomas is the transformation to high-grade diffuse large B cell lymphomas (DLBL). To investigate the mechanisms of clonal evolution in the transformation to DLBL, we performed longitudinal molecular analyses of immunoglobulin (Ig), V(H)DJ(H) gene sequences expressed in cases of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL) that transformed to DLBL. Among the neoplastic CLL and SLL cells and their respective high-grade transformants, there was no evidence for a clonotypic shift or acquired mutations in the expressed Ig V(H)DJ(H) gene segments, as further confirmed by a specific and sensitive PCR-single strand polymorphism analysis. In contrast, among the FL cells there was a high degree of intraclonal diversification with highly divergent V(H)DJ(H) gene sequences. Despite this intraclonal heterogeneity, the related DLBL expressed a collinear but unique V(H)DJ(H) gene sequence. The intraclonal genealogical tree for the FL case demonstrated that the DLBL emerged in association with unique V(H)DJ(H) gene mutational events. Among the intraclonal FL and related DLBL transformants, the nature and distribution of the Ig V(H)DJ(H) gene mutations were consistent with antigenic selection. Thus, clonal evolution in the transformation from low- to high-grade B cell lymphoma may involve distinct pathways which vary according to the cellular origin and the type of the progenitor B cell tumor.     

Hodgkin's disease variant of Richter's syndrome. Two cases and literature review

We report the clinical and immunohistological features of two cases of chronic lymphocytic leukaemia (CLL) with Hodgkin's transformation. These cases occurred in a 70-year-old man with a three-year history of CLL and in a 76-year-old man with a few months history of CLL. Microscopic examination showed the presence of large tumor cells with the morphological and immunophenotypic features of classical Hodgkin and Reed-Sternberg (R-S) cells, in a background of otherwise typical B-CLL. The transformation of CLL into large B cell lymphoma (Richter's syndrome) is a well-documented phenomenon. Only rarely does CLL transform into Hodgkin's lymphoma, but this diagnosis is often easy and offers few differential diagnoses. The major points of interest lie in the pathogenetic relationship between CLL and Hodgkin's disease, and in the potential clinical implications of this peculiar condition. Literature on the subject indicates that identical IgH gene rearrangements in micromanipulated R-S and CLL cells have been identified in 7/12 cases. In these patients, the R-S and CLL cells belong to the same clonal population, suggesting a progression from the underlying CLL cells. This group appears to have a poor prognosis, identical to classical Richter's syndrome. In other cases, the R-S cells were often Epstein-Barr virus (EBV) positive and did not share the clonal rearrangements identified in CLL cells, suggesting that Hodgkin's disease in these patients could represent a second malignancy, EBV-related and favored by immunosuppression, associated with a better prognosis.     

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive diffuse large B-cell lymphoma.

To clarify the cell origin of CD5+ diffuse large B-cell lymphoma (DLBCL), we analyzed and compared the variable region of the immunoglobulin heavy chain gene (VH gene) in eight cases of CD5+ DLBCL and 23 cases of other CD5+ B-cell neoplasms; 10 cases of chronic lymphocytic leukemia (CLL), one case of small lymphocytic lymphoma, one case of hairy cell leukemia, and 11 cases of mantle cell lymphoma. CD5+ DLBCL were comprised of two cases of de novo lymphoma of nodal origin, five cases of de novo lymphoma of extranodal origin, and one case of Richter transformation. Whereas all cases of mantle cell lymphoma except one showed a germ line or low mutation frequency of the rearranged VH gene, the rearranged VH genes in both CD5+ CLL and CD5+ DLBCL were heterogeneous. The degree of somatic mutation of CD5+ CLL and CD5+ DLBCL ranged between approximately 0 to 15.0% and 0.7 to 12.9%, respectively. High frequency of expression of the VH4 family in both CD5+ CLL and CD5+ DLBCL was found. Moreover, none of the three cases of CD5+ DLBCL examined exhibited intraclonal diversity. These findings may be common characteristics of the rearranged VH gene of CD5+ CLL and CD5+ DLBCL and suggested that the cell origin of CD5+ DLBCL was the same as that of CD5+ CLL.     

Artificial intelligence strategy integrating morphologic and architectural biomarkers provides robust diagnostic accuracy for disease progression in chronic lymphocytic leukemia

Artificial intelligence-based tools designed to assist in the diagnosis of lymphoid neoplasms remain limited. The development of such tools can add value as a diagnostic aid in the evaluation of tissue samples involved by lymphoma. A common diagnostic question is the determination of chronic lymphocytic leukemia (CLL) progression to accelerated CLL (aCLL) or transformation to diffuse large B-cell lymphoma (Richter transformation; RT) in patients who develop progressive disease. The morphologic assessment of CLL, aCLL, and RT can be diagnostically challenging. Using established diagnostic criteria of CLL progression/transformation, we designed four artificial intelligence-constructed biomarkers based on cytologic (nuclear size and nuclear intensity) and architectural (cellular density and cell to nearest-neighbor distance) features. We analyzed the predictive value of implementing these biomarkers individually and then in an iterative sequential manner to distinguish tissue samples with CLL, aCLL, and RT. Our model, based on these four morphologic biomarker attributes, achieved a robust analytic accuracy. This study suggests that biomarkers identified using artificial intelligence-based tools can be used to assist in the diagnostic evaluation of tissue samples from patients with CLL who develop aggressive disease features. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Hodgkin's disease variant of Richter's syndrome clonally related to chronic lymphocytic leukemia arises in ZAP-70 negative mutated CLL

Chronic lymphocytic leukemia (CLL) may derive from either immunoglobulin V(H) gene unmutated (na?ve) or mutated (antigen-experienced) post-germinal center B-cells. Richter's syndrome denotes the transformation of CLL into aggressive B-cell lymphoma. Most Richter's syndrome cases are secondary diffuse large B-cell lymphomas, but some are Hodgkin's disease variants. Hodgkin's lymphoma is thought to originate from germinal center or post-germinal center B-cells with evidence of somatic V(H) hypermutation. Taking into account CLL and Hodgkin's lymphoma histogenesis, hypothetically only CLL derived from V(H) mutated B-cells can clonally progress to Hodgkin's lymphoma variant of Richter's syndrome. To test our hypothesis, we analyzed the CLL ZAP-70 status as a surrogate for the V(H) mutational status in four patients with subsequent Hodgkin's disease variants of Richter's syndrome. In all three cases with proven or suspected clonal relationship between Hodgkin and Reed-Sternberg- and leukemia cells, the CLL samples remained negative for ZAP-70, corresponding to CLL histogenesis from V(H) mutated B-cells. These empirical data suggest that the histological and clinical diversity of Richter's transformation could be to a part explained by the different origin of CLL, with Hodgkin's disease variants arising probably only in V(H) mutated CLL.     

The expression of Bcl‐2 by proliferating cells varies in different categories of B‐cell lymphoma

Masir N, Jones M, Lee A M, Goff L K, Clear A J, Lister A, Marafioti T & Mason D Y
(2010) Histopathology 56 , 617–626 The expression of Bcl‐2 by proliferating cells varies in different categories of B‐cell lymphoma Aims: To investigate the relationship between Bcl‐2 protein expression and cell proliferation at single‐cell level in B‐cell lymphomas using double‐labelling techniques. Methods and results: The relationship between Bcl‐2 protein expression and cell proliferation was explored in 124 cases of B‐cell lymphoma using double immunofluorescence labelling for Bcl‐2 and Ki67. In follicular lymphoma, marginal zone lymphoma and a subset of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), neoplastic cells tended to lose Bcl‐2 when they are in cell cycle. This pattern is usually maintained in both follicular lymphoma and CLL/SLL when they undergo high‐grade transformation. In mantle cell lymphoma, diffuse large B‐cell lymphoma and a subset of CLL/SLL, the inverse relationship (between Bcl‐2 and Ki67) was not observed, i.e. the proliferating cells tended to show co‐expression of Bcl‐2. Conclusions: In low‐grade lymphomas, including those that are transformed, Bcl‐2 expression is lost when cell proliferate. However, in more aggressive tumours (i.e. mantle cell and de novo diffuse large B‐cell lymphomas) the inverse Bcl‐2/Ki67 relationship was not observed. It would be of interest to explore the clinical implications in lymphoma of the presence and absence of the inverse Bcl‐2/Ki67 pattern.     

Richter syndrome in B-cell chronic lymphocytic leukemia

Richter syndrome (RS) is well known as a secondary high‐grade lymphoma, mostly diffuse large B‐cell lymphoma (DLBCL) developed in patients with B‐cell chronic lymphocytic leukemia (B‐CLL). In this review, we describe clinicopathological, histological, immunophenotypical and genetic findings of RS. The patients with RS, regardless of transformation of pre‐existing clone or de novo malignant clone, were resistant to conventional combined chemotherapy and died within months of diagnosis. Molecular techniques can provide convincing results for the clonal relationship of RS to pre‐existing B‐CLL. When RS carries a same rearrangement band or a same sequence as B‐CLL by Southern blotting or nucleotide sequence analyses of immunoglobulin heavy and/or light chain genes, it is suggested to that RS transforms from original B‐CLL. These analyses have showed that approximately two‐thirds of RS cases evolved from a B‐CLL clone. How and where does the B‐CLL clone evolve to RS? The genetic alteration of transforming B‐CLL clone into RS has been addressed. Abnormalities of chromosomes 11 and 14 were most frequently involved in RS, but non‐specific. In addition, RS does not include chromosomal translocation between Ig locus and oncogenes or rearrangements of bcl‐6 gene, both of which were found in some de novo DLBCL. Several candidates, such as mutation of p53 gene and abnormalities of cyclin dependent kinase inhibitor, have been proposed to play an important role in the transformation of a part of B‐CLL. However, there is still uncertainly as to how B‐CLL progresses or develops into RS.     

The relationship between Hodgkin's disease and non-Hodgkin's lymphoma.

The final Workshop of the meeting focused on cases of Hodgkin's disease (HD) in combination with non-Hodgkin's lymphoma (NHL), either T, B, or anaplastic large cell (ALC) type. The cases selected for this session fell into five categories: nodular lymphocyte-predominance Hodgkin's disease (NLPHD) with NHL, B cell chronic lymphocytic leukemia (CLL) with HD-like transformation, follicular lymphoma (FL) with HD or anaplastic large cell lymphoma (ALCL) (composite or discordant), HD following mycosis fungoides (MF), and HD following ALCL. Taken together, these cases left the participants with the distinct impression that there is likely to be some biological relationship between HD and a variety of T cell and B cell NHL.     

Immunophenotypic and gene probe analysis of a case of Richter's syndrome

A rare case of diffuse large cell lymphoma (DLL) arising in the stomach of a patient with long-standing chronic lymphocytic leukemia (CLL) has been examined by a combination of immunophenotypic and gene probe methods. Both the resected lymphoma and the CLL (obtained from an infiltrate in perigastric lymph nodes) expressed surface membrane markers consistent with a B-cell origin (HLA-DR+; B1+; B4+), but surface membrane immunoglobulin (SmIg) could be detected only on the CLL cells (SmIgM lambda+). Neither neoplasm expressed cytoplasmic immunoglobulin. DNA probe analysis using the Southern blot method and probes to the joining (J-H) region of the immunoglobulin heavy chain gene and to the constant (C) regions of the immunoglobulin kappa and lambda light chain genes revealed different light and heavy chain gene rearrangements in the two neoplasms. These findings suggest that the large cell lymphoma arose from a different clone than the CLL and the development of large cell lymphoma may have represented a de novo neoplastic event in a predisposed person.     

Fine-needle aspiration in non-Hodgkin lymphoma: evaluation of cell size by cytomorphology and flow cytometry

We studied 48 non-Hodgkin lymphoma (NHL) fine-needle aspiration (FNA) specimens with initial cytomorphology (CM) and flow cytometry (FC) and subsequent surgical biopsy of the same lesion to determine whether a reliable diagnosis of large cell lymphoma or large cell transformation could be made. CM was evaluated by examining 200 lymphocytes in each specimen. FC was performed by analyzing monoclonal or abnormal B-cell populations. Percentages of large cells were evaluated by CM and FC and results correlated with the histologic diagnosis. All small cell NHLs showed fewer than 40% large cells by CM and FC; 100% (9/9; FC) and 67% (6/9; CM) of diffuse large B-cell lymphomas demonstrated greater than 40% large cells. Variable numbers of large cells were detected in grade III follicular lymphoma, low-grade lymphoma with partial large cell transformation, and large B-cell lymphoma containing fewer than 10% neoplastic cells. By using combined CM and FC, large cell lymphoma and large cell transformation can be diagnosed reliably by FNA if greater than 40% large cells are present. Surgical biopsy is necessary when there is necrosis, fewer than 10% neoplastic cells by FC, or fewer than 40% large cells with clinical signs of transformation.     

骨髓活检组织淋巴瘤的病理诊断和分型

目的 探讨组织形态改变、免疫组织化学、基因重排在淋巴瘤骨髓侵犯的病理诊断和分型中的作用。材料与方法 对62例甲醛固定、石蜡包埋的骨髓活检组织,分别做了组织学、EnVision法观察和免疫球蛋白重链(IgH)基因和TCRγ基因重排检测。结果 慢性淋巴细胞性白血病／小淋巴细胞淋巴瘤(CLL／SLL)的异型淋巴细胞呈小梁间结节状或散在分布,有时可见假滤泡结构。滤泡型淋巴瘤(FCL)表现为结节性小梁旁或小梁间的浸润,结节内小淋巴样细胞松散聚集。淋巴浆细胞性淋巴瘤(LPL)主要为小梁间弥散浸润,在小而圆的淋巴细胞间可见散在数量不等的浆细胞样淋巴细胞。边缘区淋巴瘤(MZL)则见模糊的或界限不清的小梁间或小梁旁结节,一些细胞胞质透明。套细胞性淋巴瘤(MCL)异型细胞小到中等大小,缺乏副免疫母细胞和假滤泡。毛细胞性淋巴瘤(HCL)瘤细胞胞膜多清晰,胞质丰富透明,常形成荷包蛋样表现。霍奇金病可见大核瘤细胞,核仁明显。T-非霍奇金淋巴瘤(NHL)浸润骨髓主要为小梁间间质性散在或弥漫分布,胞质多透明,核有芋艿样或脑回状改变,DLBL造血细胞间体积大的瘤细胞散在或弥漫分布。CD3对T细胞来源、CD20和CD79对B细胞来源淋巴瘤有鉴别诊断价值,cyclin D1和(SD5阳性对MCL具有诊断性价值,bcl-2和CD10阳性则对FCL具有诊断性意义,而CLL／SLL除了(SD20和CD79阳性外,也可CD5和CD23阳性。HCL的瘤细胞CD25强阳性。CD15、CD30和Fascin也适用于骨髓霍奇金病的诊断。骨髓中CLL／SLL,LPL,MZL及DLBL的IgH重排率(80％、60％、66．7％、70％)及T—NHL的TCRγ重排率(66．7％)较高。结论 综合组织形态改变、免疫组织化学和IgH／TCRγ重排检测,有助于淋巴瘤骨髓侵犯的诊断和分型,有助于发现骨髓中为数不多的淋巴瘤细胞。     

Expression of Ki-67 nuclear antigen in B and T cell lymphoproliferative disorders.

AIMS: To determine whether the proliferation rates of tumour cells may relate to prognosis and reflect disease activity. METHODS: Blood mononuclear cells from 155 patients with B cell (n = 120) or T cell (n = 35) chronic lymphoproliferative disorders were tested with the monoclonal antibody Ki-67 by indirect immunoperoxidase or immunoalkaline phosphatase techniques. B cell diseases included chronic lymphocytic leukaemia (CLL), CLL in prolymphocytic transformation (CLL/PL), prolymphocytic leukaemia (B-PLL) and non-Hodgkin's lymphoma (B-NHL) in leukaemic phase. The T cell diseases comprised large granular lymphocyte (LGL) leukaemia, T-PLL, and T-NHL. RESULTS: These showed significantly higher proportions of Ki-67 positive cells in T cell (11.2%) than in B cell (2.9%) disorders (p < 0.001). The highest values were found in NHL of both B and T cell types, particularly when low grade disease transformed to high grade. The lowest percentages of Ki-67 positive cells were found in CLL (1.4%) and LGL leukaemia (1.7%); intermediate values were seen in B PLL (3.3%) and T PLL (5.8%). CONCLUSIONS: There is a positive correlation between prognosis and proliferation rates in chronic B and T cell lymphoproliferative disorders. Estimation of Ki-67 in circulating leukaemic cells could be used to determine prognosis in low grade malignancies.     

2 cases of Richter's syndrome]

Two cases of Richter's syndrome are reported (in a 62 and 64 years old man) consistent with the appearance of B cell lymphoma of high malignancy in the course of CLL (low malignancy B cell lymphoma). In one patient, after 8-, and in the other one--after 53 months since the diagnosis of CLL, there was rapid clinical deterioration with lymphadenopathy, hepato- splenomegaly, fever and progressive cachexia, anemia and thrombocytopenia and leukopenia, unrelated to treatment. Both patients died, 4 and 3 months respectively, since the appearance of these symptoms. In the first cases Richter's syndrome was diagnosed histopathologically from the autopsy material. In the liver, spleen, adrenals and bone marrow, in addition to the characteristic infiltrates of CLL (small lymphocytes) there were areas of large cell proliferation consistent with high malignancy lymphoma. In the other case, the infiltrates of large cell lymphoma were found in the gall bladder removed because of acute cholecystitis, and in the lymph node from the hepatic hilar area. Immunocytochemical studies performed on the biopsy material indicated that the neoplastic cells had markers of B lymphocytes and cytoplasmic IgM kappa, as lymphocytes of CLL. In patients with CLL, who display rapid clinical deterioration and general symptoms with cachexia, the possibility of Richter's syndrome should be considered, and appropriate morphological studies performed.     

Primary digestive Richter's syndrome.

The clinical and morphologic transformation of 3 to 5% of chronic lymphocytic leukemia (CLL) to diffuse large-cell lymphoma (DLCL) is commonly referred to as Richter's syndrome. Richter's syndrome occurs mostly in lymph nodes and may represent a second neoplasm or a transformation from the same clonal population. Clinical features in six patients with digestive Richter's syndrome were recorded. Paired samples of CLL and DLCL were investigated by immunohistological analysis (n = 6) and by polymerase chain reaction (PCR) for immunoglobulin heavy-chain gene rearrangement (n = 4). Histological examination revealed the involvement of the gastrointestinal tract by DLCL of B-cell phenotype (n = 6). The same monoclonal rearrangement between CLL and DLCL was demonstrated by PCR and sequencing analyses in two patients. The monoclonal rearrangement was different between CLL and DLCL in only one case. Median survival was 22 months for five patients receiving chemotherapy, suggesting that digestive Richter's syndrome has a better prognosis than nodal Richter's syndrome. Indeed, appropriate surgical resection combined with chemotherapy led to partial or complete remission in four patients.     

Selective central nervous system tropism of primary central nervous system lymphoma

Primary Central nervous system lymphoma (PCNSL) is most frequently a diffuse large B cell lymphoma (DLBCL), which is confined to the Central nervous system (CNS). We performed an experiment in which lymphoma cells from a PCNSL patient were implanted subcutaneously in an athymic mouse. The lymphoma cells were shown to home to the CNS with histologic evaluations of the brain showing multiple large B cells in blood vessels consistent with intravascular large B cell lymphoma (IVL). We did not find any evidence of lymphoma at the site of implantation or other locations. The findings are consistent with highly selective tropism of PCNSLforthe CNS and its vasculature.