Simultaneous occurrence of B-cell chronic lymphocytic leukemia and chronic myeloid leukemia with further evolution to lymphoid blast crisis

The coexistence of chronic myeloid leukemia (CML) and B-cell chronic lymphocytic leukemia (CLL) in the same patient is rare. A 71-year-old woman developed a B-lineage lymphoid blast crisis at 18 months after diagnosis of Ph-positive CML. At this time, a lymphoid cell population with morphologic and immunophenotypic features of CLL was demonstrated. The retrospective review of the tests performed at diagnosis and thereafter disclosed the presence of lymphoid nodules in the initial bone marrow biopsy in the absence of lymphocytosis. Subsequently, there was an appearance of moderate lymphocytosis in the following months. Therefore, diagnosis of CML and coexistent CLL was established. Although a transient remission of blast crisis was achieved, blast cells reappeared two months later and the patient died shortly afterwards. Molecular studies of the immunoglobulin heavy chain gene (IH) rearrangement pattern point to the origin of the diseases in two different cell clones. In addition, previously published cases of simultaneous CLL and CML are reviewed.     

Origin of the Hodgkin/Reed-Sternberg cells in chronic lymphocytic leukemia with "Hodgkin's transformation"

A lymphoma with the characteristic features of Hodgkin's disease (HD) occasionally develops in patients with B-cell chronic lymphocytic leukemia (CLL), and has been called Richter's syndrome with HD features. In such cases, large tumor cells have the morphological and immunophenotypic features of classical Hodgkin and Reed-Sternberg (H-RS) cells. However, it is not known whether the H-RS cells arise from transformation of the underlying CLL cells or from a different pathological process. We report herein a study of the clonal relationship between the CLL cells and the H-RS cells in three cases of Richter's syndrome with HD features by using a single cell assay. We isolated single CLL cells and H-RS cells from immunostained tissue sections by micromanipulation. The immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of each cell was amplified by the polymerase chain reaction (PCR). The products were then compared by gel electrophoresis and nucleotide sequencing. The IgH CDRIII sequences from the H-RS cells were identical to those from the CLL cells in two cases. In one case, the clonal relationship between the two types of cells could not be determined because PCR products could not be obtained from any of the H-RS cells. This study shows that the H-RS cells and the CLL cells belong to the same clonal population in some cases of Richter's syndrome with HD features. Furthermore, our findings indicate that mature B cells can undergo transformation to cells with the features of H-RS cells, in association with a cellular background typical of HD. This study also supports recent findings suggesting that the H-RS cells in classical HD are derived from transformed B cells.     

DNA content and expression of PCNA and p53 in Hodgkin's disease and Hodgkin's-like B-cell lymphoma

DNA ploidy (by image cytometry) and expression of proliferating cell nuclear antigen (PCNA) and p53 tumor suppressor gene product (by immunohistochemistry) were investigated in 15 cases of Hodgkin's disease (HD) and 12 cases of HD-like B-cell lymphoma (HD-like NHL). Reed-Sternberg (RS) cells and their variants were DNA aneuploid in all cases. However, the fraction of hyperoctaploid tumor cells was higher in HD than in HD-like NHL. PCNA expression was high in neoplastic cells (> 50%) and variable (5-40%) in reactive lymphocytes in both HD and HD-like NHL. p53 positivity was found in RS cells and their variants in 64% of HD cases, but only in 25% of cases of HD-like NHL. Our results support the suggestion that HD-like B-cell lymphomas should be considered as highly malignant non-Hodgkin's lymphomas rather than Hodgkin's disease.     

Hodgkin's disease in the very young child. Apropos of 11 cases

Hodgkin's disease (HD) in children of 4 years of age or younger is seldom reported. It seems more frequent in developing countries. We report on 11 cases out of 115 cases of HD in patients of 15 years of age or younger observed between 1980 and 1991. The youngest patient was 29 months old and the median age was 2 years 11/12. The male/female ratio was 2.6. Mixed cellularity was found in six cases, lymphocytic predominance in two cases and nodular sclerosis in two cases. B symptoms were observed in four cases. Four patients had stage II, three stage III and four stage IV disease. Chemotherapy consisted of MOPP/ABVD in all cases. One patient received mantle field radiation therapy. Of ten evaluable patients, seven achieved complete remission, three patients were lost to follow-up in partial remission before achieving the treatment program. There were no relapses so far and no death attributable to toxicity. The follow-up ranges from 2 to 8 years. These data indicate the high frequency of HD in very young patients and suggest that chemotherapy alone is very efficient in this subset of patients.     

2-Chlorodeoxyadenosine (2-CdA) in the treatment of patients with relapsed chronic lymphocytic leukemia

This study attempts to characterize the response of patients with chronic lymphocytic leukemia (CLL) to the purine analog 2-chlorodeoxyadenosine (2-CdA). We have treated 10 patients with 2-CdA, at a dose 0.05-0.1 mg/kg/daily, for 7 days as a 2-hour infusion. Mean age was 54.6 years (range, 34-68 years). Mean time from diagnosis to treatment with 2-CdA was 37.0 months (range, 8-84 months). All the studied patients had received preliminary therapy consisting of other than 2-CdA chemotherapeutic regimens. Eight out of 10 patients had Rai stage III-IV disease. Four patients had Coombs positive hemolytic anemia before 2-CdA treatment. Seven patients responded to 2-CdA. Two complete remission (CR) and 5 partial remission (PR) were achieved. All patients but one with Coombs positive autoimmune positive hemolytic anemia achieve complete resolution of hemolysis. Severe neutropenia was frequent, and serious infections were noted in 20%, 43% and 50% of cases during the first, second and third course of 2-CdA, respectively. We conclude that 2-CdA is an effective agent in relapsed CLL patients, particularly in cases complicated by autoimmune hemolytic anemia.     

Isolation of viable Hodgkin and Reed-Sternberg cells from Hodgkin disease tissues

Hodgkin disease (HD) is characterized by a small number of malignant Hodgkin and Reed-Sternberg (H/RS) cells among a major population of nonmalignant cells. The analysis of H/RS cells has been hampered by their low frequency and fragility. Here, we describe the isolation of viable H/RS cells from HD affected tissues by high gradient magnetic cell sorting (MACS) according to expression of CD30. The cells were enriched to a purity of up to 50%. H/RS cells were distinguished from other CD30(+) cells by the expression of CD15, their size and granularity. No CD30/CD15 double-positive cells could be enriched from a lymph node affected by the lymphocyte predominant subtype of HD, activated lymph nodes or peripheral blood of healthy donors. For two cases of HD individual MACS-purified H/RS cells and H/RS cells micromanipulated from tissue sections of the same lymphoma specimens were analyzed for Ig gene rearrangements. In both cases, identical V gene rearrangements were amplified from both sources of H/RS cells, showing that H/RS cells were successfully enriched. Moreover, the finding that in both cases no additional Ig gene rearrangements other than the ones identified in the H/RS cells micromanipulated from tissue sections were amplified from the MACS-purified H/RS cells further supports the monoclonality of these cells throughout the affected lymph nodes. The isolation of viable H/RS cells ex vivo is prerequisite for a direct study of gene expression by those cells and of their interaction with cells in their vicinity.     

Detection of Epstein-Barr virus in transformations of low-grade B-cell lymphomas after fludarabine treatment

Fludarabine is a highly effective chemotherapeutic agent for chronic lymphocytic leukemia/small lymphocytic lymphoma and is also active in other B-cell lymphoproliferative disorders. Although highly efficacious in destroying the malignant B-cells, fludarabine also causes T-cell lymphopenia and immunosuppression. We present five patients given fludarabine for low-grade B-cell lymphoproliferative disorders who showed transformation of the primary neoplasm to a higher grade tumor. Immunohistologic antibody studies were performed on paraffin-embedded tissue sections of the initial tissue (when available) and on the follow-up biopsy specimens for CD20, CD3, CD45RO, CD43, CD30, CD15, and latent membrane protein (LMP-1) for Epstein-Barr virus (EBV). The initial diagnoses in these five patients included chronic lymphocytic leukemia/small lymphocytic lymphoma (three cases), follicle center lymphoma (one case), and Waldenstrom's macroglobulinemia (one case). All of the follow-up biopsy specimens showed scattered Hodgkin's-like cells, and two of the five also showed foci of large-cell transformation. The Hodgkin's-like cells showed CD30 immunoreactivity in four of the five cases and CD15 immunoreactivity in three of the five. Strong immunoreactivity of the large, atypical, Hodgkin's-like cells for LMP-1 of EBV was noted in four cases; in the remaining case, this finding was equivocal. In situ hybridization for EBV-encoded RNA was positive in four of the five cases. Molecular studies by polymerase chain reaction (PCR) showed the presence of EBV in three of the five cases. PCR for detection of immunoglobulin heavy chain demonstrated identical monoclonal rearrangements in the original lymphoma and transformation in one case with available material. The CD4 lymphocyte count in each patient was less than 550/microL, indicating cellular dysfunction. Transformation of low-grade non-Hodgkin's lymphomas after fludarabine therapy might be associated with EBV and severe immunosuppression.     

Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma. PATIENTS AND METHODS: Fifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttransplantation if graft-versus-host disease (GVHD) was not present. RESULTS: Eleven patients had engraftment of donor cells, and the remaining four patients promptly recovered autologous hematopoiesis. Eight of 11 patients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine patients (22.2%) who had refractory or untested disease at the time of study entry (P = .04). CONCLUSION: These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonablative preparative regimen to produce engraftment and GVL against lymphoid malignancies. The ability to induce remissions with donor lymphocyte infusion in patients with CLL, Richter's, and low-grade and intermediate-grade lymphoma is direct evidence of GVL activity against these diseases. This approach appears to be most promising in patients with chemotherapy-responsive disease and low tumor burden.     

Chronic lymphocytic leukaemia with binucleated lymphocytes

Chronic lymphocytic leukaemia (CLL) is a monoclonal proliferation usually involving B cells and composed of mature lymphoid cells. Distinct morphologic subtypes have been recognized according to lymphocyte size, nuclear:cytoplastic ratio and nucleolus. However the presence of characteristically binucleated lymphocytes in patients fulfilling criteria for CLL diagnosis has never been described. We here report immunological and cytogenetic studies of four patients with CLL but with binucleated lymphocytes. Moreover, trisomy 12, known to be associated with atypical morphology in CLL, was detected in two of these four patients. We suggest that this be considered as a possible new entity.     

Clinical experience with fludarabine and its immunosuppressive effects in pretreated chronic lymphocytic leukemias and low-grade lymphomas

Fludarabine monophosphate (FAMP) is a new adenine nucleoside analogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) and low-grade non-Hodgkin lymphomas (NHLs). Here, the clinical experience and side effects with FAMP are reported in 77 patients with pretreated CLL (59 B-CLL, 2 T-CLL) and low-grade NHLs (9 immunocytic lymphomas including 5 Waldenstr?m's macroglobulinaemia, 2 centrocytic (cc) and 5 centroblastic-centrocytic (cb-cc) NHLs). 70/77 patients are evaluable for response. All except 8 patients were pretreated with one to four different regimens and had progressive disease. FAMP was administered at a dosage of 25 mg/m2 daily for 5 days as 30 minute infusion every fifth week. Partial (PR) or complete remission (CR) was achieved in 38/56 (68%) and 3/56 (5%) of evaluable patients with CLL, respectively. In 7/8 (1 x CR, 6 x PR) evaluable patients with immunocytic lymphoma and in 3/6 (3 x PR) patients with cc or cb-cc lymphoma remissions were obtained. The probability of progression-free survival was 66% and the event-free survival was 25% and 22% at 12 and 18 months. The median progression-free survival until relapse or death, however, was only 7 months (2-20+). Major toxic effects included infections in 22 patients (grade 3 and 4 WHO), granulocytopenia (mainly grade 3) and nausea in 8 patients (mainly grade 1). 19/22 patients were in PR at the time of occurrence of infectious complications. Meanwhile, 14 patients died due to septicaemia, pneumonia or other infections. Nine patients developed severe septicaemia, 4 patients had pneumocystis carinii or aspergillus pneumonias. The high infection rate may not only be due to hypogammaglobulinaemia and granulocytopenia induced by FAMP but also to a remarkable decrease of CD4+ cells from a median of 2479 to 241 CD4+ cells/microliters after 6 cycles of FAMP. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. It is concluded that FAMP is effective even in patients with advanced CLL and low-grade NHLs refractory to multiple chemotherapy regimens. However, FAMP has a marked suppressive effect on granulocytes and T-lymphocytes, predominantly CD4+ lymphocytes.     

Intravascular large B-cell lymphoma: the CD5 antigen is expressed by a subset of cases

The CD5 antigen is a T-cell associated marker that is also usually expressed by two B-cell neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. We observed CD5 antigen expression in a subset of cases of intravascular large B-cell lymphoma (IVLBL), and we report here five cases. The patients, two men and three women, ranged in age from 59 to 81 years. Biopsy specimens were obtained from kidney, lung, bone marrow, abdominal wall, and neck, the latter involving a lymphangioma. All of the cases had histologic features typical of IVLBL, with large and atypical lymphoid cells located predominantly within blood vessels. Immunohistochemical studies performed using routinely fixed, paraffin-embedded tissue sections showed that the neoplastic cells were B cells, positive for the CD20 antigen and negative for the CD3 or CD43 antigens. All cases were also positive for the CD5 antigen. One case had an immunoglobulin heavy chain gene rearrangement shown by using a polymerase chain reaction method. The finding of CD5 antigen expression in a subset of IVLBL cases adds to other evidence in the literature suggesting that IVLBL is a heterogeneous entity. We considered the possibility that these cases were related to or represented unusual histologic forms of transformation from either chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma. All of the cases, however, were negative for the CD23 antigen and cyclin D1 (bcl-1) protein, which is evidence against this interpretation. The biologic significance of CD5 antigen expression in cases of IVLBL is uncertain. These neoplasms might arise from a separate lineage of CD5-positive B cells or from a specific, early stage of B-cell differentiation. Alternatively, some investigators have suggested that CD5 antigen expression by B cells is a marker of activation.     

Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia

PURPOSE: CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B- and T-cell lymphomas and leukemias. We report the results of a multicenter phase II trial that used CAMPATH-1H in previously chemotherapy-treated patients with chronic lymphocytic leukemia (CLL). MATERIALS AND METHODS: Twenty-nine patients who had relapsed after an initial response (n = 8) or were refractory (n = 21) to chemotherapy were treated with CAMPATH-1H administered as a 30-mg 2-hour intravenous (IV) infusion thrice weekly for a maximum period of 12 weeks. RESULTS: Eleven patients (38%) achieved a partial remission (PR) and one (4%) a complete remission (CR) (response rate, 42%; 95% confidence interval [CI], 23% to 61%). Three of eight patients (38%) with a relapse and nine of 21 refractory patients (43%) responded to CAMPATH-1H therapy. CLL cells were rapidly eliminated from blood in 28 of 29 patients (97%). CR in the bone marrow was obtained in 36% and splenomegaly resolved completely in 32%. Lymphadenopathy was normalized in only two patients (7%). The median response duration was 12 months (range, 6 to 25+). World Health Organization (WHO) grade IV neutropenia and thrombocytopenia developed in three (10%) and two patients (7%), respectively. Neutropenia and thrombocytopenia recovered in most responding patients during continued CAMPATH-1H treatment. Lymphopenia (< 0.5 x 10(9)/L) occurred in all patients. Two patients had opportunistic infections and four had bacterial septicemia. CONCLUSION: CAMPATH-1H had significant activity in patients with advanced and chemotherapy-resistant CLL. The most pronounced effects were noted in blood, bone marrow, and spleen. Preferential clearance of blood may allow harvesting of uncontaminated blood stem cells for use in high-dose chemotherapy protocols.     

The vascular compartment hampers accurate determination of teniposide penetration into brain tumor tissue

Pleural effusion represents a frequent feature both of Hodgkin's (HL) and non-Hodgkin's (NHL) lymphoma. The aims of the present study were: 1) to analyse the diagnostic accuracy of thoracoscopy as compared to pleural cytology in patients with lymphoma and concurrent pleural effusion; and 2) to evaluate the effectiveness of chemical pleurodesis with the tetracycline derivative, rolitetracycline. Seventeen patients with pleural effusion and concurrent lymphoma (10 NHL and seven HL) were studied. Analysis of pleural fluid revealed the presence of lymphoma cells in six cases (four NHL and two HL); histopathological examination of samples obtained by thoracoscopy was consistent with pleural infiltration by NHL in eight cases and by HL in six cases. Overall sensitivities of pleural cytology and histology were 35 and 82%, respectively. Following chemical pleurodesis, complete response was observed in five of the 17 cases (two NHL and three HL), partial response in four cases (two NHL and two HL), whereas failure was observed in the remaining eight cases. Two patients who had presented failure underwent subsequent pleurectomy by thoracotomy (one case of HL) or video-thoracoscopy (one case of NHL). Complete response was observed in both cases following this treatment. No major complication was recorded after chemical pleurodesis or pleurectomy. Thoracoscopy may be considered a useful tool to evaluate the involvement of pleural space in patients presenting with pleural effusion in the course of lymphoma. Chemical pleurodesis plays an important role in the palliative treatment of this condition. Further studies are necessary to assess the role of pleurectomy in the treatment of such patients.     

Effects of prednisolone in 6 cases of glucocorticoid receptor-positive CLL

The effect of treatment with prednisolone on clinical and laboratory variables was studied in 6 patients with chronic lymphocytic leukaemia (CLL). The laboratory variables analyzed on the leukaemic cells were surface immunoglobulin (S-Ig), sheep red blood cell receptors (SRBC), proliferative activity (PI) and glucocorticoid receptor (GR). In all cases the CLL was of B-cell type and the leukaemic cells contained a significant amount of GR. 4 out of 6 patients had a progressive disease with increased PI. On treatment they went into clinical remission, which was paralleled by a reduction in the leukaemic B-cell number and in PI. The amount of GR was unaffected. In 2 patients with nonprogressive disease, prednisolone produced no clearcut effect on clinical or laboratory variables.     

Isolated U-fiber involvement in MS: preliminary observations

Mantle cell lymphoma is a distinct clinicopathological entity associated with t(11;14) and cyclin D1 overexpression. The majority of cases show uniform morphological and phenotypic features characterized by a monotonous proliferation of small-to-medium-sized irregular B cells that express CD5 and bright surface immunoglobulin IgM and IgD. By sequence analysis of the rearranged immunoglobulin heavy chain variable genes (VH), it has been shown that these lymphoma cells carry little if no somatic mutations, as described for the fetal CD5+ cells or B1 cells. Besides mantle cell lymphoma with classic histological features, a morphological variant of mantle cell lymphoma with blastic features and a more aggressive clinical course has been described. To investigate whether this variant is closely related, by the cell of origin, to typical cases, we analysed the presence and the pattern of somatic mutations of the VH genes in a series of nine cases diagnosed as such. Our cases of blastic mantle cell lymphomas rearrange most frequently VH4 and VH3 family genes. In three cases there was a complete homology to published germline genes, and a near complete homology was documented in another three. In contrast, the remaining three cases showed somatic mutations in their rearranged VH genes. Mutation analysis revealed evidence for antigen selection in one of these three cases. Taken together, these data are similar to those of normal adult-type B1 cells and those described for chronic lymphocytic leukaemia (CLL) but slightly different to those reported for classic mantle cell lymphoma. It is likely that blastic mantle cell lymphoma as well as CLL originates from adult-type B1 cells. More cases will need to be studied to determine whether classic mantle cell lymphoma is different from the blastic subtype and if it arises from fetal-type B1 cells.     

Primary pulmonary lymphoma--clinical review from a single institution in Singapore

Primary pulmonary lymphoma is a rare and vexing subset of extranodal non-Hodgkin's lymphoma. We report 11 cases and provide a brief literature review. We also highlight an unusual case of a relapsed peripheral T-cell primary lung lymphoma that underwent apparent spontaneous remission. Eleven cases of primary pulmonary lymphoma treated in our institution were studied for their clinical characteristics, behaviour, response to treatment and clinical outcome. The median duration of follow up was 26 months. The mean age was in the 50s and the presenting symptoms generally respiratory and non-specific. LDH levels did not correlate with either stage or grade of disease. Lower lobe involvement was most common and nodules and mass-like lesions the main radiologic feature. Small lymphocytic lymphoma accounted for the majority of cases and were indolent in behaviour. Good symptom control and radiologic response was achieved with chemotherapy in disseminated low grade lung lymphomas. Combination chemotherapy was effective in the aggressive lymphomas. In conclusion, Small lymphocytic lymphoma of the lung is an indolent disease with a long symptom-free survival even after recurrence. Our series confirms the clinical characteristics of primary pulmonary lymphoma. The role of Ling Zhi in effecting the spontaneous remission in the peripheral T-cell lymphoma is speculative.     

Clinical utility of immunoglobulin heavy chain gene rearrangement identification for tumour cell detection in multiple myeloma

To clarify the cellular origin of de novo CD5+ diffuse large B-cell lymphoma (CD5+ DLBL), particularly in comparison with other CD5+ B-cell neoplasms such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), we analyzed the nucleotide sequence of the Ig heavy chain variable region (IgVH) genes of de novo CD5+ DLBL cases. All 4 cases examined had extensive somatic mutations in contrast with CLL or MCL. The VH gene sequences of de novo CD5+ DLBL displayed 86.9% to 95.2% homology with the corresponding germlines, whereas those of simultaneously analyzed CLL and MCL displayed 97.6% to 100% homology. The VH family used was VH3 in 1 case, VH4 in 2 cases, and VH5 in 1 case. In 2 of 4 examined cases, the distribution of replacement and silent mutations over the complementarity determining region and framework region in the VH genes was compatible with the pattern resulting from the antigen selection. Clinically, CD5+ DLBL frequently involved a variety of extranodal sites (12/13) and lymph node (11/13). Immunophenotypically, CD5+ DLBL scarcely expressed CD21 and CD23 (3/13 and 2/13, respectively). These findings indicate that de novo CD5+ DLBL cells are derived from a B-1 subset distinct from those of CLL or MCL.     

Prevention of maternal and developmental toxicity in rats via dietary inclusion of common aflatoxin sorbents: potential for hidden risks

The chromosomal translocation t(11;14)(q13;q32) fuses the IGH and CCND1 genes and leads to cyclin D1 overexpression. This genetic abnormality is the hallmark of mantle cell lymphoma (MCL), but is also found in some cases of atypical chronic lymphocytic leukemia (CLL), characterized by a poor outcome. For an unequivocal assessment of this specific chromosomal rearrangement on interphase cells, we developed a set of probes for fluorescence in situ hybridization (FISH). Northern blotting was performed for analysis of the cyclin D1 expression in 18 patients. Thirty-eight patients, with either a typical MCL leukemic phase (17 patients) or atypical CLL with an MCL-type immunophenotype, i.e., CD19-, CD5+, CD23-/low, CD79b/sIgM(D)++, and FMC7+ (21 patients), were analyzed by dual-color interphase FISH. We selected an IGH-specific BAC probe (covering the JH and first constant regions) and a commercially available CCND1 probe. An IGH-CCND1 fusion was detected in 28 of the 38 patients (17 typical MCL and 11 cases with CLL). Cyclin D1 was not overexpressed in two patients with typical MCL and an IGH-CCND1 fusion. In view of the poor prognosis associated with MCL and t(11;14)-positive CLL, we conclude that this set of probes is a valuable and reliable tool for a rapid diagnosis of these entities.     

Lung transplantation in cystic fibrosis

PURPOSE: To assess the non-cutaneous involvement in primary B-cell non-Hodgkin's lymphoma (NHL) of the skin. PATIENTS AND METHODS: Data from 45 patients with B-cell NHL of the skin were retrospectively analysed. The patients were diagnosed on histologic and immunocytochemical grounds between June 1977 and July 1993, and 14 cases were selected for their exclusively cutaneous initial involvement. Initial treatment, response to therapy, disease-free survival characteristics of relapse and therapeutic sequence were evaluated in every case. RESULTS: Cutaneous involvement presented as nodules or patches, on a single location, in 12 cases, or disseminated, in 2 others. No prognostic factor could be identified, and complete remission was attained in all cases. Cutaneous relapse was seen in 7 patients after 4 to 108 months since diagnosis. Extracutaneous dissemination was not seen in any case, and 13 patients are alive and disease-free. A 90 year-old woman died of toxic complications. CONCLUSIONS: The clinical facts reported here confirm the not too aggressive behaviour of certain B-cell cutaneous NHL, probably related with their origin on the skin itself.     

Dacryocystitis associated with malignant lymphoma of the lacrimal sac

BACKGROUND: Tumors of the lacrimal sac are unusual, and lymphomas of the lacrimal sac are quite rare. Four patients with a history of well-differentiated, small cell lymphoma or chronic lymphocytic leukemia presented with either acute or chronic dacryocystitis and epiphora due to lymphomatous infiltration of the lacrimal sac. METHODS: All four patients underwent dacryocystorhinostomy with lacrimal sac biopsy. All tissues underwent complete histopathologic evaluation including immunohistochemical studies for cell surface markers and, in addition, were compared with previous biopsies performed for the initial diagnosis of lymphoma. FINDINGS: All biopsies demonstrated small cell well-differentiated lymphoma on histologic and immunofluorescent examination. No patient demonstrated orbital involvement on computed tomography. One patient had previously diagnosed chronic lymphocytic leukemia and one patient demonstrated diffuse lymph node involvement on postoperative systemic evaluation. All four patients underwent additional chemotherapy. No recurrence of dacryocystitis or epiphora occurred. CONCLUSION: Four patients presented with dacryocystitis secondary to lacrimal sac lymphoma. Lymphomatous lacrimal sac infiltration is an unusual cause of dacryocystitis. Biopsy of the lacrimal sac plays a diagnostically important role in dacryocystorhinostomy even in the absence of obvious tumorous involvement of the lacrimal sac mucosa.