Small Lymphoid Cells Research Articles

Mantle cell lymphoma-like solitary polypoid tumor of the esophagus: a case report

IntroductionPrimary mantle cell lymphoma of the esophagus is quite rare, and we report here a case of a submucosal polypoid tumor of the esophagus that was pathologically similar, but not identical, to mantle cell lymphoma.Case presentationA 66-year-old man underwent surgery in our hospital for a submucosal tumor of the esophagus. Histopathologically, the submucosal tumor uniformly showed a vague, nodular pattern composed of a regular proliferation of CD3-CD10-CD20+CD79a+bcl2+ small lymphoid cells with islands of abortive CD10+Ki67+ germinal centers, without evidence of marginal zone formation or lymphoepithelial lesions. These features were consistent with mantle cell lymphoma. However, the proliferating cells weakly expressed the D-type cyclins, IgD and IgM. The tumor was diagnosed as a “mantle cell lymphoma-like tumor”. Postoperative examination confirmed no tumour involvement in other organs. The patient was treated with rituximab postoperatively and has been disease free for more than 28 months after surgery.ConclusionThe present case might be regarded as a “hyperplastic change of the mantle zone” without the molecular features of mantle cell lymphoma, a case that adds to the limited clinicopathological data on B-lymphoproliferative diseases of the esophagus.

Small cell variant of peripheral T-cell lymphoma, not otherwise specified: a clinicopathologic and immunophenotypic analysis

To study the clinicopathologic features and differential diagnosis of small cell variant of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). The clinicopathologic features of 5 cases of small cell variant of PTCL, NOS were retrospectively reviewed, with immunohistochemical study, T-cell receptor (TCR) gene rearrangement analysis and evaluation for Epstein-Barr virus (EBV) status. All the 5 patients were males. The mean age was 52.6 years. The median duration before diagnosis was 1 month. Clinically, 3 patients presented in stage IV and 2 in stage III. Four of them had generalized lymphadenopathy and splenomegaly. Hepatomegaly and massive effusion were found in 1 and 2 cases, respectively. Marrow involvement was detected in 3 of the 4 patients with bone marrow biopsy performed and one of them also accompanied by lymphocytosis. Histologically, the involved lymph nodes showed partial or complete effacement of nodal architecture and replacement by a monomorphous population of small lymphoid cells. Scanty large lymphoid cells were also identified in 4 cases. Increase in number of blood vessels was noticed in two of them as well. Immunohistochemically, the lymphoma cells in all cases expressed two or more of the T-cell markers and CD43. The staining for CD20, TdT, CD56 and granzyme B was negative. CD99 expression was noted in 3 of the 4 cases. The Ki-67 index ranged from 5% to 15%. Clonal TCRgamma gene rearrangement was detected in the 4 cases studied and one of them also showed TCRbeta gene rearrangement. In-situ hybridization for EBV-encoded RNA was negative in the 4 cases studied. Follow up information was available in 3 of the 5 cases. All of the 3 patients died of the disease, with an average survival of 21.7 months. Small cell variant of PTCL, NOS represents a rare disease entity which often presents in advanced tumor stage and carries a poor prognosis.

Infectious agents and lymphoma development: molecular and clinical aspects

This review is focused on the role of infectious agents in the development of some lymphoma entities. Associations involving bacterial infections mostly regard marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT)-type. Some paradigmatic examples of these associations include the Helicobacter pylori-related gastric MALT lymphoma and the more recently reported links between Chlamydophila psittaci and ocular adnexal MALT lymphomas and Borrelia burgdorferi and cutaneous MALT lymphomas. The well-documented association between Epstein-Barr virus infection and related lymphoproliferative disorders are analysed as an example of lymphotropic virus with tumourigenic activity. Molecular, biological and clinical features as well as therapeutic implications of these associations are analysed and future perspectives in this field are discussed.

Midline Malignant Reticulosis In Birnin Kebbi, Nigeria : A Case Report

We report the case of a 45-year old woman with a six-month history of persistent headache, right nasal obstruction, recurrent epistaxis and right eye swelling. Examination revealed obvious facial asymmetry, enophthalmos, right maxillary and zygomatic swelling with an intranasal mass exhibiting contact bleeding. Plain roentgenograms revealed erosion of the surrounding bones. Patient had right lateral rhinotomy to clear the tumour and arrest epistaxis. Histological examination of the biopsy revealed a polymorphic neoplasm composed of a mixture of small lymphoid cells and atypical large histiocytoid cells with foci of necrosis. These features were consistent with midline malignant reticulosis. This is a relatively rare condition and this is the first case recorded in this centre. Keywords: Midline malignant reticulosis; Histopathology; Rare Sahel Medical Journal Vol. 11 (3) 2008: pp. 102-104

A Case of CD5 Negative Chronic Lymphocytic Leukemia

Neoplastic lymphoid cells of chronic lymphocytic leukemia (CLL) typically co-express CD5 and CD23. CD5-negative CLL is a rare variant of CLL; only 1 case of it has been reported in Korea. We describe a case of CD5-negative CLL. A 48-year-old female complained of a palpable neck mass that had been present for over 1 year. The initial WBC count was 7,300/, with 69% lymphocytes. A CT scan revealed multiple enlarged lymph nodes, both of each in the neck, axilla, and common iliac areas. The athologic results of the cervical lymph node was consistent with small lymphocytic lymphoma, of which tumor cells do not express CD5. In a bone marrow study, neoplastic lymphoid cells comprise 34.8% of all nucleated cells, which showed small size, round nuclei with clumped chromatin, and sparse cytoplasm. Immunophenotyping of small lymphoid cells displayed phenotypes that were CD45-, CD23-, CD20-, and CD19-positive, but CD5-negative. The patient was diagnosed with CD5-negative CLL, and has been followed up for 2.5 years after chemotherapy.

Lymphoplasmacytoid Lymphoma in a Cow

Lymphoplasmacytoid lymphoma was found in an 8-year-old Holstein cow uninfected with bovine leukemia virus (BLV). The neoplastic tissue was composed of lymphoid and plasmacytoid cells, and intracytoplasmic IgM (lambda) was detected in the latter. The diagnosis was based on the presence of small lymphoid cells and the expression of CD5, which were suggestive of a close relationship with chronic lymphocytic leukemia. Areas of immunoblastoid cells were reminiscent of histologic progression into immunoblastic lymphoma. The neoplastic cells at different stages of differentiation were distinct from those of BLV-associated pleomorphic lymphoma.

Immunophenotypic analysis of cerebrospinal fluid cell populations with the Cell-Dyn Sapphire haematology analyser: method feasibility and preliminary observations

Cerebrospinal fluid (CSF) samples (n=50) from patients with neurological disease (bacterial infection, viral infection, neuroborreliosis and multiple sclerosis) were analysed to characterize cell populations by fluorescent immunocytometry with the CD-Sapphire haematology analyser. Reagent combinations applied to all CSF samples comprised CD3/CD19/HLA-DR and CD4/CD8, with some being further analysed using CD3/CD4, CD3/CD16 and CD3/CD25 protocols. Of the 50 samples, 11 were excluded because of high proportions of nonviable cells (n=2) or insufficient cell numbers (n=9). Apart from bacterial infection with granulocytosis, all diagnostic groups showed high proportions (51.4-77.0%) of CD3+ T cells. There was a modest association between T-cell and B-cell counts, but absolute B-cell numbers exceeded 5 cells/microl in only 7/39 cases (neuroborreliosis, n=6; bacterial meningitis, n=1). CD3/Ia antigen (activation) co-expression was low and only exceeded 5% in 7/39 samples with no diagnostic correlation. Primary CD4+ and CD8+ T-cell subsets showed similar quantitative trends and CD4/CD8 co-analysis revealed the presence in all diagnostic groups (neuroborreliosis and multiple sclerosis in particular) of a CD4+CD8int fraction that was predominantly CD3+ and CD16- and had a morphological profile consistent with small lymphoid cells. Supplementary CD-Sapphire cellular immunological analysis of most CSF samples is feasible using the procedure detailed in this communication.

Mantle cell lymphoma with partial involvement of the mantle zone: an early infiltration pattern of mantle cell lymphoma?

Most patients with mantle cell lymphoma present with a diffuse or nodular infiltration of the involved organs at diagnosis. We present two patients with a rare morphological variant, displaying a partial involvement of the mantle zone. Patient 1 presented with an enlarged inguinal lymph node, which showed marked follicular hyperplasia with singly spread Cyclin D1+ small lymphoid cells in the mantle zones. An additional lymph node biopsy taken 3 months later showed the same pattern. Patient 2 presented with a classical mantle cell lymphoma with lymph node, bone marrow and gastro-intestinal involvement. However, revision of an appendectomy specimen taken 4 years earlier showed pronounced follicular hyperplasia with singly spread Cyclin D1+ small lymphoid cells in the mantle zones. Mantle cell lymphoma with partial involvement of the mantle zone has rarely been reported and many represent an early manifestation of mantle cell lymphoma. Our cases also illustrate that the inclusion of an anti-cyclin D1 antibody in the diagnostic panel of antibodies to study unexplained follicular hyperplasia, might be advised.

A case of MALT lymphoma of the palate suggested to be related to Sjoegren syndrome

A case of MALT lymphoma arising in the hard palate is reported. A 33-year-old woman was referred to us because of a swelling in the left side of the hard palate. The mass, measuring 31×x18mm, was soft and elastic with a smooth surface. The tumor was surgically removed, and postoperative irradiation was performed. The pathological diagnosis of the specimen was MALT lymphoma. The lesion consisted of small centrocyte-like lymphoid cells. Immunohistological examination showed that the neoplastic cells were positive for CD20 and negative for CD5, CD10, and CyclinDl. Reactivity for Bcl-2 was positive in the neoplastic colonizing B cells, except for the germinal center cells. After surgery Sjogren's syndrome (SS) was diagnosed. Therefore, SS-related MALT lymphoma was suggested in our patient. There has been no recurrence of the lesion as of 1 year after treatment.

The implications of an incidental chronic lymphocytic leukaemia in a resection specimen for colorectal adenocarcinoma

BackgroundColorectal cancer and B cell chronic lymphocytic leukaemia (CLL) have a significant incidence, which are increasing with the aging population. Evidence has been presented in the literature to suggest that the synchronous presentation of colorectal cancer and B cell CLL may be more than simply coincidental for these two common malignancies. We report an unusual case of a presumed B cell CLL diagnosed on the basis of histological analysis of lymph nodes recovered from a resection specimen for rectal adenocarcinoma. We considered aetiological factors which may have linked the synchronous diagnosis of the two malignancies and the potential implications for the natural history of the two malignancies on one another.Case presentationA 70-year-old male underwent low anterior resection with total mesorectal excision for a rectal adenocarcinoma. His co-morbid conditions were chronic obstructive airways disease and ischaemic heart disease. General examination revealed no lymphadenopathy. Full blood count, urea and electrolytes and liver function tests were all within normal limits. As well as confirming a pT3 N1 adenocarcinoma, histological analysis showed lymph nodes with an infiltrate of small lymphoid cells. Immunohistochemical studies showed these cells to be in keeping with B cell CLL.ConclusionWhilst unable to identify any common aetiological factors in the two malignancies in our patient, immunosuppression and genetic abnormalities have been identified as possible bases for an observed epidemiological association between colorectal cancer and haematological malignancies. Examples such as our case of synchronous diagnosis of two malignancies in a patient are likely to increase with the aging population. The potential affects of one malignancy on the natural history of the other warrants further study. In our case, we considered that slow progression of the B cell CLL may increase the risk of recurrent rectal adenocarcinoma.

Diagnostic, pronostic et traitement chez les patients avec une leucémie lymphoïde chronique

B-Chronic lymphocytic leukaemia (CLL) is the most frequent of chronic leukaemias. It is defined by a durable absolute lymphocytosis (> 4 × 10 9/l) with small mature lymphoid cells in the peripheral blood. Immunological score established on five criterias (positivity of CD5 and CD23, negativity of the FMC7 and weak expression of sIg and CD22 or CD79b) is four or five. The Binet classification defines three stages of different evolution: the stage A (65% of the cases) and B (28%) without or with three areas involved at least, in the absence of anaemia or thrombopenia and the stage C with anaemia (haemoglobin lower than 10 g/dl) or thrombopenia (platelets lower than 100 × 10 9/l). Patients with stage A will a few progress quickly and conversely others will remain stable with no evolution for very long periods. Four markers with prognosis value were recently identified and allow to adopt new therapeutic strategies according to the presence or not of these markers. These factors are lymphocytes doubling time, serum thymidine kinase, cytogenetic abnormalities including del(11) and del(17), +12 and del(13), and the immunoglobulin mutational profile. The therapeutic strategies evolved these last years and call, if criteria of gravity are present, to chemotherapy (purines analogs associated or not with cyclophosphamid) and immunotherapy (anti-CD20 and/or anti-CD52 monoclonal antibody).

Successful radiotherapy in a patient with primary rectal mucosa-associated lymphoid tissue lymphoma without the API2-MALT1 fusion gene: A case report and review of the literature

Primary rectal MALT lymphoma is rare comprising less than 1% of MALT lymphomas. A 26-year-old man was referred to our hospital because of constipation and abdominal fullness. Colonoscopy revealed multiple submucosal tumors in rectum. Histopathological examination showed dense proliferation of small lymphoid cells, but lymphoepithelial lesions were not observed. The cells were CD5(−), CD10(−), CD20(+) and cyclinD1(−). The patient was diagnosed as having MALT lymphoma. The patient was negative for API2-MALT1 gene, and radiotherapy was performed and CR was achieved. With the accumulation of cases, establishment of a treatment strategy for primary rectal MALT lymphoma is expected in the future.

Successful treatment of primary cutaneous follicle centre lymphoma with topical 5% imiquimod

Conflicts of interest: none declared. Sir, Imiquimod, a topical immune response modifier, has potent antitumour activity through local augmentation of innate and cell‐mediated immunity.1 It is increasingly being used to treat a wide variety of cutaneous tumours, including cutaneous T‐cell lymphomas.2, 3 It has not previously been shown to be fully efficacious for the treatment of cutaneous B‐cell lymphoma. We report a 59‐year‐old man with primary cutaneous follicle centre lymphoma successfully treated with topical 5% imiquimod. Our patient presented with a 5‐year history of multiple asymptomatic lesions grouped over the lateral surface of his upper right arm. Individual lesions had gradually appeared and enlarged over this time. Examination revealed smooth‐surfaced soft dermal papules and nodules (Fig. 1a). There was no associated palpable lymphadenopathy, nor organomegaly. Skin biopsy showed a lymphoid lesion involving superficial and deep dermis. The epidermis was intact and a Grenz zone was present (Fig. 2). On higher magnification, the infiltrate was noted to be polymorphic and composed of intermixed small and large lymphoid cells, with sparse germinal centres.

Solitary Intestinal Lymphoid Tissue Provides a Productive Port of Entry for Salmonella enterica Serovar Typhimurium

Oral infection of mice with Salmonella enterica serovar Typhimurium results in the colonization of Peyer's patches, triggering a vigorous inflammatory response and immunopathology at these sites. Here we demonstrate that in parallel to Peyer's patches a strong inflammatory response occurs in the intestine, resulting in the appearance of numerous inflammatory foci in the intestinal mucosa. These foci surround small lymphoid cell clusters termed solitary intestinal lymphoid tissue (SILT). Salmonella can be observed inside SILT at early stages of infection, and the number of infected structures matches the number of inflammatory foci arising at later time points. Infection leads to enlargement and morphological destruction of SILT but does not trigger de novo formation of lymphoid tissue. In conclusion, SILT, a lymphoid compartment mostly neglected in earlier studies, represents a major site for Salmonella invasion and ensuing mucosal pathology.

Sequence analysis proves clonal identity in five patients with typical and blastoid mantle cell lymphoma

AbstractMantle cell lymphoma (MCL) is typically composed of small irregular lymphoid cells. Blastoid variants, composed of lymphoblast-like (classic type) or large (pleomorphic type) cells, arise de novo or in patients with typical MCL. Although it has been assumed that blastoid variant represents histologic transformation of typical MCL, the clonal relationship between the two tumors has rarely been assessed at the molecular level. We identified five patients with typical MCL who subsequently developed the blastoid variant. There were two men and three women with a median age of 65 years (range, 34–70) at diagnosis of typical MCL involving lymph nodes. The median interval between typical and blastoid MCL was 36 months (range, 11–103). Subsequent blastoid variant MCL involved soft tissue (two), lymph node (one), ileum (one), or rectum (one). All typical and blastoid neoplasms were positive for CD20, cyclin D1, and monotypic surface immunoglobulin light chain, and all typical cases were positive for CD5. Two blastoid neoplasms lost CD5 expression, one of which aberrantly expressed CD10. Immunostaining for Ki-67 showed a median proliferative fraction of 20% in typical and 70% in blastoid neoplasms. Sequence analysis of the VDJ regions of the rearranged IgH allele proved clonal identity in each set of paired samples in all five patients. These results support the concept that blastoid MCL arising in patients with typical MCL represents histologic transformation of the original neoplastic clone.

A Case of Bronchus-Associated Lymphoid Tissue(BALT) Lymphoma Treated with Lobectomy

The bronchus-asociated lymphoid tissue(BALT) lymphoma is a low-grade primary malignant lymphoma that originates from bronchus associated lymphoid tissue. A 67-year-old woman was admitted for evaluation of cough, sputum, rhinorrhea which had persisted for one month. Physical examination showed decreased breathing sound on the left upper lung field. High resolution chest computed tomography demonstrated consolidation which showed air-bronchogram and surrounding ground glass opacity in left upper lobe. These findings implicated inactive tuberculosis, organizing pneumonia, or bronchiolo-alveolar carcinoma. The histologic findings from percutaneous needle aspiration biopsy revealed aggregated atypical small lymphoid cells with lymphoepithelial lesions. With immunohistochemical staining, the atypical lymphoid cells reacted positively with CD 20 antibody and negatively with CD 3 antibody. Thus, we could diagnosed her as a patient with BALT lymphoma. After left upper lobectomy, she has been well without recurrence of the disease for 14 months. In this country of Republic of Korea, it was the 1st case of BALT lymphoma surgically treated when histological diagnosis had been done. Based on this case, we wanted to demonstrate the importance of early histological diagnosis and treatment of BALT lymphoma.

Angioimmunoblastic T-cell Lymphoma Developed with Lymphocytic Pleural Effusion

Angioimmunoblastic T-cell lymphoma (AILT) is a rare variant of nodal and aggressive lymphoma. It is sometimes difficult to distinguish AILT from reactive lymphoid hyperplasia from the histopathological aspect. We report a case of AILT which developed with bilateral pleural effusion. The effusion consisted predominately of small lymphoid cells. Analyses of the effusion showed trisomy 3, and rearranged bands of TCR beta gene. Flow cytometry showed a very small amount of CD10-positive cells. Although we could not further identify the tumor cells in this case, analysis of pleural effusion cells will increase our understanding of the pathogenesis and the pathophysiology of AILT.

Clinical, histopathological and immunophenotypical findings in five horses with cutaneous malignant lymphoma

This study documents the clinical, histopathological, immunohistochemical and flow-cytometric findings in five horses with cutaneous non-epidermotropic malignant lymphoma (ML). The median survival time after discovery of the first subcutaneous nodules was 3.8 years (range 2–5 years: n = 4). Histologically, the cutaneous ML had a pleiomorphic structure and contained a mixture of large reticulo-endothelial cells, medium-large sized lymphoid cells with a rounded nucleus and small nucleoli, many medium sized lymphoid cells with irregular nuclei, and some small lymphoid cells. Immunohistochemically (IHC) the lymphoid cells were positive for the pan-T-lymphocyte marker CD3 but negative for the B-lymphocyte markers CD21 and kappa and lambda immunoglobulin light chains. Although routine haematological examination revealed no abnormalities in the horses with cutaneous ML, changes in the peripheral blood lymphocyte population were apparent flow-cytometrically. Compared to clinically healthy horses, a decreased total percentage of cells was recorded in the lymphocyte gate. In three horses with cutaneous ML, an increase in CD4 positive cells was noticed in the monocyte gate. Flow-cytometric analysis of tumour cells collected by fine needle aspiration (FNA) suggested that the cutaneous MLs consisted primarily of CD4 and CD8 positive T-lymphocytes. The results were compared to those of a monomorphic multicentric T- and a monomorphic multicentric B-cell lymphoma. The results of immunohistochemistry and flow-cytometry were largely but not completely in accordance. In conclusion, the results of this study suggest that cutaneous non-epitheliotropic malignant lymphomas in the horse are of T-cell origin and that, after improvement of its accuracy, flow cytometric analysis of FNAs might become a useful aid to rapid tumour identification.

Distal Limb Infiltration by Transformed Lymphoplasmacytoid Lymphoma.

We report 2 cases of lymphoplasmacytoid lymphoma (LPCL) with aggressive, high-grade transformation accompanied by extensive distal lower limb skeletal disease.Case 1: a 26-year-old man with stage IVA anaplastic Ki-1+ NHL achieved durable CR1 with VAPEC-B induction, AC consolidation & mediastinal radiotherapy. In 1997 he re-presented with lymphadenopathy: biopsy & marrow showed small CD20+CD79a+ B lymphocytes with IgM(κ) light chain restriction & increased mature plasma cells, but no evidence of anaplastic NHL. He received VAD (×6) & autologous PBSCT (melphalan 200mg/m2) to CR1. Relapse in 2004 was treated with cyclophosphamide & dexamethasone, then fludarabine (×4). Ten months later he presented with B symptoms & painful right tibial swelling. MR showed multiple medullary lesions in proximal femoral shafts, tibiae & upper fibulae. CT confirmed widespread lymphadenopathy & bilateral renal deposits. Marrow had dense infiltrate of CD20+CD79a+ small lymphoid cells with additional immature CD20+CD79a+ blasts, consistent with transformation to high-grade DLBCL. New complex cytogenetics included XXY with t(14;22) (IGH rearrangement), add(1q), del(6q), del(9p) & trisomy 3. He received R-mini-BEAM (×2) & 2nd PBSCT (R-BEAM conditioning) in 2006 using residual 1997 PBSCH, acheiving CR4 with bony regression on MRI. Four months later B symptoms & right tibial pain recurred & the disease is currently being held by rituximab & steroid.Case 2 was diagnosed with WM/LPCL in 1996, aged 54, following 8 years history of IgM MGUS. He received chlorambucil (1996), CVP (×6) (1997), fludarabine (×5) (1999/2000), chlorambucil (2001) rituximab (×8), further fludarabine (×3) (June 2003) & repeated R-CVP (2004/5). In Sept 2005 he presented with lower limb & right heel pain. MR revealed diffuse abnormality within tibiae, fibulae & distal femorae: a soft tissue mass infiltrated the right talus bone, & left calcaneus, talus & anterior malleolus showed patchy involvement. Biopsy of right talus yielded small lymphocytes, lymphoplasmacytoid cells & plasma cells, strongly CD20+ & κ light chain restricted (with smaller % CD138+ cells), in keeping with lymphoplasmocytic lymphoma. Bisphosphonate exacerbated the pain & single fraction of radiotherapy had no effect. He received salvage R-CVP (×6), reducing paraprotein from 6.9 to 2.7g/L. Nevertheless, the bone deposits continue to cause significant discomfort.Transformation of WM/LPCL to high-grade lymphoma is rare but well-described. Lin et al. describe DLBCL transformation in 13% cases, at median 44 months after diagnosis & associated with poor outcome. Seven of the 12 cases had received cladrabine. Purine analogues have been implicated in pathogenesis of Richter's syndrome, in which CLL transforms to aggressive NHL (estimated <3% CLL patients). MRI reliably demonstrates marrow involvement in WM/LPCL but changes are diffuse. In contrast to MM, focal skeletal MR abnormalities are not observed in WM/LPCL.We present 2 cases of LPCL with focal distal lower limb bone involvement. The focal nature of skeletal involvement in sites not active in adult haemopoeisis (& atypical for LPCL or MM involvement), with B symptoms & rapidly progressive NHL are unusual features. Other features include >10year disease course, multiple lines of therapy (incl. purine analogues) & high-grade transformation/behaviour. Involvement of distal bones (e.g. talus) is rare in NHL, & we could find no previous reports of focal distal lower limb LPCL. We observe that LPCL can undergo high-grade transformation (analogous to Richter's syndrome) with distinct trophic phenotype, & postulate that purine analogues may be implicated in selecting for this behaviour.

Bone Marrow Histopathological and Molecular Changes of Small B-Cell Lymphomas after Rituximab Therapy: Comparison with Clinical Response and Patients' Outcome

This study correlates bone marrow changes after Rituximab (RTX) treatment with the clinical characteristics and outcome of 26 patients with small B-cell lymphomas. The percentage, phenotypic profile and clonality pattern of bone marrow lymphoid infiltrate were analysed before and after RTX treatment. Clinical, histological and molecular responses to RTX were correlated to the clinical outcome of the patients. Sixteen out of twenty-six patients obtained a complete clinical remission (CR). A favourable histology--follicular lymphoma (FL), hairy cell leukaemia (HCL) and marginal zone lymphoma (MZL)--was associated with a higher frequency of clinical CR and histological remission (HR), in comparison with mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL) and lymphoplasmacytic lymphoma (LPL). Two patterns of bone marrow HR were observed: 1) complete lymphoid cell disappearance (9 patients); or 2) nodular/interstitial T-cell infiltration (10 patients). Three histological persistence (HP) patterns were observed: 1) persistence of CD20+ small lymphoid cells in 1 patient with MCL; 2) loss of CD20 antigen expression in 4 patients with CLL; or 3) persistence only of clusters of monotypic plasma cells in 2 patients with LPL. CR and HR were strongly correlated. The percentage of lymphomatous infiltrate after RTX was higher in patients who subsequently died of the disease. Molecular response showed no correlations with the further clinical course in 12 patients achieving a complete clinical remission. In conclusion, bone marrow morphological and immunohistochemical analysis with a restricted panel of antibodies is useful to avoid 42% false positive and 85% false negative interpretations. Persistence of monoclonality after RTX might have a role in evaluating the molecular pattern of CD20-negative clones that can emerge after RTX as a tumoral escape to therapy.