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Splenic Marginal Zone Lymphoma (SMZL), with or without villous lymphocytes (VL+/-), is a low-grade lymphoproliferative disorder with constant involvement of the bone marrow (BM). Different BM infiltration patterns, mainly intra-sinusoidal, interstitial and nodular, have been described. Adhesion molecules (AMs) constitute a heterogeneous group of antigenic receptors playing a major role in leukocyte recruitment, in lymphocyte homing and in cellular-mediated immune response. Evolution and pattern of the BM infiltrate could be influenced by a variable expression of AM on SMZL lymphocytes. The degree and pattern of BM infiltration and the immunohistochemical expression of AM (H-CAM, BL-CAM, L-selectin, PSGL-1, E-selectin, ICAM-1, VCAM-1 and Beta-1 integrin) among the different infiltration patterns were evaluated in BM biopsies of 38 patients with SMZL and graded according to a semi-quantitative score ranging from 0-4 and based on the percentage of positive cells. An intra-sinusoidal infiltration was constantly observed, alone or in conjunction with other patterns. H-CAM and BL-CAM showed a moderate-to-high degree of positivity in the intra-sinusoidal infiltrate (median expression grade-3) and were expressed in the neoplastic lymphocytes independently from the pattern. PSGL-1 was mostly expressed in the perisinusoidal region and in case of interstitial infiltration (grade-2). ICAM-1 and VCAM-1 were selectively expressed in the nodules as a reticular meshwork located in the core region (grade-2); VCAM-1 was also expressed in the perinodular endothelia. E-selectin, L-selectin and beta-1 integrin proved constantly negative. These data suggest that different expression of AM can influence the modality of BM infiltration in SMZL.

Background: Splenic marginal zone cell lymphoma (SMZL) is a low grade B-cell lymphoma in which patients can have circulating villous lymphocytes and can show a peculiar intrasinusoidal bone marrow (BM) infiltration. Splenectomy is the reported treatment of choice for these patients. The objective of this study was to evaluate the effects of splenectomy on patients with BM lymphomatous infiltration., Methods: BM biopsies of 16 patients with SMZL were studied morphologically and immunohistochemically. In 12 patients, BM biopsies were taken before and after splenectomy. Four patients did not undergo splenectomy, and their BM biopsies were performed with an approximately 1 year interval., Results: BM infiltration ranged from 10% to 40% of overall cellularity and was mostly of the intrasinusoidal type. After splenectomy, BM infiltration tended to become frankly nodular and showed an increase in tumor burden. Nonsplenectomized patients showed an unmodified picture., Conclusions: Splenectomy seems to induce important changes in patients with BM infiltration, probably through the lack of microenvironmental factors on circulating cells. These effects suggest reconsidering the role of splenectomy in the treatment of patients with SMZL.

A particular type of lymphomatous bone marrow infiltration defined as intrasinusoidal and occurring in seven patients with splenomegaly and mild to moderate thrombocytopenia is reported. Immunocytochemistry highlighted the intrasinusoidal pattern and showed a mature B-cell phenotype. Four patients underwent splenectomy and a diagnosis of splenic marginal cell lymphoma was made. The disease course seems to be chronic and quite indolent. All patients are alive and well; follow-up ranges from 2 to 42 months. The value of bone marrow biopsy as a primary diagnostic tool in splenic marginal zone lymphomas is discussed.

Bone marrow cellularity and extent of fibrotic change were determined in nineteen patients with polycythemia vera, treated with interferon-alpha (IFN) for 1 year. The cellularity was evaluated with an interactive semiautomatic method using Leitz TAS plus microscope: in particular, number and size of megakaryocytes were evaluated after immunostaining with Y2/51 (CD 61); reticulin content was studied by light microscope with a semiquantitative method. Before IFN therapy mean cellularity was 80.5% (+/- 13.7). After 6 and 12 months mean cellularity was 75.4% and 68.4% respectively. Six months after cessation of IFN therapy the cellularity was 69.1%. A decrease of the number, density and morphometrical parameters of megakaryocytes was also remarked. Reticulin fibrosis was mild in 13 cases and moderate in 6 cases before IFN therapy. Reticulin content was unmodified during therapy in all cases but two, in which fibrosis changed from mild to moderate. In conclusion IFN therapy is to be considered a good method in polycythemia vera for the control of proliferative activity of bone marrow but with IFN therapy one cannot determine regression of marrow fibrosis.

One hundred and seventy bone marrow biopsies from patients with chronic myeloproliferative disorders (CMPDs) were evaluated for the presence of lymphoid nodules (LNs) and were immunostained using a panel of monoclonal antibodies (UCHL1, 4KB5 and L26) recognizing different lymphocyte antigens. LNs were found in 35% of cases of idiopathic thrombocythaemia, 24.6% of myelofibrosis/osteomyelosclerosis, 18.2% of polycythaemia vera 12.1% of chronic myeloid leukaemia and 19.2% of borderline cases. Varying degrees of immunohistochemical positivity for the three antibodies tested were found. LNs were always made up of variable proportions of both T- and B-lymphocytes with a prevalence of T-cells. This latter observation suggests that bone marrow LNs in CMPDs could be an expression of reactivity.

Franco V, Florena A M, Ascani S, Paulli M, Salvato M & Pileri S A (2004) Histopathology 44, 381–386 CD27 distinguishes two phases in bone marrow infiltration of splenic marginal zone lymphoma To investigate CD27 expression in splenic marginal zone lymphoma (SMZL), an indolent low-grade B-cell lymphoma with constant involvement of the bone marrow, especially with an intrasinusoidal pattern. It is not clear if the neoplastic clone is composed of virgin or somatically mutated B cells. CD27 is reported to be a hallmark of memory B cells. We evaluated 64 bone marrow biopsy specimens (BMBs) from 36 patients with SMZL for the expression of CD27. For comparison, splenectomy specimens of patients with traumatic splenic rupture or with SMZL were used. All BMBs showed lymphomatous infiltration. When located in the marrow sinusoids, neoplastic cells were CD27– in all cases and therefore corresponded to naive B cells. In nodular/interstitial infiltration, the cells were CD27+ and therefore corresponded to memory B cells. No difference in immunohistochemical expression of B and T antibodies was found between intrasinusoidal and interstitial/nodular infiltration. CD27 was constantly expressed in the splenic marginal zone of normal spleen, surgically removed for trauma, and in seven out of 10 spleens with SMZL. We propose the existence of two different phases of neoplastic progression with, first, expansion of a virgin B clone in the bone marrow and, following exposure to antigen, a re-colonization of the bone marrow. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the production of C1q using bone marrow stromal cells.

Aims: Essential thrombocythaemia (ET) and primary myelofibrosis (PMF) share some clinical and pathological features, but show different biological behaviour and prognosis. The latest contributions to understanding the nature of these disorders have focused on bone marrow microenvironment remodelling and proliferative stress, recognising megakaryocytes (MKCs) as "key-cells". The aim of this study was to investigate the apoptotic profile of ET and PMF MKCs in order to further characterise the biology of these disorders. Methods: Bone marrow biopsy samples from 30 patients with ET, and 30 patients with PMF, were immunophenotypically studied for the expression of pro-apoptotic (Fas, Fas-L, Bax, Bad) and anti-apoptotic (Bcl-2, Bcl-XL, hTERT (human telomerase reverse transcriptase)) molecules and the "executioner" molecule caspase-3. The fraction of MKCs undergoing apoptosis was assessed by deoxynucleotidyl transferase-mediated dUTP nick-end labelling. Results: Only the mitochondrial pathway seemed to be involved in MKC apoptosis. The anti-apoptotic molecule Bcl-XL was predominantly found in ET MKCs (50.5% of ET MKCs versus 35% of PMF MKCs; p = 0.036), while pro-apoptotic molecules Bax and Bad showed a prevalent expression in PMF MKCs (30.5% of ET MKCs versus 55% of PMF MKCs; 41% of ET MKCs versus 52% of PMF MKCs; p = 0.001 and p = 0.068, respectively). A significant fraction of PMF MKCs were committed to apoptosis according to caspase-3 expression and TUNEL, while only few ET cells were committed to apoptosis. hTERT was significantly more expressed in PMF (32% of ET MKCs versus 46% of PMF MKCs; p = 0.022), in agreement with the proliferative nature of this disease. Conclusions: It was found that ET and PMF MKCs, which barely differ in terms of morphology and aggregation, are characterised by markedly different apoptotic profiles. The rather high apoptotic fraction of PMF was able to support the fibrotic nature of this process, while the anti-apoptotic profile of ET cells fits well with their "steady" maturative state. [ABSTRACT FROM AUTHOR]