Is sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp identical to inflammatory pseudotumour? Report of 16 cases.

AIMS: To report 16 cases of sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp. METHODS AND RESULTS: Patients were selected in two phases. An initial group of seven patients was diagnosed with SANT based on the presence of angiomatoid nodules. Sheets of inflammatory fibrosis were found in three patients, resembling inflammatory pseudotumour (IPT); nine further cases of IPT were reviewed. Angiomatoid nodules were detected, leading to the diagnosis of SANT in all cases. The splenic mass (10-150 mm in diameter) was polycyclic, composed of multiple small nodules of loose connective tissue comprising myofibroblasts and a dense network of capillaries as well as some remnants of sinuses. Collagenous fibrosis surrounded them. Bands or large sheets of fibrosis, infiltrated by various inflammatory cells, particularly polytypic plasmacytes, resembling IPT, were present in 10 cases. CONCLUSIONS: SANT of the red pulp is a distinct benign pseudotumorous lesion of the spleen characterized by the presence of angiomatoid nodules. We observed such angiomatoid nodules in all our cases of splenic IPT, which were not follicular dendritic cell or myofibroblastic tumours. We therefore recommend careful examination for angiomatoid nodules in all suspected cases of splenic IPT.

Primary mediastinal anaplastic alk-1-positive large-cell lymphoma of T/NK-cell type expressing CD20.

We describe an unusual case of ALK-1-positive primary mediastinal lymphoma with the morphology of an anaplastic large-cell lymphoma (ALCL) of T/NK cell type but expressing CD20. This tumour had T/NK morphology and immunophenotype, as demonstrated by its expression of CD30, EMA, ALK-1, CD7 and TiA-1 and the lack of expression of B-cell markers other than CD20. The significance of such a co-expression of a B cell-associated antigen in a case of ALCL of T/NK cell type is discussed.

Marginal zone lymphoma of both spleen and kidney displaying transformation into large B-cell lymphoma.

We report a case of simultaneous involvement of the spleen and the left kidney in a marginal zone lymphoma with a monotypic lymphoplasmacytic cell component, which transformed into a diffuse large B-cell lymphoma of the immunoblastic type. PCR showed that the small and large B-cell populations carried the same type of immunoglobulin heavy chain gene rearrangement. This type of rearrangement was detected in the spleen, the latero-aortic lymphadenopathy and the kidney demonstrating that it is the same lymphoma that affected both organs and the lymph nodes. Primary renal lymphoma is very rare and only a few cases of renal marginal zone lymphoma, MALT type, have been reported. Involvement of simultaneous multiple sites has been described in MALT type lymphoma, but splenic involvement secondary to renal MALT lymphoma seems to have never been observed. Nevertheless, in our case the huge size of the spleen associated with splenic hilar node involvement is consistent with primary splenic marginal zone lymphoma. The extension into latero-aortic lymph nodes of this lymphoma can explain secondary kidney involvement. The nodal Kaposi's sarcoma observed in this patient of Mediterranean origin was probably coincidental.

Initial lesions of classical Hodgkin's lymphoma of the nodular sclerosis type.

The necessity of correct diagnostics of initial lesions of Hodgkin's lymphoma is underlined. The correct assessment may relate of more than 90% of such observation to 90% of noduler sclerosis. The criteria similar to those of WHO are suggested for the differentiation with mixed-cell or lymphoid preponderance.

[Plasma cell leukaemia]. / La leucémie à plasmocytes.

We report a case of primary plasma cell leukaemia, with an absolute count of plasma cells of 53 Giga/L, diagnosed in a 83-year-old woman. The patient's condition improved, with no circulating plasma cells after 3 weeks of treatment, in response to the combination of thalidomide and dexamethasone administered for 5 days followed by thalidomide alone. The clinical presentation, the morphological, flow cytometric and pathophysiological characteristics of the plasma cell leukaemia and the treatment are summarised in this paper.

Further phenotypic evidence that nodular, lymphocyte-predominant Hodgkin's disease is a large B-cell lymphoma in evolution.

Five cases of nodular, lymphocyte predominant Hodgkin's disease (nLP HD), in which an association with (n = 3) and transformation to (n = 2) large cell lymphoma (LCL) were found, were studied with monoclonal antibodies against B-, T-, and Reed-Sternberg (R-S) cell-associated antigens and epithelial membrane antigen (EMA) on paraffin sections. Both lymphocytic (L) and histiocytic (H) cells of nLP HD and lymphoma cells of LCL expressed multiple B-cell-associated antigens (detected by LN-1/CDw75, L26, MB2, DBB.42, DBA.44, DND.53, DNA.7 antibodies) but did not react with antibodies against T-cell-associated (MT1, UCHL1/CD45RO) (one exception for CD45RO in LCL) and R-S cell-associated (Leu-M1/CD15, Ber-H2/CD30) antigens. EMA was expressed by L and H cells in all cases and conserved in LCL cells, emphasizing the frequent expression of EMA by the diagnostic cells of nLP HD. An antibody (BNH9) against blood group-related antigens (H and Y oligosaccharide antigens) that does not normally react with lymphoid cells was found to be reactive with few L and H cells in two of five and most LCL cells in four of five cases. The finding might be indicative of abnormal activation of lymphoid cells. The data reinforce current implications that nLP HD is a B-cell malignancy in evolution and that it is not truly representative of Hodgkin's disease in terms of biological and clinical behavior.

Splenic marginal zone lymphoma with or without plasmacytic differentiation.

We report a series of 31 cases of splenic marginal zone lymphomas with an enlarged spleen and a multimicronodular macroscopic pattern. Two groups, A and B, were distinguished based on the presence (A) or absence (B) of a lymphoplasmacytic component with monoclonal immunoglobulin expression in the cytoplasm. There were no differences between the groups as far as age, sex, spleen weight, and progression. The only difference was the presence in group A of a monoclonal serum component and autoimmune disorders, particularly autoimmune hemolytic anemia. In most cases in which a liver and/or bone marrow biopsy was performed, lymphomatous infiltration was detected. Seven cases had a seric monoclonal IgM of 5 g/L or more and liver or bone marrow infiltration, corresponding to the definition of Waldenstrom's macroglobulinemia. Lymphoma cells had a monocytoid, centrocytoid and, in group A, lymphoplasmacytic morphology. The lymphomatous cells were positive for CD20, CD45 RA, and bcl-2. They expressed IgD in 9 cases, partially in 6, and were negative for IgD in 9 of the 24 cases studied. Progression seems to be slow, with a long survival. Three patients presented with transformation into a large B-cell lymphoma, which was responsible for death in two patients.

Incidence of haematological malignancies in French Polynesia between 1990 and 1995.

To determine the incidence of haematological malignancies in French Polynesia from 1990 to 1995, we collected cases from the local cancer registry, sanitary evacuation files and all the histopathology and clinical biology laboratories. All leukaemias, non Hodgkin's lymphomas, and multiple myelomas incidence was slightly lower among French Polynesians than among Maoris from New-Zealand and Hawaiians of Hawaii. Standardised Incidence Ratio (SIR) for Hodgkin's disease among females was 0.08 when comparing to Hawaiians and 0.33 when comparing to Maoris. Other salient features were a high proportion of high grade and Burkitt's lymphoma, the absence of Hodgkin's disease after 40 years of age, a low incidence of chronic lymphoid leukaemia, and a high non lymphoblastic/lymphoblastic acute leukaemia ratio in childhood. This study stresses the peculiar incidence of some haematological malignancies in this south pacific area.

LAV-like viral particles in lymph node germinal centers in patients with the persistent lymphadenopathy syndrome and the acquired immunodeficiency syndrome-related complex: an ultrastructural study of 30 cases.

The detection of LAV- or HTLV III-type viral particles in lymph node germinal centers from patients with the persistent lymphadenopathy syndrome (LAS) or the acquired immunodeficiency syndrome (AIDS)-related complex (ARC) is an important diagnostic factor in the prodromal stages of AIDS. These particles, the morphology of which is defined, are situated solely in the extracellular spaces delimited by cytoplasmic extensions of the dendritic reticular cells. Often few in number, they were found in 26 of the 30 lymph nodes studied, selected uniquely on the basis of light microscopic criteria (predominantly follicular lymphoid hyperplasia). The four negative nodes contained no, or fewer than two, germinal centers in the samples taken for ultrastructural study. The diagnosis of the LAS or the ARC was always confirmed clinically and biologically. Thus, lymph node biopsy and the corresponding ultrastructural study are important steps in the diagnosis of AIDS.

Bone marrow involvement by disseminated toxoplasmosis in acquired immunodeficiency syndrome: the value of bone marrow trephine biopsy and immunohistochemistry for the diagnosis.

A bone marrow biopsy was performed on four patients with acquired immune deficiency syndrome (AIDS) for a long-running course fever of unknown origin associated with a recent pancytopenia. In the four cases, striking histological similarities, such as interstitial edema, foci of necrosis and only few scattered or clustered histiocytes, were found. Near or in the foci of necrosis, free forms, and pseudocysts of Toxoplasma gondii were observed not only in the cytoplasm of macrophages and of some granulocytes, but also within megakaryocytes. No sign of other parasitic, bacterial, or fungus infection has been found. The diagnosis was confirmed by immunohistochemistry in the four cases and ultrastructural examination in one case. This case study stresses the importance of bone marrow histological changes for the diagnosis of severe toxoplasmosis in AIDS patients and particularly the localization of T gondii within the cytoplasm of megakaryocytes.

Disseminated superficial porokeratosis after autologous bone marrow transplantation.

A case of disseminated superficial porokeratosis (DSP) is reported in a black man 5 years after autologous bone marrow transplantation (BMT) for acute promyelocytic leukemia. Porokeratosis is a rare hyperkeratotic disorder arising from clonal keratinocytes with a high potential to develop squamous cell carcinoma. Inherited forms are classical but recent observations of acquired porokeratosis have been reported in immunocompromized patients (AIDS, immune disorders, immune suppressive drugs or organ transplantation). Two cases of DSP have been reported after allogeneic BMT in patients treated for chronic GVHD. Our case is the first one after autologous BMT, in a black man, on no immunosuppressive drug at the time of diagnosis of DSP. Hematopoietic and immune reconstitution was apparently complete. The cancer-prone character of porokeratosis could be favored by total body irradiation used in conditioning regimen. Thus, porokeratosis has to be associated with other late effects after BMT such as HCV seropositivity, cataract and infertility that were observed in this patient.

An unusual case of mycosis fungoides presenting as sarcoidosis or granulomatous mycosis fungoides.

The authors describe a case of cutaneous and lymph node granulomas first reported as sarcoidosis. As skin sarcoidlike reactions disappeared, the development of typical histologic and immunopathologic features of cutaneous mycosis fungoides suggested granulomatous mycosis fungoides. This case illustrates the difficulties in differentiating true systemic sarcoidosis associated with mycosis fungoides from sarcoidlike reactions when extensive granulomas obscure the underlying cutaneous lymphoma. This report emphasizes the utility of immunohistochemical analysis to identify the early cutaneous T-lymphomatous infiltrate, initially admixed with epithelioid and giant cell granulomas. This technique also made it possible to characterize a Ki-1-positive anaplastic large-cell lymphoma when the transformation of mycosis fungoides into highly malignant lymphoma occurred in the lymph node.

Thymic pseudotumorous enlargement due to follicular hyperplasia in a human immunodeficiency virus sero-positive patient. Immunohistochemical and molecular biological study of viral infected cells.

An enlargement of the thymus suggesting a tumor was discovered in a 28-year-old man who had early-stage acquired immune deficiency syndrome. A biopsy was performed. The adipose involuted thymus, with persistence of many Hassall's corpuscles, was judged to be a large lymphoid follicular hyperplasia. This follicular hyperplasia was similar to that previously described for lymph nodes, spleen, and other lymphoid tissues at earlier stages of human immunodeficiency virus infection, before the development of acquired immune deficiency syndrome. Human immunodeficiency virus RNA and p24 human immunodeficiency virus protein were detected in the hyperplastic germinal centers (lymphocytes and follicular dendritic infected cells), and also in many cells that may have been either lymphocytes and/or epithelial cells in the interfollicular areas. The tissue was negative for Epstein-Barr virus DNA sequences, as determined by the polymerase chain reaction. These observations identify the first state of infection of the thymus in a human immune deficiency virus-infected adult, preceding the severe involution with lymphoid depletion observed in all fatal cases of acquired immunodeficiency syndrome in which the thymus has been analyzed.

Hairy cell leukemia. Diagnosis of bone marrow involvement in paraffin-embedded sections with monoclonal antibody DBA.44.

The new monoclonal antibody DBA.44 recognizes an unknown fixation-resistant B-cell differentiation antigen expressed by mantle zone lymphocytes, reactive immunoblasts, monocytoid B cells, and a small proportion of high- and low-grade lymphomas. Among node-based lymphomas, the strongest membrane staining was observed in centroblastic, immunoblastic, and monocytoid B-cell lymphomas. In studying bone marrow biopsy specimens from 166 patients with hairy cell leukemia, strong positive staining of surface membrane 'hairy' features of leukemic cells was observed in routinely fixed and decalcified bone marrow biopsy specimens of nearly all cases. The antibody distinguished hairy cell leukemia from the more common B-cell chronic lymphocytic leukemia and bone marrow infiltrates of typical lymph node-based lymphomas by immunomorphologic criteria. DBA.44 was valuable to (1) confirm the diagnosis of hairy cell leukemia, (2) estimate the bone marrow density of hairy cell leukemia before and after treatment, and (3) make the diagnosis of hairy cell leukemia in ambiguous cases, which are all properties that indicate its usefulness in the practice of diagnostic hematopathology.

Mantle cell lymphoma, in leukaemic phase with prominent splenomegaly. A report of eight cases with similar clinical presentation and aggressive outcome.

Mantle cell lymphoma (MCL) is a well-defined peripheral B-cell lymphoma usually diagnosed upon peripheral lymph node biopsy. We report eight cases of peripheral B-cell leukaemia that demonstrate presumptive evidence of mantle cell characteristics. The patients had a median age of 68.5 years, and five were male. All presented with an enlarged spleen without any peripheral lymphadenopathies, and they were leukaemic at presentation (median lymphocytosis, 38x10(9)/l). Morphological diagnosis of MCL was very difficult in five cases but easier in three because we were able to analyse either pre- or post-mortem lymph nodes and spleen. The immunophenotype of blood lymphocytosis using flow cytometry, the presence of a t(11;14)(q13;q32) and a cyclin D1 expression by leukaemic cells all fit with the diagnosis of MCL. All patients progressed and died with a median overall survival of 8 months. Multifocal areas of transformation in blastoid or large cell variants were observed in the three autopsied patients. In summary, one should consider the diagnosis of MCL at presentation in leukaemic phase even in the absence of peripheral adenopathies.

Spleen localization of light chain deposition disease associated with sea blue histiocytosis, revealed by spontaneous rupture.

Splenic involvement by a light chain deposition disease (LCDD) associated with sea-blue histiocytosis occurred in a 55-year-old man presenting with LCDD of the kidney without myeloma. Lambda light chain deposits were demonstrated by immunohistochemistry in vessel walls and along the ring fibres of the red pulp sinuses. Accumulation of sea blue histiocytes in the cords was also present. Stiffness of the walls of the red pulp sinuses resulting from light chain deposits may have induced accumulation and destruction of circulating blood cells. Lipid catabolism with production of ceroids may have resulted in lipidic histiocytosis with a sea blue histiocyte pattern.

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition.

Clinical and hematological abnormalities can occur in patients receiving intravenous fat emulsions as part of a long-term parenteral nutrition; they consist of hepatosplenomegaly and peripheral blood cytopenia(s). These abnormalities lead to bone marrow examination which revealed numerous macrophages laden with blue staining pigment granules and separate lipid vacuoles, presenting the typical histochemical characteristics of sea-blue histiocytes. Thus, long-term parenteral nutrition including fat-emulsion sources may represent a further condition in addition to the wide variety of disorders which can be associated with sea-blue histiocytosis. Moreover, in view of its clinical and morphological presentation, this storage pathological state could be compared with the so-called sea-blue histiocyte syndrome described by Silverstein and colleagues.

Epstein-Barr virus-associated lymphoproliferative disease during methotrexate therapy for psoriasis.

BACKGROUND: Epstein-Barr virus (EBV)-associated lymphoproliferative disorders have recently been observed during treatment of rheumatoid arthritis and dermatomyositis with low-dose methotrexate. OBSERVATION: A patient with psoriasis developed a B-cell lymphoproliferative disorder during long-term treatment with low-dose methotrexate. The lymphoid cells expressed EBV latent membrane protein 1, and the EBV viral genome was present as demonstrated by in situ hybridization. Evaluation for EBV clonality showed that the lymph node contained clonal EBV DNA. Polymerase chain reaction studies confirmed that the B-cell lymphoproliferative disorder was mainly monoclonal, suggesting that the disorder arose from a single EBV-infected B-cell clone. CONCLUSIONS: Lymphoproliferative disorders associated with Epstein-Barr virus in which the clinicopathological presentation is similar to those occurring in patients after transplantation may be observed in patients with psoriasis treated with methotrexate. While it is impossible to rule out a fortuitous occurrence of an EBV-associated lymphoproliferative disorder and psoriasis treated with methotrexate in the same patient, EBV appears to be critical in the pathogenesis of the lymphoproliferative disorder in this patient.

Primary uveal B immunoblastic lymphoma in a patient with AIDS.

A case of primary intraocular malignant lymphoma without cerebral involvement is reported in a 30-year-old man with acquired immunodeficiency syndrome. The study of the enucleation specimen showed a B immunoblastic lymphoma with a CD30 positive anaplastic large cell component. There was no involvement of the adnexal structures of the orbit. The patient subsequently completed non-surgical staging showing no extension of the tumour. The clinical course was rapidly fatal with dissemination to the pericardium and pleura.

Effect of ribonuclease A and deoxyribonuclease I on immunostaining of Ki-67 in fixed-embedded sections.

Immunostaining of the cell cycle-associated Ki-67 antigen was studied on routinely formalin-fixed and paraffin-embedded tissue sections, using the Ki-67-specific monoclonal antibody MIB-1. Immunomorphological analysis of the Ki-67 immunostaining pattern was carried out following tissue pre-treatments including combinations of microwave heating and trypsinization, as well as of ribonuclease and deoxyribonuclease pre-digestion of the sections. The nucleolar Ki-67 immunostaining after slide pre-treatment by microwave heating followed by trypsinization was reduced only by ribonuclease pre-digestion, if this latter was used before heating. Ki-67 immunostaining was not significantly reduced by deoxyribonuclease treatment. We conclude that Ki-67, located in the nucleoli, may be associated there with nucleolar RNA.