Stephan Falk

Littoral Cell Angioma: A Novel Splenic Vascular Lesion Demonstrating Histiocytic Differentiation

Seventeen cases of a novel type of vascular tumor of the spleen are described. The lesions, whose size ranges from minute foci to large nodules almost completely replacing the splenic tissue, are composed of anastomosing vascular channels resembling splenic sinus and have irregular lumina, often featuring papillary projections and cyst-like spaces; they are lined by tall endothelial cells that slough off into the vascular lumina and show hemophagocytosis. Atypical cells are absent and mitotic activity very low. In contrast to normal sinus endothelia, which express only FVIIIag, neoplastic cells express both endothelial (FVIII-AG, BMA 120) and histiocytic (KP1, lysozyme) antigens; occasionally S-100 protein is also present. The morphologic and immunohistochemical findings in this tumor reflect the dual differentiation potential of the reticuloendothelial cells lining the splenic sinus, justifying the term littoral cell angioma, and recognize a distinct entity that is different from other vascular lesions of the spleen, notably angiosarcoma. This distinction is all the more important because the clinical behaviour of this lesion is apparently benign.

Primary malignant lymphomas of the spleen. A morphologic and immunohistochemical analysis of 17 cases.

Seventeen cases of primary malignant lymphoma of the spleen (PMLS) were identified among 500 splenectomy specimens showing involvement by Hodgkins disease or non‐Hodgkins lymphoma. All PMLS represented non‐Hodgkins lymphoma and most of them were of B‐cell origin. in two cases PMLS were associated with hamartomas of the spleen (splenomas). Histologic and immunohistochemical studies did not reveal any differences between PMLS and disseminated malignant lymphomas with splenic involvement with regard to morphologic features, immunophenotype, host cell infiltrates, or proliferation activity. the reasons for the infrequent occurrence of primary lymphomas in the spleen may not be sought in a special immunophenotype of PMLS, a vigorous host response in the spleen, or in a lower proliferation activity of splenic lymphomas.

Hamartomas of the spleen: a study of 20 biopsy cases

Twenty hamartomas of the spleen were studied by histological, immuno‐ and enzyme‐histochemical methods. In all cases nodules of varying size resembling proliferation of splenic red pulp structures were present that exhibited considerable morphological variation with regard to plasmacytosis, extramedullary haematopoiesis and phagocytic activity of macrophages. Splenic red pulp structures could be identified by immuno‐ and enzyme‐histochemical markers reacting with sinus endothelium, including Factor VIII related antigen, proteinase inhibitors and nonspecific esterases. In conjunction with the absence of organized lymphoid tissue and of dendritic reticulum cells these studies allow the differentiation of splenic hamartomas from haemangiomas that may possess a deceptively similar morphological appearance.

MYELOKATHEXIS TREATED WITH RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (rhGM-CSF)

presence of a clonal P-TcR gene rearrangement (Fig lB), which was not associated with HTLV-I infection (negative by ELIZA). The IgJh, IgCK and M-bcr gene loci were all in the germline configuration. A course of miniCHOP (French Cooperative Group on chronic lymphocytic leukaemia, 1986) was given which resulted in transient reduction of lymphocytes but no change in symptoms or dermal oedema and induration. The patient subsequently received low dose prednisone (7.5-10 mg/d) and 400 mg/d of CsA, which was subsequently decreased according to the clinical response. As indicated in Fig 1A. this resulted in a progressive decrease of both CD3 /CD4 + lymphocytes and eosinophils. resolution of pruritus and dermal changes within 6 weeks, and repopulation of the peripheral blood by CD3 + /CD4 + and CD3 + /CD8 + lymphocytes. Repeat analysis of the P-TcR gene at day 450 showed that only about 5% of circulating lymphocytes still contained the clonal rearrangement which corresponded to a treatment associated reduction of total clonal CD4 + lymphocytes exceeding 99%. The CsA induced response in this case extends the limited list of reports documenting the effect of CsA in clonal T-cell disorders. In cutaneous T-cell lymphoma, CsA induced responses are usually partial and of short duration but improvement up to 2 years has been described (Moreland et al, 1985: Kreis et al. 1988: Street et al, 1990). CsA has also been successfully used to control severe neutropenia associated with large granular lymphocyte (LGL) lymphocytosis (Pastor & Sayas, 1989). and to block production of IL-5 by Tcells in some patients with the idiopathic hypereosinophilic syndrome (Raghavachar et al, 198 7). Collectively, these observations suggest that autocrine and paracrine mechanisms of growth factor stimulation may be important in the pathogenesis of some chronic T-cell disorders, given that the major effect of CsA is to block the production of a wide variety of cytokines and/or their receptors.

Pathophysiological mechanisms of HIV-induced defects in haematopoiesis: pathology of the bone marrow.

Bone marrow biopsies of 96 HIV1-infected patients were analysed histologically and by immuno- and enzyme histochemical techniques. Independently of the stage of disease, the bone marrow frequently exhibits hypercellularity and features of dysplastic haemopoiesis combined with mesenchymal alterations. In situ immunohistochemical analysis shows that there is a marked reduction in expression of the proliferation-associated nuclear antigen recognized by the Ki67 antibody. Comparison with non-infected controls reveals that there is a reduction in CD34+/myeloperoxidase-/naphthol AS-D chloroacetate- progenitor cells and an overproportional decrease in CD8+ lymphocytes in the bone marrow. Double staining revealed the presence of gag-coded HIV1 proteins in the above-mentioned CD34+ progenitor cells, in myelopoiesis cells, megakaryocytes and above all, in CD68+/acid phosphatase+ and alkaline phosphatase+ bone marrow reticular cells. From the latter results, it was concluded that HIV1-infected reticular cells may be disturbed in their ability to produce factors responsible for the short-range regulation of haemopoietic activity.

Hodgkin's disease and sinus histiocytosis with massive lymphadenopathy‐like changes

Sinus histiocytosis with massive lymphadenopathy (SHML) is a disorder of unknown origin which is only infrequently associated with lymphoid neoplasms. We report the first two cases of Hodgkins disease with simultaneous SHML‐like changes in the same lymph node.

Splenic Megakaryocytopoiesis in Primary (Idiopathic) Osteomyelofibrosis

An immunohistochemical and morphometric study has been performed on splenic tissue of 10 patients with primary (idiopathic) osteomyelofibrosis (OMF) to determine characteristic features of megakaryocytopoiesis in myeloid metaplasia. Using the periodic acid-Schiff reaction (PAS) and particularly the monoclonal antibody CD61 (Y2/51), all elements of this cell lineage including precursors could be identified. In comparison with bone marrow specimens from our file material (40 patients with OMF, 15 control cases) which were processed in a similar way, megakaryocytes in the spleen revealed significant differences. These differences included smaller cell sizes, a disturbed nuclear-cytoplasmic ratio, and a conspicuous increase in the relative frequency of promegakaryoblasts. In conclusion, extramedullary megakaryocytopoiesis in OMF did not only show more pronounced abnormalities of differentiation, but also a higher degree of immaturity. Our finding of a significant accumulation of megakaryocytic precursors in the spleen as opposed to the bone marrow, corroborates the so-called filtration theory which has been introduced to explain the evolution of splenic myeloid metaplasia in OMF.

The spleen in HIV infection — morphological evidence of HIV-associated macrophage dysfunction

One-hundred spleens from HIV-infected patients which were studied by conventional morphological and immunohistochemical methods exhibited alterations in lymphatic tissue as well as in the mononuclear phagocyte system (MPS); these were probably related directly to HIV infection of lymphocytes and MPS cells. There was ample evidence of impairment of macrophage activation, accompanied by decreased expression of functional markers and an enhanced reactivity with antibodies against S100 protein. This impairment of macrophage function is related to the particular morphology and aggressive clinical behaviour of some opportunistic infections in AIDS.

The Spleen in Acquired Immunodeficiency Syndrome (AIDS)

72 spleens from AIDS patients were studied by histologic and immunohistochemical methods. Apart from the opportunistic infections and malignancies typically occurring in AIDS patients (malignant lymphomas, Kaposis sarcoma, mycobacterial infections, cryptococcosis, cytomegalovirus infections) morphological changes probably directly attributable to HIV infection were noted that progressed from follicular hyperplasia with nearly normal periarteriolar lymphoid sheaths to atrophy of follicles and severe cellular depletion of T cell areas with concomitant plasmacytosis and occurrence of small giant cells. At the same time the number of Protein S-100 positive cells markedly increased; in some cases almost all pulp cord macrophages expressed the antigen. In addition, the sinus endothelia strongly expressed protease inhibitors.

The spleen in osteomyelofibrosis: A morphological and immunohistochemical study of 30 cases

30 spleens from patients with biopsy proven primary osteomyelofibrosis were studied by histological and immunohistochemical methods. The presence of trilinear haematopoiesis along the splenic circulatory pathway supports the theory that the spleen acquires haematopoietic precursor cells by filtration of the peripheral blood. In addition, impairment of intrasplenic circulation with subsequent red pulp congestion, pulp cord fibrosis and haemophagocytosis is of importance for the pathogenesis of both marked splenic haematopoiesis and complications due to hypersplenism.