Frequent expression of haemopoietic and non-haemopoietic antigens by reactive plasma cells: an immunohistochemical study using formalin-fixed, paraffin-embedded tissue

Unlike other B cells, plasma cells (PC) react with only a few antibodies against haemopoietic antigens. We investigated 36 specimens exhibiting a reactive increase in PC numbers (i.e. plasmacytosis, PC hyperplasia) with a broad panel of antibodies suitable for use on formalin-fixed, paraffin-embedded tissue, and compared the findings with those obtained in 51 cases of multiple myeloma (plasmacytoma). Regardless of the immunostaining pattern for immunoglobulin light and heavy chains, reactive PC reacted with at least two and at most six of seventeen antibodies detecting haemopoietic antigens [Ber- H2lCD30 (91%), anti-leucocyte common antigen (LCA)/CD45 (86%), KP1lCD68 (64%), MB2 (57%), 4KB51CD45RA (37%), DF-TllCD43 (28%), UCHL11 CD45RO (20%), L26lCD20 (17%), MT2 (14%) and Mac387 (g%)], and with at least one and at most four of six antibodies against non-haemopoietic antigens [antiepithelia1 membrane antigen (EMA) (94%), antivimentin (77%), anti-pan-cytokeratinIKL1 (74%), BMA120 (51%) and HMB45 (14%)]. Five antibodies stained reactive PC significantly more often than neoplastic PC: Ber-H2lCD30 (ps 0.0000), KPllCD68 (ps 0.0000), anti-LCAlCD4.5 (ps 0.0000), anti-EMA (p5 0.0339) and anti-pancytokeratinIKL1 (ps 0.0000). The more frequent and more heterogeneous expression of antigens by reactive PC suggests that the aberrant immunoreactivity of neoplastic PC in plasmacytoma is not due to the process of malignant transformation in an early step of B-cell differentiation, but could reflect the heterogeneity of antigen expression by normal PC

Systemic mast cell disease (mastocytosis). General aspects and histopathological diagnosis

Systemic mast cell disease/mastocytosis (SMCD) is best defined as a multitopic proliferation of cytologically andlor functionally abnormal tissue mast cells (TMC). SMCD preferentially involves the bone marrow, skin, spleen, liver, and lymph nodes. The histopathological diagnosis of SMCD may be very difficult to make, and the disease is often not considered in the differential diagnosis of lymphoreticular neoplasia. In suspected cases of SMCD, basic dyes such as Giemsa and toluidine blue are useful to demonstrate the specific metachromatic granules of TMC. The naphthol AS-D chloroacetate esterase reaction has also proved to be very reliable for enzyme-histochemical identification of TMC. Major diagnostic problems may arise in cases of malignant or «aggressive» SMCD exhibiting tissue infiltrates consisting predominantly of highly atypical, non-metachromatic TMC, which are usually also only weakly reactive for chloroacetate esterase. Immunostaining with antibodies against the mast cell-specific proteases tryptase and chymase has proved to be of great value for establishing the correct diagnosis in such cases. Anti-tryptase antibodies have major diagnostic significance due to their extremely high sensitivity and specificity. The classification of SMCD is controversial, but there is increasing support for the differentiation of at least two major subtypes that differ in prognosis: (i) a benign or «indolent» variant in which skin involvement (urticaria pigmentosa-like skin lesions) is usual, but associated malignant hematological disorders are rare; and (ii) a malignant or «aggressive» variant where skin involvement is usually absent but concomitant malignant hematological disorders (myelodysplastic and myeloproliferative syndromes and acute non-lymphocytic leukemias) are very common. Preliminary molecular biological studies of a few cases of malignant SMCD using the recently developed HUMARA assay have yielded evidence that the disease is monoclonal

Eosinophils and eosinophil-associated disorders: immunological, clinical, and molecular complexity

Eosinophils and their mediators play a crucial role in various reactive states such as bacterial and viral infections, chronic inflammatory disorders, and certain hematologic malignancies. Depending on the underlying pathology, molecular defect(s), and the cytokine- and mediator-cascades involved, peripheral blood and tissue hypereosinophilia (HE) may develop and may lead to organ dysfunction or even organ damage which usually leads to the diagnosis of a HE syndrome (HES). In some of these patients, the etiology and impact of HE remain unclear. These patients are diagnosed with idiopathic HE. In other patients, HES is diagnosed but the etiology remains unknown — these patients are classified as idiopathic HES. For patients with HES, early therapeutic application of agents reducing eosinophil counts is usually effective in avoiding irreversible organ damage. Therefore, it is important to systematically explore various diagnostic markers and to correctly identify the disease elicitors and etiology. Depending on the presence and type of underlying disease, HES are classified into primary (clonal) HES, reactive HES, and idiopathic HES. In most of these patients, effective therapies can be administered. The current article provides an overview of the pathogenesis of eosinophil-associated disorders, with special emphasis on the molecular, immunological, and clinical complexity of HE and HES. In addition, diagnostic criteria and the classification of eosinophil disorders are reviewed in light of new developments in the field