Myelodysplastic Syndromes/Neoplasms: Morphological and Immunohistochemical Features and Standard Evaluation

Abstract

Myelodysplastic syndromes (MDS) comprise a group of clonal hematopoietic stem cell disorders characterised by dysplasia in at least one major myeloid cell line and signs of bone marrow insufficiency with subsequent cytopenia. The updated WHO classification of MDS defines several subtypes including refractory cytopenia (anemia, neutropenia and/or thrombocytopenia), refractory anemia (RA) with ring sideroblasts (RARS), refractory cytopenia with multilineage dysplasia and RA with excess of blast cells (RAEB). While isolated recfractory neutropenia and thrombocytopenia are very rare disease categories, refractory cytopenia with multilineages dysplasia, RARS and refractory anemia with excess of blasts are much more frequently observed. One peculiar subtype of MDS is defined by the presence of an isolated cytogenetic abnormality, in particular del(5q). The diagnostic approach to MDS should include not only cytomorphological evaluation of blood and bone marrow smears but also histological analysis of a bone marrow trephine biopsy specimen and molecular/cytogenetic findings. Some rare subvariants of MDS are not included in the WHO classification system but represent special disorders which can only be recognised by histological investigation: (1) hypocellular MDS, (2) MDS with fibrosis, and (3) MDS associated with systemic mastocytosis (SM) in the setting of a so-called SM-AHNMD (“associated clonal hematologic non-mast cell disorder”). While cytological atypia of blood cells is easilyrecognisable in smear preparations only histologic investigation of the bone marrow enables detection of reticulin fibrosis, small blast cell infiltrates and clustering of megakaryocytes. Therefore, immunohistochemical analysis with antibodies against the stem cell-associated antigen CD34, at least one platelet-related antibody (CD42, CD61), and an antibody against mast cell tryptase is recommended in all cases of suspected MDS. Differential diagnostic aspects include a broad variety of non-neoplastic and neoplastic disorders, especially overt acute myeloid leukemia (AML) but also systemic mastocytosis considering that more than one neoplasm may develop and co-exist in the same patient.