Differential Diagnoses of Systemic Mastocytosis in Routinely Processed Bone Marrow Biopsy Specimens: A Review

Diagnosis of systemic mastocytosis (SM) is mainly based on the
morphological demonstration of compact mast cell infiltrates in
various tissue sites. In almost all patients such infiltrates are
detected in the bone marrow. Reliable immunohistochemical markers
for the diagnosis and grading of SM have been established, but
various differential diagnoses including myeloproliferative
neoplasms, basophilic and eosinophilic leukemias may be very
difficult to delineate. Even more challenging is the recognition of
hematological neoplasms with signs of mast cell differentiation but
not fulfilling diagnostic criteria for SM, especially the rare
myelomastocytic leukemia. It is also important to separate the
reactive state of mast cell hyperplasia from indolent variants of
SM, especially those with a very low degree of bone marrow
infiltration and absence of compact mast cell infiltrates. When the
lymphocytic component of the SM infiltrate is very prominent, SM
may be confused with an indolent lymphoma, especially
lymphoplasmacytic lymphoma which almost always shows a marked
reactive increase in mast cells. In aggressive and leukemic
variants of SM, mast cells may be very atypical and devoid of
metachromatic granules. This hypogranulation can be regarded as
cellular atypia and may lead to the misdiagnosis aspect of
monocytic leukemia or histiocytic neoplasm. Regarding
immunohistochemical anomalies, mast cells in aggressive and
leukemic SM have been found to express CD30 (Ki1-antigen). Thus,
anaplastic large cell lymphoma or Hodgkin's disease may first be
considered rather than SM. There is increasing evidence that most
patients with long-standing adult-type urticaria pigmentosalike
skin lesions have in fact indolent SM. Therefore, such skin lesions
are an important clue to the correct diagnosis in these patients.
However, in aggressive or leukemic SM skin lesions are usually
absent and then the correct diagnosis relies on an appropriate
investigation of bone marrow biopsy specimens using both SM-related
immunohistochemical markers (tryptase, KIT, CD25, CD30) but also
markers excluding potential differential diagnoses. Investigation
for presence of the activating KIT point mutation D816V is very
helpful to establish a correct diagnosis of SM in all the difficult
cases exhibiting a low degree of bone marrow infiltration or
puzzling morphological findings. Copyright (C) 2010 S. Karger AG,
Basel