The stromal composition of mast cell aggregates in systemic mastocytosis

Systemic mastocytosis is a stem cell disorder characterized histologically by the presence of multifocal compact aggregates of mast cells in at least one extracutaneous organ with or without evidence of skin lesions. The mast cell aggregates are accompanied by fibrosis, which is often significant. However, in spite of its frequent occurrence and severity, little is known about its characteristics. In this study, we evaluated the composition of the fibrotic mast cell aggregates by studying eight bone marrow biopsies and two spleens involved by systemic mastocytosis, and compared the findings with those observed in other fibrotic bone marrow disorders such as primary myelofibrosis and metastatic malignancy. Histochemistry and immunohistochemistry were used to evaluate: (a) extracellular matrix (reticulin, trichrome, collagen IV, laminin); (b) stromal reticulum cells (low-affinity nerve growth factor receptor); (c) presence of myofibroblastic differentiation (smooth muscle actin) and (d) microvessel density (CD34). We found that all cases showed marked reticulin and collagen fibrosis. However, unlike primary myelofibrosis and metastatic malignancy, which are usually associated with increased low-affinity nerve growth factor receptor positivity, its expression was low in all cases of systemic mastocytosis. Myofibroblastic differentiation was only focally detected in two of eight bone marrow biopsies. In all cases, the systemic mastocytosis lesions were largely devoid of type IV collagen and laminin. The latter findings were in contrast with those seen in cases of primary myelofibrosis and metastatic malignancy where smooth muscle actin, collagen IV and laminin were expressed in most cases. Also in contrast with the other two conditions, only minimal vascularity was detectable within the fibrotic mast cell lesions. These findings indicate that systemic mastocytosis exhibits a distinct pattern of stromal change, and suggest that the fibrogenetic mechanism in systemic mastocytosis is most likely different from that of other bone marrow neoplasms which are also associated with fibrosis.