Systemic mastocytosis

* Context.-Mast cells may be increased as a reactive mastocytosis in various hematologic disorders and malignant neoplasms, as well as in systemic mast cell disease (SMCD). There are no statistical differences in mast cell numbers in reactive mastocytosis and SMCD; however, SMCD usually reveals dyspoietic mast cells and other dyspoietic bone marrow elements. In addition, SMCD is frequently (45%) associated with myeloproliferative disorders (MPDs) (17%) and myelodysplastic syndromes (MDSs) (28%). Thus, it has been suggested that SMCD may represent one aspect of a hematologic disorder that involves multiple bone marrow lineages.

Objective.-To perform a systematic evaluation of MPDs and MDSs without SMCD for dyspoietic mast cells.

Design.-A total of 55 MPDs or MDSs were reviewed, including 20 cytogenetically proven chronic myeloid leukemias, 6 essential thrombocythemias, 2 polycythemia veras, 21 cytogenetically proven MDSs, and 6 chronic myelomonocytic leukemias. Cases of idiopathic myelofibrosis were not included due to lack of spicules. The bone marrow aspirates were reviewed for an increase in mast cells (1+ to 3+), dyspoietic features within mast cells (decreased cytoplasmic granularity, uneven granule distribution), and a predominance of fusiform mast cells.

Results.-All cases, except 2 MDSs, had evaluable bone marrow spicules. Of interest, the MPDs were significantly more associated with increased and dyspoietic mast cells (57% and 61%, respectively) than were the MDSs (11% and 4%, respectively). The 2 polycythemia veras and 6 chronic myelomonocytic leukemias did not reveal increased or dyspoietic mast cells.

Conclusions.-These findings indicate that MPDs (chronic myeloid leukemia and essential thrombocythemia) frequently contain neoplastic mast cells as the spectrum of abnormal bone marrow cells. This feature, in conjunction with other parameters, may possibly be useful in the differential diagnosis of MPDs and MDSs. Our findings, compared with the previously reported findings in SMCD, suggest that SMCD may be more closely related to MPDs than to MDSs.

(Arch Pathol Lab Med. 2005;129:219-222)

Systemic mast cell disease (SMCD) is a rare disorder characterized by the accumulation of mast cells in a variety of sites, including the bone marrow, spleen, liver, and skin.1-5 However, mast cells may also be increased as a reactive mastocytosis in various hematologic disorders and malignant neoplasms.3,4,6,7 The SMCD cannot be distinguished from reactive mastocytosis based solely on the quantity of mast cells, since it has been determined that there are no statistical differences in mast cell numbers in reactive mastocytosis and SMCD. However, SMCD usually reveals dyspoietic mast cells and other dyspoietic bone marrow elements (ie, erythroid, myeloid, and megakaryocytic cells), which aid in the distinction between reactive mastocytosis and SMCD.8

In addition, SMCD frequently occurs (45%) in association with myeloproliferative disorders (MPDs) (17%), myelodysplastic syndromes (MDSs) (287%), and acute myeloid leukemia.9-18 Thus, it has been suggested that SMCD may represent one aspect of a hematologie disorder that involves multiple bone marrow lineages. A systematic evaluation of MPD and MDS cases without SMCD for the approximate quantitation of mast cells and the presence of dyspoietic mast cells has not been performed. Such a study is of interest to determine whether dysplastic changes are present in the mast cells of these lesions and whether they occur as frequently as in SMCD. In addition, such a study may reveal findings that are useful for the differential diagnosis of MPDs and MDSs.

MATERIALS AND METHODS

A total of 55 well-established MPD or MDS cases were retrospectively reviewed. These cases included 20 cytogenetically proven chronic myeloid leukemias, 6 essential thrombocythemias, 2 polycythemia veras, 21 cytogenetically proven MDSs, and 6 chronic myelomonocytic leukemias. The MDSs included refractory anemia with ringed sideroblasts (3), sideroblastic anemia (1), refractory cytopenias (5), refractory cytopenias with excess blasts (3), RAEB-I (1), MDS not otherwise specified (2), high-grade MDS (2), MDS with fibrosis (2), and secondary MDS (1). cases of idiopathic myelofibrosis were not included due to the uniform lack of spicules for review in these cases. The bone marrow aspirates were reviewed for the presence of spicules, an increase in mast cells (1+, average of 3-5 mast cells per 60× oil-immersion field; 2+, >5-10; and 3+, >10), dyspoietic features within mast cells (ie, significantly decreased cytoplasmic granularity and uneven granule distribution), and a predominance of fusiform mast cells.

RESULTS

All cases, except 2 MDS cases (those with fibrosis), had evaluable bone marrow spicules. The Table demonstrates the results of the retrospective, cytomorphologic review by hematologie disease type. Of interest, the MPDs were significantly more associated with increased numbers of mast cells (57%) (Figure 1, A) and dyspoietic and fusiform mast cells (Figure 1, B and C) than were the MDS cases (11% and 4%, respectively) (Figure 2, A through C). Mast cells were most commonly increased and dyspoietic or fusiform in chronic myeloid leukemia (70% and 80%, respectively). The 2 cases of polycythemia vera and the 6 cases of chronic myelomonocytic leukemia did not reveal an increase in mast cells or dyspoietic mast cells. The MDS cases that revealed increased numbers of mast cells included a high-grade MDS (1), a refractory anemia with ringed sideroblasts (1), and a refractory cytopenia (1). Thus, the relatively rare finding of increased mast cells in MDS did not correlate with any specific subtype of MDS. The high-grade MDS with increased mast cells was also the only MDS case associated with dyspoietic (hypogranulated) mast cells.

COMMENT

Although there are no statistical differences in mast cell numbers in reactive mastocytoses and SMCD, dyspoietic mast cells are characteristic of SMCD. However, as mentioned previously, SMCD frequently occurs in association with other hematologie disorders, including MPDs, MDSs, and acute myeloid leukemias. This association has led to the suggestion that SMCD represents one aspect of a hématologie disorder that involves multiple bone marrow lineages. In addition, some MPD or MDS cases may have a mild, diffuse increase in mast cell numbers, unassociated with SMCD, which may be a part of the clonal bone marrow proliferation. However, a critical cytomorphologic analysis of the mast cells in these conditions has not been previously described. Therefore, we decided to systematically review cases of MPDs or MDSs without SMCD to determine whether dysplastic changes are present in the mast cells of these lesions and whether they occur as frequently as in described cases of SMCD.

We have demonstrated that the chronic MPDs (ie, chronic myeloid leukemia and essential thrombocythemia) frequently contain neoplastic mast cells as the spectrum of abnormal cells in the bone marrow. In fact, in chronic myeloid leukemia, a higher percentage (80%) of cases reveal dyspoietic mast cells than merely increased mast cells (70%). A lesser percentage of essential thrombocythemia cases revealed increased mast cells (33%) and dyspoietic mast cells (17%), when compared with the chronic myeloid leukemia cases. Of interest, none of the polycythemia vera cases revealed increased or dyspoietic mast cells. Thus, the finding of increased and dyspoietic mast cells, in combination with additional clinical and laboratory data, may be useful in excluding polycythemia vera.

In addition, we have shown that increased and dyspoietic mast cells are significantly more characteristic of MPDs (ie, chronic myeloid leukemia and essential thrombocythemia) than MDSs. Of note, the relatively rare findings of increased or dyspoietic mast cells in MDSs did not correlate with any specific subtype of MDS. Since no cases of chronic myelomonocytic leukemia were associated with increased or dyspoietic mast cells, these findings, in combination with additional clinical and laboratory data, may aid in exclusion of this diagnosis and differentiation from a chronic MPD.

Lastly, our findings, compared with the previously reported findings in SMCD, suggest that SMCD may be more closely related to chronic MPDs than to MDSs. Perhaps SMCD arises in a background of a chronic MPD, such as chronic myeloid leukemia or essential thrombocythemia, since they are frequently associated and share the findings of increased and dyspoietic mast cells. Based on our findings, it is not clear how one would distinguish between a chronic MPD and an early SMCD associated with one of these chronic MPDs. The clinical significance of such a distinction is also unclear.

References

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Cherie H. Dunphy, MD

Accepted for publication October 4, 2004.

From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill.

The author has no relevant financial interest in the products or companies described in this article.

Reprints: Cherie H. Dunphy, MD, Department of Pathology and Laboratory Medicine, CB#7525, University of North Carolina, Chapel Hill, NC 27599-7525 (e-mail: cdunphy@unch.unc.edu).

Copyright College of American Pathologists Feb 2005
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