Findings from a Malaysian case study have shown the comorbid presence of systemic mastocytosis (SM) in a 4-year-old girl with amyloid myeloid leukemia (AML) with the t(8;21) translocation. The report of this rare case has been recently published in the Bangladesh Journal of Medical Science.
Mastocytosis comprises a heterogeneous group of conditions that are caused by clonal and neoplastic infiltration of mast cells. Manifestations of the disorders vary from skin lesions, as seen in cutaneous mastocytosis, to the aggressive form of the disease known as SM, in which mast cells can invade the organs of the body and cause organ failure.
According to the 2016 World Health Organization (WHO) classification system, SM can be categorized into five clinical groups with prognostic significance:
- Indolent SM
- Smoldering SM
- SM with an associated hematologic neoplasm (SM-AHN)
- Aggressive SM
- Mast cell leukemia
“AML has been concurrently identified with SM in 32% of patients, which is more than is typically thought to occur,” the study authors wrote.
They added that the disorder should not be diagnosed merely based on the SM disorder, however, but based on the presence of AML cells as well.
Read more about SM therapies
In this patient, the diagnosis of SM was confirmed, according to the WHO classification system, based on one major criterion (the presence of multifocal clusters of abnormal mast cells in the bone marrow) and two minor criteria (elevated serum tryptase concentration, presence of the KIT D816V mutation and/or abnormal mast cell CD25 expression).
Mastocytosis presents between birth and 2 years of age in approximately 55% of cases, in children younger than 15 years in around 10% of cases and in children older than 15 years in about 35% of cases. The treatment of SM-AHN targets mainly the AHN component if the presence of an aggressive disorder such as AML is reported.
The patient underwent a variety of laboratory examinations. Findings from a trephine biopsy revealed a homogeneous population of blast cells, which were positive for CD34, CD117 and MPO. Results of cytogenetic analysis showed results consistent with a diagnosis of AML with t(8;21).
The AML-12 protocol was initiated in the patient. Findings from a surveillance bone marrow assessment after induction chemotherapy showed hypocellular marrow with no increase in myeloblasts. Although trephine biopsy revealed no rise in blast cells, abnormal mast cells were observed, which were distributed throughout the marrow spaces.
Based on immunohistochemical staining, expression of mast cell tryptase, CD117, and CD68 was detected, but not CD25. There were a negligible number of positive blast cells observed. The patient was thus diagnosed with SM associated with t(8;21)(q22;q22) AML. Induction therapy was initiated, but she unfortunately died from severe neutropenic sepsis that occurred post-induction chemotherapy.
“Concurrent development of SM with AML is exceedingly rare,” the authors wrote. Pediatric patients with t(8;21) AML-SM may represent a high-risk group of individuals in spite of favorable cytogenetics. Patients with comorbid SM and AML t(8;21) frequently are refractory to induction chemotherapy, with high rates of relapse reported among these individuals. Thus, the detection of concomitant SM at diagnosis of t(8;21) AML has important prognostic implications.
“To the best of our knowledge, SM-AML with a t(8;21) translocation in young girls is rarely reported in our country,” the authors stated. “We recommend examining all cases of AML with t(8;21) for the presence of SM via morphology, immunophenotyping, and mutational analysis studies.”
