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Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia.

Pullarkat ST, Pullarkat V, Kroft SH, Wilson CS, Ahsanuddin AN, Mann KP, Thein M, Grody WW, Brynes RK - J Hematop (2009)

Bottom Line: We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM.In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission.SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, CHS, A7-149, Los Angeles, CA, 90095-1732, USA, spullarkat@mednet.ucla.edu.

ABSTRACT
Although KIT mutations are present in 20-25% of cases of t(8;21)(q22;q22) acute myeloid leukemia (AML), concurrent development of systemic mastocytosis (SM) is exceedingly rare. We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM. In the majority of these cases, a definitive diagnosis of SM was made after chemotherapy, when the mast cell infiltrates were prominent. Deletion 9q was an additional cytogenetic abnormality in four cases. Four of the ten patients failed to achieve remission after standard chemotherapy and seven of the ten patients have died of AML. In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission. SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications.

No MeSH data available.


Related in: MedlinePlus

a Pretreatment bone marrow aspirate (case 3) showing predominantly myeloblasts admixed with rare mast cells. Note the hypergranular cytoplasm within the mast cells (Wright-Giemsa, ×500). b Day 14 post-treatment bone marrow aspirate (case 3) with prominent mast cell infiltrate (Wright-Giemsa, ×200). c Immunohistochemistry for tryptase (case 3) highlights the mast cell infiltrate (×200). d Mast cells show expression of CD25 (case 3), a characteristic feature of neoplastic mast cells (×200)
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Fig1: a Pretreatment bone marrow aspirate (case 3) showing predominantly myeloblasts admixed with rare mast cells. Note the hypergranular cytoplasm within the mast cells (Wright-Giemsa, ×500). b Day 14 post-treatment bone marrow aspirate (case 3) with prominent mast cell infiltrate (Wright-Giemsa, ×200). c Immunohistochemistry for tryptase (case 3) highlights the mast cell infiltrate (×200). d Mast cells show expression of CD25 (case 3), a characteristic feature of neoplastic mast cells (×200)

Mentions: The patients ranged in age from 26 to 67 years and included three males and seven females. None of the patients had urtricaria pigmentosa or other evidence of extramedullary mast cell involvement except for one published case that showed hepatic infiltration with mast cells after AML induction therapy [17]. Symptoms related to mast cell mediator release were not reported in any of the patients. All cases had morphologic and immunophenotypic features of AML with maturation (FAB-M2). Leucocytosis was present at diagnosis in six of seven patients in whom initial blood counts were available. Patient 4 had metastatic breast cancer and had undergone anthracycline-containing combination chemotherapy. She developed SM with t(8;21)(q22;q22) AML 1 year after initiation of chemotherapy. In nine of the ten cases, increased bone marrow mast cells were noted at the time of AML diagnosis In case 4, SM was diagnosed following three cycles of consolidation chemotherapy for AML. In that case, the bone marrow biopsies at diagnosis were reevaluated, but failed to demonstrate coexisting SM. An activating exon 17 KIT mutation was detected in seven of nine cases in whom this data is available. Three patients had D816V, two had D816Y, and one carried the D816H mutation. In one case (case 6) the exact mutation was not analyzed while another (case 4) carried an A814S mutation in addition to D816V. It is noteworthy that four of the ten cases had chromosome 9q deletion as an additional cytogenetic abnormality. Of the eight cases where immunophenotype data on the myeloblasts was available by flow cytometry, four of eight cases reported dim expression of CD19 and five of eight cases showed CD56 expression (Table 1). Bone marrow pathology of a representative case is shown in Fig. 1.Fig. 1


Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia.

Pullarkat ST, Pullarkat V, Kroft SH, Wilson CS, Ahsanuddin AN, Mann KP, Thein M, Grody WW, Brynes RK - J Hematop (2009)

a Pretreatment bone marrow aspirate (case 3) showing predominantly myeloblasts admixed with rare mast cells. Note the hypergranular cytoplasm within the mast cells (Wright-Giemsa, ×500). b Day 14 post-treatment bone marrow aspirate (case 3) with prominent mast cell infiltrate (Wright-Giemsa, ×200). c Immunohistochemistry for tryptase (case 3) highlights the mast cell infiltrate (×200). d Mast cells show expression of CD25 (case 3), a characteristic feature of neoplastic mast cells (×200)
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Related In: Results  -  Collection

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Fig1: a Pretreatment bone marrow aspirate (case 3) showing predominantly myeloblasts admixed with rare mast cells. Note the hypergranular cytoplasm within the mast cells (Wright-Giemsa, ×500). b Day 14 post-treatment bone marrow aspirate (case 3) with prominent mast cell infiltrate (Wright-Giemsa, ×200). c Immunohistochemistry for tryptase (case 3) highlights the mast cell infiltrate (×200). d Mast cells show expression of CD25 (case 3), a characteristic feature of neoplastic mast cells (×200)
Mentions: The patients ranged in age from 26 to 67 years and included three males and seven females. None of the patients had urtricaria pigmentosa or other evidence of extramedullary mast cell involvement except for one published case that showed hepatic infiltration with mast cells after AML induction therapy [17]. Symptoms related to mast cell mediator release were not reported in any of the patients. All cases had morphologic and immunophenotypic features of AML with maturation (FAB-M2). Leucocytosis was present at diagnosis in six of seven patients in whom initial blood counts were available. Patient 4 had metastatic breast cancer and had undergone anthracycline-containing combination chemotherapy. She developed SM with t(8;21)(q22;q22) AML 1 year after initiation of chemotherapy. In nine of the ten cases, increased bone marrow mast cells were noted at the time of AML diagnosis In case 4, SM was diagnosed following three cycles of consolidation chemotherapy for AML. In that case, the bone marrow biopsies at diagnosis were reevaluated, but failed to demonstrate coexisting SM. An activating exon 17 KIT mutation was detected in seven of nine cases in whom this data is available. Three patients had D816V, two had D816Y, and one carried the D816H mutation. In one case (case 6) the exact mutation was not analyzed while another (case 4) carried an A814S mutation in addition to D816V. It is noteworthy that four of the ten cases had chromosome 9q deletion as an additional cytogenetic abnormality. Of the eight cases where immunophenotype data on the myeloblasts was available by flow cytometry, four of eight cases reported dim expression of CD19 and five of eight cases showed CD56 expression (Table 1). Bone marrow pathology of a representative case is shown in Fig. 1.Fig. 1

Bottom Line: We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM.In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission.SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, CHS, A7-149, Los Angeles, CA, 90095-1732, USA, spullarkat@mednet.ucla.edu.

ABSTRACT
Although KIT mutations are present in 20-25% of cases of t(8;21)(q22;q22) acute myeloid leukemia (AML), concurrent development of systemic mastocytosis (SM) is exceedingly rare. We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM. In the majority of these cases, a definitive diagnosis of SM was made after chemotherapy, when the mast cell infiltrates were prominent. Deletion 9q was an additional cytogenetic abnormality in four cases. Four of the ten patients failed to achieve remission after standard chemotherapy and seven of the ten patients have died of AML. In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission. SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications.

No MeSH data available.


Related in: MedlinePlus