Submitting Author: Bhagat, Govind, MD
Institution: Columbia University Medical Center
Additional authors:Tatyana Gindin, M.D., Ph.D., Bachir Alobeid, M.D., Daniela Hoehn, M.D., Ph.D.
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN

73-year-old male with history of myelodysplastic syndrome (MDS), diagnosed in the Dominican Republic 7 years previously, presented to an outside hospital with complaints of upper abdominal pain for the past 6 months that worsened 5 days prior to presentation, dysphagia to solid foods and a 40 pound weight loss over the past 4 months. The patient also reported that in the past he had developed dizziness and hypotension shortly after receiving a pneumococcal vaccine. At presentation he was found to have thrombocytopenia, macrocytosis, mild monocytosis and mild anemia. A serologic test for HIV was negative. Endoscopy showed gastric mucosal erythema, normal esophagus and duodenum. Colonoscopy showed diverticulosis of the sigmoid colon. A CT scan of the abdomen and pelvis reported lesions suggestive of liver metastases, retroperitoneal adenopathy, diffuse bone metastases, hepatosplenomegaly, ascites, and pleural effusion. Bone marrow and liver biopsies were performed. The liver biopsy showed an extensive infiltrate of atypical mast cells, while the bone marrow biopsy showed features of MDS in addition to the infiltrate of atypical mast cells. A diagnosis of systemic mastocytosis with associated hematologic non-mast cell clonal disease was rendered. Due to a lack of response to Imatinib 400mg daily, therapy was switched to Nilotinib 400mg twice daily. Apart from the persistent flank pain and abdominal discomfort, the patient is ambulatory and doesn’t feel restricted in his daily activities currently.

Biopsy fixation details: Formalin

Bone marrow biopsy:

Sections of bone marrow core biopsy and aspirate clot preparation showed markedly hypercellular for age (90% cellularity). Maturing cells of the myeloid and erythroid lineage were present, with latter exhibiting megaloblastic features. Mild increase in myeloblasts was noted. Scattered small and/or hypolobated megakaryocytes were noted. An extensive infiltrate of atypical mast cells was present, accounting for approximately 50% of all marrow nucleated cells. The mast cells comprised a morphologic spectrum, including numerous spindle and many large atypical forms. The extent of mast cell granulation was variable with a Giemsa stain, with some cells showing abundant coarse granules, while others showed few small granules or no discernable granules. Eosinophils were seen in areas of mast cell infiltration, as were a few lymphoid aggregates.

Bone marrow aspirate:

The marrow was hypercellular and showed trilineage dysplasia. The dysplastic changes in the myeloid lineage included left shifted, hypogranular forms and pseudo-Pelger neutrophils. Megaloblastic changes of the erythroid precursors were apparent and scattered binucleated forms and cells showing nuclear contour abnormalities and karyorrhexis were seen. Blasts, including some with monocytic features, comprised 8% of all marrow nucleated elements. Scattered mast cells as well as clusters of atypical mast cells were present, ranging from 15% to focal areas with >60% mast cells, overall the mast cells accounted for approximately 20% of all marrow nucleated elements. Numerous promastocytes were noted and scattered metachromatic blasts were also seen. The aspirate clot preparation and marrow aspirate smears showed adequate iron stores and the presence of numerous ring sideroblasts.

Liver biopsy:

The portal tracts were expanded by an infiltrate of atypical mast cells (oval to spindle forms with elongated nuclei and scant pale cytoplasm). Bile duct injury and bile ductular reaction were apparent. Scattered eosinophils were present. The lobules showed no significant inflammation or cholestasis, but patchy sinusoidal dilatation was present and occasional mast cells were seen within sinusoids.

Bone marrow biopsy: The neoplastic mast cells expressed CD117, however only a minority (less than a third) expressed mast cell tryptase.

Flow cytometry on the aspirate sample performed elsewhere reported no elevation in blasts.

Liver biopsy: The neoplastic mast cells expressed CD117 and CD25 and scattered mast cells stained for mast cell tryptase.

Bone marrow biopsy sample showed normal male karyotype

C-KIT exon 17 (D816V) and exon 8 (D419H) mutations were detected

This is a rare case of systemic mastocytosis with associated hematologic non-mast cell clonal disease (high grade MDS associated with ring sideroblasts). The extent of marrow infiltration by atypical mast cells is suggestive of mast cell leukemia associated with 2 C-KIT mutations, however no circulating mast cells were detected and the patient’s clinical course has been relatively stable despite the extent of disease.

Systemic mastocytosis with associated hematologic non-mast cell clonal disease

1. Mast cell leukemia (aleukemic)

2. Refractory anemia with excess blasts type 1 (RAEB-I)

Systemic mastocytosis with associated hematologic non-mast cell clonal disease

1. Mast cell leukemia (aleukemic)

2. Refractory anemia with excess blasts type 1 (RAEB-1)

Case 263