Submitting Author: Ryan, Russell James Hubbard, MD
Institution: Massachusetts General Hospital
Additional authors:Robert Paul Hasserjian, MD
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN

The patient was a 61 year-old male with no significant past medical history who presented to an outside hospital with a one month history of generalized fatigue, abdominal pain, nausea, vomiting, and loss of appetite. Laboratory studies were notable for leukocytosis and elevated alkaline phosphatase. An abdominal CT scan showed a thickened gallbladder wall with multiple gallstones and an enlarged spleen with multiple lesions interpreted as infarcts. The patient underwent laparoscopic cholecystectomy for presumed acute cholecystitis. On postoperative day 1, he experienced mental status changes and intermittent hypotension requiring pressors and intubation and was transferred to our institution. On admission, the patient was noted to have an extensive urticarial rash on his torso, which was felt to represent an anaphylactoid drug reaction and which resolved upon steroid administration. CBC showed hematocrit 25.1%, platelet count 57 x 109/L, and white blood count 50.6 x 109/L, with a manual differential of 42% neutrophils, 20% lymphocytes, 12% monocytes, 2% eosinophils, 15% bands, 2% metamyelocytes, 1% myelocytes, and 6% primitive cells. The latter had moderate amounts vacuolated cytoplasm with purple-red cytoplasmic granules, irregular or bilobed nuclei, finely reticular chromatin, and prominent nucleoli. Rare blasts with scant, agranular cytoplasm were also seen. Acute promyelocytic leukemia was suspected clinically and therapy with ATRA and hydroxyurea was initiated. A bone marrow biopsy was performed. The patient experienced worsening renal failure and marked elevations of serum uric acid and phosphate consistent with tumor lysis syndrome. He developed progressive lactic acidosis, coagulopathy, and multi-organ system failure, and expired on hospital day 6.

The posterior iliac crest bone marrow biopsy was fixed in B+ and decalcified in RapidCal Immuno. The core biopsy showed a markedly hypercellular marrow (95% cellular), with sheets of primitive blast forms comprising 80% of the cellularity. The blasts had abundant pale cytoplasm and irregular, often bilobed nuclei with primitive chromatin. Rare blasts showed clumps of metachromatic cytoplasmic granules on Giemsa stain. No aggregates of mature mast cells were seen. Megakaryocytes were increased, with abnormal small and large forms with hypolobated nuclei. Reticulin was not increased.

The aspirate smear showed 80% primitive cells and blasts with variably granulated cytoplasm and nuclear features similar to those seen in the peripheral blood. The blasts were negative by cytochemical stain for myeloperoxidase, with only rare blasts staining for non-specific esterase.

Flow cytometry on the peripheral blood and bone marrow demonstrated the following phenotype on the primitive cells: CD117+, CD13+, CD33+, CD64+, CD25, CD45dim+, CD2dim+, CD4dim+, CD9dim+, CD22dim+, and CD34-, HLA-DR-, MPO-, CD14-, TdT-, CD56-, and CD15-.

Immunohistochemistry on the core biopsy showed the blasts to be strongly positive for CD117 and mast cell tryptase, weakly positive for CD68, focally positive for lysozyme, and negative for CD34, CD123, CD31, and CD61.

Bone marrow karyotype was as follows:

40,XY,-2,der(3)t(1;3)(q21;p21),der(3)t(3;14)(p1?3;q1?3),add(4)(q3?5),-5,add(7)(q2?2),del(10)(q2?4q2?5),-12,-14,-16,add(16)(p13),add(18)(q21),der(19)t(12;19)(q13;q13),-20,-22,+1-4mar[cp5]/42,XY,der(2)t(2;12)(q31;q13),der(3)t(3;14),add(3)(p24),add(4)(q3?5),der(4)add(4)(p16)del(4)(q3?3),-5,del(6)(p2?3),del(10),-12,-12,-14,-16,add(16),add(18),-20,-22,+3-4mar[cp12]/46,XY[3]

FISH analysis was negative for a rearrangement of the RARA locus at 17q21. KIT gene sequencing is in progress.

Unusual presentation of mast cell leukemia, initially mimicking acute cholecystitis with leukemoid reaction, and later acute promyelocytic leukemia. The urticarial rash was likely due to mast cell degranulation rather than anaphylactoid drug reaction as initially suspected. Mast cell leukemia is a rare entity, classified under mastocytosis rather than as a subtype of acute myeloid leukemia (WHO 2008). This case behaved in a very aggressive manner and had a highly complex karyotype including losses of chromosomes 5 and 7q, cytogenetically resembling acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). The marked megakaryocytic atypia was another unusual feature reminiscent of AML-MRC.

Mast cell leukemia

Case 244