Case 50

Submitting Author: Vasef, Mohammad A, MD
Institution: University of New Mexico Health Sciences
Session: Extramedullary manifestations of myeloid neoplasms

HISTORY

The patient is a 13-year-old female who initially presented to her primary care physician in June of 2010 for bilateral breast lumps. Ultrasound studies revealed multiple solid-appearing bilateral masses, ranging from 1.2 cm to 1.8 cm in diameter, which were thought to be fibroadenomas given the patient’s age. Bilateral ultrasound-guided needle core biopsies were performed on the largest masses and sent to us in consultation and diagnosed as myeloid sarcoma. A subsequent bone marrow showed 33% myeloblasts and was diagnosed as acute myeloid leukemia. A CT scan performed after induction chemotherapy (Cytarabine, Daunorubicin, Etoposide regimen) revealed persistent disease in the bilateral breasts. The day 33 bone marrow had 5% myeloblasts. Following re-induction chemotherapy in August 2010, a repeat CT showed enlarging breast masses and a new 3.8 cm in diameter posterior chest wall mass. At the end of re-induction, the bone marrow had 4% myeloblasts. Due to progression of the extramedullary myeloid neoplasms, treatment was changed to a Mitoxantrone/AraC based protocol. She developed septic shock during treatment with multiple pulmonary nodules that were negative for organisms. Subsequent CT and PET scans showed increased uptake in the right upper chest and lateral chest wall. After completion of the intensified chemotherapy, the bone marrow reportedly had 4% blasts. In November of 2010, the patient received Clofarabine, Cyclosporine and Etoposide per TACL T2007-002 protocol with significant complications including interstitial nephritis with tubular injury and pulmonary aspergillosis. A bone marrow in December 2010 was reportedly markedly hypocellular with no significant myeloblasts population. An attempt was made to prepare the patient for stem cell transplantation but she became ineligible upon development of uncontrolled HHV6 viremia. The patient expired in February 2011.

DETAILS

The H&E-stained histologic sections of formalin-fixed paraffin embedded needle core biopsies of bilateral breast masses showed sheets of blastic appearing cells.

The outside CBC performed 2 days after needle core biopsies of the breast masses reportedly revealed a WBC count of 4X10^9/L, hemoglobin of 12.9 gm/dL, hematocrit of 37.7%, MCV of 86 fL, and a platelet count of 242,000. Review of a peripheral blood smear reportedly showed no circulating blasts.

A subsequent bone marrow biopsy reportedly showed 33% myeloblasts.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Paraffin immunohistochemical stains performed on needle core biopsies of the breasts revealed that the blastic appearing cells are positive for CD34, CD117, myeloperoxidase, TdT and CD43 and negative for CD3, CD20, tryptase, lyzosyme and CD79A.

Flow cytometric analysis on the bone marrow aspirate reportedly identified a population of myeloid blast expressing CD34, CD13, CD33, CD7, CD56 and HLA-DR consistent with the diagnosis of acute myeloid leukemia.

CYTOGENETIC FINDINGS

Cytogenetic analysis of the bone marrow revealed: 46,XX,t(1;2)(p36.1;p21)[15]/46,XX[5]

MOLECULAR FINDINGS

PCR analysis performed on bone marrow reportedly identified FLT3 ITD with an allelic ratio of 0.29

INTERESTING FEATURES

The interesting features of this myeloid sarcoma coinciding with bone marrow involvement by acute myeloid leukemia include:

1. The unusual initial presentation of myeloid leukemia as bilateral breast masses in a 13-year-old patient

2. The absence of cytopenias or circulating blasts at presentation

3. Progression of extramedullary myeloid sarcoma refractory to aggressive chemotherapy in the patient despite achievement of bone marrow remission

PROPOSED DIAGNOSIS

Myeloid sarcoma

CONSENSUS DIAGNOSIS

Acute myeloid leukemia with FLT3 ITD mutation involving bone marrow and bilateral breast masses (myeloid sarcomas)