Submitting Author: Hosking, Paul Robert, MD
Institution: Columbia University Medical Center, New York, NY
Additional authors:Bachir Alobeid, MD, Govind Bhagat, MBBS, Daniela Hoehn, MD PhD
Session: Extramedullary manifestations of myeloid neoplasms

14 month-old female with a medical history of secundum atrial septal defect, patent ductus arteriosis and pulmonary airway malformation, type II (CPAM type 2, CCAM type 2), status-post complete resection (RML and RLL) at month 4. Now presenting with asymptomatic, palpable neck mass with progressive enlargement over a 1 month with initial outside diagnosis of possible insect bite. No B symptoms.

MRI imaging studies: large, left-sided contrast enhancing cervical mass with involvement of C1-C2, intracranial invasion into the inferior occiput with compression of the cerebellum and impeding spinal impingement. Labs: CBC: WBC: 6.9, Hb: 11.5, Hct: 33.3, Platelets: 321, MCV: 78.9 (75% lymph, 19% neutr, retic count 0.8.), PT/ PTT/ INR: WNL, AFP/ beta HCG: negative, LDH: 532, Alk Phos 197 U/L

Differential diagnostic considerations ranged from small round blue cell tumors of childhood to other rare sarcomas (particularly within the context of DICER1 tumor predisposition syndrome associated with pleuropulmonary blastoma) to hematopoeitic neoplasms. Incisional biopsy of mass was performed October 2012.

CT chest/abd/pelvis post biopsy: multifocal lesions: bilateral kidneys, liver, pancreatic head retroperitoneal LAD and bony lesions.

Diagnostic Neck Mass

• Gross: multiple pieces of soft tissue measuring approximately 2.5 x 2 x 1.5 in aggregate. Intraoperative consultation revealed “Infiltrative cellular process involving skeletal muscle“. Specimens were divided/submitted for flow cytometry, cytogenetics, molecular studies and permanent sections (formalin fixed/ paraffin embedded).

• Hematoxylin and eosin (H&E) stained slides showed a diffuse infiltrate of large neoplastic cells involving soft tissue and skeletal muscle with multiple foci of necrosis. Neoplastic cells were large, irregular with oval to irregular nuclei, prominent nuclear contours, vesicular chromatin, occasional conspicuous nucleoli and a moderate amount of amphophilic cytoplasm. Apoptotic bodies and mitotic figures (including atypical mitoses) were easily identified.

Staging Marrow Examination

• Bone marrow core needle trephine biopsies (left and right posterior iliac crests) were fixed in Bouin solution. Bone marrow aspiration was sent for morphological evaluation, cytogenetic analysis and flow cytometry.

• Core needle biopsies (H&E) were of suboptimal quality, subcortical, with marked aspiration and tissue drop out artifact showing a diffuse and interstitial infiltrate of medium to large size cells with irregular nuclei, predominantly inconspicuous nucleoli, irregular nuclei contour and moderate amount of eosinophilic cytoplasm. Remaining bone marrow elements were present, markedly decreased and with progressive maturation.

• Wright- Giemsa stained aspirate smears demonstrated a population of blasts which with patchy distribution, averaging around 20% of marrow nucleated cells. Blasts were medium to large in size, with round/oval nuclei, evenly dispersed, powdery to lacey nuclear chromatin with 1 to 2 large prominent nucleoli and moderate to abundant basophilic to blue-grey cytoplasm with rare azurophilic granules. No Auer Rods present.

Neck Mass

IHC analysis: Multiple non-hematopoietic markers performed by surgical pathology were negative (chromogranin, synaptophysin, Melan A, myogenin, perpeherin, HMB-45, cytokeratin, EMA, WT-1, HHF-35, desmin, S-100, MyoD1). Neoplastic cells were positive for: CD4, CD33, CD43, CD45, CD56, CD68, CD99,(subset dim), CD117(subset dim), CD123 (subset dim), INI-1, FLI-1 and Lysozyme. Neoplastic cells were negative for CD1A, CD3, CD20, CD21, CD23, CD30, CD34, CD35, CD163 and MPO. Ki-67 highlighted a proliferation index of up to 70%.

Flow cytometric analysis detected an aberrant cell population (up to 90% of gated cells) positive for CD4, CD16/56, CD33, CD52, CD117, (subset), CD123 and HLA-DR (bright), with questionable dim expression of CD2. The cells were negative for cCD3, CD3, CD14, MPO and TdT.

Staging Marrow Examination

IHC analysis: Neoplastic cells were positive for CD56, CD68, CD117 (subset), CD123 (subset) and negative for CD34.

Flow cytometric analysis detected an aberrant blast population (5% of total cells analyzed) which was positive for CD4, CD13 (subpopulation dim), CD16/CD56, CD33, CD43, CD64, CD117, HLA-DR (bright). The cells were negative for sCD3, cCD3, CD7, CD19, CD34, CD1a, CD25, CD30, CD14, TdT and MPO. In addition there was a minute population of CD19+/CD10+ cells present in the CD45dim gate, consistent with hematogones.

G-banding karyotype analysis of Neck Mass

46,XX,t(9;11)(p21;q23)[2]/46,idem,-3,+der(3)t(1;3)(q24;p25)[4]/46,XX[11]

In a subclone, an additional abnormality [der(3)t(1;3)(q24;p25)] is seen resulting in partial trisomy 1q.

G-banding karyotype analysis of Staging Marrow:

46,XX,t(9;11)(p21;q23),add(17)(p13)[8]/46,idem,der(3)t(1;3)(q24;p25)[5]/46,XX[8]

In a subclone, an additional abnormality [der(3)t(1;3)(q24;p25)] is seen resulting in partial trisomy 1q.

Neck mass and staging bone marrow aspirate: polyconal IgH and TCR rearrangement

Asymptomatic child with multifocal involvement by MLL positive AML with monocytic differentiation; Primary presentation as cervical soft tissue mass.

MLL + ACUTE LEUKEMIA WITH MONOCYTIC DIFFERENTIATION presenting as

SOFT TISSUE INFILTRATE/ MYELOID SARCOMA WITH MONOCYTIC DIFFERENTIATION

Acute myeloid leukemia with t(9;11), MLL gene rearrangement, involving bone marrow and neck mass (myeloid sarcoma)

Case 298