Submitting Author: Hart, Edward Hubert, MD
Institution: University of Utah and ARUP Laboratories
Additional authors:Perkins, S.L., Toydemir, R., Salama, M.E.
Session: Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1

The patient is a 65-year-old male who presented with leukocytosis and left axillary lymphadenopathy.

1.) Excisional biopsy of left axillary mass:

Gross Examination:

5.0 x 3.0 x 2.0 cm piece of soft tan tissue containing a single enlarged lymph node measuring approximately 3.0 x 1.5 x 1.0 cm.

Microscopic examination:

H+E sections revealed an enlarged lymph node, almost completely effaced by an infiltrate of lymphoblastic cells, exhibiting high N:C ratios, round to variably irregular nuclear contours, dispersed chromatin, distinct but non-prominent nucleoli, and scant cytoplasm. The lymphoblasts were seen to permeate representative portions of the lymph node capsule, extending into the perinodal adipose tissue. Numerous eosinophils were seen in the background. Frequent mitotic figures, many of which were atypical, and numerous karyorrhectic cells were present.

2.) Bone marrow biopsy:

CBC data

: WBC: 24.83 K/MCL, RBC: 6.82, HGB: 18.3 G/DL, HCT: 56.9%, MCV: 83.4 FL,

MCH: 26.8 PG, MCHC: 32.2 G/DL, RDW: 16.4%, PLT: 107 K/MCL

Differential Count (100 cells): 67% segmented neutrophils, 7% bands, 6% lymphocytes, 11% monocytes, 5% eosinophils, 3% basophils, 1% metamyelocytes.

Blood Smear Morphology: The erythrocytes were increased in number, normocytic and normochromic, with mild anisopoikilocytosis and polychromasia. The leukocytes were markedly increased in overall number with an absolute neutrophilia, monocytosis, eosinophilia, and basophilia. The neutrophils showed adequate segmentation and granulation. There was a mild left shift with occasional band neutrophils, infrequent metamyelocytes, and rare myelocytes present. The lymphocytes included small mature and occasional large reactive forms. The platelets were decreased in number and adequately granulated.

Bone marrow aspirate smear (500 cells; %):

1.0% myeloblasts, 2.6% promyelocytes, 9.8% myelocytes, 17.6% metamyelocytes, 18.6% band neutrophils, 17.0% segmented neutrophils, 6.2% eosinophils, 0.4% basophils, 1.2% pronormoblasts 1.2%, basophilic normoblasts 2.2%, polychromatophilic normoblasts 8.2%, orthochromatic normoblasts 3.2%, monocytes 6.6%, plasma cells 0.8%, lymphocytes 4.6%

M:E Ratio 4.9

Morphologic Summary: The bone marrow aspirate was spiculate, richly cellular, and adequate for evaluation, with trilineage hematopoiesis, and an elevated M:E ratio of 5.4. The erythroid series was composed of a full spectrum of maturational stages with no significant dyserythropoiesis. The myeloid series was composed of a full spectrum of maturational stages with unremarkable segmentation and granulation. Blasts were normal in number, accounting for approximately 1% of the total nucleated marrow elements. Occasional morphologically unremarkable megakaryocytes were present. No atypical cellular infiltrates or aggregates were identified by morphology.

An iron special stain was performed on the aspirate smear and showed mildly decreased storage iron, with no ring sideroblasts identified.

Bone marrow particle clot section: The particle clot section contained abundant fragments of marrow tissue and was similar in cellular composition and morphology to the aspirate smear and core biopsy specimens.

Bone marrow core biopsy: The core biopsy specimen was composed of trabecular bone with adequate intervening marrow elements. The marrow was markedly hypercellular for the patient's age at approximately 90-95%. There was trilineage hematopoiesis with granulocytic hyperplasia and generally unremarkable localization of the erythroid and myeloid precursors. Megakaryocytes appeared adequate in number, and were distributed evenly and in occasional loose clusters. Some of the megakaryocytes showed mildly dysmorphic nuclear segmentation patterns including both hyper- and hypolobated forms.

Reticulin special stain performed on the core biopsy specimen showed no significant reticulin fibrosis (MF-0/3).

Flow cytometric analysis performed on the left axillary lymph node revealed a population of atypical T-lymphoblasts, comprising 93% of the total leukocytes, and expressing CD1a, CD2, cCD3, CD4, CD5, CD7, partial CD8, partial/dim TdT, and lacking surface CD3 and CD34, consistent with T-lymphoblastic leukemia/lymphoma.

Flow cytometric analysis performed on the bone marrow aspirate specimen showed no evidence of malignancy.

Chromosomal analysis performed on the bone marrow aspirate revealed an abnormal

46,XY,t(8;13)(p12;q12)[20] male chromosome complement with translocation between chromosome 8 and 13.

Myeloproliferative disorder FISH panel performed on the bone marrow aspirate showed a 8p12(5'FGFR1) partial deletion, likely lost during the rearrangement of this locus.

The concurrent presentation of T-lymphoblastic lymphoma and myeloid neoplasm, both of which exhibit a prominent eosinophilic component, along with the cytogenetic findings are diagnostic of leukemia/lymphoma associated with FGFR1 rearrangement/precursor T-cell lymphoblastic lymphoma, myeloid neoplasm. The myeloid neoplasm is best classified as chronic myelomonocytic leukemia (CMML), despite the lack of significant dysplastic features, given that other requirements including monocytosis (>1x10 K/MCL) are met. The erythrocytosis however, is unusual.

Leukemia/Lymphoma associated with FGFR1 rearrangement/precursor T-cell lymphoblastic lymphoma, chronic myelomonocytic leukemia

Myeloid and lymphoid neoplasm with FGFR1 rearrangement, t(8;13)(p12;q12), presenting with T lymphoblastic lymphoma, and subsequent chronic myelomonocytic leukemia with eosinophilia

Case 432