Case 265 - PowerPoint Presentation

Slide1

Case 265

Hina Naushad, M.D., Timothy C. Greiner M.D., Radwa El Behery M.D., Greg Bociek M.D., Phuong L. Nguyen M.D. University of Nebraska Medical CenterMayo ClinicSlide2

History

24-year-old male who developed drenching night sweats and bilateral neck fullness Lymphadenopathy and splenomegaly on physical examSlide3

CD34Slide4

TDT

CD1a

CD99

Ki-67Slide5

CD3

CD4

CD7

CD8Slide6

Immunophenotype 2010 LN

PositiveCD3, CD7, CD4, CD43, CD45, BCL2, CD1a, CD99, TdTNegativeCD8, CD20, CD30, CD34, CD117, BCL6, MPOSlide7

Staging Bone Marrow 2010

CBCWBC 10.7, HGB 11.9, PLT 234 Differential countneutrophils 55%, lymphs 17%, monos 13%, eosinophils 13%, basophils 1%. Slide8

CD3Slide9

Marrow (3) - Wright

Giemsa

- Peripheral bloodSlide10

Immunophenotype 2010 Marrow

Flow CytometryNo immunophenotypic abnormalitiesNo lymphoblastsIHCCD3 and CD20 scattered small T and B cellsSlide11

Initial Local Dx and Therapy

LN Bx: T-Lymphoblastic lymphomaBM Bx: Myeloid HyperplasiaHe received 6 cycles of Hyper-CVAD chemotherapy and had maintenance therapy with methotrexate and 6-MP A tyrosine kinase inhibitor was not usedSlide12

Follow up - 2012

Lymphadenopathy recurredT-Lymphoblastic lymphoma again identified in the lymph nodesMyeloid hyperplasia with eosinophils again seen in the restaging marrowSeparate components in LN and marrow just like in 2010Slide13

FISH and Mutation Analysis

Bone Marrow Neg: BCR-ABL, FGFR1, PDGFRB, ETV6, Neg: KIT mutationPositive: CH1C2 deletion by FISH in 2012 BM (Mayo)We returned to the 2010 lymph node biopsy and FISHed it for CHIC2 deletion: PositiveHe was treated with a “Vanderbilt regimen” and underwent an allotransplant in 2013Slide14

Heterozygous deletion of one allele (red/yellow signal lost)Slide15

Interesting Features

This patient developed both a lymphoid and myeloid neoplasm associated with eosinophiliaThe CHIC2 deletion indicates a FIP1L1/PDGRFA fusion transcript as described in the 2008 WHO classification The

lymphoblastic lymphoma and the myeloid neoplasm

occurred completely separately and recurred separately Slide16

Panel Request for Discussion

Spectrum of clinical/pathologic characteristics of myeloid/lymphoid neoplasms with PDGFRA-FIPIL1 What is a possible mechanism for eosinophilia in this case?Slide17

Spectrum of

Disease With a FIP1L1/PDGRFA RearrangementAcute myeloid leukemiaChronic eosinophilic leukemiaLymphoblastic lymphoma/leukemia: T or BSlide18

Spectrum of Disease:

Previous Case Reports of Simultaneous Lymphoid and Myeloid Neoplasms Case 1Case 2Case 3Case 4Age58 M

45 M

33 M

42M

LAD

Yes

Yes

Yes

Yes

Spleen

Yes

Yes

Yes

LN

DxT-LBL N,E,T-LBL N,ET-LBLT-LBLCD4 or CD8CD4CD4CD4CD4 CD8BM DxAML-eosinEosin MPDCEL

Eosin MPNT-LBLT-LBL---*Later B-LBL

1&2 : Metzgeroth G, et al. Leukemia 2007

3: Capovilla M, et al. European J Haematol 2007

4: Huang et al. Leukemia 2012Slide19

Panel Request for Discussion

Spectrum of clinical/pathologic characteristics of myeloid/lymphoid neoplasms with PDGFRA/FIPIL1 What is a possible mechanism for eosinophilia in this case?Slide20

What is the mechanism of eosinophilia?

PDGFRA encodes for the receptor tyrosine kinase, platelet-derived growth factor receptor ABreakpoints occur in the juxtamembrane domain“The 4q12 deletion removes negative regulatory motifs encoded 5’ to the exon 12 breakpoint leading to constitutive activation of this receptor”Slide21

What is the mechanism of eosinophilia? (Continued)

The activated fusion protein is capable of promoting eosinophil-lineage commitment in hematopoietic progenitor cells “in vitro”

Stover et al, PNAS 2006

Fukushima, J Biol Chem 2009

Montgomery et al., Archives of Path 2013Slide22

Proposed Diagnosis

Myeloid and lymphoid neoplasm with PDGFRA rearrangement

Consensus Diagnosis

Myeloid and lymphoid neoplasm with PDGFRA rearrangement, presenting with T-lymphoblastic lymphoma and

myeloproliferative

neoplasm with eosinophilia