Myeloid neoplasm with PCM1-JAK2 presenting with hepatosplenomegaly - - PowerPoint PPT Presentation

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Myeloid neoplasm with PCM1-JAK2 presenting with hepatosplenomegaly - - PowerPoint PPT Presentation

Jun 07, 2023 347 likes •565 views

Myeloid neoplasm with PCM1-JAK2 presenting with hepatosplenomegaly Case 376 Magdalena Czader, MD, PhD Indiana University Indianapolis, IN Clinical history 13-year-old Caucasian male with a history of ulcerative colitis Presented

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Myeloid neoplasm with PCM1-JAK2 presenting with hepatosplenomegaly Case 376

Magdalena Czader, MD, PhD Indiana University Indianapolis, IN

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Clinical history

  • 13-year-old Caucasian male with a history of ulcerative colitis
  • Presented with progressive hepatosplenomegaly and underwent liver

biopsy as a work-up for possible primary sclerosing cholangitis or autoimmune hepatitis

  • CBC:

WBC 13x109/L with eosinophilia (3.3x109/L) hemoglobin 11.2 g/dL MCV 77 fL RDW 17.3% platelet count of 187x109/L

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Liver biopsy

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Liver biopsy

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Liver biopsy

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Bone marrow biopsy

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Prominent eosinophilia

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Expanded erythroid islands

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Hemoglobin A CD117

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Loose megakaryocyte clusters

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Reticulin stain

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CD34

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Peripheral blood smear

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46,XY,t(8;9)(p22;p24)[21]/Nonclonal[2]/46,XY[2]

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Proposed diagnosis

Myeloid neoplasm with PCM1-JAK2

2016 WHO classification: Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2 Provisional entity: Myeloid/lymphoid neoplasms with PCM1-JAK2

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PCM1 PCM1-JAK2 JAK2

JH2 PTK domain JH2 PTK domain Coiled-coil domains Pericentriolar Material 1 (PCM1)

  • Localized in cytoplasmic granules-centriolar satellites
  • Recruits proteins necessary for centrosome replication
  • Microtubule organization
  • Blocking with antibodies or siRNA leads to disorderly

centrosome organization SH2 SH2

PCM1-JAK2 rearrangement

Dammermann et al. Dev Cell 2004 Bousquet et al. Oncogene 2005 Murati et al. Leukemia 2005

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JAK2 JAK2 JAK2 mutations Decreased autoregulation Hypersensitivity to growth factor PV, PMF, ET PCM1-JAK2 Increased

  • ligo/dimerization

Growth factor independent CEL, aCML, MDS/MPN-U, AML, ALL STAT5 STAT5

TRANSCRIPTION ACTIVATION

Protracted Aggressive

Adopted from Smith & Fan Human Pathol 2008

Other partner genes: ETV6, BCR, SSBP2, PAX5, SEC31A

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Diverse presentations of myeloid and lymphoid neoplasms with PCM1-JAK2

MPN PMF, PMF in transformation, CEL MDS/MPN aCML, MDS/MPN-U Acute Leukemias AML including erythroleukemia, myeloid sarcoma, B and T-ALL/LBL

*Rare case of T cell lymphoma

Stewart et al. Am J Hematol 1990 Reiter et al. Cancer Res 2005 Murati et al. Leukemia 2005 Patterer et al. Ann Hematol 2013 Bain and Ahmad Br J Haematol 2014 Song et al. Ann Lab Med 2016

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  • 35 cases
  • 30 males
  • Median age 47 (range 12-75 years)
  • CBC:
  • Variable leukocytosis: 11.8-435x109/L
  • Left shift
  • Frequent eosinophilia

Diverse presentations of myeloid and lymphoid neoplasms with PCM1-JAK2

Stewart et al. Am J Hematol 1990 Reiter et al. Cancer Res 2005 Murati et al. Leukemia 2005 Patterer et al. Ann Hematol 2013 Bain and Ahmad Br J Haematol 2014 Song et al. Ann Lab Med 2016

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Common features of myeloid neoplasms with PCM1-JAK2

  • Male predominance
  • Hepatosplenomegaly
  • Hypercellular bone marrow
  • Bone marrow fibrosis
  • Eosinophilia
  • Prominent erythropoiesis with left shift
  • Frequent transformation to acute leukemia
  • Complete and partial responses to ruxolitinib

(rare cases reported)

Stewart et al. Am J Hematol 1990 Bain and Ahmad Br J Haematol 2014 Reiter et al. Cancer Res 2005 Lierman et al. Blood 2012 Murati et al. Leukemia 2005 Rumi et al. JCO 2013 Patterer et al. Ann Hematol 2013 Schwaab et al. Ann Hematol 2015

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Panel diagnosis

Myeloid/lymphoid neoplasm with PCM1-JAK2