Hematology Oncology · Year 2 · from Hematology Oncology

Case 2: Primary Myelofibrosis

Patient Presentation

Demographics: 72-year-old female

Chief Complaint: Fatigue, early satiety, and night sweats

History of Present Illness: The patient has had progressive fatigue for 6 months, requiring transfusions for symptomatic anemia. She reports early satiety after eating small amounts and left upper quadrant discomfort. She has night sweats and has lost 15 pounds unintentionally. She also notes easy bruising.

Physical Examination:

  • Blood pressure: 118/72 mmHg
  • Weight: 58 kg (down from 65 kg)
  • General: Cachectic, pale
  • Abdomen: Massive splenomegaly extending to pelvis (15 cm below costal margin)
  • Hepatomegaly: 4 cm below right costal margin
  • Ecchymoses on extremities

Workup and Results

Laboratory Studies:

  • Hemoglobin: 7.8 g/dL
  • WBC: 4,200/mcL
  • Platelets: 85,000/mcL
  • LDH: 650 U/L (elevated)

Peripheral Blood Smear:

  • Tear-drop cells (dacrocytes)
  • Leukoerythroblastosis (nucleated RBCs, immature WBCs)
  • Large, bizarre platelets

Bone Marrow:

  • "Dry tap" on aspiration
  • Biopsy: Marked reticulin and collagen fibrosis
  • Megakaryocyte atypia with clustering
  • CD34+ blasts: 3%

Molecular Testing:

  • JAK2 V617F: Positive (60% of cases)

DIPSS Score:

  • Age >65, Hgb <10, WBC >25K absent, blasts <1%, constitutional symptoms present
  • Intermediate-2 risk

Clinical Image

Peripheral blood smear demonstrating characteristic findings of primary myelofibrosis: tear-drop cells (dacrocytes), nucleated red blood cells, and immature myeloid precursors (leukoerythroblastosis).

Diagnosis

Primary Myelofibrosis, JAK2-positive, DIPSS Intermediate-2

Diagnostic features:

  • Bone marrow fibrosis with "dry tap"
  • Leukoerythroblastic blood picture
  • Tear-drop cells
  • Massive splenomegaly from extramedullary hematopoiesis
  • Constitutional symptoms

Discussion

This case illustrates primary myelofibrosis:

  • Reactive Fibrosis: The lecture clarifies that bone marrow fibrosis is reactive, not clonal - it results from cytokines released by megakaryocytes (particularly TGF-beta and PDGF).
  • Extramedullary Hematopoiesis: The lecture explains that massive splenomegaly results from extramedullary hematopoiesis as the fibrotic marrow becomes inadequate. The spleen and liver resume fetal hematopoietic function.
  • "Dry Tap": The lecture identifies a "dry tap" on bone marrow aspiration as characteristic of myelofibrosis due to extensive fibrosis.
  • Leukoerythroblastosis: The lecture describes the leukoerythroblastic blood picture (nucleated RBCs and immature WBCs) as reflecting disrupted marrow architecture releasing immature cells.

Treatment Plan

  1. Transplant Evaluation:
  • Only curative option
  • Consider if intermediate-2/high risk and eligible
  • Age and comorbidities limiting factors
  1. JAK Inhibitor (Symptomatic Relief):
  • Ruxolitinib 15-20 mg twice daily
  • Reduces splenomegaly and constitutional symptoms
  • Does not cure disease or eliminate clone
  1. Anemia Management:
  • Transfusion support
  • Consider erythropoietin-stimulating agents
  • Danazol may help some patients
  • Luspatercept in selected patients
  1. Splenectomy (Consideration):
  • For refractory symptomatic splenomegaly
  • High surgical risk; reserved for select cases
  1. Monitoring:
  • CBC monthly initially
  • Watch for blast transformation (5-30% risk)

Teaching Points

  1. Myelofibrosis causes "dry tap" on marrow aspiration
  2. Tear-drop cells (dacrocytes) are characteristic
  3. Leukoerythroblastosis = nucleated RBCs + immature WBCs
  4. Massive splenomegaly is from extramedullary hematopoiesis
  5. Allogeneic transplant is only curative treatment

All cases for this lecture as Markdown