What is the best course of action for a patient with Polycythemia Vera (PV) who presents with a painful lymph node in the neck under the jaw?

Urgent Evaluation for Lymphoma Transformation in Polycythemia Vera

A patient with polycythemia vera presenting with a painful lymph node in the neck under the jaw requires immediate evaluation for disease transformation to acute leukemia or lymphoma, as PV carries a 6.8% risk of leukemic transformation and can rarely transform to lymphoma. 1

Immediate Diagnostic Workup

Critical First Steps

• Obtain a complete blood count with differential immediately to assess for new cytopenias, worsening leukocytosis, or circulating blasts that would suggest leukemic transformation 1
• Perform urgent imaging of the neck (ultrasound or CT) to characterize the lymph node size, consistency, and presence of other enlarged nodes 2
• Arrange for excisional lymph node biopsy if the node is persistently enlarged (>1 cm), firm, or associated with constitutional symptoms (fever, night sweats, weight loss), as fine needle aspiration is insufficient for diagnosing lymphoma 2

Disease Transformation Assessment

• Check lactate dehydrogenase (LDH) as markedly elevated levels suggest aggressive disease transformation 3
• Review peripheral blood smear for circulating blasts, dysplastic features, or leukoerythroblastic picture that would indicate progression to myelofibrosis or acute leukemia 1, 4
• Assess for constitutional symptoms including unexplained fever, drenching night sweats, or unintentional weight loss >10% body weight over 6 months 2

Risk Context for PV Patients

Transformation Rates

• Leukemic transformation occurs in approximately 6.8% of PV patients overall, with 10-year rates around 3% 1, 4
• Progression to myelofibrosis occurs in 12.7% of patients, which itself carries increased risk of further transformation 1
• The 20-year rate of leukemic transformation is approximately 4% 5

High-Risk Features Requiring Urgent Action

• New or worsening cytopenias (especially thrombocytopenia or anemia) in a previously stable PV patient 4
• Rapidly enlarging splenomegaly or new hepatomegaly 2
• Persistent unexplained fever without infectious source 2
• Bone pain or constitutional symptoms 5

Alternative Diagnoses to Consider

Infectious Causes

• Reactive lymphadenitis from local infection (dental abscess, pharyngitis, skin infection in the head/neck region) is the most common cause of painful cervical lymphadenopathy 3
• Painful nodes favor reactive/infectious etiology over malignancy, but this cannot be assumed in a PV patient given transformation risk 3

Non-Transformation PV-Related Causes

• Extramedullary hematopoiesis can rarely present as lymphadenopathy, though this is more common in post-PV myelofibrosis 5
• Concurrent infection in an immunocompromised patient if receiving cytoreductive therapy 2

Management Algorithm

If Lymph Node Biopsy Shows Lymphoma or Leukemia

• Immediate hematology-oncology referral for staging and treatment planning 2
• Discontinue current PV cytoreductive therapy pending oncology evaluation, as treatment paradigm will shift entirely 2
• Maintain hematocrit control with phlebotomy if still needed, but defer aspirin if thrombocytopenia develops 1

If Lymph Node Biopsy Shows Reactive Changes

• Identify and treat underlying infection (antibiotics for bacterial causes, observation for viral causes) 3
• Continue standard PV management including phlebotomy to maintain hematocrit <45% and low-dose aspirin 1, 4
• Re-evaluate lymph node in 2-4 weeks to ensure resolution; persistent adenopathy requires repeat biopsy 3

If Imaging/Labs Suggest Myelofibrotic Transformation

• Perform bone marrow biopsy to assess for reticulin/collagen fibrosis and exclude acute leukemia 5
• Consider JAK2 inhibitor therapy (ruxolitinib) if symptomatic splenomegaly or constitutional symptoms are present 1, 4
• Reassess cytoreductive strategy as post-PV myelofibrosis requires different management than PV 5

Critical Pitfalls to Avoid

• Do not assume painful lymphadenopathy is benign in a PV patient without tissue diagnosis, as transformation can present with atypical features 1
• Do not delay biopsy if the node persists beyond 2-4 weeks or has concerning features (firm, fixed, >2 cm, associated constitutional symptoms) 2
• Do not attribute new cytopenias to PV therapy alone without excluding disease transformation through bone marrow examination 4
• Do not continue hydroxyurea or other cytoreductive agents if acute leukemia is suspected, as this may worsen cytopenias and delay appropriate therapy 2

Ongoing PV Management During Evaluation

• Maintain hematocrit <45% with therapeutic phlebotomy to reduce thrombotic risk during the diagnostic workup 1, 4
• Continue low-dose aspirin (81 mg daily) unless platelet count falls below 50 × 10⁹/L or active bleeding occurs 4
• Monitor complete blood count weekly during the evaluation period to detect rapid changes suggesting transformation 6