What is the appropriate evaluation and treatment approach for an adult patient with a history of lymphoma and chemotherapy, presenting with a hoarse voice?

Hoarse Voice in a Lymphoma Patient: Evaluation and Management

A patient with lymphoma history presenting with hoarseness requires urgent laryngoscopy to evaluate for recurrent laryngeal nerve involvement, vocal cord paralysis, or direct laryngeal infiltration, as these findings indicate mediastinal or cervical lymph node disease requiring immediate restaging and treatment modification.

Immediate Diagnostic Evaluation

Direct Laryngeal Assessment

• Perform flexible laryngoscopy within 24-48 hours to visualize vocal cord function and identify unilateral or bilateral vocal cord paralysis, which suggests recurrent laryngeal nerve compression from mediastinal or cervical adenopathy 1, 2.
• Look specifically for vocal cord immobility, asymmetric movement, or direct mucosal involvement by lymphomatous tissue 3.

Complete Restaging Workup

• Obtain CT scan of neck, chest, abdomen, and pelvis immediately to identify bulky mediastinal disease, cervical lymphadenopathy, or masses compressing the recurrent laryngeal nerve 4, 5.
• FDG-PET scan is mandatory for accurate assessment of disease extent and metabolic activity, as hoarseness in this context suggests active disease requiring treatment 4, 5.
• Measure the mediastinal mass ratio (maximum horizontal thoracic diameter) to identify bulky disease (>1/3 thoracic diameter), which alters treatment approach 5.

Laboratory Assessment

• Complete blood count with differential to assess for cytopenias suggesting bone marrow involvement 5.
• LDH and uric acid levels as markers of tumor burden and risk for tumor lysis syndrome 6.

Critical Differential Diagnosis Considerations

Lymphoma-Related Causes

• Recurrent or progressive disease with mediastinal or cervical lymphadenopathy compressing the recurrent laryngeal nerve (most common cause in this population) 2, 3.
• Direct laryngeal infiltration by lymphoma (rare but possible) 1.
• Superior vena cava syndrome with associated mediastinal mass 2.

Treatment-Related Causes

• Bleomycin pulmonary toxicity if patient received ABVD chemotherapy, which can present with respiratory symptoms and voice changes 4.
• Vincristine neuropathy affecting cranial nerves (though recurrent laryngeal nerve involvement is uncommon) 1.

Non-Lymphoma Causes to Exclude

• Post-intubation injury if patient had recent procedures 3.
• Thyroid dysfunction from neck irradiation (check TSH, FT3, FT4) 4.
• Infectious laryngitis or vocal cord inflammation 3.

Management Algorithm Based on Findings

If Imaging Reveals Relapsed/Progressive Disease

• Obtain repeat lymph node biopsy to confirm relapse and verify histology, as transformation can occur (especially if relapse >12 months from initial diagnosis) 4, 6.
• For transplant-eligible patients: initiate rituximab-based salvage chemotherapy (R-DHAP or R-ICE) followed by high-dose chemotherapy with autologous stem cell transplant 6.
• For transplant-ineligible patients: alternative salvage regimens such as R-GEMOX with consideration of involved-field radiotherapy 6.

If Imaging Shows Localized Compressive Disease

• Consider urgent involved-field radiotherapy to the compressive mass to rapidly relieve recurrent laryngeal nerve compression and restore vocal cord function 4, 6.
• Systemic therapy should still be initiated based on overall disease burden 6.

If No Active Lymphoma Identified

• Evaluate for bleomycin toxicity with pulmonary function tests and high-resolution chest CT if patient received ABVD 4.
• ENT consultation for direct laryngeal management (voice therapy, possible medialization procedures for vocal cord paralysis) 3.
• Monitor thyroid function if patient received neck irradiation 4.

Common Pitfalls to Avoid

• Never delay laryngoscopy assuming hoarseness is benign laryngitis—in lymphoma patients, this symptom indicates structural disease until proven otherwise 2, 3.
• Do not initiate treatment without tissue confirmation if this represents new relapse, as histologic transformation occurs and alters treatment selection 4, 6.
• Avoid administering bleomycin if pulmonary toxicity is suspected, as continued exposure increases mortality risk 4.
• Do not overlook superior vena cava syndrome, which may coexist with recurrent laryngeal nerve palsy and requires urgent intervention 2.

Monitoring During Treatment

• Serial laryngoscopy every 2-4 weeks during treatment to assess vocal cord function recovery 3.
• Repeat imaging at mid-treatment (after 2-3 cycles) with FDG-PET to assess metabolic response 4.
• Cardiovascular and pulmonary function monitoring given prior anthracycline and bleomycin exposure 4.