What is the diagnosis and appropriate management for a patient presenting with orange sputum and stool, along with a significantly enlarged lymph node in the left neck?

Diagnostic Approach to Orange Sputum/Stool with Large Left Cervical Lymph Node

This presentation requires urgent tissue diagnosis via excisional lymph node biopsy to rule out lymphoma or mycobacterial infection, as the combination of constitutional symptoms (orange discoloration suggesting rifampin therapy or mycobacterial disease) and a large cervical lymph node demands immediate pathologic evaluation. 1

Critical Initial Assessment

The orange discoloration of sputum and stool is highly suggestive of rifampin therapy, indicating the patient may already be under treatment for mycobacterial disease (tuberculosis or nontuberculous mycobacteria). 2 This clinical context fundamentally changes the differential diagnosis for the cervical lymphadenopathy.

Red Flags Requiring Immediate Action

• Lymph node >2 cm in diameter warrants urgent workup 3
• Supraclavicular location is highly suspicious for malignancy 4, 5
• Firm, fixed, or rubbery consistency suggests malignancy or mycobacterial infection 3, 5
• Duration >2 weeks without resolution eliminates simple reactive lymphadenopathy 2, 3

Mandatory Diagnostic Workup

Immediate Laboratory Studies

• Complete blood count with differential to assess for cytopenias or leukocytosis 1
• Comprehensive metabolic panel including liver enzymes, alkaline phosphatase, and albumin 1
• Lactate dehydrogenase (LDH) as a marker of tumor burden 1
• Tuberculin skin test or interferon-gamma release assay to distinguish tuberculosis from NTM 2
• Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C, and HIV screening before any treatment 1

Essential Imaging

• Contrast-enhanced CT scan of chest, abdomen, and pelvis as the initial radiologic study 1
• Chest X-ray as baseline to evaluate for pulmonary involvement 1
• Consider PET-CT for staging if lymphoma is confirmed after tissue diagnosis 1

Tissue Diagnosis (Non-Negotiable)

Excisional lymph node biopsy is the gold standard and must be performed. 1, 4 Fine-needle aspiration is inadequate for initial diagnosis and should not be accepted. 1 The tissue must be sent for:

• Routine histology and immunohistochemistry 6
• Mycobacterial culture (both tuberculosis and NTM) 2, 7
• Acid-fast bacilli staining 8
• Molecular testing for t(11;18) translocation if MALT lymphoma suspected 6

Differential Diagnosis Priority

1. Mycobacterial Lymphadenitis (Most Likely Given Orange Secretions)

In adults, tuberculous lymphadenitis accounts for >90% of culture-proven mycobacterial cervical lymphadenitis, making it the predominant mycobacterial cause. 2 The orange discoloration strongly suggests rifampin therapy is already initiated.

• Tuberculous lymphadenitis presents with unilateral, non-tender cervical adenopathy 2
• Distinguishing tuberculosis from NTM is critical because treatment and public health notification requirements differ fundamentally 2
• If already on rifampin therapy, the persistent lymph node may indicate treatment failure, drug resistance, or incorrect diagnosis 2

2. Marginal Zone Lymphoma (MALT Type)

Nodal marginal zone lymphoma (NMZL) typically presents with disseminated lymphadenopathy (mostly cervical and abdominal) and is often advanced at presentation. 6 However, the orange secretions make this less likely unless the patient coincidentally has both conditions.

• Approximately one-third of NMZL cases represent nodal dissemination of extranodal MALT lymphoma 6
• Staging must rule out primary extranodal disease, particularly gastric involvement 6

3. Suppurative Cervical Lymphadenitis

Immunocompromised status, male sex, and prior inadequate treatment are predictors for abscess formation requiring surgical drainage. 7 However, the chronic presentation (>2 weeks) and orange secretions make acute bacterial infection less likely.

Management Algorithm

If Mycobacterial Disease Confirmed:

1. Review current rifampin regimen and assess for drug resistance 2
2. Complete surgical excision may be required if medical therapy fails 2
3. Ensure public health notification if tuberculosis is confirmed 2

If Lymphoma Confirmed:

1. For localized gastric MALT lymphoma: Test for H. pylori and initiate eradication therapy as sole initial treatment 6
2. For systemic disease: Consider systemic chemotherapy and/or rituximab 6
3. For H. pylori-negative or treatment-failure cases: Involved-field radiotherapy (30-40 Gy) for stage I-II disease 6

If Abscess Formation Present:

Abscess drainage and appropriate antibiotic treatment should be considered immediately. 7 Pathogen isolation and tissue biopsy must be performed to ensure accurate diagnosis. 7

Critical Pitfalls to Avoid

• Do not prescribe empiric antibiotics without clear signs of bacterial infection, as this delays diagnosis if malignancy is present 3
• Do not accept fine-needle aspiration as adequate tissue for initial diagnosis 1
• Do not assume benignity based solely on imaging 1
• Do not delay hepatitis B screening, as reactivation can occur with chemotherapy and anti-CD20 therapy 1
• Do not mistake NTM lymphadenitis for bacterial infection and treat with inappropriate antibiotics 2

Urgent Next Steps

1. Obtain excisional biopsy within 48-72 hours 1, 4
2. Hold rifampin temporarily until tissue diagnosis confirms mycobacterial disease
3. Complete staging workup with contrast-enhanced CT and laboratory studies 1
4. Consult infectious disease and hematology/oncology simultaneously given dual diagnostic possibilities