In a 32-year-old female with systemic lupus erythematosus on methotrexate who presents with lymphadenopathy and a lymph node biopsy showing Langerhans-type giant cells, what is the diagnosis?

Diagnosis: Sarcoidosis

The most likely diagnosis in this patient is sarcoidosis, which commonly presents with lymphadenopathy and noncaseating granulomas containing Langerhans-type giant cells (multinucleated giant cells) in patients with autoimmune conditions including systemic lupus erythematosus. 1, 2

Pathologic Confirmation

• The presence of Langerhans giant cells (multinucleated giant cells) within noncaseating granulomas is a characteristic histopathologic feature of sarcoidosis, not to be confused with Langerhans cell histiocytosis which requires CD1a, S100, and Langerin positivity 1, 3
• Sarcoidosis granulomas are compact, tightly formed collections of epithelioid histiocytes and multinucleated giant cells that remain discrete, with sparse surrounding lymphocytic infiltrate and perilymphatic distribution 1
• The diagnosis requires three criteria: (1) compatible clinical presentation, (2) pathologic evidence of noncaseating granulomas, and (3) exclusion of infections (tuberculosis, atypical mycobacteria) and malignancy (lymphoma) 2, 4

Critical Differential Considerations

You must actively exclude alternative diagnoses before confirming sarcoidosis:

• Tuberculosis and atypical mycobacterial infection must be ruled out with special stains (AFB) and cultures on the biopsy specimen, as these can present identically but require completely different treatment 1
• Lymphoma was found in 10-25% of patients presenting with lymphadenopathy initially suspected to be sarcoidosis, making tissue diagnosis mandatory 1
• Methotrexate-induced granulomatous reactions are possible but rare; however, the drug does not typically cause this presentation in SLE patients 5, 6
• Hypersensitivity pneumonitis can show poorly formed granulomas but typically has more robust surrounding inflammatory infiltrate with plasma cells, which would be noted on pathology 1

Methotrexate Context

• Methotrexate is used in SLE primarily for persistent joint and skin manifestations, allowing steroid dose reduction, but does not typically induce granulomatous lymphadenopathy 5, 6
• The presence of granulomas in this clinical context is far more consistent with concurrent sarcoidosis than a drug reaction 1, 2

Required Additional Workup

Before finalizing the diagnosis, you must:

• Confirm microorganism stains (AFB, GMS, PAS) and cultures are negative on the biopsy specimen 1
• Obtain chest imaging (chest X-ray or CT) to evaluate for bilateral hilar lymphadenopathy, which occurs in 90% of sarcoidosis cases and would strongly support the diagnosis 2, 4
• Check serum ACE levels and calcium levels, though these are supportive rather than diagnostic 2
• Perform tuberculin skin test or interferon-gamma release assay to exclude latent tuberculosis 1

Clinical Significance in SLE Patients

• Sarcoidosis can coexist with SLE and other autoimmune conditions; the presence of one does not exclude the other 1, 4
• Lymph node involvement in sarcoidosis generally indicates self-limited disease that may not require treatment beyond the underlying SLE management 1
• However, if systemic sarcoidosis is confirmed with pulmonary or other organ involvement, corticosteroid therapy may be required in addition to current SLE treatment 2

Common Pitfall to Avoid

• Do not assume this is Langerhans cell histiocytosis based solely on the term "Langerhans giant cells" - this terminology refers to multinucleated giant cells seen in granulomas (sarcoidosis, tuberculosis), whereas Langerhans cell histiocytosis requires specific immunohistochemical markers (CD1a+, S100+, Langerin+) that would have been mentioned if present 1, 3