A 48-year-old woman with no significant past medical history apart from elective bilateral breast implantation 10 years prior, presented with new onset of fever, rigors, night sweats and shortness of breath. Initial workup revealed microcytic anemia (Hb 8.9 g/dL, MCV 78 fL leukopenia and elevated CRP 143 mg/dL and ESR >130 mm/h). Chest CT scan revealed 3 cm pericardial effusion with large conglomerate mediastinal lymph nodes (LN) and scant tree-in-bud opacities on lung images. She underwent pericardiocentesis and transthoracic paratracheal LN biopsy which were negative for infection or malignancy.
Due to progressive cough, fatigue, night sweats and weight loss further diagnostic testing including bronchoscopy and endobronchial ultrasound (EBUS) were performed. Fine needle aspirates (FNA) demonstrated caseating granulomatous inflammation with growth of MAC on broth culture but no evidence of malignancy. Interferon gamma release assay was negative and sputum with PCR for mycobacterium tuberculosis, were all negative. Subsequently, one of three sputum cultures grew MAC (broth) but all other microbiologic cultures remained negative. Additional testing for alternative infectious etiologies including HIV, syphilis, cytomegalovirus, toxoplasma, aspergillus, cryptococcus and histoplasma were negative. She underwent further LN assessment via mediastinoscopy which again revealed caseating granulomatous inflammation and growth of MAC (broth). Flow cytometry, performed on EBUS and mediastinoscopy samples were negative for malignancy.
Based on the finding of MAC on two separate LN cultures and biopsy finding of non-caseating granuloma, with no alternative diagnosis, she was started on daily triple antibiotic therapy with Ethambutol 1200 mg, Azithromycin 500 mg and Rifampin 600 mg. However, she failed to demonstrate any improvement in her clinical condition after 6 months of therapy. Further diagnostic testing inclusive of a bone marrow biopsy returned negative for malignancy. Repeat whole body CT imaging demonstrated widespread lymphadenopathy along with a new right ovarian mass. An extensive workup focused on evaluation for underlying malignancies or secondary immunodeficiencies was carried out. CA-125, CA19-9, CEA biomarkers were normal, LDH levels remained <200 U/L. Gynecology was consulted for the ovarian mass which was determined to be benign. Further immunologic evaluation demonstrated low CD3, CD4 and CD56 levels. A rheumatology profile including ANA, extended autoimmune panel, rheumatoid factor, vasculitis panel, anti-CCP were all within normal limits. Ultimately, a core biopsy of an iliac LN demonstrated abnormal CD30-positive lymphoid infiltrate, suspicious for Hodgkin's lymphoma (HL). An excisional left supraclavicular lymph node biopsy was performed, confirming the diagnosis of Hodgkin's lymphoma along with histologic evidence of granulomatous inflammation and AFB smear positivity.
The subject was started on steroids followed by initiation of chemotherapy whilst being maintained on MAC treatment with Ethambutol and Azithromycin three times a week. Rifampin had to be discontinued due to persistent leukopenia. The patient tolerated chemotherapy well with symptomatic improvement, however an interim Positron Emission Tomography (PET)/CT scan revealed residual disease with widespread hypermetabolic lymphadenopathy involving the neck, mediastinum, and abdomen. The chemotherapeutic regimen was subsequently escalated and follow-up PET/CT scan demonstrating overall decrease in the tumor volumetric activity with minimal disease relating to either residual MAC/granulomatous inflammation or Hodgkin's disease. A repeat excisional biopsy of cervical LNs was negative for lymphoma but revealed necrotizing granuloma with negative AFB cultures Patient is currently doing well on continued suppressive MAC treatment with Ethambutol and Azithromycin while undergoing close surveillance for any recurrence of her lymphoma.