Presentation:
51-year-old morbidly obese female (BMI 47.8 kg/m2) with history of type-2 diabetes mellitus and polycystic ovarian syndrome presented with chest tightness, wheezing, dyspnea, dry cough and low-grade fever in November 2019. She had no history of tobacco or alcohol use. Her examination at that time revealed no obvious abnormality. No palpable lymphadenopathy. Laboratory indices were within normal limits except white cell count of 13,000/µL with absolute neutrophil count of 11,000/µL (normal range [NR], 1600-7700/µL) and absolute lymphocyte count (ALC) of 1120/µL (NR, 1300-3200/µL). Computed tomography (CT) demonstrated bilateral pulmonary masses with diffuse bilateral hilar and mediastinal adenopathy, and mild splenomegaly. (Figure 1A) Lung mass on right side measured 4x4 cm and left side 3x3 cm. Serum calcium, vitamin D and angiotensin converting enzyme levels were within normal limits. CT guided needle biopsy of left hilar mass and mediastinal lymph node returned negative for malignancy. Flow cytometry of biopsy specimen showed normal lymphoid cell population. Lung parenchyma showed dense fibro-collagenous tissue with focal alveolar plugs (Masson bodies). She was empirically treated for pneumonia and was discharged home.
In February 2020, she presented for a follow-up PET-CT scan which showed hypermetabolic bilateral lung masses with standardized metabolic activity (SUV) of 11.8. (Figure 1B, 1C) Multiple mediastinal lymph nodes were hypermetabolic with a left para-tracheal lymph node measuring SUV of 5.1. Previously biopsied lymph node was noted to have an SUV of 1.4 only, thus explaining possibility of obtaining biopsy from an unaffected lymph node. Endobronchial ultrasound guided needle biopsy of mediastinal lymph node and left lung mass was then performed which again returned negative for malignancy. At that time, she was started on prednisone 20 mg per day for presumed sarcoidosis.
In May 2020, she presented again with worsening of similar symptoms. Repeat CT scan of Chest showed increase in size of the lung masses with left measuring 5x5 cm and right mass measuring 6x6 cm. (Figure 1D, 1E) Due to persistent concern of malignancy, patient was prepared for open mediastinal lymph node and lung mass biopsy under general anesthesia. She developed hypoxemia and respiratory arrest during the procedure. She was successfully resuscitated, and the procedure was aborted. She was eventually discharged home with no plans to reattempt biopsy due to high risk of peri-operative mortality.
In July 2020, she had dyspnea and hypoxemia with saturations of 87% on baseline 2 liters of supplemental oxygen. She reported night sweats and a weight loss of 28 pounds in the past one and a half months. On examination, her respiratory rate was 29/minute with oxygen saturations 95% on 5 L. She appeared in mild respiratory distress. Bilateral wheezing was heard. Laboratory tests showed hyperglycemia with blood sugar 450 mg/dL (NR, 70-99 mg/dL) and hyperkalemia of 5.8 mmol/L (NR, 3.5-5.1 mmol/L). White cell count was elevated at 14,000/µL with neutrophilia and low ALC of 570/µL. C-reactive protein 14.86 mg/dL (normal <0.5 mg/dL). Levofloxacin was started for presumed pneumonia. She tested negative for SARS-Cov-2 virus. Repeat chest CT scan showed enlarging pulmonary and hilar masses bilaterally with moderate splenomegaly and mesenteric lymphadenopathy. Mediastinal adenopathy appeared worsened with right para-tracheal lymph node conglomerate measuring 4.6 x 4.5 cm.
Differential diagnosis is still broad in a patient with multiple negative biopsies. The suspicion of malignancy was still high due to new presentation of unintentional weight loss, night sweats and increasing size of lung and hilar masses. Primary lung cancer, lymphoma, mediastinal tumor, and fungal infections were all in the differentials. Infectious workup including blood cultures, urine cultures, sputum cultures were negative. Microbial cell-free DNA test was also negative for any pathogens in the serum.1 Two days after admission, on a careful bedside examination by third year medical student, supraclavicular lymphadenopathy was noticed. Neck CT confirmed multiple superficial and deep left neck cervical lymph nodes with largest measuring 1.9 x 1.5 cm. (Figure 1F) General surgery team performed an excisional lymph node biopsy under local anesthesia. Biopsy showed presence of diffuse large B-cell lymphoma (DLBCL) with cells positive for CD20, CD21, CD30 and PAX-5. (Figure 2) Immunohistochemistry demonstrated dual expression for BCL2 and MYC proteins. Fluorescence in situ hybridization (FISH) studies on the biopsy specimen confirmed rearrangement of BCL6. No rearrangement of MYC or BCL2 and no fusion of MYC and IGH was observed. Bone marrow biopsy did not reveal lymphomatous involvement. Final diagnosis was confirmed to be stage 4, DLBCL, non-germinal center B-cell type. Our patient received 6 cycles of R-CHOP regimen and tolerated it well with minor complications of grade 2 peripheral neuropathy and transient immune thrombocytopenic purpura. Follow up PET-CT scan showed significant reduction in hyper-metabolic activity in the hilar regions and right upper lobe mass area.