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.