Case 1. Diffuse large B cell lymphoma. A 58-year-old female presented after 2 months with right chest and back pain with no fever ( Figure 4A ). A CT scan revealed destruction of the 9th thoracic vertebra and the right appendix with paravertebral soft tissue shadow ( Figure 4B ). Magnetic resonance imaging (MRI) revealed abnormal signals of the 9th thoracic vertebra and right arch with swelling of the surrounding soft tissue. Pathologic results of the bone biopsy indicated infection. The patient was treated empirically with vancomycin and fosfomycin (switched to linezolid due to nausea and vomiting) administered i.v. for 3 weeks. The patient developed paralysis of the lower extremities and difficulty urinating. Repeated MRI showed that the lesion had become significantly larger with spinal compression. Onco-mNGS analysis failed to detect microorganisms in her peripheral blood, but revealed deletions and duplications of large segments in several chromosomes that generated a strong abnormal CNV-based tumor signal ( Figure 4C ). This finding encouraged treating physicians to obtain a second bone biopsy; the result revealed diffuse large B cell lymphoma of the non-germinal center B cell type ( Figure 4D ). The patient received R-CHOP chemotherapy afterwards and the symptoms were mildly relieved. The fluctuation in chromosomal variation was much smoother in the fourth, compared to previous, Onco-mNGS tests suggesting that the proportion of tumor cells had decreased.
Case 2. NK/T cell lymphoma. A 23-year-old male presented after 2 weeks of fever and vomiting. Upon admission, the patient exhibited a low platelet count (45x109/L) and elevated levels of inflammatory markers (C-protein: >199 mg/L; procalcitonin: 13.92 ng/mL). Tests for pathogens that included Epstein-Barr virus (EBV), cytomegalovirus (CMV), cryptococcus, tuberculosis, and parasites were negative; blood cultures for bacteria, acid-fast bacilli, and fungi were also negative. A PET-CT scan showed an enlarged spleen with increased uptake of FDG indicator. The patient underwent two diagnostic bone marrow punctures and a splenectomy; the results, however, did not support a definitive diagnosis. The patient was treated empirically with meropenem, vancomycin, doxycycline, gentamycin, and trimethoprim-sulfamethoxazole administered sequentially, but became worse with progressive hepatic deterioration (total bilirubin: 356.4 micromol/L). The results of a third bone marrow biopsy revealed NK/T cell lymphoma. Onco-mNGS results showed disruptions in several chromosomes indicative of a tumor. This was confirmed by the results of a third bone marrow smear. Unfortunately, this information was not considered a priori by the attending physicians and the patient soon died of tumor progression.
Case 3. Lung adenocarcinoma. A 71-year-old female presented after 2 months of cough and sputum, but no fever. Her chest CT scan showed pneumonia; Mycoplasma pneumoniae-specific IgM antibody was positive. She was treated with cefuroxime and azithromycin administer i.v. for 6 days, then switched to oral moxifloxacin for 10 days. The patient did not improve in clinical or radiological presentation. Repeated, M. pneumoniae serum antibody was negative. Bronchoscopy was conducted, but tests for pathogens including bacteria, acid-fast bacteria, and fungi in BALF were negative. Tumor markers in this patient, i.e., CA199, CEA, CA125, CY211 and SCC, were in the normal range. The patient received a pulmonary lobectomy and the pathological result indicated lung adenocarcinoma.