A 65-year-old Chinese female patient presented a gradually increased mass (4x3 cm) in the left thigh and three separated black skin lesions (1x1 cm or less) on the left foot in December 2015. The resection of the mass in the left thigh and the largest skin lesion on the left foot was performed on December 4, 2015. The pathological exploration showed malignant melanoma with necrosis but no nerve or vascular invasion. The chest computed tomography (CT) scan (Figure 1A) showed a shadow at the posterior segment of the right upper lobe of the lung. However, neither respiratory nor systemic symptoms, such as cough, weight loss, fever, and night sweats, were observed. For the first-line treatment, high-dose IL-2 was the preferred treatment, as is the case for medically fit metastatic melanoma patients for >20 years. Thus, IL-2 was administered to the patient at a dose of 64,000 IU/kg, qd, on days 1-10, repeated every 14 days for 6 cycles. However, a node in the left thigh around the surgical margin (1.5x1.5 cm) and two new lymph nodes in the left groin (2x1 cm) were observed, indicating progressive disease. Another chest CT scan (Figure 1B), performed in March 2016, suggested a slightly reduced lesion of the right lobe of the lung.
Then, the patient initiated pembrolizumab treatment at a dose of 2 mg/kg every 3 weeks since June 2016. After 3 cycles of immunotherapy, all the nodes contracted remarkably. Nevertheless, the patient developed fatigue and dry mouth and skin, raising suspicion of Sjogren's syndrome with a positive concentration of the autoimmune antibody RO52 in the peripheral blood test. Thus, the administration of pembrolizumab at 2 mg/kg was continued at every 4 weeks for another 7 cycles until January 2017. The patient responded to pembrolizumab, and the nodes in the left thigh or groin, except for two black skin lesions at the bottom of left foot (decreasing in size from 0.5x0.3 to 0.2x0.1 cm), disappeared, as evaluated by ultrasonic scan in October 2016; however, tolerant oral ulcer, fatigue, and vitiligo were observed.
In February 2017, the patient presented about 10 mL of bloody sputum daily for a week without cough, night sweats, fever, or weight loss. The chest CT (Figure 1C) showed the increased size of the lesion in the right upper lobe without lymphadenopathy or pleural effusion. BALF was collected, and transbronchial lung biopsy was performed. Unconcentrated BALF was tested positive for GeneXpert Mycobacterium tuberculosis (MTB)/RIF with low semi-quantitative value. Additionally, mutations in rpoB gene that confer rifampicin resistance were not detected. The liquid culture and drug sensitivity test for BALF indicated MTB to be drug sensitive. Both examinations confirmed the diagnosis of active pulmonary TB. The transbronchial lung biopsy specimen showed a large amount of caseous necrosis (Figure 2A and B) with mediate lymphocyte infiltrate but few acid-fast bacilli. The number of CD4 and CD8 in the peripheral blood was significantly higher than the normal range (1,544/microL and 712/microL, respectively). Consequently, immunotherapy was paused and anti-TB drugs of isoniazid 0.3, qd, rifampin 0.45, qd, pyrazinamide 1.0, qd, and ethambutol 0.75, qd (HRZE) were administered according to the body weight. Bloody sputum ceased with anti-TB treatment 1-week posttreatment and the sputum culture for MTB was negative after 4 weeks. However, the patient complained of nausea and vomiting during the anti-TB treatment since week 4, and the liver function test showed the abnormal level of alanine aminotransferase 240 U/L, aspartate aminotransferase 277 U/L, and total bilirubin 42 micromol/L. Thus, the anti-TB treatment was suspended and liver-protecting drugs were administered. After 2 weeks, the liver function recovered and clinical symptoms improved significantly. HRZ was challenged again; however, the level of transaminases increased and isoniazid-induced fever was observed. Considering the negative sputum culture and side effects of HRZ, the administration of isoniazid, rifampin, and pyrazinamide was discontinued. The second-line anti-TB regimen, including streptomycin 0.75, qd, ethambutol 0.75, qd, and moxifloxacin 0.4, qd, was administered for 4 months. The chest CT scan (Figure 1D) showed that the right pulmonary lesion had shrunk significantly in April 2017. Therefore, the patient was challenged with pembrolizumab monthly for 2 more cycles with the concurrent use of three anti-TB drugs. Combination of PD-1 inhibition and anti-TB treatment kept the patient fit with normal liver function and slightly improved dry mouth. Notably, no steroids were administered throughout the treatment. Then, the patient underwent radical resection of the remaining two black skin lesions at the bottom of the left foot on July 12, 2017, and histology did not show any tumor cells indicating a complete response. Subsequently, the patient was subjected to two consolidation treatments with pembrolizumab per month (total 14 cycles). Anti-TB therapy was discontinued in August 2017. Also, she was under medical surveillance every 3-6 months, and no recurrence was detected. Finally, the patient was under follow-up until the drafting of this case report.
The study was approved by the Clinical Research Ethics Committee of Shenzhen People's Hospital, China. Written consent was obtained from the patient and her relatives for publication of the case report.
CT image. (C) Infiltration of the right upper lobe of lung worsened after PD-1 inhibition.