Characteristics of KTRs complicated with TB or cancer
We performed literature searching in PubMed database with the keywords: (tuberculosis) AND (lung cancer OR lung carcinoma) AND (kidney transplant OR renal transplant). The search was limited to English literature and other language literature with English abstract. To our best knowledge, this was the first time to report co-existence of pulmonary tuberculosis and lung malignancy in a kidney transplant recipient. However, when using Mesh terms “kidney transplant” & “tuberculosis” (KT/TB) from 2016 to 2020, and finally found 21 cases (Table S1). The KT/TB patients were mainly middle-aged, with the median age 48.29. Gender was not associated with TB incidence. Of 21 KT/TB patients, 10 (47.6%) had none underlying disease. Among the remaining 11 patients, 5 had diabetes and 3 had hypertension. Meanwhile, extra-pulmonary TB was predominant, with 17 of 21 cases (80.95%). The median onset time of TB was 7 months post transplant, with the shortest 3 months and the longest 12 years. Diagnosis of TB mostly depended on culture of MTB and qPCR for MTB DNA through the biopsy samples from lesions. RIPE scheme (rifampicin, isoniazid, pyrazinamide and ethambutol) was the most common anti-TB therapy (10/21, 47.62%). The prognosis of KT/TB patients seemed to be optimistic.
As well, the literatures about KT complicated with lung cancer (LC) from 2016 to 2020 were summarized in Table S2. In China, a single-center analysis reported that 0.5% of KTR developed lung cancer from 1988 to 2015 in a southern hospital of China . The mean age of KT/LC patients was 50.2 ± 8.3 years at transplantation. The average interval from renal transplantation to cancer diagnosis was 65.7 ± 20.1 months. In France, a case-control study analyzed retrospectively all KT/LC cases in three French Renal Transplant Units from 2003 to 2012 and found that LC incidence was 1.89/1000 person-years from 2008 to 2012 . The median interval of time from KT to LC diagnosis was 7 years (range 0.5–47 years). In our case, the adenocarcinoma in the right lung might occur 6 years post KT.
Relationship between TB and cancer
As we know, TB is the major public health threat of human, causing approximately 10 million new infection and 1.2 million death among HIV-negative people worldwide in 2019 . In the meantime, based on the data of “Statista” website, lung cancer has the highest rate of death among different cancer types and causes 23 death per 100,000 population in the world in 2020. Actually, co-existence of TB and lung cancer has been well-described [14, 15]. At one hand, inflammatory process is one of the potential factors of cancer. Pulmonary TB is considered as the most important inflammation-inducing factors in the lungs [16, 17]. Additionally, it’s proposed that TB could cause chromosome breakage of bronchial epithelium and the bacterial DNA could also integrate into the chromosome of cells, leading to neoplastic transformation . At the other hand, lung cancer may cause re-activation or recurrence of latent TB in turn [18, 19]. Immunotherapy of cancer often includes immunosuppressors, predisposing the patients to an immunocompromised state that latent tuberculosis infection is reactivated .
Although both the right upper and lower lung were adenocarcinoma, but the specific subtype was different. After kidney transplantation, the patient took immunosuppressant and anti-rejection drugs for a long term. Thus, he was at a status of low immunity and weak autoimmune monitoring, who was prone to develop cancer. In this case, TB was diagnosed earlier and the cancer was at stage IA. We inferred that TB developed first and induced neoplastic transformation. The cancer cells may grow adherently along the acinar duct, resulting in obvious enlargement of the lesion 2 years later. However, the right lower cavity-like nodules develop more slowly in comparison. Because the causes are not exactly the same, the subtypes are different, and ultimately the prognosis and course of the disease are not necessarily the same.
Challenges on definite diagnosis of TB and lung cancer
Because most individuals presented with atypical and unspecific symptoms and the radio-logical findings between TB and lung cancer were very similar, challenges remain on diagnosing co-existence of tuberculosis and lung cancer [14, 21]. In this case, the presence of cavitary lesion on the chest CT image indicated possible TB infection. Nevertheless, cavities on thoracic images occasionally indicated various infections, autoimmune conditions, or primary and metastatic malignancies . Moreover, the heterogeneous pattern of FDG uptake increase may provide clues to the presence of double pathologies: infection and malignancy . Therefore, CT-guided PTNB was applied for definite diagnosis, which provided high accuracy, sensitivity, and specificity for both malignancy and infection . A recent research revealed that CT-guided PTNB had overall diagnostic accuracy of 83% (19/20) in the evaluation of pulmonary consolidation lesions .
Challenges on anti-TB treatment in KTRs
Anti-TB medications in KTRs caused a high mortality from 12 to 16.7% all over the world . In addition, drug-drug interactions with immunosuppressive drugs might lead to potential renal or liver toxicity . The well-known “first line” anti-TB regimen includes isoniazid, rifampicin, pyrazinamide and ethambutol. In this case, rifampicin was firstly excluded because of its renal toxicity. Pyrazinamide was not used as it would lead to hyperuricemia and influence the renal function. A recent retrospective study proved that concurrent chemotherapy (anti-cancer and anti-TB chemotherapy) was effective and safe for treating cancer patients with active TB . However, immune checkpoint inhibitors such as PD-1/PD-L1 were widely used on cancer treatment, which may induce reactivation of LTBI or develop active TB . Fortunately, this patient only required anti-TB therapy since the cancer lesions were resected by surgery.
In conclusion, this case described a rare phenomenon of co-existence of smear-negative pulmonary TB and lung adenocarcinoma in KTRs, which highlighted the clinical awareness of co-occurrence of TB and de novo malignancy after renal transplant and emphasized the value of biopsy and 18F-FDG-PET in early diagnosis of TB and cancer. The anti-TB therapy should consider the complicated drug–drug interactions with immunosuppressive agents, and anti-cancer medications.