In our case, the patient was misdiagnosed with advanced lung cancer according to the PET/CT, whereas the bone biopsy and EBUS results suggested an early-stage malignancy, sarcoidosis involved ilium, which was finally confirmed by a pathologic analysis of the surgically resected sample. Sarcoidosis is a multiorgan disease that manifests as non-caseating granulomas of unknown etiology. Sarcoidosis may involve all organs to different degrees. However, bone involvement is rare, with an incidence of 3.4% [1], and such lesions are easily misdiagnosed as bone metastases. A bone biopsy is important for an accurate diagnosis, as it is difficult to differentiate bone metastases and sarcoidosis on PET/CT and MRI [2]. Tumor and nodule reactions may coexist in lymph nodes of patients with non-small cell lung cancer, but they are rare [3]. Of the 1029 cases of sarcoidosis, 50 patients were initially diagnosed with malignant tumors after sarcoidosis, 36 cases of malignant tumors were not associated with sarcoidosis, the length of time between the diagnosis of sarcoidosis and malignant tumors (> 1 year), the involvement of organ system (different from nodules and cancer), and the treatment of no potential carcinogenic sarcoidosis. And 7 cases of subsequent cancer diagnosis may be related to sarcoidosis treatment. The diagnosis of sarcoidosis in 7 cases resulted in a one-month to two-year delay in the final cancer diagnosis, including Hodgkin's lymphoma, mucosa-associated lymphoid tissue tumor, lymphomatoid granuloma, head and neck squamous cell carcinoma, seminoma and skin T-cell lymphoma [4].
According to previous research, sarcoidosis patients have a significantly increased risk of malignant tumors[4–6]. Patients diagnosed with sarcoidosis were later discovered to have malignant tumors, either because the diagnosis of sarcoidosis was based on the granulomatous response to malignant tumors, or because the treatment of sarcoidosis was related to malignant tumors, or because sarcoidosis patients were essentially at risk for malignant tumors. Therefore, patients who have been identified with sarcoidosis need to have a screening for malignant tumors as part of both their physical examination and their follow-up care[4–6].The link between cancer and sarcoidosis is not well understood. Patients with known sarcoidosis may have subsequent or concomitant malignancy. Although the underlying mechanism is unclear, this event may be related to a chronic inflammatory response[7]. Some studies found that cancer patients with granuloma had a higher chance of survival and a lower incidence of stage 4 disease (OR = 0.195, 95% CI 0.073–0.521, p = 0.001). Granuloma can be employed as a prognostic biomarker, and the 2-, 4-, 6-, and 10-year survival rates following cancer diagnosis are greatly improved. Although the actual mechanism of granuloma formation is unknown, it is possible that they are immunological reactions to tumor components. If proven, they could be employed as immunotherapy treatment biomarkers[8]. Active sarcoidosis is distinguished by increased local expression of T helper 1 (Th1) and Th17 chemokines and cytokines such as IFN-, TNF-, IL-17A, and IL-22. In Th17 cells, lower levels of cytotoxic T lymphocyte antigen 4 (CTLA-4) and higher levels of PD-1 (programmed death 1) restrict the inflammatory response. The immune response of sarcoidosis and tumor patients increases sarcoidosis-related inflammation by maintaining low levels of anti-inflammatory CTLA-4 expression while limiting tumor-specific T cell activation, which is characterized by elevated PD-1 expression. Allows malignancies to evade the immune system and spread[9, 10].
Our results suggest that a multidisciplinary team and sequential diagnostic biopsies is necessary for achieving a correct diagnosis and avoiding unnecessary surgery or insufficient treatments. Sarcoidosis is most commonly found in solid or blood cancers before, during, or after the development of the disease. In many circumstances, diagnosis might be difficult and necessitates careful diagnostic testing.