Discussion and Conclusion
Although miliary tuberculosis is the most known cause of miliary infiltrates on chest imaging, other differential diagnoses including pneumoconiosis, fungal infections, sarcoidosis, histoplasmosis, primary lung cancer, and hematogenous spread of non-pulmonary malignancies [12] can mimic this radiographic finding. Rarely, primary lung adenocarcinoma could be the etiology of miliary nodules on chest radiography [13]. While renal cancers are the most likely solid organ malignancies that can manifest with a miliary pattern on chest imaging [14], primary cancers of the thyroid, melanoma, trophoblastic tumors and sarcomas also can display a similar radiologic feature. Chest CT has the highest sensitivity for detecting lung metastases in patients with suspected metastatic MTC [3]. The distribution of miliary nodules on chest CT can be centrilobular, perilymphatic or random [15]. Random micronodular patterns are seen in entities such as hematogenous spread of malignancies, in line with the case reported here. Moreover, micronodules that are seen in hematogenous spread of malignancies to the lungs mainly have a basal predominance. This finding was also observed on the chest radiography and CT scan of this patient. In patients with MTC, lung metastases are commonly accompanied with mediastinal lymph node metastases [3]; however, no mediastinal lymphadenopathy was evident on chest imaging of our patient.
Non-specific clinical symptoms such as, fever, chills, cough, and weight loss can be associated with infectious diseases other thanmycobacterium tuberculosis as well as malignancies. Patients with MTC may present with systemic symptoms such as diarrhea and flushing due to the secretion of serum calcitonin, calcitonin gene-related peptide and other hormones from parafollicular C-cells [16]. In this specific case, our patient was mistakenly treated with anti-tuberculosis drugs since her clinical symptoms as well as radiologic findings were compatible with a diagnosis of miliary pulmonary tuberculosis. Taken together, establishing a diagnosis of miliary tuberculosis should be based on the combination of radiologic, histologic and microbiologic examinations. Nevertheless, it is worthy to note that a negative AFB sputum smear result should not exclude a diagnosis of miliary tuberculosis as this test is only positive in a small percentage of patients with disseminated disease [15].
Thyroid FNA is a useful and reliable tool with a diagnostic yield of 50 to 80% for medullary thyroid carcinoma [17-19]; however, this percentage is increased with the addition of immunohistochemical staining for calcitonin [20,21]. Among the secretory products of C-cells, calcitonin and carcinoembryonic antigen (CEA) are the most valuable biomarkers in patients with MTC. Studies have shown that the concentration of these tumor biomarkers in patients’ sera is associated with the C-cell mass [3]. Unlike calcitonin, CEA does not play a role in the early diagnosis of MTC; in fact, baseline serum CEA levels are measured preoperatively for determining the extent of disease after surgery [22]. Histologically, MTC cells are usually round, spindle-shaped or polyhedral and are arranged in the shape of sheets or nests with peripheral palisading. Moreover, MTC cells are typically discohesive or weakly cohesive on aspiration cytology [2,3]. Our observations were consistent with these findings.
The significant prognostic value of tumor stage in patients with MTC [23,24] underlines the importance of early detection of this aggressive tumor. The 10-year overall survival rate for patients with stage IV disease is reported to be as low as 21%. Some patients, however, may survive for longer years [24]. Considering the increasing number of cases with MTC presenting with miliary nodules on conventional chest imaging, observation of this radiologic pattern should prompt a possible diagnosis of metastatic MTC, even in cases without clinically palpable thyroid nodules. MTCs appearing with a miliary pattern on radiography could be erroneously diagnosed as miliary tuberculosis, leading to a delay in the detection of cancer and ultimately higher stages of disease.
Ethics approval and consent to participate: This study was approved by the ethics committee of Shahid Beheshti University of Medical Sciences.
Consent for publication: Written informed consent was obtained from the patient for publication of this case report, including accompanying images.
Competing interests: The authors declare that they have no competing interests.
Funding: This study did not receive funding from any sources.