Case presentation
A 58-year-old woman presented with a history of shortness of breath, fever, chills and productive cough with non-blood-stained sputum. Her symptoms had initiated approximately 8 months prior to admission and had progressed during the last 2 weeks. She did not complain of excessive perspiration at night, dysphagia or hoarseness. However, she mentioned unintentional weight loss of about 25 kilograms within the last 6 months. The patient did not have a history of head and neck irradiation, but was a passive smoker. She denied exposure to tuberculosis and similar symptoms in any of her close family members. Her past medical history was only significant for hypothyroidism for which she received medication (levothyroxine 100 mcg once daily). She had no family history of malignancy or pulmonary disease. The patient was referred to our hospital for further investigation due to the lack of clinical response to anti-tuberculosis therapy that had been initiated after a suspicion of miliary tuberculosis in another center. On physical examination, she was hemodynamically stable with a blood pressure of 130/80 mmHg. She had a normal respiratory rate (12 breaths/min), a body temperature of 37.8 °C, was not tachycardic (pulse rate 84/bpm) and had an oxygen blood saturation of 98% on room air. No thyroid nodule was discovered by palpation and no mass, swelling or cervical lymphadenopathy was detectable on examination of the neck. Pulmonary exam revealed clear lungs on auscultation.
In our hospital, a diagnostic work-up was performed for the patient following admission. Laboratory examinations revealed a TSH of 0.08 (normal range, 0.35-4.9 mU/L), a fT4 of 0.7 (normal range, 0.76-2.24 ng/dL) and an elevated serum calcitonin level (128 pg/mL). Other blood tests were within normal limits. On imaging, chest radiography demonstrated bilateral diffuse micronodules with a miliary pattern, characterized by multiple, small 1-3 mm nodular infiltrates (Fig 1). Considering the most probable differential diagnoses of miliary tuberculosis, primary lung cancer or metastatic malignancies, non-contrast-enhanced computed tomography (CT) of the chest was performed, which showed numerous small lung nodules with a random distribution, and a confluent mass within the right lung (Fig 2). Furthermore, results were negative for acid-fast bacilli (AFB) smear and culture, mycobacterium tuberculosis was not detected by polymerase chain reaction (PCR), and blood cultures conveyed negative results for infectious diseases. These findings as well as the right-sided mass on CT made miliary tuberculosis a less likely diagnosis. Later, the patient underwent thyroid ultrasonography. On ultrasound, a left-sided solid hypoechoic nodule measuring 5 x 4.5 mm in size with irregular borders, a taller-than-wide shape and multiple punctuate echogenic foci were observed, compatible with Thyroid Imaging Reporting and Data System (TI-RADS) 5 [11]. Also, bilateral malignant-looking cervical lymph nodes were detected within zones 2 and 3. These findings prompted an ultrasound-guided fine-needle aspiration (FNA) biopsy, and cytological examination showed isolated and loose clusters of ovaloid atypical cells (Fig 3).
The patient also underwent bronchoscopy with trans-bronchial lung biopsy, which demonstrated atypical cells infiltrating the lung parenchyma. These cells showed a positive reaction for CK7, TTF1, CD56, CEA, chromogranin, and calcitonin by immunohistochemistry (IHC) (Fig 4). Regarding the histological and cytological findings, a diagnosis of MTC stage IV was confirmed, and the patient underwent treatment with sorafenib 400mg twice daily. Unfortunately, about two and a half months after diagnosis, the patient died of disease.