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.