INTRODUCTION: Amyloidosis is characterized by extracellular deposition of insoluble fibrillar proteins in organs and tissues. Classification depends on identifying the precursor protein responsible for the formation of the fibril deposits. We describe a patient with a markedly abnormal chest CT secondary to amyloidosis, stimulated by calcitonin from metastatic medullary thyroid carcinoma.
CASE PRESENTATION: A 25-year-old Indian male presented with 6 months of diarrhea, weight loss, and upper body flushing after showering. He was successfully treated for malaria 10 years ago, was taking no medications, and smoked infrequently. He denied recent travel, pets, or occupational exposures. He was thin with muscle wasting, but had normal vital signs, and an unremarkable pulmonary and abdominal examination. Complete blood count, metabolic and thyroid studies, ESR, urinalysis, stool studies, and upper and lower endoscopy were all normal. CT scan of the abdomen was also unremarkable, yet incidentally his chest CT revealed diffuse bilateral reticulonodular infiltrates without adenopathy. Pulmonary function studies demonstrated moderate restriction. Fiberoptic bronchoscopy revealed no endobronchial lesions and a non diagnostic bronchoalveolar lavage. However, the microscopic examination of the transbronchial biopsy, after staining with Congo red and viewed under polarized light, was positive for amyloid. Evaluation to identify the origin of the amyloid included a normal serum and urine immunofixation and a normal echocardiogram. There was no evidence of amyloid in the gastrointestinal tract or bone marrow. Re-evaluation of the transbronchial biopsy by a pulmonary pathologist identified atypical spindle cells, suggestive of neuroendocrine tumor such as carcinoid or medullary thyroid carcinoma. Urinary 5-hydroxyindolacetic acid values were normal, yet levels of serum calcitonin and carcinoembryonic antigen were elevated more than a thousand-fold. Thyroid ultrasound identified a 3 × 2 cm nodule, and biopsy confirmed medullary thyroid carcinoma. There was no other evidence for multiple endocrine neoplasia syndrome. The patient was treated for symptomatic diarrhea and offered systemic chemotherapy for medullary thyroid carcinoma with pulmonary metastasis.
DISCUSSIONS: Amyloidosis usually involves deposits of polymers of light chains or amyloid A protein in multiple organs. When deposits are limited to the respiratory system, it portends a favorable prognosis, whereas pulmonary amyloid associated with a systemic disease has a median survival of 16 months. Other proteins or polypeptides can polymerize and be deposited as amyloid fibrils, as occurs in certain prion diseases or Alzheimer's. In our case, calcitonin polymers stimulated formation of amyloid fibrils. Medullary thyroid carcinoma produces excessive calcitonin causing pulmonary amyloidosis and our patient's symptoms of diarrhea, flushing, and weight loss. With pulmonary metastases, our patient's only therapeutic option was systemic chemotherapy.
CONCLUSION: Our clinical case highlights an extremely uncommon cause of diffuse pulmonary amyloidosis secondary to metastatic medullary thyroid carcinoma.
DISCLOSURE: Won Lee, None.