Ectopic Cushing’s Linked to Rare Head and Neck Cancer in Case Study

A patient was diagnosed with Cushing’s syndrome caused by a very rare cancer known as small cell carcinoma of the uvula — the small tissue that hangs at the back of the throat — in a case study that scientists think might be unique.

The study, “The First Report of Small Cell Cancer of the Uvula Presenting With Ectopic Adrenocorticotropic Hormone Syndrome,” was published in the World Journal of Oncology.

“To our knowledge, this is only the second case of [small cell carcinoma] of the uvula described in literature, and the first associated with any paraneoplastic syndrome,” the investigators wrote.

Paraneoplastic (meaning “associated with cancer”) Cushing’s syndrome, also known as ectopic Cushing’s syndrome, arises from the overproduction of adrenocorticotropic hormone (ACTH) by a malignant tumor outside the pituitary gland – most commonly, small cell lung cancer.

Small cell carcinomas are more common in older men, those in their 60s or 70s. Small cell carcinoma of the head and neck is extremely rare, with the most common site for such disease being the larynx, or voice box.

Moreover, there’s a relatively small number of articles reporting small cell carcinoma of the oropharynx — the part of the throat at the back of the mouth behind the oral cavity, which includes the uvula.

Investigators from the Advocate Illinois Masonic Medical Center, in Chicago, described the case of a 62-year-old woman with sore throat, difficulty swallowing, and nasal voice, who was admitted to the hospital with low potassium levels (hypokalemia).

The patient had been smoking since she was a child, plus had a history of alcohol abuse, high blood pressure and chronic obstructive pulmonary disease. She also complained of weight gain and generalized swelling. A  brother was previously diagnosed with nasopharyngeal cancer, which affects the part of the throat connecting the back of the nose to the back of the mouth (the pharynx).

An examination revealed a uvular lesion and a computed tomography (CT) scan showed an abnormal mass in her throat with several enlarged lymph nodes, and the team suspected the same type of cancer as the brother .

“Biopsy of the lesion in the oropharynx revealed small cell cancer of the uvula … the patient was referred to the oncology clinic and on follow-up visit, she had shortness of breath and excess wheezing,” the scientists wrote.

Further physical examination and laboratory testing revealed an enlarged uvula, swollen legs, a high white blood cell count, low platelet count, and mildly elevated liver enzymes.

Imaging studies were suggestive of pneumonia, so the clinical team began treatment with azithromycin and ceftriaxone (both antibiotics), together with supplemental oxygen and bronchodilators to relieve her respiratory symptoms.

Magnetic resonance imaging (MRI) of the brain showed a mass in the lateral extension of the nasopharynx known as the fossa of Rosenmuller, which is consistent with small cell carcinoma of the uvula.

Researchers also noted thickening of the dura mater, the tough outer layer of tissue that covers and protects the brain and spinal cord, which led them to believe that the cancer might have spread.

Additional workup to determine the stage of the tumor revealed metastasis in the liver. While in the hospital, the woman had continuous high blood sugar and low potassium levels.

Such biochemical changes were suggestive of Cushing’s syndrome, since overproduction of ACTH leads to elevated cortisol levels, which in turn lowers potassium and raises blood sugar levels.

Blood testing showed high ACTH levels (479 pg/mL; normal range is -10-60 pg/mL), confirming ectopic Cushing’s syndrome due to excessive ACTH secretion by the small cell carcinoma of the uvula, the primary malignant mass revealed in the imaging scans.

“Patient was diagnosed with late metastatic small cell carcinoma of the uvula and she was determined to be a poor candidate for chemotherapy given worsening [low platelet count] and generally poor condition,” the investigators stated.

They proposed palliative radiotherapy because of dural metastases, but the patient refused. Instead, she approved “comfort measures and was accordingly set up for home hospice care upon discharge.”