Activating BRAF mutation in sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid gland: two case reports and review of the literature

A 70-year-old Caucasian woman presented with a 2-month history of dysphagia, unintentional weight loss, and hoarseness. Physical examination revealed a right-sided thyroid mass. Computed tomography (CT) showed a large right thyroid mass arising from the posterior margin, invading the cricoid cartilage, and abutting the esophagus and trachea, measuring 3 cm × 2.7 cm. Laryngoscopy revealed a paralyzed right vocal cord and a right subglottic mass. Fine-needle aspiration of the thyroid mass revealed histology consistent with PTC. Preoperative positron emission tomography (PET) did not show distant metastasis, although the finding was significant for right kidney hydronephrosis. She was taken to the operating room with intent to perform total thyroidectomy with locoregional debulking. However, intraoperative frozen pathology of the involved recurrent laryngeal nerve and a level VI lymph node were concerning for squamous cell carcinoma. Given this unexpected intraoperative diagnosis, she subsequently underwent total thyroidectomy with bilateral neck dissection and laryngopharyngectomy with sacrifice of the right and left recurrent laryngeal nerves. The patient also underwent percutaneous endoscopic gastrostomy and tracheostomy tube placement.

Three months after initial presentation, the patient received ablation with 154.2 mCi of radioactive iodine (¹³¹I) for treatment of the PTC. A post-therapy whole-body scan done 1 week later showed focal uptake at the midline of the lower neck consistent with residual thyroid tissue or functioning metastasis, without evidence of distant metastatic disease.

One month after ¹³¹I ablation, the patient’s PET/CT scan revealed an interval development of a fluorodeoxyglucose avid 1.5-cm pulmonary nodule adjacent to left hilum within the left upper lobe and an 8 × 5-cm mass in the lower pole of the right kidney, which was biopsied (Fig. 1). The biopsy was morphologically consistent with metastatic SMECE (Fig. 2), and the tumor was also positive for BRAF V600E mutation. Two months after the ¹³¹I ablation, the patient received adjuvant external beam radiation. She received 54 Gy at 1.8 Gy per fraction to bilateral neck levels 2–6 along with superior mediastinal nodes. The thyroid bed, right neck levels 2–5, left neck levels 2–4, and peritracheal nodes went up to 60 Gy at 2 Gy per fraction. Repeat CT of the chest 1 year after initial presentation showed a new left suprahilar 3.2 cm × 2.3-cm mass with innumerable pulmonary nodules, increase in size of pleura-based density at the right lower lobe base of 3.8 × 1.1 cm, and left hilar lymphadenopathy. She presented several times for failure to thrive, which was thought secondary to the radical surgery. Her course was also complicated by acute renal failure and hematuria. Given rapid growth of metastatic lesions and declining functional status, she pursued hospice care and subsequently died within 1 year of diagnosis.

A 73-year-old Caucasian woman with a history of PTC treated with total thyroidectomy at the age of 34 years presented to an outside institution with a recurrent right neck mass. She had not been routinely seen by any providers until this recurrence. She underwent right neck dissection, but the mass was found to be adherent to the carotid artery and esophagus, precluding complete resection. Pathology again revealed PTC. This was followed by treatment with 150 mCi of ¹³¹I 2 months postoperatively with subsequent whole-body scan uptake in the thyroid bed without evidence of distant metastasis. She was offered adjuvant external beam radiation to the neck but declined.

One year later, CT of the neck revealed a heterogeneously enhancing and partially necrotic mass within the right thyroidectomy bed extending posteriorly to the esophagus and involving the right recurrent laryngeal nerve. The mass measured 2.2 × 3.0 × 2.8 cm in its respective anterior-posterior, transverse, and craniocaudal dimensions. She was referred to our institution for surgical resection and underwent right radical neck dissection and wide local excision of the neck mass, though it was noted that residual tumor plaque on the carotid and trachea were unable to be fully resected.

Pathology revealed components of both classic PTC and SMECE. There was also a background of lymphocytic thyroiditis, and the tumor involved all margins, indicating that the tumor likely arose from a thyroid remnant. Upon immunohistochemistry, both PTC and SMECE stained positive for CK AE1/AE3 and negative for calcitonin. The PTC component stained positive for thyroglobulin, whereas SMECE was negative (Fig. 3). The SMECE-involved areas of the specimen were scattered to diffusely positive for CK5/6 and p63. BRAF V600E mutation was identified by PCR in both the PTC and SMECE tumors. The patient continued to follow up with her outside provider and had another treatment with ¹³¹I. Unfortunately, the dose of ¹³¹I administered and the post-therapy whole-body scan result were not available.