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Thyroid

(7.01) An Unusual case of Incidental Papillary Thyroid Carcinoma with Mature Bone Formation in Patient with Long Standing Multi-Nodular Goiter.

Thursday, May 9, 2024
2:30 PM – 2:45 PM CDT
Location: ePoster Showcase, Empire Ballroom Foyer, Level 2
Introduction : Papillary Thyroid Carcinoma (PTC) is one of the most common thyroid follicular epithelial-derived cancers, with an incidence rate of 13.5 per 100,000 persons. Histologically, PTC is frequently associated with calcifications like psammoma bodies but rarely with osseous metaplasia and ectopic bone formation (EBF).

Case(s) Description : A 60yo female presented to seek help for hyperthyroidism. She was diagnosed with Multinodular goiter (MNG) in 2013, at which time her thyroid ultrasound showed a diffusely enlarged gland with near complete replacement of normal thyroid tissue by heterogeneous nodules without any clearly identified suspicious nodules. CT neck confirmed the ultrasound findings with coarse calcifications but no definite microcalcifications. Her TFTs were initially normal, but slowly became hyperthyroid. In 2019, she was prescribed Methimazole, but compliance was questionable, and she remained hyperthyroid on labwork. By 2023, she had developed hyperthyroid symptoms, including anxiety, palpitations, and heat intolerance. Labs revealed TSH < 0.01 pg/mL (0.35-4.94) and free T4 of 1.9 ng/dL (0.8-1.8). She endorsed compressive symptoms and agreed to surgical treatment. Intraoperatively, the thyroid was noted to be hard, fibrotic, and markedly enlarged with multiple nodules. The tissue was inflamed, and adhered to the trachea and the recurrent laryngeal nerve. On pathology, a 1.8 cm incidental tumor was identified as PTC (follicular and classic subtypes) with microscopic extrathyroidal invasion to the strap muscles. Tumor cells were present at the margin where it was adhered to the trachea. Within the carcinoma, large areas of degenerative changes with fibrinous hemorrhage, osseous metaplasia, and EBF were noted.

Discussion :

Dystrophic calcifications are often detected in nodular goiters, especially in areas of remodeling - such as post-hemorrhage, rupture of colloid cysts, or along needle biopsy tracts. Hemorrhage and hemorrhagic cystic degeneration are common findings in PTC but maturation of this calcified tissue to mature bone is extremely rare. Osseous metaplasia and EBF can be defined as the presence of heterotrophic normal bony tissue within soft tissue. The exact etiopathogenesis of the osseous changes in PTC remains unclear. Most theories describe the involvement of signaling proteins called bone morphogenetic proteins (BMPs) and activin receptor-like kinase (ALK), which are essentially BMP receptors as osteo-inductive factors. At least 30 types of BMPs have been associated with EBF. Concomitant upregulation of ALK1 is another mechanism. Preexisting calcification may also serve as a template for bone formation in PTC, putting these patients at higher risk for local osseous growth. Risk factors for EBF include older age, extrathyroidal invasion, and higher staging, as evident from previous studies. We perceive that these histopathological changes transpire from the complex interplay of many factors at the molecular level, proving the need for deeper research. In summary, we report a rare case of MNG with PTC and EBF. Though the exact cause for EBF is not known, BMPs play a significant role in leading to local osseous changes.