A thyroid gland with over 30 foci of papillary thyroid carcinoma with activating BRAF V600E mutation

Abstract

Summary Multifocal papillary thyroid carcinoma (PTC) is common and the number of tumor foci rarely exceeds ten. The mechanism of multifocal disease is debated, with the two main hypotheses consisting of either intrathyroidal metastatic spread from a single tumor or independent multicentric tumorigenesis from distinct progenitor cells. We report the case of a 46-year-old woman who underwent total thyroidectomy and left central neck lymph node dissection after fine-needle aspiration of bilateral thyroid nodules that yielded cytological findings consistent with PTC. Final pathology of the surgical specimen showed an isthmic dominant 1.5 cm classical PTC and over 30 foci of microcarcinoma, which displayed decreasing density with increasing distance from the central lesion. Furthermore, all malignant tumors and lymph nodes harbored the activating BRAF V600E mutation. The present case highlights various pathological features that support a mechanism of intraglandular spread, namely a strategic isthmic location of the primary tumor, radial pattern of distribution and extensive number of small malignant foci and BRAF mutational homogeneity. Learning points: Multifocal papillary thyroid carcinoma (PTC) is commonly seen in clinical practice, but the number of malignant foci is usually limited to ten or less. There is no clear consensus in the literature as to whether multifocal PTC arises from a single or multiple distinct tumor progenitor cells. Strategic location of the dominant tumor in the thyroid isthmus may favor intraglandular dissemination of malignant cells by means of the extensive lymphatic network. An important pathological finding that may be suggestive of intrathyroidal metastatic spread is a central pattern of distribution with a reduction in the density of satellite lesions with increasing distance from the dominant focus. PTCs originating from the isthmus with intraglandular metastatic dissemination behave more aggressively. As such, a more aggressive treatment course may be warranted, particularly with regard to the extent of surgery.

Surgical Extent of Central Lymph Node Dissection for Papillary Thyroid Carcinoma Located in the Isthmus: A Propensity Scoring Matched Study

“…In addition, with the improvement of diagnostic procedures, most of the tumor diameter is small when it is detected. Nevertheless, PTC confined to isthmus has been reported to be more aggressive than the nodule located at lobes (15)(16)(17). Young Chan Lee et al (18) considered that isthmic PTC was more likely to be accompanied by capsule invasion and the pretracheal or prelaryngeal lymph nodes metastasis, being consistent with the other studies reported (19,20).…”

“…Nevertheless, PTC confined to isthmus has been reported to be more aggressive than the nodule located at lobes ( 15 – 17 ). Young Chan Lee et al.…”

Oncosuppressor-Mutated Cell-Based Diagnostic Platform for Liquid Biopsy Diagnoses Benign Head and Neck Masses and Predicts Malignancy in Thyroid Nodules: Results from a Consecutive Cohort of Patients

“…In such instances, molecular analysis of FNAC samples has recently gained in popularity as an adjunct to microscopic cytological evaluation. Many molecular markers, such as BRAF and RAS mutations and gene product aberrations, are promising as diagnostic and prognostic markers [15-17]. In general, molecular testing offers high specificity and positive predictive value, but sensitivity is low [18].…”