Subcentimetric papillary thyroid carcinoma with extensive lymph node and brain metastasis: case report and review of literature.

Summary: We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case. Learning points: Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival. PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome. Brain metastasis although rare indicate aggressive phenotypic features. Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.

Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) usually presents an excellent prognosis, but some patients present with aggressive metastatic disease. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We aimed to determine the role of genetic alterations in PTC patient outcomes (recurrent/persistent disease, structural disease, and disease-specific mortality (DSM)). The series included 241 PTC patients submitted to surgery, between 2002-2015, in a single hospital. DNA was extracted from tissue samples of 287 lesions (primary tumors and metastases). Molecular alterations were detected by Sanger sequencing. Primary tumors presented 143 BRAF, 16 TERTp, and 13 RAS mutations. Isolated TERTpmut showed increased risk of structural disease (HR = 7.0, p < 0.001) and DSM (HR = 10.1, p = 0.001). Combined genotypes, BRAFwt/TERTpmut (HR = 6.8, p = 0.003), BRAFmut/TERTpmut (HR = 3.2, p = 0.056) and BRAFmut/TERTpwt (HR = 2.2, p = 0.023) showed increased risk of recurrent/persistent disease. Patients with tumors BRAFwt/TERTpmut (HR = 24.2, p < 0.001) and BRAFmut/TERTpmut (HR = 11.5, p = 0.002) showed increased risk of structural disease. DSM was significantly increased in patients with TERTpmut regardless of BRAF status (BRAFmut/TERTpmut, log-rank p < 0.001; BRAFwt/TERTpmut, log-rank p < 0.001). Our results indicate that molecular markers may have a role in predicting PTC patients' outcome. BRAFmut/TERTpwt tumors were prone to associate with local aggressiveness (recurrent/persistent disease), whereas TERTpmut tumors were predisposed to recurrent structural disease and DSM.

Molecular Pathology of Non-familial Follicular Epithelial-Derived Thyroid Cancer in Adults: From RAS/BRAF-like Tumor Designations to Molecular Risk Stratification.

This review addresses the impact of molecular alterations on the diagnosis and prognosis of differentiated thyroid carcinoma (DTC), including papillary, follicular, and well-differentiated carcinoma NOS, as well as oncocytic neoplasms. The molecular characterization of DTC is based upon the well-established dichotomy of BRAF-like and RAS-like designations, together with a remaining third group, less homogeneous, composed of non-BRAF-/non-RAS-like tumors. The role of BRAF V600E mutation in risk stratification is discussed in the clinico-pathological context, namely, staging and invasive features of classic papillary thyroid carcinoma (PTC) and histopathological variants carrying an excellent prognosis (microPTC) or a guarded prognosis, including the aggressive variants tall cell and hobnail cell PTCs. In follicular patterned tumors, namely, follicular thyroid carcinoma (FTC), with or without oncocytic features, the most prevalent molecular alteration are RAS mutations that do not carry prognostic significance. The only genetic alteration that has been proven to play a role in risk stratification of PTC and FTC is TERT promoter (TERTp) mutation.

Clinicopathological Features as Prognostic Predictors of Poor Outcome in Papillary Thyroid Carcinoma.

Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients' outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients' files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, p = 0.015), venous invasion (OR = 16.7, p = 0.022), and lateral compartment LNM (OR = 26.7, p = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, p = 0.008), lymph vessel invasion (OR = 6.9, p < 0.001), and gross ETE (OR = 16.1, p = 0.001) were predictors of structural disease status; male gender (OR = 2.9, p = 0.011), lymph vessel invasion (OR = 2.8, p = 0.006), and incomplete resection margins (OR = 4.6, p < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient's surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients.

Simultaneous gastric and colic laparoscopic adjustable gastric band migration. Complication of bariatric surgery.

Laparoscopic adjustable gastric banding (LAGB) is a minimally invasive treatment for morbid obesity, which has proved its safety, efficiency, and reversibility. Postoperative complications are rare and might be related with the reservoir, connecting tube, or with the band itself. The lack or unspecificity of clinical signs and symptoms makes the diagnosis of gastric band erosion difficult. The authors present the case of a 54-year-old female, submitted to laparoscopic adjustable gastric banding in April 2004 (BMI = 40 kg/m(2)). During the first year, she reduced her body mass index to 30 and remained stable thereafter. In August 2008, while investigating a moderate colicky abdominal pain, she was submitted to a colonoscopy that showed part of the band inside the transverse colon. Two exams were performed: the abdominal CT scan, which showed the connecting tube inside the transverse colon lumen and the lap band which was apparently well positioned around the stomach, and an upper digestive endoscopy that revealed band migration to the stomach lumen. The patient underwent laparoscopic band removal and closure of both stomach and colon walls, thus treating the fistula. LAGB erosion and migration is a late complication of this surgery that frequently needs surgical removal. LAGB migration to colon or stomach is described in literature isolated. Simultaneous erosion to stomach and colon lumen, with a gastrocolic fistula formation, has never been described before, making this case a unique one.