Cytological Characteristics of Postoperative Metastases of Papillary Thyroid Cancer During the Development of Secondary Radioiodine Refractoriness

Radioiodine refractoriness is the main problem in the diagnosis and treatment of papillary thyroid carcinoma. The aim of the study was to investigate the cytological and immunocytochemical changes of thyrocytes in fine-needle aspiration smears of thyroid papillary cancer metastases in the course of the development of secondary radioiodine resistance. A total of 70 postoperative metastases of thyroid papillary cancer (secondary radioiodine refractory metastases, previously responsive to radioiodine, that eventually loses the ability to radioiodine accumulation, radioiodine-avid metastases, primary radioiodine-refractory metastases), immunohistochemical staining of thyroid peroxidase, thyroglobulin, cytokeratin 17 and cytological analysis were performed. Revealing the presence of specific cellular phenotypes and structures in punctuates, a low percentage of thyroid peroxidase and thyroglobulin-positive thyrocytes allows the development of the method of cytological prediction of the radioiodine therapy effectiveness

Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures: Total or cortical-sparing adrenalectomy. Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2\u2009cm; P\u20091.5\u2009cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8\u2009cm vs 652.8\u2009cm (94% vs 85% by 10 years; P\u2009=\u20090.020; 80% vs 50% at 10 years; P\u2009=\u20090.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8\u2009cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs

morbidity of prophylactic node dissection in the central neck area in patients with papillary thyroid carcinoma

The benefits of prophylactic central neck dissection (PCND) in patients with papillary thyroid carcinoma (PTC) have not been clearly demonstrated so far and should be weighed against the potential risks of the procedure. The aim of the study was to assess the recurrent laryngeal nerve and parathyroid risks of PCND after total thyroidectomy in patients with PTC and to compare the results with those obtained in patients who underwent total thyroidectomy only. METHODS: We selected 100 patients who underwent a total thyroidectomy: 50 for nontoxic benign multinodular goiter (Group 1) and 50 for PTC (Group 2). Patients with PTC had no evidence of macroscopic lymph node invasion during surgery and underwent, in addition to the total thyroidectomy, a PCND. All of the 100 patients were operated on by two experienced endocrine surgeons. All patients had pre- and postoperative investigations of vocal cord movements. Calcemia and phosphoremia were systematically evaluated preoperatively and on day 1 and day 2 after surgery. All patients presenting a postoperative calcemia below 1.90 mmol/l were considered to present an early postoperative hypoparathyroidism and received calcium-vitamin D therapy. The hypoparathyroidism was considered permanent when calcium-vitamin D therapy was still necessary 1 year after surgery. RESULTS: None of the patients presented permanent nerve palsy. There were three cases of transient nerve palsy (6%) in Group 1 and two (4%) in Group 2. In Group 1 there was no permanent hypoparathyroidism and four cases of transient hypoparathyroidism (8%). In Group 2, seven patients presented transient hypoparathyroidism (14%) and two patients (4%) remained with definitive hypoparathyroidism. CONCLUSION: After total thyroidectomy for PTC, PCND does not increase recurrent laryngeal nerve morbidity but it is responsible for a high rate of hypoparathyroidism, especially in the early postoperative course. Even taking into account the possible benefits, the results make it difficult to advocate PCND as a routine procedure in all patients presenting a PTC

latent subclinical medullary thyroid carcinoma: diagnosis and treatment

Sporadic medullary thyroid carcinoma (SMTC) is usually diagnosed at a clinical stage often associated with lymph node involvement. Hence surgical treatment does not result in definitive cure in many patients. Studies have demonstrated that routine measurement of serum basal calcitonin (CT) in patients with nodular thyroid disease allows preoperative, early diagnosis of unsuspected SMTC. The aim of this work was to assess the results of surgery in patients operated on for subclinical SMTC detected preoperatively by measurement of serum CT. Results were compared with those obtained in patients with SMTCs diagnosed at a clinical stage and operated on during the same period. During a 4-year period (1993–1996) 24 SMTCs were diagnosed and treated in our department. They were diagnosed at a clinical stage in 13 patients (group 1): palpable thyroid tumor (n 5 11), palpable metastatic lymph node (n 5 6), distant metastases (n 5 4). In nine cases the diagnosis was made by both fine-needle aspiration cytology and serum CT measurement. In the four other cases the initial cytology was incorrect, but the diagnosis was revised on the basis of elevated basal CT values. In 11 patients (group 2) presenting with nodular thyroid disease, SMTC was not clinically detectable. SMTC was preoperatively suspected by elevated CT levels: basal CT > 10 pg/ml and pentagastrin-stimulated CT peak > 100 pg/ml. One patient in group 1 with distant metastases was not operated on. All of the other 12 patients underwent total thyroidectomy and extensive lymph node dissection. The mean size of the tumors was 27 mm. Lymph node involvement was found in nine patients. After surgery, CT levels returned to normal in five patients but remained elevated in five others; the two remaining patients died of distant metastases. All 11 patients in group 2 underwent total thyroidectomy and central neck dissection. None of the 11 patients had nodal extension. All 11 patients are biochemically cured. It was concluded that routine measurement of basal serum CT in those with nodular thyroid disease allows early, preoperative diagnosis of subclinical SMTC and improves the results of surgery

The penetrance of MEN2 pheochromocytoma is not only determined by RET mutations

Multiple endocrine neoplasia type 2 (MEN2) is a rare syndrome subdivided into 2 main entities: MEN2A and MEN2B (Donis-Keller et al. 1993, Mulligan et al. 1993, Eng et al. 1996). Genetic results can predict the natural history of medullary thyroid carcinoma (MTC) depending on the mutation of RET. This is the basis for ATA guidelines giving different ages to perform early thyroidectomy in such patients (Wells et al. 2015). MEN2A and MEN2B are also characterized by the occurrence of pheochromocytoma (PHEO), though less frequent than MTC. PHEO is a chromaffin tumor arising from the medullar zone of the adrenals and responsible for mortality if left undiagnosed (Lenders et al. 2005). Precise comparative large-scale epidemiological data on PHEO penetrance in different geographical zones are however missing in the literature as the majority of published studies were coming from a single Center or a single country