DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection.

Some pediatric papillary thyroid carcinoma (PPTC) cohorts have suggested a preliminary correlation with respect to DICER1 mutation status and histomorphology in both benign and malignant follicular cell-derived nodules; however, the data regarding correlates of DICER1-related sporadic PPTCs subtyped based on the 2022 WHO classification criteria are largely unavailable. The current study investigated the status of hotspot DICER1 mutations with clinical, histological and outcome features in a series of 56 patients with PPTCs with no clinical or family history of DICER1-related syndromic manifestation. Fifteen (27%) PPTCs harbored BRAF p.V600E. Eight (14%) cases of PPTCs harbored DICER1 mutations with no associated BRAF p.V600E. DICER1 mutations were identified in exons 26 and 27. A novel D1810del (c.5428_5430delGAT) mutation was also detected. We also confirmed the absence of hotspot DICER1 mutations in the matched non-tumor tissue DNA in all 8 DICER1-related PPTCs. The mean age of DICER1-harboring PPTCs was 15.1 (range: 9-18) years whereas the rest of this cohort had a mean age of 14.8 (range 6-18) years. With the exception of one PPTC, all DICER1-related PPTCs were seen in females (female-to-male ratio: 7). The female to male ratio was 3.8 in 48 DICER1-wild type PPTCs. In terms of histological correlates, 5 of 8 (63%) DICER1-mutant PPTCs were invasive encapsulated follicular variant papillary thyroid carcinomas (FVPTCs) including 4 minimally invasive FVPTCs and 1 encapsulated angioinvasive FVPTC, whereas the remaining 3 PPTCs were infiltrative classic papillary thyroid carcinomas (p < 0.05). The incidence of DICER1 mutations was 19.5% in BRAF p.V600E-wild type PPTCs. Sixty-three percent of DICER1 hotspot mutations occurred in invasive encapsulated FVPTCs, and this figure represents 38% of invasive encapsulated FVPTCs. Only one (12%) patient with DICER1-related disease showed a single lymph node with micro-metastasis. Unlike DICER1-wild type patients, no distant metastasis is identified in patients with DICER1-related PPTCs. The current series expands on the surgical epidemiology of somatic DICER1-related PPTCs by correlating the mutation status with the clinicopathological variables. Our findings underscore that female gender predilection and enrichment in low-risk follicular-patterned PTCs are characteristics of DICER1-related PPTCs.

Is craniocaudal dissection of recurrent laryngeal nerve safer than lateral approach: a prospective randomized study comparing both techniques by using continuous intraoperative nerve monitoring.

Purpose: This study was performed to compare the real-time electromyographic (EMG) changes and the rate of recurrent laryngeal nerve (RLN) injury in craniocaudal and lateral approaches for RLN during thyroidectomy. Methods: One hundred twelve and 86 patients were prospectively randomized to receive lateral (group 1) or craniocaudal (group 2) approach to RLN, respectively, under continuous intraoperative nerve monitoring. Results: Loss of signal (LOS) occurred in 7 (2.0%) of 356 nerves at risk (NAR). LOS was significantly associated with repeated adverse EMG changes and presence of RLN entrapment at the ligament of Berry (LOB), which was accompanied by other clinicopathological or anatomical features, such as tubercle of Zuckerkandl (TZ), extralaryngeal branching, hyperthyroidism, autoimmune thyroid disease (ATD), or thyroid lobe volume of >29 cm3 (P = 0.001 and P = 0.030, respectively). The rate of repeated adverse EMG changes and LOS in the NARs with LOB entrapment accompanied by other clinicopathological and anatomical features was higher in group 1 vs. group 2 (11.1% vs. 2.2%, respectively and 9.7% vs. 0%, respectively; P = 0.070). The total rate of vocal cord palsy (VCP) was significantly higher in group 1 than in group 2 (P = 0.005). The rate of permanent VCP showed no significant difference between the 2 groups. Conclusion: The craniocaudal approach to the RLN is safer than the lateral approach in the RLNs with entrapment at the LOB accompanied by other features, such as TZ, extralaryngeal branching, hyperthyroidism, ATD, or high thyroid lobe volume.

Surgical approaches for papillary microcarcinomas: Turkey's perspective.

OBJECTIVES: The incidence of papillary microcarcinomas, which are defined as thyroid cancers of <10mm in size, has been increasing in the last decade. Herein, we present internet-based questionnaire results performed by the Turkish Association of Endocrine Surgery with the aim to evaluate the perspective of the management of papillary microcarcinomas in Turkey. MATERIAL AND METHODS: The user-friendly questionnaire consisted of 13 questions in total. These questions mainly addressed the surgical management of nodules and cancer of <1 cm in size. Patient management before, during, and after surgical intervention was also included; additionally, the "active surveillance approach" was questioned. RESULTS: There were 420 responders in total who were of multidisciplinary origin (endocrinologists, surgeons, nuclear medicine specialists, pathologists, and oncologists). Total thyroidectomy was the predominant treatment approach (65%) for the classical type of microcarcinoma limited in one lobe, whereas in cases of microcarcinomas incidentally diagnosed during hemithyroidectomy, complementary surgery approach was advised by 40% of the responders. The responders found capsule invasion (86%) and patient based management (94%) of high importance. The percentage of the responders who recommended radioactive iodine ablation in incidental cancers having no aggressive criteria was 51%. The survey participants that were against routine central dissection in these cases accounted for 73% of the responders. The recommendation of active surveillance (follow-up without any interventional therapy) was limited with 9% responders. CONCLUSION: The results of the questionnaire demonstrated that there have been various choices in Turkey for the surgical treatment of the papillary microcarcinomas.

Bilateral patterns and motor function of the extralaryngeal branching of the recurrent laryngeal nerve.

PURPOSE: To evaluate the bilateral patterns and motor function of the extralaryngeal branches (ELB) of the recurrent laryngeal nerve(RLN). METHODS: This study included 500 consecutive patients who underwent total thyroidectomy. Intraoperative nerve monitoring (IONM) was used in 230 patients. Demographic data, indications for surgery, the bilateral patterns of ELB of the RLN, electromyographic activity of the ELB, distance between the branching point to the entrance into the larynx, and the rate of postoperative morbidity were analyzed. RESULTS: The overall rate of ELB was 27.6% (276/1000). A single trunk of the RLN on both sides was found in 269 (54%) patients, whereas ELB on both sides was observed in 45 (9%) patients. The rates of ELB on the left and right sides were 26.6 and 28.6%, respectively. Of the 89 branched nerves which were dissected using IONM, an evoked motor response was present in 100% of the anterior branches and 5.6% of the posterior branches. The mean branching distance of the RLN was significantly greater in female patients than in male patients on the left side (p = 0.031). The patterns of ELB showed no significant difference in male and female patients. The rates of postoperative transient and permanent hypoparathyroidism and unilateral RLN palsy were 21.6 and 2.8%, and 3.2 and 0.8%, respectively. The rate of RLN palsy was higher in branched nerves compared to those with a single trunk (0.75 vs 0.3%; p = 0.2). CONCLUSION: Unilateral ELB of the RLN might be observed in approximately 1/4 of the patients, while bilateral branching is rare. A few number of posterior branches of the RLN can have motor function. The RLN's with ELB might have a higher risk of injury compared to those with a single trunk.

Surgical Treatment in Papillary Thyroid Microcarcinoma.

Despite the notable increasing incidence of papillary thyroid microcarcinoma (PTMC), the optimal treatment of the patients with PTMC remains controversial. Because of no consensus about its treatment, the suggested treatment varies from active surveillance alone to total thyroidectomy. Although the 2015 revised American Thyroid Association guideline recommends hemithyroidectomy as the first-line treatment, active surveillance has also been discussed and accepted as another approach for the patients with PTMC. However, the same guideline does not recommend fine needle aspiration biopsy for nodules sized <1 cm, even it is suspicious. In such situation, neither active surveillance nor hemithyroidectomy could be discussed, with a lack of objective cytologic data about the nodules sized <1 cm. In this situation, the decision to perform FNAB to the nodules <1 cm in size depends on the performer of the thyroid ultrasonography. In this invited review, we have discussed the diagnosis and prognostic factors for PTMCs. We have also discussed surgical strategies as the accepted the first-line treatment in patients with PTMC.

Preoperative adrenal artery embolization followed by surgical excision of giant hypervascular adrenal masses: report of three cases.

BACKGROUND: Transcatheter arterial embolization (TAE) is an effective minimally invasive adjunct to surgery for the management and/or palliation of adrenal tumors. METHODS: In this case study, we reported three patients who underwent preoperative TAE before adrenalectomy for large hypervascular adrenal tumors. All patients underwent preoperative embolization 24 h before the operation and were then followed up at the intensive care unit surgery. RESULTS: The largest diameter of the adrenal lesions ranged between 8 and 17 cm. Hypertensive attack occurred in one patient with pheochromocytoma during embolization. No other complications associated with the procedure was noted. The adrenal tumors were totally excised in all patients. The major intraoperative findings associated with preoperative embolization were marked reduction in hypervascularity and the decrease in the size of collateral vessels. No major hemorrhage necessitating blood transfusion were noted during surgery. CONCLUSIONS: Preoperative embolization of large hypervascular adrenal masses could reduce perioperative blood loss by reducing tumor vascularity.

Recurrent Hepatocellular Carcinoma in the Right Adrenal Gland 11 Years After Liver Transplantation for Hepatocellular Carcinoma: a Case Report and Literature Review.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and extrahepatic metastases are typically found during disease progression. The incidence of adrenal metastasis (AM) from HCC in autopsy series ranges from 4.6 to 12.5%, and it is the second most common site of metastasis after the lungs. To date, there have been few reports of patients who underwent adrenalectomy for isolated AM from HCC after liver transplantation (LT). A woman aged 55 years was referred to our clinic for the evaluation of a right adrenal mass that was detected by abdominal ultrasonography at another center. She had undergone liver transplantation secondary to HCC and acute liver failure due to cryptogenic liver cirrhosis 138 months previously. She had been followed up for 5 years following LT after which she declined to continue with further follow-up. After radiologic and biochemical evaluation, she underwent adrenalectomy and the histopathologic examination revealed a 10 × 8 × 7-cm adrenal mass, which was considered to be an isolated AM from HCC. To our knowledge, this is the first case of isolated AM from HCC in the literature that was diagnosed 138 months after liver transplantation. Isolated AM from HCC after LT is rare and might be detected a long time after LT. Curative surgical resection of isolated metachronous AM from HCC in the absence of disseminated disease might provide for an acceptable disease-free period after adrenalectomy.

The Results of Ultrasonography-Guided Percutaneous Radiofrequency Ablation in Hyperparathyroid Patients in Whom Surgery Is Not Feasible.

BACKGROUND: The aim of the study was to evaluate the results of ultrasonography (US)-guided percutaneous radiofrequency ablation (RFA) in hyperparathyroid patients who refused surgery or had high surgical risks. PATIENTS AND METHODS: Five patients with hyperparathyroidism (HPT) underwent US-guided RFA for a single hyperfunctioning parathyroid lesion. Post-ablation serum calcium and parathormone (PTH) assays were performed. All patients underwent imaging studies 6 months after the ablation to visualize the post-ablation change in the size of the treated parathyroid lesions. RESULTS: All patients were normocalcemic on the post-ablation 1st day and 6th month. The post-ablation PTH levels were normal in three patients but remained elevated in two patients. The size of the parathyroid lesion was ≥30 mm in the two patients with elevated PTH, whereas the lesion was smaller than 30 mm in those with normal post-ablation PTH values. CONCLUSION: Although this is a limited case series, it demonstrates the potential feasibility of RFA for HPT. Benefits were achieved particularly in patients with small parathyroid lesions.

Single-incision laparoscopic adrenalectomy.

BACKGROUND: The aim of this study was to compare outcome measures between conventional transabdominal laparoscopic adrenalectomy and single-incision laparoscopic adrenalectomy (SILA). METHODS: Between January 2006 and April 2010, a total of 96 patients underwent laparoscopic adrenalectomy. Of these, 74 (77.1%) underwent conventional transabdominal laparoscopic adrenalectomy (group 1) and 22 (32.9%) underwent SILA (group 2). Age, sex ratio, tumor size, operating time, blood loss, postoperative visual analog pain scale (VAS) scores, and duration of hospitalization were compared between the two groups. RESULTS: The mean ages of the patients in groups 1 and 2 were 43.4 ± 12.3 and 43.3 ± 10 years, respectively (P = 0.7). The female:male ratios in groups 1 and 2 were 1.6:1 and 4.5:1, respectively (P < 0.0001). The mean tumor size was significantly larger in group 1 than in group 2 (4.7 ± 1.5 vs. 3.34 ± 1.06 cm, respectively; P = 0.093). No significant difference was found between group 1 and group 2 with respect to the mean operating time (68.4 ± 20.8 vs. 63.9 ± 16.9 min, respectively; P = 0.36) or the level of intraoperative blood loss (38 ± 26.5 vs. 48.4 ± 62.4 ml, respectively; P = 0.26). The postoperative VAS score was significantly lower in group 2 than in group 1 (2.05 ± 0.57 and 3.28 ± 0.63, respectively; P < 0.0001). The length of hospital stay was significantly higher in group 1 than in group 2 (3.04 ± 1.2 and 2.45 ± 0.96 days, respectively; P = 0.04). CONCLUSION: The findings of the present study suggest that SILA is as safe as conventional transabdominal laparoscopic adrenalectomy. Furthermore, SILA is associated with less pain and better cosmesis than the conventional laparoscopic procedure.

Excision efficiency of radioguided occult lesion localization in reoperative thyroid and parathyroid surgery.

BACKGROUND: The purpose of this study was to investigate the efficiency of a radioguided occult lesion localization technique in reoperative thyroid and parathyroid procedures in patients who had undergone previous neck exploration for thyroid or parathyroid disease. METHODS: Twenty-one consecutive patients who were scheduled for reoperative thyroid or parathyroid surgery were studied. The indication for reoperation was recurrent papillary thyroid cancer (PTC) in eight patients, completion thyroidectomy for PTC in eight patients who had previously undergone a bilateral subtotal thyroidectomy, recurrent goiter in two patients, primary hyperparathyroidism in two patients, and recurrent parathyroid cancer in one patient. Ninety minutes before surgery, 0.1 mL of Technetium-99m (0.2 mCi)-labeled macroaggregated albumin was injected directly into the lesion under ultrasonographic guidance. During surgery, a handheld gamma probe was used to localize and excise the lesions. The background and postexcisional site radioactivities were compared to confirm the completeness of each procedure. The radiation dose in the operating room environment, duration of surgery, and postoperative complication rates were evaluated in all patients. In patients with PTC, the change in serum thyroglobulin (Tg) following surgery was noted. RESULTS: Thirty lesions were marked and excised. The postexcisional bed gamma counts (610 ± 141) were markedly decreased compared with the pre-excisional site counts (21,415.8 ± 4993.4; p = 0.0001). The ratio of the postexcisional and background counts (4.6 ± 4.3) was significantly lower than the ratio of the pre-excisional and background counts (173.7 ± 156.4; p = 0.0001). The mean operation duration was 53.3 ± 7.5 minutes. The dose absorbed by the hands of the surgeon was estimated as 0.07 ± 0.02 and 0.15 ± 0.05 millisievert/h when one or three lesions were marked, respectively. One patient developed postoperative transient hypoparathyroidism. After surgery, serum Tg levels dropped to <2 ng/mL in 86% (6/7) of the patients with PTC whose preoperative serum Tg was elevated. CONCLUSIONS: The radioguided occult lesion localization technique was efficient in the perioperative identification of thyroid and parathyroid tumors in patients who were undergoing reoperation for PTC and hyperparathyroidism.

Single-incision laparoscopic left adrenalectomy.

BACKGROUND: Single-incision laparoscopic surgery (SILS) has gained an interest and popularity in the recent years. Although minimally invasive adrenal surgery replaced the open adrenalectomy, SILS adrenalectomy is a step forward technique that improves the cosmesis, decreases acsess related morbidity, and increases the postoperative recovery. We report our first experience with single-incision transperitoneal left adrenalectomy in a patient with Conns' syndrome. CASE: A 46-year-old female patient with a diagnosis of Conns' syndrome underwent single-incision transperitoneal laparoscopic left adrenalectomy. SILS port (Covidien, Norwalk, CT) was used through a 2-cm incision and additional one 5-mm trocar used through one of the holes of SILS port to solve the smoke problem. The operative time was ended in 50 minutes, and no peroperative complication was encountered. The patient was discharged at the second postoperative day. CONCLUSION: SILS adrenalectomy is a safe procedure for a benign adrenal lesion in experienced hands. Further studies are needed to evaluate the special benefits of this technique.

Anti-CD10 (56C6) is expressed variably in adrenocortical tumors and cannot be used to discriminate clear cell renal cell carcinomas.

In the evaluation of retroperitoneal masses, the practicing pathologist faces a dilemma when making a diagnosis based on histology given the often overlapping morphologic appearances of the adrenocortical carcinoma, renal cell carcinoma (RCC), and hepatocellular carcinoma (HCC). CD10 is expressed in a membranous fashion in the vast majority of clear cell RCCs; therefore, it is widely used for distinction from its mimics. However, its expression is not well-investigated in adrenal cortical tumors. We examined CD10 expression in 47 surgically resected adrenocortical tumors (26 adenomas and 21 carcinomas) and compared with 20 clear cell RCCs and 25 HCCs. Twenty HCCs (80%), 18 RCCs (90%), 11 adrenocortical carcinomas (52%), and 18 adrenocortical adenomas (69%) were positive for CD10. HCCs were characterized by a canalicular staining, and clear cell RCCs exhibited membranous or mixed membranous-cytoplasmic staining. Adrenocortical tumors displayed mainly cytoplasmic staining. Four adrenocortical carcinomas and one adenoma also displayed the membranous staining pattern. Despite the relatively small number of samples, our preliminary results revealed that adrenocortical tumors may express CD10 (Clone: 56C6). The most important point from this paper is the fact that anti-CD10 expression has not been previously reported in adrenocortical carcinomas. This suggests that CD10 does not seem to be a useful marker for discriminating clear cell RCCs from adrenocortical tumors since CD10 expression does not rule out the possibility of adrenocortical tumors. This feature should be kept in mind when constructing an antibody panel for an epithelial tumor that involves the adrenal gland and kidney, especially in small biopsy specimens.