Preoperative Role of RAS or BRAF K601E in the Guidance of Surgery for Indeterminate Thyroid Nodules.

BACKGROUND: RAS and K601E BRAF mutations are not a reliable indicator of malignancy in fine-needle aspirations (FNA) of thyroid indeterminate cytologic nodules. We aimed to evaluate the histologic characteristics, the risk of malignancy associated with such mutations in FNA and their potential interest for preoperative clinical management of nodules. METHODS: We evaluated 69 indeterminate thyroid nodules with RAS or K601E BRAF mutations with available histopathologic follow-up. All FNA specimens were indeterminate according to the thyroid Bethesda system. Diagnosis of malignant, benign or indolent neoplasms was classified according to 2017 WHO classification. Carcinoma, NIFTP (noninvasive follicular thyroid neoplasm with papillary-like features) and WDTUMP (well-differentiated tumor of uncertain malignant potential) were considered "surgical," as they require surgical excision. Adenoma was considered "non-surgical." The risk of malignancy and the risk of "surgical disease" were evaluated. RESULTS: Pathologic evaluation of the 69 mutated nodules demonstrated benign, indolent and malignant histology in 17 cases (25%), 21 cases (30%) and 31 cases (45%), respectively. The risk of malignancy was 45%, and the risk of surgical disease was 75%. The majority of carcinomas were a follicular variant of papillary thyroid carcinoma. On follow-up, there have been no recurrences to date. CONCLUSION: Preoperative RAS or BRAF K601E mutations detection in cytologic indeterminate thyroid nodules carries a high risk of surgical disease and may benefit from surgical management. Most surgical lesions harboring those mutations are low-risk tumors, which may be in favor of an initial lobectomy.

Molecular testing of BRAF, RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy.

OBJECTIVE: Liquid-based (LB)-FNA is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. However, up to 30% of LB-FNA remain indeterminate according to the Bethesda system. Use of molecular biomarkers has been recommended to improve its pathological accuracy but implementation of these tests in clinical practice may be difficult. Here, we evaluated feasibility and performance of molecular profiling in routine practice by testing LB-FNA for BRAF, N/HRAS and TERT mutations. METHODS: We studied a large prospective cohort of 326 cases, including 61 atypia of undetermined significance, 124 follicular neoplasms, 72 suspicious for malignancy and 69 malignant cases. Diagnosis of malignancy was confirmed by histology on paired surgical specimen. RESULTS: Mutated LB-FNAs were significantly associated with malignancy regardless of the cytological classification. Overall sensitivity was 60% and specificity 89%. Importantly, in atypia of undetermined significance and follicular neoplasm patients undergoing surgery according to the Bethesda guidelines, negative predictive values were 85.4% and 90% respectively. TERT promoter mutation was rare but very specific for malignancy (5.5%) suggesting that it could be of interest in patients with indeterminate cytology. CONCLUSIONS: Mutation profiling can be successfully performed on thyroid LB-FNA without any dedicated sample in a pathology laboratory. It is an easy way to improve diagnostic accuracy of routine LB-FNA and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.

A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

Fine-needle aspiration biopsy with ultrasound guidance in patients with malignant melanoma and palpable lymph nodes.

BACKGROUND: Recurrence after treatment of stage I-II melanoma involves regional lymph nodes in about 50% of patients. A reliable method is needed to evaluate lymph node status (metastatic or not) in the case of palpable lymph nodes. OBJECTIVES: To evaluate the efficiency of fine-needle aspiration biopsy (FNAB) in examining clinically detected suspicious lymph node in patients followed up after surgical removal of stage I-II melanoma. PATIENTS AND METHODS: One hundred and twenty FNABs were performed in 67 patients with a suspicious node in an open study conducted in a French melanoma regional referral centre, Hôpital de l'Hôtel-Dieu. Cytodiagnosis was classified as positive, negative, inadequate or inconclusive. Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios were calculated after final histopathological evaluation. RESULTS: Fifty-eight of 120 FNABs were positive (48%), 50 of 120 (42%) were negative, four of 120 (3%) were inconclusive and eight of 120 (7%) were inadequate. Among the 108 FNABs in which a definitive diagnosis could be given, sensitivity was 98.2% [95% confidence interval (CI) 90.7-99.9] and specificity was 96.1% (95% CI 86.8-98.9). CONCLUSIONS: FNAB under ultrasound guidance is an efficient tool to discriminate better between cases in which surgical treatment of the lymph node basin should be performed and patients who should return for follow-up. Surgical treatment appears to be required in cases of positive FNAB or in inconclusive cases.

[Capillary hemangioma of the spleen on conventional and contrast-enhanced US]. / Hémangiome capillaire splénique en échographie conventionnelle et avec produit de contraste.

We report a case of splenic vascular neoplasm in a 75 year old asymptomatic woman. CT and enhanced sonography were not consistent with a typical hemangioma. Splenectomy was finally realised and pathologic exam showed a capillary hemangioma with thrombosis. The imaging appearance of splenic hemangiomas may be complex because of splenic topography, size and complicating features. The differentiation of these lesions from malignant disease may not be possible.

[Primary juvenile hyperparathyroidism. Report of 24 cases]. / Hyperparathyroïdies primaires juvéniles. A propos de 24 observations.

AIM OF THE STUDY: Primary hyperparathyroidism usually affects elderly patients. Juvenile primary hyperparathyroidism is rare, and raises diagnostic and prognostic problems. The aim of this retrospective study on 24 patients is to establish clinical, histological, and therapeutic features of juvenile primary hyperparathyroidism. PATIENTS AND METHODS: From 1986 to 2001, 673 patients were treated for primary hyperparathyroidism in our department. Twenty four patients were younger than 30 years old (3.5%). There were 14 women and 10 men. Mean age was 23 year (14-30). Clinical manifestations, pathologics findings and postoperative results were studied. RESULTS: Sixteen patients presented a sporadic form of primary hyperparathyroidism with a single adenoma. Clinical manifestations were renal symptoms in 11 cases and acute hypercalcemia syndrome in 2 cases. Seven patients had a NEM I syndrome: parathyroid lesions were 6 hyperplasia and one adenoma. A 27 years old woman presented a recurrent familial isolated hyperparathyroidism. She was operated on 10 years before and at reoperation parathyroid carcinoma was found. Nineteen patients were cured after a post operative follow up ranging from 3 to 168 months. One patient had an asymptomatic hypercalcemia recurrence. Two patients presented permanent hypoparathyroidism treated with calcitriol and calcium. CONCLUSION: Sporadic forms represent majority of cases of juvenile hyperparathyroidism. Renal manifestations are usual. Nevertheless, multiple endocrine neoplasia type 1 has to be evocated.

Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with type II diabetes.

AIMS/HYPOTHESIS: Non-alcoholic steatohepatitis is frequent in Type II (non-insulin-dependent) diabetes mellitus and can lead to fibrosis and cirrhosis. The interindividual variability in the occurrence of nonalcoholic steatohepatitis suggests, however, a genetic modulation. Microsomal triglyceride transfer protein (MTP) is necessary for the assembly and secretion of VLDL and when the protein is not functional, such as in abetalipoproteinaemia, a steatohepatitis occurs. We therefore assessed the association between a functional polymorphism in the promoter region of MTP gene (-493 G/T) and the biological features of steatohepatitis in Type II diabetic patients. METHODS: We studied 271 patients with Type II diabetes. Determination of -493 G/T polymorphism was made by PCR-RFLP. Increased liver enzymes were used as surrogates of liver steatosis and alanine aminotransferase concentration was the outcome variable for the multivariate analysis. Liver ultrasonography was available for a subgroup of patients with newly diagnosed diabetes. RESULTS: The proportion of patients with increased alanine aminotransferase was higher in GG than in GT and TT subgroups (23%, 11% and 6%, respectively, p = 0.01). Additionally, patients with high alanine aminotransferase concentrations were more likely to be young (p = 0.01), male (p = 0.001), obese (p = 0.04) and have low HDL-cholesterol (p = 0.01). In multivariate analysis, the MTP genotype was independently associated with alanine aminotransferase concentration (p = 0.0023) as well as sex and body mass index but not HDL-cholesterol. CONCLUSION/INTERPRETATION: The -493 G/T MTP gene polymorphism is associated with biological surrogates of steatohepatitis in patients with Type II diabetes. The G allele which is responsible for a decrease in MTP gene transcription is prone to increase the intrahepatic triglycerides content, conferring by this a genetic susceptibility for steatohepatitis.

[Surgery for primary hyperparathyroidism in 1998. Apropos of 66 patients and 3 methods of approach]. / Les opérations pour hyperparathyroïdie primaire en 1998. A propos de 66 patients et de trois voies d'abord.

STUDY AIM: The aim of this prospective study was to assess the advantages and disadvantages of cervicotomy, selective lateral approach and video-assisted surgery in the treatment of primary hyperparathyroidism (HPT 1). PATIENTS AND METHODS: During 1998, 66 patients were operated on for HPT 1 in the same center. There were 48 women and 18 men (mean age: 58 years, range: 21-84), familial HPT 1 or MEN1 excluded. The interventions were performed via classical cervicotomy (n = 32), via selective lateral approach (n = 8) and were video-assisted (n = 25). A mediastinal adenoma was removed via cervicotomy and another one via left thoracoscopy. The procedure was associated with intraoperative parathormone (PTH) quick-assay. Calcium testing was controlled before leaving the hospital and 2 months later. RESULTS: A double adenoma and 65 single adenomas were confirmed by pathological report. Circulating PTH levels, 20 minutes after removal of the adenoma, always decreased significantly. In video-assisted procedures, there were 11 conversions to open cervicotomy (44%) and morbidity consisted of one case of laryngeal nerve paralysis. At the end of the study, all patients except one had a normal calcium level. CONCLUSION: Video-assisted parathyroidectomy is feasible but requires a preoperative localisation of the adenoma and intraoperative PTH quick-assay. Its main benefit in cervical adenoma is to reduce the scar and in mediastinal adenoma to avoid sternotomy. With the elective approach, results are similar to those of video-assisted surgery and the procedure is much easier to perform. Classical cervicotomy is still the best option in case of previous cervicotomy, of simultaneous thyroidectomy, of negative preoperative imaging and in elderly patients less concerned about cosmetic benefit.

[Excision of a parathyroid adenoma of the aorto-pulmonary window under thoracoscopy]. / Exérèse sous thoracoscopie première d'un adénome parathyroïdien de la fenêtre aorto-pulmonaire.

OBJECTIVES: Neck exploration is usually required in all cases of primary hyperparathyroidism. Without a precise localization preoperatively cervicotomy may be unsuccessful, especially in case of an ectopic adenoma. CASE REPORT: A patient with primary hyperparathyroidism due to a solitary adenoma localized in the middle mediastinum was identified on preoperative computed tomography and technetium-99m-sestamibi radionuclide scan. The tumor was successfully removed at thoracoscopy without neck exploration. DISCUSSION: Preoperative localization of primary hyperparathyroid tumors is not indicated in all patients. In some selected cases (acute hypercalcemia, reoperation, serious illness) prior neck exploration would be useful in guiding the surgeon.

MRI and CT in a case of pituitary abscess.

We report the case of a woman admitted for hypopituitarism of sudden onset, in whom conventional radiography, CT and MRT suggested a pituitary tumour with supra- and intrasellar extensions. The surgical findings and the clinical course under antibiotic therapy transformed this diagnosis into one of pituitary abscess by a pyogenic micro-organism. Pituitary abscess is an exceptional lesion. Despite the advent of CT and MRI, its preoperative diagnosis remains difficult. However, the presence of an intrasellar expansive process with liquid centre and contrast-enhanced outline should suggest the possibility of an abscess, particularly when the pituitary lesion is associated with a sphenoidal sinus effusion.

[Ultrasonic diagnosis in scrotal pathology. Apropos of 137 tests]. / Apport de l'échographie dans la pathologie des bourses. A propos de 137 examens.

Ultrasound imaging of scrotum in 137 patients detected 31 inflammatory lesions of epididymis or testis, 8 tumors, 23 cystic lesions, 21 hydroceles and 19 other affections. Medical or surgical treatment was instituted in 63% of patients, the other 37% failing to attend. Therapy was effective in 90.5% of cases (100% of fluid lesions, 80.6% of inflammatory lesions and 87.5% of tumors). Ultrasound imaging appears to be an excellent complement to clinical examination, when findings are insufficient or when examination is difficult because of severe pain, allowing identification of the fluid or solid nature of a lesion. It is also of specific value for diagnosis of subclinical tumors, surveillance of patients at risk and detailed investigation of inflammatory lesions.