THE LEARNING CURVE AND PERFORMANCE OF A NEWLY ESTABLISHED THYROID FINE-NEEDLE ASPIRATION CENTER.

Context: Thyroid fine-needle aspiration (FNA) cytology is the best tool for preoperative diagnosis of thyroid carcinoma; however, its learning curve is poorly described. Our aim was to assess the learning curve of a new thyroid FNA center involving unexperienced operator and pathologist. Methods: We retrieved from our tertiary endocrinology center database all thyroid FNA procedures done by a single operator (endocrinologist with no experience in FNA) between 2018 and 2021. Cytology was assessed by two pathologists with limited or no experience in thyroid cytology. We also got the corresponding sex, age, nodule diameter, EU-TIRADS score, Bethesda category and final pathology report. Results: There were 1872 FNA in 1618 patients. Proportion of Bethesda 1 nodules decreased significantly (p for trend=0.003) from 17% in the first 100 FNA procedures to 4% in the 401-500 group of procedures, and remained constant between 9% and 4% (p for trend=NS) for the rest of the study. Proportion of Bethesda 2 rose steady from 26% in the first 100 nodules to 80.1% in the last 241 nodules (p for trend<0.001). Indeterminate lesions (Bethesda 3 and 4) decreased significantly (p for trend=0.001) from 16% and 35% in the first 100 nodules to 2.5% and 5.8% in the last 241 lesions. Proportions of Bethesda 5+6 categories varied non-significantly over time. There were no time trends in the malignancy rate of surgically removed nodules. Conclusions: At least 300 procedures are needed to reach the standard performance. A steadily state for the whole center is obtained after about 500 procedures.

HIGH RISK OF PARATHYROID CARCINOMA AND GENETIC SCREENING IN THE FIRST DIAGNOSED ROMANIAN FAMILY WITH HYPERPARATHYROIDISM-JAW TUMOR SYNDROME AND A GERMLINE MUTATION OF THE CDC73 GENE.

CONTEXT: Hyperparathyroidism-jaw tumour (HPT-JT) syndrome is a rare autosomal dominant cause of familial hyperparathyroidism associated with ossifying fibromas (OF) of the maxillofacial bones and increased risk of parathyroid carcinoma, caused by inactivating germline mutation of the cell division cycle 73 (CDC73) gene. OBJECTIVE: To report the first Romanian family with HPT-JT and genetic screening of CDC73 gene. SUBJECTS AND METHODS: Mutational analysis of the CDC73 gene and genetic screening of the family of a proband with HPT-JT. Histological diagnosis of parathyroid tumors (WHO criteria) and immunohistochemistry (parafibromin) were performed. RESULTS: Three of the six screened family members had evidence of PHPT and surgically proven parathyroid tumours. Two of the three affected members had parathyroid carcinomas and one had two parathyroid adenomas. Genetic screening of CDC73 gene revealed that 4 of 6 patients showed a heterozygous germline deletion of one nucleotide: c.128-IVS1+1 delG. All the three affected patients, resulted to be carriers of the CDC73 mutation, but each one bearing a different CDC73 polymorphism. CONCLUSIONS: We identified a new CDC73 germline mutation in a Romanian family of HPT-JT. Analysis of clinical phenotypes in the four mutated individuals confirmed the incomplete penetrance and the variable clinical expression of the disease.

MENOPAUSAL ANDROGEN EXCESS - ASSOCIATED CARDIO-METABOLIC RISK: CLUES FOR OVARIAN LEYDIG CELL TUMOUR (CASE REPORT AND MINI-REVIEW OF LITERATURE).

BACKGROUND: Ovarian Leydig cell tumour is a very rare steroid hormones producing mass, causing clinical and biochemical hyperandrogenism. Even if the level of evidence is based on case studies, many authors (but not all) agree that raised androgens increase the cardio-metabolic risk thus early diagnosis and treatment are necessary On the other hand, the endocrine features pointing an ovarian tumour source of testosterone do not indicate the specific histological finding which needs a post-operative conformation. CASE PRESENTATION: We report a case of a 60-year-old woman with a 4-year history of progressive virilisation in association with hypertension, high number of red blood cells, impaired glucose tolerance and dyslipidemia. Total testosterone was 20 times above normal with suppressed gonadotropins, inadequate for menopause. Trans-vaginal ultrasound and pelvic and abdominal computerized axial tomography imaging revealed a right ovarian solid nodule, and no evidence of alteration in the adrenal glands. Total hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathology and immunohistochemistry confirmed the diagnosis of Leydig cell tumour. After surgery, androgen levels returned to normal and the doses of anti-hypertensive drugs were reduced. CONCLUSIONS: The hyperandrogenic state with elevated plasma testosterone and progressive signs of virilization raises suspicion of an ovarian androgen-secreting tumor. For a postmenopausal patient with hyperandrogenism the diagnosis of Leydig cell tumour should be considered. However, the exact diagnosis is provided by post-operative histological exam. Prolonged exposure to hyperandrogenism may generate cardiovascular abnormalities and metabolic syndrome which after tumor excision and removal of the source of androgen hormones are expected to significantly improve.

Mixed tumor: mucinous papillary cystadenocarcinoma associated with arrhenoblastoma.

A case of a 41-year old woman with an enlargement of the inferior part of the abdomen is presented. An echographic examination established the diagnosis of a right ovarian cyst. During the operation, a 14-cm (5 1/2") tumor, presenting a large ruptured cyst and solid mass, was found. From the cystic activity, a viscous fluid was oozing. On the left ovary, a 4 cm (1 1/2") cyst was also found. Within this case report, we underline the unusual association of a mucinous papillary cystadenocarcinoma with an arrhenoblastoma in the right ovary together with the presence of an cystadenoma in the left ovary.

Case study of appendiceal carcinoid during pregnancy.

The carcinoid tumor of the appendix is one of the most common tumors of the appendix, but one of the rarest anatomic locations of carcinoids. The prognosis is very good, as most tumors are incidentally discovered during surgery for acute or sub-acute appendicitis. The diagnosis is exceptional when combined with pregnancy. We present such a case of a 27-year-old female patient. An emergency appendectomy was performed, and soon after, pregnancy was confirmed. The patient had a tumor smaller than 1 cm in diameter, at the tip of the appendix. The immunochemistry revealed the neuroendocrine profile by positive reaction for chromogranin A and synaptophysin, with a ki-67 profile at an undetectable level. After surgery, the neuroendocrine markers and the octreoscan were negative, consequently indicating a favorable prognosis. Further follow-up is necessary, even though not all the authors recommend it (considering the low index to the associated metastases, especially for small appendiceal tumors). A short review of the literature is presented, starting with this case report.

Malignant insulinoma with hepatic and pulmonary metastases associated with primary hyperparathyroidism. Case report and review of the literature.

Malignant insulinomas are rare tumors (10% of insulinomas) that often present as mnulticentric macro nodules with multiple liver metastases before diagnosis. We report the case of a 55 year old female with a medical history of severe hypoglycemic attacks for two months. Blood tests showed a decreased value of glycemia (30 mg/dl) associated with increased insulin level (l6 microU/ml) and an increased glycemia/insulinemia ratio of 1.87 supporting the diagnosis of insulinoma. Abdominal CT showed a 1.5 cm mass localized in the head of the pancreas with disseminated hepatic tumors, confirmed as neuroendocrine metastases by biopsy (which proved the presence of a malignant insulinoma). Primary hyperparathyroidism was diagnosed based on mild elevation of calcium (10.4 mg/dl) associated with a high level of PTH (71.2 pg/ml). The coexistence of the two endocrinopathies suggested the presence of type 1 multiple endocrine neoplasia (MEN 1). Because of multiple hepatic masses and liver function impairment, surgery and hepatic artery embolization were not performed. Somatostatin analog therapy was started with symptomatic control in the beginning, but rapid loss of beneficial effect. Finally, systemic chemotherapy with doxorubicin was administered, but the disease was progressive and after three months we decided to stop it. The patient died at home after one month, probably in hypoglycemic coma.