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Purpose:: Differentiated thyroid cancer (DTC) is the most common endocrine neoplasm, with a rising incidence and a long life expectancy. It has recently been suggested that patients with low- and intermediate-risk DTC with a good response to treatment at one year could be followed up using only highly sensitive immunoassays for thyroglobulin (Tg). The aim of this study was to examine the serum Tg levels in a series of DTC patients with histologically proven persistent or recurrent diseases. Methods:: The study involved 50 consecutive patients being routinely followed up at our center, whose clinical, histological, and biochemical data were retrospectively collected. Results:: The false-negative rate of ultrasensitive serum Tg assay was 14.3% (5/35) overall, and limited to anti-thyroglobulin autoantibodies (TgAb)-negative patients. Among them, only one patient had an excellent response to treatment at one-year follow-up and was diagnosed with a 4 mm recurrence, after more than seven years of periodic ultrasounds. The size of the neck lesion documented in the histological report was slightly larger in patients with detectable as opposed to negative Tg values (P< 0.05). Conclusions:: Serum highly sensitive Tg is undetectable in a proportion of patients with a proven persistent or recurrent DTC. The reasons behind this phenomenon are still unknown. However, in low/intermediate-risk patients cured at one-year follow-up, highly sensitive Tg without neck US seems an appropriate strategy for patients’ management.

To assess the role of clinical, biochemical, and morphological parameters, as added to cytology, for improving pre-surgical diagnosis of palpable thyroid nodules. Patients with a palpable thyroid nodule were eligible if surgical intervention was indicated after a positive or suspicious for malignancy FNAC (TIR 4–5 according to the 2007 Italian SIAPEC-IAP classification), or two inconclusive FNAC at a ≥3 months interval, or a negative FNAC associated with one or more risk factor. Reference standard was histological malignancy diagnosis. Likelihood ratios of malignancy, sensitivity, specificity, negative (NPV), and positive predictive value (PPV) were described. Multiple correspondence analysis (MCA) and logistic regression were applied. Cancer was found in 433/902 (48%) patients. Considering TIR4–5 only as positive cytology, specificity, and PPV were high (94 and 91%) but sensitivity and NPV were low (61 and 72%); conversely, including TIR3 among positive, sensitivity and NPV were higher (88 and 82%) while specificity and PPV decreased (52 and 63%). Ultrasonographic size ≥3 cm was independently associated with benignity among TIR2 cases (OR of malignancy 0.37, 95% CI 0.18–0.78). In TIR3 cases the hard consistency of small nodules was associated with malignity (OR: 3.51, 95% CI 1.84–6.70, p< 0.001), while size alone, irrespective of consistency, was not diagnostically informative. No other significant association was found in TIR2 and TIR3. The combination of cytology with clinical and ultrasonographic parameters may improve diagnostic definition of palpable thyroid nodules. However, the need for innovative diagnostic tools is still high.

There is considerable variability in the surgical approach to differentiated thyroid cancer regarding the decision to explore and remove central or central and lateral compartment lymph nodes. Much as sentinel lymph node sampling has improved the decision to remove axillary nodes for breast cancer, vital dye and lymphoscintigraphy with lymph node sampling may direct the surgical approach to differentiated thyroid cancer.

To investigate whether further, diagnostic procedures should be recommended in patients with slight increase of preoperative serum basal calcitonin (bCT) levels in whom surgical treatment can be recommendable. Fourteen consecutive patients with nodular thyroid disease underwent thyroidectomy in our center for suspected medullary thyroid microcarcinoma (MTC) because their serum bCT levels were slightly higher than the upper limit of normal range. Serum bCT was measured by radioimmunoassay, normality range = 0–20 ng/L. Surgical specimens were examined by the same pathologist using histologic and immunohistochemistry techniques. An extensive search for parafollicular C-cell hyperplasia (CCH) and/or microscopic MTC foci was performed. At preoperative ultrasound, a single thyroid nodule was depicted in three patients while a multinodular goiter in 11. The bCT values ranged between 24.4 and 94.6 ng/L, median 42.2 ng/L while the pentagastrin-stimulated CT (sCT) values by pentagastrin test ranged between 61.5 and 1,262 ng/L, median 245.0 ng/L. Total thyroidectomy was performed in 13 patients, and lobectomy in the other one; central node dissection was also performed in eight cases. At histology, MTC was diagnosed in nine patients (64.3 %), showing a median maximum diameter of 6.1 mm (range, 1.5–17 mm); CCH was diagnosed in the other five patients (35.7 %). The pentagastrin stimulation test was obtained in all patients. It is worth noting that a very high increase of sCT >100 ng/mL was observed in 5/9 patients with MTC and in 2/4 patients with HCC, therefore suggesting the absence of a relationship between the entity of response to pentagastrin test with a specific pathology (MTC vs. HCC). In six patients, the MTC was the nodule on which preoperative FNAC had been performed, while in other three patients preoperative FNAC had been performed on a different nodule from the MTC. Based on our experience, in case of the pentagastrin stimulation test with sCT <100 ng/L and a single nodule, the CT assay on FNAC may be useful, subsequently lobectomy with definitive histological diagnosis is recommended. In case of the Pg test with sCT <100 ng/L and bilateral goiter, total thyroidectomy with histological diagnosis is recommended. In this way, as for the surgical procedure, total thyroidectomy is recommended in cases of bilateral goiter, while lobectomy can be offered for cases with single nodes with serum dosage of bCT in the strict follow up. In case of the pentagastrin stimulating test with sCT <100 ng/L and bilateral goiter, total thyroidectomy with histological diagnosis is recommended.

Medullary thyroid carcinoma accounts for 2% to 5% of thyroid malignancies, of which 75% are sporadic and the remaining 25% are hereditary and related to multiple endocrine neoplasia type 2 syndrome. Despite a genotype-phenotype correlation with specific germline RETmutations, knowledge of pathways specifically associated with each mutation and with non-RET-mutated sporadic MTC remains lacking. Gene expression patterns have provided a tool for identifying molecular events related to specific tumor types and to different clinical features that could help identify novel therapeutic targets. Using transcriptional profiling of 49 frozen MTC specimens classified as RETmutation, we identified PROM1, LOXL2, GFRA1, and DKK4as related to RETM918Tand GALas related to RET634mutation. An independent series of 19 frozen and 23 formalin-fixed, paraffin-embedded (FFPE) MTCs was used for validation by RT-qPCR. Two tissue microarrays containing 69 MTCs were available for IHC assays. According to pathway enrichment analysis and gene ontology biological processes, genes associated with the MTCM918Tgroup were involved mainly in proliferative, cell adhesion, and general malignant metastatic effects and with Wnt, Notch, NFκB, JAK/Stat, and MAPK signaling pathways. Assays based on silencing of PROM1 by siRNAs performed in the MZ-CRC-1 cell line, harboring RETM918T, caused an increase in apoptotic nuclei, suggesting that PROM1 is necessary for survival of these cells. This is the first report of PROM1overexpression among primary tumors.

Abstract: Background: Adrenal surgery has been radically changed by laparoscopy and it is reasonable to wonder whether the increase in the number of adrenalectomies is entirely justified. There is still debate on the transperitoneal versus the retroperitoneal approach, the advantages and drawbacks of which are discussed here. Methods: Between 1983 and 2007, we performed 279 adrenalectomies in 264 consecutive patients, divided into two groups: before and after the advent of laparoscopic adrenalectomy (LA). We analyzed the factors that increased the number of adrenalectomies in recent years. The LAs were further divided into three consecutive periods and the morbidity and conversion rates, and mean operating times were compared. Results: More procedures were performed after the advent of LA, i.e., 55 (19.7%) beforehand versus 224 (80.3%) afterwards, irrespective of the type of disease, for instance: incidentaloma, 17.6% versus 82.4% (p < 0.0001); pheochromocytoma, 20.7% versus 79.3% (p < 0.0001); Conn’s disease, 19.8% versus 80.2% (p < 0.0001); Cushing’s disease, 17.2% versus 82.8% (p < 0.0001); cortical carcinoma, 30% versus 70% (p < 0.001). Analyzing the three LA periods, operating times were the only statistically significant variable (p < 0.0001). Conclusions: The progressive increase in the number of adrenalectomies performed is due more to a better understanding of adrenal disease than to the availability of minimally invasive techniques. The choice of a laparoscopic approach (trans- or retroperitoneal) should depend on the surgeon’s experience.

Abstract: Objective: Laparoscopic adrenalectomy (LA) has become the gold standard technique for almost all the adrenal masses, but several Authors still debate about LA in pheochromocytoma. Background: The purpose of this study was to compare feasibility and safety of LA for pheo and analyze the results relative to LA for incidentaloma, Conn’s disease and Cushing’s disease. Methods: Between January 1994 and March 2006, 167 LAs were carried out in 160 consecutive patients at our Department and 46 of them were affected by pheo, 60 by Conn’s disease, 34 by adrenal incidentaloma and 20 by Cushing’s disease. The following parameters were statistically analysed: Side and size of lesion, conversion to open adrenalectomy (OA), operating time, length of hospital stay, intraoperative blood pressure variations, blood loss, blood transfusion, need for postoperative analgesia, resumption of oral nutrition and postoperative complications. Results: Successful LA was performed in 159 out of 167 cases (95.2%). Significant statistical advantages were observed for pheo, even if its average size was larger (p > 0.001), in terms of average operating time (p < 0.001), average length of hospital stay (p < 0.001), average intraoperative blood loss (p > 0.001), postoperative analgesia (p < 0.001), oral nutrition (p < 0.001). LA for patients with Cushing’s disease (average length of hospital stay and intraoperative blood loss, p < 0.023 and p > 0.002 respectively) and with adrenal incidentaloma (intraoperative blood loss p < 0.009) seems to be a more challenging procedure. Conclusion: The evaluation of this relatively large monoinstitutional experience suggests that LA could be considered the most suitable method for removing pheochromocytoma. This tumour tends to be larger than most functional cortical adenomas, neverthless it allows even a significant reduction in operating time with a faster recovery.

Debate exists in the literature about the optimal treatment to be adopted in patients with locally advanced differentiated thyroid carcinoma. We aimed to better define the most appropriate diagnostic and therapeutic protocol for this type of tumour.

The clinical and histopathological records of 149 consecutive patients with papillary thyroid microcarcinoma (PTMC), homogeneously studied and operated on by the same surgeon in the period 1990 to 2001, were reviewed. After a mean 6.5-year follow-up, three cases of loco-regional recurrence (2) were observed. These three patients had all undergone partial thyroidectomy only and tumour relapse occurred in the residual thyroid tissue. No recurrence was observed in patients treated by total thyroidectomy and 131I. At variance with other reported series, no lymph node recurrence was observed in our series, in particular in the group of 23 patients with evidence of nodal metastases at initial diagnosis (three of whom were revealed by 131I scan after surgery). Therefore, a preventive effect of 131I treatment in our patient population can be hypothesized. However, prolonged follow-up will be necessary to clarify this. Due to the inability of current imaging modalities to select pre-operatively PTMC patients at risk for recurrence (presence of thyroid capsular invasion, multifocality and microscopic lymph node metastases), it appears reasonable to offer the patient total thyroidectomy when a pre-operative diagnosis of PTMC is reached. Moreover, the policy of our thyroid cancer centre is that, in these patients, post-surgical 131I scan should be obtained in order to detect unknown metastatic deposits, and 131I treatment should also be considered in patients with poor clinical and histopathological prognostic factors. In contrast, in patients operated on for benign thyroid disease and with delayed diagnosis of PTMC at definitive histopathological examination, re-operation might be avoided in the presence of unifocal disease without thyroid capsular invasion and with ultrasound-‘normal’ residual thyroid tissue. Close clinical and ultrasound follow-up is recommended, especially in patients who have undergone conservative surgery only.

We report a case of very rare adrenal tumor. A 54-year-old patient was classified as affected by bilateral adrenal incidentaloma that surprisingly, on histology resulted solitary fibrous tumors. Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm. Only five cases of localization of SFT in adrenal gland are reported in the literature, while the frequency of retroperitoneum localization is more frequent, about 30 cases. Immunohistochemically, SFT can be positive for CD34 antigen, vimentin, CD99, and bcl-2 and usually negative for cytokeratins, chromogranin A, NSE, neurofilaments, synoptophysin, and S-100. Surgical excision remains the main treatment in fact the recurrence is locoregional and correlated with positive margins due to incomplete excision, while distant metastases are correlated with atypical or malignant features.

The spontaneous rupture of a parathyroid adenoma accompanied by extracapsular hemorrhage is a rare, potentially fatal, condition and is a cervicomediastinal surgical emergency.