Simonetta Piana

Prognostic Factors Affecting Neck Lymph Node Recurrence and Distant Metastasis in Papillary Microcarcinoma of the Thyroid: Results of a Study in 445 Patients

BACKGROUND The management of thyroid papillary microcarcinoma (PMC) is controversial. Total thyroidectomy, thyroid lobectomy/isthmectomy, and even no treatment have been proposed. We investigated the clinical course and prognostic factors for disease recurrence and distant metastasis in 445 patients with PMC. METHODS Data from 445 patients diagnosed with PMC in the period from 1978 to 2003 were reviewed and analyzed. Total thyroidectomy was performed in 404 patients and loboisthmusectomy in 41. Neck dissection took place in 226 patients (49.7%), with 166 of only the central compartment and 60 of both the central and lateral compartments. Radioiodine ((131)I) ablation treatment was given to 389 patients. RESULTS Median tumor size was 7 mm (range 1-10 mm). PMC was multifocal in 156 cases (35%) and bilateral in 60 cases (13.5%). Extrathyroidal tumor extension (pT3) and neck lymph node metastasis (pN1) were present in 133 (30%) and 182 (40.9%) patients, respectively. Capsular invasion without extrathyroidal tumor extension was observed in 39 (8.7%) patients. Mean follow-up was 5.3 (range 1-26) years. Seventeen (3.8%) patients had recurrence or persistence of disease: neck recurrence (NR) in 12 (2.7%), distant metastasis (DM) in four (0.9%), NR + DM in one (0.2%). One patient (0.2%) died of the disease. Capsular invasion, extrathyroidal tumor extension (pT3), and neck lymph node metastasis at presentation (pN1) were the only independent risk factors for NR and/or DM occurrence (p < 0.05). Patients not showing these features, who were treated with loboisthmusectomy only, never experienced disease recurrence. CONCLUSION Total thyroidectomy seems advisable in PMC with extrathyroidal extension and neck lymph node metastasis at presentation. Capsular invasion without extrathyroidal extension may suggest aggressive tumor behavior and require radical treatment.

A novel hyaluronan-based gel in laparoscopic adhesion prevention: preclinical evaluation in an animal model

OBJECTIVE To evaluate the effectiveness of a crosslinked hyaluronan solution (ACP gel) in the prevention of postsurgical adhesions in laparoscopic surgery. DESIGN A randomized blinded study using a rabbit model in laparoscopic surgery. SETTING A standardized surgical trauma in the rabbit uterine horn to induce adhesion formation. ANIMALS Sixty-four sexually matured female New Zealand white rabbits weighing 2.5 to 3.0 kg and aged 3-4 months. INTERVENTION(S) After trauma, group 1 (n = 22) received no treatment, group 2 animals (n = 20) received oxidized-regenerated cellulose (Interceed [TC7]) in group 3 (n = 22) 5 mL of ACP gel were applied on the lesion. MAIN OUTCOME MEASURE(S) Six weeks after laparoscopy, a laparotomy was performed and the adhesions were scored according to Blauers scoring system. RESULT(S) 66% of the untreated animals and 85% of the animals treated with Interceed presented with severe adhesions, whereas only 35% of the ACP gel treatment group had significant adhesions. The mean ( +/- SEM) increased adhesion score was 2.24 +/- 0.26 in the untreated group, 2.45 +/- 0.22 in the Interceed group, and was 1.25 +/- 0.28 in the ACP gel group. CONCLUSION(S) This study revealed that ACP gel holds promise as a novel resorbable biomaterial for the reduction of postoperative adhesions after laparoscopic surgery.

Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy

BACKGROUND The current guidelines for the management of basal cell carcinoma (BCC) suggest a different therapeutic approach according to histopathologic subtype. Although dermatoscopic and confocal criteria of BCC have been investigated, no specific studies were performed to evaluate the distinct reflectance confocal microscopy (RCM) aspects of BCC subtypes. OBJECTIVES To define the specific dermatoscopic and confocal criteria for delineating different BCC subtypes. METHODS Dermatoscopic and confocal images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Frequencies of dermatoscopic and confocal parameters are provided. Univariate and adjusted odds ratios were calculated. Discriminant analyses were performed to define the independent confocal criteria for distinct BCC subtypes. RESULTS Eighty-eight BCCs were included. Dermatoscopically, superficial BCCs (n=44) were primarily typified by the presence of fine telangiectasia, multiple erosions, leaf-like structures, and revealed cords connected to the epidermis and epidermal streaming upon RCM. Nodular BCCs (n=22) featured the classic dermatoscopic features and well outlined large basaloid islands upon RCM. Infiltrative BCCs (n=22) featured structureless, shiny red areas, fine telangiectasia, and arborizing vessels on dermatoscopy and dark silhouettes upon RCM. LIMITATIONS The retrospective design. CONCLUSION Dermatoscopy and confocal microscopy can reliably classify different BCC subtypes.

Accuracy of dermoscopic criteria for discriminating superficial from other subtypes of basal cell carcinoma

BACKGROUND The management of basal cell carcinoma (BCC) depends, among other factors, on its histopathologic subtype. Although dermoscopic criteria of BCC have been investigated, the possible role of dermoscopy in predicting the tumor subtype remains unclear. OBJECTIVES We sought to assess the diagnostic accuracy of dermoscopic criteria for differentiating superficial BCC (sBCC) from other BCC subtypes. METHODS Dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver operating characteristic curves. RESULTS In all, 77 sBCCs and 258 non-sBCCs were included. Maple leaf-like areas, short fine superficial telangiectasia, multiple small erosions, and shiny white-red structureless areas were potent predictors of sBCC, each making its diagnosis over 5-fold more likely. Conversely, the presence of arborizing vessels, blue-gray ovoid nests, and ulceration gave 11-fold, 15-fold, and 3-fold increased possibility for the diagnosis of non-sBCCs, respectively. Based on the results of the multivariate analysis, we propose a diagnostic algorithm that can predict the diagnosis of sBCC with a sensitivity of 81.9% and a specificity of 81.8%. LIMITATIONS The retrospective design and the inclusion of only Caucasian patients are limitations. CONCLUSION Dermoscopy is reliable in differentiating sBCC from other BCC subtypes.

TERT promoter mutations are associated with distant metastases in Papillary Thyroid Carcinoma

OBJECTIVE Transcriptional activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were reported at high frequency in aggressive poorly differentiated and anaplastic thyroid cancers. By contrast, the relevance of these mutations in the metastatic behavior of well-differentiated thyroid cancer is still to be defined. The aim of this work was to investigate the frequency of TERT promoter mutations in a remarkable cohort of well-differentiated papillary thyroid carcinoma that developed distant metastases (DM-PTCs) and to establish whether these mutations may be predictive of metastatic behavior. DESIGN We analyzed the frequency of TERT promoter mutations in a group of 43 highly aggressive DM-PTCs. As controls, we analyzed these mutations in a group of 78 PTCs without distant metastases (control-PTCs). The possible correlation between TERT promoter mutations and BRAF V600E mutation was also investigated. METHODS TERT promoter mutational status was evaluated by direct sequencing of the hotspot harboring the C228T and the C250T mutations. RESULTS In the overall cohort of 121 PTCs analyzed, 17% of cases (21/121) carried a mutation in the TERT promoter. Noticeably, 33% of DM-PTCs were mutated in the TERT promoter while only 9% of the control-PTCs showed a mutation in this locus. We also observed a positive association between BRAF V600E and TERT C228T mutations in the cohort of DM-PTCs. CONCLUSIONS These results indicate that TERT promoter mutations are associated with the development of distant metastases in PTCs and may help in predicting aggressive behavior in this type of tumor.

Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer

Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

BRAFV600E Mutation Does Not Mean Distant Metastasis in Thyroid Papillary Carcinomas

CONTEXT The oncogenic BRAFV600E mutation has been frequently associated with aggressive behavior of papillary thyroid carcinomas. However, controversy exists on the consistency of these data, and very little is known about the relationship between this genetic alteration and the tendency of papillary thyroid carcinoma (PTC) to develop metastasis at distant sites. STUDY DESIGN We analyzed by direct sequencing the frequency of BRAFV600E mutation within a group of 47 highly aggressive PTC, which had developed distant metastases. As control, we analyzed the BRAFV600E mutation in a group of 75 PTC without distant metastases who were disease free for a minimum 7-yr follow-up. RESULTS The BRAFV600E mutation was present in 29.8% of the distantly metastatic PTC, whereas it was detected in about 44.0% of the control tumors. CONCLUSION These results clearly prove that the BRAFV600E mutation is not associated with the development of distant metastases or fatal outcome in PTC and may not predict aggressive behavior in this type of tumor.

Allele Percentage of the BRAF V600E Mutation in Papillary Thyroid Carcinomas and Corresponding Lymph Node Metastases: No Evidence for a Role in Tumor Progression

CONTEXT The relevance of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) as a negative prognostic factor is a subject of intense debate. This mutation has been associated with several clinicopathological features, but the lack of consistency among data does not support its usefulness as marker of tumor aggressiveness and poorer outcome. Due to the genetic heterogeneity of the tumor, both the occurrence and the allele percentage of the BRAF mutation should be considered to unravel this controversy. OBJECTIVE We aimed to evaluate the impact of the BRAF V600E mutation occurrence and the allele percentage on the metastatic process in PTCs. STUDY DESIGN The presence and allele percentage of the BRAF mutation were determined by pyrosequencing in 132 cases of well-differentiated PTCs with (n = 37) or without lymph node metastases (LNMs) (n = 95) and in 40 LNMs matched with 35 PTCs. RESULTS No significant differences were observed in either the occurrence or the allele percentage of V600E mutation between the 2 groups of PTCs with or without LNMs. The LNMs were heterogeneous for the V600E mutation as the primary lesions. CONCLUSIONS In this study, the occurrence and percentage of the BRAF V600E mutated allele was not preferentially associated with the development of metastases and the average mutated allele percentage decreased as the tumor progresses from the primary site to the lymph node metastatic sites. These observations support the need to reevaluate the role of the BRAF V600E mutation as a negative prognostic marker in PTCs.

Dedifferentiated acinic cell carcinoma of the parotid gland with myoepithelial features

Dedifferentiated acinic cell carcinoma of the salivary gland is an uncommon variant of acinic cell carcinoma, characterized by the coexistence of both an usual low-grade acinic cell carcinoma and a high-grade dedifferentiated component, as well as by an accelerated clinical course. We describe a case of acinic cell carcinoma of the parotid gland in a 67-year-old woman, which recurred 4 times after surgery and radiotherapy. The recurrences consisted of residual foci of acinic cell carcinoma intermingled with a high-grade epithelial proliferation; the latter was focally constituted by cells with morphologic and immunohistochemical features of myoepithelium.

Evaluating ex vivo fluorescence confocal microscopy images of basal cell carcinomas in Mohs excised tissue.

Fluorescence confocal microscopy (FCM) is an emerging technology for rapid imaging of excised tissue, without the need for frozen‐ or fixed‐section processing. Basal cell carcinomas (BCCs) can be detected in Mohs excisions although few studies have described the major BCC findings as seen on FCM.