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The prognostic role of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) has not been fully established since few studies on this topic are currently available in the literature. In the present study, we conducted a systematic review and metanalysis of literature data in order to determine if PNI could be an independent prognostic predictor of patient's survival in VSCC. Four electronic databases (PubMed, ISI Web of Science, Scopus and Google Scholar) were searched from their inception to December 2021 for all studies assessing the prognostic value of PNI in VSCC. Multivariate hazard ratios (HRs) for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were pooled. Six studies with 1048 patients were included. PNI was significantly associated with decreased OS (HR = 2.687; p 0.001), DSS (HR = 2.375; p = 0.014) and PFS (HR = 1.757; p = 0.001), with no statistical heterogeneity among studies and no significant risk of bias across studies. The present meta-analysis highlights that PNI is independently associated with unfavorable prognosis in patients with VSCC. Therefore, PNI should be included in the pathological report of VSCC and considered in combination with other risk factors as a possible criteria for prognostic assessment adjuvant treatment planning inclusion.

Cytology of serous effusions is an important diagnostic tool for the diagnosis of cancer, staging, and prognosis of the patient. Herein, we retrospectively applied the International System for Reporting Serous Fluid Cytopathology (TIS) and provided the corresponding risks of malignancy (ROMs).Pleural, pericardial, and peritoneal effusion samples were retrieved from the archives of our department and reclassified according to the TIS. The ROM for each category was calculated based on available surgical follow-up.A total of 3790 effusions were studied. Pleural samples (1292) were reclassified as follows: 27 (2.1%) as non-diagnostic (ND), 1014 (78.5%) as negative for malignancy (NFM), 86 (6.6%) as atypia of undetermined significance (AUS), 29 (2.3%) as suspicious of malignancy (SFM), and 136 (10.5%) as malignant (M). Pericardial samples (241) were reclassified as follows: 4 (1.6%) as ND, 173 (71.8%) as NFM, 10 (4.1%) as AUS, 7 (3%) as SFM, and 47 (19.5%), as M. Peritoneal cases (2257) were re-categorised as follows: 31 (1.4%) as ND, 1897 (84%) as NFM, 39 (1.7%) as AUS, 53 (2.4%) as SFM, and 237 (10.5%) as M. The respective ROM values for each category were 18.5%, 15%, 45.3%, 93%, and 100% in pleural effusions; 25%, 13.2%, 35%, 100%, and 100% in pericardial effusions; and 19.3%, 10.4%, 43.5%, 100%, and 100% in peritoneal effusions.Pleural, pericardial, and peritoneal cytology show high specificity and moderate sensitivity in the evaluation of serous effusions. The ROMs reported in our study were mostly concordant with those published according to the TIS.

BACKGROUND The global pandemic of the coronavirus disease 2019 represents a major concern for health services worldwide, and has also induced major changes in cytopathology practice. AIM We aimed to verify the diagnostic performance of cytological evaluation under a new safety protocol during the pandemic compared to the standard pre-pandemic procedure. We also aimed to assess how cytological diagnoses and sampling were impacted during the pandemic period compared to the pandemic-free period in 2019. MATERIALS AND METHODS Cytological samples of peritoneal washings taken during the first 10 months of the pandemic emergency in Italy (March 11, 2020 to January 11, 2021) were compared to samples from the preceding 10-month time frame (May 11, 2019 to March 10, 2020). RESULTS One hundred ninety-five specimens were analysed in the present study. We observed no noticeable differences in cytological diagnoses during the pandemic period compared to the pre-pandemic period. The case numbers by diagnostic category for the pre-pandemic vs pandemic periods, respectively, were as follows: non-diagnostic, 0 vs 0 cases; negative for malignancy, 86 vs 52 cases; atypia of uncertain significance, 7 vs 1 cases; suspicious for malignancy, 0 vs 2 cases; malignant, 42 vs 4 cases. CONCLUSION While a consistent reduction in the number of cytological examinations has been observed during the COVID-19 period, our institutional safety protocol for processing cytological samples did not affect the diagnostic reliability of peritoneal washing cytology.

DOG1 is a transmembrane protein originally discovered on gastrointestinal stromal tumors and works as a calcium-activated chloride channel protein. There are a limited number of articles on the potential utility of this antibody in the diagnosis of salivary gland tumors in routine practice. In this study, we aimed to investigate the role of DOG1 as an immunohistochemical marker in patients with salivary acinic cell carcinoma (ACC) through meta-analysis. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2010 to September 2021. The literature search revealed 148 articles, of which 20 were included in the study. The overall rate of DOG1 expression in salivary acinic cell carcinoma was 55% (95% CI = 0.43–0.58). Although ACC is a challenging diagnosis, paying careful attention to the cytomorphological features in conjunction with DOG1 immunostaining can help to reach an accurate diagnosis.

Primary auricular melanoma is rarely reported. Approximately, it accounts for 1% to 4% of all cutaneous melanoma. Early literature suggested that melanoma of the ear is more aggressive than other melanomas, with a propensity for spreading to both regional lymph nodes and distant sites. Here, we present a case of cytological pleural metastasis from auricular melanoma in a 43-year-old woman. Immunohistochemical staining showed that the tumors cells were positive for S-100 protein and Melan-A. The mutation of the v-raf murine sarcoma viral oncogene homolog B (BRAF)V600E was demonstrated on Sanger sequencing. To our knowledge, this is the first report describing the cytomorphology of metastatic auricular melanoma in pleural effusion.

Background The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in cytology and cell block samples is rarely performed, and its diagnostic value in cytology has not been well established. In this study, we sought to determine if VE1 is suitable for fine needle aspiration (FNA) and cell block methods. Methods A total of 86 patients who had BRAF V600E mutations were investigated with molecular and immunocytochemical (ICC) analysis in 45 FNA and 41 cell blocks. In total, 83 (96.5%) patients underwent surgical treatment. Assessment of BRAF V600E mutation status was performed in 72 (83.7%) cases. Results Among the 72 cases analysed, 54 cases agreed (ICC+/BRAF+ or ICC-/BRAF-), seven cases were false positive (ICC+/BRAF-) and 11 cases were false negative (ICC-/BRAF+). False negative cases were not detected in the cell block method. The statistical analysis showed that sensitivity and specificity of ICC for detecting the BRAF V600E mutation were 61% and 77% in FNA samples and 100% and 73% in cell block. Conclusion The use of antibody VE-1 is a reliable method and a negative result of VE1 immunostaining might help to save time and money, restricting the molecular test to antibody-positive cases only. The identification of the aggressive variants of papillary carcinoma might be enabled by the expression of the antibody in neoplastic cells with tall cell features.

Background Ovarian adult granulosa cell tumours are low-grade malignant sex cord-stromal neoplasm with a low recurrence rate. Prognostic factors for recurrence include tumor stage, tumor rupture in Stage I neoplasms and the presence of residual tumors after surgery. However, in recurrent tumors, prognostic factors for overall survival (OS) are lacking. In the present paper, we conducted a systematic meta-analysis with the aim to assess prognostic factors for OS in patients with recurrent GCT. Methods Electronic databases were searched for all studies assessing prognostic factors in recurrent adult granulosa cell tumor of the ovary. Student T test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p value Results Eleven studies analyzing 102 recurrent tumors were included in the systematic review. Tumor stage and localization of recurrent tumors were significantly associated with OS on Kaplan-Meier analysis; Cox regression analysis showed a HR of 0.879 for the stage II, of 3.052 for the stage III, and of 2.734 for stage IV tumor was significantly associated with OS (p = 0.037); observed HRs for abdominal and thoracic locations were of 2.405 and of 4.024, respectively. Conclusions In conclusion, the present article emphasizes the prognostic significance of tumor stage > II and extrapelvic anatomic sites of recurrences in patients with recurrent granuolase cell tumors of the ovary.

Background: To date, useful diagnostic applications of p16 IHC have been documented in gynecological pathology both for HPV-related and non-HPV-related lesions. In the present article, we reported our experience with the novel anti-p16 INK4a antibody (clone BC42), whose expression was tested across all different gynecologic neoplasms, we also compared it to the traditional E6H4 clone. Moreover, we discussed and explored all the diagnostic applications of p16 IHC in gynecologic pathology. Methods: Consultation cases covering a 5-year period (2016–2020) regarding gynecological neoplastic and non-neoplastic lesions in which immunohistochemistry for p16, clone E6H4 was originally performed, were retrospectively retrieved from the files of our institution. Immunohistochemical staining for p16ink4a (BC42) [Biocare Medical group-Paceco USA, Bioptica Milan] and p16ink4a (E6H4) [Ventana Medical Systems-Arizona USA, Roche] was performed by using the Ventana automated immunostainer (Ventana Medical Systems, Tucson, AZ, USA). The immunostaining pattern was defined as negative, focal/patchy, or diffuse. Results: A total of 196 cases, represented by 36 high-grade SIL/CIN3 of the uterine cervix, 30 cervical adenocarcinomas, 22 cervical squamous cell carcinoma, 70 endometrial carcinomas, 25 high grade serous ovarian carcinomas, 6 uterine adenomatoid tumors, and 10 uterine leiomyosarcomas were included in this study. Results showed concordant staining quality of both clones on all tested neoplastic tissues. Conclusions: The novel anti-p16 antibody (BC42 clone) appeared as an alternative to the current E6H4 for use in gynecological neoplasms, offering similar levels of positivity and equally reliable staining results.

Objective Malignant mesothelioma (MM) is usually diagnosed by histological examination of tissue samples; however, effusion cytology offers an opportunity to identify a strong possibility for mesothelioma diagnosis at an early stage. We conducted a retrospective analysis of cytological specimens from a large series of histologically proven MM diagnosed over 19 years. The cases were reviewed and reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC). Methods A total of 450 cases were identified. Cytological analysis was present in 210 patients (164 pleural and 46 peritoneal effusions). All cases were reviewed and reclassified according to the proposed ISRSFC scheme. A comparison among the cytomorphological features was made throughout the different diagnostic categories. Results The 210 cases were histologically diagnosed as follows: 192 (91.4%) cases had an epithelioid type and 18 (8.6%) had a sarcomatoid subtype of MM. The cytological cases were reclassified as follows: 2 (0.9%) as non-diagnostic (ND), 81 (38.6%) as negative for malignancy (NFM), 4 (1.9%) as atypia of undetermined significance (AUS), 11 (5.2%) as suspicious for malignancy (SFM), 112 (53.4%) as malignant (MAL). Sarcomatoid cells in the MAL category were characterised cytomorphologically by more pronounced discohesion. In comparison with the epithelioid subtype, the tumour cells appeared solitary with moderate or marked nuclear pleomorphism, and irregular chromatin. Conclusions It is important to recognise the cytological characteristics of this aggressive entity to suggest an early and precise possible diagnosis. Morphological features, coupled with clinico-radiological data may help the clinicians in adequately managing the patients.

Alveolar rhabdomyosarcoma (ARMS) commonly occurring in children and adolescents, is a rare and aggressive soft tissue malignancy demonstrating rapid growth and dissemination. Although their histopathologic and immunohistochemical findings are well known, cytomorphological features on serous effusions have not been well documented. A case of metastatic rhabdomyosarcoma diagnosed on cytological examination of the pericardial fluid cytology and discuss the diagnostic difficulties that were encountered in this case has been presented.

Background: The diagnostic role of Wilms’ tumor 1 (WT1) is well known in gynaeco-pathological setting, since it is considered a specific marker of serous histotype and adnexal origin. Moreover, its oncogenic role has been recently highlighted in many cancers and it has also been regarded as a promising target antigen for cancer immunotherapy. However, the relationship between its expression and prognostic role in uterine cancer remains unclear. We analyzed the diagnostic and prognostic role of WT1 expression in patients with uterine carcinoma by completing a search using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the PICOS (Participants, Intervention, Comparison, Outcomes, Study Design) model through PubMed, Scopus and Web of Science databases to identify studies that fit our search criteria. The objective of the current meta-analysis was to investigate the diagnostic and prognostic role of WT1 expression in patients with uterine carcinoma. Materials and Methods: A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to April 2020. Studies were considered eligible if they evaluated the WT1 expression in uterine carcinoma. Results: In total, 35 articles were identified that used uterine carcinoma criteria and provided data for 1616 patients. The overall rate of WT1 expression in uterine carcinoma was 25%. The subgroup analysis of uterine cancer types revealed that WT1 was expressed differently among different histotypes (endometrioid, clear cell, serous carcinoma and carcinosarcoma). Discussion and Conclusions: The WT1 immunohistochemical expression is not limited to serous histotype and/or ovarian origin. In fact, a significant proportion of endometrial adenocarcinomas can also show WT1 immunoreactivity. Moreover, our study suggests that WT1 may be a potential marker to predict the prognosis of patients with uterine cancer, but more studies are needed to confirm its role in clinical practice.

Objective To identify in which cases after cytological diagnosis, the Bladder EpiCheck test could represent an effective tool in non-muscle invasive bladder carcinoma or an useless expence. Materials and methods 375 patients diagnosed with non-muscle invasive bladder cancer, 269 with high grade urothelial carcinoma and 106 with carcinoma in situ, were treated and followed for 1 year. The treatment was an intravesical instillation of Bacillus Calmette-Guerin in 305 patients and Mitomycin-C in 70 patients. During the follow-up patients were evaluated by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. Bladder EpiCheck test was performed together with cytology in all cases. Results Analyzing Bladder Epicheck results for each category defined by the Paris System for Reporting Urinary Cytology, we found that the Episcore >60 correlates with histological diagnosis of high grade urothelial carcinoma (HGUC) in atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma (P = 0.0002 Odds Ratio 0.05926 95% Confidence Interval from 0.01127 to 0.3116 and P = 0.0009 Odds Ratio 0.03155 95% Confidence Interval from 0.001683 to 0.5914, Fisher's exact test, respectively), while in Negative for high grade urothelial carcinoma and HGUC patients Episcore is not helpful to identify cases with histological diagnosis of HGUC (P = 0.101 and P = 0.58 Fisher's exact test, respectively). Considering an Episcore ≥ 90 in the HGUC cytological group, this seems not to be correlated with a histological diagnosis of HGUC (P = 0.090 Fisher's exact test). Conclusions Cytology and Bladder EpiCheck test in combination may have the potential to reduce cystoscopies in the follow-up of non-muscle invasive bladder cancer only for cytological diagnoses of atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma . Moreover, in patients with a cytological diagnosis of Negative for high grade urothelial carcinoma or HGUC, cytology alone seems to be safe and cost-effective.

Deciding whether patients with a cytologically indeterminate thyroid nodule should be referred for surgery or for active surveillance is an important challenge for clinicians. The aim of this study was to evaluate the performance of a novel dual-component molecular assay as an ancillary molecular method for resolving indeterminate thyroid nodule cytology. We selected 156 thyroid nodules from those that had undergone fine-needle aspiration processed by liquid-based cytology and surgical resection between June 2016 and December 2017. The sample set included 63 nodules cytologically classified as indeterminate, and 93 other nodules randomly selected from those with non-diagnostic, benign, suspicious, or malignant cytology. Nucleic acids from each nodule were subjected to next-generation sequencing analysis for mutation detection in 23 genes and to digital polymerase chain reaction (PCR) evaluation for miR-146b-5p expression levels. Used alone, mutation analysis in the indeterminate subset (cancer prevalence: 22.5%) displayed high sensitivity (89%) and NPV (96%). In contrast, the miR-146b-5p assay offered high specificity (93%) and PPV (93%). Combined use of both analyses improved panel performance by eliminating false-negative results. These preliminary data suggest that a dual-component molecular test can increase the diagnostic accuracy of thyroid cytology alone by reducing the number of nodules that will be classified as indeterminate and increasing those that can be reliably classified as benign. If these findings are confirmed, this test can be considered for use in clinical practice and is expected to reduce diagnostic surgery and health care costs, and to improve patient quality of life.

Background Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and represents the causative agent of a potentially fatal disease. The spread of the infection and the severe clinical disease have led to the widespread adoption of social distancing measures. Special attention and efforts to protect or reduce transmission have been applied at all social levels, including health care operators. Hence, this reports focuses on the description of a new protocol for the safe management of cytological samples processed by liquid‐based cytology (LBC) with an evaluation of the changes in terms of morphology and immunoreactivity. Methods From March 11 to April 25, 2020, 414 cytological cases suspicious for SARS‐CoV‐2 were processed with a new virus‐inactivating method suggested by Hologic, Inc, for all LBC specimens. Results The samples showed an increased amount of fibrin in the background. A slight decrease in cellular size was also observed in comparison with the standard method of preparation. Nonetheless, the nuclear details of the neoplastic cells were well identified, and the immunoreactivity of the majority of those cells was maintained. The cell blocks did not show significant differences in morphology, immunoreactivity, or nucleic acid stability. Conclusions Despite some minor changes in the morphology of the cells, the results of this study highlight that the adoption of the new protocol for the biosafety of LBC‐processed samples in pathology laboratories is important for minimizing the risk for personnel, trainees, and cytopathologists without impairing the diagnostic efficacy of the technique., This article provides a description of a new procedure and an evaluation of the changes in terms of morphology and cell immunoreactivity that this technique produces in cellular material from patients with coronavirus disease 2019.

Background Micropapillary and plasmacytoid variants of urothelial carcinoma (UC) exhibit very aggressive clinical behavior. To date, only a small number of cytology cases have been reported in either of these variants. Herein, we report 15 cases of UC with combined micropapillary and plasmacytoid features based on urine cytology. Methods We performed a retrospective analysis of all patients with carcinoma of bladder with predominant plasmacytoid and micropapillary histology who had been seen from 2005 to 2017. A total of 15 cases (six cases of plasmacytoid variant and nine cases of micropapillary variant of bladder cancer) with urine specimen were evaluated. The cytomorphological features were compared between two histological variants. Results Fifteen urine cytology cases with the diagnosis of high-grade UC were investigated. The ratio man to women was 5:1 with a median age of 79 years (range: 72-90 years). Single-cell pattern, flat sheets, three-dimensional clusters, micropapillae, nuclear grade, cytoplasmic vacuoles, and necrosis, were evaluated in urine samples of micropapillary variant. The cytological features of plasmacytoid are characterized by large, discohesive, isolated tumor cells that have abundant, thick cytoplasm, and eccentrically located, hyperchromatic nuclei with coarse chromatin and inconspicuous nucleoli. Conclusion It is important to recognize the cytological characteristics of these uncommon but aggressive entities to determine a precise diagnosis. Attention to morphological features, together with clinical history and appropriate immunohistochemical studies may be useful to urologist in pre-operative planning and may lead to a more aggressive surgical approach.

Background Chemohyperthermia (C-HT) or electromotive drug administration (EMDA) are alternative therapies to radical cystectomy in patients with non-muscle-invasive bladder cancer who do not respond to intravesical therapy with bacille Calmette-Guerin. Methods The authors investigated a group of 87 patients with a diagnosis of high-grade non-muscle-invasive bladder carcinoma or carcinoma in situ. Of these, 45 patients received EMDA of mitomycin (EMDA/MMC) and 42 patients were treated with C-HT and mitomycin therapy (C-HT/MMC). In accordance with the Paris System for Reporting Urinary Cytology, a cytological diagnosis was made and patients with diagnoses of atypical urothelial cells (AUC), suspicious high-grade urothelial carcinoma (SHGUC), or high-grade urothelial carcinoma also underwent histological bladder biopsies. Results In accordance with the Paris System for Reporting Urinary Cytology, the AUC cases may have cytological features of SHGUC present on atypical degenerated cells. In analyzing the AUC group without the SHGUC cases diagnosed on the basis of degenerated urothelial cells, the authors found a significant association between the AUC category and a negative histological biopsy. The SHGUC group, including cases with a SHGUC diagnosis rendered on degenerated urothelial cells, was associated with high-grade urothelial carcinoma or carcinoma in situ (P = .0269 for patients treated with EMDA/MMC and P = .0049 for patients treated with C-HT/MMC). Conclusions In the urine samples from patients treated with EMDA/MMC or C-HT/MMC, a diagnosis of SHGUC could be made even on degenerated urothelial cells when considering cellular degeneration as a "physiological" consequence of the treatment that involves either normal or neoplastic cells. Cancer Cytopathol 2018;126:200-6. © 2018 American Cancer Society.

The accurate preoperative diagnosis of thyroid nodular lesions represents a real problem for physicians, endocrinologists, and surgeons. The pivotal role of the pathologist is to characterize as best as possible these lesions to enable the patient to receive a timely and appropriate treatment. FNAC (fine-needle aspiration cytology) is the only test that can provide a definitive preoperative diagnosis especially for benign and malignant nodules. Their sensitivity and specificity are reported to be 68–98% and 56–100%, respectively, in different studies [1, 2].

Objective The current tools available for detecting malignant neoplasms in the cerebrospinal fluid (CSF) are neurological examination, followed by neuroimaging, cytology and molecular techniques. To highlight the role of cytology the diagnosis of metastatic tumours in CSF samples, we present our experience using cytospin and ThinPrep liquid-based cytology. Methods A retrospective analysis was conducted using the pathological records of 8181 cytological specimens of CSF, which were diagnosed over a 17-year period. Between 2000 and 2014, a total of 6994 CSF samples were processed using cytospin method and 1187 specimens were examined using ThinPrep method in the period between 2015 and 2017. Results The most frequent metastatic neoplasm of the first period was non-Hodgkin lymphoma; in the second period the commonest malignancy found was brain tumour (glioblastoma and medulloblastoma). The samples processed by cytospin revealed cytolysis and haemorrhage, while the cases processed by ThinPrep had a clear background. Ten false-positive cases belonging to the suspicious category were processed by cytospin, while there was only one false positive case in the group processed by ThinPrep. The positive predictive value was 95% in cytospin and 100% in Thin Prep with comparable sensitivity, specificity, diagnostic accuracy and negative predictive values. Conclusions CSF cytology is a reliable technique for identifying malignancy in CSF. ThinPrep technology can be applied with good results in terms of clear background, cell enrichment, better nuclear details and high cellularity per slide.

BACKGROUND Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a challenge for the diagnosis and management of thyroid carcinoma. Some authors have proposed histological criteria that are able to distinguish NIFTPs from invasive follicular variant of papillary thyroid carcinoma (I-FVPTC). Hence, NIFTPs may have repercussions in the diagnostic categories on fine-needle aspiration. In the current study, the authors evaluated the criteria for NIFTPs on liquid-based cytology samples. METHODS The authors recorded all 61 liquid-based cytology samples proved to be histological FVPTC between January 2013 and March 2016 and analyzed the architectural, cytoplasmic, and nuclear parameters. They compared them with a cohort of 40 PTC cases and 20 follicular adenoma cases. RESULTS The authors reported 37 NIFTP cases and 24 I-FVPTC cases at histology. The cytological diagnoses of follicular nodules in the NIFTP cases were twice those found in the I-FVPTC cases (54.1% vs 29.2%). The number of positive for malignancy cases among the NIFTPs were approximately half those of I-FVPTC cases. When compared with I-FVPTCs, 70% of the NIFTP cases demonstrated a nuclear size .05). A predominant microfollicular pattern was recognized in both NIFTPs and I-FVPTCs (97.3% vs 100%). CONCLUSIONS The majority of NIFTPs appear to be devoid of nuclear pseudoinclusions and papillary structures, thereby allowing the inclusion in the follicular nodule cases. Nuclear size and microfollicular clusters may suggest the discrimination between NIFTPs and I-FVPCs. Cancer Cytopathol 2016. © 2016 American Cancer Society.

BACKGROUND The current study compared ThinPrep urinary cytology and conventional cytospin urinary cytology in the diagnosis of bladder cancer, applying the Paris System for Reporting Urinary Cytology. METHODS Between January 2010 and December 2011, a total of 3659 urine samples were processed using conventional cytospin methods. Between January 2012 and December 2013, a total of 4186 urine cytological cases were analyzed using ThinPrep methods. In 131 cases (65 processed by conventional cytospin and 66 processed by ThinPrep), a subsequent biopsy was performed. The authors reclassified these cases according to the Paris System and an analysis between the 2 methods with regard to bladder biopsies was performed. RESULTS No significant differences were observed in terms of sensitivity and specificity between the 2 methods in cases with positive cytology for high-grade carcinoma. According to the Paris System, cases of atypical urothelial cells (AUC) and atypical urothelial cells suspicious for high-grade carcinoma (AUC-H) that were processed using cytospin did not correlate with urothelial carcinoma or with negative biopsies; conversely, the AUC cases processed using ThinPrep appeared to correlate with negative histological biopsies or low-grade urothelial carcinoma. CONCLUSIONS The results of the current study demonstrated that according to the Paris System, there were no significant differences in sensitivity or specificity for the diagnosis of high-grade urothelial carcinoma or AUC-H between the 2 methods. Cases of AUC should be easy to recognize using Thin Prep rather than cytospin and only AUCs diagnosed with ThinPrep were found to be statistically linked to negative cases for carcinoma or with low-grade urothelial carcinoma. Cancer Cytopathol 2016;124:519–23. © 2016 American Cancer Society.

Background. Extra-mammary Paget’s disease (EMPD) is a rare neoplasm of epithelial origin, whose precise incidence is not clear. Starting from what is already known, we performed a systematic review and meta-analysis to investigate in male and female patients the immunohistochemical expression of biological markers that could serve as potential prognostic/therapeutic factors, including only human epidermal growth factor receptor 2 (HER2/neu), Estrogen Receptor (ER), Progesterone Receptor (PR), and Androgen Receptor (AR). Methods. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to June 2020. Results. A total of 27 studies with 713 patients assessed the role of HER2/neu, AR, ER, and PR expression in male and female with EMPD. The overall rate of HER2/neu expression was 30%, the expression’s rate for ER and AR was 13% and 40%, respectively, and the overall rate for PR was 8%. The subgroup analysis revealed that there is a different expression of molecular markers between male and female patients. Conclusions. This study revealed that AR status and HER2/neu overexpression/amplification have been shown as two fundamental pathogenetic pathways in both female and male patients affected by EMPD.

In this study, we have examined 67 cytology specimens from patients from 2014 to 2016. The ratio man to women was 4:1 with a median age of 75 years (range: 55-87 years). Thin-Prep processed urinary cytology specimens demonstrated large urothelial cells, with cytologic features of malignancy, thus including hypochromatic nuclei with occasional peripherally accentuated chromatin rim. The cytological diagnosis of High Grade Urothelial Carcinoma (HGUC) was made in 55 patients while 12 specimens were classified as Atypical Urothelial Cells (AUC). This cases represent the 15% of the HGUC and the 4% of the AUC cases diagnosed in our department between 2016 to 2018. Of note, is the fact that in AUC cases, hypochromatic irregular urothelial cells were the only type of cells with malignant features observed in the specimen, and therefore, according to the Paris System criteria, the absence of nuclear hyperchromasia precludes a diagnosis of suspicious high grade urothelial carcinoma (SHGUC) or High Grade Urothelial Carcinoma (HGUC). Subsequent biopsy diagnosis of high grade urothelial carcinoma confirmed the cytological diagnosis of HGUC in 55 patients but also in all 12 patients with a AUC cytologic diagnosis. Our study series support the hypothesis that malignant urothelial cells with hypochromatic nuclei seen in urine cytologic specimens can be diagnostic for HGUC based on their very large nuclei, high nuclear cytoplasmatic ratio (N/C) >0.7, irregular nuclear outlines and coarse (frequently peripheral) chromatin in the absence of hyperchromasia.

It is a diagnostic challenge to differentiate benign and malignant thyroid neoplasms made up of Hurthle (or oncocytic) cells on cytologic material. They are large, polygonal cells with marked eosinophilic, granular cytoplasm reflective of overly abundant mitochondria. These cells commonly occur in nodular goiters and dominant adenomatous or hyperplastic nodules though they may also be the predominant component of neoplastic lesions. There are significant controversies concerning the optimal management of patients with oncocytic cell carcinoma. This review provides an overview of the most significant studies addressing the distinction between benign and malignant Hurthle cell lesions on cytology and histology.

Well-differentiated carcinoma (WDC) accounts for up to 90% of all thyroid cancers. The presence of a minor poorly differentiated (PD) component (mainly insular pattern) might represent an additional critical parameter for patients' prognosis and outcome. The role of both CXCR4 (a chemokine inducing cytoskeletal rearrangement and cell adhesion) and BRAF mutation have been studied in WDC (mainly papillary thyroid cancer and its variants), highlighting their critical role in tumor progression, local infiltration, and metastases. We discussed the clonal heterogeneity through the prognostic role of CXCR4 and BRAF mutation in WDC with a minor PD/insular component. Of our 16 WDC cases with a PD/insular component, up to 40% underwent surgery. The cases were subclassified according to the PD percentage as (1)

The treatment of non muscle-invasive bladder cancer (NMIBC) encompasses a range of different procedures. Electromotive drug administration (EMDA) and chemo-hyperthermia (C-HT; Synergo) represent a minimally-invasive methods of intravesical instillation of therapeutic agents as mitomycin C (MMC). We selected patients with high grade NMIBC, BCG non responder, treated with EMDA/MMC and C-HT/MMC and we also examined the morphological changes in urine cytology samples. During the period from 2012 to 2014, 110 patients with high grade NMIBC, BCG refractory were selected. All cases examined were classified according to The Paris System Classification as negative for high urothelial carcinoma (NHGUC) or atypical urothelial cells (AUC) with a mean of follow-up of 15 months and the cytological diagnosis were confirmed by histological biopsies. In particular 50 patients were treated with EMDA/MMC and 60 patients underwent to C-HT/MMC. The morphological changes were evaluated in urine samples processed by Thin Prep method. In the 50 patients treated with EMDA/MMC, 35 samples were classified as NHGUC and 15 cases were classified as AUC, while in the 60 patients treated with C-HT/MMC, 43 samples were NHGUC and 17 cases were classified AUC. The increase of cellularity and nuclear size with the alteration of nuclear/cytoplasmatic ratio (N/C) were common in patients treated with EMDA/MMC and C-HT/MMC without clinical and histological evidence of recurrence of neoplasia. The hyperchromasia and irregular nuclear chromatin were rarely observed. The irregular nuclear membrane rarely identified in urine cytology after EMDA/MMC treatment, is a feature present in patients C-HT/MMC treated.

Objective FNA biopsy is considered as the most accurate method for the selection of patients with thyroid nodules that need for surgery or for the wait and see management. The aim of the present study is to clarify the risk of malignancy for the cytological data classified according to the 2014 Italian reporting system. Methods We report a retrospective analysis of 4043 patients in our institution's experience during the period April 2014 through December 2016 with the Italian reporting system for thyroid cytology. Results The diagnostic incidences of the 4043 cases were as follows: 9.8% TIR1; 1.3% TIR1C; 70% TIR2; 6.6% TIR3A; 4.5% TIR3B; 2.4% TIR4; 5.2% TIR5. A repeated aspiration was carried out in 68 out of 269 cases (25%) classified as TIR3A. A total of 407 cases with cytology underwent surgical resection. A malignant neoplasm was detected in 261 out of 407 (64%) cases. Regarding TIR3B, surgical excision was undertaken in 109 cases, which included 42 high-risk lesions and 67 Hurthle cell neoplasms. The risk of malignancy was significantly higher in the former compared to the latter (50% vs 9%; P

The thyroid is a rare site of clinically detectable tumor metastases; even though the gland is a highly vascularized structure, the frequency of metastases in the routine practice is less than 0.2% of all thyroid malignancies. The purpose of our meta-analysis is to evaluate the frequency of metastatic diffusion from other primary tumors to the thyroid gland and to suggest the best possible treatment through an evidence-based study. Relevant studies were identified by searching the following databases: PubMed, Scopus, and Web of Science. We selected all English-written articles published from 1995 to 2015. Studies were considered eligible if they reported the timing of metastatic spread and the site of the primary tumor in respect to the diaphragmatic region. Case reports were not included. Twenty-eight studies accounted for 514 patients. The rate of metachronous metastases was 69%. Fifty-three percent of primaries originated from the infradiaphragmatic region. Fine needle aspiration biopsy (FNAB) was done in 154 patients and 195 patients were treated mostly with surgery. A prevalence of primary tumors from the infradiaphragmatic region and of metachronous metastases was observed. Knowledge of the clinical history and the ancillary techniques can improve the sensitivity and accuracy of FNAB. Thyroidectomy may be considered a more effective treatment than radio-chemotherapy.

Background Thyroid Metastases (TM) represent a rare entity with an estimated variability ranging between 0 and 24%. Fine needle aspiration cytology (FNAC) might be useful in discriminating between primary and TM nodules especially when ancillary techniques (i.e., immunocytochemistry-ICC) are carried out. Methods We herein appraised a series of 20 TM on FNAC analyzed between 2000 and 2013. We included eight male and 12 female patients. The cytological cases were processed with both liquid based (LBC) and conventional cytology. Results We reported 2.2% TM out of 910 malignancies. Our TM cases resulted as: six lung (LG), five gastro-intestinal (GI), five breast (B), three larynx (LX), and one clear cell renal carcinoma (CCRC) metastases. All the patients had a previous known cancer history. Although the cytological features were likely to suspect a TM, the application of ICC panels was contributive in 100% cases. None of TMs resulted as a unique localization whereby two cases underwent total thyroidectomy (including one B and one CCRC) and 18 TM were treated with radio-chemotherapy approaches. Conclusions FNAC empowered the diagnostic workup of patients with TM avoiding useless surgical approach. The low sensitivity of cytology might be reinforced by the application of ancillary techniques. In contrast with the reported predominant rate of kidney metastatic carcinomas, our findings underlined that intestinal cancer as well as lung and breast are the most common TM. TM are frequently multifocal and in a contest of a systemic disease so that a tailored therapy seems to be the best treatment Diagn. Cytopathol. 2015;43:374–380. © 2014 Wiley Periodicals, Inc.

BACKGROUND It has been generally demonstrated that the valine-to-glutamic acid substitution at position 600 (V600E) in the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene is an effective diagnostic/prognostic marker mainly for papillary thyroid carcinoma (PTC). The detection of this mutation typically has been achieved using DNA-based techniques. The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. The authors investigated molecular and immunocytohistochemical BRAF analyses in a prospective series of samples from patients with PTC. METHODS Fifty-five prospective cytohistologic samples that were diagnosed as PTC were studied using both DNA BRAF testing and the VE1 antibody. The intensity of VE1 expression was graded from 0 (negative) to 3+ (strong). RESULTS All diagnoses were histologically confirmed. In total, 37 samples with mutated BRAF and 18 samples with wild-type BRAF were reported with 100% cytohistologic concordance. Cytologic VE1 expression revealed 25 negative samples (including 16 with 0 expression and 9 with 1+ expression) and 30 positive samples (including 16 with 2+ expression and 14 with 3+ expression). On histology, there were 27 negative samples (20 with 0 expression and 7 with 1+ expression) and 28 positive samples (14 with 2+ expression and 14 with 3+ expression). Four specimens with the BRAF mutation had discrepancies in VE1 intensity between cytology and histology. Furthermore, 6 BRAF-mutated samples produced negative VE1 results. CONCLUSIONS Although it has limitations, the VE1 antibody represents a feasible first-line approach for evaluating BRAF mutation status and may be a valid tool in the selection of samples for molecular analysis. The current report highlights the statistically significant difference between molecular and VE1 positivity in PTC (P

ObjectiveIn the field of fine-needle aspiration cytology, the category of suspicious for malignancy (SM) thyroid lesions, that bears 55–85% risk of malignant histology, is a challenging topic in which morphology alone is not always able to make a correct diagnosis. Recently, immunocytochemistry (ICC) has been referred to as helpful in differentiating low- and high-malignant risk lesions andBRAFactivating mutations have been identified in a significant amount of papillary thyroid carcinomas (PTC). The introduction of the liquid-based cytology (LBC) may simplify the application of these techniques to thyroid cytology.DesignOur aim is to evaluate the diagnostic and prognostic role of both ICC andBRAFmutation for the SM category on LBC.MethodsFrom October 2010 through June 2011, 113 LBC cytological cases (including 37 SM and 76 PTC) underwent surgery. All cases were studied forBRAFmutation and ICC.ResultsICC resulted positive in 26 (86.6%) histologically malignant SM with 15 of which (40.5%) expressing aBRAFmutation. Overall, 63 cases showed aBRAFmutation resulting in PTC. Concerning the prognostic role ofBRAFmutation for the two categories, we reported a significant correlation with multifocality, nodal involvement and extra-capsular invasion (PConclusionsSpecial techniques such as ICC and molecular markers might be successfully carried out on LBC-processed material. For both categories, ICC is more sensitive whereasBRAFanalysis is an interesting support due to its high specificity adding a prognostic value in both SM and PTCs.

// Esther Diana Rossi 1,* , Tommaso Bizzarro 1,* , Maurizio Martini 1 , Patrizia Straccia 1 , Celestino Pio Lombardi 2 , Alfredo Pontecorvi 3 , Luigi Maria Larocca 1,** and Guido Fadda 1,** 1 Division of Anatomic Pathology and Histology, Universita Cattolica del Sacro Cuore, “Agostino Gemelli” School of Medicine, Rome, Italy 2 Division of Endocrine Surgery, Universita Cattolica del Sacro Cuore, “Agostino Gemelli” School of Medicine, Rome, Italy 3 Division of Endocrinology, Universita Cattolica del Sacro Cuore, “Agostino Gemelli” School of Medicine, Rome, Italy * These authors have contributed equally to this work ** These authors share the seniorship Correspondence to: Esther Diana Rossi, email: // Keywords : elderly patients, thyroid lesions, malignancies, liquid based cytology, immunocytochemistry, Gerotarget Received : December 16, 2015 Accepted : January 30, 2016 Published : February 23, 2016 Abstract We assess the role of thyroid fine needle aspiration cytology(FNAC) in our series of elderly patients. The growing subset of people aged older than 70 years has shown an increased incidence of thyroid diseases which need to be studied in order to reduce the percentage of surgical treatments in patients with higher likelihood of co-morbidities and associated life risk. We compared Follicular/Indeterminate Neoplasms(FN) and suspicious of malignancy(SM) with pediatric and adult cohorts. We discussed the role of immunocytochemistry-ICC to refine diagnoses. Four hundred and eighty out of 3539FNACs(13.5%) in elderly patients, were surgical followed-up. They included: 35Inadequate, 188benign(BL), 164FN/AUS, 49SM and 44positive for malignancy (PM). All PM and 95.7%BL were histological confirmed. The malignant rate was 24.3% mostly diagnosed as papillary thyroid carcinomas. An ICC panel (HBME-1 and Galectin-3) was carried out on liquid based cytology (LBC) and performed on FN/AUS, SM and PM.We found concordant positive ICC in 69.3%malignancies and concordant negative ICC in 97.6%benign follicular adenomas. Among FNs, 42.9%malignant histologic cases had concordant positivity whilst 97.4%benign histology had negative panel.Thyroid FNAC shows high feasibility in elderly patients. ICC helps in reducing the number of useless thyroidectomies and providing a more adequate clinical and/or surgical selection in elderly patients.

Thyroid Metastases (TM) represent a rare entity with an estimated variability ranging between 0 and 24%. Fine needle aspiration cytology (FNAC) might be useful in discriminating between primary and TM nodules especially when ancillary techniques (i.e., immunocytochemistry-ICC) are carried out.We herein appraised a series of 20 TM on FNAC analyzed between 2000 and 2013. We included eight male and 12 female patients. The cytological cases were processed with both liquid based (LBC) and conventional cytology.We reported 2.2% TM out of 910 malignancies. Our TM cases resulted as: six lung (LG), five gastro-intestinal (GI), five breast (B), three larynx (LX), and one clear cell renal carcinoma (CCRC) metastases. All the patients had a previous known cancer history. Although the cytological features were likely to suspect a TM, the application of ICC panels was contributive in 100% cases. None of TMs resulted as a unique localization whereby two cases underwent total thyroidectomy (including one B and one CCRC) and 18 TM were treated with radio-chemotherapy approaches.FNAC empowered the diagnostic workup of patients with TM avoiding useless surgical approach. The low sensitivity of cytology might be reinforced by the application of ancillary techniques. In contrast with the reported predominant rate of kidney metastatic carcinomas, our findings underlined that intestinal cancer as well as lung and breast are the most common TM. TM are frequently multifocal and in a contest of a systemic disease so that a tailored therapy seems to be the best treatment.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provides a 6-tier diagnostic framework using uniform criteria in reports of thyroid aspirates. One of the major advantages of this framework is its association with defined risks of malignancy, allowing standardized management algorithms for each diagnosis. The objective of the current meta-analysis was to demonstrate the feasibility of using TBSRTC among specimens in the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm or suspicious for neoplasm (FN/SFN) categories. The authors also evaluated both the morphologic features and the risk of malignancy in the presence of Hurthle cells.A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2008 to December2014. Studies were considered eligible only if they evaluated the risk of malignancy for specimens in the AUS/FLUS and/or FN/SFN categories and included surgical follow-up.In total, 51 articles were identified that used TBSRTC criteria and provided data for a total of 145,928 fine-needle aspiration (FNA) specimens. Of these, FNAs that had surgical follow-up were selected among the AUS/FLUS (N = 4475) and FN/SFN (N = 3202) specimens. The overall rate of malignancy was 27% for the AUS/FLUS category and 31% for the FN/SFN category.The AUS category was characterized by limited reported follow-up and surgical outcome. The data demonstrated that FNAs with an AUS diagnosis had a higher risk of malignancy than the risk according to published TBSRTC criteria, whereas the percentage of malignancy in FNAs with an FN/SFN diagnosis did not differ from that according to TBSRTC. Hurthle cell lesions represent a challenging category, underlying the importance of further studies to define whether they can be diagnosed in the AUS/FLUS category rather than the FN/SFN category.

Objectives Our aim was to evaluate the feasibility and diagnostic accuracy of liquid-based cytology (LBC) on lymph node fine needle aspiration (FNA). FNA may fulfil a challenging role in the evaluation of the majority of primary (benign and malignant) diagnoses as well as metastatic lymph node lesions. Although the morphological features may be quite easily recognized, cytological samples with a scant cellular component may raise some issues. Methods We appraised 263 cytological lymph nodes from different body regions analysed between January and December 2013, including 137 male and 126 female patients, and processed with LBC. Results The cytological diagnoses included 160 benign and 103 malignant lesions. We reported 35 benign and 73 malignant lesions from 108 with surgical follow-up. The latter malignant series included 68 metastatic lesions, four suspicious for malignancy and one inadequate sample. The cytological diagnoses were supported by 62 conclusive immunocytochemical and 28 molecular analyses. Of the 108 cases, we documented 35 true negatives, 72 true positives, one false negative and no false positives, resulting in 98.6% sensitivity, 100% specificity, 99% diagnostic accuracy, 97.2% negative predictive value and 100% positive predictive value. Conclusions FNA represents the first diagnostic tool in lymph node management and a reliable approach in order to avoid an excision biopsy. Furthermore, LBC is a feasible method for ancillary tests for which methanol-fixed samples are suitable, such as immunocytochemistry and molecular analysis.

Thyroglossal duct cancer is a rare entity, occurring in 1.5 % of all thyroglossal duct cysts (TDC). A definitive consensus about its neoplastic origin has not been established as two contrasting theories exist, one proposing an origin in extra-thyroid remnants and the other a metastatic localization of a primary thyroid cancer. We compare morphological and molecular characteristics of both thyroglossal and thyroid carcinomas in a case series from our institute. We evaluated histology of 80 TDC. In 12 cases, prior cytological evaluation had been performed by liquid-based cytology (LBC). The BRAF gene was examined for mutations, and the histology of both thyroglossal duct and synchronous thyroid carcinoma was reevaluated. In 9 out of 80 (11 %) TDC cases, a papillary thyroid cancer (PTC) was diagnosed. In five out of nine (56 %) thyroglossal carcinomas, a synchronous thyroid cancer was diagnosed: 3 PTC and 2 follicular variant PTC (FVPC). In five thyroglossal carcinomas, mutated BRAF (V600E) was found, three in PTC and in thyroglossal as well as in the synchronous tumor in the thyroid. All the patients are in a disease-free status and still alive. Our results suggest that the majority of thyroglossal carcinomas most likely develop as a primary malignancy from a thyroid remnant. Neither the presence of V600E BRAF mutations nor that of a well-differentiated thyroid carcinoma changed the outcome or disease-free survival. We suggest that a diagnosis of thyroglossal carcinoma should be followed by a detailed evaluation of the thyroid gland. In the absence of clinical and radiological thyroid alterations, follow-up as for thyroid cancer is the correct management.

Objective Large non-functioning parathyroid cysts represent a rare entity with a benign clinical course. They may be misdiagnosed as thyroid cystic neoplasms on fine needle aspiration cytology (FNAC), resulting in inappropriate surgical treatment. We evaluated our institutional experience in the diagnosis of large parathyroid cystic lesions underlining all the differential diagnoses and pitfalls. Methods In the period between 1998 and 2012, we reported the cytology of eight large (>2.5 cm) parathyroid cystic lesions (all female patients) with histological control. The aspirations were performed with a 25-gauge needle with ultrasonographic guidance. The aspirated material was processed with liquid-based cytology (LBC). All the patients had normal serum parathyroid hormone (PTH) and calcium. Results The cytological samples showed a fluid watery component without colloid and few or absent epithelial cells. The resulting negativity for thyroglobulin and positivity for PTH, carried out on the cystic fluids, suggested parathyroid lesions rather than either thyroid cystic lesions (including follicular thyroid neoplasm) or cystic malignant lesions. All the patients underwent surgery without complications. Conclusions To the best of our knowledge, this is one of the largest series with cytohistological evaluation of large parathyroid cysts. The incidence of large parathyroid cysts remains controversial as most patients are asymptomatic. FNAC may be performed with conclusive results in the majority of cystic cases. The detection of PTH and calcium on the cystic liquid is likely to achieve a correct cytological diagnosis, allowing adequate treatment and ruling out a more frequent thyroid lesion.

BACKGROUND The current study was conducted to investigate the role of thyroid fine-needle aspiration cytology (FNAC) in the authors' pediatric series. Thyroid pediatric FNAC has been reported to have conflicting sensitivity and specificity in different series. The authors evaluated their thyroid cytological series mainly for the categories of 1) follicular/indeterminate neoplasms with atypical cells of indeterminate significance (FN/AUS) and 2) suspicious for malignancy (SM). In this setting, the application of immunocytochemistry (ICC) is likely to allow a correct diagnosis. METHODS A total of 64 of 247 pediatric FNACs (26%) that were processed with liquid-based cytology had surgical follow-up. An ICC panel (Hector Battifora mesothelial cell-1 [HBME-1] and galectin-3) was performed on liquid-based cytology. A positive immunopanel was defined by a concordant positivity. RESULTS These 64 cases were cytologically diagnosed as 4 cases of cystic hemorrhagic lesions, 23 benign lesions (BL), 17 FN/AUS cases, 11 SM cases, and 9 positive for malignancy (PM) cases. All PM and BL cases were histologically confirmed. The rate of malignancy was 31.2%, including 1 case of follicular carcinoma, 9 cases of classic papillary thyroid carcinomas (PTC), and 10 PTC variants (7 follicular variant of PTC, 1 macrofollicular variant, and 2 sclerosing diffuse variants). The immunopanel was performed on the categories of FN/AUS, SM, and PM. The data highlighted a concordant positive ICC in 87% of malignancies and a concordant negative ICC in 100% of benign follicular adenomas. CONCLUSIONS Thyroid FNAC represents a valuable/feasible tool in childhood. The higher incidence of histological malignancies justifies the cytological application of ancillary techniques (ie, ICC or molecular panels), thereby enabling a more adequate surgical selection based on the effective distinction of high-risk and low-risk lesions mainly for the categories of FN/AUS and SM. Cancer (Cancer Cytopathol) 2014;122:359–367. © 2014 American Cancer Society.

Aim Thyroid cancer represents the first endocrine malignant neoplasm, accounting for 1% of human malignancy. The majority of which are well-differentiated cancer representing up to 90% of thyroid cancer and pursuing a favorable clinical course. The groups of poorly differentiated thyroid cancer (PDC) and anaplastic thyroid cancer (ATC) have a poor outcome and need a strict clinical surveillance. Materials and methods Thirty-four cases including 23 PDC/insular cancer and 9 ATC were examined for the expression of an immunohistochemical panel made up by HBME-1, galectin-3, and β-catenin and correlated either with histologic prognostic parameters or the overall surveillance. Results HBME-1 and galectin-3 were expressed in 100% of the PDC/insular cases and in none of the ATC cases. The data for β-catenin pointed out an 80% expression (12/15) in the PDCs and only a focal and nonspecific positivity in the ATCs. A β-catenin-positive expression was found in all patients with a worse outcome/death and in the presence of vascular invasion and metastatic disease. All 3 PDC patients with β-catenin negativity are alive, whereas only 41% (5/12) are alive in the β-catenin-positive group. Conclusions Our data set up the idea that PDC represents an intermediate step in the biological process of dedifferentiation of thyroid tumors toward ATC. This shift is underlined by the β-catenin expression, which seems to be related to a worse prognostic behavior. HBME-1 and galectin-3 show a similar pattern in PDC compared with well-differentiated carcinoma, whereas they are not expressed, as well as β-catenin, in anaplastic carcinomas.

The presence of ectopic thyroid tissue is a frequent diagnostic feedback related to a possible histogenetic abnormality or a result of post-surgical seeding. The important challenge is the diagnostic definition of its nature, which could lead to a different therapeutic approach. We describe a case with all the possible implications and differential diagnoses supported by the application of immunohistochemistry and BRAF-V600E molecular detection. A 36-year-old girl with a left thyroid nodule underwent surgery with a diagnosis of angio-invasive tall cell variant of papillary carcinoma without lymph-node metastases. The patient history revealed a previous right lobectomy in another institution ten years before. The right neck dissection was histologically characterized by the presence of thymic residual and evidence of microfollicular microfoci (less than 1mm) of thyroid tissue. Thyroid tumor cells were positive for thyroglobulin, TTF-1, HBME-1 and Galectin-3, while the residual ectopic thyroid tissue showed positivity only for TTF-1 and thyroglobulin. The molecular tests on the thyroid nodule revealed the presence of BRAF-V600E mutation, but wild type BRAF in the ectopic tissue. The histo-morphological definition of these remnants plays the most important role, but the application of immunohistochemistry and molecular biology may help to reach a conclusive diagnosis.