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Background. The diagnosis of follicular lesions is a grey zone in thyroid fine-needle aspiration (FNA) cytology. Our study aims to verify if staining with Emerin is a helpful marker of the follicular variant of papillary thyroid carcinoma (FVPTC) in the differential diagnosis of follicular-patterned lesions. Methods. We designed both a prospective study on smears and Thin Prep specimens to prove the feasibility of the procedure and a retrospective study on 78 FNA cell-blocks from cases which, after surgery, turned out to be either benign (34 cases) or malignant lesions (44, of which 31 PTC). From each sample, we obtained two slides, one stained with Hematoxylin and Eosin (H&E) and the other with immunohistochemistry (IHC) for Emerin. In Thy3 cases, HBME-1 and Gal 3 stains were also done. Two observers gave a judgement in Thy categories (British Thyroid Association) on H&E, Emerin, HBME-1 and Gal 3 stained slides. Results. The prospective study demonstrated that Emerin staining is an effective tool for nuclear membrane decoration and amplification of nuclear irregularities. In the retrospective study, inter-observer agreement proved higher in Emerin-stained slides (K of Cohen-Fleiss = 0.6890) than H&E-stained slides (K of Cohen-Fleiss = 0.4878). Sensitivity and overall accuracy were higher for Emerin (respectively, 77.27% and 84.61%) than H&Estained slides (respectively, 36.36% and 62.82%). Emerin staining proved able to identify all cases of PTC, including all cases of FVPTC. In Thy3 cases, Emerin’s sensitivity and specificity (64% and 96%) proved higher than HBME-1’s (60% and 88%), and Gal3’s (61% and 68%). Conclusions. Emerin stain, is a useful tool in the cytological diagnosis of thyroid lesions. It enhances detection of nuclear irregularities typical of PTC, thus helping to solve inconclusive FNA cases, mainly in those cases of FVPTC with a reduced expression of nuclear irregularities in the traditional stains (H&E).

Although endoscopic ultrasound combined with fine needle aspiration (EUS-FNA) is rapidly becoming the preferred diagnostic approach for the sampling and diagnosis of gastrointestinal and mediastinal malignancies, there are limited data as to its use in the diagnosis of lymphoproliferative disorders. Therefore, we carried out a retrospective evaluation of the performance of EUS-guided FNA combined with flow cytometry (FC) as a tool to improve overall sensitivity and specificity in the diagnosis of lymphoma.Of 1560 patients having EUS-guided FNA during the period of the study, a total of 56 patients were evaluated by cytology with FC after EUS-FNA. There was adequate material to perform FC analysis for all but one case.EUS-FNA-FC gave a diagnosis of lymphoma in 11 cases and of reactive lymphadenopathy in 20. A specific histological type was defined by FC alone in eight cases. The remaining cases were diagnosed later by cytology and cell block sections: 13 carcinomas, nine granulomatous lymphadenopathies and one mediastinal extramedullary haematopoiesis. One case was considered only suspicious for lymphoma on cytology and FC but was not confirmed on molecular analysis and one had insufficient material for FC.Our results show that a combination of EUS-FNA-FC is a feasible and highly accurate method, which may be used for the diagnosis and subtyping of deep-seated lymphoma, providing a significant improvement to cytomorphology alone both for diagnosis and treatment planning, as long as immunocytochemistry is available for non-lymphoma cases.

Background: Pancreatic Neuroendocrine Tumors (PNTs) are relatively uncommon tumors that account for 1 to 2% of all pancreatic neoplasms. The aim of this report is to describe the cytomorphologic and immunocytochemical features of PNTs obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and to compare them with the histological results. Design: Forty cases diagnosed with PNTs based on EUS-FNA were studied retrospectively (from 2003 to 2010). Clinical data, EUS findings, cytological and immunocytochemical features were reviewed with particular attention to the on-site slides. The final histopathologic diagnosis from twenty-three patients was also available for comparison. Results: The case series was of 40 patients (20 men, 20 women), ranging in age from 30 years to 75 years. The mean size of the tumors by EUS was 29 mm (range, 8-100 mm). The average number of FNA per patient to obtain adequate material was 3. The most helpful cytologic findings for the diagnosis of PNTs were: i) high cellularity sample ii) monotonous, poorly cohesive population of small or medium-sized cells iii) granular chromatin (salt and pepper) and iv) plasmacytoid morphology. Immunocytochemistry (positivity for chromogranin A and/or synaptophysin) on cell blocks confirmed the neuroendocrine differentiation of tumors in all patients and Ki67 index was effective for distinguishing well differentiated from high/grade PNTs (p=0.001). The cytological diagnosis of PNT was histologically confirmed in 23 cases (57%) submitted to surgical resection Conclusions: EUS-FNA is an efficient and accurate procedure for the diagnosis of PNTs and may have a role in determining management strategy.

Introduzione. La citologia su striscio delle vie biliari extraepatiche effettuata con spazzolino (brushing endoscopico) è il metodo più utilizzato per la valutazione delle lesioni delle vie biliari extraepatiche, ma presenta scarsa sensibilità. Per migliorarne la potenzialità diagnostica, presentiamo una nuova ed originale metodica che permette di effettuare un esame citologico ottimale del materiale ago-aspirato. Metodi. Lo spazzolino viene immediatamente immerso in metanolo e inserito nelle biocassette per l’inclusione in paraffina. Vengono tagliate delle sezioni parallele e consecutive lungo l’asse maggiore, fino al core metallico; successivamente il blocco di paraffina viene ruotato di 180° e nuove sezioni vengono effettuate sul lato opposto. Le sezioni, colorate in Ematossilina e Eosina e con Alcian Blue Mucine, hanno mostrato piccoli frammenti di mucosa, di cellule infiammatorie aggregate o di carcinoma, con un’ottima fissazione, permettendo una diagnosi definitiva accurata in quasi la totalità dei casi esaminati. Infatti 112 campioni citologici di brushing endoscopici delle vie biliari extraepatiche (67 M; 45 F), raccolti all’Ospedale “Molinette”, Università di Torino, tra Gennaio 2002 e Agosto 2006, sono stati inclusi nel nostro studio. Tutti i pazienti avevano una diagnosi definitiva istologica e un follow-up clinico medio di 21 mesi. Risultati. Confrontando questa originale metodica su 112 casi consecutivi di brushing endoscopico con la diagnosi istologica su pezzo operatorio, abbiamo osservato: 87% di sensibilità, 100% di specificità, 100% di valore predittivo positivo (VPP) e 91% di valore predittivo negative (NPV). La metodica inoltre, confrontata con la diagnosi clinica dopo almeno 6 mesi di follow-up, ha mostrato: 88% sensibilità, 100% specificità, 100% VPP e 96% VPN. Conclusioni. In conclusione questa nuova metodica è altamente sensibile e specifica, limitando all’1% le diagnosi non idonee, con una concordanza con la diagnosi istologica pari all’88% (K-value).

Neuroendocrine (NE) cells are uncommon in primary adenocarcinoma (AC) and other glandular lesions of the bladder, with no recent study series concerning its significance in differential diagnosis, prognosis or biologic significance.Sixteen primary bladder AC (enteric-type [n = 71, mucinous [n = 6] and not otherwise specified [NOS] [n = 31), 4 cases of urothelial carcinoma with glandular differentiation, 20 cases of glandular cystitis and 3 urachal remnants with intestinal metaplasia constituted the study series. In addition, 20 specimens of normal-looking urothelium, 15 conventional urothelial carcinomas and 5 small cell carcinoma (SCC) cases were included for comparison. NE differentiation included detection of chromogranin A, neuron-specific enolase (NSE) and synaptophysin by immunohistochemistry. The statistical analysis included the chi2 or Fisher exact test.Chromogranin A-positive cells were present in 60% (11 of 16) of primary AC, all of enteric or mucinous type, but not in any of the 3 NOS-type AC investigated. NE differentiation in bladder AC subtypes resulted in highly significant differences between enteric or mucinous vs. NOS type (p = 0.0023). NE differentiation was also different in urachal vs. nonurachal AC (p = 0.020) and primary bladder AC vs. conventional invasive urothelial carcinoma (p0.001). Synaptophysin-positive cells were seen in 2 (12.5%) of the 16 primary AC cases, and NSE was negative in the 16 primary bladder AC. All urachal remnants and 70% of glandular cystitis examples had chromogranin A-immunoreactive cells. One of 4 urothelial carcinomas with glandular differentiation had chromogranin A-immunoreactive cells, but this was not significant when compared with primary AC (p = 0.1). Normal-looking bladder urothelium and conventional urothelial carcinoma specimens had no chromogranin A-immunoreactive cells. The 5 SCC cases investigated were positive for chromogranin A. No correlation was found between NE differentiation and outcome of primary bladder AC or urothelial carcinoma with glandular differentiation.Primary bladder AC, cystitis glandularis and urachal remnants with intestinal metaplasia showed variable degrees of NE differentiation, with no apparent clinical correlation or prognostic significance. However, the absence of NE differentiation in NOS-type primary bladder AC may help in better defining this uncommon subtype of primary bladder AC.

Using flow cytometry, gross genomic alterations, defined as DNA ploidy, and the fraction of S-phase cells, can be calculated in bladder cancer cells. In aneuploid superficial bladder cancer the recurrence rate has been reported to be three times higher than in diploid forms. A correlation between the S-phase fraction and progression has been reported for G1-G2/Ta-T1 tumours, but not for G3/Ta-T1. The aim of our study is to evaluate whether the traditional cytometric parameters can be used as valid predictors of early recurrences and progression in G1-G2/Ta-T1 and G3/Ta-T1 bladder cancer patients and to compare the proliferation indexes as defined by S-phase fraction and 67Ki monoclonal antibody in the two groups of patients.

Recent studies have investigated the possibility that p53 protein and some macroscopic tumoral features, such as diameter and focality of the lesion, play a significant prognostic role in bladder cancer progression. A retrospective study was conducted on papillary grade-I stage-Ta transitional cell carcinoma (TCC) of the bladder.p53 expression was evaluated using the immunohistochemical method. A group of 31 patients with papillary grade-I and stage-Ta TCC of the bladder with no recurrence or who recurred with no histological grading and staging variation in a 4-year mean follow-up period was compared with 28 grade-I and stage-Ta papillary TCC patients who underwent recurrences and a worsening in histological grading (grade II or grade III) or staging (T1) within the same period of time. The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein products of the mutated p53 tumor-suppressor gene, when independently evaluated in comparison with other tumoral prognostic factors, are associated with tumor recurrence and progression in patients with Ta papillary grade-I TCC of the bladder.Our data show that when a p53 threshold of0% was considered, 53.6% of patients with tumor progression in the follow-up period were p53-positive compared with only 16.1% of the nonprogressing group (chi 2 = 6, p = 0.02). On the contrary, p53 failed to show any value in predicting progression when a 5% threshold was considered (chi 2 = 1.12, p = 0.92). The multifocality of the tumoral lesion and recurrent tumor was highly predictive of tumor progression for both variables (chi 2 = 5.16, p = 0.003, and chi 2 = 0.23, p = 0.006, respectively). Multivariate analysis revealed p53 nuclear overexpression (at a threshold of0%) to be a single valuable prognostic factor of progression (OR = 10.20, p = 0.009) and recurrence (OR = 54.19, p = 0.01).Our results lead to the conclusion that p53 immunohistochemical detection has no prognostic value in predicting tumoral relapse or progression of TaGI TCC of the bladder when a 5% positivity threshold is considered. On the contrary, when a p53 nuclear labelling of0% is considered as positive staining, this tumor marker becomes highly predictive of tumor recurrence and progression. These findings seem therefore to suggest the use of a slight p53 positivity (0%) as a valid tool in predicting the clinical behavior of TaGI bladder TCC. The prognostic impact of a multifocal lesion and a recurrent tumor as markers of progression is also confirmed by these results.

Albumin is a specific product of normal and transformed hepatocytes, but unfortunately its immunohistochemical demonstration proves unreliable because of diffusion artifacts. An in situ hybridization procedure to reveal albumin mRNA was applied to fine needle aspiration specimens of liver nodes with the aim of testing the usefulness of this marker in the cytological diagnosis of hepatocellular carcinomas (HCC). A 51-base pair oligonucleotide probe was labeled with digoxigenin and used on paraffin sections of alcohol-fixed cell blocks. A series of 97 cases originally interpreted, on the basis of cytology alone, as "hepatocellular carcinoma" (62 cases), as "carcinoma cells, not otherwise specified" (15 cases), as "adeno-carcinoma" (16 cases), and as "non-epithelial neoplastic cells" (4 cases), was studied. In all cases, clinical and follow-up information was obtained; a diagnosis of HCC was reached with certainty in 44 cases and suspected in 22. Thirty-one other cases were proven to be bile duct adenocarcinomas or metastatic tumors. Taking into account proven cases only, albumin mRNA was found in 42/44 HCC and in none of the control cases (sensitivity, 95.5%; specificity, 100%). Of 22 cytologically suspected HCC, albumin mRNA was positive in 19 cases. Also, high grade pleomorphic HCCs expressed albumin gene, and this finding is of value in the differential diagnosis with liver metastases of anaplastic tumors from lung, adrenal, pancreas, etc. The diagnosis of HCC on a cytological basis is becoming increasingly important because most cases are unresectable and have to be included in different therapeutic protocols.(ABSTRACT TRUNCATED AT 250 WORDS)