Do we really need fine-needle biopsy needle for an ultrasound-guided biopsy of pancreatic adenocarcinoma? A retrospective study.

OBJECTIVE: Endoscopic ultrasound (EUS)-guided FNB was not demonstrated to be better than EUS fine-needle aspiration (FNA) to obtain adequate samples for diagnosis of pancreatic tumors. We report our experience using a 22-gauge needle aspiration to obtain both cytologic and histologic samples. PATIENTS AND METHODS: In a total of 232 patients (51% men), 22-gauge needles (Cook Medical) were used to obtain a cytological sample (between 2008 and 2016, Cohort A) and a cytologic and a histologic sample (between 2016 and 2019, Cohort B) to evaluate the usability of this needle to collect material for cytologic and histologic examination. MOSE was used. RESULTS: Pancreatic adenocarcinoma was diagnosed in 76/113 (68%) patients in Cohort A and in 88/119 (74%) in Cohort B. Non-diagnostic sampling occurred in 30/113 (26%) patients in Cohort A and in 25/119 (21%) in Cohort B. The median number of passages was three in both cohorts. Lesions were in the head/uncinated process 57% vs. 51% and body/tail 43% vs. 49% in Cohorts A and B, respectively; the mean tumor size was 34.5 mm (SD 10.7) in Cohort A and 35.4 mm (SD 14.7) in Cohort B. CONCLUSIONS: FNA needle (22-gauge) with adequate passes, MOSE determination and adequate processing of specimens, provided FNA and FNB specimen collection.

A multicenter validation of the revised version of the Milan system for reporting salivary gland cytology (MSRSGC).

INTRODUCTION: Fine-needle aspiration cytology (FNAC) is a basic step in the diagnosis of salivary gland tumors that have a wide variety of histological types. The recent Milan system for reporting salivary gland cytopathology (MSRSGC) can correlate the risk of malignancy with precise cytological features. A revised version was recently proposed to improve the surgical relevance and facilitate uniform management. MATERIAL AND METHODS: A multicenter study retrospectively used the original and revised MSRSGC criteria to classify a series of patients who received surgery after FNAC. RESULTS: We enrolled 503 patients from three tertiary centers. The risk of malignancy for the MSRSGC resulted 19.5% in cat. I, 14.3% in cat. II, 17.6% in cat. III, 3.6% in cat. IVa, 24.6% in cat. IVb, 66.7% in cat. V, and 96.8% in cat. VI. The results from the revised MSRSGC were consistent with the original values. CONCLUSION: The MSRSGC is a promising classification system. In our opinion, the revised version of the MSRSGC supplements FNAC with some crucial clinical information and can better identify the appropriate treatment in each category.

Cytology and direct human papillomavirus testing on fine needle aspirates from cervical lymph node metastases of patients with oropharyngeal squamous cell carcinoma or occult primary.

OBJECTIVE: Cervical lymph node fine needle aspirates (FNAs) may represent the only specimens available for an initial characterisation of patients with lymphadenopathy. Morphology and human papillomavirus (HPV) DNA presence were evaluated in FNAs collected from patients with oropharyngeal squamous cell carcinoma (OPSCC) or cancer of unknown primary (CUP). FNA HPV results were compared with those of the respective formalin-fixed paraffin-embedded (FFPE) primary cancer. METHODS: Liquid-based cytology was performed on FNAs collected in PreservCyt. HPV-DNA was analysed by the INNO-LiPA HPV genotyping Extra II on both cytological and FFPE samples. The CINtec® Histology Kit was used to assess p16 expression in cancer tissues. RESULTS: Forty-seven FNAs were collected from OPSCC and 16 from CUP patients. Cancer cells were found in 35/47 cases (74.5%), while 11 (23.4%) showed only necrosis and one (2.1%) was negative for malignancy. HPV-DNA was detected in 30/47 FNAs (63.8%), mostly harbouring HPV16 (90.0%). An excellent agreement was observed between the FNA and corresponding FFPE HPV status (raw agreement: 97.5%; Cohen κ: 0.94). The HPV test result on the necrotic FNAs completely matched that of the respective primary cancer. FNA HPV testing correctly identified 26/27 HPV-driven OPSCCs (96.3%). HPV was detected in nine of 16 FNAs (56.2%) from CUP patients. CONCLUSIONS: HPV status of metastatic cervical lymph node FNAs reflects that of the corresponding primary OPSCCs even when cell integrity in the FNA is not preserved and only necrotic debris are present. In patients with initial CUP, HPV-positivity on the FNA may guide the diagnostic workup and therapeutic management, since it suggests an oropharyngeal origin.

Natural history and clinical outcome of differentiated thyroid carcinoma: a retrospective analysis of 1503 patients treated at a single institution.

BACKGROUND: The study evaluates clinical presentation and outcome of differentiated thyroid cancer (DTC) on a large series of patients homogeneously managed. PATIENTS AND METHODS: A cohort of 1503 DTC followed according to a standardized protocol entered the study. Main outcome measures were clinical presentation at the diagnosis, survival, morbidity and prognostic risk factors. RESULTS: Median age at diagnosis was 46 years. Papillary cancer and low pathological tumor-node-metastasis stages represented >80% of cases. Cancer specific survival at 5, 10 and 15 years was 98.6%, 94.7% and 87.4%; 10-year disease-free and progression-free survivals were 96.8% and 17.1%, respectively. Cancer-specific mortality rate was 2.5% [95% confidence interval (CI) 1.7% to 3.4%], recurrence rate was 0.6 % while morbidity rate was 12.6% (95% CI 11% to 14%). Response to radioiodine treatment is the strongest predictor of a good outcome in multivariate analysis (hazard ratio 211, P < 0.0001). Other independent predictor variables are sex, age, histology and distant metastases for survival and metastases for morbidity. CONCLUSIONS: A rigorous initial therapeutic approach leads to a better survival and a very low morbidity. Patients who do not respond to radioiodine treatment have a worse prognosis.

Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

Bone of the hands as unusual metastastatic site of renal cell carcinoma.

Metastases to the bones of the hands and feet (acrometastases) represent an uncommon site of recurrence of renal cell carcinoma (RCC). Although challenging, the prompt recognition of solitary acrometastasis from RCC is of crucial importance, since surgical resection of the acrometastasis in the absence of active systemic disease has been reported as beneficial for a subgroup of patients with RCC. Here, we report the case of a patient with RCC metastatic to the left index finger treated with surgical resection of the acrometastasis who shortly thereafter developed progressive disease despite such an aggressive surgical approach.

HPV genotypes concordance between sex partners.

The HPV genotype concordance in the sexual couples could support the sexual viral transmission of HPV infection. The present study contains a case-report of a stable Italian sex couple harbouring the same five HPV genotypes in their genital samples. The female partner, affected by vulvar condilomatosis, evidenced positivity in her cervicovaginal scraping with high risk HPV DNA Hybrid Capture 2 test and was negative at liquid-based performed Pap Test and at colposcopic examination. The male partner was clinically healthy regarding his external genitalia. In both male and female genital scrapings, the following HPV genotypes were detected by means of a PCR-based assay: 6, 16, 53, 73 and 84. This considerably high genotype concordance does not appear to be casual and supports, in our opinion, the hypothesis that genital HPV types are sexually transmitted agents

Incidence of human papillomavirus infection in oral leukoplakia. Indications for a viral aetiology.

Epidemiological and experimental studies have indicated a possible role of human papillomavirus (HPV) in the etiopathogenesis of oral premalignant lesions and tumors. The aim of this study was to establish the incidence of HPV infection and the typing of genotypes in some patients with nonmalignant oral cavity pathology and healthy subjects. We selected 80 subjects affected by the following pathologies: oral leukoplakia (20), squamous cell papilloma (6), various forms of stomatitis (30), lichen planus (15), burning mouth syndrome (BMS, 9). Ten healthy subjects were used as control. The patients underwent a brushing directly on the lesion or on the lower gums and on the dorsal surface of the tongue and a new, sensitive method of in situ hybridization (ISH) with colorimetric signal amplification was used for HPV detecting. The samples were tested with a Mix probe, which identifies most of the HPV genotypes and, in positive cases, the specific probe for the 6-11, 31-33-51 and 16-18 genotypes, was used. Leukoplakia and papilloma were , therefore, associated with the HPV infection, differently from the other pathologies and healthy oral mucosa (chi-squared < 0.005). In conclusion, according to our findings, HPV is a specific risk factor for the development of oral premalignant lesions.

Malignant glucagonoma. New options of treatment.

Few cases of malignant glucagonomas have been described in the literature. In this paper we present a case of a 77-year-old woman with necrolytic migratory erythema and high plasma glucagon and chromogranin A levels caused by a neuroendocrine tumour. An abdominal CT scan suggested a pancreatic lesion and two liver metastases. The patient underwent pancreatic debulking and liver metastasectomy. Histological and immunohistochemical investigations revealed a well differentiated neuroendocrine tumour with vascular invasion and scattered immunopositivity for somatostatin receptors. The patient was treated with octreotide (20 mg i.m. every 28 days) for three years without side effects. Three months after surgery symptoms of disease recurred accompanied by hyperglucagonaemia and newly diagnosed liver lesions. The patient was treated with octreotide (30 mg i.m. every 28 days) and interferon-alpha (6 MU s.cc 3 times per week) plus three cycles of hepatic chemoembolisation. Symptoms resolved after the first month of therapy, hormone levels decreased compared to untreated levels and metastatic growth slowed as observed by radiographic evidence. The patient is now asymptomatic with persistent hepatic disease and normal serum glucagon levels forty months after primary treatment. So far, only few immunohistochemical studies are reported on malignant glucagonoma and combined treatment schedules. We demonstrated, for the first time, a scattered immunopositivity for somatostatin receptors in a malignant glucagonoma. For this reason, the somatostatin analogs therapy was instituted. A combined antiproliferative medical treatment and the hepatic chemoembolization have been able to control tumor growth and disease symptoms for a long time after surgery.

Small hyperechogenic nodules in thyroiditis: usefulness of cytological characterization.

Small hyperechogenic nodules occurring in thyroiditis frequently raise the question of their nature requiring additional evaluation. Given the scarcity of the studies addressing this issue, we have investigated whether cytopathological analysis of fine needle aspirates (FNA) of these lesions may be of diagnostic relevance. In this preliminary study, we submitted to cytopathological analysis 10 nodular lesions as well as the normal counter-lateral tissue. In none but one of the cases analyzed, the cytopathology was able to detect differences between the hyperechogenic models and the hypoechogenic parenchyma suggesting that these lesions bear no-clinical relevance. Therefore, FNA of these nodules is not advisable and should be limited to those with defined at risk clinical features.

Gastrointestinal stromal tumors of the stomach. A ten-year surgical experience.

Gastrointestinal stromal tumors show an increasing incidence. Immunohistochemistry is mandatory to make differential diagnosis with other mesenchimal tumors. We retrospectively reviewed 15 primary stomach GISTs operated during the last decade. Gastroscopy, Ultrasonography and CT scan were employed to obtain the diagnosis. Tumor size ranged from 1.5 to 30 cm in diameter. Treatment consisted of curative surgical resection without sistematic lymph node dissection. A wedge resection was sufficient in 8 cases. In 2 patients a distal subtotal gastrectomy was required and in 1 a total enlarged gastrectomy with pancreaticosplenectomy was performed. 4 GISTs were incidentally discovered and removed during surgical procedures for other gastrointestinal malignancies. In 4 cases a laparoscopic wedge resection was possible. In all cases postoperative course was uneventful. No adjuvant treatment was administered. Concerning the follow-up, two patients died for local and distant relapse while 13 are still alive (most of them operated during the last three years). GISTs show a very unpredictable clinical course and curative surgery is the only potential effective curative treatment.

HER-2/neu oncogene amplification and chromosome 17 aneusomy in endometrial carcinoma: correlation with oncoprotein expression and conventional pathological parameters.

The objective of the present study was to evaluate the correlation between HER-2 gene amplification and HER-2 protein overexpression in endometrial carcinoma using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We also analyzed chromosome 17 aneusomy and the association between these biological parameters and conventional clinicopathological variables. FISH analysis was performed on 73 selected paraffin-embedded sections from endometrial carcinomas which previously had HER-2 status determined immunohistochemically using monoclonal antibodies (MoAb) 300G9 and CB11. Using a ratio of more than two oncogene signals/centromere to indicate amplification, a total of 42 out of the 73 endometrial tumors included in this study resulted positive by FISH where as protein overexpression was identified in 29 out of 73 with a concordance rate of 74.3%. However, when the mean signals/centromere per nucleus increased (ratio > 4 < or = 5) a higher concordance between the two assays was seen (p = 0.007). In addition, HER-2 amplification was significantly correlated with tumor stage (p = 0.021) and myometrial invasion (p = 0.010), whereas chromosome 17 polisomy showed a positive correlation only with myometrial invasion (p = 0.004) No significant correlation was found between HER-2 gene amplification, chromosome 17 aneusomy and patient outcome. Nevertheless, the probability of a 5 year overall survival decreased from 70% to 43%, respectively, for ratio > 2 < or = 4 and ratio > 4 < or = 5 when we grouped the amplified cases on the basis of HER-2:CEP17 ratio. In conclusion, molecular characteristics provide objective data that may be useful in predicting prognosis in patients with endometrial cancer.

Rapid modification of aggressiveness of a primary non-Hodgkin lymphoma of uterine cervix.

Primary malignant lymphoma of the uterine cervix is an extremely rare condition, with only about 100 cases reported in international literature. The diagnosis can be difficult, as stated by some authors finding only 10 up to 40% of cases of cervical lymphoma diagnosed by positive cytology. We present a case of primary malignant lymphoma of the cervix in a 57 year old woman treated at the Department of Gynecological Oncology at the Regina Elena Cancer Institute in Rome, with a sudden and unfavorable outcome.

Sentinel node in gastric cancer surgery.

Sentinel Node (SN) biopsy studies have been recently applied to gastric cancer. In this series, 40 selected patients operated for gastric adenocarcinoma located in the lesser curvature and/or anterior wall of the body and antrum, underwent an intraoperative dye lymphography. The lymphatic ducts and nodes were visualized and a SN was evidenced in all cases. This was removed and a frozen section examined. In all cases a radical D2-3 gastrectomy was performed and histology, molecular biology, RT-PCR research of micrometastases (CEA-mRNA), were determined on the specimens. Correlations between T and histological status of SN and regional nodes were done. In 16 cases the SN was negative and all the resected regional nodes were negative too. In 15 cases the SN node was positive and other nodes in other stations were found to be positive as well. In 2 cases the SN was negative but other nodes, in the same stations and in others, were positive (false negative = 5%). In 7 cases the SN was the only node in which metastases occurred, 3 demonstrated by conventional histology and 4 detected by RT-PCR. In these 7 cases the SN was the only involved node out of all resected nodes, thus demonstrating to be the real first node along the lymphatic routes from the tumour. This experience seems to confirm the existence of a Sentinel Node and that each gastric adenocarcinoma has its own lymphatic basin in which metastasis can occur. Although a prudent attitude towards the indications resulting from these observations is required, in selected cases a controlled and tailored lymphoadenectomy could be adopted.

Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions.

BACKGROUND: Thyroid cancer is the most common endocrine malignant disease, but preoperative diagnosis remains a challenge. Fine-needle aspiration cytology has greatly improved the clinical management of thyroid nodules, but the preoperative characterisation of follicular lesions is very difficult. Many patients are thus referred to surgery more for diagnosis than for therapeutic necessity. We undertook an international multicentre study to assess the usefulness of immunohistocytochemical staining for two potential markers of malignant thyrocytes. METHODS: Expression of galectin-3 and CD44v6 was tested on 1009 thyroid lesions (tissue specimens and cytological cell-blocks) and 226 fresh cytological samples obtained preoperatively by ultrasound-guided fine-needle aspiration of thyroid nodules (prospective analysis). The test used monoclonal antibodies specific for CD44v6 and galectin-3, the indirect avidin-biotin complex immunoperoxidase method, and 3-amino-9-ethyl-carbazole as substrate. FINDINGS: The sensitivity, specificity, positive predictive value, and diagnostic accuracy of this test method (for coexpression of the two markers) in the prospective analysis were 88%, 98%, 91%, and 97%, respectively. The sensitivity and specificity of galectin-3 immunodetection alone in discriminating benign from malignant thyroid lesions were more than 99% and 98% respectively, and the positive predictive value and diagnostic accuracy were 92% and 99%. INTERPRETATION: The integration of galectin-3 immunostaining with conventional cytomorphological and clinical diagnostic procedures represents a sensitive and reliable diagnostic approach for preoperative identification of thyroid carcinomas. This test method improves the diagnostic accuracy of conventional cytology and provides the molecular basis for a new nosological assignation of the not yet classified thyroid neoplasms of indeterminate malignant behaviour.

Immunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and ras protein product in colorectal adenomas, carcinomas, and adjacent nonneoplastic mucosa.

The normal mucosa-adenoma-carcinoma sequence in colon pathology provides an attractive model of tumor progression. The role of tumor suppressor genes, oncogenes, and proliferative markers in tumorogenesis has evolved considerably in the last decade. By immunohistochemistry means, we have studied p53, bcl-2, c-myc, p21-ras, ki67, and fatty acid synthase (a fatty-acid-synthesizing enzyme) in normal, dysplastic, and neoplastic mucosa. The results were correlated with clinicopathological features and overall survival (OS). Formalin-fixed, paraffin-embedded archival material from 100 nonconsecutive adenomas and 100 adenocarcinomas (ADCs), including adjacent-to-tumor nonneoplastic mucosa (ANNM), from patients with a 5-year follow-up period were studied. Negative controls were obtained from colon resections for nonneoplastic disease. Fatty acid synthase was associated with ADC (P = 0.0001). p53 protein was associated with high-grade dysplasia adenoma (AHGD), ADC (P = 0.0001), and pT stage (P = 0.003). bcl-2 was associated with adenomas with low-grade dysplasia (P = 0.009); c-myc was associated with ANNM (P = 0.005) and pT stage (P = 0.006). p21-ras was associated with AHGD (P = 0.0001) and ANNM (P = 0.01). Ki67 was associated with AHGD (P = 0.02) and ADC (P = 0.0001). Univariate analysis on neoplastic tissue revealed histological grade, pT stage, pN stage, p21-ras, and p53 to be significant markers of OS; p21-ras, p53, and c-myc were reliable markers when evaluated on ANNM. Multivariate analysis revealed pT stage, pN stage, and p21-ras to be independent prognosticators of OS on ADC; p21-ras and c-myc staining in the ANNM were correlated with worse survival (OS). We suggest that the evaluation in concert of clinicopathological data and immunohistochemical markers on both normal and abnormal colon tissue provides an attractive model of tumor progression; moreover, it may give important messages about the prediction of survival.

[The value of the Pap test in the diagnostic approach to HPV infection of the cervix uteri]. / Valore del Pap-test nell'approccio diagnostico dell'infezione da HPV della cervice uterina.

HPV infection of the low genital tract is the most diffuse STD world wide. For this reason it's necessary to follow a simple flow chart to reach a correct diagnosis and to practice an adequate therapy. The authors relate on their experience in the management of a group of patients they have observed in a STD clinic. In this group it was executed a diagnostic protocol including Pap test, in situ hybridization, dot blot and histologic examination on tissue biopsies. From the analysis of the obtained data, the authors state that the Pap test is very useful to start in the diagnostic protocol, for it is precise, inexpensive and allows to identify the patients to follow with further diagnostic procedures such as colposcopy and histologic examination, in order to reach an exhaustive diagnosis and to assess the proper therapy.