In stage II/III lymph node positive breast cancer patients less than 55 years of age, keratin 8 expression in lymph node metastases but not in the primary tumor is an indicator of better survival

Axillary lymph node status is one of the most important prognostic variables for breast cancer (BC). To investigate and understand the clinical, histopathological and biological factors that affect prognosis in node positive young breast cancer patients, we compared the phenotype of 100 primary tumours with their corresponding loco- regional lymph node (LN) metastases using conventional immunohistochemistry (IHC) markers currently in use for molecular classification of breast cancer. By comparing the expression of ER, PR, HER-2, Ki67, K8, K5/6 and vimentin, we found that expression of HER-2, Ki67, K8 and vimentin is frequently lost in lymph node metastases. Between the primary tumour and corresponding lymph node metastases expression of keratins K8 and K5/6 significantly changed. Expression of K8 in lymph node metastases, but not in primary tumours, segregates patients in two sub-groups with different outcome. Survival of patients with K8 positive LN metastases at 5 years in comparison with patients with K8 negative LN metastases was 75% vs 48%, at 10 years 62% vs 22% and at 20 years 53% vs 14%(p<0.001). K8 immunostaining of tissue from the lymph node metastasis allows defining a sub-group of lymph node positive BC patients with a highly unfavourable outcome, for whom therapeutic options might have to be reconsidered

Sentinel lymph node biopsy in squamous cell carcinoma of the head and neck: 10 years of experience

Sentinel node (SN) biopsy of head and neck cancer is still considered investigational, and agreement on the width of the surgical sampling has not yet been reached. From May 1999 to Dec 2009, 209 consecutive patients entered a prospective study: 61.7% had primary tumour of the oral cavity and 23.9% of the oropharynx. SN was not found in 26 patients. Based on these data and definitive histopathological analysis, we proposed six hypothetic scenarios to understand the percentage of neck recurrences following different treatments Among patients with identified SN, 54 cases were pN+: 47 in SN and 7 in a different node. Considering the six hypothetic scenarios: "only SN removal", "SN level dissection", "neck dissection from the tumour site to SN level", "selective neck dissection of three levels (SND)", "dissection from level I to IV" and "comprehensive I-V dissection", neck recurrences could be expected in 6.5%, 3.8%, 2.18%, 2.73%, 1.09% and 1.09% of cases, respectively. SN biopsy can be considered a useful tool to personalize the surgical approach to a N0 carcinoma. The minimum treatment of the neck is probably dissection of the levels between the primary tumour and the level containing the SN(s). Outside the framework of a clinical study, the best treatment can still be considered SND

Correlation between IgA tissue transglutaminase antibody ratio and histological finding in celiac disease.

OBJECTIVES: Positivity of both immunoglobulin A anti-tissue transglutaminase (TTG) and anti-endomysium antibodies (EMA) has a positive predictive value of nearly 100% for celiac disease (CD). The objective of the present study was to evaluate whether patients of any age, with high pretest probability of CD and high titre of anti-TTG and EMA positivity, have a high probability of intestinal damage and may not require the biopsy for final diagnosis. METHODS: A retrospective analysis of 412 consecutively referred patients, age range 10 months to 72 years, who underwent small-bowel biopsy for suspicion of CD and positivity to both anti-TTG and EMA, was performed at 4 Italian centers. Biopsies were evaluated independently by 2 pathologists using Marsh modified classification; in cases of dissimilar results, a third pathologist examined the biopsy. The final histological finding diagnosis was expressed as the prevalent or highest score assigned by the pathologist board. RESULTS: Three hundred ninety-six patients (96.1%) had histological findings consistent with CD (grade 2 and 3a, 3b, or 3c of modified Marsh classification). An anti-TTG ratio ≥ 7 was able to identify with the 3 assays used (Celikey, anti-TTG immunoglobulin A, EuTTG) all of the patients with significant mucosal damage (Marsh ≥ 2) independent of age and sex; specificity and positive predictive value were 100%. An anti-TTG ratio >20 was more specific (99.8%) for identification of patients with villous atrophy (Marsh 3 a, b, or c). CONCLUSIONS: Patients with positivity of anti-TTG ≥ 7-fold cutoff, confirmed by positivity to EMA, have a high-degree probability of duodenal damage. In selected conditions, a duodenal biopsy may be avoided and a confirmed greatly positive anti-TTG result could be the basis to prescribe a gluten-free diet

CDKN1B mutation and copy number variation are associated with tumor aggressiveness in luminal breast cancer

The CDKN1B gene, encoding for the CDK inhibitor p27kip1, is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra-deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor-positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27kip1 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell-free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27kip1 protein truncation, leading to loss of most of the protein or of its C-terminal domain. Using a gene-editing approach in a luminal breast cancer cell line, MCF-7, we observed that the expression of p27kip1 truncating mutants that lose the C-terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C-terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley &amp; Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

Contributo del patologo nella diagnostica del carcinoma della tiroide

\ue8 ben noto il ruolo centrale del patologo nella diagnostica di noduli tiroidei nella selezione dei casi da inviare all'intervento chirurgico, nella diagnostica intra- e post-operatoria e nella stadiazione delle forme maligne. Anche nel follow up dei pazienti operati per carcinoma talvolta il patologo viene consultato per la conferma delle metastasi locoregionali. La diagnostica istocitopatologica dei carcinomi della tiroide costituisce, citando Masson, "...la pi\uf9 grande lezione di umilt\ue0 per il patologo..."

Diagnostic value of pleural cytology together with pleural CEA and VEGF in patients with NSCLC and lung metastases from breast cancer

Background: Pleural effusion (PE) is common in patients with advanced non-small cell lung cancer (NSCLC) and lung metastases from breast cancer, accounting for at least 20-30% of cases. Unfortunately, many patients with malignant PE exhibit a negative pleural cytology (PC), and thus further invasive diagnostic procedures, including VAT-guided biopsy, are required. The aim of this study was to evaluate the diagnostic value of PC together with pleural carcinoembryonic antigen (pCEA) and vascular endothelial growth factor (pVEGF) assay in cancer patients with PE. Methods: Thirty-six patients with suspicious PE scheduled to undergo VAT-guided biopsy underwent both PC and pCEA and pVEGF measurement before surgery. There were 20 (55.6%) males and 16 (44.4%) females, with an overall median age of 67 (range 40-82 years). Patients with non-diagnostic cytology were excluded from the study. pCEA was measured with automated method of immuno-chemiluminescence (LOCI, Dimension Vista, Siemens HD, Camberley, UK), while pVEGF with an enzyme-linked immunosorbent assay (ELISA) commercially available kit. According to previously obtained data from laboratory archival information, the optimum cutoff levels were 5 ng/mL and 6 ng/mL for pCEA and pVEGF, respectively. Results: Final pathology showed 10 (27.8%) patients with NSCLC, 13 (36.1%) with lung metastases, and 13 (36.1%) with benign PE. The age did not differ between groups (p=0.59). The sensitivity, specificity and accuracy of PC, and pleural CEA and VEGF are reported in the Table. The area under the curve (AUC) of the ROC curve of PC+pCEA+pVEGF in combination was 0.921 (95% CI: 0.513-0.973), and the diagnostic accuracy was 97.2%. Conclusions: In patients with PE, according to our results, the measurement of pleural CEA and VEGF, and PC evaluation together reached a very good accuracy and 100% specificity, and should be suggested in all cancer patients when a noninvasive evaluation of a PE is required as non-invasive procedure