Purpose Parathyroid carcinoma (PC) is remarkable for its rare occurrence and challenging diagnostics. PC accounts for 0.1-5 % cases of primary hyperparathyroidism (PHPT). The differentiation from benign tumours is difficult even by morphological criteria. To address these issues, we assessed the PC frequency in two separate European PHPT cohorts and evaluated the demographic, clinical, morphological and molecular background. Methods A retrospective study was carried out, using continuously maintained database (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014) of PHPT patients from two tertiary referral university hospitals in Europe. The demographic, clinical data and frequency of PC among surgically treated PHPT was detected. Immunohistochemistry (IHC) was performed to detect parafibromin, representing protein product of HRPT2 gene and proliferation marker Ki-67. Results Both PHPT cohorts were characterised by close mean age values (58.6 and 58.0 years) and female predominance. The frequency of PC differed significantly between the cohorts: 2.1 vs. 0.3 %; p=0.004. PC was characterised by invariable complete loss of parafibromin contrasting with parathyroid adenomas. The proliferation fraction was similar in both PC cohorts (10.6 and 11.0 %). PC showed significantly higher proliferation fraction than typical parathyroid adenomas (1.6 %), atypical adenomas (1.6 %) or adenomas featuring focal loss of parafibromin (2.2 %). Conclusions PC frequency can range significantly between the two European cohorts. The differences can be attributable to selection bias of patients referred for surgery and are not caused by discordant definition of malignant parathyroid histology. Diffuse loss of parafibromin and increased proliferation fraction by Ki-67 are valuable adjuncts in PC diagnostics due to significant differences with various clinical and morphological subtypes of adenoma.

The study represents a comprehensive retrospective morphological and immunohistochemical profiling of pancreatic neuroendocrine neoplasms (PNENs) in order to reveal the associations between morphological and molecular parameters. The local tumour spread (T), presence of metastases in regional lymph nodes (N) and distant organs (M), tumour grade (G) and resection line status (R) by pathology findings (pTNMGR), mitotic activity, perineural, vascular and lymphatic invasion were assessed in 16 surgically resected PNENs. By immunohistochemistry, expression of Ki-67, p53, p27, p21, cyclin D1, Bcl-2, E-cadherin, CD44, vimentin, cyclooxygenase 2 (COX-2), microvascular density, and cytokeratin (CK) spectrum, along with neuroendocrine, intestinal and squamous markers were detected. Descriptive statistics, Chi-square test, Spearman's rank correlation, Mann-Whitney and Kruskal-Wallis methods were applied; p < 0.05 was considered significant. Ki-67, CK19, p63, vimentin and COX-2 were significantly up-regulated in PNENs in comparison to benign pancreatic islets. A complex network of morphological and molecular associations was identified. Ki-67 correlated with PNEN size (p = 0.022), the World Health Organization 2004 and 2010 classification grades (p = 0.021 and p = 0.002), stage (p = 0.028) and mitotic count (p = 0.007) but among molecular markers -with CK19 (p = 0.033) and vimentin (p = 0.045). CK19 was significantly up-regulated in PNENs, having higher pT (p = 0.018), pR (p = 0.025), vascular (p = 0.020), perineural (p = 0.026) and lymphatic invasion (p = 0.043). In conclusion, proliferation activity (by Ki-67), E-cadherin, vimentin and CK19 are important molecular characteristics of PNENs due to significant associations with morphological tumour characteristics, pTNMGR and invasive growth.

No abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumours with dismal prognosis.

SummaryDespite the fact that the appendix is one of the rarest anatomic localization of neuroendocrine tumours (NETs) in the digestive system, the appendicular neuroendocrine tumour (A-NET) remains among the most common tumours of the appendix. The A-NET usually presents as a small solitary lesion revealed only after pathological examination of appendix that has been surgically removed for acute appendicitis. Only 18 papers in the Pubmed database are dedicated to A-NET in pregnancy. Here we present a well-documented case of A-NET in a pregnant lady. Key words: pregnancy, appendix, neuroendocrine tumour. CASE REPORT Neuroendocrine Tumour of the Appendix in PregnancyAndrejs Vanags*,**, Ilze Strumfa*, Zane Simtniece*, Jānis Gardovskis*,** *Riga Stradins University, Latvia **Pauls Stradins Clinical University Hospital, Riga, Latvia AIM OF THE DEMONSTRATIONWe present thoroughly documented case of A-NET of the appendix in a pregnant female in order to demonstrate a rare tumour in an unusual clinical setting. CASE REPORTA 24-year-old female with progressive 2 nd pregnancy of 35 weeks was admitted to the hospital due to dull pain in the epigastrium. There was no evidence of previous similar episodes. The ultrasonography (US) revealed slightly enlarged spleen reaching 14x4.7 cm as the only abnormality. By foetal US, foetus corresponded to the gestational age of 34 weeks and 4 days. The laboratory investigations demonstrated low haemoglobin level 117 g/L [laboratory reference interval 131-175 g/L] and increased white blood cell (WBC) count 12.9 x10 9 /L [4.0-9.8x10 9 /L]. A surgeon consulted patient on the same day. Progressive pain in the lower part of abdomen was established by the second visit of surgeon on the next morning; a diarrhoea episode was also revealed. C-reactive protein (CRP) level was progressively increasing from 7.5 mg/L to 58.7 mg/L [0-5.0 mg/L]. The indications for appendectomy were set up and the operation was performed by the McBurney laparotomy approach. No specific local findings were found during the exploration of the abdominal cavity. The appendix was compressed by the uterus; it was located behind the caecum. No palpable mass and no peritoneal fluid was revealed during the laparotomy. However, the apex of the appendix visually was slightly enlarged and the appendix was removed. The wound healed by primary intention without any local or general complications. After the operation, CRP level decreased to 19.5 mg/L and WBC count regressed to 5.4 x10 9