Individual risk calculator to predict lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

BACKGROUND: Lymph node metastasis (LNM) is possible after endoscopic resection of early esophageal adenocarcinoma (EAC). This study aimed to develop and internally validate a prediction model that estimates the individual risk of metastases in patients with pT1b EAC. METHODS: A nationwide, retrospective, multicenter cohort study was conducted in patients with pT1b EAC treated with endoscopic resection and/or surgery between 1989 and 2016. The primary end point was presence of LNM in surgical resection specimens or detection of metastases during follow-up. All resection specimens were histologically reassessed by specialist gastrointestinal pathologists. Subdistribution hazard regression analysis was used to develop the prediction model. The discriminative ability of this model was assessed using the c-statistic. RESULTS: 248 patients with pT1b EAC were included. Metastases were seen in 78 patients, and the 5-year cumulative incidence was 30.9 % (95 % confidence interval [CI] 25.1 %-36.8 %). The risk of metastases increased with submucosal invasion depth (subdistribution hazard ratio [SHR] 1.08, 95 %CI 1.02-1.14, for every increase of 500 µm), lymphovascular invasion (SHR 2.95, 95 %CI 1.95-4.45), and for larger tumors (SHR 1.23, 95 %CI 1.10-1.37, for every increase of 10 mm). The model demonstrated good discriminative ability (c-statistic 0.81, 95 %CI 0.75-0.86). CONCLUSIONS: A third of patients with pT1b EAC experienced metastases within 5 years. The probability of developing post-resection metastases was estimated with a personalized predicted risk score incorporating tumor invasion depth, tumor size, and lymphovascular invasion. This model requires external validation before implementation into clinical practice.

Lymphovascular invasion quantification could improve risk prediction of lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma.

AIM: To quantify lymphovascular invasion (LVI) and to assess the prognostic value in patients with pT1b esophageal adenocarcinoma. METHODS: In this nationwide, retrospective cohort study, patients were included if they were treated with surgery or endoscopic resection for pT1b esophageal adenocarcinoma. Primary endpoint was the presence of metastases, lymph node metastases, or distant metastases, in surgical resection specimens or during follow-up. A prediction model to identify risk factors for metastases was developed and internally validated. RESULTS: 248 patients were included. LVI was distributed as follows: no LVI (n = 196; 79.0%), 1 LVI focus (n = 16; 6.5%), 2-3 LVI foci (n = 21; 8.5%) and ≥4 LVI foci (n = 15; 6.0%). Seventy-eight patients had metastases. The risk of metastases was increased for tumors with 2-3 LVI foci [subdistribution hazard ratio (SHR) 3.39, 95% confidence interval (CI) 2.10-5.47] and ≥4 LVI foci (SHR 3.81, 95% CI 2.37-6.10). The prediction model demonstrated a good discriminative ability (c-statistic 0.81). CONCLUSION: The risk of metastases is higher when more LVI foci are present. Quantification of LVI could be useful for a more precise risk estimation of metastases. This model needs to be externally validated before implementation into clinical practice.

Agreement on endoscopic ultrasonography-guided tissue specimens: Comparing a 20-G fine-needle biopsy to a 25-G fine-needle aspiration needle among academic and non-academic pathologists.

BACKGROUND AND AIM: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. METHODS: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens. RESULTS: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P < 0.001) and classification according to Bethesda (ĸ = 0.45 vs ĸ = 0.61, P < 0.001). This equally applied for expert academic and non-academic pathologists and for pancreatic and lymph node specimens. Sample quality was also rated higher for FNB, but agreement ranged from poor (ĸ = 0.04) to fair (ĸ = 0.55). Histology provided better agreement than cytology, but only when a core specimen was obtained with FNB (P = 0.004 vs P = 0.432). CONCLUSION: This study shows that the 20-G FNB outperforms the 25-G FNA needle in terms of diagnostic agreement, independent of the background and experience of the pathologist. This endorses use of the 20-G FNB needle in both expert and lower volume EUS centers.

Improved diagnostic stratification of digitised Barrett's oesophagus biopsies by p53 immunohistochemical staining.

AIMS: Interobserver agreement for dysplasia in Barrett's oesophagus (BO) is low, and guidelines advise expert review of dysplastic cases. The aim of this study was to assess the added value of p53 immunohistochemistry (IHC) for the homogeneity within a group of dedicated gastrointestinal (GI) pathologists. METHODS AND RESULTS: Sixty-single haematoxylin and eosin (HE) slide referral BO cases [20 low-grade dysplasia (LGD); 20 high-grade dysplasia (HGD); and 20 non-dysplastic BO reference cases] were digitalised and independently assessed twice in random order by 10 dedicated GI pathologists. After a 'wash-out' period, cases were reassessed with the addition of a corresponding p53 IHC slide. Outcomes were: (i) proportion of 'indefinite for dysplasia' (IND) diagnoses; (ii) interobserver agreement; and (iii) diagnostic accuracy as compared with a consensus 'gold standard' diagnosis defined at an earlier stage by five core expert BO pathologists after their assessment of this case set. Addition of p53 IHC decreased the mean proportion of IND diagnoses from 10 of 60 to eight of 60 (P = 0.071). Mean interobserver agreement increased significantly from 0.45 to 0.57 (P = 0.0021). The mean diagnostic accuracy increased significantly from 72% to 82% (P = 0.0072) after p53 IHC addition. CONCLUSION: Addition of p53 IHC significantly improves the histological assessment of BO biopsies, even within a group of dedicated GI pathologists. It decreases the proportion of IND diagnoses, and increases interobserver agreement and diagnostic accuracy. This justifies the use of accessory p53 IHC within our upcoming national digital review panel for BO biopsy cases.

[Skin disorder as an indication of viral infection]. / Huidafwijking als aanwijzing voor virusinfectie.

BACKGROUND: Gianotti-Crosti syndrome (GCS) is a dermatosis primarily affecting children between 2 and 6 years of age. It is characterized by multiple, itching, monomorphous, pink to red-brown papules or papulovesicles between 1 and 5 mm in size. GCS is associated with viral infections such as hepatitis B virus and Epstein-Barr virus (EBV). It is often accompanied by fever, hepatosplenomegaly and lymphadenopathy. The syndrome is self-limiting and disappears within 2 months. No treatment is therefore required. CASE DESCRIPTION: We report a case of a 16-year-old female who presented with itching papulovesicles on the extremities and on the buttocks. She was diagnosed with GCS because of the clinical findings, histopathological tests and positive EBV serology. CONCLUSION: GCS can also affect patients older than 6 years of age. Moreover, this syndrome may be a first sign of infection with Epstein-Barr virus, hepatitis B virus, HIV or other viral infections.

Immunohistochemical evaluation of a panel of tumor cell markers during malignant progression in Barrett esophagus.

Histopathologic grading of dysplasia in Barrett esophagus (BE) shows substantial interobserver and intraobserver variation. We used immunohistochemical analysis with a set of tumor cell markers, ie, epidermal growth factor receptor (EGFR), ERBB2 (HER2/neu), MYC, CDKN2A (p16), SMAD4, MET, CCND1 (cyclin D1), CTNNB1 (beta-catenin), and TP53 (p53), in histologic sections of endoscopic biopsies of 86 patients with BE in various stages of neoplastic progression. The markers, except SMAD4, were scored as 0 (<1% of cells stained), 1 (1%-25%), 2 (26%-50%), or 3 (>50%). All markers, except EGFR, showed a significant trend for immunohistochemical protein overexpression during malignant progression in BE (P <.01). When the successive stages along the metaplasia-low-grade dysplasia (LGD)-high-grade dysplasia (HGD)-adenocarcinoma axis were compared, protein overexpression of beta-catenin separated LGD from metaplasia, whereas protein overexpression of cyclin D1 and p53 discriminated HGD from LGD (all P <.001). beta-Catenin can be helpful for a diagnosis of LGD in BE, although it stains positively in a subset only, whereas p53 remains an appropriate marker to define HGD. In case of doubt, cyclin D1 can be added to separate LGD from HGD in BE.