Risk stratification of papillary thyroid microcarcinomas via an easy-to-use system based on tumor size and location: clinical and pathological correlations.

INTRODUCTION: We aimed to determine whether two clinically accessible parameters, tumor size and location within the thyroid, correlate with clinicopathological features that are predictors of high risk in papillary thyroid microcarcinomas (PTMCs). MATERIALS AND METHODS: PTMC cases were obtained from the database of the Department of Pathology, Emergency County Hospital, Târgu Mures, Romania. Four tumor groups were created based on tumor size and location: Group I (≥5 mm, subcapsular), Group II (≥5 mm, nonsubcapsular), Group III (<5 mm, subcapsular), and Group IV (<5 mm, nonsubcapsular) PTMCs. Clinicopathological features and follow-up data were compared by univariate and multivariate analysis. RESULTS: Our study included 164 PTMCs (n=70/20/19/55 in Groups I∕II∕III∕IV, respectively). High-grade morphological features, such as plump pink cells (p=0.010), tumor desmoplasia (p=0.022) and sclerosis (p=0.001), infiltrative tumor borders (p=0.005), positive resection margins (p=0.005), invasion into the perithyroid adipose tissue (p=0.001), irregular nuclear membranes (p=0.004), and pseudoinclusions (p=0.001) were significantly more prevalent among Group I PTMCs. Group IV PTMCs were characterized by a paucity of the above-mentioned morphological features, while Group II and III PTMCs displayed intermediate morphological profiles. CONCLUSIONS: Group I PTMCs proved to be associated with more aggressive morphological features and might need a more careful clinical approach.

Histopathological and perioperative factors influencing the length of hospital stay and patients' outcome after radical cystectomy for urothelial carcinoma.

INTRODUCTION: Length of hospital stay (LOS) is considered as a key factor in estimating outcomes after radical cystectomy (RC) in urothelial carcinoma (UC) patients. We aimed to assess whether clinical perioperative (age, gender, type of urinary diversion technique) and histopathological factors [UC variant, primary tumor, node, metastasis (pTNM) staging] could be a determining factor for LOS, as well as its influence on overall survival (OS) in a single institution, retrospective cohort study. PATIENTS, MATERIALS AND METHODS: We included a total of 69 UC patients that had RC performed in our Department during November 2011 and October 2018. Regular LOS was considered arbitrarily up to 12 days. All factors were analyzed in relation to LOS, using the chi-square and the Mann-Whitney tests. Impact of LOS on survival was assessed using the Kaplan-Meier and the Cox regression methods. RESULTS: Age was associated to increased LOS (p=0.042), as well as the type of urinary diversion (p=0.003). Patients with complex diversion were found more frequently in the prolonged LOS group (ileal conduit p=0.006, Mainz pouch p=0.15, Camey neobladder p=0.517). Histopathologically, N stage had a significant association to LOS (p=0.044). Survival analysis showed decreased survival in the prolonged LOS group (p=0.653). Cox regression found no influence of LOS (p=0.653), advanced age (p=0.518) or type of urinary diversion on OS. CONCLUSIONS: Advanced age, the complexity of urinary diversion and lymph node involvement were found as associated factors for prolonged LOS in RC patients. The impact of LOS on survival is uncertain, requiring larger, in-depth studies.

Histopathological predictive factors for the overall survival rate in patients with urothelial carcinoma of the bladder treated by radical cystectomy: a Romanian cohort study.

INTRODUCTION: Urothelial carcinoma (UC) variants are considered as having a more aggressive behavior and a more advanced stage at presentation than conventional UC. However, the evidence supporting the role of UC variants on overall survival (OS) is conflicting. We aimed to assess the impact of demographic factors (age at surgery, gender) and tumor characteristics [conventional∕variant UC, associated carcinoma in situ (CIS), associated papillary component, Tumor, Node, Metastasis (TNM) staging, positive surgical margins] on OS in a series of patients treated for UC in our Department. PATIENTS, MATERIALS AND METHODS: We performed a retrospective, cohort study and included 69 UC patients treated by radical cystectomy (RC) in our Department over an eight-year period, with complete follow-up information. Associations of UC variants as well as demographic and morphological factors with OS were assessed using univariable and multivariable Cox analysis. RESULTS: Our data showed that UC variants were statistically significantly associated with the presence of distant metastases (p=0.036) and positive surgical margins (p=0.009), but had no influence on OS (p=0.504). Further on, we demonstrated that age at surgery (p=0.045), tumor stage (p=0.012), lymph node involvement (p=0.009), and presence of positive surgical margins (p=0.002) had a statistically significant influence on OS both by univariable and multivariable Cox analysis. CONCLUSIONS: Age, tumor stage and lymph node involvement, as well as positive surgical margins represent prognostic factors in RC patients. UC variants were more likely to be associated to metastases and positive surgical margins but had no influence on OS.

Morphological features predictive for BRAF(V600E) mutation in papillary thyroid microcarcinomas.

BACKGROUND: The B-Raf proto-oncogene serine∕threonine kinase (BRAF) V600E (BRAF(V600E)) mutation represents a very specific marker for papillary thyroid carcinoma (PTC), including microcarcinomas (PTMCs). However, assessment of the BRAF(V600E) mutational status is expensive and not available in all pathology laboratories. AIM: We aimed to evaluate if we can identify those morphological features that could predict the presence of the BRAF(V600E) mutation in a series of PTMCs. MATERIALS AND METHODS: Nineteen PTMCs with analysis of 25 tumor foci were included. The following histological features were evaluated: size of the tumor, multifocality, extrathyroidal extension, tumor's border, characteristic PTC nuclear features, tumor-associated stromal reaction and histological variant. All PTMCs foci were subject to real-time polymerase chain reaction (RT-PCR) amplification targeting the BRAF gene. BRAF(V600E) mutation was assessed by high resolution melting (HRM) analysis and confirmed by Sanger sequencing. Morphological features associated with BRAF(V600E) positive and BRAF(V600E) negative PTMCs were compared using the two-tailed Fisher's exact test, with α set at ≤0.05. RESULTS: Out of the 25 PTMC foci, 16 (64%) were BRAF(V600E) negative, whereas nine (36%) were BRAF(V600E) positive. Our data showed that subcapsular localization (p=0.013), conventional histological type (p=0.05) and tumor-associated stromal reaction (moderate∕extensive fibrosis) (p=0.032) were significantly associated with the mutation. CONCLUSIONS: We have demonstrated the value of several morphological features in predicting a BRAF(V600E) mutation profile in PTMCs. All these parameters should be documented in the histopathological report, as they seem to be associated with this mutation and could serve as a risk stratification tool in the selection of patients in need for adjuvant post-surgery therapy.

A rare case of signet-ring cell carcinoma associated with poorly differentiated adenocarcinoma of the non-ampullary duodenum.

Primary duodenal cancer is a rare entity accounting for only 0.3% of all gastrointestinal cancers. Histopathologically, most duodenal cancers are mucin-producing adenocarcinomas, 34% being poorly differentiated. Signet-ring cell (SRC) carcinoma is extremely uncommon in the duodenum. Herein, we report a rare case of SRC carcinoma associated with poorly differentiated adenocarcinoma of the non-ampullary duodenum in a 74-year-old woman. The patient was admitted to the hospital for persistent epigastric pain, significant weight loss and hypochromic microcytic anemia. Esophago-gastro-duodenoscopy revealed a protruded lesion, with ulceration in the second portion of the duodenum, above the papilla. The patient was referred to surgery and pancreatico-duodenectomy with lymph node dissection was performed. The tumor consisted predominately of SRCs, Periodic Acid Schiff (PAS)-Alcian blue positive. The tumor cells were CDX2, cytokeratin (CK) 7 and CK 18/8 positive, which suggested a primary upper gastrointestinal tract site of origin. Immunostaining for mucin (MUC) 2 and MUC5AC was also positive demonstrating the duodenal goblet cells differentiation with a mixed gastric-foveolar and intestinal phenotype. Based on the morphological features and the immunohistochemical profile, a diagnosis of SRC carcinoma associated with poorly differentiated adenocarcinoma of the non-ampullary duodenum was set.

The storage period of the formalin-fixed paraffin-embedded tumor blocks does not influence the concentration and purity of the isolated DNA in a series of 83 renal and thyroid carcinomas.

Optimal recovery of nucleic acids from formalin-fixed paraffin-embedded (FFPE) tissues is highly dependent on a series of pre-extraction steps, mainly related (but not limited) to fixation. The aim of our study was to investigate if the storage period of the FFPE blocks had a significant effect on the isolated DNA. We examined the quantity and purity of the isolated DNA from 83 FFPE blocks, corresponding to malignant thyroid (n=28) and renal (n=55) carcinomas that had been stored in our department for up to eight years. The DNA extraction protocol was based on a precipitation method (MasterPure™ DNA Purification Kit, Epicentre), in accordance to the manufacturer instructions, optimized in our laboratory. A spectrophotometer was used to determine the yield (A260) and purity (A260/A280 ratio) of the isolated DNA. We successfully isolated good DNA quantity and purity from all our study cases (mean concentration: 223.4 ± 104.16 ng/µL; mean A260/A280 ratio: 1.68 ± 0.09). Moreover, no statistically significant differences were observed between tumor blocks stored for 2-3 years and 7-8 years, respectively, both in terms of DNA quantity (p=0.196) and purity (p=0.663). In conclusion, we successfully validated an efficient, reproducible DNA extraction technique that provided a good range of DNA concentrations and purity, regardless the type of tissue (thyroid or kidney). Moreover, we demonstrated that the storage period of the FFPE blocks does not have a significant influence on the DNA quantity and purity.