Steatotic and Steatohepatitic Hepatocellular Carcinomas: Features in a Series With Predominantly Viral Etiology.

Hepatocellular carcinomas (HCCs) with steatohepatitis and steatosis are reported with varying definitions and clinicopathologic features. We aimed to search the attributes of steatohepatitic hepatocellular carcinoma (SH-HCC) and steatotic-HCC in our series. A retrospective clinicopathologic analyses of 150 HCCs and immunostaining for C-reactive protein (CRP) and serum amyloid A (SAA) were performed. Tumors were reclassified as all SH-HCC, limited SH-HCC, typical SH-HCC (steatohepatitic features in >5%, 5% to 50%, and ≥50% of the tumor, respectively), steatotic-HCC, and classic HCC (C-HCC). Group comparisons were made using Kruskal-Wallis and Kaplan-Meier tests. The background etiology in all SH-HCCs was pure viral in 51.4%, nonalcoholic steatohepatitis (NASH)/alcoholic liver disease (ALD) alone/mixed in 34.3%, and unidentified in normal liver in 14.3%. All SH-HCCS (n=35, 23.3%) and typical SH-HCCs (n=13, 8.6%) had higher NASH/ALD. Limited SH-HCCs (n=22, 14.6%) had higher ALD (all P<0.05). Typical SH-HCCs tended to have more NASH (P=0.054). Steatotic-HCCs (n=13, 9%) and C-HCCs (n=102, 68%) had higher pure viral etiology and serum CRP (all P<0.05). CRP and SAA were positive in 69% and 27% of the tumors, respectively. SAA positivity correlated with ALD (P=0.026). In the overall group disease-free survival rates at 1, 5, 10, and 20 years were 97.0%, 82.3%, 79.6%, and 77.2%, respectively. Demographics, tumor characteristics, CRP and SAA positivity, and survival were similar between the groups (P>0.05). SH-HCC is heterogenous in terms of underlying etiologies, and can be seen in NASH/ALD, pure viral and noncirrhotic/normal background. The ≥50% cutoff for the definition of SH-HCC can lead to overlook ALD-related SH-HCC. Steatotic-HCC seems more similar to C-HCC rather than SH-HCC, but none of them feature as a different prognostic group.

How Does It Feel to Be a Pathologist in Turkey? Results of a Survey on Job Satisfaction and Perception of Pathology.

OBJECTIVE: Job satisfaction affects productivity and professional performance in many aspects; however, there is limited data regarding pathologists' job satisfaction. Hence, in this study, we aimed to evaluate surgical pathologists' job satisfaction in Turkey. MATERIALS AND METHODS: We conducted a 59-item web-based survey questioning respondents' institutional background, history of training, continuing education status/research activities, physical conditions, professional well-being, and job satisfaction level. Likert-type and open/ close ended questions were asked and scored. The participants were also asked to complete the Minnesota Satisfaction Questionnaire-Short Form. RESULTS: Of the 321 respondents, 75% were female, the median age was 41 years (range 28-71 years), experience as a pathologist ranged between 0.12 and 44 years (mean 11.4±9.16 years). Academic pathologists, senior pathologists with ≥20 years of experience, and pathologists working at large institutions and living in developed cities expressed better physical conditions, higher satisfaction with working conditions and, therefore, higher overall job satisfaction (p < 0.05). 98% agreed that pathologists have a critical impact on patient management; however, the majority ( > 80%) thought that patients barely know what pathologists do and other physicians rarely understand the difficulty and limitations in pathology practice. 82% were happy to have chosen pathology but 45% reported to experience the feeling of being "burnt out". CONCLUSIONS: Our findings suggest that younger pathologists are less satisfied with their jobs and a surgical pathologist's job satisfaction increases with the physical and technical quality of the pathology laboratory/institution, and years of experience. Pathologists seem to be aware of their important role in patient management although they think that pathology remains "invisible" to many physicians and patients.

The pursuit of understanding multinucleated giant cells in indeterminate and malignant thyroid cytology samples.

BACKGROUND: Multinucleated giant cell (MGC) present in a variety of non-neoplastic and neoplastic lesions of the thyroid on cytology samples. We aimed to investigate whether certain MGC features that can help us in routine cytopathology practice. METHOD: One hundred and thirty seven cases thyroid fine-needle aspiration material, which was diagnosed as indeterminate or malignant according to the Bethesda categorization, were reviewed. All cytomorphological features of the MGCs were documented. These features correlated with Bethesda categories and the final diagnosis of the subsequent surgical specimen. RESULTS: The presence of the MGCs was identified in 42% of the samples (58 cases-total 236 MGCs). Eighty eight of them (37%) had dense cytoplasm, 148 of them had foamy cytoplasm. The mean number of dense and foamy MGC per case was higher in the malignant category (3.2 for dense MGC and 6 for foamy MGC per case). All dense MGCs were found to be in patients with papillary thyroid carcinoma (PTC). Remarkably, follicular patterned lesions had less often dense MGC compared to papillary patterned lesions (16.6% and 46.8% respectively). We detected a nuclear irregularity in 49 dense MGC (55%), groove-like features in 24 dense MGC (27.2%), and presence of some material/cell in 8 dense MGC (9%). CONCLUSION: The presence of dense MGC is an important finding for guiding accurate Bethesda categorization, especially in indeterminate and malignant categories. Besides, the presence of some material or cell in MGCs cytoplasm can be an important indicator for the prognosis of the PTC cases.

Atypical goblet cell hyperplasia occurs in CPAM 1, 2, and 3, and is a probable precursor lesion for childhood adenocarcinoma.

Congenital pulmonary airway malformation (CPAM) is a developmental disorder. Types 1-2-3 are the more common ones. Atypical goblet cell hyperplasia (AGCH) in CPAM might be a precursor lesion for pulmonary adenocarcinomas. In nine out of 33 CPAM cases, types 1-3 showed foci of goblet cell proliferations. As these cells completely replace normal epithelium, we prefer to name these proliferations AGCH. In 5 cases, adenocarcinomas were seen (AC). All cases were analyzed for proteins possibly being associated with CPAM development: fibroblast growth factor 10 (FGF10) and receptor 2 (FGFR2), forkhead box A1 (FOXA1) and A2 (FOXA2), MUC protein 5AC (MUC5AC), human epidermal growth factor receptor 2 (erbB2, HER2/neu), hepatocyte nuclear factor 4α (HNF4α), SOX2, and Ying Yang protein 1 (YY1). By next generation sequencing, AGCH and adenocarcinomas were evaluated for driver mutations. Expression for FGF10, FGFR2, FOXA1, and FOXA2 was seen in CPAM epithelium and stroma, but not differently in AGCH and AC. SOX2 was positive in CPAM epithelium and AGCH, however weakly in AC. YY1 and MUC5AC showed more intense staining in AGCH and AC than in CPAM epithelium. HER2 was intensely expressed in AC and less intensely in AGCH, but not in CPAM epithelium. KRAS mutation in exon 2 was detected in all AGCH and AC, but was absent in CPAM epithelia. AGCH can arise in CPAM types 1-3. Oncogenic KRAS mutation seems to be the oncogenic driver already in AGCH, proving its role as a precursor lesion for adenocarcinoma. It might upregulate HER2 at the protein level. YY1 seems to be involved in carcinogenesis.

Brush Biopsy Sample Quality: Preliminary Investigation of a Metal Brush Prototype

Objective: To qualitatively investigate whether a prototype brush composed of metal bristles collects oral epithelial cells effectively for cytological evaluation of oral mucosal lesions. Material and Methods: Twenty patients with suspicious oral mucosal lesions were enrolled. Patients were asked to gargle with saline and to deposit the oral rinse into specimen cup. Then, oral mucosal cell samples were collected using a metal oral brush, via sweeping motion. Punch biopsy was performed for histological examination. All samples were evaluated with liquid based cytology (LBC) according to the cellularity, the depth of the epithelial layer, cellular integrity by an oral pathologist. Results: Oral rinse provided samples with 100% cellular integrity and cellularity, mostly from the intermediary layers. With metal brush, both inadequate cellularity and cellular integrity was observed in 25% of the cases. Cellular integrity was adequate in 65%, cellularity was adequate in 45% of the lesions. Samples were dominantly from the intermediary layers, but in one case, metal brush collected cells from the parabasal layer. Conclusion: The narrow spiral pitch and width of metal bristles may have resisted to release the cellular samples collected. With adjustment of the spiral pitch and diameter of metal brush bristles, its' efficacy could be enhanced.

Thioredoxin interacting protein promotes invasion in hepatocellular carcinoma.

BACKGROUND: Considerable evidence suggests that oxidative stress plays an essential role in the progression of hepatocellular carcinoma (HCC). While acquired resistance to oxidative stress is the main driver of aggressive cell phenotype, the underlying mechanisms remain unknown. Here, we tested the hypothesis that elevated expression of Thioredoxin-interacting protein (TXNIP) is a main regulator of the aggressive phenotype in HCC. MATERIALS AND METHODS: To test this hypothesis, we measured TXNIP expression levels in 11 HCC cell lines by qPCR and western blotting. In addition, 80 pairs of HCC tissues and matched liver tissues of 73 cases, as well as 11 normal liver tissue samples were examined by immunohistochemistry. Besides, TXNIP expression levels were analyzed by Oncomine Platform in seven independent microarray datasets. Finally, the functional role of TXNIP in HCC was investigated in vitro and in vivo by silencing and overexpression studies. RESULTS: Our results show that TXNIP expression is significantly increased in HCC compared to non-tumor counterparts (p < 0.0001) as well as to normal (p < 0.0001) and cirrhotic (p < 0.0001) liver tissues. Moreover, stable overexpression of TXNIP in HCC cells (i) significantly increases ROS levels, (ii) induces EMT phenotype, (iii) increases motility, invasion and 3D branching tubulogenesis, (iv) decreases apoptosis, and (v) elevates in vivo metastasis in zebrafish embryos. Finally, we identify sinusoidal/stromal and cytoplasmic TXNIP staining patterns as risk factors for intrahepatic vascular invasion (p:0.0400). CONCLUSION: Our results strongly suggest that overexpression of TXNIP has a pivotal role in HCC progression by inducing cell survival, invasion, and metastasis.