A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification.

BACKGROUND: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. METHODS: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). RESULTS: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. CONCLUSIONS: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Gastric Inverted Polyps-Distinctive Subepithelial Lesions of the Stomach: Clinicopathologic Analysis of 12 Cases With an Emphasis on Neoplastic Potential.

Gastric inverted polyps (GIPs) are rare gastric polyps characterized by a submucosal inverted growth of mucosal components. Because of their rarity, they are not well characterized and are diagnostically challenging. We examined 12 cases of GIPs arising in 8 male and 4 female patients (mean age: 56 y). Most GIPs (11/12, 92%) occurred as a single, rounded subepithelial lesion in the body or fundus (mean size: 14.9 mm). Histologically, GIPs consisted of gastric-type glandular epithelium and smooth muscle component, growing in an endophytic manner; however, they displayed significant morphologic variations. We classified GIPs into 3 subtypes by the following features: communication with the mucosal surface, smooth muscle boundary, and tissue organization. The defining characteristics of type 1 were a mucosal communicating structure at the center and a well-defined smooth muscle boundary, resulting in a characteristic low-magnification morphology of a round vase. Type 2 had an organized glandular proliferation with smooth muscle boundary and no central communicating structure. Type 3 GIPs had no mucosal communicating structure or smooth muscle boundary; its key histologic feature was the lobular organization pattern produced by proliferations of cystic or hyperplastic glands and smooth muscle. All type 1 GIPs exhibited coexisting adenocarcinoma (3 cases) or stromal proliferation (3 cases). Three patients with type 2 GIP had separate adenocarcinoma. None of the type 3 GIPs had accompanying carcinoma. In conclusion, GIPs are a heterogenous group showing different morphology and clinical behavior. Notably, type 1 GIP could be considered a precancerous lesion with the potential to develop adenocarcinoma.

PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms.

BACKGROUND: Recent findings in molecular pathology suggest that genetic translocation and/oroverexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. Weinvestigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues. METHODS: A total of 113 cases of surgically resected salivary gland neoplasms at the NationalCancer Center from January 2007 to March 2017 were identified. Immunohistochemical stainingof PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays. RESULTS: Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showednuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphicadenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary glandneoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissuesSOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expressionwas observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not inother benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors.Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%)malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and onemyoepithelial carcinoma with focal AdCC-like histology. CONCLUSIONS: PLAG1 expression is specificto pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor,but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology isunclear in the surgical specimen.

The expression of FAS-associated factor 1 and heat shock protein 70 in ovarian cancer.

OBJECTIVE: In this study, we evaluated the expression of FAS-associated factor 1 (FAF1) and heat shock protein 70 (HSP70) in normal ovary and ovarian cancer, and also analyzed the correlation between FAF1 and HSP70 in ovarian cancer. METHODS: The patient group consisted of 29 unrelated Korean women diagnosed as ovarian cancers and control samples were obtained from 7 patients who underwent oophorectomy for benign disease of uterus, and normal ovary was confirmed histologically from biopsy. We examined FAF1 and HSP70 expression by western blot analysis and immunohistochemical staining in normal ovary and ovarian cancer. Furthermore, we examined a correlation between FAF1 and HSP70 in ovarian cancer. RESULTS: The expression of FAF1 was lower in ovarian cancer than that in normal ovary (P=0.02), and the expression of HSP70 was increased in ovarian cancer in comparison to that in normal ovary (P=0.03). The expression of FAF1 was decreased in advanced stages (stage III or stage IV) as compared with early stages (stage I or stage II) (P=0.01). The expression of HSP70 was not significantly related with ovarian cancer histology (P=0.10), but the expression of HSP70 was most increased with papillary serous carcinomas and undifferentiated ovarian cancer. The expression of FAF1 was inversely correlated with the expression of HSP70 in ovarian cancer (Spearman correlation coefficience=-0.47). CONCLUSION: We concluded that the expression of FAF1 or HSP70 each seems to have a meaning as a biomarker for early detection of ovarian cancer. The expressions of FAF1 and HSP70 seem to be more valuable in predicting ovarian cancer when used together because of their inverse correlation. This is the first study about the expression of FAF1 in ovarian cancer and the correlation between FAF1 and HSP70 expression in ovarian cancer.

The effects of the Trendelenburg position and intrathoracic pressure on the subclavian cross-sectional area and distance from the subclavian vein to pleura in anesthetized patients.

BACKGROUND: The effects of maneuvers to increase intrathoracic pressure and of Trendelenburg position on the cross-sectional area (CSA) of the subclavian vein (SCV) and the relationship between the SCV and adjacent structures have not been investigated. METHODS: In ultrasonography-guided SCV catheterization (N = 30), the CSA of the SCV and the distance between the SCV and pleura (DSCV-pleura) were determined during 10-second airway opening, and 10-second positive inspiratory hold with 20 cm H2O in the supine position (S-0, and S-20) and the 10° Trendelenburg position (T-0, and T-20). In addition to a statistical significance of P < 0.05, CSA and DSCV-pleura differences of ≥15% were defined as clinically relevant changes. RESULTS: CSA (mean [95% confidence interval]) in S-20, T-0, and T-20 (1.02 [0.95-1.14] cm(2), 1.04 [0.95-1.15] cm(2), and 1.14 [1.04-1.24] cm(2), respectively) was significantly larger than a CSA in S-0 (0.93 [0.86-1.00] cm(2), all P < 0.001). However, only the increase of CSA in T-20 vs S-0 (0.21 cm(2), 23.2%) was clinically meaningful (≥15%). The number of patients who showed CSA increase ≥15% was more in S-0 to T-20 (57%) compared with those in S-0 to S-20 (23%) and S-0 to T-0 (27%). DSCV-pleura measurements (mean) in S-20 and T-20 (0.61 and 0.60 cm) were significantly shorter than those in S-0 (0.70 cm, all P < 0.001), but the reductions of DSCV-pleura were not clinically meaningful (≥15%). CONCLUSIONS: The combined application of inspiratory hold and Trendelenburg position provided a greater and more relevant degree of CSA increase without compromising DSCV-pleura, which may facilitate SCV catheterization. Further investigations are needed to determine whether these results affect the success rate of catheterization and the risk of procedural injury.