Anatomic pathology selected abstracts

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Correspondence: Dr. Emad A. Rakha at emad.rakha@nottingham.ac.uk or emad.rakha@nuh.nhs.uk

Differential expression patterns of GATA3 in vulvar intraepithelial neoplasia

The two main precursors of vulvar squamous cell carcinoma, usual and differentiated vulvar intraepithelial neoplasia, have a distinctive etiology, pathogenesis, and natural history. Usual-type vulvar intraepithelial neoplasia (VIN) is often associated with high-risk human papillomavirus (HPV), and differentiated VIN has de novo p53 genetic alterations that are unrelated to HPV infection. GATA-binding protein 3 (GATA3) is a tumor suppressor that shows increased expression in several types of human malignancies, including breast and bladder carcinomas. Little is known about the expression of GATA3 in vulvar squamous neoplasms. The authors have systematically examined the expression of GATA3 in 119 vulvar lesions and neoplasms, including 20 cases of lichen sclerosus, 12 cases of lichen simplex chronicus, 30 cases of usual-type VIN, 34 cases of differentiated VIN, and 23 cases of squamous cell carcinoma. Similar to adjacent non-neoplastic epidermis, moderate to strong GATA3 expression was retained in all cases of lichen sclerosus, lichen simplex chronicus, and usual-type VIN. However, in comparison, the GATA3 immunostaining pattern in differentiated VIN was distinct. Partial or complete loss of GATA3 expression in the basal layer with or without loss in the parabasal layer was observed in 30 of 34 (88 percent) differentiated VIN cases. Significant loss of GATA3 expression was observed in all (seven) squamous cell carcinomas associated with usual-type VIN and in 13 of 16 (81 percent) of those associated with differentiated VIN. There was no significant correlation between loss of GATA3 expression and overexpression of p53 in differentiated VIN. The study shows that loss of GATA3 expression is seen in the vast majority (87 percent) of vulvar squamous cell carcinomas. Downregulation of GATA3 may be an early event during tumorigenesis in differentiated VIN but not in HPV-related usual-type VIN. These data suggest that application of GATA3 immunohistochemistry along with p53 may be a useful tool in diagnosing VIN.

Goyal A, Zhang G, Yang B. Differential expression patterns of GATA3 in usual and differentiated types of vulvar intraepithelial neoplasia: potential diagnostic implications. Mod Pathol. 2018;31:1131–1140.

Correspondence: Dr. Bin Yang at yangb@ccf.org

Risk of lymph node metastasis in early gastric cardiac carcinomas

Clinical decision-making about endoscopic versus surgical resection of early gastric cardiac carcinoma remains challenging because of uncertainty about risk of lymph node metastasis. The authors conducted a multicenter study to investigate risk factors for lymph node metastasis in early gastric cardiac carcinoma. Guided by World Health Organization diagnostic criteria, they studied 2,101 radical resections of early gastric carcinoma for risk factors associated with lymph node metastasis, including tumor location, gross pattern, size, histology type, differentiation, invasion depth, and lymphovascular and perineural invasion. The authors found that the risk of lymph node metastasis was significantly lower in early gastric cardiac carcinomas (6.7 percent; 33 of 495) compared with early gastric noncardiac carcinomas (17.1 percent; 275 of 1,606; P < .0001). In early gastric cardiac carcinoma, no lymph node metastasis was identified in intramucosal carcinoma and uncommon types of carcinomas, irrespective of gross pattern, size, histologic type, differentiation, and invasion depth. Ulceration, size greater than 3 cm, and submucosal invasion were not significant independent risk factors for lymph node metastasis. In 33 early gastric cardiac carcinomas with lymph node metastasis, either lymphovascular invasion or poor differentiation was present in 16 (48.5 percent) cases, and both were present in six cases. Using multivariate analysis, independent risk factors of lymph node metastasis in early gastric cardiac carcinoma included lymphovascular invasion (odds ratio [OR], 7.6; 95 percent confidence interval [CI], 2.8–20.2; P < .0001) and poor differentiation (OR, 6.0; 95 percent CI, 1.4–25.9; P < .05). The authors concluded that lymph node metastasis was not identified in early gastric cardiac intramucosal carcinoma and uncommon types of carcinoma. The risk of lymph node metastasis was also significantly lower in tumors with submucosal invasion, especially for cases without lymphovascular invasion or poor differentiation. These results lend support to the role of endoscopic therapy in treating patients with early gastric cardiac carcinoma.

Huang Q, Cheng Y, Chen L, et al. Low risk of lymph node metastasis in 495 early gastric cardiac carcinomas: a multicenter clinicopathologic study of 2101 radical gastrectomies for early gastric carcinoma. Mod Pathol. 2018;31:1599–1607.

Correspondence: Dr. Qin Huang at qinhuang0122@​gmail.com