Pathology of Mucinous Appendiceal Tumors and Pseudomyxoma Peritonei

Abstract

Neoplasms of the appendix are rare, but because of their unusual presentation and unpredictable biologic behavior, it is important to diagnose them correctly. Mucinous tumors account for 58 % of malignant tumors of appendix in SEER database and the remaining are carcinoids. The mucinous appendiceal tumors have a potential to spread to the peritoneum and viscera in the form of gelatinous material with or without neoplastic cells resulting in Pseudomyxoma peritonei. (PMP) PMP is a clinical entity that has a unique biological behavior and can arise from seemingly benign tumors to frankly malignant ones. Several classifications exist for PMP of which Ronnet's classification has been the most popular. In 2010, the WHO proposed a 2 tier classification that classified PMP as either low grade or high grade based on the presence of mucin, cytological and architectural features. According to this classification when the underlying cause for PMP is an appendiceal tumor it is always a mucinous adenocarcinoma rather than a mucocoele or adenoma and these terms should no longer be used. This system of classification helps in predicting the behavior of the tumor and proper treatment strategies. The understanding of the pathogenesis of the disease has also improved with identification of newer biomarkers and molecular genetic alterations. IHC markers CK 20, CDX2 and MUC2 are found to be positive in these tumors in addition to KRAS mutation and loss of heterozygosity in some gene loci. Proper histopathologic classification and predicting the tumor behavior requires a close interaction between the pathologist and the surgeon. The use of the combined modality treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has led to a 5-year survival ranging from 62.5 % to 100 % for low grade, and 0 %-65 % for high grade disease. This article focuses on the etiopathogenesis, clinical behavior, diagnosis and classification of mucinous tumors of the appendix and pseudomyxoma peritonei.

Keywords: Cytokeratin; Cytoreductive surgery; Hyperthermic intraperitoneal chemotherapy; Immunohistochemistry; Psuedomyxoma peritonei.

Fig. 1

Schematic representation of the events resulting in the development of PMP. The pathologic process starts with a neoplastic transformation of the appendiceal goblet cells and development of a primary mucinous tumor (1). Overproduction of mucin and obstruction of the appendiceal lumen lead to the development, and subsequent rupture, of a mucocele (2). shedded tumor cells gain access to the peritoneal cavity and circulate with the peritoneal fluid (3). Accordingly, tumor cells redistribute and accumulate within the dependent portions of the peritoneal cavity (3*, downward arrows) as well as at the peritoneal fluid reabsorption sites (3**, upward arrows). Reproduced with permission from Ref .

Fig. 2

a Acellular mucin b organizing mucin c neoplastic cells with low grade features d neoplastic cells with high grade features