Secreted mucins in pseudomyxoma peritonei: pathophysiological significance and potential therapeutic prospects

Abstract

Pseudomyxoma peritonei (PMP, ORPHA26790) is a clinical syndrome characterized by progressive dissemination of mucinous tumors and mucinous ascites in the abdomen and pelvis. PMP is a rare disease with an estimated incidence of 1–2 out of a million. Clinically, PMP usually presents with a variety of unspecific signs and symptoms, including abdominal pain and distention, ascites or even bowel obstruction. It is also diagnosed incidentally at surgical or non-surgical investigations of the abdominopelvic viscera. PMP is a neoplastic disease originating from a primary mucinous tumor of the appendix with a distinctive pattern of the peritoneal spread. Computed tomography and histopathology are the most reliable diagnostic modalities. The differential diagnosis of the disease includes secondary peritoneal carcinomatoses and some rare peritoneal conditions. Optimal elimination of mucin and the mucin-secreting tumor comprises the current standard of care for PMP offered in specialized centers as visceral resections and peritonectomy combined with intraperitoneal chemotherapy. This multidisciplinary approach has reportedly provided a median survival rate of 16.3 years, a median progression-free survival rate of 8.2 years and 10- and 15-year survival rates of 63% and 59%, respectively. Despite its indolent, bland nature as a neoplasm, PMP is a debilitating condition that severely impacts quality of life. It tends to be diagnosed at advanced stages and frequently recurs after treatment. Being ignored in research, however, PMP remains a challenging, enigmatic entity. Clinicopathological features of the PMP syndrome and its morbid complications closely correspond with the multifocal distribution of the secreted mucin collections and mucin-secreting implants. Novel strategies are thus required to facilitate macroscopic, as well as microscopic, elimination of mucin and its source as the key components of the disease. In this regard, MUC2, MUC5AC and MUC5B have been found as the secreted mucins of relevance in PMP. Development of mucin-targeted therapies could be a promising avenue for future research which is addressed in this article.

Proactive Management for Gastric, Colorectal and Appendiceal Malignancies: Preventing Peritoneal Metastases with Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

“…PMP has an estimated incidence of 1-2 in a million [98] and is listed by the National Organization for Rare Disorders as a rare disease [99]. Appendiceal mucinous neoplasms are considered equally rare tumors with an age-adjusted incidence of 0-12 cases per 1 million individuals per year [100].…”

Pseudomyxoma Peritonei: A Case Report of an Incidental Finding at Cesarean Section

“…The pathologic process begins with neoplastic transformation of the appendiceal goblet cells that, upon appendiceal perforation, continue to proliferate into the peritoneal cavity. Through maintenance of mucin expression, intraperitoneal mucin amasses resulting in voluminous PMP [10].…”

“…Amini and co-workers explored several novel approaches to mucin production including glucocorticoids and COX inhibition amongst others [10]. This may present an adjunct area of treatment in the future.…”

Pseudomyxoma peritonei in a pediatric patient: A case report and literature review

“…[1][2][3][4] PMP has different forms of presentation and is classified into three subtypes: disseminated peritoneal adenomucinosis (DPAM), which includes histopathologically benign peritoneal lesions; peritoneal mucinous carcinomatosis (PMCA), which includes malignant lesions of a more aggressive course; and a third borderline subtype called peritoneal mucinous carcinomatosis, which exhibits intermediate features. [5][6][7] It has an indolent behavior, with nonspecific clinical manifestations resulting from the compression of intraabdominal structures, such as distension and pain, mechanical or functional intestinal obstruction, intestinal habit changes, nutritional failure and malnutrition secondary to increased pressure, fistulae, and infection. 1,2,8 Although ovary and appendix are implicated as the most common primary sites, PMP may also originate from other sites such as the ovarian tubes, pancreas, spleen and small intestine, while in some cases the primary site remains unknown.…”