Secondary Logo

Journal Logo

Pseudomyxoma Peritonei

Pathology, a Historical Overview, and Proposal for Unified Nomenclature and Updated Grading

Bradley, Robert F., MD*; Carr, Norman J., FRCPath

doi: 10.1097/PCR.0000000000000305
Reviews
Open
SDC

Pseudomyxoma peritonei (PMP) is a clinically distinctive form of malignancy that typically arises from the appendix and is characterized by bulky accumulation of mucinous tumor deposits in the peritoneal cavity. It has defied stable pathologic categorization ever since first being described in the late 19th century. Since the early 20th century, many accounts have emphasized the bland histology of those cases arising from appendiceal precursors that had been considered benign, in contrast to higher-grade cases with more conventionally malignant histology. Beginning in the late 20th century, this was exemplified by divided nomenclature, with “carcinoma” phraseology being reserved for cases with clear-cut high-grade morphology. Such a divided approach is rendered problematic by the spectrum of atypia in many cases, including a significant subset with “intermediate” features. More recently, unified nomenclature has been favored for PMP of appendiceal origin, with an emphasis on tiers of grading. The goal is a clinically relevant and objectively reproducible grading scheme for what appears to be the spectrum of one clinicopathological entity (except perhaps for cases purely composed of signet-ring cells). Currently proposed consensus criteria focus on the distinction of cases of PMP as low grade, high grade, or high grade with signet-ring cells.

From the *Department of Pathology, University of South Carolina School of Medicine, Professional Pathology Services, Columbia, SC; and

Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Cellular Pathology, University Hospital Southampton, Southampton, United Kingdom.

Reprints: Robert F. Bradley, MD, One Science Ct, Suite 200, Columbia, SC 29203. E-mail: robert.bradley@ppspath.com.

The authors have no funding or conflicts to declare.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Pseudomyxoma peritonei” (PMP) is the clinical term applied to a neoplastic condition characterized by relentless accumulation of grossly evident mucinous tumor deposits in the peritoneal cavity. Pseudomyxoma peritonei almost always originates from a mucinous neoplasm of the appendix. The tendency of malignant cells from the appendix to produce abundant extracellular mucin, slowly infiltrating the peritoneum and underlying tissues with a low propensity for nodal or hematogenous spread relative to overall tumor bulk, accounts for the peculiarity of these tumors when compared with more conventional adenocarcinomas arising from other intestinal sites. Since the 19th century, controversies have persisted regarding the pathology of PMP, largely confounded by the distinctly bland histologic appearance of most cases.

The mucinous tumors that cause PMP characteristically produce the largest volumes of disease in the pelvis, paracolic gutters, greater omentum, under the right hemidiaphragm, in the retrohepatic space, and at the ligament of Treitz.1 These tumors also may encase the splenic capsule, and in females, the ovaries are often diffusely infiltrated, sometimes causing massive multiloculated cystic lesions. This characteristic pattern of disease, with relative sparing of the serosa of the peristaltically active small bowel and accumulation where peritoneal fluid is likely reabsorbed, has been called the “redistribution phenomenon.” The clinical designation of PMP is typically reserved for cases with spread of mucinous tumor beyond a localized focus, with spread throughout the abdominopelvic cavity. A very small proportion of PMP cases may also arise from the colon or rarely from other sites such as the pancreas, urachus, or appendiceal-type mucinous tumors arising in ovarian teratomas.2–4

Although usually slow growing, PMP proves fatal without definitive treatment (current standard being extensive “cytoreductive” abdominal surgery combined with hyperthermic intraperitoneal chemotherapy). Patients with high-grade disease are sometimes given systemic neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy after assessment of tumor response. A subset of patients with low-grade disease may remain asymptomatic for prolonged intervals, but most patients who are managed by repeat surgical debulking alone will succumb to intestinal obstruction, terminal starvation, and/or surgical complications.

Back to Top | Article Outline

HISTORICAL BACKGROUND

The condition was first noted in the 19th century as ovarian surgery became prevalent; included among the earliest accounts are descriptions of a “colloid cancer” of the peritoneum or ovary that was usually dealt with by partial evacuation and drainage of gelatinous contents, with disastrous results.5 Three major theories had developed by the end of the 19th century:

  • (1) Myxomatous peritonitis: Several of the earliest reports (Virchow, Mennig, Wendeler) suggested that it represented a peculiar myxomatous degeneration of the peritoneum secondary to nonspecific serosal irritation, including descriptions such as “peritonitis myxomatosa” and “peritonitis gelatinosa.”6,7
  • (2) Foreign body peritonitis: The most influential early descriptions of the pathology of this disease came from Werth8 in 1884, a German gynecologic surgeon who considered the condition to be a type of foreign body reaction to the insoluble and tenacious “pseudomucin” of ruptured ovarian cysts instead of a true myxomatous disease of the peritoneum. Werth8 thereby invented the phrase “pseudomyxoma peritonei” and strongly urged that the disease was a “plastic foreign-substance peritonitis” reactive to the gelatinous contents of ruptured ovarian cysts.7,9,10 Of note, the distinction of ovarian “pseudomucin” from mucus formed elsewhere in the body remained ubiquitous in reports of this disease until the mid-20th century and was based on chemical methodologies (eg, clotting upon acidification with acetic acid) that are no longer considered reliable for diagnosis.10,11
  • (3) Metastatic neoplasia: In contrast to the aforementioned theories favoring some form of peritonitis (either producing or reacting to the gelatinous component), Olshausen, in 1884, held the view that PMP was a metastatic neoplasm involving the peritoneum, further supported by the work of Pfannenstiel in 1890.7 In 1901, Frankel reported PMP in a male patient with an appendiceal mucinous lesion and also favored Olshausen's metastatic formation theory, suggesting that implantation metastases are usually found microscopically if a thorough search is made,12 thereby originated the now-accepted theory that PMP is “not merely a question of gelatinous matter found adhering to the peritoneum, but that, in addition, a new growth occurs.”7 The prototypically low cellularity of PMP, combined with historically limited microscopic sampling, seemed to favor the initial popularization of Werth's “pseudomyxoma peritonei” theory of a reaction to inert pseudomucin, along with similar descriptions such as “chronic pseudomyxomatous peritonitis.”5 Histologic descriptions supporting Olshausen's metastatic formation theory continued to accumulate in the first half of the 20th century, and the neoplastic/metastatic nature of PMP was eventually accepted. There were also further reports in the early 20th century associating PMP with appendiceal mucinous tumors, but until the 1990s, most of the relevant literature was devoted to ovarian mucinous tumors being the primary source of PMP in females.9,10,13 Grossly prominent ovarian involvement as noted in gynecologic reports contrasts with the near-normal gross appearance of the appendix in many cases of PMP. In patients with PMP, the entire appendix should be submitted for microscopic evaluation, even if grossly normal, usually revealing a low-grade mucinous neoplasm with thinning/fibrosis of the underlying appendiceal wall as evidence of prior transmural invasion. In other cases of PMP, the appendix may be grossly absent because of neoplastic obliteration. In 1991, Young et al14 analyzed 22 cases of PMP with ovarian involvement, carefully reviewed the preceding literature, and concluded that the ovarian tumors came from the appendix. A series of reports soon followed to bolster their observations with immunohistochemical and molecular methods.15–22
Back to Top | Article Outline

Modern Controversies (Divided vs Unified Nomenclature)

Since the neoplastic/metastatic nature of PMP began to be recognized in the late 19th century, a persistent source of confusion has been that commonly encountered well-differentiated cases of PMP, despite malignant clinical behavior, exhibit neoplastic epithelium morphologically similar to their histologically bland precursor lesions: mucinous appendiceal tumors that were widely considered “adenomas” until recently, despite frequent trespassing of normal histologic barriers with underrecognized obliteration of surrounding tissue layers, starting with loss of lamina propria at the earliest stage. Such low-stage appendiceal tumors are now more appropriately referred to as low-grade appendiceal mucinous neoplasms (LAMNs) because of their propensity to invade the appendiceal wall subtly (low-grade “pushing” invasion with a broad front) and eventually cause PMP, thereby exhibiting cancerous biological traits.23 The historical ambiguity regarding the nature of PMP is exemplified by the following quote from a review by Jeffries9 in 1932: “Pseudomyxoma peritonei is clinically a fatal disease, although pathologically it may be malignant or benign.” This evolving clinical/pathologic discrepancy with reference to the cancerous nature of low-grade appendiceal mucinous tumors has led some to use divided nomenclature for the histology of PMP. The most influential example of divided nomenclature is the 1995 study of PMP by Ronnett et al,24 in which the most well-differentiated cases (historically “benign”-appearing cases attributed to appendiceal adenomas) were separately designated as disseminated peritoneal adenomucinosis (DPAM). This terminology with a benign connotation was used in contrast to peritoneal mucinous carcinomatosis (PMCA), which was applied to cases with more classically “malignant” cytohistologic features (or PMCA-I/D if showing intermediate/hybrid or discordant features), somewhat complicated by the fact that most of the PMCA cases in that study were of colonic origin. The distinction of LAMN versus mucinous adenocarcinoma by Misdraji et al,23 insofar as it has been applied to cases of fully developed PMP, is another example of divided terminology. Others have favored unified terminology for appendiceal PMP across its morphologic spectrum, to be further refined by histologic grading instead of using differing terminologies.25–29 As will be discussed below, unified nomenclature is favored by evidence that appendiceal PMP is essentially one clinicopathologic form of malignancy with a broad spectrum of histologic differentiation.

In 2006, Bradley et al25 suggested unified nomenclature using the term “mucinous carcinoma peritonei” (MCP) for all variants of appendiceal PMP. Cases of PMP previously called DPAM and other well-differentiated variants previously called PMCA-I were combined as low-grade MCP (MCP-L), whereas moderately and poorly differentiated cases (previously called PMCA) were classified as high-grade MCP (MCP-H). This was partially based on similar survival curves for DPAM and well-differentiated hybrid cases that were previously called PMCA-I (except for “hybrid” cases with signet-ring cells, which were considered poorly differentiated by Bradley et al25—an important contrast to the study of Ronnett et al24). This limitation of the “low grade” designation to well-differentiated cases while assigning “high grade” to moderately and poorly differentiated cases is a notable exception to the current norm for grading of intestinal carcinomas.27 Analogous to other human malignancies, the occasional tendency toward nodal involvement and/or hematogenous metastases is associated with increasing histologic grade of PMP/MCP. However, a similar tendency among all grades toward parenchymal invasion of abdominal organs, particularly the muscular bowel wall, spleen, liver, myometrium, and ovaries, in addition to frequent omental caking, favors unified pathologic nomenclature denoting malignancy (MCP) for appendiceal PMP across its entire spectrum of histologic differentiation (Fig. 1). In a study by Carr et al.26 of 274 cases of PMP in 2012, there was not a significant correlation between histologic grade and the frequency of organ invasion

FIGURE 1

FIGURE 1

Pathologic studies continue to suggest that the lowest histologic grade of PMP/MCP be reserved for the most well-differentiated end of the histologic spectrum.28–30 It is unclear to what extent the inclusion of cases with acellular mucin only (cases excluded from analysis by Bradley et al25 but up to 8% of grade 1 cases in a study by Davison et al30) may be a confounding factor in some analyses. Nevertheless, most investigators favor that the low-grade category be reserved for cases with distinctly bland histology, for example, minimal or mild cytologic atypia, low cellularity, and no evidence of “destructive” invasion (ie, high-grade patterns of invasion detailed later in this review). Also, studies indicate that the presence of signet-ring cells carries a significantly adverse prognosis, currently favoring a 3-tier grading system of PMP in which grade 3 is reserved for cases with unequivocal signet-ring cells.28,30–32

Reflective of the above accumulation of findings regarding PMP in the pathology literature, the current consensus classification as reported by Carr et al31 provides 3 categories: low grade, high grade, and high grade with signet-ring cells:

  • PMP grade 1 = MCP-L
  • PMP grade 2 = MCP-H
  • PMP grade 3 = MCP-H with signet-ring cells

Of note, all cases should have a predominance of extracellular mucin (and clinical/macroscopic features of PMP/mucinous ascites) to be included under this classification. Per the aforementioned consensus classification and a subsequent collaborative review by Carr et al,31,32 DPAM and PMCA should be considered “synonymous” alternative terminology for MCP-L and MCP-H, respectively. This essentially provides a grading system of PMP that should be applicable across all institutions, similar to the schemes suggested by Davison et al30 and Shetty et al.28 “Low-grade” MCP applies to cases of PMP that are cytologically bland to mildly atypical (well differentiated/grade 1), and MCP-H is reserved for cases that are moderately to poorly differentiated (grade 2–3, reserving grade 3 for cases with a signet-ring cell component). Regarding the relationship of histologic grading to molecular findings, KRAS mutations are identified in most grades 1 and 2 cases but are generally lacking in grade 3 cases with a predominance of signet-ring cells. The appendix is often obliterated by tumor in grade 3 cases, and an underrecognized subset of these cases may originate from “goblet cell carcinoid” tumors (which rarely exhibit KRAS mutations).30

The above referenced consensus classification is a positive development in the quest for more consistent terminology and grading in cases of appendiceal PMP, but clear challenges remain. A continuing source of confusion is the morphologic dividing line between grade 1 and grade 2. Disseminated peritoneal adenomucinosis and MCP-L (PMP1, etc) are highly overlapping categories but are not exactly “synonymous” according to their original descriptions. A subset of MCP-L, as originally described, exhibits well-differentiated atypia that would have previously been considered PMCA-I and not DPAM. Additional evidence that many of the well-differentiated subset of cases previously designated PMCA-I could be reclassified as grade 1 MCP (MCP-L), as suggested by Bradley et al, is provided by an international registry study with the largest reported number of cases pooled from multiple institutions.33 Chua et al33 examined the outcome of 2259 patients with PMP of appendiceal origin from 16 institutions worldwide over an 18-year period, with standardized treatment protocols. This study included data regarding the pathologic classifications of PMP as DPAM, PMCA, or PMCA-I according to the Ronnett criteria, as independently assigned by each site. Outcomes were similar for DPAM and PMCA-I tumors (5-year overall survival of 81% for DPAM and 78% for PMCA-I vs 59% for PMCA), analogous to the aforementioned findings of Bradley et al.34 A significant proportion of this disputably “intermediate” subset may also be reflected in the findings of Davison et al,30 in which 12% of their low-grade (grade 1 of 3) cases demonstrated “increased proliferation” characterized as “either a questionable microscopic area of destructive invasion or nuclear atypia beyond that typical for low grade but insufficient for an unequivocal label of high-nuclear grade, accounting for less than 10% of the tumor.” Similar to the experience of Bradley et al, there was no significant difference of overall survival from other low-grade cases.30 Regardless of the implications of the above discussion for refined histologic grading, the inherent difficulty of finding a clear “low versus high grade” dividing line between the very well-differentiated and the more atypical “intermediate” cases of PMP/MCP illustrates that PMP is a singular malignancy for which unified nomenclature seems more appropriate than diverse diagnostic categories.25,27

The unified pathologic terminology of “mucinous carcinoma peritonei” helps to clarify that the phraseology of “pseudomyxoma peritonei” actually refers to a mucin-producing epithelial malignancy involving peritoneum in a clinically distinctive manner. Histologic grading of MCP of appendiceal origin can be further refined insofar as proves clinically relevant, analogous to all other mucinous carcinomas of gastrointestinal origin.

Back to Top | Article Outline

Updated Approach to Grading

To date, the clearest refinement of the histologic grading of appendiceal PMP/MCP, most easily applicable to the aforementioned consensus, was provided by Davison et al30 in 2014. As detailed in that study, key morphologic features that are associated with worse overall survival and justify a high-grade (grade 2) designation include any of the following: high cytologic grade, high tumor cellularity, specifically high-grade patterns of “destructive” invasion, and angiolymphatic or perineural invasion. As mentioned previously, grade 3 is assigned to cases with a signet-ring cell component.

Low-grade morphology is characterized by pseudostratified or flat strips of epithelium with mild nuclear atypia, a low-grade pattern of “pushing” invasion across a broad front, and overall maintenance of cellular polarity (Figs. 2A, B); high-grade cytology entails vesicular nuclei with prominent nucleoli, cellular stratification, cribriform or micropapillary architecture, and clearly elevated mitotic activity (Fig. 3). High cellularity, estimated for the entire case at low magnification, is defined as at least 20% epithelial cells within mucin pools. High-grade invasion is defined by any of the following: (1) irregularly infiltrative glands or single cells associated with desmoplasia (Fig. 4), (2) expansile cribriform growth (Fig. 5), or (3) small clusters or single cells within small mucin pools with or without desmoplasia (Fig. 6). The latter “small mucin pool pattern,” as described by Davison et al,30 is the most common pattern of destructive invasion in high-grade cases. For the purposes of this review, angiolymphatic or perineural invasion may also be considered “destructive invasion” and is very unlikely to occur in the absence of other adverse histologic features. A subset of low-grade (grade 1) cases may exhibit focal destructive-type invasion involving at most a single low-power field (40×) or focal areas (<10% of total tumor) with nuclear stratification and mild to moderate nuclear enlargement (Fig. 7). Regarding the potential discrepancy between grade 2 and grade 3 cases, more than focal areas with signet-ring cell morphology (>10% of cells) should be identified to qualify as grade 3, given that degenerating tumor cells and even histiocytes floating in mucin pools may often exhibit signet-ring cell-like morphology (Figs. 8, 9). One study suggests that signet cells isolated to mucin pools are less prognostically significant than those found invading tissue, which may relate to the aforementioned distinction of bona fide signet cells from potential mimics.35

FIGURE 2

FIGURE 2

FIGURE 3

FIGURE 3

FIGURE 4

FIGURE 4

FIGURE 5

FIGURE 5

FIGURE 6

FIGURE 6

FIGURE 7

FIGURE 7

FIGURE 8

FIGURE 8

FIGURE 9

FIGURE 9

Back to Top | Article Outline

CONCLUSIONS

In summary, PMP is a mucinous epithelial malignancy, characteristically from the appendix, with a distinctive clinical presentation and a relatively broad spectrum of histologic differentiation. This spectrum of aggressiveness is best reflected by histologic grading based upon a limited set of morphologic criteria, without need for further divided nomenclature that might imply disparate clinical entities. The term “mucinous carcinoma peritonei” with a 3-tiered grading scheme is currently favored. Grade 1 (low grade) should be reserved for cases lacking any significantly adverse histologic features, except for cases with limited foci of “increased proliferation” or other “intermediate” features that fall short of a clear-cut high-grade designation, as previously described. Grade 2 (high-grade) cases fulfill at least one of the following criteria: high cellularity, high-grade cytology, or a high-grade invasion pattern (including the underappreciated “small mucin pool pattern”). Cases with a bona fide signet-ring cell component are considered grade 3 (high grade with signet-ring cells). This unified approach to the pathology of PMP will allow for more standardized and prognostically valuable diagnostic reporting.

Back to Top | Article Outline

REFERENCES

1. Sugarbaker PH. Pseudomyxoma peritonei. A cancer whose biology is characterized by a redistribution phenomenon. Ann Surg 1994;219(2):109–111.
2. Rosenberger LH, Stein LH, Witkiewicz AK, et al. Intraductal papillary mucinous neoplasm (IPMN) with extra-pancreatic mucin: a case series and review of the literature. J Gastrointest Surg 2012;16:762–770.
3. Agrawal AK, Bobinski P, Grzebieniak Z, et al. Pseudomyxoma peritonei originating from urachus—case report and review of the literature. Curr Oncol 2014;21:e155–e165.
4. Vang R, Gown AM, Zhao C, et al. Ovarian mucinous tumors associated with mature cystic teratomas: morphologic and immunohistochemical analysis identifies a subset of potential teratomatous origin that shares features of lower gastrointestinal tract mucinous tumors more commonly encountered as secondary tumors in the ovary. Am J Surg Pathol 2007;31:854–869.
5. Wilson T. Gelatinous glandular cysts of the ovary, and the so-called pseudomyxoma of the peritoneum. Proc R Soc Med 1913;6(Obstet Gynaecol Sect):9–42.
6. Myer MW. A malignant type of pseudomyxoma peritonei penetrating the spleen and colon. Ann Surg 1907;45(6):838–851.
7. Aickin RTG. Pseudomyxoma Peritonei [doctoral thesis]. University of Edinburgh; 1904.
8. Werth R. Kliniche und anastomische untersuchungen zur lehre von der bauchgeschwullsten und der laparotomy. Pseudomyxoma Paeritonei. Arch Gynecol Obstet 1884;24:100–118.
9. Jeffries JW. Pseudomyxoma peritonei. Ann Surg 1932;96(2):215–218.
10. Lewis EG. Pseudomyxoma of the peritoneum. Surg Gynecol Obstet 1914;19(6):757–760.
11. Wynn R. Histochemical observations on ovarian “pseudomucin”. Am J Obstet Gynecol 1962;83(1):80–86.
12. Frankel E. Uber das sogenanute pseudomyxoma peritonei. Med Wochenschr 1901;48:965–970.
13. Trotter W. Peritoneal pseudomyxoma originating from the vermiform appendix. Br Med J 1910;19:687–689.
14. Young RH, Gilks CB, Scully RE. Mucinous tumors of the appendix associated with mucinous tumors of the ovary and pseudomyxoma peritonei. A clinicopathological analysis of 22 cases supporting an origin in the appendix. Am J Surg Pathol 1991;15:415–429.
15. Chuaqui RF, Zhuang Z, Emmert-Buck MR, et al. Genetic analysis of synchronous mucinous tumors of the ovary and appendix. Hum Pathol 1996;27:165–171.
16. Cuatrecasas M, Matias-Guiu X, Prat J. Synchronous mucinous tumors of the appendix and the ovary associated with pseudomyxoma peritonei: a clinicopathologic study of six cases with comparative analysis of c-Ki-ras mutations. Am J Surg Pathol 1996;20:739–746.
17. Prayson RA, Hart WR, Petras RE. Pseudomyxoma peritonei: a clinicopathologic study of 19 cases with emphasis on site of origin and nature of associated ovarian tumors. Am J Surg Pathol 1994;18:591–603.
18. Ronnett BM, Kurman RJ, Zahn CM, et al. Pseudomyxoma peritonei in women: a clinicopathologic analysis of 30 cases with emphasis on site of origin, prognosis, and relationship to ovarian mucinous tumors of low malignant potential. Hum Pathol 1995;26:509–524.
19. Ronnett BM, Shmookler BM, Diener-West M, et al. Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma peritonei in women. Int J Gynecol Pathol 1997;16:1–9.
20. Ronnett BM, Shmookler BM, Sugarbaker PH, et al. Pseudomyxoma peritonei: new concepts in diagnosis, origin, nomenclature, and relationship to mucinous borderline (low malignant potential) tumors of the ovary. Anat Pathol 1997;2:197–226.
21. Ronnett BM, Kurman RJ, Shmookler BM, et al. The morphologic spectrum of ovarian metastases of appendiceal adenocarcinomas: a clinicopathologic and immunohistochemical analysis of tumors often misinterpreted as primary ovarian tumors or metastatic tumors from other gastrointestinal sites. Am J Surg Pathol 1997;21:1144–1155.
22. Szych C, Staebler A, Connolly DC, et al. Molecular genetic evidence supporting the clonality and appendiceal origin of pseudomyxoma peritonei in women. Am J Pathol 1999;154:1849–1855.
23. Misdraji J, Yantiss RK, Graeme-Cook FM, et al. Appendiceal mucinous neoplasms. Am J Surg Pathol 2003;27:1089–1103.
24. Ronnett BM, Zahn CM, Kurman RJ, et al. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis: a clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to ‘pseudomyxoma peritonei’. Am J Surg Pathol 1995;19:1390–1408.
25. Bradley RF, Stewart JH IV, Russell GV, et al. Pseudomyxoma peritonei of appendiceal origin: a clinicopathologic analysis of 101 patients uniformly treated at a single institution, with literature overview. Am J Surg Pathol 2006;30:551–559.
26. Carr NJ, Finch J, Ilesley IC, et al. Pathology and prognosis in pseudomyxoma peritonei: a review of 274 cases. J Clin Pathol 2012;65:919–923.
27. Bradley RF, Cortina G, Geisinger KR. Pseudomyxoma peritonei: review of the controversy. Curr Diagn Pathol 2007;13(5):410–416.
28. Shetty S, Natarajan B, Thomas P, et al. Proposed classification of pseudomyxoma peritonei: influence of signet ring cells on survival. Am Surg 2013;79:1171–1176.
29. Grotz TE, Royal RE, Mansfield PF, et al. Stratification of outcomes for mucinous appendiceal adenocarcinoma with peritoneal metastasis by histological grade. World J Gastrointest Oncol 2017;9(9):354–362.
30. Davison JM, Choudry HA, Pingpank JF, et al. Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade. Mod Pathol 2014;27:1521–1539.
31. Carr NJ, Cecil TD, Mohamed F, et al. A consensus for classification and pathologic reporting of pseudomyxoma peritonei and associated appendiceal neoplasia: the results of the Peritoneal Surface Oncology Group International (PSOGI) modified Delphi process. Am J Surg Pathol 2016;40:14–26.
32. Carr NJ, Bibeau F, Bradley RF, et al. The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei. Histopathology 2017;71(6):847–858.
33. Chua TC, Moran BJ, Sugarbaker PH, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol 2012;30:2449–2456.
34. Nakakura EK. Pseudomyxoma peritonei: more questions than answers. J Clin Oncol 2012;30(20):2429–2430.
35. Sirintrapun SJ, Blackham AU, Russell G, et al. Significance of signet ring cells in high-grade mucinous adenocarcinoma of the peritoneum from appendiceal origin. Hum Pathol 2014;45(8):1597–1604.
Keywords:

appendiceal mucinous neoplasm; mucinous carcinoma peritonei; pseudomyxoma peritonei

© 2019 Lippincott Williams & Wilkins, Inc.