There is considerable controversy regarding the most appropriate terminology for appendiceal mucinous tumors and pseudomyxoma peritonei because tumors that resemble appendiceal adenomas can disseminate to the peritoneum and cause the death of the patient. Most of the debate is due to philosophical differences regarding the nature of pseudomyxoma peritonei. One viewpoint is that pseudomyxoma peritonei results from rupture of an adenoma of the appendix, with seeding of the peritoneum by low-grade neoplastic, but noninvasive mucinous epithelium. Investigators with this viewpoint classify pseudomyxoma peritonei as disseminated peritoneal adenomucinosis.¹ The opposing view is that peritoneal dissemination is equivalent to carcinoma and that the source appendiceal tumors are actually adenocarcinomas.²,³ However, the criteria for invasion in appendiceal tumors are poorly defined, and their proposed classifications reflect the difficulty of assigning them into benign or malignant categories (Table 19.1).¹, ², ³, ⁴ and ⁵ The Armed Forces Institute of Pathology proposed that appendiceal mucinous neoplasms be classified as adenomas, tumors of uncertain malignant potential, and invasive mucinous carcinoma, based on tumor stage.² That scheme defines adenomas as mucinous neoplasms confined to the mucosa with intact muscularis mucosae, whereas tumors with infiltrative mural invasion or proliferation of neoplastic epithelium outside the appendix (pseudomyxoma peritonei) are considered to be carcinomas. More problematic tumors that show “pushing” invasion with tongues of epithelium dissecting outward in a “diverticulum-like” fashion or acellular mucin outside the appendix associated with loss of the muscularis mucosae are classified as mucinous tumor of uncertain
malignant potential. Others define the uncertain malignant potential category as tumors with involvement of the proximal margin, tumors with mucin or epithelium in the appendiceal wall that is not clearly invasive, and cases in which the possibility of extraappendiceal epithelium cannot be excluded.⁵,⁶ Some have suggested that, to avoid nomenclature confusion, the entire spectrum of mucinous tumors, from adenomas to mucinous tumors with presumed pushing invasion and pseudomyxoma peritonei, be classified using a single-term, low-grade appendiceal mucinous neoplasms (LAMN) and that the pathology report describes the stage of disease.⁴ In its most recent classification of gastrointestinal tumors, the World Health Organization adopted this terminology to describe low-grade carcinomas but maintained the term adenoma for tumors confined to the mucosa.⁷

Adenomas are benign tumors of the appendix that are often incidental lesions detected in appendectomy specimens obtained for other reasons, but they can present with right lower quadrant pain and infrequently a palpable right lower quadrant mass. They might not produce any gross abnormalities or can cause cystic dilatation due to accumulation of tenacious mucin, but they do not display mucin on the external surface. Adenomas are confined to the appendiceal mucosa and surrounded by intact muscularis mucosae, although the lymphoid tissue of the lamina
propria is often atrophic (Figure 19.1).²,⁴,⁸ Tumors are composed of a villous or flat proliferation of mucinous epithelial cells with abundant intracytoplasmic mucin (Figure 19.2). Deeper glands typically have straight luminal edges, although serrated architecture may also be present, mimicking the appearance of a serrated polyp, as discussed in Chapter 20.¹,² Mucin accumulation frequently produces cystic dilatation of the appendix, in which case the term cystadenoma may be applied. Cystadenomas mostly contain a flat, undulating epithelial cell lining with infrequent villous areas that distinguish these lesions from retention cysts (Figure 19.3).²,⁴,⁸,⁹

Appendiceal mucinous adenomas display a spectrum of cytologic atypia, which is classified as low- or high-grade dysplasia in the same manner as in other parts of the gastrointestinal tract. Most tumors are low grade with nuclear hyperchromasia, pseudostratification, rare mitoses, and apoptotic nuclear debris.⁴,⁹,¹⁰ High-grade tumors show a greater degree of nuclear pleomorphism with stratification and loss of cell polarity equivalent to intraepithelial carcinoma (Figure 19.4). However, appendiceal mucinous adenomas have no potential for aggressive clinical behavior and are cured by appendectomy. Mucinous neoplasms associated with mural changes, such as disruption of the muscularis mucosae or replacement of the muscularis mucosae by fibrous tissue, or with extraappendiceal mucin are better classified as LAMN to convey some degree of uncertainty regarding the biologic potential of the lesion.

LAMN resemble appendiceal adenomas but have the propensity to spread to the peritoneum, recur, and result in the death of the patient. They contain mucinous epithelium and display a villous architecture or undulating, flat luminal surface. Unlike adenomas, LAMN show pushing invasion through the muscularis mucosae, hyalinizing fibrosis of the muscularis mucosae, or frank rupture of the appendix with extruded mucin. Unfortunately, criteria for mural invasion in appendiceal mucinous neoplasms are not well defined. As a result, they have been variably classified as ruptured adenomas, tumors of uncertain malignant potential, and adenocarcinomas reflecting the difficulty of classifying them as benign or malignant (Table 19.1).¹, ² and ³,⁵,⁷, ⁸ and ⁹,¹¹,¹² The most recent World Health Organization classification scheme denotes low-grade mucinous tumors with pushing invasion as LAMN, whereas the term mucinous adenocarcinoma is reserved for high-grade tumors or those with conventional invasion.⁷ Both low- and high-grade mucinous neoplasms that extend beyond the muscularis mucosae are staged as adenocarcinomas in the seventh edition of the American Joint Committee on Cancer (AJCC) Staging Manual.¹³