J Pathol Transl Med.  2021 Jul;55(4):247-264. 10.4132/jptm.2021.05.28.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms

• Kang DW
• Kim Bh
• Kim JM
• Kim J
• Chang HJ
• Chang MS
• Sohn JH
• Cho MY
• Jin SY
• Chang HK
• Han HS
• Kim JY
• Kim HS
• Park DY
• Park HY
• Lee SJ
• Lee W
• Lee HS
• Kang YN
• Choi Y
• The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists

• KMID: 2518425
• DOI: http://doi.org/10.4132/jptm.2021.05.28

Abstract

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Keyword

Appendiceal mucinous neoplasm; Disseminated peritoneal mucinous disease; Standardization; Pathologic diagnosis

Figure

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  Fig. 1. Low-grade appendiceal mucinous neoplasm (LAMN). (A) A LAMN demonstrates a “pushing invasion” or tongue-like protrusion into the appendiceal wall. (B) A LAMN reveals a pushing growth by the mucinous epithelium into the appendiceal wall, which should not be considered as infiltrative invasion. (C) A LAMN shows a “pushing border” or broad-front border by the epithelium. (D) A LAMN reveals a flat or papillary epithelium associated with the loss of the lamina propria, obliteration of muscularis mucosae, and atrophy of submucosa and muscularis propria.

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  Fig. 2. Various microscopic features of a low-grade appendiceal mucinous neoplasm. (A) Low-grade cytologic features with pencil-like nuclei maintaining the nuclear polarity. (B) The neoplastic mucinous epithelium may have a villous architecture with loss of lamina propria and muscularis mucosae. (C) The appendiceal wall exhibits extensive fibrosis. (D) The neoplastic epithelium displays an undulating or short wave-like architecture. (E) The appendiceal wall is dissected by mucin. (F) Rupture of the wall by mucin and/or cells outside the appendix.

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  Fig. 3. Mimickers of appendiceal mucinous neoplasm. (A) Acute suppurative appendicitis. (B) An appendiceal diverticulum presents pushing growth by abundant mucin and acute suppurative inflammation. Note that a lower magnification often leads to the identification of the diverticulum. (C) Retention cyst without a lining epithelium. (D) Appendiceal endometriosis.

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  Fig. 4. High-grade appendiceal mucinous neoplasm (HAMN). (A) A HAMN shows the same low-power architectural features as low-grade appendiceal mucinous neoplasm without infiltrative invasion. (B) A HAMN is characterized by high-grade cytology, including enlarged and vesicular nuclei with full-thickness stratification, loss of nuclear polarity, prominent nucleoli, and sometimes mitotic figures.

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  Fig. 5. Appendiceal serrated lesions. (A) A sessile serrated lesion without dysplasia is a common microscopic finding to the colorectum counterpart, displaying deep crypt serration and dilated bases. Note that the muscularis mucosae are intact. (B) Serrated dysplasia, low grade presents adenoma-like dysplasia in the crypt base.

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  Fig. 6. Pathologic staging of low-grade appendiceal mucinous neoplasms (LAMNs). (A) A LAMN confined to the appendiceal wall is designated as pTis(LAMN). (B) Acellular mucin or mucinous epithelium may frequently extend into the muscularis propria; however, the pT stage is defined as pTis. Note that pT1 and pT2 do not apply to LAMN. (C) A LAMN extends to the subserosa or mesoappendix and is classified as pT3. (D) Acellular mucin or mucinous epithelium penetrating the serosal surface is classified as pT4a. (E) The tumor directly invades into the adjacent intestinal segment by way of the serosa, e.g., invasion of the ileum (pT4b). (F) Acellular mucin on the serosal surface with inflammatory reaction and neovascularization (pT4a).

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  Fig. 7. Various histologic features of appendiceal mucinous adenocarcinoma and signet-ring cell carcinoma. (A) Mucinous adenocarcinoma presents within the appendiceal wall. (B) Moderately differentiated (G2) mucinous adenocarcinoma exhibits high-grade cytology and demonstrates infiltrating glands associated with desmoplastic stroma. (C) Mucinous adenocarcinoma markedly distorts the appendix with dissecting cellular pools present within the appendiceal wall. (D) Poorly differentiated (G3) mucinous adenocarcinoma demonstrates high-grade cytology and signet-ring cells. (E) Signet-ring cell carcinoma (G3, poorly differentiated) essentially replaces the entire wall of the appendix. (F) Neoplastic signet-ring cells are seen in single cells or small clusters within the dissecting mucin pools.

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  Fig. 8. Histologic features of disseminated peritoneal mucinous tumors. (A) A disseminated peritoneal mucinous tumor of low-grade (G1, well-differentiated) without destructive invasion. The tumor cells resemble those of low-grade appendiceal mucinous neoplasm. (B) A disseminated peritoneal mucinous tumor of high-grade (G2, moderately differentiated) cytology. High-grade cytology corresponds to moderately differentiated (G2) mucinous adenocarcinoma. (C) High-grade (G3) mucinous carcinoma peritonei with signet-ring cells presents high-grade cytology and invasive signet-ring cell component, equivalent to the poorly differentiated mucinous adenocarcinoma. (D) Isolated signet-ringlike cells float within mucin pools. Degenerating tumor cells or histiocytes may exhibit signet-ring-like morphology.

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  Fig. 9. Histologic features of non-mucinous adenocarcinoma and goblet cell adenocarcinoma. (A) Co-existing adenoma and non-mucinous adenocarcinoma of the appendix. (B) Low-grade adenoma of the appendix resembles conventional adenoma of the colorectum. The mucosal architecture is well preserved with intact muscularis mucosae without a pushing invasion pattern. (C) Non-mucinous adenocarcinoma displays moderately differentiated and 50% to 95% gland formation. (D) Low-grade (G1) goblet cell adenocarcinoma shows small clusters composed of cohesive goblet cells and a few Paneth-like cells, displaying mostly low-grade patterns. (E) Low-grade (G1) goblet cell adenocarcinoma, immunohistochemistry of synaptophysin shows positive expression in neuroendocrine cells. (F) High-grade (G3) goblet cell adenocarcinoma displays >50% high-grade patterns.

Reference

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