Low grade appendiceal mucinous neoplasm

Introduction

LAMN is a rare entity accounting for 1% of gastrointestinal neoplasm and is found in less than 0.3% of appendectomy specimen.it is an incidental finding during operative exploration and is often diagnosed late. Grossly, appendix may be unremarkable or may appear mucin filled, cystically dilated tissue. The appendix wall may appear thin, fibrotic, hyalinised or calcified with smooth or granular appearance. The most feared complication is seeding into peritoneum leading to pseudomyxoma peritonei, in late stage of disease. PSOGI (2016) proposed diagnostic terminology of primary appendiceal neoplasm along with criteria of defining LAMN while AJCC 8th edition defined grading and staging of LAMN.1 We reported two cases of LAMN with one involving peritoneum and one confined to appendix only.

Case History

Case 1

A 45-year old female came with pain in abdomen since 7days. Abdominal CT scan revealed recent complicated appendicitis with periappendiceal collection and left ovarian simple cyst measuring 4.9X4.3 cm. Serum tumour markers were not done. Emergency appendicectomy done. Grossly, we received appendix measuring 5cmx3cm which on cut surface show thickened wall and periappendiceal gray white myxoid area. Entire specimen was submitted. Microscopy showed circumferential involvement of the mucosa by mucin rich epithelium involving at least one segment of appendix (Figure 1 a and 1b), pushing invasion (diverticulum like growth) of epithelium (Figure 2), loss of muscularis mucosa (Figure 2), fibrosis of sub mucosa (Figure 2) and serosa showed acellular mucin (Figure 3). On which diagnosis was made as LAMN. Patient was re-operated for right hemicolectomy and left oophorectomy. Intra-operatively mucinous deposits were seen in pelvic cavity which were acellular on microscopy and colon was unremarkable with acellular mucinous deposits on serosa. Left ovary was submitted for frozen section and diagnosis was given as benign mucinous cystic neoplasm (Figure 4). IHC was done on ovarian section in which it was CK20 (Figure 5 a), CDX2 (Figure 5 b), CEA (Figure 5 c) positive and CK7 (Figure 5 d), PAX8 (Figure 5 e) negative.

Figure 1

Figure 2

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Figure 4

Figure 5

On the basis of it, diagnosis was made as LAMN with Pseudomyxoma peritonei with secondary involvement of left ovary. And staged as pT4aM1a.

Discussion

LAMN is a rare entity with female predominance and it is mostly seen in 5th to 6th decade of life.1 Entire appendix should be submitted for histological examination of LAMN as it is an incidental finding and most of the patients are presented with acute appendicitis.1 PSOGI (2016) classifies it as non-invasive neoplasm, while according to AJCC 8th edition, it is graded as G1, well differentiated mucinous neoplasm.1 In our case 1, it was staged as T4aM1a (AJCC 8th edition) as tumour was penetrating the visceral peritoneum, and acellular mucin was involving the serosa of the appendix and peritoneum without identifiable tumour cells; while in case 2, it was staged as Tis as tumour was confined to muscularis propria. Extra-appendiceal mucin is of utmost importance for proper staging, prognosis and modes of management. Differential diagnosis of LAMN are Mucinous adenocarcinoma, serrated polyp and villous adenoma. In mucinous adenocarcinoma, infiltrative pattern with high grade cytological features are seen while in serrated polyp (localized serrated epithelial lesion) and villous adenoma (dysplasia, focal tubulovillous architecture) show retention of muscularis mucosa.1 Psuedomyxoma peritonei is defined as presence of intraperitoneal mucin with or without associated mucin producing epithelium. The histologic grade of peritoneal disease is considered as extremely important criteria as it more likely influences prognosis and should be used for staging purposes.2 Currently, 3- tiered grading scheme is favoured to classify PMP as Grade 1(low grade), Grade 2 (high grade) and Grade 3 (high grade with signet-ring cells).2 This unified approach of grading will allow for more standardized and valuable diagnostic reporting. There are few scenario which shows discordant grading between primary and peritoneal disease at that time overall grading should be done according to peritoneal disease.1 e.g. if primary appendix is G1 and peritoneal disease G2; then overall grade should be assigned as G2. Recent immunohistochemical, molecular and genetic evidence supports that, psuedomyxoma peritonei concomitant with ovarian and appendiceal neoplasm has its origin in appendix in most of the cases and secondary involvement of the peritoneum and ovaries.3 Ovarian involvement in LAMN is often bilateral and show two distinctive histological features, “scalloped” glands and sub epithelial stromal clefts (Figure 4), whereas primary borderline ovarian mucinous tumours are more often associated with reactive cellular stroma and histiocyte aggregates.4 All the cases of female with appendiceal mucinous neoplasm, the ovaries should be meticulously examined and vice versa. IHCs like CK7, CK20, CDX2 and PAX8 and SATB2 are useful for the same.4 In summary, for grading and staging of mucinous neoplasm of appendix and Pseudomyxoma Peritonei; unified approach should be used for standardized diagnostic reporting. Extra-appendiceal mucin is important for staging and prognosis. The grade of peritoneal disease influences prognosis and should be used for staging purposes. Pseudomyxoma Peritoneii with simultaneous appendix and ovarian neoplasm should be treated as primary appendiceal tumour.

Source of Funding

None.

Conflict of Interest

The authors declare no conflict of interest.