Imaging of appendiceal mucinous epithelial neoplasms: A narrative review

Abstract

Appendiceal mucinous epithelial neoplasms are uncommon tumors of the gastrointestinal tract, yet they pose a relevant clinical challenge because of their diverse pathological spectrum, unpredictable biological behavior, and frequent incidental detection. Despite their rarity, these lesions are of particular importance due to their tendency to produce mucin and, in some cases, to disseminate within the peritoneal cavity, resulting in pseudomyxoma peritonei, a condition associated with substantial morbidity and complex treatment pathways. Clinical presentation is often vague or misleading, with symptoms that may resemble acute appendicitis or other right lower quadrant diseases, leading to delayed recognition and suboptimal initial management. Imaging therefore plays a decisive role throughout the diagnostic process. Computed tomography is the primary modality for initial assessment and surgical planning, especially in acute settings, whereas magnetic resonance imaging provides a more accurate evaluation of peritoneal spread and overall tumor burden, particularly when diffusion-weighted imaging and the signal characteristics of mucin are considered. Although radiological findings do not allow reliable grading of these tumors, specific features such as mural abnormalities, calcifications, and extra-appendiceal mucin are critical for assessing disease extent and supporting appropriate multidisciplinary decision-making.

Key Words: Pseudomyxoma peritonei; Appendiceal mucinous epithelial neoplasms; Mucocele; Mucinous adenocarcinoma; Magnetic resonance imaging

Core Tip: Appendiceal mucinous epithelial neoplasms are rare but clinically significant tumors with heterogeneous behavior and frequent nonspecific presentation, often leading to delayed diagnosis. Their major complication is pseudomyxoma peritonei, caused by mucin dissemination within the peritoneal cavity. Imaging plays a central role in detection, characterization, and staging: Computed tomography is the diagnostic cornerstone, while magnetic resonance imaging provides superior assessment of peritoneal disease. Recognizing key imaging features is essential for appropriate classification, prognostic stratification, and guiding multidisciplinary management.

INTRODUCTION

Appendiceal neoplasms are rare entities, accounting for less than 1% of all gastrointestinal tumors, yet they represent a clinically relevant diagnostic challenge because of their heterogeneous histology, variable biological behavior, and frequent incidental presentation. Among them, mucinous epithelial neoplasms constitute the most common subgroup, representing approximately 70% of epithelial appendiceal tumors. Their estimated incidence is approximately 0.2-0.6 cases per 100000 individuals per year and they are incidentally identified in about 0.2%-0.7% of appendectomy specimens. These lesions are associated with significant morbidity, primarily due to their potential to rupture and disseminate mucin within the peritoneal cavity, leading to pseudomyxoma peritonei (PMP)[1]. They are most frequently diagnosed in middle-aged and older adults, with a peak incidence between the fifth and seventh decades of life. Several studies have reported a slight female predominance, particularly in patients presenting with PMP, likely due to the frequent involvement of the ovaries and initial misdiagnosis as primary ovarian pathology. Clinically, appendiceal mucinous epithelial neoplasms (AMNs) often present with nonspecific symptoms or mimic acute appendicitis, adnexal masses, or other right lower quadrant pathologies. As a result, misdiagnosis or delayed diagnosis is not uncommon, with important prognostic and therapeutic implications. The burden of disease is mainly related to the development of PMP, which occurs in approximately 20% of patients and is associated with complex surgical management, high healthcare costs, and reduced quality of life[2]. Imaging plays a pivotal role in the detection, characterization, staging, and follow-up of these tumors. A thorough understanding of their imaging spectrum is therefore essential for radiologists, particularly in distinguishing benign from malignant lesions, identifying complications, and guiding multidisciplinary management.

CLASSIFICATION OF APPENDICEAL TUMORS

The appendix is composed of several histological layers, including epithelium, muscularis mucosae, submucosa, muscularis propria, and serosa. Its epithelial lining contains enterocytes, goblet cells, and enterochromaffin cells, while the mucosa and submucosa also include lymphoid tissue. Each of these cellular components can give rise to distinct neoplastic entities. Based on histogenesis, appendiceal tumors include epithelial neoplasms (mucinous and non-mucinous), goblet cell tumors, neuroendocrine tumors, lymphomas, and mesenchymal tumors[3]. The two most widely accepted classification systems are those proposed by the World Health Organization and the Peritoneal Surface Oncology Group International. According to the Peritoneal Surface Oncology Group International consensus, appendiceal tumors are broadly categorized into mucinous epithelial neoplasms, which include low-grade appendiceal mucinous neoplasms (LAMN), high-grade appendiceal mucinous neoplasms (HAMN), and mucinous adenocarcinomas; non-mucinous epithelial neoplasms, comprising adenomas and adenocarcinomas of colorectal type; epithelial tumors with neuroendocrine differentiation, such as neuroendocrine tumors and goblet cell carcinoma; and mesenchymal neoplasms[4]. The 2019 World Health Organization fifth edition classifies appendiceal epithelial lesions into LAMN, HAMN, and adenocarcinomas, including mucinous adenocarcinoma, signet ring cell carcinoma, and non-mucinous (colorectal-type) adenocarcinoma. Goblet cell adenocarcinomas and neuroendocrine neoplasms are also included among epithelial tumors[5]. These classifications are essential not only for pathological reporting but also for prognostic stratification and imaging interpretation.

HISTOLOGICAL VARIANTS OF MUCINOUS EPITHELIAL NEOPLASMS

From a histopathological perspective, mucinous epithelial neoplasms encompass a spectrum of lesions with distinct biological behavior[6].

Mucocele

A mucocele is a potential precancerous condition which represents abnormal dilatation of the appendiceal lumen due to intraluminal accumulation of mucin and may arise from both non-neoplastic obstruction and mucin-secreting epithelial tumors. While simple retention cysts are benign, neoplastic mucoceles are frequently associated with low-grade or HAMN and, less commonly, mucinous adenocarcinoma. In this context, the mucocele reflects an early or intermediate stage in the neoplastic continuum, in which progressive epithelial dysplasia and mucin overproduction lead to luminal expansion and thinning of the appendiceal wall, particularly when related to mucinous epithelial neoplasms.

LAMN are characterized by low-grade cytologic atypia, absence of infiltrative invasion, and confinement to the appendiceal wall, typically limited to the muscularis propria. When restricted to the appendix and without rupture, LAMN generally demonstrate indolent behavior and favorable prognosis. However, extra-appendiceal mucin dissemination significantly worsens outcomes. Recent advances in molecular pathology have identified recurrent genetic alterations in LAMN, most notably mutations in KRAS and GNAS.

HAMN share architectural features with LAMN but display high-grade cytological atypia. Although they lack overt infiltrative invasion, their biological behavior is more aggressive, with a higher risk of peritoneal dissemination and recurrence. HAMN frequently harbor additional mutations such as TP53, PIK3CA, and alterations in cell cycle regulation pathways.

Mucinous adenocarcinoma mucinous adenocarcinomas exhibit infiltrative invasion of the appendiceal wall and may be well, moderately, or poorly differentiated. The presence of signet ring cells is associated with an unfavorable prognosis. Histologically, these tumors often show complex glandular architecture and clustered growth patterns, correlating with aggressive imaging features.

PMP

LAMN, HAMN, mucinous adenocarcinomas with or without signet ring cells, and goblet cell carcinoids may all become complicated by rupture, leading to the development of PMP. PMP is a clinical syndrome defined by the presence of mucin, with or without neoplastic epithelial cells, within the peritoneal cavity and along the serosal surfaces of abdominal and pelvic organs. The progressive accumulation of mucinous ascites gives rise to the characteristic appearance known as jelly belly[4]. Once released into the peritoneal cavity, mucin follows the physiological circulation of peritoneal fluid through the so-called redistribution phenomenon, resulting in preferential accumulation at specific sites. The pelvis, paracolic gutters, omentum, and hepatic capsule are typically involved early, while the mesentery is initially spared due to its mobility. In contrast, fixed segments of the small intestine, such as the region of the ligament of Treitz, as well as areas affected by postoperative adhesions, may show early involvement. Mucinous implants do not invariably contain viable neoplastic cells; however, their presence is associated with a poorer prognosis[7]. The clinical presentation of PMP is highly variable and often nonspecific. Many patients are asymptomatic, other patients may present with right lower quadrant pain mimicking acute appendicitis, which occurs in more than 50% of cases, as well as gastrointestinal bleeding or intestinal obstruction. The most common symptoms include progressive abdominal distension, swelling, and pain, and by the time of diagnosis, most patients already have advanced disease[2].

ROLE OF IMAGING

Imaging plays a central role in the diagnosis and management of AMN, enabling detection, characterization, staging, and follow-up of disease. In the acute and incidental setting, cross-sectional imaging is often the first modality to suggest the diagnosis, while computed tomography (CT) and magnetic resonance imaging (MRI) provide complementary information for lesion characterization and assessment of disease extent, which is crucial for appropriate therapeutic planning. Key imaging features to evaluate include appendiceal diameter, wall characteristics, presence of mural nodules, periappendiceal fat stranding, and, most importantly, evidence of extra-appendiceal mucin or peritoneal implants; local invasion is suggested by irregular or nodular wall thickening, disruption of the appendiceal wall, and infiltration of adjacent structures, including the cecum, terminal ileum, or mesoappendix.

Assessment of resectability is primarily based on the extent and distribution of peritoneal disease; high tumor burden, extensive small bowel or mesenteric involvement, and disease at critical anatomical sites (e.g., hepatic hilum or root of the mesentery) are associated with incomplete cytoreduction and poorer surgical outcomes. From a surgical perspective, patients with localized, non-invasive disease are generally suitable for simple appendectomy, whereas right hemicolectomy is indicated in cases with cecal involvement, appendiceal base infiltration, or when imaging raises suspicion of adenocarcinoma. Conversely, patients with disseminated peritoneal disease may be considered candidates for cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), depending on the overall tumor burden and the likelihood of achieving complete cytoreduction.

Ultrasound

Ultrasound (US) represents a first-line imaging modality for the evaluation of the appendix, with reported sensitivity and specificity of 88% and 93%, respectively, for the diagnosis of appendicitis. It may demonstrate secondary signs suggestive of malignancy, such as an appendiceal mucocele, locoregional lymphadenopathy, or ascites, and it allows differentiation between appendiceal and ovarian masses. The main limitations of US are its operator dependence and its limited ability to accurately stage disease. In addition, US plays a role in identifying other anatomical structures within the right lower quadrant, particularly the ovary, which must be differentiated from a possible appendiceal mass[8]. Suspicious US features of appendiceal neoplasia include marked appendiceal dilatation (often > 15 mm in diameter), a cystic or mucocele-like appearance with low-level internal echoes, mural irregularity or focal wall thickening, loss of the normal layered wall structure, the presence of internal septations or mural nodules, and complex periappendiceal fluid collections or an associated soft-tissue mass. When these findings are present, an underlying neoplastic process should be suspected and further evaluation with CT and MRI is recommended for lesion characterization, local staging, and assessment of extra-appendiceal extension.

CT

Contrast-enhanced and unenhanced CT is the initial imaging modality for the evaluation of right lower quadrant pain or diffuse abdominal pain[9]. Coronal reconstructions are particularly useful for identifying the ileocecal valve and cecum and for accurately localizing the appendix[10]. CT is also considered the preoperative diagnostic staging (Table 1) gold standard. Moreover, CT is essential for assessing disease extent and identifying potential complications, including inflammation, intussusception, torsion, ureteral compression, and associated peritoneal pathology[2]. The diagnosis of AMNs is primarily based on the identification of an appendiceal mucocele. Detection of a mucocele should prompt careful evaluation for extra-appendiceal mucin. Only when mucin extends into the peritoneal cavity beyond the periappendiceal region of the right lower quadrant is the diagnosis of PMP established[11]. CT sensitivity can reach up to 94% for lesions larger than 5 cm; however, sensitivity markedly decreases to 19%-28% for lesions smaller than 1 cm[4].

Table 1 TNM staging system for appendiceal mucinous epithelial neoplasm, according to the current classification criteria, including definitions of primary tumor (T), regional lymph node involvement (N), and distant metastasis (M), with corresponding stage groupings.

TNM staging	Current classification criteria
Primary tumor (T)	Tx	Primary tumor cannot be assessed
	T0	No evidence of primary tumor
	Tis	Carcinoma in situ (intramucosal carcinoma; invasion of the lamina propria or extension into but not through the muscularis mucosae)
	T1	Tumor invades the submucosa
	T2	Tumor invades the muscularis propria
	T3	Tumor invades the subserosa or the mesoappendix
	T4 (T4a, T4b)	Tumor invades the visceral peritoneum, including acellular mucin or mucinous epithelium involving the serosa of the appendix or mesoappendix; tumor invades directly invades adjacent organs or structures
Lymph nodes (N)	NX	Regional lymph nodes cannot be assessed
	N0	No tumor involvement of regional lymph node(s)
	N1 (N1a, N1b, N1c)	Tumor involvement of one to three regional lymph nodes; tumor involvement of one regional lymph node; tumor involvement of two or three regional lymph nodes; no tumor involvement of regional lymph nodes, but there are tumor deposits in the subserosa or mesentery
	N2	Tumor involvement of four or more regional lymph nodes
Distant metastasis (M)	M0	No distant metastasis
	M1	Distant metastasis
	M1c	Metastasis to sites other than peritoneum

MRI

MRI is generally reserved for patients in whom CT is contraindicated. It may also be considered when there is suspicion of neoplastic rupture, for the evaluation of peritoneal implants, or to differentiate cystic ovarian lesions[12]. The presence of mucin, characterized by high water content, typically appears as hypointense on T1-weighted images and hyperintense on T2-weighted images. However, the presence of oligosaccharides within the mucin may result in increased T1 signal intensity in these tumors. Increasing complexity of the internal architecture and a higher proportion of solid tumor components correlate with a higher grade of malignancy. Therefore, contrast-enhanced MRI is essential to demonstrate enhancing solid components, which are suggestive of malignant transformation[3]. Thanks to its superior contrast resolution, combined with delayed contrast enhancement and fat-suppressed sequences, MRI achieves a sensitivity of 84% for the detection of small peritoneal implants (< 1 cm), compared with 54% for CT[13]. Increased cellularity leads to diffusion restriction on high b-value diffusion-weighted imaging (DWI), a feature that may be useful for early detection of malignancy and for differentiating tumor tissue from adjacent ascites, acellular mucin, and bowel contents[14]. Following CRS and HIPEC, surveillance MRI is capable of detecting early recurrence with greater accuracy than serum tumor markers including cancer antigen 125, carcinoembryonic antigen, and cancer antigen 19-9[15].

Further investigations

18FDG positron emission tomography has low sensitivity for the evaluation of appendicular mucinous neoplasms due to their hypocellularity; instead, it provides important information on the staging of appendicular neuroendocrine tumors and lymphoma[16]. The utility of positron emission tomography and CT scans is still under investigation and has limited value in mucinous neoplasms[16]. The role of diagnostic laparoscopy is primarily to identify the resectability of lesions, perform biopsies and avoid unnecessary laparotomies in advanced stages as they often require more aggressive management with the need for chemotherapy. Furthermore, exploration of the entire abdominal cavity and retroperitoneum may not be initially recommended and should be performed in selected cases. Colonoscopy is not a screening tool for appendicular cancer, it is in fact useful for excluding synchronous cancer in patients with appendiceal carcinoma of the colonic type or in neuroendocrine tumors[17]. There is no universally accepted standard for follow-up in these patients, and surveillance strategies are generally individualized. Current recommendations suggest clinical and imaging follow-up every six months or annually during the first six years after treatment[18,19].

IMAGING FEATURES

Mucocele

In US, an appendicular mucocele typically appears as an ovoid, cystic mass with heterogeneous internal content located in the right lower quadrant, with a variable internal echostructure. The sonographic features suggestive of mucocele include the presence of internal concentric and stratified echogenic layers that confer the characteristic onion-skin appearance of the appendix, acoustic shadowing due to dystrophic calcifications of the appendiceal wall, which are present in less than 50% of cases and are characteristic of porcelain appendicitis, and a pear-shaped morphology caused by predominant dilatation of the proximal portion of the appendix due to luminal obstruction and progressive accumulation of mucosal secretions[3,10]. The onion-bulb pattern refers to the concentric echogenic layers representing lamellar mucin. When this finding is identified in the right lower quadrant in the presence of a well-demarcated and normally located ovary, the diagnosis of appendicular mucocele is strongly supported[5]. On CT, a mucocele appears as a hypodense round cystic lesion or as a tubular lesion with wall enhancement, located at the expected site of the appendix. The wall thickness may be variable, but there is generally no periappendiceal inflammation or abscess formation, which helps distinguish mucocele from acute appendicitis. An increase in appendiceal diameter greater than 15 mm on CT supports the diagnosis of mucocele, with a reported sensitivity of 83% and specificity of 93%[2]. The identification of an appendicular mucocele should prompt a careful search for extraluminal mucin, which may be located in the periappendiceal space, within the peritoneal cavity, or attached to the surfaces of abdominal and pelvic organs, particularly near the ovaries and the intestine[3]. Mucinous implants typically appear hypodense and are most commonly found in the pericecal mesentery, the pouch of Douglas, the rectovesical pouch, the perihepatic space, and the omentum. A rare variant of appendicular mucocele is myxoglobulosis, which on CT is identified by the presence of multiple intraluminal calcified spherules[20]. A mucocele may become infected and develop intraluminal gas or air-fluid levels, wall thickening, and increased attenuation of the surrounding fat, although these features may overlap with those of a primary tumor[21]. Atypical imaging features include inverted mucocele, small bowel obstruction, intussusception, coexisting appendicitis, appendicular rupture, and PMP[10]. On MRI, an appendicular mucocele generally shows imaging characteristics of simple fluid, although signal intensity may vary depending on the protein content of the mucin[22]. It typically manifests as a cystic pericecal mass that is hyperintense on T2-weighted sequences. Signal intensity on T1-weighted sequences is variable and dependent on mucin content, but is most often hypointense. Mucin extravasation is likewise hyperintense on T2-weighted sequences[23].

Appendicular mucinous neoplasm

CT is recommended in all patients presenting with clinical signs of appendicitis, as this presentation may conceal an underlying neoplasm. Suspicion should be raised in the presence of cystic appendiceal dilatation with a luminal diameter exceeding 15 mm or when mural calcifications are identified[24]. Wall calcifications are suggestive of a neoplastic process and are responsible for the characteristic appearance of the so-called porcelain appendix, although they are detected in fewer than 50% of cases[25]. CT typically demonstrates a well-defined cystic mass adjacent to the cecum, frequently with a retrocecal location, characterized by hypodense fluid content. One of the most widely accepted CT criteria for differentiating acute appendicitis from an appendiceal mucinous neoplasm is an appendiceal wall thickness greater than 6 mm[26]. In clinical practice, however, this distinction is often challenging, as the inflammatory changes seen in appendicitis may closely resemble the findings associated with mucin leakage following rupture of a mucinous neoplasm, making the two entities difficult to distinguish on imaging alone. Imaging differentiation between low-grade and HAMN remains difficult. Lesion size, attenuation, and wall thickness may be similar in both entities, and additional findings such as calcifications, internal septations, periappendiceal fat changes, and the presence of intraperitoneal free fluid are nonspecific and do not reliably indicate histologic grade (Figures 1 and 2). On MRI, an appendiceal mucinous neoplasm appears as a tubular structure in the right lower quadrant, contiguous with the cecum, showing low signal intensity on T1-weighted sequences and high signal intensity on T2-weighted sequences. The presence of mucin may increase signal intensity on pre-contrast T1-weighted images. Furthermore, emerging evidence suggests a potential correlation between molecular profiles and imaging phenotypes; for instance, lesions with GNAS mutations are often associated with abundant mucin production, which may manifest as marked cystic dilatation and high signal intensity on T2-weighted sequences. Conversely, tumors with more aggressive molecular features, such as TP53 mutations, tend to demonstrate solid components, irregular wall thickening, and increased enhancement, reflecting higher cellularity and invasive behavior. The early adoption of MRI has proven useful in distinguishing mucinous lesions of the appendix from other cystic pathologies of the right lower quadrant, particularly in differentiating appendiceal masses from cystic ovarian lesions[27].

Figure 1 Contrast-enhanced computed tomography images of a 56-year-old woman with low-grade appendiceal mucinous neoplasms, diagnosed on histopathological examination. A: Abdominal ultrasound shows a tubular, appendiceal lesion measuring approximately 55 mm × 20 mm, with hyperechoic to anechoic content and thickened walls; B: Axial contrast-enhanced computed tomography scan demonstrating appendiceal dilatation with low-attenuation mucinous content and smooth walls.

Figure 2 Contrast-enhanced computed tomography images of a 68-year-old male patient. A: Axial image showing a high-grade appendiceal mucinous neoplasms, presenting as a well-defined, tubular appendiceal mass with low-attenuation mucinous content and mild wall enhancement; B: Axial image demonstrating pseudomyxoma peritonei, characterized by low-attenuation mucinous ascites, and mild peritoneal thickening, consistent with mucinous peritoneal spread.

Mucinous adenocarcinoma

On CT, characteristic findings include nodular or irregular thickening of the appendiceal wall and the presence of periappendiceal soft tissue deposits[28]. Additional imaging features such as abnormal morphology, hypodense intraluminal content, internal septations, irregular or asymmetric wall thickening, mural calcifications, soft tissue enhancement, periappendiceal fat stranding, and intraperitoneal free fluid are suggestive of malignant behavior and possible regional spread, favoring the diagnosis of low-grade appendiceal mucinous neoplasm or mucinous adenocarcinoma[26] (Figure 3). On MRI, the presence of mural nodularities, thick internal septa, and marked wall thickening supports the diagnosis of adenocarcinoma. Wall calcifications and intraluminal gas related to appendiceal rupture may be observed as susceptibility artifacts, although these findings are more readily and reliably detected on CT[29].

Figure 3 Contrast-enhanced computed tomography images in a 73-year-old man with mucinous appendiceal signet ring cell carcinoma. A: Axial image demonstrating grade II hydronephrosis secondary to extrinsic ureteral compression by the tumor, associated with diffuse increased attenuation and stranding of the visceral abdominal fat, consistent with pseudomyxoma peritonei; B: Coronal reconstruction showing a poorly marginated appendiceal mass lesion; associated stranding of the abdominal visceral fat is also appreciable.

PMP

The onset of PMP is characterized by distinctive imaging features, including mucinous ascites, peritoneal soft-tissue implants, omental caking, and involvement of the gastrointestinal tract and ovaries[30]. However, the detection of peritoneal disease remains a significant challenge with current imaging modalities and is strongly influenced by both lesion size and anatomical location. CT demonstrates a sensitivity ranging from 59% to 94% for lesions larger than 5 cm, which decreases markedly to 19%-28% for lesions smaller than 1 cm and to 11%-28% for those smaller than 0.5 cm. Sensitivity also varies according to the affected region. In a retrospective study, lesions located in the ileocecal area showed the lowest detection rates, ranging from 11% to 28%, followed by the right subdiaphragmatic region, with sensitivities between 11% and 22%, and the omentum and transverse colon, with a sensitivity of approximately 25%. Detection rates for lesions involving the small bowel and its mesentery range from 18% to 55%[13]. For optimal assessment of peritoneal disease, a multidetector CT protocol with both oral and intravenous contrast is recommended. Oral contrast is strongly encouraged to distend the gastrointestinal tract and improve lesion conspicuity; typically, a solution of 15 mL of contrast mixed with 475 mL of water is administered, with a total of three bottles given at 20-minute intervals over one hour. Intravenous contrast should be administered, and imaging acquired in the portal venous phase to optimize enhancement of peritoneal implants. Optional rectal contrast, consisting of 30 mL diluted in 300 mL of warm tap water, may be used to better delineate the rectum and distal sigmoid colon when clinically indicated. Thin-slice acquisition with multiplanar reconstructions is recommended to maximize detection of small peritoneal nodules, omental caking, and subtle serosal involvement[31]. Recent evidence has also highlighted the potential complementary role of US and CT in the assessment of PMP. In a large retrospective study, Han et al[32] demonstrated that a combined US-CT peritoneal cancer index (PCI) provides a more accurate preoperative estimation of tumor burden compared with either modality alone and is able to predict the likelihood of complete CRS. In particular, higher US-CT PCI values and the presence of mesenteric involvement were identified as independent predictors of incomplete cytoreduction. This combined approach leverages the strengths of both techniques, with US offering high-resolution, real-time evaluation of selected abdominal regions, particularly in superficial, while CT provides a comprehensive and reproducible overview of whole-abdomen disease distribution[32]. MRI provides high soft-tissue contrast and functional information for peritoneal disease assessment. The examination begins with a coronal three-plane localizer for anatomical orientation, followed by two-dimensional single-shot fast spin-echo sequences in coronal and axial planes to provide a rapid overview. Three-dimensional Dixon-based sequences should be acquired for fat-water separation and accurate lesion characterization, while DWI in axial planes allows detection of cellular tumor deposits. T2-weighted respiratory-triggered fat-saturated sequences in the axial plane improve contrast between fluid, fat, and soft tissue lesions. Three-dimensional T1-weighted Dixon sequences both pre- and post-contrast are useful to map anatomy and evaluate enhancement patterns of peritoneal implants. Finally, two-dimensional steady-state free-precession fat-saturated sequences and two-dimensional T1-weighted post-contrast fat-saturated sequences in the axial plane should be performed to enhance the detection of small nodules and subtle serosal involvement. This multiparametric approach enables a comprehensive evaluation of peritoneal carcinomatosis, assessing lesion morphology, distribution, and functional characteristics[31] (Figure 4). MRI has been shown to be superior to CT for the detection of peritoneal implants in PMP, particularly when combining DWI with delayed post-gadolinium T1-weighted sequences with fat suppression[14]. Mucinous implants and so-called pseudoascites typically appear as loculated collections with high signal intensity on T2-weighted images within the peritoneal cavity, producing a characteristic scalloping of the serosal surfaces of solid organs and displacement of hollow viscera, with intestinal obstruction occurring in more advanced stages[4]. Parenchymal invasion may be observed at sites of serosal involvement, and linear or punctate calcifications within mucinous deposits can also be present[10]. On contrast-enhanced MRI, an increased nodular soft-tissue component within the implants suggests more advanced disease; however, this finding should not be confused with peritoneal carcinomatosis, which does not typically produce scalloping of solid organ surfaces. DWI further facilitates the identification of solid nodules within PMP, thereby suggesting high-grade disease[14]. More recently, diffusion-weighted MRI has been shown to significantly improve both sensitivity and specificity in the detection of peritoneal metastases, achieving sensitivities of 85%-90% for peritoneal deposits smaller than 1 cm. In a study by Low et al[13], preoperative MRI was compared with CT and was found to accurately predict tumor volume in 91% of patients, whereas CT achieved this in only 50%. Moreover, MRI detected small bowel involvement in 92% of cases, compared with 48% for CT. These results were subsequently confirmed by a larger study, which also emphasized that accurate interpretation of MRI, particularly for small bowel assessment, requires a high level of radiological expertise[33]. On the basis of this evidence, MRI has been established as an approved modality for both preoperative evaluation and postoperative surveillance in patients with disseminated disease who have undergone CRS or HIPEC[10].

Figure 4 Magnetic resonance imaging of a 62-year-old man with low-grade appendiceal mucinous neoplasms. A: Axial T2-weighted image demonstrating the appendiceal tumor, characterized by high signal intensity consistent with its mucinous content; B: Axial T1-weighted image showing the same lesion, with relatively low signal intensity compared to adjacent soft tissues; C: Diffusion-weighted imaging (b = 800 second/mm²) depicting Glissonian peritoneal implants with high signal intensity, consistent with peritoneal dissemination.

PCI

A major contribution to prognostic stratification and surgical planning in patients with PMP is provided by the PCI, which is used to quantify the extent of intraperitoneal disease at laparoscopy and on preoperative CT or MRI. The PCI is a standardized scoring system based on the assessment of the size of the largest tumor deposit across 13 abdominopelvic regions, including nine regions in the abdomen and pelvis and four regions involving the small bowel[33]. This approach allows a systematic and reproducible evaluation of disease burden and plays a key role in preoperative decision-making. From a radiological perspective, a comprehensive description of all mucinous implants is essential, particularly at critical anatomical sites such as the hepatic hilum, lesser omentum, peri-caval region, peritoneal surfaces, diaphragmatic domes, abdominal and pelvic solid organs, and the gastrointestinal tract, including the stomach, small bowel, and colon. Accurate reporting of disease distribution in these locations is crucial to guide surgeons in achieving complete cytoreduction. The presence of tumor implants larger than 5 cm in the jejunum, proximal ileum, or adjacent mesentery, as well as small bowel or ureteral obstruction and extension to the upper abdomen, is typically associated with high-grade PMP and is predictive of a less favorable surgical outcome[34].

PAUSE method

An additional structured reporting approach has been proposed by the Peritoneal Malignancy Institute of Basingstoke in the form of the PAUSE method. This acronym refers to five key elements: PCI score (P), abdominal wall involvement and ascites (A), unfavorable sites of disease such as periportal involvement, root of the mesentery, ligament of Treitz, pelvic sidewall disease, and sacral involvement (U), small bowel and mesenteric disease (S), and the presence of extraperitoneal disease (E). Incorporation of the PAUSE method into radiological reports provides surgeons with clinically relevant information that facilitates appropriate patient selection for CRS combined with HIPEC[35].

DIFFERENTIAL DIAGNOSES

The imaging appearance of appendiceal mucinous neoplasms and PMP overlaps with a broad spectrum of pathological entities, particularly cystic lesions of the right lower quadrant and right adnexa, making differential diagnosis challenging[10] (Table 2). Because of their anatomical proximity to the cecum and appendix, both neoplastic and non-neoplastic conditions involving the right ovary or fallopian tube may closely simulate appendiceal disease, while inflammatory processes such as acute appendicitis or peri-appendiceal abscess can further obscure the underlying pathology. From a diagnostic standpoint, accurate determination of the lesion’s site of origin is crucial. Radiologists should systematically evaluate the relationship between the mass and key anatomical landmarks, particularly the cecal pole, appendix, and right ovary, and assess whether a normal ovary can be confidently identified and separated from the lesion. Cross-sectional imaging with CT or MRI, integrated with clinical and laboratory data, usually provides decisive clues. Distinction between appendiceal mucocele and acute appendicitis may be particularly difficult, as the two conditions can coexist and inflammation may mask the underlying lesion[36,37]. An inflamed mucocele can closely resemble uncomplicated appendicitis; however, CT findings such as cystic dilatation of the appendix, mural calcifications, and a maximal luminal diameter greater than 15 mm should raise suspicion for an underlying mucinous neoplasm. When these features are associated with typical inflammatory signs, the possibility of a mucocele should be suggested, as this has relevant surgical implications and may warrant right hemicolectomy rather than simple appendectomy[38]. In women, appendiceal mucoceles are frequently misinterpreted as gynecological pathology, particularly right adnexal cystic masses or lesions of tubal origin, as they commonly occur between the fifth and seventh decades of life and present as well-defined cystic structures in the right hemipelvis. MRI is especially valuable in this setting, as its multiplanar capability and superior soft-tissue contrast allow more accurate identification of the organ of origin. Failure to recognize an appendiceal mucocele may lead to inappropriate preoperative biopsy or intraoperative rupture, with subsequent mucin spillage and development of PMP[38]. Differentiation between appendiceal mucinous tumors and primary ovarian mucinous neoplasms remains inherently challenging due to their close anatomical relationship, nonspecific serum tumor markers, and the frequent secondary ovarian involvement by appendiceal tumors, which may mimic a primary ovarian origin. Given the higher prevalence of ovarian neoplasms, appendiceal mucinous tumors are often overlooked, further increasing the risk of misdiagnosis[39]. In PMP, gelatinous mucin, often containing neoplastic epithelial cells, progressively fills the peritoneal cavity and exerts a mass effect on abdominal organs. On imaging, this pattern may resemble disseminated ovarian mucinous neoplasms; however, features such as scalloping of the serosal surfaces of solid organs, loculated mucinous collections, relative sparing of the small bowel, and the presence of an appendiceal primary favor the diagnosis of PMP. LAMN and mucinous adenocarcinomas represent the most common underlying causes. Clinical presentation is often nonspecific, ranging from acute appendicitis-like symptoms to progressive abdominal distension or a palpable mass[39]. Additional diagnostic pitfalls include obstructive cecal neoplasms causing secondary dilatation of an otherwise normal appendix, in which a mass-like or circumferentially thickened cecum at the appendiceal origin represents the key distinguishing feature. Finally, lymphoid hyperplasia may mimic an inverted appendiceal mucocele within the cecal lumen, appearing as a well-circumscribed intraluminal cystic lesion. This entity should be differentiated from enteric duplication cysts and cystic degeneration of solid neoplasms through careful assessment of enhancement patterns, wall characteristics, and anatomical relationships[25].

Table 2 Differential diagnoses of appendiceal mucinous epithelial neoplasm.

Diagnosis	Typical location/origin	Key imaging features (US/CT/MRI)	Helpful differential clues
Appendiceal mucocele/appendiceal mucinous epithelial neoplasm	Appendix, contiguous with cecum	Well-circumscribed ovoid or pyriform cystic mass; “onion-skin” appearance on US; low-attenuation content on CT; T2 hyperintense on MRI; mural or curvilinear calcifications; possible wall thickening or mural nodules	Continuity with cecal pole; separation from right ovary; calcified wall highly suggestive
Acute appendicitis	Appendix	Dilated appendix (> 6 mm), wall thickening and hyperenhancement, peri-appendiceal fat stranding, possible appendicolith	Lack of marked cystic dilatation; absence of mural calcifications or layered mucin
Inflamed mucocele + appendicitis	Appendix	Cystic appendiceal dilatation (> 13 mm), mural calcifications, associated inflammatory changes	Combination of mucocele features and acute inflammation; critical for surgical planning
Peri-appendiceal abscess	Peri-appendiceal region	Irregular fluid collection with thick enhancing walls, gas bubbles, surrounding inflammatory fat stranding	Ill-defined margins; lack of smooth wall and calcifications
Right tubo-ovarian abscess	Adnexa	Complex multiloculated cystic mass; thick enhancing walls; restricted diffusion; surrounding inflammatory changes	Tubal configuration; associated pelvic inflammatory disease; normal appendix
Hydrosalpinx	Fallopian tube	Tubular, elongated cystic structure; incomplete septa; “waist sign”; T2 hyperintense	Tubular morphology; separate from cecum and appendix
Ovarian mucinous tumor	Ovary	Large multilocular cystic mass; variable signal intensity (“stained glass” appearance on MRI); enhancing septa or solid components	Ovarian origin; absence of cecal continuity; more common than appendiceal mucinous epithelial neoplasm
Ovarian serous tumor	Ovary	Unilocular or multilocular cyst; papillary projections; solid enhancing components	Papillary excrescences; ascites without scalloping
Peritoneal inclusion cyst	Peritoneal spaces	Multiloculated fluid collection conforming to peritoneal recesses; ovary trapped within cyst	History of surgery/inflammation; ovary seen inside lesion
Lymphocele	Retroperitoneal or pelvic	Thin-walled homogeneous fluid collection; no enhancement; no calcifications	Post-surgical context; stable over time
Enteric duplication cyst	Adjacent to bowel	Well-defined cystic lesion; double-wall sign; no enhancement	Pediatric or incidental finding; fixed bowel relationship
Cecal carcinoma with appendiceal dilatation	Cecum	Mass-like or circumferential cecal wall thickening; secondary appendiceal dilatation	Primary cecal lesion; solid enhancing mass
Pseudomyxoma peritonei	Peritoneal cavity	Low-attenuation mucinous ascites; loculated collections; scalloping of solid organ surfaces; omental caking; peritoneal implants	Scalloping and relative small bowel sparing are highly characteristic
Lymphoid hyperplasia/inverted appendix	Cecal lumen	Well-circumscribed intraluminal lesion; cystic appearance	No mural calcifications; normal appendix externally

MRI: Magnetic resonance imaging; CT: Computed tomography; US: Ultrasound.

CHALLENGES AND FUTURE PERSPECTIVES

Despite substantial advances in cross-sectional imaging, several limitations persist in the evaluation of AMNs. In particular, reliable differentiation between low-grade and high-grade lesions remains challenging, as conventional morphologic criteria often overlap. Similarly, the detection of small peritoneal implants continues to be constrained by spatial resolution limits and the subtle nature of early peritoneal dissemination, even with optimized CT and MRI protocols. Future progress is expected to rely on the integration of advanced imaging techniques with quantitative image analysis. Radiomics enables the extraction of high-dimensional imaging features that are not appreciable to the human eye and may serve as biomarkers of tumor grade, biological aggressiveness, and prognosis[40]. In parallel, artificial intelligence and machine learning algorithms are increasingly being developed to enhance lesion detection, improve segmentation accuracy, support automated or semi-automated PCI calculation, and reduce interobserver variability in disease assessment. The emerging field of radiogenomics further supports the concept that cross-sectional imaging may act as a non-invasive surrogate marker of tumor biology. In this context, advanced MRI techniques, particularly DWI, may provide indirect insights into tumor cellularity and microstructural architecture, while radiomics-based approaches allow quantitative characterization of imaging phenotypes potentially associated with specific molecular alterations. From a therapeutic standpoint, targeted treatment options in AMNs remain limited. The high prevalence of KRAS mutations largely explains the poor response to anti-epidermal growth factor receptor therapies, whereas less frequent but potentially actionable alterations, including BRAF V600E, PIK3CA mutations, or rare human epidermal growth factor receptor 2 amplifications, may identify small subsets of patients eligible for personalized therapeutic strategies, typically extrapolated from colorectal cancer management paradigms. Within this framework, the integration of molecular profiling with imaging-derived biomarkers may improve risk stratification and therapeutic decision-making, particularly in advanced or unresectable disease[6]. Overall, the convergence of advanced imaging, radiomics, and molecular pathology is expected to progressively shift the management of AMNs toward a more precise and individualized approach, integrating imaging, histopathological, and genomic data within a comprehensive precision medicine model.

CONCLUSION

AMNs are rare tumors characterized by heterogeneous biological behavior and a substantial risk of peritoneal dissemination, most notably in the form of PMP. Their often nonspecific clinical presentation frequently results in delayed or inaccurate diagnosis, with significant implications for prognosis and therapeutic strategy. Imaging plays a central role in detection, characterization, staging, and follow-up. CT represents the diagnostic cornerstone in the acute and preoperative setting, whereas MRI, particularly when incorporating DWI and evaluation of the characteristic T1 hyperintensity of protein-rich mucin, provides superior assessment of peritoneal involvement and overall disease burden, both before and after CRS and HIPEC. Although imaging cannot reliably differentiate low-grade from high-grade lesions, specific features such as mural irregularity, calcifications, extra-appendiceal mucin, and typical patterns of peritoneal spread are crucial in guiding clinical management.