Introduction

Appendiceal mucinous neoplasms are uncommon tumours whose pathological features and clinical behaviour differ substantially from conventional colorectal adenocarcinoma [1–4]. Their rarity, heterogeneous presentation, and repeated changes in terminology have made cross-study comparison difficult and management uncertain [1–3, 5]. Within this spectrum, low-grade appendiceal mucinous neoplasm (LAMN) is now well-recognised, whereas high-grade appendiceal mucinous neoplasm (HAMN) remains less clearly defined in clinical practice despite increasing diagnostic recognition [1, 3, 6].

Both entities share the non-infiltrative architecture of appendiceal mucinous neoplasia, but HAMN is distinguished by high-grade cytologic atypia; placing it in a biologically ambiguous position between LAMN and invasive mucinous adenocarcinoma [1, 3, 6]. Since its formal recognition in the Peritoneal Surface Oncology Group International (PSOGI) classification and subsequent incorporation into modern staging systems, HAMN has posed persistent clinical uncertainty: how aggressively to stage it, whether extended resection is warranted, and how intensively to follow patients [1, 3, 6, 7]. That uncertainty is compounded by discordance between pathology nomenclature and tumour-node-metastasis based staging, and by the small size of most published HAMN cohorts [2, 6, 7].

Recent evidence has clarified the picture without fully resolving it. Larger contemporary cohorts show that HAMN is more often associated with peritoneal dissemination and higher-grade peritoneal disease than LAMN [6, 8]. Yet in patients with a non-perforated appendix, HAMN outcomes appear closer to those of LAMN than to those of appendiceal adenocarcinoma, and nodal metastases are exceptionally uncommon in non-disseminated disease [2, 6, 8]. These observations challenge the assumption that high-grade cytology alone justifies more aggressive surgery.

This review summarises the current literature on LAMN and HAMN, with emphasis on classification, clinically relevant pathological distinctions, prognostic implications, and management. The aim is to synthesise the available evidence into a practical clinical framework, clarifying where HAMN aligns with LAMN, where it differs, and which controversies remain unresolved.

Evolution of terminology and classification

The terminology of appendiceal mucinous neoplasms has long been inconsistent, complicating both interpretation of the literature and clinical decision making. Older terms such as mucocele, mucinous cystadenoma, and mucinous cystadenocarcinoma were widely used, but they mixed the gross description with histopathological diagnosis and often failed to reflect biological behaviour [5, 9]. Lesions with bland cytology but genuine risk of rupture, peritoneal spread, and pseudomyxoma peritonei were particularly difficult to classify within the traditional benign vs. malignant framework. The same lesion could consequently be labelled differently across institutions and time periods, making meaningful comparison of outcomes problematic [9].

A major step toward standardization came with the 2016 PSOGI modified Delphi consensus. That process explicitly rejected the continued use of cystadenoma for these lesions, supported the term LAMN, and introduced HAMN for appendiceal mucinous tumours that lack infiltrative invasion but show high-grade cytologic atypia. The term mucinous adenocarcinoma was reserved for lesions with infiltrative invasion [1]. This distinction formally acknowledged that appendiceal mucinous neoplasia does not fit a simple adenoma-to-carcinoma sequence, and that cytologic grade and growth pattern must be interpreted together. The same consensus also standardised the terminology of peritoneal disease, distinguishing acellular mucin from low-grade, high-grade, and signet ring cell associated mucinous carcinoma peritonei [1, 10].

The 2019 World Health Organisation classification consolidated this shift by simplifying the nomenclature of non-neuroendocrine appendiceal epithelial tumours and reinforcing the move away from older, ambiguous labels. In practical terms, it brought routine diagnostic language closer to the PSOGI framework, making it easier to distinguish serrated lesions, LAMN, HAMN, and invasive mucinous adenocarcinoma as biologically distinct categories [3, 9]. Even so, formal terminological agreement did not fully eliminate interpretive difficulty, particularly in lesions showing pushing growth, mural fibrosis, mucin dissection, or limited extra-appendiceal mucin without overt destructive invasion [9].

Staging has remained more controversial than nomenclature. The American Joint Committee on Cancer 8^th edition recognised that LAMN behaves differently from conventional adenocarcinoma and therefore introduced a specific staging logic, including the category pTis(LAMN) for disease confined to the appendiceal wall [11]. This reflects a fundamental biological point: LAMN lesions may lack destructive invasion yet still carry a risk of peritoneal dissemination if rupture or extra-appendiceal spread occurs. Recurrence risk in LAMN is therefore driven less by the depth of mural involvement than by the serosal involvement, perforation, and whether extra-appendiceal mucin is acellular or contains neoplastic epithelium [11, 12].

High-grade appendiceal mucinous neoplasm occupies a less comfortable position within this framework. Although it shares the non-infiltrative, pushing pattern of appendiceal mucinous neoplasia, its high-grade cytology has led current College of American Pathologists/American Joint Committee on Cancer-related guidance to stage it in the same way as mucinous adenocarcinoma, rather than under the special LAMN category [2, 7, 12]. This creates an important conceptual tension: the terminology implies a non-invasive neoplasm, whereas the staging system treats it more like invasive carcinoma. That tension helps explain why the literature on HAMN remains difficult to compare and why management recommendations have historically varied more than for LAMN [2, 12].

Overall, the last decade has brought substantial progress. Terminology is now much more uniform than in older literature, and the distinction between LAMN, HAMN, and invasive mucinous adenocarcinoma is clearer than before. However, staging, prognostic interpretation, and treatment translation still lag behind nomenclature. This is particularly true for HAMN, which remains the least stable category at the interface between non-invasive appendiceal neoplasia and invasive mucinous malignancy [2, 7, 12].

LAMN vs. HAMN: the clinically relevant distinction

The distinction between LAMN and HAMN is not merely semantic. It reflects an effort to classify appendiceal mucinous tumours that share a non-infiltrative pattern of growth yet differ in cytologic grade and, to some extent, in biological behaviour. For clinicians, the key question is whether this histological distinction translates into different risks of peritoneal dissemination, different surgical implications, and different surveillance requirements [6, 9].

Both entities share the non-infiltrative architecture of appendiceal mucinous neoplasia, in contrast to the destructive infiltrative invasion seen in mucinous adenocarcinoma. This architectural point is central: HAMN should not be equated with invasive carcinoma. It occupies an intermediate position, retaining the growth pattern of appendiceal mucinous neoplasia but showing unequivocal high-grade cytologic atypia, in contrast to the bland or mildly atypical epithelium of LAMN [1, 6, 12].

This distinction matters because appendiceal mucinous neoplasms do not follow the conventional adenoma-carcinoma sequence. In colorectal oncology, high-grade cytology is a strong surrogate for aggressive behaviour and malignant transformation. In the appendix, that relationship is less direct. A lesion may show high-grade atypia without infiltrative invasion, yet still follow a clinical course distinct from both classic LAMN and overt adenocarcinoma. High-grade appendiceal mucinous neoplasm is therefore a biologically relevant category, but one whose exact clinical weight remains incompletely defined [5, 6, 9, 12].

The practical purpose of the LAMN-HAMN distinction is twofold. First, it prevents undercalling lesions with frankly high-grade cytologic features as merely low-grade. Second, it prevents overcalling all high-grade mucinous appendiceal lesions as adenocarcinoma when infiltrative invasion is absent. The consequences of these two errors differ substantially: underdiagnosis may obscure the risk of aggressive peritoneal disease, while overdiagnosis may lead to unnecessarily radical surgery in lesions that do not behave like node positive invasive carcinoma [1, 6, 12].

The clinical relevance of the LAMN-HAMN distinction becomes clearer when disease extent is considered. In appendix-confined, non-perforated disease, the available literature increasingly suggests that HAMN behaves more similarly to LAMN than to invasive mucinous adenocarcinoma. High-grade cytology alone does not appear sufficient to justify routine right hemicolectomy or systemic treatment. In contrast, when HAMN is associated with perforation, extra-appendiceal mucin, or established peritoneal dissemination, it behaves less favourably than LAMN, with a greater tendency toward higher-grade peritoneal disease. The biological difference between the two entities may exist at baseline, but its practical significance becomes most apparent once disease extends beyond the appendix [2, 6, 8].

This has several practical implications. First, HAMN should not be interpreted in isolation: the pathology label must be integrated with perforation status, margin status, extra-appendiceal mucin, peritoneal deposit cellularity, and radiologic or operative evidence of dissemination. Second, the distinction between HAMN and mucinous adenocarcinoma remains critical, because lymph node metastases – expected in invasive carcinoma – are distinctly uncommon in non-disseminated HAMN. Third, the LAMN-HAMN distinction matters for patient counselling: although both can be associated with pseudomyxoma peritonei, risk stratification should be more nuanced than a simple low risk vs. high risk dichotomy [2, 6–8].

A further reason this distinction remains challenging is the imperfect alignment between nomenclature and staging. Low-grade appendiceal mucinous neoplasm is now recognised as a non-invasive appendiceal neoplasm with specific patterns of spread and recurrence, and is staged accordingly. High-grade appendiceal mucinous neoplasm, however, remains in a more ambiguous position: clearly not equivalent to LAMN, yet not fitting within the category of invasive adenocarcinoma. This mismatch drives the variable recommendations seen in the literature, particularly around extended colectomy, surveillance intensity, and the interpretation of positive margins or limited extra-appendiceal mucin [2, 6, 7, 12–14].

The most useful clinical framework is therefore not purely microscopic, but contextual. Low-grade appendiceal mucinous neoplasm and HAMN are related but not identical non-infiltrative mucinous neoplasms. Cytologic grade is the key differentiating feature, but management is determined by the combination of histologic category and disease extent and not by grade alone. This explains why contemporary recommendations increasingly support conservative treatment for localised HAMN, while still recognising that HAMN warrants closer attention than LAMN when perforation or peritoneal spread is present [2, 6, 7, 13]. The clinically relevant differences between LAMN and HAMN are summarised in Table 1.

Overall, the distinction between LAMN and HAMN is clinically meaningful but should be interpreted with restraint. The evidence supports neither putting both entities into one category nor routinely treating HAMN as equivalent to invasive appendiceal carcinoma. High-grade appendiceal mucinous neoplasm is a distinct diagnosis whose implications depend heavily on context, and that setting, more than the label alone, determines prognosis and guides treatment [2, 6, 7, 12].

Clinical behaviour and prognostic implications

The clinical course of appendiceal mucinous neoplasms is driven less by the diagnostic label than by the interaction between histologic category and disease extent. For both LAMN and HAMN, prognosis changes substantially once disease extends beyond the appendix. The most important prognostic variables are appendix perforation, extra-appendiceal mucin, the presence or absence of neoplastic epithelium within peritoneal deposits, peritoneal disease burden, and completeness of cytoreduction when surgery is required [6, 11, 15].

For localised LAMN, outcomes are generally excellent when the lesion is confined to the appendix and lacks adverse features. In a recent retrospective series, recurrence was confined to patients with more advanced local disease (particularly T4 lesions) and was associated with appendiceal perforation and acellular mucin on the serosa. Appendectomy was sufficient for pTis(LAMN) and T3 disease in the absence of additional risk factors. These findings support the view that LAMN behaves indolently until the appendiceal wall is breached and mucin, with or without epithelial cells, reaches the peritoneal cavity [11, 16].

High-grade appendiceal mucinous neoplasm is more difficult to place prognostically because it combines non-infiltrative architecture with high-grade cytology, and most published cohorts remain small. The most informative contemporary study is the recent RENAPE multicentre analysis of 443 patients treated by right colectomy with lymph node dissection, including 34 with HAMN, 246 with LAMN, and 163 with appendiceal adenocarcinoma. In that series, no lymph node metastases were identified in either HAMN or LAMN, whereas nodal disease was present in 17.8% of appendiceal adenocarcinomas. Importantly, among patients without appendiceal perforation, those with HAMN had overall and progression-free survival similar to patients with LAMN and better than those with adenocarcinoma. By contrast, among patients with appendix perforation, patients with LAMN had better overall and progression-free survival than those with HAMN or adenocarcinoma [6, 8].

This distinction between non-perforated and perforated disease is probably the key prognostic factor for HAMN [6, 8]. The RENAPE study also showed that when peritoneal metastases were present, HAMN was associated with a significantly higher proportion of high-grade peritoneal disease than LAMN [8]. That observation supports a nuanced interpretation of HAMN: it does not appear to mimic adenocarcinoma in terms of lymphatic spread, but once the appendix is perforated and dissemination occurs, its peritoneal phenotype may be more aggressive than that of LAMN [2, 6, 8]. High-grade cytology in the primary lesion appears to have limited prognostic impact in the absence of appendiceal perforation, but becomes substantially more relevant when associated with trans serosal dissemination [6, 8, 12].

The composition of peritoneal deposits further refines prognosis. Contemporary staging distinguishes intraperitoneal acellular mucin, classified as M1a, from cellular peritoneal disease, classified as M1b [11, 17]. This distinction is clinically meaningful. In a recent single-institution cytoreductive surgery with hyperthermic intraperitoneal chemo-therapy (CRS/HIPEC) series, patients with M1a disease had no recurrences and only one death during follow-up, whereas patients with M1b, G1 disease had substantially worse recurrence-free and overall survival [11, 17]. The authors argued that acellular mucin in the peritoneal cavity should not be regarded as equivalent to true metastatic disease. This is especially relevant in LAMN, where the presence of mucin outside the appendix does not automatically imply the same prognosis as cellular peritoneal dissemination [11, 17].

Once pseudomyxoma peritonei is established, prognosis depends on both tumour biology and technical operability. In a 193-patient series from a German tertiary referral centre, low-grade histology, low peritoneal cancer index (PCI), and complete cytoreduction (CC0) were independent favourable factors for both overall and progression- free survival, whereas elevated tumour markers were associated with recurrence risk and were more often seen in HAMN [10, 15]. These data reinforce that grade matters, but they also show that grade is not the sole driver of outcome. The burden of peritoneal disease and the ability to achieve complete macroscopic resection remain central determinants of long-term results [10, 15].

The same principle is reflected in the broader pseudomyxoma peritonei literature. Complete CRS followed by HIPEC is the standard treatment for resectable peritoneal disease, and long-term survival after successful CRS/HIPEC can be substantial [10, 18]. Even among patients undergoing treatment for pseudomyxoma peritonei (PMP), histologic grade remains a key prognostic determinant, with low-grade disease associated with more favourable outcomes than high-grade disease [10, 17]. Once patients progress to disseminated peritoneal disease, prognosis therefore depends on peritoneal grade, PCI, and completeness of cytoreduction and not on primary tumour terminology alone [10, 17, 18].

The available evidence suggests a layered prognostic framework. First, appendix-confined non-perforated LAMN has an excellent prognosis after local treatment [11, 16]. Second, appendix-confined non-perforated HAMN behaves much more like LAMN than like invasive adenocarcinoma [2, 6]. Third, perforation is a major biological inflection point for both entities, opening the door to peritoneal dissemination [6, 16]. Fourth, once dissemination occurs, prognosis depends on whether peritoneal deposits are acellular or cellular, on peritoneal disease grade, and on whether CC0 is feasible [10, 15, 17]. This framework is more clinically useful than treating the LAMN-HAMN distinction as either trivial or absolute [6, 16].

Overall, current data support a cautious but clinically meaningful separation of LAMN and HAMN [6, 10]. In localised disease without perforation, the difference should not be overstated [2, 6]. High-grade appendiceal mucinous neoplasm may still follow a favourable course. It should not be dismissed either, because HAMN is more closely linked to high-grade peritoneal dissemination once spread occurs [6]. The key prognostic lesson is contextual: disease extent sets the baseline risk, while grade refines that risk once dissemination has occurred [10, 11, 17].

Current management principles

Current management of LAMN and HAMN is best under-- stood as a staged, context-dependent strategy rather than a fixed histology-based algorithm. The first principle is an accurate definition of the lesion and its extent. Contemporary consensus documents emphasise expert pathology review, cross-sectional imaging when dissemination is suspected, and multidisciplinary evaluation in patients with perforation, extra-appendiceal mucin, or established peritoneal disease [4, 7, 13, 19]. The Chicago Consensus frames initial assessment around histologic subtype, burden of peritoneal disease, and the presence of non-peritoneal metastases, using computed tomography or magnetic resonance imaging (MRI) to estimate disease extent and operability [13].

For localised disease, appendectomy is the key therapeutic procedure. In LAMN confined to the appendix, it is generally sufficient when margins are negative and there is no perforation, extra-appendiceal mucin, or neoplastic epithelium [7, 19]. The same approach is increasingly applied to HAMN confined to a non-perforated appendix [7, 8]. The American Society of Colon and Rectal Surgeons (ASCRS) guideline states that appendectomy alone is typically sufficient for HAMN, provided invasive adenocarcinoma is excluded on comprehensive pathological assessment, and the RENAPE study further supports this approach in the absence of perforation [7, 8].

A related operative principle is to avoid iatrogenic rupture. The German S2k-guideline for LAMN emphasises that, even when the lesion is discovered incidentally, the primary surgical objective should be prevention of intra-abdominal perforation [19]. The guideline advises conversion to open surgery if laparoscopic appendectomy cannot be performed safely, and recommends inspection of the entire abdominal cavity [19]. Although LAMN focused, this technical logic applies equally when HAMN is suspected, since perforation is one of the strongest determinants of subsequent peritoneal risk [8, 19].

Routine right hemicolectomy should not be regarded as standard treatment for non-disseminated LAMN or HAMN [2, 7, 8, 20]. This is one of the clearest shifts in the modern literature. The RENAPE cohort found no lymph node metastases in LAMN or HAMN, while nodal disease was present in appendiceal adenocarcinoma [8]. A systematic review of localised LAMN and HAMN treated by right hemicolectomy likewise concluded that evidence does not support routine colectomy in non-disseminated disease [2]. These findings align with the Chicago Consensus, which discourages routine right hemicolectomy for non-invasive mucinous neoplasms and favours limited additional resection, such as appendiceal cuff resection or partial caecectomy, when margin management is necessary [13]. By contrast, ASCRS continues to recommend oncologic right hemicolectomy for non-metastatic appendiceal adenocarcinoma, given its substantial risk of regional nodal metastasis [13, 19].

Positive margins and limited extra-appendiceal mucin require careful interpretation [13, 14]. In non-invasive mucinous neoplasms, a positive appendiceal margin does not automatically mandate right hemicolectomy [13, 14]. The Chicago Consensus explicitly recommends conservative local resection in this setting [13]. When perforation, extra-appendiceal mucin, or neoplastic epithelium outside the appendix is present, management becomes more individualised [7, 13, 19]. The consensus distinguishes between localised acellular mucin, widespread acellular mucin, and cellular peritoneal disease, because these scenarios carry different biological weight [13]. Localised resected acellular mucin may be observed; widespread acellular mucin prompts consideration of diagnostic laparoscopy and, in selected cases, CRS with intraperitoneal chemotherapy; cellular peritoneal disease is managed more aggressively [13, 19].

Established peritoneal disease should be managed in specialised centres with the aim of CC0 [10, 18, 19]. When appendiceal peritoneal metastases are encountered incidentally, the Chicago Consensus recommends limiting surgery to diagnostic procedures, most commonly appendectomy if feasible and peritoneal biopsy, and avoiding extensive resection or partial debulking at that stage [13]. For resectable pseudomyxoma peritonei, complete CRS with HIPEC has become the preferred definitive treatment [10, 18]. The recent multisocietal consensus explicitly endorses CRS and HIPEC as the standard of care for operable, resectable pseudomyxoma peritonei [18].

The decision to escalate from appendectomy to peritoneal surgery is therefore not driven by the LAMN or HAMN identification alone, but by the dissemination pattern, peritoneal grade, disease burden, and resectability [10, 13]. For low-grade peritoneal disease, CC0 is the main determinant of long-term outcome [13]. Excellent survival can be achieved even with high disease burden if complete resection is feasible. Operative planning should prioritise CC0 rather than routine colectomy, which is not always necessary even in the setting of low-grade appendiceal mucinous neoplasms with peritoneal disease [13, 18].

The role of systemic chemotherapy is much more limited in localised LAMN and HAMN than in invasive appendiceal adenocarcinoma. The Chicago Consensus recommends systemic therapy mainly within multimodality treatment for appendiceal adenocarcinoma, signet ring cell adenocarcinoma, high-grade mucinous carcinoma peritonei, and other aggressive phenotypes, generally using colorectal type regimens [7, 13]. The updated ASCRS guidance similarly reserves systemic chemotherapy for metastatic or node positive disease, HAMN, and adenocarcinoma with peritoneal metastases, while not recommending it routinely for LAMN or well-differentiated mucinous adenocarcinoma with peritoneal spread. In appendix-confined disease, systemic therapy has no established role; in disseminated HAMN, the decision should be individualised within a multidisciplinary setting [7, 10, 13].

Current management principles are increasingly coherent [7, 13, 19]. Appendix-confined, non-perforated LAMN and HAMN are managed with appendectomy alone after an expert pathology review [7, 8, 19]. Right hemicolectomy is reserved for invasive adenocarcinoma rather than routinely applied to non-invasive mucinous neoplasms [2, 7, 13]. Perforation, extra-appendiceal mucin, cellular peritoneal disease, and established pseudomyxoma peritonei shift management toward specialist referral, staging, and consideration of CRS/HIPEC [10, 13, 19]. Treating HAMN as either identical to LAMN in every setting or automatically analogous to invasive carcinoma is unhelpful; the evidence supports neither position [6–8].

Surveillance and unresolved controversies

Surveillance after resection of appendiceal mucinous neoplasms remains one of the least standardised aspects of care. Formal postoperative surveillance protocols are absent, and current recommendations are largely consensus based rather than trial driven. As a result, follow-up intensity still varies widely between centres, particularly for patients with localised disease, limited extra-appendiceal mucin, or a diagnosis of HAMN rather than LAMN [7, 19, 21, 22].

For low-risk localised disease, guidance has become more conservative. The 2025 ASCRS guideline states that patients with LAMN or HAMN who undergo margin negative appendectomy for appendix-confined disease rarely develop pseudomyxoma peritonei; frequent long-term imaging is therefore usually of little value and surveillance should be individualised [7]. Localised non-perforated LAMN may not require posttreatment surveillance at all. Incidental HAMN without perforation or peritoneal involvement can generally be managed with appendectomy alone, though expert pathology review and multidisciplinary discussion are advised given the rarity of HAMN and the need to exclude associated invasive adenocarcinoma [7].

At the other end of the spectrum, the German S2k-guideline proposes a structured regimen for LAMN and PMP, recommending tumour markers including CEA, CA 19-9, and CA 125, contrast-enhanced MRI of the abdomen and pelvis when feasible, and six-monthly follow-up for five years with longer surveillance in selected cases. This is a useful model of organised follow-up, but it is a LAMN-focused document and cannot be extrapolated automatically to HAMN [19].

Recent surveillance data support a risk-adapted rather than uniform approach [21, 22]. In a structured Irish surveillance programme, progression to pseudomyxoma peritonei occurred in 6% of patients overall; the risk of progression was highest within the first three years after diagnosis and was associated with M1b disease and mucin extending beyond the right iliac fossa [21]. A Mayo Clinic series similarly reported a low overall recurrence risk after LAMN resection, but identified selected higher-risk features, including acellular mucin confined to the right lower quadrant and tumour size < 2 cm. Together, these studies argue against a universal surveillance schedule for all patients after appendectomy [21–23].

Several controversies remain unresolved. The first concerns HAMN specific follow-up. Although current data suggest that non-perforated HAMN can often be managed with appendectomy alone, no HAMN specific surveillance framework is supported by robust prospective evidence [7, 8]. The strongest available cohort shows that HAMN without perforation has a prognosis similar to LAMN, whereas perforated HAMN behaves less favourably and is associated with more high-grade peritoneal disease. This strongly suggests that perforation status and peritoneal involvement should influence follow-up intensity, but the exact schedule remains uncertain [7, 8].

The second controversy concerns limited extra-appendiceal mucin, particularly when confined to the right lower quadrant. The Chicago Consensus distinguishes between no extra-appendiceal mucin, localised acellular mucin, widespread acellular mucin, and cellular peritoneal disease, and does not treat these situations as prognostically equivalent [13]. The 2025 ASCRS guideline similarly notes that management of limited peritoneal involvement with cellular or acellular mucin remains controversial [7]. This is clinically important because cellularity often cannot be established intraoperatively with confidence, and that uncertainty directly affects decisions about observation, repeat surgery, or referral for CRS/HIPEC [7, 13, 19].

A third unresolved issue is the significance of positive margins and adjunctive tests. For non-perforated localised LAMN, limited data suggest that a microscopically positive appendectomy margin does not necessarily predict recurrence and may not warrant additional treatment [7, 14]. That reassurance is less secure for HAMN, where the evidence base is much smaller [6, 7]. Routine peritoneal cytology is not recommended, and its role in appendiceal neoplasms remains uncertain. Emerging biomarkers such as peritoneal ctDNA are promising but investigational, and are not yet ready for routine surveillance algorithms [7].

The current literature supports a pragmatic conclusion. Surveillance should be minimal or omitted in truly low risk, appendix-confined, margin-negative disease, particularly for LAMN and likely also for selected HAMN [7, 19, 21, 22]. More structured and prolonged follow-up is warranted when perforation, indeterminate margins, extra-appendiceal mucin, peritoneal disease, or high-grade features are present. What remains absent is a validated risk stratified framework integrating histology, perforation status, mucin cellularity, and dissemination pattern into a single standardised algorithm [7, 19, 21, 22]. Until such data are available, multidisciplinary interpretation remains essential.

Conclusions

The distinction between LAMN and HAMN has improved the conceptual framework of appendiceal mucinous neoplasia, but its clinical implications are still not fully standardised. Current evidence supports treating these entities as related but not equivalent [1, 6, 7, 12]. Low-grade appendiceal mucinous neoplasm remains a better defined lesion, whereas HAMN occupies a less stable position between low-grade appendiceal mucinous neoplasia and invasive mucinous adenocarcinoma.

From a practical perspective, the key message is that disease extent is at least as important as the diagnostic label in determining clinical management [10, 11]. Appendix- confined, non-perforated LAMN has an excellent prognosis after appendectomy, and the available literature increasingly suggests that non-perforated HAMN follows a similarly favourable course [7, 8, 11, 16]. Perforation, extra- appendiceal mucin, and peritoneal dissemination are the key biological turning points for both entities, with HAMN more closely associated with high-grade peritoneal disease once spread occurs [6, 8, 11].

These observations have direct management implications. Routine right hemicolectomy is difficult to justify for non-disseminated LAMN or HAMN in the absence of invasive adenocarcinoma [2, 7, 8, 20]. Instead, appendectomy with careful pathological assessment is usually sufficient for localised disease, while patients with perforation or peritoneal involvement should be evaluated in specialist centres with expertise in cytoreductive surgery and HIPEC [7, 8, 19]. Surveillance should likewise be risk adapted rather than uniform, although the optimal follow-up strategy, particularly for HAMN, remains uncertain [7, 19, 21, 22].

The current literature supports a balanced interpretation of HAMN. It should not be collapsed into LAMN, nor routinely managed as invasive appendiceal carcinoma [6–8]. The most clinically useful approach is to integrate histologic category with perforation status, extra-appendiceal disease, and peritoneal phenotype [6–8, 13]. Future work should focus on refining HAMN specific staging, surveillance, and treatment algorithms, which remain the least developed areas of the field.