Abstract
Objective
To assess the frequency and predictive performance of clinicopathological factors associated with for incidental appendiceal neoplasms and complicated appendicitis in the geriatric population.
Methods
Adult appendectomy cases (≥18 years) performed from 2016 to 2024 were retrospectively reviewed. Age-based grouping classified patients as non-geriatric (18-64 years) or geriatric (≥65 years). Demographic data, laboratory findings, appendicitis type, and histopathology were recorded.
Results
Of the 859 patients, 16.3% were geriatric. Complicated appendicitis occured at a higher rate in geriatric group (31.1% vs. 12.5%; p<0.001). Incidental neoplasms were identified in 29 of 859 patients (3.4%). Detection was markedly more frequent in the ≥65 age group (15.0%) than in younger patients (1.1%; p<0.001). Malignant tumors accounted for 4.3% of cases in older patients, compared with 0.6% in the younger group (p=0.002). Age was independently associated with the presence of neoplasm (p<0.001). Receiver operating characteristic analysis supported an age threshold of 61 years, with an area under the curve of 0.87 (sensitivity, 79.3%; specificity, 83.1%).
Conclusion
Advanced age increases the risk of neoplasia and of a complicated clinical course in acute appendicitis. Clinical decisions should be individualized by taking into account age, clinical and radiological findings, and multiple inflammatory markers.
Introduction
Appendiceal neoplasms (AN) are rare entities, with a substantial proportion diagnosed incidentally during routine histopathological examination following appendectomy(1). They account for less than 0.5% of all gastrointestinal malignancies and have historically been reported in approximately 1% of appendectomy specimens(2). However, recent reports describe higher detection rates of AN, likely influenced by more comprehensive pathological examination of resected specimens(3-5).
ANs encompass a wide histopathological spectrum, including well-differentiated neuroendocrine tumors (NETs), low- and high-grade mucinous neoplasms, and adenocarcinomas(3). While NETs predominantly occur in younger individuals and tend to be small and localized, mucinous neoplasms and adenocarcinomas are more common in older populations and may exhibit a more aggressive clinical course(4).
The clinical presentation of ANs is often non-specific; patients usually have either classic symptoms of acute appendicitis or non-specific abdominal pain. Therefore, even in routine cases of appendicitis, a meticulous histopathological assessment is essential to detect underlying malignancies(5). The incidence of ANs increases with age, particularly in patients over 50 presenting with appendicitis(3, 4). Furthermore, the increasing adoption of non-operative management strategies for appendicitis raises additional concerns regarding the risk of missed occult neoplasms(5).
The limited availability of reliable clinical markers other than age and imaging findings has increased interest in hematological and biochemical composite indicators. In this context, parameters such as the hemoglobin, albumin, lymphocytes, platelets (HALP) score and the systemic immune-inflammation index (SIII) are valuable in predicting complications and prognosis in gastrointestinal tract tumors. Lower HALP scores are thought to indicate compromised nutritional reserve alongside systemic inflammation, and have been correlated with poorer prognosis(6, 7). Nonetheless, the clinical utility of these indices in ANs remains poorly defined. Particularly in the elderly, these biomarkers may facilitate earlier recognition of ANs and their aggressive subtypes.
In this study, we explored the occurrence and pathological spectrum of incidental appendiceal tumors among elderly individuals and examined whether HALP and SII provide meaningful predictive information in this setting.
Materials and Methods
This retrospective cohort comprised adult patients who were treated with appendectomy between 2016 and 2024 at the Department of General Surgery, Aydın Adnan Menderes University. Eligibility was restricted to individuals aged 18 years or above. Only cases with confirmed histopathological findings were analyzed, while negative appendectomy specimens were excluded. For comparative analysis, participants were stratified by age into non-geriatric (18-64 years) and geriatric (≥65 years) categories.
Demographic characteristics (age, sex), laboratory parameters [white blood cell count, neutrophils, lymphocytes, platelets, C-reactive protein (CRP), hemoglobin, albumin], histopathological findings, the type of appendicitis (complicated or uncomplicated), and the presence and subtypes of neoplasms were retrospectively retrieved from hospital records and patient charts.
The following formula was used for biomarker calculation: HALP score=hemoglobin (g/L)×albumin (g/L)×lymphocyte count (×10⁹/L)÷platelet count (×10⁹/L). SIII=neutrophil count (×10⁹/L)×platelet count (×10⁹/L)÷lymphocyte count (×10⁹/L). Appendicitis was classified as complicated when perforation, abscess formation, or gangrene were identified.
The research ethics approval was obtained from the Ethical Review Board of the Aydın Adnan Menderes University Ethical Committee (approval no: 2025/284, date: 02.10.2025). The study was performed in compliance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants for the use of their clinical data and protected health information.
Statistical Analysis
Statistical analyses were performed with IBM SPSS Statistics (26.0; IBM Corp., Armonk, NY, USA). Normality of continuous variables was evaluated using the Kolmogorov-Smirnov and Shapiro-Wilk tests. Continuous data are reported as mean ± standard deviation when normally distributed, and as median (range) otherwise. Categorical variables are presented as numbers and percentages. Between-group comparisons were performed using the chi-square test or Fisher’s exact test for categorical variables, and Student’s t-test or the Mann-Whitney U test for continuous variables, depending on the distribution. Predictor candidates that showed significance in univariate testing and were deemed clinically meaningful were examined using receiver operating characteristic (ROC) curve analysis, with area under the curve (AUC) estimates reported. Where applicable, effect sizes are provided alongside 95% confidence intervals (CIs). The optimal cut-off value was selected based on the Youden index. A p-value of <0.05 was considered statistically significant in all analyses.
Results
Between 2016 and 2024, 870 appendectomies were performed at our tertiary referral center. Histopathological analysis revealed negative appendectomies in 11 cases (1.3%), with comparable rates between groups (p=0.1703). After excluding these cases, the final cohort consisted of 859 patients: 140 (16.3%) were geriatric and 719 (83.7%) were non-geriatric. The overall mean age was 43.6 years. The mean age in the geriatric group was 71.7 years (65-91), while it was 38.1 years (18-62) in the non-geriatric group. In the overall cohort, men accounted for 56.2% and women for 43.8%. The incidence of complicated appendicitis was more often in the geriatric group (31.1%) than the non-geriatric group (12.5%) (p<0.0001). The overall incidence of incidental AN was 3.4% (29/859). Among these, 65.5% (n=19) were benign and 34.5% (n=10) were malignant. Incidental neoplasms were more often detected in geriatric group (15.0%) than in non-geriatric group (1.1%) (p<0.0001). Malignant tumors were detected in 1.2% of the total cohort and was more common in geriatric group (4.3%) than in non-geriatric group (0.6%) (p=0.002). Among the 29 patients diagnosed with neoplasms, the most common neoplasm was low-grade appendiceal mucinous neoplasm (LAMN), accounting for 41.4%. In both age groups, LAMN was the most frequent benign subtype, whereas NET was the most common malignant subtype (Table 1).
Logistic regression,advancing age was independently associated with AN [odds ratio (OR)=1.09, 95% CI: 1.06-1.12; p<0.001]. Age showed substantial discriminative ability for neoplasm detection in ROC analysis (AUC: 0.87). An age threshold of 61 years provided optimal discrimination (sensitivity 79.3% and specificity 83.1%) (Figure 1). Figure 2 displays the age distribution of patients diagnosed with incidental neoplasms.
Among geriatric patients, inflammatory markers differed significantly between complicated and uncomplicated appendicitis. CRP, neutrophil count, and SII values were higher in patients with complicated appendicitis (p<0.001, p=0.047, and p=0.008, respectively). Conversely, HALP scores were lower in complicated cases (p=0.007) (Table 2). ROC analysis was performed to evaluate how well laboratory parameters discriminated complicated appendicitis. CRP emerged as the most powerful biomarker (AUC: 0.748, p<0.001), demonstrating good discriminative ability. SII showed a moderate diagnostic performance (AUC: 0.652, p<0.001). In contrast, the HALP score (AUC: 0.345, p=0.814) exhibited poor diagnostic accuracy, limiting its utility as an independent clinical predictor (Table 3). The ROC curves for complicated vs. non-complicated cases in the geriatric group are displayed in Figure 3. In the ROC curve analysis to predict the presence of a neoplasm, none of the parameters showed significant discrimination (p>0.05).
Discussion
Although incidental ANs are rare in patients undergoing appendectomy for acute appendicitis, they hold substantial clinical significance. In most cases, the diagnosis is not anticipated preoperatively and is instead made through postoperative histopathological analysis. Earlier reports was reported AN incidence rates ranging from 0.5% to 2.5%(8-10). However, the incidence has been reported to be higher in current studies than in previous literature. Dohner et al.(11) reported a 3.7% rate of neoplasms in a retrospective single-center study, while Gómez Báez et al.(12) reported a 3.2% rate. Our study was consistent with this pattern and detected neoplasms at a rate of 3.4%.
The presence of incidental ANs in elderly patients has been a matter of long-standing debate in the literature. Advanced age represents a significant predisposing factor for underlying neoplasia in patients presenting with acute appendicitis. Numerous recent chorts have demonstrated a marked rise in the likelihood of tumor detection with advancing age(8, 13-18). Fransvea et al.(19) reported neoplasia rates of 13% among individuals over 40 years, compared to only 3.8% in those under 30. Our findings align with this evidence, revealing a significantly higher rate of neoplasms in the geriatric group (15.0% vs. 1.1%, p<0.0001). Malignancy was more frequent in the elderly (4.3% vs. 0.6%, p=0.002). Higher age corresponded to greater odds of neoplasia (OR=1.09; 95% CI: 1.06-1.12; p<0.001), and ROC analysis confirmed a strong discriminative performance (AUC: 0.87), with 61 years identified as the optimal cut-off. These findings highlight the need to keep underlying neoplasia in elderly patients presenting with acute appendicitis. Even in available literature supporting non-operative approaches, the risk of missed malignancy ranges from 0.7% to 2.5%(11). In patients aged ≥65 managed conservatively, this incidence was reported to reach 3.9%(17). Therefore, the diagnostic and therapeutic advantages of appendectomy should be strongly considered, especially in geriatric patients and in those with high clinical and imaging suspicion. Notably, our data showed that the rate of negative appendectomy did not increase in elderly patients (p=0.1703), suggesting that concerns about “unnecessary surgery” in this population may be overstated. Conversely, diagnostic delays may pose greater risks, including disease complications and undetected malignancy.
AN exhibit a broad histopathological spectrum. LAMNs a are frequently encountered among benign or premalignant neoplasms, whereas NETs are most prevalent among malignant types(8, 20-23). Consistent with the literature, our series showed that the majority of benign and premalignant neoplasms were LAMNs, whereas NETs and adenocarcinomas were the most common malignant subtypes. Although our data and prior reports indicate that a significant portion of ANs are low-grade or have limited malignant potential, the risk of invasive cancer should not be underestimated.
In acute appendicitis, CRP has long been used as a marker associated with disease severity(19). Recently, additional indices, including SIII and HALP scores, were evaluated in this context(24, 25). In our study, the incidence of complicated appendicitis was higher in geriatric patients than in non-geriatric patients (31.1% vs. 12.5%; p<0.0001). Among geriatric patients with complicated appendicitis, CRP, neutrophil count, and SIII values were higher than in uncomplicated cases (p<0.001, p=0.0479, and p=0.0083, respectively). The HALP score was notably lower (p=0.007). In ROC analysis, CRP demonstrated the strongest diagnostic performance (AUC: 0.744; p<0.001). SIII (AUC: 0.672; p=0.007) demonstrated moderate discriminatory ability. Although complicated cases were characterized by lower HALP scores (p=0.007), the ROC performance was limited (AUC: 0.339; p=0.0028). These results support the use of combined inflammatory markers rather than reliance on a single parameter to improve clinical accuracy. However, none of the biomarkers studied exhibited significant predictive value for AN (p>0.05).
Study Limitations
A number of limitations should be acknowledged. Most notably, the retrospective, single-center nature of the study may have increased the risk of selection bias. In addition, changes in pathology sampling protocols and reporting standards between 2010 and 2024 may have caused measurement inconsistencies. The absence of long-term oncologic outcomes limits the interpretation of prognostic implications.
Acute appendicitis in elderly patients may exhibit distinct biological behavior. Age should be recognized as a major determinant of AN. Each case of appendicitis in an elderly patient must be approached as a potential neoplasm, with surgical and follow-up strategies tailored accordingly. Therefore, in elderly patients with diagnostic uncertainty, early surgical intervention should be strongly considered. This approach will facilitate the timely diagnosis of potentially occult neoplasms. Our findings, consistent with the current literature, support a more aggressive approach to the management of acute appendicitis in elderly individuals. Considering that the histopathological spectrum of ANs mostly consists of lesions with a better prognosis, appendectomy may provide adequate treatment in many cases. However, the need for additional oncologic treatment is more likely in the geriatric population.
Conclusion
Both our data and the current literature indicate that the likelihood of neoplasia and complicated disease is markedly higher among elderly patients with acute appendicitis. Management strategies should be planned, taking this reality into account. Even when considering non-operative approaches, the potential for underlying malignancy must be carefully assessed. Personalized treatment decisions should incorporate patient age, clinical and radiological findings, and laboratory profiles. Prospective multicenter cohorts are warranted to strengthen clinical decision-making algorithms.
