Acute appendicitis, first recognized in the 18th century as a distinct clinical entity, continues to be a leading cause of emergency abdominal surgeries worldwide. Despite its classic symptomatology of migratory right iliac fossa pain, diagnostic certainty is often elusive, leading to significant rates of negative appendectomies [1]. Historically, diagnosis relied solely on clinical acumen, but the incorporation of imaging technologies and scoring systems has altered the landscape. Nevertheless, histopathological confirmation remains the gold standard for diagnosis. Emerging demographic trends, including an increase in atypical presentations among the pediatric and elderly populations, further complicate timely diagnosis. Understanding the clinicopathological correlation in appendicitis remains vital for improving surgical outcomes and reducing morbidity [2].

This review synthesizes data from recent studies (post-2015) on acute appendicitis. Databases were searched using terms such as “acute appendicitis,” “clinicopathological correlation,” “negative appendectomy,” and “emerging diagnostic trends.” Only English-language studies involving human subjects were included. A focus was placed on articles addressing clinical presentation variability, imaging findings, histopathological confirmations and diagnostic challenges in contemporary surgical practice.

Demographic Patterns

Recent studies highlight a changing demographic profile of acute appendicitis. Although it traditionally affects young adults, there has been an increase in incidence among the pediatric and geriatric age groups [1,2]. Male predominance persists, with a reported male-to-female ratio ranging from 1.2:1 to 1.8:1 [1,3].

Clinical Presentations

While right lower quadrant pain remains the hallmark symptom, atypical presentations such as flank pain, suprapubic discomfort and generalized abdominal pain are increasingly reported, particularly in cases of retrocecal or pelvic appendices [4,5]. Classical signs such as McBurney’s point tenderness, Rovsing’s sign and rebound tenderness retain diagnostic value but are absent in a significant subset.

Diagnostic Modalities

Ultrasonography, despite being operator-dependent, remains a frontline imaging tool due to its non-invasive nature and cost-effectiveness. However, Computed Tomography (CT) scans offer superior sensitivity and specificity, particularly in equivocal cases, achieving diagnostic accuracies above 95% [6,7]. The role of Magnetic Resonance Imaging (MRI) is expanding, especially in pediatric and pregnant populations to avoid radiation exposure [8].

Histopathological Spectrum

Histopathological examination continues to be indispensable. Typical findings include neutrophilic infiltration of the muscularis propria, suppurative inflammation and gangrenous changes. Rare findings such as neuroendocrine tumors, parasitic infections and mucinous neoplasms have been identified, underlining the necessity for routine histopathological assessment post-appendectomy [9,10].

Negative Appendectomy Rates

Negative appendectomy rates remain around 10–20% globally, despite improvements in imaging and scoring systems [11]. These rates are higher among females, particularly in reproductive age, where gynecological differentials complicate the diagnosis [12].

Despite the evolution of diagnostic strategies, acute appendicitis diagnosis remains challenging due to its protean clinical manifestations. High rates of atypical presentation necessitate a high index of suspicion. Clinical scoring systems like the Alvarado score and Pediatric Appendicitis Score have aided risk stratification but are not fail-proof [13,14].

Advances in imaging, particularly the use of low-dose CT, have significantly reduced negative appendectomy rates without a corresponding increase in perforation rates [6]. However, in low-resource settings, reliance on clinical judgment remains high, emphasizing the continued relevance of thorough physical examination and risk assessment.

Histopathology not only confirms acute appendicitis but also detects incidental pathologies that can alter patient management, such as carcinoid tumors or parasitic infections. Therefore, the practice of sending all appendectomy specimens for histopathological examination should continue, regardless of intraoperative findings.

Acute appendicitis presents ongoing diagnostic challenges despite technological advancements. Variations in clinical presentation and limitations of imaging underscore the indispensable role of histopathological examination. A multimodal diagnostic approach combining careful clinical assessment, judicious imaging and routine histopathology offers the best strategy for optimizing outcomes and reducing negative appendectomy rates.

1. Ferris, M., et al. "Pediatric appendicitis: Epidemiology, diagnosis and management." Pediatric Emergency Care, vol. 33, no. 3, 2017, pp. 215–219.

2. Podda, M., et al. "Appendicitis in the elderly: A Diagnostic challenge." International Journal of Surgery, vol. 56, 2018, pp. 80–85.

3. Howell, E.C., et al. "Epidemiology and burden of appendicitis." Annals of Surgery, vol. 270, no. 5, 2019, pp. 891–898.

4. Limaiem, F., et al. "Clinical presentations of retrocecal appendicitis: A review." Cureus, vol. 12, no. 2, 2020, Article ID e6892.

5. Ma, K.W., et al. "Variability in appendiceal location and Its clinical implications." Journal of Gastrointestinal Surgery, vol. 23, no. 5, 2019, pp. 991–998.

6. Kim, H.Y., et al. "Accuracy of CT in diagnosis of appendicitis: Systematic review and meta-analysis." Radiology, vol. 288, no. 3, 2018, pp. 717–726.

7. Pickhardt, P.J., et al. "Diagnostic performance of multidetector CT in diagnosing appendicitis." Annals of Internal Medicine, vol. 166, no. 10, 2017, pp. 730–741.

8. Aspelund, G., et al. "Ultrasonography/MRI versus CT in appendicitis evaluation." Pediatrics, vol. 140, no. 1, 2017, Article ID e20170092.

9. Bhangu, A., et al. "Acute appendicitis: Modern understanding of pathogenesis, diagnosis and management." The Lancet, vol. 386, no. 10000, 2015, pp. 1278–1287.

10. Carr, N.J., et al. "The Pathology of acute appendicitis: An Update." Histopathology, vol. 72, no. 1, 2018, pp. 110–118.

11. Sammalkorpi, H.E., et al. "Negative appendectomy rate: trends and influences." World Journal of Surgery, vol. 41, no. 3, 2017, pp. 693–698.

12. Di Saverio, S., et al. "Diagnosis and treatment of acute appendicitis: 2020 WSES guidelines." World Journal of Emergency Surgery, vol. 15, no. 1, 2020, Article ID 27.

13. Kularatna, M., et al. "Comparison of scoring systems for diagnosing appendicitis: A Meta-Analysis." Journal of Medical Imaging and Radiation Oncology, vol. 61, no. 3, 2017, pp. 349–355.

14. Naik, N.D., et al. "Pediatric appendicitis score: Diagnostic Performance in children." World Journal of Pediatric Surgery, vol. 2, no. 3, 2019, Article ID e000028.