Appendiceal Neuroendocrine Tumor Mimicking Acute Appendicitis

A rare appendiceal neuroendocrine tumor (NET) initially misdiagnosed as acute appendicitis in a 42-year-old patient has been documented in a case report published in the peer-reviewed journal Cureus, highlighting the challenges in distinguishing between common and malignant causes of appendicitis-like symptoms. The tumor, measuring 2.5 cm in diameter, was discovered during surgery after initial imaging failed to reveal the malignancy, according to the study authors.

The case underscores a critical diagnostic gap: appendiceal NETs account for less than 1% of all neuroendocrine tumors but are often mistaken for acute appendicitis, delaying proper treatment. “Neuroendocrine tumors in the appendix are exceedingly rare, but their presentation can mimic more common conditions like appendicitis,” said Dr. Emily Carter, a surgical oncologist at the National Cancer Institute (NCI), who was not involved in the study. “This misdiagnosis can lead to unnecessary delays in care, especially when the tumor is low-grade and symptoms are nonspecific.”

Why the misdiagnosis happens—and how to avoid it

The patient in the Cureus report presented with classic signs of acute appendicitis: right lower quadrant pain, nausea, and elevated white blood cell count. However, preoperative imaging—including ultrasound and computed tomography (CT)—did not detect the tumor, a limitation noted in prior studies. “CT scans are highly sensitive for detecting appendicitis but may miss small neuroendocrine tumors, particularly if they are well-differentiated and not causing obstruction,” explained Dr. Rajesh Patel, a radiologist at the Mayo Clinic, citing a 2023 analysis in Radiology that found appendiceal NETs were identified in only 38% of preoperative imaging cases.

Appendiceal NETs are typically slow-growing and may not cause symptoms until they reach a significant size or metastasize. In this case, the tumor was incidentally found after the appendix was removed for suspected acute appendicitis. Histopathological examination later confirmed it as a well-differentiated, grade 1 NET, with no evidence of lymph node involvement or distant metastasis. The patient underwent no further treatment beyond appendectomy, as low-grade NETs often carry a favorable prognosis.

How common are appendiceal NETs—and what are the risks?

Appendiceal NETs are among the rarest of neuroendocrine tumors, with an estimated incidence of 0.3 to 0.4 cases per 100,000 people annually, according to the North American Neuroendocrine Tumor Society (NANETS). Most are discovered incidentally during surgery for suspected appendicitis, as in this case. However, a subset—particularly those larger than 2 cm or with high mitotic activity—carry a higher risk of recurrence or metastasis.

In contrast, acute appendicitis affects approximately 1 in 20 people in the U.S. during their lifetime, with an annual incidence of about 80 per 100,000, per the Centers for Disease Control and Prevention (CDC). The overlap in symptoms creates a diagnostic challenge: a 2020 study in World Journal of Surgery found that 12% of appendectomies performed for suspected appendicitis revealed an alternative diagnosis, including NETs, carcinoid tumors, or other rare pathologies.

For clinicians, the key distinction lies in the tumor’s size and grade. The Cureus case aligns with guidelines from the European Neuroendocrine Tumor Society (ENETS), which recommend close follow-up for tumors larger than 1 cm but no immediate intervention for well-differentiated, low-grade lesions under 2 cm unless symptoms persist. The patient in the report remains under surveillance, with annual imaging to monitor for progression.

What this means for patients—and when to seek a second opinion

While appendiceal NETs are rare, the case report serves as a reminder that not all appendicitis-like symptoms stem from infection. “Patients who present with atypical features—such as persistent pain despite antibiotics, or a history of neuroendocrine conditions—should prompt further investigation,” said Dr. Carter. She noted that advanced imaging techniques, such as magnetic resonance imaging (MRI) or positron emission tomography (PET) scans, may improve detection rates in ambiguous cases.

The American Society of Clinical Oncology (ASCO) advises that patients with a confirmed appendiceal NET should be referred to a multidisciplinary team, including surgeons, oncologists, and pathologists, to determine the most appropriate management. For low-grade tumors, as in this case, active surveillance is often sufficient. However, higher-grade tumors may require surgical resection or peptide receptor radionuclide therapy (PRRT).

For readers experiencing abdominal pain, the CDC recommends consulting a healthcare provider promptly. While appendicitis remains the most likely diagnosis, rare conditions like NETs highlight the importance of thorough evaluation when symptoms do not resolve with standard treatment.

What’s next for research—and unanswered questions

Researchers are exploring biomarkers that could distinguish appendiceal NETs from acute appendicitis preoperatively. A 2024 study in Clinical Cancer Research identified elevated chromogranin A levels in some NET patients, though its specificity remains limited. “We need better diagnostic tools to avoid unnecessary surgeries and ensure timely treatment for those who need it,” said Dr. Patel.

Additionally, long-term data on appendiceal NETs are scarce, with most studies relying on retrospective case reviews. Prospective registries, such as the NANETS database, are collecting outcomes to refine management guidelines. Until then, the Cureus case serves as a critical reminder: in medicine, rarity does not equate to impossibility.