Carcinoid Tumors: Epidemiology, Pathogenesis, Classification, Symptoms, Diagnosis, Staging, Management and Prevention

Carcinoid Tumors

~Introduction

Carcinoid tumors are a group of rare, slow-growing malignant tumors that arise from neuroendocrine cells. Neuroendocrine cells are specialized cells that have characteristics of both nerve cells and hormone-producing endocrine cells. These tumors belong to a broader category known as Neuroendocrine Tumors (NETs). Carcinoid tumors most commonly develop in the gastrointestinal tract and the lungs, but they can occur in many other organs of the body.

Although carcinoid tumors often grow slowly and may remain asymptomatic for many years, they can become aggressive and metastasize, especially to the liver. Some carcinoid tumors secrete biologically active substances such as serotonin, leading to a distinct clinical condition known as carcinoid syndrome.

With improved diagnostic techniques and greater awareness, the incidence of carcinoid tumors has increased in recent decades. However, their diagnosis is often delayed due to nonspecific symptoms and indolent growth patterns.

~Historical Background

The term “carcinoid” was first introduced in 1907 by the German pathologist Siegfried Oberndorfer. He used the term to describe tumors that appeared to behave less aggressively than typical carcinomas. The word carcinoid literally means “carcinoma-like.”

Initially, carcinoid tumors were considered benign or low-grade malignancies. However, it is now well established that all carcinoid tumors possess malignant potential, although the degree of aggressiveness varies significantly.

~Epidemiology

• Carcinoid tumors account for approximately 1–2% of all malignancies

• Incidence: about 2–5 cases per 100,000 population per year

• Most commonly diagnosed between 50 and 70 years of age

• Slightly more common in females

• Increased incidence in recent years due to:

  • Improved imaging techniques

  • Increased use of endoscopy

  • Better pathological classification

~Cell of Origin and Pathogenesis

Carcinoid tumors arise from enterochromaffin cells, a type of neuroendocrine cell found throughout the body, especially in the gastrointestinal tract and respiratory system. These cells produce various hormones and peptides, including:

• Serotonin

• Histamine

• Bradykinin

• Tachykinins

• Prostaglandins

The exact cause of carcinoid tumor development is not fully understood. However, several factors may contribute:

• Genetic mutations

• Chronic inflammation

• Hormonal stimulation

• Environmental factors

Some carcinoid tumors are associated with genetic syndromes, such as:

• Multiple Endocrine Neoplasia type 1 (MEN-1)

• Neurofibromatosis type 1

~Classification of Carcinoid Tumors

Carcinoid tumors are classified based on site of origin, histological features, and biological behavior.

1. Based on Site of Origin

a. Gastrointestinal Carcinoid Tumors

These account for about 70% of all carcinoid tumors.

• Small intestine (especially ileum) – most common

• Appendix

• Rectum

• Stomach

• Colon

b. Pulmonary Carcinoid Tumors

• Arise in the bronchi

• Account for about 20–25%

• Divided into:

  • Typical carcinoid

  • Atypical carcinoid

c. Other Sites

• Pancreas

• Ovary

• Thymus

• Testis

• Gallbladder

2. Based on Histological Grade

According to the World Health Organization (WHO):

• Well-differentiated neuroendocrine tumors (NETs)

  • Low grade (Grade 1)

  • Intermediate grade (Grade 2)

• Poorly differentiated neuroendocrine carcinomas

  • High grade (Grade 3)

Carcinoid tumors generally fall into the well-differentiated category.

~Clinical Features

General Symptoms

Many carcinoid tumors are asymptomatic and discovered incidentally. When symptoms occur, they are often vague and nonspecific:

• Abdominal pain

• Weight loss

• Fatigue

• Anemia

• Diarrhea

Site-Specific Symptoms

Gastrointestinal Carcinoids

• Abdominal cramps

• Bowel obstruction

• Gastrointestinal bleeding

• Intussusception

Pulmonary Carcinoids

• Persistent cough

• Hemoptysis

• Wheezing

• Recurrent pneumonia

Carcinoid Syndrome

Definition

Carcinoid syndrome is a group of symptoms caused by the release of serotonin and other vasoactive substances into the systemic circulation. It usually occurs when the tumor has metastasized to the liver, bypassing hepatic metabolism.

Clinical Features of Carcinoid Syndrome

• Flushing of face and neck

• Chronic watery diarrhea

• Bronchospasm

• Abdominal pain

• Palpitations

Carcinoid Heart Disease

Long-standing carcinoid syndrome may lead to fibrosis of heart valves, especially:

• Tricuspid valve

• Pulmonary valve

This results in:

• Tricuspid regurgitation

• Right-sided heart failure

~Diagnosis

1. Biochemical Investigations

• 24-hour urinary 5-HIAA (5-hydroxyindoleacetic acid)

  • Breakdown product of serotonin

  • Elevated in carcinoid syndrome

• Serum chromogranin A (CgA)

  • Useful tumor marker

  • Elevated in most neuroendocrine tumors

2. Imaging Studies

• CT scan of abdomen and chest

• MRI for liver metastases

• Somatostatin receptor imaging:

  • Gallium-68 DOTATATE PET scan (high sensitivity)

3. Endoscopy

• Upper GI endoscopy

• Colonoscopy

• Bronchoscopy (for lung carcinoids)

4. Histopathology

Microscopic features include:

• Uniform round cells

• “Salt and pepper” chromatin

• Nests, trabeculae, or rosette patterns

Immunohistochemistry markers:

• Chromogranin A

• Synaptophysin

• CD56

~Staging

Staging depends on the site of tumor and is usually based on the TNM classification:

• T – Tumor size and invasion

• N – Lymph node involvement

• M – Distant metastasis

Common metastatic sites include:

• Liver

• Lymph nodes

• Bone

• Lung

~Management of Carcinoid Tumors

1. Surgical Treatment

Surgery is the mainstay of treatment and offers the best chance for cure.

• Local excision for small tumors

• Segmental resection for intestinal carcinoids

• Lobectomy for pulmonary carcinoids

• Debulking surgery for metastatic disease

2. Medical Management

Somatostatin Analogues

• Octreotide

• Lanreotide

• Control symptoms of carcinoid syndrome

• Slow tumor growth

Interferon-alpha

• Used in selected cases

• Enhances immune response

3. Targeted Therapy

• Everolimus

• Sunitinib
  Used in advanced or metastatic disease

4. Peptide Receptor Radionuclide Therapy (PRRT)

• Uses radiolabeled somatostatin analogues

• Delivers targeted radiation to tumor cells

5. Chemotherapy

Limited role due to slow-growing nature of carcinoids
Used mainly in:

• Poorly differentiated tumors

• Advanced metastatic disease

~Prognosis

Prognosis depends on:

• Tumor site

• Size

• Grade

• Presence of metastasis

5-Year Survival Rates

• Localized disease: 80–95%

• Regional spread: 60–80%

• Distant metastasis: 30–50%

Appendiceal and rectal carcinoids have a better prognosis, while colonic and pancreatic carcinoids tend to be more aggressive.

~Complications

• Bowel obstruction

• Carcinoid crisis (life-threatening)

• Carcinoid heart disease

• Liver failure due to metastasis

~Prevention and Screening

There are no established screening programs for carcinoid tumors due to their rarity. However:

• Early evaluation of unexplained symptoms

• Regular follow-up in high-risk genetic syndromes

• Surveillance imaging in known cases

~Conclusion

Carcinoid tumors are rare neuroendocrine malignancies with diverse clinical presentations and biological behaviors. Although many grow slowly and remain asymptomatic for years, they have malignant potential and may lead to serious complications such as carcinoid syndrome and cardiac involvement. Early diagnosis is often challenging due to nonspecific symptoms, but advancements in imaging and biochemical markers have significantly improved detection.

Surgical resection remains the cornerstone of treatment, while medical and targeted therapies play an important role in symptom control and disease stabilization. With appropriate management and long-term follow-up, many patients with carcinoid tumors can achieve prolonged survival and good quality of life.