What are the other Names for this Condition? (Also known as/Synonyms)

• Esophageal Neuroendocrine Neoplasm
• Neuroendocrine Neoplasm of Oesophagus
• Oesophageal Neuroendocrine Neoplasm

What is Neuroendocrine Neoplasm of Esophagus? (Definition/Background Information)

• Esophageal neoplasms with neuroendocrine differentiation include low, intermediate, and high- grade tumors and carcinomas. These are extremely rare and malignant
• The majority of Neuroendocrine Neoplasms of Esophagus are well-differentiated (low and intermediate grade) neuroendocrine tumors that are histologically graded as G1 and G2. Some are high-grade and denoted G3 (neuroendocrine carcinomas)
• The different types of neuroendocrine neoplasms include:
  • Grade 1 neuroendocrine tumor (low-grade); previously called carcinoids tumor
  • Grade 2 neuroendocrine tumor (intermediate-grade)
  • Grade 3 neuroendocrine carcinoma (high-grade, poorly-differentiated tumors that include large cell and small cell neuroendocrine carcinomas)
• The tumor is diagnosed under a microscope, on examination of the cancer cells by a pathologist. This classification of the tumor is important, as it may dictate the type of treatment to be provided and its prognosis
• Esophageal Neuroendocrine Neoplasms typically affects middle-aged and older adults. The esophagus is a part of the upper gastrointestinal tract and is also known as the ‘food-pipe’
• The risk factors for Neuroendocrine Neoplasm of Esophagus include heavy smoking history and Barrett esophagus (a disorder of the food-pipe). The cause of tumor formation is generally unknown
• Neuroendocrine Neoplasms of Esophagus are frequently diagnosed incidentally, when examining the individual for other medical conditions. Superficial tumors are generally painless and asymptomatic, while advanced cases present swallowing difficulties and chest and upper abdominal pain
• The treatment of choice is a surgical excision of the tumor with clear margins followed by radiation therapy/chemotherapy. In case of a rare spread of the cancer to other regions, a combination of treatments may be considered by the healthcare provider
• The prognosis primarily depends upon a set of several factors including the stage and grade of the tumor. Generally, low-grade tumors have better prognosis than high-grade tumors (small cell or large cell neuroendocrine carcinomas). In general, the prognosis of Neuroendocrine Neoplasm of Esophagus is excellent with its surgical removal

Who gets Neuroendocrine Neoplasm of Esophagus? (Age and Sex Distribution)

• Esophageal Neuroendocrine Neoplasms constitute between 1-7% of all esophageal carcinoma types. These tumors are extremely rare; only, about 100 cases have been recorded in the medical literature
• Around 3% of neuroendocrine tumors (NETs) are observed in the esophagus and are usually found incidentally
• It is frequently observed in middle-aged and older adults
• Both males and females are affected, though the condition is much more common in males
• All races and ethnic groups are at risk for the condition

What are the Risk Factors for Neuroendocrine Neoplasm of Esophagus? (Predisposing Factors)

The risk factors for Neuroendocrine Neoplasm of Esophagus include the following: (a combination of factors may be present in some individuals)

• Smoking tobacco is a major risk factor; most affected individuals have a history of chronic and heavy tobacco smoking
• Presence of Barrett esophagus, which is a condition that results in the transformation of the normal esophageal lining (squamous epithelial lining) to the lining that is similar to the intestinal lining (columnar epithelial lining). It is commonly noted (along-with smoking) in almost all neuroendocrine neoplasms
• Achalasia, a rare condition that makes it difficult for food to pass through the food-pipe, is occasionally noted in some individuals

Other risk factors for esophageal tumors may include:

• Alcohol consumption
• Diet: Lack of fresh vegetables and fruits, fish and fresh meat, dairy products; also, a high consumption of processed meat (such as barbecued meat)
• Nutritional deficiencies
• Radiation therapy for breast cancer (especially in women)
• Presence of certain genetic disorders

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Neuroendocrine Neoplasm of Esophagus? (Etiology)

The exact cause of development of Neuroendocrine Neoplasm of Esophagus is unknown.

• In general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor
• Many cancer types are caused by genetic mutations. These can occur, due to inherited mutations, or mutations that occur due to environmental factors 
• The transformation of normally healthy cells into cancerous cells may be the result of genetic mutations. Mutations allow the cancer cells to grow and multiply uncontrollably to form new cancer cells
• These tumors can invade nearby tissues and adjoining body organs, and even metastasize and spread to other regions of the body

What are the Signs and Symptoms of Neuroendocrine Neoplasm of Esophagus?

Neuroendocrine Neoplasm of Esophagus may present the following signs and symptoms:

• Neuroendocrine tumors (NETs) are typically polyp-shaped small-sized tumors
  • NET G1 (low-grade) tumors are highly-uncommon in the esophagus. They are found incidentally, since the tumors are small and slow-growing
  • NET G2 (intermediate-grade) tumors are more common and diagnosed usually when metastasis has already taken place
• The tumors are rarely known to ulcerate (mostly observed with NET G2)
• Neuroendocrine carcinomas (NECs) are highly-aggressive, show deep penetration into the walls, and are found in advanced stages
• They are often seen with Barrett esophagus and adenocarcinoma. True carcinoid tumors when seen with Barrett esophagus are associated with adenocarcinomas too
• Most tumors are located in the distal esophagus (nearer to the esophagogastric junction and stomach)
• Tumors in the upper and middle-third portion of the esophagus are extremely rare
• Large tumors may cause narrowing of esophagus
• Commonly observed symptoms for advanced cancer are swallowing difficulties, chest pain (retrosternal pain), upper abdominal pain (epigastric pain), narrowing of esophagus can cause regurgitation or vomiting sensation
• Advanced tumors invade into the esophageal wall beyond the submucosal surface
• Large tumors may cause a pressure effect by compressing adjoining structures and organs
• Large tumors may ulcerate and bleed and become painful
• Involvement of lymph nodes is not usually noted

How is Neuroendocrine Neoplasm of Esophagus Diagnosed?

A diagnosis of Neuroendocrine Neoplasm of Esophagus may involve the following:

• A thorough medical history and physical examination
• X-ray of the chest
• CT or MRI scan of the chest: For advanced cases and to check cancer growth and spread, including lymph node involvement
• Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the upper gastrointestinal tract
• Endoscopic ultrasonography: During this procedure, fine needle aspiration biopsy (FNAB) can be performed on the affected area. This is good technique for tumor detection including tumor invasion parameters, and whether nearby lymph nodes are affected (tumor staging)
• Endocytoscopy: It is a non-invasive technique helpful for invasive carcinomas that are located superficially
• Early cancer lesions may be detected using narrow band imaging technique
• Barium swallow
• Whole body PET scans to determine how far the cancer has spread to other organ systems

Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor is necessary to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways which include: 

• Fine needle aspiration (FNA) biopsy of the tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor and the tumor may be misdiagnosed. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Core biopsy of the tumor 
• Open biopsy of the tumor

Tissue biopsy:

• A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Note:

• Esophageal Neuroendocrine Neoplasms are diagnosed through esophagogastroscopy with tissue biopsies. The biopsies may be performed during incidental or routine surveillance or due to presence of symptoms such as difficulty in swallowing
• No established TNM staging classifications are available for these neoplasms; nevertheless, many healthcare providers may choose to stage the tumors on a staging system similar to that for esophageal carcinomas

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Neuroendocrine Neoplasm of Esophagus?

The complications of Neuroendocrine Neoplasm of Esophagus may include the following:

• Emotional distress due to the presence of cancer
• Ulceration of the tumor can lead to secondary infections of bacteria and fungus
• Compression of the underlying nerve, which can affect nerve function
• Severe obstruction of the food-pipe with pain, leading to difficulties in eating. This can lead to extreme weight loss due to malnutrition
• Perforation or rupture of the esophagus can lead to the formation of fistulas
• Stricture formation of esophagus
• The tumor can metastasize to the local and distant lymph nodes and to distant regions. However, this is extremely rare
• Carcinoid syndrome can occur in rare cases
• Recurrence of the tumor following treatment
• Side effects of chemotherapy (such as toxicity) and radiation
• Damage to the muscles, vital nerves, and blood vessels, during surgery
• Post-surgical infection at the wound site is a potential complication

How is Neuroendocrine Neoplasm of Esophagus Treated?

There are no well-established treatment protocols for Neuroendocrine Neoplasm of Esophagus. However, surgery is the preferred treatment modality for esophageal tumors.  The treatment may also include a combination of radiation therapy and chemotherapy.

• When the tumor is confined to the surface, then endoscopic mucosal/submucosal resection (or surgical removal via endoscopy) is undertaken
• Esophagectomy or surgery to remove part (or all) of esophagus
• If the tumor has metastasized, then a combination of chemotherapy, radiation therapy, and invasive procedures may be used to treat the tumor
• In some cases, neoadjuvant therapy (chemotherapy and/or radiation therapy) is considered prior to surgery
• Follow-up care with regular screening and check-ups are very important and encouraged

How can Neuroendocrine Neoplasm of Esophagus be Prevented?

Currently, there are no known methods to prevent Esophageal Neuroendocrine Neoplasm occurrence. However, the risk for the condition may be lowered through the following considerations:

• Complete avoidance of smoking or chewing tobacco
• Early diagnosis of Barrett esophagus can help prevent it from progressing into esophageal cancer
• Treatment of GERD to reduce damage to the esophagus
• Bringing about certain lifestyle changes, such as diet adjustments to reduce fatty food and caffeine intake, reduction of alcohol intake
• Consuming a diet that is rich in whole grains, vegetables, and fruits
• Correcting any nutritional imbalances through adequate vitamin and mineral supplementation
• Taking foods rich in vitamin D and calcium
• Physical activities and regular exercising
• In order to avoid a relapse, or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory, due to its metastasizing potential and possibility of recurrence. Often several years of active vigilance is necessary.

What is the Prognosis of Neuroendocrine Neoplasm of Esophagus? (Outcomes/Resolutions)

• In majority of cases, the prognosis of Neuroendocrine Neoplasms of Esophagus is generally excellent with long-term survival. Metastasis of the tumor to local and distant lymph nodes is very rarely observed. However, the prognosis is mainly based on the tumor grade and stage of cancer
• In general, the prognosis of the tumor depends upon a set of several factors, which include: 
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Individuals with bulky disease may have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur 
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

Additional and Relevant Useful Information for Neuroendocrine Neoplasm of Esophagus:

The following DoveMed website links are useful resources for additional information:

http://www.dovemed.com/diseases-conditions/cancer/