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Merkel Cell Carcinoma : A Rare Neuroendocrine Tumor

Jan 6, 2021


Dietary and lifestyle modifications may help manage different symptoms and treatment side-effects in neuroendocrine tumors such as Merkel Cell Carcinoma. While nutritional intervention including Vitamin D and Niacin supplementation may have potential benefits in Merkel Cell Carcinoma and other neuroendocrine tumors by improving quality of life or treatment outcomes, amine rich foods, alcoholic beverages, spicy foods and milk and dairy products should be avoided in case of carcinoid syndromes in neuroendocrine tumor patients, especially in those with liver metastasis. A personalized nutrition plan with the right foods and supplements customized for the specific cancer type and treatment is important to gain benefits and stay safe.

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Neuroendocrine Tumors and Merkel Cell Carcinoma

Neuroendocrine cells are similar to nerve cells and receive signals from the nervous system, and respond by making and releasing hormones just like what the cells of the endocrine system do (endocrine cells). Neuroendocrine tumours or NETs are rare cancers that start in these neuroendocrine cells. 

Merkel cells are found at the base of the top layer of the skin. Merkel cell carcinoma is a rare, aggressive type of skin cancer which starts in the Merkel cells of the sun-exposed skin. It is also known as the neuroendocrine carcinoma of the skin, since Merkel cells are a type of neuroendocrine cells which share some features with nerve cells and hormone-making cells. Another name for Merkel cell carcinoma is trabecular cancer.

Every year, around 2000 Merkel cell carcinoma cases are diagnosed in the United States. According to the data from people diagnosed with Merkel Cell Carcinoma between 2009 and 2016, 5-year relative survival rates for this rare cancer is 64%. (SEER data; American Cancer Society). The incidence of this cancer is about 0.45 per 100,000 persons per year.

Symptoms, treatment, diet for Merkel Cell Carcinoma and other Neuroendocrine tumors with carcinoid syndromes

Risk Factors for Merkel Cell Carcinoma

The risk of Merkel Cell Carcinoma is higher in White men who are aged above 70 years compared to African Americans or Hispanics. 90% of Merkel Cell Carcinoma is diagnosed in white people. 

The common risk factors for Merkel Cell Carcinoma include:

  • Exposure to ultraviolet (UV) rays from the sun, tanning beds and psoriasis treatments
  • Weakened immune system
  • Merkel cell polyomavirus (MCV) infection : Merkel Cell Carcinoma is associated with Merkel cell polyomavirus in more than 80% of cases.
  • Light coloured Skin
  • Advanced age

Signs/Symptoms of Merkel Cell Carcinoma

Merkel cell carcinoma usually appears as a single painless lump on sun-exposed skin. The sign/symptom of Merkel cell carcinoma is a fast-growing, painless, firm and raised nodule on the skin which is pink, red or violet in color. Merkel cell carcinoma usually appears on the face, head or neck, but they can develop anywhere on the body. Merkel cell carcinoma can spread rapidly to surrounding lymph nodes.

Consult your doctor if you find a mole or nodule that is fastly growing, changing in size, shape or color.

Carcinoid Syndrome : Merkel cell carcinoma usually metastasizes (spread) to lymph nodes, liver, lung, bone, and the brain and occasionally may also spread to the gastrointestinal tract. (Kristina A. Matkowskyj et al, Rare Tumors 2011) A collection of symptoms called the carcinoid syndrome usually occurs in neuroendocrine tumor patients with liver metastasis, due to production and release of serotonin directly in the bloodstream, which otherwise used to be degraded by the liver. 

Typical symptoms of carcinoid syndrome include: 

  • Diarrhoea
  • Loss of appetite
  • Flushing of the skin
  • Faster heart rate
  • Breathlessness

Treatments for Merkel Cell Carcinoma

The prognosis and treatments of Merkel cell carcinoma depend on various factors including the stage of the cancer (tumor size and the extent of spread to other parts of the body), site of the cancer, general health and medical history of the patient, depth of tumor growth into the skin, age of the patient and whether it is newly diagnosed or the cancer has recurred. 

The standard treatments for Merkel cell carcinoma include :

  • Surgery to remove the tumor with or without lymph node dissection – It is often the first line of treatment for Merkel cell carcinoma
  • Radiation therapy – Radiation therapy post surgery helps reduce the recurrence of this disease
  • Chemotherapy – Mostly used when the cancer has spread to the lymph nodes and other parts of the body or if the cancer reappears after initial treatments
  • Immunotherapy – Mostly used to help your immune system fight cancer.

The chances of recurrence of this cancer is very high.

Need for Right Nutrition/Diet in Neuroendocrine Tumors

A diet/nutrition including the right foods and supplements may help alleviate issues associated with the symptoms such as carcinoid syndromes, improve quality of life and boost immunity of neuroendocrine tumor patients. However, some foods and supplements may trigger or worsen the symptoms and may also have an impact on treatment outcomes and quality of life.

Foods/Diet/Other Factors that may Aggravate Carcinoid Symptoms in Neuroendocrine Tumors

1. Amine Rich Foods

A diet including foods rich in amines such as tyramine, dopamine and histamine can lead to carcinoid symptoms such as flushing in neuroendocrine tumors. (Barbara Altieri et al, Rev Endocr Metab Disord., 2018; Anezka C Rubin de Celis Ferrari et al, Clinics (Sao Paulo)., 2018)

Following are some examples of amine rich foods

  • Alcoholic beverages
  • Aged cheeses
  • Smoked, salted, or pickled fish and meats
  • Yeast extracts
  • Fermented foods such as tofu, miso, sauerkraut, fish sauce, soy sauce

Following foods have moderately high amounts of amines:

  • Caffeinated drinks (sodas and coffee)
  • Chocolate
  • Avocados
  • Bananas
  • Raspberries
  • Nuts (Brazil nuts, peanuts, coconuts)

2. Alcoholic beverages

Patients with Neuroendocrine tumors should mandatorily avoid alcoholic beverages to prevent symptoms like flushing, increased heart rate and severe gastro-intestinal issues.  (Barbara Altieri et al, Rev Endocr Metab Disord., 2018; Anezka C Rubin de Celis Ferrari et al, Clinics (Sao Paulo)., 2018)

3. Spicy foods 

Spicy foods also trigger carcinoid symptoms like flushing. Very hot spices such as black pepper, chillies and cayenne pepper may trigger flushing or induce diarrhea in some patients. Hence, neuroendocrine tumor patients should avoid spicy foods. (Barbara Altieri et al, Rev Endocr Metab Disord., 2018)

4. Heavy Physical Exercises

Increase in adrenergic activities, such as certain heavy physical exercises may lead to the release of carcinoid-related substances. However, doing appropriate exercises and maintaining a healthy weight is important. (Anezka C Rubin de Celis Ferrari et al, Clinics (Sao Paulo)., 2018)

5. Milk and Dairy Products

Avoid milk and dairy products and replace them with lactose free drinks and products to avoid worsening symptoms like diarrhea in neuroendocrine tumor patients. (Barbara Altieri et al, Rev Endocr Metab Disord., 2018)

Somatostatin receptors are highly expressed in Merkel cell carcinoma and many other neuroendocrine tumors. Milk products can also worsen the impact of certain drugs like statins (which tries to reduce the circulating growth hormone levels), as milk can increase both growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. (Luigi Barrea et al, Clin Nutr., 2017)

Additionally, Neuroendocrine Tumor patients with carcinoid symptoms should avoid:

  • Heavy/Larger/Feast meals
  • High fat meals – Avoid red meat and add lean meat such as fish
  • Raw tomatoes – Raw tomatoes are susceptible to salmonella contamination which can lead to diarrhea.

Nutritional Interventions that may be beneficial for Neuroendocrine Tumor/Merkel Cell Carcinoma Patients

1. Vitamin D

A study done by the researchers from different Universities in France on 89 Merkel Cell Carcinoma patients found Vitamin D deficiency in 65.1% of the patients. The study also found that Vitamin D deficiency was independently associated with greater tumor size at diagnosis and higher metastasis/spread and recurrence. (M Samimi et al, J Eur Acad Dermatol Venereol., 2014)

Another meta-analysis by researchers from the Trinity College Dublin in Ireland and University of Edinburgh in UK based on data from 44165 cases obtained from 64 studies through literature search in online databases found that higher circulating 25-hydroxyvitamin D was associated with better overall survival and progression-free survival. (P G Vaughan-Shaw et al, Br J Cancer., 2017)

Hence, nutritional intervention involving Vitamin D supplementation might be beneficial in improving treatment outcomes in patients with Merkel Cell Carcinoma. 

2. Niacin

In Neuroendocrine Tumors with excess serotonin release, a potential nutritional intervention may be to include niacin-rich foods. This is because Niacin deficiency, resulting from the increased tryptophan metabolism into serotonin, could lead to dermatitis, diarrhea, dementia, and pellagra. (Barbara Altieri et al, Rev Endocr Metab Disord., 2018)

Some examples of Food sources of Niacin are:

  • Poultry and Fish
  • Grain Products
  • Legumes, Nuts, and Soy products

For the management of diarrhea in neuroendocrine tumors, patients should :

  • Substitute raw vegetables with cooked vegetables and rice. 
  • Consume less fatty foods
  • Consume electrolyte replacements drinks, instead of carbonated soft drinks or fruit juice with pulp.
  • Consume Lactose-free beverages and products instead of regular milk and dairy products

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Dietary and lifestyle modifications should be an integral component for managing different symptoms of the neuroendocrine tumors such as Merkel Cell Carcinoma. This may help improve the symptoms, quality of life and nutritional status of the Merkel Cell Carcinoma patients while undergoing treatment and may also help improve the treatment outcomes. Vitamin D and Niacin supplementation may have potential benefits in Merkel Cell Carcinoma or other neuroendocrine tumors. However, avoid amine rich foods, alcoholic beverages, spicy foods and milk and dairy products in case of carcinoid syndromes in neuroendocrine tumor patients with liver metastasis.

Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer. Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.