Small cell neuroendocrine carcinoma

Small cell neuroendocrine carcinoma is an aggressive type of cancer that develops from neuroendocrine cells. These are specialized cells that have traits of both hormone-producing cells and nerve cells. This type of cancer is fast-growing and tends to spread quickly to other parts of the body. It is classified as a neuroendocrine carcinoma because the cancer cells share characteristics with normal neuroendocrine cells.

Where in the body is this type of cancer found?

Small cell neuroendocrine carcinoma can develop in various parts of the body, though it is most commonly found in the following locations:

• Lungs: This is the most common site, where it is referred to as small cell lung cancer.
• Head and neck: This type of cancer can develop in various parts of the head and neck, but the larynx (voice box) is the most common site. Other areas in the head and neck region, such as the nasal cavity or pharynx, can also be affected, though much less frequently.
• Cervix: Small cell neuroendocrine carcinoma can affect the cervix in some women.
• Prostate: In men, this type of cancer may develop in the prostate.
• Bladder: It can also occur in the urinary bladder.
• Gastrointestinal tract: This type of cancer may develop in the esophagus, stomach, pancreas, or intestines.
• Skin: When small cell neuroendocrine carcinoma develops in the skin, it is called Merkel cell carcinoma.

What causes small cell neuroendocrine carcinoma?

The cause of small cell neuroendocrine carcinoma varies depending on where in the body it develops.

• Lungs: The most common cause of small cell lung cancer is smoking, and nearly all cases are linked to tobacco use.
• Head and neck: Smoking is also a significant risk factor for small cell neuroendocrine carcinoma in this region, particularly when the larynx is involved.
• Cervix: In the cervix, this type of cancer is often associated with infection by the human papillomavirus (HPV).
• Prostate: In the prostate, small cell neuroendocrine carcinoma may arise after previous treatment for prostate cancer, particularly in patients who have received hormone therapy.
• Bladder: In the bladder, smoking is a known risk factor, though other environmental exposures may play a role.
• Skin: Merkel cell carcinoma, the form of this cancer found in the skin, is associated with ultraviolet (UV) radiation exposure and infection by the Merkel cell polyomavirus.

What are the symptoms of small cell neuroendocrine carcinoma?

The symptoms of small cell neuroendocrine carcinoma depend on where the cancer is located:

• Lungs: Patients may experience shortness of breath, coughing, chest pain, or wheezing.
• Larynx: Symptoms may include hoarseness, difficulty swallowing, and a persistent sore throat.
• Cervix: In the cervix, symptoms might include abnormal vaginal bleeding, pelvic pain, or pain during intercourse.
• Prostate: Men with prostate small cell neuroendocrine carcinoma may experience difficulty urinating, blood in the urine, or pelvic pain.
• Bladder: Symptoms may include blood in the urine, frequent urination, or pelvic discomfort.
• Skin (Merkel cell carcinoma): Patients may notice a rapidly growing, firm, painless nodule on the skin, often in sun-exposed areas.

Metastatic disease is common in small cell neuroendocrine carcinoma, meaning the cancer often spreads to other parts of the body, such as the lymph nodes. For many patients, the first symptoms may be related to the spread of the cancer, with signs like swollen lymph nodes or pain in areas where the cancer has spread.

How is this diagnosis made?

The diagnosis of small cell neuroendocrine carcinoma is typically made through a biopsy, where a small sample of tissue is taken from the tumour and examined under a microscope by a pathologist. The pathologist looks for certain features in the cells that are characteristic of this type of cancer, such as small, round cells with scant cytoplasm and neuroendocrine markers.

What does small cell neuroendocrine carcinoma look like under the microscope?

Under the microscope, small cell neuroendocrine carcinoma is made up of small, round cells that have hyperchromatic (dark-staining) nuclei and very little cytoplasm. The cells often form sheets or clusters. One of the defining features of this type of cancer is its high rate of mitosis, meaning the cells are rapidly dividing. The cells may also show “nuclear molding,” where the cells appear to press against each other, causing the nuclei to change shape. Another common feature seen in these tumours is crush artifact, which happens when the fragile tumour cells are distorted or damaged during the biopsy process.

What other tests may be performed to confirm the diagnosis?

In addition to examining the tissue under a microscope, pathologists often use a test called immunohistochemistry (IHC) to confirm the diagnosis. Immunohistochemistry is a test that uses special antibodies to detect specific proteins in the cells of a tumour. In this test, the tissue sample is treated with antibodies that bind to proteins commonly found in small cell neuroendocrine carcinoma. When the antibodies bind to the proteins, they cause the cells to change colour, which the pathologist can see under the microscope. This helps confirm the type of cancer.

For small cell neuroendocrine carcinoma, the tumour cells are typically positive for markers such as cytokeratins, chromogranin, synaptophysin, and CD56, which are proteins often found in neuroendocrine cells. The cells may also express TTF-1, mainly when the cancer arises in the lungs.

What is the prognosis for a person diagnosed with small cell neuroendocrine carcinoma?

Small cell neuroendocrine carcinoma is an aggressive type of cancer that tends to grow and spread quickly. The prognosis depends on several factors, including the location of the tumour, whether it has spread to other parts of the body, and the patient’s overall health. Unfortunately, because it often spreads early, many patients are diagnosed at an advanced stage. Treatment usually involves a combination of chemotherapy, radiation therapy, and sometimes surgery, but the outlook is often poor, particularly when the cancer has metastasized.