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

• SCNEC of Uterus
• Small Cell Neuroendocrine Carcinoma of Uterine Corpus
• Uterine Small Cell Neuroendocrine Carcinoma

What is Small Cell Neuroendocrine Carcinoma of Uterus? (Definition/Background Information)

• Small Cell Neuroendocrine Carcinoma of Uterus is a rare subtype of neuroendocrine endometrial cancer. They are usually high-grade tumors that arise from the body of the uterus. The cancer shows similar morphological features of other neuroendocrine tumors, such as of small cell carcinoma of lung. When examined by a pathologist under the microscope, the tumor consists of small neuroendocrine cells
• Even though there are no specific risk factors for the development of Small Cell Neuroendocrine Carcinoma of Uterus, there are generally established risk factors for endometrial cancers including obesity, poorly-controlled diabetes, positive family history of endometrial cancer, and polycystic ovarian syndrome. The exact cause of the cancer is unknown, but it may be due to certain genetic abnormalities
• Most these tumors are detected and diagnosed in women aged 50 years and older (postmenopausal women). The majority of Small Cell Neuroendocrine Carcinoma of Uterus cases are detected and diagnosed at an early stage due to frequent abnormal vaginal bleeding, which is a major indicative sign. Additional signs and symptoms may include pelvic pain, pain during sex, and urination difficulties
• If Small Cell Neuroendocrine Carcinoma of Uterus is diagnosed early, then a surgical removal of the uterus usually eliminates the cancer. The earlier the stage of cancer at detection and the lower the grade of the cancer, the better is the prognosis. In general, Uterine Small Cell Neuroendocrine Carcinoma has a poorer prognosis compared to other subtypes of endometrial cancers

Who gets Small Cell Neuroendocrine Carcinoma of Uterus? (Age and Sex Distribution)

• Neuroendocrine carcinomas of the uterus account for less than 1% of all endometrial cancers in women
• Most Small Cell Neuroendocrine Carcinoma of Uterus cases are observed in women aged 50 years and older (average age 60 years). Women under the age of 40 years are rarely diagnosed with cancers of the endometrium
• All racial and ethnic groups are affected by this cancer type; the condition is observed worldwide in women

What are the Risk Factors for Small Cell Neuroendocrine Carcinoma of Uterus? (Predisposing Factors)

Currently, there are no specific risk factors for Small Cell Neuroendocrine Carcinoma of Uterus, since they are very rare. However, the following factors are noted to increase the risk for the development of endometrial cancer:    

• Advancing age: The cancer may generally develop in females of all ages, but are seldom diagnosed in women younger than 40 years. The risk increases as one ages, although most cases occur between the ages 55 and 70 years
• Obesity: Obese women have an elevated risk for developing the condition
• Menstrual cycle: Women who got their period before the age of 12 years, and those who reached menopause after age 55 years have an elevated risk. The longer the duration between menarche and menopause, the greater is the risk. This is due to hormonal influences during the reproductive period on the endometrial tissue
• Polycystic ovarian syndrome (PCOS): Polycystic ovarian syndrome is a condition in which women’s hormones are out of balance. It is one of the most common endocrine disorders in women
• Family history: Small Cell Neuroendocrine Carcinoma of Uterus may be prevalent in families. Individuals with an associated history of colon cancer may be at a significantly higher risk. Individuals with one or more immediate family members or relatives with a history of colon cancer or non-polyposis colorectal cancer (HNPCC), may have an increased risk
• Endometrial hyperplasia: It is an abnormal overgrowth of the endometrium that is usually caused by hormonal effects. Hyperplasia is not a type of cancer; however, women with atypical endometrial hyperplasia have a much greater risk for getting endometrial cancer in their lifetime
• Poor dietary choices: Individuals, taking a diet that consists of foods high in animal fat, may have an increased risk for developing this cancer type
• Tamoxifen therapy: Women, on the hormone therapy drug tamoxifen, to treat or prevent breast cancer may be at an increased risk. Nevertheless, women are advised to discuss the risk and benefits of the therapy with their physician
• Estrogen therapy for a long duration
• Diabetes: Researchers believe this may be linked to the high obesity rates found in individuals with type II diabetes
• Radiation therapy: Women who had had radiation therapy to the pelvis for other cancers are at an increased risk
• High blood pressure
• History of breast cancer and ovarian cancer
• Any other condition causing hormonal imbalance in the body, such as use of birth-control pills or pregnancy
• Use of intrauterine contraceptive devices (IUDs)

Note: Nulliparous women, or women who have never been pregnant, are not known to have an increased risk for neuroendocrine tumors of uterus.

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 Small Cell Neuroendocrine Carcinoma of Uterus? (Etiology)

The exact cause and mechanism of formation of Small Cell Neuroendocrine Carcinoma of Uterus is unknown. Some researchers believe that the tumor occurs due to genetic mutations within the cells in the endometrium (the lining of the uterus). Many cases are seen to involve abnormalities in chromosomes 4, 8, and 10.

• 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
• 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

Currently, medical research is being conducted to determine the exact cause of Small Cell Neuroendocrine Carcinoma of Uterus.

What are the Signs and Symptoms of Small Cell Neuroendocrine Carcinoma of Uterus?

Due to the absence of significant signs and symptoms in the initial periods, Small Cell Neuroendocrine Carcinoma (SCNEC) of Uterus is generally diagnosed at a later stage. However, if there are associated underlying conditions presenting overlapping signs and symptoms, there could be a delay in diagnosis.

The signs and symptoms that are typically observed early in SCNEC of Uterus include:

• Postmenopausal abnormal vaginal bleeding, spotting, or discharge; vaginal bleeding is the most common symptom
• Painful and difficulty during urination
• Pain during sexual intercourse
• Abdominal pain (the pain is usually a pelvic pain)
• Small cell neuroendocrine carcinomas are generally bulky masses at the time of diagnosis, which has invaded into the smooth muscle tissue (myometrium)
• The generally arise from the uterine corpus (body of the uterus); they are not known to arise from the cervix

In more advanced cases, the following signs and symptoms may be observed:

• Abdominal swelling due to the mass or due to fluid accumulation in the belly (called ascites)
• Persistent feeling of abdominal bloating with nausea or vomiting
• Changes in bowel movements, such as constipation
• Feeling full soon, after eating less
• Loss of appetite with weight loss
• Fatigue, feeling tired easily
• Frequent urination (polyuria)

How is Small Cell Neuroendocrine Carcinoma of Uterus Diagnosed?

There is a variety of tests healthcare providers may use to detect, locate, and diagnose Small Cell Neuroendocrine Carcinoma of Uterus and if it has potentially spread to other regions. A surgical procedure called a biopsy (usually performed by an obstetrician-gynecologist) is the main test a healthcare provider relies on to make a definitive diagnosis of SCNEC of Uterus.

The diagnostic tools may include:

• A thorough physical examination and a complete medical history evaluation is very vital to the diagnosis
• Pelvic examination: During a pelvic examination, a physician exams the uterus, vagina, ovaries, fallopian tubes, bladder, and rectum to check for any abnormal changes in these organs
• Complete blood count (CBC) with differential of white blood cells
• Liver function test (LFT)
• Blood tests called serum tumor markers that include:
  • CA-125 test
  • Human chorionic gonadotropin (hCG)
  • Alpha-fetoprotein (AFP)
  • Lactate dehydrogenase (LDH)
  • Inhibin (hormone)
  • Estrogen and testosterone levels
• Hysteroscopy: During hysteroscopy, a physician inserts a tiny telescope through the cervix into the uterus. This procedure is used to remove small amounts of the endometrium for pathological examination
• Cystoscopy:  During cystoscopy, a physician inserts a narrow tube called cystoscope, to look directly into the bladder to see if cancer from endometrium has spread to the bladder. To make an individual more comfortable during this test, a local anesthetic is usually administered
• Proctoscopy: During proctoscopy, a physician inserts a narrow tube called proctoscope, to look directly into the rectum to see if cancer from endometrium has spread to the rectum. To make an individual more comfortable during this test, a general anesthetic is usually administered.
• Dilation and curettage (D&C) of the uterus: If the biopsy was inadequate in procuring enough tissue samples, or a physician is unsure whether cancer exists, a procedure called dilation and curettage may be necessary. A D&C of the uterus procedure involves opening the cervix and surgically removing the inner lining and tissue present in the uterus. To make an individual more comfortable during this procedure, a general anesthetic is usually administered
• X-ray of the abdomen and pelvic region
• Chest X-ray: Chest X-rays are used to detect if the cancer has spread to the lung
• Barium enema X-ray
• Computerized tomography (CT) scan of the abdomen and pelvic region: Also known as CAT scan, this radiological procedure creates detailed three-dimensional images of structures inside the body. CT scans are not tools of preference to detect Small Cell Neuroendocrine Carcinoma of Uterus. Although CT scans may be helpful in detecting recurrences, or if the cancer has metastasized to other organs
• MRI scan of abdomen and pelvic region
• Transvaginal ultrasound: Transvaginal ultrasound inserts an ultrasound probe into the vagina designed to take pictures of the insides of the uterus
• Vascular radiological studies of abdomen and pelvic region
• Positron emission tomography (PET scan): A PET scan is a nuclear medicine imaging technique that uses three-dimensional images to show how tissue and organs are functioning. A small amount of radioactive material is required with this test. The radioactive material may be injected into a vein, inhaled, or swallowed. It may be performed to see if the cancer has metastasized/spread to other regions
• Exploratory laparoscopy (diagnostic laparoscopy): This is a procedure wherein the abdomen is examined using a minimally invasive technique. During this procedure, a tissue biopsy and tissue for culture are performed. A minimally invasive approach helps decrease the complications and length of stay at the hospital. A diagnostic laparoscopy is also helpful in establishing the staging of the tumor
• Colonoscopy: A colonoscopy may be performed to assess the extent of tumor spread
• Whole body bone scan
• Endometrial biopsy: A biopsy refers to a medical procedure that involves the removal of cells or tissues, which are then examined by a pathologist under a microscope. After putting together the clinical findings, special studies on tissues (if needed), and the microscope findings, the pathologist arrives at a definitive diagnosis. Sometimes, the pathologist may perform special studies that may include immunohistochemical stains, histochemical stains, molecular testing, and very rarely, electron microscopic studies. Examination of the biopsy under a microscope by a pathologist is considered to be the gold standard in arriving at a conclusive diagnosis

Note:

• Pap smear is not a good screening tool for Small Cell Neuroendocrine Carcinoma of Uterus
• The Uterine Small Cell Neuroendocrine Tumors share similarity with small cell carcinomas of the lung
• Despite the presenting symptoms, many cases are detected at an advanced stage

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 Small Cell Neuroendocrine Carcinoma of Uterus?

The complications of Small Cell Neuroendocrine Carcinoma of Uterus include:

• Emotional distress due to the presence of cancer
• If detected late, the cancer can spread into the surrounding organs, making it difficult to successfully treat using surgical interventions
• The cancer can metastasize (spread) to the fallopian tube, ovary, cervix, bone, liver, lung, and brain. If metastasis to the lymph nodes are noted, then usually it is to the pelvic and para-aortic lymph nodes
• Perforation in the uterus, which may occur during a diagnostic D&C or endometrial biopsy procedure
• Sexual dysfunction can take place as a side effect of surgery, chemotherapy, or radiation therapy
• Recurrence of the cancer following incomplete surgical removal

How is Small Cell Neuroendocrine Carcinoma of Uterus Treated?

The treatment of Small Cell Neuroendocrine Carcinoma of Uterus may depend upon a consideration of the following set of factors:

• The histological subtype of the cancer
• Stage of the cancer
• Size and location of the tumor
• Severity of the signs and symptoms
• Age of the individual
• Overall health status of the individual
• The treatment preferences of the individual

In most cases, a combination of chemotherapy (drugs), radiation therapy, and surgical procedures is employed by the healthcare provider to treat the condition.

Surgery for Small Cell Neuroendocrine Carcinoma of Uterus: The recommended treatment for women with the cancer is to have the uterus surgically removed. The surgical treatment options a healthcare provider may recommend include:

• Hysterectomy: In this procedure, the uterus and cervix are removed. This is done by making an incision on the abdomen (termed abdominal hysterectomy), or through the vagina (termed vaginal hysterectomy), or by using a laparoscope (termed laparoscopic hysterectomy). Surgery is performed under general or epidural anesthesia, though the ability to have children is lost. Complications, such as bleeding, infection, or damage to the urinary tract, or the intestinal system may occur in rare cases
• Radical hysterectomy: The uterus, cervix, the upper part of the vagina and tissues, next to the uterus are removed. Additionally, some pelvic lymph nodes may also be surgically taken out. The surgery is performed under anesthesia and may be carried out, via an incision made on the abdomen or by using laparoscopy. With this invasive procedure, the ability to have children is lost. Rarely, complications such as bleeding, infection, or damage to the urinary tract or the intestinal system, may occur. Removal of lymph nodes may lead to swelling of legs (lymphedema)
• Hysterectomy (abdominal) with salpingo-oophorectomy: It is a surgical procedure involving the removal of the uterus, and of the fallopian tube and ovary (salpingo-oophorectomy)
• Pelvic exenteration: The uterus, tissues surrounding the uterus, cervix, pelvic lymph nodes, and the upper part of the vagina, are removed. In addition, depending on the tumor spread, the remainder of the vagina, the bladder, rectum, and a part of the colon, may also be removed. Recovery from this surgery may take a long period of time
• A debulking surgery to reduce the tumor mass, followed by a combination of chemotherapy and radiation therapy may be employed in some instances. The debulking procedure helps the chemotherapy treatment in being more effective, because there is lesser tumor mass left for the drugs to act on. Chemotherapy may be administered before debulking or after debulking procedure, depending on each individual’s circumstances

During surgery, the surgeon will also examine the surrounding areas of the uterus looking for signs to see if the cancer has metastasized (spread) locally. After surgical treatment, the attending healthcare provider will discuss the details of the cancer with the individual.

Chemotherapy for Small Cell Neuroendocrine Carcinoma of Uterus:

• Chemotherapy is a treatment that uses drugs to kill cancer cells. In this treatment for Small Cell Neuroendocrine Carcinoma of Uterus, combinations of two or more chemotherapy drugs are usually used.
• These drugs may be administered intravenously (through a vein in the arm), or orally (in a pill-form). Drugs inserted into the bloodstream traveling through the body and kill cancer cells.
• Such drugs may be recommended for individuals with advanced SCNEC of Uterus that has spread to other body parts 

Radiation therapy for Small Cell Neuroendocrine Carcinoma of Uterus:

• Radiation therapy attempts to destroy cancer cells by aiming high-energy beams at the cancer cells
• Radiation therapy can either be administered by a machine outside the body (external beam radiation) or administered internally, by a device positioned directly at, or close to the malignant tumor, inside the vagina (a procedure known as brachytherapy)
• Radiation therapy may be used before surgery to decrease the size of a tumor, thus allowing for easy removal, or after surgery to kill any remaining cancer cells

Radiation therapy and chemotherapy are sometimes used as a combination tool.

Hormone therapy: Hormonal therapy is a medical treatment used for women with advanced Small Cell Neuroendocrine Carcinoma of Uterus that has metastasized beyond the uterus. The treatment options include taking medications that affect the hormone levels in the body:

• Synthetic progestin: Synthetic progestin, a type of hormone progesterone, may help prevent the development and progression of Small Cell Neuroendocrine Carcinoma of Uterus cells
• Luteinizing hormone (LH): Also called lutropin, this hormone therapy drug helps lower an individual’s estrogen level in the body, or decrease the body’s ability to use the available estrogen. Small Cell Neuroendocrine Carcinoma of Uterus cells rely on estrogen (the primary female sex hormone) to proliferate, and thus, administering LH drugs may cause the cancer cells to die out

How can Small Cell Neuroendocrine Carcinoma of Uterus be Prevented?

Currently, there are no known and available methods to prevent Small Cell Neuroendocrine Carcinoma of Uterus. However, various steps may be taken to help decrease the incidence risk:

• Physical activity: Obesity increases the risk of Small Cell Neuroendocrine Carcinoma of Uterus due to additional related risk factors, such as increased estrogen level, polycystic ovary syndrome, reduced physical activity, and a diet high in saturated fats. Therefore, individuals with higher physical activity levels have a decreased risk of developing Small Cell Neuroendocrine Carcinoma of Uterus
• Pregnancy: During pregnancy, the estrogen levels are lowered. Being pregnant may lower a woman’s risk for Small Cell Neuroendocrine Carcinoma of Uterus. Women, who have multiple pregnancies in their lifetime, may have a decreased risk
• Combination of oral contraceptives: Taking a combination of oral contraceptives, such as estrogen and progestin, decrease the risk of Small Cell Neuroendocrine Carcinoma of Uterus. The protective effect of a combination of oral contraceptives increases, the longer they are taken; it may even last several years after usage is stopped
• Adequate consumption of fruits and vegetables: A healthy diet, low in saturated fats and rich in many fruits and vegetables, may help decrease one’s risk for Small Cell Neuroendocrine Carcinoma of Uterus. Regular consumption of soy-based foods, incorporated into a diet, also decreases one’s risk
• The US Preventive Services Task Force (USPSTF) currently does not have any recommendation for screening against endometrial cancer for the general population. Tests, such as trans-vaginal ultrasonography and Pap smears, are not useful as screening tools
• The US-based National Cancer Institute (NCI) recommends that women, who are at an elevated risk for cancers of the endometrium, take regular (annual) examinations
• Early diagnosis with close monitoring and treatment of the tumor is important. A timely tumor recognition and prompt treatment will help in having optimal outcomes
• Regular medical screening at periodic intervals with blood tests, radiological scans, and physical examinations are mandatory, due to risk of metastasis and recurrence of the tumor, for individuals who have already endured the cancer. Often several years of active vigilance is necessary

What is the Prognosis of Small Cell Neuroendocrine Carcinoma of Uterus? (Outcomes/Resolutions)

• The prognosis of Small Cell Neuroendocrine Carcinoma of Uterus depends upon a set of several factors that include:
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Stage of cancer: 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
  • Histological subtype of the tumor
  • WHO grade of the tumor: Tumors that are graded 1 and 2 have better prognoses than grade 3 tumors
  • Hormone-receptor status of the cancer such as estrogen receptor (ER) and progesterone receptor (PR)
  • Cell growth rate of the carcinoma
  • Menopausal status of the women
  • 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
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of the regional lymph nodes, which can adversely affect the prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical respectability 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 of breast cancer: 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
• The prognosis of Small Cell Neuroendocrine Carcinoma of Uterus is typically poor in a majority of cases. Very rarely, the prognosis has been reported to be favorable, when the cancer is confined to the uterus
• In general, women with endometrial cancer have a survival rate of approximately 92% after 1 year, and 95% at 5 years, if the cancer has not spread. However, if the cancer has metastasized (spread), the survival rate at 5 years is only 23%
• 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 (like cardio-toxicity). This chiefly impact the elderly adults, or those who are already affected by other medical conditions. Individuals, who tolerate chemotherapy sessions better, generally have better outcomes

Additional and Relevant Useful Information for Small Cell Neuroendocrine Carcinoma of Uterus:

According to the World Cancer Research Fund International (WCRF International), endometrial cancer is the 6th most commonly diagnosed cancer in women. Also, each year, approximately around 350,000 new cases are diagnosed in women worldwide.