Genital leiomyoma

Uterine Leiomyomas are benign tumors that affect 70% of European people with uteri and more than 80% African descent people with uteri by the time they turn 50 years of age. Although, only 30% of people with uteri experience symptoms.[3] Of those with uterine leiomyomas, 29% result in hospitalizations.[4] One-third of patients with these fibroids experience life-threatening anemia, a condition where the body does not have enough oxygen due to lack of red blood cells to carry oxygen throughout the body.[5] These tumors are mainly treated by performing hysterectomies, a procedure in which the uterus is removed, and account for approximately 40-60% of all performed hysterectomies.[4][6] Symptoms are dependent on the location of the tumor, which may occur in the submucosal (under the mucous membranes and lines the inner part of some organs), intramural (within the walls of the organs), or subserosal areas (under the serosa and lines the outer part of some organs).

Nipple-Areolar leiomyoma is a rare type of genital leiomyoma. It presents as either unilateral or bilateral growth of benign tumor of the smooth muscle that can be painful, tender, and inflamed.[7] They are typically less than 2 cm in length.[8] Since this is an extremely rare tumor, with only 50 cases reported in literature, it often only reported to physicians due to chronic nipple pain.[9]

Vaginal paraurethral leiomyoma is another type of genital leiomyoma that is also less common compared to other types of leiomyoma. It presents as a benign tumor of the smooth muscle in the genitourinary tract, which includes urinary and genital organs, that can grow rapidly during pregnancy. On the other hand, the tumor tend to decrease in size upon menopause. This may be due to the growth of tumor that is dependent on hormones. There is not a definite cause for the development of the disease, but one that was hypothesized is that it originates from a blood vessel tissue and smooth muscle fiber residue in an embryo. Imaging and histopathological examination is used for diagnosis of the disease. Furthermore, treatment of the disease is to surgically remove the tumor.[10]

Vulvar Leiomyomas are one the most prominent types of genital leiomyomas. Lesions to the vulva may be up to 15 cm in length and they are reported to be acutely painful. Enlargement of these leiomyomas may occur during pregnancy.[8]

Scrotal leiomyoma is considered to be an extremely rare type of genital leiomyoma. Because leiomyomas in the scrotum are usually painless and slowly grows over time, there is a delay in physician referral, with an average of 6–7 years. Physician referral usually occurs when people notice their testicles growing and getting heavier.[11] A review of 11,000 cases of benign and malignant tumors of the scrotum found 11 cases of scrotal leiomyoma. Scrotal leiomyomas can affect males of any age and race, but are more common in Caucasians from the ages of 40-60. The tumor in the scrotum has an average diameter of 6.4 cm.[12]

Development and progression of uterine leiomyomas may be contributed by changes in gene regulation or mutation of genes found to be associated with uterine fibroids. Abnormalities of these genes may initiate the formation or growth of these tumors.[15] Modification of signaling pathways and genes (e.g. CYP1A1, CYP1b1, and MED12) exhibits a correlation with the development and growth of tumors in the uterus.[6]

The occurrence of uterine leiomyomas is mostly common during reproductive years. This suggests that the role of ovarian hormones, estrogen and progesterone, is important in the development of this disease. Studies have shown that the development of tumors rely on these hormones and that tumors have shown to affect estrogen metabolism as it can increase the amount both its estrogen and progesterone receptors.[16]

Long-term results suggests that diets that are mostly plant-based, composed of fruits and vegetables, and rich in Vitamin D have a positive effect on the development of diseases, including uterine leiomyomas. On the other hand, alcohol, coffee, and red meat may have an effect on the progression or growth of these diseases based on observational and epidemiological studies.[17]

At the age of 35, incidence is reported to be 60% in African-American with-uterus persons and 40% in Caucasian with-uterus persons. By the age of 50, the incidence of uterine fibroids was >80% in African-American with uterus persons and >70% of Caucasian with uterus persons.[18]

Recurrence of uterine leiomyomas 4–5 years after removal occurs up to 59% of the time for with-uterus persons of African origin.[19]

People with uteri who delay their first pregnancy past the age of 30 are at a higher risk for uterine fibroids.[20]

Specific genetic alterations may play a role in the development of uterine leiomyomas. A mutation of a single mesenchymal cell, a stem cell that plays an important role in making and repairing bone, and fat - found in the bone marrow and adipose tissues, with the involvement of progesterone and 17 b-estrodiol can lead to these fibroids.[21]

Some early studies report early age onset of menstruation increases the risk of developing fibroids. However, the biological mechanism of how this occurs is not well understood and further investigation is needed.[22]

The occurrence of benign tumors of the nipple commonly starts at the age of 20 and peaks around the age of 40 to 50. Growth of nipple-areolar leiomyomas may increase even after menopause.[23]

A 41-year-old-male presented with a yellow nodule in the upper left areola. He reported mild pain and itching, but denied other symptoms. Sebaceous glands, epidermal hyperplasia, and tumor nests were among the numerous findings that lead to preceded a diagnosis of diagnosis of areolar leiomyoma with sebaceous hyperplasia. Characteristics of the leiomyoma included positive for estrogen and progesterone receptors and high expression of epidermal growth factor, insulin-like growth factor 1, and fibroblast growth factor-2. It is suspected that these growth factors led to the growth of the leiomyoma through an autocrine process.. The patient declined resection and the region has remained stable since.[31]

A 67-year-old-female presented with a growing mass on the left breast areolar region. The patient had been taking methotrexate to treat her rheumatoid arthritis. Magnetic resonance imaging revealed led to a conclusion that the tumor arose from the areola. A biopsy led to a diagnosis of diffuse large, non GC B-cell lymphoma that was suspected to be associated with methotrexate. The tumor reduced in size following the withdrawal of methotrexate. Three months later, another tumor developed in the areolar region of the opposite breast.[32]

A 35-year-old-female presented with a painful lump in the right nipple. The patient reported the lump occurred after a breastfeeding injury 3 years prior to coming into the outpatient center. The tumor has been growing ever since. A biopsy was performed to confirm the leiomyoma in the nipple.[9]

A 48-year-old-female presented with several uterine fibroids that were asymptomatic. The tumor was removed vaginally which revealed to be a vaginal leiomyoma. Vaginal leiomyomas are rare and removal by vaginal route is the preferred treatment option.[33]

A 39-year-old-male presented with a dull aching pain in the right scrotum. The patient had a history of his right scrotum slowly growing for the past year. There were no other symptoms of urinary tract infections (UTIs), cough, fever, weight loss, or night sweats. Further examination and an ultrasound scan found a firm mass in the right scrotum with a size of 6 cm x 4 cm that was inseparable from the testis. The patient underwent a right radical orchiectomy, or a surgical operation to remove the one or more testicles, since malignancy of the tumor could not be determined. The patient recovered and was discharged home after the operation.[12]

A 71-year-old-male presented with a large and heavy left scrotum that has been growing for 10 years. Further examination confirmed a firm tumor in the left scrotum that was attached to the testis. The tumor was measured to be 11 cm in diameter. The patient underwent orchidectomy, or surgical removal of the testicle.[11]