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Uterine Leiomyoma and Leiomyosarcoma

Uterine leiomyomas (or uterine fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility) are benign Benign Fibroadenoma tumors arising from smooth muscle cells in the uterine myometrium. Leiomyosarcomas, however, are malignant tumors, arising de novo (not from fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility). With a lifetime risk of > 70% for both African American and Caucasian women, fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility are common. Conversely, leiomyosarcomas are rare. Leiomyosarcomas may present similarly to uterine fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility making preoperative diagnosis challenging. Both conditions present with abnormal bleeding, pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and/or bulk symptoms. A fibroid is identified as a hypoechoic Hypoechoic A structure that produces a low-amplitude echo (darker grays) Ultrasound (Sonography), well-circumscribed, round mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast on pelvic ultrasound. A leiomyosarcoma is usually diagnosed on a postoperative specimen. Depending on patient symptoms and preference, treatment for leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility may include surgical resection or medical options to reduce bleeding and/or bulk. Management of leiomyosarcoma, which carries a poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas, may include adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund's adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination chemotherapy Chemotherapy Osteosarcoma based on stage.

Last updated: 25 Feb, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Epidemiology

Leiomyomas are benign Benign Fibroadenoma, smooth muscle tumors arising from the uterine myometrium, whereas leiomyosarcomas are aggressive, malignant tumors of the myometrium.

Leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility

  • The most common pelvic tumor Tumor Inflammation in women
  • Occur in reproductive-age women:
    • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency ↑ with age during the reproductive years
    • May be diagnosed (but do not form) after menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause
  • Estimated lifetime risks:
    • African American women: 80%
    • Caucasian women: 70%

Leiomyosarcoma

  • Very rare
  • < 10% of uterine corpus cancers
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency
    • 3–7 per 100,000
    • 1 per 500 in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship undergoing surgery for a myometrial mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
  • Peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 40–60 years old

Pathophysiology

Leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility

  • Monoclonal tumor Tumor Inflammation of the uterine myometrium
  • Arises from myocytes Myocytes Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts. Muscle Tissue: Histology 
  • Contains a considerable amount of collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology
  • Round, firm, rubbery, well-circumscribed, white-tan mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast(es)
  • Responsive to estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy:
    • ↑ In pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • ↓ After menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause

Predisposing factors:

  • Race: African American > Caucasian women
  • Reproductive factors:
    • Nulliparity ( pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care is a progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones dominant state → a reprieve from chronic estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy exposure Exposure ABCDE Assessment that can stimulate leiomyomas)
    • Early menarche Menarche The first menstrual cycle marked by the initiation of menstruation. Menstrual Cycle
    • Late menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Family history Family History Adult Health Maintenance of fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility

Classification:

  • Intramural:
    • Located within the myometrial wall
    • May extend into the cavity/subserosa or be completely contained within the wall
    • Most common overall
  • Submucosal:
    • Located just under the endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development
    • Distorts the endometrial cavity
    • Most often responsible for abnormal bleeding and fertility challenges
    • May be pedunculated growing into the endometrial cavity on a stalk
  • Subserosal:
    • Located just beneath the serosa
    • Most likely to cause bulk symptoms
  • Pedunculated:
    • Growing off of the uterine corpus on a stalk 
    • Can torse and cause acute pain Acute pain Intensely discomforting, distressful, or agonizing sensation associated with trauma or disease, with well-defined location, character, and timing. Pain Management
  • Cervical:
    • Originating within the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy
    • Rare
Uterine fibroids

Uterine fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility (location):
Subserosal fibroid (beneath the serosa), submucosal fibroid (under the endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development), intramural fibroid (in the myometrial wall), pedunculated fibroid (growing off the uterine corpus on a stalk)

Image by Lecturio.

Leiomyosarcoma

  • Malignant tumors of the uterine corpus
  • Arise de novo (not from leiomyomas)

Patterns:

  • Bulky, fleshy mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast invading the uterine wall
  • Polypoid mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast projecting into the endometrial cavity

Differentiated from leiomyomas by the degree of:

Predisposing factors:

  • ↑ Risk in African American women
  • Older age and postmenopausal status
  • Tamoxifen Tamoxifen One of the selective estrogen receptor modulators with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium. Antiestrogens use
  • History of pelvic radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma

Clinical Presentation

Presentations of leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility and leiomyosarcoma can be clinically indistinguishable.

Both leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility and leiomyosarcoma may be asymptomatic.

Menstrual/bleeding symptoms

  • Heavy menstrual bleeding Heavy menstrual bleeding Excessive menstrual blood loss (objectively defined as > 80 mL blood loss/cycle). Can be based on heavy flow, as determined by the patient Abnormal Uterine Bleeding
  • Prolonged menstrual bleeding
  • Intermenstrual or postcoital bleeding (especially with fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility prolapsed through the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy)
  • Postmenopausal bleeding

Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways symptoms

  • Dysmenorrhea
  • Pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Dyspareunia Dyspareunia Recurrent genital pain occurring during, before, or after sexual intercourse in either the male or the female. Primary Ovarian Insufficiency (painful intercourse)
  • Acute pain Acute pain Intensely discomforting, distressful, or agonizing sensation associated with trauma or disease, with well-defined location, character, and timing. Pain Management from:
    • Leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility degeneration
    • Torsion of pedunculated lesions

Bulk-related symptoms

  • Pelvic pressure
  • ↑ Urinary frequency
  • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation (with rectal compression Compression Blunt Chest Trauma)
  • Pelvic mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast

Reproductive dysfunction

  • Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility (caused by distortion Distortion Defense Mechanisms of the endometrial cavity)
  • Recurrent pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care loss
  • Other obstetric complications

Diagnosis

Workup for leiomyomas and leiomyosarcomas are the same, but there are no tests or findings with high positive predictive value Positive predictive value The positive predictive value is the percentage of people with a positive test result who actually have the disease among all people with a positive result, regardless of whether or not they have the disease. Epidemiological Values of Diagnostic Tests for sarcomas.

Pelvic exam

  • Asymmetrically enlarged uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy with an irregular contour
  • Small fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility will not enlarge the size of the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy.

Imaging and endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD)

  • Transvaginal ultrasound Transvaginal Ultrasound Obstetric Imaging (1st step):
    • Sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques for detecting leiomyomas: 95%–100%
    • Hypoechoic Hypoechoic A structure that produces a low-amplitude echo (darker grays) Ultrasound (Sonography), well-circumscribed, round mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
    • Calcifications → degenerating fibroid
    • Features concerning for leiomyosarcoma: mixed echogenicity, central necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage, irregular vessel distribution
  • Saline infusion sonogram Sonogram Chorioretinitis (follow-up test):
    • Sterile Sterile Basic Procedures saline is injected into the endometrial cavity to distend it during vaginal sonography Sonography The visualization of deep structures of the body by recording the reflections or echoes of ultrasonic pulses directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1. 6 to 10 megahertz. Diagnostic Procedures in Gynecology in order to evaluate intracavitary lesions.
    • Used in cases of suspected submucosal fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Hysteroscopy Hysteroscopy Endoscopic examination, therapy or surgery of the interior of the uterus. Diagnostic Procedures in Gynecology: allows for evaluation and simultaneous treatment of intracavitary pathology, including submucosal fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility
  • Pelvic MRI:
    • Rarely indicated (helps in planning surgeries)
    • Leiomyomas: dark, homogenous T2 images 
    • Leiomyosarcomas: ill-defined margins
  • Findings with high negative predictive value for sarcoma:
    • Typical leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility appearance on MRI (dark, homogenous T2 images)
    • Absence of calcifications
Radiology of uterine fibroids

A 49-year-old woman with a history of menorrhagia:
A: Transabdominal ultrasound image showing a bulky uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy with 10 cm submucosal fibroid (between cursors)
B: Sagittal Sagittal Computed Tomography (CT) T2 weighted MRI in the same patient shows the submucosal fibroid (arrowhead) is heterogeneous, indicating degeneration. Also shown is a 2.5 cm cervical fibroid (arrow).

Image: “ Menorrhagia” by Department of Radiology, Norfolk & Norwich University Hospital, Colney Lane, Norwich, Norfolk, NR4 7UY, United Kingdom. License: CC BY 2.0

Definitive diagnosis requires histologic examination

  • Endometrial biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
    • Unlikely to diagnose leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility or leiomyosarcoma
    • Used to rule out other causes of abnormal bleeding
  • Intraoperative evaluation

Management and Prognosis

Medical management for leiomyomas

General management:

To treat bleeding symptoms (1st-line medical management):

  • Hormonal:
    • Progestins Progestins Compounds that interact with progesterone receptors in target tissues to bring about the effects similar to those of progesterone. Primary actions of progestins, including natural and synthetic steroids, are on the uterus and the mammary gland in preparation for and in maintenance of pregnancy. Hormonal Contraceptives: levonorgestrel-releasing intrauterine device ( IUD IUD Inhalant use disorder is a substance use disorder defined by pathologic consumption of inhalant substances (such as glue, paint, or lighter fluid) in order to reach a euphoric feeling. Individuals administer inhalers through the mouth (commonly known as huffing) or sniff them through the nose. The effect lasts for only several minutes. Inhalant Use Disorder)
    • Combined hormonal contraceptives Hormonal contraceptives Hormonal contraceptives (HCs) contain synthetic analogs of the reproductive hormones estrogen and progesterone, which may be used either in combination or in progestin-only formulations for contraception. Hormonal Contraceptives (pills, patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes, vaginal ring Vaginal Ring Hormonal Contraceptives)
  • Nonhormonal: antifibrinolytics ( tranexamic acid Tranexamic acid Antifibrinolytic hemostatic used in severe hemorrhage. Hemophilia)

To treat bulk or pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways symptoms (1st line) or bleeding symptoms (2nd line):

Gonadotropin-releasing hormone Gonadotropin-releasing hormone A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone. Gnrh is produced by neurons in the septum preoptic area of the hypothalamus and released into the pituitary portal blood, leading to stimulation of gonadotrophs in the anterior pituitary gland. Puberty (GNRH) analogs:

  • Elagolix Elagolix Antiestrogens (GNRH antagonist)
  • Leuprolide Leuprolide A potent synthetic long-acting agonist of gonadotropin-releasing hormone that regulates the synthesis and release of pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone. Antiestrogens (GNRH agonist)
  • Both agonists and antagonists completely suppress follicle-stimulating hormone ( FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle) → ↓ estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility shrink
  • Limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation therapy to 6–12 months to prevent osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis.

Surgical management for leiomyomas

  • Hysteroscopic resection:
    • Only useful for submucosal leiomyomas
    • 1st-line treatment for submucosal fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility associated with:
  • Myomectomy:
    • Removal of leiomyomas from the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy
    • Used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who wish to retain fertility with nonsubmucosal leiomyomas
  • Hysterectomy:
    • Removal of the entire uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy
    • Considered definitive treatment for leiomyomas
    • 1st line if leiomyosarcoma is suspected
  • Alternatives to surgical resection:
    • Uterine artery Uterine Artery A branch arising from the internal iliac artery in females, that supplies blood to the uterus. Uterus, Cervix, and Fallopian Tubes: Anatomy embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding
      • ↓ Blood supply to fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
      • Beneficial for bleeding and bulk symptoms
      • Should not be used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship desiring future fertility
    • Focused ultrasound surgery: high-intensity ultrasound induces necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage

Management and prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas of leiomyosarcomas

Leiomyosarcomas are usually only diagnosed following surgery for presumed fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility. Management decisions are typically made after an initial procedure:

  • Total hysterectomy if not already performed
  • Adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination therapy depending on stage:
    • Chemotherapy Chemotherapy Osteosarcoma
    • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma is still investigational

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas:

  • Generally poor
  • ↑ Risk of recurrence
  • 5-year, disease-specific survival: 66%

Differential Diagnosis

The differential diagnoses of uterine mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast and/or pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways include:

  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care: may present as an enlarging uterine mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast with increasing pelvic pressure, bulk symptoms, and bleeding abnormalities if there are obstetric complications (e.g., subchorionic hemorrhage). Diagnosis is made with a pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test and confirmed via ultrasound. 
  • Endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis: the ectopic implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week of functional endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development outside the uterine cavity, leading to potentially severe dysmenorrhea, inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, and fertility challenges. Ultrasound may show an endometrioma Endometrioma Endometriosis (ovarian cyst filled with endometrial tissue Endometrial tissue The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Endometriosis), but will not demonstrate a uterine mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast. Treatment usually involves suppression Suppression Defense Mechanisms of the endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development with progestins Progestins Compounds that interact with progesterone receptors in target tissues to bring about the effects similar to those of progesterone. Primary actions of progestins, including natural and synthetic steroids, are on the uterus and the mammary gland in preparation for and in maintenance of pregnancy. Hormonal Contraceptives, or, in more severe cases, GNRH analogs/laparoscopic treatment.
  • Adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis: endometrial implants Endometrial Implants Endometriosis within the uterine myometrium, which lead to heavy, prolonged, and often painful menstrual bleeding similar to leiomyomas. The implants cause the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy to become symmetrically enlarged, boggy, and globular. Discrete masses are not present, which distinguishes adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis from leiomyomas on ultrasound. Management is similar to endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis. However, adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis also commonly includes a hysterectomy for definitive treatment.
  • Endometrial polyps Endometrial polyps Endometrial polyps are pedunculated or sessile projections of the endometrium that result from overgrowth of endometrial glands and stroma around a central vascular stalk. Endometrial polyps are a few millimeters to a few centimeters in size, can occur anywhere within the uterine cavity, and, while usually benign, can be malignant, particularly in postmenopausal women. Endometrial Polyps: arise from an overgrowth in the endometrial epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology. Polyps are usually (though not always) benign Benign Fibroadenoma and typically present with abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding (if symptomatic at all). Endometrial polyps Endometrial polyps Endometrial polyps are pedunculated or sessile projections of the endometrium that result from overgrowth of endometrial glands and stroma around a central vascular stalk. Endometrial polyps are a few millimeters to a few centimeters in size, can occur anywhere within the uterine cavity, and, while usually benign, can be malignant, particularly in postmenopausal women. Endometrial Polyps are best seen with a saline-infusion sonogram Sonogram Chorioretinitis and appear as a pedunculated intracavitary mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast (compared to most submucosal fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility, which are less likely to have a stalk). Treatment (and definitive diagnosis) is by hysteroscopic resection.
  • Other malignancies: other malignancies of the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy or reproductive organs may also present with enlarged uterine mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast and/or abnormal bleeding. The most important malignancies to consider include uterine carcinosarcoma, endometrial carcinoma, and metastases from other organs (especially the ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy, fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy, cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy, and vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy). A leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility is often easily differentiated from other malignancies on ultrasound. An endometrial biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma and a pap smear Pap smear Cytological preparation of cells collected from a mucosal surface and stained with Papanicolaou stain. Cervical Cancer Screening are the best options to identify endometrial and cervical cancers, respectively.

References

  1. Stewart, E.A. (2020). Uterine fibroids (leiomyomas): Differentiating fibroids from uterine sarcomas. In Chakrabarti, A. (Ed.), UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/uterine-fibroids-leiomyomas-differentiating-fibroids-from-uterine-sarcomas
  2. Memarzadeh, S. and Berek, J.S. (2019). Uterine sarcoma: Classification, epidemiology, clinical manifestations, and diagnosis. In Chakrabarti, A. (Ed.), UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/uterine-sarcoma-classification-epidemiology-clinical-manifestations-and-diagnosis
  3. Stewart, E.A., and Laughlin-Tommaso S.K.(2020). Uterine fibroids (leiomyomas): Epidemiology, clinical features, diagnosis, and natural history. In Chakrabarti, A. (Ed.), UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/uterine-fibroids-leiomyomas-epidemiology-clinical-features-diagnosis-and-natural-history
  4. Stewart, E.A., and Laughlin-Tommaso S.K.(2021). Uterine fibroids (leiomyomas): Histology and pathogenesis. In Chakrabarti, A. (Ed.), UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/uterine-fibroids-leiomyomas-histology-and-pathogenesis
  5. Stewart, E.A. (2021). Uterine fibroids (leiomyomas): Treatment overview. In Chakrabarti, A. (Ed.), UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/uterine-fibroids-leiomyomas-treatment-overview
  6. Crum, C.P. (2005). The female genital tract. In Kumar, V., Abbas, A.K., and Fausto, N. (Eds). Robbins and Cotran Pathologic Basis of Disease (7th ed., pp. 1089-1090). 

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