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Uterine Leiomyoma

DPC 2014: Clinical Practicum Presentation Term 2

Patrick Hyppolite

on 23 November 2011

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Transcript of Uterine Leiomyoma

49 Y old Female

CC: dyspnea, Menses over a month, dysphagia and mammogram referral
History of CC:
PMH of anemia and HTN presents to office visit with heavy vaginal bleeding for 30 days. No history of similar episode. She has been bleeding through one pad per day, no clots. She is not compliant with Iron tablets. Last menstrual period was 2/1. She denies sexual activity for last year. AS has DOE with walking 2 blocks and up 1 flight of stairs. No chest pain. 3 weeks ago patient had difficulty swallowing Motrin tablet and went to Mercy Hospital she had EGD in ED. She continues to have difficulty swallowing solids not liquids.

ROS: no chest pain, no nausea, no vomiting, no abdominal pain, no fever, no headache, no lightheadedness, no syncopal episode, no back pain, no rectal bleeding no dysuria

Medications: HCTZ 50mg 1 tablet once/day
Past Medical History: Seasonal allergies, Anemia, Goiter, Pre-DM
Surgical History: Tonsillectomy 2006, Excision of Intraductal Papilloma 2009, Tubal ligation 1999

Family History: Father - Deceased Brain Cancer,
Mother alive - Fibroids, Hysterectomy, Hypothryoidism, Bradycardia

Vital Signs: BP 140/100, HR 80, RR 18, afebrile

Physical Examination: well nourished, disheveled and appears distraught. HEENT: tymphanic membranes pearly bilaterally, pink or pale conjunctiva, EOMI bilaterally, PERRLA, turbinates normal, nose clear oropharynx no erythema. ORAL CAVITY: moist mucous membranes. NECK: normal ROM of C spine, nodule palpated nodules on the right and left lobes of the thyroid. HEART: 2/6 systolic murmur, RRR, normal S1S2. Chest: normal LUNGS: clear to auscultation bilaterally, no wheezes/rhonchi /rales. ABDOMEN: soft NT/ND BS present, normal without tenderness, no masses, no organomegaly, NEUROLOGIC EXAM: CN II-XII grossly intact . SKIN: normal, no rash or skin lesions, good turgor, moist and warm. EXTREMITIES: capillary refill present, no clubbing, no edema, no cyanosis. PSYCH Alert, awake and oriented

Goiter, Multinodular nontoxic
Screen Mammogram

1. Dyspnea - advised to proceed to ED if symptoms gets worst (d-dimer, ekg stat (due to high blood pressure and sob), ckmb and troponin, CXR)
2. GYN referral for menorrhagia (pelvic exam, imaging)
3. Hypertension - Stop HCTZ tablet 50mg orally once a day, START Micardis HCT tablet 40-12.5mg orally 1 tablet once a day for 30days Refill 3, Iron 325 (65 Fe) mg 1 tablet twice a day, Vitamin D 1000 UNIT 1 tablet twice a day
Lab order: Comp. Metabolic Panel, CBC, Lipid Panel, Hemoglobin A1C, TSH + Free T4, 25-Hydroxy Vitamin D, RPR, Rfx on RPR/Confirm TP-PA
4. Dysphagia - Stressed to make a appointment with Head and Neck Specialist. If increased symptoms go to ED
Referral to Head and Neck Specialist
5. Screen for Mammogram: Diagnostic Imaging
6. HIV Counseling: Lab HIV-1 Antibodies
7. Goiter: Diagnostic testing First Visit on 3/3/11 Reason for Appointment - Follow for results

History of Present Illness
49 year old female presents for follow up lab results. Patient denies new problems
Denies: Blurred vision, Chills, Cynosis. Diaphoresis. Dizziness. Palpitations. Chest pain

Vital Signs 134/88 HR 74 RR 16, afebrile

Past Orders
Potassium, Serum 3.4 (3.5-5.2 mmol/L)
Hemoglobin 6.6 (11.5-15.0 g/dl)
Hematocrit 24.5 (34.0-44.0%)
MCV 56 (80-98fL)
MCH 15.2 (27.0-34.0 pg)
MCHC 26.9 (32.0-36.0 g/dl)
RDW 21.4 (11.7-15.0%)
Platelets 559 (140-415x10E3/ul)
Neutrophils 37 (40-74%)
Carbon Dioxide total 19 (20-32 mmol/L)
Ferritin, Serum 2 (13-150 ng/mL)
Fasting Glucose 114 (65-99 mg/dl)
Hemoglobin A1c 5.7 (4.8-5.6%)
Hgb A 98.7 (94.0-98.0%)
UIBC 407 (150-375 ug/dL)
Iron Serum 8 (35-155 ug/dL)
Iron Saturation 2 (15-55%)
LDL Cholesterol conc. 115 (0-99 mg/dL)
TSH 0.926 (0.450-4.500)
T4, Free (Direct) 1.00 (0.82-1.77ng/dL)
Vitamin D, 25-Hydroxy 5.2 (32.0-100.0ng/ml)
all others are WNL

SOB seconardily to Anemia
Vitamin D deficiency


1. Hypertension: Increase Micardis HCT Tablet, 40-12.5 mg, orally 2 tablets, once a day
2. Anemia: Iron Tablet 325 (65 Fe) mg, orally, 1 tablet, 3 times a day
Encourage patient to have Iron rich diet. Patient was advised again to see the GYN
3. Prediabetes: patient was told to eat a healthy diet
4. Vitamin D deficiency: 1000 unit, orally, 1 tablet, 2x a day, Start Vitamin D (Ergocalciferol) Capsule 50000 unit, orally, 12, 1 capsule, once a week, 90 days
5. Hyperlipidemia: patient told to maintain low cholesterol diet Follow up Visit 3/10/11 Radiology Group


No mammographic evidence of malignancy. Recommend routine annual mammography
No cystic or solid masses are identified in either breast. There is no abnormal acoutic shadowing.

Impression: Postoperative scarring on the right otherwise normal sonogram of bilateral breasts Differential Diagnosis:

Uterine Leiomyoma
Endometrial Polyp
Endolymphatic Stromal Myosis
Von Willebrand's Disease
Ovarian Carcinoma
Hypothyroidism Uterine Leiomyoma Agenda

Present our patient AS
Anatomy of Uterus
Histophysiology of the Uterus
Histopathology of Leiomyoma
Leiomyoma vs Leiomyosarcoma
Back to AS
WrapUp Anatomy of the Uterus vesicouterine pouch
rectouterine pouch (cul-de-sac of Douglas)
paravesical fossa
pararectal fossa
Broad ligament of the uterus
Has three parts:
Round ligament of the uterus
Ovarian ligament
Endopevic fascia
Uterosacral (sacrogenital) ligament
Transverse cervical ligament (cardinal ligament)
Pubocervial (pubovesical) ligament
Female Internal Genitalia
Uterus is anteverted

Features of the uterus:
Body ral sides

Uterine tube

Ovary – is ovoid with a tubual (distal) extremity and a uterine (proximal) extremity. Ovarian vessels enter the tubal extremity of the ovary, ligament of the ovary is attached to the uterine extremity. Ovary sits in the ovarian fossa (shallow depression in the lateral pelvic wall bounded by the ureter, external iliac vein and uterine tube)

the ureters crosses inferior to the uterine artery and superior to the vaginal artery

Internal Iliac Artery and Sacral Plexus

Uterine artery –
Divides into a large superior branch and a smaller branch
Uterine artery has close relationship to the lateral fornix Correlation of ovarian and menstrual cycles with levels of their controlling hormones.The cyclic development of ovarian follicles and the corpus luteum, controlled by the pituitary gonadotropins FSH and LH, lead to cyclic shifts in the levels of the major ovarian hormones: steroidal estrogens and progesterone. Estrogen stimulates the proliferative phase of the uterine cycle and its level peaks near the day of ovulation, which marks the midpoint of the ovarian cycle. After ovulation the corpus luteum forms and produces both progesterone and estrogens, which together promote growth and development of the endometrial functional layer. Unless fertilization and implantation of an embryo occur, regression of the corpus luteum leads to declining levels of the steroid hormones and failure of the new endometrial tissue to be maintained. This tissue sloughs off as the menstrual flow, the first day of which is taken to mark day 1 of both the ovarian cycle and the uterine cycle. The basal layer of endometrium is not sensitive to the loss of progesterone and is retained during menstruation, serving to regenerate the functional layer during the ensuing proliferative phase. Stratum functionale Stratum basale Stratum vasculare Proliferative, secretory, and premenstrual phases in the uterus.The major phases of the uterine cycle overlap, but produce distinctly different and characteristic changes in the functional layer (F) closest to the lumen (L) with little effect on the basal layer (B) and myometrium (M). Characteristic features of each phase include the following. During most of the proliferative phase (a and d) the functional layer is still relatively thin, the stroma is more cellular and the glands (G) are relatively straight, narrow, and empty. In the secretory phase (b and e) the functional layer is less heavily cellular and perhaps four times thicker than the basal layer. The tubular glands have wider lumens containing secretory product and coil tightly up through the stroma, giving a zig-zag or folded appearance histologically. Superficially in the functional layer, lacunae (La) are widespread and filled with blood. The short premenstrual phase (c and f) begins with constriction of the spiral arteries, which produces hypoxia that causes swelling and dissolution of the glands (G). The stroma of the peripheral functionalis is more compact and that near the basal layer typically appears more sponge-like during this time of blood stasis, apoptosis and breakdown of the stromal matrix. a: X20; b and c: X12; d, e, and f: X50. All H&E. Uterus. Most of the uterine wall is composed of the myometrium, consisting of multiple interwoven layers of well-vascularized smooth muscle. The inner layer of the uterus, corresponding to a mucosa, is the endometrium. (a): The micrograph shows the basal layer (B) of the endometrium, bordering the myometrium (M). The basal layer contains the basal ends of the uterine glands (G) and many small arteries (A) embedded in a distinctive connective tissue stroma with many fibroblasts, ground substance and primarily fine type III collagen, but no adipocytes. X100. Mallory trichrome. (b): Superficial to the basal layer of the endometrium is its functional layer, the part that changes histologically and functionally depending on estrogen levels. This micrograph shows only functional layer and includes parts of the long uterine glands (G) as well as one spiral artery (A). X100. Mallory trichrome. (c): The surface epithelium (SE) lining the endometrium is simple columnar, with many cells having cilia (arrow). The underlying stroma (S) has an extensive microvasculature, much ground substance, and fibroblastic cells with large, active nuclei. X400. Mallory trichrome. Patrick Hyppolite OMS I
New York College of Osteopathic Medicine
Preceptor: Michelle Reed, D.O.
Garden City, NY 11530 Uterine leiomyoma (commonly called fibroids)
Most leiomyoma have normal karyotype but 40% have a single chromosomal abnormality
a balanced translocation between chromosomes 12 and 14: (i.e. t(12:14)(q14-q15;q23-q24)), partial deletions of the long arm of chromosome 7 (i.e., del(7)(q22-q23)), trisomy 12 and rearrangements fo 6p, 3q and 10q.
The rearrangements of 12q14 and 6p involving the HMGIC and HMGIY genes respectively (Both genes encode closely related DNA binding factors that regulate chromatin structure Morphology

Leiomyomas are sharply circumscribed, discrete, round (whorled pattern) tumors that vary in size (visible nodules to filling the pelvis)
Rarely involve the uterine ligament, lower uterine ligaments, lower uterine segment
Benign variants of leiomyoma include atypical tumors with nuclear atypia and giant cells: Benign metastasizing leiomyoma (lungs) and Disseminated peritoneal leiomyomatosis (nodules in peritoneum
Malignant transformational (leiomyosarcoma) within a leiomyoma is extremely rare Clinical Presentation

asymptomatic (even with extensive amount of tumors...esp in pregnant women)
menorrhagia (abnormal excessive bleeding)
urinary frequency (compression on the bladder)
acute pain (can progress if tumor is infarcted or twisted on its pedicle blood supply is compromised)
impaired fertility
increase spontaneous abortion, fetal malpresentation, uterine inertia that leads to postpartum hemorrhage (in pregnant women)
Asymptomatic myomas should be examined every 6 months Leiomyosarcoma

More than half the eventually metastasize through the bloodstream into lungs, bone and brain; dissemination throughout abdominal cavity is possible
grow in two patterns: bulky fleshy masses that invade the uterine wall or polypoid masses that project into the uterine lumen indicate a malignancy when presence of 10 or more mitoses per 10 high power (400x) fields (5 mitoses per 10 high power fields are sufficient for malignancy FIGURE 22-32  A, Leiomyomas of the myometrium. The uterus is opened to reveal multiple tumors in submucosal (bulging into the endometrial cavity), intramural, and subserosal locations that display a firm white appearance on sectioning. B, Leiomyoma showing well-differentiated, regular, spindle-shaped smooth muscle cells associated with hyalinization. FIGURE 22-33  Leiomyosarcoma. A, A large hemorrhagic tumor mass distends the lower corpus and is flanked by two leiomyomas. B, The tumor cells are irregular in size and have hyperchromatic nuclei with numerous mitotic figures (arrows). The appearance of leiomyomas will vary depending on the degree and type of degeneration present. A. Cystic degeneration (arrow) seen within this submucous fibroid. B. Typical histologic architecture of leiomyomas. C. Hyaline degeneration is identified by abundant pink glassy hyaline that is seen interspersed between smooth muscle cells. (Courtesy of Dr. Raheela Ashfaq.) References:

Robbins and Cotran, Pathologic Basis of Disease 8th Edition, Saunders Elsevier, 2012
Ross and Pawlina , Histology: A Text and Atlas 6th Edition, Lippincott Williams &Wilkins, 2011
Guyton and Hall , Textbook of Medical Physiology, Saunder Elsevier, 2012
Mescher, Junqueira's Basic Histology Text and Atlas, 12th Edition, www.accessmedicine.com
Schorge, Schaffer, Halvorson, Hoffman, Bradshaw, Cunningham, Williams Gynecology, www.accessmedicine.com
Brunicardi, Andersen, Billiar, Dunn, Hunter, Matthews, Pollock, Schwartz's Principles of Surgery, 9th Edition, www.accessmedicine.com
Drinville, Memarzadeh, Current Diagnosis & Treatment Obstretics & Gynecology, 10th Edition, www.accesmedicine.com Acknowledgements

Thank you to

Dr. Michelle Reed
Ms. Elizabeth Dinapoli
Dr. Portanova
Dr. McMahon
Dr. Hutak
To the DPC Staff

And all of you here today! Bring it Back to AS

Family History of Fibroids
African American are 2-3x more likely
In her 5 decade so chances increase by 50%
Imaging Studies : Ultrasonography (subserous and pendunculated myomas) and MRI or hysterography (confirm intramural or submucous myomas)
Depot medroxyprogesterone (150mg every 28 days) or danazol/mifepristone (4oo-800mg once daily orally) <stop bleeding>
Depot leuprolide (3.75mg monthly) or nafarelin (0.2-0.4mg internasally) <reversible hypogonadism>
Surgerical measures: total abdominal, vaginal or laparoscopy assisted vaginal hysterectomy (preserve fertility - myomectomy)
Emergency surgery is needed if patient severly bleeding, torsion of penduculated myoma, pressure on the ureters, bladder or bowel, pedunculated or cervical myomas that protrude through the cervix
Submucous myomas can be removed using hysteroscope and laser resection instruments Future Learning Issues:

Anatomy of the Female Reproductive Systeim
Histophysiology of the Female Reproductive Tract
Pharmacology of Gonadal Hormones and its Inhibitors
Pathology of Endometrial Disorders and Endometrial Neoplasia Leiomyoma vs Leiomyosarcoma no mitotic index Leiomyoma vs Leiomyosarcoma Leiomyoma vs Leiomyosarcoma Leiomyoma vs Leiomyosarcoma Leiomyoma vs Leiomyosarcoma Leiomyoma vs Leiomyosarcoma Leiomyoma vs Leiomyosarcoma histologically nuclear atypia, mitotic index and zonal necrosis circumscribed borders present but possess distant autonomy with myometrium, discrete, round, firm tumors arise from myometrium, beneath the endometrium and beneath the serosa normal karyotype extremely well differentiated to highly anaplastic, pleomorphic lesions arise de novo from the myometrium or endometrial stromal precursor cell have complex highly variable karyotypes that include deletions Striking tendency to recur after removal Surgical removal is curative Occurs during reproductive age, premenopausal and postmenopausal: peak incidence is between 40 and 60 years old Occurs during reproductive age
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