Neoplasms of the breast and reproductive tract (PEARLS)

PANCE Blueprint Reproductive System (7%)

Neoplasms of the Breast and Reproductive Tract

Condition	Location & Features	Treatment
Benign
Fibroadenoma	Breast; mobile, firm, painless, well-circumscribed mass in young women	Observation or excision if symptomatic
Fibrocystic changes	Breast; cyclic breast pain, multiple cysts, often bilateral	Supportive care, NSAIDs, OCPs
Intraductal papilloma	Breast; bloody nipple discharge, no mass	Surgical excision
Breast abscess	Breast; painful, fluctuant mass with erythema, typically lactating women	I&D + antibiotics
Fibroid (leiomyoma)	Uterus; asymptomatic or menorrhagia, pelvic pressure	Observation, OCPs, myomectomy or hysterectomy
Endometrial hyperplasia (w/o atypia)	Uterus; postmenopausal bleeding, thickened endometrium	Progestin therapy, monitor with repeat biopsy
Ovarian cyst (functional)	Ovary; asymptomatic or pelvic pain, often resolves spontaneously	Observation or NSAIDs
Polycystic ovary syndrome (PCOS)	Ovary; multiple small cysts, irregular menses, hirsutism, insulin resistance	OCPs, metformin, weight loss
Hydatidiform mole (benign GTD)	Uterus; abnormal pregnancy with grape-like vesicles, ↑β-hCG	Suction D&C, monitor β-hCG
Malignant
Breast cancer (invasive ductal)	Most common (80%) Breast; hard, immobile, irregular mass, nipple retraction, peau d’orange Spiculated mass or architectural distortion Often unifocal and unilateral	Surgery, radiation, chemo, hormonal therapy
Breast cancer (invasive lobular)	Second most common (~10–15% of cases) Breast; bilateral, multicentric, less likely to form a discrete mass Often diagnosed at later stage due to subtle findings	Surgery + adjuvant therapy
Inflammatory breast cancer	Breast; rapid-onset breast erythema, edema (peau d’orange), no discrete mass, often tender and mistaken for mastitis; poor prognosis	Neoadjuvant chemotherapy, then mastectomy + radiation
Paget disease of the breast	Nipple/areola; eczematous lesion with underlying carcinoma	Mastectomy ± radiation
Endometrial carcinoma	Uterus; postmenopausal bleeding, abnormal ultrasound findings	Hysterectomy ± radiation or chemo
Ovarian cancer (epithelial)	Ovary; bloating, ascites, pelvic mass, often advanced at diagnosis	Surgery + chemo
Cervical intraepithelial neoplasia (CIN II/III)	Cervix; abnormal Pap smear, precancerous lesions	LEEP, ablation, or close monitoring
Cervical cancer (SCC)	Cervix; postcoital bleeding, friable lesion, HPV-related	Surgery, radiation, chemo
Choriocarcinoma	Uterus; malignant gestational trophoblastic disease (GTD), very high β-hCG, hemoptysis if metastases Develops after a molar pregnancy, miscarriage, or abortion	Chemotherapy (methotrexate or actinomycin D)
Vaginal carcinoma	Upper 1/3 posterior vaginal wall; painless vaginal bleeding, mass, or discharge; associated with HPV (16, 18) and often secondary to cervical or vulvar cancer	Radiation therapy ± surgical excision
Vulvar carcinoma	Vulva; pruritus, ulcerated or exophytic lesion, HPV or lichen sclerosus-related	Surgical excision ± radiation

Malignant Reproductive Neoplasms

Breast Cancer	Patient will present as → a 66-year-old female with concern over a mass she felt in her left breast on recent breast self-examination. She denies any nipple discharge and reports a negative family history of breast or other cancers. Physical examination confirms the presence of a painless, firm, irregular, and immobile lump in the superolateral quadrant of the left breast; there are no evident overlying skin changes, and there is no notable axillary lymphadenopathy on palpation. A mammogram is performed, with results seen here. Breast Cancer is the most common malignancy in women Risk factors (increased exposure to estrogen): Menarche before age 12 Advanced maternal age of first full-term pregnancy, no pregnancies Menopause after age 52 Breast mass- immobile, irregular Nipple retraction, bloody nipple discharge Types: Invasive Ductal Carcinoma (IDC) (most common 80%) Invasive Lobular Carcinoma (ILC) (second most common, ~10–15% of cases), frequently bilateral Paget's disease of the nipple (1%), chronic eczematous, itchy, scaling rash on the nipples and areola Inflammatory breast cancer (2%) red, swollen, warm, and itchy breast, often with nipple retraction and peau d'orange (NO LUMP) Tumors may be Estrogen receptor (ER) positive 75%, Progesterone receptor (PR) positive 65%, and HER2 positive 25% Mammography screening (USPSTF guidelines): Average-risk women: Begin biennial mammography at age 40 Continue through age 74 Screening every 2 years is recommended to balance benefits (reduced mortality) and harms (false positives, overdiagnosis) Women aged 75 and older: Insufficient evidence to recommend for or against screening; individualized decisions based on health status and life expectancy High-risk women (e.g., BRCA1/BRCA2 mutation carriers, strong family history): Annual screening with breast MRI and mammography starting at age 25–30, depending on specific risk factors Consider risk assessment tools (e.g., Gail model) and genetic counseling for personalized plans Note: The USPSTF no longer recommends individualized decision-making for women aged 40–49, as screening starting at 40 is now standard for average-risk women Average risk breast cancer screening guidelines: Risk calculators for the average woman include: Breast Cancer Risk Assessment Tool: Online Calculator (The Gail Model) The Breast Cancer Surveillance Consortium’s Risk calculator Tyrer-Cuzick (IBIS) TX: Segmental mastectomy (lumpectomy) followed by breast irradiation in all patients and adjunctive chemotherapy in women with positive nodes, stage I and stage II, with tumors less than 4 cm in diameter Anti-estrogen Tamoxifen is useful in tumors that are premenopausal ER-positive – binds and blocks the estrogen receptor in the breast tissue Aromatase inhibitors are useful in postmenopausal ER-positive patients with breast cancer, reducing the production of estrogen Monoclonal AB treatment is useful in patients with HER2 positivity (Human Epidermal Growth Factor Receptor) Mammogram demonstrating breast cancer. Image by NIH Senior Health via Wikimedia Commons, Public Domain.
Cervical cancer	Patient will present as → a 45-year-old female with post-coital bleeding and painful intercourse. On exam, you notice a friable, bleeding cervical lesion. The cytological evaluation shows a high-grade squamous intraepithelial lesion (HSIL/CIN2/3). She is referred for colposcopy and directed biopsies. What clinical triad is strongly indicative of cervical cancer extension to the pelvic wall? Unilateral leg edema, sciatic pain, ureteral obstruction Cervical cancer is the third most common type of cancer Up to 80% of patients present with abnormal vaginal bleeding, most commonly postmenopausal Only 10% note postcoital bleeding Less frequent symptoms include vaginal discharge and pain 80% are squamous cells and arise from the squamocolumnar junction of the cervix (transformational zone) Risk factors for carcinoma of the cervix ⇒ Multiple sexual partners, early age at first intercourse, early first pregnancy, and HPV positive HPV is 99% of the reason for cervical cancer, types that cause cancer are 16,18,31 and 33. Especially types 16, 18 Associated with cigarette smoking USPSTF guidelines for cervical cancer screening Screening for cervical cancer every 3 years with cervical cytology alone in women aged 21 to 29 years For women aged 30 to 65 years, the USPSTF recommends screening every 3 years with cervical cytology alone, every 5 years with high-risk human papillomavirus (hrHPV) testing alone, or every 5 years with hrHPV testing in combination with cytology (cotesting) Do not screen women younger than 21 years Do not screen women who have had a hysterectomy with removal of the cervix and do not have a history of a high-grade precancerous lesion (ie, cervical intraepithelial neoplasia [CIN] grade 2 or 3) or cervical cancer Do not screen women > 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer Adequate prior screening is defined as three consecutive negative Pap tests or two consecutive negative co-tests within the past 10 years, with the most recent test occurring within the last five years DX: Friable, bleeding cervical lesion on exam Biopsy of gross lesions and colposcopically directed biopsies are the definitive means of diagnosis The majority of cases (80%) are invasive squamous cell types usually arising from the ectocervix TX: Resect and/or chemotherapy and radiation Stage 1: conservative, simple, or radical hysterectomy Stage 2 +: chemo +/– radiation 5-year survival– Stage 1: 85%-90% Stage 2: 65% Stage 3: 29% Stage 4: 21% DES-exposed cervix showing cervical structural changes. Image via Wikimedia Commons, public domain.
Ovarian Cancer	Patient will present as → a 66-year-old woman who complains of abdominal fullness, bloating, fatigue, and weight loss. She underwent menopause 17 years ago and has never had children. She had a pelvic mass, but her PAP smear is atrophic. CA-125 levels are elevated. A transvaginal ultrasound demonstrates an ovarian mass concerning for malignancy. Ovarian cancer is the second most common type of GYN cancer in women (the first is endometrial cancer) Population: 40-60 years of age, ascites, abdominal pain ⇒ 75% diagnosed at an advanced stage If a woman has ascites, ovarian cancer is the most likely tumor to be found Protective factors for the risk of ovarian cancer include multiparity, OCP use, and breastfeeding Use of oral contraceptives: 5 years of use decreases risk by 20%; 15 years by 50% Risk factors: nulligravidity (or infertility), early menarche, late menopause, endometriosis 90% are epithelial tumors ⇒ germ cell tumors are more common in patients < 10 years old DX: Diagnose with transvaginal ultrasound, then biopsy Serum tumor marker CA-125 ⇒ BRCA1 gene is associated with 5% of cases TX: Stage 1A or 1B—Surgical excision alone (abdominal hysterectomy and bilateral salpingo-oophorectomy) Other stages—Surgical resection followed by adjuvant chemotherapy or radiation Monitor CA-125 afterward to assess disease progress Preoperative transvaginal ultrasonography (a) detected an isoechoic solid mass in the right pelvic cavity (approximately 10 cm in size) with an ill-defined boundary between the lesion and the uterus, and T2-weighted magnetic resonance imaging of the ovarian tumor in (b) the horizontal and (c) the sagittal planes. The mass was later identified as a fibroma. Image by Diagnostic Pathology. License: CC BY 4.0
Endometrial cancer	Patient will present as → a 53-year-old woman with no period for four years and is now having abnormal bleeding and bleeding after intercourse. She has lower abdominal pain, pelvic heaviness, and bloating, and feels as though she may have her menses. A transvaginal ultrasound shows endometrial thickness of 12 mm. An endometrial biopsy is performed and confirms endometrial adenocarcinoma. Endometrial cancer is the most common gynecologic malignancy and the fourth most common malignancy in women in the US The cardinal symptom is postmenopausal vaginal bleeding ⇒ One-third of women with postmenopausal bleeding have endometrial CA Bleeding in postmenopausal women is CA until proven otherwise Most often adenocarcinoma Risk factors for endometrial cancer: Obesity, nulliparity, early menarche, late menopause, unopposed estrogen stimulation, hypertension, gallbladder disease, DM, prior ovarian, endometrial, or breast cancer 50% of women with endometrial cancer will have an abnormal PAP smear Diagnosis: Endometrial biopsy is the gold standard definitive diagnostic test Endometrial biopsy is indicated in all postmenopausal women vaginal bleeding TX: Usually total hysterectomy and bilateral salpingo-oophorectomy, pelvic radiation therapy with or without chemotherapy for stage II or III cancer Endometrial cancer involving the uterine lining. Illustration by Blausen Medical Communications, Inc. via Wikimedia Commons, CC BY 3.0.
Vaginal and Vulvar Cancer	Patient will present as → a 65-year-old African American woman, gravida 4, para 4, with a smoking history and past HPV infection, presents with 3 months of postmenopausal vaginal bleeding, pelvic pain, and dyspareunia. She states that the bleeding is usually light and intermittent but has recently increased in frequency and volume. She hasn’t had a Pap smear in over a decade. On examination, a 2cm firm, irregular mass is found on the anterior vaginal wall. Biopsy reveals poorly differentiated squamous cell carcinoma, and the CT scan indicates local invasion into the bladder wall. (vaginal neoplasms) Patient will present as → a 50-year-old female with vaginal itching and irritation, red/white ulcerative crusted lesions on the vulva (vulvar cancer) What are the known risk factors for vulvar/vaginal carcinoma? HPV infection, Smoking, Coexisting cervical carcinoma, In utero exposure to DES Vaginal Cancer Rare: 1% of gynecological malignancies, and it is usually secondary to another cancer Peak incidence at 60-65 years of age Squamous cell carcinoma represents 95% caused by HPV Adenocarcinoma caused by DES exposure The most common location of vaginal carcinoma is the upper one-third of the posterior vaginal wall Usually presents as changes in the menstrual period and/or abnormal vaginal bleeding TX: with radiation therapy Stage III vaginal cancer with spread into the pelvic wall and/or regional lymph nodes. Illustration by Cancer Research UK via Wikimedia Commons, CC BY-SA 4.0. Patient will present as → a 50-year-old female with vaginal itching, and irritation, red/white ulcerative crusted lesions on the vulva Vulvar Cancer Peak incidence is at 50 years old Vaginal pruritus is the most common presentation (70% will present with this symptom) 90% are squamous cell cancers and melanoma. Risks include HPV subtypes 16, 18, and 31 – pruritic black lesions DX: Application of acetic acid or staining with toluidine blue may help direct optimal biopsy location TX: Vulvectomy and lymph node dissection Paget’s – pruritic red lesions TX: Local resection Right-sided vulvar carcinoma on axial CT imaging. Image by Hellerhoff via Wikimedia Commons, CC BY-SA 3.0.