Obgyn · Year 3 · from Obgyn

Case 2: Endometrial Cancer with Lynch Syndrome

Patient Demographics

  • Age: 48 years
  • Sex: Female
  • Occupation: Real estate agent

Chief Complaint

"I've had heavy, irregular bleeding for the past 4 months."

History of Present Illness

The patient presents with a 4-month history of abnormal uterine bleeding. Previously, she had regular monthly menstrual cycles, but for the past 4 months, she has had prolonged heavy bleeding lasting 10 to 14 days each month, sometimes with only 1 week interval between episodes. She reports passing large clots and soaking through a super tampon every 1 to 2 hours on her heaviest days. She also notes watery vaginal discharge between bleeding episodes. She denies pelvic pain, weight loss, or change in bowel or bladder habits. She has not yet reached menopause. Her BMI has been stable around 26 kg/m2.

Past Medical History

  • G3P3, all vaginal deliveries
  • No prior surgeries
  • No history of abnormal Pap smears
  • Never used hormone therapy or oral contraceptives
  • Colonoscopy 3 years ago with one tubular adenoma removed

Family History (Significant)

  • Father diagnosed with colon cancer at age 52
  • Paternal grandmother with endometrial cancer at age 54
  • Paternal uncle with colon cancer at age 48
  • Paternal aunt with ovarian cancer at age 60
  • No known genetic testing in family

Physical Examination Findings

  • Vital Signs: BP 122/78 mmHg, HR 74 bpm, BMI 26 kg/m2
  • General: Well-appearing woman, not obese
  • Abdomen: Soft, non-tender, non-distended, no masses
  • Pelvic: Normal external genitalia, moderate amount of blood in vaginal vault, cervix appears normal, uterus slightly enlarged (approximately 10-week size), mobile, non-tender, ovaries not palpable

Diagnostic Workup

  • Urine Pregnancy Test: Negative
  • Complete Blood Count: Hemoglobin 9.8 g/dL (anemia from chronic blood loss), MCV 76 fL (microcytic), ferritin 8 ng/mL (iron deficiency)
  • TSH: 2.1 mIU/L (normal)
  • Transvaginal Ultrasound: Uterus measures 11 x 8 x 7 cm, endometrial thickness 18 mm (thickened), heterogeneous endometrial echo with increased vascularity on Doppler, no focal myometrial masses, ovaries normal
  • Endometrial Biopsy: Endometrioid adenocarcinoma, FIGO grade 2

Tumor Molecular Testing:

  • Immunohistochemistry for MMR proteins: Loss of MLH1 and PMS2 expression
  • MLH1 Promoter Methylation: Negative
  • Microsatellite Instability (MSI) Testing: MSI-High

Diagnosis

Endometrial Cancer, Endometrioid Adenocarcinoma, Grade 2

  • Suspected Lynch Syndrome based on:
  • Loss of MLH1/PMS2 on IHC
  • Negative MLH1 promoter methylation (excludes sporadic cause)
  • MSI-High
  • Strong family history meeting Amsterdam II criteria
  • Relatively young age at diagnosis (48 years)
  • Non-obese patient (atypical for sporadic endometrial cancer)

Surgical Staging

Procedure Performed:

  • Robotic-assisted total laparoscopic hysterectomy
  • Bilateral salpingo-oophorectomy
  • Sentinel lymph node mapping and biopsy
  • Peritoneal washings

Surgical Findings:

  • Uterus with fundal tumor
  • Both sentinel lymph nodes identified (bilateral) using ICG fluorescence
  • No gross extrauterine disease

Final Pathology:

  • Endometrioid adenocarcinoma, Grade 2
  • Tumor size: 3.5 cm
  • Myometrial invasion: 8 mm of 18 mm total myometrial thickness (less than 50%)
  • Lymphovascular space invasion: Absent
  • Cervical stromal invasion: Absent
  • Bilateral sentinel lymph nodes: Negative for metastatic disease (0/2)
  • Peritoneal cytology: Negative
  • Ovaries and fallopian tubes: No evidence of malignancy

Final Stage: FIGO Stage IA (tumor confined to endometrium/less than 50% myometrial invasion, negative nodes)

Genetic Testing Results

  • Germline Testing: Pathogenic variant in MLH1 gene confirmed
  • Diagnosis: Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer syndrome)

Management Plan

Adjuvant Therapy:

  • Stage IA, Grade 2, no LVSI = Low-risk category
  • No adjuvant therapy recommended per NCCN guidelines for low-risk disease
  • Observation with surveillance

Lynch Syndrome Management:

For the Patient:

  1. Colonoscopy surveillance: Every 1-2 years (already had adenoma at prior colonoscopy)
  2. Upper endoscopy: Consider screening for gastric/small bowel cancer every 3-5 years
  3. Ovarian cancer risk: Already addressed with bilateral salpingo-oophorectomy at time of hysterectomy
  4. Urinalysis: Annual screening for urinary tract cancers
  5. Consider aspirin: Emerging data suggests may reduce Lynch-associated cancer risk

Cancer Risk Discussion:

  • Colorectal cancer: 40-80% lifetime risk
  • Ovarian cancer: 10-15% lifetime risk (now eliminated)
  • Urinary tract cancer: Elevated risk
  • Other cancers: Stomach, small bowel, biliary tract, pancreas, brain

Genetic Counseling for Family:

  1. First-degree relatives have 50% chance of carrying MLH1 mutation
  2. Cascade genetic testing recommended for:
  • Three children
  • Two siblings
  • Father (if still living)
  1. If positive, family members need enhanced surveillance:
  • Colonoscopy starting age 20-25 or 2-5 years before youngest cancer diagnosis in family, whichever is earlier
  • Female relatives: Discuss risk-reducing hysterectomy and BSO after childbearing

Cancer Surveillance Schedule:

  • Physical examination and CA-125: Every 3 months for first year, then every 6 months for years 2-3
  • No routine imaging unless symptoms develop
  • Annual colonoscopy given personal history of adenoma and Lynch syndrome
  • Endometrial cancer surveillance not needed (hysterectomy performed)

Prognosis

  • Stage IA endometrioid endometrial cancer: >95% 5-year survival
  • Primary concern is Lynch syndrome-related second primary cancers, particularly colorectal cancer
  • Compliance with surveillance protocols essential for early detection

Clinical Image

Image Description: Transvaginal ultrasound image demonstrating a thickened, heterogeneous endometrium measuring 18 mm in a premenopausal woman with abnormal uterine bleeding. The endometrial echo is irregular with increased vascularity on Doppler imaging. These findings are suspicious for endometrial pathology requiring tissue sampling.

Attribution: Endometrial cancer ultrasound findings as described in radiology literature. Information on Lynch syndrome testing from medical genetics resources.

All cases for this lecture as Markdown