# Clinical Cases: Gynecologic Oncology

## Case 1: Advanced Ovarian Cancer

### Patient Demographics
- **Age:** 58 years
- **Sex:** Female
- **Occupation:** Retired teacher

### Chief Complaint
"I've had progressive bloating and abdominal swelling for the past 3 months."

### History of Present Illness
The patient presents with a 3-month history of progressive abdominal distension, early satiety, and a 15-pound unintentional weight loss despite the increasing abdominal girth. She reports feeling full after eating only small amounts and has noticed her pants becoming tighter around the waist. She describes vague, constant lower abdominal discomfort and pelvic pressure. She also notes increased urinary frequency over the past 6 weeks. She initially attributed her symptoms to irritable bowel syndrome but became concerned when symptoms persisted despite dietary modifications. She denies vaginal bleeding, nausea, vomiting, or change in bowel habits. Her last menstrual period was at age 52, and she has been postmenopausal for 6 years without hormone therapy.

### Past Medical History
- Hypertension, well-controlled on lisinopril
- Hyperlipidemia on atorvastatin
- G2P2, both vaginal deliveries
- No prior surgeries
- Never used oral contraceptives
- Family history of breast cancer in maternal aunt (age 62)

### Family History
- Mother deceased at 68 from ovarian cancer (diagnosed at age 65)
- Maternal aunt with breast cancer at age 62
- Father deceased at 78 from lung cancer (smoker)
- Sister alive at 56, healthy
- No known genetic testing in family

### Physical Examination Findings
- **Vital Signs:** BP 138/82 mmHg, HR 78 bpm, BMI 26 kg/m2
- **General:** Cachectic-appearing woman with notable abdominal distension
- **Lymph Nodes:** No palpable cervical, supraclavicular, axillary, or inguinal lymphadenopathy
- **Chest:** Clear to auscultation, decreased breath sounds at right base
- **Abdomen:** Markedly distended with positive fluid wave indicating ascites, umbilicus everted, diffuse fullness on palpation, no distinct masses palpable due to ascites, no hepatomegaly appreciated
- **Pelvic:** External genitalia normal, vaginal mucosa atrophic, cervix atrophic-appearing, uterus not well delineated due to ascites, bilateral irregular nodular masses felt in the adnexa, fixed nodularity in the cul-de-sac (cul-de-sac implants)

### Diagnostic Workup
- **CA-125:** 1,842 U/mL (markedly elevated; normal <35 U/mL)
- **HE4:** 428 pmol/L (elevated)
- **ROMA Score:** High probability of malignancy
- **Complete Blood Count:** Hemoglobin 10.2 g/dL (mild anemia), WBC 8,200/microL, Platelets 412,000/microL (reactive thrombocytosis)
- **Comprehensive Metabolic Panel:** Albumin 2.8 g/dL (low), otherwise normal
- **CT Chest/Abdomen/Pelvis with Contrast:**
  - Large-volume ascites throughout the abdomen and pelvis
  - Bilateral complex adnexal masses, right measuring 8.5 cm and left measuring 6.2 cm
  - Omental thickening and nodularity consistent with omental caking
  - Multiple peritoneal implants along the paracolic gutters and diaphragmatic surfaces
  - Small right pleural effusion with pleural nodularity suspicious for metastatic disease
  - No parenchymal liver or lung metastases
  - Mildly enlarged pelvic and para-aortic lymph nodes
- **Chest X-ray:** Small right pleural effusion
- **Paracentesis:** 3.5 liters of serosanguinous fluid removed
  - Cytology: Positive for adenocarcinoma, immunohistochemistry consistent with high-grade serous carcinoma (PAX8+, WT1+, p53 mutant pattern)

### Diagnosis
**High-Grade Serous Ovarian Carcinoma, FIGO Stage IVA**
- Stage IVA based on malignant pleural effusion
- Histology confirmed via ascitic fluid cytology as high-grade serous carcinoma
- Strong family history concerning for hereditary breast-ovarian cancer syndrome

### Staging (FIGO 2014)
- **Stage IV:** Distant metastases
  - **IVA:** Pleural effusion with positive cytology
  - Extensive peritoneal carcinomatosis with omental involvement
  - Bilateral adnexal masses

### Management Plan

**Multidisciplinary Team Discussion:**
- Gynecologic oncologist, medical oncologist, interventional radiology, genetic counselor

**Assessment of Resectability:**
- CT findings suggest extensive disease with omental caking and diaphragmatic implants
- Laparoscopic assessment recommended to determine feasibility of primary cytoreduction vs. neoadjuvant chemotherapy

**Selected Treatment Pathway - Neoadjuvant Chemotherapy:**

Given extensive peritoneal disease and patient's nutritional status (low albumin, weight loss):
1. **Neoadjuvant chemotherapy (NACT)** x 3-4 cycles followed by interval debulking surgery
2. Benefits of NACT approach:
   - Similar overall survival to primary debulking in trials
   - Lower surgical morbidity
   - Allows assessment of platinum sensitivity
   - Time for nutritional optimization

**Chemotherapy Regimen:**
- **Carboplatin** AUC 5-6 intravenously Day 1
- **Paclitaxel** 175 mg/m2 intravenously Day 1
- Cycle every 21 days for 3-4 cycles before interval surgery

**Add Bevacizumab:**
- Consider adding **bevacizumab** 15 mg/kg IV q3 weeks to first-line chemotherapy and as maintenance (ICON7 and GOG-218 data support improved PFS in advanced disease)

**Interval Debulking Surgery (after NACT):**
- Goal: Complete gross resection (R0) - no visible residual disease
- Procedures may include:
  - Total abdominal hysterectomy and bilateral salpingo-oophorectomy
  - Omentectomy
  - Peritoneal stripping of affected surfaces
  - Diaphragm stripping or resection if involved
  - Splenectomy if splenic hilum involved
  - Bowel resection if necessary for complete cytoreduction
  - Pelvic and para-aortic lymphadenectomy

**Post-Surgical Chemotherapy:**
- Complete 6 total cycles of carboplatin/paclitaxel
- Continue bevacizumab maintenance for up to 15 months total if used

**Maintenance Therapy:**
- **PARP inhibitor** maintenance if tumor demonstrates BRCA mutation or homologous recombination deficiency (HRD)
- Send tumor tissue for **BRCA1/2 somatic mutation** testing
- **Germline BRCA testing** given family history (mother with ovarian cancer, aunt with breast cancer)

**Genetic Testing and Counseling:**
1. Refer to genetic counselor urgently
2. Order germline BRCA1/BRCA2 testing
3. Consider expanded panel including RAD51C, RAD51D, BRIP1
4. If BRCA positive:
   - Patient qualifies for PARP inhibitor maintenance (olaparib, niraparib)
   - Family members should be offered testing
   - Risk-reducing surgery for sisters/daughters if carriers

**Supportive Care:**
1. Nutritional support with dietitian referral
2. Serial paracentesis as needed for symptom control
3. DVT prophylaxis (high VTE risk with ovarian cancer)
4. Psychological support

**Follow-up and Surveillance:**
- CA-125 with each chemotherapy cycle
- CT imaging after 3 cycles to assess response before interval surgery
- Post-treatment: CA-125 every 3 months for 2 years, then every 6 months
- CT imaging only if CA-125 rises or symptoms develop

### Prognosis
- Stage IVA high-grade serous ovarian cancer
- 5-year survival approximately 20-30%
- BRCA mutation (if present) associated with better response to platinum chemotherapy and PARP inhibitors
- Optimal cytoreduction to no residual disease is the most important prognostic factor

### Clinical Image
![Ovarian Cancer CT Imaging](case_01_image.jpg)

**Image Description:** Contrast-enhanced CT scan of the abdomen and pelvis demonstrating advanced ovarian cancer. Key findings include large-volume ascites, bilateral complex adnexal masses with solid and cystic components, omental thickening ("omental cake") representing peritoneal carcinomatosis, and peritoneal implants along the paracolic gutters. These findings are characteristic of stage III-IV epithelial ovarian cancer.

**Attribution:** CT imaging findings in ovarian cancer as described in Radiopaedia (https://radiopaedia.org/articles/ovarian-tumours) and RadioGraphics imaging literature.

---

## 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)
3. 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
![Endometrial Cancer on Ultrasound](image_01.jpg)

**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.

---

## Case 3: Cervical Cancer - Locally Advanced

### Patient Demographics
- **Age:** 42 years
- **Sex:** Female
- **Occupation:** Hotel housekeeper

### Chief Complaint
"I've had vaginal bleeding after sex and a foul-smelling discharge for the past 2 months."

### History of Present Illness
The patient presents with a 2-month history of postcoital bleeding and intermenstrual spotting. She describes the bleeding as bright red, occurring within hours of intercourse, requiring a panty liner. She also reports a persistent foul-smelling, blood-tinged vaginal discharge. Over the past 3 weeks, she has developed dull lower back pain and left leg swelling. She denies urinary symptoms, constipation, or weight loss. She has not had a Pap smear in over 10 years due to lack of health insurance and access to care. She immigrated from Central America 15 years ago.

### Past Medical History
- G4P4, all vaginal deliveries
- No prior surgeries
- No known medical conditions
- Never received HPV vaccination (not available during her adolescence)
- Last Pap smear approximately 12 years ago (reportedly normal)
- Smoker: 1 pack per day for 20 years

### Social History
- First sexual intercourse at age 16
- Lifetime 4 sexual partners
- Married for 18 years, monogamous
- Works as hotel housekeeper
- 20 pack-year smoking history, current smoker

### Physical Examination Findings
- **Vital Signs:** BP 118/76 mmHg, HR 82 bpm, BMI 28 kg/m2
- **General:** Well-appearing woman in no acute distress
- **Abdomen:** Soft, non-tender, no palpable masses
- **Lower Extremities:** Left leg edema, 2+ pitting to mid-thigh
- **Pelvic/Rectal Examination:**
  - External genitalia normal
  - Speculum examination reveals a large friable, exophytic cervical mass approximately 5 cm in diameter with necrotic areas and contact bleeding
  - Bimanual examination: cervical mass is fixed, extending to the left parametrium; palpable fullness in the left parametrium extending toward but not reaching the pelvic sidewall; uterus not mobile
  - Rectovaginal examination: parametrial involvement confirmed bilaterally, more prominent on left; rectal mucosa intact

### Diagnostic Workup
- **Cervical Biopsy:** Squamous cell carcinoma, keratinizing type, HPV-related (p16 positive)
- **HPV Testing:** High-risk HPV positive (type 16)
- **Complete Blood Count:** Hemoglobin 10.8 g/dL, WBC 9,200/microL, Platelets 298,000/microL
- **Comprehensive Metabolic Panel:** Creatinine 1.4 mg/dL (elevated), BUN 28 mg/dL
- **MRI Pelvis:**
  - Cervical mass measuring 5.2 x 4.8 x 4.5 cm
  - Tumor extends into bilateral parametria (left greater than right)
  - Left parametrial extension approaches but does not reach pelvic sidewall
  - Left external iliac lymph node measuring 2.2 cm (suspicious for metastasis)
  - Left hydroureter and hydronephrosis secondary to ureteral obstruction
  - Bladder and rectal mucosa appear intact
- **CT Chest/Abdomen:** No pulmonary metastases, no para-aortic lymphadenopathy, left hydronephrosis confirmed
- **PET-CT:** Intense FDG uptake in cervical mass (SUV 18), left external iliac node (SUV 12), and left common iliac node (SUV 8); no distant metastatic disease
- **Cystoscopy:** Bladder mucosa intact, no tumor invasion
- **Examination Under Anesthesia:** Confirmed bilateral parametrial involvement, tumor does not reach pelvic sidewalls

### Diagnosis
**Cervical Cancer, Squamous Cell Carcinoma, FIGO Stage IIIC1**
- IIB features: Parametrial invasion bilaterally
- IIIC1: Pelvic lymph node involvement (elevated to Stage III per 2018 FIGO staging)
- Associated left ureteral obstruction with hydronephrosis

### Staging (2018 FIGO)
- **Stage IIIC1:** Pelvic lymph node metastasis only
  - Tumor 5 cm with bilateral parametrial involvement
  - Positive pelvic lymph nodes on imaging
  - No para-aortic nodal involvement
  - No distant metastases

### Management Plan

**Immediate Interventions:**
1. **Left ureteral stent placement** by interventional radiology/urology to relieve obstruction and preserve renal function before treatment
2. Smoking cessation counseling (critical - smoking reduces radiation therapy effectiveness and increases complications)
3. Nutritional assessment and optimization

**Primary Treatment - Definitive Chemoradiation:**

*Radiation therapy is standard of care for stage IIB and above - NOT surgery*

**External Beam Radiation Therapy (EBRT):**
- 45-50 Gy to the pelvis in 25 fractions over 5 weeks
- Extended field to include para-aortic region if positive nodes at that level (not needed in this case)
- Intensity-modulated radiation therapy (IMRT) to minimize bowel and bladder toxicity

**Concurrent Chemotherapy:**
- **Cisplatin** 40 mg/m2 IV weekly during external beam radiation (5-6 weekly doses)
- Radiosensitizer - improves survival by 30-50% compared to radiation alone

**Intracavitary Brachytherapy:**
- Following completion of EBRT
- Tandem and ovoid or ring applicator placement
- Total brachytherapy dose to achieve cumulative dose of 80-90 Gy to point A
- Critical for local control

**Treatment Timeline:**
- Total treatment duration should not exceed 8 weeks (delays worsen outcomes)
- Weekly cisplatin during weeks 1-5 of EBRT
- Brachytherapy typically during weeks 5-7

**Supportive Care During Treatment:**
1. Antiemetics for cisplatin-induced nausea
2. IV hydration with cisplatin
3. Monitor renal function (already compromised)
4. Manage radiation-induced diarrhea, cystitis, fatigue
5. Nutritional support
6. Vaginal dilator use to prevent stenosis (starting after treatment)

**Monitoring During Treatment:**
- Weekly CBC and metabolic panel
- Clinical examination to assess tumor response
- Renal function monitoring (ureteral stent in place)

**Post-Treatment Surveillance:**
- Physical examination and Pap smear every 3 months for first 2 years
- Imaging (PET-CT or MRI) at 3-6 months post-treatment to assess response
- If complete response: continue surveillance
- If residual disease: consider salvage options (exenteration if localized)

**Why Not Surgery?**
- Stage IIB or higher with parametrial involvement is NOT treated surgically as primary therapy
- Combining radical hysterectomy with radiation increases morbidity without improving survival
- Chemoradiation is the standard of care for locally advanced cervical cancer

**Counseling Points:**
- Treatment is curative intent with 60-70% 5-year survival for stage IIIC1
- Radiation will induce permanent menopause
- Sexual function counseling - vaginal stenosis prevention with dilators
- Smoking cessation is critical
- Treatment should not be delayed

### Prognosis
- Stage IIIC1 cervical cancer: approximately 60-70% 5-year survival with optimal chemoradiation
- Favorable prognostic factors: squamous histology, complete response to treatment
- Negative factors: large tumor size, nodal involvement, continued smoking

### Clinical Image
![Cervical Cancer on MRI](image_03.png)

**Image Description:** Sagittal T2-weighted MRI image of the pelvis demonstrating a large cervical mass with high signal intensity disrupting the normal cervical stroma. The tumor extends into the parametria bilaterally. Associated left hydroureter is visible secondary to ureteral obstruction by the tumor mass. The bladder and rectum appear intact without evidence of mucosal invasion.

**Attribution:** MRI findings in cervical cancer staging as described in radiology literature and Radiopaedia cervical cancer staging resources.

---

## Summary of Key Learning Points

1. **Ovarian cancer** presents late (70% stage III/IV) with nonspecific symptoms; high-grade serous is most common histology; management involves cytoreductive surgery and platinum-based chemotherapy; BRCA testing should be offered to all patients

2. **Lynch syndrome** is the most common hereditary cause of endometrial cancer; universal tumor testing with IHC for MMR proteins is recommended; positive Lynch syndrome has implications for patient surveillance and family testing

3. **Locally advanced cervical cancer** (stage IIB and beyond) is treated with definitive chemoradiation, NOT surgery; concurrent cisplatin improves survival; total treatment duration should not exceed 8 weeks

4. **PARP inhibitors** represent a major advance in ovarian cancer maintenance therapy for BRCA-mutated and HRD-positive tumors

5. **Sentinel lymph node mapping** has become standard for surgical staging of endometrial cancer and reduces lymphadenectomy morbidity

6. **Genetic testing** should be considered in gynecologic cancers with family history suggestive of hereditary syndromes or specific histologic/molecular features