High-Grade Serous Ovarian Adenocarcinoma Case – Comprehensive Study Notes

Patient Profile and Clinical Presentation

• 65-year-old Filipino female, “Ma. Ana Tee”
  • Post-menopausal age bracket with highest incidence of ovarian carcinoma
  • Past medical history: mild, well-controlled hypertension only
  • No chronic liver disease, tuberculosis, or other chronic infections
• Chief complaints (2 weeks)
  • Progressive shortness of breath (SOB)
  • Increasing abdominal distension
• Vital signs (stable)
  • BP $130/80\text{ mmHg}$ • HR $88\,\text{bpm}$ • RR $20\,/\text{min}$ • T $36.8^{\circ}\text{C}$ • SpO$_2$ $96\%$ (room air)
• Physical findings
  • Chest: ↓ breath sounds over right lower lung; no crackles/wheezes
  • Abdomen: moderate distension, shifting dullness → ascites
  • No rebound tenderness, hepatosplenomegaly, palpable mass, peripheral edema, skin stigmata of chronic liver disease, or lymphadenopathy

Definitions of Key Terms (Condensed)

• Ascites – pathologic intraperitoneal fluid accumulation
• Dyspnea – subjective SOB
• Shifting dullness – percussion sign of free fluid
• Hepatosplenomegaly – concurrent liver + spleen enlargement
• Stigmata of chronic liver disease – spider angiomas, palmar erythema, caput medusae, etc.
• Hypertension – persistent BP > $130/80\text{ mmHg}$ (per ACC/AHA)
• Lymphadenopathy – pathologic nodal enlargement

Sample Collection & Processing Overview

• Blood (venipuncture)
  • CBC/ESR → lavender-top (EDTA)
  • Serum chem/CA-125 → SST or plain red-top
• Urine (mid-stream clean-catch) → routine urinalysis
• Pleural fluid (thoracentesis)
  • Chemistry/ADA: plain or heparinized
  • Cell count → EDTA
  • Microbiology → sterile container
  • Cytology → heparinized/plain
• Ascitic fluid (paracentesis) → tube set identical to pleural

Analytical Principles of Ordered Tests

• Urinalysis – Sysmex UF-4000 flow cytometry (scatter + fluorescence)
• CBC/ESR – Sysmex XN-10 (impedance + fluorescence flow cytometry)
• Serum chemistry – VITROS 5600 (MicroSlide/MicroTip/MicroWell, etc.)
• Gram stain – crystal-violet–iodine retention
• Culture – inoculation on selective media → isolate pathogens
• Imaging
  • Chest X-ray – differential absorption of ionizing radiation
  • CT – rotating X-ray beam + computer reconstruction
  • Abdominal US – high-frequency sound reflection

Pre-Analytical & Analytical Interferences (Key Points)

• Urine: menstrual contamination, disinfectant in container, collection timing
• Blood: prolonged tourniquet, hemolysis, wrong tube/order of draw
• Pleural/Ascitic: traumatic tap, inadequate volume, labeling errors
• Testing phase: hemolysis, lipemia, icterus (CBC/Chem), pH shift (pleural), bacterial overgrowth (urine)

Laboratory Results & Interpretation

• Urinalysis – entirely within normal limits.

• Serum Chemistry

• Electrolytes, renal & hepatic panels: all normal
• CA-125 $=1{,}300\,\text{U/mL}$ (≫ ULN $35\,\text{U/mL}$) → strong ovarian cancer marker

• CBC & ESR

• Hgb $10.5\,\text{g/dL}$, Hct $32\%$ → normocytic normochromic anemia of chronic disease
• ESR $60\,\text{mm/hr}$ → marked chronic inflammation/malignancy

• Pleural Fluid (Right)

• Cloudy yellow; TP $4.2\,\text{g/dL}$; LDH $350\,\text{U/L}$; glucose $55\,\text{mg/dL}$; WBC $1{,}200/\mu L$ (80 % lymphocytes)
• Light’s criteria:
  \frac{\text{Pleural Protein}}{\text{Serum Protein}}=\frac{4.2}{6.5}=0.64>0.5 → exudate
  \frac{\text{Pleural LDH}}{\text{Serum LDH}}=\frac{350}{220}=1.59>0.6 → exudate
• ADA $12\,\text{U/L}$ (<40) → TB unlikely
• Cytology: atypical glandular cells, IHC CK7+, CK20-, PAX8+, WT1+, p53+ → Müllerian/ovarian serous adenocarcinoma

• Ascitic Fluid

• Cloudy; TP $3.8\,\text{g/dL}$ (exudate)
• Albumin $2.0\,\text{g/dL}$; Serum Alb $3.8\,\text{g/dL}$ → SAAG:
  $\text{SAAG}=3.8-2.0=1.8\,\text{g/dL}$ (>1.1 indicates portal HTN component; malignancy can show mixed picture)
• WBC $950/\mu L$, 75 % lymphocytes; ADA $9\,\text{U/L}$ → TB unlikely
• Cytology: suspicious malignant cells (confirmation pending)

Imaging Findings

• Chest X-ray: moderate right pleural effusion, costophrenic angle blunting
• Abdominal ultrasound: complex right adnexal mass ≈ $6\,\text{cm}$ with septations + moderate ascites
• CT Abdomen: peritoneal thickening & omental nodularity → peritoneal carcinomatosis

Differential Diagnosis ("Big 4") – Key Discriminators

Combined clinical + laboratory picture most consistent with ovarian primary.

Final Diagnosis

High-grade serous ovarian adenocarcinoma (HG-SOC) with peritoneal carcinomatosis and malignant right-sided pleural effusion.

Diagnostic Criteria Synopsis

• Age/sex: post-menopausal woman
• Physical: ascites + isolated right pleural effusion
• Hematology: anemia of chronic disease, ↑ESR
• Chemistry: CA-125 > $1{,}000\,\text{U/mL}$
• Pleural fluid: exudate, malignant cytology with Müllerian IHC profile
• Ascitic fluid: exudate, suspicious cells, SAAG > $1.1\,\text{g/dL}$
• Imaging: adnexal mass, peritoneal thickening/omental caking, pleural effusion

Epidemiology & Pathogenesis (Essentials)

• Ovarian cancer = 7th most common female malignancy worldwide; 5th in Philippines (2020: 5,395 new cases; 3,379 deaths)
• HG-SOC origin: serous tubal intra-epithelial carcinoma (STIC) at fimbrial end ⇒ exfoliation to ovary/peritoneum
  • Early TP53 loss → genomic instability
  • BRCA1/2 mutations ↑ risk (defective homologous recombination repair)
• Spread pattern
  1. Intra-peritoneal seeding → ascites, omental cake
  2. Trans-diaphragmatic lymphatic channels/defects → right pleural space
• Pathophysiologic links to labs
  • VEGF & cytokines ↑ vascular permeability → exudative effusions
  • Chronic inflammation → ↑ESR, anemia of chronic disease (↑hepcidin ↓ iron availability)
  • Peritoneal irritation → ↑CA-125

Major Complications

• Bowel / bladder obstruction
• Large-volume ascites → malnutrition, pedal edema
• Distant metastasis (lung, liver, nodes)
• Neuropathy, pelvic pain, fatigue → ↓ quality of life
• Ultimately death without effective control

Treatment Strategy (Standard of Care)

1. Neoadjuvant chemotherapy (3–4 cycles)
   • Carboplatin + Paclitaxel ± Bevacizumab (q3w)
2. Interval debulking surgery aiming for R0 (TAH-BSO, omentectomy, cytoreduction)
3. Adjuvant chemotherapy (same doublet × 3–4 cycles)
4. Maintenance
   • PARP inhibitors (Olaparib, Niraparib) esp. if BRCA/HRD+
   • Anti-angiogenic (Bevacizumab)
5. Symptom control
   • Thoracentesis, paracentesis, diuretics, opioids, oxygen
   • Anemia management: iron, PRBC, ESA
   • Supportive: anti-emetics (Ondansetron), laxatives, anticoagulation, PPIs
6. Monitoring & follow-up
   • Serial CA-125, imaging, labs; genetic testing (BRCA 1/2); early palliative care

Prevention & Risk Reduction

• Combined oral contraceptives (≥5 yrs use ↓ risk ≈50 %)
• Surgical options for high-risk women
  • Bilateral salpingo-oophorectomy (BSO)
  • Bilateral salpingectomy with ovarian retention (BSOR)
  • Tubal ligation, hysterectomy (modest risk ↓)
• Parity & breastfeeding decrease lifetime ovulatory cycles
• Genetic counseling/testing for BRCA1/2; prophylactic surgery if positive

Advanced / Adjunct Diagnostic Modalities

Key Equations & Cut-offs to Memorize

• Light’s criteria (exudate when any true):
  \frac{\text{Pleural Protein}}{\text{Serum Protein}}>0.5
  \frac{\text{Pleural LDH}}{\text{Serum LDH}}>0.6
  \text{Pleural LDH}>\tfrac23 \text{ULN Serum LDH}
• SAAG: \text{SAAG}=\text{Serum Albumin}-\text{Ascites Albumin}
  • \text{SAAG}\ge1.1\,\text{g/dL} → portal HTN related
  • \text{SAAG}<1.1\,\text{g/dL}$$ → malignancy, TB, pancreatitis, etc.

Ethical & Practical Notes

• Early detection remains challenging; >70 % present with advanced disease.
• Equity issue: access to CA-125, imaging, and cytology services in low-resource settings.
• Genetic counseling essential to inform relatives of hereditary risk (BRCA, HRD).
• Palliative care integration improves symptom burden and quality of life.

Study Pearls

• Isolated right pleural effusion + ascites + elevated CA-125 in elderly woman → think ovarian carcinoma.
• HG-SOC almost universally harbors TP53 mutation; BRCA status guides PARP inhibitor use.
• Always apply Light’s criteria to effusions; memorize numeric cut-offs.
• CA-125 is useful for monitoring but nonspecific for screening.
• VEGF mediates malignant effusion formation; Bevacizumab targets this pathway.