What is the prognosis for a 9cm adult granulosa cell tumor with follicle-stimulating hormone (FSH), progesterone receptor (PR), and estrogen receptor (ER) positivity, telomerase reverse transcriptase (TERT) c228t promoter mutation, and phosphatidylinositol 3-kinase catalytic alpha (PIK3CA) mutation, without forkhead box L2 (FOX2L), and with preoperative rupture?

Prognosis for 9cm Adult Granulosa Cell Tumor with Preoperative Rupture

This tumor carries a significantly worse prognosis than typical adult granulosa cell tumors, with preoperative rupture being the single strongest independent predictor of recurrence and the 9cm size exceeding the 5cm threshold associated with adverse outcomes. 1, 2

Key Prognostic Factors Present in This Case

Tumor Rupture (Most Critical Factor)

• Preoperative tumor rupture is the only independent predictive factor for recurrence in molecularly-defined adult granulosa cell tumors, with ruptured tumors showing significantly higher relapse rates compared to intact stage IA disease 2
• Intraperitoneal tumor rupture is one of the most consistently reported adverse prognostic factors across multiple ESMO guidelines 1
• This automatically classifies the tumor as at least stage IC, which has worse prognosis than stage IA 2

Tumor Size (9cm)

• Tumor size >5cm has uncertain but likely adverse prognostic value, and your 9cm tumor substantially exceeds this threshold 1
• Larger tumor size has been associated with increased recurrence risk in recent cohort studies 3

Molecular Profile Considerations

• The presence of TERT c228t promoter mutation is strongly associated with disease recurrence and progression, with 64% incidence in recurrent tumors versus only 26% in primary non-recurrent tumors 4
• The PIK3CA mutation does not independently define prognosis or hormone sensitivity in granulosa cell tumors 4
• The absence of FOXL2 mutation (implied by "without FOX2L") is unusual, as virtually all adult-type granulosa cell tumors harbor the pathognomonic FOXL2 402C→G mutation 1, 5

Expected Clinical Course

Recurrence Risk

• With tumor rupture present, this patient faces substantially elevated recurrence risk compared to the baseline 32% recurrence rate for molecularly-defined adult granulosa cell tumors 2
• The median time to first relapse is typically 7.4 years, with 75% of relapses occurring within 10 years 2
• However, recurrences can occur up to 20-37 years after initial diagnosis, necessitating lifelong surveillance 1, 4

Mortality Risk

• Of patients who develop recurrence, 48% die of disease, typically within a median of 15.3 years from initial diagnosis 2
• Multiple-site recurrences are common, and nearly half occur asymptomatically 2

Recommended Management Approach

Immediate Surgical Management

• Complete surgical staging with total abdominal hysterectomy and bilateral salpingo-oophorectomy (if postmenopausal) is mandatory, including infracolic omentectomy, biopsies of diaphragmatic peritoneum, paracolic gutters, pelvic peritoneum, and peritoneal washings 4
• Lymph node dissection only if nodes appear grossly abnormal 4
• Endometrial curettage must be performed to exclude concomitant uterine cancer given the hormone receptor positivity 1, 4

Adjuvant Chemotherapy (Strongly Indicated)

• Platinum-based chemotherapy with BEP regimen (bleomycin, etoposide, cisplatin) for 3-4 cycles is recommended for ruptured tumors, as this represents high-risk stage IC disease 4, 1
• Alternative option is carboplatin/paclitaxel for 6 cycles 1
• The presence of TERT mutation further supports aggressive adjuvant therapy 4

Surveillance Strategy (Lifelong and Intensive)

• Inhibin B levels every 2-4 months for the first 2 years, as this is the most sensitive tumor marker 4, 6
• CT abdomen/pelvis/chest every 3-6 months for the first 2 years 4
• Continue surveillance every 6 months beyond 5 years indefinitely, given the TERT mutation and rupture history 4

Critical Pitfalls to Avoid

• Do not assume standard stage IA prognosis applies - the rupture fundamentally changes risk stratification 2
• Do not discontinue surveillance after 5 years - recurrences occur decades later, especially with TERT mutation 4
• Do not use hormone therapy as primary adjuvant treatment - platinum-based chemotherapy is required for high-risk features 4
• Do not omit endometrial evaluation - the ER/PR positivity increases risk of concomitant endometrial pathology 1, 4

Quality of Life Considerations

• The need for lifelong surveillance creates ongoing psychological burden and healthcare utilization 2
• BEP chemotherapy carries risks of pulmonary toxicity (bleomycin), ototoxicity and nephrotoxicity (cisplatin), requiring careful monitoring 1
• Late recurrences often require multiple surgical procedures and chemotherapy lines, significantly impacting long-term quality of life 2