For a patient whose hysteroscopic biopsy suggested serous endometrial carcinoma but final surgical pathology reveals grade 2 endometrioid carcinoma with 46 % myometrial invasion, no lymph‑vascular space invasion, no cervical involvement, and no extra‑uterine disease, what is the appropriate adjuvant management?

Adjuvant Management for Discordant Histopathology: Hysteroscopy Serous vs. Final Endometrioid

Treat Based on Final Surgical Pathology

For this patient with grade 2 endometrioid carcinoma, 46% myometrial invasion, no LVSI, no cervical involvement, and no extrauterine disease, the appropriate adjuvant management is observation or vaginal brachytherapy. The final surgical pathology supersedes the hysteroscopic biopsy findings, and this patient's disease characteristics place her in the intermediate-risk category for endometrioid carcinoma 1, 2.

Understanding the Discordance

Why Hysteroscopic Biopsies Are Unreliable

• Preoperative biopsies have only moderate concordance with final pathology (correlation coefficient 0.52), with concordance rates of 73% for grade 1,52% for grade 2, and 53% for grade 3 tumors 3.
• Hysteroscopic-guided biopsies achieve 80% concordance for detecting endometrial cancer overall, but can miss the true histologic subtype in 20-30% of cases 4.
• Serous carcinoma is particularly prone to sampling error on small biopsies, and mixed tumors containing both serous and endometrioid components are common 5, 6.
• The final surgical specimen provides definitive diagnosis because it allows complete evaluation of the entire tumor, whereas biopsies sample only a small portion 1, 7.

Clinical Implication of the Discordance

• When serous carcinoma is suggested on biopsy but final pathology shows pure endometrioid histology, treat according to the final pathology 6.
• Mixed tumors containing <25% serous differentiation behave like endometrioid carcinoma, while those with ≥50% serous differentiation behave like pure serous carcinoma 6.
• Since your final pathology shows grade 2 endometrioid with no mention of serous component, this is treated as pure endometrioid carcinoma 1.

Risk Stratification for This Patient

Stage IB, Grade 2 Classification

• With 46% myometrial invasion (which is <50%), this patient has Stage IA disease by 2009 FIGO criteria 8.
• Grade 2 endometrioid histology with <50% myometrial invasion and no LVSI places her in the intermediate-risk category 2.
• The absence of LVSI is critical—LVSI positivity would reclassify her to high-intermediate risk requiring more aggressive therapy 1, 2.

Prognostic Factors Present

• Favorable factors: No LVSI, no cervical involvement, no extrauterine disease, <50% myometrial invasion 1, 2.
• Intermediate-risk factor: Grade 2 histology 2.
• Five-year survival for surgical stage I endometrial cancer with no adverse risk factors beyond grade and myometrial invasion is 92.7% 1.

Recommended Adjuvant Treatment Options

Primary Recommendation: Observation

• Observation alone is the standard of care for intermediate-risk endometrioid endometrial carcinoma, supported by Level I evidence 2.
• The GOG 99 and PORTEC-1 trials demonstrated that pelvic radiation reduces locoregional recurrence but does not improve overall survival in intermediate-risk patients 1, 2.
• For Stage IA, Grade 2 disease without adverse risk factors, observation is preferred by NCCN guidelines 1.

Alternative Option: Vaginal Brachytherapy

• Vaginal brachytherapy can be considered if additional intermediate-risk factors are present, such as age ≥60 years 1.
• PORTEC-2 trial showed excellent vaginal and pelvic control rates with vaginal brachytherapy alone, with significantly less toxicity than pelvic radiation 1.
• Common regimens include 3 fractions of 7 Gy at 0.5 cm depth or 5 fractions of 6 Gy to the vaginal surface 1.
• Brachytherapy should begin as soon as the vaginal cuff heals, but no later than 12 weeks after surgery 1.

What NOT to Do

• Do not use pelvic external beam radiation unless additional high-risk features emerge (age ≥70 years with LVSI would be category 2B indication) 1.
• Do not use chemotherapy—cisplatin-based chemoradiation is reserved for high-risk disease (Grade 3 with ≥50% invasion, Stage II-III, or non-endometrioid histologies) 2.
• Do not treat based on the hysteroscopic biopsy showing serous features—the final pathology is definitive 6, 7.

Common Pitfalls to Avoid

Overtreatment Based on Initial Biopsy

• The initial serous carcinoma diagnosis on hysteroscopy might prompt consideration of aggressive therapy, but this would be inappropriate overtreatment 2.
• Serous carcinoma requires chemotherapy ± radiation, but this patient has pure endometrioid carcinoma on final pathology 2.
• Adding chemoradiation to intermediate-risk endometrioid carcinoma provides no survival benefit and adds significant gastrointestinal and hematologic toxicity 2.

Misclassifying the Stage

• With 46% myometrial invasion, this is Stage IA (<50% invasion), not Stage IB (≥50% invasion) 8.
• This distinction is critical because Stage IB, Grade 2 with adverse factors might warrant pelvic radiation, whereas Stage IA, Grade 2 typically does not 1.

Ignoring Age and LVSI Status

• If the patient is ≥60 years old, vaginal brachytherapy becomes more strongly recommended even without other adverse factors 1.
• If LVSI were present (which it is not in this case), the patient would be reclassified to high-intermediate risk requiring vaginal brachytherapy ± pelvic radiation 1, 2.

Surveillance Strategy

• Regular follow-up with pelvic examination and attention to symptoms is appropriate 1.
• Most recurrences in intermediate-risk patients occur in the vagina, which are typically detected by symptoms or examination rather than imaging 1.
• Vaginal dilator use should be discussed if brachytherapy is chosen, beginning 2-4 weeks after completion 1.