Where do cervical and endometrial adenocarcinomas typically metastasize to?

Metastatic Sites for Cervical and Endometrial Adenocarcinoma

Cervical Adenocarcinoma Metastatic Pattern

Cervical adenocarcinoma primarily metastasizes to pelvic lymph nodes, followed by para-aortic lymph nodes, with distant spread to lungs, liver, bones, and brain. 1

Lymphatic Spread

• Pelvic lymph nodes are the dominant site of metastasis, with metastases occurring more frequently to the internal/external iliac and obturator lymph nodes (P2 region) compared to para-aortic nodes 2
• Para-aortic lymph node metastases are significantly associated with common iliac and sacral lymph node (P1) positivity 2
• Lymph node metastases occur in up to 50% of bulky stage IB and II cervical cancers 3
• The risk of lymph node metastasis is strongly associated with tumor volume; microinvasive carcinomas have very low rates of parametrial and lymph node involvement 3

Distant Metastases

• Hematogenous spread occurs to lungs, liver, bones, and brain 3
• Cervical adenocarcinoma can metastasize to the ovaries, particularly HPV-related endocervical adenocarcinomas, which may present as unilateral masses (65.5% of cases) that can simulate primary ovarian tumors 4
• Extension into the lower uterine segment/corpus endometrium may increase risk of ovarian metastases, possibly through retrograde uterine/transtubal spread 4

Endometrial Adenocarcinoma Metastatic Pattern

Endometrial adenocarcinoma exhibits a distinct lymphatic spread pattern that is intermediate between cervical and ovarian cancer, metastasizing almost equally to both pelvic and para-aortic lymph nodes, with distant spread to lungs, bones, liver, and brain. 2

Lymphatic Spread

• Pelvic lymph node metastases occur in approximately 10% of endometrial cancer patients 3
• In 30% of cases with pelvic lymph node involvement, para-aortic lymph nodes are also involved 3
• The incidence of both para-aortic and pelvic lymph node metastases is 67%, much higher than cervical cancer (36%) and similar to ovarian cancer (61%) 2
• Para-aortic lymph node involvement alone (without pelvic nodes) occurs in 7% of cases 2
• Metastases extend to pelvic and para-aortic lymph nodes as classified in FIGO stage IIIC 1

Predictors of Lymphatic Metastasis

• Lymphovascular space invasion (LVSI) is the strongest predictor of lymph node metastases, particularly when assessed by immunohistochemistry with antibodies against factor VIII-related antigen or CD31 3
• Depth of myometrial invasion is an independent predictor of lymphatic metastasis 3, 5
• Tumor grade is independently associated with lymphatic metastasis 5
• MELF (microcystic, elongated, and fragmented) glandular invasion pattern predicts lymph node metastases 3
• Cervical involvement is NOT an independent predictor of lymphatic metastasis when controlling for uterine factors 5

Distant Metastases

• Endometrioid and clear cell carcinomas metastasize hematogenously to lungs, bones, liver, and brain, and can rarely manifest as solitary metastases 3
• Serous carcinomas show extensive peritoneal spread, similar to ovarian cancer 3
• Stage IVB includes distant metastases to intra-abdominal and/or inguinal lymph nodes 1
• Vaginal metastases are classified as stage IIIB 1

Direct Extension

• Tumor can invade the serosa and/or adnexa (stage IIIA) 1
• Bladder and/or bowel mucosa invasion occurs in stage IVA disease 1

Key Clinical Pitfall

A critical distinction is that endometrial cancer has a unique lymphatic spread pattern where it can directly metastasize to both pelvic AND para-aortic lymph nodes simultaneously, unlike cervical cancer which spreads primarily to pelvic nodes first 2. This has important implications for surgical staging, as comprehensive pelvic and para-aortic lymphadenectomy extending to the renal veins should be considered for adequate staging 6, 7.