Uterus
General
Staging-carcinoma and carcinosarcoma


Topic Completed: 31 January 2019

Minor changes: 28 July 2020

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PubMed search: Staging[TIAB] corpus uteri (carcinoma OR carcinosarcoma)

Carlos Parra-Herran, M.D.
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Cite this page: Parra-Herran C. Staging-carcinoma and carcinosarcoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusstaging.html. Accessed November 26th, 2020.

Pathologic TNM staging of carcinoma and carcinosarcoma of the corpus uteri, AJCC 8th edition and FIGO 2018 update
Definition / general
  • International Federation of Gynecology and Obstetrics (Fédération Internationale de Gynécologie et d'Obstétrique, FIGO) recommends surgical / pathologic staging of uterine carcinoma (which now includes carcinosarcoma)
  • Clinical staging is assigned only if primary radiation or chemotherapy is indicated over primary surgery (record as cT, cN, cM)
  • Clinical and pathologic staging is used if the surgeon feels systemic regional lymph node sampling is not indicated
  • Otherwise, surgical / pathologic staging is indicated, assigned at the time of definitive surgical management
  • Initial stage should not be changed due to disease progression or recurrence or based on response to initial radiation therapy or chemotherapy that precedes primary tumor resection
  • American Joint Committee on Cancer (AJCC) / TNM system now includes staging categories for lymph node metastases according to metastatic tumor size: isolated tumor cells (ITCs), micrometastases and macrometastases
Essential features
Primary tumor [pT] and FIGO () stage
  • pTX: primary tumor cannot be assessed
  • pT0: no evidence of primary tumor
  • pT1 (I): tumor confined to corpus uteri
    • pT1a (IA): tumor limited to endometrium or invades < 50% of the myometrium
    • pT1b (IB): tumor invades ≥ 50% of the myometrium
  • pT2 (II): tumor invades stromal connective tissue of the cervix but does not extend beyond uterus
  • pT3 (III): tumor involving serosa, adnexa, vagina or parametrium
    • pT3a (IIIA): tumor involves serosa or adnexa (direct extension or metastasis)
    • pT3b (IIIB): vaginal involvement (direct extension or metastasis) or parametrial involvement
  • pT4 (IVA): tumor invades bladder mucosa or bowel mucosa (bullous edema is not sufficient to classify a tumor as pT4)


Notes:
  • Endocervical glandular involvement only should be considered as stage I and not stage II
  • pTis is no longer a staging category
  • Myometrial invasion:
    • According to the ISGYP recommendations, this variable should be reported as "none of less than half (< 50%)" or "half or more (≥ 50%)" of the myometrial wall thickness
    • This approach is relatively easy and obviates in most cases the need to locate the endomyometrial junction (which is difficult when the junction is completely obliterated or not sampled in the sections)
    • In addition, other variables than can be reported include myoinvasion in terms of absolute numbers (invasive carcinoma depth in mm / myometrial thickness in mm) and the percentage of myometrial wall involved by tumor (a derivative of the absolute measurements in mm)
    • Assessment should be performed at the deepest point of tumor invasion on a full thickness section of the wall spanning from mucosal surface to serosa (Figure 1)
    • Involvement of adenomyosis by carcinoma does not by itself portend a worse prognosis
      • These cases behave similarly to stage IA tumors (Gynecol Oncol 1990;37:401, Int J Gynecol Pathol 2010;29:445)
      • Carcinoma is confined to the endometrium / adenomyosis when:
        • Focus of carcinoma has a round or ovoid shape with a smooth and convex outer contour (regardless of its size) (Figure 2)
        • Outer contour smoothly continues with adjacent uninvolved endomyometrial interface
        • Residual endometrial type stroma or benign endometrial glands are present in the periphery or within the focus
        • There is no significant desmoplastic reaction
    • If myometrial invasion arises from areas of adenomyosis, the location of the deepest myoinvasive point with respect to the entire uterine wall should be recorded (inner versus outer wall) (Figure 3)
      • There is controversy in whether to assign stage IA or IB to a carcinoma with foci of invasion in the outer wall arising from adenomyosis
        • By stating the location of the invasive carcinoma, these lesions will be classified as stage IB
      • Of note, if the foci are few and clearly arising from deep adenomyosis, this should be noted in the report
        • There is emerging evidence showing that these lesions behave more indolently, similar to stage IA tumors (Mod Pathol 2019;32:1029A)
      • If, on the other hand, myoinvasive carcinoma from adenomyosis is rather extensive and seen throughout the wall, it is better to apply the approach described above and classify the tumor as stage IB (Int J Gynecol Pathol 2019;38:S93)
    • If the tumor is exophytic at the point of deepest myometrial invasion, the nearest endomyometrial junction should be identified and depth should be measured from that point
      • Same recommendation applies to tumors arising from or involving an endometrial polyp
    • If the carcinoma at the point of deepest invasion involves a leiomyoma, the myometrial thickness should be obtained at that point anyway (in other words, including the leiomyoma) (Int J Gynecol Pathol 2019;38:S93)
    • In tumors with microcystic, elongated and fragmented (MELF) pattern of invasion, the presence of desmoplasia alone is sufficient to determine the deepest area of tumor invasion
    • Lymphovascular space invasion (LVI) should not be included in the assessment of myometrial invasion
  • Cervical stromal involvement:
    • Presence of cervical stromal involvement defines stage II
    • Depth of invasion into the cervical stroma and margin status should be reported, as it may influence adjuvant radiation treatment (Brachytherapy 2019;18:606)
    • Assessment of cervical involvement is inconsistent between gynecologic pathologists (Am J Surg Pathol 2011;35:289)
    • Uppermost endocervical mucinous gland in the section should be considered as the upper limit of the endocervix
      • If unsure whether tumor is in cervix or lower uterine segment, identify the most proximal endocervical mucinous gland, which will define the boundary between these anatomic locations (Figures 4 and 5)
    • Stromal invasion can be seen as obviously infiltrative glands or cells with desmoplasia or as complex architecture relative to the normal endocervical glandular compartment
    • Carcinoma confined to the surface or to endocervical glands can be reported but does not modify stage or impact prognosis
    • It is recommended to measure depth of invasion into the cervix in mm and the thickness of the cervical wall at that level
      • Alternatively, it can be reported in terms of invasion confined to 1/3 of the wall, 2/3 of the wall or extending to the outer third of the wall
    • It is recommended to measure the distance between tumor and margin: distal cervical / vaginal mucosa and parametrial margins
  • Serosal involvement:
    • Involvement of the uterine serosa is and adverse prognostic factor and warrants a stage IIIA
    • Involvement of the serosa is diagnosed when the tumor perforates through the mesothelium lined outer surface of the uterus; this is seen as an area of disruption of the serosa with tumor involvement, sometimes with soft tissue or other structures attached to it
    • According to ISGYP guidelines, tumor infiltrating the entire myometrial thickness and reaching submesothelial fibroconnective tissue should also be reported as serosal involvement (Int J Gynecol Pathol 2019;38:S93)
  • Adnexal involvement (versus synchronous ovarian carcinoma):
    • Distinguishing between the following is relevant for staging and treatment:
      • Synchronous ovarian and endometrial tumors
      • Primary endometrial with metastatic ovarian involvement
      • Primary ovarian with metastatic endometrial involvement
    • However, it is often difficult to separate these scenarios on pathologic examination and one may only suggest one possibility over the others
    • Synchronous ovarian carcinoma is present in up to 30% of reproductive age women with endometrial cancer (Int J Womens Health 2014;6:691, Obstet Gynecol 2005;106:693)
      • When present, synchronous ovarian and endometrial carcinomas usually have the same histologic type (vast majority are low grade endometrioid)
      • Synchronous endometrial and ovarian endometrioid carcinoma have good prognosis, similar to those with only endometrial or only ovarian stage I cancer (Int J Gynecol Cancer 2014;24:54, Clin Cancer Res 2008;14:5840)
    • Features that support 2 synchronous carcinomas include:
      • Different histologic types or tumor grades
      • Endometrial carcinoma has absent or only superficial myometrial invasion
      • Ovarian carcinoma is confined to the ovary
      • Absence of lymphovascular space invasion
      • Different patterns of mismatch repair (MMR) or hormone receptor expression by IHC
    • Conversely, secondary ovarian involvement by a primary endometrial tumor should be considered when:
      • Endometrial tumor has deep myometrial invasion, lymphovascular space invasion, serosal or parametrial involvement
      • Bilateral ovarian involvement
      • Ovarian tumor involves surface and has extensive lymphovascular space invasion
      • Both tumors show similar MMR and hormone receptor expression by IHC
Regional lymph nodes [pN] and FIGO () stage
  • pNX: regional lymph nodes cannot be assessed
  • pN0: no regional lymph node metastasis
    • pN0(i+): isolated tumor cells in regional lymph node(s) ≤ 0.2 mm
  • pN1 (IIIC1): regional lymph node metastasis to pelvic lymph nodes
    • pN1mi: regional lymph node metastasis (> 0.2 mm but ≤ 2 mm in diameter) to pelvic lymph nodes
    • pN1a: regional lymph node metastasis (> 2 mm in diameter) to pelvic lymph nodes
  • pN2 (IIIC2): regional lymph node metastasis to paraaortic lymph nodes, with or without positive pelvic lymph nodes
    • pN2mi: regional lymph node metastasis (> 0.2 mm but ≤ 2 mm in diameter) to pelvic lymph nodes
    • pN2a: regional lymph node metastasis (> 2 mm in diameter) to pelvic lymph nodes

Notes:
  • Emerging data shows that patients with low volume disease (ITCs and micrometastases) have better recurrence free survival compared to those with macrometastatic nodal disease (Ann Surg Oncol 2016;23:1653, Gynecol Oncol 2017;146:240)
  • When measuring size of tumor within lymph nodes, tumor foci should be measured separately; then the largest individual size is reported
  • It is recommended to report extranodal extension, if present (although its significance is for now uncertain)
Distant metastasis [pM] and FIGO () stage
  • pM0: no distant metastasis
  • pM1 (IVB): distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease or lung, liver or bone; it excludes metastasis to paraaortic lymph nodes, vagina, pelvic serosa or adnexa)
Stage grouping and FIGO stage
Stage 0: Tis N0 M0
Stage I: T1 N0 M0
Stage IA: T1a N0 M0
Stage IB: T1b N0 M0
Stage II: T2 N0 M0
Stage III: T3 N0 M0
Stage IIIA: T3a N0 M0
Stage IIIB: T3b N0 M0
Stage IIIC1: T1 - 3 N1 M0
Stage IIIC2: T1 - 3 N2 M0
Stage IVA: T4 any N M0
Stage IVB: any T any N M1
Histopathology - degree of differentiation
  • G1: ≤ 5% of a nonsquamous or nonmorular solid growth pattern
  • G2: 6 - 50% of a nonsquamous or nonmorular solid growth pattern
  • G3: > 50% of a nonsquamous or nonmorular solid growth pattern

Notes on pathologic grading:
  • Notable nuclear atypia, inappropriate for the architectural grade, raises the grade by 1 (1 to 2 and 2 to 3); although it has been suggested that tumors with significant nuclear atypia are classified as grade 3 regardless of the architecture
  • Serous, clear cell and carcinosarcoma are high risk and considered grade 3
  • Adenocarcinomas with benign squamous elements (squamous metaplasia) are graded according to the glandular component
Diagrams / tables

Contributed by Carlos Parra-Herran, M.D.

Table 1. Staging of endometrial carcinoma as per FIGO (2018 update) and AJCC 8th edition
FIGO (2018) AJCC (2018) Description
I T1 Tumor confined to the uterus
1A T1a Tumor confined to the endometrium or invades < 50% of the myometrial wall
1B T1b Tumor invades > 50% of the myometrial wall
II T2 Tumor infiltrates cervical stroma
III T3, N1 Tumor extends outside the uterus
IIIA T3a Tumor involves serosa or adnexa (direct extension or metastases)
IIIB T3b Tumor involves vagina or parametria (direct extension or metastases)
IIIC N1 Tumor with pelvic or paraaortic lymph node metastasis
IIIC1 N1 mi Micrometastases in pelvic lymph nodes (> 0.2 mm or 200 cells but ≤ 2 mm)
N1a Macrometastases in pelvic lymph nodes (> 2 mm in size)
IIIC2 N2 mi Micrometastases in paraaortic lymph nodes (> 0.2 mm or 200 cells but ≤ 2 mm)
N2a Macrometastases in paraaortic lymph nodes (> 2 mm in size)
IV T4, M1 Tumor invades bladder or bowel mucosa or involves distant organs
IVA T4 Tumor invades bladder mucosa or bowel mucosa
IVB M1 Distant metastases (including intraabdominal metastases and inguinal lymph nodes;
excluding metastases to vagina, pelvic serosa or adnexa)
N0i+ Isolated tumor cells in regional lymph nodes*

* Isolated tumor cells (ITCs) category is recognized in the AJCC (TNM) system but not in the FIGO system

Images hosted on other servers:

Endometrial carcinoma

Microscopic (histologic) images

Contributed by Carlos Parra-Herran, M.D.

Depth of myometrial invasion

Endometrial carcinoma involving adenomyosis

Myometrial invasion from adenomyosis

Cervical involvement by endometrial carcinoma (pT2)

Board review style question #1
The defining feature of stage T3a / IIIA carcinoma of the uterine corpus is:

  1. Involvement of bladder or rectal mucosa
  2. Involvement of cervical stromal tissue
  3. Involvement of uterine serosa or adnexa
  4. Involvement of vagina or parametrial tissue
  5. Pelvic lymph node metastases
Board review answer #1
C. Involvement of uterine serosa or adnexa

Reference: Uterus - Staging - corpus uteri - carcinoma and carcinosarcoma

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