Cervix
Adenocarcinoma
Endometrial adenocarcinoma (cytology)
Last author update: 1 July 2017
Last staff update: 10 June 2024
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PubMed search: Cervix cytology endometrial adenocarcinoma [title]
Table of Contents
Definition / general | Essential features | Pathophysiology | Etiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Cytology description | Cytology images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Baardsen E, Rosa M, Parra-Herran C. Endometrial adenocarcinoma (cytology). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixendometrialadenocarcinomacyto.html. Accessed December 26th, 2024.
Definition / general
- 10th most common type of cancer, representing 3.6% of all new cancer cases in the United States (SEER - Cancer Statistics Review 1975 - 2014)
- Most common invasive gynecologic malignancy; approximately 25.7 new cases per 100,000 women per year
- Predominantly a tumor of postmenopausal women
- Peak incidence in women in their late 50s and early 60s
- Rare in women younger than 40
- 90% present with abnormal vaginal bleeding, including menorrhagia, metrorrhagia and postmenopausal bleeding
- Two types: type 1 (classic or usual) and type 2 (variant types)
- Type 1 is more common, approximately 80% of endometrial adenocarcinomas
- Type 2 includes FIGO grade 3 endometrioid endometrial adenocarcinomas and those variants with nonendometrioid histology (serous, clear cell, undifferentiated, carcinosarcoma)
- Most common extracolonic cancer in women with Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome)
Essential features
- Cervical Pap testing is not recommended for screening endometrial pathology; however, exfoliated malignant cells may be present in cervicovaginal cytology preparations
- Cytologic findings are dependent on the grade of the tumor; histologic grade 1 tumors shed few abnormal cells with minimal atypia, whereas higher grade tumors shed cells exhibiting greater pleomorphism
- Testing for high risk HPV is negative
Pathophysiology
- Type 1 (classic or usual):
- Prolonged exposure to endogenous or exogenous estrogen leads to continued proliferation of the endometrium
- Evolves through endometrial intraepithelial neoplasia (EIN) / atypical hyperplasia to adenocarcinoma (FIGO grade 1)
- Type 2 (variant types):
- Most occur "de novo" with no identifiable precursor lesion
- Serous intraepithelial carcinoma is the proposed preinvasive precursor lesion of endometrial serous carcinoma
Etiology
- Type 1 (classic or usual):
- Unopposed hyperestrogenism, usually in the context of chronic anovulation, obesity or estrogen hormone replacement therapy
- Type 2 (variant types):
- Uncertain; often no history of hyperestrogenism
Clinical features
- Cervical smear is 45% sensitive in detecting endometrial adenocarcinoma (Acta Cytol 2003;47:410)
- Cervical smear is useful to detect cervical involvement of endometrial carcinoma (Acta Cytol 2002;46:284)
- ThinPrep may be more sensitive than conventional smears (Cancer 2002;96:338, Diagn Cytopathol 2000;23:260)
- Low risk (< 2%) of nodal spread if normal cervical smear (Obstet Gynecol 2003;101:445)
Diagnosis
- Cervical Pap test is primarily a screening test for cervical lesions and is not intended for detection of endometrial lesions; however, if atypical glandular cells are seen, further investigation is required to rule out neoplasia (Asian Pac J Cancer Prev 2017;18:1145)
- Per the American Society for Colposcopy and Cervical Pathology (ASCCP) Updated Consensus Guidelines for Managing Abnormal Cervical Cancer Screening Tests and Cancer Precursors (2014), the initial work up for women of all ages with atypical endometrial cells on Pap screening is endocervical and endometrial sampling
- Cervical Pap cytology is atypical, suspicious or positive for malignancy in 38% to 90% of endometrial adenocarcinomas (Diagn Cytopathol 2007;35:448)
Prognostic factors
- Type 1 (classic or usual):
- Tend to have a favorable prognosis after hysterectomy
- Type 2 (variant types):
- Generally has a poor prognosis
- Histologic type, FIGO stage, histologic grade, angiolymphatic invasion (particularly for stage 1 tumors), ER, p53, HER2 and ploidy
Case reports
- 40 year old woman with a history of polycystic ovaries with peritoneal keratin granulomatosis associated with endometrioid adenocarcinoma (Case Rep Obstet Gynecol 2017;2017:1863215)
- 45 year old woman with synchronous endometrial and ovarian cancer (Anticancer Res 2017;37:969)
- 62 year old woman with intestinal differentiated mucinous adenocarcinoma of the endometrium with sporadic MSI high status (Diagn Pathol 2017;12:39)
Treatment
- Grade 1: hysterectomy is treatment of choice for patients whom fertility is not a consideration
- Young women who desire fertility preservation may be treated nonsurgically
- Postoperative radiation if myometrial invasion > 50% thickness
- Grade 2: initial treatment is hysterectomy with postoperative radiation therapy to patients with myometrial invasion
- Grade 3: most cases have invaded the myometrium at the time of hysterectomy; adjuvant chemotherapy is often warranted
Cytology description
- Small, tight clusters or single round cells
- Enlarged (become larger with increasing grade of tumor), hyperchromatic nuclei
- Small to prominent nucleoli (become larger with increasing grade of tumor)
- Scant, cyanophilic, often vacuolated cytoplasm
- Mitotic figures and apoptotic bodies present
- Intracytoplasmic neutrophils within single cells or small groups ("bags of polys")
- In liquid based preparations, three dimensional groups and clusters or papillary configuration are common
- "Watery" or finely granular tumor diathesis is variably present; in liquid based preparations, it is often less prominent and identified as finely granular debris clinging to the periphery of clusters of cells
Cytology images
Contributed by Marilin Rosa, M.D. and Carmen Luz, M.D.
Endometrial adenocarcinoma
Endometrial group with atypia
Images hosted on other servers:
Various images
Positive stains
- Estrogen receptor (ER) [nuclear], progesterone receptor (PR) [nuclear], PAX8 [nuclear]
- CA-125: low specificity [luminal], vimentin: low specificity [cytoplasmic]
Negative stains
- Carcinoembryonic Antigen (CEA): low specificity [cytoplasmic]
- p16 (usually negative or only focally positive) [nuclear, cytoplasmic]
- HPV ISH
Molecular / cytogenetics description
- In 2013, the Cancer Genome Atlas (TCGA) Research Network published an integrated genomic characterization of endometrial carcinoma based on genomic data from array and sequencing based technologies; it proposed a classification that separates endometrial carcinomas into four groups (Nature 2013;497:67):
- Ultramutated cancers with DNA polymerase epsilon (POLE) mutations:
- Microsatellite stable tumors that account for 6% of low grade and 17% of high grade endometrioid endometrial carcinomas
- Hypermutated cancers with defective mismatch repair (MMR) and microsatellite instability (MSI):
- Exhibit frequent MLH1 promoter methylation and reduced MLH1 gene expression
- Account for 29% of low grade and 54% of high grade endometrioid endometrial carcinomas
- Low mutation rate cancers with low frequency DNA copy number abnormalities:
- Almost all (92%) of tumors have somatically altered PI3K pathway
- Accounts for 60% of low grade and 9% of high grade endometrioid carcinomas; 2% of serous carcinomas and 25% of mixed histology carcinomas
- Low mutation rate cancers with high frequency DNA copy number abnormalities:
- Accounts for > 95% of serous carcinomas and 75% of mixed histology carcinomas
- Ultramutated cancers with DNA polymerase epsilon (POLE) mutations:
Differential diagnosis
- Endocervical adenocarcinoma in situ:
- Distinction from invasive endometrial adenocarcinoma is problematic and often not possible in cytology specimens
- If tumor diathesis is present or cells are round with prominent nucleoli, the tumor is more likely invasive adenocarcinoma
- Endocervical polyp:
- Large vacuolated cells associated with neutrophils
- Histology reveals polyp with reactive endocervical cells
- No feathering, nuclear palisading or chromatin clearing present
- Intrauterine device (IUD) effect:
- Associated with IUD use
- Cells are indistinguishable morphologically from those of endometrial adenocarcinoma but their cellularity is scant
- Microglandular hyperplasia:
- Associated with contraceptive drugs and pregnancy
- Cytologic features vary and may include clear cells or aggregates of cells in strips, sheets, papillae, rosettes or corolla-like arrangements
- Should have no or rare foci of atypia, mitotic figures, apoptotic bodies or watery diathesis present (Pathologica 1993;85:607)
- Adenocarcinoma of other sites:
- Endocervical:
- Cells are more columnar and more commonly shed as sheets of cells in comparison to endometrial adenocarcinoma cells, which are more round and tend to exfoliate as single cells and small clusters
- Histiocytes are not seen in endocervical adenocarcinoma
- Usually the cytopathologist can only suggest or favor one site over another and final classification is made on histology
- Extrauterine / metastatic:
- Rare cells with features dependent on primary location
- Diathesis is usually absent
- Ovarian and tubal:
- More commonly associated with psammoma bodies
- Vaginal:
- Rare and often associated with a maternal history of DES exposure during pregnancy
- Endocervical:
Additional references
Board review style question #1
A 22 year old woman undergoes routine Pap screening. Her results reveal atypical endometrial cells. What is the next best step in the management of this patient?
- Diagnostic excisional procedure with interpretable margins
- Endocervical and endometrial sampling
- Immediate loop electrosurgical excision
- Repeat cotesting at 12 months
- Repeat cytology at 12 months
Board review style answer #1
B. Endocervical and endometrial sampling: per the American Society for Colposcopy and Cervical Pathology (ASCCP) Updated Consensus Guidelines for Managing Abnormal Cervical Cancer Screening Tests and Cancer Precursors (2014), the initial work up for women of all ages with atypical endometrial cells on Pap screening is endocervical and endometrial sampling.
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Reference: Endometrial adenocarcinoma (cytology)
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Reference: Endometrial adenocarcinoma (cytology)
