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Uterus (excludes Cervix)

Epithelial tumors

Squamous cell carcinoma

Reviewer: Mohamed Mokhtar Desouki, MD, PhD (see Reviewers page)
Revised: 22 August 2011, last major update August 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.


● Primary uterine squamous cell carcinoma is rare, and associated with pyometra


● Rare tumors are considered verrucous carcinoma if have deep pushing border


● Primary endometrial squamous cell carcinoma is uncommon, accounting for 0.1% to 0.5% of all uterine cancers; most cases are extensions of cervical primary
● Co-existing primary adenocarcinoma of endometrium helps establish that the squamous component is of endometrial origin
● Predisposing factors include: chronic pyometra (present in 30% of cases), cervical stenosis, uterine prolapse or inversion, endometrial squamous metaplasia, history of pelvic radiation

Clinical features

● Most often found in white non-obese women age 67+ years
● Presents with vaginal bleeding in 69% of cases
● 36% of woman are nulliparous
● Not caused by estrogen, not associated with HPV

Prognostic factors

● Lymphovascular and myometrial invasion are poor prognostic factors
● Survival is 70-80% in stage I tumors, but only 20-25% with stage III tumors


● Surgery with postsurgical radiation or chemotherapy

Gross description

● Resembles endometrioid carcinomas on gross examination, but occasionally may be white and sometimes have a condylomatous appearance

Micro description

● Criteria for diagnosis include: (1) no co-existing adenocarcinoma, (2) no continuity between tumor and cervical squamous epithelium, and (3) no invasive cervical squamous cell carcinoma
● Often prominent keratinization, as well as areas which appear benign
● Some tumors have prominent spindle cell growth pattern suggesting a diagnosis of sarcomatoid squamous cell carcinoma
● Papillary squamous cell carcinoma is a variant that consists of papillary structures with thin, fibrovascular cores covered by several layers of squamous epithelium with large amounts of cytoplasm and pleomorphic and hyperchromatic nuclei

Micro images

Squamous cell carcinoma

No glandular component was seen in this tumor, and no involvement of the cervix was present

The tumor cells have clear cytoplasm and might be mistaken for clear cell adenocarcinoma, but keratinization and other evidence of squamous differentiation were present elsewhere

Endometrioid adenocarcinoma with squamous differentiation

This well-differentiated adenocarcinoma contains large foci of benign-appearing, squamous epithelium (adenocarcinoma with squamous metaplasia or adenoacanthoma)

Several morules appear in this well-differentiated adenocarcinoma. Note that the glandular component of this case is malignant by the usual criteria. Figures 81 and 82 show details of the morules in this case (figures 80-82 are from the same patient)

This morule from the case illustrated in figure 80 is surrounded by malignant but well-differentiated glands. The cells of the morule do not show keratinization or intracellular bridges but do demonstrate sheet-like growth, eosinophilic and glassy cytoplasm, and a decreased, nuclear/cytoplasmic ratio compared with the immediately adjacent glandular cells; most of them are spindle shaped. This tumor may be designated as adenocarcinoma with squamous or morular metaplasia or adenoacanthoma, but most importantly, the glandular component is well-differentiated or grade I

This is a detail of another morule from the same case illustrated in figures 80 and 81. Note the central necrosis, which does not imply malignant squamous differentiation

In this tumor, the glandular component is poorly differentiated, and the non-keratinizing, squamous component is cytologically malignant, focally spindled, and invades at the top center and bottom center into the surrounding reactive stroma. This tumor may also be designated as adenosquamous carcinoma

In this adenosquamous carcinoma, the glandular component is poorly differentiated, and the squamous element is histologically malignant, keratinizing and invasive

This adenosquamous carcinoma shows mostly the squamous component, except for a single malignant gland located slightly above and to the left of the center. The squamous component is judged malignant by the usual cytologic criteria, as well as by mitotic activity and destructive stromal invasion. More importantly, the glandular component of this tumor was poorly differentiated

In this case, the squamous elements are cytologically malignant (adenosquamous carcinoma). Some of the squamous cells appear to drop off into the surrounding stroma to create a pseudosarcomatous pattern

Cytology images

Adenocarcinoma with squamous differentiation (endometrial aspirate): the clumped tumor cells toward the center of the illustration represent adenocarcinoma, but the two spindled cells with an eosinophilic cytoplasm at the upper left indicate a squamous component

Positive stains

● p63; Ki-67 (15%), vimentin
● Also p21, p27, bcl2, BAG1, VEGF, Chk2

Negative stains

● ER, PR, HPV, CK 8/18, CK7, CK20

Differential Diagnosis

● Cervical squamous cell carcinoma (see above)
● Endometrioid carcinoma with massive squamous differentiation
● Secondary spread from cervical squamous cell carcinoma
● Squamous metaplasia
● Lesions of intermediate trophoblast

End of Uterus > Epithelial tumors > Squamous cell carcinoma

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