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Uterus (excludes Cervix)

Epithelial tumors

Serous carcinoma


Reviewer: Mohamed Mokhtar Desouki, MD, PhD (see Reviewers page)
Revised: 23 August 2011, last major update August 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

Definition
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● Type 2 (non-endometrioid) carcinoma, often arises in black, multiparous and nonobese women
● Associated with endometrioid adenocarcinoma, clear cell carcinoma and ovarian serous carcinoma

Terminology
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● Also called papillary serous carcinoma, uterine papillary serous carcinoma (UPSC), endometrial type 2 tumor

Epidemiology
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● Compared to endometrioid carcinoma, UPSC is less common (10%), older age, and more common in black vs. white women
● Associated with p53 mutations (considered an early event), usually clinically understaged

Etiology
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● Not associated with estrogen secretion as endometrioid tumors are; may follow radiation therapy for cervical carcinoma
● Associated with atrophic endometria

Clinical features
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● Presents with vaginal bleeding
● Resembles ovarian serous carcinoma and spreads throughout abdomen in a similar manner; may metastasize to bladder, simulating a bladder primary
● May be a superficial endometrial tumor with extensive peritoneal disease, suggesting tubal or angiolymphatic invasion
● Minimally invasive disease: no myometrial invasion; usually cured if NO extrauterine involvement by careful staging; may have minimal disease involving ovarian surface epithelium, serous adenofibroma or omentum; similar behavior as endometrial intraepithelial carcinoma if 1 cm or less of tumor

Prognostic factors
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● Often recurs and death common from tumor spread, despite aggressive surgery, chemotherapy or radiotherapy
● 40% with stage I disease die of disease, 60% will get retroperitoneal involvement

Treatment
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● Extended surgical staging and tumor debulking
● Adjuvant therapy with taxane and platinum based combination chemotherapy, with or without radiation therapy
● Do not respond to progesterone therapy

Gross description
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● Uterus is small for a high-grade tumor
● Associated with endometrial polyps and is often polypoid
● 25% have primary endocervical involvement
● Drop metastases to vagina are common
● Transtubal spread is common, may create ovarian implants and omental tumor nodules

Micro description
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● Resembles ovarian serous carcinoma; usually well-formed papillae (thick and thin) or tubules with “lobster claw” appearance containing highly pleomorphic tumor cells containing prominent nucleoli, small detached buds and tufts
● May have glandular pattern and resemble villoglandular carcinoma on low power
● Prominent myometrial invasion, frequent mitotic activity and necrosis
● Usually marked desmoplastic response resembling carcinosarcoma; angiolymphatic invasion common; 40% have psammoma bodies
● Associated with endometrial atrophy, not hyperplasia
● Abrupt transition from normal to serous carcinoma is common
● Considered high-grade and is not graded using FIGO
● Note: if one gland is serous, consider tumor to be aggressive (others say must be 25% of tumor)
● Minimally invasive serous carcinoma: no myometrial invasion

Micro images
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Typical broad fibrovascular cores lined by stratified cells, forming secondary papillae and cellular buds


In this field, papillae are small and complex, and cells are poorly differentiated


Complex papilloglandular pattern with slit-like lumina, in contrast to round lumina of endometrioid carcinoma


Complex papilloglandular pattern with exfoliation of small groups of cells into lumina


Classic small but round hyperchromatic nuclei; also necrotic debris and exfoliated tumor cells in lumina; fibrovascular stromal cores of papillae are infiltrated by lymphocytes


Invasion of myometrial lymphatics, psammoma bodies within papillary nests of tumor cells


Extensive invasion of myometrial lymphatics is evident, with moderate lymphocytic response

Cytology description
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● 2/3 have malignant pap smears since buds and tufts break off
● Features of high-grade malignancy with readily identified malignant features, but site of origin may be unknown
● Positive peritoneal cytology upgrades the stage

Positive stains
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● p53 (useful for differentiating from endometrioid carcinoma), CK7, CA125; also p16, Ki67 (high index) and vimentin

Negative stains
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● ER (may be low level), PR, CEA, CK20

Molecular description
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● Most cases are aneuploid
● Mutations of TP53 represent the most well characterized alteration in >90% of cases, but 50% have loss of p53 (TP53) function
● Also HER2/neu overexpression (18-61%), EGFR overexpression (36-56%, Br J Cancer 2009;100:89), PIK3CA mutations (15%, Gynecol Oncol 2009;113:370)
● Claudin-3 and claudin-4 are highly expressed; PTEN mutations are rare
● 63% of cases showed loss of heterozygosity of chromosome 1p

Differential Diagnosis
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Clear cell carcinoma: may have overlapping features, distinction not important since management is same
● Minimally invasive disease may resemble eosinophilic metaplasia or complex hyperplasia with atypia

End of Uterus > Epithelial tumors > Serous carcinoma


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