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Uterus (excludes Cervix)

Epithelial tumors

Small cell carcinoma


Reviewer: Mohamed Mokhtar Desouki, MD, PhD (see Reviewers page)
Revised: 25 August 2011, last major update August 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

Definition
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● Aggressive carcinoma of definite endometrial origin resembling small cell carcinoma of the lung and other organs
● Note: 25-50% of typical endometrial adenocarcinomas contain some endocrine cells

Terminology
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● Also called oat cell carcinoma of endometrium, neuroendocrine small cell carcinoma of endometrium

Epidemiology
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● Uncommon, <1% of endometrial carcinomas, ~60 cases reported in English literature
● Mean age 60 years, range 23-78 years

Sites
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● Originates at body or isthmus with no cervical involvement
● Nonprimary cases may originate in cervix and extend to uterine corpus

Etiology
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● Unknown
● Heterotopic nuclear localization of beta-catenin may play a role in invasion and be associated with aggressive behavior
● Associated with endometrioid adenocarcinoma, adenosquamous carcinomas, mixed mullerian tumors and endometrial stromal sarcomas in some cases, but pure tumors also reported

Clinical features
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● Abnormal vaginal bleeding or pain related to metastatic tumor
● No reported cases in nulliparous patients

Case reports
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● 59 year old woman (J Reprod Med 2010;55:81), 87 year old woman (Arch Gynecol Obstet 2010;282:413)

Prognostic factors
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● Stage I tumors have 5 year survival of 60%

Treatment
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● Total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic and paraaortic lymph node dissection, followed by radiation therapy and chemotherapy (Semin Oncol 2007;34:57)

Gross description
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● Bulky, polypoid, ill-defined with invasion of myometrium

Micro description
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● Resembles small cell carcinoma at different sites
● Cells are small to intermediate size forming sheets, cords and nests, as well as single cells with scanty cytoplasm, hyperchromatic nuclei and high mitotic rate (Am J Surg Pathol 1994;18:364)
● Zonal necrosis and vascular invasion are common
● Complex atypical endometrial hyperplasia may be present adjacent to the tumor

Micro images
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Resembles small cell carcinoma of lung

Cytology description
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● Cytologically similar to counterparts in lung and other sites
● Small tumor cells arranged as single cells or in groups and cords with barely visible cytoplasm, darkly staining nuclei with finely stippled chromatin with characteristic molding and inconspicuous nucleoli (Acta Cytol 1998;42:978)
● Differential diagnosis includes adenocarcinoma with neuroendocrine features, small cell non-keratinizing squamous cell carcinoma, endometrial stromal sarcoma, rhabdomyosarcoma, primitive neuroectodermal tumor, non-Hodgkin's lymphoma, metastatic breast carcinoma

Cytology images
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Pleural fluid

Positive stains
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● Keratin, neuron specific enolase, CD56, synaptophysin, chromogranin (occasionally); also p16, c-KIT, PDGFRA (J Reprod Med 2010;55:81, Arch Gynecol Obstet 2010;282:413)

Negative stains
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● Chromogranin (usually), vimentin, muscle-specific actin, desmin, alpha-fetoprotein, S100, glial fibrillary acid protein, CD45

EM description
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● Cytoplasmic dense core secretory granules and indistinct cell junctions (J Obstet Gynaecol Res 1997;23:9)
● Intense nuclear beta-catenin accumulation and cyclin D1 immunoreactivity restricted to carcinoma cells invading lymphatic vessels, although no mutation in exon 3 of the beta-catenin gene or exon 15 of the APC gene

Differential Diagnosis
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● Endometrial carcinomas with argyrophil cells
● Metastatic small cell carcinoma, particularly from cervix
● Mixed mullerian tumors
● Stomal sarcoma
● Primitive neuroectodermal tumor
● Eosinophilic metaplasia
● Complex hyperplasia with atypia
● Clear cell carcinoma

End of Uterus > Epithelial tumors > Small cell carcinoma


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