Revisión carcinoma de endometrio

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Review Article

Endometrioid Carcinoma of the Uterine Corpus: A Review of Its Pathology With Emphasis on Recent Advances andProblematic Aspects

*Philip B. Clement and Robert H. Young

*Departments of Pathology, Vancouver General Hospital and Health Sciences Center and the University of British Columbia,Vancouver, British Columbia, Canada; and James Homer Wright Pathology Laboratories of the Massachusetts General

Hospital and Department of Pathology, Harvard Medical School, Boston, Massachusetts, U.S.A.

Summary: This review considers the pathologic features of endometrioid carcinomaof the uterine corpus, which accounts for approximately 80% of endometrial adeno-carcinomas, with an emphasis on its histologic features, recent advances, and prob-lematic aspects. In addition to typical endometrioid carcinoma, the variants of endo-metrioid carcinoma covered include secretory carcinoma, villoglandular endometrioidcarcinoma, endometrioid carcinoma with small nonvillous papillae, endometrioid car-cinomas with microglandular and sertoliform patterns, and endometrioid carcinomaswith metaplastic changes. These changes include a variety of different appearances of squamous epithelia (ranging from mature and keratinizing to immature with onlysubtle evidence of a squamous nature), clear cells, surface changes resembling syn-cytial metaplasia or microglandular hyperplasia, ciliated cells, oxyphilic cells, andspindled epithelial cells (sarcomatoid carcinoma). The last is one of several variantsthat may cause a biphasic appearance, all of which should be distinguished from themalignant mllerian mixed tumor. Rare findings in endometrioid carcinomas includehyalinization, psammoma bodies, and foci of stromal metaplasia such as osteoid.Unusual growth patterns of endometrioid carcinomas include involvement of adeno-myosis, the diffusely infiltrating pattern of myoinvasion, and a previously unem-phasized pattern of myoinvasion with pinched off glands that may be cystic or havea pseudovascular appearance, often with a myxoid stromal reaction. Other aspects of endometrioid carcinoma discussed are its immunoprofile, grading, cervical involve-ment (including a hitherto undescribed burrowing pattern of extension within thecervix that can result in underdiagnosis of stage IIB disease), carcinoma arising in thelower uterine segment, carcinoma arising in polyps and adenomyomas, carcinoma inyoung women, tamoxifen-related carcinoma, associated ovarian endometrioid carci-noma, and peritoneal keratin granulomas. Finally, the differential diagnosis of endo-metrioid carcinoma is briefly considered with a section on benign mimics, includingcurettage-related changes, menstrual changes, adenomyosis-related problems,metaplastic changes, atypical polypoid adenomyoma, radiation atypia, and papillaryproliferations, and a section on metastatic colonic carcinoma. Key Words:UterusEndometriumCarcinomaEndometrioid.

Address correspondence and reprint requests to Dr. Robert H. Young, Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114.

Advances in Anatomic PathologyVol. 9, No. 3, pp. 145184 2002 Lippincott Williams & Wilkins, Inc., Philadelphia

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HISTORICAL PERSPECTIVEAND INTRODUCTION

As with almost all major forms of neoplasia, the firstcertain mention of endometrial carcinoma is lost in the

sands of time. Much of the nineteenth century literatureon uterine cancer was dominated by coverage of cancerof the uterin cervix, and discussion of carcinoma of thecorpus was either nonexistent or cursory at best. In 1900,cancer of the corpus received its first detailed analysis inwhat we consider to be the first major text on uterinecancer. That work transformed knowledge of this subjectby the extent, depth, and quality of the coverage. In thatbook, one of Dr. Thomas S. Cullens great trilogy of gynecologic pathology texts (1,2) entitled Cancer of theUterus (3), 8 of 26 chapters were devoted to the topic.Two chapters dealt with symptomatology and treatment,and the remaining chapters were exclusively or predomi-

nantly on gross and microscopic features (Fig. 1), withseparate chapters on differential diagnosis and squamouscell carcinoma. Approximately 220 pages were devotedto the subject, and they are accompanied by the beautifulillustrations of the legendary medical illustrator MaxBrdel (4) and his colleagues. Subsequent to Cullenstimeless work, there were relatively few advances of great note until the last three decades.

Until recently, endometrial adenocarcinoma was con-sidered relatively homogeneous, and discussion of mor-phologic variants in standard texts up to circa 1980 wasusually limited and restricted to issues such as the sig-nificance of squamous elements being of benign (adeno-

acanthoma) or malignant (adenosquamous carcinoma)appearance, the presence of secretory change or mucin-ous differentiation in some cases, and the existence of occasional clear cell carcinomas. There has, however,been a great expansion of interest in the topic dating tothe recognition of serous carcinoma, which became es-tablished as an entity during the late 1970s and early1980s (57). Entry into the lexicon of serous carcinomarequired that the usual form of endometrial carcinomareceive its own designation. We are not certain who firstapplied the term endometrioid (used in the ovary since1961, *) to these tumors, but the earliest use of it in theliterature pertaining to endometrial carcinoma that wehave been able to find was by Hendrickson and Kempson(8) in their well-known book of 1980. The term quickly

became accepted and was incorporated in the 1994World Health Organization classification of endometrialcarcinomas (9). Serous carcinoma subsequently receivedso much attention in the coverage of endometrial carci-noma that although some attention was focused on nuances

of the morphology of endometrioid carcinoma, some as-pects of its pathologic characterization have been over-looked or underemphasized. It is the purpose of thisreview to highlight unusual aspects and to discuss time-honored issues in the pathology of endometrioid carci-noma. A subsequent review also to appear in this Journalconsiders nonendometrioid carcinomas of the corpus(10).

Our primary purpose here is to discuss in detail thehistologic features of endometrioid adenocarcinomas of the corpus (which account for approximately 80% of endometrial adenocarcinomas) with emphasis on histo-logic variants. Although the histologic distinction of

typical endometrioid carcinoma from other histologictypes of endometrial carcinoma is usually straightfor-ward, the wide variety of subtypes of endometrioid car-cinoma, some recently described, can result in diagnosticproblems, including their potential misclassification as amore aggressive histologic type of endometrial carcinoma.The differential diagnosis of endometrioid adenocarci-noma with complex atypical endometrial hyperplasia isnot considered here, because it is a topic unto itself andhas been extensively discussed in the recent literature.

CLASSIFICATION OF MORPHOLOGICVARIANTS OF ENDOMETRIOIDADENOCARCINOMAS OF THE

UTERINE CORPUS

The listing in Table 1 is used to highlight the variouspatterns, cell types, and miscellaneous other changes thatmay be encountered in endometrioid carcinomas of theuterine corpus. Knowledge of these features is importantto the pathologist so as to facilitate correct recognition of the tumor, but some of them would not necessarily re-quire specific mention in the pathology report, becausetheir presence has no bearing on behavior or treatment; anotation may be indicated, particularly when a feature isconspicuous. Two or even more of these variant featuresmay be present in individual tumors, sometimes makingthe diagnosis particularly challenging, but for convenienceof coverage, each change is considered on its own.

Endometrioid carcinomas with a significant compo-nent of a second cell type (arbitrarily defined as >10%)are placed in the category of a carcinoma of mixed celltype according to the recommendations of the WorldHealth Organization. As such, they organizationally be-

* According to Long and Taylor, the term endometrioid was in-troduced in 1961 by Santesson to refer to ovarian tumors with theappearance of endometrial carcinoma. Santesson was the first investi-gator to note the relatively high frequency of these tumors in the ovary(24.4% in his study). (Long ME, Taylor HC Jr. Endometrioid carci-noma of the ovary. Am J Obstet Gynecol 1964;90: 936950.)

P. B. CLEMENT AND R. H. YOUNG146

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long in the second part of this exploration of the patho-logic characterization of endometrial carcinoma to bepublished later (10). Endometrioid carcinomas with acomponent of another subtype accounting for less than10% of the tumor (which nosologically still belong in theendometrioid group) are discussed in a later section, be-cause even a minor component of a second cell type maybe associated with diagnostic problems.

GROSS FEATURES

The variants of endometrioid carcinoma are indistin-guishable on gross examination. In some cases, particu-larly those in which most of the tumor has been removedby curettage, grossly visible tumor may not be apparentdespite obvious tumor on microscopic examination. Con-versely, one should not mistake the lush thick endome-trium of the late secretory phase for carcinoma. Visibletumors vary from sessile polypoid masses that may fillthe endometrial cavity (Plate 1A) to nodules or irregularthickened plaques that may be localized or diffuse. The

FIG. 1. (A) Typical endometrioid adenocarcinoma with branching tubular glands. ( B) Endometrioid carcinoma with squamous differentiation of themorular type (adenoacanthoma). The typical intraglandular location of the squamous elements is seen. (Reproduced, from Cullen TS. Cancer of theuterus . Philadelphia: WB Saunders, 1909; Figs. 189 and 200.)

TABLE 1. Endometrioid carcinomas of the uterine corpus

TypicalSecretoryWith papillae

VilloglandularSmall nonvillous papillae

MicroglandularSertoliformWith metaplastic changes

Squamous differentiationClear cell change, not otherwise specifiedSurface changes resembling syncytial metaplasia or

microglandular hyperplasiaCiliated cellsOxyphilic (or oncocytic) cellsWith spindled epithelial cells (sarcomatoid)

With a poorly differentiated carcinomatous componentWith other patterns

Diffuse growth with low-grade cytologyExtensive hyalinizationPinched off glands that may be cystic or pseudovascular

With other rare findingsPsammoma bodiesStromal metaplasia (e.g., osteoid)

With


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surface of the tumor is typically irregular or shaggy.Some high-grade tumors may diffusely infiltrate themyometrium with limited mucosal abnormality. Grossevaluation is sometimes difficult when numerous largeleiomyomas distort and bulge irregularly into the endo-

metrial cavity. In such cases, small foci of carcinomabetween the leiomyomas may be overlooked. Occasionaltumors are confined to the lower uterine segment as dis-cussed later. The neoplastic tissue is typically pale tan towhite and soft, but it is occasionally firm or even gritty.Foci of hemorrhage, necrosis, or both are often visible,especially in poorly differentiated tumors. Myometrialinvasion by similar tissue is grossly evident in somecases but is often only detectable microscopically. Asimilar comment pertains to cases in which carcinomainvolves adenomyosis, an issue discussed in detail later.Rarely, tumor involving adenomyosis is evident grosslyas white neoplastic tissue that cuffs small cysts (Fig. 2).

Assiduous gross inspection of the cervix should be per-formed to detect tumor spread, but the latter is oftendiscovered only on microscopic examination of routinelysubmitted sections of cervix. Rare endometrioid carcino-mas have been confined to one horn of a bicornuateuterus (11).

MICROSCOPIC FEATURES OF TYPICALENDOMETRIOID CARCINOMA

The amount of tumor and its topography in hysterec-tomy specimens are highly variable. Most of the endo-metrium may be lined but not thickened by tumor, or the

tumor may have striking focality and an abrupt inter-face with nonneoplastic endometrium. In other cases, thetumor may be multifocal within a background of endo-metrial hyperplasia. In some cases, there is strikingpolypoid intracavitary growth of tumor without anymyometrial invasion, whereas in other cases, strik-ing myometrial invasion may be seen in cases with mini-mal tumor in the endometrium or none at all if curet-tage has removed it. In occasional cases of small-volumedisease, a biopsy or curettage entirely removes the tu-mor, and the hysterectomy specimen is negative. Spe-cific aspects related to patterns of invasion, includingoccasional differences in the morphology of the neoplas-tic glands when they invade, are considered separatelylater.

Typical endometrioid carcinomas (see Plate 1B) arecomposed of tubular glands, most of which are mediumsized but may range from small to large and cystic. Theglands are generally round to oval but may be angulated

FIG. 2. Endometrioid carcinoma involving adenomyosis. The sec-tioned surface of the myometrium shows many white foci of tumor,mostly with well-defined margins and some with central cysts repre-senting the foci of adenomyosis involved by the carcinoma.

Revisión carcinoma de endometrio

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