Serous EIC as an early form of uterine papillary serous carcinoma: recent progress in understanding its pathogenesis and current opinions regarding pathologic and clinical management.

Uterine papillary serous carcinoma (UPSC) is anaggressive form of endometrial cancer, that has a dismalprognosis [1–3]. Since its etiology is virtually unknown,physicians and research scientists who battle this diseasehave tried to identify its precursor lesions in order toimprove disease management through early detection.The term endometrial intraepithelial carcinoma (EIC), asa putative dprecursor lesionT of UPSC, was first proposed bySherman et al. in 1992 [3] and formalized by Ambros et al.in 1995 [4]. Almost at the same time, Spiegel described thesame disease as endometrial carcinoma in situ (ECIS) [5].EIC or ECIS was defined morphologically as replacementof endometrial surface epithelium and glands withoutmyometrial or stromal invasion by frankly malignant cellsidentical to UPSC tumor cells [3–5]. The terms of EIC andECIS, however, were challenged by Zheng et al. [6] byproposing a term called uterine surface carcinoma (USC)mainly because this putative precursor lesion is commonlyassociated with extrauterine serous carcinoma [3,4,7–12]and it does not just behave like intraepithelial carcinoma orcarcinoma in situ although morphologically no myometrialinvasion is associated. With similar reasons, Wheeler et al.proposed another term as minimal uterine serous carcinoma(MUSC, any non-invasive uterine serous carcinoma lessthan1cmingreatestdimension)[12]. This putativeprecursor lesion of UPSC is now being referred as serousEIC by the WHO classification [13]. The terminology ofthis endometrial lesion causes confusion in terms of itsbehavior and management. This commentary recommendsthat serous EIC be considered an early form of UPSC andprovides management guidelines based on our experienceand that of others.Does serous EIC behave like a truly intraepithelialcarcinoma? The significant number of serous EIC or stage1A UPSC presenting concurrently with extrauterine diseaseand its high recurrence rate argues strongly against serousEIC being an intraepithelial, that is, an in situ form ofUPSC. Wheeler et al. [12] reported on 21 serous EIC caseswithout myometrial invasion. Of these 21 patients, 7 wereassociated with extrauterine disease. Silva and Jenkins [11]reported on 16 cases of non-invasive UPSC in endometrialpolyps. Ten of them had clinical stage IA disease atpresentation. Of these 10 patients, 6 experienced abdominalrecurrences and 4 died of their diseases. Carcangiu et al. [7]reported 2 of the 13 stage IA UPSC cases died of diseasewith intra-abdominal carcinomatosis at 10 and 14 monthsafter their initial complete surgical staging. Recently,Slomovitz, et al. reviewed 32 serous EIC or stage 1A cases.Among the 32 patients without uterine invasion, surgicalstaging revealed that 13 (40%) had stage III or stage IVdisease [14]. It is currently unknown whether the size (lessthan one versus one cm or bigger) of non-invasive uterineserous carcinoma yields a prognostic difference.We recently reviewed 9 serous EIC cases (lesion lessthan 1 cm in size) and 8 stage 1A UPSC (lesions equal orlarger than 1 cm but no myometrial invasion) accessionedfrom the years 2000 to 2004 in the Department of Pathologyof Yale-New Haven Hospital. All 17 cases had completesurgical staging including omentectomy. We found that 6