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CASE REPORT Table of Contents   
Year : 2008  |  Volume : 51  |  Issue : 4  |  Page : 512-514
Endometrial intraepithelial carcinoma: A case report and brief review

1 Department of Cellular Pathology, The Princess Alexandra Hospital, Harlow, Essex CM20 1QX, United Kingdom
2 Department of Pathology, Dr. Ram Manohar Lohia Hospital, New Delhi, India

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This case report describes the precursor lesion of uterine papillary serous carcinoma (UPSC). A 65-year-old post-menopausal female presented with prolapse and vaginal discharge and underwent a hysterectomy revealing an atrophic endometrium, highly atypical endometrial glands, the lining cells of which showed pseudostratification, hobnailing, a high nuclear to cytoplasmic ratio, and prominent nucleoli. A p53 immunoreactivity score of 8 and a MIB-1 index of 80% was obtained leading to a diagnosis of endometrial intraepithelial carcinoma (EIC). Since serous EIC is commonly associated with extra-uterine serous carcinoma, it is a uniquely aggressive precursor lesion. Molecular studies support the hypothesis that EIC is a precursor of both uterine and extra-uterine invasive serous carcinomas. This is why the treatment protocol for EIC cases is total abdominal hysterectomy (TAH), accompanied by a staging procedure. In our patient, EIC was limited to the endometrium; associated with an excellent clinical outcome.

Keywords: Endometrial intraepithelial carcinoma, p53, uterine papillary serous carcinoma

How to cite this article:
Ram M, Bharadwaj M, Yadav R. Endometrial intraepithelial carcinoma: A case report and brief review. Indian J Pathol Microbiol 2008;51:512-4

How to cite this URL:
Ram M, Bharadwaj M, Yadav R. Endometrial intraepithelial carcinoma: A case report and brief review. Indian J Pathol Microbiol [serial online] 2008 [cited 2023 Jan 29];51:512-4. Available from:

   Introduction Top

The morphologic and clinical features of typical uterine papillary serous carcinoma (UPSC) have been well delineated but its precursor lesion, as defined by recent morphologic and molecular studies, has received little attention. [1]

   Case Report Top

A 65-year-old female presented with uterovaginal prolapse and whitish vaginal discharge since 6 months. She had undergone 6 normal-term vaginal deliveries and had reached menopause 20 years earlier. A vaginal examination revealed an atrophic uterus. A speculum examination showed 3 rd degree uterovaginal prolapse. Other investigations were normal.

Pathological findings

The hysterectomy specimen showed an atrophic uterus measuring 5x3x2 cm with an endometrial thickness of approximately 2 mm. The microscopic examination showed an atrophic endometrium with endometrial glands lined by atypical cells showing pseudostratification with focal hobnailing, a high nuclear to cytoplasmic ratio, dense cytoplasm, and hyperchromatic nuclei with prominent nucleoli. Increased mitotic activity (approximately 8-10 per 10 hpf), with atypical mitotic figures was seen [Figure 1]. Formalin fixed paraffin-embedded tissue blocks were used for evaluation with p53 monoclonal antibody and MIB-1(ki-67). Esophageal adenocarcinomas, known to overexpress p53 and demonstrate high proliferative rates, were used as positive controls. A negative control without a primary antibody was also evaluated. A p53 immunoreactivity score of 8 and MIB-1 index of 80% was obtained. Therefore, a final diagnosis of endometrial intraepithelial carcinoma (EIC) was made.

   Discussion Top

According to the latest reports by Zheng, et al. [2] the putative precursor lesion of UPSC, previously designated as EIC, endometrial adenocarcinoma in situ, or uterine surface carcinoma, is now being referred to as serous EIC. [1],[2],[3],[4]

Serous EIC is defined morphologically as the replacement of the endometrial surface epithelium and/or glands by frankly malignant cells that resemble the UPSC cells with high-grade nuclei. [1],[5] Serous EIC is commonly associated with extrauterine serous carcinoma. [5],[6] Since it has a capacity to spread even when myometrial invasion is not present, serous EIC is not a true intraepithelial carcinoma, hence differing from carcinoma in situ at other organ sites. Due to the above considerations, serous EIC is considered as an early form of UPSC rather than a precursor lesion only. It is for this reason that the authors Zheng, et al. [2] prefer the term uterine surface carcinoma to describe and emphasize the uniquely aggressive nature of this UPSC precursor lesion.

The differential diagnoses include eosinophilic metaplasia, papillary syncytial metaplasia and tubal metaplasia, which are ruled out by the observation of the minimal nuclear atypia in metaplastic changes, vis a vis the marked atypia of EIC. The next clue is the increased number of mitotic figures, including abnormal forms seen in EIC, but very rare in metaplastic changes. [7] Soslow, et al. [7] highlight the importance of immunostaining for p53 and MIB-1 in the differentiation. EIC is a proliferative lesion with a high MIB-1 index. EIC also expresses p53 in a strong and diffuse manner, which is incompatible with a benign metaplastic lesion. Extensive EIC replacing benign glands in a polyp may be misinterpreted as complex atypical hyperplasia or endometrioid carcinoma. But both these latter lesions typically contain low grade nuclei and not the anaplastic nuclei seen in EIC. Moreover, the background is important, which is hyperplastic in endometrioid lesions and atrophic in serous lesions. Finally, the age also has to be kept under consideration, which is a decade younger in metaplasias, atypical hyperplasia, and endometrioid carcinoma, as compared with EIC. The last differential diagnostic problem is clear cell carcinoma. But, EIC is not composed of clear cells, lacks the distinctive architectural patterns of clear cell carcinoma, and displays strong and diffuse immunostaining for p53 more frequently.

Serous EIC is commonly (up to two-thirds of the cases) associated with extrauterine serous carcinoma, [5] even when EIC is unassociated with coincident uterine serous carcinoma (USC). [7] Molecular studies support the hypothesis that EIC is a precursor of both uterine and extrauterine invasive serous carcinoma [Figure 2].

Immunostaining for p53 in cases of EIC has certain distinct advantages, such as, confirming the presence of flat EIC at the endometrial surface and highlighting subtle foci of EIC and pagetoid spread into glands. [4] Rare EICs may contain mutant p53 proteins that are not detectable with routine anti-p53 antibodies. Therefore, an entirely negative p53 immunohistochemical result does not guarantee the absence of malignancy. [8]

The treatment protocol for EIC cases is total abdominal hysterectomy, accompanied by a staging procedure, including omentectomy, lymph node sampling, bilateral pelvic and peri-aortic lymphadenectomy, and pelvic washings. Our patient was subsequently subjected to a staging procedure, which was negative (confined to the endometrium). When these lesions are confined to an endometrial polyp and/or the endometrium proper, the clinical outcome is excellent. [9]

Take home messages

EIC has a propensity to develop in polyps and can be focal and easily missed on low-power examination. When the lesion is confined to an endometrial polyp and/or the endometrium proper, the clinical outcome is excellent. Therefore, endometrial polyps in older women should be examined carefully. [9]

EIC can be associated with invasive, extrauterine serous carcinomatosis. Hence, the finding of EIC in an endometrial curettage specimen should prompt a thorough search for an invasive uterine and/or extrauterine serous carcinoma. Recognition of EIC in curettings and biopsies can help the pathologist in diagnosing serous carcinoma before a hysterectomy is performed, therefore enabling appropriate staging at the time of surgery.

   References Top

1.Spiegel GW. Endometrial carcinoma in situ in postmenopausal women. Am J Surg Pathol 1995;19:417-32.  Back to cited text no. 1  [PUBMED]  
2.Zheng W, Khurana R, Farahmand S, Wang Y, Zhang ZF, Felix JC. p53 Immunostaining as a significant adjunct diagnostic method for uterine surface carcinoma: Precursor of Uterine Papillary Serous Carcinoma. Am J Surg Pathol 1998;22:1463-73.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Silverberg SG, Mutter GL, Kurman RJ, Kubik-Huch RA. Tumors of the uterine corpus: Epithelial tumors and related lesions. In: Tavassoli FA, Devilee P, editors. World Health Organisation classification of tumors. Pathology and Genetics: Tumors of the breast and female genital organs. Lyon, France: IARC Press 2003. p. 224-5.  Back to cited text no. 3    
4.Sherman ME, Bur ME, Kurman RJ. p53 in endometrial cancers and its putative precursors: Evidence for diverse pathways of tumorigenesis. Hum Pathol 1995;26:1268-74.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Sherman ME, Bitterman P, Rosenshein NB, Delgado G, Kurman RJ. Uterine serous carcinoma: A morphologically diverse neoplasm with unifying clinicopathologic features. Am J Surg Pathol 1992;16:600-10.  Back to cited text no. 5  [PUBMED]  
6.Zheng W, Schwartz PE. Serous EIC as an early form of UPSC. Recent progress of its pathogenesis and current opinions of clinical management. Gynecol Oncol 2005;95:579-82.  Back to cited text no. 6    
7.Soslow RA, Pirog E, Isacson C. EIC with associated peritoneal carcinomatosis. Am J Surg Pathol 2000;24:726-32.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Tashiro H, Isacson C, Levine R, Kurman RJ, Cho KR, Hedrick L. p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis. Am J Pathol 1997;150:177-85.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Hui P, Kelly M, O'Malley DM, Tavassoli F, Schwartz PE. Minimal uterine serous carcinoma: A clinicopathological study of 40 cases. Mod Pathol 2005;18:75-82.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]

Correspondence Address:
Manisha Ram
85, Wedgewood Drive, Church Langley, Harlow, CM17 9PY
United Kingdom
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.43744

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  [Figure 1], [Figure 2]

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