Uterine serous carcinoma and endometrial intraepithelial carcinoma arising in endometrial polyps: report of 5 cases, including 2 associated with tamoxifen therapy

doi:10.1016/S0046-8177(03)00335-6

Human Pathology

Volume 34, Issue 9, September 2003, Pages 939-943

https://doi.org/10.1016/S0046-8177(03)00335-6 Get rights and content

Abstract

Uterine serous carcinoma (USC) is the prototype of type II endometrial cancer. Endometrial intraepithelial carcinoma (EIC) is the precursor lesion of USC, Rarely, USC and EIC may arise within and be largely confined to otherwise benign endometrial polyps. This report describes 5 such cases. The patients ranged in age from 67 to 89 years, with a mean age of 75 years. In 2 of the cases there was a history of tamoxifen therapy. In 2 cases USC or EIC was confined to the endometrial polyp, and in 3 cases there was focal involvement of nonpolypoid endometrium. In 1 case there was a single small focus of extrauterine tumor within an ovarian vascular channel. In 2 cases the invasive tumor within the polyp also contained areas of endometrioid adenocarcinoma, and in 2 cases there was a component of clear cell carcinoma. In all cases USC and EIC were strongly reactive for p53 and showed a high proliferation index with MIB1. Two cases were negative with estrogen receptor, and 3 cases exhibited positive staining. The cases reported herein show that USC and EIC may rarely arise in benign endometrial polyps and that extrauterine involvement may be present without myometrial infiltration. Because 2 of the patients had been taking tamoxifen, this raises the possibility of an association between tamoxifen and the development of USC and EIC in the endometrial polyps that are characteristic of this medication.

Section snippets

Materials and methods

The cases were identified from the files of the Department of Pathology, Royal Group of Hospitals Trust, Belfast and Department of Pathology, Belfast City Hospital Trust, Belfast. All slides were reviewed by a gynecologic pathologist (W.G.M.).

Clinical details

Patient age was 89 in case 1, 72 in case 2, 79 in case 3, 67 in case 4, and 69 in case 5, for a mean age of 75 years. All patients presented with postmenopausal bleeding. The patients in cases 1 and 3 had been taking tamoxifen for breast cancer for 10 and 6 years, respectively. In all cases, a diagnosis of tumor consistent with EIC or USC had been made on endometrial biopsy or curettage.

Pathological findings

All operative specimens consisted of a uterus, cervix, and bilateral ovaries and fallopian tubes. In all

Discussion

The 5 cases reported herein confirm the tendency for EIC and USC to involve, and sometimes be confined to, otherwise benign endometrial polyps. EIC, the precursor lesion of USC, is characterized by an abrupt transition from atrophic endometrium to in situ carcinoma. Preexisting glands are lined by cells resembling the cells of USC with markedly pleomorphic nuclei, a high nuclear-to-cytoplasmic ratio, nuclear hyperchromatism, and a high mitotic rate, often with abnormal mitoses. Psammoma bodies

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Frequently involving an endometrial polyp, minimal uterine serous carcinoma (MUSC) represents the earliest recognizable forms of endometrial serous carcinoma. The aim of this study was to provide a comprehensive morphological and clinical outcome assessment of MUSC involving endometrial polyp. A total of 77 fully staged MUSCs involving endometrial polyp were identified, including 53 MUSCs confined to polyp and 24 nonpolyp confined tumors. Extrauterine disease was found in 17% (9/53) of polyp-confined MUSCs compared to 41.7% (10/24) of nonpolyp confined tumors (p = 0.02). Lymphovascular invasion was observed in 3.8% (2/53) of polyp-confined cases compared to 25% (6/24) of nonpolyp confined cases (p = 0.047). Lymph node metastasis was observed in 11.3% (6/53) of polyp-confined cases, compared to 29.2% (7/24) of nonpolyp confined cases (p = 0.058). Positive pelvic washing cytology was seen in 18.9% (10/53) of polyp-confined versus 37.5% (9/24) of nonpolyp confined tumors (p = 0.078). Overall, 58 of 77 (75.3%) patients had low tumor stage (57 stage I cases and 1 stage II case) and only two patients (3.5%) had a recurrence. In contrast, 19 of 77 (24.7%) patients had advanced stage (stage III or IV) disease and 17 (89.5%) patients had recurrence (p < 0.0001). Only one of 57 low-stage patient (1.7%) versus 11 of 19 high-stage patients (57.8%) died of the tumor (p < 0.0001). Five of 53 (9.4%) patients with polyp-confined MUSC and 7 of 24 (29.2%) patients with nonpolyp confined MUSC died of the disease (p = 0.03). In conclusion, while a small percentage of MUSCs exist without the involvement of an endometrial polyp, a close topographic relationship between MUSC and the endometrial polyp is confirmed in this largest series, supporting the theory that most if not all MUSCs arise in an EMP. Patients with MUSC without extrauterine spread have an excellent prognosis. Compared to patients with MUSC confined to an endometrial polyp, patients with MUSC extending to the background endometrium have a significantly higher risk for high-stage disease at presentation.
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Endometrial cancers originate from epithelial cells lining the uterus and account for ~76,000 deaths annually among women worldwide. Histopathological subtypes of endometrial cancer include endometrioid and serous carcinomas, as well as carcinosarcomas. Recent whole exome sequencing of these three subtypes, including an integrated genomic analysis of endometrioid and serous endometrial cancers by The Cancer Genome Atlas, has uncovered both distinguishing and shared molecular features within their genomic landscapes. Consequently, we now understand that endometrioid and serous endometrial cancers can be classified into four distinct molecular subgroups: POLE (ultramutated), microsatellite instability (hypermutated), copy number low (microsatellite stable), and copy number high (serous-like). In this chapter, we review the current state of knowledge of endometrial cancer genomics, both in the context of histopathological subtypes and their underlying molecular subgroups, with an emphasis on the genes and pathways that are frequently perturbed.
Concurrent endometrial intraepithelial carcinoma (EIC) and endometrial hyperplasia
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More recently, p53 signature was proposed to be a precursor lesion of EIC because of the presence of p53 mutation in benign appearing endometrial glands [11,12]. Although mixed endometrioid and serous adenocarcinomas were previously reported [13,14], the concurrence of their precursor lesions, endometrial hyperplasia and EIC and p53 signature has not been studied. In current study, we report 5 cases where EIC and p53 signature are associated with endometrial hyperplasia.
Endometrial cancer is one of the most common gynecological neoplasms in the United States. It is divided into type I and type II carcinomas based on histological features. The mixed endometrioid (type I) and serous (type II) adenocarcinomas of endometrium were reported in previous studies. The concurrence of their precursor lesions was not studied. In current study, we present five cases with concurrent precursor lesions of endometrioid (endometrial hyperplasia) and serous adenocarcinomas (endometrial intraepithelial carcinoma and p53 signature). Due to the potential progressive clinical outcome of precursor lesions of serous adenocarcinoma, caution needs to be performed to identify endometrial intraepithelial carcinoma and p53 signature in the background of endometrial hyperplasia.
Early stage papillary serous or clear cell carcinoma confined to or involving an endometrial polyp: Outcomes with and without adjuvant therapy
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Given the limited extent of disease but aggressive biologic behavior of UPSC/CC it is unclear whether adjuvant therapy is warranted. While case reports and small series have been published mainly in the pathology literature [16–19], these often include all stages of UPSC, with inconsistent description of the adjuvant treatment given or details of patients' clinical outcomes. We conducted a retrospective review of our institution's incidence and clinical outcomes of patients with surgical stage IA UPSC/CC involving a polyp observed after surgery or given adjuvant therapy (radiation, chemotherapy, or both).
To investigate clinical outcomes of stage IA uterine papillary serous (UPSC) and clear cell carcinoma (CC) arising from or associated with a polyp.
From 1995 to 2011, we identified 51 cases of stage IA UPSC (67%), CC (8%) or mixed histology (26%) endometrial cancer. Of these, 32 had disease confined to polyp (seven with no residual disease after hysterectomy), 14 had surface spread, 1 had myometrial invasion (MMI) and 4 had both. The majority of patients did not receive adjuvant therapy (80%). Patients given adjuvant treatment (either platinum-based chemotherapy alone, radiation alone, or a combination of the two) had incomplete staging or abnormal cytology.
At mean follow-up of 58.3 months, only 4 patients had progressed, via pelvic adenopathy, carcinomatosis or both. There were no vaginal cuff recurrences. Kaplan–Meier 5 year estimates were pelvic control of 92.1%, disease-free survival 93% and OS 80.6%. Only 9% (3/32) of cases confined to polyp progressed. One responded to salvage chemoradiation, but two died despite salvage. Only 5% (1/19) of cases with surface and MMI progressed. On univariate analysis, only MMI and abnormal/positive cytology were significantly associated with increased pelvic recurrence (MMI p = 0.0059, cytology p = 0.0036) and worse DFS (MMI p = 0.0018, cytology p = 0.0054). Two patients given adjuvant treatment developed new gynecologic malignancies.
In our study, patients with limited UPSC/CC disease involving a polyp who have complete workup did well without adjuvant therapy, with recurrence rates similar to UPSC/CC stage IA disease. Late and extensive pelvic relapses may occur in the few who do relapse.
Serous carcinoma arising in endometrial polyps: Clinicopathologic study of 4 cases
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2) Omental involvement is frequent (transtubal metastasis should be mainly pelvic). In the reported case series, USC was associated with an EP in approximately 80% of cases, and half of the cases were confined to an EP [4,5,13]. All of our cases were associated with an EP.
Uterine serous carcinoma (USC) is a rare variant of endometrial cancer that is not related to increased estrogen level; rather, it arises in a background of atrophic endometrium. Our aim was to describe clinicopathologic features of 4 cases of USC arising in endometrial polyps (EPs). The mean age of the patients at presentation was 53 years (range, 50-61 years). All patients presented with postmenopausal bleeding. In 3 patients, endometrial curretings were done before surgery, which was reported as EP with superficial foci of USC, EP with few clusters of atypical cells, and high-grade serous carcinoma, respectively. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and omental sampling. The uterine cavity showed an EP in all cases ranging in size from 2 to 3.5 cm (mean, 3 cm). The hysterectomy specimens revealed USC in EP as well as the adjacent endometrium in 3 patients. The nonneoplastic endometrium was atrophic in all cases. Residual tumor was not found in the endometrium in 1 case. Omental metastatic deposits were found in all cases. Tumor deposits were also seen in the serosa of uterus, fallopian tubes, and parametrium in 1 case. Two patients died of disease 2 years after diagnosis. The remaining 2 patients are alive after a follow-up of 3 years, respectively. In conclusion, USC is a rare aggressive tumor, and to establish the diagnosis, it is important to look for the small foci of the tumor in the atrophic endometrium and on the surface of the polyps as these patients are likely to harbor additional disease in the uterus or extrauterine sites. The postmenopausal group is at high risk for developing these tumors; therefore, all the endometrial biopsies/curettings and the EPs in this age group should be thoroughly sampled.

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Case studyUterine serous carcinoma and endometrial intraepithelial carcinoma arising in endometrial polyps: report of 5 cases, including 2 associated with tamoxifen therapy

Abstract

Section snippets

Materials and methods

Clinical details

Pathological findings

Discussion

Hum Pathol

Hum Pathol

Gynecol Oncol

Hum Pathol

Cancer statistics, 1996

CA Cancer J Clin

Endometrial carcinomaTwo or three entities

Int J Gynecol Cancer

Uterine papillary serous carcinomaA highly malignant form of endometrial adenocarcinoma

Am J Surg Pathol

Endometrial carcinoma in situ in postmenopausal women

Am J Surg Pathol

Serous carcinoma in endometrial polyps

Mod Pathol

Stage IA uterine serous carcinomaa study of 13 cases

Am J Surg Pathol

Case study
Uterine serous carcinoma and endometrial intraepithelial carcinoma arising in endometrial polyps: report of 5 cases, including 2 associated with tamoxifen therapy