GYNECOLOGIC ONCOLOGY 60, 224–227 (1996)ARTICLE NO. 0029

High-Grade Endometrial Carcinoma in Secretory Endometriumin Young Women: A Report of Five Cases1

JAMES SCURRY, FRCPA,*,2 ALISON BRAND, FRCS(C),† PENELOPE SHEEHAN, M.B., B.S.,†AND ROBERT PLANNER, FRACOG†

*Departments of Pathology and †Gynecologic Oncology, Mercy Hospital for Women, Clarendon Street, East Melbourne 3002, Australia

Received February 21, 1995

carcinoma were premenopausal and 1.5% were under theFive cases of high-grade carcinoma occurring adjacent to secre- age of 40 [2]. Younger women were more likely to be over-

tory endometrium are described. One of the patients had the Lynch weight. Endometrial carcinoma is rare between the ages ofII syndrome, the others appeared to be sporadic. None of these 15 and 25 years, but when it does occur, it is almost invari-cases appeared to be related to hyperestrogen. The presenting ably of the estrogen-dependent type and associated with asymptom in four was abnormal vaginal bleeding, and the other very good prognosis [3, 4]. It would seem that, in general,case was found incidentally in the course of investigations for

the younger the woman, the more likely her carcinoma isinfertility. There were delays in diagnosis due to the patients notestrogen-dependent.seeking medical attention for abnormal bleeding, a reluctance of

Endometrial carcinoma occurring in secretory endome-clinicians to perform dilatation and curettage, and difficulty intrium is uncommon. Pooling the results of 17 different seriespathologic interpretation of the curettings. The interpretive prob-of endometrial carcinoma in premenopausal women, Quinnlems related to extremely small volumes of tumor, difficulty in

distinguishing carcinoma from menstrual endometrium, and dif- et al. found that 24 of 178 cases of endometrial carcinomaficulty in determining whether a carcinoma was endometrial rather occurred in secretory endometrium [2]. Paradoxically, endo-or endocervical in origin. The tumors were aggressive, manifest metrial cancer occurring in secretory endometrium usuallyby their high grade and stage. The importance of these cases is to resembles the estrogen-dependent type [5].impress upon clinicians and pathologists that endometrial carci- Estrogen-independent tumors in young women have beennoma may occur in young women without any of the usual risk rarely reported in the literature. Honore et al. describe twofactors. q 1996 Academic Press, Inc.

patients, one occurred in a setting of proliferative endome-trium, the other in oral contraceptive-induced atrophy, butto the best of our knowledge, none have been reported inINTRODUCTIONnormal secretory endometrium [6]. We present five cases

In 1983, Bokhman published his theory of two patho- of estrogen-independent endometrial carcinomas in womengenic mechanisms of endometrial carcinoma: estrogen- ages 28 to 43 years, four occurring in a setting of normaldependent and -independent [1]. He found that estrogen- secretory or menstrual endometrium and one on progesta-dependent carcinomas were more common and occurred tional agents, and discuss their significance.in hyperestrogenic women with endometrial hyperplasia.They were typically low grade with little, if any, myome- CASE REPORTStrial invasion, progestagen-sensitive, and prognosticallyfavorable. In contrast, estrogen-independent carcinomas Clinical features are summarized in Table 1.occurred in women without evidence of hyperestrogen andthese tumors tended to be poorly differentiated, deeply Case 1invasive, progestagen-insensitive, and prognostically un-favorable. A 43-year-old woman, gravida 3, para 2, weighing 62.5

kg, presented to her local doctor with a 6-month history ofQuinn et al. found that 14.5% of patients with endometrialintermenstrual bleeding. She smoked 50 cigarettes a day.Her father and three brothers had histories of colonic cancer,

1 This work was supported in part by the Nova Scotia Division of theand she had symptoms of irritable bowel syndrome for 2Canadian Cancer Society.years. She was initially treated with progestagens for 12 To whom correspondence and reprint requests should be addressed.

Fax: (03) 9416 1931. month, but when her symptoms failed to improve she was

2240090-8258/96 $18.00Copyright q 1996 by Academic Press, Inc.All rights of reproduction in any form reserved.

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225HIGH-GRADE ENDOMETRIAL CARCINOMA IN YOUNG WOMEN

TABLE 1Clinical Features of Five Cases of Estrogen-Independent Endometrial Carcinomas in Young Women

Gravidity, Initial Delay beforeCase Age parity Symptoms, duration treatment diagnosis Definitive treatment

1 43 G3P2 6 months, Progestagen 1 month TAH, BSO, nodes,bleeding omentectomy

2 34 G0P0 3 months, Progestagen 12 months Radical TAH, nodesintermenstrual bleeding

3 28 P0G0 60 months Nil Nil TAH, BSO, nodesinfertility

4 41 G5P5 3 months, Nil 9 months Radical TAH, BSO, nodesirregular bleeding

5 37 G2P1 9 months, Nil Nil TAH, BSO, nodes,irregular bleeding omental biopsy

Note. G, gravida; P, para; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy.

referred for further investigation. Hysteroscopy and dilata- and epirubicin with no response, and development of supra-clavicular node metastasis occurred. She was treated withtion and curettage were performed and a diagnosis of endo-

metrial carcinoma was made on the curettings. A total ab- radiotherapy to her para-aortic and supraclavicular nodes.Coincidentally she developed severe hypercalcemia, with andominal hysterectomy and bilateral salpingo-oophorectomy,

pelvic and para-aortic lymphadenectomy, and omentectomy elevated parathyroid hormone and normal levels of para-thyroid hormone-related protein.were performed.

The pathologic prognostic factors are shown in Table 2.Case 2In Case 1, histopathologic examination revealed a grade III,

stage IIIa endometrioid carcinoma of the endometrium, with A 34-year-old nulligravida, weighing 58 kg, presented topositive washings and negative nodes. her local doctor with 34 months’ intermenstrual bleeding.

She had a past history of high-grade intraepithelial neoplasiaFollow-up. Postoperatively she was commenced on 10mg of medroxyprogesterone acetate per day to control (CIN 3) 9 years previously, which had been successfully

treated with radical electrocoagulation. She was a nonsmokerflushes. After continued altered bowel habit, she had a colon-oscopy which revealed a cecal carcinoma. A right hemico- and was not hypertensive or hyperglycemic. The patient was

treated initially with progestagen therapy for 3 months andlectomy was performed 6 months after her initial operation.At laparotomy, her endometrial tumor was found to have was then referred when her symptoms failed to improve.

Dilatation and curettage were performed and a diagnosismetastasized to the para-aortic nodes above the level of theprevious dissection. She received 3 courses of cis-platinum of endometrial hyperplasia made. Despite treatment with

TABLE 2Pathologic Prognostic Factors in Five Cases of Estrogen-Independent Carcinoma in Young Women

Depth of myometrial Hormoneinvasion over total Grade CLS Peritoneal Lymph receptors Stage

Case thickness (FIGO) invasion washings nodes (fm/mg) (FIGO 1985)

1 8/26 mm 3 Pos, ext Pos P neg, E 10, IIIaPA neg Pr 13

2 10/20 mm 3 Pos Sus P neg, E 2, IIbPA n/p Pr 119

3 20/20 mm 3 Pos Neg P neg, E 47, IIIcPA pos Pr ú700

4 13/32 mm 2 Pos Neg P neg, E 5, IIbPA neg Pr 81

5 6/10 mm 2 Pos, ext Pos P pos, E 658, IIIcPA neg Pr 29

Note. Receptors E, estrogen; Pr, progestagen; n/p, not performed; pos, positive; neg, negative; ext, extensive; P, pelvic; PA, para-aortic; CLS, capillarylymph space.

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226 SCURRY ET AL.

medroxyprogesterone for 8 months and a combined oral con- until tubal ligation. There was no family history of cancer.Regular pap smears were negative. Her abnormal bleedingtraceptive pill for 2 months, her abnormal bleeding contin-

ued. One year after her initial presentation, she was referred was not investigated for 12 months when her symptomsworsened. She was treated with norethisterone and a dilata-for colposcopy following a pap smear suggestive of adeno-

carcinoma. Examination revealed a barrel-shaped cervix tion and curettage was performed. Curettings showed poorlydifferentiated adenocarcinoma, which was suspected to bewith an endocervical lesion deep in the canal. Endometrial

curettings showed a poorly differentiated adenocarcinoma of endocervical origin in view of her age and the lack ofrecognized risk factors for endometrial carcinoma. Colpos-which was initially considered to be of endocervical origin.

A radical hysterectomy and pelvic lymphadenectomy was copy was performed and cervical biopsies taken. The patientwas then treated with radical hysterectomy, bilateral sal-performed with conservation of the ovaries.

Histopathologic examination revealed a grade II, stage IIb pingo-oophorectomy, and pelvic and para-aortic lymphade-nectomy.endometrioid carcinoma of the endometrium with negative

washings and nodes. Histopathologic examination revealed a grade II, stage IIbendometrioid carcinoma of the endometrium.Follow-up. Due to the change of diagnosis, a bilateral

salpingo-oophorectomy was subsequently performed. The Follow-up. The patient received no further treatmenttubes and ovaries showed no remarkable features. The pa- and is alive without evidence of disease at 30 months.tient was commenced on oral medroxyprogesterone for

Case 5flushes and remains well with no evidence of recurrence at60 months following her operation.

A 37-year-old woman, gravida 2, para 1, weighing 60kg presented to her local doctor with a 9-month history ofCase 3abnormal vaginal bleeding. She had a positive family history

A 28-year-old Ethiopian nulligravida weighing 64 kg pre- of cancer in that her mother died at aged 37 of disseminatedsented for investigation of infertility of 5 years’ duration. carcinoma. She stopped smoking 7 weeks earlier and wasShe was a nonsmoker and neither hypertensive nor hypergly- normotensive and euglycemic. She was not on the oral con-cemic. Her only exogenous hormone had been the combined traceptive pill. A dilatation and curettage was performedoral contraceptive pill when first married. There was no and a diagnosis of endometrial carcinoma was made. Shefamily history of cancer. Her most recent pap smear 1 month underwent a total abdominal hysterectomy and bilateral sal-prior to presentation was normal. Her menstrual periods were pingo-oophorectomy, pelvic and para-aortic lymph node dis-normal. Dilatation and curettage, performed as a routine in- section, and omental biopsy.fertility investigation, revealed secretory endometrium with Histopathologic examination revealed a grade III, stagetiny foci of poorly differentiated adenocarcinoma of uncer- IIIc endometrioid carcinoma of the endometrium with posi-tain origin. To exclude a possible translocation artifact, a tive pelvic nodes.repeat curettage was performed, but failed to show tumor. Follow-up. Due to lymph node involvement, she wasNevertheless, in view of slight uterine enlargement and a treated with pelvic radiotherapy and was clinically free ofmass not completely consistent with a fibroid on ultrasound, disease at 4 months.a total abdominal hysterectomy was performed, and afterintraoperative confirmation of endometrial carcinoma, a bi-

DISCUSSIONlateral salpingo-oophorectomy and pelvic and para-aorticlymph node dissection were completed.

These five cases of endometrial carcinoma fit the clinico-Histopathologic examination revealed a grade III, stage

pathologic profile of estrogen-independent endometrial car-IIIc endometrioid carcinoma of the endometrium with nega-

cinomas. Four carcinomas all occurred in normal secretorytive washings but metastases to para-aortic nodes.

endometrium, indicating that these patients were ovulating.Follow-up. Postoperatively the patient was treated with The fifth occurred in a patient on a progestational agent.

megavoltage therapy to the pelvis and para-aortic disease, None of the patients had features of hyperestrogen or theand at 16 months remains alive and well, with no evidence usual risk factors associated with estrogen-dependent endo-of recurrent disease. metrial carcinomas, such as obesity, diabetes, or hyperten-

sion. There was no ovarian pathology. No exogenous hor-Case 4

mones were taken apart from the combined oral contracep-tive pill which was taken for limited periods by three of theA 41-year-old, gravida 5, para 5, woman weighing 68 kg

presented to her local doctor with a history of 12 months women and which would be expected to give a protectiveeffect against the development of estrogen-dependent endo-of abnormal vaginal bleeding. She was a smoker, but not

hypertensive nor hyperglycemic. Her only exogenous hor- metrial carcinoma [7].The unusual features of these cancers were the young agemone intake had been the combined oral contraceptive pill

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227HIGH-GRADE ENDOMETRIAL CARCINOMA IN YOUNG WOMEN

of the patients, occurrence in secretory endometrium, and The father and three brothers of one of our cases (Case 1)and the patient herself developed nonpolyposis colon cancer.the aggressive nature of their disease. The adverse prognostic

factors of high stage and grade of disease, deep myometrial This family fit the criteria of the Lynch II syndrome. Theother four patients would appear to be sporadic.invasion, positive peritoneal cytology, and lymph node me-

tastases were in keeping with the aggressive nature of the The fact that the cancers occurred in a setting of secretoryendometrium cannot be used to argue that estrogen has nodisease.

The diagnoses in four of the five cases were delayed for role in the pathogenesis of these tumors. Case 2 had a historyof endometrial hyerplasia, which is hormone-dependent.various reasons. There was a delay of 6 and 9 months in the

patients seeking medical attention for abnormal bleeding in Case 4 had been treated with norethisterone which wouldhave converted all her endometrium to secretory. RisbergCases 2 and 5. Because endometrial carcinoma was not con-

sidered, there was a delay of 9 months in Case 4 between et al. postulated that carcinoma in secretory endometriumdeveloped from ‘‘progesterone refractory’’ areas of prolifer-time of presentation and curettage. Despite the low probabil-

ity of the occurrence of endometrial carcinoma, endometrial ative endometrium and therefore could still be estrogen-de-pendent [5]. However, unlike our cases, their four cases weresampling is indicated in cases of young women with abnor-

mal vaginal bleeding for prompt diagnosis and treatment. categorized as estrogen-dependent carcinomas because theywere low grade, noninvasive, and with a good prognosis.The diagnosis of endometrial carcinoma was made cor-

rectly in only two of the five cases on initial curettage. In In summary, the diagnosis of estrogen-independent endo-metrial carcinoma in young women is difficult because carci-two cases (Cases 2 and 3), the volume of tumor in the initial

curette was so small as to cause problems. In Case 2 small noma is often not considered likely and therefore there is areluctance to perform dilatation and curettage for abnormalballs of tumor could not be distinguished from condensed

endometrial stroma in menstrual endometrium, leading to a bleeding. In addition, once sufficient curettings are obtained,there may be difficulties in interpretation by the pathologist.delay of 10 months. At subsequent curettage, the tumor was

so poorly differentiated that it was misinterpreted as poorlyREFERENCESdifferentiated squamous cell carcinoma from the cervix, un-

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nique, Gynecol. Oncol. 15, 32–41 (1983).In estrogen-independent cancers, hereditary factors may6. Honore, L. H., and Davey, S. J. Endometrial carcinoma in youngbe important. There are least two forms of inherited endome-

women: A report of four cases, J. Reprod. Med. 34, 845–849 (1989).trial carcinoma, the Lynch II syndrome and a predisposition7. Schiffman, M. H., and Brinton, L. A. Epidemiology, in Blaustein’sfor endometrial cancer alone. In the Lynch II syndrome

Textbook of gynecologic pathology (R. Kurman, Ed.), Springer-Verlag,males and females are at an increased risk of developing New York, 4th ed., pp. 1215–1216 (1994).nonpolyposis colon cancer and other adenocarcinomas; fe- 8. Mecklin, J.-P., Jarvinem, H. J., and Peltopallio, P. Cancer familiy syn-males are at risk of developing ovarian carcinoma and 20– drome: Genetic analysis of 22 Finnish families, Gastroenterology 90,

328–333 (1986).30% of affected women develop endometrial carcinoma [8].

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