Aging Clin Exp Res DOI 10.1007/s40520-014-0211-5
CASE REPORT
Primary squamous cell carcinoma of the endometrium in elderly women: a report of four cases Giorgio Bogani • Stefano Uccella • Antonella Cromi • Maurizio Serati • Jvan Casarin • Nicoletta Donadello Fabio Ghezzi
•
Received: 20 November 2013 / Accepted: 28 February 2014 Ó Springer International Publishing Switzerland 2014
Abstract Pure squamous cell carcinoma arising in the endometrium represents a rare entity, accounting for \1 % of all endometrial malignancies. Limited data about pathogenetics’ and behaviours’ features are available. Of consequence, there is no consensus about classification and different therapeutic option. Four cases of elderly patients (aged [ 65 years) affected by pure squamous cell carcinoma of the endometrium are presented. Known risk factors for endometrial squamous metaplasia (i.e., pelvic inflammatory disease and cervical stenosis) were observed in two patients. Patients with a disease limited to the uterine corpus had favourable prognosis after surgery ± radiotherapy, while one patient with lymph nodes involvement and another who refused staging and/or adjuvant therapy had recurrent disease. Primary squamous cell carcinoma of the endometrium is rare and aggressive occurrence, characteristic of elderly patients. Radical surgery and adjuvant radiotherapy should be administered. Keywords Squamous cell Endometrial cancer Uterine cancer Ichthyosis uteri
new cases diagnosed in the United States during 2013 [1]. Although some endometrial neoplasms are characterized by focal squamous differentiation, primary endometrial squamous cell carcinoma (PESCC) are extremely rare, accounting for \1 % of all malignancies of the corpus uteri. Since the first report published by Gebhard in 1892, only few cases of PESCC have been published [2]. Here, we report four cases of PESCC in elderly women.
Cases Between January 1990 and December 2012, among 749 patients who had surgery for endometrial carcinoma, at the Gynecological Department of the University of Insubria (Varese, Italy), 4 (0.5 %) cases of PESCC were registered. Patients’ characteristics are listed in Table 1. All women were older than 65 years (66–74 years old). They had normal pre-operative cervical evaluation. Past medical history was noteworthy for conservative treatment for pelvic inflammatory disease in one case (Case 1) and cervical stenosis (Case 3) in another. Two other patients were affected by pelvic organ prolapse.
Introduction
Case 1
Endometrial cancer is the most common gynecological malignancy in developed countries, with more than 44,000
A 74-year-old woman had dilatation and curettage due to the occurrence of abnormal uterine bleeding. Histological examination showed the presence of squamous cell carcinoma. Cervical cancer (arising from the squamous epithelium of the endocervix) was suspected and radical hysterectomy, bilateral salpingo-ophorectomy (BSO) and pelvic lymphadenectomy (PL) were carried out. Pathology revealed a moderate differentiated (grade 2) PESCC, with myometrial invasion [50 % and no nodal metastases.
G. Bogani (&) S. Uccella A. Cromi M. Serati J. Casarin N. Donadello F. Ghezzi Department of Obstetrics and Gynecology, University of Insubria, Del Ponte Hospital, Piazza Biroldi 1, 21100 Varese, Italy e-mail: [email protected]
123
Aging Clin Exp Res Table 1 Primary endometrial squamous cell carcinoma Year
Age
Years of menopause
Treatment
Complications
Stage
Recurrence (site)
DFS (months)
Treatment
OS (months)
Outcome
Case 1
1994
74
20
Surgery; RT
Asymptomatic lymphoceles
IB
No
//
//
180
NED
Case 2
2002
67
13
Surgerya
–
IA
Yes (pelvis)
79
Surgery, RT
100
DOD
Case 3
2004
66
10
Surgery; RT
–
IIIC1
Yes (lung)
21
Chemo-therapy
46
DOD
Case 4
2012
73
23
Surgery
–
IA
No
//
//
12
NED
Year year of primary treatment, Age age of patient at the time of diagnosis Stage stage of disease was based on FIGO 2009 surgical staging [1], RT radiotherapy (external beam radiation therapy, 50.4 Gy), DFS disease-free survival, OS overall survival, NED no evidence of disease, DOD died of disease a
The patient refused surgical staging/adjuvant therapy after primary treatment
Case 2 Grade 3 PESCC was incidentally diagnosed after the patient had undergone vaginal hysterectomy and BSO for genital prolapse. Invasion of the myometrium was limited to the inner half [stage IA (FIGO stage system 2009 [1])]. Staging and/or adjuvant therapy proposed (due to the consistent risk of lymphatic spread in grade 3 non-endometrioid endometrial cancer [1]), but the patient refused. Case 3 The patient underwent laparoscopic hysterectomy, BSO and PL after hysteroscopic diagnosis of PESCC. Definitive pathology report revealed a moderately differentiated (grade 2) PESCC with myometrial invasion [50 %; multiple lymph nodes metastases were observed. External beam radiotherapy was administered (50.4 Gray over 6 weeks). Pulmonary recurrence was observed after 21 months. Case 4 The patient affected by symptomatic uterine prolapse, without history of abnormal uterine bleeding and with an unremarkable ultrasound examination, underwent vaginal hysterectomy plus BSO. Histology showed the presence of well differentiated (grade 1) PESCC arising in the endometrium. The carcinoma has not invaded the myometrium. At definitive histology the uterine cervix was unremarkable in all cases.
Discussion Diagnosis of PESCC is based on Fluhmann criteria (1928). Briefly, it is mandatory to exclude: cervical carcinoma
123
involving the endometrium, coexistent endometrial adenocarcinoma, and contiguity between the endometrial cancer and the squamous cervix epithelium [3]. Indeed most squamous cell cancers which extend to the endometrium arise from the cervical epithelium [2]. There is no consensus about the aetiopathogenesis and all the proposed theories are based on few reports. Some authors suggest that PESCC may develop from total squamous differentiation of the endometrium (i.e., ‘‘ichthyosis uteri’’) associated with irritative status (e.g., pelvic inflammatory disease, cervical stenosis) or other chronic conditions (e.g., vitamin A deficiency, senile involution, radiation-therapy) [2–4]. Other different theories include human-papillomavirus infection, malignant transformation of pluripotent precursor cells or the presence of heterotopic cervical tissue within the endometrium [2–4]. Interestingly, in agreement with the available literature [3, 4], our investigation underlines the correlation between older age and PESCC. In fact, all women diagnosed with PESCC were older than 65 years. We can speculate that the main reason is the association between aging and the aforementioned risk factors [4]. Hence, probably due to the growing of geriatric population and the ‘‘feminization of aging’’ phenomena, among older population, number of women outnumber men at every age, the incidence and the interest for this uncommon disease will increase. Survival data of patients affected by PESCC are scarce and controversial. The few available data suggest that these malignancies have a mixed behavior resembling both endometrial and cervical cancer. For this reason women with early-stage disease have a favorable prognosis, whereas in case of locally advanced cancer, survival is generally poor. In these latter cases, adjuvant treatment for local (radiotherapy) and systemic disease control (platinum-based chemotherapy) should be administered. However, owing to the vulnerability of geriatric population, a careful balance between different approaches is paramount.
Aging Clin Exp Res
Surgical and adjuvant treatments in the elderly should be performed efficiently not only to maximize their potential life span, but also maintain the dignity of life and health expectancy [5]. In conclusion PESCC seems to correlate with aging and senile modification/involution of the uterine corpus. Owing to the rarity of this disease, multi-institutional studies are needed to address the concern about the extension of primary surgical treatment and the efficacy of adjuvant therapy in this frail population. Conflict of interest The authors declared no conflicts of interest. No founding sources support this investigation.
2.
3.
4.
5.
endometrial cancer: current evidence. J Obstet Gynaecol Res 40:301–311. doi:10.1111/jog.12344 Gebhard C (1892) Ueber die vom oberfla¨chenepithel ausgehenden carcinomformen des uterusko¨rpers sowie u¨ber den hornkrebs des cavum uteri. Z Geburtshilfe Gynakol 24:1–21 Thomakos N, Galaal K, Godfrey KA, Hemming D, Naik R, Hatem MH, Lopes A (2008) Primary endometrial squamous cell carcinoma. Arch Gynecol Obstet 278:177–180. doi:10.1007/s00404008-0567-x Nicolae A, Preda O, Nogales FF (2011) Endometrial metaplasias and reactive changes: a spectrum of altered differentiation. J Clin Pathol 64:97–106. doi:10.1136/jcp.2010.085555 Noale M, Limongi F, Scafato E, Maggi S, Crepaldi G (2012) Longevity and health expectancy in an ageing society: implications for public health in Italy. Ann Ist Super Sanita 48:292–299
References 1. Bogani G, Dowdy SC, Cliby WA, Ghezzi F, Rossetti D, Mariani A (2014) Role of pelvic and para-aortic lymphadenectomy in
123
CASE REPORT
Primary squamous cell carcinoma of the endometrium in elderly women: a report of four cases Giorgio Bogani • Stefano Uccella • Antonella Cromi • Maurizio Serati • Jvan Casarin • Nicoletta Donadello Fabio Ghezzi
•
Received: 20 November 2013 / Accepted: 28 February 2014 Ó Springer International Publishing Switzerland 2014
Abstract Pure squamous cell carcinoma arising in the endometrium represents a rare entity, accounting for \1 % of all endometrial malignancies. Limited data about pathogenetics’ and behaviours’ features are available. Of consequence, there is no consensus about classification and different therapeutic option. Four cases of elderly patients (aged [ 65 years) affected by pure squamous cell carcinoma of the endometrium are presented. Known risk factors for endometrial squamous metaplasia (i.e., pelvic inflammatory disease and cervical stenosis) were observed in two patients. Patients with a disease limited to the uterine corpus had favourable prognosis after surgery ± radiotherapy, while one patient with lymph nodes involvement and another who refused staging and/or adjuvant therapy had recurrent disease. Primary squamous cell carcinoma of the endometrium is rare and aggressive occurrence, characteristic of elderly patients. Radical surgery and adjuvant radiotherapy should be administered. Keywords Squamous cell Endometrial cancer Uterine cancer Ichthyosis uteri
new cases diagnosed in the United States during 2013 [1]. Although some endometrial neoplasms are characterized by focal squamous differentiation, primary endometrial squamous cell carcinoma (PESCC) are extremely rare, accounting for \1 % of all malignancies of the corpus uteri. Since the first report published by Gebhard in 1892, only few cases of PESCC have been published [2]. Here, we report four cases of PESCC in elderly women.
Cases Between January 1990 and December 2012, among 749 patients who had surgery for endometrial carcinoma, at the Gynecological Department of the University of Insubria (Varese, Italy), 4 (0.5 %) cases of PESCC were registered. Patients’ characteristics are listed in Table 1. All women were older than 65 years (66–74 years old). They had normal pre-operative cervical evaluation. Past medical history was noteworthy for conservative treatment for pelvic inflammatory disease in one case (Case 1) and cervical stenosis (Case 3) in another. Two other patients were affected by pelvic organ prolapse.
Introduction
Case 1
Endometrial cancer is the most common gynecological malignancy in developed countries, with more than 44,000
A 74-year-old woman had dilatation and curettage due to the occurrence of abnormal uterine bleeding. Histological examination showed the presence of squamous cell carcinoma. Cervical cancer (arising from the squamous epithelium of the endocervix) was suspected and radical hysterectomy, bilateral salpingo-ophorectomy (BSO) and pelvic lymphadenectomy (PL) were carried out. Pathology revealed a moderate differentiated (grade 2) PESCC, with myometrial invasion [50 % and no nodal metastases.
G. Bogani (&) S. Uccella A. Cromi M. Serati J. Casarin N. Donadello F. Ghezzi Department of Obstetrics and Gynecology, University of Insubria, Del Ponte Hospital, Piazza Biroldi 1, 21100 Varese, Italy e-mail: [email protected]
123
Aging Clin Exp Res Table 1 Primary endometrial squamous cell carcinoma Year
Age
Years of menopause
Treatment
Complications
Stage
Recurrence (site)
DFS (months)
Treatment
OS (months)
Outcome
Case 1
1994
74
20
Surgery; RT
Asymptomatic lymphoceles
IB
No
//
//
180
NED
Case 2
2002
67
13
Surgerya
–
IA
Yes (pelvis)
79
Surgery, RT
100
DOD
Case 3
2004
66
10
Surgery; RT
–
IIIC1
Yes (lung)
21
Chemo-therapy
46
DOD
Case 4
2012
73
23
Surgery
–
IA
No
//
//
12
NED
Year year of primary treatment, Age age of patient at the time of diagnosis Stage stage of disease was based on FIGO 2009 surgical staging [1], RT radiotherapy (external beam radiation therapy, 50.4 Gy), DFS disease-free survival, OS overall survival, NED no evidence of disease, DOD died of disease a
The patient refused surgical staging/adjuvant therapy after primary treatment
Case 2 Grade 3 PESCC was incidentally diagnosed after the patient had undergone vaginal hysterectomy and BSO for genital prolapse. Invasion of the myometrium was limited to the inner half [stage IA (FIGO stage system 2009 [1])]. Staging and/or adjuvant therapy proposed (due to the consistent risk of lymphatic spread in grade 3 non-endometrioid endometrial cancer [1]), but the patient refused. Case 3 The patient underwent laparoscopic hysterectomy, BSO and PL after hysteroscopic diagnosis of PESCC. Definitive pathology report revealed a moderately differentiated (grade 2) PESCC with myometrial invasion [50 %; multiple lymph nodes metastases were observed. External beam radiotherapy was administered (50.4 Gray over 6 weeks). Pulmonary recurrence was observed after 21 months. Case 4 The patient affected by symptomatic uterine prolapse, without history of abnormal uterine bleeding and with an unremarkable ultrasound examination, underwent vaginal hysterectomy plus BSO. Histology showed the presence of well differentiated (grade 1) PESCC arising in the endometrium. The carcinoma has not invaded the myometrium. At definitive histology the uterine cervix was unremarkable in all cases.
Discussion Diagnosis of PESCC is based on Fluhmann criteria (1928). Briefly, it is mandatory to exclude: cervical carcinoma
123
involving the endometrium, coexistent endometrial adenocarcinoma, and contiguity between the endometrial cancer and the squamous cervix epithelium [3]. Indeed most squamous cell cancers which extend to the endometrium arise from the cervical epithelium [2]. There is no consensus about the aetiopathogenesis and all the proposed theories are based on few reports. Some authors suggest that PESCC may develop from total squamous differentiation of the endometrium (i.e., ‘‘ichthyosis uteri’’) associated with irritative status (e.g., pelvic inflammatory disease, cervical stenosis) or other chronic conditions (e.g., vitamin A deficiency, senile involution, radiation-therapy) [2–4]. Other different theories include human-papillomavirus infection, malignant transformation of pluripotent precursor cells or the presence of heterotopic cervical tissue within the endometrium [2–4]. Interestingly, in agreement with the available literature [3, 4], our investigation underlines the correlation between older age and PESCC. In fact, all women diagnosed with PESCC were older than 65 years. We can speculate that the main reason is the association between aging and the aforementioned risk factors [4]. Hence, probably due to the growing of geriatric population and the ‘‘feminization of aging’’ phenomena, among older population, number of women outnumber men at every age, the incidence and the interest for this uncommon disease will increase. Survival data of patients affected by PESCC are scarce and controversial. The few available data suggest that these malignancies have a mixed behavior resembling both endometrial and cervical cancer. For this reason women with early-stage disease have a favorable prognosis, whereas in case of locally advanced cancer, survival is generally poor. In these latter cases, adjuvant treatment for local (radiotherapy) and systemic disease control (platinum-based chemotherapy) should be administered. However, owing to the vulnerability of geriatric population, a careful balance between different approaches is paramount.
Aging Clin Exp Res
Surgical and adjuvant treatments in the elderly should be performed efficiently not only to maximize their potential life span, but also maintain the dignity of life and health expectancy [5]. In conclusion PESCC seems to correlate with aging and senile modification/involution of the uterine corpus. Owing to the rarity of this disease, multi-institutional studies are needed to address the concern about the extension of primary surgical treatment and the efficacy of adjuvant therapy in this frail population. Conflict of interest The authors declared no conflicts of interest. No founding sources support this investigation.
2.
3.
4.
5.
endometrial cancer: current evidence. J Obstet Gynaecol Res 40:301–311. doi:10.1111/jog.12344 Gebhard C (1892) Ueber die vom oberfla¨chenepithel ausgehenden carcinomformen des uterusko¨rpers sowie u¨ber den hornkrebs des cavum uteri. Z Geburtshilfe Gynakol 24:1–21 Thomakos N, Galaal K, Godfrey KA, Hemming D, Naik R, Hatem MH, Lopes A (2008) Primary endometrial squamous cell carcinoma. Arch Gynecol Obstet 278:177–180. doi:10.1007/s00404008-0567-x Nicolae A, Preda O, Nogales FF (2011) Endometrial metaplasias and reactive changes: a spectrum of altered differentiation. J Clin Pathol 64:97–106. doi:10.1136/jcp.2010.085555 Noale M, Limongi F, Scafato E, Maggi S, Crepaldi G (2012) Longevity and health expectancy in an ageing society: implications for public health in Italy. Ann Ist Super Sanita 48:292–299
References 1. Bogani G, Dowdy SC, Cliby WA, Ghezzi F, Rossetti D, Mariani A (2014) Role of pelvic and para-aortic lymphadenectomy in
123
