Journal of Obstetrics and Gynaecology, 2014; Early Online: 1–2 © 2014 Informa UK, Ltd. ISSN 0144-3615 print/ISSN 1364-6893 online
CASE REPORT
Cervical uterine cancer in a virgin young woman – Case report I. Pestana1, A. Costa1,2, R. Gorgal1, R. Mota1, R. Portugal3 & V. Paiva1
J Obstet Gynaecol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 06/30/15 For personal use only.
1Department of Gynecology and Obstetrics, Centro Hospitalar de S.
João, Porto, Portugal, 2Department of Gynecology and Obstetrics, Faculdade de Medicina, Universidade do Porto, Porto, Portugal, and 3Department of Anatomopathology, Centro Hospitalar de S. João, Porto, Portugal DOI: 10.3109/01443615.2014.992870 Correspondence: Ines Pestana, MD, Department of Gynecology and Obstetrics, Centro Hospitalar S. João, Al Prof Hernani Monteiro 4200-Porto, Portugal. Tel: ⫹ 351 910350959. E-mail: [email protected] Figure 1. Infiltrative endo-cervical adenocarcinoma, haematoxylin–eosinx40.
Introduction Cancer of the uterine cervix is the second most frequent neoplasia (Globocan 2008; Ries et al 2007). Human papillomavirus (HPV) is the major aetiological factor, which can be detected in 99.7% of cervical cancers (Walboomers et al. 1999). We present a rare case of primary adenocarcinoma of the cervix in a HPV-negative virgin.
Case Clinical presentation An 18-year-old Caucasian woman was admitted with a two-week history of abnormal genital bleeding, initially treated with an oral contraceptive. The patient’s medical history was unremarkable and she denied ever having any type of sexual contact. Physical examination confirmed moderate genital bleeding. The hymen was intact. Speculum and digital vaginal examinations were not performed. The uterus and the ovaries were of normal appearance on abdominal pelvic ultrasound examination. Serum analyses revealed hypochromic, microcytic anaemia at 8.6 g/dl. She was prescribed oral iron and the dose of contraceptive was increased. After ten days, the genital haemorrhage worsened and her haemoglobin dropped to 7.1 g/dL. Speculum and rectovaginal examination revealed a 3–4 cm, exophytic, friable, painless mass protruding from the external cervical ostium of uterus, free and painless vaginal pouches, a normal anteverted palpable uterus, impalpable adnexa, free parametria and 1.5-cm palpable left inguinal adenomegaly. Biopsy of the protruding cervical mass revealed an undifferentiated malignant tumour of the cervix with lymphovascular invasion (Figure 1). Oncological evaluation With this result, it was essential to decide whether this was a malignant primary or a metastatic cervical tumour. Cervical cytology HPV testing (PCR) was negative. Other sexually transmitted infections, such as syphilis, HIV, and hepatitis B and C, were eliminated. Oncological markers (SCC, CEA and CA 125) were within the normal range. Core biopsy of the left inguinal adenomegaly was negative for malignant neoplasia. The pelvic magnetic resonance imaging revealed heterogeneity of the posterior portion of the cervix, free parametria, no signs of adjacent organ invasion (vagina, bladder or rectum), no adenomegaly and no hydronephrosis. The cervico-thoraco-abdominal tomography scan, upper and lower digestive tract endoscopy, cystoscopy, breast ultrasound and dermatological evaluation were
unremarkable. Positron emission tomography (PET) scan showed no evidence of extra-cervical disease. Oncological treatment Cold conization showed an undifferentiated carcinoma of the cervix with 6-mm superficial extension, perineural and venous vascular space involvement and free margins. One month later, she underwent radical abdominal hysterectomy (Piver II) with ovarian transposition to the parietocolic gutters. The final histological specimen revealed a high-grade (G3/4) adenocarcinoma of the cervix (9-mm superficial extension and 10-mm depth invasion) with lymphovascular space involvement and lymphovascular involvement of the parametria. The disease-free surgical margin was 20 mm in the vagina and 6 mm in the parametria. Pelvic lymph nodes were disease-free. The patient was FIGO stage of class IIB due to left parametrium lymphovascular involvement. The patient was treated with adjuvant oncological therapy with external pelvic radiotherapy, vaginal brachytherapy and radiosensitising cis-platinum chemotherapy weekly for 6 weeks concomitantly. Oncological evolution Three months after completion of adjuvant radiochemotherapy, the patient remained asymptomatic; however, a thoracic tomography scan revealed bilateral pulmonary parenchymal nodules suggesting distant malignant neoplasic progression, which was confirmed by pulmonary Computarized Tomography (CT)-guided biopsy. Planned pulmonary resection in two time-deferred surgical interventions was not performed in accordance with the patient’s wishes. Only unilateral pulmonary resection of the pulmonary metastases was performed. She decided to seek dendritic cell therapy combined with hyperthermia abroad. Two months after initiation of the latter treatment, thoracic TC scan revealed enlargement of the mediastinum with an 8-cm mass, dissemination of the metastatic parenchymal disease, and pleural and pericardial effusion. Palliative chemotherapy was proposed at the multidisciplinary consultation, which was refused by the patient. She died fourteen months after diagnosis.
Comment Cancer of the cervix is almost exclusively associated with HPV (Bohmer et al. 2003; Liebrich et al. 2008). In 1982, a case of invasive
2
I. Pestana et al.
J Obstet Gynaecol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 06/30/15 For personal use only.
squamous carcinoma of the cervix in a 15-year-old girl was published, but the HPV infection was not excluded (Dekel et al. 1982) and another paper describes the case of the youngest Japanese girl to be diagnosed with endocervical clear-cell adenocarcinoma (Yabushita et al. 2008). The case of a 17-year-old virgin with advanced cervical cancer was recently published in the literature, again without eliminating HPV (vertical HPV transmission remains a possibility) (Roberts et al. 2013). Similar to our case, the patient died a few months after diagnosis. Although the number of cases in the literature is small, the few reported cases have tended to be fatal, but it is not clear whether this is due to delay in diagnosis or the more aggressive nature of these tumours. Current guidelines do not recommend any type of screening in virgins. The particular interest on this case is not only due to its rarity, but the low level of suspicion in virgins, meaning that there is no consensus for predicting such clinical situations. This is due to the rarity of the condition and the difficulty of the diagnosis in this low-risk group of women. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References Bohmer G, van den Brule AJ, Brummer O, et al. 2003. No confirmed case of human papillomavirus DNA-negative cervical intraepithelial neoplasia grade 3 or invasive primary cancer of the uterine cervix among 511 patients. American Journal of Obstetrics and Gynecology 189:118–120. Dekel A, Van Iddekinge B, Leiman G. 1982. Invasive squamous carcinoma of the cervix in a 15-year-old girl. A case report and review of the literature. South African Medical Journal 61:628–629. Globocan. 2008. Cancer Incidence, Mortality and Prevalence Worldwide. IARC Liebrich C, Brummer O, Von Wasielewsk R, et al. 2008. Primary cervical cancer truly negative for high-risk human papillomavirus is a rare but distinct entity that can affect virgins and young adolescents. Europena Journal of Gynaecological Oncology 30:45–48. Ries LAG, Melbert D, Krapcho M et al. 2007. SEER Cancer Statistics Review, 1975–2004. National Cancer Institute; Bethesda, MD Roberts OA, Owonikoko KM, Abdus-Salam AA et al. 2013. Advanced carcinoma of the cervix in a 17-year-old girl. Journal of Obstetrics and Gynaecology 747–748. Walboomers JM, Jacobs MV, Manos MM, et al. 1999. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. Journal of Pathology 189:12–19. Yabushita H, Kanyama K, Sekiya R et al. 2008. Clear-cell adenocarcinoma of the uterine cervix in a 17-year-old adolescent. International Journal of Clinical Oncology 13:552–554.
CASE REPORT
Cervical uterine cancer in a virgin young woman – Case report I. Pestana1, A. Costa1,2, R. Gorgal1, R. Mota1, R. Portugal3 & V. Paiva1
J Obstet Gynaecol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 06/30/15 For personal use only.
1Department of Gynecology and Obstetrics, Centro Hospitalar de S.
João, Porto, Portugal, 2Department of Gynecology and Obstetrics, Faculdade de Medicina, Universidade do Porto, Porto, Portugal, and 3Department of Anatomopathology, Centro Hospitalar de S. João, Porto, Portugal DOI: 10.3109/01443615.2014.992870 Correspondence: Ines Pestana, MD, Department of Gynecology and Obstetrics, Centro Hospitalar S. João, Al Prof Hernani Monteiro 4200-Porto, Portugal. Tel: ⫹ 351 910350959. E-mail: [email protected] Figure 1. Infiltrative endo-cervical adenocarcinoma, haematoxylin–eosinx40.
Introduction Cancer of the uterine cervix is the second most frequent neoplasia (Globocan 2008; Ries et al 2007). Human papillomavirus (HPV) is the major aetiological factor, which can be detected in 99.7% of cervical cancers (Walboomers et al. 1999). We present a rare case of primary adenocarcinoma of the cervix in a HPV-negative virgin.
Case Clinical presentation An 18-year-old Caucasian woman was admitted with a two-week history of abnormal genital bleeding, initially treated with an oral contraceptive. The patient’s medical history was unremarkable and she denied ever having any type of sexual contact. Physical examination confirmed moderate genital bleeding. The hymen was intact. Speculum and digital vaginal examinations were not performed. The uterus and the ovaries were of normal appearance on abdominal pelvic ultrasound examination. Serum analyses revealed hypochromic, microcytic anaemia at 8.6 g/dl. She was prescribed oral iron and the dose of contraceptive was increased. After ten days, the genital haemorrhage worsened and her haemoglobin dropped to 7.1 g/dL. Speculum and rectovaginal examination revealed a 3–4 cm, exophytic, friable, painless mass protruding from the external cervical ostium of uterus, free and painless vaginal pouches, a normal anteverted palpable uterus, impalpable adnexa, free parametria and 1.5-cm palpable left inguinal adenomegaly. Biopsy of the protruding cervical mass revealed an undifferentiated malignant tumour of the cervix with lymphovascular invasion (Figure 1). Oncological evaluation With this result, it was essential to decide whether this was a malignant primary or a metastatic cervical tumour. Cervical cytology HPV testing (PCR) was negative. Other sexually transmitted infections, such as syphilis, HIV, and hepatitis B and C, were eliminated. Oncological markers (SCC, CEA and CA 125) were within the normal range. Core biopsy of the left inguinal adenomegaly was negative for malignant neoplasia. The pelvic magnetic resonance imaging revealed heterogeneity of the posterior portion of the cervix, free parametria, no signs of adjacent organ invasion (vagina, bladder or rectum), no adenomegaly and no hydronephrosis. The cervico-thoraco-abdominal tomography scan, upper and lower digestive tract endoscopy, cystoscopy, breast ultrasound and dermatological evaluation were
unremarkable. Positron emission tomography (PET) scan showed no evidence of extra-cervical disease. Oncological treatment Cold conization showed an undifferentiated carcinoma of the cervix with 6-mm superficial extension, perineural and venous vascular space involvement and free margins. One month later, she underwent radical abdominal hysterectomy (Piver II) with ovarian transposition to the parietocolic gutters. The final histological specimen revealed a high-grade (G3/4) adenocarcinoma of the cervix (9-mm superficial extension and 10-mm depth invasion) with lymphovascular space involvement and lymphovascular involvement of the parametria. The disease-free surgical margin was 20 mm in the vagina and 6 mm in the parametria. Pelvic lymph nodes were disease-free. The patient was FIGO stage of class IIB due to left parametrium lymphovascular involvement. The patient was treated with adjuvant oncological therapy with external pelvic radiotherapy, vaginal brachytherapy and radiosensitising cis-platinum chemotherapy weekly for 6 weeks concomitantly. Oncological evolution Three months after completion of adjuvant radiochemotherapy, the patient remained asymptomatic; however, a thoracic tomography scan revealed bilateral pulmonary parenchymal nodules suggesting distant malignant neoplasic progression, which was confirmed by pulmonary Computarized Tomography (CT)-guided biopsy. Planned pulmonary resection in two time-deferred surgical interventions was not performed in accordance with the patient’s wishes. Only unilateral pulmonary resection of the pulmonary metastases was performed. She decided to seek dendritic cell therapy combined with hyperthermia abroad. Two months after initiation of the latter treatment, thoracic TC scan revealed enlargement of the mediastinum with an 8-cm mass, dissemination of the metastatic parenchymal disease, and pleural and pericardial effusion. Palliative chemotherapy was proposed at the multidisciplinary consultation, which was refused by the patient. She died fourteen months after diagnosis.
Comment Cancer of the cervix is almost exclusively associated with HPV (Bohmer et al. 2003; Liebrich et al. 2008). In 1982, a case of invasive
2
I. Pestana et al.
J Obstet Gynaecol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 06/30/15 For personal use only.
squamous carcinoma of the cervix in a 15-year-old girl was published, but the HPV infection was not excluded (Dekel et al. 1982) and another paper describes the case of the youngest Japanese girl to be diagnosed with endocervical clear-cell adenocarcinoma (Yabushita et al. 2008). The case of a 17-year-old virgin with advanced cervical cancer was recently published in the literature, again without eliminating HPV (vertical HPV transmission remains a possibility) (Roberts et al. 2013). Similar to our case, the patient died a few months after diagnosis. Although the number of cases in the literature is small, the few reported cases have tended to be fatal, but it is not clear whether this is due to delay in diagnosis or the more aggressive nature of these tumours. Current guidelines do not recommend any type of screening in virgins. The particular interest on this case is not only due to its rarity, but the low level of suspicion in virgins, meaning that there is no consensus for predicting such clinical situations. This is due to the rarity of the condition and the difficulty of the diagnosis in this low-risk group of women. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References Bohmer G, van den Brule AJ, Brummer O, et al. 2003. No confirmed case of human papillomavirus DNA-negative cervical intraepithelial neoplasia grade 3 or invasive primary cancer of the uterine cervix among 511 patients. American Journal of Obstetrics and Gynecology 189:118–120. Dekel A, Van Iddekinge B, Leiman G. 1982. Invasive squamous carcinoma of the cervix in a 15-year-old girl. A case report and review of the literature. South African Medical Journal 61:628–629. Globocan. 2008. Cancer Incidence, Mortality and Prevalence Worldwide. IARC Liebrich C, Brummer O, Von Wasielewsk R, et al. 2008. Primary cervical cancer truly negative for high-risk human papillomavirus is a rare but distinct entity that can affect virgins and young adolescents. Europena Journal of Gynaecological Oncology 30:45–48. Ries LAG, Melbert D, Krapcho M et al. 2007. SEER Cancer Statistics Review, 1975–2004. National Cancer Institute; Bethesda, MD Roberts OA, Owonikoko KM, Abdus-Salam AA et al. 2013. Advanced carcinoma of the cervix in a 17-year-old girl. Journal of Obstetrics and Gynaecology 747–748. Walboomers JM, Jacobs MV, Manos MM, et al. 1999. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. Journal of Pathology 189:12–19. Yabushita H, Kanyama K, Sekiya R et al. 2008. Clear-cell adenocarcinoma of the uterine cervix in a 17-year-old adolescent. International Journal of Clinical Oncology 13:552–554.
