Journal of Obstetrics and Gynaecology
ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20
Metastatic small-cell carcinoma of the cervix during pregnancy M. J. Canto, N. Pons, I. Mendez, A. Reus & F. Ojeda To cite this article: M. J. Canto, N. Pons, I. Mendez, A. Reus & F. Ojeda (2014) Metastatic smallcell carcinoma of the cervix during pregnancy, Journal of Obstetrics and Gynaecology, 34:2, 204-205 To link to this article: http://dx.doi.org/10.3109/01443615.2013.845550
Published online: 23 Jan 2014.
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Date: 05 November 2015, At: 16:12
204
Obstetric Case Reports
Metastatic small-cell carcinoma of the cervix during pregnancy M. J. Canto1,3, N. Pons1, I. Mendez2, A. Reus1 & F. Ojeda1,3 Department of 1Obstetrics and Gynaecology, 2Pathology, Hospital General of Granollers and 3Universitat Internacional de Catalunya, Barcelona, Spain DOI: 10.3109/01443615.2013.845550 Correspondence: M. J. Canto, Department of Obstetrics and Gynaecology, Hospital General de Granollers, Avda. Francesc Ribas s/n, 080400, Granollers, Barcelona, Spain. E-mail: [email protected]
Downloaded by [University of Florida] at 16:12 05 November 2015
Introduction Neuroendocrine small-cell carcinoma of the uterine cervix (NESCCC) is a very uncommon tumour, accounting for less than 2% of all cervical malignancies. This entity mixes clinical and biological characteristics of both cervical neoplasms, such as local aggressiveness and smallcell carcinoma of any site, such as propensity for early metastasis and lymph node spread at early stages. Moreover, screening with cytology is useless, since NESCCC is thought to arise from argyrophilic cells or subcolumnar cells, which, combined with the lack of in situ component and rapid growth, makes prior Papanicolaou smears often negative (Perrin et al. 1996). Consequently, the prognosis is usually worse than that for stage-comparable poorly-differentiated squamous cell carcinoma of the cervix (Gardner et al. 2011). Only a few cases occurring during pregnancy have been reported (Teefey et al. 2012), showing an aggressive clinical course and poor prognosis. We report a case of a woman with cystic hepatic metastases of a NESCCC diagnosed at the postpartum period.
Case report A 30-year-old primigravida, with no significant past medical history, presented at 36 weeks’ gestation, with premature rupture of the membranes. Speculum examination detected pooling of liquor in the posterior fornix of the vagina and revealed a closed cervix, with a 3 cm Nabothian cyst-like nodule in the anterior lip. Transvaginal ultrasonography showed a cervical length of 26 mm and the cystic nature of the nodule. She had a negative cervical Papanicolaou smear 1 year earlier. Since the woman presented with a blood pressure of 145/95 and ⫹⫹⫹ of qualitative proteinuria at admission, and also complained of progressive bilateral leg oedema during the last week, a likely pre-eclampsia was diagnosed.
Induction of labour with prostaglandins was indicated, while intravenous perfusion of antibiotics, labetalol and magnesium sulfate was initiated. A healthy male infant weighing 2,450 g with Apgar scores 9–10 at 1–5 min was delivered. When the birth canal was explored, the cervical cyst had ruptured and was draining a mucous secretion. Blood pressure normalised in the first days postpartum, but the oedema worsened and transaminases increased markedly. Of note, her physical exam revealed a distended abdomen with hepatomegaly. Abdominal ultrasound and abdominopelvic CT scan showed a massively enlarged liver with multiple cysts and the existence of several small nodules in both lung bases, which were confirmed by chest CT. IgG and IgE for Echinococcus, and serum tumour markers (CA125, CA19.9, CEA and CA15.3) showed as normal. In view of the possibility that a metastatic process of unknown origin was present, a PET was performed, showing an increased uptake in uterine cervix and multiple images through the liver, pelvis, sacrum, right breast and lungs, suggestive of metastases (Figure 1). Thus, a thorough gynaecological examination was performed by an experienced gynae-oncologist, which showed an area of stony consistency at the level corresponding to the previously found ruptured cyst. A biopsy of this cervical area was taken and revealed a poorlydifferentiated NESCCC, with a mitotic index of 80%. Immunohistochemical study revealed positivity for pancytokeratin-7 (CK-7), neuronal cell adhesion molecule (CD-56) (Figure 2), chromogranin A (CgA), synaptophysin (Syn) and p16, and was negative for thyroid transcription factor (TTF-1), CK-20, vimentin and p53. Stage IV-B NESCCC was diagnosed, and the first cycle treatment with cisplatin and etoposide was administered. However, 1 month postpartum, the patient showed a progressive systemic deterioration, with severe respiratory distress and clinical suspicion of pulmonary thromboembolism. Unfortunately, the patient died, despite intensive management. Her family refused permission for autopsy. At the time of writing, her child is 14 months old and is developing as a healthy child, without any evidence of metastatic disease.
Discussion Only 16 cases of NESCCC during pregnancy have been reported to date (Teefey et al. 2012). The presenting symptom is usually vaginal bleeding, though in some cases, clinical or biochemical evidence of ectopic hormone production may be present. A cervical mass at gynaecological examination, with a polypoid growth of NESCCC has also been described (Ohwada et al. 2001). Cystic liver metastases are rare, but mainly described in neuroendocrine or gynaecological malignant tumours (McDermott 1987; Estermann et al. 1996). Cystic formation is probably due to infarction with liquefaction necrosis of tumour nodules. To our knowledge, this
Figure 1. PET showing increased uptake in uterine cervix and multiple images through the liver.
Downloaded by [University of Florida] at 16:12 05 November 2015
Obstetric Case Reports 205
Figure 2. Immunohistochemically stained section of NESCCC showing positive labelling (brick red coloured) for CD56 in the membranes of the cells.
is the first case of cystic liver metastatic NESCCC described during pregnancy. Histologically, NESCCC is similar to small-cell carcinoma of the lung. It consists of round to spindle-shaped cells with scanty cytoplasm, granular nuclei and absent or inconspicuous nucleoli. Analogous to small-cell lung cancer, the diagnosis of NESCCC is aided by immunohistochemical staining for common neuroendocrine markers, including synaptophysin (Syn), chromogranin A (CgA) and CD56 (Wagenaar 1999). Also, thyroid transcription factor (TTF-1) has been found to be positive with a high intensity in pulmonary small-cell carcinoma, but negative or positive with a low intensity in the extrapulmonary compartment. Accordingly, our patient showed this immunohistochemical profile. The staging of NESCCC follows that for traditional cervical cancer. However, given the high rate of distant metastatic spread of these cancers, PET/CT imaging may be reasonable to consider in the extension study. On the other hand, brain metastases are more uncommon, thus a head CT is usually not required on the initial evaluation for NESCCC (Gardner et al. 2011). Usually, the clinical course of NESCCC is dismal. In 2011, guidelines for the management of this condition were published, suggesting a multimodality approach (Gardner et al. 2011). For early stages, a multimodality therapeutic strategy is needed, including surgical resection with radical hysterectomy, pelvic radiotherapy and chemotherapy, with etoposide and platinum (Gardner et al. 2011). For advanced stage disease, metastatic sites are treated with platinum-based combination chemotherapy. While initial response rates are high (50–79%), recurrence or progression are frequent (Gardner et al. 2011). Due to the aggressiveness of the tumour, pregnant women diagnosed with NESCCC should undergo definitive therapy, regardless of gestational age, thus expectant management waiting for delivery at term should be discouraged (Teefey et al. 2012). Cancer during pregnancy is a rare event. Nevertheless, vertical transmission of maternal small-cell lung cancer to the fetus (Teksam
et al. 2004) and a case of placental involvement in NESCCC (Wang et al. 2005) have been described. For this reason, our woman’s infant underwent MRI at 1 month of life and is currently undergoing strict clinical and imaging follow-up. Fortunately, he remains healthy at the age of 14 months. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Estermann F, Thiebault S, Turnani C et al. 1996. Pseudocystic metastases of carcinoma of the uterine cervix mimicking polycystic liver disease. Gastroenterologie Clinique et Biologique 20:1125–1128. Gardner GJ, Reidy-Lagunes D, Gehrig PA. 2011. Neuroendocrine tumors of the gynecologic tract: A Society of Gynecologic Oncology (SGO) clinical document. Gynecologic Oncology 122:190–198. McDermott EW. 1987. Metastatic carcinoid tumor presenting as a hepatic pseudocyst. Irish Journal of Medical Science 56:149–150. Ohwada M, Suzuki M, Hironaka M et al. 2001. Neuroendocrine small cell carcinoma of the uterine cervix showing polypoid growth and complicated by pregnancy. Gynecologic Oncology 81:117–119. Perrin L, Bell J, Ward B. 1996. Small cell carcinoma of the cervix of neuroendocrine origin causing obstructed labour. Australian and New Zealand Journal of Obstetrics and Gynaecology 1:85–87. Teefey P, Orr B, Vogt M et al. 2012. Neuroendocrine carcinoma of the cervix during pregnancy: A case report. Gynecologic Oncology Reports 2:73–74. Teksam M, McKinney A, Short J, Casey SO, Truwit CL. 2004. Intracranial metastasis via transplacental (vertical) transmission of maternal small cell lung cancer to fetus: CT and MRI findings. Acta Radiológica 45:577–579. Wagenaar SS. 1999. New WHO-classification of lung and pleural tumors. Nederlands Tijdschrift voor Geneeskunde 143:984–990. Wang Z, Cao S, Lai X, Yang Y, Guo Z. 2005. Placental metastasis from a case of neuroendocrine small cell carcinoma of the uterine cervix complicating pregnancy. Journal of Chinese Electron Microscopy Society 24:520–523.
ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20
Metastatic small-cell carcinoma of the cervix during pregnancy M. J. Canto, N. Pons, I. Mendez, A. Reus & F. Ojeda To cite this article: M. J. Canto, N. Pons, I. Mendez, A. Reus & F. Ojeda (2014) Metastatic smallcell carcinoma of the cervix during pregnancy, Journal of Obstetrics and Gynaecology, 34:2, 204-205 To link to this article: http://dx.doi.org/10.3109/01443615.2013.845550
Published online: 23 Jan 2014.
Submit your article to this journal
Article views: 50
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijog20 Download by: [University of Florida]
Date: 05 November 2015, At: 16:12
204
Obstetric Case Reports
Metastatic small-cell carcinoma of the cervix during pregnancy M. J. Canto1,3, N. Pons1, I. Mendez2, A. Reus1 & F. Ojeda1,3 Department of 1Obstetrics and Gynaecology, 2Pathology, Hospital General of Granollers and 3Universitat Internacional de Catalunya, Barcelona, Spain DOI: 10.3109/01443615.2013.845550 Correspondence: M. J. Canto, Department of Obstetrics and Gynaecology, Hospital General de Granollers, Avda. Francesc Ribas s/n, 080400, Granollers, Barcelona, Spain. E-mail: [email protected]
Downloaded by [University of Florida] at 16:12 05 November 2015
Introduction Neuroendocrine small-cell carcinoma of the uterine cervix (NESCCC) is a very uncommon tumour, accounting for less than 2% of all cervical malignancies. This entity mixes clinical and biological characteristics of both cervical neoplasms, such as local aggressiveness and smallcell carcinoma of any site, such as propensity for early metastasis and lymph node spread at early stages. Moreover, screening with cytology is useless, since NESCCC is thought to arise from argyrophilic cells or subcolumnar cells, which, combined with the lack of in situ component and rapid growth, makes prior Papanicolaou smears often negative (Perrin et al. 1996). Consequently, the prognosis is usually worse than that for stage-comparable poorly-differentiated squamous cell carcinoma of the cervix (Gardner et al. 2011). Only a few cases occurring during pregnancy have been reported (Teefey et al. 2012), showing an aggressive clinical course and poor prognosis. We report a case of a woman with cystic hepatic metastases of a NESCCC diagnosed at the postpartum period.
Case report A 30-year-old primigravida, with no significant past medical history, presented at 36 weeks’ gestation, with premature rupture of the membranes. Speculum examination detected pooling of liquor in the posterior fornix of the vagina and revealed a closed cervix, with a 3 cm Nabothian cyst-like nodule in the anterior lip. Transvaginal ultrasonography showed a cervical length of 26 mm and the cystic nature of the nodule. She had a negative cervical Papanicolaou smear 1 year earlier. Since the woman presented with a blood pressure of 145/95 and ⫹⫹⫹ of qualitative proteinuria at admission, and also complained of progressive bilateral leg oedema during the last week, a likely pre-eclampsia was diagnosed.
Induction of labour with prostaglandins was indicated, while intravenous perfusion of antibiotics, labetalol and magnesium sulfate was initiated. A healthy male infant weighing 2,450 g with Apgar scores 9–10 at 1–5 min was delivered. When the birth canal was explored, the cervical cyst had ruptured and was draining a mucous secretion. Blood pressure normalised in the first days postpartum, but the oedema worsened and transaminases increased markedly. Of note, her physical exam revealed a distended abdomen with hepatomegaly. Abdominal ultrasound and abdominopelvic CT scan showed a massively enlarged liver with multiple cysts and the existence of several small nodules in both lung bases, which were confirmed by chest CT. IgG and IgE for Echinococcus, and serum tumour markers (CA125, CA19.9, CEA and CA15.3) showed as normal. In view of the possibility that a metastatic process of unknown origin was present, a PET was performed, showing an increased uptake in uterine cervix and multiple images through the liver, pelvis, sacrum, right breast and lungs, suggestive of metastases (Figure 1). Thus, a thorough gynaecological examination was performed by an experienced gynae-oncologist, which showed an area of stony consistency at the level corresponding to the previously found ruptured cyst. A biopsy of this cervical area was taken and revealed a poorlydifferentiated NESCCC, with a mitotic index of 80%. Immunohistochemical study revealed positivity for pancytokeratin-7 (CK-7), neuronal cell adhesion molecule (CD-56) (Figure 2), chromogranin A (CgA), synaptophysin (Syn) and p16, and was negative for thyroid transcription factor (TTF-1), CK-20, vimentin and p53. Stage IV-B NESCCC was diagnosed, and the first cycle treatment with cisplatin and etoposide was administered. However, 1 month postpartum, the patient showed a progressive systemic deterioration, with severe respiratory distress and clinical suspicion of pulmonary thromboembolism. Unfortunately, the patient died, despite intensive management. Her family refused permission for autopsy. At the time of writing, her child is 14 months old and is developing as a healthy child, without any evidence of metastatic disease.
Discussion Only 16 cases of NESCCC during pregnancy have been reported to date (Teefey et al. 2012). The presenting symptom is usually vaginal bleeding, though in some cases, clinical or biochemical evidence of ectopic hormone production may be present. A cervical mass at gynaecological examination, with a polypoid growth of NESCCC has also been described (Ohwada et al. 2001). Cystic liver metastases are rare, but mainly described in neuroendocrine or gynaecological malignant tumours (McDermott 1987; Estermann et al. 1996). Cystic formation is probably due to infarction with liquefaction necrosis of tumour nodules. To our knowledge, this
Figure 1. PET showing increased uptake in uterine cervix and multiple images through the liver.
Downloaded by [University of Florida] at 16:12 05 November 2015
Obstetric Case Reports 205
Figure 2. Immunohistochemically stained section of NESCCC showing positive labelling (brick red coloured) for CD56 in the membranes of the cells.
is the first case of cystic liver metastatic NESCCC described during pregnancy. Histologically, NESCCC is similar to small-cell carcinoma of the lung. It consists of round to spindle-shaped cells with scanty cytoplasm, granular nuclei and absent or inconspicuous nucleoli. Analogous to small-cell lung cancer, the diagnosis of NESCCC is aided by immunohistochemical staining for common neuroendocrine markers, including synaptophysin (Syn), chromogranin A (CgA) and CD56 (Wagenaar 1999). Also, thyroid transcription factor (TTF-1) has been found to be positive with a high intensity in pulmonary small-cell carcinoma, but negative or positive with a low intensity in the extrapulmonary compartment. Accordingly, our patient showed this immunohistochemical profile. The staging of NESCCC follows that for traditional cervical cancer. However, given the high rate of distant metastatic spread of these cancers, PET/CT imaging may be reasonable to consider in the extension study. On the other hand, brain metastases are more uncommon, thus a head CT is usually not required on the initial evaluation for NESCCC (Gardner et al. 2011). Usually, the clinical course of NESCCC is dismal. In 2011, guidelines for the management of this condition were published, suggesting a multimodality approach (Gardner et al. 2011). For early stages, a multimodality therapeutic strategy is needed, including surgical resection with radical hysterectomy, pelvic radiotherapy and chemotherapy, with etoposide and platinum (Gardner et al. 2011). For advanced stage disease, metastatic sites are treated with platinum-based combination chemotherapy. While initial response rates are high (50–79%), recurrence or progression are frequent (Gardner et al. 2011). Due to the aggressiveness of the tumour, pregnant women diagnosed with NESCCC should undergo definitive therapy, regardless of gestational age, thus expectant management waiting for delivery at term should be discouraged (Teefey et al. 2012). Cancer during pregnancy is a rare event. Nevertheless, vertical transmission of maternal small-cell lung cancer to the fetus (Teksam
et al. 2004) and a case of placental involvement in NESCCC (Wang et al. 2005) have been described. For this reason, our woman’s infant underwent MRI at 1 month of life and is currently undergoing strict clinical and imaging follow-up. Fortunately, he remains healthy at the age of 14 months. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Estermann F, Thiebault S, Turnani C et al. 1996. Pseudocystic metastases of carcinoma of the uterine cervix mimicking polycystic liver disease. Gastroenterologie Clinique et Biologique 20:1125–1128. Gardner GJ, Reidy-Lagunes D, Gehrig PA. 2011. Neuroendocrine tumors of the gynecologic tract: A Society of Gynecologic Oncology (SGO) clinical document. Gynecologic Oncology 122:190–198. McDermott EW. 1987. Metastatic carcinoid tumor presenting as a hepatic pseudocyst. Irish Journal of Medical Science 56:149–150. Ohwada M, Suzuki M, Hironaka M et al. 2001. Neuroendocrine small cell carcinoma of the uterine cervix showing polypoid growth and complicated by pregnancy. Gynecologic Oncology 81:117–119. Perrin L, Bell J, Ward B. 1996. Small cell carcinoma of the cervix of neuroendocrine origin causing obstructed labour. Australian and New Zealand Journal of Obstetrics and Gynaecology 1:85–87. Teefey P, Orr B, Vogt M et al. 2012. Neuroendocrine carcinoma of the cervix during pregnancy: A case report. Gynecologic Oncology Reports 2:73–74. Teksam M, McKinney A, Short J, Casey SO, Truwit CL. 2004. Intracranial metastasis via transplacental (vertical) transmission of maternal small cell lung cancer to fetus: CT and MRI findings. Acta Radiológica 45:577–579. Wagenaar SS. 1999. New WHO-classification of lung and pleural tumors. Nederlands Tijdschrift voor Geneeskunde 143:984–990. Wang Z, Cao S, Lai X, Yang Y, Guo Z. 2005. Placental metastasis from a case of neuroendocrine small cell carcinoma of the uterine cervix complicating pregnancy. Journal of Chinese Electron Microscopy Society 24:520–523.
