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Metastasis of choriocarcinoma to lumbar and sacral column
European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 110–113
Case report
Metastasis of choriocarcinoma to lumbar and sacral column Renato Augusto Menegaz, Andre´a Duarte Resende, Cle´ber Se´rgio da Silva, Ana Cristina Macedo Barcelos, Eddie Fernando Candido Murta* Discipline of Gynecology and Obstetrics, Faculty of Medicine of Triaˆngulo Mineiro, Av. Getu´lio Guarita´, s/n, 38025-440 Uberaba, MG, Brazil Received 21 January 2003; received in revised form 9 April 2003; accepted 5 September 2003
Abstract We describe the case of a patient who reported a 4-month history of edema in the lower right limb, which was accompanied by pain and paresthesia and which progressed to flaccid paraplegia. Two years earlier she had undergone a uterine curettage for hydatidiform mole. Metastases of a choriocarcinoma to the lumbar and sacral segments of the column were diagnosed. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Gestational trophoblastic neoplasia; Metastasis; Spinal column; Neurological alterations; Flaccid paraplegia
1. Introduction Choriocarcinoma is a malignant form of gestational trophoblastic neoplasia (GTN). It can appear after an intrauterine or an ectopic pregnancy and is more common after hydatiform mole. The most common locations for metastases are the lungs and the vulvo-vaginal region, and they are found less commonly in the brain and liver [1]. Other sites of metastasis, such as the skin or bones, are extremely rare [2,3]. Few cases of bone metastases have been described in the literature, and in most of these the pelvic bones have been affected [3–6]. To our knowledge, no cases of metastases in the lumbar spine have been reported in the literature. In this work, we report the case of a patient with molar metastases to the lungs and to the lumbar and sacral spine.
2. Case report The female patient was 45 years old (gravida 2, para 0, having undergone abortion on two occasions). She was admitted to the Gynecology and Obstetrics Ward of the Teaching Hospital attached to the Faculdade de Medicina do Triaˆngulo Mineiro (FMTM) on 7 December 1999. The referral was made by the neurosurgical team who attended to her in the Emergency Department. She reported having *
Corresponding author. Tel.: þ55-34-3318 5326; fax: þ55-34-3318 5342. E-mail address: [email protected] (E.F.C. Murta).
had edema in the lower right limb for 4 months, accompanied by pain, paresthesia and flaccid paraplegia, which had become incapacitating, impeding her in walking. There was no improvement with the use of ordinary analgesics. Her medical history included curettage on two occasions. The first curettage had been done 2 years earlier (1997) in another hospital because of a hydatidiform mole (anatomopathological result), and she had not subsequently returned for follow-up. Six months later, another curettage had been performed at a different hospital because of abnormal uterine bleeding, which ceased after the procedure (no histological results available). Again, she did not return for follow-up. On examination, the patient was found to have bilateral hypotrophy of the upper and lower legs, with paresthesia, especially in the right leg, and motor-sensitive paraparesis (dermatomes L-1 to S-5). Urinary incontinence had resulted from neurosensory loss. She was admitted as an inpatient with a diagnosis of radicular compression syndrome (cauda equina syndrome). A chest X-ray showed nodular opacity compatible with pulmonary metastases distributed in both lungs. Transvaginal ultrasonography with Doppler showed a uterus volume of 88.5 cm3 and heterogeneous echo texture caused by the presence of cystic images on the anterior wall of the uterus, corresponding to arteriovenous fistulae. The adnexa were normal. Ultrasonography of the abdomen and computerized tomography of the cranium were normal. Bone scintigraphy showed hyperfixation of the tracer in the L-2, L-3 and L-5 projections, characterizing an increase in osteogenic activity (Fig. 1). Magnetic resonance imaging
0301-2115/$ – see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2003.09.029
R.A. Menegaz et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 110–113
111
cular structures and was extruded via the L3–4 and L4–5 neuroforamina, thus causing invasion of the iliopsoas muscles. The L-4 planes exhibited hypersignal in T2-weighted images, which suggests microfractures or reactional hyperemia. The dissemination pattern was indicative of metastatic deposition (Figs. 2–4). The blood level of b-hCG was 22,400 mUi/ml. A clinical diagnosis of molar metastasis to the lungs and sacrolumbar column was made. The patient refused to have biopsies taken from the uterus, lungs, and spinal column. She underwent chemotherapy in the form of seven cycles of EMACO (day 1: etoposide/actinomycin-D/methotrexate; day 2: etoposide/actinomycin-D; day 8: vincristine/cyclophosphamide) and 21 radiotherapy sessions with a total dose of 4500 cGy, in a linear accelerator, to the lumbar and sacral spine over 5 weeks, in addition to clinical support. With physiotherapy there was an improvement in the neurological status, and she became able to walk around. She progressed with decreasing levels of b-hCG given in weekly doses, reaching a dose of 23.5 mUi/ml on 4 May 2000. The nodular images in the lungs regressed. The white cell count was checked regularly during each cycle of chemotherapy, and the patient did well, with improvement of her neurological symptoms. Nonetheless, she did not complete the seventh chemotherapy cycle before her death on 14 May 2000 from sepsis caused by febrile neutropenia, in spite of antibiotic therapy. Fig. 1. Bone scintigraphy showing hyperfixation of the tracer in the lumbar spine (arrows).
of the lumbar spine showed a predominantly extrathecal intracanalicular process extending from L-2 to S-1. This process was holding back and compressing the thecal-radi-
3. Discussion The most frequent site of metastases from choriocarcinoma is in the lungs, and vulvo-vaginal, cerebral, and hepatic foci are also found [1]. Baklouti et al. [3] reported the case of a 34-year-old patient with metastases in the lungs
Fig. 2. Sagital T1-weighted spin echo pre-contrast image shows geographical area of signal change (hypointesity) in posterior aspect of L-3 vertebral body (arrow), corresponding to increased radiopharmaceutical uptake (Fig. 1) and highly suggestive of vertebral metastasis. An extensive isointense intra-/ extradural mass lesion extends from L-2 to S-1 (between asterisks).
112
R.A. Menegaz et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 110–113
Fig. 3. Transverse T1-weighted spin echo post-gadolinium image at the level of L-2 demonstrates a non-uniform pattern of enhancement of the soft tissue mass, which encroaches upon the thecal sac (large arrows), invading paraspinal fat planes through both neuroforamina (small arrows).
Fig. 4. Sagittal fast spin echo T2-weighted image shows signal heterogeneity of the predominant epidural mass (between asterisks). In the posterior twothirds of the L-4 vertebral body, a hypointense area is observed (arrow).
and pelvic bones (iliac and ischio-pubic bones) and invasion of soft tissues, who was treated with polychemotherapy based on actinomycin-D, cisplatin, and vepeside and achieved a complete response to the treatment. Chama et al. [2] reported on a 40-year-old patient with skin metastases treated using polychemotherapy, which brought about their resolution. The rarity of metastasis in sites such as the muscloskeletal system and the skin can be seen from the data cited with few case reports [3–6]. In the case we have described, the patient presented with metastases to the lungs and to the bones of the sacral and lumbar spine. Although we did not have any
anatomopathological observations relating to the lumbar column, the improvement in the neurological status after chemotherapy and radiotherapy suggested that such metastases were present. Moreover, on magnetic resonance imaging, signal abnormality was seen at the basivertebral plexus, which is also suggestive of tumor invasion and was consistent with the scintigram, while in the posterior two-thirds of the L-4 vertebral body a hypointense area was observed, even though the scintigraphy did not show hyperfixation; this was also thought to represent bone metastasis. Cauda equina syndrome is linked with the level of the metastasis.
R.A. Menegaz et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 110–113
It must be emphasized that the patient did not return for follow-up after either of the two curettages she had undergone earlier; this may have contributed to a late diagnosis, which in turn played its part in the development culminating in metastasis of the choriocarcinoma. We did not have access to any histological information relating to the second curettage. Probably, if a histological investigation had been done at that time, it would have been possible to make diagnosis of choriocarcinoma and the patient’s poor evolution could have been avoided. In Brazil, there is no system of central notification for these specific cases, and the decision on whether GTN patients are followed up is the responsibility of the hospital or institute where the patient was treated or of the treating physician. When a chemotherapy scheme has been implemented in cases of molar metastasis, the cure rate has mostly been good. Yingna et al. [7] reported 51 cases of GTN metastasis to the vagina that were treated using polychemotherapy, and complete remission was achieved in 44 cases. The drugs utilized in the clinical treatment have varied widely between institutions. Gurlit et al. [8] reported four cases of choriocarcinoma, in one of which there was metastasis to the lungs and in one there was a vaginal metastasis. Low-risk patients according to the Bagshawe score were treated with methotrexate and high-risk patients, with PEB (platinum, etoposide, and bleomycin), with a good response in all cases [9]. In the case of our patient, we utilized the EMACO scheme with a good response. The white cell count was checked regularly during each cycle of chemotherapy, and she continued very well. Notwithstanding, after the last cycle of chemotherapy the patient died from complications of sepsis. Even so, the treatment for malignant forms of GTN must include chemotherapy in light of the good results reported in the literature. Radiotherapy can also be utilized when bone metastases are present [5]. In our case, the combined treatment with chemotherapy and radiotherapy improved the neurological symptoms. Nevertheless, the place of radiotherapy must be better investigated.
113
Bone metastases secondary to choriocarcinoma are exceptional. Nonetheless, they are a possibility that must be considered in patients with a history of hydatidiform mole who seem to have received inadequate treatment or who have neurological symptoms or signs.
Acknowledgements We thank Viviane Beatriz Rodrigues Matos, Rodrigo Delfino Nascimento, Jose´ Luiz Weffort, Alfredo Leboreiro Fernandez, and Edilson Barbosa de Souza for technical assistance and CNPq (Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´ gico) for financial support. CNPq (Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´ gico) provided financial support.
References [1] Droz JP, L’homme C. Les tumeurs trophoblastiques gestationnelles. Rev Prat 1992;42:817–22. [2] Chama CM, Nggada HA, Nuhu A. Cutaneous metastasis of gestational choriocarcinoma. Obstet Gynecol 2002;77:249–50. [3] Baklouti S, Elleuch H, Kammoun MH, Sellami S. Me´ tastase osseuse re´ le´vatrice d’un choriocarcinome placentaire. A propos d’un cas Int Orthop 1995;19:190–2. [4] Surwit EA, Hammond EA. Treatment of metastatic trophoblastic disease with poor prognosis. Obstet Gynecol 1980;55:565–70. [5] Azab M, Pejovic MH. Prognostic factors in gestational trophoblastic tumors. A multivariate analysis. Cancer 1988;62:585–92. [6] Vani R. Choriocarcinoma following term pregnancy with bone metastasis. Int J Gynecol Obstet 1993;40:252–3. [7] Yingna S, Xiang Y, Xiuyu Y, Hongzhao S. Clinical characteristics and treatment of gestational trophoblastic tumor with vaginal metastasis. Gynecol Oncol 2002;84:416–9. [8] Gurlit L, Sampe S, Goeschen R, Krech R, Hartlapp HJ, Bohmer S. Typical forms of choriocarcinoma in clinical practice—diagnosis and therapeutic course in 4 patients. Zentralbl Gynakol 2001;123:383–9. [9] Bagshawe KD. High-risk metastatic trophoblastic disease. Obstet Gynecol Clin North Am 1988;15:531–43.
Case report
Metastasis of choriocarcinoma to lumbar and sacral column Renato Augusto Menegaz, Andre´a Duarte Resende, Cle´ber Se´rgio da Silva, Ana Cristina Macedo Barcelos, Eddie Fernando Candido Murta* Discipline of Gynecology and Obstetrics, Faculty of Medicine of Triaˆngulo Mineiro, Av. Getu´lio Guarita´, s/n, 38025-440 Uberaba, MG, Brazil Received 21 January 2003; received in revised form 9 April 2003; accepted 5 September 2003
Abstract We describe the case of a patient who reported a 4-month history of edema in the lower right limb, which was accompanied by pain and paresthesia and which progressed to flaccid paraplegia. Two years earlier she had undergone a uterine curettage for hydatidiform mole. Metastases of a choriocarcinoma to the lumbar and sacral segments of the column were diagnosed. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Gestational trophoblastic neoplasia; Metastasis; Spinal column; Neurological alterations; Flaccid paraplegia
1. Introduction Choriocarcinoma is a malignant form of gestational trophoblastic neoplasia (GTN). It can appear after an intrauterine or an ectopic pregnancy and is more common after hydatiform mole. The most common locations for metastases are the lungs and the vulvo-vaginal region, and they are found less commonly in the brain and liver [1]. Other sites of metastasis, such as the skin or bones, are extremely rare [2,3]. Few cases of bone metastases have been described in the literature, and in most of these the pelvic bones have been affected [3–6]. To our knowledge, no cases of metastases in the lumbar spine have been reported in the literature. In this work, we report the case of a patient with molar metastases to the lungs and to the lumbar and sacral spine.
2. Case report The female patient was 45 years old (gravida 2, para 0, having undergone abortion on two occasions). She was admitted to the Gynecology and Obstetrics Ward of the Teaching Hospital attached to the Faculdade de Medicina do Triaˆngulo Mineiro (FMTM) on 7 December 1999. The referral was made by the neurosurgical team who attended to her in the Emergency Department. She reported having *
Corresponding author. Tel.: þ55-34-3318 5326; fax: þ55-34-3318 5342. E-mail address: [email protected] (E.F.C. Murta).
had edema in the lower right limb for 4 months, accompanied by pain, paresthesia and flaccid paraplegia, which had become incapacitating, impeding her in walking. There was no improvement with the use of ordinary analgesics. Her medical history included curettage on two occasions. The first curettage had been done 2 years earlier (1997) in another hospital because of a hydatidiform mole (anatomopathological result), and she had not subsequently returned for follow-up. Six months later, another curettage had been performed at a different hospital because of abnormal uterine bleeding, which ceased after the procedure (no histological results available). Again, she did not return for follow-up. On examination, the patient was found to have bilateral hypotrophy of the upper and lower legs, with paresthesia, especially in the right leg, and motor-sensitive paraparesis (dermatomes L-1 to S-5). Urinary incontinence had resulted from neurosensory loss. She was admitted as an inpatient with a diagnosis of radicular compression syndrome (cauda equina syndrome). A chest X-ray showed nodular opacity compatible with pulmonary metastases distributed in both lungs. Transvaginal ultrasonography with Doppler showed a uterus volume of 88.5 cm3 and heterogeneous echo texture caused by the presence of cystic images on the anterior wall of the uterus, corresponding to arteriovenous fistulae. The adnexa were normal. Ultrasonography of the abdomen and computerized tomography of the cranium were normal. Bone scintigraphy showed hyperfixation of the tracer in the L-2, L-3 and L-5 projections, characterizing an increase in osteogenic activity (Fig. 1). Magnetic resonance imaging
0301-2115/$ – see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2003.09.029
R.A. Menegaz et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 110–113
111
cular structures and was extruded via the L3–4 and L4–5 neuroforamina, thus causing invasion of the iliopsoas muscles. The L-4 planes exhibited hypersignal in T2-weighted images, which suggests microfractures or reactional hyperemia. The dissemination pattern was indicative of metastatic deposition (Figs. 2–4). The blood level of b-hCG was 22,400 mUi/ml. A clinical diagnosis of molar metastasis to the lungs and sacrolumbar column was made. The patient refused to have biopsies taken from the uterus, lungs, and spinal column. She underwent chemotherapy in the form of seven cycles of EMACO (day 1: etoposide/actinomycin-D/methotrexate; day 2: etoposide/actinomycin-D; day 8: vincristine/cyclophosphamide) and 21 radiotherapy sessions with a total dose of 4500 cGy, in a linear accelerator, to the lumbar and sacral spine over 5 weeks, in addition to clinical support. With physiotherapy there was an improvement in the neurological status, and she became able to walk around. She progressed with decreasing levels of b-hCG given in weekly doses, reaching a dose of 23.5 mUi/ml on 4 May 2000. The nodular images in the lungs regressed. The white cell count was checked regularly during each cycle of chemotherapy, and the patient did well, with improvement of her neurological symptoms. Nonetheless, she did not complete the seventh chemotherapy cycle before her death on 14 May 2000 from sepsis caused by febrile neutropenia, in spite of antibiotic therapy. Fig. 1. Bone scintigraphy showing hyperfixation of the tracer in the lumbar spine (arrows).
of the lumbar spine showed a predominantly extrathecal intracanalicular process extending from L-2 to S-1. This process was holding back and compressing the thecal-radi-
3. Discussion The most frequent site of metastases from choriocarcinoma is in the lungs, and vulvo-vaginal, cerebral, and hepatic foci are also found [1]. Baklouti et al. [3] reported the case of a 34-year-old patient with metastases in the lungs
Fig. 2. Sagital T1-weighted spin echo pre-contrast image shows geographical area of signal change (hypointesity) in posterior aspect of L-3 vertebral body (arrow), corresponding to increased radiopharmaceutical uptake (Fig. 1) and highly suggestive of vertebral metastasis. An extensive isointense intra-/ extradural mass lesion extends from L-2 to S-1 (between asterisks).
112
R.A. Menegaz et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 110–113
Fig. 3. Transverse T1-weighted spin echo post-gadolinium image at the level of L-2 demonstrates a non-uniform pattern of enhancement of the soft tissue mass, which encroaches upon the thecal sac (large arrows), invading paraspinal fat planes through both neuroforamina (small arrows).
Fig. 4. Sagittal fast spin echo T2-weighted image shows signal heterogeneity of the predominant epidural mass (between asterisks). In the posterior twothirds of the L-4 vertebral body, a hypointense area is observed (arrow).
and pelvic bones (iliac and ischio-pubic bones) and invasion of soft tissues, who was treated with polychemotherapy based on actinomycin-D, cisplatin, and vepeside and achieved a complete response to the treatment. Chama et al. [2] reported on a 40-year-old patient with skin metastases treated using polychemotherapy, which brought about their resolution. The rarity of metastasis in sites such as the muscloskeletal system and the skin can be seen from the data cited with few case reports [3–6]. In the case we have described, the patient presented with metastases to the lungs and to the bones of the sacral and lumbar spine. Although we did not have any
anatomopathological observations relating to the lumbar column, the improvement in the neurological status after chemotherapy and radiotherapy suggested that such metastases were present. Moreover, on magnetic resonance imaging, signal abnormality was seen at the basivertebral plexus, which is also suggestive of tumor invasion and was consistent with the scintigram, while in the posterior two-thirds of the L-4 vertebral body a hypointense area was observed, even though the scintigraphy did not show hyperfixation; this was also thought to represent bone metastasis. Cauda equina syndrome is linked with the level of the metastasis.
R.A. Menegaz et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 110–113
It must be emphasized that the patient did not return for follow-up after either of the two curettages she had undergone earlier; this may have contributed to a late diagnosis, which in turn played its part in the development culminating in metastasis of the choriocarcinoma. We did not have access to any histological information relating to the second curettage. Probably, if a histological investigation had been done at that time, it would have been possible to make diagnosis of choriocarcinoma and the patient’s poor evolution could have been avoided. In Brazil, there is no system of central notification for these specific cases, and the decision on whether GTN patients are followed up is the responsibility of the hospital or institute where the patient was treated or of the treating physician. When a chemotherapy scheme has been implemented in cases of molar metastasis, the cure rate has mostly been good. Yingna et al. [7] reported 51 cases of GTN metastasis to the vagina that were treated using polychemotherapy, and complete remission was achieved in 44 cases. The drugs utilized in the clinical treatment have varied widely between institutions. Gurlit et al. [8] reported four cases of choriocarcinoma, in one of which there was metastasis to the lungs and in one there was a vaginal metastasis. Low-risk patients according to the Bagshawe score were treated with methotrexate and high-risk patients, with PEB (platinum, etoposide, and bleomycin), with a good response in all cases [9]. In the case of our patient, we utilized the EMACO scheme with a good response. The white cell count was checked regularly during each cycle of chemotherapy, and she continued very well. Notwithstanding, after the last cycle of chemotherapy the patient died from complications of sepsis. Even so, the treatment for malignant forms of GTN must include chemotherapy in light of the good results reported in the literature. Radiotherapy can also be utilized when bone metastases are present [5]. In our case, the combined treatment with chemotherapy and radiotherapy improved the neurological symptoms. Nevertheless, the place of radiotherapy must be better investigated.
113
Bone metastases secondary to choriocarcinoma are exceptional. Nonetheless, they are a possibility that must be considered in patients with a history of hydatidiform mole who seem to have received inadequate treatment or who have neurological symptoms or signs.
Acknowledgements We thank Viviane Beatriz Rodrigues Matos, Rodrigo Delfino Nascimento, Jose´ Luiz Weffort, Alfredo Leboreiro Fernandez, and Edilson Barbosa de Souza for technical assistance and CNPq (Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´ gico) for financial support. CNPq (Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´ gico) provided financial support.
References [1] Droz JP, L’homme C. Les tumeurs trophoblastiques gestationnelles. Rev Prat 1992;42:817–22. [2] Chama CM, Nggada HA, Nuhu A. Cutaneous metastasis of gestational choriocarcinoma. Obstet Gynecol 2002;77:249–50. [3] Baklouti S, Elleuch H, Kammoun MH, Sellami S. Me´ tastase osseuse re´ le´vatrice d’un choriocarcinome placentaire. A propos d’un cas Int Orthop 1995;19:190–2. [4] Surwit EA, Hammond EA. Treatment of metastatic trophoblastic disease with poor prognosis. Obstet Gynecol 1980;55:565–70. [5] Azab M, Pejovic MH. Prognostic factors in gestational trophoblastic tumors. A multivariate analysis. Cancer 1988;62:585–92. [6] Vani R. Choriocarcinoma following term pregnancy with bone metastasis. Int J Gynecol Obstet 1993;40:252–3. [7] Yingna S, Xiang Y, Xiuyu Y, Hongzhao S. Clinical characteristics and treatment of gestational trophoblastic tumor with vaginal metastasis. Gynecol Oncol 2002;84:416–9. [8] Gurlit L, Sampe S, Goeschen R, Krech R, Hartlapp HJ, Bohmer S. Typical forms of choriocarcinoma in clinical practice—diagnosis and therapeutic course in 4 patients. Zentralbl Gynakol 2001;123:383–9. [9] Bagshawe KD. High-risk metastatic trophoblastic disease. Obstet Gynecol Clin North Am 1988;15:531–43.