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Originally published as JCO Early Release 10.1200/JCO.2008.16.4129 on October 6 2008 © 2008 American Society of Clinical Oncology.
Gestational Choriocarcinoma Mimicking a Uterine Adenocarcinoma
Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Campus of Imperial College Hospitals NHS Trust; Imperial College London, School of Medicine & Department of Biosurgery and Surgical Technology, St Mary's Hospital, Paddington, London, United Kingdom
Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Campus of Imperial College Hospitals NHS Trust, London, United Kingdom In August 2006, a 45-year-old woman presented to her local hospital with vaginal bleeding. She had two previous full-term pregnancies, the most recent of which was 20 years ago. Her urine β-human chorionic gonadotrophin (β-hCG) was positive and serum levels measured 170,000 IU/L (normal < 5 IU/L). The patient was certain she was not pregnant as her partner had undergone a vasectomy 16 years earlier. An abdominal ultrasound revealed an abnormal uterus with two suspicious lesions. Within 2 hours, she developed a major vaginal hemorrhage and underwent an emergency hysterectomy, a bilateral salpingo-oophorectomy, and an omentectomy. Postoperatively, the serum β-hCG fell to 4,500 IU/L. Macroscopically, the uterus was enlarged with a hemorrhagic and necrotic tumor arising within the cavity (Figure 1A, macroscopic appearance of the hemorrhagic necrotic tumor within the uterine cavity). Microscopy showed an invasive high-grade adenocarcinoma infiltrating the myometrium, with some areas demonstrating choriocarcinomatous differentiation (immunostaining for β-hCG, and cytokeratin). Vascular invasion was present, but there was no evidence of tumor outside the uterus. The cytology from peritoneal washings was negative. The tumor was initially diagnosed as a primary epithelial uterine tumor with choriocarcinomatous differentiation, but was referred to the gestational trophoblastic disease center at Charing Cross (London, United Kingdom) for a further opinion. Review of the histological features concurred with the initial diagnosis of a primary uterine adenocarcinoma, with some elements displaying choriocarcinomatous and placental site trophoblastic tumor differentiation (Fig 1B, Photomicrographs of uterine tumor showing areas of adenocarcinoma [hematoxylin and eosin {H & E} x40]; 1C, adenocarcinoma [H & E x100]; 1D choriocarcinoma [H & E x40]; and 1E, placental site trophoblastic tumor [H & E x200]). To ensure that this was a nongestational tumor, we genotyped the patient, her partner, and the tumor as previously described.1 There were five informative microsatellite polymorphisms. Strikingly, both paternal and maternal alleles were present in the tumor, indicating that this was in fact a gestational cancer. A computed tomography body scan to determine disease extent was normal. However, incomplete disease resection was indicated by an inappropriately slow fall in the serum hCG concentration after surgery. Therefore chemotherapy was commenced using etoposide, methotrexate, and dactinomycin, alternating weekly with cyclophosphamide and vincristine.2 The patient's β-hCG concentration normalized and treatment was completed in December 2006 (Figure 2, graph of serum β-hCG levels plotted against time course of treatments: hysterectomy plus bilateral salpingo-oophrectomy, etoposide methotrexate, and dactinomycin, cyclophosphamide and vincristine, paclitaxel and etoposide, and paclitaxel and cisplatinum). A rise in hCG 3 weeks later indicated relapse, so additional therapy was necessary with paclitaxel and cisplatin alternating biweekly with paclitaxel and etoposide,3 which was completed in March 2007. Since then she remains in remission and is likely cured.4
It is well recognized that epithelial tumors including uterine adenocarcinomas can phenotypically appear as choriocarcinomas secreting hCG, but genetic analysis confirms a nongestational origin. Recognition of this is important, as the outlook for such patients is poor and represents that of the epithelial tissue of origin.5 In contrast, gestational trophoblastic tumors including choriocarcinoma and placental site trophoblastic tumors have not, to our knowledge previously been described to histologically masquerade as epithelial tumors. Here, we describe a case where this masquerading has occurred, as the tumor phenotype suggested uterine adenocarcinoma rather than a gestational tumor. Fortunately, genetic analysis revealed the true origin of the tumor, enabling the institution of appropriate life-saving chemotherapy. Indeed, without this analysis, our patient would have received pelvic radiotherapy (standard treatment for women with pelvic spread of uterine adenocarcinomas). This therapy would have been unlikely to save her. Our case highlights a fundamental feature of all cancers—their genetic and epigenetic instability. This results in many gains and losses in function of genes and proteins. Some of these genes and proteins may generate alterations in the phenotypic appearance of tumors. This can lead the histopathologist to misdiagnose the origin of the cancer, resulting in inappropriate therapy. So how should this case alter the general management of women who have epithelial tumors with trophoblastic differentiation? We believe that it remains essential to perform genetic analysis to determine the presence or absence of paternal genes in these tumors. This will enable appropriate life-saving chemotherapy to be given for those patients identified to have gestational cancers. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
ACKNOWLEDGMENTS We thank the National Commissioning Group for their continued support. M.J.S. also acknowledges support from a Cancer Research UK/Department of Health Experimental Cancer Medicine Centre grant. NOTES published online ahead of print at www.jco.org on October 6, 2008 REFERENCES 1. Seckl MJ, Fisher RA, Salerno GA, et al: Choriocarcinoma and partial hydatidiform moles. Lancet 356:36-39, 2000[CrossRef][Medline] 2. McNeish IA, Strickland S, Holden L, et al: Low-risk persistent gestational trophoblastic disease: Outcome following initial treatment with low-dose methotrexate and folinic acid, 1992-2000. J Clin Oncol 20:1838-1844, 2002 3. Osborne R, Covens A, Mirchandani D, et al: Successful salvage of relapsed high-risk gestational trophoblastic neoplasia patients using a novel paclitaxel-containing doublet. J Reprod Med 49:655-661, 2004[Medline] 4. Powles T, Savage PM, Stebbing J, et al: A comparison of patients with relapsed and chemo-refractory gestational trophoblastic neoplasia. Br J Cancer 96:732-737, 2007[CrossRef][Medline] 5. Fisher RA, Savage PM, MacDermott C, et al: The impact of molecular genetic diagnosis on the management of women with hCG-producing malignancies. Gynecol Oncol 107:413-419, 2007[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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