Pediatric Hematology and Oncology, 31:362–365, 2014 C Informa Healthcare USA, Inc. Copyright ISSN: 0888-0018 print / 1521-0669 online DOI: 10.3109/08880018.2013.879399
LETTER
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Maastricht on 07/01/14 For personal use only.
Primary Ovarian Malignant Melanoma Arising in Teratomatous Component of Mixed- Germ Cell Tumor in a Child: Case report ¨ or ¨ uk, ¨ MD,1 Hacı Ahmet Demir, MD,1 Suna Emir, MD,1 Derya Ozy Asuman Nihan Haberal, MD,2 Meral Bugdaycı, MD,3 ¨ un, ¨ MD4 and ˙Ibrahim Otg 1
Division of Pediatric Oncology, Ankara Children’s Hematology and Oncology Hospital, Ankara, Turkey; 2 Department of Pathology, Baskent University, Faculty of Medicine, Ankara, Turkey; 3 Department of Pathology, Faculty of Medicine, Hacettepe University, Ankara, Turkey; 4 Department of Pediatric Surgery, Faculty of Medicine, Baskent University, Ankara, Turkey
Primary ovarian malignant melanoma arising in teratomatous component of germ cell tumors is seen extremely rare with most reports being only of single cases and small series in reproductive aged woman and mostly from cystic teratoma, whereas information on pediatric presentation is sparse. This case is reported for being extremely rare tumor. Keywords germ cell tumor, malignant melanoma, teratomatous component
INTRODUCTION Primary ovarian malignant melanoma arising in teratomatous component of germ cell tumors is seen extremely rare with most reports being only of single cases and small series in reproductive aged woman and mostly from cystic teratoma, whereas information on pediatric presentation is sparse [1–3]. This case is reported for being extremely rare tumor. Case Report An 11-year-old female referred to our pediatric oncology center after unilateral salpingo-oophorectomy was performed due to left ovarian mass (20 × 12 × 10 cm in diameters). On physical examination, she has surgical incision scar of abdomen. Serum human chorionic gonadotropin (β-hCG) was 58.89 IU/L, α fetoprotein (AFP) 21.69 ng/mL, and lactate dehydrogenase was 1147 IU/L. The computed tomography (CT) of thorax showed metastatic foci in mediastinum and subpleural regions. Histopathological investigation revealed anaplastic form of dysgerminoma (Ki-67 > 80%, p53 positivity 80%) (Figure 1A and 1B). After third cycles BEP (cisplatin, etoposide, and bleomycine), thorax CT and the serum tumor markers were normal, but Received 24 December 2013; accepted 25 December 2013. ¨ oruk, Address correspondence to Derya Ozy¨ ¨ MD, Division of Pediatric Oncology, Ankara Children’s Hematology and Oncology Hospital, Ankara, Turkey. E-mail: [email protected]
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Maastricht on 07/01/14 For personal use only.
Letter
FIGURE 1 The histopathology and immunohistochemistry of dysgerminoma; (A) Hematoxylin and eosin stain (H&E stain or HE stain) and (B) OCT3/4 stain.
abdomen CT showed a mass of 3.5 × 2 cm in diameters at the left paraaortic and infrarenal regions. After sixth BEP cycles the mass persisted. 18-FDG-PET-CT revealed inactive residual calcified mass. The imaging investigation showed twofold increase in size at second month of follow up period and second-look surgery was performed. The mass was removed and its diameters were 4.2 × 3.4 × 3 cm, macroscopically. The cut surface was partially solid and cystic. There were some mixoid and calcified areas (Figure 2A). Histopathological examination revealed a Grade 3 immature teratoma with malignant melanoma foci (Figure 2B, 2C, and 2D). Malignant melanoma areas showed diffuse strong positive reaction with MELAN- A (Figure 2E), HMB-45 (Figure 2F), and CD 117 antibodies. In addition, tumor areas were focally positive with S-100 and vimentin antibodies. PLAP, CK AE1/AE3, OCT-4, and CD 30 antibodies were negative at the tumor site. Beta HCG and EMA antibodies were also negative. After total resection of residual tumor, adjuvant chemotherapy was not administered due to clear margins of the tumor and not found any metastatic foci in staging studies. At the sixth month of follow-up period, she presented with multiple metastatic foci to liver and lung. Liver biopsy showed malignant melanoma metastasis. Tumor cells showed diffuse positive immunohistochemical reaction for HMB-45 and S-100 protein, focal positive immunohistochemical reaction for melan-A and c-kit expression was also noted. The chemotherapy was started consisting of vincristine, dacarbasine, and interferon alfa. Imatinib mesylate was also added to the treatment because of c-kit expression. The patient died with progressive disease at 10th month of treatment. DISCUSSION Ovarian tumors comprise 25% of all pediatric germ cell tumors. Dysgerminoma is the most common malignant ovarian tumor in children. It may occur in a pure form or as a component of a mixed malignant germ cell tumor [4]. Pure dysgerminoma is endocrinologically inactive. The hormonal activity indicates the presence of a functioning component, placing the tumor into a mixed germ cell category [5]. Our case was not pure dysgerminoma, because AFP and B-hCG levels were increased in initial diagnosis. Also, second-look surgery was revealed immature teratoma together with malignant melanoma foci. C Informa Healthcare USA, Inc. Copyright
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Maastricht on 07/01/14 For personal use only.
¨ oruk ¨ et al. D. Ozy¨
FIGURE 2 Histopathological findings of immature teratoma with malignant melanoma foci; (A) Macroscobic appearance of the excised mass, (B) histopathological imaging of immature teratoma, (C) and (D) Hematoxylin and eosin stain of malignant melanoma, (E) Melan A stain, and (F) HMB45 stain.
Teratoma with a malignant somatic component is a rare entity in childhood and it can be epithelial (i.e., carcinoma) or mesenchymal (i.e., neuroblastoma or sarcoma) origin. Also, it can be found in all the sites of occurrence of teratomas, such as: sacroccocigeal, CNS, testicular, ovarian, mediastinal, retroperitoneal, and some other rare primary sites [6]. While teratoma with malignant transformation is a rare but well recognized phenomen in adult germ cell tumors, data on pediatric case are lacking [7]. Although there is no consensus about optimal treatment of teratoma with malignant transformation, complete surgical resection of the tumor or resection of residual disease after systemic therapy has been suggested. The role of adjuvant chemotherapy remains unclear. Chemotherapy should be specific for histologic component [6, 7]. Negative (18)F-FDG PET studies do not exclude the presence of disease, mainly because of the presence of teratoma [8]. Although the FDG PET results of our case were revealed inactive residual tissue, histopathologic study showed immature teratom with malignant melanoma foci. Also, growing teratoma syndrome was excluded. Pediatric Hematology and Oncology
Letter
Growing teratoma syndrome is defined as enlarging masses of mature teratoma following chemotherapy for malignant nonseminomatous germ-cell tumors [9]. In conclusion, we want to point out the necessity to check all teratoma tissue in germ cell tumors, due to other malignant micro foci could be present at diagnosis and/or relapse. Declaration of Interest
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Maastricht on 07/01/14 For personal use only.
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. REFERENCES [1] Gupta D, Deavers MT, Silva EG, et al. Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases. Am J Surg Pathol. 2004;28(6):771–780. [2] Boughton RS, Hughmanick S, Marin-Padilla M. Malignant melanoma arising in an ovarian cystic teratoma in pregnancy. J Am Acad Dermatol. 1987;17(5 Pt 2):871–875. [3] Tham KT, Ma PH, Kung TM. Malignant melanoma in an ovarian cystic teratoma. Hum Pathol. 1981;12(6):577–579. [4] Weinblatt ME, Ortega JA. Treatment of children with dysgerminoma of the ovary. Cancer. 1982;49(12):2608–2611. [5] Zuntova A, Sumerauer D, Teslik L, et al. [Ovarian dysgerminoma in children and adolescents. Retrospective clinico-pathologic study]. Cas Lek Cesk. 2004;143(4):246–252. [6] Terenziani M, D’Angelo P, Bisogno G, et al. Teratoma with a malignant somatic component in pediatric patients: the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience. Pediatr Blood Cancer. 2010;54(4):532–537. [7] Biskup W, Calaminus G, Schneider DT, et al. Teratoma with malignant transformation: experiences of the cooperative GPOH protocols MAKEI 83/86/89/96. Klin Padiatr. 2006;218(6):303–308. [8] Johns Putra L, Lawrentschuk N, Ballok Z, et al. 18F-fluorodeoxyglucose positron emission tomography in evaluation of germ cell tumor after chemotherapy. Urology. 2004;64(6):1202–1207. [9] Nimkin K, Gupta P, McCauley R, et al. The growing teratoma syndrome. Pediatr Radiol. 2004; 34(3):259–262.
C Informa Healthcare USA, Inc. Copyright
LETTER
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Maastricht on 07/01/14 For personal use only.
Primary Ovarian Malignant Melanoma Arising in Teratomatous Component of Mixed- Germ Cell Tumor in a Child: Case report ¨ or ¨ uk, ¨ MD,1 Hacı Ahmet Demir, MD,1 Suna Emir, MD,1 Derya Ozy Asuman Nihan Haberal, MD,2 Meral Bugdaycı, MD,3 ¨ un, ¨ MD4 and ˙Ibrahim Otg 1
Division of Pediatric Oncology, Ankara Children’s Hematology and Oncology Hospital, Ankara, Turkey; 2 Department of Pathology, Baskent University, Faculty of Medicine, Ankara, Turkey; 3 Department of Pathology, Faculty of Medicine, Hacettepe University, Ankara, Turkey; 4 Department of Pediatric Surgery, Faculty of Medicine, Baskent University, Ankara, Turkey
Primary ovarian malignant melanoma arising in teratomatous component of germ cell tumors is seen extremely rare with most reports being only of single cases and small series in reproductive aged woman and mostly from cystic teratoma, whereas information on pediatric presentation is sparse. This case is reported for being extremely rare tumor. Keywords germ cell tumor, malignant melanoma, teratomatous component
INTRODUCTION Primary ovarian malignant melanoma arising in teratomatous component of germ cell tumors is seen extremely rare with most reports being only of single cases and small series in reproductive aged woman and mostly from cystic teratoma, whereas information on pediatric presentation is sparse [1–3]. This case is reported for being extremely rare tumor. Case Report An 11-year-old female referred to our pediatric oncology center after unilateral salpingo-oophorectomy was performed due to left ovarian mass (20 × 12 × 10 cm in diameters). On physical examination, she has surgical incision scar of abdomen. Serum human chorionic gonadotropin (β-hCG) was 58.89 IU/L, α fetoprotein (AFP) 21.69 ng/mL, and lactate dehydrogenase was 1147 IU/L. The computed tomography (CT) of thorax showed metastatic foci in mediastinum and subpleural regions. Histopathological investigation revealed anaplastic form of dysgerminoma (Ki-67 > 80%, p53 positivity 80%) (Figure 1A and 1B). After third cycles BEP (cisplatin, etoposide, and bleomycine), thorax CT and the serum tumor markers were normal, but Received 24 December 2013; accepted 25 December 2013. ¨ oruk, Address correspondence to Derya Ozy¨ ¨ MD, Division of Pediatric Oncology, Ankara Children’s Hematology and Oncology Hospital, Ankara, Turkey. E-mail: [email protected]
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Maastricht on 07/01/14 For personal use only.
Letter
FIGURE 1 The histopathology and immunohistochemistry of dysgerminoma; (A) Hematoxylin and eosin stain (H&E stain or HE stain) and (B) OCT3/4 stain.
abdomen CT showed a mass of 3.5 × 2 cm in diameters at the left paraaortic and infrarenal regions. After sixth BEP cycles the mass persisted. 18-FDG-PET-CT revealed inactive residual calcified mass. The imaging investigation showed twofold increase in size at second month of follow up period and second-look surgery was performed. The mass was removed and its diameters were 4.2 × 3.4 × 3 cm, macroscopically. The cut surface was partially solid and cystic. There were some mixoid and calcified areas (Figure 2A). Histopathological examination revealed a Grade 3 immature teratoma with malignant melanoma foci (Figure 2B, 2C, and 2D). Malignant melanoma areas showed diffuse strong positive reaction with MELAN- A (Figure 2E), HMB-45 (Figure 2F), and CD 117 antibodies. In addition, tumor areas were focally positive with S-100 and vimentin antibodies. PLAP, CK AE1/AE3, OCT-4, and CD 30 antibodies were negative at the tumor site. Beta HCG and EMA antibodies were also negative. After total resection of residual tumor, adjuvant chemotherapy was not administered due to clear margins of the tumor and not found any metastatic foci in staging studies. At the sixth month of follow-up period, she presented with multiple metastatic foci to liver and lung. Liver biopsy showed malignant melanoma metastasis. Tumor cells showed diffuse positive immunohistochemical reaction for HMB-45 and S-100 protein, focal positive immunohistochemical reaction for melan-A and c-kit expression was also noted. The chemotherapy was started consisting of vincristine, dacarbasine, and interferon alfa. Imatinib mesylate was also added to the treatment because of c-kit expression. The patient died with progressive disease at 10th month of treatment. DISCUSSION Ovarian tumors comprise 25% of all pediatric germ cell tumors. Dysgerminoma is the most common malignant ovarian tumor in children. It may occur in a pure form or as a component of a mixed malignant germ cell tumor [4]. Pure dysgerminoma is endocrinologically inactive. The hormonal activity indicates the presence of a functioning component, placing the tumor into a mixed germ cell category [5]. Our case was not pure dysgerminoma, because AFP and B-hCG levels were increased in initial diagnosis. Also, second-look surgery was revealed immature teratoma together with malignant melanoma foci. C Informa Healthcare USA, Inc. Copyright
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Maastricht on 07/01/14 For personal use only.
¨ oruk ¨ et al. D. Ozy¨
FIGURE 2 Histopathological findings of immature teratoma with malignant melanoma foci; (A) Macroscobic appearance of the excised mass, (B) histopathological imaging of immature teratoma, (C) and (D) Hematoxylin and eosin stain of malignant melanoma, (E) Melan A stain, and (F) HMB45 stain.
Teratoma with a malignant somatic component is a rare entity in childhood and it can be epithelial (i.e., carcinoma) or mesenchymal (i.e., neuroblastoma or sarcoma) origin. Also, it can be found in all the sites of occurrence of teratomas, such as: sacroccocigeal, CNS, testicular, ovarian, mediastinal, retroperitoneal, and some other rare primary sites [6]. While teratoma with malignant transformation is a rare but well recognized phenomen in adult germ cell tumors, data on pediatric case are lacking [7]. Although there is no consensus about optimal treatment of teratoma with malignant transformation, complete surgical resection of the tumor or resection of residual disease after systemic therapy has been suggested. The role of adjuvant chemotherapy remains unclear. Chemotherapy should be specific for histologic component [6, 7]. Negative (18)F-FDG PET studies do not exclude the presence of disease, mainly because of the presence of teratoma [8]. Although the FDG PET results of our case were revealed inactive residual tissue, histopathologic study showed immature teratom with malignant melanoma foci. Also, growing teratoma syndrome was excluded. Pediatric Hematology and Oncology
Letter
Growing teratoma syndrome is defined as enlarging masses of mature teratoma following chemotherapy for malignant nonseminomatous germ-cell tumors [9]. In conclusion, we want to point out the necessity to check all teratoma tissue in germ cell tumors, due to other malignant micro foci could be present at diagnosis and/or relapse. Declaration of Interest
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Maastricht on 07/01/14 For personal use only.
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. REFERENCES [1] Gupta D, Deavers MT, Silva EG, et al. Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases. Am J Surg Pathol. 2004;28(6):771–780. [2] Boughton RS, Hughmanick S, Marin-Padilla M. Malignant melanoma arising in an ovarian cystic teratoma in pregnancy. J Am Acad Dermatol. 1987;17(5 Pt 2):871–875. [3] Tham KT, Ma PH, Kung TM. Malignant melanoma in an ovarian cystic teratoma. Hum Pathol. 1981;12(6):577–579. [4] Weinblatt ME, Ortega JA. Treatment of children with dysgerminoma of the ovary. Cancer. 1982;49(12):2608–2611. [5] Zuntova A, Sumerauer D, Teslik L, et al. [Ovarian dysgerminoma in children and adolescents. Retrospective clinico-pathologic study]. Cas Lek Cesk. 2004;143(4):246–252. [6] Terenziani M, D’Angelo P, Bisogno G, et al. Teratoma with a malignant somatic component in pediatric patients: the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience. Pediatr Blood Cancer. 2010;54(4):532–537. [7] Biskup W, Calaminus G, Schneider DT, et al. Teratoma with malignant transformation: experiences of the cooperative GPOH protocols MAKEI 83/86/89/96. Klin Padiatr. 2006;218(6):303–308. [8] Johns Putra L, Lawrentschuk N, Ballok Z, et al. 18F-fluorodeoxyglucose positron emission tomography in evaluation of germ cell tumor after chemotherapy. Urology. 2004;64(6):1202–1207. [9] Nimkin K, Gupta P, McCauley R, et al. The growing teratoma syndrome. Pediatr Radiol. 2004; 34(3):259–262.
C Informa Healthcare USA, Inc. Copyright
