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Bilateral Ovarian Burkitt's Lymphoma: Successful Treatment with Preservation of Ovarian Function
Case Report Bilateral Ovarian Burkitt's Lymphoma: Successful Treatment with Preservation of Ovarian Function Anselm Chi-wai Lee MBBS, FRCPCH 1,*, Chan Hon Chui MBBS, FRCS 2 1 2
Children's Haematology & Cancer Centre, Mount Elizabeth Hospital, Singapore Surgery Centre for Children, Mount Elizabeth Medical Centre, Singapore
a b s t r a c t Background: Bilateral ovarian Burkitt's lymphoma was diagnosed in a 10-year-old girl who presented with abdominal pain, constipation, and signs of ovarian torsion. Case: Left salpingo-oopherectomy and biopsy of the right ovary were carried out as initial surgical intervention. She remained well in first complete remission at 25 months after multiagent chemotherapy, with pubertal development on clinical examination, hormonal measurements, and pelvic sonography. Summary and Conclusion: Although rare, Burkitt's lymphoma should be included in the differential diagnosis of bilateral ovarian tumors in childhood, and more conservative surgical management is indicated to preserve ovarian function and fertility. Key Words: Burkitt's lymphoma, Fertility preservation, Non-Hodgkin lymphoma, Ovarian neoplasms
Introduction
Sporadic Burkitt's lymphoma involving both ovaries is an uncommon clinical entity but is repeatedly reported in the medical literature.1e8 It is a diagnostic and therapeutic challenge, especially in the setting of an acute abdomen. A lymphomatous diagnosis is often not suspected in ovarian tumors, and there is a tendency for complete resection of the diseased organs during exploratory laparotomy. Given the highly successful outcomes of contemporary chemotherapy for childhood B-cell non-Hodgkin lymphoma,9 pediatric surgical teams should consider the possibility of non-Hodgkin lymphoma in children presenting with bilateral ovarian masses and resort to less mutilating surgery to preserve ovarian function. To the best of our knowledge, the girl described in the following report is the first child who has recovered with an intact and functioning ovary. Case
A 10-year-old girl of Chinese descent presented with acute abdominal pain associated with increasing constipation. A lower abdominal mass was detected at the local hospital, and computed tomography revealed multiple masses on both sides of the pelvis (Fig. 1A and B). Physical examination at our institution showed a prepubertal child in distress with abdominal pain, suggestive of ovarian torsion. At emergency laparotomy, bilateral adnexal masses were found (Fig. 1C). A left salpingo-oopherectomy was first
The authors indicate no conflicts of interest. * Address correspondence to: Dr. Anselm Chi-wai Lee, MBBS, FRCPCH, Children's Haematology & Cancer Centre, Mount Elizabeth Hospital, Level 4, 3 Mount Elizabeth, Singapore 228510; Phone: þ65-67312673; fax: þ65-62354924 E-mail address: [email protected] (A.-w. Lee).
carried out. Following the frozen section, which showed the presence of a small round cell tumor, a biopsy sample was taken of the left adnexal mass. There was no tumor spillage during the operation. The final histopathologic features and immunocytochemistry confirmed the diagnosis of Burkitt's lymphoma. Positron emission tomography showed metabolically avid lesions in para-aortic lymph nodes and in the right maxilla. The bone marrow and cerebrospinal fluid were clear of malignancy. Chemotherapy based on an LMB89 protocol9 was commenced 10 days postoperatively (Table 1). She completed the treatment uneventfully in 13 weeks. Repeat positron emission tomography at 6 weeks and after the completion of treatment showed the disease in continuous remission. At 25 months of follow-up, she remained disease free with bilateral breast development, increased volume in the remaining ovary with follicles on sonography, and serum estradiol (211.0 pmol/L) and gonadotropin levels (follicular stimulating hormone, 5.0 IU/L, luteinizing hormone, 0.67 IU/L) in the pubertal ranges.
Summary and Conclusion
Lymphomas account for 10% of childhood malignancies and are one of the most curable cancers. In Nigeria and probably parts of Africa where the endemic form of Burkitt's lymphoma prevails, about half of the ovarian tumors seen in patients under 20 years of age are Burkitt's lymphoma.10 In other parts of the world, non-Hodgkin lymphoma that primarily affects the ovary is rare.11 Osborne and Robboy12 studied 42 cases of ovarian lymphoma and noted 16 patients were younger than 20 years. Among them, 10 (63%) had Burkitt's or Burkitt-like lymphoma. Interestingly, lymphoma affecting the ovaries tended to be bilateral (55%) in their series.
1083-3188/$ - see front matter Ó 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jpag.2014.09.013
e106
A.-w. Lee, C.H. Chui / J Pediatr Adolesc Gynecol 28 (2015) e105ee107
Fig. 1. A) Coronal CT showing a larger, multiloculated mass of 14 cm in maximum dimension on the left side of the pelvis and a smaller mass of 6 cm on the right. (B) Transverse CT showing the bilateral pelvic masses. (C) Bilateral adnexal tumors on exploratory laparotomy viewed from the head of the patient. The left adnexal mass is labelled “L” and the right sided mass “R” in the inserts.
Malignant ovarian neoplasms in childhood are usually first managed surgically with salpingo-oopherectomy. Complete excision is necessary for the more common germ cell tumors and the sex cord stromal tumors. Fertility preservation is generally not an issue for unilateral disease,
Table 1 Chemotherapeutic Regimen for the Reported Patient Reduction phase: days 1-7 Vincristine 1 mg/m2 day 1 Cyclophosphamide 300 mg/m2 day 1 Prednisolone 60 mg/m2/d, days 1-7 Intrathecal methotrexate 15 mg and hydrocortisone 15 mg day 1 Induction 1: days 8-28, induction 2: days 29-49 Vincristine 2 mg/m2 days 8 and 29 Prednisolone 60 mg/m2/d, days 8-12 and 29-33 Methotrexate 3 g/m2 days 8 and 29 Cyclophosphamide 250 mg/m2 q 12 h, days 9-11 and 30-32 Doxorubicin 60 mg/m2 days 9 and 30 Intrathecal methotrexate 15 mg and hydrocortisone 15 mg, days 9, 13, 30, and 34 Consolidation 1: days 50-70, consolidation 2: days 71-91 Methotrexate 3 g/m2 days 50 and 71 Cytarabine 100 mg/m2/d, days 51-56 and 72-77 Intrathecal methotrexate 15 mg and hydrocortisone 15 mg, days 51 and 72 Intrathecal cytarabine 30 mg and hydrocortisone 15 mg, days 56 and 77
but patients with bilateral ovarian tumors will invariably be left with gonadal failure. Childhood Burkitt's lymphoma, on the other hand, is a highly curable disease with chemotherapy alone. Thus, the occurrence of Burkitt's lymphoma as bilateral ovarian tumors would present as a diagnostic and therapeutic challenge to the pediatric surgeons and oncologists. A review of the literature revealed 8 cases of bilateral ovarian Burkitt's lymphoma in patients younger than 20 years (Table 2). Five of them received bilateral salphingo-oopherectomy at the time of diagnosis,1e3,6,8 and 2 patients were managed by biopsy only.4,5 Five of these 6 patients had widespread disease in the peritoneum with or without distant metastases. In the other patient who had only disease limited to the ovary, a unilateral excision was carried out while the other side of the ovary underwent biopsy.7 There were 2 deaths among these cases. The child who received minimal chemotherapy as adjuvant therapy died from disease relapse.2 A 20-year-old young woman died shortly after an extensive abdominal surgery.8 Of the other 4 patients whose treatment and follow-up information were described, they all survived in remission with contemporary multiagent chemotherapy catered for
A.-w. Lee, C.H. Chui / J Pediatr Adolesc Gynecol 28 (2015) e105ee107
e107
Table 2 Reported Cases of Bilateral Ovarian Burkitt's Lymphoma in Pediatric Patients Age, y 6 7 10 13 15
Presentation Abdominal pain Abdominal pain, vomiting Abdominal mass, weight loss Abdominal mass, fever
Extragonadal disease Uterus Absent Intra-abdominal and bone metastases Peritoneal metastases
20
Abdominal pain, vomiting Intra-abdominal and gastric metastases Abdominal mass, fever Hepatic, lung and spinal metastases Abdominal pain Absent
20
Abdominal distension
10
Abdominal pain, constipation
15
Surgical treatment
Chemotherapy
Bilateral salpingo-oopherectomy Bilateral salpingo-oopherectomy Bilateral salpingo-oopherectomy
Local regimen Cyclophosphamide alone LMB89-based regimen
Biopsy only
LMB89-based regimen
Biopsy only
LMB89-based regimen
Bilateral salpingo-oopherectomy
Not mentioned
Outcome
Ref
Not mentioned Died from relapse In remission at 22 months post therapy In remission at 6 months post therapy In remission at end of therapy Not mentioned
1 2 3 4 5 6
Left salpingo-oopherectomy; right Berlin-Frankfurt-Munstere In remission at 36 months 7 ovarian biopsy based regimen from diagnosis Intra-abdominal Bilateral salpingo-oopherectemy, No Died shortly after surgery 8 metastases right hemicolectomy Regional nodes and right Left salpingo-oopherectomy; right LMB89-based regimen In remission at 25 months This report maxillary metastases ovarian biopsy post therapy
Burkitt's lymphoma.3e5,7 This group included the 3 patients whose ovarian tumors underwent biopsy only at the time of diagnosis. This is consistent with the larger group of patients in modern series of Burkitt's lymphoma in whom bulky disease can be managed without mutilating surgery. While there is no follow-up information about preservation of ovarian function in any of the reported cases, our case report indicates that an affected child can go into puberty with a functioning ovary despite bilateral lymphomatous disease in the gonads. In conclusion, the diagnosis of Burkitt's lymphoma should be considered in children presenting with bilateral ovarian tumors, and a more conservative approach in the initial surgical management is justified.
2. 3.
4. 5. 6. 7. 8. 9.
10.
References 1. Khan WA, Deshpande KA, Kurdukar M, et al: Primary Burkitt's lymphoma of endometrium and bilateral ovaries in a 6-year-old female: report of a
11. 12.
rare entity and review of the published work. J Obstet Gynecol Res 2013; 39:1484 Pickleman JR, Straus FH II, Griffin ED, et al: Burkitt's lymphoma: an unusual childhood tumor. Ann Surg 1972; 176:25 Onimoe GI, Kahwash S, Termuhlen A, et al: Bilateral Burkitt lymphoma of the ovaries: a report of a case in a child with Williams syndrome. Case Rep Med 2011; 2011:327263 Cyriac S, Srinivas L, Mahajan V, et al: Primary Burkitt's lymphoma of the ovary. Afr J Paediatr Surg 2010; 7:120 Ziade F, von der Weid N, Beck-Popovic M, et al: Burkitt's lymphoma e an atypical presentation. BMC Pediatr 2012; 12:113 Weekes LR: Burkitt's lymphoma of the ovaries. J Natl Med Assoc 1986; 78:609 Ng SP, Leong CF, Nurismah MI, et al: Primary Burkitt lymphoma of the ovary. Med J Malaysia 2006; 61:363 Zhianpour M, Sirus M: Primary ovarian Burkitt's lymphoma with peritoneal and retroperitoneal metastasis. Iran J Radiol 2008; 5:35 Patte C, Auperin A, Gerrard M, et al: Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood 2007; 109:2773 Junaid TA: Ovarian neoplasms in children and adolescents in Ibadan, Nigeria. Cancer 1981; 47:610 Schultz KA, Sencer SF, Messinger Y, et al: Pediatric ovarian tumors: a review of 67 cases. Pediatr Blood Cancer 2005; 44:167 Osborne BM, Robboy SJ: Lymphomas or leukemia presenting as ovarian tumors: an analysis of 42 cases. Cancer 1983; 52:1933
Children's Haematology & Cancer Centre, Mount Elizabeth Hospital, Singapore Surgery Centre for Children, Mount Elizabeth Medical Centre, Singapore
a b s t r a c t Background: Bilateral ovarian Burkitt's lymphoma was diagnosed in a 10-year-old girl who presented with abdominal pain, constipation, and signs of ovarian torsion. Case: Left salpingo-oopherectomy and biopsy of the right ovary were carried out as initial surgical intervention. She remained well in first complete remission at 25 months after multiagent chemotherapy, with pubertal development on clinical examination, hormonal measurements, and pelvic sonography. Summary and Conclusion: Although rare, Burkitt's lymphoma should be included in the differential diagnosis of bilateral ovarian tumors in childhood, and more conservative surgical management is indicated to preserve ovarian function and fertility. Key Words: Burkitt's lymphoma, Fertility preservation, Non-Hodgkin lymphoma, Ovarian neoplasms
Introduction
Sporadic Burkitt's lymphoma involving both ovaries is an uncommon clinical entity but is repeatedly reported in the medical literature.1e8 It is a diagnostic and therapeutic challenge, especially in the setting of an acute abdomen. A lymphomatous diagnosis is often not suspected in ovarian tumors, and there is a tendency for complete resection of the diseased organs during exploratory laparotomy. Given the highly successful outcomes of contemporary chemotherapy for childhood B-cell non-Hodgkin lymphoma,9 pediatric surgical teams should consider the possibility of non-Hodgkin lymphoma in children presenting with bilateral ovarian masses and resort to less mutilating surgery to preserve ovarian function. To the best of our knowledge, the girl described in the following report is the first child who has recovered with an intact and functioning ovary. Case
A 10-year-old girl of Chinese descent presented with acute abdominal pain associated with increasing constipation. A lower abdominal mass was detected at the local hospital, and computed tomography revealed multiple masses on both sides of the pelvis (Fig. 1A and B). Physical examination at our institution showed a prepubertal child in distress with abdominal pain, suggestive of ovarian torsion. At emergency laparotomy, bilateral adnexal masses were found (Fig. 1C). A left salpingo-oopherectomy was first
The authors indicate no conflicts of interest. * Address correspondence to: Dr. Anselm Chi-wai Lee, MBBS, FRCPCH, Children's Haematology & Cancer Centre, Mount Elizabeth Hospital, Level 4, 3 Mount Elizabeth, Singapore 228510; Phone: þ65-67312673; fax: þ65-62354924 E-mail address: [email protected] (A.-w. Lee).
carried out. Following the frozen section, which showed the presence of a small round cell tumor, a biopsy sample was taken of the left adnexal mass. There was no tumor spillage during the operation. The final histopathologic features and immunocytochemistry confirmed the diagnosis of Burkitt's lymphoma. Positron emission tomography showed metabolically avid lesions in para-aortic lymph nodes and in the right maxilla. The bone marrow and cerebrospinal fluid were clear of malignancy. Chemotherapy based on an LMB89 protocol9 was commenced 10 days postoperatively (Table 1). She completed the treatment uneventfully in 13 weeks. Repeat positron emission tomography at 6 weeks and after the completion of treatment showed the disease in continuous remission. At 25 months of follow-up, she remained disease free with bilateral breast development, increased volume in the remaining ovary with follicles on sonography, and serum estradiol (211.0 pmol/L) and gonadotropin levels (follicular stimulating hormone, 5.0 IU/L, luteinizing hormone, 0.67 IU/L) in the pubertal ranges.
Summary and Conclusion
Lymphomas account for 10% of childhood malignancies and are one of the most curable cancers. In Nigeria and probably parts of Africa where the endemic form of Burkitt's lymphoma prevails, about half of the ovarian tumors seen in patients under 20 years of age are Burkitt's lymphoma.10 In other parts of the world, non-Hodgkin lymphoma that primarily affects the ovary is rare.11 Osborne and Robboy12 studied 42 cases of ovarian lymphoma and noted 16 patients were younger than 20 years. Among them, 10 (63%) had Burkitt's or Burkitt-like lymphoma. Interestingly, lymphoma affecting the ovaries tended to be bilateral (55%) in their series.
1083-3188/$ - see front matter Ó 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jpag.2014.09.013
e106
A.-w. Lee, C.H. Chui / J Pediatr Adolesc Gynecol 28 (2015) e105ee107
Fig. 1. A) Coronal CT showing a larger, multiloculated mass of 14 cm in maximum dimension on the left side of the pelvis and a smaller mass of 6 cm on the right. (B) Transverse CT showing the bilateral pelvic masses. (C) Bilateral adnexal tumors on exploratory laparotomy viewed from the head of the patient. The left adnexal mass is labelled “L” and the right sided mass “R” in the inserts.
Malignant ovarian neoplasms in childhood are usually first managed surgically with salpingo-oopherectomy. Complete excision is necessary for the more common germ cell tumors and the sex cord stromal tumors. Fertility preservation is generally not an issue for unilateral disease,
Table 1 Chemotherapeutic Regimen for the Reported Patient Reduction phase: days 1-7 Vincristine 1 mg/m2 day 1 Cyclophosphamide 300 mg/m2 day 1 Prednisolone 60 mg/m2/d, days 1-7 Intrathecal methotrexate 15 mg and hydrocortisone 15 mg day 1 Induction 1: days 8-28, induction 2: days 29-49 Vincristine 2 mg/m2 days 8 and 29 Prednisolone 60 mg/m2/d, days 8-12 and 29-33 Methotrexate 3 g/m2 days 8 and 29 Cyclophosphamide 250 mg/m2 q 12 h, days 9-11 and 30-32 Doxorubicin 60 mg/m2 days 9 and 30 Intrathecal methotrexate 15 mg and hydrocortisone 15 mg, days 9, 13, 30, and 34 Consolidation 1: days 50-70, consolidation 2: days 71-91 Methotrexate 3 g/m2 days 50 and 71 Cytarabine 100 mg/m2/d, days 51-56 and 72-77 Intrathecal methotrexate 15 mg and hydrocortisone 15 mg, days 51 and 72 Intrathecal cytarabine 30 mg and hydrocortisone 15 mg, days 56 and 77
but patients with bilateral ovarian tumors will invariably be left with gonadal failure. Childhood Burkitt's lymphoma, on the other hand, is a highly curable disease with chemotherapy alone. Thus, the occurrence of Burkitt's lymphoma as bilateral ovarian tumors would present as a diagnostic and therapeutic challenge to the pediatric surgeons and oncologists. A review of the literature revealed 8 cases of bilateral ovarian Burkitt's lymphoma in patients younger than 20 years (Table 2). Five of them received bilateral salphingo-oopherectomy at the time of diagnosis,1e3,6,8 and 2 patients were managed by biopsy only.4,5 Five of these 6 patients had widespread disease in the peritoneum with or without distant metastases. In the other patient who had only disease limited to the ovary, a unilateral excision was carried out while the other side of the ovary underwent biopsy.7 There were 2 deaths among these cases. The child who received minimal chemotherapy as adjuvant therapy died from disease relapse.2 A 20-year-old young woman died shortly after an extensive abdominal surgery.8 Of the other 4 patients whose treatment and follow-up information were described, they all survived in remission with contemporary multiagent chemotherapy catered for
A.-w. Lee, C.H. Chui / J Pediatr Adolesc Gynecol 28 (2015) e105ee107
e107
Table 2 Reported Cases of Bilateral Ovarian Burkitt's Lymphoma in Pediatric Patients Age, y 6 7 10 13 15
Presentation Abdominal pain Abdominal pain, vomiting Abdominal mass, weight loss Abdominal mass, fever
Extragonadal disease Uterus Absent Intra-abdominal and bone metastases Peritoneal metastases
20
Abdominal pain, vomiting Intra-abdominal and gastric metastases Abdominal mass, fever Hepatic, lung and spinal metastases Abdominal pain Absent
20
Abdominal distension
10
Abdominal pain, constipation
15
Surgical treatment
Chemotherapy
Bilateral salpingo-oopherectomy Bilateral salpingo-oopherectomy Bilateral salpingo-oopherectomy
Local regimen Cyclophosphamide alone LMB89-based regimen
Biopsy only
LMB89-based regimen
Biopsy only
LMB89-based regimen
Bilateral salpingo-oopherectomy
Not mentioned
Outcome
Ref
Not mentioned Died from relapse In remission at 22 months post therapy In remission at 6 months post therapy In remission at end of therapy Not mentioned
1 2 3 4 5 6
Left salpingo-oopherectomy; right Berlin-Frankfurt-Munstere In remission at 36 months 7 ovarian biopsy based regimen from diagnosis Intra-abdominal Bilateral salpingo-oopherectemy, No Died shortly after surgery 8 metastases right hemicolectomy Regional nodes and right Left salpingo-oopherectomy; right LMB89-based regimen In remission at 25 months This report maxillary metastases ovarian biopsy post therapy
Burkitt's lymphoma.3e5,7 This group included the 3 patients whose ovarian tumors underwent biopsy only at the time of diagnosis. This is consistent with the larger group of patients in modern series of Burkitt's lymphoma in whom bulky disease can be managed without mutilating surgery. While there is no follow-up information about preservation of ovarian function in any of the reported cases, our case report indicates that an affected child can go into puberty with a functioning ovary despite bilateral lymphomatous disease in the gonads. In conclusion, the diagnosis of Burkitt's lymphoma should be considered in children presenting with bilateral ovarian tumors, and a more conservative approach in the initial surgical management is justified.
2. 3.
4. 5. 6. 7. 8. 9.
10.
References 1. Khan WA, Deshpande KA, Kurdukar M, et al: Primary Burkitt's lymphoma of endometrium and bilateral ovaries in a 6-year-old female: report of a
11. 12.
rare entity and review of the published work. J Obstet Gynecol Res 2013; 39:1484 Pickleman JR, Straus FH II, Griffin ED, et al: Burkitt's lymphoma: an unusual childhood tumor. Ann Surg 1972; 176:25 Onimoe GI, Kahwash S, Termuhlen A, et al: Bilateral Burkitt lymphoma of the ovaries: a report of a case in a child with Williams syndrome. Case Rep Med 2011; 2011:327263 Cyriac S, Srinivas L, Mahajan V, et al: Primary Burkitt's lymphoma of the ovary. Afr J Paediatr Surg 2010; 7:120 Ziade F, von der Weid N, Beck-Popovic M, et al: Burkitt's lymphoma e an atypical presentation. BMC Pediatr 2012; 12:113 Weekes LR: Burkitt's lymphoma of the ovaries. J Natl Med Assoc 1986; 78:609 Ng SP, Leong CF, Nurismah MI, et al: Primary Burkitt lymphoma of the ovary. Med J Malaysia 2006; 61:363 Zhianpour M, Sirus M: Primary ovarian Burkitt's lymphoma with peritoneal and retroperitoneal metastasis. Iran J Radiol 2008; 5:35 Patte C, Auperin A, Gerrard M, et al: Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood 2007; 109:2773 Junaid TA: Ovarian neoplasms in children and adolescents in Ibadan, Nigeria. Cancer 1981; 47:610 Schultz KA, Sencer SF, Messinger Y, et al: Pediatric ovarian tumors: a review of 67 cases. Pediatr Blood Cancer 2005; 44:167 Osborne BM, Robboy SJ: Lymphomas or leukemia presenting as ovarian tumors: an analysis of 42 cases. Cancer 1983; 52:1933