Childhood primary mesenteric seminoma
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《美国医学杂志》
1 Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiodiagnosis, Dr. B. R. A. Institute Rotary Cancer Hospital, New Delhi, India
Abstract
We report an 11-year-old child who presented with an abdominal lump and was diagnosed as having an extragonal primary mesenteric seminoma. Patient was treated with 4 cycles of combination chemotherapy cisplatin, etoposide and bleomycin; he is now disease free for 2 years. We discuss and review extragonadal germ cell tumors arising from the mesentery and their management.
Keywords: Seminoma; Extragonadal; Mesentery
Yolk sac tumors, teratomas and embryonal carcinomas are the common pediatric germ cell tumors. Seminomas, though common in adults, are rare in children. Extragonadal seminoma is a disease of young adult males, median age being 37 years (range 18-70 years); it is very rare in children. Retroperitoneum and mediastinum are the common sites,[1] mesentery as the primary site has not been reported so far.
Case Report
An 11-year-old male presented with abdominal pain, weight loss and anorexia of 3 months duration at an outside hospital; details of physical examination are not available at initial presentation. Ultrasound of abdomen revealed a 96mm X 72mm X 55 mm left- sided abdominal mass. He underwent laparotomy and the mass was resected at the outside hospital, histopathology of that was suggestive of non hodgkin's lymphoma, and patient was then referred to our center after surgery.
At our center, patient had symptoms of abdominal pain. On examination, he was found to have an ill-defined epigastric mass. There was no lymphadenopathy or hepatosplenomegaly. Genitals were normal. Routine hemogram and biochemical parameters were normal. Serum LDH was elevated at 394 units/ml (normal < 280 units/ml). Serum alpha feto protein and beta HCG were normal. CT scan of abdomen revealed a mesenteric mass alongwith celiac, portal and retroperitoneal lymphadenopathy. Ultrasound of the testes and CT scan of chest were normal. A review of the MRI abdomen, performed prior to the surgery, revealed a mass that was suggestive of mesenteric origin Figure1. No abdomino-pelvic lymphadenopathy or organomegaly was noted in the abdominal MRI.
Histopathology review of the operated specimen revealed the diagnosis of seminomatous germ cell tumor Figure2. There were no non-seminomatous elements. The tumor cells were positive for epithelial membrane antigen. A detailed immunohistochemical staining was performed to rule out other malignancies in view of the uncommon presentation of germ cell tumor in the mesentery. Immunohistochemical markers for pan-cytokeratin, B-cell (CD20), T-cell (CD3), myeloperoxidase, ALK protein (to rule out anaplastic large cell lymphoma) and CD68 (macrophage) were negative. Thus, a final diagnosis of primary mesenteric seminomatous germ cell tumor (GCT) was made.
He was treated with 4 cycles of cisplatinum, etoposide and bleomycin (PEB) chemotherapy every 3 weekly. Symptoms of abdominal pain resolved and the abdominal mass was not palpable after the first cycle of chemotherapy. A repeat CT scan abdomen after 3 cycles of chemotherapy revealed evidence of 3 cm hypodense lesion in the mesentery below the body of pancreas, which was non-vascular and likely to be due to postoperative changes. There was complete disappearance of retroperitoneal lymphadenopathy. Ultrasound abdomen post 4 cycles of chemotherapy revealed a 3 cm well-defined hypoechoic mass inferior to the pancreatic head. No second look surgery was performed as the mass seen on ultrasound was thought to be due to postoperative changes. The patient was followed up with physical examination and regular ultrasound examination of the abdomen. Patient has been doing well on follow up with ultrasound abdomen being normal and he is now 2 years post therapy with no evidence of disease recurrence.
Discussion
The present case was unique in its presentation as a primary seminomatous GCT arising from the mesentery. The mesenteric origin of the tumor was evident on the MRI of abdomen. Further, in the histopathology section, the tumor cells appeared to be infiltrating the intestinal wall from outside and thus likely to be originating from the mesentery or retroperitoneum. Serum alpha feto protein and beta-HCG were normal thereby conferring with the pathological diagnosis of seminoma and absence of non-seminomatous elements in the tumor specimen. Ultrasound testes was normal thereby ruling out a primary testicular origin of tumor.
Surgical therapy is the therapy of choice in benign GCT, such as teratoma. With malignant GCT, removal is indicated, if possible. However, given the availability of effective chemotherapy, resection should not be undertaken to the point of sacrificing vital structures. After initial chemotherapy, second-look surgery may be done to achieve complete remission in selected patients. Patients generally receive four cycles of chemotherapy, and those with residual disease undergo surgery. Those with malignant disease in resected specimen received two additional cycles of chemotherapy. PEB chemotherapy[2] is standard chemotherapy for germ cell tumors and includes bleomycin 15 units/m 2 on day 1, etoposide 100 mg/m 2 on days 1 through 5, and cisplatin 20 mg/m 2 on days 1 through 5. This therapy results in cure rates of more than 80%.
Extragonadal germ cell tumors (EGGCT) usually occur in the midline. This is due to complex migratory patterns of the embryonal gonads. The primordial germ cells first become evident in the extraembryonic yolk sac by the fourth week of gestation. By the fifth week, the germ cells migrate through the mesentery to the gonadal ridge. This migration appears to be mediated by the c-kit receptor and its ligand, stem cell factor, or steel factor. Primordial germ cells express c-kit. Stem cell factor is expressed with an increasing gradient from yolk sac to gonadal ridge, guiding germ cells to the gonadal ridge.[3],[4],[5] In animal models, primordial germ cells not expressing c-kit are unable either to migrate to the gonad or to proliferate during this migration. EGGCT are presumed to arise from germ cells that have migrated aberrantly.
Among the EGGCT, seminomas are more common in males older than 20 years,[6] and are unusual below 20 years of age.[7] To the best of our knowledge, the present case, 11 years of age is the youngest extragonadal - extracranial seminomatous GCT to be reported in English literature so far. The common locations, in order of frequency, are sacro-coccygeal region, mediastinum, central nervous system and retroperitoneum,[6] other sites include pancreas, uterus and neck.[8] This case adds mesentery as one of the rare sites of extragonadal seminomatous GCT. There is one other case of mesenteric seminoma reported in French literature.[9] Though rare, possibility of mesenteric seminomatous GCT should be considered in a child with an abdominal mass.
References
1. Bokemeyer C, Droz JP, Horwich A, et al. Extragonadal seminoma: An International multicenter Analysis of Prognostic Factors and Long Term Treatment outcome. Cancer 2001; 91: 1394-1401.
2. Cushing B, Giller R, Cullen JW, Marina NM, Lauer SJ, Olson TA et al. Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study-Pediatric Oncology Group 9049 and Children's Cancer Group 8882. J Clin Oncol 2004; 22 : 2691-700.
3. Strohmeyer T, Reese D, Press M, Ackermann R, Hartmann M, Slamon D. Expression of the c-kit proto-oncogene and its ligand stem cell factor in normal and malignant human testicular tissue. J Urol 1995; 153 : 511-515.
4. Coucouvanis EC, Jones PP. Changes in proto-oncogene expression correlated with general and sex-specific differentiation in murine primordial germ cells. Mech Dev 1993; 42 : 49-58.
5. Lamb DJ. Growth factors and testicula development. J Urol 1993; 150 : 583-592.
6. Cushing B, Perlman EJ, Marina NM, Castleberry RP. Germ Cell Tumors. In Pizzo PA, Poplack DG. eds. Principles and Practice of Pediatric Oncology. 4th edn. Philadelphia; Lippincott Williams and Wilkins, 2002; 1091-1114.
7. Young R, Scully R. Germ cell tumors: non-seminomatous tumors, occult tumors, effects of chemotherapy in testicular tumors. Chicago; ASCP Press, 1990: 37.
8. Hsu YJ, Pai Lu, Chen YC et al. Extragonadal germ cell tumours in Taiwan: An analysis of treatment results of 59 patients. Cancer 2002; 95 : 766-774.
9. Dubois A, Janbon C, Lepeyrie H, Marty-Double C. Mesenteric Seminoma: apropos of a case. Gastroenterol Clin Biol 1986; 10 : 437-438.(Bakhshi Sameer, Singh Dev)
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiodiagnosis, Dr. B. R. A. Institute Rotary Cancer Hospital, New Delhi, India
Abstract
We report an 11-year-old child who presented with an abdominal lump and was diagnosed as having an extragonal primary mesenteric seminoma. Patient was treated with 4 cycles of combination chemotherapy cisplatin, etoposide and bleomycin; he is now disease free for 2 years. We discuss and review extragonadal germ cell tumors arising from the mesentery and their management.
Keywords: Seminoma; Extragonadal; Mesentery
Yolk sac tumors, teratomas and embryonal carcinomas are the common pediatric germ cell tumors. Seminomas, though common in adults, are rare in children. Extragonadal seminoma is a disease of young adult males, median age being 37 years (range 18-70 years); it is very rare in children. Retroperitoneum and mediastinum are the common sites,[1] mesentery as the primary site has not been reported so far.
Case Report
An 11-year-old male presented with abdominal pain, weight loss and anorexia of 3 months duration at an outside hospital; details of physical examination are not available at initial presentation. Ultrasound of abdomen revealed a 96mm X 72mm X 55 mm left- sided abdominal mass. He underwent laparotomy and the mass was resected at the outside hospital, histopathology of that was suggestive of non hodgkin's lymphoma, and patient was then referred to our center after surgery.
At our center, patient had symptoms of abdominal pain. On examination, he was found to have an ill-defined epigastric mass. There was no lymphadenopathy or hepatosplenomegaly. Genitals were normal. Routine hemogram and biochemical parameters were normal. Serum LDH was elevated at 394 units/ml (normal < 280 units/ml). Serum alpha feto protein and beta HCG were normal. CT scan of abdomen revealed a mesenteric mass alongwith celiac, portal and retroperitoneal lymphadenopathy. Ultrasound of the testes and CT scan of chest were normal. A review of the MRI abdomen, performed prior to the surgery, revealed a mass that was suggestive of mesenteric origin Figure1. No abdomino-pelvic lymphadenopathy or organomegaly was noted in the abdominal MRI.
Histopathology review of the operated specimen revealed the diagnosis of seminomatous germ cell tumor Figure2. There were no non-seminomatous elements. The tumor cells were positive for epithelial membrane antigen. A detailed immunohistochemical staining was performed to rule out other malignancies in view of the uncommon presentation of germ cell tumor in the mesentery. Immunohistochemical markers for pan-cytokeratin, B-cell (CD20), T-cell (CD3), myeloperoxidase, ALK protein (to rule out anaplastic large cell lymphoma) and CD68 (macrophage) were negative. Thus, a final diagnosis of primary mesenteric seminomatous germ cell tumor (GCT) was made.
He was treated with 4 cycles of cisplatinum, etoposide and bleomycin (PEB) chemotherapy every 3 weekly. Symptoms of abdominal pain resolved and the abdominal mass was not palpable after the first cycle of chemotherapy. A repeat CT scan abdomen after 3 cycles of chemotherapy revealed evidence of 3 cm hypodense lesion in the mesentery below the body of pancreas, which was non-vascular and likely to be due to postoperative changes. There was complete disappearance of retroperitoneal lymphadenopathy. Ultrasound abdomen post 4 cycles of chemotherapy revealed a 3 cm well-defined hypoechoic mass inferior to the pancreatic head. No second look surgery was performed as the mass seen on ultrasound was thought to be due to postoperative changes. The patient was followed up with physical examination and regular ultrasound examination of the abdomen. Patient has been doing well on follow up with ultrasound abdomen being normal and he is now 2 years post therapy with no evidence of disease recurrence.
Discussion
The present case was unique in its presentation as a primary seminomatous GCT arising from the mesentery. The mesenteric origin of the tumor was evident on the MRI of abdomen. Further, in the histopathology section, the tumor cells appeared to be infiltrating the intestinal wall from outside and thus likely to be originating from the mesentery or retroperitoneum. Serum alpha feto protein and beta-HCG were normal thereby conferring with the pathological diagnosis of seminoma and absence of non-seminomatous elements in the tumor specimen. Ultrasound testes was normal thereby ruling out a primary testicular origin of tumor.
Surgical therapy is the therapy of choice in benign GCT, such as teratoma. With malignant GCT, removal is indicated, if possible. However, given the availability of effective chemotherapy, resection should not be undertaken to the point of sacrificing vital structures. After initial chemotherapy, second-look surgery may be done to achieve complete remission in selected patients. Patients generally receive four cycles of chemotherapy, and those with residual disease undergo surgery. Those with malignant disease in resected specimen received two additional cycles of chemotherapy. PEB chemotherapy[2] is standard chemotherapy for germ cell tumors and includes bleomycin 15 units/m 2 on day 1, etoposide 100 mg/m 2 on days 1 through 5, and cisplatin 20 mg/m 2 on days 1 through 5. This therapy results in cure rates of more than 80%.
Extragonadal germ cell tumors (EGGCT) usually occur in the midline. This is due to complex migratory patterns of the embryonal gonads. The primordial germ cells first become evident in the extraembryonic yolk sac by the fourth week of gestation. By the fifth week, the germ cells migrate through the mesentery to the gonadal ridge. This migration appears to be mediated by the c-kit receptor and its ligand, stem cell factor, or steel factor. Primordial germ cells express c-kit. Stem cell factor is expressed with an increasing gradient from yolk sac to gonadal ridge, guiding germ cells to the gonadal ridge.[3],[4],[5] In animal models, primordial germ cells not expressing c-kit are unable either to migrate to the gonad or to proliferate during this migration. EGGCT are presumed to arise from germ cells that have migrated aberrantly.
Among the EGGCT, seminomas are more common in males older than 20 years,[6] and are unusual below 20 years of age.[7] To the best of our knowledge, the present case, 11 years of age is the youngest extragonadal - extracranial seminomatous GCT to be reported in English literature so far. The common locations, in order of frequency, are sacro-coccygeal region, mediastinum, central nervous system and retroperitoneum,[6] other sites include pancreas, uterus and neck.[8] This case adds mesentery as one of the rare sites of extragonadal seminomatous GCT. There is one other case of mesenteric seminoma reported in French literature.[9] Though rare, possibility of mesenteric seminomatous GCT should be considered in a child with an abdominal mass.
References
1. Bokemeyer C, Droz JP, Horwich A, et al. Extragonadal seminoma: An International multicenter Analysis of Prognostic Factors and Long Term Treatment outcome. Cancer 2001; 91: 1394-1401.
2. Cushing B, Giller R, Cullen JW, Marina NM, Lauer SJ, Olson TA et al. Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study-Pediatric Oncology Group 9049 and Children's Cancer Group 8882. J Clin Oncol 2004; 22 : 2691-700.
3. Strohmeyer T, Reese D, Press M, Ackermann R, Hartmann M, Slamon D. Expression of the c-kit proto-oncogene and its ligand stem cell factor in normal and malignant human testicular tissue. J Urol 1995; 153 : 511-515.
4. Coucouvanis EC, Jones PP. Changes in proto-oncogene expression correlated with general and sex-specific differentiation in murine primordial germ cells. Mech Dev 1993; 42 : 49-58.
5. Lamb DJ. Growth factors and testicula development. J Urol 1993; 150 : 583-592.
6. Cushing B, Perlman EJ, Marina NM, Castleberry RP. Germ Cell Tumors. In Pizzo PA, Poplack DG. eds. Principles and Practice of Pediatric Oncology. 4th edn. Philadelphia; Lippincott Williams and Wilkins, 2002; 1091-1114.
7. Young R, Scully R. Germ cell tumors: non-seminomatous tumors, occult tumors, effects of chemotherapy in testicular tumors. Chicago; ASCP Press, 1990: 37.
8. Hsu YJ, Pai Lu, Chen YC et al. Extragonadal germ cell tumours in Taiwan: An analysis of treatment results of 59 patients. Cancer 2002; 95 : 766-774.
9. Dubois A, Janbon C, Lepeyrie H, Marty-Double C. Mesenteric Seminoma: apropos of a case. Gastroenterol Clin Biol 1986; 10 : 437-438.(Bakhshi Sameer, Singh Dev)