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Approach to diagnosis and treatment of pediatric primary tumors of the diaphragm
Journal of Pediatric Surgery (2006) 41, 1722 – 1726
www.elsevier.com/locate/jpedsurg
Approach to diagnosis and treatment of pediatric primary tumors of the diaphragm Michaela Cadaa,*, J. Ted Gerstleb, Jeffrey Traubicic, Bo-Yee Ngand, Michael L. Capraa a
Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8 Department of Surgery, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8 c Department of Diagnostic Imaging, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8 d Department of Laboratory Medicine and Pathobiology, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8 b
Index words: Primary neoplasm; Tumor; Diaphragm
Abstract Background/Purpose: Tumors of the diaphragm in the pediatric population are extremely rare. We present 5 cases diagnosed at the Hospital for Sick Children, Toronto, and together with a review of the world literature, provide an approach to the diagnosis and management of these tumors. Methods: A clinical retrospective review of patients diagnosed as having primary diaphragmatic tumor (PDT) at the Hospital for Sick Children as well as a review of the world literature. Results: Forty-one cases of PDT in the pediatric population have been described from 1868 to 2005 inclusive. There is an equal incidence in boys and girls, they are found with the same frequency on the left as on the right, and 78% are malignant. Rhabdomyosarcoma is the most commonly occurring malignant tumor. The mean age at diagnosis is 10 years. bChest-associatedQ symptoms are more common than babdomen-associatedQ symptoms. Imaging often fails to identify the site of origin as the diaphragm. Surgery is the cornerstone of therapy for PDT. Conclusion: A multidisciplinary team approach is needed for successful treatment and management of PDT. D 2006 Elsevier Inc. All rights reserved.
Primary tumors of the diaphragm are rare, with fewer than 200 cases having been described over the last 137 years [1-4]. Commonly presenting in the fourth and fifth decades of life, primary diaphragmatic tumors (PDTs) in childhood are therefore exceptional. The rarity, together with nonspecific and variable clinical presenting features, results in a chal-
lenging initial diagnosis. We present 5 cases of pediatric PDT diagnosed at the Hospital for Sick Children (HSC), Toronto, and together with a review of the world literature, provide an approach to the diagnosis and management of these tumors.
1. Materials and methods * Corresponding author. Division of Haematology/Oncology, 555 University Avenue, 9th floor Black Wing, Toronto, Ontario, Canada M5G 1X8. Tel.: +1 416 813 8885. E-mail address: [email protected] (M. Cada). 0022-3468/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2006.05.073
This study is divided into 2 components—a literature review and a clinical retrospective review of patients diagnosed with PDT at the HSC. The literature review
Approach to diagnosis and treatment of pediatric primary tumors of the diaphragm
1723
confirmed necrotic tissue only. The patient received 3 postoperative cycles of PEB chemotherapy and remains tumor-free three and a half years later.
2.2. Case 2
Fig. 1 Coronal T1-weighted MRI image demonstrating a large, predominantly left-sided, upper abdominal mass possibly arising from the left lateral segment of the liver.
was conducted by searching MEDLINE, EMBASE, COCHRANE, and CINAHL health sciences–related databases using the following key words: primary neoplasm, tumor, and diaphragm. The database of the department of pathology at HSC was used, following approval by the Research Ethics Board of HSC, to identify patients with histological confirmation of involvement of the diaphragm with tumor between the years 1975 and 2005 inclusive. Clarification from the pathology report and/or patient’s hospital chart of the 34 cases so found was required to further identify cases of primary diaphragmatic involvement. Five such cases were thus confirmed.
2. Cases 2.1. Case 1 A 23-month-old boy presented with a 1-week history of a left-sided abdominal swelling and pain in the left chest. Abdominal examination revealed a tender left upper quadrant mass. Ultrasound demonstrated a large tumor within the left lobe of the liver. Computed tomography (CT) and magnetic resonance imaging (MRI) scans confirmed a large, complex, heterogeneous, and exophytic mass arising from the lateral segment of the left lobe of the liver, abutting the falciform ligament (Fig. 1). a-Fetoprotein (AFP) was elevated at 1, 700, and 800 lg/L, and a b-hCG was normal at less than 2 U/L. An ultrasound-guided needle biopsy of the mass revealed histology consistent with a yolk sac tumor (YST). After 2 cycles of PEB (cisplatin, etoposide, bleomycin) chemotherapy, repeat imaging revealed the tumor to be reduced in size and separate from the liver. A complete surgical resection was subsequently achieved with the intraoperative findings revealing tumor originating from the anteromedial portion of the left diaphragm without hepatic involvement. Biopsies of nodules found on the right hemidiaphragm and omentum
A 22-month-old boy presented with sudden onset of abdominal pain and mild tachypnea. Chest x-ray revealed a large right pleural effusion and a soft tissue mass in the region of the liver. Ultrasound demonstrated a mass, possibly arising from the liver. Computed tomography and MRI scans, however, confirmed the mass to be in the upper abdominal quadrant, lower posterior mediastinum, and chest, apparently arising from the diaphragm and possibly infiltrating the liver. a-Fetoprotein was elevated at 93,000 lg/L, and b-human chorionic gonadotropin (hCG) was normal. Following a nondiagnostic ultrasound-guided biopsy of the mass, an open biopsy and exploratory thoracotomy were performed. This revealed a large mass originating in the right medial hemidiaphragm with surrounding satellite nodules but with no liver invasion. Histology was consistent with pure YST. The patient received 4 cycles of PEB chemotherapy, followed by complete surgical resection. A Gore-Tex patch was required to repair the diaphragm. Fourteen years later, the patient remains free of tumor and is an avid cross-country runner.
2.3. Case 3 A girl with neurofibromatosis type I, seizures, and developmental delay had progressive scoliosis that required surgical correction at the age of 12 years. At surgery, she was found to have multiple thoracic nodules on the left hemidiaphragm, not visible on prior chest or spinal x-rays. Multiple biopsies confirmed these to be benign plexiform neurofibromas that caused no further symptoms. The patient was transferred to an adult facility after her 17th birthday with no subsequent data available.
Fig. 2 Coronal T2-weighted MRI image demonstrating a large suprahepatic mass compressing the liver.
1724
M. Cada et al. abdominal ultrasound revealed a hypoechoic soft tissue mass with specks of calcification in the region of the upper abdominal wall, anterior to and separate from the liver. A CT scan revealed the same mass but could not delineate its relationship to the right hemidiaphragm. An MRI showed this mass to arise from the right hemidiaphragm, to extend along the length of it and in between the right and left lobes of the liver, resulting in the compression of the dome of the liver and obstruction of the inferior vena cava (Fig. 3). This resulted in the formation of collateral blood vessels and Budd-Chiari syndrome of the liver. Serum lactate dehydrogenase, AFP, and b-hCG were normal. Urine was negative for vanillylmandelic acid and homovanillic acid. A needle biopsy was consistent with myofibroma. The baby was stabilized and eventually discharged to the care of her parents. She will return in a few months for surgical resection.
Fig. 3 Coronal T2-weighted MRI image demonstrating a right hemidiaphragm mass, compressing the liver and insinuating between its right and left lobes.
2.4. Case 4 A 3.5-year-old boy presented with a 6-month history of increasing abdominal girth, prominence of the anterior superficial abdominal veins, and a 2-month history of intermittent night sweats, fevers, and abdominal pain. Abdominal examination revealed a distended abdomen, everted umbilicus, prominent anterior abdominal veins, and a firm right upper quadrant mass extending 10 cm below the right subcostal margin. a-Fetoprotein, b-hCG, and liver enzymes were normal. Abdominal ultrasound demonstrated a large mass involving both the right and left lobes of the liver. A CT scan revealed a large heterogeneous liver mass elevating the right hemidiaphragm and compressing the atria and inferior vena cava. Magnetic resonance imaging confirmed a large heterogeneous suprahepatic mass, presumably arising from the right hemidiaphragm and compressing the liver (Fig. 2). Percutaneous needle biopsy histology was consistent with embryonal rhabdomyosarcoma with focal anaplasia. Treatment was commenced with chemotherapy, following a contemporary Intergroup Rhabdomyosarcoma Study protocol. At week 20 of treatment, a complete resection was performed, necessitating resection of a portion of pericardium, the majority of the right hemidiaphragm, and a wedge resection of the liver. The pericardium and diaphragm were repaired using a Gore-Tex patch. The patient completed treatment with further chemotherapy and radiotherapy (RT) and remains tumor-free 1 year after presentation.
2.5. Case 5 A baby girl was delivered by elective cesarean birth at 37 weeks for fetal hydrops and ascites seen on regular antenatal scan. At delivery, she was in moderate respiratory distress requiring continuous positive airway pressure. Her abdomen was grossly distended, with dilated abdominal veins and hepatomegaly of 4 cm below the costal margin. An
3. Discussion The reported 5 cases of PDTs diagnosed at the HSC in a 30-year period reflect the rare incidence and demonstrate the complexity of clinical presentation, the diagnostic challenges and treatment of these tumors. The first reported case of a PDT was discovered in an adult autopsy for an unrelated cause of death and was diagnosed as fibroma in 1868 [5]. Subsequently, between 1868 and 2005, there have been less than 200 cases reported in the English literature. Including our series, 41 of these tumors have been found in patients 18 years of age or less [1-3,6-22]. In reviewing this cohort of patients, there is an equal incidence of PDT in boys and girls, they are found with equal frequency on the right and on the left, and most (n = 32, 78%) are malignant. Rhabdomyosarcoma is the most commonly occurring malignant tumor (Table 1); lymphangioma and hemangioma
Table 1 Breakdown of PDT described in the literature and at HSC according to histological type Malignant
n = 32
Benign
n=9
Rhabdomyosarcoma
16
2
4
Cystic lymphangioma Hemangioma
2
3 3
Lipoma Neurilemmoma
1 1
1 1 1 1
Bronchial cyst Neurofibroma Myofibroma
1 1 1
Undifferentiated sarcoma Yolk sac tumor Extraosseous Ewing sarcoma Hemangioendothelioma Hemangiopericytoma Pheochromocytoma Malignant nerve-sheath tumor Primitive neuroectodermal tumor Sarcoma not otherwise specified
1 1
Approach to diagnosis and treatment of pediatric primary tumors of the diaphragm
Fig. 4
1725
Distribution of PDT according to age in years.
are examples of benign tumors. The mean age at diagnosis is 10 years, with an equal number of cases in the first and second decades of life (Fig. 4). The presentation of children with diaphragmatic tumors is variable, depending on age at presentation, size of mass, involvement of adjacent organs or metastatic disease, and tumor histology. bChest-associatedQ symptoms are more common than babdomen-associatedQ symptoms at presentation. Including our series, detailed information is available for 26 patients, 18 of which presented with one or a combination of chest- and/or abdomen-associated symptoms. Further analysis showed that 8 children had chest pain at presentation, 6 had shortness of breath, 4 had cough, 1 had a visible chest mass, 1 had chest asymmetry, and 1 had hemothorax. Abdominal distention was the presenting sign in 4 children, abdominal pain in 3, and an abdominal mass in 2. Of the 26 children, 6 presented buniquely,Q and discovery of the diaphragmatic tumor was an incidental finding in 2 cases (1, Cada). Of the remaining 15 children for whom detailed information is not available, clinical presentation was reported by authors to be a combination of chest or back pain, shortness of breath, and cough in 14 cases [6]. No information was available for 1 child [22]. In our series, 3 of 5 patients had a combination of chest- and abdomen-associated symptoms. Unique-presenting symptoms have been reported in 6 of the 26 children. Hydrops fetalis and neonatal respiratory failure at the time of delivery have been described in a newborn with diaphragmatic hemangioma [17] and in our newborn with diaphragmatic myofibroma. One adolescent boy presented with recurrent lung infection that was not responsive to antibiotic therapy [16]. Progressive dysphagia, secondary to a diaphragmatic rhabdomyosarcoma, has been described in a 12-year-old boy [19]. Palpitations, vomiting, and intermittent, severe hypertension were the clinical manifestations of a diaphragmatic pheochromocytoma in an 11-year old boy [20]. Finally, paraneoplastic features of fingernail clubbing and
painless joint swelling associated with a diaphragmatic neurilemoma have been reported in a 5-year-old girl [1]. Identifying the site of origin of tumors in the diaphragmatic area may be difficult. No single modality of imaging has demonstrated superiority in this challenging task. Use of ultrasound, CT scan, and MRI in combination are clearly indispensable in this regard; however, even the use of all 3 modalities together may not clearly identify the site of tumor origin. The liver, pericardium, lung, spleen, and pancreas have erroneously been labeled as sites of origin of PDT. In cases of right-sided masses, radiologists often mistakenly assign the liver as the site of origin. Our experience is consistent with this. Information on the origin of tumor at presentation is available in 18 cases. In only 6 patients (33%), tumors were correctly identified to have origins from the diaphragm after imaging was completed and before treatment initiation. Four of these tumors were right-sided. An unclear site of origin or wrong assignment of site of origin occurred in 12 cases. Seven of these masses were right sided. Thus, it seems to be equally difficult to assign an originating location of a diaphragmatic tumor, irrespective of the side on which it is found. In some cases, even after tumor shrinkage with chemotherapy treatment, repeat imaging has been unable to identify site of tumor origin. Exploratory surgery with biopsy may be helpful in providing this information. Treatment of malignant PDT follows the generic oncology tenet of biopsy or surgical resection, chemotherapy, and RT depending on the tumor type. Surgery remains the cornerstone of treatment in PDT, the timing of which is dictated by the resectability of the tumor. Germ cell tumors, for example, YST, may prove to be the exception and may not require surgery because of their sensitivity to chemotherapy; patients may go into complete remission following chemotherapy treatment only. In most cases, up-front complete surgical resection is not possible in view of invasion of surrounding vital organs and/or metastatic
1726 disease [6], limiting initial surgical intervention to a biopsy only. In the chemotherapy-sensitive tumors, the appropriate chemotherapy regimen should be initiated in an attempt to shrink the tumor, thus allowing a complete, delayed surgical resection. A tumor-free resection margin is the desired goal to maximize the potential of cure and minimize the chance of local recurrence. In part, treatment-related morbidity is directly proportional to the intensity of the adjuvant RT that may be required. Planning of the RT dose and target volume is critical, as it should not exceed the tolerance of the surrounding critical organs, specifically the lung and liver. Developments in RT techniques, for example, intensity modulated radiation therapy, brachytherapy, and proton beam RT, may be appropriately used to deliver effective RT with the least morbidity. To ensure complete surgical resection, a portion of the hemidiaphragm will usually have to be sacrificed, necessitating repair with a muscular flap or exogenous material such as polytetrafluoroethylene (PTFE or Gore-Tex). Vascularized muscular flaps, such as the Simpson internal oblique muscle flap and the latissimus dorsi muscle flap, have the advantage of growth potential and should be used if technically feasible. In conclusion, the inherent challenges involved in establishing an accurate diagnosis and thereafter delivering appropriate, effective, and safe treatment for children with PDT requires the input of a multidisciplinary team including radiologists, pathologists, surgeons, radiotherapists, and oncologists.
References [1] Wiener MF, Chou WH. Primary tumors of the diaphragm. Arch Surg 1965;90:143 - 51. [2] Olafsson G, Rausing A, Holen O. Primary tumors of the diaphragm. Chest 1971;59(5):568 - 70. [3] Weksler B, Ginsberg RJ. Tumors of the diaphragm. Chest Surg Clin N Am 1998;8(2):441 - 7. [4] Anderson LS, Forrest JV. Tumors of the diaphragm. Am J Roentgenol Radium Ther Nucl Med 1973;119(2):259 - 65. [5] Grancher M. Tumeur Vegetente du Centre Phrenique du Diaphragme. Bull Soc Anat Paris 1868;43:385.
M. Cada et al. [6] Raney RB, Anderson JR, Andrassy RJ, et al. Soft-tissue sarcoma of the diaphragm: a report from the Intergroup Rhabdomyosarcoma Study Group from 1972-1997. J Pediatr Hematol Oncol 2000;22(6): 510 - 4. [7] Peery TM, Smith WA. Rhabdomyosarcoma of the diaphragm. Am J Cancer 1939;35:416 - 21. [8] Gupta AK, Mitra DK, Berry M. Primary embryonal rhabdomyosarcoma of the diaphragm in a child: case report. Pediatr Radiol 1999; 29:823 - 5. [9] Seo T, Ito T, Ishiguro Y, et al. Lymphangioma of the right diaphragm. Pediatr Surg Int 1992;7(5):384 - 6. [10] Olsen L, Gustafsson G, Kreuger A, et al. An unusual case of hemangioma of the left diaphragm in a child: successful use of lyodura S for repair of the diaphragmatic defect. Pediatr Surg Int 1995;10(4):259 - 60. [11] Traubici J., Daneman A., Hayes-Jordan A., et al. Primary Germ Cell Tumour of the Diaphragm. J Ped Surg 2004;39:1578 - 80. [12] De Liz Medeiros CW, Kondo W, Baptista Jr I, et al. Primary rhabdomyosarcoma of the diaphragm: a case report and literature review. Rev Hosp Clin Fac Med Sao Paulo 2002;57(2):67 - 72. [13] Vade A, Bova D, Borge M, et al. Imaging of primary rhabdomyosarcoma of the diaphragm. Comput Med Imaging Graph 2000;24: 339 - 42. [14] Federici S, Casolari E, Rossi F, et al. Rhabdomyosarcoma of the diaphragm in a 4-year-old girl. Z Kinderchir 1986;41:303 - 5. [15] Kekomaki M, Ekfors TO, Nikkanen V, et al. Intrapleural endodermal sinus tumor arising from the diaphragm. J Pediatr Surg 1984;19(3): 312 - 4. [16] Ko SF, Ng SH, Lee TY, et al. Pedunculated malignant peripheral nerve-sheath tumor of the diaphragm presenting as recurrent lung infection: ultrasound diagnosis. Br J Radiol 2003;76:574 - 6. [17] Cacciaguerra S, Vasta G, Di Benedetto AG, et al. Neonatal diaphragmatic hemangioma. J Pediatr Surg 2001;36(9):21 - 2. [18] Smerdely MS, Raymond G, Fisher KL, et al. Primitive neuroectodermal tumor of the diaphragm: case report. Pediatr Radiol 2000; 30:702 - 4. [19] Eustace S, Fitzgerald E. Primary rhabdomyosarcoma of the diaphragm: an unusual cause of adolescent pseudo-achalasia. Pediatr Radiol 1993;23(8):622 - 3. [20] Buckley KM, Whitman GJ, Chew FS. Diaphragmatic pheochromocytoma. AJR Am J Roentgenol 1995;165(2):260. [21] Eroglu A, Kurkcuoglu IC, Karaoglanoglu N, et al. Extraskeletal Ewing sarcoma of the diaphragm presenting with hemothorax. Ann Thorac Surg 2004;78(2):715 - 7. [22] Vano J, Fernandez L, Mayayo E. Primary rhabdomyosarcoma of the diaphragm in a 4-year-old child—favorable course 5 years after surgery and chemotherapy. Ann Chir 1988;42(8):617 - 9.
www.elsevier.com/locate/jpedsurg
Approach to diagnosis and treatment of pediatric primary tumors of the diaphragm Michaela Cadaa,*, J. Ted Gerstleb, Jeffrey Traubicic, Bo-Yee Ngand, Michael L. Capraa a
Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8 Department of Surgery, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8 c Department of Diagnostic Imaging, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8 d Department of Laboratory Medicine and Pathobiology, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8 b
Index words: Primary neoplasm; Tumor; Diaphragm
Abstract Background/Purpose: Tumors of the diaphragm in the pediatric population are extremely rare. We present 5 cases diagnosed at the Hospital for Sick Children, Toronto, and together with a review of the world literature, provide an approach to the diagnosis and management of these tumors. Methods: A clinical retrospective review of patients diagnosed as having primary diaphragmatic tumor (PDT) at the Hospital for Sick Children as well as a review of the world literature. Results: Forty-one cases of PDT in the pediatric population have been described from 1868 to 2005 inclusive. There is an equal incidence in boys and girls, they are found with the same frequency on the left as on the right, and 78% are malignant. Rhabdomyosarcoma is the most commonly occurring malignant tumor. The mean age at diagnosis is 10 years. bChest-associatedQ symptoms are more common than babdomen-associatedQ symptoms. Imaging often fails to identify the site of origin as the diaphragm. Surgery is the cornerstone of therapy for PDT. Conclusion: A multidisciplinary team approach is needed for successful treatment and management of PDT. D 2006 Elsevier Inc. All rights reserved.
Primary tumors of the diaphragm are rare, with fewer than 200 cases having been described over the last 137 years [1-4]. Commonly presenting in the fourth and fifth decades of life, primary diaphragmatic tumors (PDTs) in childhood are therefore exceptional. The rarity, together with nonspecific and variable clinical presenting features, results in a chal-
lenging initial diagnosis. We present 5 cases of pediatric PDT diagnosed at the Hospital for Sick Children (HSC), Toronto, and together with a review of the world literature, provide an approach to the diagnosis and management of these tumors.
1. Materials and methods * Corresponding author. Division of Haematology/Oncology, 555 University Avenue, 9th floor Black Wing, Toronto, Ontario, Canada M5G 1X8. Tel.: +1 416 813 8885. E-mail address: [email protected] (M. Cada). 0022-3468/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2006.05.073
This study is divided into 2 components—a literature review and a clinical retrospective review of patients diagnosed with PDT at the HSC. The literature review
Approach to diagnosis and treatment of pediatric primary tumors of the diaphragm
1723
confirmed necrotic tissue only. The patient received 3 postoperative cycles of PEB chemotherapy and remains tumor-free three and a half years later.
2.2. Case 2
Fig. 1 Coronal T1-weighted MRI image demonstrating a large, predominantly left-sided, upper abdominal mass possibly arising from the left lateral segment of the liver.
was conducted by searching MEDLINE, EMBASE, COCHRANE, and CINAHL health sciences–related databases using the following key words: primary neoplasm, tumor, and diaphragm. The database of the department of pathology at HSC was used, following approval by the Research Ethics Board of HSC, to identify patients with histological confirmation of involvement of the diaphragm with tumor between the years 1975 and 2005 inclusive. Clarification from the pathology report and/or patient’s hospital chart of the 34 cases so found was required to further identify cases of primary diaphragmatic involvement. Five such cases were thus confirmed.
2. Cases 2.1. Case 1 A 23-month-old boy presented with a 1-week history of a left-sided abdominal swelling and pain in the left chest. Abdominal examination revealed a tender left upper quadrant mass. Ultrasound demonstrated a large tumor within the left lobe of the liver. Computed tomography (CT) and magnetic resonance imaging (MRI) scans confirmed a large, complex, heterogeneous, and exophytic mass arising from the lateral segment of the left lobe of the liver, abutting the falciform ligament (Fig. 1). a-Fetoprotein (AFP) was elevated at 1, 700, and 800 lg/L, and a b-hCG was normal at less than 2 U/L. An ultrasound-guided needle biopsy of the mass revealed histology consistent with a yolk sac tumor (YST). After 2 cycles of PEB (cisplatin, etoposide, bleomycin) chemotherapy, repeat imaging revealed the tumor to be reduced in size and separate from the liver. A complete surgical resection was subsequently achieved with the intraoperative findings revealing tumor originating from the anteromedial portion of the left diaphragm without hepatic involvement. Biopsies of nodules found on the right hemidiaphragm and omentum
A 22-month-old boy presented with sudden onset of abdominal pain and mild tachypnea. Chest x-ray revealed a large right pleural effusion and a soft tissue mass in the region of the liver. Ultrasound demonstrated a mass, possibly arising from the liver. Computed tomography and MRI scans, however, confirmed the mass to be in the upper abdominal quadrant, lower posterior mediastinum, and chest, apparently arising from the diaphragm and possibly infiltrating the liver. a-Fetoprotein was elevated at 93,000 lg/L, and b-human chorionic gonadotropin (hCG) was normal. Following a nondiagnostic ultrasound-guided biopsy of the mass, an open biopsy and exploratory thoracotomy were performed. This revealed a large mass originating in the right medial hemidiaphragm with surrounding satellite nodules but with no liver invasion. Histology was consistent with pure YST. The patient received 4 cycles of PEB chemotherapy, followed by complete surgical resection. A Gore-Tex patch was required to repair the diaphragm. Fourteen years later, the patient remains free of tumor and is an avid cross-country runner.
2.3. Case 3 A girl with neurofibromatosis type I, seizures, and developmental delay had progressive scoliosis that required surgical correction at the age of 12 years. At surgery, she was found to have multiple thoracic nodules on the left hemidiaphragm, not visible on prior chest or spinal x-rays. Multiple biopsies confirmed these to be benign plexiform neurofibromas that caused no further symptoms. The patient was transferred to an adult facility after her 17th birthday with no subsequent data available.
Fig. 2 Coronal T2-weighted MRI image demonstrating a large suprahepatic mass compressing the liver.
1724
M. Cada et al. abdominal ultrasound revealed a hypoechoic soft tissue mass with specks of calcification in the region of the upper abdominal wall, anterior to and separate from the liver. A CT scan revealed the same mass but could not delineate its relationship to the right hemidiaphragm. An MRI showed this mass to arise from the right hemidiaphragm, to extend along the length of it and in between the right and left lobes of the liver, resulting in the compression of the dome of the liver and obstruction of the inferior vena cava (Fig. 3). This resulted in the formation of collateral blood vessels and Budd-Chiari syndrome of the liver. Serum lactate dehydrogenase, AFP, and b-hCG were normal. Urine was negative for vanillylmandelic acid and homovanillic acid. A needle biopsy was consistent with myofibroma. The baby was stabilized and eventually discharged to the care of her parents. She will return in a few months for surgical resection.
Fig. 3 Coronal T2-weighted MRI image demonstrating a right hemidiaphragm mass, compressing the liver and insinuating between its right and left lobes.
2.4. Case 4 A 3.5-year-old boy presented with a 6-month history of increasing abdominal girth, prominence of the anterior superficial abdominal veins, and a 2-month history of intermittent night sweats, fevers, and abdominal pain. Abdominal examination revealed a distended abdomen, everted umbilicus, prominent anterior abdominal veins, and a firm right upper quadrant mass extending 10 cm below the right subcostal margin. a-Fetoprotein, b-hCG, and liver enzymes were normal. Abdominal ultrasound demonstrated a large mass involving both the right and left lobes of the liver. A CT scan revealed a large heterogeneous liver mass elevating the right hemidiaphragm and compressing the atria and inferior vena cava. Magnetic resonance imaging confirmed a large heterogeneous suprahepatic mass, presumably arising from the right hemidiaphragm and compressing the liver (Fig. 2). Percutaneous needle biopsy histology was consistent with embryonal rhabdomyosarcoma with focal anaplasia. Treatment was commenced with chemotherapy, following a contemporary Intergroup Rhabdomyosarcoma Study protocol. At week 20 of treatment, a complete resection was performed, necessitating resection of a portion of pericardium, the majority of the right hemidiaphragm, and a wedge resection of the liver. The pericardium and diaphragm were repaired using a Gore-Tex patch. The patient completed treatment with further chemotherapy and radiotherapy (RT) and remains tumor-free 1 year after presentation.
2.5. Case 5 A baby girl was delivered by elective cesarean birth at 37 weeks for fetal hydrops and ascites seen on regular antenatal scan. At delivery, she was in moderate respiratory distress requiring continuous positive airway pressure. Her abdomen was grossly distended, with dilated abdominal veins and hepatomegaly of 4 cm below the costal margin. An
3. Discussion The reported 5 cases of PDTs diagnosed at the HSC in a 30-year period reflect the rare incidence and demonstrate the complexity of clinical presentation, the diagnostic challenges and treatment of these tumors. The first reported case of a PDT was discovered in an adult autopsy for an unrelated cause of death and was diagnosed as fibroma in 1868 [5]. Subsequently, between 1868 and 2005, there have been less than 200 cases reported in the English literature. Including our series, 41 of these tumors have been found in patients 18 years of age or less [1-3,6-22]. In reviewing this cohort of patients, there is an equal incidence of PDT in boys and girls, they are found with equal frequency on the right and on the left, and most (n = 32, 78%) are malignant. Rhabdomyosarcoma is the most commonly occurring malignant tumor (Table 1); lymphangioma and hemangioma
Table 1 Breakdown of PDT described in the literature and at HSC according to histological type Malignant
n = 32
Benign
n=9
Rhabdomyosarcoma
16
2
4
Cystic lymphangioma Hemangioma
2
3 3
Lipoma Neurilemmoma
1 1
1 1 1 1
Bronchial cyst Neurofibroma Myofibroma
1 1 1
Undifferentiated sarcoma Yolk sac tumor Extraosseous Ewing sarcoma Hemangioendothelioma Hemangiopericytoma Pheochromocytoma Malignant nerve-sheath tumor Primitive neuroectodermal tumor Sarcoma not otherwise specified
1 1
Approach to diagnosis and treatment of pediatric primary tumors of the diaphragm
Fig. 4
1725
Distribution of PDT according to age in years.
are examples of benign tumors. The mean age at diagnosis is 10 years, with an equal number of cases in the first and second decades of life (Fig. 4). The presentation of children with diaphragmatic tumors is variable, depending on age at presentation, size of mass, involvement of adjacent organs or metastatic disease, and tumor histology. bChest-associatedQ symptoms are more common than babdomen-associatedQ symptoms at presentation. Including our series, detailed information is available for 26 patients, 18 of which presented with one or a combination of chest- and/or abdomen-associated symptoms. Further analysis showed that 8 children had chest pain at presentation, 6 had shortness of breath, 4 had cough, 1 had a visible chest mass, 1 had chest asymmetry, and 1 had hemothorax. Abdominal distention was the presenting sign in 4 children, abdominal pain in 3, and an abdominal mass in 2. Of the 26 children, 6 presented buniquely,Q and discovery of the diaphragmatic tumor was an incidental finding in 2 cases (1, Cada). Of the remaining 15 children for whom detailed information is not available, clinical presentation was reported by authors to be a combination of chest or back pain, shortness of breath, and cough in 14 cases [6]. No information was available for 1 child [22]. In our series, 3 of 5 patients had a combination of chest- and abdomen-associated symptoms. Unique-presenting symptoms have been reported in 6 of the 26 children. Hydrops fetalis and neonatal respiratory failure at the time of delivery have been described in a newborn with diaphragmatic hemangioma [17] and in our newborn with diaphragmatic myofibroma. One adolescent boy presented with recurrent lung infection that was not responsive to antibiotic therapy [16]. Progressive dysphagia, secondary to a diaphragmatic rhabdomyosarcoma, has been described in a 12-year-old boy [19]. Palpitations, vomiting, and intermittent, severe hypertension were the clinical manifestations of a diaphragmatic pheochromocytoma in an 11-year old boy [20]. Finally, paraneoplastic features of fingernail clubbing and
painless joint swelling associated with a diaphragmatic neurilemoma have been reported in a 5-year-old girl [1]. Identifying the site of origin of tumors in the diaphragmatic area may be difficult. No single modality of imaging has demonstrated superiority in this challenging task. Use of ultrasound, CT scan, and MRI in combination are clearly indispensable in this regard; however, even the use of all 3 modalities together may not clearly identify the site of tumor origin. The liver, pericardium, lung, spleen, and pancreas have erroneously been labeled as sites of origin of PDT. In cases of right-sided masses, radiologists often mistakenly assign the liver as the site of origin. Our experience is consistent with this. Information on the origin of tumor at presentation is available in 18 cases. In only 6 patients (33%), tumors were correctly identified to have origins from the diaphragm after imaging was completed and before treatment initiation. Four of these tumors were right-sided. An unclear site of origin or wrong assignment of site of origin occurred in 12 cases. Seven of these masses were right sided. Thus, it seems to be equally difficult to assign an originating location of a diaphragmatic tumor, irrespective of the side on which it is found. In some cases, even after tumor shrinkage with chemotherapy treatment, repeat imaging has been unable to identify site of tumor origin. Exploratory surgery with biopsy may be helpful in providing this information. Treatment of malignant PDT follows the generic oncology tenet of biopsy or surgical resection, chemotherapy, and RT depending on the tumor type. Surgery remains the cornerstone of treatment in PDT, the timing of which is dictated by the resectability of the tumor. Germ cell tumors, for example, YST, may prove to be the exception and may not require surgery because of their sensitivity to chemotherapy; patients may go into complete remission following chemotherapy treatment only. In most cases, up-front complete surgical resection is not possible in view of invasion of surrounding vital organs and/or metastatic
1726 disease [6], limiting initial surgical intervention to a biopsy only. In the chemotherapy-sensitive tumors, the appropriate chemotherapy regimen should be initiated in an attempt to shrink the tumor, thus allowing a complete, delayed surgical resection. A tumor-free resection margin is the desired goal to maximize the potential of cure and minimize the chance of local recurrence. In part, treatment-related morbidity is directly proportional to the intensity of the adjuvant RT that may be required. Planning of the RT dose and target volume is critical, as it should not exceed the tolerance of the surrounding critical organs, specifically the lung and liver. Developments in RT techniques, for example, intensity modulated radiation therapy, brachytherapy, and proton beam RT, may be appropriately used to deliver effective RT with the least morbidity. To ensure complete surgical resection, a portion of the hemidiaphragm will usually have to be sacrificed, necessitating repair with a muscular flap or exogenous material such as polytetrafluoroethylene (PTFE or Gore-Tex). Vascularized muscular flaps, such as the Simpson internal oblique muscle flap and the latissimus dorsi muscle flap, have the advantage of growth potential and should be used if technically feasible. In conclusion, the inherent challenges involved in establishing an accurate diagnosis and thereafter delivering appropriate, effective, and safe treatment for children with PDT requires the input of a multidisciplinary team including radiologists, pathologists, surgeons, radiotherapists, and oncologists.
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