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Mediastinal Tumors and Cysts in the Pediatric Patient
Symposium on Surgery of the Chest
Mediastinal Tumors and Cysts in the Pediatric Patient Lorin D. Whittaker, Jr., M.D., and Hugh B. Lynn, M.D.
Tumors and cysts of the mediastinum are less common in children than in adults. Indeed, the absence or rarity of pericardial coelomic cysts (two cases reported) and of intrathoracic thyroid and parathyroid tumors among children contrasts with their incidence in adults. The various kinds have the same anatomic predilections as in adults, however (Table 1); and localization to a specific mediastinal compartment enhances the accuracy of preoperative diagnosis. While certain lesions are nearly always located in a specific mediastinal compartment (for example, neurogenic tumors, teratomas), others are less consistently restricted in location and commonly involve more than one compartment (for instance, lymph node lesions, vascular tumors, enterogenous cysts).
GENERAL"CLINICAL DATA In 1935 to 1968, inclusive, 105 patients less than 16 years old were treated at the Mayo Clinic for primary mediastinal tumors (Table 2). Symptoms Mediastinal tumors may produce symptoms and signs because of their size or consistency, or especially by compression or actual invasion of various structures such as bronchi, the superior vena cava, or the spinal cord. Usual presenting symptoms are cough, dyspnea, and pain, the latter more commonly occurring with malignant tumors. However, approximately half of the children with mediastinal tumors or cysts are asymptomatic and their lesions are discovered during routine roentgenographic examination of the chest. Physical findings often are within normal limits. Positive findings, such as decrease or absence of breath sounds in the affected hemithorax, are obtained in a minority of cases. Additional findings may include Horner's syndrome, signs and symptoms of spinal-cord compression, dysphagia, intercostal-nerve neuralgia, and evidence of superior vena caval obstruction. In general, these latter observations should not be interpreted as absolute evidence for malignancy Surgical Clinics of North America- Vol. 53, No.4, August 1973
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Table 1. Anatomic Distribution of Types of Tumors and Cysts in Mediastinal Compartments of Children Superior mediastinum Cystic hygroma Vascular tumors Neurogenic tumors Anterior mediastinum Thymoma Thymic cyst, thymic hyperplasia Teratoma Germinoma Vascular tumors Lymphoma Middle mediastinum Granuloma Lymphoma Metastatic lesions Alimentary-tract duplications Bronchogenic cysts Hypertrophic lymph nodes Posterior mediastinum Neurogenic tumors Alimentary-tract duplications Thoracic meningocele
Table 2. Mediastinal Cysts and Tumors in Patients Less Than 16 Years Old: Mayo Clinic, 1935 to 1968 CLASSIFICATION
Neurogenic Ganglioneuroma Neuroblastoma Neurofibroma Ganglioneuroblastoma Plexiform neuroma N eurofibrosarcoma Teratoma Lymphoma Alimentary-tract duplications Cystic hygroma Bronchogenic cyst Hemangioma Granuloma Angiosarcoma Thymic cyst Thymic hyperplasia Thyroid Lipomyxosarcoma Hamartoma Hemangiopericytoma Miscellaneous TOTAL
NO.
37 16 11 6 2
21 9
7 6 5
3 3 2 2 2
4 105
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or unresectability. It is true, however, that patients with malignant lesions are more frequently symptomatic than those with benign lesions. Diagnosis Normal results usually are obtained from all the routine laboratory tests but chest roentgenography. The roentgenograms should be made in the posteroanterior and lateral projections to facilitate localization of the lesion. Esophagograms may be useful, especially in delineating benign lesions such as enterogenous cysts. Bronchoscopy, esophagoscopy, bronchography, and angiography are rarely indicated for diagnostic purposes. Bone-marrow aspiration may be useful, and urinary catecholamine determinations as well, when it seems a posteriorly situated tumor might be a neuroblastoma. A skeletal survey also should be made preoperatively in that circumstance. Treatment The best treatment for primary mediastinal cysts and tumors is surgical excision. Thoracotomy is usually necessary for diagnosis and should carry minimal risk. In a majority of these cases, no drainage tubes are necessary if air leaks from lung parenchyma are controlled and hemostasis is satisfactory at the time of wound closure. The cooperation of the anesthesiologist will enable the surgeon to remove a suction catheter from the corner of the incision as the wound is closed without leaving a significant amount of air in the pleural space. All patients old enough to cooperate are encouraged to blow up as many balloons as possible in the early postoperative days. A humid atmosphere is maintained by a facial mask enlarged to permit more freedom of head movement. Antibiotics are not administered routinely. It is rare for intravenous fluids to be required beyond 24 hours after surgery. For lesions which cannot be completely excised, or for certain malignant conditions, adjunctive chemotherapy or radiation therapy may be employed.
MORE COMMON SPECIFIC TUMORS Neurogenic Tumors Primary intrathoracic neurogenic tumors are commonly classified by origin. Tumors which contain all the nerve components are neurofibromas. In children they may be associated with generalized neurofibromatosis of von Recklinghausen, but amount to only a small percentage of primary thoracic neurogenic tumors. Tumors of nerve-sheath origin are neurilemmomas. These are uncommon and nearly always benign in pediatric patients. The plexiform neuroma consists of tangled nerve tissue in fusiform and nodular masses and frequently is associated with skeletal and neurologic abnormalities. 6 Among the primary intrathoracic neurogenic tumors in the pediatric age group, those of nerve-cell origin are by far the most common. Though proposed classifications differ, it is generally agreed that these tumors range from the highly malignant immature neuroblastoma to the well-
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differentiated, always benign ganglioneuroma. Between these extremes is the ganglioneuroblastoma, which contains some features of both. These thoracic neurogenic tumors arise almost exclusively in the posterior mediastinum, or more accurately the paravertebral sulcus. Ganglioneuromas in children occur most frequently in the thoracic cavity, whereas neuroblastomas and ganglioneuroblastomas are considerably more often extrathoracic. In our experience with 37 intrathoracic neurogenic tumors in infants and children, 43% were ganglioneuromas and 30% neuroblastomas. Neurogenic tumors may produce symptoms by the effects of circulating catecholamines. Varying degrees of elevation of urinary concentrations of vasoactive substances, their precursors, and metabolites have been found in patients with thoracic neuroblastomas and ganglioneuroblastomas. Hypertension, diarrhea, perspiration, pallor, and palpitations have been the most frequent signs and symptoms. Determination of serum and urinary catecholamine metabolites has been useful in the follow-up period for evaluating the efficacy of treatment and detecting recurrences before clinical evidence appears. The diagnosis of neurogenic tumor is suggested by roentgenologic evidence of a posterior mediastinal mass (Fig. 1), and neuroblastomas in particular may have scattered punctate calcification which is diagnostic. The neuroblastomas are large, meaty-appearing tumors with apparently ill-defined invasive margins, although the capsule is often intact as a definite fibrous structure. Surgical removal is the treatment of choice, but complete excision of a neuroblastoma is frequently impossible. In the absence of widespread metastasis or known bone metastasis, as much of the primary tumor as possible should be removed. 4 An intraspinal extension that compresses the cord may be removed by a staged procedure with initiallaminectomy,7 but it seems better to combine the stages into a single operation. Postoperative therapy includes the use of
Figure 1. Views showing rounded density behind right side of heart of l-year-old asymptomatic boy. Complete removal of mass was accomplished, and pathologist reported ganglioneuroblastoma. Radiation was administered postoperatively. Patient is alive and well 8 years later.
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radiation and chemotherapeutic agents, primarily vincristine and cyclophosphamide. Metastasis to bone is a grave prognostic sign, for nearly all patients with such involvement die. Spontaneous maturation of neuroblastoma to the less malignant ganglioneuroblastoma and benign ganglioneuroma is a rare phenomenon. The classic report of spontaneous maturation was made by Cushing and Wolbach in 1927. Spontaneous regression is a perplexing capability of the neuroblastoma, but happens rarely. Biochemical factors which affect normal maturation of the immature cells and stimulation of ganglion-cell production have been discussed as possible causes of such differentiation. 2 • 8 Of the 11 Mayo Clinic patients with neuroblastoma, only 8 could be traced for follow-up in 1972. Four of these were still living and well from 7 to 15 years after resection.
Alimentary-Tract Duplications Mediastinal duplications of the alimentary tract have also been termed mediastinal gastric cysts, enteric cysts, enterocystomas, duplication cysts, and arch enteric cysts. To classify these malformations as intestinal duplications seems useful, though their actual origin remains unclear. Frequently associated with thoracic duplication are anomalies of the lower cervical and upper thoracic vertebrae, including hemivertebrae, incomplete fusion of neural arches, spina bifida, and scoliosis. Duplications of the foregut may be lined by esophageal epithelium or by gastric or enteric mucosa. Some are intimately associated with a portion of the esophagus, sharing a common muscle wall. Others are distinctly separate from the esophagus, and typically appear on the chest roentgenogram as a posterior mediastinal mass (Fig. 2). These usually are mediastinal extensions of duplications originating in the abdomen. A cyst of any of these types may rupture into a lung or bronchus.
Figure 2. Views reveal well-circumscribed mediastinal mass behind heart in 13-year-old asymptomatic boy. At surgery this mass was found lateral and posterior to esophagus. Pathologist reported enterogenous cyst, 7.5 em in length.
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Surgical excision is the treatment of choice. The associated inflammatory disease may require conservative pulmonary resection. Bronchogenic Cysts In adults, bronchogenic cysts are commonly asymptomatic; but in the early pediatric years they frequently produce symptoms, cause respiratory embarrassment, and increase susceptibility to infections. The possibility that these effects are due to such disorders as bronchiectasis and pulmonary sequestration often leads to bronchoscopy, bronchography, and even aortography. Disability related to recurrent infections is the usual indication for surgery, but impingement on the airway is a more urgent reason. Pulmonary resection may be required because of associated pneumonitis and suppuration, but this is more common with intrapulmonary bronchogenic cysts. Mediastinal bronchogenic cysts may distort the bronchial lumen by pressing against the more supple membranous component of the wall. If infection has not supervened, these cysts can be removed completely with minimal morbidity, and the patient will remain free of recurrence. Mediastinal Teratomas Teratomas are tumors containing elements of the three germ layers, and their tissues are foreign to the region in which they are located. Teratomas commonly contain dermal, dental, bony, cartilaginous, neural, vascular, alimentary-tract, and respiratory tissue. The tumors may be predominantly solid or cystic, but usually are a mixture of each form. "Dermoid cyst" is the name commonly given to a cystic teratoma which has produced primarily ectodermal products-brain, hair, teeth, sebaceous material, and squamous epithelium. Most of the mediastinal teratomas are benign; and in the Mayo Clinic series, 18 (86%) of 21 mediastinal teratomas in children were benign. The majority of mediastinal teratomas are asymptomatic during the pediatric years, although even huge symptomatic tumors at birth have been reported. Symptoms appear as the lesion, by its bulk, compresses adjacent lung parenchyma or major bronchi. The contents of the teratoma may become infected hematogenously or by communication with bronchi. Secondary pneumonitis from rupture of the teratoma into the adjacent lung may result in expectoration of teratoma components, such as sebaceous material or hair. The anteriorly situated mass shown in the chest roentgenogram may be identified more specifically by the characteristic calcification of a tooth or layering of the lipid contents of a dermoid cyst (Fig. 3). The treatment is surgical excision, including the contiguous portion of the lung if it is irreparably damaged. Most malignant teratomas are steadily progressive, and the fatal outcome has not been prevented in pediatric patients by adjunctive chemotherapy or radiation. In the Mayo Clinic series, all three patients w~th malignant teratoma were dead within 16 months ~er operation. Cystic Hygroma Cystic hygroma is a benign congenital tumor of lymphatic origin whose multilocular cavities are lined with endothelium. This lesion is
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Figure 3. Views reveal huge, well-circumscribed mass in asymptomatic 10-year-old boy, filling lower two-thirds of left hemithorax and causing shift of heart to right. Inferior aspect of tumor shows some calcification. Benign teratoma weighing 1750 gm was completely removed.
located most commonly in the neck and infrequently in the mediastinum. However, extension of a cervical tumor may involve the mediastinum. Lim et al. found published reports of 30 cases of cervico-mediastinal cystic hygroma and added 9 cases from the Mayo Clinic. Only one patient in their series was more than 4 years old. The cervico-mediastinal lesion usually is obvious on examination because of being partly in the neck; and, especially in infants, obvious respiratory distress may be associated with it. But the strictly mediastinal tumor may cause no symptoms and is more often discovered in the older age group. When palpable cervically, the lesion usually seems fairly soft and poorly circumscribed. Chest roentgenograms show a soft-tissue density, usually in the antero-superior mediastinum (Fig. 4). The treatment is excision, though the pseudopodal form of its growth and extension makes it difficult to excise completely. The lymphatic tissue is insinuated between tissue planes and surrounds vital vessels and nerves. While it is desirable to remove as much of the hygroma as possible, the involvement of vital structures may prevent completeness. Satisfactory results may be obtained, even though a portion of the lesion is left attached to such structures. It is preferable to approach the cervico-mediastinal lesion initially through the neck and usually this approach suffices. If the mediastinal component cannot be removed by this route, however, supplemental thoracotomy may be added. And for strictly mediastinal lesions, thoracotomy is necessary. Chylothorax associated with a mediastinal hygroma is shown in Figure 5. This rare complication presents challenging diagnostic and therapeutic problems, although the basic solution is control of the escaping chyle by excision of the hygroma.
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Figure 4. Views reveal marked superior mediastinal widening with deviation of the trachea anteriorly in 5-month-old girl. Soft tissue mass in lower right neck increased 3 to 4 times in size when she cried. Cervical approach permitted nearly total removal of cervicomediastinal cystic hygroma.
Figure 5. View of 7-year-old boy with diffuse mediastinal and pulmonary cystic hygroma and right pleural effu ion of chylous fluid .
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Tumors of Thymic Origin In infancy and early childhood years, the large size of the thymus relative to the mediastinum is responsible for the anterior mediastinal widening in the chest roentgenogram, with a characteristic notch often identifiable in posteroanterior or oblique views, which separates the inferior border of the thymus from the cardiac silhouette. Although this physiologic enlargement may be noted roentgenologically, it rarely is responsible for symptoms of airway obstruction. A cardiothymic shadow which appears abnormal may be studied more thoroughly by means of serial chest roentgenograms. However, two of our patients with thymic hyperplasia were explored for thymic enlargement that preoperatively could not be differentiated from a pathologic process (Fig. 6). Irradiation of the thymus is to be avoided, because it may be carcinogenic; and we have not resorted to administration of adrenal corticoids to try to reduce the size of the tumor.3 Thymic cysts occur infrequently. Two were encountered in our series, both benign. Theoretically such cysts may be located at any level from the neck to the diaphragm, but usually they are found near the base of the heart. Solid thymic tumors are rare in pediatric patients. We have
Figure 6. Routine views (A and B) of 15-year-old asymptomatic boy with widening of right mediastinum. At fluoroscopy mass was observed to pulsate. C, Contrast study reveals normal esophagus. D, Thoracic aortogram appears normal. At surgery, hyperplastic thymus was excised.
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not encountered a child with myasthenia gravis and a thymoma. For thymic-tumor surgery, the anterior approach via median sternotomy provides the best exposure. Tumors of Blood-Vessel Origin Hemangiomas of the skin and mucous membranes are encountered often in the pediatric years; and if the patient has a cutaneous or mucosal hemangioma and a mediastinal mass, the diagnosis of mediastinal hemangioma should be considered; but mediastinal hemangiomas are rare. Angiography has not been helpful, because the contrast medium usually does not opacify the tumor. Even though histologically benign, these tumors tend to extend locally into surrounding structures, occasionally making surgical excision difficult. Recurrence after excision is rare. Lymph-Node Pathology Woods in 1965 found only 13 published reports of mediastinal granuloma in the pediatric age group and added a single case. All of the patients were symptomatic; half presented with severe airway obstruction. Roentgenologically these lesions typically appear as rounded, well-circumscribed, calcified masses in the middle mediastinum (Fig. 7). Surgical excision is elected when symptoms occur or when the diagnosis is in doubt. The dense fibrotic inflammation surrounding the lesion may make total excision difficult, but partial excision fortunately does not lead to infection problems, nor to recurrent mediastinal granulomatous disease. Mediastinal lymph-node involvement in leukemia or lymphoma usually is part of a generalized widespread process. Infrequently, primary mediastinal lymphoma is localized well enough so complete surgical excision can be accomplished (Fig. 8). At the present time patients also are
Figure 7. Views of 13·year-old girl with fever, chest pain, and pericardial friction rub reveal mid-mediastinal mass with calcification. At surgery mediastinal granuloma was encountered.
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* Figure 8. Posteroanterior roentgenogram (A) and tomogram (B) of upper mediastinum of asymptomatic 15-year-old boy reveal elongated mass in right upper mediastinum and left deviation of trachea. Total removal of this giant follicular lymphosarcoma was accomplished and the patient is alive and well 10 years later.
given radiation therapy and chemotherapy for mediastinal lymphoma, in the hope that the usual grave prognosis for childhood lymphoma can be improved. Sarcoidosis and tuberculous adenopathy of the mediastinum often can be diagnosed by means other than surgical exploration of the thorax. Positive response to a tuberculin test and evidence of a primary complex are highly suggestive of tuberculosis. Associated uveitis, cutaneous nodules, and cervical adenopathy are sufficient to alert the physician to the possible diagnosis of sarcoidosis. Angiofollicular hyperplasia, which may resemble thymoma roentgenographically, is a rare benign cause of lymph-node enlargement affecting the older pediatric patient.
Miscellaneous Lesions Pediatric intrathoracic meningocele is rare, usually does not cause symptoms, and appears as a well-rounded mass in the paravertebral position on the chest roentgenogram. Infrequent among adults and distinctly rare in the pediatric age group are pericardial coelomic cysts, chemodectomas, pheochromocytomas, liposarcomas, choriocarcinomas, seminomas, and thoracic-duct cysts. Signs of a pancreatic pseudocyst extending into the mediastinum may resemble those of a primary mediastinal tumor, and so may the signs of extramedullary hematopoiesis occurring in the paraspinal region of the thorax.
CONCLUSIONS Mediastinal masses in children may not cause symptoms. Their detection on routine roentgenograms should lead to further studies, and the
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lack of symptoms should never be taken as an indication that the lesion is benign. The high incidence of malignancy in mediastinal tumors of infants and children makes thoracotomy a logical diagnostic and therapeutic step.
REFERENCES 1. Cushing H, Wolbach SB: The transformation of a malignant paravertebral sympathicoblastoma into a benign ganglioneuroma. Am J Pathol 3:203-216, 1927 2. Goldstein MN, Burdman JA, Journey LJ: Long-term tissue culture of neuroblastomas. II. Morphologic evidence for differentiation and maturation. J Nat! Cancer Inst 32: 165199, 1964 3. Haller JA Jr, Mazur DO, Morgan WW Jr: Diagnosis and management of mediastinal masses in children. J Thorac Cardiovasc Surg 58:385-392, 1969 4. Koop CE, Kiesewetter WB, Horn RC: Neuroblastoma in childhood: survival after major surgical insult to the tumor. Surgery 38:272-278, 1955 5. Lim RA, Divertie MB, Harrison EG Jr, et al: Cervico-mediastinal cystic hygroma. Dis Chest 40:265-274, 1961 6. Raffensperger J, Cohen R: Plexiform neurofibromas in childhood. J Pediatr Surg 7:144151, 1972 7. Svien HJ, Seybold WD, Thelen EP: Intraspinal and intrathoracic tumor with paraplegia in a child: report of case. Proc Staff Meet Mayo Clin 25:715-720,1950 8. Wilkerson JA, Van De Water JM, Goepfert H: Role of embryonic induction in benign transformation of neuroblastomas. Cancer 20: 1335-1342, 1967 9. Woods LP: Mediastinal histoplasma granuloma causing tracheal compression in a 4-yearold child. Surgery 58:448-452, 1965
Mediastinal Tumors and Cysts in the Pediatric Patient Lorin D. Whittaker, Jr., M.D., and Hugh B. Lynn, M.D.
Tumors and cysts of the mediastinum are less common in children than in adults. Indeed, the absence or rarity of pericardial coelomic cysts (two cases reported) and of intrathoracic thyroid and parathyroid tumors among children contrasts with their incidence in adults. The various kinds have the same anatomic predilections as in adults, however (Table 1); and localization to a specific mediastinal compartment enhances the accuracy of preoperative diagnosis. While certain lesions are nearly always located in a specific mediastinal compartment (for example, neurogenic tumors, teratomas), others are less consistently restricted in location and commonly involve more than one compartment (for instance, lymph node lesions, vascular tumors, enterogenous cysts).
GENERAL"CLINICAL DATA In 1935 to 1968, inclusive, 105 patients less than 16 years old were treated at the Mayo Clinic for primary mediastinal tumors (Table 2). Symptoms Mediastinal tumors may produce symptoms and signs because of their size or consistency, or especially by compression or actual invasion of various structures such as bronchi, the superior vena cava, or the spinal cord. Usual presenting symptoms are cough, dyspnea, and pain, the latter more commonly occurring with malignant tumors. However, approximately half of the children with mediastinal tumors or cysts are asymptomatic and their lesions are discovered during routine roentgenographic examination of the chest. Physical findings often are within normal limits. Positive findings, such as decrease or absence of breath sounds in the affected hemithorax, are obtained in a minority of cases. Additional findings may include Horner's syndrome, signs and symptoms of spinal-cord compression, dysphagia, intercostal-nerve neuralgia, and evidence of superior vena caval obstruction. In general, these latter observations should not be interpreted as absolute evidence for malignancy Surgical Clinics of North America- Vol. 53, No.4, August 1973
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Table 1. Anatomic Distribution of Types of Tumors and Cysts in Mediastinal Compartments of Children Superior mediastinum Cystic hygroma Vascular tumors Neurogenic tumors Anterior mediastinum Thymoma Thymic cyst, thymic hyperplasia Teratoma Germinoma Vascular tumors Lymphoma Middle mediastinum Granuloma Lymphoma Metastatic lesions Alimentary-tract duplications Bronchogenic cysts Hypertrophic lymph nodes Posterior mediastinum Neurogenic tumors Alimentary-tract duplications Thoracic meningocele
Table 2. Mediastinal Cysts and Tumors in Patients Less Than 16 Years Old: Mayo Clinic, 1935 to 1968 CLASSIFICATION
Neurogenic Ganglioneuroma Neuroblastoma Neurofibroma Ganglioneuroblastoma Plexiform neuroma N eurofibrosarcoma Teratoma Lymphoma Alimentary-tract duplications Cystic hygroma Bronchogenic cyst Hemangioma Granuloma Angiosarcoma Thymic cyst Thymic hyperplasia Thyroid Lipomyxosarcoma Hamartoma Hemangiopericytoma Miscellaneous TOTAL
NO.
37 16 11 6 2
21 9
7 6 5
3 3 2 2 2
4 105
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or unresectability. It is true, however, that patients with malignant lesions are more frequently symptomatic than those with benign lesions. Diagnosis Normal results usually are obtained from all the routine laboratory tests but chest roentgenography. The roentgenograms should be made in the posteroanterior and lateral projections to facilitate localization of the lesion. Esophagograms may be useful, especially in delineating benign lesions such as enterogenous cysts. Bronchoscopy, esophagoscopy, bronchography, and angiography are rarely indicated for diagnostic purposes. Bone-marrow aspiration may be useful, and urinary catecholamine determinations as well, when it seems a posteriorly situated tumor might be a neuroblastoma. A skeletal survey also should be made preoperatively in that circumstance. Treatment The best treatment for primary mediastinal cysts and tumors is surgical excision. Thoracotomy is usually necessary for diagnosis and should carry minimal risk. In a majority of these cases, no drainage tubes are necessary if air leaks from lung parenchyma are controlled and hemostasis is satisfactory at the time of wound closure. The cooperation of the anesthesiologist will enable the surgeon to remove a suction catheter from the corner of the incision as the wound is closed without leaving a significant amount of air in the pleural space. All patients old enough to cooperate are encouraged to blow up as many balloons as possible in the early postoperative days. A humid atmosphere is maintained by a facial mask enlarged to permit more freedom of head movement. Antibiotics are not administered routinely. It is rare for intravenous fluids to be required beyond 24 hours after surgery. For lesions which cannot be completely excised, or for certain malignant conditions, adjunctive chemotherapy or radiation therapy may be employed.
MORE COMMON SPECIFIC TUMORS Neurogenic Tumors Primary intrathoracic neurogenic tumors are commonly classified by origin. Tumors which contain all the nerve components are neurofibromas. In children they may be associated with generalized neurofibromatosis of von Recklinghausen, but amount to only a small percentage of primary thoracic neurogenic tumors. Tumors of nerve-sheath origin are neurilemmomas. These are uncommon and nearly always benign in pediatric patients. The plexiform neuroma consists of tangled nerve tissue in fusiform and nodular masses and frequently is associated with skeletal and neurologic abnormalities. 6 Among the primary intrathoracic neurogenic tumors in the pediatric age group, those of nerve-cell origin are by far the most common. Though proposed classifications differ, it is generally agreed that these tumors range from the highly malignant immature neuroblastoma to the well-
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differentiated, always benign ganglioneuroma. Between these extremes is the ganglioneuroblastoma, which contains some features of both. These thoracic neurogenic tumors arise almost exclusively in the posterior mediastinum, or more accurately the paravertebral sulcus. Ganglioneuromas in children occur most frequently in the thoracic cavity, whereas neuroblastomas and ganglioneuroblastomas are considerably more often extrathoracic. In our experience with 37 intrathoracic neurogenic tumors in infants and children, 43% were ganglioneuromas and 30% neuroblastomas. Neurogenic tumors may produce symptoms by the effects of circulating catecholamines. Varying degrees of elevation of urinary concentrations of vasoactive substances, their precursors, and metabolites have been found in patients with thoracic neuroblastomas and ganglioneuroblastomas. Hypertension, diarrhea, perspiration, pallor, and palpitations have been the most frequent signs and symptoms. Determination of serum and urinary catecholamine metabolites has been useful in the follow-up period for evaluating the efficacy of treatment and detecting recurrences before clinical evidence appears. The diagnosis of neurogenic tumor is suggested by roentgenologic evidence of a posterior mediastinal mass (Fig. 1), and neuroblastomas in particular may have scattered punctate calcification which is diagnostic. The neuroblastomas are large, meaty-appearing tumors with apparently ill-defined invasive margins, although the capsule is often intact as a definite fibrous structure. Surgical removal is the treatment of choice, but complete excision of a neuroblastoma is frequently impossible. In the absence of widespread metastasis or known bone metastasis, as much of the primary tumor as possible should be removed. 4 An intraspinal extension that compresses the cord may be removed by a staged procedure with initiallaminectomy,7 but it seems better to combine the stages into a single operation. Postoperative therapy includes the use of
Figure 1. Views showing rounded density behind right side of heart of l-year-old asymptomatic boy. Complete removal of mass was accomplished, and pathologist reported ganglioneuroblastoma. Radiation was administered postoperatively. Patient is alive and well 8 years later.
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radiation and chemotherapeutic agents, primarily vincristine and cyclophosphamide. Metastasis to bone is a grave prognostic sign, for nearly all patients with such involvement die. Spontaneous maturation of neuroblastoma to the less malignant ganglioneuroblastoma and benign ganglioneuroma is a rare phenomenon. The classic report of spontaneous maturation was made by Cushing and Wolbach in 1927. Spontaneous regression is a perplexing capability of the neuroblastoma, but happens rarely. Biochemical factors which affect normal maturation of the immature cells and stimulation of ganglion-cell production have been discussed as possible causes of such differentiation. 2 • 8 Of the 11 Mayo Clinic patients with neuroblastoma, only 8 could be traced for follow-up in 1972. Four of these were still living and well from 7 to 15 years after resection.
Alimentary-Tract Duplications Mediastinal duplications of the alimentary tract have also been termed mediastinal gastric cysts, enteric cysts, enterocystomas, duplication cysts, and arch enteric cysts. To classify these malformations as intestinal duplications seems useful, though their actual origin remains unclear. Frequently associated with thoracic duplication are anomalies of the lower cervical and upper thoracic vertebrae, including hemivertebrae, incomplete fusion of neural arches, spina bifida, and scoliosis. Duplications of the foregut may be lined by esophageal epithelium or by gastric or enteric mucosa. Some are intimately associated with a portion of the esophagus, sharing a common muscle wall. Others are distinctly separate from the esophagus, and typically appear on the chest roentgenogram as a posterior mediastinal mass (Fig. 2). These usually are mediastinal extensions of duplications originating in the abdomen. A cyst of any of these types may rupture into a lung or bronchus.
Figure 2. Views reveal well-circumscribed mediastinal mass behind heart in 13-year-old asymptomatic boy. At surgery this mass was found lateral and posterior to esophagus. Pathologist reported enterogenous cyst, 7.5 em in length.
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Surgical excision is the treatment of choice. The associated inflammatory disease may require conservative pulmonary resection. Bronchogenic Cysts In adults, bronchogenic cysts are commonly asymptomatic; but in the early pediatric years they frequently produce symptoms, cause respiratory embarrassment, and increase susceptibility to infections. The possibility that these effects are due to such disorders as bronchiectasis and pulmonary sequestration often leads to bronchoscopy, bronchography, and even aortography. Disability related to recurrent infections is the usual indication for surgery, but impingement on the airway is a more urgent reason. Pulmonary resection may be required because of associated pneumonitis and suppuration, but this is more common with intrapulmonary bronchogenic cysts. Mediastinal bronchogenic cysts may distort the bronchial lumen by pressing against the more supple membranous component of the wall. If infection has not supervened, these cysts can be removed completely with minimal morbidity, and the patient will remain free of recurrence. Mediastinal Teratomas Teratomas are tumors containing elements of the three germ layers, and their tissues are foreign to the region in which they are located. Teratomas commonly contain dermal, dental, bony, cartilaginous, neural, vascular, alimentary-tract, and respiratory tissue. The tumors may be predominantly solid or cystic, but usually are a mixture of each form. "Dermoid cyst" is the name commonly given to a cystic teratoma which has produced primarily ectodermal products-brain, hair, teeth, sebaceous material, and squamous epithelium. Most of the mediastinal teratomas are benign; and in the Mayo Clinic series, 18 (86%) of 21 mediastinal teratomas in children were benign. The majority of mediastinal teratomas are asymptomatic during the pediatric years, although even huge symptomatic tumors at birth have been reported. Symptoms appear as the lesion, by its bulk, compresses adjacent lung parenchyma or major bronchi. The contents of the teratoma may become infected hematogenously or by communication with bronchi. Secondary pneumonitis from rupture of the teratoma into the adjacent lung may result in expectoration of teratoma components, such as sebaceous material or hair. The anteriorly situated mass shown in the chest roentgenogram may be identified more specifically by the characteristic calcification of a tooth or layering of the lipid contents of a dermoid cyst (Fig. 3). The treatment is surgical excision, including the contiguous portion of the lung if it is irreparably damaged. Most malignant teratomas are steadily progressive, and the fatal outcome has not been prevented in pediatric patients by adjunctive chemotherapy or radiation. In the Mayo Clinic series, all three patients w~th malignant teratoma were dead within 16 months ~er operation. Cystic Hygroma Cystic hygroma is a benign congenital tumor of lymphatic origin whose multilocular cavities are lined with endothelium. This lesion is
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Figure 3. Views reveal huge, well-circumscribed mass in asymptomatic 10-year-old boy, filling lower two-thirds of left hemithorax and causing shift of heart to right. Inferior aspect of tumor shows some calcification. Benign teratoma weighing 1750 gm was completely removed.
located most commonly in the neck and infrequently in the mediastinum. However, extension of a cervical tumor may involve the mediastinum. Lim et al. found published reports of 30 cases of cervico-mediastinal cystic hygroma and added 9 cases from the Mayo Clinic. Only one patient in their series was more than 4 years old. The cervico-mediastinal lesion usually is obvious on examination because of being partly in the neck; and, especially in infants, obvious respiratory distress may be associated with it. But the strictly mediastinal tumor may cause no symptoms and is more often discovered in the older age group. When palpable cervically, the lesion usually seems fairly soft and poorly circumscribed. Chest roentgenograms show a soft-tissue density, usually in the antero-superior mediastinum (Fig. 4). The treatment is excision, though the pseudopodal form of its growth and extension makes it difficult to excise completely. The lymphatic tissue is insinuated between tissue planes and surrounds vital vessels and nerves. While it is desirable to remove as much of the hygroma as possible, the involvement of vital structures may prevent completeness. Satisfactory results may be obtained, even though a portion of the lesion is left attached to such structures. It is preferable to approach the cervico-mediastinal lesion initially through the neck and usually this approach suffices. If the mediastinal component cannot be removed by this route, however, supplemental thoracotomy may be added. And for strictly mediastinal lesions, thoracotomy is necessary. Chylothorax associated with a mediastinal hygroma is shown in Figure 5. This rare complication presents challenging diagnostic and therapeutic problems, although the basic solution is control of the escaping chyle by excision of the hygroma.
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Figure 4. Views reveal marked superior mediastinal widening with deviation of the trachea anteriorly in 5-month-old girl. Soft tissue mass in lower right neck increased 3 to 4 times in size when she cried. Cervical approach permitted nearly total removal of cervicomediastinal cystic hygroma.
Figure 5. View of 7-year-old boy with diffuse mediastinal and pulmonary cystic hygroma and right pleural effu ion of chylous fluid .
MEDIASTINAL TUMORS AND CYSTS IN THE PEDIATRIC PATIENT
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Tumors of Thymic Origin In infancy and early childhood years, the large size of the thymus relative to the mediastinum is responsible for the anterior mediastinal widening in the chest roentgenogram, with a characteristic notch often identifiable in posteroanterior or oblique views, which separates the inferior border of the thymus from the cardiac silhouette. Although this physiologic enlargement may be noted roentgenologically, it rarely is responsible for symptoms of airway obstruction. A cardiothymic shadow which appears abnormal may be studied more thoroughly by means of serial chest roentgenograms. However, two of our patients with thymic hyperplasia were explored for thymic enlargement that preoperatively could not be differentiated from a pathologic process (Fig. 6). Irradiation of the thymus is to be avoided, because it may be carcinogenic; and we have not resorted to administration of adrenal corticoids to try to reduce the size of the tumor.3 Thymic cysts occur infrequently. Two were encountered in our series, both benign. Theoretically such cysts may be located at any level from the neck to the diaphragm, but usually they are found near the base of the heart. Solid thymic tumors are rare in pediatric patients. We have
Figure 6. Routine views (A and B) of 15-year-old asymptomatic boy with widening of right mediastinum. At fluoroscopy mass was observed to pulsate. C, Contrast study reveals normal esophagus. D, Thoracic aortogram appears normal. At surgery, hyperplastic thymus was excised.
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not encountered a child with myasthenia gravis and a thymoma. For thymic-tumor surgery, the anterior approach via median sternotomy provides the best exposure. Tumors of Blood-Vessel Origin Hemangiomas of the skin and mucous membranes are encountered often in the pediatric years; and if the patient has a cutaneous or mucosal hemangioma and a mediastinal mass, the diagnosis of mediastinal hemangioma should be considered; but mediastinal hemangiomas are rare. Angiography has not been helpful, because the contrast medium usually does not opacify the tumor. Even though histologically benign, these tumors tend to extend locally into surrounding structures, occasionally making surgical excision difficult. Recurrence after excision is rare. Lymph-Node Pathology Woods in 1965 found only 13 published reports of mediastinal granuloma in the pediatric age group and added a single case. All of the patients were symptomatic; half presented with severe airway obstruction. Roentgenologically these lesions typically appear as rounded, well-circumscribed, calcified masses in the middle mediastinum (Fig. 7). Surgical excision is elected when symptoms occur or when the diagnosis is in doubt. The dense fibrotic inflammation surrounding the lesion may make total excision difficult, but partial excision fortunately does not lead to infection problems, nor to recurrent mediastinal granulomatous disease. Mediastinal lymph-node involvement in leukemia or lymphoma usually is part of a generalized widespread process. Infrequently, primary mediastinal lymphoma is localized well enough so complete surgical excision can be accomplished (Fig. 8). At the present time patients also are
Figure 7. Views of 13·year-old girl with fever, chest pain, and pericardial friction rub reveal mid-mediastinal mass with calcification. At surgery mediastinal granuloma was encountered.
MEDIASTINAL TUMORS AND CYSTS IN THE PEDIATRIC PATIENT
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* Figure 8. Posteroanterior roentgenogram (A) and tomogram (B) of upper mediastinum of asymptomatic 15-year-old boy reveal elongated mass in right upper mediastinum and left deviation of trachea. Total removal of this giant follicular lymphosarcoma was accomplished and the patient is alive and well 10 years later.
given radiation therapy and chemotherapy for mediastinal lymphoma, in the hope that the usual grave prognosis for childhood lymphoma can be improved. Sarcoidosis and tuberculous adenopathy of the mediastinum often can be diagnosed by means other than surgical exploration of the thorax. Positive response to a tuberculin test and evidence of a primary complex are highly suggestive of tuberculosis. Associated uveitis, cutaneous nodules, and cervical adenopathy are sufficient to alert the physician to the possible diagnosis of sarcoidosis. Angiofollicular hyperplasia, which may resemble thymoma roentgenographically, is a rare benign cause of lymph-node enlargement affecting the older pediatric patient.
Miscellaneous Lesions Pediatric intrathoracic meningocele is rare, usually does not cause symptoms, and appears as a well-rounded mass in the paravertebral position on the chest roentgenogram. Infrequent among adults and distinctly rare in the pediatric age group are pericardial coelomic cysts, chemodectomas, pheochromocytomas, liposarcomas, choriocarcinomas, seminomas, and thoracic-duct cysts. Signs of a pancreatic pseudocyst extending into the mediastinum may resemble those of a primary mediastinal tumor, and so may the signs of extramedullary hematopoiesis occurring in the paraspinal region of the thorax.
CONCLUSIONS Mediastinal masses in children may not cause symptoms. Their detection on routine roentgenograms should lead to further studies, and the
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lack of symptoms should never be taken as an indication that the lesion is benign. The high incidence of malignancy in mediastinal tumors of infants and children makes thoracotomy a logical diagnostic and therapeutic step.
REFERENCES 1. Cushing H, Wolbach SB: The transformation of a malignant paravertebral sympathicoblastoma into a benign ganglioneuroma. Am J Pathol 3:203-216, 1927 2. Goldstein MN, Burdman JA, Journey LJ: Long-term tissue culture of neuroblastomas. II. Morphologic evidence for differentiation and maturation. J Nat! Cancer Inst 32: 165199, 1964 3. Haller JA Jr, Mazur DO, Morgan WW Jr: Diagnosis and management of mediastinal masses in children. J Thorac Cardiovasc Surg 58:385-392, 1969 4. Koop CE, Kiesewetter WB, Horn RC: Neuroblastoma in childhood: survival after major surgical insult to the tumor. Surgery 38:272-278, 1955 5. Lim RA, Divertie MB, Harrison EG Jr, et al: Cervico-mediastinal cystic hygroma. Dis Chest 40:265-274, 1961 6. Raffensperger J, Cohen R: Plexiform neurofibromas in childhood. J Pediatr Surg 7:144151, 1972 7. Svien HJ, Seybold WD, Thelen EP: Intraspinal and intrathoracic tumor with paraplegia in a child: report of case. Proc Staff Meet Mayo Clin 25:715-720,1950 8. Wilkerson JA, Van De Water JM, Goepfert H: Role of embryonic induction in benign transformation of neuroblastomas. Cancer 20: 1335-1342, 1967 9. Woods LP: Mediastinal histoplasma granuloma causing tracheal compression in a 4-yearold child. Surgery 58:448-452, 1965