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Mediastinal masses in infants and children
Mediastinal masses in infants and children Between the years 1954 and 1972, 109 patients with a mediastinal mass were treated at Children's Memorial Hospital. The children ranged in age from 2 hours to 16 years. Management of such patients is dependent primarily upon three factors: the age of the patient, the presenting symptoms, and the position of the mass on anterior and lateral chest roentgenograms. In this series, 50 patients had benign lesions and 59 had malignant tumors. At the most recent follow-up, 47 per cent of the children with malignant lesions were still alive.
William J. Pokorny, M.D. (by invitation), and Joseph O. Sherman, M.D. (by invitation), Chicago, Ill. Sponsored by F. S. Idriss, M.D., Chicago, Ill.
In
infants and children, most intrathoracic tumors are located in or adjacent to the mediastinum. These tumors represent a wide variety of cell types requiring many different forms of surgical and nonsurgical treatment. The purpose of this paper is to review our management of all children who presented at Children's Memorial Hospital between 1954 and 1972 with radiologic evidence of a mediastinal mass.
CUnicai material The hospital records of 109 patients from 2 hours to 16 years of age with a mediastinal mass were reviewed. In addition, the long-term follow-up of most of the patients with malignant tumors was obtained by reviewing the records of the Children's Memorial Hospital Tumor Board. There were 50 benign and 59 malignant tumors. From Children's Memorial Hospital and The Department of Surgery, Northwestern University Medical School, Chicago, Ill. 60614. Read at the Fifty-fourth Annual Meeting of The American Association for Thoracic Surgery, April 22, 23, and 24, 1974. Address for reprints: Joseph O. Sherman, M.D., Children's Memorial Hospital, 2300 Children's Plaza, Chicago, Ill. 60614.
Seventy-one thoracotomies were performed with one operative death. At the time of last follow-up, 47 per cent of the patients with malignant tumors were alive. Thirty-four masses were discovered in infants less than 2 years of age and 75 in children over 2 years of age (Table I). The proportion of benign and malignant tumors was about equal in both groups, but the survival of patients with malignant tumors was age dependent (Table II). Eighty-eight per cent of the patients less than 2 years of age survived, whereas only 33 per cent of the older patients survived. This difference in survival rates is due to the large number of the more favorable neuroblastomas in infants and the more common occurrence of lymphosarcoma and undifferentiated sarcoma in the older patients. The presenting symptoms of the patients with benign masses also correlated with age. Seventeen of the 18 infants under 2 years of age presented with significant respiratory distress which usually started shortly after birth. Only 11 of the 32 older children with benign masses had respiratory tract symptoms, and these symptoms tended to be less severe.
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Table I. Mediastinal masses in infants and children
years)
No. of children (2-16 years)
13 2 0 1 4
5 6 6 2 10
4 0 6 0
3 27 1 3
1 2 1 34
5 2 5 75
No. of infants Diagnosis
Total No.
18 Neuroblastoma 8 Ganglioneuroblastoma Ganglioneuroma 6 3 Plexiform neurofibroma 14 Duplication cyst Angiomatous malfor7 mation 27 Lymphoma 7 Thymic hyperplasia 3 Thymic cyst Undifferentiated sarcoma 6 4 Teratoma (benign) Other 6 Totals 109
(0-2
Classification of mediastinal tumors One of the most important factors in the preoperative evaluation of the child with a mediastinal mass is the localization of the mass on chest roentgenography. All of the organs of the mediastinum are in a relatively fixed position, and tumors of these organs can be classified by dividing the mediastinum into three areas based on easily discernible anatomic structures as seen on lateral chest x-ray films: the anterior mediastinum, the middle mediastinum, and the paravertebral sulcus. 1 The anterior mediastinum is bounded by the sternum, thoracic inlet, and the anterior border of the heart. Most of the tumors found in the anterior mediastinum are teratomas and tumors of the thymus. The middle mediastinum is located between the anterior border of the heart and the anterior border of the vertebral bodies. Most of the middle mediastinal tumors are lymphomas or duplication cysts. The paravertebral sulcus, which is located posterior to the anterior border of the vertebral bodies, is not part of the mediastinum but is included here because the neurogenic tumors arise in this area. Ninety-two per cent of the mediastinal
masses in the series were located in one of the three compartments described. Tumors of the paravertebral sulcus. All but 4 of the 39 tumors in the paravertebral sulcus were neurogenic tumors (Table III). As a group the neurogenic tumors which arise from the nerve roots and sympathetic ganglia in the paravertebral sulcus are wellcircumscribed masses on chest roentgenography. Spicules of calcium may be seen in the neuroblastomas and ganglioneuroblastomas. Due to their close proximity to the vertebral foremen, they may extend into the closed space of the vertebral column and produce signs of spinal cord compression. A positive bone marrow biopsy is not a contraindication to excision of the primary mass. As Evans- has pointed out, a positive bone marrow biopsy, with no other evidence of distant spread, carries a favorable prognosis. Since the result of bone marrow examination will have no effect on the operative procedure, it may be performed at the time of operation with the child asleep. A positive skeletal survey carries a grave prognosis." 4 An esophagogram frequently confirms the extrinsic compression of a posterior mediastinal mass but is unnecessary in most patients. Bronchoesophagoscopy and mediastinoscopy are of little value. The level of urinary vanillyl mandelic acid (VMA) is only occasionally elevated in patients with neuroblastoma of the mediastinum." Of the 9 patients tested, only 3 had an elevated VMA. All of the 5 patients with ganglioneuroblastoma tested showed normal levels. However, the urinary VMA may be useful to follow postoperatively when it has been elevated preoperatively, since an elevation in the postoperative period may be the first indication of recurrence. None of the patients showed a postoperative elevation of the VMA level. The survival of patients with neuroblastoma was not related to the type of surgical therapy. Of the 13 patients less than 2 years of age, 3 had biopsy, 5 had partial excision, and 5 had total excision of the tumor mass.
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December, 1974
Table II. Survival of patients with malignant mediastinal tumors No. of infants (0-2 years)
Diagnosis Neuroblastoma Ganglioneuroblastoma Lymphosarcoma Hodgkin's disease Undifferentiated sarcoma Totals
92% (12 of 13) 100% ( 2 of 2)
Nine of the 12 surviving patients have been followed for more than 2 years. All 5 of the patients over 2 years of age had biopsy of the tumor and all died. During the period reviewed, there was no standard protocol for treating these patients. However, because of the good prognosis for children under 2 years of age treated by total or partial resection of the tumor, there has been a tendency to more conservative surgery. Those patients in whom the entire tumor was not removed usually received chemotherapy and radiation after surgery. The patients under 2 years of age usually had localized but invasive tumor. Only 1 had a positive bone marrow biopsy, and none had a positive skeletal survey. All 5 of the children over 2 years of age had advanced disease at the time of diagnosis. They were subjected to biopsy of the tumor followed by radiation and chemotherapy. All 8 patients with ganglioneuroblastoma had total or subtotal resection. Postoperatively 3 had radiation and 1 had radiation and chemotherapy. All are surviving without evidence of recurrent disease. Six patients with ganglioneuroma were seen at Children's Memorial Hospital. On chest roentgenography, the masses were well defined with evidence of rib erosion in 2 patients. In all 6 patients, the tumors were relatively large and were totally excised. Follow-up was from 6 months to 5 years with no evidence of recurrent disease. The least common neurogenic tumor in our series was plexiform neurofibroma, which was diagnosed in 3 patients. These patients, all under 4'h years of age, presented with a firm, fixed neck mass and
0% ( 0 of 1) 88% (14 of 16)
No. of children (2-16 years) 0% 100% 0% 67% 40% 33%
( 0 ( 6 ( 0 ( 6 ( 2 (14
of 5) of 6) of 18) of 9) of 5) of 43)
Table III. Tumors in the paravertebral sulcus Diagnosis Neuroblastoma Ganglioneuroblastoma Ganglioneuroma Plexiform neurofibroma Undifferentiated sarcoma Hydatid cyst Total
No. of patients 18 8 6 3 3 1 39 (36% of series)
Table IV. Tumors in the middle mediastinum Diagnosis Lymphoma Lymphosarcoma Hodgkin's disease Duplication cyst Bronchogenic cyst Esophageal duplication Granuloma Esophageal adenoma Total
No. of patients 15 9 11 3 3 1
42 (39% of series)
x-ray evidence of a mediastinal mass. All 3 patients have recurrent tumor despite many attempts at surgical excision. Raffensperger and Cohen" recently reviewed this problem and stressed the extreme difficulty in controlling this disease. Tumors of the middle mediastinum. Thirty-nine per cent of the patients presented with a mass in the middle mediastinum (Table IV). Lymphomas and duplication cysts were the most common masses and were seen mainly in children over 2 years of age.
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Table V. Lymphomas of the mediastinum Type
No. of patients
A verage duration of symptoms
Average length of survival
Hodgkin's disease Lymphosarcoma
9 15
5 months 5 weeks
6 alive at last follow-up 11 months
Lymphomas. Twenty-two per cent of the patients were found to have lymphosarcoma or Hodgkin's disease. In addition, 3 of the patients presented with malignant thymomas of the anterior mediastinum, which are histologically similar to lymphosarcoma and carry the same grave prognosis. They will be discussed with the other thymic tumors. Although patients with lymphosarcoma and Hodgkin's disease present with bilateral mediastinal widening on chest x-ray films, the lymphosarcomas tend to be larger, more lobulated masses. The 15 patients with lymphosarcoma had symptoms for an average of 5 weeks before admission, as compared to 5 months for the 9 patients with Hodgkin's disease (Table V). Of the 10 boys and 5 girls with primary mediastinal lymphosarcoma, 8 had moderately severe respiratory symptoms, 3 had signs of superior vena cava syndrome, and 5 had pleural effusions. Hepatosplenomegaly was not a common finding. Respiratory symptoms and signs were absent in the patients with Hodgkin's disease. The diagnosis of lymphosarcoma was made by cervical lymph node biopsy in 6, thoracotomy in 4, bone marrow biopsy in 4, and thoracentesis in 1 patient. All have died of their disease. The longest survival period after diagnosis was 22 months, and the average survival period was 11 months. All but 1 of the 15 patients were treated with radiation and chemotherapy. X-ray films were available for review in 9 patients, all of whom showed marked regression of the mediastinal mass after radiotherapy. Although the mediastinal component of lymphosarcoma can be controlled initially by radiation, these tumors are discovered when the disease is widespread, and longterm survival periods have not been re-
ported. The survival rate in all forms of childhood lymphosarcoma is reported to be 21 per cent; however, of 50 patients with mediastinal lymphosarcoma reported in four reviews, there were no 5 year survivors and no resectable tumors.s? Survival with lymphosarcoma occurs only in cases of primary involvement of superficial lymph nodes of the extremities or in small bowel lymphosarcoma; in the latter condition, early detection is possible because of the frequent association of intussusception and bowel obstruction. All of the children with Hodgkin's disease presented with nonspecific symptoms such as malaise and fever. The physical examination revealed peripheral adenopathy or hepatomegaly in most patients. The chest x-ray films showed bilateral hilar enlargement in 6 and right hilar enlargement in 3 patients. In all 9 patients, the diagnosis was made by biopsy of peripheral lymph nodes. Five of the patients received radiation and chemotherapy, 3 received radiation, and 1 received chemotherapy. At the time of last follow-up, 3 patients were dead, the average survival period being 4~ years. The remaining 6 patients have been followed for an average of 3 ~ years. Comment. Lymphosarcoma carries a very grave prognosis except in those few patients discovered with early localized disease. Because of the marked radiosensitivity of these tumors, operative intervention should be limited to diagnosis except in the occasional child whom the surgeon feels has a completely resectable tumor and has no evidence of extramediastinal involvement. With the excellent long-term results now reported with surgical staging followed by aggressive chemotherapy and radiation for Hodgkin's disease, surgery probably should
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Mediastinal masses in infants and children 873
December, 1974
be limited to procedures necessary for making a diagnosis. Duplication cysts. Bronchogenic cysts and esophageal duplications occur in the middle mediastinum and may cause respiratory distress especially in the younger patient. 10. 11 Of 14 children with duplication cysts, 11 had bronchogenic cysts and 3 had esophageal duplications. The bronchogenic cysts were thin-walled cysts containing thick viscid fluid. They were lined by respiratory epithelium and had a small amount of smooth muscle and occasionally cartilage in their wall. Eight of the 11 children with bronchogenic cysts had homogenous radiopaque densities in the area of the carina on chest roentgenography. In the remaining 3, no mass was seen but the diagnosis was suspected because of recurrent respiratory symptoms, unilateral or bilateral emphysema, and posterior deviation of the esophagus on esophagography. Three of the patients with bronchogenic cysts presented before 5 months of age, and all had stridor beginning shortly after birth. Of the 8 children over 2 years of age, 3 had mild respiratory infections and the remaining 5 were asymptomatic. The 3 esophageal duplications were lined by gastric or esophageal mucosa and had a well-developed muscle wall with a myenteric plexus. One infant was 13 months old and had had recurrent stridor beginning shortly after birth. Of the 2 older children, 1 presented with dysphagia and the other with substernal pain. The latter patient had a thoracoabdominal duplication lined with gastric mucosa, which ended blindly in the gastrohepatic ligament. Tumors of the anterior mediastinum. Anterior mediastinal tumors were uncommon in this series, even if patients with thymic "hyperplasia" are included. Only 17 per cent of the patients had an anterior mediastinal mass (Table VI). Thymic tumors. Thirteen patients had thymic masses, 3 of which were malignant thymomas. All 3 patients had exploratory operations, but only 1 tumor was thought to be resectable. Unfortunately, the thy-
Table VI. Tumors in the anterior
mediastinum Diagnosis
Thymic "hyperplasia" Teratoma Malignant thymoma Thymic cyst Lipoma Undifferentiated sarcoma Total
No. of patients 7 4
3 3 1 1 19 (17% of series)
moma recurred and the patient required a second exploratory operation 2lh years later. She died 1 year after the second resection. All 3 received radiation and chemotherapy. The 2 patients whose tumors were not resected died 2 and 7 months, respectively, after initial thoracotomy. Three patients had thymic cysts. The masses were discovered as an incidental finding on chest x-ray films taken for other reasons. The 3 cysts were resected without difficulty. Between 1954 and 1964, 7 patients between 2 weeks and 28 months of age were seen at Children's Memorial Hospital for "hyperplasia" of the thymus. Six of the 7 had had episodes of mild respiratory distress beginning shortly after birth. Three of the 7 had bronchoscopy, and 2 of them were found to have anteroposterior compression of the trachea. One of these 2 children underwent thoracotomy, and a large thymus measuring 4 by 6 em. and weighing 51.5 grams was removed. The child's respiratory symptoms improved postoperatively. None of the patients had symptoms suggestive of myasthenia gravis. Teratomas. Four patients had benign anterior mediastinal teratomas. Two were infants less than 7 months old, and both had histories of dyspnea beginning at birth. The older children were 12 and 13 years of age. One gave a 2 week history of fever and fatigue and the other complained of substernal pain. All 4 were treated by thoracotomy and total excision of the mass. The 4 children are living and free of disease from 2 to 3 years after resection. In a
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Table VII. Tumors not localized to one mediastinal compartment Diagnosis
Angiomatous malformation Cystic hygroma Hemangioma Undifferentiated sarcoma Total
No. of patients
5 2 2 9 (8% of series)
review of 50 children with teratomas; Carney" found 17 of the tumors primary to the mediastinum. Only 3 of the 17 mediastinal teratomas were malignant. Tumors not localized to one mediastinal compartment. Eight per cent of our patients presented with mediastinal masses occupying more than one mediastinal compartment (Table VII). Both patients with mediastinal hemangiomas presented with a large mediastinal mass, and 1 of them had a long history of hemoptysis. Neither mass was thought to be resectable at Children's Memorial Hospital. One of the 2 patients underwent a second exploratory operation at another hospital and died shortly after an attempted total excision. The second patient had a subtotal resection of the mass and has done well postoperatively. Cystic hygroma. Cystic hygromas are congenital malformations resulting from a failure of the primary lymphatic sacs to establish drainage into the venous system. The final position of the cystic hygroma depends on the structure to which the sequestrated sac is attached. Five patients under 2'>'2 years of age were treated for mediastinal cystic hygroma during the period of the study. Two had extension of the tumor outside the mediastinum, one to the axilla and one to the neck. Two patients were asymptomatic, whereas 3 had symptoms of cough and stridor. All underwent surgical excision. The one recurrence was in a 3Yz-week-old infant with a large cervicomediastinal cystic hygroma who required tracheostomy at 1 month of age. The patient died 2 months after initial partial excision as a result of airway compression.
These tumors may be very large and may involve the anterior and middle mediastinal compartments from the diaphragm to the thoracic inlet. In an occasional child, the presenting complaint will be a soft cystic supraclavicular mass. In all patients with a cervical or axillary cystic hygroma, chest roentgenograms should be taken to rule out an intrathoracic extension of the mass. Total excision is the optimum therapy because of the risk of respiratory compromise. If the entire mass is not removed, there is danger of recurrence. Scarring with iodine may be attempted. Discussion
The three most important factors in deciding how to manage an infant or child with a mediastinal mass are the age of the patient, the presenting symptoms, and the position and shape of the mass on anterior and lateral x-ray films of the chest. A mass in the paravertebral sulcus of a patient at any age is probably a neurogenic tumor. With the exception of neuroblastoma in the child over 2 years of age, all neurogenic tumors have an excellent prognosis, and excision should be limited to that part of the tumor which can be safely removed without causing unnecessary morbidity and risk of death. The older children with neuroblastoma tend to have more advanced disease, and our only hope for more cures is earlier diagnosis. All types of masses found in the middle mediastinum are rare in patients less than 2 years of age. The most common middle mediastinal mass in infants, bronchogenic cyst, is frequently not radiopaque but should be suspected in an infant with repeated episodes of respiratory distress and unilateral or bilateral emphysema. Duplication cysts in patients over 2 years of age rarely produce severe respiratory distress. They are recognizable by the presence of a small spherical mass in the region of the carina, by unilateral or bilateral emphysema, or by posterior displacement of the esophagus noted on barium swallow.
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In patients over 2 years of age, the most common middle mediastinal tumor, lymphosarcoma, can be differentiated from Hodgkin's disease by the presenting respiratory symptoms and by its classical appearance on chest roentgenograms. Anterior mediastinal masses are uncommon in infants and children and account for only 12 per cent of all of our tumors if patients with thymic "hyperplasia" are excluded. Thymic masses and teratomas are the most common tumors, and all except the malignant thymoma are usually resectable. Cystic hygromas tend to be large and involve more than one mediastinal compartment. They are usually encountered in patients less than 3 years of age and, on roentgenography, present as radiopaque densities near the thoracic inlet, occasionally extending from the diaphragm to the neck. Frequently, there is a cervical or axillary component which may be the presenting sign. Early surgical excision is the treatment of choice. REFERENCES
2 3
4
5
Shields, T. W.: Primary Tumors and Cysts of the Mediastinum, in Shields, T. W., editor: General Thoracic Surgery, Philadelphia, 1972, Lea & Febiger, Publishers, p. 908. Evans, A. E., D'Angio, G. J., and Randolph, J.: A Proposed Staging for Children With Neuroblastoma, Cancer 27: 374, 1971. Filler, R. M., Traggis, D. G., Jaffe, N., and Vawter, G. F.: Favorable Outlook for Children With Mediastinal Neuroblastoma, J. Pediatr. Surg. 7: 136, 1972. Fortner, J., Nicastri, A., and Murphy, M. L.: Neuroblastoma: Natural History and Results of Treating 133 Cases, Ann. Surg. 167: 132, 1968. Raffensperger, J., and Cohen, R.: Plexiform Neurofibromas in Childhood, J. Pediatr. Surg, 7: 144, 1972.
6 Bailey, R. J., Burgert, E. 0., Jr., and Dahlin, D. C.: Malignant Lymphoma in Children, Pediatrics 28: 985, 1961. 7 Jones, B., and Klingberg, W. G., Lymphosarcoma in Children: A Report of 43 Cases and Review of the Recent Literature, J. Pediatr. 63: 11, 1963. 8 Rosenberg, S. A., Diamond, H. D., Dargeon, H. W., and Craver, L. F.: Lymphosarcoma in Childhood, N. Eng!. J. Med. 259: 505, 1958. 9 LaFranchi, S., and Fonkalsrud, E. W.: Surgical Management of Lymphatic Tumors of the Mediastinum in Children, J. THORAC. CARDIOVASC, SURG. 65: 8, 1973. 10 Opsahl, T., and Berman, E. J.: Bronchogenic Mediastinal Cysts in Infants, Pediatrics 30: 372, 1962. 11 Eraklis, A. J., Griscom, N. T., and McGovern, J. B.: Bronchogenic Cysts of the Mediastinum in Infancy, N. Eng!. J. Med. 281: 1150, 1969. 12 Carney, J. A., Thompson, D. P., Johnson, C. L., and Lynn, H. B.: Teratomas in Children: Clinical and Pathologic Aspects, J. Pediatr. Surg. 7: 271, 1972.
Discussion DR. ROBERT G. PONTIUS Pittsburgh, Pa.
I enjoyed very much the precise analysis and presentation of this large series of children with mediastinal masses. I rise to present a new subcategory: multiple mediastinal neoplasms. A chest film of a 12-year-old boy shows displacement of the heart into the right chest, a huge anterior mediastinal shadow, and a second smaller shadow posteriorly. A left pleural effusion was aspirated and tube drainage established. Bronchoscopy showed deviation of the trachea to the right and extrinsic compression of the left bronchus. At surgery, the anterior tumor was adherent to both lungs and contiguous with the thymus. Its complete resection extended into the neck. Areas of necrosis suggested malignancy, but subsequent complete microscopic examination led to the diagnosis of benign cystic teratoma. The second tumor removed from the posterior sulcus was a ganglioneuroma. Thirteen years later the patient continues to enjoy a normal life.
William J. Pokorny, M.D. (by invitation), and Joseph O. Sherman, M.D. (by invitation), Chicago, Ill. Sponsored by F. S. Idriss, M.D., Chicago, Ill.
In
infants and children, most intrathoracic tumors are located in or adjacent to the mediastinum. These tumors represent a wide variety of cell types requiring many different forms of surgical and nonsurgical treatment. The purpose of this paper is to review our management of all children who presented at Children's Memorial Hospital between 1954 and 1972 with radiologic evidence of a mediastinal mass.
CUnicai material The hospital records of 109 patients from 2 hours to 16 years of age with a mediastinal mass were reviewed. In addition, the long-term follow-up of most of the patients with malignant tumors was obtained by reviewing the records of the Children's Memorial Hospital Tumor Board. There were 50 benign and 59 malignant tumors. From Children's Memorial Hospital and The Department of Surgery, Northwestern University Medical School, Chicago, Ill. 60614. Read at the Fifty-fourth Annual Meeting of The American Association for Thoracic Surgery, April 22, 23, and 24, 1974. Address for reprints: Joseph O. Sherman, M.D., Children's Memorial Hospital, 2300 Children's Plaza, Chicago, Ill. 60614.
Seventy-one thoracotomies were performed with one operative death. At the time of last follow-up, 47 per cent of the patients with malignant tumors were alive. Thirty-four masses were discovered in infants less than 2 years of age and 75 in children over 2 years of age (Table I). The proportion of benign and malignant tumors was about equal in both groups, but the survival of patients with malignant tumors was age dependent (Table II). Eighty-eight per cent of the patients less than 2 years of age survived, whereas only 33 per cent of the older patients survived. This difference in survival rates is due to the large number of the more favorable neuroblastomas in infants and the more common occurrence of lymphosarcoma and undifferentiated sarcoma in the older patients. The presenting symptoms of the patients with benign masses also correlated with age. Seventeen of the 18 infants under 2 years of age presented with significant respiratory distress which usually started shortly after birth. Only 11 of the 32 older children with benign masses had respiratory tract symptoms, and these symptoms tended to be less severe.
869
The Journal of
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Thoracic and Cardiovascular Surgery
Table I. Mediastinal masses in infants and children
years)
No. of children (2-16 years)
13 2 0 1 4
5 6 6 2 10
4 0 6 0
3 27 1 3
1 2 1 34
5 2 5 75
No. of infants Diagnosis
Total No.
18 Neuroblastoma 8 Ganglioneuroblastoma Ganglioneuroma 6 3 Plexiform neurofibroma 14 Duplication cyst Angiomatous malfor7 mation 27 Lymphoma 7 Thymic hyperplasia 3 Thymic cyst Undifferentiated sarcoma 6 4 Teratoma (benign) Other 6 Totals 109
(0-2
Classification of mediastinal tumors One of the most important factors in the preoperative evaluation of the child with a mediastinal mass is the localization of the mass on chest roentgenography. All of the organs of the mediastinum are in a relatively fixed position, and tumors of these organs can be classified by dividing the mediastinum into three areas based on easily discernible anatomic structures as seen on lateral chest x-ray films: the anterior mediastinum, the middle mediastinum, and the paravertebral sulcus. 1 The anterior mediastinum is bounded by the sternum, thoracic inlet, and the anterior border of the heart. Most of the tumors found in the anterior mediastinum are teratomas and tumors of the thymus. The middle mediastinum is located between the anterior border of the heart and the anterior border of the vertebral bodies. Most of the middle mediastinal tumors are lymphomas or duplication cysts. The paravertebral sulcus, which is located posterior to the anterior border of the vertebral bodies, is not part of the mediastinum but is included here because the neurogenic tumors arise in this area. Ninety-two per cent of the mediastinal
masses in the series were located in one of the three compartments described. Tumors of the paravertebral sulcus. All but 4 of the 39 tumors in the paravertebral sulcus were neurogenic tumors (Table III). As a group the neurogenic tumors which arise from the nerve roots and sympathetic ganglia in the paravertebral sulcus are wellcircumscribed masses on chest roentgenography. Spicules of calcium may be seen in the neuroblastomas and ganglioneuroblastomas. Due to their close proximity to the vertebral foremen, they may extend into the closed space of the vertebral column and produce signs of spinal cord compression. A positive bone marrow biopsy is not a contraindication to excision of the primary mass. As Evans- has pointed out, a positive bone marrow biopsy, with no other evidence of distant spread, carries a favorable prognosis. Since the result of bone marrow examination will have no effect on the operative procedure, it may be performed at the time of operation with the child asleep. A positive skeletal survey carries a grave prognosis." 4 An esophagogram frequently confirms the extrinsic compression of a posterior mediastinal mass but is unnecessary in most patients. Bronchoesophagoscopy and mediastinoscopy are of little value. The level of urinary vanillyl mandelic acid (VMA) is only occasionally elevated in patients with neuroblastoma of the mediastinum." Of the 9 patients tested, only 3 had an elevated VMA. All of the 5 patients with ganglioneuroblastoma tested showed normal levels. However, the urinary VMA may be useful to follow postoperatively when it has been elevated preoperatively, since an elevation in the postoperative period may be the first indication of recurrence. None of the patients showed a postoperative elevation of the VMA level. The survival of patients with neuroblastoma was not related to the type of surgical therapy. Of the 13 patients less than 2 years of age, 3 had biopsy, 5 had partial excision, and 5 had total excision of the tumor mass.
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Mediastinal masses in infants and children
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87 1
December, 1974
Table II. Survival of patients with malignant mediastinal tumors No. of infants (0-2 years)
Diagnosis Neuroblastoma Ganglioneuroblastoma Lymphosarcoma Hodgkin's disease Undifferentiated sarcoma Totals
92% (12 of 13) 100% ( 2 of 2)
Nine of the 12 surviving patients have been followed for more than 2 years. All 5 of the patients over 2 years of age had biopsy of the tumor and all died. During the period reviewed, there was no standard protocol for treating these patients. However, because of the good prognosis for children under 2 years of age treated by total or partial resection of the tumor, there has been a tendency to more conservative surgery. Those patients in whom the entire tumor was not removed usually received chemotherapy and radiation after surgery. The patients under 2 years of age usually had localized but invasive tumor. Only 1 had a positive bone marrow biopsy, and none had a positive skeletal survey. All 5 of the children over 2 years of age had advanced disease at the time of diagnosis. They were subjected to biopsy of the tumor followed by radiation and chemotherapy. All 8 patients with ganglioneuroblastoma had total or subtotal resection. Postoperatively 3 had radiation and 1 had radiation and chemotherapy. All are surviving without evidence of recurrent disease. Six patients with ganglioneuroma were seen at Children's Memorial Hospital. On chest roentgenography, the masses were well defined with evidence of rib erosion in 2 patients. In all 6 patients, the tumors were relatively large and were totally excised. Follow-up was from 6 months to 5 years with no evidence of recurrent disease. The least common neurogenic tumor in our series was plexiform neurofibroma, which was diagnosed in 3 patients. These patients, all under 4'h years of age, presented with a firm, fixed neck mass and
0% ( 0 of 1) 88% (14 of 16)
No. of children (2-16 years) 0% 100% 0% 67% 40% 33%
( 0 ( 6 ( 0 ( 6 ( 2 (14
of 5) of 6) of 18) of 9) of 5) of 43)
Table III. Tumors in the paravertebral sulcus Diagnosis Neuroblastoma Ganglioneuroblastoma Ganglioneuroma Plexiform neurofibroma Undifferentiated sarcoma Hydatid cyst Total
No. of patients 18 8 6 3 3 1 39 (36% of series)
Table IV. Tumors in the middle mediastinum Diagnosis Lymphoma Lymphosarcoma Hodgkin's disease Duplication cyst Bronchogenic cyst Esophageal duplication Granuloma Esophageal adenoma Total
No. of patients 15 9 11 3 3 1
42 (39% of series)
x-ray evidence of a mediastinal mass. All 3 patients have recurrent tumor despite many attempts at surgical excision. Raffensperger and Cohen" recently reviewed this problem and stressed the extreme difficulty in controlling this disease. Tumors of the middle mediastinum. Thirty-nine per cent of the patients presented with a mass in the middle mediastinum (Table IV). Lymphomas and duplication cysts were the most common masses and were seen mainly in children over 2 years of age.
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Thoracic and Cardiovascular Surgery
Table V. Lymphomas of the mediastinum Type
No. of patients
A verage duration of symptoms
Average length of survival
Hodgkin's disease Lymphosarcoma
9 15
5 months 5 weeks
6 alive at last follow-up 11 months
Lymphomas. Twenty-two per cent of the patients were found to have lymphosarcoma or Hodgkin's disease. In addition, 3 of the patients presented with malignant thymomas of the anterior mediastinum, which are histologically similar to lymphosarcoma and carry the same grave prognosis. They will be discussed with the other thymic tumors. Although patients with lymphosarcoma and Hodgkin's disease present with bilateral mediastinal widening on chest x-ray films, the lymphosarcomas tend to be larger, more lobulated masses. The 15 patients with lymphosarcoma had symptoms for an average of 5 weeks before admission, as compared to 5 months for the 9 patients with Hodgkin's disease (Table V). Of the 10 boys and 5 girls with primary mediastinal lymphosarcoma, 8 had moderately severe respiratory symptoms, 3 had signs of superior vena cava syndrome, and 5 had pleural effusions. Hepatosplenomegaly was not a common finding. Respiratory symptoms and signs were absent in the patients with Hodgkin's disease. The diagnosis of lymphosarcoma was made by cervical lymph node biopsy in 6, thoracotomy in 4, bone marrow biopsy in 4, and thoracentesis in 1 patient. All have died of their disease. The longest survival period after diagnosis was 22 months, and the average survival period was 11 months. All but 1 of the 15 patients were treated with radiation and chemotherapy. X-ray films were available for review in 9 patients, all of whom showed marked regression of the mediastinal mass after radiotherapy. Although the mediastinal component of lymphosarcoma can be controlled initially by radiation, these tumors are discovered when the disease is widespread, and longterm survival periods have not been re-
ported. The survival rate in all forms of childhood lymphosarcoma is reported to be 21 per cent; however, of 50 patients with mediastinal lymphosarcoma reported in four reviews, there were no 5 year survivors and no resectable tumors.s? Survival with lymphosarcoma occurs only in cases of primary involvement of superficial lymph nodes of the extremities or in small bowel lymphosarcoma; in the latter condition, early detection is possible because of the frequent association of intussusception and bowel obstruction. All of the children with Hodgkin's disease presented with nonspecific symptoms such as malaise and fever. The physical examination revealed peripheral adenopathy or hepatomegaly in most patients. The chest x-ray films showed bilateral hilar enlargement in 6 and right hilar enlargement in 3 patients. In all 9 patients, the diagnosis was made by biopsy of peripheral lymph nodes. Five of the patients received radiation and chemotherapy, 3 received radiation, and 1 received chemotherapy. At the time of last follow-up, 3 patients were dead, the average survival period being 4~ years. The remaining 6 patients have been followed for an average of 3 ~ years. Comment. Lymphosarcoma carries a very grave prognosis except in those few patients discovered with early localized disease. Because of the marked radiosensitivity of these tumors, operative intervention should be limited to diagnosis except in the occasional child whom the surgeon feels has a completely resectable tumor and has no evidence of extramediastinal involvement. With the excellent long-term results now reported with surgical staging followed by aggressive chemotherapy and radiation for Hodgkin's disease, surgery probably should
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Mediastinal masses in infants and children 873
December, 1974
be limited to procedures necessary for making a diagnosis. Duplication cysts. Bronchogenic cysts and esophageal duplications occur in the middle mediastinum and may cause respiratory distress especially in the younger patient. 10. 11 Of 14 children with duplication cysts, 11 had bronchogenic cysts and 3 had esophageal duplications. The bronchogenic cysts were thin-walled cysts containing thick viscid fluid. They were lined by respiratory epithelium and had a small amount of smooth muscle and occasionally cartilage in their wall. Eight of the 11 children with bronchogenic cysts had homogenous radiopaque densities in the area of the carina on chest roentgenography. In the remaining 3, no mass was seen but the diagnosis was suspected because of recurrent respiratory symptoms, unilateral or bilateral emphysema, and posterior deviation of the esophagus on esophagography. Three of the patients with bronchogenic cysts presented before 5 months of age, and all had stridor beginning shortly after birth. Of the 8 children over 2 years of age, 3 had mild respiratory infections and the remaining 5 were asymptomatic. The 3 esophageal duplications were lined by gastric or esophageal mucosa and had a well-developed muscle wall with a myenteric plexus. One infant was 13 months old and had had recurrent stridor beginning shortly after birth. Of the 2 older children, 1 presented with dysphagia and the other with substernal pain. The latter patient had a thoracoabdominal duplication lined with gastric mucosa, which ended blindly in the gastrohepatic ligament. Tumors of the anterior mediastinum. Anterior mediastinal tumors were uncommon in this series, even if patients with thymic "hyperplasia" are included. Only 17 per cent of the patients had an anterior mediastinal mass (Table VI). Thymic tumors. Thirteen patients had thymic masses, 3 of which were malignant thymomas. All 3 patients had exploratory operations, but only 1 tumor was thought to be resectable. Unfortunately, the thy-
Table VI. Tumors in the anterior
mediastinum Diagnosis
Thymic "hyperplasia" Teratoma Malignant thymoma Thymic cyst Lipoma Undifferentiated sarcoma Total
No. of patients 7 4
3 3 1 1 19 (17% of series)
moma recurred and the patient required a second exploratory operation 2lh years later. She died 1 year after the second resection. All 3 received radiation and chemotherapy. The 2 patients whose tumors were not resected died 2 and 7 months, respectively, after initial thoracotomy. Three patients had thymic cysts. The masses were discovered as an incidental finding on chest x-ray films taken for other reasons. The 3 cysts were resected without difficulty. Between 1954 and 1964, 7 patients between 2 weeks and 28 months of age were seen at Children's Memorial Hospital for "hyperplasia" of the thymus. Six of the 7 had had episodes of mild respiratory distress beginning shortly after birth. Three of the 7 had bronchoscopy, and 2 of them were found to have anteroposterior compression of the trachea. One of these 2 children underwent thoracotomy, and a large thymus measuring 4 by 6 em. and weighing 51.5 grams was removed. The child's respiratory symptoms improved postoperatively. None of the patients had symptoms suggestive of myasthenia gravis. Teratomas. Four patients had benign anterior mediastinal teratomas. Two were infants less than 7 months old, and both had histories of dyspnea beginning at birth. The older children were 12 and 13 years of age. One gave a 2 week history of fever and fatigue and the other complained of substernal pain. All 4 were treated by thoracotomy and total excision of the mass. The 4 children are living and free of disease from 2 to 3 years after resection. In a
The Journol of
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Pokorny and Sherman
Thoracic and Cardiovascular Surgery
Table VII. Tumors not localized to one mediastinal compartment Diagnosis
Angiomatous malformation Cystic hygroma Hemangioma Undifferentiated sarcoma Total
No. of patients
5 2 2 9 (8% of series)
review of 50 children with teratomas; Carney" found 17 of the tumors primary to the mediastinum. Only 3 of the 17 mediastinal teratomas were malignant. Tumors not localized to one mediastinal compartment. Eight per cent of our patients presented with mediastinal masses occupying more than one mediastinal compartment (Table VII). Both patients with mediastinal hemangiomas presented with a large mediastinal mass, and 1 of them had a long history of hemoptysis. Neither mass was thought to be resectable at Children's Memorial Hospital. One of the 2 patients underwent a second exploratory operation at another hospital and died shortly after an attempted total excision. The second patient had a subtotal resection of the mass and has done well postoperatively. Cystic hygroma. Cystic hygromas are congenital malformations resulting from a failure of the primary lymphatic sacs to establish drainage into the venous system. The final position of the cystic hygroma depends on the structure to which the sequestrated sac is attached. Five patients under 2'>'2 years of age were treated for mediastinal cystic hygroma during the period of the study. Two had extension of the tumor outside the mediastinum, one to the axilla and one to the neck. Two patients were asymptomatic, whereas 3 had symptoms of cough and stridor. All underwent surgical excision. The one recurrence was in a 3Yz-week-old infant with a large cervicomediastinal cystic hygroma who required tracheostomy at 1 month of age. The patient died 2 months after initial partial excision as a result of airway compression.
These tumors may be very large and may involve the anterior and middle mediastinal compartments from the diaphragm to the thoracic inlet. In an occasional child, the presenting complaint will be a soft cystic supraclavicular mass. In all patients with a cervical or axillary cystic hygroma, chest roentgenograms should be taken to rule out an intrathoracic extension of the mass. Total excision is the optimum therapy because of the risk of respiratory compromise. If the entire mass is not removed, there is danger of recurrence. Scarring with iodine may be attempted. Discussion
The three most important factors in deciding how to manage an infant or child with a mediastinal mass are the age of the patient, the presenting symptoms, and the position and shape of the mass on anterior and lateral x-ray films of the chest. A mass in the paravertebral sulcus of a patient at any age is probably a neurogenic tumor. With the exception of neuroblastoma in the child over 2 years of age, all neurogenic tumors have an excellent prognosis, and excision should be limited to that part of the tumor which can be safely removed without causing unnecessary morbidity and risk of death. The older children with neuroblastoma tend to have more advanced disease, and our only hope for more cures is earlier diagnosis. All types of masses found in the middle mediastinum are rare in patients less than 2 years of age. The most common middle mediastinal mass in infants, bronchogenic cyst, is frequently not radiopaque but should be suspected in an infant with repeated episodes of respiratory distress and unilateral or bilateral emphysema. Duplication cysts in patients over 2 years of age rarely produce severe respiratory distress. They are recognizable by the presence of a small spherical mass in the region of the carina, by unilateral or bilateral emphysema, or by posterior displacement of the esophagus noted on barium swallow.
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December, 1974
In patients over 2 years of age, the most common middle mediastinal tumor, lymphosarcoma, can be differentiated from Hodgkin's disease by the presenting respiratory symptoms and by its classical appearance on chest roentgenograms. Anterior mediastinal masses are uncommon in infants and children and account for only 12 per cent of all of our tumors if patients with thymic "hyperplasia" are excluded. Thymic masses and teratomas are the most common tumors, and all except the malignant thymoma are usually resectable. Cystic hygromas tend to be large and involve more than one mediastinal compartment. They are usually encountered in patients less than 3 years of age and, on roentgenography, present as radiopaque densities near the thoracic inlet, occasionally extending from the diaphragm to the neck. Frequently, there is a cervical or axillary component which may be the presenting sign. Early surgical excision is the treatment of choice. REFERENCES
2 3
4
5
Shields, T. W.: Primary Tumors and Cysts of the Mediastinum, in Shields, T. W., editor: General Thoracic Surgery, Philadelphia, 1972, Lea & Febiger, Publishers, p. 908. Evans, A. E., D'Angio, G. J., and Randolph, J.: A Proposed Staging for Children With Neuroblastoma, Cancer 27: 374, 1971. Filler, R. M., Traggis, D. G., Jaffe, N., and Vawter, G. F.: Favorable Outlook for Children With Mediastinal Neuroblastoma, J. Pediatr. Surg. 7: 136, 1972. Fortner, J., Nicastri, A., and Murphy, M. L.: Neuroblastoma: Natural History and Results of Treating 133 Cases, Ann. Surg. 167: 132, 1968. Raffensperger, J., and Cohen, R.: Plexiform Neurofibromas in Childhood, J. Pediatr. Surg, 7: 144, 1972.
6 Bailey, R. J., Burgert, E. 0., Jr., and Dahlin, D. C.: Malignant Lymphoma in Children, Pediatrics 28: 985, 1961. 7 Jones, B., and Klingberg, W. G., Lymphosarcoma in Children: A Report of 43 Cases and Review of the Recent Literature, J. Pediatr. 63: 11, 1963. 8 Rosenberg, S. A., Diamond, H. D., Dargeon, H. W., and Craver, L. F.: Lymphosarcoma in Childhood, N. Eng!. J. Med. 259: 505, 1958. 9 LaFranchi, S., and Fonkalsrud, E. W.: Surgical Management of Lymphatic Tumors of the Mediastinum in Children, J. THORAC. CARDIOVASC, SURG. 65: 8, 1973. 10 Opsahl, T., and Berman, E. J.: Bronchogenic Mediastinal Cysts in Infants, Pediatrics 30: 372, 1962. 11 Eraklis, A. J., Griscom, N. T., and McGovern, J. B.: Bronchogenic Cysts of the Mediastinum in Infancy, N. Eng!. J. Med. 281: 1150, 1969. 12 Carney, J. A., Thompson, D. P., Johnson, C. L., and Lynn, H. B.: Teratomas in Children: Clinical and Pathologic Aspects, J. Pediatr. Surg. 7: 271, 1972.
Discussion DR. ROBERT G. PONTIUS Pittsburgh, Pa.
I enjoyed very much the precise analysis and presentation of this large series of children with mediastinal masses. I rise to present a new subcategory: multiple mediastinal neoplasms. A chest film of a 12-year-old boy shows displacement of the heart into the right chest, a huge anterior mediastinal shadow, and a second smaller shadow posteriorly. A left pleural effusion was aspirated and tube drainage established. Bronchoscopy showed deviation of the trachea to the right and extrinsic compression of the left bronchus. At surgery, the anterior tumor was adherent to both lungs and contiguous with the thymus. Its complete resection extended into the neck. Areas of necrosis suggested malignancy, but subsequent complete microscopic examination led to the diagnosis of benign cystic teratoma. The second tumor removed from the posterior sulcus was a ganglioneuroma. Thirteen years later the patient continues to enjoy a normal life.