Primary mediastinal masses

General Thoracic Surgery

Primary mediastinal masses A comparison of adult and pediatric populations Since 194462 pediatric patients with primary cysts and tumors of the mediastinum have been operated on at our institution. We compared this group with 195 adult patients with similar diagnoses who were operated on during this period. Comparisons were made with regard to histologic type, location, presenting symptoms, physical findings, and surgical complications. We found significant increases in the prevalence of lymphoma in adults (41/195 versus 4/62, p < 0.05) and of neurogenic tumors in children (21/62 versus 24/195, p < 0.05). There were no significant differences in the prevalence of thymic tumors (51/195 versus 22/62), germ cell tumors (24/195 versus 4/62), and cysts (32/195 versus 15/62). There was no difference in the prevalence of symptomatic patients (99/195 versus 36/62). The prevalence of malignancy has increased in both groups since 1970 (2/28 versus 16/34 in children, p < 0.01; and 14/56 versus 69/139 in adults, p < 0.05). This is attributed to a rise in the prevalence of malignant neurogenic tumors in children and to an increase in the prevalence of lymphomas in adults. Tumor size, location, and the presence of symptoms were predictive of malignancy in the adult population but not in the pediatric population. No difference existed in mortality and morbidity between the two groups. All three pediatric deaths were directly related to loss of airway control as a result of mass effect from the tumor. Definite differences exist between the adult and pediatric populations with regard to mediastinal tumors. These differences need to be considered carefully when evaluating and planning treatment for a child with a mediastinal mass. (J THORAC CARDIOVASC SURG 1993;106:67-72)

Kenneth S. Azarow, MD, Richard H. Pearl, MD, Robert Zurcher, MD, Fred H. Edwards, MD, and Amram J. Cohen, MD, Washington, D.C., and Bethesda, Md.

Differences exist between adult and pediatric populations with mediastinal tumors. A significant difference in histologicdistribution of these tumors, as wellas frequenFrom the Departments of Thoracic Surgery and the Division of Pediatric Surgery, Walter Reed Army Medical Center, Washington, D.C., and the Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Md. The opinions herein are those solely of the authors and do not represent those of the United States Army or the Department of Defense. Received for publication Jan. 21, 1992. Accepted for publication July 2, 1992. Address for reprints: Amram J. Cohen, MD, Walter Reed Army Medical Center, Thoracic Surgery Service, 4th Floor, Washington, DC 20307-5001.

12/1/40785

cy of symptoms in children compared with adults has been suggested.!:? A direct statistical comparison has not been made, however. Two recent series have documented changes in the histologic distribution of mediastinal masses as well as symptomatology and prevalence of malignancy in patients with such tumors. Both series included children and adults.f-? Thus it remains unclear whether these changes are more prevalent in the pediatric population or in the adult population. At our institution we have treated mediastinal masses in children and adults consistently for the past five decades. Accordingly, we analyzed our experience with mediastinal tumors by separating the pediatric and adult populations. Our goal was to examine temporal trends 67

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6 8 Azarow et al.

Table I. Tumor histology in the pediatric population Histologic type

Benign

Malignant

Total

Thymic Thymoma Hyperplasia Cyst Enlarged thymus Ectopic Lipoma Sarcoma Subtotal

2 3 2 3 I I 0 12

0 0 0 0 0 0 I I

2 3 2 3 I I I 13 (21%)

Cyst Bronchogenic Enteric Pericardial Miscellaneous Subtotal

7 4 I 3 15

0 0 0 0 0

7 4 I 3 15(25%)

0 0 8 9

7 6 0 0 13

7 6 8 I 22 (35%)

4 4

0 0

4 4 (6%)

0

I 3 4 (6%)

Neurogenic Ganglioneuroblastoma Neuroblastoma Ganglioneuroma Neurilemmoma Subtotal Germ cell Teratoma Subtotal

I

0

I 3 4

Vascular Hemangioma Hemangiopericytoma Subtotal

2 I 3

0 0 0

2 I 3 (5%)

I

0

I 1(2%)

Total

Histologic class Thymus Neurogenic Cyst Lymphoma Germ cell Vascular Miscellaneous

Adults

Children

Benign Malignant Benign Malignant p Value 33 22 32 0 14 2 9

18 2 0 41 10 0 12

12 9 15 0 4 3 I

I 13 0 4 0 0 0

NS <0.05 NS <0.05 NS NA NA

NA, Not applicable because of small sample size; NS, not significant.

Lymphoma Hodgkin's Non-Hodgkin's Subtotal

Miscellaneous Gastric duplication Subtotal

Table II. Comparison of adults versus children for histologic type

0

I

0

44

18

62

and perform a statistical comparison between the two groups.

Methods The records of patients undergoing operation for mediastinal masses at our institution from January 1944 until June 1991 were reviewed. The patients were divided into pediatric and adult populations. The pediatric population consisted of patients all less than 18 years of age. Inclusion criteria included all patients who underwent operations for primary mediastinal masses. Masses that were resected because they were thought to be primary tumors at the time of operation were included. Patients with metastatic disease of the mediastinum or masses of infectious cause were excluded. The charts were

obtained from the Thoracic Surgery Clinic charts, WaIter Reed inpatient records, Walter Reed Tumor Registry, and Hematology/Oncology clinic files. Each chart was reviewed for demographic data, presenting symptoms, physical examination, operative findings, pathology, postoperative morbidity and mortality, and long-term follow-up. For the purposes of this study the mediastinum was divided into anterior, middle, and posterior compartments as described by Burkell and associates. to x2 Analysis was used to compare differences between the two populations and look for preoperative predictors of malignancy. Yates correlation was used for groups less than 30. Differences were considered significant if the p value was less than 0.05.

Results A total of 257 patients met the inclusion criteria. Ages ranged from newborn to 69 years, with a mean of 27.7 + 18.6. The male to female ratio was 7:5. Sixty-two patients (24%) were less than 18 years of age. There was no significant difference in sexual distribution between the pediatric and adult populations (36/26 versus 114/ 81,p<0.05). The tumor histology for the pediatric population is shown in Table I. Neurogenic tumors were the most common, with cysts second and thymic tumors third. Lymphoma and germ cell tumors accounted for 6% each. Table II compares tumor type and number of malignancies between the two groups. Histologic types between the two groups were statistically different for neurogenic tumors and lymphomas (24/195 versus 22/62,p < 0.05 and 41/195 versus 4/62, p < 0.05). The percentages of patients with malignant disease in the pediatric group (25%) and the adult group (43%) were not statistically different. The increase in malignancy rate over time for both groups is represented in Fig. I. There was a significant

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Azarow et ai.

69

Malignancy Rate

100

/

.:

80

40 20

o o

~ ~

~~_-

------

L/

1 (1960-69) 2 (1960-69) 3(1970-79)

~_----

--+

.>

60

----_._~

~

4(1980-89)

_

-

5 (1990-91)

Decade -

Children

-+- Adults

Fig. 1. Lineargraph demonstrates the increasing rate of malignancy with time in both adult and pediatricpopulations. increase in patients with malignancy after 1970 in both groups (2/28 versus 16/34, p < 0.01; and 14/56 versus 69/139, p < 0.05). In the adult population this was caused by an increased prevalence of lymphoma 0/56 before 1970 versus 38/139 after 1970, p < 0.05). In children this was attributed to the increased prevalence of malignant neurogenic tumors (2/28 before 1970 versus 11/34 after 1970, p < 0.05). The most common location of mediastinal tumors in the adult group was the anterior compartment. The children differ from the adults in the location of their tumors (Fig. 2). Most malignant tumors in adults occur in the anterior compartment, while most malignant tumors in children occur in the posterior compartment (Table III). Fifty-two percent of the adults were asymptomatic while 42% of the children had no symptoms (p = not significant). Chest pain was the most common symptom in the adult group, while respiratory symptoms were most common in children (Table IV). Factors previously recognized'' as risk factors for malignancy in our entire population (size, anterior location, and symptoms) were analyzed separately in the pediatric and adult populations. In the adults, anterior location was associated with malignancy (71/126 versus 12/69, p < 0.01), as was symptomatology (55/99 versus 27/96, p < 0.05). In children neither factor was predictive of a diagnosis of malignancy. Size was not evaluated in the pediatric population; it was highly predictive of malignancy, however (p < 0.001), in the adult population, with lesions greater than 7 em having greater than a 50% prevalence of malignancy. The morbidity and mortality in both groups are shown in Table V. The total complication rates, 19% for children and 16%for adults, were not significantly different. There

Posterior 32 Fig. 2. Pie chart demonstrates the preponderance of posterior mediastinal masses in the pediatric population. were three deaths in the pediatric group. One neonate, aged 3 days, had a large neurenteric cyst. He was moribund upon presentation because of hypoxia caused by airway compression. He aspirated during induction of anesthesia and was unable to be intubated because of the size of his mass. The second death was in a 6-year-old child who was operated on for an anterior mediastinal mass diagnosed as lymphoblastic lymphoma. In this child bronchospasm developed upon attempted intubation, and the child could not be resuscitated. The third death was in a 21-month-old child who had a neuroblastoma that

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Table III. Tumor location: Adults versus children Children

Adults Location

Benign

Malignant

Total

Benign

Malignant

Total

Anterior

55

126

18

16 41

19 50

5 21

6 (p= NS) I ]1

24

Middle Posterior

71 (p < 0.01) 3 9

6 32

NS. Not significant.

Table IV. Characterization ofpopulation and tumor histology by symptoms Children

Adults Symptom

Benign

Malignant

Total

Benign

Malignant

Total

Asymptomatic

69

27

96

20

6

26

Respiratory Chest pain Malaise Dysphagia SVCS Combined Miscellaneous

II 18 3 3 0 I 8

14 19 I 0 4 13 4

25 37 4 3 4 14 12

13 5 0 I 0 6 0

5 0 I 0 0 2 2

18 5 1 I 0 8 2

Total symptoms

44

55

99

25

10

35

(p < 0.05)

(p

= NS)

SVCS, Superior vena cava syndrome; NS, not significant.

was seen initially as a large mediastinal mass. His death occurred as a consequence of postoperative aspiration leading to respiratory arrest. The adult deaths were attributable to uncontrolled malignancy in the postoperative period.

Discussion Walter Reed Army Medical Center is a tertiary care center with a referral base that has not changed for the duration of this study.* Our referral base is broad and is not skewed toward pediatric or adult patients. Thus comparison of our pediatric patients with mediastinal tumors with our adult population should reflect true differences in mediastinal tumors between children and adults. The distribution of tumor histology in our pediatric population differs from our adult data. It also differs in some respects from previous reports.l ' -14 Neurogenic tumors have been cited as the most common solid primary mediastinal tumor in children.P Our study confirms this finding. In addition, we found a higher proportion of neurogenic tumors in children compared with our adult population (p < 0.05). Thymic tumors were the second most common pediatric tumor in our series (21%). This differs with the greater portion of the literature- 5, 6 but *Department of the Army Health Services Command Regulation 10-1. Organization and Functions Manual, Washington, D.C., 1989.

concurs with some." We found no significant difference in the prevalence of thymic tumors between children and adults. However, there was a difference in the type of thymic tumors. In adults, thymoma represented 50% of the thymic lesions. In contrast, thymoma represented 15% of the thymic lesions in children undergoing operations. Patients with thymic hyperplasia and enlarged thymus were included only when the surgeon resected these lesions assuming they were tumors at the time of operation. Lymphoma represented 6% of our pediatric tumors. This small number reflects our institutional policy of reporting only cases in which the tumor was confined to the mediastinum. Reports of large numbers of lymphomas in pediatric series have included tumors whose diagnosis was made by extrathoracic biopsy' Others have confirmed that lymphoma confined to the mediastinum is rare,13 which is supported by our data. Our study demonstrates an increased prevalence of such tumors confined to the mediastinum in adults compared with children (41/195 versus 4/62, p < 0.05; see Table II). The prevalence of germ cell tumors and cysts of the mediastinum is comparable with the prevalence reported in the literature.v ' There is no significant difference in prevalence of these tumors in adults compared with children. There were no malignant germ cell tumors in chil-

The Journal of Thoracic and Cardiovascular Surgery Volume 106, Number 1

dren, whereas 42% of the germ cell tumors were malignant in adults. Tumor location differed between children and adults (see Table III). Anterior mediastinal tumors were most common in adults while posterior mediastinal tumors accounted for more than half of the tumors in children. The higher proportion of tumors in the posterior area of the pediatric population is a reflection ofthe tumor's neurogenic origin in that area of the mediastinum. Several authors have reported an increased prevalence of malignancy and symptomatology in the pediatric population." 12 We found neither a higher malignancy rate nor more symptomatic patients in the pediatric population. We suspect prior reports may reflect skewed referral patterns. Children with respiratory symptoms that may represent anesthetic risk or children who have potentially malignant tumors may be referred to a specialized institution, whereas asymptomatic children with benign-appearing lesions will be treated upon diagnosis. A second possibility for no significant increase in symptomatic pediatric patients could be location of the tumors in this population. The higher proportion of posterior mediastinal tumors in our pediatric population, with fewer contiguous structures to produce symptoms, may negate the effect of the small mediastinum in children. We demonstrated a difference in the type of presenting symptoms in the two populations. At initial presentation adults more commonly had chest pain, while children primarily had respiratory symptoms. This has been documented previously.l' In combined populations anterior location of the tumor, symptoms related to the tumor, and size were predictive of malignancy.t- 9 Multivariate analysis of our adult population confirmed these factors as predictors of malignancy. In our pediatric population univariate analysis could not demonstrate either the anterior area of the mediastinum nor the presence of symptoms to be predictive of malignancy. The large number of neurogenic malignancies and the number of symptomatic children with benign tumors eliminated these factors as predictors of malignancy. Several large series of combined populations with mediastinal masses have shown an increasing rate of malignancy primarily because of an increased prevalence of lyrnphoma.f 9 Our pediatric population also shows an increasing rate of malignancy, but this is because of an increasing prevalence of malignant neurogenic tumors. No increased prevalence of lymphoma could be demonstrated in the pediatric population. While no statistical difference existed in mortality between children and adults, a difference in anesthetic

Azarow et ai.

7I

Table V. Complications Mortality and morbidity Children

Adults

Type

(N=62)

(N = 195)

Total major Atelectasis (bronchoscopy used) Pneumonia Horner's syndrome Paraplegia Phrenic nerve injury Pericarditis Penumothorax Wound dehiscence Pulmonary embolus Myocardial ischemia Pleural effusion (thoracostomy performed) Sepsis

7 (II %) 2

19 (9%) 2

I I I 2

0 0 0 5 I 2 I 2 2 3

Total minor Unilateral vocal cord paralysis Transfusion reaction Seroma Elevated hemidiaphragm (no respiratory insufficiency) Atelectasis (no bronchoscopy performed) Tracheobronchitis Pleural effusion (no thoracostomy performed) Death Total major, minor, death

2 (3%) I

9 (4%) I

I

0 I 2

I 3 3 (5%) 12 (19%)

3 (1%) 31 (16%)

p= NS NS. Not significant.

risk is suggested. All three pediatric deaths resulted from inability to adequately ventilate the lungs in the perioperative period. This has been observed by others.l'" 17 and extreme caution is warranted while anesthetizing a small child who has a large mediastinal mass. REFERENCES I. GrosfeldJL, WeinbergM, KelmannJW, Clatworthy HW. Primary mediastinal neoplasms in infants and children. Ann Thorac Surg 1981; 12:179-88. 2. Haller JA, Mazur DO, Morgan WM. Diagnosis and management of mediastinal masses in children. J THORAC CARDIOVASC SURG 1969;58:385-93. 3. Heimburger IL, BattersbyJS. Primary mediastinaltumors of childhood. J THORAC CARDIOVASC SURG 1965;50:92103. 4. King RM, Telander RL, Smithson WA, et al. Primary mediastinal tumors in childhood. J Pediatr Surg 1982; 17:512-9.

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Primary tumors of the mediastinum. Chest 1972;62:297303. Lack EE, Weinstein HJ, Welch KJ. Mediastinal germ cell tumors in childhood. J THORAC CARDIOVASC SURG 1985; 89:826-35. Mullin B, Richardson JD. Primary anterior mediastinal tumors in children and adults. Ann Thorac Surg 1986; 42:338-45. Robush JL, Gardner IL, Boyd NC, Ehrenhaft JL. Mediastinal tumors: review of 186 cases. J THoRAc CARDlOVASC SURG 1973;65:216-22. Sabiston DC, Scott HW. Primary neoplasms and cysts of the mediastinum. Ann Surg 1952;136:777-97. Azizham RG, Dudgeon DL, Buck JR, et al. Life threatening airway obstruction as a complication to the management of mediastinal masses in children. J Pediatr Surg 1985;20:816-22. Kirks DR, Fram EK, Vock P, Effmann EL. Tracheal compression by mediastinal masses in children. CT evaluation. Am J Radiol 1983;141:647-52.