Germ Cell, Mesenchymal, and Thymic Tumors of the Mediastinum

By Deborah F. Billmire
Philadelphia, Pennsylvania

Germ cell, mesenchymal, and thymic tumors of the mediasti- immature or well differentiated. The variety of tissues
num are an uncommon and heterogeneous group of neo- present provides the opportunity for considerable com-
plasms. Together they account for less than 25% of mediasti-
plexity in the gross characteristics of the mass. Cystic
nal tumors in childhood. The majority of these tumors are
found in the anterior and superior mediastinum, but germ areas frequently are seen because of enclosed areas of
cell tumors and mesenchymal tumors may be located in all secretory epithelium, and calcification may be present
compartments. They share a broad range of histological because of attempted bone formation. Most germ cell
subtypes and clinical behavior, tendency to be large in size, tumors are fairly large with size ranging from 6 to 16 cm.
and a requirement for complete surgical excision as the
The lack ofrestrictive boundaries to the mediastinum has
major requirement for successful therapy.
Copyright © 1999 by W.B. Saunders Company been proposed as a permissive factor that allows signifi-
cant growth before these tumors are discovered. 7 These
large heterogeneous tumors with combinations of benign
HIS UNUSUAL SUBSET of mediastinal tumors
T may be found in any location within the mediasti-
num. Although germ cell, mesenchymal, and thymic
and malignant elements may be misdiagnosed when
incisional biopsies are performed and if the tumor is not
adequately sectioned during pathological examination.
tumors are defined by histological characteristics, there is
Assessment of the response to chemotherapy for malig-
a broad variation in presentation, therapy, and outcome
nant tumors also will be affected by the presence of
within each subgroup.
benign components of the tumor that are not chemosensi-
tive.
GERM CELL TUMORS The clinical behavior of immature mediastinal terato-
mas appears to be age dependent. In children under 15
Germ cell tumors are the third most common neoplasm
years of age, excision is curative. Older children are
of the mediastinum after lymphoma and neurogenic
prone to recurrence and aggressive disease progression. 8
tumors. They account for 6% to 18%1-4 of mediastinal
The malignant elements of seminoma, dysgerminoma,
tumors in children and most often arise in the anterior
and embryonal carcinoma must be recognized by their
mediastinum with an origin in or near the thymus gland.
histological features and have no associated serum mark-
A small subset with distinctive clinical features has an
ers that can be followed. Malignant tumors that have
intrapericardial location with origin from the ascending
followed the differentiation pathway to extraembryonic
aorta, and rare cases arising in the posterior mediastinum
structures, however; secrete characteristic proteins, which
also have been seen.
may be detected in the serum. These protein markers may
Germ cell tumors are an interesting and very heteroge-
aid in recognition of the tumor type and provide a useful
neous group of neoplasms that are believed to arise from
indicator of success or relapse with chemotherapy. Tu-
primitive totipotential cells derived from an early event in
mors with yolk sac (also called endodermal sinus)
embryogenesis. They may be found in many locations, elements secrete the marker alpha-fetoprotein (AFP) ,
particularly in the midline and para-axial sites. The
which has an in vivo half-life of 4 days. This protein also
mediastinum is the third most common site of origin for
is produced in significant amounts by the normal fetal
germ cell tumors and accounts for 7% of these tumors
liver and yolk sac resulting in higher levels for healthy
overall.
newborns than in older children. Interpretation of AFP
The totipotential nature of the cell of origin allows for
levels in the first year of life is facilitated by the graph
great diversity in type and degree of differentiation of the
depicting the normal range for healthy infants developed
neoplastic cell. The tumors range from homogeneous
by Tsuchida et al 9 (Fig 2). Tumors with elements of
masses of primitive embryonal tissues to well-differenti-
choriocarcinoma secrete the glycoprotein beta human
ated teratomas. The potential p athways for differentiation
chorionic gonadotrophin (B-HCG). This is a hormone
are outlined in Fig 1. Germ cell tumors may contain any
or all of the cell types listed. Overall, 86% of mediastinal
germ cell tumors are benign. 5 Most of the malignant From the Department of Surgery, Allegheny University of the Health
tumors are mixed tumors containing some element of Sciences, Sf Christophers Hospitalfor Children, Philadelphia, PA.
Address reprint requests to Deborah F. Billmire, MD, Department of
teratoma as well as malignant components. A teratoma is
Surgery, Allegheny University of Health Sciences, St Christopher s
a germ cell tumor that contains tissues derived from all Hospital for Children, Front St and Erie Ave, Philadelphia, PA 19134.
three germ layers: endoderm, mesoderm, and ectoderm. Copyright © 1999 by WB. Saunders Company
The elements derived from each germ layer may be 1055-8586/99/0802-0007$ 10.00/0

Seminars in Pediatric Surgery, Vol 8. No 2 (May). 1999: pp 85-91 85

86 DEBORAH F. BILLMIRE

that present with congestive heart failure are a special

subgroup that should raise the index of suspicion for the
rare intrapericardial teratoma. lO •11 These patients almost
always have pericardial effusion with some element of
tamponade. Echocardiogram shows rotation as well as
EMBRYONIC ECTODERM.
displacement of the heart caused by the intimate associa-
MESOOERM.ENDODERM tion of the tumor with the ascending aorta. 12 Older
children may also present with respiratory complaints but
more often will complain of chest pain. Signs and
symptoms of superior vena cava syndrome also may be
Fig 1. Histogenetic relationship of the various tumors derived
from the primitive germ cell (from Grosfeld and Billmire,5 modified
seen. Other unusual presentations of mediastinal germ
after Teilum et al"'. (Reprinted with permission."' cell tumors have included rupture into the pleural space
with the acute onset of respiratory distress and rupture
normally produced by the placenta and has an in vivo into the bronchus with expectoration of hair.13 Function-
half-life of 2 to 3 days. Levels throughout infancy and ing ectopic tissue in the well-differentiated teratomas has
childhood are quite low in the absence of malignancy. produced massive hemoptysis from erosion of ulcerated
ectopic gastric mucosal 4 and hypoglycemia from ectopic
Presentation pancreatic islet tissue. 15 Precocious puberty may be seen
The symptoms that lead to the diagnosis of mediastinal in boys with germ cell tumors that secrete B-HCG. This
germ cell tumor are nonspecific but somewhat age combination of findings also should raise the suspicion of
dependent. Most children have a subacute course with Klinefelter's Syndrome. Klinefelter's Syndrome is seen
symptoms ranging from several days to several weeks. in up to 20% of boys with nonseminatous germ cell
These tumors may occur at any age but tend to be tumors of the mediastinum. 16
clustered in infancy and after puberty. Infants usually Chest radiographs will show the presence of a medias-
have respiratory symptoms including tachypnea and tinal mass, which is usually in the anterior and superior
wheezing. Diminished breath sounds may be noted on mediastinum. There may be bulging extension into one or
one side of the chest if the tumor is eccentric with both hemithoraces. A small number of mediastinal germ
preferential extension into one hemithorax. The clinical cell tumors originate in the posterior mediastinumY
picture may mimic or be accompanied by pneumonia Calcification is seen in 35% of mediastinal germ cell
caused by associated bronchial compression. Neonates tumors. 18 Computerized axial tomographic (CAT) scan is
helpful to further define the mass and its relationship to
1,000,000
surrounding structures. The finding of a complex mass
with cystic and solid areas accompanied by irregular
calcifications is highly suggestive of germ cell tumor. The
100,000
~ cystic areas usually have a relatively thick wall, which
differs from that seen with cystic hygroma and thymic or
pericardial cysts.
10,000 \ 1
Treatment
E
The surgical approach to mediastinal germ cell tumors
~,.'
,
Cl 1,000
c
== varies depending on the tumor size and location. As with
a. all other tumors in the anterior mediastinum, consider-
u..
< 100
'-..
ation should be given to the risk of airway and great
• • •• ~
vessel compression. It is not unusual for infants to require
intubation for respiratory distress at the time of presenta-
10 tion. Despite the large size of many of these tumors,
I difficulties with anesthetic induction are rare. Malignant
Il"'r-t-,.. tumors with evidence of local invasion and metastatic
spread have occasionally been subjected to initial image-
11111
guided percutaneous biopsy under sedation. Caution
30 60 90 120 150 180 210 240 270 300 must be used in the interpretation of this limited sample
AGE IN DAYS from such a heterogeneous tumor. In these situations, the
Fig 2. Normal range for AFP in the first year of life. 95% prediction
finding of elevation in the tumor markers AFP or B-HCG
band enclosed by curves. (Reprinted with permission.·' will be helpful in confirming the suspicion of malignancy.
GERM CELL, MESENCHYMAL, AND THYMIC TUMORS
Surgical resection of the tumor is an essential component
of therapy. Benign tumors are treated by excision only
and often have a good plane of dissection in spite of their
large size. 7 If left untreated, the natural history of benign
teratomas is death from compression of vital structures. 7
Malignant tumors also should be resected at diagnosis if
possible. The finding of adherence to local structures,
especially pericardium and phrenic nerve, is common in
these cases. Platinum-based chemotherapy regimens com-
bined with bleomycin and etoposide are currently used
with survival rates of 55% to 70%.19 Tumors that are
unresectable at diagnosis may be explored after induction
chemotherapy. In many cases, a large mass may persist
even if the tumor markers have returned to the normal
range. This may not indicate a treatment failure because
many of these tumors are heterogeneous with large areas
of benign tissue (Fig 3). Benign areas that are cystic may
actually enlarge during therapy, a phenomenon that has
long been recognized as the "growing teratoma syn-
drome."20 All children deserve a reexploration for poten-
tial resection and rebiopsy when a mass effect persists
after chemotherapy. 21
MESENCHYMAL TUMORS
Mesenchyme is the embryonic connective tissue de-
rived from the mesodermal layer of the trilaminar em-
bryo.22 It provides the cell of origin for supporting
structures such as fibrous tissue and fat, muscle, cartilage,
bone, lymphatic tissue, and blood vessels. Cystic hy-
groma, lymphangioma, and hemangioma are an impor-
tant subgroup that will be discussed in a separate chapter.
The remaining mesenchymal tumors are all rare and
account for only 5% of mediastinal tumors in collected
series. I -4 Most information is available as isolated case
reports or small reviews with limited follow-up data.
Mesenchymal Tumors of Fat Cell Origin
This subgroup includes lipoma, lipoblastoma, and
liposarcoma. Lipomas may occur at any age and are soft,
slow-growing tumors that often are asymptomatic. If
symptoms are present, they usually are secondary to local
pressure with cough, chest pain, or dysphagia. 23 ,24 Some
lipomas originate within the thymus gland and are called
thymolipomas. Other sites of origin include the anterior
or superior mediastinum and the posterior mediastinum
within the wall of the esophagus. Lipomas are not
calcified and have uniform low density on computerized
axial tomography (CAT) scan. They should be treated by
total excision and have a low recurrence rate. Lipoblas-
toma is a tumor of infancy. Most cases occur within the
first year of life, and the tumor is rarely seen after 3 years
of age. 25 It is more common in boys and may be well
circumscribed or multicentric. Histologically, these tu-
mors are composed of embryonal fat and have a promi-
87
nent vascular network. Lipoblastoma may be locally
invasive and is prone to local recurrence but does not
metastasize. The treatment is complete excision with
prolonged follow-up. Liposarcoma is a rare tumor of
childhood. Only 11 % of liposarcomas in children origi-
nate in the mediastinum. 26 It may occur at any age with
infants and adolescents accounting for most cases. Most
tumors are a myxoid variant but a variety of histological
subtypes may be seen. The tumor may arise within the
thymus gland27 or in other areas of the mediastinum.
Most patients are asymptomatic but chest pain and
respiratory complaints may occur. Liposarcomas are low
density by CAT scan, but areas of necrosis and calcifica-
tion sometimes are found (Fig 4). Local recurrence is
common after excision, and distant metastasis to lung and
liver may occur. Radiation and chemotherapy (vincris-
tine, dactinomycin, cyclophosphamide) have been used
with variable results.
Mesenchymal Tumors of Muscle Cell Origin
This subgroup of tumors includes leiomyoma, rhabdo-
myosarcoma, extraosseous Ewings, epithelioid sarcoma,
and undifferentiated sarcoma. 28 The tumors may arise in
any compartment of the mediastinum. 29 Pleura and
diaphragm frequently are the site of origin. Mediastinal
sarcomas may be seen at all ages in childhood, and most
patients are symptomatic at presentation. In addition to
the more common complaints of pain and respiratory
difficulties, hemoptysis also has been reported. 3o On CAT
scan, these are large soft tissue masses. Epithelioid
sarcoma may show calcification or bone formation. 30
Surgical resection is the cornerstone of therapy for these
tumors. Difficulties in complete resection frequently are
noted because of invasion of critical neighboring struc-
tures. Procedures that include sacrifice of lung, superior
vena cava, pericardium, and vertebra have been reported
to achieve this goal,29 The accuracy of margin status also
may pose a challenge because these tumors may extend
along pleural surfaces without clear boundaries. In a
recent review by Andrassy et al,31 the local recurrence
rate of group I patients (complete resection) was higher
than that for group II patients (microscopic residual).
Most group I patients did not receive any further therapy,
but nearly all group II patients received local radiation
therapy. It was suggested that the determination of true
margin status could be difficult and posed problems with
accurate staging. Overall survival rate was better for
localized disease, but local recurrence was common. The
critical location of these tumors may cause mortality
from local recurrence even without distant metastases.
Multimodal therapy including radiation and chemother-
apy are required with emphasis on complete surgical
excision whenever possible.
88 DEBORAH F. BILLMIRE

Fig 3. A 16-month-old girl presented with 2-week history of fever and respiratory symptoms (A,BI. AFP was markedly elevated, and biopsy
result of a lung metastasis ICI confirmed yolk sac histology. Chemotherapy produced tumor shrinkage and normalization of AFP after four cycles
(D,EI. Despite continued therapy, the large remaining mass remained stable and was resected after two additional cycles. Histology results
showed only residual benign teratomatous elements. (Photos courtesy Barbara Cushing, MD.I
GERM CELL, MESENCHYMAL, AND THYMIC TUMORS
Fig 4. CAT scan of a 15-year-old girl with liposarcoma involving
the posterior mediastinum with tran~dlaphragmatic extension to the
abdomen. Adherence to the inferior vena cava is evident, and
calcified area may be seen in the low-density tumor.
Mesenchymal Tumors of Cartilage Cell Origin
Extraskeletal chondrosarcoma has been reported in the
posterior mediastinum in children during the second
decade of life. 32 These tumors present with pain. CAT
scan shows a soft tissue mass with punctate calcification
that may be confused with neuroblastoma. Despite adher-
ence to surrounding structures, a plane of dissection may
be achieved, allowing complete resection. Of two chil-
dren treated by excision only, one was well at 6-year
follow-up, and one had local recurrence.
THYMIC TUMORS
The thymus develops during the sixth week of gesta-
tion from paired primordia in the ventral portion of the
third pharyngeal pouch. Over the next 3 to 4 weeks, there
is a migratory descent into the thorax, which follows a
path from the pyriform sinus, through the thyrohyoid
membrane, between the carotid artery and vagus nerve to
lie in the anterior mediastinum at the level of the aortic
arch. 33,34 The endodermal derivative has a primitive
lumen (the thymopharyngeal duct), which becomes oblit-
erated during development. There also is an ingrowth of
lymphocytes from the surrounding mesenchyme that
contributes to the formation of the thymic lobules. Thus,
there are two primary cell types within the thymus that
can give rise to neoplasia: epithelial cells and lympho-
cytes. The supporting mesenchyme of the thymus also
may give rise to various neoplasms, but these will be
discussed separately. The finding of germ cell tumors
arising in the thymus is presumed to be because of
migration of totipotential cells into the thymus during
early development and will be discussed with other germ
cell tumors of the mediastinum. Primary tumors and cysts
of the thymus may be found anywhere along the embryo-
logical pathway of descent of the thymus gland and
frequently involve the neck as well as the mediastinum.
89
Thymoma and Thymic Carcinoma
These are rare neoplasms derived from the epithelial
and lymphoid components of the thymus. The behavior
of thymic tumors in children is not well understood
because of the rare incidence, the variable morphology
that often requires special stains and electron microscopy
for accurate diagnosis, and the broad spectrum of clinical
behavior. Overall, there have been less than 50 primary
thymic epithelial neoplasms reported in childhood.35
Thymic carcinoma is defined by the overt recognition of
malignant features by cytological examination including
cytological atypia and mitotic index. The most common
malignant patterns are anaplastic tumors or small cell
carcinomas with neuroendocrine features. This is in
contrast to adults that usually exhibit well-differentiated
squamous or lymphoepithelial carcinoma. 36 Pediatric
thymic carcinomas are aggressive malignancies that
usually cause chest pain and shortness of breath. Local
invasion of surrounding structures with metastases to
lung, liver, and bone are common at diagnosis. Death
within 6 months of presentation frequently is seen. 37 ,38
Thymomas are a varied spectrum of primary thymic
tumors with bland cytological features and no overt
histological evidence of malignancy.39 In spite of the
innocent histological picture, their clinical behavior ranges
from a well-encapsulated focal lesion that is cured by
simple excision to a pattern of local invasion and
metastatic spread with eventual death. In a large review
of thymoma in adults from the Mayo Clinic, 32% had
evidence of local invasion and 6% had metastasis at
diagnosis. There was a local recurrence rate of 15% in
patients who had undergone complete surgical resection,
and the 5-year survival rate was 67%.39
Data on pediatric patients with thymoma is limited, but
similar clinical behavior ranging from successful primary
resection to multiple recurrences and death have been
reported. 35,40,41
Presentation of thymic tumors ranges from asymptom-
atic discovery on chest x-ray to chest pain and shortness
of breath. Superior vena cava syndrome may occur, and
pericardial and pleural effusions often are noted with
malignant lesions. CAT scan demonstrates an anterior
mediastinal mass that may be solid or mixed with cystic
and solid components. 40 Calcification has been described
in 2% to 25% of cases. 40 ,42
For all thymic neoplasms, surgery is the mainstay of
therapy. Complete resection including contiguous struc-
tures if necessary should be the goal. 38 ,42 For malignant
lesions, postoperative chemotherapy and radiation have
been used with limited success.
Thymic Cysts
Thymic cysts are benign tumors that are believed to
originate from remnants of the thymopharyngeal duct. An
90
alternative explanation is that the cyst is a consequence of
degeneration in Hassall's corpuscles. They may be uni-
locular or multilocular and contain clear fluid. Most are
asymptomatic, but hemorrhage into the cyst cavity with
enlargement may produce tracheal compression and
acute respiratory distress. 34 The cyst may be localized
entirely in the mediastinum or in the neck but frequently
includes both sites. Thymic cysts should be treated by
surgical excision to prevent complications of local expan-
sion and to confirm the histology. Other thymic lesions,
which may have a cystic appearance, include nodular
sclerosing Hodgkin's disease,4o seminoma, and cystic
teratoma,43 Cervical lesions with mediastinal extension
(Fig 5) often can be excised through a transverse cervical
incision. 44 Contained mediastinal cysts may be ap-
proached by either median sternotomy or thoracotomy
depending on their size and location. A recurrence rate of
2% has been reported for thymic cysts in adults, but this
has not been seen in children. 34
Myasthenia Gravis and the Thymus
The relationship between myasthenia gravis and abnor-
malities of the thymus has long been recognized in adults.
Overall, approximately 82% of adults with myasthenia
gravis have an abnormality of the thymus gland, and 15%
have a thymoma. 42 Other autoimmune disorders that have
been associated with thymoma in adults include inflam-
matory bowel disease, collagen vascular disease, hypo-
gamma globulinemia, and hypoplastic or aplastic anemia.
In childhood, abnormalities of the thymus usually are
an isolated phenomenon, but occasional links to other
disorders have been noted. In 1985, Furman et al45
reported on a 4-year-old girl with respiratory symptoms
from a large thymoma. She also had evidence of muscle
weakness by history. Postoperatively she had florid
symptoms of myasthenia gravis with a positive edropho-
nium (Tensilon) test result and required 7 days of
mechanical ventilation. They were able to find only five
other cases of myasthenia gravis associated with thy-
moma in childhood. Youssef46 reported eight children
with myasthenia gravis who underwent thymectomy for
significant symptoms. None had thymoma, but four had
lymphoid hyperplasia. Six of the patients had dramatic
improvement with complete recovery at 3 to 11 years of
follow-up. He emphasized the importance of "radical"
thymectomy, which is achieved by median sternotomy
REFERENCES
1. King M, Telander RL, Smithson WA, et al: Primary mediastinal
tumors in children. J Pediatr Surg 17:512-519, 1982
2. Azarow KS, Pearl RH, Zurcher R, et al: Primary mediastinal
masses. J Thorac Cardiovasc Surg 106:67-72, 1993
3. Grosfeld JL, Skinner MA, Rescorla Fl, et al: Mediastinal tumors
in children: Experience with 196 cases. Ann Surg One 1:121-127, 1994
4. Massie RJH, Van Asperen PP, Mellis CM: A review of open
DEBORAH F. BILLMIRE
Fig 5. A 4-year-old girl presented with a large neck mass extend-
ing deep into the anterior mediastinum by CAT scan. A multiloculated
thymic cyst was excised through a transverse cervical incision
without difficulty.
with removal of the thymus and all fatty tissue of the
mediastinum from the diaphragm to the pharynx. Thy-
moma also has been seen in association with aplastic
anemia in a child. 47
Human Immunodeficiency Virus and the Thymus
Approximately 2% of human immunodeficiency virus
(HlV)-infected patients in the United States are in the
pediatric age group.48 These children are at increased risk
of malignancy as well as unusual infections caused by
their immune compromised state. A recent disease entity
involving the thymus has been described in these chil-
dren. Eight of the 440 pediatric HIV patients followed up
by the pediatric branch of the National Cancer Institute
were noted to have an asymptomatic anterior mediastinal
mass on routine chest x-ray.49 CAT scan showed a
multiseptated cystic mass of the thymus with characteris-
tic features in all patients. Five of the eight patients also
had lymphoid interstitial pneumonitis. Five children had
open wedge biopsy, and one had complete resection of
the mass. Histological examination showed distorted
architecture with follicular hyperplasia and cysts but no
evidence of malignancy. The mass resolved in two
patients and decreased in three of the others. They
recommended careful observation with serial CAT scans
in children with HIV who demonstrate the typical CAT
scan findings of multi septate cystic lesions of the thymus
as long as there are no signs of malignancy and no clinical
symptoms that may be attributed to the mass.
biopsy for mediastinal masses. J Paediatr Child Health 33:230-233,
1997
5. Grosfeld JF, Billmire DF: Teratomas in infancy and childhood.
CurrProbICancer9:1-53,1985
6. Teilum G, Albrechtsen R, Nongaard-Pederson B: Immunofluores-
cent localization of alpha-feto protein synthesis in endodermal sinus
tumor (yolk sac tumor). Acta Pathol MicrobioI Scand 82:586-588, 1974
GERM CELL, MESENCHYMAL, AND THYMIC TUMORS
7. Lack EE, Weinstein HJ, Welch KJ: Mediastinal germ cell tumors
in childhood. J Thorac Cardiovasc Surg 89:826-835,1985
8. Ouimet EM, Macchiarini P, Suc B, et al: Germ cell tumors of the
mediastinum. Cancer 72: 1894-190 I, 1993
9. Tsuchida Y, Endo Y, Saito S, et al: Evaluation of alpha-fetoprotein
in early infancy. J Pediatr Surg 13:155-156, 1978
10. Deenadayalu RP, Tuuri D, Dewall RA, et al: Intrapericardial
teratomas and bronchogenic cyst. J Thorac Cardiovasc Surg 67:945-
952, 1974
II. ZereHa JT, Halpe DCE: Intrapericardial teratoma-neonatal cardio-
respiratory distress amenable to surgery. J Pediatr Surg 15:961-963,
1980
12. Arciniegas E, Hakimi M, Farooki ZQ: Intrapericardial teratoma
in infancy. J Thorac Cardiovasc Surg 79:306-311,1980
13. Thompson DP, Moore TC: Acute thoracic distress in childhood
due to spontaneous rupture of a large mediastinal teratoma. J Pediatr
Surg 4:416-421,1969
14. Robertson JM, Fee HJ, Mulder DG: Mediastinal teratoma
causing life-threatening hemoptysis. Am J Dis Child 135: 148-150, 1981
15. Honicky RE, dePapp EW: Mediastinal teratoma with endocrine
function . Am J Dis Child 126:650-653, 1973
16. Zon R, OraziA, Neiman RS, et al: Benign hematologic neoplasm
associated with mediastinal mature teratoma in a patient with klinefel-
ter's syndrome: A case report. Med Pediatr OncoI23:376-379, 1994
17. Karl SR, Dunn J: Posterior mediastinal teratomas. J Pediatr Surg
20:508-510,1985
18. Carney JA, Thompson DP, Johnson CL, et al: Teratomas in
children: Clinical and pathologic aspects. J Pediatr Surg 7:271-282,
1972
19. Berkow RL, Kelly DR: Isolated CNS metastasis as the first site
of recurrence in a child with germ cell tumor of the mediastinum. Med
Pediatr Oncol 24:36-39, 1995
20. Logothetis CJ, Samuels ML, Trindade A, et al: The growing
teratoma syndrome. Cancer 50:1629-1635,1982
21. Uchiyama M, Iwafuchi M, Matsuda Y, et al: Mediastinal yolk sac
tumor in a young girl: Case report and review of the literature. J Pediatr
Surg 31:1318-1321,1996
22. Copenhauer WM, Bunge RP, Bunge MB: The connective tissues,
in Bailey's Textbook of Histology. Baltimore, MD, Williams & Wilkins,
1971, pp 109-135 (Chap 5)
23. Mahomed AA, Beale P, Puri P: Mediastinal lipoma in children.
Pediatr Surg Int 13:218-219, 1998
24. Hasan N, Mandhan P: Respiratory obstruction caused by lipoma
of the esophagus. J Pediatr Surg 29: 1565-1566, 1994
25. Stringel G, ShandJing B, Mancer K, et al: Lipoblastoma in
infants and children. J Pediatr Surg 17:277-280, 1982
26. Castleberry RP, Kelly DR, Wilson ER, et al: Childhood liposar-
coma: Report of a case and review of the literature. Cancer 54:579-584,
1984
27. Klimstra DS, Moran CA , Perino G, et al: Liposarcoma of the
anterior mediastinum and thymus: A clinicopathologic study of 28
cases. Am J Surg PathoI19:782-791, 1995
91
28. Maurer HM, Gehan EA, Beltangady M, et al: The intergroup
rhabdomyosarcoma study-II. Cancer 71: 1904-1922, 1993
29. Burt M, Ihde JK, Hajdu SI, et al: Primary sarcomas of the
mediastinum: Results of therapy. J Thorac Cardiovasc Surg 115:671-
680, 1998
30. Gross E, Rao BN, Pappo A, et al: Epithelioid sarcoma in
children. J Pediatr Surg 31:1663-1665,1996
31. Andrassy RJ, Wiener ES, Raney RB, et al: Thoracic sarcomas in
children. Ann Surg 227:170-173, 1998
32. Suster S, Moran CA: Malignant cartilaginous tumors of the
mediastinum: Clinicopathological study of six cases presenting as
extraskeletal soft tissue masses. Hum PathoI28:588-594, 1997
33. Skandalakis IE, Grau SW, Todd NW: Pharynx and its derivative,
in Embryology for Surgeons. Baltimore, MD, Williams and Wilkins,
1994, pp 17-64 (Chap 2)
34. Wagner CW, Vinocur CD, Weintraub WH, et al: Respiratory
complications in cervical thymic cysts. J Pediatr Surg 23:657-660, 1988
35. Ramon y Cajal S, Suster S: Primary thymic epithelial neoplasms
in children. Am J Surg Pathol 15:466-474, 1991
36. Suster S, Rosai J: Thymic carcinoma: A clinicopathologic study
of 60 cases. Cancer 67: 1025-1032, 1991
37. Bowie PR, Teizeira OHP, Carpenter B, et al: Malignant thymoma
in a nine year old boy presenting with pleuropericardial effusion. J
Thorac Cardiovasc Surg 77:777-778,1979
38. Spigland N, Di Lorenzo M, Youssef S, et al: Malignant tymoma
in children: A20 year review. J Pediatr Surg 25 :1143-1146,1990
39. Lewis JE, Wick MR, Scheithauer BW, et al: Thymoma: A
clinicopathologic review. Cancer 60:2727-2743, 1987
40. Lam WWM, Chan FL, Lau YL, et al: Paediatric thymoma:
Unusual occurrence in two siblings. Pediatr RadioI23:124-126, 1993
41. Dehner LP, Martin SA, Sumner HW: Thymus related tumors and
tumor-like lesions in childhood with rapid clinical progression and
death. Hum Pathol 8:53-66, 1977
42. Cohen II, Templeton A, Philips AK: Tumors of the thymus. Med
Pediatr Oncol 16: 135-141 , 1988
43. Moran CA, Suster S: Mediastinal seminomas with prominent
cystic changes: A clinicopathologic study of 10 cases. Am J Surg Pathol
19:1047-1053, 1995
44. Welch KJ, Tapper D, Vawter GP: Surgical treatment of thymic
cysts and neoplasms in children. I Pediatr Surg 14:691-698, 1979
45. Furman WL, Buckley PI, Green AA, et al: Thymoma and
myasthenia gravis in a 4-year-old child: Case report and review of the
literature. Cancer 56:2703-2706, 1985
46. Youssef S: Thymectomy for myasthenia gravis in children. J
PediatrSurg 18:537-541, 1983
47. Talerman A, Amigo A: Thymoma associated with a regenerative
and aplastic anemia in a 5-year-old child. Cancer 21 :1212-1218, 1968
48. American Academy of Pediatrics: HIV infection, in Peter G (ed):
1997 Red Book: Report of the Committee on Infections Diseases. ed 24.
Elk Grove Village, IL, American Academy of Pediatrics, 1997, p 285
49. Udo Kontny H, Sleasman JW, Kingma DW, et al: Multilocular
thymic cysts in children with human immunodeficiency virus infection:
Clinical and pathologic aspects. J Pediatr 131 :264-270, 1997