Documentos de Académico
Documentos de Profesional
Documentos de Cultura
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
Surgical resection of the tumor is an essential component nent vascular network. Lipoblastoma may be locally
of therapy. Benign tumors are treated by excision only invasive and is prone to local recurrence but does not
and often have a good plane of dissection in spite of their metastasize. The treatment is complete excision with
large size. 7 If left untreated, the natural history of benign prolonged follow-up. Liposarcoma is a rare tumor of
teratomas is death from compression of vital structures. 7 childhood. Only 11 % of liposarcomas in children origi-
Malignant tumors also should be resected at diagnosis if nate in the mediastinum. 26 It may occur at any age with
possible. The finding of adherence to local structures, infants and adolescents accounting for most cases. Most
especially pericardium and phrenic nerve, is common in tumors are a myxoid variant but a variety of histological
these cases. Platinum-based chemotherapy regimens com- subtypes may be seen. The tumor may arise within the
bined with bleomycin and etoposide are currently used thymus gland27 or in other areas of the mediastinum.
with survival rates of 55% to 70%.19 Tumors that are Most patients are asymptomatic but chest pain and
unresectable at diagnosis may be explored after induction respiratory complaints may occur. Liposarcomas are low
chemotherapy. In many cases, a large mass may persist density by CAT scan, but areas of necrosis and calcifica-
even if the tumor markers have returned to the normal tion sometimes are found (Fig 4). Local recurrence is
range. This may not indicate a treatment failure because common after excision, and distant metastasis to lung and
many of these tumors are heterogeneous with large areas liver may occur. Radiation and chemotherapy (vincris-
of benign tissue (Fig 3). Benign areas that are cystic may tine, dactinomycin, cyclophosphamide) have been used
actually enlarge during therapy, a phenomenon that has with variable results.
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 Mesenchymal Tumors of Muscle Cell Origin
after chemotherapy. 21 This subgroup of tumors includes leiomyoma, rhabdo-
myosarcoma, extraosseous Ewings, epithelioid sarcoma,
MESENCHYMAL TUMORS and undifferentiated sarcoma. 28 The tumors may arise in
Mesenchyme is the embryonic connective tissue de- any compartment of the mediastinum. 29 Pleura and
rived from the mesodermal layer of the trilaminar em- diaphragm frequently are the site of origin. Mediastinal
bryo.22 It provides the cell of origin for supporting sarcomas may be seen at all ages in childhood, and most
structures such as fibrous tissue and fat, muscle, cartilage, patients are symptomatic at presentation. In addition to
bone, lymphatic tissue, and blood vessels. Cystic hy- the more common complaints of pain and respiratory
groma, lymphangioma, and hemangioma are an impor- difficulties, hemoptysis also has been reported. 3o On CAT
tant subgroup that will be discussed in a separate chapter. scan, these are large soft tissue masses. Epithelioid
The remaining mesenchymal tumors are all rare and sarcoma may show calcification or bone formation. 30
account for only 5% of mediastinal tumors in collected Surgical resection is the cornerstone of therapy for these
series. I -4 Most information is available as isolated case tumors. Difficulties in complete resection frequently are
reports or small reviews with limited follow-up data. noted because of invasion of critical neighboring struc-
tures. Procedures that include sacrifice of lung, superior
Mesenchymal Tumors of Fat Cell Origin vena cava, pericardium, and vertebra have been reported
This subgroup includes lipoma, lipoblastoma, and to achieve this goal,29 The accuracy of margin status also
liposarcoma. Lipomas may occur at any age and are soft, may pose a challenge because these tumors may extend
slow-growing tumors that often are asymptomatic. If along pleural surfaces without clear boundaries. In a
symptoms are present, they usually are secondary to local recent review by Andrassy et al,31 the local recurrence
pressure with cough, chest pain, or dysphagia. 23 ,24 Some rate of group I patients (complete resection) was higher
lipomas originate within the thymus gland and are called than that for group II patients (microscopic residual).
thymolipomas. Other sites of origin include the anterior Most group I patients did not receive any further therapy,
or superior mediastinum and the posterior mediastinum but nearly all group II patients received local radiation
within the wall of the esophagus. Lipomas are not therapy. It was suggested that the determination of true
calcified and have uniform low density on computerized margin status could be difficult and posed problems with
axial tomography (CAT) scan. They should be treated by accurate staging. Overall survival rate was better for
total excision and have a low recurrence rate. Lipoblas- localized disease, but local recurrence was common. The
toma is a tumor of infancy. Most cases occur within the critical location of these tumors may cause mortality
first year of life, and the tumor is rarely seen after 3 years from local recurrence even without distant metastases.
of age. 25 It is more common in boys and may be well Multimodal therapy including radiation and chemother-
circumscribed or multicentric. Histologically, these tu- apy are required with emphasis on complete surgical
mors are composed of embryonal fat and have a promi- 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 89
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