Mediastinal Tumors

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Last modified 26/02/2015

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Mediastinal Tumors

The mediastinum can be divided into three compartments (Fig. 25-1). The anterior one contains the thymus, vessels, lymphoid structures, and nerves. The middle one contains the trachea, main-stem bronchi, the heart and great vessels, and the hilar lymph nodes. The posterior mediastinum accommodates the aorta, the thoracic esophagus, and the sympathetic nerve chains.

The tracheobronchial tree derives from the embryonic foregut that is innervated by neural crest cells that form the sympathetic chains. Embryonal germ cells migrate toward their final settlement in the gonads through the anterior mediastinum. The thymus primordia from the third pharyngeal pouches migrate into the anterior mediastinum and fuse to form a single organ. Finally, huge vascular structures develop in the mediastinum. All these embryonal events explain the nature of the tumors located in each compartment. Their most frequent location is summarized in Table 25-1.

Clinical Features

Mediastinal tumors and cysts are occasionally diagnosed before birth and may even benefit from prenatal instrumentation.1 However, most of them remain silent during infancy and are discovered serendipitously. Respiratory embarrassment, orthopnea, stridor, wheezing, severe distress, and superior vena cava syndrome are occasionally seen. Large anterior tumors may cause sternal bulging. Recurrent laryngeal or phrenic nerve palsies or Horner syndrome may also lead to diagnosis. Sudden paraplegia can occur in dumbbell tumors involving the spinal cord. Finally, secretion of catecholamines, α-fetoprotein, or gonadotropins may also uncover the tumor.

Diagnostic Methods

Plain radiographs of the thorax or ultrasonography may show widening of the superior mediastinal shadow or masses in either hemithorax.2,3 Computed tomography (CT) provides information about the location of the tumor, its cystic or solid nature, depicting calcifications, necrotic areas, and widening of the spinal foramina in cases with intraspinal extension. Calcifications are suggestive of neuroblastoma or teratoma, but other tumors, such as lymphangiomas or histiocytoses, can also have calcified areas.4,5 CT is crucial for assessing the patency of the airway and the risks of anesthesia.6 Magnetic resonance imaging (MRI) is used to better define the nature of the masses of vascular origin, and also for evaluating intraspinal invasion.7,8

For many tumors, histology, cell markers, and molecular biology features can be identified before undertaking operative therapy. Cells can be obtained by biopsy of cervical or suprasternal lymph nodes, by fine needle aspiration (FNA), or by pleural or pericardial fluid aspiration.9–11 When this is not feasible, operative biopsy or excision is required. Thoracoscopy12,13 or anterior mini-thoracotomy through the bed of the second or third rib (the Chamberlain approach)14,15 may provide material for biopsy or for complete removal. Mediastinoscopy is rarely used in children.16

Principles of Management

Children with anterior mediastinal masses can undergo respiratory collapse after induction of anesthesia. Ventilation can be critically difficult, particularly in children with lymphoma. Cross-sectional surfaces of the tracheal lumen decreased by 50% or more on CT scan carry a high anesthetic risk.14 These patients also have marked reductions in the maximum expiratory flow rates, and special modalities of anesthesia (e.g., spontaneous ventilation, laryngeal mask, rigid tubes) may be necessary.6

Except for lymphomas that respond to chemotherapy and/or radiotherapy and in which surgery is usually adjuvant, mediastinal tumors should be removed. Median sternotomy17 or standard thoracotomy are the preferred approaches. Sternotomy extended to the neck allows safe approach for large cervicothoracic masses (Fig. 25-2).18 Thoracoscopy is an alternative approach, and should respect the principles of oncologic surgery, avoiding spillage of tumor cells or fluids (particularly true for germ cell tumors).17,19,20 Robotic surgery has also been described.21

Lymphoma

Non-Hodgkin Lymphoma (NHL)

This systemic disease is one of the more frequent mediastinal tumors characterized by massive proliferation of lymphoblasts in the lymph nodes. These cells can ontogenically differentiate into B-cells (related to humoral immunity and produced in the bone marrow) and T-cells (involved in cellular immunity and processed in the thymus). In children, B-cells cause undifferentiated Burkitt or non-Burkitt lymphomas, which together constitute about 50% of all lymphomas. T-cells cause lymphoblastic lymphomas (about 40%) that are generally found in the thymus and/or anterior mediastinal lymph nodes. The remaining 10% correspond to large cell lymphomas. These are similar to undifferentiated tumors, but may be of T- or B-cell origin and appear on either side of the diaphragm.

Undifferentiated lymphomas express surface IgM and CD19 and CD20 antigens, whereas lymphoblastic lymphomas contain the enzyme TdT (terminal deoxynucleotidyl transferase) and express T-cell markers such as CD5 and CD7.22 Burkitt-type lymphomas often have 8 : 14, and less often 8 : 22 or 2 : 8 translocations, involving the MYCC proto-oncogene, whereas T-cell lymphomas occasionally have 14q11 translocations.15,23

At the time of diagnosis, NHLs are usually spread beyond the original site and involve the regional nodes and distant organs such as the pleural or pericardial spaces or the bone marrow. (In this case, they are indistinguishable from acute lymphoblastic leukemia.)

Rapid growth of mediastinal lymphomas may cause respiratory distress, wheezing, orthopnea, cervicofacial edema, and jugular ingurgitation. Systemic symptoms are possible, and bone marrow invasion causes hematologic disturbances. Enlarged lymph nodes may become palpable in the neck, axillae, and supraclavicular or suprasternal regions.

Imaging depicts an enlarged mediastinum and airway involvement. Pleural or pericardial fluid can often be obtained for cytologic analysis.11 If neither peripheral lymph nodes nor fluids are available for biopsy or cytology, FNA or biopsy by thoracoscopy or the anterior Chamberlain approach may be necessary. In all cases, the anesthetic risks and precautions should be emphasized.24

Mediastinal NHL cases are stage III except when bone marrow and/or central nervous system are involved (stage IV).25 Gallium-67 isotopic scanning may be helpful for staging.26,27 The role of combined positron emission tomography (PET) and CT in children is still undefined.

Mediastinal NHL respond well to chemotherapy and corticosteroids, and the contribution of surgery is limited to retrieval of biopsy material for cytologic assessment. Chemotherapy leads to long-term survival in more than 80% of these children.25,28

Hodgkin Lymphoma

Mediastinal Hodgkin lymphoma is less frequent and occurs more often in adolescents. The main feature is the Reed–Sternberg cell, the malignant counterpart of the dendritic interdigitating cell that has a role in antigen presentation. These cells are embedded in lymph nodes in which the proportions of fibrous stroma, lymphocytes, and plasma cells are variable, allowing classification into lymphocyte predominant, lymphocyte depleted, mixed cellularity, and nodular sclerosis types. Most children with Hodgkin lymphoma have the nodular sclerosis type, but the youngest ones may have lymphocyte predominant or mixed cellularity varieties.29 Hodgkin lymphoma originates in one group of lymph nodes and spreads to contiguous or distant nodes. Accurate staging is imperative before selection of the treatment protocol. The Ann Arbor classification of four stages with subgroups, according to the presence or absence of systemic symptoms, remains the most widely used system, but mapping of the involved organs or lymph node groups requires refined imaging tools.

Hodgkin lymphoma may be localized primarily in the mediastinum and may cause the same compressive effects as NHL (Fig. 25-3). Biopsies of extrathoracic nodes are sometimes possible. If not, the Chamberlain operation or thoracoscopy should be used. The preference for chemotherapy over radiotherapy has limited the use of staging laparotomy in children. This should be reserved for cases with thoracic stage II cases in which localized radiotherapy as the sole treatment requires excluding transdiaphragmatic involvement.30 PET/CT seems promising as a noninvasive staging modality.29,31

Surgery is not usually the primary treatment of Hodgkin lymphoma, except in very localized cases. However, it may occasionally be needed in children.32

Germ Cell Tumors

The primitive germ cells may produce various types of tumors. Gonadal germ cells cause seminoma or dysgerminoma whereas totipotential cells can cause yolk sac tumors and choriocarcinoma (extraembryonic) or teratomas (embryonic). In fact, these different components can be found in the same tumor.

Teratomas

These comprise only 8–16% of the tumors in this region and are uncommon in children.33,34 They consist of solid or organoid masses containing tissues derived from all three blastodermic layers. Their histologic features are heterogeneous and may include cystic or solid areas as well as mature and immature components. Their incidence is higher in individuals with Klinefelter syndrome.35,36

Mediastinal teratomas originate most often from the thymus or pericardium and are therefore anterior. They are as frequent in girls as in boys, in contrast to the situation in adults in whom there is a clear male predominance.37,38 They develop relatively early in fetal life, and may cause hydrops and fetal demise.1,39 These masses can be diagnosed prenatally (Fig. 25-4), but they are more often detected after birth because of respiratory distress or later in life because of vague symptoms (thoracic or cervical pain, dyspnea). The diagnosis is often incidental. Mediastinal teratomas should be suspected whenever a mass with or without calcifications is detected in the anterior mediastinal compartment. However, this diagnosis often is not made until the operation. Most mediastinal teratomas are benign in children, but the prognosis is definitely worse if they contain elements of yolk sac, embryonal carcinoma, seminoma, germinoma, or choriocarcinoma.35,40,41 Some of these lesions may induce precocious puberty or detectable pancreatic secretions.35,42

Operative excision is the treatment of choice. Median sternotomy allows excellent exposure, but lateral thoracotomies may be preferred when the tumor extends into either hemithorax. Thoracoscopy has also been used.43 Chemotherapy with carboplatin, bleomycin, and etoposide may allow for complete removal after tumor shrinkage in cases that cannot be initially excised.35 Although wide adherence to adjacent tissues usually makes a complete resection difficult, it is essential to avoid recurrence. In fact, these tumors have an excellent prognosis when resection is complete. α-Fetoprotein is a good tumor marker because it is usually elevated in malignant and immature tumors and very seldom in mature ones.44