Adult Chest Surgery

Chapter 137. Resection of Benign Anterior and Middle Mediastinal Cysts and Tumors 

Primary mediastinal tumors are divided for the convenience of diagnosis and surgical approach into three compartments: anterior, middle, and posterior. Each compartment is specific for certain tumors. Rarely does a benign tumor arising in one compartment actively invade another unless it becomes so large in size that it occupies the neighboring space. Furthermore, each compartment has a different malignant potential attributable to the nature of the mediastinal tumors endemic to that space (Table 137-1). This chapter concerns benign mediastinal tumors of the anterior and middle mediastinum (Fig. 137-1); posterior mediastinal tumors are described in Chap. 138.

Table 137-1. Classification of Mediastinal Tumors and Cysts

BENIGN

MALIGNANT

Thymic

Hyperplasia

Invasive thymoma

Thymic cysts

Thymic carcinoma

Encapsulated thymoma

Thymic neuroendocrine tumors

Thymolipoma

Thymic lymphoma

Germ cell tumors

Mature teratoma

Immature teratoma (age >15)

Immature teratoma (age <15)

Teratoma with malignant transformation

Mature teratoma with immature elements <50% of the tumor volume

Seminoma

 

Nonseminomatous germ cell tumors

 

Mixed germ cell tumors

Endocrine tumors

Multinodular substernal goiter

Substernal thyroid cancer

Substernal thyroid

 

Parathyroid substernal adenomas

 

Parathyroid substernal cysts

 

Lymph node masses

Infectious hyperplasia

Lymphoma

Sarcoid hyperplasia of lymph nodes

Metastatic lymphatic enlargement

Castleman's disease

 

Mesenchymal tumors

Lipomatosis

Liposarcoma

Lipoma

 

Fibroma

 

Hemangioma

Angiosarcoma

Hemangioendothelioma

 

Hemangiopericytoma

Malignant hemangiopericytoma

Lymphangioma

Lymphangiosarcoma

Cystic hygroma

 

Mediastinal lymphangioma

Lymphangiopericytoma

Lymphangiomatosis

 

Cysts

Bronchogenic

 

Pericardial

 

Esophageal duplication cysts

 

Mesothelial cysts

 

 

Adapted with permission from ref. 5.

Figure 137-1.

 

Mediastinal tumors are divided for the convenience of diagnosis and surgical approach into three compartments: anterior, middle, and posterior.

The differentiation between benign and malignant mediastinal tumors depends on three major factors: mediastinal location, patient age, and the presence or absence of symptoms.1,2 The pragmatic consequence of dividing benign from malignant mediastinal tumors affects not only overall survival and tumor recurrence but also treatment protocols and surgical approach. Surgical standards mandate the use of larger incisions for resecting malignant mediastinal tumors to prevent local metastasis and to account for factors of size, diffuse adherence, hypervascularity, and local invasion to adjacent structures.However, this is not the case for benign tumors, where the only constraints are patient safety and procedural morbidity. Once these parameters are met, there is greater freedom of choice as to surgical approach, and the only limitations are port placement and incision size, which must be designed to accommodate tumor removal.

Mediastinal tumors are more often benign than malignant (two-thirds are benign). However, tumor status is location-dependent, with malignant potential increasing as one progresses from the posterior to the anterior mediastinal compartment. In a large series of mediastinal tumors, the malignant potential was 59% for anterior mediastinal tumors, 29% for middle mediastinal tumors, and 16% for posterior mediastinal tumors.4

The age of the individual is also a factor in determining the malignant potential. Younger patients are more likely to suffer from neurogenic tumors (the majority are benign), lymphomas, or germ cell tumors (the majority are teratomas) compared with older patients, who tend to have anterior mediastinal tumors, which are often malignant.4–8 Benign tumors are commonly asymptomatic; thus they often are discovered as incidental findings accompanying parallel investigations for other symptoms. Malignant tumors are commonly symptomatic,2,5 possibly related to tumor size, local compression, or systemic symptoms. Malignant mediastinal tumor product expression (e.g., adrenocorticotropic hormone, beta-human chorionic gonadotropin, alpha-fetoprotein, calcium, parathyroid hormone, and acetylcholine receptor antibody levels) or the systemic consequences of these tumors (e.g., myasthenia gravis, pure red blood cell anemia, and agammaglobulinemia), which are suggestive of the malignant potential of a mediastinal mass, thereafter strongly influence the surgical approach. CT-guided mediastinal biopsy is often helpful for separating malignant from benign mediastinal tumors and determining malignant tumors that may require preoperative treatment (e.g., germ cell tumors, Castleman's disease, and possibly thymomas) from tumors that are treated nonsurgically (e.g., lymphomas and multicentric Castleman's disease).

Primary mediastinal tumors arise from mediastinal structures or from local invasion of adjacent mediastinal spaces either from slow growth of the tumor into the neighboring space or because of the arrest of embryonic cells with later tumor growth. Uncommon primary mediastinal tumors usually are mesenchymal. These tumors represent fewer than 10% of primary mediastinal tumors and have a higher prevalence and malignant potential in children.9

BENIGN ANTERIOR MEDIASTINAL TUMORS

Benign anterior mediastinal tumors commonly refer to endocrine tumors, benign thymic masses, teratomas, or lymphoid hyperplasia.

Endocrine Tumors

Substernal goiter is described in Chapter 133. Parathyroid adenomas can manifest in the mediastinum; 20% of patients with parathyroid adenomas have tumors that extend into the mediastinum, but most can be extracted by a neck incision. Parathyroid cysts usually are associated with the inferior parathyroid glands and are classified as functioning or nonfunctioning on the basis of elevated parathyroid hormone levels.Mediastinal exploration is necessary for ectopic mediastinal parathyroid adenomas or cysts, which occur in only 2% of patients; such glands may be reached by thoracoscopic exploration.10 Accurate preoperative localization of these glands can be obtained with technetium sestamibi CT scanning, which, if positive, also can aid with intraoperative localization by gamma probe thoracoscopic identification of the tumor. Confirmation of tumor removal is achieved by intraoperative parathormone assay.11

Thymic Tumors

Benign thymic tumors consist of thymic hyperplasia, thymic cysts, thymolipomas, and lymphoepithelial thymomas. Thymic hyperplasia may occur in association with myasthenia gravis and as an idiopathic response to administration of multiple medical drugs. However, it often occurs with no association to any medical condition. Thymolipoma is an uncommon tumor composed of mature adipose cells and lymphoepithelial cells. The etiology of this tumor is unknown; calcifications and cystic degeneration may occur, as well as the lymphoepithelial component, which may lead to the diagnosis of a mediastinal lipoma. Thymic cysts may occur on a congenital or acquired basis. The acquired form occurs in response to thymic inflammation. The difficulty is in differentiating these tumors from the cystic degeneration that occurs in invasive thymoma. Resection or aspiration may be used to treat these cysts.Surgical resection of benign thymic conditions can be accomplished by many approaches depending on the size of the tumor, the body habitus of the individual, and the experience of the surgeon. Surgical resection for thymic hyperplasia is described in Chapters 134, 135, and 136. A number of surgical approaches can be used for mediastinal tumor removal, including benign thymic conditions. These are summarized in Table 137-2.

Table 137-2. Surgical Approaches for Benign Thymic Conditions

Sternal-sparing procedures

·   Parasternal approach either unilateral or bilateral or in combination with a suprasternal or infrasternal approach32 (see Fig. 137-7)

·   Transcervical route

·   VATS approach33 (see Figs. 137-3 and 137-5)

·   Sternal lift procedure30,31 (see Fig. 137-4)

·   Robotic assisted minimally invasive mediastinal surgery (the expense of the robot is offset by the use of simple cautery instead of more expensive cautery devices)34 (see Fig. 137-6)

 

Sternotomy approaches

·   Partial or complete vertical sternotomy (see Fig. 137-8)

·   Partial or complete sternotomy in combination with a fourth space anterior thoracotomy (trapdoor incision) (see Fig. 137-9)

·   Transverse sternotomy (clamshell incision) (see Fig. 137-10)

 

 

Figure 137-3.

 

Port placement for a VATS approach to benign anterior mediastinal tumors via the right chest.

 

Figure 137-4.

 

A sternal lift procedure can improve visualization of the anterior mediastinal operative field.

 

Figure 137-5.

 

Port placement for a VATS approach to benign middle mediastinal tumors from the right chest.

 

Figure 137-6.

 

Sternal-sparing robotic surgery approach to mediastinal tumors.

 

Figure 137-7.

 

Parasternal approach.

 

Figure 137-8.

 

Partial or vertical sternotomy.

 

Figure 137-9.

 

Partial or complete sternotomy with anterior thoracotomy.

 

Figure 137-10.

 

Transverse sternotomy (clamshell incision).

Thymoma

Thymoma is divided into benign and malignant forms based on the degree of factors of cellular atypia and local invasion. It is more appropriately divided into benign thymoma, invasive thymoma, and thymic carcinoma. Irrespective of the pathologic evaluation of cellular atypia, and irrespective of size, at least 30% of thymomas exhibit capsular involvement and invasion of surrounding structures.2,5 This local infiltration may be impossible to determine preoperatively, which leads to surgical approaches that allow for the invasive possibility of thymoma. Surgical procedures that permit wide margins to prevent local recurrence are considered standard therapy (Fig. 137-2); however, there is ongoing debate in the surgical literature as to the role of thoracoscopy for small, encapsulated thymoma. The video-assisted thoracic surgery (VATS) approach for thymoma is described in the chapter on surgical resection of malignant mediastinal tumors (see Chap. 139).

Figure 137-2.

 

Surgical procedures that permit wide margins to prevent local recurrence are considered standard therapy for thymoma. Shown here is a bilateral clamshell incision.

Teratomas

Teratomas account for 5–10% of all mediastinal tumors, with 95% occurring in the anterior mediastinum and 3–5% in the posterior mediastinum.12,13 There is no sex predilection, and most patients present without symptoms with large tumors. Benign teratomas include mature teratomas (45–75% of patients), mature teratomas with immature elements comprising less than 50% of the volume, and immature teratomas, which occur almost exclusively in patients younger than age 15.5,14 Symptoms related to these tumors usually include pain and occasionally cough, with the possible expectoration of hemoptysis, hair, or sebum.12 Complete excision of mediastinal teratomas is strongly desired to prevent recurrent tumor formation or the complications of chronic fistula formation with infection.15 This may be difficult to do by a VATS approach because of dense adhesions to neighboring structures and owing to the requirement for adequate access sites for large tumor delivery.12

Castleman's Disease

Castleman's disease (i.e., angiofollicular hyperplasia) is a benign form of marked lymph node hyperplasia usually occurring in the mediastinum (70% of patients); it commonly occurs in the anterior compartment, but it can occur in any lymphatic area or rarely in nonnodal areas.16,17 Histologically, it is divided into the hyaline-vascular form (91% of patients, commonly in a solitary location) and the plasma cell form (9% of patients, likely found in multicentric locations). These tumors are unusual and may portend other malignancies. The hyaline-vascular form usually is benign, and recurrence occurs rarely after complete surgical removal, although vascular neoplasms and occasionally lymphomas may occur in long-term follow-up.16–18 The plasma cell variant is often multicentric and aggressive. Its proliferative potential may be attributed to high levels of the cytokine interleukin 6, which may induce Kaposi-like endothelial vascular neoplasms and lymphomas. The solitary and multicentric plasma cell forms of Castleman's disease are strongly associated with infection by human herpesvirus 8, which may induce interleukin 6 production by virally encoded particles into native strands of DNA.18

Surgical resection, by a thoracoscopic route, if possible, is the primary treatment of the localized forms of both types of Castleman's disease. Preoperative angiography and embolization may be helpful to reduce the increased vascularity of these tumors.16,17 Antihuman monoclonal antibodies against interleukin 6 and anti-CD20 monoclonal antibodies against CD20+ B-lymphocytes are potential treatment strategies for the multicentric variant of Castleman's disease, once the diagnosis is confirmed histologically.16,19 Other potential molecular targets for this disease are human herpes virus 8 and angiogenesis factors.19 Both variants of the disease require long-term surveillance for vascular tumors or lymphomas.

BENIGN MIDDLE MEDIASTINAL TUMORS

The classification of mediastinal cysts is based on etiology and encompasses bronchogenic cysts, esophageal duplication cysts of foregut origin, mesothelial-derived pericardial/pleural cysts, thymic cysts, and other miscellaneous cysts. Foregut cysts are believed to result from abnormal budding or division of the primitive foregut20,21 and share a similar embryogenesis to congenital cystic lesions of the lung parenchyma.21,22 In a broad sense, these disease entities are categorized into bronchopulmonary foregut malformations, such as pulmonary sequestration, congenital cystic adenomatoid malformation, congenital lobar emphysema, and bronchogenic pulmonary cysts.

Bronchogenic and Pericardial Cysts

Mediastinal cysts may arise from numerous sources and include lymphangiomas (i.e., cystic hygromas), meningoceles, thymic cysts, parathyroid cysts, pericardial cysts, pancreatic cysts, thoracic duct cysts, teratomatous cysts, and foregut cysts (e.g., bronchogenic, esophageal and neuroenteric). Mediastinal cysts are reported to represent 18–25% of all primary mediastinal mass lesions. Bronchogenic cysts and pericardial cysts are the most common according to Takeda and colleagues and Magee and colleagues.23,24 Bronchogenic cysts are found most commonly in the middle mediastinum, but they also may occur in any of the mediastinal compartments, as described by Ribet and colleagues and Cioffi and colleagues.25,26 Bronchogenic and pericardial cysts in adults typically are asymptomatic and present as an incidental finding on routine chest roentgenograms. Diagnosis usually is confirmed by chest CT scan demonstrating a simple cyst with low attenuation. Expectant management in the young, asymptomatic patient with classic features of a bronchogenic or pericardial cyst on CT scan can be performed, with appropriate follow-up by interval CT scans. However, if the diagnosis of a simple cyst is uncertain because the attenuation of the cyst contents is high or if the cyst is multiloculated, then surgical resection is indicated. Likewise, if the cyst becomes clinically symptomatic or infected, then cyst excision is warranted. Some authorities suggest surgical resection of asymptomatic cysts because of the high rate of future symptom development, which could jeopardize surrounding mediastinal structures.26 Mediastinal cysts often represent ideal lesions for resection by minimally invasive techniques.26,27 Surgical excision offers the advantages of complete and definitive treatment, elimination of the mediastinal mass and prevention of any potential complications, relief of symptoms when present, and histologic evaluation. It is important to emphasize that these cysts can be very adherent and difficult to excise from adjacent vital structures. Incomplete resection may result in a recurrence or continued fluid production by the residual cyst wall; when the cyst cannot be removed completely, partial excision with cautery destruction of the epithelial mucosal lining is an acceptable alternative, as described by Ferguson.28

Pericardial cysts are uncommon mediastinal anomalies. They result from failure of one or more fetal lacunae to coalesce into the pericardium. They commonly appear multilocular, but most are unilocular and contain clear, water-like fluid. Most cysts are found in the right costophrenic angle, and as many as a third of patients may have associated symptoms. Unlike bronchogenic cysts, which carry a risk of infection, pericardial cysts usually follow a benign course and infrequently need intervention. Thoracoscopy is recommended for symptomatic lesions and when the diagnosis is uncertain, as described by Song and colleagues.29

BENIGN MEDIASTINAL MESENCHYMAL TUMORS

Mesenchymal tumors of the mediastinum are rare (fewer than 5–10% of all primary mediastinal tumors); 55% of these tumors are malignant, and they may occupy any compartment5,9 (see Table 137-1). These tumors have various origins, including tumors of adipose tissue: lipomatosis, liposarcoma, and lipoma. The predominant vascular tissue tumor is the hemangioma, of which there are three variants: cavernous, capillary, and venous. Surgical excision is the best treatment for hemangioma, possibly accompanied by treatment with interferon-2. The lymphatic tissue tumors include lymphangioma (e.g., cystic lymphangioma or cavernous lymphangioma). These tumors are associated with several syndromes (e.g., Gorham's disease, Klippel-Trenaunay syndrome, and Servelle-Martorell disease), and they may cause severe intractable chylous effusions. They also have a tendency to envelope surrounding structures, which prevents their complete removal and may lead to postoperative chylous leak. The tumors of fibrous or myofibroblastic origin include mediastinal fibromatosis and solitary fibrous tumor of the mediastinum. Tumors of muscle origin include the leiomyomas.

SURGICAL TECHNIQUES

VATS Surgery for Anterior or Middle Mediastinal Tumors

The selection of minimal-access surgical approach for mediastinal tumors will depend on the size and location of the tumor (anterior/superior, anterior/inferior, or middle mediastinum) as well as the invasion or involvement of neighboring structures. The thoracic surgeon contemplating a VATS approach for mediastinal surgery should be prepared to convert to either a thoracotomy or a sternotomy as appropriate for unexpected mediastinal findings. Access to the anterior mediastinum by thoracoscopic or robotic approaches can be performed with single- or two-lung ventilation. Bilateral lung ventilation with low tidal volumes for anterior tumors may be as effective as single-lung ventilation if the patient is positioned appropriately so that lung ventilation obscures only the posterior and middle mediastinum. The patient may be placed supine or with the chest elevated 30 degrees, which permits anterior visualization with two-lung ventilation. Middle or posterior mediastinal VATS surgery or the full lateral position will require absence of ventilation to the ipsilateral lung.

In general, benign anterior mediastinal tumors are accessed primarily from the right chest with camera ports placed in the fifth or sixth intercostal space in the midaxillary line (Fig. 137-3). Other accessory ports for manipulation and removal of the tumor are placed in the second to fourth intercostal spaces as needed. The left chest also can be accessed when the anterior chest is included in the operative field for direct observation of the left phrenic nerve or if a left-sided resection is needed. VATS surgery via the left chest approach is more difficult than that on the right side because of impingement of the heart on the operative field.

Unique techniques to improve visualization of the anterior mediastinal operative field are a sternal lift procedure30 (Fig. 137-4) and a video-assisted subxiphoid approach, as described by Hsu and colleagues.31 Cystic lesions of the mediastinum may be dissected or marsupialized more easily if they are decompressed by intraoperative needle aspiration. Bipolar or unipolar cautery or a Harmonic scalpel will help to dissect these tumors from surrounding structures while minimizing bleeding from small vessels. Middle mediastinal benign tumors are also accessed principally from the right chest with the camera port placed in the fourth or fifth intercostal space in the midaxillary line (Fig. 137-5).

SUMMARY

It is important to separate benign anterior and middle mediastinal lesions from their malignant counterparts. This often can done on the basis of location, age, symptoms, and biochemical markers. Minimally invasive techniques have been introduced that permit sternal-sparing surgery for the removal of benign mediastinal tumors. Sternotomy approaches still may be still required, however, for benign large tumors, hypervascular tumors, or those with significant adhesions to surrounding mediastinal structures.

EDITOR'S COMMENT

Historically, mediastinal cysts and benign conditions were surgical conditions because preoperative imaging was limited or misleading. In contrast, modern imaging techniques not only clarify the likely diagnosis, but also estimate the likelihood of secondary complications (local compression, infection, etc.). With advances in imaging technology, an increasing percentage of these patients will not require surgery.

–SJM

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