Masses of the Anterior Mediastinum



  • Lymphoid follicular thymic hyperplasia (autoimmune thymitis): Replacement of the thymic cortex with multiple lymphoid follicles and germinal centers. The tissue retains its shape but may become enlarged. This occurs primarily in myasthenia gravis. This form of hyperplasia can also be associated with systemic lupus erythematosus, thyrotoxicosis, and Addison’s disease.

  • True thymic hyperplasia: Enlargement of the thymus without disruption of normal histological architecture. It is associated with thyrotoxicosis, Graves’ disease, acromegaly, and red cell aplasia. Another form of true thymic hyperplasia is thymic rebound. This is the enlargement of the thymus just after the resolution of a stressful event such as chemotherapy.

  • Thymolipoma: Benign, slow-growing lesion of adipose and lymphoepithelial thymic tissue. These tumors may grow to a very large size.

  • Thymic cysts: These are fluid-filled cysts that can be congenital or acquired. The acquired form is most common and can develop following radiation for Hodgkin’s disease and be of no consequence. However, they may be seen in thymomas, lymphomas, and seminomas; therefore, they require further malignancy workup. They can also be seen in systemic inflammatory diseases such as lupus and Sjögren’s syndrome. The congenital type of thymic cyst represents a benign remnant of the thymopharyngeal duct.

  • Thymoma: Thymic neoplasm distinguishes itself from thymic carcinoma both by histology and by its indolent behavior. Once the tumor’s surrounding capsule has been traversed, it is referred to as invasive thymoma. This lesion is associated with paraneoplastic syndromes, which include myasthenia gravis, acquired hypogammaglobulinemia, and pure red cell aplasia.

  • Thymic lymphoma: The thymus is most commonly invaded by the nodular sclerosing type of Hodgkin’s lymphoma (HL) than any other type of lymphoma. The non-Hodgkin’s lymphoma (NHL) types seen most often are T-cell lymphoblastic lymphoma and primary mediastinal large B-cell lymphoma.

  • Thymic carcinoid: A neuroendocrine malignant disorder that is aggressive but exceedingly rare. It is associated with multiple endocrine neoplasia (MEN) 1 syndrome.

  • Thymic germ cell tumor: They can be either benign or malignant lesions that originate from mediastinal germ cells. They include benign or malignant teratoma, seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and mixed types. Seminomas are locally invasive whereas the nonseminomatous malignant germ cell tumors present frequently with distant metastatic lesions.


  • Thymic hyperplasia: 50% to 70% of patients with myasthenia gravis have thymic lymphoid hyperplasia.

  • Thymolipoma accounts for 1% to 10% of all thymic tumors. It can affect any age group but most commonly young adults.

  • Thymic cysts are found in 3% of identified anterior mediastinal masses.

  • Thymoma: Accounts for 20% of all mediastinal tumors and 50% of anterior mediastinal masses. The overall incidence is 0.15 cases per 100,000. The peak incidence is found in the fourth to sixth decades of life and equally in both genders.

    • Although 34% of thymomas are found to directly invade their capsules and grow into surrounding structures and 75% of those lesions involve pleura or pericardium, only 3% of thymomas metastasize outside the chest.

    • Ten to fifteen percent of patients with myasthenia gravis are found to have thymomas. Forty percent of thymoma patients have a paraneoplastic condition, of which 20% to 25% is myasthenia gravis. Ten percent of thymoma patients have hypogammaglobulinemia, and 5% to 10% have red cell aplasia.

  • Malignant thymoma is an indolent tumor arising from the thymic epithelial cells located in the anterior mediastinum. These tumor cells spread via regional metastases or invade surrounding structures including the pleural space.

  • Thymic lymphoma: Of those patients newly diagnosed with Hodgkin’s disease, about one third will have thymic enlargement. The thymus may be the primary site of the lymphoma or enlarged secondary to invasion of adjacent lymph nodes. Two percent of patients with NHL will have thymic medullary B-cell lymphoma. It is slightly more common in women, and patients present at a median age of 30 years.

  • Thymic carcinoid: Rare disorder seen in approximately 3% of patients with multiple endocrine neoplasia type 1 syndrome. It has a high male predominance, and the average patient is between 30 and 40 years of age at the time of diagnosis. This tumor is almost never associated with Cushing’s syndrome or carcinoid when it is part of the MEN 1 syndrome. However, 30% to 40% of sporadic cases have Cushing’s syndrome.

  • Thymic germ cell tumor: The most common sites for extragonadal germ cell tumors are within or around the thymus. They are usually seen in adolescents or young adults and represent 15% of anterior mediastinal masses. Sixty to eighty percent are benign, but when malignant, 90% are in men. The most common type is the benign teratoma. Approximately 20% of patients with nonseminomatous germ cell tumors have Klinefelter’s syndrome, which is a frequent cause of mortality in these patients.


  • In true thymic hyperplasia , the normal thymus architecture is preserved, whereas in follicular thymic hyperplasia , there is a replacement with multiple lymphoid follicles and germinal centers.

  • Thymolipoma: Lesions contain mature adipose cells and normal thymic tissue. Histologically, there are no germinal centers with the frequent presence of cystic degeneration of the Hassall bodies.

  • Thymic cyst: Biopsy should show foci of normal tissue, because imaging studies cannot rule out the possibility of malignancy.

  • Thymoma: Keratin-containing, p63-positive thymic epithelium characterized by no more than moderate atypia on microscopy.

  • Malignant thymoma: A tissue sample is required for diagnosis of malignant thymoma and to rule out other possible diagnoses including lymphoma and thymic carcinoma. Peripherally located lesions can be accessed via computed tomography (CT)–guided core biopsy or an anterior mediastinotomy (which provides a larger piece of tissue and higher diagnostic yield), whereas paratracheal tumors may be approached via bronchoscopy or mediastinoscopy. Histolologic features consist of a mixture of keratin-positive neoplastic epithelial cells and lymphocytes subdivided by fibrous bands ( Figs. 42-1 through 42-4 ).

    Figure 42-1

    Histopathologic specimen obtained via computed tomography–guided core pleural biopsy shows a neoplastic proliferation composed of a mixture of lymphocytes and keratin-positive epithelial cells with fibrous bands consistent with thymoma (H&E stain, 10×).

    Figure 42-2

    Histopathologic specimen obtained via computed tomography–guided core pleural biopsy shows a neoplastic proliferation composed of a mixture of lymphocytes and keratin-positive epithelial cells with fibrous bands consistent with thymoma (H&E stain, 100×).

    Figure 42-3

    Histopathologic specimen obtained via computed tomography–guided core pleural biopsy shows a mixture of keratin positive neoplastic epithelial cells and lymphocytes subdivided by fibrous bands consistent with thymoma (Keratin stain, 10×).

    Figure 42-4

    Histopathological specimen obtained via CT guided core pleural biopsy shows a mixture of keratin positive neoplastic epithelial cells and lymphocytes subdivided by fibrous bands consistent with thymoma (Keratin stain, 10×).

  • Thymic lymphoma: HL shows classic Reed-Sternberg cells on microscopy with CD15 and CD30 positivity. Thymic large B-cell lymphoma is a distinct entity of B-cell lymphoma. Microscopy frequently shows mononuclear Reed-Sternberg cell variants, cells with pale “clear” cytoplasms and with clear delicate bands of fibrosis and unlike other B-cell lymphomas, often lacks surface immunoglobulin G (IgG). However, as seen in other B-cell lymphomas, it will demonstrate CD19, CD20, and CD22 positivity.

  • Thymic carcinoid: It is a neuroendocrine tumor histologically similar to atypical bronchial carcinoids. It is characterized by homogenous polygonal cells arranged in a rosette or trabecular pattern lacking lymphocytic and epithelial components.

  • Thymic germ cell tumor: Benign teratoma contains mature tissue from different cell lines such as fat, cartilage, muscle, and bone. If a teratoma is found to have fetal or neuroendocrine tissue, it is considered a malignant tumor.


  • The thymus is a lymphopoietic organ in which T-cell maturation primarily takes place. The size and contour of this gland change dramatically over one’s lifetime. At around age 20 years, 80% of the gland has undergone fatty involution, which is complete after the age of 60 years.

  • The thymus, a bilobed organ at the base of the neck, travels into the anterior compartment of the mediastinum. It lies behind the manubrium and the pericardium. The inferior aspect reaches the level of the 4th rib.

  • Ectopic thymus tissue may be found in any of the mediastinal compartments and even the neck. More commonly, a lobe of the thymus can be found posterior to the brachiocephalic vein.

  • The blood supply of the thymus comes primarily from the internal mammary arteries via the anterior intercostal and mediastinal branches. The gland may also receive branches from the inferior thyroid arteries.


Clinical Presentation

  • Most thymic masses present as an incidental finding on chest imaging. For example, 90% of thymomas identified in one large study were asymptomatic at the time of diagnosis.

  • Patients may complain of a nonspecific chest fullness or mild pain.

  • If the lesions are large enough to compress central pulmonary structures, they may present as recurrent lung infections or shortness of breath. Dyspnea may again be seen with associated recurrent pulmonary effusions or paralysis of the phrenic nerve due to extension of the tumor into the nerve.

  • Facial plethora may be evident secondary to compression of the superior vena cava.

  • Both thymoma and follicular thymic hyperplasia are associated with myasthenia gravis.

    • This disorder is characterized by reduction in muscle strength from somatic or autonomic muscles used repeatedly without rest.

    • The most common initial presentation, appearing in 65% of patients, is that of ocular muscle weakness. The patient will note diplopia or the clinician will observe progressive ptosis in a patient asked to stare at an object without blinking.

    • Patients may complain of difficulty swallowing secondary to pharyngeal muscle weakness or dysarthria secondary to weakness in the glossal muscles.

    • In 1% of patients, the initial presentation is respiratory failure.

  • Patients with invasive thymoma are typically diagnosed in the fourth or fifth decade of life.

    • They present with constitutional symptoms or symptoms related to tumor compression.

    • In severe cases, malignant thymoma results in superior vena cava syndrome due to local invasion and compression.

  • Thymic lymphoma: Owing to the fast growing nature of mediastinal B-cell lymphoma, respiratory symptoms are pronounced at onset, with 30% to 50% presenting with clinical evidence of superior vena cava obstruction. Masses larger than 10 cm at presentation are commonly seen. The mass may even be palpable in the supraclavicular fossa.

  • Thymic carcinoid: These patients may present with a history of parathyroid, enteropancreatic endocrine tissue (insulinoma) and/or anterior pituitary gland neoplasms as part of the MEN 1 syndrome. The tumor progresses insidiously, and the majority of patients present with an abnormal chest x-ray (CXR), chest CT, or gradual chest discomfort. The rare patients who have clinical carcinoid syndrome will complain of episodic facial flushing accompanied by a presyncopal sensation. They may also complain of frequent diarrhea. Cushing’s syndrome is more commonly seen than carcinoid syndrome when the patient does not have MEN 1 syndrome. The presentation of Cushing’s syndrome includes progressive obesity with characteristic large fat pads behind the neck and above the clavicles, poorly controlled chronic hypertension, skin atrophy, and purple abdominal striae.

  • Thymic germ cell tumor: Patients with benign teratomas can have large mediastinal masses without any symptoms. However, teratomas can cause local injury if they contain active pancreatic tissue producing amylase. In this setting, the patient may present with recurrent effusions, chest pain, tamponade via inflammation of the surrounding tissues, or a cough that may lead to expectoration of the oily contents of the teratoma.


Laboratory Studies

  • Seventy to ninety percent of patients with myasthenia gravis have a positive acetylcholine receptor antibody test, and this test is extremely specific for the disease.

  • In red cell aplasia, the patient has profound anemia with a reticulocyte count of virtually zero.

  • If thymic carcinoid is suspected, the patient may have elevated parathyroid levels with hypercalcemia, elevated prolactin, serotonin, gastrin or insulin levels as part of the multiple MEN 1 syndrome.

  • When not part of the MEN 1 syndrome, thymic carcinoid may cause Cushing’s syndrome. This can be diagnosed by showing an elevated 24-hour urinary excretion of cortisol. These patients are also at risk for carcinoid syndrome, the diagnosis of which is achieved through the measurement of 24-hour serotonin (5-hydroxyindoleacetic acid) urinary excretion. This test is 75% sensitive and almost 100% specific.

  • More aggressive thymic germ cell tumors such as choriocarcinomas, embryonal cell carcinomas, and yolk sac tumors typically express alpha-fetoprotein (AFP) or human chorionic gonadotropin (hCG).

Imaging Studies

  • Positron emission tomography (PET) Scan

    • Not commonly used to classify thymic masses as young adults or people following stressful events can show an increase in fluorodeoxyglucose (FDG) uptake with a normal thymus. The PET scan does not differentiate between thymic hyperplasia and a thymic malignancy. It can be used to look for nodal or distant metastases.

  • CT Scan

    • The maximum anteroposterior diameter for a normal thymus is 1.8 cm for people younger than 20 years of age and 1.3 cm in older people.

    • Thymoma

      • Appears as a homogenous, well-defined mass extending to one side of the anterior mediastinum that is usually 5 to 10 cm at the time of diagnosis. They are usually not associated with adenopathy ( Fig. 42-5 ).

        Figure 42-5

        Contrast-enhanced computed tomography scan shows a partially lobulated, homogeneously enhancing anterior mediastinal mass. Histopathologic analysis demonstrated an invasive thymoma.

      • Thymomas may have areas of calcification and may extend to and even traverse the diaphragm via the retrocrural space.

      • Other radiographic features that are more commonly seen with invasive thymomas include calcification or cystic spaces within the mass and local invasion with pleural effusion and thickening. It is unusual for the disease to present as a massive pleural and mediastinal based mass ( Fig. 42-6 ).

        Figure 42-6

        Contrast-enhanced computed tomography scan shows a large mediastinal- and pleural-based mass with calcification and loculated pleural effusion. Histopathologic analysis demonstrated an invasive thymoma.

      • In severe cases, a malignant thymoma can invade the superior vena cava ( Fig. 42-7 ).

        Figure 42-7

        Contrast-enhanced computed tomography scan shows a homogeneously enhancing anterior mediastinal mass with invasion of the superior vena cava. Histopathologic analysis demonstrated an invasive thymoma.

      • The CT scan should be performed with intravenous (IV) contrast (preferably given in an IV in the left arm) to assess the brachiocephalic vessels for surgical consideration.

      • The images can show occlusion; however, they are imprecise for distinguishing vessel abutment from invasion.

    • Thymolipoma: It appears as a mediastinal mass of fat or soft tissue attenuation connected to the thymus by a small pedicle. This mass is often described as bell shaped. It may also appear as diffuse fatty involvement without a discrete lesion. Thymolipomas may be very large.

    • Thymic cyst: Cystic structures with clearly defined walls form classic thymic cysts ( Fig. 42-8 ). Congenital lesions are usually unilocular, whereas acquired lesions are multilocular. Thymic cysts may be associated with thymomas or lymphoma. Resection is the only way to absolutely differentiate between a benign cyst versus a cystic thymoma or lymphoma.

      Figure 42-8

      Contrast-enhanced computed tomography scan shows a homogeneous, smooth anterior mediastinal mass with water density attenuation and well-defined cyst walls. Histopathologic analysis demonstrated a cystic thymoma.

    • Thymic germ cell tumor: Teratomas usually are well-defined, round lesions with cystic and solid areas. Areas of fat and calcification may be present and represent the different tissue types within. Lesions lacking clear margins or distinct tissue types are more likely to be malignant. Teratoma usually contain an oily substance and may contain structures such as teeth.

  • Magnetic resonance imaging (MRI) scan

    • Thymoma: The MRI scan may assess invasion better than a CT scan ( Fig. 42-9 ). The thymoma generally has similar signal characteristics to normal thyroid tissue and usually enhances homogenously; however, evidence of cyst formation, hemorrhage, and necrosis may also be seen.

      Figure 42-9

      Magnetic resonance imaging scan showing an anterior mediastinal mass with clear invasion of the superior vena cava. Histopathologic analysis demonstrated an invasive thymoma.

  • Nuclear imaging

    • Octreotide scan: A radiolabeled somatostatin analogue is administered and has been found to bind to more than 80% of neuroendocrine tumors, such as thymic carcinoid , to aid in tumor identification and localization.

  • Other testing

    • Edrophonium (tensilon) test: This is the most rapid test for myasthenia gravis in which a cholinesterase inhibitor is administered in a carefully monitored condition to clinically observe for reversal of the characteristic weakness of the disorder. This test is 90% sensitive but may be falsely positive in a number of neuromuscular conditions.

    • Electromyography (EMG): Repetitive stimulation electromyography is only 50% sensitive for myasthenia gravis unless single-fiber EMG is used, which boosts the sensitivity to 90%. The single-fiber EMG is a specialized test not commonly available in most hospitals.

Tissue Diagnosis

  • If tumor markers (β-hCG and alpha-feto protein) are elevated, the diagnosis is mediastinal germ cell tumor so no tissue diagnosis is needed.

  • Otherwise, the appearance of the lesion on CT scan helps if an incisional biopsy or a resection should be performed. A thymectomy should be performed for small, apparently encapsulated lesions. Larger masses with indistinct margins should be biopsied first to determine if the mass is a lymphoma or to diagnose a stage 3 thymoma for neoadjuvant treatment.

  • If a resectable thymoma is suspected, it is usually resected through a median sternotomy.

  • If lymphoma is suspected, an anterior mediastinotomy (Chamberlain procedure) is performed to obtain adequate tissue for diagnosis. This involves a 3- to 4-cm incision over the cartilaginous portion of the second rib. This is usually an outpatient procedure. Intraoperative frozen sections as well as fine-needle aspirations (FNAs) are poor at distinguishing between lymphomas and thymomas. The surgeon usually waits till the permanent section slides are available to decide to proceed with thymectomy for thymoma. FNA does not provide enough material for flow cytometry. A core needle biopsy may provide sufficient material to make the diagnosis.

  • Patients in whom lymphoma is suspected should be examined for lymphadenopathy because performing tissue biopsy from an easy-to-access lymph node is far easier than obtaining tissue directly from the thymus.


  • Thymolipoma: This tumor is not associated with any malignancy, or immunologic or endocrine disorders. Surgical removal is curative.

  • Thymoma: Lesions in which the capsule remains intact (noninvasive thymomas) have an 80% 5-year survival rate. Those lesions that invade beyond the capsule (invasive thymomas) have only a 23% 5-year survival rate. Owing to advancements in the management of myasthenia gravis, this paraneoplastic syndrome does not affect prognosis.

  • Thymic lymphoma:

    • Primary mediastinal large B-cell lymphoma, unlike diffuse B-cell lymphoma, rarely extends to extrathoracic structures. However, it aggressively invades lung, pericardium and even breast. Rarely, this tumor can involve bone marrow, and a bone marrow biopsy is required for accurate staging.

    • Typical chemotherapy regimens for mediastinal large B-cell lymphoma have an approximate 70% survival rate after 2 years ; however, some newer chemotherapy trials have shown initial survival rates of greater than 90%.

    • Bulky tumors (greater than 50% of the transverse diameter of the chest) have a worse prognosis.

    • The most widely recognized predictor of outcome for primary mediastinal B-cell lymphoma is the level of success of the initial round of chemotherapy. Because there is a poor correlation between the size of the residual mediastinal mass post-chemotherapy and the rate of recurrence, nuclear imaging is of great value. A bulky mediastinal mass that remains after a round of therapy can represent simply a collection of fibrotic tissue.

    • There are many other types of thymic lymphomas that are associated with extremely high mortality rates, but they are exceedingly rare.

  • Thymic carcinoid: This condition has a poor prognosis, with more than 70% of patients developing metastases within 5 years. However, the tumors may progress slowly so that long-term survival with distant metastases does occur.

  • Thymic germ cell tumor: It is very rare for mature teratomas to transform into cancer, and generally resection of teratomas is curative. Malignant germ cell tumors account for 1% to 4% of mediastinal tumors. Among the malignant germ cell tumors, seminomas have a considerably better prognosis because they are very responsive to radiation and chemotherapy. They have a 60% to 80% long-term survival rate. The nonseminomatous germ cell tumors are much more aggressive, with 85% to 95% presenting with at least one metastasis. Even with aggressive therapy, few of these patients live beyond 1 year and almost no patients have survived beyond 5 years.


  • For treatment of myasthenia gravis, in one large study, therapeutic or prophylactic thymectomy has shown no advantage over medical management of the illness alone. This retrospective review of 1976 patients from 1940 to 2000 showed that medical management alone produced increasingly better remission rates than a thymectomy. However, certain scenarios did show significant benefit of thymectomy, such as in women who are ventilator dependent. Other series have shown significant benefit to thymectomy, with a 40% complete remission for myasthenia gravis after thymectomy and improvement in another 40%.

  • Thymoma:

    • The Masaoka stage is currently the most widely used staging system for thymomas and helps to determine the management plan ( Table 42-1 ).

      • Stage I malignant thymoma demonstrates encapsulation without microscopic capsular invasion.

      • Stage II disease involves invasion of mediastinum or microscopic capsular invasion.

      • Stage III malignant thymomas show invasion into surrounding structures, including the pericardium, great vessels, and lung.

      • Stage IVA malignant thymoma involves the pleural or the pericardial metastases.

      • Stage IVB disease includes lymphogenous or hematogenous metastases.

      • Chemotherapy and radiation improve survival for patients with stage III or IV thymomas. These are typically performed in a neoadjuvant setting.

      • Postoperative radiation for stage II patients is controversial, but a recent meta-analysis showed no difference in prognosis with that of stage I patients, with or without irradiation.

      TABLE 42-1 ▪


      Stage Characteristics
      Stage I Macroscopically encapsulated with no microscopically detectable capsular invasion
      Stage II Macroscopic invasion of mediastinal fatty tissue or mediastinal pleura, or microscopic invasion into the capsule
      Stage III Macroscopic invasion into surrounding structures (pericardium, great vessels, lung)
      Stage IV A Pleural or pericardial dissemination
      Stage IV B Lymphogenous or hematogenous metastases

      From Masaoka A, Monden Y, Nakahara K, et al. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48:2485-2492.

  • Surgery: Complete surgical removal of the tumor, thymus, and surrounding fat is the common practice for stage I to II thymomas. Leaving any residual tissue has been associated with a reoccurrence of myasthenia gravis.

    • Technique

      • Thymectomy may be performed transcervically, with video-assisted thoracic surgery (VATS), or with a median sternotomy. Most surgeons prefer to use a median sternotomy for thymectomy if there is a tumor. VATS can be used if the tumor is small and for thymectomy in myasthenia gravis when there is no tumor. The VATS approaches include right VATS, left VATS, bilateral VATS, and unilateral VATS with a neck incision to facilitate removal of the horns of the thymus.

      • In stages I and II, the goal of the thymectomy is a complete anterior mediastinal exenteration, including the thymus, thymic horns that end on the inferior border of the thyroid, and pericardial fat pad. Basically, all the tissue from the pericardium to the inner table of the sternum and from the diaphragm to the thyroid is resected. Structures invaded by the tumor, such as the pleura, lung, pericardium, and an occluded innominate vein may also be resected. Approximately 30% of what was considered preoperatively to be stage I will be found to have invasive disease.

      • In stages III to IVa, a median sternotomy is used with aggressive resection of any of the invaded structures because a complete removal (R0 resection) may be curative. Such patients may require wedge resections of invaded lung, reconstruction of an invaded superior vena cava, and even sacrificing of an invaded phrenic nerve. Myocardial invasion makes complete resection impossible; however, aggressive debulking may be associated with improved long-term survival.

  • Thymic lymphoma: The treatment of HL is complex and outside the scope of this chapter. Mediastinal primary B-cell lymphoma is generally treated with anthracycline-based chemotherapy with frequent restaging because this tumor can progress during treatment. Some sources recommend high-dose chemotherapy, followed by autologous stem cell transplantation because it is tolerated well by the predominantly young patient population. Local radiation is also appropriate following the initial round of chemotherapy in stage I and nonbulky stage II disease. T-cell lymphoblastic lymphoma is a rare tumor type for which the primary therapy also includes chemotherapy and irradiation. The role of surgery for this disease is limited to the initial biopsy for diagnosis or repeat biopsy of a residual mass after treatment to determine if there is scarring or a residual cancer. However, the exact management of this malignancy is still controversial.

  • Thymic carcinoid: Prophylactic thymectomy is recommended in patients during parathyroidectomy in the setting of the multiple endocrine neoplasia type 1 syndrome due to the high mortality of thyroid carcinoid should it present itself. In addition, thymectomy may remove ectopic parathyroid glands. The incidence of an ectopic parathyroid located within thymic tissue ranges from 12% to 39%.

  • Thymic germ cell tumor: Benign teratomas should be completely excised because there is a small risk of malignant transformation. Seminomas are extremely radiosensitive, and local radiation combined with perioperative cisplatin-based chemotherapy has been very effective. Surgical resection of nonseminomatous tumors is challenging and associated with a 4% mortality rate given the extensive invasion at time of diagnosis. Persistent elevation of tumor markers means persistent cancer; however, if the markers normalize and there is a residual mass, the thymus should be resected en bloc to determine if there is residual scar, benign teratoma, or persistent cancer. Analysis of the surgical pathology will help determine the need for additional chemotherapy.

  • Complications

    • Mortality for thymectomy should be less than 2%, even for patients requiring extensive resections.

    • Rates of injury to the phrenic or recurrent laryngeal nerves in thymectomy has been as much as 2% ; however, many trials have shown no such complications.

    • The anesthesiologist should take extra consideration in the choice in neuromuscular blockers in the setting of patients with myasthenia gravis.

    • In patients who undergo mediastinal irradiation for thymic tumors, adverse consequences include the following:

      • Pneumonitis, first presenting itself 1 to 3 months after exposure.

      • Cardiac complications include coronary artery disease, pericarditis, cardiomyopathy and valvular heart disease. The risk of cardiovascular death has been shown to be proportional to the amount of radiation exposure in patients who have received mediastinal irradiation for Hodgkin’s disease.

      • Exposure of the great vessels to radiation has been known to cause radiation-induced vasculopathy as late as 10 years following the initial insult. However, modern irradiation techniques have greatly reduced this risk.

      • Radiation increases the risk of lung cancer by 50%, and the incidence of radiation-induced chest sarcomas is about 0.3%.



Primary mediastinal lymphoma is a type of solid neoplasm that originates in lymphocytes usually in lymphoid tissue contained within the mediastinum. It is generally a rare entity; however, when it does occur, lymphoma usually occurs in the anterior mediastinum and may be associated with widespread disease. HL comprises the majority of lymphoma in the anterior mediastinum, whereas NHL comprises a smaller percentage.


  • The three most common histological types of mediastinal lymphoma are HL, large B-cell lymphoma, and lymphoblastic lymphoma.

  • Primary mediastinal lymphoma is a distinct clinical subset of lymphoma and comprises about 10% of lymphoma in the mediastinum.

Hodgkin’s Lymphoma

  • Represents 50% to 75% of mediastinal lymphomas

  • Has an incidence of approximately 2 to 4 cases per 100,000 people per year

  • Shows a bimodal distribution incidence peaking in young adulthood and again after age 50 years.

  • For mediastinal-predominant disease, prevalence peaks in young women during the third decade of life, whereas it is unaffected by age in men.

  • Of the four subtypes, the nodular sclerosing subtype represents more than two thirds of cases.

Non-Hodgkin’s Lymphoma

  • Represents 15% to 25% of mediastinal lymphomas

  • The overall incidence of NHL is greatest in those with a mean age of 55 years old.

  • Demographically, the incidence is higher in white men

  • Large B-cell lymphoma

    • Mean age of presentation is 30 to 35 years old.

    • Bimodal age distribution is seen.

      • First peak is seen between 33 and 39 years of age.

        • The female-to-male ratio is 2:1.

        • High frequency of occurrence in the anterior mediastinum

      • Second peak is seen in men at a mean age of 65 years.

  • Lymphoblastic lymphoma

    • Generally, a disease of children and adolescent boys

    • Can be seen in all age groups

    • The mean age is 28 years old.


Hodgkin’s Lymphoma

  • Nodular sclerosing is the most common subtype.

    • Shows nodular collections of lymphoid tissue

    • Lobules are separated by dense bands of fibrous proliferation.

    • The presence of Reed-Sternberg (RS) cells is pathognomonic for HL

      • The RS cells seen in mediastinal HL often has a lacunar morphology.

        • Show prominent nucleoli, multilobed nuclei on a background of clear cytoplasm

        • Classic RS cells show bilobed nuclei (owl’s eyes) with eosinophilic nucleoli

Diffuse Large B-cell Lymphoma

  • Mediastinal large B-cell lymphoma comprises 7% to 10% of all diffuse large B-cell lymphomas and about 2.5% of all NHL.

  • Thought to arise from medullary B-cells in the thymus.

    • Tumor consists of large lymphoid cells with nuclear morphology that may resemble centroblasts, large centrocytes, or multilobed cells.

      • Nuclear pleomorphism can be so prominent that the neoplasm resembles an anaplastic carcinoma or sarcoma.

      • Also seen is diffuse proliferation of large cells with abundant eosinophilic cytoplasm, large vesicular nuclei, and prominent nucleoli.

        • Ten percent of mediastinal B-cell lymphomas exhibit a prominent clearing of the cytoplasm, a variant that has been referred to as primary mediastinal clear cell lymphoma of B-cell origin.

      • Presence of sclerosing stroma is very characteristic seen in 38% to 100% of cases.

        • This sclerosing stroma of thick hyaline connective tissues can separate the tumor into epithelial nests.

        • This can sometimes mimic the appearance of a seminoma or carcinoma.

Lymphoblastic Lymphoma

  • Highly aggressive leukemia/lymphoma

    • Classified by The Revised European American Lymphoma Classification (REAL) classification as a precursor B-lymphoblastic or precursor T-lymphoblastic leukemia/lymphoma.

    • Acute lymphoblastic leukemia (ALL), which is considered to be the leukemic phase of this leukemia/lymphoma.

  • Characterized by diffuse infiltrate non-cohesive lymphoid cells

    • Cells are of intermediate size and show scanty cytoplasm with very fine nuclear chromatin.

      • Nucleoli are usually absent, and there are a high number of mitotic figures per high power field.

    • Lack of a dense fibrous stroma and may show a prominent admixture of tingible body macrophages

    • This can give a characteristic “starry sky” appearance on histopathology.


  • Knowledge of mediastinal anatomy is important in determining the etiology of masses and the surgical approach.

  • The mediastinum is generally divided into four compartments ( Fig. 42-10 ).

    • Anterior mediastinum

      • Anterior border is the sternum

      • Posterior border is the heart and brachiocephalic vessels

      • Superior border is the aortic arch

      • Inferiorly border is the diaphragm

    • Superior mediastinum

      • Sternum to the vertebral bodies

      • Top of aortic arch to the thoracic inlet

      • Note: anterior and superior compartments may be combined into one compartment (anterosuperior compartment)

    • Middle mediastinum

      • Bounded by the pericardial sac

      • Superior border is the fourth thoracic vertebrae

    • Posterior mediastinum

      • Anterior border is the posterior border of the heart and the trachea

      • Posterior border are the thoracic vertebrae

    Figure 42-10

    Lateral chest radiograph depicting anatomic subdivisions of the mediastinum.

    (From Townsend CM, Beauchamp RD, Evers BM, Mattos KL, editors. Sabiston textbook of general surgery. 17th ed. New York: Elsevier; 2004.)


Hodgkin’s Lymphoma

  • A large proportion of patients develop systemic symptoms before the discovery of lymphadenopathy.

    • Typical “B” symptoms of fever, weight loss, and night sweats, and weight loss are common.

      • Pel-Ebstein fever is the characteristic, although uncommon, intermittent fever associated with HL.

        • Recurs at variable intervals of several days or weeks and lasts for 1 to 2 weeks before waning.

    • Additional symptoms include fatigue, pruritus, and chest pain with injestion of alcohol.

  • 60% of patients have mediastinal adenopathy at the time of diagnosis.

  • Common presentation is the incidental finding of a mediastinal mass on a radiograph.

    • These can often be large and asymptomatic.

    • Rarely causes pleural/pericardial effusions

    • Bulky mediastinal disease may cause superior vena cava (SVC) syndrome

    • Can cause symptoms like chest pain, dyspnea, and cough, but these are also uncommon.

Primary Mediastinal Large B-cell Lymphoma

  • Frequently present with locally invasive anterior mediastinal mass

  • Usually originating in the thymus

  • Presents frequently with airway compromise and SVC syndrome

    • A report of 30 patients showed SVC syndrome was present in 57% of those patients.

    • Eighty percent of patients had radiographic signs of SVC involvement, even without clinical syndrome.

    • Pleural and pericardial effusions were also common.

  • Relapses tend to be in tissues outside of the lymph nodes.

    • Liver, gastrointestinal tract, kidneys, ovaries, and central nervous system are common sites.

Lymphoblastic Lymphoma

  • Can be very aggressive and present very dramatically when mediastinum is involved

    • Mediastinal mass is present in 80% of patients at presentation.

    • Can have common symptoms of cough, dyspnea, and wheezing

    • Tracheal compression causes stridor.

    • SVC syndrome, cardiac tamponade, and tracheal obstruction are more life-threatening presentations that have been known to occur with this type of lymphoma.

  • Generally present with more advanced disease

    • Extranodal involvement

    • Generalized lymphadenopathy



  • Tissue biopsy is necessary for all types of HL and NHL in order to guide management.

  • Mediastinal nodes may be biopsied with mediastinoscopy, mediastinotomy, or endobronchial ultrasound (EBUS). If there is a large anterior mediastinal mass, paralysis with induction of anesthesia may lead to tracheal compression that can occasionally be life-threatening. In these cases, awake intubation may be indicated.

  • Morphology on histologic examination as well as immunophenotyping play key roles in determining treatment.

    • HL

      • Immunohistochemical profile is usually biomarker positive for CD15 and CD30 cells.

      • Important negative biomarkers include LCA (CD45RO) and keratin.

        • The absence of keratin excludes thymoma from the diagnosis.

    • NHL

      • Large B-cell lymphoma

        • Usually express B-cell–associated antigens, which include CD19, CD20, CD22, and CD79a.

        • They are also usually CD45 positive and CD15 negative.

        • Markers such as HMB-45, keratin, and placental alkaline phosphatase (PLAP) should be tested to exclude other possible tumors, i.e., melanoma, thymoma, and seminomas.

        • Rarely are of T-cell origin and show markers consistent with that immunophenotype.

      • Lymphoblastic lymphoma

        • In more than 80% of cases, the cells are of T-cell origin

        • A wide spectrum is seen in terms of differentiation: (1) Early—CD2, CD5, and CD7 positive; CD1, CD3, CD4, and CD8 negative; (2) Intermediate—CD1, CD2, CD5, CD7, CD4 and CD8 positive; CD3 negative; (3) Mature—CD2, CD3, CD5, CD7, CD4 and CD8 positive; (4) Study showed that the majority of a series of 31 T-cell lymphoblastic lymphomas were intermediate (62%); (5) Also showed that terminal deoxynucleotidyl transferase (TdT) was virtually positive in all cases, which can also serve as a marker.

Imaging Studies

  • CXR study

    • The chest radiograph is abnormal in up to 76% of patients with HL ( Table 42-2 )

      • Shows enlargement of paratracheal and prevascular lymph nodes

      TABLE 42-2 ▪


      Site Involved Hodgkin’s Disease, % (n = 164) Non-Hodgkin’s Disease, % (n = 136)
      Intrathoracic disease (any site) 67 43
      Anterior mediastinum 46 13
      Tracheobronchial nodes 45 13
      Paratracheal nodes 40 13
      Hilar nodes 21 8
      Subcarinal nodes 11 4
      Internal mammary nodes 7 1
      Posterior mediastinum 5 11
      Lung 12 5
      Pleura 7 11

      Adapted from Filly R, Blank N, Castellino RA. Radiographic distribution of intrathoracic disease in previously untreated patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Radiology 1976;120:277-281.

    • Not as helpful in NHL

      • Less than half of all patients with NHL have abnormal chest radiographs.

      • Half of patients have isolated intrathoracic nodal disease that does not involve the paratracheal or prevascular nodes.

  • CT Scan

    • HL

      • Eighty-five percent of patients with newly diagnosed HL have thoracic involvement on chest CT scans ( Fig. 42-11 ).

        Figure 42-11

        Contrast-enhanced computed tomography scan shows bulky anterior mediastinal adenopathy with associated loculated pleural effusion. Histopathologic analysis demonstrated nodular sclerosing Hodgkin’s lymphoma.

      • Mediatinal involvement includes

        • Discrete lymph nodes

        • Bulky, matted nodes

        • Discrete or infiltrating thymic mass

      • Typically are homogenous and have the same attenuation as that of soft tissue

      • Larger masses with coalescent nodes can demonstrate heterogenous areas, which may represent areas of necrosis and even hemorrhage.

    • NHL

      • Helpful in determining the extent of disease in patients with early-stage disease

      • Helps to determine radiation portals in patients with no other extrathoracic disease

      • Determining recurrence in patients that have already been treated

        • More limited in patients with advanced stage disease that were untreated.

        • Patients with normal chest radiographs that had been treated.

  • MRI ( not usually used for evaluation of lymphoma)

    • HL

      • Shows a homogenous mass

        • Low signal intensity on T1-weighted imaging

        • High signal intensity on T2-weighted images

        • T2-weighted MRIs can demonstrate increased signal intensity from baseline to help differentiate disease recurrence versus residual fibrotic mass after therapy

    • NHL

      • Has a role in distinguishing residual disease in those patients that have been treated

  • Nuclear Imaging

    • PET scanning can be especially useful for staging and disease response for both NHL and HL


Hodgkin’s Lymphoma

  • Staging is usually done clinically according to the Ann Arbor classification, which was subsequently modified at the Cotswold’s conference ( Table 42-3 ).

    • Extranodal and bulky disease

      • Extranodal (“e”) refers to extranodal contiguous extension (i.e., proximal or contiguous extranodal disease) that can be encompassed within an irradiation field appropriate for nodal disease of the same anatomic extent.

        • The importance of extranodal disease on prognosis is that it shows a striking difference between patients with essentially localized extralymphatic organ involvement, which is contiguous with an involved lymph node region, and disseminated extralymphatic involvement.

      • “X” is used if bulky disease is present.

        • Can have an important role in prognosis and treatment especially with disease in the mediastinum.

        • A node or nodal mass must be 10 cm or greater to be recorded as bulky.

        • Bulky also refers to wide transverse diameter of the mediastinal mass on a standard posteroanterior chest radiogram greater than one third of the maximal diameter of the chest wall at its pleural surfaces, usually at the level of the diaphragm.

    TABLE 42-3 ▪


    Stage Characteristics
    1 Involvement of one lymph node region or lymphoid structure
    2 Two or more lymph node regions on same side of the diaphragm
    3 Lymph nodes on both sides of the diaphragm
    4 Involvement of extra nodal sites
    A No symptoms
    B Fever, night sweats, weight loss >10% in 6 months
    X Bulky disease (greater than one third widening of the mediastinum or >10 cm diameter of nodal mass)
    E Involvement of single, contiguous, or extra nodal site

    Adapted from Yung L, Linch D. Hodgkin’s lymphoma. Lancet 2003; 361: 943–951.

  • There have been numerous studies to identify prognostic factors

    • Distinguishing between favorable and unfavorable especially in early stage (stages I and II) disease.

    • The main prognostic factors

      • Presence of “B” symptoms (designate stage A for absent or B for present)

      • Erythrocyte sedimentation rate (ESR) and both the number of involved sites and the bulk of disease

    • For advanced disease (stages III and IV), International Prognostic Score (IPS), includes the following unfavorable markers:

      • Serum albumin less than 4 g/dL (40 g/L)

      • Hemoglobin less than 10.5 g/dL (105 g/L)

      • Male gender

      • Age older than 45 years

      • Stage IV disease

      • White blood cell count 15,000/μL or more

      • Lymphocyte count less than 600/μL, or less than 8% of the white blood cell count

    • The presence of a greater number of these factors predicted a higher chance of lack of freedom from disease at 5 years.


  • Ann Arbor staging classification

  • Modified for staging of NHL

    • Focuses on number of tumor sites—nodal or extranodal

    • Location

    • Presence or absence of “B” symptoms

  • This staging system has been proven to be much less useful for NHL than for HL.

    • NHL frequently metastasizes through hematogenous routes.

  • Prognosis is far more dependent on histopathology.

    • Secondarily influenced by clinical parameters, including age, presence of extranodal disease, performance status, and stage (I/II versus III/IV).

  • Thus, staging in most cases of NHL as a group focuses more on the identification of early-stage (I/II) and late-stage (III/IV) disease.

    • The following factors are associated with shorter disease free survival and shorter overall survival:

      • Age older than 60

      • Serum lactate dehydrogenase (LDH) concentration greater than normal

      • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more

      • Ann Arbor clinical stage III or IV

      • More than one involved extranodal disease site.

    • Presence of each factor gives 1 point

      • Low risk—international prognostic index (IPI) score of zero or one

      • Low intermediate risk—IPI score of two

      • High intermediate risk—IPI score of three

      • High risk—IPI score of four or five

    • Five-year overall survivals for scores:

      • of 0 to 1, 73%

      • 2, 51%

      • 3, 43%

      • 4 to 5, 26%,


Hodgkin’s Lymphoma

  • Chemotherapy either alone or combined with radiotherapy has converted HL from a uniformly fatal disease to one that is curable in approximately 75% of patients worldwide.

  • Stage I-II—poor prognosis

    • ESR greater than 50 mm/h

    • ESR greater than 30 mm/h in the presence of B symptoms

    • Mediastinal mass exceeding 0.35 of the intrathoracic diameter at T5/6

    • Four or more sites of disease

  • Treatment

    • Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for three to four cycles.

      • Followed by irradiation to the involved field of 30 Gy (36 Gy in some patients) to the initially involved lymph node site.

    • Alternative is chemotherapy alone for six cycles or radiation therapy alone with larger fields.

    • Lower relapse rate in the first regimen.

  • Stage IIIA

    • Combination chemotherapy with total nodal irradiation in patients with non-bulky and limited upper abdominal disease

  • Stage IIIB

    • Chemotherapy usually with ABVD is the primary treatment option.

    • There are newer regimens being studied, i.e., the Stanford V protocol.

      • Doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone, combined with radiation to bulky lymph node sites 5 cm or more in diameter (Stanford V regimen) in patients with bulky mediastinal stage II, stage III, or stage IV disease.

  • Stage IV

    • Chemotherapy with ABVD is the primary modality with nodal irradiation in patients with bulky disease sites.


  • Mediastinal large B-cell lymphoma

    • At present, standard of care is to use combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

    • This is usually used in conjunction with Rituximab (R-CHOP).

    • In limited-stage disease, radiation therapy is usually added.

  • Lymphoblastic lymphoma/leukemia

    • Treated in a similar fashion to ALL.

      • Induction—patients generally enter complete remission (CR) after this therapy.

      • Consolidation—for 4 to 6 months after achievement of CR

      • Maintenance—24 to 36 months after finishing consolidation phase,

      • Prophylactic central nervous system CNS radiation if CR attained.

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Jun 24, 2019 | Posted by in CARDIAC SURGERY | Comments Off on Masses of the Anterior Mediastinum

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