Bartosz Chmielowski and Dennis A. Casciato
I. PRIMARY TUMORS OF THE MEDIASTINUM
A. General features
1. Anatomy. The mediastinum is bounded by the sternum anteriorly, the thoracic vertebral bodies posteriorly, the diaphragm inferiorly, and the first thoracic vertebrae superiorly. Its lateral boundaries are the parietal and pleural surfaces of the lungs. The mediastinum is arbitrarily divided into anterior, middle, and posterior segments by the heart and great vessels.
2. Incidence. The annual incidence of mediastinal tumors is 2/1 million population. Of mediastinal tumors, 75% are benign. Many are detected serendipitously in chest radiographs obtained for other reasons.
a. The most common mediastinal masses are thymoma, teratoma, goiter, and lymphoma. Most mediastinal malignancies represent lymphomas or metastatic cancers from other sites.
b. Lymphomas can involve the anterior, middle, or posterior mediastinum. Hodgkin lymphoma is the most common cause of isolated mediastinal disease among the lymphomas; the nodular sclerosing subtype has a predilection for the anterior mediastinum. Other lymphomas are infrequendy limited to the mediastinum at the time of diagnosis. Lymphomas are discussed in Chapter 21.
c. Mediastinal goiters without a cervical component are rare. They usually descend into the left anterosuperior mediastinum. Infrequently, they descend behind the trachea into the middle and posterior mediastinum. Mediastinal goiters contain foci of malignancy rarely.
3. Age and sex. Most of the tumors show no sexual predilection. Mediastinal teratomas usually arise after the age of 30 years. Benign thymomas may occur in any age group. Thymic carcinomas are more common in elderly men. Tumors of nerve tissue origin may occur at any age but are more common in children.
4. Symptoms and signs. Presenting symptoms depend on the tumor location, type, and rate of growth. Symptoms are more likely to be present with rapidly growing, malignant tumors. Hypertrophic osteoarthropathy can occur with any primary mediastinal tumor, particularly sarcomas.
a. Anterior mediastinal tumors can present with retrosternal pain, dyspnea, upper airway obstruction, and development of collateral venous circulation over the chest. Dullness to percussion may be observed over the upper sternum.
b. Posterior mediastinal tumors can cause tracheal compression (cough and dyspnea), phrenic nerve compression (hiccoughs or diaphragm paralysis), involvement of left recurrent laryngeal nerve (hoarseness), esophageal compression (dysphagia), vena cava obstruction, Horner syndrome or pain, or palsies in the brachial or intercostal nerve distribution.
B. Tumors of the anterior and middle mediastinum
1. Thymomas represent 20% of all mediastinal tumors and are the most common cause of anterior mediastinal masses. The peak frequency of the diagnosis is between 40 and 60 years of age. They are composed of cells of both lymphocytic and epithelial origin. Thymomas are benign in 70% of cases and are locally invasive in 30%. Only 1% of thymic tumors are thymic carcinomas. Invasive thymomas involve the pericardium, myocardium, lung, sternum, and large mediastinal vessels. Disseminated metastases are uncommon.
Histologic details have had little bearing on prognosis or evaluation of malignant potential; invasiveness of a thymoma at surgery is the best index of its malignancy. The World Health Organization classification, however, appears to reflect the invasiveness and prognosis of thymic epithelial tumors (see Okumura et al., 2002). As a cautionary note, carcinoid tumors of the mediastinum may be misclassified as thymoma during cytologic interpretation of fine-needle aspirates.
a. Paraneoplastic immunologic syndromes associated with both benign and malignant thymomas occur in 50% to 60% of patients, do not affect prognosis, and may not reverse following thymectomy. These syndromes include the following:
(1) Myasthenia gravis occurs in more than half of patients with thymoma; manifestations are improved in about 70% of patients who undergo thymectomy. About 20% of patients with myasthenia gravis have thymomas. Patients suspected of having thymoma should have an assay of serum anti–acetylcholine-receptor antibody.
(2) Pure red-cell aplasia (PRCA, <5% of thymomas). About 10% of patients with PRCA have a thymoma in contemporary series. The pathophysiology of this complication is poorly understood. Thymectomy results in remission of PRCA in <20% of patients. Various immunosuppressive treatments have been attempted with variable success (cyclosporine, antithymocyte globulin), but can lead to significant morbidity, particularly with pulmonary infections.
(3) Immunodeficiency. Acquired hypogammaglobulinemia with low to absent levels of B cells and CD4+ T lymphocytopenia (Good syndrome) occurs in about 10% of patients with thymoma. Patients experience recurrent sinopulmonary infections secondary to encapsulated organisms, skin or urinary tract infections, and bacterial diarrheas. Therapy with intravenous immunoglobulins (IVIG) should be helpful in reducing the occurrence of infections.
(4) Rare paraneoplastic syndromes associated with thymoma
(a) Ectopic Cushing syndrome
(b) Polymyositis, dermatomyositis, granulomatous myocarditis
(c) Systemic lupus erythematosus
(d) Churg-Strauss syndrome, microscopic polyangiitis, isolated pauci-immune necrotizing crescentic glomerulonephritis
(e) Optic neuritis, limbic encephalitis
(f) Hypertrophic osteoarthropathy
(g) Thymoma-associated multiorgan autoimmunity (TAMA) is a rare complication of thymoma, and it resembles acute graft-versus-host disease with rash, diarrhea, and elevation of liver enzymes.
b. Therapy
(1) Surgical extirpation results in a cure rate that exceeds 95% for encapsulated, noninvasive thymomas. Less than 10% of resected encapsulated thymomas recur, sometimes years after excision. Surgery alone appears to be insufficient therapy for invasive thymomas.
(2) Radiation therapy, 4,500 to 5,000 cGy given postoperatively for locally invasive or incompletely excised thymomas, reduces the local recurrence rate from about 30% to 5% in 10 years. RT does not appear to be necessary for Masaoka stage II thymoma (microscopic transcapsular invasion or macroscopic invasion into the surrounding fatty tissue). The recurrence rate for locally invasive thymomas treated with RT alone is 20% to 30%.
(3) Combination chemotherapy regimens for locally advanced or metastatic disease usually involve cisplatin, doxorubicin, and cyclophosphamide. Corticosteroid therapy, including high doses, is also beneficial. Reports of chemotherapy efficacy are usually small phase II studies. These combinations consistently result in response rates that are >50%, less than half of those are complete responses. The median duration of complete responses in widespread disease is about 12 months. The 5-year survival rate for these patients is about 30%. For patients with locally advanced disease (for whom there is no standard therapy), it is reasonable to use induction chemotherapy first, followed by resection and RT.
(4) Somatostatin analogs, such as lanreotide (30 mg intramuscular [IM] every 14 days), combined with prednisone is effective therapy in thymic tumors refractory to standard chemotherapeutic agents as long as the tumor is positive on a octreotide scan, which reflects the presence of somatostatin receptors.
(5) Multikinase inhibitors (sunitinib, sorafenib) appear to have activity in thymomas resistant to standard chemotherapy.
2. Thymic carcinomas are obviously malignant histologically and are usually not associated with paraneoplastic syndromes. Neoplasms that are well circumscribed and low grade with a lobular growth pattern have a relatively favorable prognosis for survival (90% 5-year survival rate). High-grade thymic carcinomas are locally invasive; they are frequently associated with pleural or pericardial effusions and frequently metastasize to regional lymph nodes and distant sites. Cisplatin-based chemotherapy plus RT for high-grade tumors is associated with a 5-year survival rate of 15%. Carboplatin plus paclitaxel may also be helpful.
3. Thymic carcinoids are rare. About half have endocrine abnormalities, especially ectopic production of adrenocorticotropic hormone and multiple endocrine neoplasia syndrome, but carcinoid syndrome rarely occurs. Regional lymph node metastases and osteoblastic bone metastases develop in most patients. Metastases are often refractory to therapy.
4. Germ cell tumors (see Chapter 12). Teratomas (or dermoids) represent 10% of mediastinal neoplasms. About 10% of these are malignant, usually with a predominant epithelioid component, but occasionally with sarcomatous or endodermal elements. Malignant germ cell tumors of the mediastinum are usually large and solid.
a. Benign (mature) teratoma accounts for about 70% of mediastinal germ cell tumors, especially in children and young adults. They appear as a round, dense mass (often with a calcified capsular shell and occasionally with teeth). They are usually small with multilocular cysts and asymptomatic, but they can attain a large size. The serum of a patient with benign teratoma contains no α-fetoprotein (AFP) or β-human chorionic gonadotropin (β-hCG). These characteristics often differentiate benign teratoma from germ cell malignancy. The treatment is surgical excision.
b. Seminoma comprises only 2% to 4% of mediastinal masses, but it is the most common malignant germ cell neoplasm of the mediastinum, occurs most frequently in men 20 to 40 years of age. The lesions are rarely calcified. Less than 10% of cases have an elevated β-hCG, and none has an elevated AFP. Treatment of mediastinal seminoma is surgical excision if the tumor is small, followed by irradiation of the mediastinum and the supraclavicular nodes. For locally advanced disease, combination chemotherapy (see Chapter 12, Section VI), followed by resection of residual disease, is preferred. The 5-year survival rate for these patients is >80%.
c. Mediastinal nonseminomatous germ cell tumors are malignant, aggressive, and usually symptomatic. The prognosis is worse than for patients with mediastinal seminoma. They are usually associated with elevations of serum levels of β-hCG, AFP, or lactate dehydrogenase (LDH). Choriocarcinoma in the mediastinum presents with gynecomastia and testicular atrophy in half of all male patients. Embryonal or yolk sac tumors of the mediastinum are highly aggressive cancers that are large and bulky at the time of diagnosis.
Surgery may be required initially to establish the histologic diagnosis. Definitive treatment consists of aggressive chemotherapy as outlined for testicular cancer (see Chapter 12, Section VI) followed by resection of residual masses. Mediastinal irradiation delays the initiation of chemotherapy, compromises bone marrow reserve (thus limiting the chemotherapy doses), and probably should not be used.
5. Other anterior mediastinal masses
a. Goiter and thyroid cysts (10% of mediastinal masses)
b. Lymphomas
c. Parathyroid adenoma (10% are ectopic)
d. Rare causes of anterior mediastinal masses
(1) Thymic cysts
(2) Thymolipoma
(3) Lymphangioma (cystic hygroma)
(4) Soft tissue sarcomas and their benign counterparts
(5) Plasmacytoma
6. Middle mediastinal masses
a. Lymphomas
b. Goiter
c. Aortic aneurysm (10% of mediastinal masses in surgical series)
d. Congenital foregut cysts (20% of mediastinal masses). About 50% of foregut cysts are bronchogenic, 10% are enterogenous (including esophageal duplication), and 5% are neuroenteric.
e. Pericardial cysts
C. Tumors of the posterior mediastinum
1. Neurogenic tumors are the most common cause of a posterior mediastinal mass and constitute 75% of neoplasms in the posterior mediastinum; about 15% are malignant, and half of these are symptomatic. Among mediastinal neoplasms, neurogenic tumors constitute 20% of cases in adults and 35% of cases in children.
a. Neurofibromas and schwannomas are most common. Malignant tumor of nerve sheath origin is their malignant counterpart.
b. Sympathetic ganglia tumors originate from nerve cells rather than nerve sheath. They are rare and range from benign ganglioneuroma to malignant ganglioneuroblastoma to highly malignant neuroblastoma. Some produce a syndrome identical to pheochromocytoma.
2. Mesenchymal tumors, including lipomas, fibromas, myxomas, mesotheliomas, and their sarcomatous counterparts, are rare mediastinal tumors; more than half are malignant. Therapy necessitates surgical debulking. RT, chemotherapy, or both are used as a surgical adjuvant for treating sarcomas.
3. Other posterior mediastinal masses
a. Lymphomas
b. Goiter
c. Lateral thoracic meningocele
II. RETROPERITONEAL TUMORS
A. Etiology. Excluding renal tumors, 85% of primary retroperitoneal neoplasms are malignant. About one-sixth of cases are Hodgkin lymphoma, and one-sixth are non-Hodgkin lymphoma. Sarcomas often appear in the retroperitoneum, particularly rhabdomyosarcoma (in children), leiomyosarcoma, and liposarcoma. Germ cell tumors, adenocarcinomas, and rare neuroblastomas account for most of the remainder of cases. Carcinomas of the breast, lung, and gastrointestinal tract can metastasize to retroperitoneal structures by way of the bloodstream or the spinal venous plexus.
B. Evaluation
1. Symptoms. Back pain, upper urinary tract obstruction, and leg edema caused by lymphatic or vena cava obstruction frequently are manifestations of retroperitoneal malignancies; arterial insufficiency does not appear to occur. Some patients develop fever or hypoglycemia as paraneoplastic syndromes.
2. Laboratory studies. History, physical examination, chest radiographs, and routine blood studies are performed. Uremia can result from entrapment of the ureters. Intravenous pyelography, barium contrast study of the colon, and abdominal CT scanning are performed to evaluate the extent of tumor.
C. Management. Exploratory surgery is necessary to establish the tissue diagnosis and to attempt resection of the tumor for potential cure, particularly for sarcomas. RT is used to treat residual disease. Chemotherapy is used for patients with lymphoreticular neoplasm or with tumors that are not responsive to RT. The specific chemotherapy selected depends on the tumor type.
III. CARDIOVASCULAR TUMORS
Primary cardiac tumors are exceedingly rare. Metastasis to the heart (see Chapter 29, Section V) is more than 20 times as frequent as primary cardiac tumors. Tumors of blood vessels are mostly sarcomas, which are discussed in Chapter 17. Symptoms are largely dependent on the location of the tumor and not on the histologic type. The patients may present with symptoms of congestive heart failure because of the blood flow obstruction, arrhythmias and heart blocks secondary to direct invasion of the myocardium, pericardial effusion, or of pulmonic or peripheral embolization.
A. Malignant heart tumors include rhabdomyosarcoma, fibrosarcoma, angiosarcoma, leiomyosarcoma, and sarcoma otherwise nonspecified. Tumors usually arise in the right auricle and extend into the heart substance and valves. Their aggressive course is characterized by heart failure, angina, life-threatening arrhythmias, or cardiac rupture. They are treated with resection and frequently chemotherapy. The prognosis is generally poor; patients with low-grade sarcomas have a better prognosis.
B. Benign heart tumors
1. Myxoma is most frequently located in the left atrium. It grows into the lumen of the left atrium and leads to symptoms of mitral regurgitation and can cause a syndrome resembling microbial endocarditis with heart murmur, fever, joint pain, and systemic emboli. If myxoma is located in the right atrium, it will present like tricuspid stenosis. Patients with these findings and sterile blood cultures should have an echocardiogram, which is highly accurate for diagnosing myxoma of the heart. Some patients may require a cardiac MRI to differentiate between a tumor and thrombus. Occasionally, the diagnosis is established by the finding of myxomatous tissue in arterial embolectomy specimens. Myxomas are treated surgically, usually with a good outcome.
2. Papillary fibroelastoma usually grows as a pedunculated, mobile tumor on a heart valve. The growth is frequently complicated by a thrombotic event (i.e., cerebrovascular event, myocardial infarction, angina pectoris, peripheral or pulmonary embolism).
3. Rhabdomyoma, teratoma, fibroma, and lipoma are less common types of cardiac tumors.
C. Hemangiopericytomas, in the past, were considered to originate from pericytes. Currently, it is believed that they originate from fibroblasts and that they belong to the same spectrum of tumors as solitary fibrous tumor. Histologic appearance and grade do not closely correlate with the metastatic potential; 15% to 20% of tumors develop distant metastases.
These highly vascular tumors are treated by resection after embolic therapy. Postoperative RT may reduce local recurrence. Metastatic tumors are treated with doxorubicin-based chemotherapy; they can also respond to antiangiogenic treatments such as the combination of bevacizumab and temozolomide or sunitinib.
D. Primary intravascular sarcomas are rare tumors that present with signs of focal vascular obstruction. Venous sarcomas, particularly leiomyosarcomas, are the most common IV sarcomas. Vena cava tumors can produce Budd-Chiari syndrome, renal failure, or pedal edema; patients may present with poorly defined back or abdominal pain. CT scan or venography suggests the diagnosis. Treatment is surgical resection, when technically feasible.
IV. CARCINOSARCOMAS
Carcinosarcomas are rare tumors, which have a histologic appearance of combined sarcomatous and epithelial elements. Conceptually, they represent carcinomas that develop sarcomatous elements via metaplasia of the epithelial element. Typically, they arise in the myometrium, prostate, or lung, but can occur elsewhere.
Surgical resection is the treatment of choice. The role of postoperative irradiation is not clear. Recurrent or metastatic disease is associated with a dismal prognosis. Traditionally, ifosfamide-based chemotherapy was advocated because the treatment was directed against the sarcomatous component. Since these tumors represent carcinomas, standard chemotherapy applicable to the organ of origin is currently used.
V. ADENOID CYSTIC CARCINOMAS
Adenoid cystic carcinomas (ACC or cylindromas) are rare epithelial tumors that most often arise in salivary glands or the large airways but also can develop in the external auditory canal, nasopharynx, lacrimal glands, breast, vulva, esophagus, and other sites. The term cylindroma describes also a benign adnexal tumor that has a very different clinical behavior from ACC. These tumors have tendency to perineural spread and local recurrence after surgery is common. Lymphatic spread is much less common than hematogenous spread, especially to the lungs. Pulmonary metastases are radiologically dramatic but often have an indolent course over several years.
Primary tumors are treated surgically. Local recurrences may respond to RT. Symptom-free patients with lung metastases do not need specific treatment. Patients with symptomatic disease may respond to imatinib and occasionally to standard chemotherapy such as fluorouracil or doxorubicin.
VI. DENTAL TUMORS
A. Ameloblastomas appear to originate in odontogenic rests (remnants from the embryologic process of odontogenesis). Eighty percent occur in the mandible (70% in the molar areas). The remaining 20% of histologically similar tumors arise in other bones and, occasionally, soft tissues. Ameloblastomas are locally invasive and have a high risk for local recurrence after surgery.
Peripheral (extraosseous) ameloblastomas arise from the gingiva or mucosa and do not involve the bone. Malignant ameloblastoma does not differ histologically from benign ameloblastoma, but it is characterized by development of distant metastasis (mainly in the lungs), even years after the treatment of the primary tumor.
Therapy is by surgical resection. Some surgeons use intraoperative cauterization or cryotherapy for better local control. RT has no role in managing the tumor or recurrences.
B. Cementoma is probably an area of calcified fibrous dysplasia and not a neoplasm.
C. Other dental tumors. Ameloblastic adenomatoid tumors, calcifying epithelial odontoma, ameloblastic fibroma, dentinoma, ameloblastic odontoma, and complex odontoma are all benign tumors of the embryologic precursors of teeth. Surgical removal is the therapy of choice. Transformation into malignancy may occur, but rarely.
VII. ADAMANTINOMA
Adamantinoma is a rare tumor of long bones of the epithelial origin. The name originates from the histologic resemblance to ameloblastoma (see Section VI A). Eighty percent of cases occur in the tibia. Although it is a low-grade neoplasm, it can recur locally and can rarely metastasize to the lungs. Both primary and metastatic adamantinoma are treated surgically. The responses of metastatic adamantinoma to chemotherapy (cisplatin and etoposide) or sunitinib are anecdotal.
VIII. ESTHESIONEUROBLASTOMA
Olfactory neuroblastoma (ONB or esthesioneuroblastoma) is an uncommon malignancy of the sensory epithelium of the nasal cavity close to the cribriform plate. This tumor is considered in the differential diagnosis of poorly differentiated, small, blue round cell neoplasms. The tumor’s immunophenotype is that of a neuroendocrine tumor. Most patients present with Kadish stage B (within the paranasal cavity and paranasal sinuses) or C (extension beyond the paranasal cavity and paranasal sinuses). Aggressive biologic behavior may represent a neuroendocrine carcinoma that is not ONB.
A. Presenting features are unilateral nasal obstruction, anosmia, epistaxis, rhinorrhea, sinus pain, headache, diplopia, or proptosis. It may be an incidental finding during polypectomy or nasal septoplasty. Metastases to neck nodes develop in about 30% of patients. Intracranial extension and orbital involvement are independent factors affecting outcome.
B. Multimodality therapy has improved survival for these patients. Disease-free survival at 10 years is about 85%. Aggressive surgical resection is the treatment of choice. Postoperative or neoadjuvant RT improves local control and survival. The results of salvage therapy on relapse are very good. The use of chemotherapy is anecdotal and is usually reserved for patients with high-grade tumors or advanced or relapsed disease.
IX. PARAGANGLIOMAS
These neoplasms originate from chromaffin cells of the neural crest and develop from paraganglia tissues, which are themselves chemoreceptor organs that are distributed throughout the body in association with the sympathetic chain. Nearly half originate in the head and neck region (particularly, at the carotid bifurcation and in the temporal bone), and the remainder develop in the mediastinum, retroperitoneum, abdomen, and pelvis. A conventional concept is that pheochromocytoma is simply a paraganglioma confined to the adrenal gland (see Chapter 15, Section IV).
A. Occurrence. These uncommon neoplasms are either familial (predominantly men) or nonfamilial (predominantly women). Familial paragangliomas are usually associated with mutations in succinate dehydrogenase complex subunit B, C, or D. They are multiple at several locations in 25% to 50% of the familial type and in 10% of the nonfamilial type.
B. Natural history. Paragangliomas, which are usually considered to be benign, are characterized by slow and inexorable growth from the site of origin. Clinical course and not histology is the indicator of tumor behavior. Manifestations depend on the cellular characteristics and tumor location. About 5% of tumors are functional, manifest excessive secretion of neuropeptides and catecholamines, and produce a syndrome identical to pheochromocytoma. Metastases, which are the exception rather than the rule, develop in organs that do not contain paraganglia tissue (lungs, lymph nodes, liver, spleen, and bone marrow).
C. Evaluation. Paragangliomas must always be considered as potentially multiple, especially in patients with a family history of such tumors. Patients should be screened for evidence of excessive catecholamine secretion.
Computed tomography or MRI is useful in delineating the tumors. Arteriography may be useful for tumor embolization done just before surgery or for evaluating contralateral crossover blood supply. Radionuclide scintigraphy using 131I-metaiodobenzylguanidine (MIBG) may be helpful in localizing both paragangliomas and pheochromocytomas. These tumors have a rich blood supply; caution must be exerted not to cause hemorrhage during biopsy. Fine-needle aspiration cytology is often useful if performed carefully.
D. Treatment. Surgical extirpation is the treatment of choice, particularly for small head and neck lesions, but technical expertise in vascular surgery is mandatory. RT is effective in local control and is probably the treatment of choice for lesions that are large or erode bone, particularly in older patients. Chemotherapy is generally ineffective in patients with benign paraganglioma. Metastatic malignant paraganglioma may respond to chemotherapy; the combination of cyclophosphamide, vincristine, and dacarbazine has been used most frequently. High doses of metaiodobenzylguanidine (MIBG), a radionuclide that is used in lower doses in diagnosis of catecholamine-secreting tumors, has generated interest as a therapeutic modality. To do nothing is an acceptable option in some patients because these lesions are often well tolerated for long periods.
X. URACHAL CANCER
Urachal cancer arises in the primitive embryonic connection between the apex of the bladder and the umbilicus. Most of these tumors arise near the dome of the urinary bladder. The most common histologic type is adenocarcinoma. Adenocarcinomas evolve slowly and are asymptomatic until late in the course of disease. Urachal adenocarcinoma must be differentiated from the rare adenocarcinoma of the bladder, which is a more aggressive disease with worse prognosis.
Presenting symptoms are painless hematuria, suprapubic mass, or passage of mucus in the urine. The presence of stippled calcification of a lower midline abdominal wall mass is almost pathognomonic for urachal carcinoma. Surgical resection is the therapy of choice.
Suggested Reading
Esthesioneuroblastoma
Argiris A, et al. Esthesioneuroblastoma: the Northwestern experience. Laryngoscope 2003;113:155.
Diaz EM, et al. Olfactory neuroblastoma: the 22-year experience at one comprehensive cancer center. Head Neck 2005;27:138.
Jethanamest D, et al. Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg 2007;133:276.
Loy AH, et al. Esthesioneuroblastoma: continued follow-up of a single institution’s experience. Arch Otolaryngol Head Neck Surg 2006;132:134.
Paraganglioma
Al-Mefty O, Teixeira A. Complex tumors of the glomus jugulare: criteria, treatment, and outcome. J Neurosurg 2002;97:1356.
Gedik GK, Hoefnagel CA, Bais E, et al. 131I-MIBG therapy in metastatic phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging 2008;35:725.
Huang H, Abraham J, Hung E, et al. Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients. Cancer2008;113:2020.
Thymoma
Agarwal S, Cunningham-Rundles C. Thymoma and immunodeficiency (Good syndrome): a report of 2 unusual cases and review of the literature. Ann Allergy Asthma Immunol 2007;98:185.
Ogawa K, et al. Postoperative radiotherapy for patients with completely resected thymoma. A multi-institutional, retrospective review of 103 patients. Cancer 2002;94:1405.
Okumura M, et al. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 2002;94:624.
Palmieri G, et al. Somatostatin analogs and prednisone in advanced refractory thymic tumors. Cancer 2002;94:1414.
Rena O, et al. Does adjuvant radiation therapy improve disease-free survival in completely resected Masaoka stage II thymoma? Eur J Cardio Thoracic Surg 2007;31:109.
Thompson CA, Steensma DP. Pure red cell aplasia associated with thymoma: clinical insights from a 50-year single-institution experience. Br J Haematol 2006;135:405.
Wadhera A, Maverakis E, Mitsiades N, et al. Thymoma-associated multiorgan autoimmunity: a graft-versus-host-like disease. J Am Acad Dermatol 2007;57:683.
Other Neoplasms
DeLair D, et al. Ameloblastic carcinosarcoma of the mandible arising in ameloblastic fibroma: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:516.
Dudek AZ, Murthaiah PK, Michael Franklin M, et al. Metastatic adamantinoma responds to treatment with receptor tyrosine kinase inhibitor. Acta Oncol 2010;49(1):101.
Gondikvar SM, Gadbail AR, Chole R, et al. Adenoid cystic carcinoma: a rare clinical entity and literature review. Oral Oncol 2011;47:231
Hansel D, Epstein JI. Sarcomatoid carcinoma of the prostate: a study of 42 cases. Am J Surg Pathol 2006;30:1316.
Macchiarini P, Ostertag H. Uncommon primary mediastinal tumours. Lancet Oncol 2004;5:107.
Park MS, Araujo DM. New insights into the hemangiopericytoma/solitary fibrous tumor spectrum of tumors. Curr Opin Oncol 2009;21(4):327.
Perchinsky MJ, Lichtenstein SV, Tyers GFO. Primary cardiac tumors: forty years’ experience with 71 patients. Cancer 1997;79:1809.
Spitz FR, et al. Hemangiopericytoma: a 20-year single-institution experience. Ann Surg Oncol 1998;5:350.
Strollo DC, Rosado-de-Christenson ML, Jett JR. Primary mediastinal tumors. Chest 1997;112:511 (Part I), 1344 (Part II).