1. Anterior Mediastinal Masses
November 30, 2004
Neil J. Fernandes, M.D.

2. Anatomy of the Mediastinum
Boundaries
Superior- Thoracic inlet
Inferior- Diaphragm
Anterior- Sternum
Posterior- Vertebral bodies
Lateral- Pleura

3. Anatomy of the Mediastinum
Compartments
Anterosuperior: anterior to the pericardium, extends superiorly to the thoracic inlet
Middle: bounded by the pericardium and the diaphragm
Posterior: pericardial reflection to the posterior border of the vertebral bodies, diaphragm to first rib

4. Anatomy of the Mediastinum

5. Anatomy of the Mediastinum
Normal Contents
Anterosuperior: thymus, extrapericardial aorta and branches, IVC, SVC, lymphatic tissue
Middle: heart, intrapericardial great vessels, pulmonary hila, pericardium, trachea
Posterior: esophagus, vagus nerves, thoracic duct, sympathetic chain, descending thoracic aorta, azygous venous system

6. Mediastinal Masses Compartment % Malignant Anterosuperior 59 Middle 29
Posterior 16

7. Anterosuperior Masses
Thymus
Mediastinal Lymphoma
Germ Cell Tumor
Thyroid/Parathyroid

8. Thymus
Thymoma
Thymic carcinoma
Thymic carcinoid
Thymolipoma

9. Thymoma Presentation Most common primary anterior mediastinal tumor
M=F, most >40
Most patients are asymptomatic
Half of patients suffer have associated parathymic syndromes
myasthenia gravis
hypogammaglobulinemia
pure red cell aplasia
1/3 have chest pain, cough or dyspnea on presentation
Myasthenia gravis occurs in 30-50% of pts with thymoma. All pts should have antiacetylcholine receptor antibodies measured prior to surgery and subsequently
Hypogammaglobulinemia occurs in 10% of pts with thymoma
Pure red cell aplasia occurs in 5%, but thymoma occurs in 50% of pts with red cell aplasia

10. Thymoma Pathology Histologically benign lymphoepithelial neoplasms
Solid, surrounded by a fibrous capsule
Up to 1/3 have necrosis, hemorrhage or cysts
Up to 1/3 are invasive into mediastinal fat, pleura, pericardium, great vessels, heart and lung
Although they may seed the pleural space, pleural effusions are rare
Lymphatic and hematogenous metastases are rare

11. Thymoma
Radiology
Well-defined, rounded/lobular, mass arising from the thymus
May give rise to pleural implants, rarely associated with effusions
CT evaluation should evaluate the lung apices through the diaphragm to evaluate for vascular invasion and to rule out intrathoracic metastases
The thymus is normally located at the level of the aortic root

14. Thymoma Treatment Complete surgical excision if possible
Histologic evidence of tumor cells outside the capsule defines invasive thymoma
XRT for incompletely resected or invasive tumor
Chemotherapy has been attempted for metastatic or recurrent thymoma with cisplatin, doxorubicin and cyclophosphamide. In one study of 29 patients there were 3 CR, 12 PR and a median 5 year survival of 30%
5 year survival
10 year survival
Encapsulated
75%
63%
Invasive
50%
30%

15. Thymic Carcinoma Presentation M>F, 40s Pathology
Cytologic features of malignancy
Early local invasion, widespread lymphatic and hematogenous metastases
Radiology
Large, poorly defined, infiltrative, associated with pleural and pericardial effusions
Pleural implants are uncommon
Treatment
Etoposide/cisplatin + XRT
5-year survival ranges from 15% to 90% depending on grade

16. Thymic Carcinoid Presentation Men, 4th/5th decade
Rarely associated with carcinoid syndrome
Associated endocrine abnormalities: Cushing’s syndrome due to ectopic ACTH or MEN
73% have regional lymph node and/or distant osteoblastic bone mets
Pathology
Histologically identical to carcinoid tumor at other sites
Radiology
Vascular, large, lobulated, invasive
May have areas of hemorrhage and necrosis
Punctate, dystrophic calcification
Treatment
Complete surgical excision
Local invasion, mets to regional lymph nodes and distant mets have been treated with chemotherapy and XRT, but with poor results

17. Thymolipoma Presentation
M=F, occurs over a wide age range, median age 27
Most are asymptomatic
Pathology
Mature adipose cells and thymic tissue
Radiology
Large, soft, encapsulated
May fall into the anteroinferior mediastinum mimicking cardiomegaly or elevated hemidiaphragm
CT demonstrates a combination of fat and soft tissue densities within an encapsulated mass
Treatment
Surgical excision curative

18. Anterosuperior Masses
Thymus
Thymoma
Thymic carcinoma
Thymic carcinoid
Thymolipoma
Mediastinal Lymphoma
Germ Cell Tumor
Thyroid/Parathyroid

19. Primary Mediastinal Lymphoma
5-10% of patients with lymphoma present with primary mediastinal lesions
Primary mediastinal lymphoma represents 10-20% of primary mediastinal masses in adults and are usually in the anterosuperior compartment
Usually present with fever, weight loss and night sweats
Pain, dyspnea, stridor, SVC syndrome due to mass effects are uncommon

20. Primary Mediastinal Lymphoma
Two Types
Primary Mediastinal Hodgkin’s Lymphoma
Primary Mediastinal Non-Hodgkin’s Lymphoma
Poorly differentiated lymphoblastic
Diffuse lymphocytic
Primary Mediastinal B-cell Lymphoma

21. Primary Mediastinal Hodgkin’s Lymphoma
Presentation
Incidental mediastinal mass on chest xray is the 2nd most common presentation after asymptomatic lymphadenopathy
Mass is usually large, rarely causes retrosternal chest pain, cough, dyspnea, effusions or SVC syndrome
Bimodal age distribution maintained, however, first peak is larger in patients with mediastinal involvement
“B” symptoms: fever, weight loss (>10% body wt in 6 months), night sweats
Generalized pruritus may precede the diagnosis by up to a year and, if severe, is a negative prognostic indicator
EtOH-induced pain, most common in nodular sclerosing subtype

22. Primary Mediastinal Hodgkin’s Lymphoma
Radiology
Multiple rounded masses (lymph nodes)
Mediastinal nodal groups: prevascular, aortopulmonary, paratracheal, pretracheal, subcarinal, posterior mediastinal
Hilar nodes are considered separately
Dominant mass (nodal coalescence)
Thymic mass
May be associated with infiltration and displacement of mediastinal structures and/or extranodal extension into the sternum, chest wall, pleura, pericardium or lung
Usually homogenous attenuation on CT, but large masses may have necrosis, hemorrhage or cysts

23. Loss of paratracheal stripe

24. Anterior mediastinal and parahilar masses

25. Single node region/lymphoid structure or extralymphatic site
Modified Ann Arbor Staging for Hodgkin’s Lymphoma
Definition
Treatment
Cure 1
Single node region/lymphoid structure or extralymphatic site
XRT
>90% 2
≥2 node regions and/or extranodal organs on the same side of the diaphragm
90% 3
Node regions on both sides of the diaphragm and/or splenic involvement or contiguous involvement of an extranodal site
Chemo
A: 80-90%
B: 60-70% 4
Diffuse or disseminated involvement of extranodal organs/tissues +/- node involvement
50-60%

26. Primary Mediastinal Non-Hodgkin’s Lymphoma
Lymphocytic Lymphoma
Median age at presentation is 55, slight male predominance
Advanced disease at presentation with constitutional symptoms, generalized lymphadenopathy +/- extranodal disease

27. Primary Mediastinal Non-Hodgkin’s Lymphoma
Lymphoblastic Lymphoma
1st/2nd decade, M>F
Aggressive, high grade
Often present as a rapidly enlarging mediastinal mass which may cause compression of mediastinal contents
Similar to ALL

28. Primary Mediastinal Non-Hodgkin’s Lymphoma
Primary Mediastinal B-cell Lymphoma
3rd decade, F>M
Presents as a rapidly expanding mediastinal mass which may invade the airway, chest wall and/or adjacent structures.
Extrathoracic involvement is uncommon
Originally classified as a separate category due to its poor prognosis

29. Anterosuperior Masses
Thymus
Thymoma
Thymic carcinoma
Thymic carcinoid
Thymolipoma
Mediastinal Lymphoma
Hodgkin’s Lymphoma
Non-Hodgkin’s Lymphoma
Poorly differentiated lymphoblastic
Diffuse lymphocytic
Primary Mediastinal B-cell Lymphoma
Germ Cell Tumor
Thyroid/Parathyroid

30. Mediastinal Germ Cell Tumors
Represent 10-15% of adult anterosuperior mediastinal tumors
Account for up to 10% of all germ cell tumors in men
Arise from primordial germ cells which are displaced during embryogenesis as they migrate along the dorsal mesentery to the genital ridges
Usually occur in young adults, median age 27

31. Mediastinal Germ Cell Tumors
Three types
Teratoma
Seminoma
Nonseminomatous Germ Cell Tumor

32. Mediastinal Teratomas
Most common mediastinal germ cell tumor
Three types:
Mature: benign, well-differentiated
Immature: contains >50% immature components, may recur or metastasize
Malignant: a mature teratoma that contains a focus of carcinoma, sarcoma or malignant GCT

33. Mature Teratoma Occurs in children and young adults
Usually asymptomatic, but if large enough, may cause chest pain, dyspnea, cough or other symptoms of mediastinal compression
Contains derivatives of all three primitive germ layers including
Ectoderm: teeth, skin, hair
Mesoderm: cartilage and bone
Endoderm: bronchial, intestinal and pancreatic tissue
Expectoration of hair (trichoptysis) is rare but pathognomonic
Surgical excision is curative

34. Mature Teratoma Radiology Large Rounded to lobulated, well-defined
Protrude to one side
26% include calcifications
On CT, multilocular/cystic with fluid, soft tissue, calcium and fat densities

37. Immature Teratoma Rare Similar presentation to mature teratomas
Composed of at least 2 out of 3 germinal layers and >50% immature elements
Treated with radical resection
The roles of neoadjuvant and/or adjuvant chemotherapy are undefined

38. Mediastinal Seminoma General
Represents 40% of malignant mediastinal GCTs
Afflicts Caucasian men in 20s-30s
Only rarely represents a metastatic lesion from a testicular primary tumor, but testicular US is usually performed to rule this out
If any other germ cell tumor histology is identified in the tumor, it is treated as a mixed NSGCT
AFP normal, -HCG may be elevated in 10%

39. Mediastinal Seminoma Presentation
Slow growing tumor, usually symptomatic at diagnosis
Commonly presents with chest pain, dyspnea, cough, weight loss
Presents infrequently with SVC syndrome
Bulky, lobulated, homogeneous mass, no calcifications
Usually not invasive, but many have metastasized to regional lymph nodes, lung and/or bone by the time of diagnosis

40. Mediastinal Seminoma Treatment Chemo and XRT sensitive tumors
Small tumors are treated with primary resection followed by XRT
Advanced tumors are treated with XRT and/or four cycles of bleomycin, etoposide and cisplatin
Treatment followed by surveillance of residual tumor < 3 cm. or resection of residual tumor > 3 cm.
Long-term survival is 60-80%

41. Mediastinal Nonseminomatous Germ Cell Tumors
Five Types
Embryonal cell carcinoma
Endodermal sinus tumor: elevated AFP
Choriocarcinoma: elevated -HCG
Malignant Teratoma
Mixed

42. Mediastinal Nonseminomatous Germ Cell Tumors
NSGCTs of the mediastinum have a worse prognosis than mediastinal seminomas or teratomas
Occur in men in the age group
20% of patients also have Klinefelter’s syndrome
Also associated with i(12p)

43. Mediastinal Nonseminomatous Germ Cell Tumors
Associated with hematologic disorders, including,
Megakaryoblastic leukemia
Myelodysplasia
Malignant mastocytosis
Malignant histiocytosis
Malignant hematologic cells often have the same i(12p) lesion identified in the mediastinal tumor
Occasionally hematopoietic cells in the yolk sac portion of the tumor will have an immunohistochemical profile identical to malignant cells in the bone marrow

44. Mediastinal Nonseminomatous Germ Cell Tumors
Presentation
Common symptoms at presentation include fever, chills, weight loss, chest pain, dyspnea, SVC syndrome
Patients with choriocarcinoma and high levels of -hCG may have gynecomastia
Most have elevated AFP and/or -hCG and the combination of elevated tumor markers in a young male with a mediastinal mass may be used as an indication to begin treatment, even prior to a pathologic diagnosis

45. Mediastinal Nonseminomatous Germ Cell Tumors
Radiology
Large, irregular
Extensive areas of heterogeneous low attenuation on CT due to necrosis, hemorrhage and/or cyst formation
May invade the chest wall or adjacent structures
Metastasizes to regional lymph nodes and distant sites
Pleural and pericardial effusions are common

46. Mediastinal Nonseminomatous Germ Cell Tumors
Treatment
Four cycles BEP (bleomycin, etoposide, cisplatin) +/- XRT
Residual masses are resected and two more cycles of chemotherapy given if malignant cells are found
AFP and -hCG should be monitored to evaluate the effect of treatment and for recurrence

47. Anterosuperior Masses
Thymus
Thymoma
Thymic carcinoma
Thymic carcinoid
Thymolipoma
Mediastinal Lymphoma
Hodgkin’s Lymphoma
Non-Hodgkin’s Lymphoma
Poorly differentiated lymphoblastic
Diffuse lymphocytic
Primary Mediastinal B-cell Lymphoma
Germ Cell Tumor
Teratoma
Mature
Immature
Seminoma
Nonseminomatous Germ Cell
Embryonal cell carcinoma
Endodermal sinus tumor
Choriocarcinoma
Malignant teratoma
Mixed
Thyroid/Parathyroid

48. Mediastinal Goiter A goiter is an enlargement of the thyroid gland
The inferior poles of the thyroid normally lie superior to the thoracic inlet
A minority of people may have thyroid glands that have descended to the level of the thoracic inlet
Enlarging thyroid masses generally grow anteriorly as they are limited only by thin muscles, subcutaneous tissue and skin
Growth through the thoracic inlet can produce symptoms related to compression of normal thoracic inlet contents

49. Mediastinal Goiter The Thoracic Inlet 5x10 cm ovoid area
Anterior: Sternum
Posterior: T1 vertebral body
Lateral: First ribs
Contains trachea, esophagus, carotid arteries, jugular veins, nerves

50. Mediastinal Goiter Presentation Visible cervical goiter
Dyspnea - exertional, positional, nocturnal. May have stridor if tracheal compression is severe
Cough/Choking sensation
Dysphagia - especially if goiter is posterior
Hoarseness
Diaphragmatic paralysis
Horner’s syndrome
Venous compression
Hyperthyroidism - occurs in about 20%, usually subclinical

51. Mediastinal Goiter Physical Exam
Visible cervical goiter - present in 77-90%
Inability to identify inferior pole of thyroid by palpation, even with neck hyperextension
Tracheal deviation
Pemberton’s maneuver
Hold patient’s arms above head for 60 sec
Positive test indicated by distended neck veins, facial plethora, cyanosis, inability to swallow, worsening of dyspnea or stridor
May rarely result in impaction of goiter in thoracic inlet (“Thyroid cork” phenomenon)

52. Mediastinal Goiter Diagnostic Studies Plain films Nuclear Medicine
May demonstrate tracheal narrowing and/or deviation with widening of the mediastinum superiorly
Nuclear Medicine
Radionuclide imaging with 123-I will help to define areas of autonomous functioning tissue
May be misleading if mediastinal extension of the mass is hypofunctioning
Pulmonary Function Tests
Flow-volume loops demonstrate fixed upper airway obstruction
Fine Needle Aspiration
Indicated to evaluate for cancer if prominent discrete nodules are present or if there is a history of rapid growth, pain/tenderness, or firmness in one region

53. Mediastinal Goiter Diagnostic Studies, cont. CT
Encapsulated, lobular heterogeneous mass
Heterogeneity is due to cysts, hemorrhage and locally elevated concentrations of iodine
Coarse punctate or ring-like calcifications are common
Useful to show continuity between the cervical and mediastinal portions of the mass
CT is usually performed with the neck neutral/flexed. If the goiter extends <1.5 cm below the sternal notch it may be completely cervical on extension and thus less likely to be the cause of the patient’s symptom
If iodinated contrast is given, the patient should be pre-treated with methimazole or another anti-thyroid agent to reduce exacerbation of hyperthyroidism

56. Mediastinal Goiter Pathology Most are benign
Multinodular goiter and large follicular adenoma account for 95%
Large multinodular goiters have little functioning tissue. Usually have cystic degeneration, fibrosis, calcification, hemorrhage
Many are found to have areas of papillary thyroid cancer

57. Mediastinal Goiter Treatment
Medical management of hyperthyroidism with antithyroid medications and -blocker
Early surgical resection
Most goiters continue to enlarge
As patient ages surgical complications become more common
Difficult to rule out malignancy in mediastinal portion of tumor
Risk of hemorrhage into mass causing acute airway compression
Resection can usually be performed through a single cervical incision, but massive tumors may require sternotomy

58. Mediastinal Goiter Treatment, cont. Levothyroxine (suppressive dose)
May reduce size of multinodular goiter over time
Only helpful in patients who are euthyroid
Patients with minimal mediastinal involvement, no compressive symptoms or patients who are poor surgical candidates may benefit
Radioactive Iodine
May be useful in patients who are poor surgical candidates, if mediastinal thyroid tissue is functional
Radiation thyroiditis may worsen compressive symptoms

59. Parathyroid Adenoma Accounts for 85% of primary hyperparathyroidism
Occurs in middle-aged adults, 2:1 F:M ratio
Presents with
Asymptomatic hypercalcemia
Nephrolithiasis
Bone pain
Arthralgias/Myalgias
Peptic ulcer disease
Pancreatitis
Fatigue/Anxiety/Depression

60. Parathyroid Adenoma Embryology/Anatomy
Superior parathyroids are derived from the 4th pharyngeal pouch and lie posterior to the upper poles of the thyroid
Inferior parathyroids are derived from the 3rd pharyngeal pouch and usually lie near the lateral surface of the lower poles of the thyroid
Up to 20% of patients have ectopic parathyroid glands
The inferior parathyroids may lie anywhere along the path of descent of the thymus

61. Parathyroid Adenoma Radiology Dual-phase 99mTc-sestamibi imaging
The radiopharmaceutical is taken up within minutes of injection by both the thyroid and parathyroid glands.
The rate of washout from normal thyroid tissue is much faster than the rate from parathyroid adenoma
Early (10-15 min.) and Late (1.5-3 hr.) images of the neck and mediastinum are obtained and compared
False-positives may occur with thyroid nodules or in parathyroid hyperplasia with one dominant gland
False-negative studies can occur with very small lesions or abnormally rapid parathyroid washout

66. Parathyroid Adenoma Treatment Surgical removal US-guided EtOH ablation
bilateral neck exploration
unilateral neck exploration
minimally invasive, image-guided parathyroidectomy
US-guided EtOH ablation
Embolization

67. Anterosuperior Masses
Thymus
Thymoma
Thymic carcinoma
Thymic carcinoid
Thymolipoma
Mediastinal Lymphoma
Hodgkin’s Lymphoma
Non-Hodgkin’s Lymphoma
Poorly differentiated lymphoblastic
Diffuse lymphocytic
Primary Mediastinal B-cell Lymphoma
Germ Cell Tumor
Teratoma
Mature
Immature
Seminoma
Nonseminomatous Germ Cell
Embryonal cell carcinoma
Endodermal sinus tumor
Choriocarcinoma
Malignant teratoma
Mixed
Thyroid/Parathyroid
Goiter
Parathyroid adenoma

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