Thymoma

Epidemiology and Etiology:

• peak 55-65y
• very rare in children and adolescents
• MEN1 have higher risk
• EBV may play an etiologic role in some subsets (thymic carcinomas)
• Radiation is not a risk factor

Common sites:

• Most anterior superior mediastinum
• Sometimes neck, thyroid, pulmonary hilus
• Anywhere in mediastinum, pleura, and lung is possible

Gross features:

• Encapsulated
• Lobulated, firm, gray-white masses
• Up to 15-20cm
• Sometimes areas of cystic necrosis and calcification

Histologic features:

• Encapsulated
• Mixture of epithelial cells and lymphocytes (non-neoplastic thymocytes)
• May be separated into lobules, or completely mixed together
• Type A:
• Epithelial component with spindle to oval nuclei
• Type B:
• Epithelial component with predominantly round or polygonal appearance
• B1-B3 defined by amount of lymphocytes
• B1:
• Thick fibrous capsule usually
• predominantly composed of expanded areas which look similar to normal thymic cortex
• often organoid, lobular architecture
• lobules separated by thin or thick acellular fibrous bands
• often “starry sky” appearance due to scattered tingible-body macrophages
• also pale areas of medullary differentiation (always present)
• loosely packed lymphocytes
• Hassall’s corpuscles maybe (less numerous than normal)
• Poorly-formed epithelial groupings to large keratinized structures
• Abnormal localization adjacent to septa or tumour capsule is very typical
• lymphocyte-rich (non-neoplastic T-cells)
• scant epithelial component
• no cellular groupings
• very little atypia
• smaller nuclei and nucleoli than B2
• cystic spaces and small areas of necrosis may be present
• DDx normal / hyperplastic thymus:
• Larger lobules
• Thicker fibrous capsule
• Fibrous septa
• Predominance of cortical areas over medullary islands, which often abut on fibrous septa
• Fewer or no Hassall corpuscles
• Autoimmune regulator-positive epithelial cells (AIRE
• B2:
• Large, coarse lobular architecture with delicate septa
• Loose network of large, polygonal epithelial cells similar to epithelial cells of normal thymic cortex
• Palisades around perivascular spaces and along septa
• Large, vesicular nuclei
• Prominent large nucleoli
• Large, confluent sheets of epithelial cells may occur (but without the cytologic features of B3 thymoma)
• Background population of immature T cells usually outnumbers the neoplastic epithelial cells
• Medullary islands are missing or inconspicuous
• Hassall’s corpuscles may be present (25%), but not typical appearance
• Lymphoid follicles inside septa or perivascular spaces may be present (particularly in myasthenia gravis)
• B3:
• Lobules of confluent sheets of epithelial cells separated by thick fibrous and hyalinized septa
• Conspicuous palisades of epithelial cells around perivascular spaces and along septa
• Paucity of intraepithelial immature T cells
• Epithelial cells:
• Smaller nuclei than B2
• More irregular nuclear membranes than B2, with nuclear grooves, less vesicular chromatin
• Smaller nucleoli than B2
• No intercellular bridges
• Medullary islands and Hassall’s corpuscles are usually absent
• Small foci of keratinization may be present, mimicking Hassal’s corpuscles
• Lymphoid follicles inside septa or perivascular spaces may be present (particularly in myasthenia gravis)
• Combined B2 and B3 is common
• Steroid treatment effects:
• Accumulation of foamy macrophages in intraepithelial microscysts
• Type AB:
• Combination of A and B1 (or rarely B2) features
• Thymic carcinoma is defined by cytological malignancy
• Squamous cell
• Mucoepidermoid
• others

Immunophenotype:

Marker:	Sensitivity:	Specificity:
HMWK (epithelial cells)
CK19 (epithelial cells)
CK7 (focal; epithelial cells)
P63 (epithelial cells)	All?
CK20 (neg)
EMA (neg in B1/2, focal in B3)
CD1a (cortical, immature T cells)
TdT (cortical, immature T cells)		Normal thymus also stains
CD20 (B cells in medullary areas)
Cdk6 (low expression in thymocytes)
TTF-1 (neg)

Molecular features:

Other features:

• malignant behaviour increases in this order (A, AB, B1, B2, B3, thymic carcinoma)
• associated with autoimmune diseases (particularly types A, AB, and B)
• neuromuscular (ex. Myasthenia gravis)
• hematologic (ex. Anemia, immunodeficiencies)
• dermatologic (rare) (pemphigus, lichen planus, alopecia)
• endocrine (Addison, Cushing, Graves)
• renal (glomerulonephritis
• liver (autoimmune hepatitis)
• systemic (rare) (SLE, GVHD, systemic sclerosis)

Staging:

• T1 – completely encapsulated (invasion of capsule itself is ok)
• T2 – invasion of pericapsular connective tissue (NOT invasion of capsule itself) (note: this may be biologically meaningless…)
• T3 – invasion of neighboring structures:
• Pericardium
• Mediastinal pleura
• Thoracic wall
• Great vessels
• Lung
• T4 – pleural or pericardial dissemination
• N1 – anterior mediastinal lymph nodes (note: lymph node mets are rare in thymoma)
• N2 – other intrathoracic lymph nodes
• N3 – scalene or supraclavicular lymph nodes
• M1 – distant mets

Stage (WHO):	T	N	M	Treatment
I	T1	N0	M0
II	T2	N0	M0
III	T3	N0	M0
	T1-3	N1	M0
IV	T4	any	M0
	any	N2-3	M0
	any	any	M1

Stage (Masaoka):	T	N	M	Treatment
I	T1	N0	M0
II	T2	N0	M0
III	T3	N0	M0
IVa	T4	N0	M0
IVb	Any	N>=1	M0
	Any	N0	M>=1
	Any	N>=1	M>=1

• Note: completeness of resection is an important prognostic factor

References:

• Robbins 2005
• WHO book 2004