Mediastinum Flashcards
Tumors of anterior mediastinum (8).
Thymoma, thymic cyst.
Lymphoma.
Thyroid lesions.
Parathyroid adenoma.
Germ-cell tumors.
Paraganglioma.
Hemangioma.
Lipoma.
Tumors of the superior mediastinum (4).
Thymoma, thymic cyst.
Lymphoma.
Thyroid lesions.
Parathyroid adenoma.
Tumors of the posterior mediastinum (2).
Neurogenic tumors.
Gastroenteric cyst.
Tumors of the middle mediastinum (3).
Pericardial cyst.
Bronchial cyst.
Lymphoma.
Thymic cyst: Most common location.
Anterior mediastinum.
Acquired thymic cyst: Associations (5).
Lymphomas, esp. Hodgkin’s lymphoma.
Germ-cell tumors.
Other thymic tumors.
Congenital syphilis.
Previous thoracotomy.
Thymic cyst: Types based on gross pathology (2).
Unilocular: Thin wall; serous contents; congenital.
Multilocular: Thick wall; thick, turbid contents; acquired.
Thymic cyst: Lining (2).
Unilocular: Flat or cuboidal cells.
Multilocular: Variable but usually lined by flat cells.
Thymic cyst: Wall (3).
Unilocular: Usually no thymic remnants.
Multilocular: Thymic remnants.
Both: Inflammation, lymphoid follicles, cholesterol clefts; no differentiated soft tissue.
Cystic hygroma: Histology.
Cavernous spaces lined by flattened endothelium.
Collagenous stroma.
Thymic cyst vs. cystic thymoma.
Cystic thymoma: Thymomatous portion consists of disorganized thymic epithelium and T lymphocytes.
Bronchial cyst:
A. Age group.
B. Clinical sign.
C. Location.
A. Adults.
B. Movement with respiration.
C. Attached to trachea or main bronchus.
Bronchial cyst:
A. Lining.
B. Wall.
C. Contents.
A. Respiratory columnar epithelium, sometimes with squamous metaplasia.
B. Smooth muscle and cartilage.
C. Mucinous.
Esophageal cyst:
A. Synonym.
B. Age group.
C. Location.
A. Esophageal duplication.
B. Children and young adults.
C. At level of mid-esophagus.
Esophageal cyst:
A. Lining.
B. Wall.
C. Contents.
A. Squamous or columnar mucosa.
B. Double layer of smooth muscle is at least focally present.
C. Mucinous.
Enteric cyst:
A. Synonym.
B. Age group.
A. Foregut duplication cyst.
B. Infants and children.
Enteric cyst: Clinical associations (2).
Male sex.
Congenital anomalies of vertebrae, intestines, heart.
Enteric cyst: Location.
Posterior mediastinum, attached to vertebral column.
Enteric cyst:
A. Lining.
B. Wall.
A. Resembles lining of stomach, intestine, colon, or esophagus, complete with lamina propria.
B. Muscularis mucosae and muscularis propria; may contain ganglion cells.
Enteric cyst: Possible complications (3).
Respiratory symptoms.
Dysphagia due to compression.
Hemoptysis due to gastric acid.
Mesothelial cyst: Clinical presentation.
Usually asymptomatic.
Mesothelial cyst:
A. Lining.
B. Wall.
C. Contents.
A. Mesothelium.
B. Fibrous tissue; no smooth muscle.
C. Serous or (in some pericardial cysts) mucinous.
True thymic hyperplasia:
A. Age groups.
B. Associations (3).
A. Children; adults exposed to chemotherapy.
B. Myasthenia gravis, hyperthyroidism, other autoimmune diseases.
True thymic hyperplasia: Histology.
Same as that of normal thymus, but in an enlarged gland.
Thymic follicular hyperplasia: Associations.
Autoimmune diseases.
Thymic follicular hyperplasia:
A. Gross pathology.
B. Histology.
A. Usually normal size and weight.
B. Many follicles with germinal centers containing B lymphocytes.
Thymic follicular hyperplasia vs. normal thymic medulla.
Normal thymic medulla contains Hassall’s corpuscles.
Thymolipoma:
A. Clinical presentation.
B. Histology.
A. Dyspnea and cough due to compression.
B. Mature fat mixed with strands of normal thymic tissue.
Thymolipoma vs. thymic involution.
The involuted thymus is normal in size or small for the patient’s age.
Thymolipoma vs. lipoma.
Lipoma contains no thymic tissue.
Thymoma: Locations.
Typical: Anterior or superior mediastinum.
Others: Thymic rests elsewhere in the mediastinum or in the thyroid gland.
Thymoma: Association with myasthenia gravis (2).
About 10% of patients with MG have thymoma.
About 25-50% of patients with thymoma have MG.
Thymoma: Other associations (4).
Lambert-Eaton syndrome.
Pure red-cell aplasia.
Hypogammaglobulinemia.
Collagen-vascular diseases.
Thymoma: Most important predictor of clinical course.
Presence or absence of invasion of adjacent structures.
Thymoma: Staging system.
Stage I: Completely encapsulated.
Stage IIa: Microscopic breach of capsule.
Stage IIb: Macroscopic invasion into fat or pleura.
Stage III: Macroscopic invasion into pericardium, great vessels, or lung.
Stage IVa: Pericardial or pleural implants.
Stage IVb: Hematogenous or lymphatic spread.
Thymoma: Cellular components.
Neoplastic thymic epithelial cells:
− Oval or spindled, with bland nucleus.
− Epithelioid, with a vesicular nucleus and a large nucleolus.
Non-neoplastic T lymphocytes.
Thymoma, WHO type A: Histology.
Composed mainly of bland spindle cells.
Thymoma, WHO type AB: Histology.
Bland spindle cells mixed with many lymphocytes.
Thymoma, WHO type B: Definition.
A thymoma that consists mainly of epithelial cells, with variable numbers of mature and immature T lymphocytes.
Thymoma, WHO type B1: Histology.
Many lymphocytes and few epithelial cells.
The epithelial cells show minimal atypia.
Thymoma, WHO type B2: Histology.
Lymphocytes and epithelial cells are about equal in proportion.
The epithelial cells show mild to moderate atypia.
Thymoma, WHO type B3: Histology.
Few lymphocytes and many epithelial cells.
The epithelial cells show significant atypia, discrete cell borders, and rare mitotic figures.
WHO classification of thymomas: Correlation with histologic regions of the thymus.
Type A: Medullary.
Type AB: Mixed.
Type B: Cortical.
Thymoma: Histologic predictors of worse prognosis (4).
Predominance of epithelial cells.
Atypia of epithelial cells.
Loss of fibrous compartmentalization.
Loss of perivascular spaces.
Thymoma: Immunohistochemistry of the epithelial cells.
Positive: Pancytokeratin; p63, PAX8 (nuclear).
Thymoma: Flow cytometry.
In a lymphocyte-rich thymoma, flow cytometry can contribute to a misdiagnosis of lymphoblastic lymphoma.
Thymoma vs. lymphoblastic lymphoma.
Lymphoblastic lymphoma:
- Younger patients.
- Clonal T lymphocytes.
Spindle-cell thymoma vs. other spindle-cell tumors.
Spindle-cell sarcomas and solitary fibrous tumor do not express cytokeratin.
Thymic carcinoma: Associations (2).
May arise from thymoma.
Does not cause myasthenia gravis or pure red-cell aplasia.
Thymic carcinoma: Relative incidence.
Les common than secondary tumors of the thymus.
Primary thymic carcinoma is a diagnosis of exclusion.
Thymic carcinoma: Gross pathology (2).
Usually no capsule.
May be desmoplastic but has none of the fibrous septa of thymoma.
Thymic carcinoma vs. thymoma: Basic histologic differences (2).
Thymic carcinoma is frankly malignant.
Thymic carcinoma has lost all organotypic features.
Thymic carcinoma: Grading.
Low-grade vs. high-grade.
Thymic carcinoma: Frequent subtypes (6).
Keratinizing SCC.
Basaloid carcinoma.
Spindle-cell (sarcomatoid) carcinoma.
Clear-cell carcinoma.
Mucoepidermoid carcinoma.
Lymphoepithelioma-like carcinoma.
Lymphoepithelioma-like thymic carcinoma: Viral association.
Rarely related to EBV.
Spindle-cell thymic carcinoma: Association.
Often arises from spindle-cell thymoma.
Thymic carcinoma: Subtypes that are typically low grade (2).
Basaloid carcinoma.
Papillary carcinoma.
Thymic carcinoma: Subtypes that are typically high grade (5).
Clear-cell carcinoma.
Lymphoepithelioma-like carcinoma.
Anaplastic carcinoma.
Spindle-cell carcinoma.
Spindle-cell carcinosarcoma.
Thymic carcinoma: Non-epithelial immunohistochemical markers (2).
CD5, CD117.
Thymic carcinoma vs. epithelioid hemangioendothelioma.
Epithelioid hemangioendothelioma:
- Cytoplasmic vacuoles.
- Expression of vascular markers.
Thymic carcinoma: Prognosis.
Low-grade thymic carcinomas are cured by excision.
All others have a poor prognosis.
Neuroendocrine tumors of the thymus: Epidemiology.
Significantly more common in males.
Thymic carcinoid tumor:
A. Clinical behavior.
B. Paraneoplastic syndromes.
A. More aggressive than bronchial carcinoid; can metastasize.
B. Cushing’s syndrome, SIADH, Lambert-Eaton syndrome.
Well-differentiated neuroendocrine tumor of the thymus: Histology (4).
Fewer than 3 mitotic figures per 10 high-power fields.
Minimal atypia.
Classic organoid pattern.
No more than pinpoint foci of necrosis.
Moderately differentiated neuroendocrine tumor of the thymus: Histology (3).
3-10 mitotic figures per 10 hpf.
Loss of organoid architecture in most cases.
Moderate cytologic atypia with large nucleoli.
Poorly differentiated neuroendocrine tumor of the thymus: Histology (4).
More than 10 mitotic figures per 10 hpf.
Marked atypia or areas of small-cell carcinoma.
Total loss of organoid architecture.
Extensive necrosis.
Neuroendocrine tumor of the thymus vs. metastatic medullary carcinoma of the thyroid.
Medullary carcinoma expresses CEA.
N.B.: Neuroendocrine tumors can have amyloid-like stroma and scattered expression of calcitonin.
Neuroendocrine tumor of the thymus vs. paraganglioma.
Paraganglioma does not express cytokeratin.
Neuroendocrine tumor of the thymus: Clinical predictors of poor prognosis (2).
Association with MEN syndrome.
Production of ACTH.
Chronic mediastinitis:
A. Site.
B. Age group.
A. Anterior-superior mediastinum.
B. Most common in young adults.
Chronic mediastinitis: Causes (5).
Fungi: Histoplasma, Aspergillus.
Nocardia.
Mycobacteria.
Methysergide.
Idiopathic.
Chronic mediastinitis:
A. Radiography.
B. Possible complication (2).
A. Widened mediastinum.
B. Superior-vena-cava syndrome; compression and thrombosis of pulmonary vein.
Chronic mediastinitis: Histology.
Dense, hyalinized fibrous tissue.
Granulomas.
Hodgkin’s lymphoma of the thymus: Typical site.
Anterior mediastinum.
Hodgkin’s lymphoma of the thymus: Primary vs. secondary disease.
Primary disease: Diagnosis requires presence of classic Reed-Sternberg cells in a background consistent with Hodgkin’s lymphoma.
Secondary disease: Presence of mononuclear Reed-Sternberg-type cells in a background consistent with Hodgkin’s lymphoma is sufficient.
Hodgkin’s lymphoma of the thymus vs. sclerosing large-cell lymphoma (4).
Sclerosing large-cell lymphoma:
- Sclerosis is diffuse rather than in broad bands.
- Few or no small lymphocytes, plasma cells, or eosinophils.
- Tumor cells express B-cell markers.
- Negative for CD15 (but may express CD30).
Lymphoblastic lymphoma: Age group.
Occurs mainly (but not exclusively) in older children and adolescents.
Lymphoblastic lymphoma: Frequent clinical presentation.
Acute respiratory distress due to rapid growth of tumor.
Lymphoblastic lymphoma: Cytology (3).
Absent or inconspicuous nucleoli.
Nucleus may be convoluted and resemble a transverse section of a brain.
Necrosis can show starry-sky pattern or be extensive.
Lymphoblastic lymphoma: Immunophenotype (5,2,1).
Positive: CD1a, CD3, CD43, CD99, TdT.
Variable: CD4, CD8.
Negative: CD20.
Lymphoblastic lymphoma: Limitations of flow cytometry.
May not distinguish lymphoblastic lymphoma from the benign immature lymphocytes of lymphocyte-rich thymomas.
Castleman’s disease: Types (3).
Hyaline-vascular.
Plasma-cell (including multicentric variant).
Mixed.
Castleman’s disease: Possible signs and symptoms (7).
Fever.
Hepatosplenomegaly.
Anemia, pancytopenia.
Hypergammaglobulinemia, increased ESR.
Proteinuria.
Castleman’s disease: Malignant associations (3).
Non-Hodgkin’s lymphoma.
Carcinoma.
Kaposi’s sarcoma.
Castleman’s disease: Viruses (2).
Multicentric variant: HIV, HHV-8.
Castleman’s disease, hyaline-vascular type: Histology (4).
Hyalinization of blood vessels that supply germinal centers.
Small, hyalinized germinal centers, sometimes many within one follicle.
“Onion-skin” pattern of mantle zones.
Rich network of capillaries in the interfollicular zone.
Castleman’s disease, plasma-cell type: Histology.
Sheets of plasma cells between the follicles.
Large, reactive germinal centers.
Castleman’s disease, mixed type: Histology.
Combines features of hyaline-vascular and plasma-cell types.
Castleman’s disease: Immunohistochemistry.
CD5-positive lymphocytes congregate at the peripheral of the abnormal follicles.
Castleman’s disease: Clonality.
Typically polyclonal, being a reactive process; however, monoclonal populations of plasma cells have been described.
Severe combined immunodeficiency: Thymic histology (3).
No corpuscles of Hassall.
Few or no lymphocytes.
Lobules of spindled or polygonal epithelial cells.
AIDS: Thymic histology (2).
Severe depletion of lymphocytes.
Hassall’s corpuscles may be lost.
Graft-versus-host disease: Thymic histology (3).
Severe depletion of lymphocytes.
Hassall’s corpuscles may be lost.
Thymic epithelial cells may undergo apoptosis.
Most frequent mediastinal germ-cell tumor.
Teratoma.
Teratoma with additional malignant components: Types (4).
Type I: Teratoma with carcinoma.
Type II: Teratoma with another germ-cell tumor.
Type III: Teratoma with sarcoma.
Type IV: Teratoma with any combination of the above.
Mediastinal germinoma:
A. Typical patient.
B. Possible clinical presentations (2).
A. Male, second through fourth decade.
B. Cervical lymphadenopathy, superior-vena-cava syndrome.
Mediastinal germinoma:
A. Nucleoli of tumor cells.
B. Location of lymphocytes.
A. Described as “spiked”.
B. In the fibrous septa.
Mediastinal germinoma: Processes that can obscure the tumor cells (3).
Granulomatous reaction.
Follicular hyperplasia.
Stromal sclerosis and hyalinization.
Mediastinal germinoma: Immunohistochemistry.
Positive: PLAP, CD117, OCT-4.
Paranuclear dotlike expression of cytokeratin in 80% of cases.
Mediastinal germinoma: Special stain.
PAS.
Nonseminomatous germ-cell tumors of the thymus: Preoperative indicators of a choriocarcinomatous component.
Gynecomastia.
hCG >500 IU.
Nonseminomatous germ-cell tumors of the thymus: Associated syndrome.
Kleinfelter’s syndrome.
Yolk-sac tumor: Reticular pattern.
Netlike arrangement of variably sized spaces; also known as the microcystic pattern.
Yolk-sac tumor: Polyvesicular-vitelline pattern.
Saclike structures in a myxoid or fibrous stroma.
Yolk-sac tumor: Feature common to all types.
Intra- or extracellular hyaline globules that contain α₁-antitrypsin.
Choriocarcinoma: Cellular components.
Cytotrophoblasts.
Giant syncytiotrophoblasts.
Nonseminomatous germ-cell tumors: Frequency of immunohistochemical reactivity for ___.
A. Cytokeratin.
B. PLAP.
C. AFP.
A. All tumors.
B. About half of tumors.
C. 30% of embryonal carcinomas, most yolk-sac tumors.
Nonseminomatous germ-cell tumors: Mutation.
Isochromosome 12p.
Nonseminomatous germ-cell tumors of the thymus: Histologic indicators of poor prognosis (2).
Extrathymic invasion or metastasis on presentation.
Sarcomatoid transformation.
Nonseminomatous germ-cell tumors of the thymus: Association with hematological malignancy.
Yolk-sac tumor may give rise to AML (acute myelomonocytic or acute megakaryoblastic).
Neurogenic tumors of thymus:
A. Special property.
B. Most common.
A. More likely to show differentiation than neurogenic tumors of other sites.
B. Ganglioneuroma.
Neuroblastoma:
A. Age group.
B. Prognosis.
A. 90% of patients are <5 years old.
B. Depends on stage; average 3-year survival is 30%.
Neuroblastoma: Histology.
Small, round, blue cells (neuroblasts) forming Homer Wright pseudorosettes.
Ganglioneuroblastoma: Histology.
Neuroblastoma + ganglion cells, the latter making up more than half of the tumor.
Ganglioneuroma: Histology.
Maturing: Differentiating neuroblasts, ganglion cells, neuropil.
Mature: Sheets of Schwann cells and clusters of mature ganglion cells.
Immunohistochemical profile of ___.
A. Neuroblasts (3).
B. Schwann cells (3).
A. Neurofilament, synaptophysin, chromogranin.
B. S100, GFAP, myelin basic protein.
Neuroblastoma: Genetic findings associated with better prognosis (4).
Near-triploidy or hyperdiploidy.
Presence of 1p36 tumor-suppressor gene.
No amplification of N-MYC.
No expression of TRKA factor receptor.
Neuroblastoma: Genetic findings associated with worse prognosis (3).
Tetraploidy or near-diploidy.
Loss of heterozygosity for 1p36.
Amplification of N-MYC (>10 copies).
Most common tumor of the posterior mediastinum.
Schwannoma.
Schwannoma: Periphery.
Well-formed fibrous capsule.
Ancient schwannoma: Histology (3).
Stromal sclerosis.
Atypical nuclei.
Little or no mitotic activity.
Cellular schwannoma: Histology (3).
Highly cellular, consisting exclusively of Antoni A areas.
Variable nuclear atypia.
Low mitotic activity.
Schwannoma: Immunohistochemistry (3).
Positive:
- S100 (strong in cellular schwannoma).
- CD57.
- GFAP.
Schwannoma: Classic finding on electron microscopy.
Luse bodies, which consist of collagen fibrils with a periodicity of 130 nm.
Metastases to the thymus:
A. Most common primary sites (4).
B. Distinction from primary tumors of the thymus.
A. Trachea, bronchi, lung, esophagus.
B. Immunohistochemistry may not help; clinical history is always essential.
