Thoracic pathology Flashcards
Lungs, mediastinum
grading non-mucinous lung adenocarcinoma
Thymoma
essential and desireable dx criteria type B1
Essential:
A thymic epithelial tumour with organoid (corticomedullary) architecture with cortical predominance Dispersed, non-clustered thymic epithelial cells among densely packed lymphocytes Medullary islands are obligatory
Desirable:
Cytokeratin and/or p40/p63 stains to highlight dispersed epithelial cells Sheets of TdT-positive immature T cells interspersed with TdT-negative nodular (medullary) areas
mediastinal mass
Dx?
Key features?
Type B1 thymoma
Essential:
A thymic epithelial tumour with organoid (corticomedullary) architecture with cortical predominance Dispersed, non-clustered thymic epithelial cells among densely packed lymphocytes Medullary islands are obligatory Desirable: Cytokeratin and/or p40/p63 stains to highlight dispersed epithelial cells Sheets of TdT-positive immature T cells interspersed with TdT-negative nodular (medullary) areas
Thymic cancers
T staging (AJCC)
Thymoma
B2 essential and desireable criteria:
Essential:
Lobulated architecture Abundance of lymphocytes Polygonal/oval neoplastic epithelial cells that are more numerous than in the normal thymic cortex and often present in clusters
Desirable:
Keratin and/or p40/p63 stains to highlight the increased density of dispersed and/or clustered epithelial cells compared with the normal thymic cortex
Dediastinal lesion
Dx:
Key features:
IHC:
Associations/clin presentation:
DDx:
Type B2 thymoma.
Image: Perivascular spaces composed of a central venule surrounded by a clear space containing proteinaceous fluid and variable numbers of lymphoid cells.
Key features: Lobules of irregular size + shape, delineated by fibrous septa. Polygonal/oval epithelila cells occur among lymphocytes as interspersed single cells or clusters (i.e. >/=3contiguous cells). Perivascular spaces are common
IHC: p40/p63(+) in epi cells; TdT(+) immature T-cells; CD20 can stain some B-cells however epithelial cells are CD20(-)
Clin association: Myasthenia gravis is the first presentation in 50% of pts
DDx: B1 thymoma (medullary islands; less epi cells; less perivascular psaces); B3 thymoma (lymphocyte poor)
Mediastinal lesion:
Dx?
Key features
Thymoma type A
Essential:
A thymic epithelial tumour with bland spindle and oval, and rarely polygonal, epithelial cells with a fascicular, storiform, or haemangiopericytomatous growth pattern
Most cases lack areas of necrosis and have a low mitotic count and a low Ki-67 index
Atypical type A thymomas may have higher mitotic count and focal necrosis
Desirable:
Strong expression of epithelial markers (e.g. p63/p40)
Paucity or absence of immature TdT-positive T cells throughout the tumour
Below: This example comprises sheets of uniform polygonal cells interspersed with glandular structures and microcysts.
mediastinal lesion
Dx:
essential & desireable dx features
IHC:
Type AB thymoma
Essential:
A thymic tumour with a lobulated growth pattern
Admixed spindle cell–predominant lymphocyte-poor component (type A) and lymphocyte-rich component (type B)
Bland spindle, oval, and focally polygonal thymic epithelial cells and focal or diffuse abundance of immature T cells
In type A tumours with focal lymphocytic stroma in which lymphocytes are difficult to count, ≥ 10% area showing infiltrate of TdT-positive T cells should be classified as type AB thymoma
Desirable:
TdT immunostaining to assess TdT-positive cell density for differential diagnosis with type A thymoma
IHC: epithelial cells pancytokeratin (+); Tumour cells with aberrant expression of CD20 can be seen in both type A and type B–like areas; spindle cells (+) vimentin/EMA; T cells TdT(+)
Image: Higher magnification shows sharp transition between a lymphocyte-rich and a lymphocyte-poor area with spindle cell morphology of the epithelial cells.
mediastinal lesion
Dx:
Key features:
DDx:
B3 thymoma
Essential:
Lobulated tumour
Sheets of mildly/moderately atypical, polygonal tumour cells
Interspersed perivascular spaces
Paucity of lymphocytes
Desirable:
TdT immunostain to highlight the small population of immature T cells
DDx: B2 thymoma (lymphocyte-rich); thymic squamous cell ca (absence of a lobular growth, infiltrative rather than pushing-type invasion, lack of perivascular spaces, more-prominent nuclear atypia, and frequent presence of intercellular bridges; CD5(+) CD117(+));
Image: Sheets of tumour cells surrounding perivascular spaces. Note the paucity of lymphocytes in between tumour cells but variably numerous lymphocytes in perivascular spaces.
Below: Polygonal tumour cells with distinct cell borders and abundant eosinophilic cytoplasm. The nuclei are oval and have small indistinct nucleoli. A perivascular space is seen in the centre.
mediastinal lesion
dx:
Key features:
IHC
B1 thymoma
Essential:
A thymic epithelial tumour with organoid (corticomedullary) architecture with cortical predominance
Dispersed, non-clustered thymic epithelial cells among densely packed lymphocytes
Medullary islands are obligatory
Desirable:
Cytokeratin and/or p40/p63 stains to highlight dispersed epithelial cells
Sheets of TdT-positive immature T cells interspersed with TdT-negative nodular (medullary) areas
mesothelioma
Histopathologic subtypes
epithelioid, sarcomatoid, biphasic
mesothelioma vs reactive mesothelial hyperplasia
IHC
BAP1 and MTAP are retained in reactive mesothelial hyperplasia
mesothelial cells
Positive stains
pleural biopsy
Dx, DDx, IHC?
Epithelioid mesothelioma.
DDx: primary lung adenocarcinoma; atypical mesothelial hyperplasia, primary lung SCC
IHC: BAP1 and MTAP (for meso hyperplasi)
Claudin4 and Ber-EP4 vs WT1/calretinin/CK5/6/D2-D40 for meso vs adeno
lung cancer
Minimally invasive lung adenocarcinoma
MILA:
Essential:
A small (≤ 30 mm) solitary lepidic-predominant adenocarcinoma with an invasive component ≤ 5 mm
Invasive component to be measured includes any histological subtype other than a lepidic pattern (e.g. acinar, papillary, micropapillary, or solid, or less often colloid, enteric, fetal, or invasive mucinous adenocarcinoma) and tumour cells infiltrating myofibroblastic stroma
The following should be absent: invasion of lymphatics, blood vessels, or pleura, as well as tumour necrosis or spread through airspaces
A completely resected tumour that is entirely sampled and evaluated histologically (dx not made on small biopys or cytology)
Desirable:
The percentage of each of the invasive components should be recorded
2mm lung nodule
dx
Essential + desireable key features
DDx:
Dx: atypical adenomatous hyperplasia (putative precursor to AIS)
Essential:
Increased numbers of type II pneumocytes and club cells lining alveoli in a discontinuous monolayer
Mild atypia
Small localized lesion, usually ≤ 5 mm, discrete from surrounding alveolar parenchyma
Surrounding parenchyma devoid of inflammation or fibrosis
DDx: AIS, reactive pneumocyte hyperplasia secondary to parenchymal inflammation or fibrosis, micronodular pneumocyte hyperplasia, which shows less cytological atypia and characteristically occurs in women with lymphangioleiomyomatosis and/or tuberous sclerosis.
40M, circumscribed peripheral lung lesion, incidental finding
dx
Epidemiology
Desireable + key features
IHC
Fetal adenocarcinoma, high-grade
Low-grade fetal adenocarcinoma occurs in younger individuals, with an almost equal sex ratio { 30197546 ; 31938258 }, whereas high-grade fetal adenocarcinoma is more common in elderly men who are heavy smokers
Essential:
Adenocarcinoma resembling fetal lung airway epithelium of pseudoglandular stage
Low-grade fetal adenocarcinoma shows mild nuclear atypia and aberrant nuclear/cytoplasmic β-catenin expression
High-grade fetal adenocarcinoma shows severe nuclear atypia
High-grade fetal adenocarcinomas are frequently mixed with other adenocarcinoma patterns and should constitute ≥ 50% of the entire tumour
Desirable:
Low-grade fetal adenocarcinoma should express TTF1
High-grade fetal adenocarcinoma should have predominantly membranous β-catenin expression
Nuclear/cytoplasmic expression of β-catenin is observed in low-grade fetal adenocarcinoma, whereas membranous expression of β-catenin is predominant in high-grade fetal adenocarcinoma { 12065775 }. Low-grade fetal adenocarcinoma is positive for TTF1, whereas approximately 50% of high-grade fetal adenocarcinomas are negative. Both are frequently positive for neuroendocrine markers. High-grade fetal adenocarcinoma commonly expresses oncofetal proteins such as AFP, SALL4, and glypican-3 (GPC3) { 9537466 ; 23629442 ; 25851923 ; 28840008 ; 30197546 }.
The differentiation between low-grade fetal adenocarcinoma and high-grade fetal adenocarcinoma is essential because of the marked difference in prognosis. They need to be differentiated from pulmonary blastoma, carcinosarcoma with a high-grade fetal adenocarcinoma component, and metastatic endometrioid carcinoma
Below: low-grade fetal adeno showing morular structure with a few optically clear nuclei. The glandular cells show regular, monotonous round nuclei of low-grade atypia.
cardiac myxoma
dx key features
IHC
DDx
Essential:
Myxoma cells within a myxoid stroma
Appropriate location
Desirable:
Calretinin reactivity within the myxoma cells
Perivascular rings
+/- hemosideron is common
DDx: organizing thrombus, so-called calcified amorphous tumour (when calcification is present), papillary fibroelastoma (particularly with villiform myxomas), and other rare entities. When heterologous glands are identified, differentiation from metastatic adenocarcinoma is paramount, and this can usually be achieved with clinical history, imaging, and ancillary studies.
Below: perivascular ring structure composed of myxoma cells growing around small intratumoural blood vessels.
sclerosing pneumocytoma:
Key features
IHC
DDx
The key feature of sclerosing pneumocytoma is the presence of two cell types: cuboidal surface cells and round stromal cells, both of which are considered neoplastic. The surface cells are cuboidal and morphologically similar to type II pneumocytes. The round cells are small, with well-defined borders and central bland nuclei with fine chromatin and scant small nucleoli. The tumours typically have a combination of growth patterns: papillary, sclerotic, solid, and haemorrhagic.
IHC: Both surface and round cells are positive for EMA and TTF1. Pancytokeratin, CAM5.2, CK7, and napsin A stain the surface cells diffusely, but the round cells are usually negative or weakly positive. Neuroendocrine markers are negative. ER and PR staining has also been reported in some cases in the round cells.
DDx: carcinoid tumours and papillary adenocarcinoma. In general, the multiple growth patterns, presence of bland cytological features, a dual cell population, and the characteristic immunostaining profile discriminate sclerosing pneumocytoma from other entities.
Below: Low power showing a mixture of papillary, solid, and sclerotic patterns.
lung staging
