Thoracic pathology Flashcards

Lungs, mediastinum

1
Q

grading non-mucinous lung adenocarcinoma

A
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2
Q

Thymoma

essential and desireable dx criteria type B1

A

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
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3
Q

mediastinal mass

Dx?
Key features?

A

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
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4
Q

Thymic cancers

T staging (AJCC)

A
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5
Q

Thymoma

B2 essential and desireable criteria:

A

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
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6
Q

Dediastinal lesion

Dx:
Key features:
IHC:
Associations/clin presentation:
DDx:

A

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)

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7
Q

Mediastinal lesion:
Dx?
Key features

A

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.

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8
Q

mediastinal lesion

Dx:
essential & desireable dx features
IHC:

A

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.

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9
Q

mediastinal lesion

Dx:
Key features:
DDx:

A

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.

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10
Q

mediastinal lesion

dx:
Key features:
IHC

A

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

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11
Q

mesothelioma

Histopathologic subtypes

A

epithelioid, sarcomatoid, biphasic

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12
Q

mesothelioma vs reactive mesothelial hyperplasia

IHC

A

BAP1 and MTAP are retained in reactive mesothelial hyperplasia

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13
Q

mesothelial cells

Positive stains

A
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14
Q

pleural biopsy

Dx, DDx, IHC?

A

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

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15
Q

lung cancer

Minimally invasive lung adenocarcinoma

A

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

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16
Q

lung cancer

adenocarcinoma in situ definition

A

Essential:

A small (≤ 30 mm diameter) localized lesion comprising pure lepidic growth
Stromal, vascular, or pleural invasion, as well as spread through airspaces and invasive adenocarcinoma patterns, all absent
Adenocarcinoma cells line alveolar walls in a continuous layer; tufting and overlapping may be present
A completely resected tumour that is entirely sampled and evaluated histologically
Desirable:

Nuclear atypia and alveolar septal thickening are variable

17
Q

2mm lung nodule

dx
Essential + desireable key features
DDx:

A

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.

18
Q

40M, circumscribed peripheral lung lesion, incidental finding

dx
Epidemiology
Desireable + key features
IHC

A

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.

19
Q
A
20
Q

lung adenocarcinoma

colloid adenocarcinoma

A

Essential:
Abundant pools of extracellular mucin that distend alveolar spaces and destroy their walls
Tumour cells are mucin-filled, cuboidal to columnar, and either floating within the mucin pools or lining fibrous walls of mucin-filled spaces
≥ 50% colloid pattern when mixed with other adenocarcinoma subtypes
Distinction from metastases from the other organs
Desirable:

Bland cytology of tumour cells in mucin pools
Frequent positivity for CK7 and CDX2

21
Q

cardiac myxoma

dx key features
IHC

DDx

A

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.

22
Q

pleomorphic carcinoma

definition

A

Pleomorphic carcinoma is a poorly differentiated non-small cell lung carcinoma (non-small cell carcinoma [NSCC], including adenocarcinoma, squamous cell carcinoma [SCC], and/or large cell carcinoma [LCC]) containing at least a 10% component of spindle and/or giant cells, or a carcinoma that consists entirely of spindle and/or neoplastic giant cells. The definitive diagnosis of pleomorphic carcinoma may be rendered only in surgical specimens.

23
Q

Usual interstitual pneumonia

criteria

A

Dense fibrosis with architectural distortion (i.e., destructive scarring or honeycombing)
Predominant subpleural or paraseptal distribution of fibrosis
Patchy involvement of lung parenchyma by fibrosis
Fibroblast foci
Absence of features to suggest an alternate diagnosis

24
Q

sclerosing pneumocytoma:
Key features
IHC
DDx

A

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.

25
Q

lung staging

A
26
Q

adenocarcinoma in situ of lung.

Essential and desirable dx criteria

A

Essential:
A small (≤ 30 mm diameter) localized lesion comprising pure lepidic growth
Stromal, vascular, or pleural invasion, as well as spread through airspaces and invasive adenocarcinoma patterns, all absent
Adenocarcinoma cells line alveolar walls in a continuous layer; tufting and overlapping may be present
A completely resected tumour that is entirely sampled and evaluated histologically
Desirable:
Nuclear atypia and alveolar septal thickening are variable

27
Q

minimally invasive adenocarcinoma of the lung

Essential and desirable dx criteria.

A

Essential:
A small (≤ 30 mm) 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
Desirable:
The percentage of each of the invasive components should be recorded
The tumour can be non-mucinous (type II pneumocytes or club cells) and rarely can be mucinous or mixed mucinous and non-mucinous
If a tumour with pure lepidic growth has only been partly sampled, the diagnosis of lepidic adenocarcinoma should be rendered with a comment that the diagnosis of AIS or MIA cannot be made without complete histological sampling

28
Q

ddx small cell lung cancer

A

Large cell neuroendocrine carcinoma - light microscopic features, more abundant cytoplasm, polygonal cell shape, vesicular nuclear chromatin often w/ nucleoli (no nucleoli in SCLC)
Merkel cell (NEC of the skin) carcinoma: Mkerek cell. polyomavirus and CK20+, (-) TTF1.
Lymphoma: negative for CK, (+) for lymphoid markers
Basaloid SCC: S&D p40/p63
Carcinoid (TC vs AC): mitoses/necrosis; +/- Ki67 in crushed specimens.
Small round sarcomas (e.g. Ewing sarcoma family and those lacking EWSR1 gene rearrangement e.g. CIC-DUX4-rearranged and BCOR-CCNB3 rearranged tumours) - sometimes express NEM. FISH
SMARC4A deficient thoracic undifferentiated tumours. Loss of BRG1.

29
Q

essential and desirable dx criteria for large cell neuroendocrine carcinoma

A

Essential:
Neuroendocrine morphology: organoid nesting, trabeculae, peripheral palisading, rosettes
Non-small cell cytology: prominent nucleoli and/or moderate to abundant cytoplasm, larger cell size than SCLC (> 3 lymphocytes), and chromatin may be either granular/stippled or vesicular
High proliferation rate: > 10 mitoses/2 mm2, with a median of 70 mitoses/2 mm2
Positive immunohistochemical staining for one or more neuroendocrine markers (other than NSE)
Desirable:
Necrosis: generally in large confluent zones but may be limited to the centres of tumour nests
High Ki-67 index: > 30%, generally 40–80%
Negative p40 immunohistochemistry

30
Q

Differences between pulmonary haemartoma and chondroma?

Syndromic associations?

Stains helpful to differentiate?

A

Pulmonary hamartomas need: At least two types of benign mesenchymal tissue, most commonly hyaline cartilage, fat, and/or myxoid spindle cells, with entrapped invaginated bronchial epithelium

Pulmonary hamartomas are differentiated from monomorphic soft tissue tumours by the presence of more than one mesenchymal component. Chondromas lack entrapped epithelium, frequently show calcification / bone metaplasia, and are bounded by a fibrous pseudocapsule

SDHB immunohistochemistry may be useful; it shows abnormal loss in Carney-associated chondromas but not in hamartomas

31
Q

cardiac valve histology, describe

A
32
Q

staining for LCH?

A

Cd1a and S100 but NOT CD68

33
Q
A
34
Q

What is this and with which condition is this associated?

A

masson body or fibroblastic plug in alveoli space.

Organising pneumonia

35
Q

Interstitial pneumonia, entities but upper and lower zones…

A
36
Q

What is Carney complex?

A

AD disorder characterised by the constellation of myxomas (cardiac or otherwise) endocrinopathy (Cushing syndrome and acromegaly). and spotty skin pigmentation.

37
Q

Rhabdomyomas are a/w which hereditary conditions?

A

Tuberous sclerosis complex (germline mutations in TSC1 or TSC2)

38
Q

how do you differentiated typical vs atypical carcinoid tumours in the lung.

A

Low-grade TC has < 2 mitoses/2 mm2 and lacks necrosis, and intermediate-grade AC has 2–10 mitoses/2 mm2 and/or foci of necrosis
The number of high-power fields used for mitosis counting should be adjusted to achieve 2 mm2 according to the microscope field of view, which varies depending on the microscope manufacturer and model