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MS2 Respiratory > 9/18- Pathology of Lung Cancer > Flashcards

9/18- Pathology of Lung Cancer Flashcards

1
Q

What are some methods to diagnose lung cancer (biopsies)?

A

- Cytology (exfoliative and fine needle biopsy)

- Nonoperative biopsy (endobronchial, transbronchial)

- Operative biopsy (VATS, open procedure with/without intraoperative evaluation)

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2
Q

What are the 4 most common forms of lung cancer?

A
  • Small cell carcinoma
  • Adenocaracinoma
  • Squamous cell carcinoma
  • Large cell (undifferentiated) carcinoma

Also:

Neuroendocrine carcinomas

(small cell carcinomas actually fall under this category too)

  • Carcinoid
  • Atypical carcinoid
  • Large cell neuroendocrine carcinoma
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3
Q

What is the breakdown for major epithelial types (bronchogenic carcinomas)?

A

Nonsmall cell carcinomas = 80%

  • Adenocarcinoma (40%)
  • Squamous cell carcinoma (30%)
  • Large cell carcinoma (10%)

Small cell carcinoma = 20%

About 10-50% of lung carcinomas have combined histology

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4
Q

What are some risk factors in lung cancer? Which cancers?

A

Smoking: 10-20x non-smokers; mostly squamous and small cell carcinomas

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5
Q

What is the most frequent type of lung cancer associated with non-smokers?

A

Adenocarcinoma (specifically, AIS- adenocarcinoma in situ)

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6
Q

What is the prognosis for lung cancer?

A

Generally poor prognosis (depends on stage)

  • Only 20-30% treatable by surgical resection
  • 15% 5 year survival
  • #1 cause of cancer deaths worldwide
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7
Q

Where does lung cancer commonly metastesize?

A
  • Adrenals (> 50%), especially lower lobe tumors
  • Liver (30-50%)
  • Brain (20%)
  • Bone (20%)
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8
Q

Cancer Nomenclature,

Define:

  • Carcinoma
  • Squamous cell carcinoma
  • Adenocarcinoma
  • Small cell carcinoma
  • Large cell carcinoma
A

- Carcinoma: malignant tumor derived from epithelium

- Squamous cell carcinoma: malignant epithelial tumor resembles stratified squamous epithelium

- Adenocarcinoma: malignant epithelial tumor that forms glands (acini)

- Small cell carcinoma: malignant epithelial tumor which displays neuroendocrine differentiation

- Large cell carcinoma: malignant epithelial tumor composed of large cells with no differentiation by light microscopy

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9
Q

How does treatment differ for small vs. non-small cell carcinomas?

A

Small cell:

  • Chemo and radiation
  • Worst prognosis

Non-small cell:

  • Surgery
  • Prognosis slightly better than small cell
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10
Q

What are characteristics of squamous cell carcinoma?

  • Epidemiology
  • Aka
  • Histology
  • Location
A

Squamous cell carcinoma

  • Aka Epidermoid carcinoma

Epidemiology: M > F (slightly)

Histology:

  • Intercellular bridges (“Prickles”), desmosomes
  • Intracytoplasmic keratin
  • Commonly necrotic (included in DDx of cavitary lesion in the lung, along with TB)

Location: central (hilar)

  • Arises from bronchi
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11
Q

What is seen here?

A

Squamous cell carcinoma

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12
Q

What is seen here?

A

Squamous cell carcinoma

  • Arises from epithelium lining the airway
  • Abrupt transition into malignant tumor (left)
  • Invading into adjacent bronchial wall
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13
Q

How are squamous cell carcinomas graded?

A

Keratin production (amount)

Well-differentiated: most of the tumor makes keratin

Poor-differentiated: hard to find keratin; have to use stains

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14
Q

What is seen here?

A

Squamous cell carcinoma

  • Abundant eosinophilic cytoplasm (filled with keratin filaments)

- Keratin pearl: characteristic of well-differentiated squamous cell carcinoma

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15
Q

What is seen here?

A

Squamous cell carcinoma

  • Size comparison to lymphocytes
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16
Q

What is seen here?

A

Squamous cell carcinoma

  • Keratin pearls!!
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17
Q

What is seen here?

A

Squamous cell carcinoma: poorly differentiated

  • Large nucleoli
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18
Q

What are the 4 basic patterns of adenocarcinoma?

A
  • Acinar (glandular)
  • Papillary
  • Solid with mucin production
  • Adenocarcinoma in situ (formerly bronchioloalveolar carcinoma)

Also can have a mixed subtype

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19
Q

What is key feature of adenocarcinomas?

A

Gland formation

  • Need mucin production (may need special stains in poorly differentiated tumors)
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20
Q

Is adenocarcinoma more common in males or females?

A

Females (47% vs. 37%)

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21
Q

What is seen here?

A

Adenocarcinoma

  • Usually diagnosed by CT guided biopsy because of their peripheral location
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22
Q

What is seen here?

A

Adenocarcinoma

  • Stringy material = mucin
  • Can see mucin without staining
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23
Q

What is seen here?

A

Adenocarcinoma

  • Tumor cell with intracytoplasmic mucin
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24
Q

What is seen here?

A

Adenocarcinoma: poorly-differentiated

  • Very few glands present
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25
Q

What is seen here?

A

Papillary adenocarcinoma

  • Papillary fronds with fibrovascular cords
  • Form tufting of tumor cells
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26
Q

What is seen here?

A

Adenocarcinoma

  • Solid version of adenocarcinoma
  • Don’t see any glands; would not be able to diagnose with this picture without staining for mucin
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27
Q

What stain can be used to stain for mucin production?

A

Mucin-carnine

  • Stains mucin rose/red color
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28
Q

What are some characteristics of adenocarcinoma in situ (formerly BAC)?

  • Growth pattern
  • Biopsy results
  • Location
  • Prevalence
A

Adenocarcinoma in situ (AIS)

  • An adenocarcinoma with a pure lepidic growth pattern
  • Grows along alveolar septa with NO destruction of lung parenchyma
  • NO evidence of stromal, vascular or pleural invasion

Location:

  • Usually peripheral, often subpleural
  • May present as single nodule or widespread, bilateral, synchronous, multifocul nodules
  • May have an aerogenous spread through airways and airspaces like a pneumonia!

In biopsy samples:

  • Dx as adenocarcinoma with lepidic pattern with disclaimer that invasion cannot be excluded

Prevalence: 1-9% of lung cancers

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29
Q

What does “lepidic pattern” mean?

A

Growth along intact alveolar septa (think butterfly)

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30
Q

Epidemiology of adenocarcinoma in situ?

A

1-9% of all lung cancers

  • This is the most common type of lung cancer in non-smokers
  • Still, most AIS cases (85%) are associated with smoking
31
Q

What are the 2 histologic subtypes of AIS? Characteristics?

A

1. Mucinous

  • Spread aerogenously, forming satellite nodules that lead to consolidation “lobar pneumonia pattern”
  • Not amenable to surgery

2. Non-mucinous

  • Present as peripheral nodule
  • Amenable to surgical resection
32
Q

What is seen here?

A

Adenocarcinoma in situ

  • Nonmucinous AIS
33
Q

What is seen here?

A

Adenocarcinoma in situ (Nonmucinous?)

  • No evidence of stromal invasion
34
Q

What is seen here?

A

Adenocarcinoma in situ (Nonmucinous?)

35
Q

What is seen here?

A

Adenocarcinoma in situ (Nonmucinous?)

  • Hobnail appearance
36
Q

What is seen here?

A

Mucinous Adenocarcinoma in Situ

37
Q

What is seen here?

A

Mucinous Adenocarcinoma in Situ

38
Q

What is seen here?

A

Mucinous Adenocarcinoma in Situ

39
Q

Characteristics of Large Cell Carcinoma?

  • Histologically
  • Location
  • More in males/females
A
  • May be designated poorly differentiated non-small carcinoma
  • Undifferentiated, large polygonal cells
  • Lack of diagnostic features of squamous cell, or adenocarcinoma by Light Microscopy
  • Often have features of adenocarcinoma, less often squamous cell carcinoma, by Electron Microscopy
  • Usually peripheral and frequently necrotic
  • M:F (18%:10%)
40
Q

What is seen here?

A

Large Cell Carcinoma

  • Wouldn’t be able to tell from this picture, though
41
Q

What is seen here?

A

Large Cell Carcinoma

42
Q

What is seen here?

A

Mixed cancer

  • Both squamous and glandular differentiation
43
Q

What is the cell of origin for neuroendocrine tumors?

A

Kulchitsky cell

44
Q

What are neuroendocrine tumors of the lung?

Which are more malignant?

A

From low -> high malignancy:

  • Typical carcinoid
  • Atypical carcinoid
  • Small cell carcinoma
  • large cell neuroendocrine carcinoma
45
Q

Characteristics of typical carcinoids? (Histologically)

A
  • Organoid pattern of nests, ribbons, trabeculae or pseudo-rosettes
  • Polygonal cells
  • Stroma of delicate capillary network
  • Absence of pleomorphism, mitotic figures, and tumor necrosis (differentiates from atypical carcinoid)
  • Neuroendocrine features (IHC and EM)
46
Q

What is seen here?

A

Typical carcinoid

  • Associated stromal network
  • Grow in trabecular patterns
47
Q

What is a marker for neuroendocrine tumors used to diagnose typical carcinoid?

A

Chromogranin

48
Q

Characteristics of small cell carcinomas?

  • Location
  • Origin
  • Prognosis
  • Risk factor
  • Male vs. females
A
  • Usually central, presenting has hilar rather than parenchymal mass
  • Originate from neuroendocrine cells of bronchial epithelium, invade bronchial wall
  • Very aggressive tumor, often metastatic at time of diagnosis
  • Strong relationship with smoking (only about 1% occur in nonsmokers)
  • Treatment modality differs from nonsmall cell lung cancers
  • More in females (slightly): 18% vs. 14%
49
Q

Histological features of small cell carcinoma?

A
  • Sheets, nests, with prominent nuclear molding
  • Round, oval, or spindled cells, scant cytoplasm, finely stippled chromatin, indistinct nucleoli
  • May demonstrate extensive crush artifact, often necrotic
  • May be up to 2 to 3 x’s size of resting lymphocyte (“small” compared to squamous and adenocarcinomas)
  • Clinical, immunohistochemical and ultrastructural features of neuroendocrine differentiation
50
Q

What is seen here?

A

Small cell carcinoma

  • Hilar mass
  • Presence of metastatic disease
51
Q

What is seen here?

A

Low power of small cell carcinoma

  • Sea of blue; large nucleus and very little cytoplasm
52
Q

What is seen here?

A

High power small cell carcinoma

  • Hugging nuclei (very little cytoplasm)
53
Q

What is seen here?

A

Small cell carcinoma

54
Q

What are some characteristics of large cell neuroendocrine carcinomas?

  • Neuroendocrine features
  • Shape/morphology
  • Common features
  • Behavior
A
  • Neuroendocrine differentiation by growth pattern and ancillary tests (IHC, EM)
  • Polygonal cells, vesicular nuclei, abundant cytoplasm
  • Necrosis, pleomorphism, mitoses
  • Aggressive behavior
55
Q

What is seen here?

A

Large cell neuroendocrine carcinoma

  • Open chromatin pattern
  • Open nuclei
56
Q

What is seen here? (oops)

A

Large cell neuroendocrine carcinoma

  • Nuclear molding (like small cells) but much more cytoplasm than small cell
57
Q

What is seen here?

A

Left: Large cell neuroendocrine carcinoma

Right: small cell carcinoma

58
Q

What cellular marker can be used to diagnose neuroendocrine cells (used here for large cell NE carcinomas?)

A

CD56 (NCAM)

59
Q

What are some common genetic alterations in lung cancer? Role of each?

A

- p53 mutation: linked to smoking-induced ca’s; most common

- KRAS mutation: poor prognosis/drug resistance

- EGFR mutation*: drug response

- EML4-ALK fusion*: drug response

*EGFR and EML5-ALK are commonly found in adenocarcinomas

  • If glandular formation, it is a non-resectable tumor; want to try to treat with TK inhibitors
  • These 2 tests are mutually exclusive

t is important to subclassify NSCLC

60
Q

What is the EGFR mutation?

  • Mechanism
  • Epidemiology
  • Clinical importance
A
  • EGFR = cell surface receptor involve in regulation of cell proliferation and apoptosis
  • Mutations of TK domain -> uncontrolled proliferation (“activate mutation”) ~ oncogene
  • Frequency/mutation varies with: smoking, gender, histology
  • Mostly seen in non-smoking females
  • Mostly found in adenocarcinomas (15%)

Clinical implications: sensitive to TK inhibitor

  • Gefitinib
  • Erlotinib
61
Q

What is the EML3-ALK Gene fusion?

  • Mechanism
  • Epidemiology
  • Clinical importance
A
  • Aberrant fused gene -> abnormal fused protein (leads to uncontrolled cell growth/proliferation)

Epidemiology:

  • Fused gene most frequent in light smokers (under 10 pack yrs) or never smokers
  • Also found in younger patients (under 50 yo)
  • 1-7% of adenocarcinomas (ALK+)

Clinically:

  • ALK+ tumors are sensitive to ALK receptor kinase inhibitor Crizotinib
62
Q

What are common metastatic tumors to lung/pleura?

A
  • Lung involved by metastatic disease in 20-54% of cases (autopsy studies)
  • Usually multiple (lower lobes), up to 9% single lesion
  • Breast, GI tract, kidney, prostate, ovary
  • Lymphomas
  • Variety of sarcomas (leiomyosarcoma)
  • Melanoma
63
Q

What is seen here?

A

Metastatic colon cancer: colonic adenocarcinoma

  • Original tumor looks identical to metastasis
  • Here, confirmed by CK20 positivity (common in colorectal carcinomas)
64
Q

What is seen here?

A

Renal cell carcinoma

  • Metastasis to lung
65
Q

Characteristics of malignant mesothelioma?

  • Location
  • Prevalence
  • Prognosis
  • Risk factors
A

- Location: primary malignant neoplasm of the mesothelial lining

- Prevalence: rare, 1-2 million/yr in gen pop

- Prognosis: rapidly progressive, 50% die within 12 mo of diagnosis

Risk factors

  • Heavy asbestos exposure, latency 25-45 yrs
  • Associated with amphibole type asbestos fiber (crocidolite subtype greatest risk)
66
Q

What is seen here?

A

Malignant mesothelioma

67
Q

What is seen here?

A

Malignant mesothelioma

68
Q

What are some cytogenic techniques in lung cancer diagnosis?

A

Exfoliative

  • Sputum
  • Bronchial washing
  • Bronchial brushing
  • Bronchoalveolar lavage

Fine needle aspiration biopsy

69
Q

What are some common cytologic features of malignancy?

A
  • Larger cells than benign
  • High N:C ratio
  • Irregular nuclear borders
  • Prominent, irregular nucleoli
  • Mitosis
  • Necrosis
70
Q

What different carcinomas are these?

A

A- Squamous cell carcinoma

  • Very dense cytoplasm, reddish (Pap stain)
  • Puckering?

B- Adenocarcinoma

  • Perfect gland formation
  • Open/vesicular chromatin pattern with prominent nucleoli

C- Small cell carcinoma

  • Hyperchromatic, and large nuclei
  • Very scant cytoplasm
  • Nuclear molding
71
Q

Which carcinomas are found in the hilar region/centrally?

A
  • Squamous cell carcinoma
  • Small cell carcinoma
72
Q

Which carcinomas are found in the periphery?

A
  • Adenocarcinoma
  • Large cell carcinoma
73
Q

Describe the staging of lung cancer?

A

- Primary tumor: based on size and invasion of adjacent structures

- Regional LNs (N0-3): based on anatomic location of positive nodes,

  • N1- hilar
  • N2- mediastinal

- Distant metastasis (M0-1b):

  • M1a, seaprate tumor nodule(s)
  • M1b distant metastasis

- Stage grouping: Stage 0-IV

MS2 Respiratory (26 decks)

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