9/18- Pathology of Lung Cancer Flashcards
What are some methods to diagnose lung cancer (biopsies)?
- Cytology (exfoliative and fine needle biopsy)
- Nonoperative biopsy (endobronchial, transbronchial)
- Operative biopsy (VATS, open procedure with/without intraoperative evaluation)
What are the 4 most common forms of lung cancer?
- 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
What is the breakdown for major epithelial types (bronchogenic carcinomas)?
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
What are some risk factors in lung cancer? Which cancers?
Smoking: 10-20x non-smokers; mostly squamous and small cell carcinomas
What is the most frequent type of lung cancer associated with non-smokers?
Adenocarcinoma (specifically, AIS- adenocarcinoma in situ)
What is the prognosis for lung cancer?
Generally poor prognosis (depends on stage)
- Only 20-30% treatable by surgical resection
- 15% 5 year survival
- #1 cause of cancer deaths worldwide
Where does lung cancer commonly metastesize?
- Adrenals (> 50%), especially lower lobe tumors
- Liver (30-50%)
- Brain (20%)
- Bone (20%)
Cancer Nomenclature,
Define:
- Carcinoma
- Squamous cell carcinoma
- Adenocarcinoma
- Small cell carcinoma
- Large cell carcinoma
- 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
How does treatment differ for small vs. non-small cell carcinomas?
Small cell:
- Chemo and radiation
- Worst prognosis
Non-small cell:
- Surgery
- Prognosis slightly better than small cell
What are characteristics of squamous cell carcinoma?
- Epidemiology
- Aka
- Histology
- Location
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
What is seen here?
Squamous cell carcinoma
What is seen here?
Squamous cell carcinoma
- Arises from epithelium lining the airway
- Abrupt transition into malignant tumor (left)
- Invading into adjacent bronchial wall
How are squamous cell carcinomas graded?
Keratin production (amount)
Well-differentiated: most of the tumor makes keratin
Poor-differentiated: hard to find keratin; have to use stains
What is seen here?
Squamous cell carcinoma
- Abundant eosinophilic cytoplasm (filled with keratin filaments)
- Keratin pearl: characteristic of well-differentiated squamous cell carcinoma
What is seen here?
Squamous cell carcinoma
- Size comparison to lymphocytes
What is seen here?
Squamous cell carcinoma
- Keratin pearls!!
What is seen here?
Squamous cell carcinoma: poorly differentiated
- Large nucleoli
What are the 4 basic patterns of adenocarcinoma?
- Acinar (glandular)
- Papillary
- Solid with mucin production
- Adenocarcinoma in situ (formerly bronchioloalveolar carcinoma)
Also can have a mixed subtype
What is key feature of adenocarcinomas?
Gland formation
- Need mucin production (may need special stains in poorly differentiated tumors)
Is adenocarcinoma more common in males or females?
Females (47% vs. 37%)
What is seen here?
Adenocarcinoma
- Usually diagnosed by CT guided biopsy because of their peripheral location
What is seen here?
Adenocarcinoma
- Stringy material = mucin
- Can see mucin without staining
What is seen here?
Adenocarcinoma
- Tumor cell with intracytoplasmic mucin
What is seen here?
Adenocarcinoma: poorly-differentiated
- Very few glands present
What is seen here?
Papillary adenocarcinoma
- Papillary fronds with fibrovascular cords
- Form tufting of tumor cells
What is seen here?
Adenocarcinoma
- Solid version of adenocarcinoma
- Don’t see any glands; would not be able to diagnose with this picture without staining for mucin
What stain can be used to stain for mucin production?
Mucin-carnine
- Stains mucin rose/red color
What are some characteristics of adenocarcinoma in situ (formerly BAC)?
- Growth pattern
- Biopsy results
- Location
- Prevalence
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
What does “lepidic pattern” mean?
Growth along intact alveolar septa (think butterfly)
Epidemiology of adenocarcinoma in situ?
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
What are the 2 histologic subtypes of AIS? Characteristics?
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
What is seen here?
Adenocarcinoma in situ
- Nonmucinous AIS
What is seen here?
Adenocarcinoma in situ (Nonmucinous?)
- No evidence of stromal invasion
What is seen here?
Adenocarcinoma in situ (Nonmucinous?)
What is seen here?
Adenocarcinoma in situ (Nonmucinous?)
- Hobnail appearance
What is seen here?
Mucinous Adenocarcinoma in Situ
What is seen here?
Mucinous Adenocarcinoma in Situ
What is seen here?
Mucinous Adenocarcinoma in Situ
Characteristics of Large Cell Carcinoma?
- Histologically
- Location
- More in males/females
- 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%)
What is seen here?
Large Cell Carcinoma
- Wouldn’t be able to tell from this picture, though
What is seen here?
Large Cell Carcinoma
What is seen here?
Mixed cancer
- Both squamous and glandular differentiation
What is the cell of origin for neuroendocrine tumors?
Kulchitsky cell
What are neuroendocrine tumors of the lung?
Which are more malignant?
From low -> high malignancy:
- Typical carcinoid
- Atypical carcinoid
- Small cell carcinoma
- large cell neuroendocrine carcinoma
Characteristics of typical carcinoids? (Histologically)
- 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)
What is seen here?
Typical carcinoid
- Associated stromal network
- Grow in trabecular patterns
What is a marker for neuroendocrine tumors used to diagnose typical carcinoid?
Chromogranin
Characteristics of small cell carcinomas?
- Location
- Origin
- Prognosis
- Risk factor
- Male vs. females
- 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%
Histological features of small cell carcinoma?
- 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
What is seen here?
Small cell carcinoma
- Hilar mass
- Presence of metastatic disease
What is seen here?
Low power of small cell carcinoma
- Sea of blue; large nucleus and very little cytoplasm
What is seen here?
High power small cell carcinoma
- Hugging nuclei (very little cytoplasm)
What is seen here?
Small cell carcinoma
What are some characteristics of large cell neuroendocrine carcinomas?
- Neuroendocrine features
- Shape/morphology
- Common features
- Behavior
- Neuroendocrine differentiation by growth pattern and ancillary tests (IHC, EM)
- Polygonal cells, vesicular nuclei, abundant cytoplasm
- Necrosis, pleomorphism, mitoses
- Aggressive behavior
What is seen here?
Large cell neuroendocrine carcinoma
- Open chromatin pattern
- Open nuclei
What is seen here? (oops)
Large cell neuroendocrine carcinoma
- Nuclear molding (like small cells) but much more cytoplasm than small cell
What is seen here?
Left: Large cell neuroendocrine carcinoma
Right: small cell carcinoma
What cellular marker can be used to diagnose neuroendocrine cells (used here for large cell NE carcinomas?)
CD56 (NCAM)
What are some common genetic alterations in lung cancer? Role of each?
- 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
What is the EGFR mutation?
- Mechanism
- Epidemiology
- Clinical importance
- 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
What is the EML3-ALK Gene fusion?
- Mechanism
- Epidemiology
- Clinical importance
- 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
What are common metastatic tumors to lung/pleura?
- 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
What is seen here?
Metastatic colon cancer: colonic adenocarcinoma
- Original tumor looks identical to metastasis
- Here, confirmed by CK20 positivity (common in colorectal carcinomas)
What is seen here?
Renal cell carcinoma
- Metastasis to lung
Characteristics of malignant mesothelioma?
- Location
- Prevalence
- Prognosis
- Risk factors
- 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)
What is seen here?
Malignant mesothelioma
What is seen here?
Malignant mesothelioma
What are some cytogenic techniques in lung cancer diagnosis?
Exfoliative
- Sputum
- Bronchial washing
- Bronchial brushing
- Bronchoalveolar lavage
Fine needle aspiration biopsy
What are some common cytologic features of malignancy?
- Larger cells than benign
- High N:C ratio
- Irregular nuclear borders
- Prominent, irregular nucleoli
- Mitosis
- Necrosis
What different carcinomas are these?
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
Which carcinomas are found in the hilar region/centrally?
- Squamous cell carcinoma
- Small cell carcinoma
Which carcinomas are found in the periphery?
- Adenocarcinoma
- Large cell carcinoma
Describe the staging of lung cancer?
- 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
