Pulmonary Tumors Flashcards
Lung Tumors
Overview
- Bonchogenic carcinoma ⇒ 90-95% of primary lung tumors
- 5% are carcinoids
- Rest are misc. neoplasms including hamartoma
- Benign lung tumors rare
Lung Tumor
Epidemiology
-
Bronchogenic carcinoma
- Most common visceral malignancy
- Most common cause of cancer death worldwide
- US in 2012
- 226k new cases of lung CA
- 14% of new cancer dx
- 160k deaths d/t lung CA
- 8% of all cancer deaths
- 226k new cases of lung CA
- Since 1987, more women die of lung CA than breast CA
- Peak incidence in 6th and 7th decades
Lung Carcinoma
Etiology
-
Cigarette smoking ⇒ #1
- 40 pk-yr hx ⇒ 60x lung CA risk
- 80% of lung CA occurs in smokers or those who recently quit
- Only 11% of heavy smokers get lung CA
- Cessation of smoking for 10 years ↓ risk but never to control levels
-
10-15% of US lung CA occurs in never smokers
- Usu. adenocarcinomas in ♀
- Ionizing radiation
-
Asbestos
- Just asbestos ⇒ 5x risk
- Asbestos + smoking ⇒ 55x risk
- Air pollution ⇒ 2nd hand smoke, Radon
Precursor Lesions
4 types of precursor lesions for lung carcinoma:
- Atypical adenomatous hyperplasia
- Adenocarcinoma in situ
- Squamous dysplasia and carcinoma in situ
- Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
Not all precursor lesions will progress to invasive cancer.
Atypical Adenomatous Hyperplasia
Subtle focal thickening of lung parenchyma and hyperplasia of glandular epithelium
Adenocarcinoma In-situ
Proliferation and tufting of glandular epithelium with cellular atypia.
Does not invade into alveolar wall.
Can become invasive adenocarcinoma if process continues.
Squamous Dysplasia and Carcinoma In-situ
1st step ⇒ metaplasia of normal respiratory epithelium into squamous epithelium
2nd step ⇒ dysplasia of metaplastic sqamous epithelium, can be full thickness but does not invade down through BM
Cells can invade through BM and become Invasive Squamous Cell Carcinoma.
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia
Can become small cell carcinoma
Squamous Cell Carcinoma
Epidemiology
- 20% of lung CA
- Mostly in men
- Strong association with smoking
Squamous Cell Carcinoma
Pathogenesis
-
Usu. centrally located near hilus
- Increasingly becoming more peripheral
-
Metaplasia ⇒ dysplasia ⇒ growth & thickening by local spread ⇒ erosion of epithelial airway lining ⇒ invasion
- Metastasizes later than most other patterns
- Once invasive it can:
-
Form an intraluminal mass
- Can lead to post-obstructive PNA
- Penetrate bronchial wall and infiltrate into carina or mediastinum
- Grow into lung parenchyma
-
Form an intraluminal mass
Squamous Cell Carcinoma
Histology
- Low grade tumors
- Keratinization ⇒ squamous pearls or individual cells w/ eosinophilic, dense cytoplasm
- Intercellular bridges
- ± Central cavitation
Adenocarcinoma
Epidemiology
-
38% of lung CA
-
↑ incidence last 20 years
- May be due to cigarettes making smokers inhaler more deeply
- Expose peripheral airways where adenocarcinoma tends to form
-
↑ incidence last 20 years
-
Most common form in women
- ↑ women smokers
Adenocarcinoma
Pathogenesis
- Most located peripherally
- Starts in mucus-producing glandular cells
- Grows in various patterns
- Acinar
- Lepidic
- Papillary / micropapillary
- Mucinous
- Microinvasive
- Tumors grow more slowly
- Usually smaller than squamous carcinomas
-
Variable glandular differentiation
- May see mucin
-
Tends to metastasize more widely & earlier than squamous carcinomas
- Spread to pleura, regional LN, vessels
Adenocarcinoma
Acinar Pattern
Gland structure clearly visible.
Adenocarcinoma
Lepidic Pattern
Malignant cells grow along alveolar walls.
Adenocarcinoma
Mucinous Pattern
Satellite lesions.
Can resemble PNA.
Microinvasive
Adenocarcinoma
Tumor less than 3 cm.
Invasive component less than 5 mm.
Adenocarcinoma
Molecular Testing
Helps to determine treatment and prognosis for non-small cell lung cancers, esp. adenocarcinoma.
- Test each case of adenocarcinoma
-
EGFR mutations or other tyrosine kinases
- Targeted treatment w/ specific inhibitors
- Prolonged survival
-
Activating KRAS mutations ⇒ ~ 30%
- Associated w/ worse prognosis
-
EGFR mutations or other tyrosine kinases
Small Cell Carcinoma
Epidemiology
- 14% of lung CA
- Very strong association w/ smoking
- Most aggressive lung tumor
Small Cell Carcinoma
Pathogenesis
- Thought to arise from Kulchisky cells in bronchial epithelium
- Starts as diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
- Highly malignant ⇒ very poor prognosis
- May secrete polypeptide hormones ⇒ paraneoplastic syndrome
Small Cell Carcinoma
Histology
Small Cell Carcinoma
Treatment and Prognosis
- Surgical resection ineffective
- Sometimes sensitive to radiation and chemotherapy
- Mean survivial rate after dx ~ 1 year
Large Cell Carcinoma
Epidemiology
- 10-15% of total lung CA
- 18% of lung CA in males
- 10% of lung CA in female
Large Cell Carcinoma
Characteristics
Undifferentiated malignant epithelial tumor without characteristics of squamous cell or adenocarcinoma.
- Large Cell Neuroendocrine carcinoma is a variant
- Probably represents undifferentiated adeno- and squamous cell carcinomas
- EM show adeno and squamous differentiation
Mixed Carcinomas
Combined types occur in ~ 10% of patients:
Squamous cell carcinoma + adenocarcinoma
or
Squamous cell + small cell carcinoma
Lung Carcinoma
Clinical Effects
- Focal emphysema
- Atelectasis
- Abscesses
- SVC syndrome ⇒ venous congestion and edema of head and arm
- Pericarditis
- Pleuritis
Lung Carcinoma
Clinical Presentation
- Cough ⇒ 75%
- Weight loss ⇒ 40%
- Chest pain ⇒ 40%
- Dyspnea ⇒ 20%
Lung Cancer
Clinical Classification
Divided into two groups based on likelihood of metastasis and response to available therapies.
-
Small cell carcinomas
- Most often metastatic at time of dx
- Not amenable to surgery
- Have good initial response to chemotherapy
-
Non-small cell carcinoma
- Less likely to be metastatic at time of dx
- First perform staging
- Try surgery first if possible
Lung Cancer
Staging
‘N’ and ‘M’ factors
- Overall, > 50% of lung CA show nodal involvement @ dx
- Can spread through lymph and blood
- Sometimes metastasis is first manifestation of a problem ⇒ occult carcinoma
Lung Cancer
Metastatic Sites
- Adrenals ⇒ > 50% of cases
- Liver ⇒ 30-50%
- Brain ⇒ 20%
- Bone ⇒ 20%
Lung Cancer
Survival Rates
- One year survival rate
- 34% in 1975
- 41% in 2007
- 5 yr survival rate for all stages combined ⇒ 16%
- 52% if cancer localized to lung @ dx
- 22% w/ regional metastasis to LN
- 4% w/ distant metastasis
Paraneoplastic Syndromes
Definition
Symptom complex in cancer pts not explained by local or distant spread of tumor or by excess of hormones indigenous to tissues.
- Occurs in 1-10% of pts w/ advanced malignancies
- May represent initial manifestation
- May represent significant clinical problems
Paraneoplastic Syndromes
Manifestations
- ADH ⇒ hyponatremia
- ACTH ⇒ Cushings syndrome
- Parathyroid hormone, parathyroid hormone-related peptide, prostaglandin E, and some cytokines ⇒ hypercalcemia
- Often seen w/ lung CA
- Calcitonin ⇒ hypocalemia
- Gonadotropins ⇒ gynecomastia
- Serotonin and bradykinin ⇒ carcinoid syndrome
Lung CA Associated
Paraneoplastic Syndromes
Most tumors that produce ACTH and ADH ⇒ small cell carcinoma
Most tumors that produce hypercalcemia ⇒ squamous cell carcinoma
Lambert-Eaton Myastenic Syndrome
Muscle weakness caused by auto-Ab directed to the neuronal calcium channels.
Possibly elicited by tumor ionic channels.
Horner Syndrome
- Classic sx ⇒ enophthalmos, ptosis, miosis, anhidrosis
- Other manifestations ⇒ peripheral neuropathy, acanthosis nigricans, leukemoid reactions
-
Seen in Pancoast tumors
- Located at apex of the lung
Apical Lung Cancers
-
Tend to invade neural structures around trachea
- Including the cervical sympathetic plexus
- Can see Horner syndrome on ipsilateral side
- Tumors that cause this care called ‘Pancoast tumors’
Metastatic Tumors
to Lung
- The lung is the most common site for mestastic tumors
- See multiple nodules
- May see spread via lymphatics
- Manifests as Lymphangitic Carcinomatosis
Carcinoid Tumors
Epidemiology
- 1-5% of lung tumors
- Pts usu. < 40 y/o
- Male = female
- No known relationship to smoking
Carcinoid Tumors
Pathogenesis
- Thought to arise from Kulchitsky’s cells of bronchial mucosa
-
May secrete hormonally active polypeptides ⇒ carcinoid syndrome
- See diarrhea and flushing
- Often grow endobronchially ⇒ central lesion
- Covered by intact mucosa
- May present w/ airway obstruction
- More pleomorphic tumors ⇒ atypical carcinoids
- More agressive
- Can spread to LN
- Usually cured by resection
Carcinoid Tumors
Histology
- Sheets of uniform cells divided into “islands by CT septa
- Cells have round nuclei w/ ‘salt and pepper’ chromatin
- Neuroendocrine granules on EM
Hamartoma
- Usually composed of mature hyaline cartilage
- May contain fibrous tissue, fat, blood, vessels
- Usually incidental finging on CXR ⇒ coin lesion
Metastatic
Pleural Tumors
- Far more common than primary tumors
- Most arise from lung and breast CA
- Often see a malignant effusion
Solitary (Localized) Fibrous
Pleural Tumors
- Usually benign, local growth
- Does not usu. cause an effusion
- Not related to asbestos
Malignant Mesothelioma
Characteristics
“Primary Malignant Tumor of Pleura”
-
Most are asbestos-related
- Long latency ⇒ 10% heavily exposed develop tumor w/in 25-45 years
- Smoking does not increase risk
- 50% of pts die within 1 year of dx
- Few survive longer than 2 years
Malignant Mesothelioma
Gross Appearance
- Diffuse tumor spreads in pleural space
- Eventually encases the lung in a rind of tumor
- Often causes an effusion
- Can also be seen in pericardium and peritoneum
Malignant Mesothelioma
Histology
- Usually composed of 2 cell types
- Epithelioid cells
- Mesenchymal cells
- Can see microvilli on EM
- May see ferruginous bodies
