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Lung tumor pathology
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Lung Tumors Shahd AlAli
Pathology and Clinical
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Pathology
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Most common cause of cancer-related deaths in industrialized countries
1/3 of cancer deaths in men
Risk factors:
Cigarette smoking “contain 60 carcinogens”
Radon “formed by radioactive decay of uranium”
Asbestos
+Histological Types: Small cell carcinoma (19%)
Non small cell carcinoma (85%)
Squamous cell carcinoma 30%
Adenocarcinoma 40%
Large cell carcinoma 10%
Carcinoid tumor 5%
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Source: A.Sattar,Hussain, Fundamental of Pathology
+Etiology & Pathogenesis
Smoking is the leading cause; 85% of lung cancer occurs in smokers in “ sp: Small cell carcinoma & Squamous cell carcinoma”
Step wise progression metaplasia>dysplasia>carcinoma in situ > carcinoma
3p suppression gene loss very early event
P53 mutation / activation of KRAS oncogene > late event
Adenocarcinoma: activation of Epidermal growth factor receptor (EGFR) + KRAS
+Morphology of Small Cell Carcinoma “Oat Cell Carcinoma” Poor differentiation arise from neuroendocrine cells “Kulchtisky cells”
Correlated with smoking
Centrally located masses > extension to lung parenchyma
Involvement of hilar & mediastinal nodes
Can cause ACTH (Cushing syndrome), ADH (hypernatremia) and Eaton-Lambert syndrome
Amplicfication of myc oncogen is common
Usually respond to chemo and radiotherapy
+Small Cell Carcinoma Grossly:
Pale gray
Central location
Micro
Sheets of round fusiform cell with scant cytoplasm & finely granular chromatin
Nuclear molding
Mitotic figure
Necrosis
Cush artifact in small biopsy
Express neuroendocrine markers (chromogranin, synpatophysin, NSE and
CD56)
+Gross
“Arising centrally in this lung and spreading extensively is a small cell anaplastic (oat cell) carcinoma. The cut surface of this tumor has a soft, lobulated, white to tan appearance. The tumor seen here has caused obstruction of the main bronchus to left lung so that the distal lung is collapsed. Oat cell carcinomas are very aggressive and often metastasize widely before the primary tumor mass in the lung reaches a large size.” - webpath
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“Here is an oat cell carcinoma which is spreading along the bronchi. The speckled black rounded areas represent hilar lymph nodes with metastatic carcinoma. These neoplasms are more amenable to chemotherapy than radiation therapy or surgery, but the prognosis is still poor. Oat cell carcinomas occur almost exclusively in smokers.”-webpath
+Microscopic pattern
This is the microscopic pattern of a small cell anaplastic (oat cell) carcinoma in which small dark blue cells with minimal cytoplasm are packed together in sheets.
+Tips
Small cell carcinoma & Squamous cell carcinoma
SmokingCentralSyndrome
+Squamous cell carcinoma
Associated with smoking
Arise centrally in major bronchi
Spread to local hilar nodes
Central necrosis > cavitation
Squamous cell metaplasia>dyplasia>carcinoma in situ
Can cause distal atelectasis & infection
May produce PTHrp > hypercalcemia
+Histologically: Squamous CC
Keratin pearls
Intercellular bridges
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Pathoma
Squamous cell carcinoma A, Keratin pearls. B, Interceltular bridges. C Central location.
+Gross
“This is a squamous cell carcinoma of the lung that is arising centrally in the lung (as most squamous cell carcinomas do). It is obstructing the right main bronchus. The neoplasm is very firm and has a pale white to tan cut surface.” -webpath
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“This is a larger squamous cell carcinoma in which a portion of the tumor demonstrates central cavitation, probably because the tumor outgrew its blood supply.Squamous cell carcinomas are one of the more common primary malignancies of lung and are most often seen in smokers.” -webpath
+Adenocarcinoma Most common lung cancer in nonsmokers and females
Activating mutation of K-Ras
Associated with hypertrophic osteoarthropathy “clubbing”
Located peripherally with central scar
Glandular differentation with tubules or papillae and mucin secretion
Histological examination:
Acinar (gland forming)
Papillary
Mucinous
Metastasis widely at an early stage
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Atypical adenocarcinoma (AAH) > Adenocarcinoma in situ (AIS) > minimally invasive adenocarcinoma > invasive adenocarcinoma
AAH: well demarcated focus of epithelial proliftation 5 mm or less composed of cuboidal to low-columnar cells with cytological atypia.
AIS: (bronchoalveolar carcinoma) involve peripheral parts of the lung. Diameter of 3 cm or less, growth along preexisting structures & preservation of alveolar architecture. Can be nonmucinous, mucinous or mixed.
+Adenocarcinoma Precursors
Minimally invasive adenocarcinoma
Invasive adenocarcinoma
Tumor less than 3 cm, invasive component is 5mm or less
Tumor any size, invaded to depth > 5mm
+Gross
“This is a peripheral adenocarcinoma of the lung. Adenocarcinomas and large cell anaplastic carcinomas tend to occur more peripherally in lung. Adenocarcinoma is the one cell type of primary lung tumor that occurs more often in non-smokers and in smokers who have quit. If this neoplasm were confined to the lung (a lower stage), then resection would have a greater chance for cure. The solitary appearance of this neoplasm suggests that the tumor is primary rather than metastatic.”
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“This is another less common type of adenocarcinoma of lung known as adenocarcinoma-in-situ (formerly bronchioloalveolar carcinoma). Seen here is variant that appears grossly (and on chest radiograph) as a less well-defined area resembling pneumonic consolidation. The poorly defined mass involving the upper lobe toward the right here has a pale tan to grey appearance.”
+Microscopically
“Microscopically, the adenocarcinoma-in-situ (formerly bronchioloalveolar carcinoma) is composed of columnar cells that proliferate along the framework of alveolar septae, a so-caled "lepidic" growth pattern. The neoplastic cells are well-differentiated. These neoplasms, a form of adenocarcinoma, in general have a better prognosis than most other primary lung cancers, but they may not be detected at a low stage.”
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Atypical adenocarcinoma Adenocarcinoma in situ
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(A) Acinar growth pattern; (B) Papillary growth pattern; (C) Lepidic growth pattern; (D) Solid growth pattern
+Large Cell Carcinoma Undifferentiated malignant epithelial tumors that
lack the cytological features of small cell carcinoma, adenocarcinoma and squamous cell carcinoma
The cell have large prominent nuclei & moderate amount of cytoplasm
Has poor prognosis
Can be central or peripheral
On ultrastructure examination minimal glandular or squamous differentiation is common
+Combined Patterns
More than one line cell differentiation
Occur in 10%
Involves of the left supraclavicular node (Virchow node)
These cancers when advanced often extend to the pleura or pericardial space leading to inflammation and effusion
Compress or infiltrate the superior vena cava and cause venous congestion or the vena caval syndrome
Apical neoplasm may invade the brachial or cervical sympathetic plexus to cause severe pain in the distribution of the ulnar nerve or produce Horner syndrome.
Apical neoplasms (Pancoast tumors) destruct the 1st and 2nd rib and sometimes the thoracic vertebra
+Bronchial Carcinoid Tumor Represents 5% of all pulmonary tumors
Malignant tumors composed of cells that contain dense-core neurosecretory granules in their cytoplasm
Rarely secrete hormone active polypeptides
Classified into typical (low grade) & atypical (intermediate-grade)
Has excellent prognosis; metastasis is rare
Rarely produce carcionid syndrome serotonin secretion (flushing, diarrhea and cyanosis)
+Morphology
Most originate in main bronchi and grow in one of two patterns:
Obstructive polypoid intraluminal mass
Mucosal plaque penetrating the bronchial wall to fan out in the peribronchial tissue (collar-button lesion)
5% to 15% metastasize to hilar nodes at presentation
Distant metastases are rare
+Histologically Typical: Nests of uniform cells that have regular
round nuclei salt and pepper cromatin rare mitoses, and little pleomorphism.
Atypical: high mitotic rate (but less than small cell or large cell carcinomas) & focal necrosis.
Unlike typical carcinoids, the atypical subset may demonstrate TP53 mutation (20% to 40%)
Both express neuroendocrine markers (chromogranin, synpatophysin, NSE and
CD56)
+Carcinoid Tumors
A.Carcinoid growing as sphercal, pale mass B. Appearance of small, rounded, uniform nuclei and moderate cytoplasm
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Carcinoid tumor A, Microscopic appearance. B, Chromogranin expression by immunohistochemistry. C, Polyp-like growth in the bronchus
pathoma
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All Lung cancer types except bronchioloalveolar and bronchial carcinoid are associated with smoking.
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Clinical
+Clinical Presentation :
Hemoptysis
Bronchial obstruction
Wheezing
Coin lesion on x-ray film
Noncalcificated nodule on CT
+Metastatic disease “sites of metastases”
Bones > pain & spinal cord compression
Adrenal
Brain > changes in personality & epilepsy
Liver > jaundice and hepatomegaly
+Metastatic Tumors in The Lungs Prostate
Colon
Cervix
Breat
Bone
Bladder
+ComplicationsSPHERE S: superior vena cava syndrome
P: pancoast tumor “slide 26”
H: horner syndrome
E: pleural effusion
R: recurrent laryngeal symptoms (hoarseness) “left”
E: endocrine ADH > hypernatremia ACTH> Cushing’s syndromePTH> hypercalcemia HCG> gyncomastia
+Investigations: CXR to confirm the diagnosis
Abnormal CXR tumors appear as round shadow, with fluffy or spiked appearance edges
Evidence of cavitation, lobar collapse, pleural effusion or 2ry pneumonia
Spread to lymphatic channels give rise to lymphangitis carcinomatosis appearing like a streaky shadowing throughout the lung
+CXR
Intrapulmonary Mediastinal
+Determine the histology
Sputum examination by a cytologist for malignant cells
Bronchoscopy is used to obtain biopsies
Transthoracic fine needle aspiration biopsy under radiographic or CT screening is useful for obtaining tissue diagnosis from peripheral lesions
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Thank you :)
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