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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 :)