1. The lung and the Upper Respiratory Tract
Lung Tumors

2. Lung tumors : General features
Most are malignant.
Metastatitc neoplasms are most common.

3. Types Bronchogenic Carcinoma. Bronchial carcinoids. Lymphoma.
Hamartoma

4. Bronchogenic carcinoma
Squamous cell carcinoma ( most common)
Adenocarcinoma
Bronchial derived
Broncheoloalveolar
Larger cell carcinoma
Small cell (oat cell) carcinoma.
Non small cell carcinoma

5. Bronchogenic Carcinoma
Leading case of cancer death (M/F)
Increase in women and decreasing in men.
Age: old adult.
Etiology:
smoking of cigarettes ( amount/ years).
Asbestosis
Uranium and radiation
Air pollution
Radon

6. Molecular pathology
Non-Small Cell Lung Carcinomas (NSCLC) 70-75% of all lung Ca cases:
p16/CDKN2A & K-RAS mutations,
p53 mutation ( inhibit apoptosis).
Small Cell Lung Carcinoma (CSLC) 20-25%, TP53
& RB gene mutations ( deregulate cell cycle).

7. Squamous cell carcinoma
Central tumor
Arising from Squamous cell ( often from main bronchus)
Smoking is main etiology also caused by radon.
p53 mutation and overexpression of epidermal growth-factor receptor very common.
Morphology: next

8. Squamous cell carcinoma: The neoplasm is very firm and has a pale white to tan cut surface. Central necrosis is frequently seen.
This chest CT scan view demonstrates a large squamous cell carcinoma of the right upper lobe that extends around the right main bronchus and also invades into the mediastinum and involves hilar lymph nodes.
Central necrosis

9. Micro: nests of polygonal cells with pink cytoplasm and distinct cell borders with intercellular bridges and keratin pearl.
These tumors disseminate outside the thorax later than other histologic types.

10. Adenocarcinoma Peripheral tumor.
Sex: female. Age: much younger person.
Types:
Bronchial derived: occur in the site of previous scar (scar carcinoma). Not clearly linked to smoking.
Bronchoalveolar Ca: Not related to smoking. Multiple tumor, present as pneumonia.

11. Adenocarcinoma : peripheral tumor
K-RAS mutations are seen primarily in adenocarcinoma.
Adenocarcinoma is the one cell type of primary lung tumor that occurs more often in non-smokers.

12. Adenocarcinoma: The glandular structures formed by this neoplasm + mucin production ( mucin stained purple with PAS)

13. Bronchioloalveolar carcinoma
Appears as pneumonic consolidation.
Well differentiated tumor: better prognosis.

14. Bronchioloalveolar carcinoma is composed of columnar cells that proliferate along the framework of alveolar septae.

15. Small Cell Carcinoma: central tumor
Central tumor. Aka- oat cell carcinoma
Origin: Neuroendocrine argentaffin (Kulchitsky) cells.
Smoking is main etiology
Gene: p53 and RB tumor suppressor genes + over expression of the anti-apoptotic gene BCL2.
Poor prognosis.

16. Gross: This tumor has a soft, lobulated, white to tan appearance.
Micro: sheets of blue cells are regular, and round molded nuclei and a moderate amount of eosinophilic cytoplasm.
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.
Blue round cells

18. Large cell carcinoma Micro: large anaplastic cells. Poor prognosis
From a treatment standpoint, it is still a "non-small cell" carcinoma (like adenocarcinoma & SCC) for which the stage is the most important determinant of prognosis.

19. Next topic : Clinical features of tumors
Relax your eyes
Next topic : Clinical features of tumors

20. Clinical Common presentation: Cough, hemoptysis, weight loss.
Clubbing of the fingers.
Others:
Due to spread of tumor
Due to paraneoplastic syndromes

21. Clinical: Due to spread of tumor
Local lymph nodes metastasis;
Supraclavicular node (Virchow node).
Distant : Brain, Liver ,Bone.
Adrenals cortex (Addison’s disease- deficiency of cortical hormones- skin & mucosa hyper pigmentation)

22. Others
Superior Vena caval syndrome (common in small cell carcinoma, followed by squamous cell Ca.)
Congestion of veins of neck, face: red
Engorges jugular vein- edema in arms.
Hoarseness: recurrent laryngeal nerve invasion ( with apical tumor).
Acanthosis nigricans: black, thick skin with skin tags= axillae, groin etc (common in adenocarcinoma).

23. Clinical: Due to spread of tumor
Horner syndrome ( in Pancoast tumor ):
Seen in apical tumors due to involvement of cervical sympathetic plexus.
Features are:
Ipsilateral enophthalmos.
Ptosis, Meiosis.
Anhidrosis.

24. Clinical: Due to paraneoplastic syndromes
Squamous cell carcinoma
Secret PTH like hormone > Hypercalcemia→ renal calculi
Small cell carcinoma
Secret ACTH>Cushing syndrome= weight gain, hypertension. Skin pigmentation
Secret ADH > SIADH >
Hyponatremia= cerebral edema

25. Other Paraneoplastic syndromes in bronchogenic carcinoma
Hematologic manifestations (In adenocarcinoma).
Migratory thrombophlebitis.
Lambert-Eaton myasthenic syndrome ( In Small cell carcinoma: muscle weakness is caused by auto-antibodies directed to the neuronal calcium channel) .
Calcitonin, causing hypocalcemia.

26. Bronchial Carcinoid
Origin: Kulchitsy cells: a neuroendocrine cells that line the bronchial mucosa.
Age: mean around 40.
Gross: yellow polypoid mass.
Micro:
LM: Salt pepper.
EM: Dense core neurosecretory granules in their cytoplasm

27. Microscopy
Dense core granules
Salt pepper

28. Presentation of Carcinoid
Benign carcinoid:
Cough.
Hemoptysis, bronchiectasis.
Recurrent bronchial & pulmonary infections.
Malignant carcinoid: liver mets. and Secret serotonin > carcinoid syndrome: diarrhea and flushing on skin.

29. Hamartoma coin lesion Common Less than 2 cm.
Micro: haphazard lung tissue and cartilage.
Clinical: Present as a "coin lesion" on X-ray.
d/d of coin lesion
Granuloma are multiple.

30. Metastatic Cancer to the lungs
Multiple variably-sized masses are
seen in all lung fields.
Even the hilar nodes in this photograph demonstrate nodules of metastatic carcinoma. The nodules are usually in the periphery and do not cause major obstruction.

31. Next Topic
Mesothelioma
Pleural effusion

32. Malignant Mesothelioma
Site: The visceral or the parietal pleura.
Carcinogen: asbestosis- amphiboles by reactive free radicals.
Morphology:
Asbestos bodied are found in the tumor.
Lung gets ensheathed by tumor tissue may produce cicatrisation and atelectasis.

33. Diagnosis of malignant mesothelioma
Positive staining with:
Acid mucopolysaccharide
Keratin
Electron microscopy (EM): presence of long microvilli and abundant tonofilaments.

34. Pleural effusion Empyema- Pus in pleural cavity following abscess.
Chylothorax : Chyle (lymph)=
It is a Milky white fluid due to tumor emboli in lymphatic or in Lymphoma.
All patient present with respiratory distress, relieved when the effusion in drained by thoracentesis .

35. Pneumothorax Def: air in pleural cavity Types: Traumatic: Trauma
Spontaneous: rupture of paraseptal bulla
Tension : due to shift of the mediastinum from the midline.
Tracheal shifting to other side , and hyperresonant lung on side of injury.

37. Thank you

38. Thank you