Lung tumor pathology

1. +
Lung Tumors
Shahd AlAli
Pathology and Clinical

2. +
Pathology

3. +
 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

4. +
Histological Types:
 Small cell carcinoma (19%)
 Non small cell carcinoma (85%)
 Squamous cell carcinoma 30%
 Adenocarcinoma 40%
 Large cell carcinoma 10%
 Carcinoid tumor 5%

5. +
Source: A.Sattar,Hussain, Fundamental of Pathology

6. +
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

7. +
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

8. +
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)

9. +
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

10. +
“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

11. +
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.

12. +
Tips
Small cell carcinoma &
Squamous cell carcinoma
 Smoking
 Central
 Syndrome

13. +
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

14. +
Histologically: Squamous CC
Keratin pearls
Intercellular bridges

15. +
Pathoma
Squamous cell carcinoma
A, Keratin pearls.
B, Interceltular bridges.
C Central location.

16. +
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

17. +
“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

18. +
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

19. +
 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.

20. +
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

21. +
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.”

22. +
“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.”

23. +
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.”

24. +

25. +
Atypical adenocarcinoma Adenocarcinoma in situ

26. +
(A) Acinar growth pattern; (B) Papillary growth pattern;
(C) Lepidic growth pattern; (D) Solid growth pattern

27. +
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

28. +
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

29. +
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)

30. +
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

31. +
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)

32. +
Carcinoid Tumors
A.Carcinoid growing as sphercal, pale mass
B. Appearance of small, rounded, uniform nuclei and moderate cytoplasm

33. +
Carcinoid tumor A, Microscopic appearance. B, Chromogranin
expression by immunohistochemistry. C, Polyp-like growth in the
bronchus
pathoma

34. +
All Lung cancer types except
ronchioloalveolar and
ronchial carcinoid are
associated with smoking.

35. +
Clinical

36. +
Clinical
 Presentation :
 Hemoptysis
 Bronchial obstruction
 Wheezing
 Coin lesion on x-ray film
 Noncalcificated nodule on CT

37. +
Metastatic disease “sites of
metastases”
 Bones > pain & spinal cord compression
 Adrenal
 Brain > changes in personality & epilepsy
 Liver > jaundice and hepatomegaly

38. +
Metastatic Tumors in The Lungs
Prostate
Colon
Cervix
Breat
Bone
Bladder

39. +
Complications
SPHERE
 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 syndrome
PTH> hypercalcemia
HCG> gyncomastia

40. +
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

41. +
CXR
Intrapulmonary Mediastinal

42. +
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

43. +
Thank you :)