UNIT:050620: LUNG CANCER

PRECEPTORSHIP
6th May 2020

LUNG CANCER PATHOLOGY AND DIAGNOSIS

Dr Kibet Kibor keitany
Anatomic Pathologist,
Eldoret, Kenya.
kiborbetany@gmail.com

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INTRODUCTION

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EPIDEMIOLOGY: Why Lung cancer?

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 EPIDEMIOLOGY
• Distribution:
• Globally:
–Most frequently diagnosed Ca
–Leading cause of cancer death
• Regionally:
–Important cause of cancer morbidity
–Paucity of data, mostly undiagnosed.
–More emphasis has been on other Cancers-B,C,P,AM, C
• 40- 70 years, peak incidence in 50’s
• Determinants:
• Environmental factors: Tobacco (Cigarette) smoking, Air pollution, industrial hazards
(asbestos, Uranium, Chromium) Ionizing radiation

• Genetic factors: Stepwise accumulation of ‘Driver’ mutations

– Genetic polymorphisms in P450, DNA repair genes
– Chr’ deletions with loss of function mutations- TP53, RB,CDKN2A,FGFR1
– Oncogenic gain of function mutations- TRK-EGFR,ALK,ROS,MET, RET; KRAS
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 PATHOGENESIS

• Tobacco smoking is a key risk factor- Intensity &

Duration
• Initiation of a stepwise path to neoplastic transformation

• Precursor Pre-invasive CIS Micro-Invasive Invasive

A) Sq Metaplasia Squamous Scc in Situ Invasive SCC

BCH/GCH Dysplasia
Microinvasive
B) AAH AIS Invasive ADC
adenocarcinoma
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Sequence of events:- www.intercancer.com
CLINICAL PRESENTATION:

+ Weight loss

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 PATHOLOGY & CLASSIFICATION

• Lung cancer broadly classified into:

 Small Cell Lung Cancer
 Non- Small Cell Lung Cancer- SCC, ADC,LCC

• 2015 WHO classification of Lung tumors

 Includes other non Carcinoma lesions

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 Squamous Cell Carcinoma

• Commonest histologic type

• Highly associated with tobacco smoking
• Chr’ Del 3p,9p,17p with loss of fxn mutations
• Precursor lesions- Sq. metaplasia, Dysplasia, CIS
• Gross types: Central (Hilar), Diffuse, Peripheral (nodular)
• Keratinization, Intercellular bridges
• P40, P63, CK5/6 positive in IHC
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Central (Hilar)
Diffuse

Peripheral (nodular)
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 Histologic features

Intercellular bridges Keratinization with pearls

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 IHC

H&E P40 IHC staining

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 ADENOCARCINOMA

• Mostly in NEVER (NON)smokers, Females

• Oncogenic gain of fxn mutations- EGFR,ALK,KRAS
• Precursors are AAH & AIS
• Gross: Peripheral tumour with central scar
• Gland forming malignant cells, 5 main patterns-:
• Early metastasis
• TTF1 and Napsin A positive on IHC
• DDX: Metastasis
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 AAH
AIS, Mucinous

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AIS www.intercancer.com
ADC, Lepidic predominant
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Invasive Mucinous
(Colloid) Clear cell ADC

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 Small cell carcinoma

• Arises from “Kulchtisky” cells

• Central, highly aggressive
• Hilar and mediastinal node involvement
• myc amplification
• Associated with Paraneoplastic syndromes

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 Small cell carcinoma

Small, round blue cells, crush

artefacts, necrosis, mitosis
Neuroendocrine features

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 Large cell carcinoma
Diagnosis of exclusion:
“an undifferentiated malignant epithelial tumor that lacks the
cytologic features of small-cell carcinoma and glandular or
squamous differentiation.”
Composed of large neoplastic epithelial cells

Neuroendocrine
features

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 DIAGNOSTIC EVALUATION:

• History and physical examination

• Chest Imaging- CXR, CT
• Sputum, BAL, Brushings Cytology
• Image guided biopsy and histology
• Immunohistochemistry
• TTF1,NapsinA, P40, P63,CK5/6,Chromogranin
• PD-L1, EGFR,……etc
• Molecular studies—EGFR, KRAS, ROS etc…
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 Sputum

BW
CXR

Core needle biopsy

& Histopathology
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 IHC

Diagnostic markers
&
Predictive markers

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Questions and Comments?

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 REFERENCES

• Robbins & Cotram Pathologic basis of Disease 9th Edition

• https://www.webpathology.com/
• IHC for Diagnosis and Prediction in NSCLC: Adv Anat Pathol
Volume 25, Number 6
• Classification of Lung tumors by Dr Kamal B. S
• https://www.diomedia.com/ Rosen
• The 2015 World Health Organization Classification of Lung
Tumors
• Globocan 2018

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