This document provides an overview of lung cancer pathology. It discusses the epidemiology of lung cancer worldwide and in Ethiopia. The most common histological subtypes are adenocarcinoma and squamous cell carcinoma. Cigarette smoking is the primary risk factor. Preinvasive lesions include squamous dysplasia, atypical adenomatous hyperplasia, and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Invasive lesions are classified as non-small cell lung carcinoma (including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma) or neuroendocrine tumors. Symptoms vary depending on location but often include cough, dyspnea, and chest pain. Staging evaluates extent

1. Pathology of lung tumors
Moderator: Dr. Mulugeta (Surgeon)
Presenter: Dr. Seid A (GSR3)

2. Outline
• Introduction
• Epideimology
• Risk factors
• Pathology
• Clinical features
• Staging
• Referrences
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3. Introduction
• Worldwide, lung cancer occurred in approximately 2.1
million patients in 2018 and caused an estimated 1.8
million deaths
• In USA in 2018, there were around 234,030 new cases.
• It is the most frequent cause of death from cancer in
men and women and accounts for 13.0% of all cancer
diagnoses and 26% of all cancer deaths in USA.
• Lung cancer deaths exceed the combined total deaths
from breast, prostate, and colorectal cancer.
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4. Cont´d...
• Incidence continues to decline, though at twice the
rate for men compared to women (3% per year in men
and by 2% per year in women).
• Most patients are still diagnosed at an advanced stage
of disease(22% with regional metastasis and 57% with
distant metastasis), so therapy is rarely curative.
• African American men have both the highest incidence
and the highest death rate.
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5. July 20, 2023 5

6. Cont´d...
In Ethiopia:
• lung cancer accounted for 2.7% of the total number of all
cancers diagnosed at TASH from 2011 to 2017 (TASH
Oncology Center, unpublished data, 2018).
• A cross-sectional study was conducted at TASH among
146 patients with pathologically confirmed primary lung
cancer, diagnosed from 2015 to 2019 and recorded in the
Addis Ababa Cancer Registry at TASH.
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7. Cont´d...
• Result:
– mean age was 54 plus or minus 13 years
– 61.6% were male
– 25.3% had a history of tobacco use.
– most common clinical manifestations included cough
(88.4%,), chest pain (60.3%), and dyspnea (53.4%).
– median duration of any symptoms was 6 month
– most common radiologic features were lung mass (84.9%)
and pleural effusion (52.7%).
– Adenocarcinoma accounted for 35.7%) and SCC 19.2%
– 92.2% presented at advanced stages (stages III and IV).
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8. Cont´d...
• Conclusion:
– Adenocarcinoma was the most common histologic
type of lung cancer detected in our study, similar to
findings from other international studies.
– Nevertheless, compared with high-income countries,
lung cancer in Ethiopia presents at a younger age, a
later stage, and without considerable personal
tobacco use.
– Country-specific screening guidelines and treatment
protocols, in addition to a national tumor registry and
greater molecular mutation analyses, are needed to
improve prevention and management of lung cancer
in Ethiopia.
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9. Risk factors
• Cigarette is implicated as a
causal factor in 90% of lung
cancers in men and 80% in
women.
• Squamous cell and small
cell carcinoma are
extraordinarily rare in the
absence of cigarette
smoking.
• Cigar and pipe smoking
• Marijuana and cocaine
• Electronic cigarretes
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10. Cont´d...
• Occupational and environmental carcinogens:
– Asbestos
– Radon
– Smoke from cooking and heating
– Air pollution and diesel exhaust
• Radiation therapy
• Inflammation and benign lung disease
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11. Preinvasive lesions
1. Squamous dysplasia and carcinoma in situ:
– pseudostratified epithelium to metaplastic
squamous mucosa then to dysplasia
– Due to cigarette smoking
– Could be mild, moderate, or severe.
– CIS represents carcinoma still confined by the
basement membrane.
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12. Cont´d...
2. Atypical adenomatous hyperplasia (AAH):
– <5.0 mm, comprising proliferation of BAC, resembling
non-mucinous AIS.
– beginning stage AIS and then to adenocarcinoma.
– it is possible to detect preinvasive adenocarcinoma
lesions as early as AAH with thin section CT scan
– can be multiple, are typically small, and have a
ground-glass appearance
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13. Cont´d...
3. Diffuse idiopathic pulmonary neuroendocrine
cell hyperplasia:
– diffuse proliferation of neuroendocrine cells, without
invasion of the basement membrane.
– exist as a diffuse increase in the number of
single neuroendocrine cells, or as small lesions less
than 5.0 mm in diameter.
– Lesions over 5.0 mm in size or that breach the
basement membrane are carcinoid tumors.
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14. Invasive or malignant lesions
• Broadly divided into two main groups:
– non-small cell lung carcinoma
• large cell
• squamous cell, and
• adenocarcinoma
– Neuroendocrine tumors
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15. Cont´d...
• Adenocarcinoma:
– it is the most common type, 30% of ca in male
smokers and 40% of ca in female smokers.
– 80% and 60% of lung cancers in nonsmoking females
and males, respectively.
– F>M
– most frequent histologic subtype in women, patients
who are under 45 years of age, and Asian populations.
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16. Cont´d...
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17. Cont´d...
1. Adenocarcinoma in situ (AIS) (Tis)
– small (≤3 cm) that have pure lepidic growth
– not invasive into the stroma, vascular system, or
pleura
– very rarely mucinous, consisting of type II
pneumocytes or Clara cells.
– pure ground-glass neoplasm on CT
– 100% disease-specific survival with complete surgical
resection.
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18. Cont´d...
2. Minimally invasive adenocarcinoma (MIA)(T1mi):
– solitary lesion with <5 mm of invasion within a
predominantly lepidic growth
– very rarely mucinous.
– invasive component can be acinar, papillary,
micropapillary, and/or solid
– Appear as a part-solid nodule with a predominant
ground-glass component, but can be highly variable
– 100% survival
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19. Cont´d...
3. Lepidic predominant adenocarcinoma (LPA):
– lymphovascular invasion, pleural invasion, tumor
necrosis, or more than 5 mm of invasion are noted in
a lesion that has lepidic growth as its predominant
component
– the size of the invasive component is recorded for the
T stage
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20. Cont´d...
4. Invasive adenocarcinoma:
• Subtypes include:
– Lepidic predominant
– Acinar predominant
– Papillary predominant
– Micropapillary predominant
– Solid predominant
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21. Cont´d...
• Adenocarcinoma:
– Mostly peripheral, 13% located centrally.
– frequently discovered incidentally on routine chest
radiographs
– symptoms are due to pleural or chest wall invasion or
pleural seeding with malignant pleural effusion
– usually solid by CT scan, but can also be part-solid and
even a ground-glass nodule.
– TTF-1 and napsin A
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22. Cont´d...
• Well-differentiated tumors:
– Bubble-like or cystic lucency on CT scan in small (≤2
cm)
– extensive associated ground-glass components
– Intratumoral air bronchograms
• Poorly differntiated tumors:
– spiculations that are coarse and thick (≥2 mm)
– Pleural retraction
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23. Cont´d...
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24. Cont´d...
• Squamous Cell Carcinoma:
– 30% to 40% of lung ca
– most frequent lung ca in men
– highly correlated with cigarette smoking
– primarily in the main, lobar, or first segmental bronchi
– Symptoms include cough, hemoptysis, wheezing, dyspnea
– a more peripherally SCC may develop in a TB scar or in the
wall of a bronchiectatic cavity
– Central necrosis is frequent and may lead to the
radiographic findings of a cavity
– p40, p63, and cytokeratin 5/6
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25. Cont´d...
• Large Cell Carcinoma:
– undifferentiated NSCLC that lacks cytological and
architectural features of SCLC or SQCC
– accounts for 10% to 20% of lung cancers
– may be located centrally or peripherally
– can be confused with a large cell variant of
neuroendocrine carcinoma, but can be differentiated
by special IHC stains.
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26. Cont´d...
• Neuroendocrine Neoplasms:
– arise from cells derived from the embryologic neural
crest.
– Can be:
• neuroendocrine hyperplasia
• neuroendocrine carcinoma (NEC).
– Immunohistochemical staining for neuroendocrine
markers (chromogranins, synaptophysin, CD57, and
neuron-specific enolase) is essential to accurate
diagnosis.
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27. Cont´d...
• Grade I NEC (classic or typical carcinoid):
– is a low-grade NEC
– 80% arise in the central airway epithelium
– Occur primarily in younger patients.
– hemoptysis, with or without airway obstruction and
pneumonia is the most common presentation.
– Regional lymph node metastases are seen in 15% of
patients, but systemic spread and death from Grade I
NEC is rare
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28. Cont´d...
• Grade II NECs (atypical carcinoid):
– have a much higher malignant potential
– linked to cigarette smoking
– more likely to be peripherally located
– Lymph node metastases: 30% to 50% of patients.
– 25% of patients already have remote metastases at
diagnosis.
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29. Cont´d...
• Grade III NEC:
– large cell type tumors
– Primarily occur in heavy smokers
– mid to peripheral lung fields
– Often large with central necrosis
– high mitotic rate
– patients respond poorly to treatment and have a
poor prognosis.
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30. Cont´d...
• Grade IV NEC (SCLC):
– is the most malignant NEC and accounts for 25% of all
lung ca
– often have early, widespread metastases.
– arise primarily in the central airways
– leading producer of paraneoplastic syndromes.
– Three groups:
• pure small cell carcinoma (oat cell carcinoma),
• SCLC with a large cell component,
• combined tumors
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31. Cont´d...
• Salivary Gland type Neoplasms:
– arise from salivary-type submucosal bronchial glands
throughout the tracheobronchial tree
– histologically identical to those seen in the salivary
glands.
– The two most common are:
• adenoid cystic carcinoma
• mucoepidermoid carcinoma
– Both occur centrally due to their site of origin.
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32. Cont´d...
– Adenoid cystic carcinoma:
• slow-growing tumor
• locally and systemically invasive
• Grows submucosally and infiltrating along perineural
sheaths
– Mucoepidermoid carcinoma:
• consists of squamous and mucous cells
• graded as low or high grade, depending on mitotic rate
and degree of necrosis.
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33. Solitary pulmonary nodule
• single, well-circumscribed, spherical lesion that is 3
cm or less cm in diameter and completely
surrounded by normal aerated lung parenchyma
• majority are detected incidentally on CXR or CT
scans.
• probability of ca increases if:
– history of smoking (50% or higher for smokers
compared to 20% to 40% in never smokers).
– symptomatic
– older, male, or has had occupational exposures
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34. Cont´d...
• CT findings characteristic of benign lesions:
– small size, calcification within the nodule, and stability over
time
• Infectious granulomas arising from a variety of organisms
account for 70% to 80% of this type of benign solitary
nodules
• hamartomas are the next most common single cause,
about 10%.
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35. Cont´d...
• CT findings characteristic of malignancy include:
– growth over time
– increasing density on CT scan
– size >3 cm
– irregular, lobulated, or spiculated edges;
– finding of the corona radiata sign (consisting of fine
linear strands extending 4 to 5 mm outward and
appearing spiculated on radiographs)
– Calcification that is stippled, amorphous, or eccentric
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36. Metastatic lesions to the lung
• Routes can be hematogenous, lymphatic,
aerogenous or direct invasion.
• tumor biology and host resistance determine
mechanisms of spread, location of metastases, and
extent of growth
• Features suggestive of metastatic disease are:
– Multiplicity
– smooth, round borders on CT scan
– temporal proximity to the original primary lesion.
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37. Cont´d...
• Hematogenous metastases are most frequently
found in the capillary beds of the lung.
• Tumor cells may travel by lymphatics and occupy a
discrete position within the lung parenchyma, or
they may diffusely involve the entire lung
• aerogenous spread of tumor from one site within the
lung to another may occur: “spread through alveolar
spaces”.
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38. Clinical manifestation
• Pulmonary symptoms:
– Cough
– Dyspnea
– Wheezing
– Hemoptysis
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• Nonpulmonary thoracic
symptoms:
– Pleuritic pain
– Chest wall pain
– Radicular chest pain
– Pancoast´´s syndrome
– Hoarsness

39. Cont´d...
• Paraneoplastic Syndromes:
– systemic release of tumor-derived biologically active
materials .
– may produce symptoms even before any local
symptoms
– does not influence resectability or treatment options.
– Symptoms often abate with successful treatment.
– symptom recurrence may herald tumor recurrence.
– majority are associated with grade IV NEC (SCC)
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40. Cont´d...
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41. Staging
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42. Referrences
• Schwartz´s principle of surgery 11th edition
• Sabiston textbook of surgery 21st edition
• Shields´ general thoracic surgery 8th edition
• NCCN guidline 2022
• Uptodate 2022
• Gebremariam et al (26 May 2021) Clinical
Characteristics and Molecular Profiles of Lung
Cancer in Ethiopia; JTO Clinical and Research
Reports Vol. 2 No. 7: 100196;
https://www.sciencedirect.com/science/article/pii/
S2666364321000552
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43. THANK YOU !!
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