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Late Diagnosis Of Lung Cancer

In Resource-poor Centres
Dr. Audrey Forson
Department of Medicine
University of Ghana Medical School
AACTS Conference August 2013
Outline
• Case
• Epidemiology
• Misdiagnosis
• Clinical similarities/differences
• Diagnosis of lung cancer


Case
• 77 year old female
• Completed Anti-TB medication 6
th
month,
smear negative TB
• Cough, weight loss, never smoked

• Hemipareisis, weakness Rt sided
• CT scan chest
• MRI brain
Lung cancer
• The most important cause of cancer death in
developed countries
• High mortality, late diagnosis
• Rates are higher in men but declining.
▫ Slowing more in men than in women
▫ Declining in more young age groups
• Adenocarcinoma has replaced squamous cell
carcinoma as the commonest form of lung
cancer.
• From 1980s Adenocarcinoma has increased
markedly in all subgroups, both male and female
Cancer mortality in Ghana: No. of cases
and summary frequency rates in males



SITE No. ALL AGES RF % ASCAR
1. LIVER 428 21.3 21.15
2. HAEMATOPOIETIC ORGANS 417 20.8 15.57
3. PROSTATE 286 14.2 17.35
4. STOMACH 126 6.3 7.26
5. PANCREAS 91 4.5 5.22
6. BLADDER 91 4.5 5.07
7. LUNG 78 3.9 4.56
8. BRAIN 67 3.3 2.78
9. COLON & RECTUM 53 2.6 2.95
10. LARYNX 45 2.2 2.75
11. KIDNEY 41 2.0 1.63
12. OESOPHAGUS 39 1.9 2.42
13. BONE 34 1.7 1.35
14. BREAST 12 0.6 0.66

ALL SITES 2008 100 100



• ASCAR - age-standardized cancer ratio

Wiredu EK, Armah HB. BMC Public Health. 2006; 6: 159. A 10-year review
of autopsies and hospital mortality [1991-2000 (3659 autopsies)]

Epidemiology of Lung Cancer
• Cigarette smoking >55 carcinogens eg.
polycyclic aromatic hydrocarbons, 20-fold
increase in risk vs non-smokers
▫ In Ghana - Smoking among men 10.62%, women
2.6% (World Bank report 2010), 7%
▫ Passive smoking, envoronmental tobacco smoke
(ETS) - ¼ of cases in one study
• Occupational carcinogens - radon (underground
miners), asbestos
▫ synergy with smoking
• Indoor pollution – solid fuels for indoor cooking,
radon
Epidemiology of Lung Cancer
• Air pollution – diesel emissions, hydrocarbons
▫ Outdoor air pollution accounts for about 1 to 2%
of lung cancer cases.
• Genetics, eg.
▫ K-ras oncogene mutated in about 30% of
adenocarcinomas, almost exclusively in heavy
smokers ,
▫ epidermal growth factor receptor (EGFR)
mutation is commonly seen in never smokers and
much less common in smokers
• Micronutrients – being investigated

In developed countries
• Active smoking is responsible for 90% of lung
cancer cases,
• Occupational exposures to carcinogens account for
approximately 9 to 15% of lung cancer cases,
▫ radon causes 10% of lung cancer cases,
• Age - Older age group
• Race – in USA high prevalence in African-American
men and in non-hispanic white men
▫ 50% higher in African-Americans
▫ Low rates of lung cancer in Africa, ?recent studies
• Previously incurred lung damage – eg. from COPD
and fibrotic diseases such as pneumoconiosis.
▫ COPD a risk factor - to “remove” the effect of cigarette
smoking

Diagnostic Dilemma: Pulmonary
tuberculosis as differential diagnosis of
lung cancer

• Low prevalence of lung cancer – estimated 5 per
100,000

• High prevalence of tuberculosis – 106 per
100,000 (60 per 100,000)
• Patients with lung cancer are often
misdiagnosed as pulmonary tuberculosis, other
diagnoses, leading to delay in the correct
diagnosis

Lung cancer classification
• Non-small cell lung cancer (NSCLC)
▫ Adenocarcinoma
▫ Squamous cell carcinoma
Small cell lung cancer (SCLC)
▫ Large cell carcinoma
• Squamous cell and small cell carcinoma are
more directly linked to smoking than
adenocarcinoma
• About 10% „Never smoked‟ - disproportionately
present with adenocarcinoma and
bronchoalveolar carcinoma
Squamous cell
carcinoma
tends to be centrally
located and may
cavitate
Adenocarcinoma of lung
Adenocarcinoma in
situ or minimally
invasive
adenocarcinoma in
lung- formally known as
bronchoalveolar
carcinoma .
Lymphangitis
carcinomatosis is the
term given to tumour
spread through the
lymphatics of the lung
and is most commonly
seen in secondary
metastases usually from
adenocarcinoma.
Reasons for Misdiagnosis
In developing countries,
• Lack of awareness of the diagnosis of lung cancer,
• TB and lung cancer have common symptoms
▫ fever, cough, sputum, haemoptysis, weight loss, anorexia, lethargy, chest
pain, SOB are common to both tuberculosis and lung cancer.
• Common risk factors – smoking, chronic cough diagnosed late, comorbidties
• Inadequate infrastructure –
▫ for bronchoscopy, mediastinoscopy, CT guided biopsy, VATS (video assisted
thoracoscopic surgery), medical thoracoscopy
• Lack of a confirmatory test for smear negative TB
Other factors for TB
• Socio-economic factors, overcrowding, history of contact, substance abuse,
immune suppressed state
• Anaemia- both, no clubbing
Other factors for Lung Ca
• History of smoking, exposure to carcinogens, passive smoking, lung fibrosis
• Nicotine stained fingers, clubbing
• Hoarseness - due to vocal cord paralysis due to involvement of left recurrent
laryngeal nerve
• Ptosis, SVC obstruction
• Signs of metastases
▫ Bovine cough, bone/back pain (mets), paraneoplastic disorders
Radiology – Chest Xray
• Lung cancer - commonly a mass, +/- lung collapse
▫ Irregular margins – spiculated, but 20% smooth borders
▫ Prominent hilum (+/- hoarsenes), widened mediastinum
▫ Nodules, atelectasis, unresolving consolidation
▫ Rib erosion (+ severe chest pain),
▫ Interstitial shadowing – carcinoma in situ / adenocarcinoma (bronchoalveolar
carcinoma) , lymphangitis
▫ Occasionally normal xray
• TB - Parenchymal disease (upper lobe predilection)
▫ lymphadenopathy, nodules, miliary disease, pleural effusion, cavitation , dense
consolidation, homogeneous, or non-homogenous – air bronchograms, bronchial
▫ Fibrotic changes
Pulmonary TB 35 yr F
2 month history of
productive cough, clear
sputum, no
haemoptysis
fever, night sweats,
weight loss, anorexia,
palpitations, dyspnea
no smoking
Significant alcohol
intake, sells liquor
smear positive +++
HIV positive

18 yr Male
Pulmonary
TB
cough 2/12 ,
productive clear
sputum, no
haemoptysis,
marked weight
loss, anorexia,
night sweats, no
fever, severe
anaemia, SH
single, previous
smoker 5/day,
AFB negative,
HIV+





Lung cancer
upper lobe
mass, hilar
shadowing




Diagnosis Radiology

▫ Previous Chest xrays – past 1-2 yrs, serial xrays
 Lung cancers typically double in volume (an increase of 26% in
diameter) average, 240 days (range 30 -400 days).
▫ Chest CT scan- best to follow-up on abnormal CXR, or
symptomatic with normal CXR
 Lymph node involvement, size, nodules or masses
▫ PET scan (positron emission tomography scan): a small amount of
radioactive glucose is injected into a vein
 Increased uptake in Lung Ca, solitary nodules
▫ Detect metastases
 MRI (magnetic resonance imaging)
 Radionuclide bone scan- detects rapidly dividing cancer cells in bone
Diagnosis – obtain tissue confirmation
of lung cancer
• Sputum cytology, repeated samples
• Fiberoptic bronchoscopy
▫ Endobronchial, transbronchial biopsy, FNA, brushings
▫ BAL, washings
▫ Staging – size and location of tumor, extension to carina or trachea
useful for staging of lung cancer
• Endoscopic ultrasound (EUS), transoesophageal,
• fine-needle aspiration, tumour or LN adjacent to oesophagus
• Mediastinoscopy
• CT guided/ fluoroscopy-guided biopsy
• Special stains for detecting mucin , carcinoembryonic antigen and (CEA),
Leu-1 – 50-90% of adenocarcinoma,, not in mesothelioma

Preparation - Bronchoscopy pathway
• FBC, platelets
• INR
• Spirometry
• ECG
• CT scan, (Chest xray)
• Sputum AFB smear
• Gene Xpert – real-time PCR-based molecular testing
▫ an automated, cartridge-based nucleic acid amplification test (NAAT)
for TB - 2hrs
Pleural lesions
• Pleural aspirate – 62 – 90%
• Pleural biopsy – 44-75% yield, metastatic ds, tuberculosis
▫ closed pleural biopsies are less sensitive than pleural fluid cytology
• VATS – video-assisted thoracoscopic surgery
• Medical Thoracoscopy – 95% yield
▫ Under conscious sensation
▫ visualised biopsy
▫ Medical thoracoscopy cheaper than VATS
Above methods combined – 97%


ATS. Management of Malignant Pleural Effusions , American Journal of Respiratory and Critical
Care Medicine, Vol. 162, No. 5 (2000), pp. 1987-2001.
http://www.atsjournals.org/doi/full/10.1164/ajrccm.162.5.ats8-00
The value of biopsy
Tuberculoma
Bhatt M, Kant S, Bhaskar R. Pulmonary tuberculosis as differential diagnosis of lung
cancer. South Asian J Cancer 2012;1:36-42

In a resource poor setting what are the
Alternatives?
• In the developing world where TB prevalence is high, ATT ‘trial’ for
suspicious lung opacities may be an acceptable practice
▫ We must reach a consensus on the time limit beyond which the diagnosis
of TB must be reconsidered for poor or no response. 4-6 weeks
• Investigate all patients suspected of TB and having risk factors for lung
carcinoma with
▫ 2 sputum AFB, culture, rapid molecular tests as well as sputum cytology
for malignant cells.
▫ Yield from sputum cytology? Low - 20%. What risk factors?
• Should be referred from DOTS centres for early CT scan followed by
bronchoscopy in suspicious cases
References
• Wiredu EK, Armah HB. A 10-year review of autopsies and hospital
mortality. BMC Public Health. 2006; 6: 159.
• Alberg AJ, Samet JM. Epidemiology of Lung Cancer. CHEST 2003;
123:21S–49S
• Bhatt M, Kant S, Bhaskar R. Pulmonary tuberculosis as differential
diagnosis of lung cancer. South Asian J Cancer 2012;1:36-42
• Singh VK et al. A Common Medical Error: Lung Cancer Misdiagnosed as
Sputum Negative Tuberculosis. Asian Pacific J Cancer Prev, 10, 335-338
• ATS. Management of Malignant Pleural Effusions , American Journal of
Respiratory and Critical Care Medicine, Vol. 162, No. 5 (2000), pp. 1987-
2001