Late Diagnosis Of Lung Cancer In Resource-poor CentresDr. Audrey ForsonDepartment of MedicineUniversity 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 6th 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 % ASCAR1. LIVER 428 21.3 21.152. HAEMATOPOIETIC ORGANS 417 20.8 15.573. PROSTATE 286 14.2 17.354. STOMACH 126 6.3 7.265. PANCREAS 914.5 5.226. BLADDER 914.5 5.077. LUNG 783.9 4.568. BRAIN 673.3 2.789. COLON & RECTUM 532.6 2.9510. LARYNX 452.2 2.7511. KIDNEY 412.0 1.6312. OESOPHAGUS391.9 2.4213. BONE 341.7 1.3514. BREAST 120.6 0.66

ALL SITES 2008100 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 carcinomaSmall 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 carcinomatends 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 MisdiagnosisIn 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 clubbingOther 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 haemoptysisfever, night sweats, weight loss, anorexia, palpitations, dyspneano smokingSignificant alcohol intake, sells liquorsmear positive +++HIV positive

18 yr Male Pulmonary

TBcough 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 VATSAbove 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

TuberculomaBhatt 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