The 62-year-old female presented with cough, hemoptysis, left-sided chest pain, and shortness of breath for several months. Her history of chronic smoking and findings on examination and investigations led to a provisional diagnosis of left lung mass, most likely lung carcinoma. A biopsy confirmed squamous cell carcinoma of the left lower lobe of the lung. Further workup was needed to determine staging and treatment planning.

1. LONG CASE PRESENTATION
SUPERVISOR:
Dr. LOKENDER
PRESENTED BY:
Dr. Ambika Prasad Gupta

2. CHIEF COMPLAINTS
62 year, female, house wife, presented with the complaints of
– Cough with expectoration : 2.5 years
– Hemoptysis on and off : 2 years
– Left sided Chest pain : 3 month
– Increased shortness of breath: 2 months

3. History of present illness-
Cough with expectoration :
• 2.5 years
• Associated with scanty ,white , mucoid, expectoration
• Expectoration also associated with blood tinged sputum around 2-3 ml occasionally.
• Increased with exertion
• Not associated with foul smell
• No diurnal and postural variation
• No h/o cough syncope
• No postural variations and Diurnal variation present
• Aggravating with exertion and relieved by some medications and cough syrup.

4. History of present illness-
Hemoptysis :
• Blood tinged sputum around 2-3 ml occasionally.
• Increased with exertion
• Not associated with hematemesis and nasal bleeding
• No h/o any massive hemoptysis episode
• No h/o blood in stool and black-tarry stool.
• No h/o postural variation
• No prior history of hospitalisation for hemoptysis

5. History of present illness-
Chest pain :
• Insidious onset
• Left sided
• Dull aching
• Continuous
• No radiation
• Not associated with tingling and numbness sensation
• Not associated with postural variation
• Pain reduced with medications
• No other relieving and aggravating factor

6. History of present illness-
Breathlessness :
• Insidious onset
• Patient complaining of shortness of breath since 6 month which
was grade 1MMRC but in last 2 months gradually progressed
from MMRC grade 1 to MMRC grade 4
• Aggravated on exertion and reduced by rest
• No diurnal variation and postural variation
• No h/o of orthopnea or paroxysmal nocturnal dyspnea

7. History of present illness
H/o generalised weakness and body ache present
H/o weight loss 3-4 Kg last 6 months
Also complained of loss of appetite
Negative history-
No h/o fever
No h/o abdominal pain
No h/o burning micturation
No h/o pedal edema
No h/o loss off consciousness
No h/o any trauma and fall to chest
No h/o contact to TB patients
No h/o of rash, joint pain and stiffness

8. PAST HISTORY:
History of similar complains in the past for that patient also give history of 4 to 5
times hospital visit last 2 years but no history of hospitalization and ICU admission.
Known to have diabetes for last 4 years and is on regular OHA
Patient also gives history of hypertension on regular oral medications, no h/o
thyroid disorder, heart diseases
No h/o surgery/blood transfusion/ICD insertion
Family history:
Nothing suggestive. No family history of tuberculosis, cancer.

9. PERSONAL HISTORY:
• House wife, illiterate
• Chronic smoker, 20 beedi/day for 35 yrs stopped 5years back
• No h/o alcohol consumption and addiction to chewing tobacco
• Disturbed sleep for 2 months
• Constipation for last 15 days, not on any medications, Normal bladder habits
• No relevant h/o exposure to environmental pollutants, No h/o exposure to any
pets or birds
• No h/o any menstrual irregularities
History of ATT:
• Patient gives no prior history of ATT

10. SUMMARY
62yr old female, a chronic smoker, housewife, presented with
complains of cough with expectoration, hemoptysis, left
sided chest pain, and shortness of breath came to NITRD for
further evaluation and management as patient’s general
condition was deteriorating.

11. DIFFERENTIAL DIAGNOSIS
1. Lung carcinoma
2. COPD
3. Brochectesis
4. Pulmonary tuberculosis
5. Pulmonary vasculitis

12. General physical examination:
• Conscious, oriented to time, place and person
• Moderately built and poor nutrition, BMI of 17.16 kg/m2
• dyspnoic at rest
• using accessory muscles of respiration
• Clubbing present grade 3
• no pallor/icterus/cyanosis/pedal edema/palpable lymphadenopathy
• no engorgement of neck veins
• Patient prefers left lateral position in bed

13. General physical examination:
Vital signs :
• Temperature: 37.4 0C measured in left axilla (Afebrile)
• PR – 110/min, regular, normal volume and character, no radio-radial or
radio-femoral delay
• RR- 22/min, regular, thoraco-abdominal
• BP: 110/76mm of Hg, in right arm, in supine position
• Random blood sugar level 304 with no urinary ketones
• SpO2 – 86% on RA, 96%@1 L O2/min via Nasal prong
• JVP normal

14. SYSTEMIC EXAMINATION
Respiratory System
Upper respiratory tract : Poor oral hygiene, ENT no external abnormality seen
Lower respiratory tract
Inspection-
• Chest is bilaterally symmetrical
• Elliptical in shape
• No trachea deviation
• Chest movements reduced on left side
• Apical impulse not visible
• Not using any accessory muscles of respiration
• Intercostal spaces were full in Right hemi thorax
• No visible scars/sinus/engorged veins/swelling/fistula, bulge or hollowness

15. SYSTEMIC EXAMINATION
Palpation:
• No tenderness over the chest
• Findings of inspection were confirmed
• Trachea is central in position
• Apex beat at 5th ICS 1cm medial to MCL
• AP: Transverse diameter 5:7
• Chest expansion 4.0 cm
• Right hemi thorax 2.5 cm, Left hemi thorax 1.5cm
• Spino-scapular distance Right 2.5cm, Left 2.5cm
• No superficial swelling/tenderness
• Tactile vocal fremitus reduced on left side mammary, axillary, infra axillary
area, inter-scapular and infra scapular area rest area equal on both side

16. SYSTEMIC EXAMINATION
Percussion
• Dull note on left mammary, axillary, infra axillary area, interscapular,
infrascapular area rest area resonant note elicited on left hemi thorax
• Right hemi thorax – through out the right hemi thorax resonant
• Shifting dullness: absent
Auscultation:
• Left hemi thorax: breath sound reduced over left mammary, axillary, infra
axillary area, interscapular, infrascapular area
• Rest area vesicular breath sounds heard on left hemi thorax
• Right hemi thorax: vesicular breath sounds heard
• VOCAL RESONANCE decreased mammary, axillary, infra axillary area,
interscapular, infrascapular over left hemi thorax, rest area equal on both
side
• no added sounds heard.

17. Examination of other systems
CVS – S1 S2 heard
PA – Soft, Non-tender, No organomegaly, No free fluid, peristaltic sound
present
CNS – conscious ,oriented, GCS –normal (15/15)
Higher functions were WNL
No localizing signs elicited

18. Provisionsal diagnosis
62yr old female, a chronic smoker, presented with complains of
cough with expectoration, hemoptysis, left sided chest pain,
and shortness of breath, with history of chronic smoker,
clubbing was present on respiratory examination S/O left sided
lung mass, Most probably lung carcinoma.
For confirmation we need to further evaluation

19. Investigations
Hb-12.5g/dl
TLC-10500/mm3
DLC- N-72/L-15.2/M-12.1/E-0.6/B-0.1
Pl count-2,94,000/mm3
B Sugar(R)- 300 mg/dl
B Urea-24 mg/dl
S Creatnine-0.58 mg/dl
S. Na-133 mEq/L
S. K -3.6 mEq/L
S Protein-5.55 g/dl
S. Albumin-2.72 g/dl
S. Bilirubin-0.78/0.31 g/dl
SGOT-29
SGPT-41
S Alk Phosphotase-137.35
Sputum AFB- not found
CBNAAT sputum–M Tb
not detected
Sputum cytology –neg for
malignancy
Sputum fungal culture – sterile
Sputum pyo culture – sterile

20. Chest X-Ray

21. CT SCAN

22. CT SCAN

23. CT-SCAN

24. HRCT Scan CHEST (reported as)
• HRCT chest finding reveals bilateral emphysematous changes
and left lung mass lesion with few lower lobe centrilobular
nodular opacities and minimal left pleural effusion.
• Vertebra plana D12 vertebra
• Possibility of Neoplastic versus infective pathology.
• neoplastic more likely.
• Adv :- clinical correlation and further evaluation with
histopathological confirmation

25. HISTOPATHOLOGY
• CLINICAL HISTORY: Left lower lobe mass, trucut biopsy.
• MACROSCOPIC Multiple grey white soft tissue pieces together
measuring 4x2x1 mm.
• MICROSCOPIC Section shows fibrosis with anthracotic pigment.
Focal areas show infiltrating tumor made up of round to polygonal
cells with dense eosinophilic cytoplasm . DIAGNOSIS: Squamous
cell carcinoma.

26. LUNG CARCINOMA
• Lung cancer is the leading cause of cancer deaths worldwide in
men, and the second leading cause in women.
• Histologically lung cancer devided in to small cell carcinoma
and non small cell carcinoma.
• Non small cell carcinoma (NSCLC) has been classified
histologically as squamous cell carcinoma, adenocarcinoma,
and large cell carcinoma

27. SQUAMOUS CELL CARCINOMA
• Pathologically it is defined by either morphology or expression
of pneumocytic markers.
• Common- men
• Strongly correlated with cigarette smoking
• Two thirds of SCC occur centrally and frequently associated with
bronchial obstruction and post-obstructive pneumonia
• Cavitation is seen frequently.

28. Types of squamous cell carcinoma-
 Variants of squamous cell carcinoma in the 2004 World Health
Organization (WHO) classification system included-
• Papillary,
• Clear cell,
• Small cell, and
• Basaloid carcinoma
 These classification have been replaced with categories (2015,
WHO)
• Non-keratinizing
• Keratinizing
• Basaloid subtypes.

29. ETIOLOGY
1. TOBACCO SMOKING:-
• Most important modifiable risk factor
• 20% of all cancer deaths worldwide could be prevented by the elimination of tobacco
smoking.
• More than 80% of lung cancers develop in smokers
• Lung cancer risk is proportional to the magnitude of cigarette consumption.
• Cigar smoking and pipe smoking have been associated with increased risk for lung cancer.
Estimates of the relative risk of lung cancer in the long-term smoker compared with the
lifetime nonsmoker vary from 10- to 30-fold.
• Lung cancer risk among heavy smokers may be as high as 30 percent, compared with a
lifetime risk of lung cancer of 1 percent or less in never smokers
• Cessation before the age of 40 years reduces the risk of death associated with continued
smoking by about 90%.

30. ETIOLOGY
• The risk of lung cancer increases with both the number of cigarettes smoked per day
as well as the lifetime duration of smoking.
• Other factors like age at onset of smoking, the degree of inhalation, the tar and
nicotine content of the cigarettes, and the use of unfiltered cigarettes.
• Risk of lung cancer continues to rise with age, even after smoking cessation.
• The risk of lung cancer due to smoking marijuana or cocaine is less clear.
• The effect of e-cigarettes on the incidence of lung cancer is not well established due
to confounding effects of cigarette smoking.

31. ETIOLOGY
2. GENDER : -
• Whether women are more or less susceptible than men to the carcinogenic effects of
cigarette smoke is controversial.
• While lung cancer in never smoking women is more common than in never smoking men.
3. GENETIC FACTOR :-
• Poorly understood
• significantly increased risk for lung cancer with First-degree relatives of individuals
with specifically for persons with a family history of early-onset lung cancer less
than 60yrs.
4. RACE AND ETHINICITY :-
• Incidence of lung cancer is substantially higher among blacks,
Native Hawaiians, and other Polynesians

32. ETIOLOGY
5. AGE :-
• more than 65% of patients with lung cancer are older than 65 years.
• 31.1% of patientswith age between 65 and 74 years
• 29% between 75 and 84 years
• 8.3% are 85 years old and older.
• The mean age at the time of diagnosis is 71 years old
6.DIETARY FACTORS :—
• Diets higher in fruits and vegetables decrease the risk of lung cancer
• vitamins A, C, and E,βcarotene protective effects
• Low dietary intake of certain minerals, including magnesium, zinc, copper, and iron, is associated with increased lung cancer risk
7. BODY MASS INDEX —
• Inverse relationship between body mass index (BMI) and lung cancer.

33. ETIOLOGY
8. OCCUPATIONAL AND ENVIRONMENTAL CARCINOGENS:-
• The best known factors are asbestos and radon.
• Other exposures include arsenic, bis(chloromethyl) ether, beryllium, cadmium, chromium,
formaldehyde, ionizing radiation, nickel, polycyclic aromatic hydrocarbons, hard metal dust, and vinyl
chloride.
• Patients with asbestos exposure complicated by interstitial fibrosis (ie, asbestosis) are much more
likely to develop lung cancer. The risk of lung cancer is dose-dependent and risk appears to be
considerably higher for workers exposed to amphibole fibers than for those exposed to chrysotile
fibers .
• Smoke from cooking and heating ,wood burning increase in the incidence of lung cancer.
• Air pollution and diesel exhaust.

34. ETIOLOGY
9.OTHER ESTABLISHED AND POSSIBLE FACTORS:-
• Radiation therapy This increase in risk appears to be most pronounced in
smokers.
• Inflammation and benign lung disease risk mediated through chronic
inflammation. patients with a history of emphysema, chronic bronchitis,
pneumonia and tuberculosis.Individuals with diffuse pulmonary fibrosis
have an 8- to 14-fold increased risk for lung cancer.
• Endocrine factors The impact of estrogen and progesterone.
• Oncogenic viruses Oncogenic viruses do not have an established role.A
potential causal role for human papillomavirus (HPV) in squamous cell
carcinoma of the lung has been hypothesized,
• Patients with HIV have an elevated risk of lung cancer than patients
without HIV.

35. PATHOGENESIS
• Squamous cell carcinomas show the highest frequency of p53
mutations.
• Loss of protein expression gene RB is detected by
immunohistochemistry in 15%of squamous cell carcinomas.
• CDK-inhibitor p16 INK4 is inactivated, and its proteins roduct
lost in 65% of tumour. Her-2/neu is highly expressed in 30% of
these cancers

37. SQUAMOUS CELL CARCINOMA GROSS
• Commonly occur centrally (2/3rd cases)
• Involvement of main stem, lobar or segmental
bronchus is common
• Can also present as a peripheral mass
• CAVITATION is seen frequently
• SCC arise most often in segmental bronchi and
involvement of lobar and main-stem bronchus occurs
by extension
• Surrounding lung may exhibit lipid pneumonia,
bronchopneumonia, atelectasis

38. HISTOPATHOLOGY
• Characterised by presence of keratinisation and/or intercellular
bridges
• Keratinisation may take form of squamous pearls or individual cells
with markedly eosinophilic cytoplasm:
• Features prominent in well differentiated tumours, and are focally
seen in poorly differentiated cancers.
• Mitotic activity: higher in poorly differentiated tumors
• Squamous metaplasia, epithelial dysplasia and foci of frank
carcinoma in situ may be seen in bronchial epithelium adjacent to
the tumor mass

42. IMMUNO-HISTOCHEMISTRY

43. CLINICAL FEATURE
• lung cancer develops insidiously and is asymptomatic until late in its course.
• The signs and symptoms depend on the location and size of the tumor, the degree of obstruction, and
the existence of metastases to regional or distant sites.
A. INTRATHORACIC CLINICAL MANIFESTATIONS
• There are a wide range of symptoms ,the most common of which are cough(50-70%), hemoptysis (3-
30%), chest pain(20-40), and dyspnea(25-40).
• Cough occurs most frequently in patients with squamous cell and small cell carcinomas because of
their tendency to involve central airways .
• In smokers with hemoptysis and a nonsuspicious or normal chest radiograph, bronchoscopy will
diagnose lung cancer in approximately 5 percent of cases.
• Chest pain more common in younger compared with older patients. Pain is typically present on the
same side of the chest as the primary tumor. Dull, aching, persistent pain may occur from mediastinal,
pleural, or chest wall extension, but the presence of pain does not necessarily preclude resectability.
Although pleuritic pain may be the result of direct pleural involvement, obstructive pneumonitis or a
pulmonary embolus related to a hypercoagulable state may also cause chest pain.

44. CLINICAL FEATURE
• Dyspnea Dyspnea may be due to extrinsic or intraluminal airway obstruction,
obstructive pneumonitis or atelectasis, lymphangitic tumor spread, tumor
emboli, pneumothorax, pleural effusion, or pericardial effusion with tamponade.
Partial obstruction of a bronchus may cause a localized wheeze, heard by the
patient or by the clinician on auscultation, while stridor can result from
obstruction of the trachea.
• Hoarseness — The differential diagnosis in smoker includes both laryngeal
cancer and lung cancer. this is due to malignancy involving the recurrent
laryngeal nerve.
• Pleural involvement —can manifest as pleural thickening or nodularity without
pleural effusion or as malignant pleural effusion.
• Series report that 5 to 14 percent of patients with NSCLC and an ipsilateral
pleural effusion have resectable disease [1,2]. Surgical thoracoscopy or medical
pleuroscopy should follow two negative pleural fluid cytologies to further
evaluate the pleural space prior to surgical resection of a primary lesion.

45. CLINICAL FEATURE
• Superior vena cava syndrome —symptoms that commonly include
a sensation of fullness in the head and dyspnea. Cough, pain, and
dysphagia are less frequent.
• Physical findings include dilated neck veins, a prominent venous
pattern on the chest, facial edema
• The SVC syndrome is more common in patients with SCLC than
NSCLC.
• Pancoast syndrome — Lung cancers arising in the superior sulcus
cause a characteristic Pancoast syndrome manifested by pain ,
Horner syndrome, bony destruction, and atrophy of hand muscles.
• Pancoast syndrome is most commonly caused by NSCLC (typically
squamous cell)

46. CLINICAL FEATURE
B. CLINICAL MANIFESTATIONS OF EXTRATHORACIC METASTASES
• Lung cancer can spread to any part of the body tissue.
• The most frequent sites of distant metastasis are the liver, adrenal glands, bones, and brain.
• Bone -frequently symptomatic. Pain in the back, chest, or extremity and elevated levels of serum alkaline
phosphatase.
• Adrenal - occurring in 40 percent in one autopsy series [3], only rarely symptomatic. Occasionally, patients can
present with loss of appetite, weight loss, nausea, abdominal pain, weakness, and electrolyte imbalances
secondary to adrenal insufficiency.
• Brain -Symptoms include headache, vomiting, visual field loss, hemiparesis, cranial nerve deficit, and seizures.
• Metastasis is greatest with adenocarcinoma and least with squamous cell carcinoma.
• In patients with SCLC, metastasis to brain is present in approximately 20 to 30 percent of patients at
presentation [4]. Without prophylactic irradiation, relapse in the brain occurs in approximately one-half of
patients within two years.
• Liver – symptomatic rare, asymptomatic liver metastases may be detected at presentation by liver enzyme
abnormalities

47. GENERAL GOALS AND TIMING OF EVALUATION
• Goals The major goals to find the
1. Clinical extent and stage of disease
2. Optimal target site and modality for the first tissue biopsy
3. Specific histological subtype
4. Presence of comorbidities, secondary complications, and paraneoplastic
syndromes that influence treatment options and outcome.
5. Patient values and preferences that influence diagnostic and therapeutic choices
Diagnostic Evaluation
COMPLETE BLOOD COUNT
LIVER FUNCTION TEST
KIDNEY FUNCTION TEST
PT/INR
HIV/HBsAG/HCV

48. DIAGNOSIS
IMAGING TEST LIKE - Chest X-ray , Computed tomography (CT) scan , PET scan.
Cytologic examination of sputum/chest fluids ,lymph node for malignant cells ,
Bronchoscopy for observation of location and extent of tumor;
mediastinoscopy to establish lymphatic spread
• The preferred approach use and do biopsy as a tool to confirm both the
histopathological diagnosis and the stage of disease.
• When feasible, diagnosis and staging should be estabilished .
• However, some patients will require multiple imaging studies and/or invasive
procedures for tissue sampling.
• After confirmation of diagnosis by histopathogical examination, we should treat
the patient

49. TNM
STAGING
OF LUNG
CANCER

50. STAGING OF LUNG CANCER
• Stage 1 A - T1N0M0
• Stage 1B - T2AN0M0
• Stage 2A - T2BN0M0
• Stage 2B(N1 disease) - T1N1, T2N1,T3N0
• Stage 3A(N2 disease) - T1N2,T2N2,T3N1,T4N1,T4N0
• Stage 3B(N3 disease) -T1N3,T2N3,T3N2,T4N2
• Stage 3C - T3N3,T4N3
• Stage 4 - Tany Nany M1

51. TREATMENT
TREATMENT BASED ON STAGING OF THE DISEASES :-
A. STAGE 1A, 1B, 2A :-
• surgery plus either mediastinal lymph node dissection or intra operative bronchoscopy ,
EBUS, TBNA, mediastinoscopy for pathological staging .
• If patient not fit for surgery then give SABER (steriotactic ablative radiotherapy) and MRI
and PET we should do.
• See the tumour margin
 R0 – more than 2cm tumour free marin – only observe after sx
 R1 – less than 2 cm tumour free margin – only chemotherapy after sx
 R2 – less than 1 cm tumour free margin – chemo plus radiotherapy after sx

52. TREATMENT
B. STAGE -2B,3A,3B :-
• If N2,N3 negative then do same as previously surgery plus
either mediastinal lymph node dissection or intra operative
bronchoscopy , EBUS, TBNA, mediastinoscopy for pathological
staging
• Then see tumour margin
R0 – chemotherapy
R1 – chemotherapy plus radio therapy
R2 – chemotherapy plus radio therapy
• Rest other treatment will be same as stage 3C

53. TREATMENT
C. STAGE 3C:-
Concurrent chemo radiotherapy and give - PDL1 antibody durvalumab
D. STAGE 4 (ADVANCED DISEASE) :-
• In all cases of advance diseases always do molicular testing before treatment
initiation
• EGFR, ALK mutation see in
 In non smoker
 Small biopsy sample
 Mix pattern
• ROS, BRAF mutation
 Small biopsy sample
 Mixed pattern
• PDL-1 mutation

54. TREATMENT
Current treatment for patient with stage 4 disease with biomarker positive
• EGFR positive
 Osimertinib
 Erlotinib
 Geftinib
• ALK positive
 Alectinib
 Brigatinib
 Ceritinib
 Crizotinib
• BRAF V600E positive
 dabrafenib

55. TREATMENT
• ROS 1 positive
Crizotinib
Entrectinib
• NTRK positive
Entrectinib
• RET positive
Selpercatinib
Pralsetinib

56. TREATMENT
Treatment of lung cancer of advance disease without driver
mutation :-

57. SUMMARY
• Squamous cell cancer of lung: more common in males and
smokers
• Generally centrally located, can also cause symptoms due to
obstruction
• Apart from clinical and radiological features, the mainstay of
diagnosis is histopathology and IHC. Histological features
include: keratinisation and presence of intercellular bridges
• On IHC: p40, p63 and CK5/6 positive and TTF-1, Napsin,
Mucin,CK-7, CK 20 negative.
• Immunotherapeutic approach, along with targeted kinase
inhibitors, and antibodies are being developed and few are
under trial

58. REFERENCES
 NCCN GUIDELINES VERSION 3.2020 NON SMALL CELL LUNG CANCER
 TEXT BOOK OF FISHMANS PULMONARY DISEASES AND DISORDERS
 UPTO DATE
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pleural effusion in bronchogenic carcinoma. Chest 1978; 74:640.
2.Roberts JR, Blum MG, Arildsen R, et al. Prospective comparison of radiologic,
thoracoscopic, and pathologic staging in patients with early non-small cell lung
cancer. Ann Thorac Surg 1999; 68:1154
3. Stenbygaard LE, Sørensen JB, Olsen JE. Metastatic pattern at autopsy in non-
resectable adenocarcinoma of the lung--a study from a cohort of 259 consecutive
patients treated with chemotherapy. Acta Oncol 1997; 36:301.
4.Doyle TJ. Brain metastasis in the natural history of small-cell lung cancer: 1972-
1979. Cancer 1982; 50:752.