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RESPIRATORY LONG CASES

Edited by-

DR. MD. SANAULLAH KHAN

MBBS(DMC), BCS
FCPS (Medicine) Final Part Examinee
MRCP (UK) PACES Candidate

10 October, 2023

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Long Case-01
BRONCHIAL CARCINOMA

History
A. Symptom Analysis
Symptoms of disease ▪ Cough ± hemoptysis
▪ Chest pain
▪ SOB
▪ Systemic feature: Fever, Anorexia, Wt. loss
Symptoms of local invasion ▪ Swelling of face, neck & upper limbs, Eye congestion, SOB,
Cough, headache (SVCO)
▪ Hoarseness of voice, bovine cough (Lt recurrent laryngeal
n. palsy)
▪ Pain in shoulder, inner aspect of arm, wasting of small
muscle of hand (Pancoast’s syndrome)
▪ Problem in deglutition (Oesophageal compression)
▪ Stridor (Lower trachea/carina/principal bronchus
compression)
▪ Palpitation, SOB (Arrhythmia due to pericardial effusion)
Symptoms of Distant ▪ Back pain, Weakness of both LL (spinal cord compression),
metastasis bone pain (bony metastasis)
▪ Nodular swelling (LN)
▪ Headache, Seizure, personality change (Brain Metastasis)
▪ Abdominal distention, Jaundice (Liver Metastasis)
▪ Skin nodules (Skin Metastasis)
▪ Skin hyperpigmentation, Vomiting & Diarrhoea, Fatigue,
Abdominal pain (Adrenal Metastasis)
Symptoms of paraneoplastic ▪ Facial puffiness, proximal muscle weakness, striae
manifestations (Cushing’s)
▪ Altered level of consciousness (SIADH)
▪ ↑ urinary frequency, dyspepsia (Hypercalcemia)
▪ Tingling sensation of hands/feet, distal muscle weakness
(PN)
▪ Muscle pain, proximal muscle weakness, skin rash
(Poly/Dermatomyositis)
▪ Vertigo, speech difficulty (Cerebellar degeneration)
▪ Wasting & fasciculation of limbs, swallowing & speech
difficulty (MND)
▪ Proximal muscle weakness (Myasthenia/LEMS)
▪ Any change on amount or color of urine/frothiness, facial
puffiness, legs swelling (GN)
▪ Episodic flushing, wheezing, diarrhoea (Carcinoid)
For exclusion of DDx ▪
(No H/O)
History for common ▪ COPD*, IHD, HF, HTN, DM, CKD, CLD, Stroke,
comorbidities Hypo/hyperthyroidism, Psychiatric illness

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B. Other Histories
Past illness history ▪ H/O contact with known smear positive PTB case, Past
TB history
▪ Childhood RTI (Bronchiectasis)
Personal history ▪ Smoking history
▪ Occupational history ((Mining, Quarrying, Pottery-
Silicosis), (Ship breaking, Pipe lagging- Asbestosis),
Aircraft, Electronics industry- Berylliosis))
Drug & Treatment history ▪ Blood transfusion, FNAC/biopsy from LN, Ascitic/pleural
fluid tap, Chemotherapy/ radiotherapy received

G/E
Face, Neck ▪ Cachexia, Puffy face (GN, Cushing’s), Anemia, Jaundice,
Ptosis, Meiosis, cervical LN, SVCO features
UL ▪ Clubbing, Nicotine stain, Cyanosis, Flapping tremor,
HPOA, Low BP with postural drop, LN, Skin nodules
Chest, Abdomen ▪ Gynaecomastia (Paraneoplastic), Skin nodules
LL ▪ Bipedal Oedema (GN)
Others ▪ Urine dipstick for Prot., RBC (GN)

S/E
Respiratory System ▪ Features of Pleural effusion/Consolidation/Mass lesion/
Collapse
▪ Features of COPD
Nervous System ▪ Features of Horner’s syndrome
▪ Features of Pancoast syndrome
▪ Features of spinal cord compression (Spinal metastasis)
▪ Hemiplegia/focal neurologic deficit (Brain metastasis)
▪ Cerebellar signs (Paraneoplastic)
▪ PN (Paraneoplastic)
▪ Fundoscopy- Papilloedema (Brain metastasis, SVC
obstruction)
Abdomen ▪ Hepatomegaly, Ascites
Musculoskeletal ▪ Proximal myopathy (Cushing’s, Poly/Dermatomyositis,
Myasthenia, LEMS)
CVS ▪ Features of pericardial effusion

PDx
(According to the presentation of individual pt)
Clinical Dx (Rt/Lt sided PE/Consolidation/Collapse) due to Bronchial carcinoma with (organ
involved) metastasis

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DDx
(According to the presentation of individual pt)
1. Pulmonary/Disseminated Tuberculosis
2. Lymphoma
3. Bronchiectasis

Investigations with aim/interpretation

Aim of Invx:
▪ To confirm the Dx
▪ To establish the histological cell type
▪ To define the extent of disease

A. For diagnosis & Exclusion of differentials

i. CBC ▪ Low Hb, Lymphocytosis, high ESR

ii. CxR PA view ± lateral ▪ Features of Pleural effusion/Consolidation/Mass lesion/
view Collapse, ? Rib destruction
▪ Mediastinal lymphadenopathy
▪ Enlarged cardiac shadow (Pericardial effusion)
iii. Sputum examination ▪ To exclude PTB & pneumonia
(Gram stain, AFB
stain, Culture, Gene
Xpert, Malignant cell)
iv. Tuberculin test ▪ Positive in PTB
v. Pleural fluid study ▪ To exclude PTB & pneumonia
including gene Xpert,
ADA & malignant cell
vi. LDH ▪ Rises in case of Lymphoma

Reorder the sequence of following invx according to the presentation of individual pt-
B. For confirmation of Dx

i. CT scan of chest with ▪ To localize the mass lesion

contrast
ii. CT guided or ▪ Peripheral lesion → CT guided biopsy
Bronchoscopy with ▪ Central lesion → Bronchoscopy guided biopsy
EBUS guided biopsy
with histopathology
iii. Image guided LN ▪ To see metastasis
biopsy ▪ To establish the histological cell type (Tissue dx)
iv. Bronchoscopy with ▪ To see the malignant cells
BAL

C. To see metastasis

i. USG of W/A ▪ To see liver ± adrenal metastasis

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ii. CT scan of Abdomen, ▪ To see liver, adrenal, brain metastasis

CT scan of Brain
iii. Bone scan ▪ To see bony metastasis
iv. Thoracoscopy guided ▪ To see pleural metastasis
pleural biopsy
v. FNAC/B of skin ▪ To see metastasis
lesions, liver or bone ▪ To establish the histological cell type
marrow
vi. PET-CT ▪ For anatomical staging & detection of metastases
▪ Can detect nodules >15 mm in diameter
▪ A standardized uptake value (SUV) of >2.5 on PET is
highly suspicious for malignancy.

D. For Tx (Before starting chemotherapy)

S. creatinine, S. ▪ To assess the baseline kidney function

electrolytes
LFT (SGPT, S. ▪ To exclude liver involvement
bilirubin, S. ALP)
S. Uric acid ▪ To see baseline level
▪ To see chemotherapy induced hyperuricemia
ECG & ▪ To assess cardiac function (Anthracycline drugs causes
Echocardiography cardiomyopathy)

Staging (Harrison’s 21st)

Two parts-
▪ Anatomic Staging: determination of the location of the tumor and possible metastatic sites
▪ Physiologic Staging: an assessment of a patient’s ability to withstand various antitumor
treatments
Staging for NSCLC
TABLE: TNM Staging System for Lung Cancer (Eighth Edition)
Primary Tumor (T)
T1 Tumor ≤3 cm diameter, surrounded by lung or visceral pleura, without invasion more
proximal than lobar bronchus
T1mi Minimally invasive adenocarcinoma (pure lepidic pattern, <3 cm in greatest dimension
and <5 mm invasion) —
T1a (size <1 cm) — T1b (1 cm < size <2 cm) —T1c (2 cm < size <3 cm)
T2 Tumor >3 cm but ≤7 cm, or tumor with any of the following features:
Involves main bronchus ≥2 cm distal to carina Invades visceral pleura
Associated with atelectasis or obstructive pneumonitis that extends to the hilar
region but does not involve the entire lung
T2a Tumor >3 cm but ≤5 cm
T2b Tumor >5 cm but ≤7 cm
T3 Tumor >7 cm or any of the following:
Directly invades any of the following: chest wall, diaphragm, phrenic nerve,
mediastinal pleura, parietal pericardium, main bronchus <2 cm from carina (without
involvement of carina)
Atelectasis or obstructive pneumonitis of the entire lung
Separate tumor nodules in the same lobe

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T4 Tumor of any size that invades the mediastinum, heart, great vessels, trachea,
recurrent laryngeal nerve, esophagus, vertebral body, or carina, or with separate tumor
nodules in a different ipsilateral lobe
Nodal Stage (N)
N0 No regional lymph node metastases
N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and
intrapulmonary nodes, including involvement by direct extension
N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)

N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral

scalene, or supraclavicular lymph node(s)
Metastases (M)
M0 No distant metastasis
M1 Distant metastasis
M1a Separate tumor nodule(s) in a contralateral lobe; tumor with pleural nodules or
malignant pleural or pericardial effusion
M1b Distant metastasis (in extrathoracic organs)
M1c Multiple extrathoracic metastases to one or more organs

TABLE: TNM Stage Groupings (Eighth Edition)

Stage IA1 T1a
Stage IA2 T1b
Stage IA3 T1c N0
Stage IB T2a
Stage IIA T2b
Stage IIB T1a-T2b N1
T3 N0 M0
Stage IIIA T1-2b N2
T3 N1
T4 N0/N1
Stage IIIB T1-2b N3
T3/T4 N0/N1
T3/T4 N3
Stage IVA Any T Any N M1a/M1b
Stage IV B Any T Any N M1c

Staging for SCLC

▪ Both the Veterans Administration system and the American Joint Committee on Cancer/
International Union Against Cancer eighth edition system (TNM) be used to classify the tumor
stage.
▪ The Veterans Administration system is a distinct two-stage system dividing patients into-
i. Limited-stage disease (LD): cancer that is confined to the ipsilateral hemithorax (ipsilateral
supraclavicular nodes, recurrent laryngeal nerve involvement, and superior vena caval
obstruction etc)
ii. Extensive-stage disease (ED): overt metastatic disease by imaging or physical examination
(cardiac tamponade, malignant pleural effusion, and bilateral pulmonary parenchymal
involvement etc.) Sixty to 70% of patients are diagnosed with ED at presentation.

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Physiologic Staging
▪ Patients with a forced expiratory volume in 1 s (FEV1) of >2 L or >80% of predicted can
tolerate a pneumonectomy, and those with an FEV1 >1.5 L have adequate reserve for a
lobectomy.
▪ In patients with borderline lung function but a resectable tumor, cardiopulmonary exercise
testing could be performed as part of the physiologic evaluation. This test allows an estimate
of the maximal oxygen consumption (Vo2max). A Vo2max <15 mL/(kg.min) predicts for a
higher risk of postoperative complications.

Contraindication to thoracic surgery

▪ MI within the past 3 months is a. (within the past 6 months is a relative contraindication).
▪ Uncontrolled arrhythmias
▪ FEV1 <1 L
▪ CO2 retention (resting Pco2 >45 mmHg)
▪ DLco <40%
▪ Severe pulmonary hypertension

Clinical Findings Suggestive of Metastatic Disease

Symptoms elicited in ▪ Constitutional: weight loss >10 lb
history ▪ Musculoskeletal: pain
▪ Neurologic: headaches, syncope, seizures, extremity
weakness, recent change in mental status
Signs found on physical ▪ Lymphadenopathy (>1 cm)
examination ▪ Hoarseness, superior vena cava syndrome
▪ Bone tenderness
▪ Hepatomegaly (>13 cm span)
▪ Focal neurologic signs, papilledema
▪ Soft-tissue mass
Routine laboratory ▪ Hematocrit, <40% in men; <35% in women
tests ▪ Elevated alkaline phosphatase, GGT, SGOT, and calcium
levels

Assessment of Risk of Cancer in Patients with Solitary Pulmonary Nodules

VARIABLE RISK
LOW INTERMEDIATE HIGH
Diameter (cm) <1.5 1.5–2.2 ≥2.3
Age (years) <45 45–60 >60
Smoking status Never smoker Current smoker (<20 Current smoker (>20
cigarettes/d) cigarettes/d)
Smoking cessation Quit ≥7 years ago Quit <7 years ago Never quit
status or quit
Characteristics of nodule Smooth Scalloped Corona radiata or
margins spiculated

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Management

▪ Best managed in specialist centers by multidisciplinary teams, including oncologists,

thoracic surgeons, respiratory physicians and specialist nurses.
General Tx • Pt education and proper counselling
• Maintenance of nutrition
• Correction of symptomatic anemia
• Management of paraneoplastic endocrine manifestations
• Pain management
• Prophylaxis for tumor lysis syndrome
• ICT/Pleurodesis for malignant pleural effusion
• Psychological support
Specific Tx • It depends on the staging, histological type and patient’s
performance status
Tx of presenting other complications
Tx of co-morbidities

Tx for Non-Small Cell Lung Cancer: (Harrison’s 21st)

Algorithm:

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Stage I & II NSCLC

Surgical resection ▪ In patients with comorbidities, compromised pulmonary
reserve, and small peripheral lesions → wedge resection,
or segmentectomy, or lobectomy (preferably by VATS)
▪ In patients with central tumors and excellent pulmonary
reserve → Pneumonectomy
Radiation therapy Pt either refuse or are not suitable for surgery
▪ Stereotactic Body Radiation Therapy (SBRT)/Highly
targeted radiotherapy: 3-5 fractions delivered over 1-2
weeks (preferred)
▪ External beam radiotherapy
Adjuvant chemotherapy ▪ Not recommended for Stage IA, IB with tumor size <4cm
(see algorithm)
▪ Tx should be initiated 6-12 weeks after surgery
▪ No more than 4 cycles of therapy
Neoadjuvant ▪ In selected cases
chemotherapy ▪ Should always be made in consultation with an
experienced surgeon
Stage III NSCLC
▪ Stratified into nonbulky or bulky mediastinal LN (N2) disease
▪ Bulky N2 disease:
>2–3 cm in short-axis diameter as measured by CT
Groupings of multiple smaller lymph nodes,
Evidence of extracapsular nodal involvement, or
Involvement of more than two lymph node stations
Bulky N2 disease ▪ Concurrent chemoradiotherapy followed by a year of
immunotherapy with durvalumab or other PD-L1-directed
antibody
Absent and Nonbulky ▪ Stage IIIA (T3N1, T4N0-1) → Surgical resection followed
Mediastinal (N2, N3) by chemotherapy
Lymph Node Disease ▪ Stage IIIB (T4 disease) → Surgery is contraindicated;
Concurrent chemoradiotherapy followed by durvalumab
Known Mediastinal (N2, ▪ Concurrent chemoradiotherapy followed by durvalumab
N3) Lymph Node
Disease
Superior Sulcus Tumors ▪ Neoadjuvant chemotherapy or combined
(Pancoast Tumors) chemoradiotherapy followed by surgery is reserved for
those without N2 involvement
▪ Patients with N2 disease → Concurrent
chemoradiotherapy followed by durvalumab
▪ Metastatic disease → Palliative radiotherapy
Stage IV/Metastatic NSCLC (40% of the cases at the time of Dx)
▪ Use of pain medications
▪ Appropriate use of radiotherapy and systemic therapy (targeted therapy, immunotherapy,
and/or traditional cytotoxic chemotherapy) depending on the specific diagnosis as well as PD-
L1 tumor proportion score (TPS) and molecular subtype
▪ Metastatic or recurrent NSCLC → Cytotoxic chemotherapy in combination with
immunotherapy
▪ Second line therapy for advanced NSCLC → Docetaxel, Ramucirumab

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▪ Supportive care/Palliative care

Palliative radiotherapy for SVCO, recurrent hemoptysis, pain caused by chest wall invasion or
by skeletal metastatic deposits, obstruction of the trachea and main bronchi
Bronchoscopic laser therapy for tumors of the main bronchi
Endobronchial stenting for to maintain airway patency if extrinsic compression by malignant
nodes

Targeted therapy for NSCLC:

▪ Molecular testing is done by Next-generation sequencing (NGS), fluorescence in situ
hybridization (FISH), immunohistochemistry (IHC)

Algorithm:

Immunotherapy for NSCLC:

▪ Immune checkpoint inhibitors are used primarily in patients whose tumors do not express a
targetable genetic lesion.
▪ M/A: blocking interactions between T cells and antigen presenting cells (APCs) or tumor
cells that lead to T-cell inactivation. By inhibiting this interaction, the immune system is
effectively upregulated and T cells become activated against tumor cells.

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Tx for Small Cell Lung Cancer: (Harrison’s 21st)

Algorithm:

Limited-stage SCLC
Chemoradiotherapy ▪ Cisplatin-etoposide for four cycles
▪ Cisplatin/Carboplatin + etoposide/PD-L1 inhibitor
(atezolizumab or durvalumab) provides superior progression-
free and overall survival compared to chemotherapy alone
▪ Relapsed case → second-line chemotherapy (Topotecan,
lurbinectedin etc.)
Thoracic radiation ▪ Induction therapy for patients with good performance status
therapy (TRT) and limited-stage SCLC
▪ Most commonly, TRT is combined with cisplatin and
etoposide chemotherapy due to a superior toxicity profile

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▪ TRT should be administered with the first two cycles of

chemotherapy because later application appears slightly less
effective
Prophylactic cranial ▪ All patients either with LD-SCLC or who have responded
irradiation well to initial therapy
Extensive-stage SCLC
Radiotherapy ▪ For palliation of tumor-related symptoms such as bone pain
and bronchial obstruction

Prognosis
NSCLC
▪ Approximately 60% and over 80% of patients dying within 1 and 5 years respectively of
diagnosis. (Davidson’s 24th)
▪ The best prognosis is with well-differentiated squamous cell tumours that have not
metastasized and are amenable to surgical resection. (Davidson’s 24th)
Stage I II III IVA IVB
1 year survival 87-97% 72-79% 24-55% 23% 10%
5 year survival 68-92% 53-60% 13-36% 10% 0%
(Harrison’s 21st)

SCLC (Harrison’s 21st)

▪ Despite response rates to first-line therapy as high as 80%, the median survival ranges from
12 to 20 months for patients with LD and approximately 12 months for patients with ED
▪ The prognosis is especially poor for patients who relapse within the first 3 months of therapy
(Chemotherapy resistant disease)

Frequently Asked Questions (FAQs) & Tricky Questions

Teacher-01:
1. What are the points in favour of your dx?
2. Why is this not a case of tuberculosis?
3. Why is this not a case of bronchiectasis?
4. What are the risk factors for lung carcinoma?
5. What are the distant organs metastasized/most common site of metastasis from bronchial
carcinoma?
6. How many patients is presented with metastasis at diagnosis?
7. Where are the primary sites of secondaries in the lung?
8. What did you look for during eye examination?
9. What are the features of adenocarcinoma?
10. What are the features of small cell carcinoma?
11. What are the risk factors for bronchial carcinoma?
12. What are the causes of breathlessness in a bronchial carcinoma pt?

Teacher-02:
13. How will you investigate the/this patient (your case, not a bronchial carcinoma case)?
14. How bronchoscopy will help in this case?/Why bronchoscopy should be done?
15. What are the histological types of bronchial carcinoma?
16. What are the modalities of treatment?
17. How would you stage lung carcinoma? (Harrison’s 21st - p601)
18. What would be staging of your patient clinically?
19. How can you assess the functional/performance status of this patient?

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20. Which tumor is more amenable to surgery?

21. Which tumor is more sensitive to chemotherapy? Why is small cell carcinoma usually not
amenable to surgery?
22. What are the contraindications of surgery in non-small cell lung cancer?
23. Tell me the prognosis of your patient?

Further Reading:
▪ Davidson’s 24th Edd- 528
▪ Harrison’s 21 Edd- 594
▪ HN Sarker LC 1st Edd- 101
▪ Abdullah LC- 114
▪ Cluster of LC 2nd Edd- 109
▪ Dr. Mosarrof’s LC Note- 26
▪ Dr. Farah’s LC Note- 11

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