NSCLCa – a pictorial NSCLCa – a pictorial lessonlesson

H LordH Lord

Staging - Updated 2009!Staging - Updated 2009! International International

Staging System for Staging System for lung cancer lung cancer (simplified from (simplified from Mountain 1986 Mountain 1986 1993). Survival is 1993). Survival is based upon based upon clinical staging. clinical staging. Survival for Survival for surgically staged surgically staged patients is higher patients is higher in resected cases. in resected cases.

TX - malignant TX - malignant cells in cells in bronchopulmonary bronchopulmonary secretions but secretions but primary cancer not primary cancer not otherwise otherwise visualizedvisualized

T0 - no evidence T0 - no evidence of primary tumor; of primary tumor; Tis - carcinoma Tis - carcinoma in in situsitu..

International Staging System for lung cancer (simplified from Mountain, 1986, International Staging System for lung cancer (simplified from Mountain, 1986, 1993).1993).

Regional nodal stations for lung cancer staging (from Regional nodal stations for lung cancer staging (from Mountain, 1997).Mountain, 1997).

SurvivalSurvival Cumulative Cumulative

proportion of proportion of patients patients expected to expected to survive survive following following treatment treatment according to according to clinical clinical estimates of estimates of the stage of the stage of disease (from disease (from Mountain Mountain et et al.al., 1997)., 1997).

Squamous Cell CaSquamous Cell Ca Squamous cell Squamous cell

carcinomacarcinoma. .

A 58-year-old man A 58-year-old man who presented with who presented with increasing cough was increasing cough was found to have a large found to have a large cavitating lesion in the cavitating lesion in the right upper lung (a). right upper lung (a). (b) Chest film obtained (b) Chest film obtained four years earlier four years earlier shows a small nodule shows a small nodule that most likely that most likely represents the primary represents the primary cancer. (cancer. (

Sqamous Cell CaSqamous Cell Ca CT scan CT scan

shows a shows a localized localized cavitating cavitating lesion. lesion. Squamous Squamous cell cell carcinoma carcinoma often often presents presents with with cavitation cavitation due to due to tumor tumor necrosis.necrosis.

Squamous Cell PathologySquamous Cell Pathology Low-power Low-power

photo-photo-micrograph micrograph shows an shows an invasive invasive squamous squamous cell cell carcinoma. carcinoma.

Note the Note the distinction distinction between the between the cells at the cells at the periphery periphery and the and the keratinized keratinized cells in the cells in the centre of the centre of the island of island of tumour. tumour.

AdenocarcinomaAdenocarcinoma On routine medical examination, the chest film of a 64-year-old man shows bilateral primary lung On routine medical examination, the chest film of a 64-year-old man shows bilateral primary lung

tumours in the upper lobes; the lesion on the left side is partly obscured by the clavicle. (b) CT tumours in the upper lobes; the lesion on the left side is partly obscured by the clavicle. (b) CT scan clearly defines the irregularly shaped primary lesions (arrows). Synchronous primary lung scan clearly defines the irregularly shaped primary lesions (arrows). Synchronous primary lung cancers occur in about 3-5% of patients and can be of different histologic subgroups.cancers occur in about 3-5% of patients and can be of different histologic subgroups.

AdenocarcinomaAdenocarcinoma Adenocarcinoma. (a) Microscopic section shows the typical appearance of a gland Adenocarcinoma. (a) Microscopic section shows the typical appearance of a gland

formation. (b) On high-power view, this poorly to moderately differentiated formation. (b) On high-power view, this poorly to moderately differentiated adenocarcinoma exhibits clusters of cells with eccentric nuclei and abundant adenocarcinoma exhibits clusters of cells with eccentric nuclei and abundant cytoplasm. Note a cluster of tumour cells with a central lumen in the lower left of cytoplasm. Note a cluster of tumour cells with a central lumen in the lower left of the field. the field.

Bronchoalveolar carcinoma.Bronchoalveolar carcinoma. A 60-year-old A 60-year-old

female presented female presented with the classic with the classic features of features of advanced disease: advanced disease: increasing increasing dyspnoea on dyspnoea on exertion with a exertion with a frequent cough that frequent cough that produced large produced large amounts of frothy amounts of frothy sputum. Chest sputum. Chest radiograph shows radiograph shows extensive extensive metastases metastases throughout the throughout the lung fields with lung fields with hilar and hilar and mediastinal mediastinal adenopathy.adenopathy.

Bronchoalveolar Ca PathologyBronchoalveolar Ca Pathology Lower-power Lower-power

photomicrogphotomicrograph shows raph shows tall columnar tall columnar peg-shaped peg-shaped cells growing cells growing in a 'picket-in a 'picket-fence' fence' pattern on pattern on the alveolar the alveolar walls. walls.

Large cell carcinomaLarge cell carcinoma A 45-year-old A 45-year-old

man with a man with a history of history of chronic chronic cigarette cigarette smoking smoking developed developed increasing increasing chest pain chest pain and cough. and cough. Radiograph Radiograph shows a shows a huge primary huge primary mass mass

Large cell carcinomaLarge cell carcinoma Microscopic section reveals Microscopic section reveals

mainly undifferentiated mainly undifferentiated large cells with ovoid to large cells with ovoid to spindly shapes. Note the spindly shapes. Note the discrete cell borders and discrete cell borders and prominent nucleoli. In prominent nucleoli. In some patients with the some patients with the giant cell variant of large giant cell variant of large cell undifferentiated cell undifferentiated carcinoma, a diagnosis of carcinoma, a diagnosis of Ki-1 anaplastic large cell Ki-1 anaplastic large cell lymphoma must be lymphoma must be considered. Appropriate considered. Appropriate immunoperoxidase stains immunoperoxidase stains will establish the correct will establish the correct diagnosis diagnosis

Small cell carcinomaSmall cell carcinoma

Chest radiograph Chest radiograph of a 46-year-old of a 46-year-old man who man who presented with a presented with a cough and chest cough and chest pain shows pain shows bilateral bilateral mediastinal mediastinal nodal nodal metastases. metastases. Bronchoscopy Bronchoscopy was positive for was positive for small cell lung small cell lung cancer. cancer. Combination Combination chemotherapy chemotherapy followed by followed by mediastinal mediastinal irradiation irradiation resulted in resulted in complete complete remission. remission.

Small cell carcinomaSmall cell carcinoma Photo-Photo-

micrograph micrograph shows the shows the classic classic appearance of appearance of 'oat-like' cells. 'oat-like' cells.

Each cell is Each cell is approximately approximately twice the size of twice the size of a lymphocyte a lymphocyte and has scant and has scant cytoplasm, cytoplasm, finely dispersed finely dispersed chromatin and chromatin and an an inconspicuous inconspicuous nucleolus. nucleolus.

Carcinoid tumorCarcinoid tumor Routine chest radiograph of an Routine chest radiograph of an

18-year-old woman reveals a 18-year-old woman reveals a prominence in the right hilar prominence in the right hilar region. region.

Four years afterward she Four years afterward she developed increased developed increased breathlessness and backache breathlessness and backache and on examination was found and on examination was found to have abnormal facial hair, to have abnormal facial hair, dyspnoea at rest and signs of dyspnoea at rest and signs of mitral incompetence. mitral incompetence.

Echocardiography showed a Echocardiography showed a thickened interventricular thickened interventricular septum, reduced left septum, reduced left ventricular cavity size and ventricular cavity size and systolic posterior cusp systolic posterior cusp prolapse. prolapse.

Pulmonary function tests Pulmonary function tests indicated a marked restrictive indicated a marked restrictive defect. defect.

Patient CasesPatient Cases T1N0 (stage I) T1N0 (stage I)

adenocarcinoma.adenocarcinoma.

PA chest film in a PA chest film in a 60-year-old man 60-year-old man with hemoptysis with hemoptysis demonstrates a demonstrates a poorly defined, poorly defined, spiculated 2.5 spiculated 2.5 cm mass in the cm mass in the right lower lobe right lower lobe (RLL) (arrows).(RLL) (arrows).

The patient had The patient had

a prior a prior sternotomy and sternotomy and CABGCABG

CTCT

CT confirms CT confirms indeterminate indeterminate RLL massRLL mass

PETPET Axial PET image at the Axial PET image at the

level of the mass level of the mass demonstrates demonstrates significantly increased significantly increased uptake within the uptake within the tumor which was tumor which was proven to be an proven to be an adenocarcinoma by adenocarcinoma by bronchoscopy. bronchoscopy.

Note the normal Note the normal increased activity in increased activity in the left ventricle the left ventricle myocardium. Staging myocardium. Staging studies showed no studies showed no metastases and a metastases and a successful lobectomysuccessful lobectomy was carried out.was carried out.

Pancoast tumorPancoast tumor T3 (stage IIIA) Pancoast T3 (stage IIIA) Pancoast

tumor. This 58-year-old tumor. This 58-year-old man presented with man presented with chronic left arm and chronic left arm and shoulder pain along with shoulder pain along with progressive weakness progressive weakness of his lower arm and of his lower arm and hand.hand.

Physical examination Physical examination

showed clinical findings showed clinical findings of a superior sulcus of a superior sulcus (Pancoast) tumour:(Pancoast) tumour:

Ptosis of the left eyelid, Ptosis of the left eyelid, miosis of the pupil and miosis of the pupil and decreased sweating of decreased sweating of the left face, arm and the left face, arm and upper chest (Horner's upper chest (Horner's syndrome) and a syndrome) and a tumour mass in the lung tumour mass in the lung apex that involved the apex that involved the brachial plexus and brachial plexus and adjacent rib. adjacent rib.

PancoastsPancoasts After After

radiotherapy, radiotherapy, the the manifestations manifestations of Horner's of Horner's syndrome have syndrome have resolved. resolved.

There was also There was also improvement in improvement in his pain and his pain and neurologic neurologic symptoms. symptoms.

Pancoast tumourPancoast tumour T4 Pancoast T4 Pancoast

tumour. A 52-tumour. A 52-year-old woman year-old woman presented with presented with long-standing long-standing right shoulder right shoulder and back pain. and back pain.

Her chest film Her chest film shows a large shows a large tumour of the tumour of the right upper lobe right upper lobe that has that has destroyed the destroyed the adjacent rib. adjacent rib.

CTCT CT scan reveals rib and CT scan reveals rib and

soft tissue involvement soft tissue involvement as well as destruction of as well as destruction of an adjacent vertebral an adjacent vertebral body. body.

Biopsy showed a Biopsy showed a squamous cell squamous cell carcinoma. While in the carcinoma. While in the past Pancoast (superior past Pancoast (superior sulcus) tumours were sulcus) tumours were mostly squamous cell mostly squamous cell carcinomas, many carcinomas, many centres are now centres are now reporting more reporting more adenocarcinomas than adenocarcinomas than squamous cell type. squamous cell type.

Large cell carcinoma is Large cell carcinoma is third in frequency while third in frequency while small cell carcinoma small cell carcinoma rarely presents as a rarely presents as a Pancoast tumor.Pancoast tumor.

MRIMRI T4 (stage IIIB) Pancoast T4 (stage IIIB) Pancoast

tumour. A 60-year-old tumour. A 60-year-old man developed increasing man developed increasing right shoulder, back and right shoulder, back and arm pain. arm pain.

Chest radiograph (not Chest radiograph (not shown) revealed a mass in shown) revealed a mass in the right lung apex. Fine-the right lung apex. Fine-needle aspiration was needle aspiration was positive for poorly positive for poorly differentiated differentiated adenocarcinoma.adenocarcinoma.

T1-weighted MR image in T1-weighted MR image in the coronal plane through the coronal plane through the region of the thoracic the region of the thoracic inlet shows a Pancoast inlet shows a Pancoast tumour on the right (T). tumour on the right (T).

The tumour directly The tumour directly invades one of the upper invades one of the upper thoracic vertebral bodies thoracic vertebral bodies (arrow). (arrow).

Patient casePatient case A 48-year-old A 48-year-old

woman woman presented with presented with severe pain in severe pain in the shoulder the shoulder and arm with and arm with marked arm marked arm weakness. weakness.

T1-weighted MR T1-weighted MR image in the image in the sagittal plane to sagittal plane to the right of the right of midline shows midline shows tumor (T) tumor (T) growing into the growing into the region of region of several adjacent several adjacent neural foramina.neural foramina.

Cutaneous metastasesCutaneous metastases A 48-year-old A 48-year-old

woman with a small woman with a small cell lung cancer cell lung cancer developed developed numerous skin numerous skin lesions. lesions.

Generalized skin or Generalized skin or subcutaneous subcutaneous metastases, which metastases, which may be quite may be quite painful, often occur painful, often occur and they may be and they may be seen in all seen in all histological histological subtypes. subtypes.

In some patients, a In some patients, a solitary early skin solitary early skin metastasis may be metastasis may be the presenting sign the presenting sign of an underlying of an underlying lung tumour.lung tumour.

Liver metastasesLiver metastases CT scan of a 28-year-old CT scan of a 28-year-old

man with metastatic man with metastatic atypical carcinoid tumour atypical carcinoid tumour shows numerous shows numerous metastatic liver deposits metastatic liver deposits which developed after which developed after control of his primary control of his primary pulmonary malignancy pulmonary malignancy by surgery.by surgery.

CT is quite accurate in CT is quite accurate in detecting early detecting early metastases and use of metastases and use of contrast with CT helps contrast with CT helps rule out benign cysts rule out benign cysts which do not enhance which do not enhance with contrast. with contrast.

Ultrasound can also Ultrasound can also differentiate cystic from differentiate cystic from solid lesions.solid lesions.

Liver metastasesLiver metastases Liver Liver

metastases. metastases. Autopsy Autopsy specimen from a specimen from a patient who died patient who died of widespread of widespread small cell lung small cell lung cancer exhibits cancer exhibits numerous numerous lesions ranging lesions ranging in size from a in size from a few millimetres few millimetres to 1-2 cm. to 1-2 cm.

A similar pattern A similar pattern can be seen with can be seen with non-small cell non-small cell carcinomas. carcinomas.

Bone marrow metastasesBone marrow metastases A 62-year-old woman A 62-year-old woman

presented with upper back presented with upper back pain and neurological pain and neurological findings diagnostic of early findings diagnostic of early spinal cord compression. spinal cord compression.

Normal bone marrow Normal bone marrow appears white on this T2-appears white on this T2-weighted MRI scan due to weighted MRI scan due to fat content, except in the fat content, except in the upper spine where upper spine where metastatic lung cancer has metastatic lung cancer has replaced the bone marrow replaced the bone marrow and appears black. and appears black.

The spinal cord appears The spinal cord appears white and shows an area white and shows an area of displacement due to of displacement due to compression by tumour compression by tumour invading through the inter-invading through the inter-vertebral space (arrow).vertebral space (arrow).

Orbital metastasesOrbital metastases This 62-year-This 62-year-

old man had a old man had a lung adeno-lung adeno-carcinoma carcinoma that that metastasized metastasized to the retro-to the retro-orbital space, orbital space, resulting in resulting in proptosis and proptosis and limitation in limitation in eye motion eye motion

Hypertrophic pulmonary Hypertrophic pulmonary osteoarthropathyosteoarthropathy

A characteristic manifestation A characteristic manifestation of HPO, digit clubbing occurs in of HPO, digit clubbing occurs in about 10% of lung cancer about 10% of lung cancer patients of all histological patients of all histological subgroups, but particularly in subgroups, but particularly in adenocarcinoma. adenocarcinoma.

The disease may be early or The disease may be early or advanced. Benign tumours, advanced. Benign tumours, inflammatory disease and liver inflammatory disease and liver disease are also associated with disease are also associated with clubbing. While the clubbing. While the pathophysiology is poorly pathophysiology is poorly understood, digital clubbing, understood, digital clubbing, painful joints and tender painful joints and tender extremities - features extremities - features commonly seen in HPO - often commonly seen in HPO - often reverse dramatically after reverse dramatically after successful thoracotomy, successful thoracotomy, radiotherapy, or chemotherapy.radiotherapy, or chemotherapy.