apichat tantraworasin m.d., ph.d., frcs(t) general thoracic

Apichat Tantraworasin M.D., Ph.D., FRCS(T) General Thoracic Surgery Unit, Department of

Surgery, Faculty of Medicine, Chiang Mai University

วัตถุประสงค์การเรียนรู้

1. ทราบถึงอุบัติการณ์ ปัจจัยเส่ียง พยาธิสภาพ อาการและอาการแสดง การวินิจฉัยและการรักษาผู้ป่วยมะเร็งปอด

2. ทราบถึงอุบัติการณ์ ปัจจัยเส่ียง พยาธิสภาพ อาการและอาการแสดง การวินิจฉัยและการรักษา ผู้ป่วยท่ีมีก้อนใน mediastinum

Lung Cancer Incidence

Risk factors

Pathology and staging

Clinical presentation

Diagnostic procedure

Treatment

Cancer statistics, 2013

CA: A Cancer Journal for Clinicians Volume 63, Issue 1, pages 11-30, 17 JAN 2013 DOI: 10.3322/caac.21166

http://onlinelibrary.wiley.com/doi/10.3322/caac.21166/full#fig1

http://onlinelibrary.wiley.com/doi/10.3322/caac.v63.1/issuetoc

http://onlinelibrary.wiley.com/doi/10.3322/caac.21166/full





Trends in Cancer Incidence and Death Rates by Sex, United States, 1975 to 2009.
















Trends in Death Rates Among Males for Selected Cancers, United States, 1930 to 2009
















Trends in Death Rates Among Females for Selected Cancers, United States, 1930 to 2009




Lung Cancer: Risk factors

Cigarette smoking

• Primary cause of lung cancer

• Approximately 75% of all lung cancers worldwide in 2007

• Risk : Number of cigarettes smoked and the number of years of smoking

Polycyclic aromatic hydrocarbons DNA mutation

Lung Cancer: Risk factors Relative Risk of Lung Cancer in Smokers

Smoking Category Relative Risk

Never smoked 1.0

Currently smoke 15.8–16.3

Formerly smoked

Years of abstinence

1–9 5.9–19.5

10–19 2.0–6.1

>20 1.9–3.7


• Smoking cessation

• The risk never drops to that of people who never smoked

• 53% of cancers in women are not related to smoking

• 62% : adenocarcinomas

• Environmental tobacco smoke

• Residential radon

• Cooking oil vapors

• Indoor coal and wood burning

• Genetic factors: family history, CYP1A1 Ile462Val polymorphism, XRCC1 variants

• Viral factors: HPV 16 and 18


Other risk factors

Exposure to a number of industrial compounds

• Asbestos ( additive effect with cigarette smoking)

• Arsenic, and chromium compounds

COPD

History of tuberculosis with secondary scar formation

Lung Cancer: Pathology and staging

A. Preinvasive Lesions (Precancerous lesions)

1. Squamous Dysplasia and Carcinoma In Situ

2. Atypical Adenomatous Hyperplasia

3. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

B. Invasive or Malignant Lesions

1. Non–Small Cell Lung Carcinoma

2. Small cell lung carcinoma


Non-small cell carcinoma

• Squamous cell carcinoma

• Adenocarcinoma

• Adeno-squamous cell carcinoma

• Large cell carcinoma

• Neuroendocrine neoplasm


Squamous Cell Carcinoma • 30 - 40% of lung cancers

• Male > female

• Highly correlated with cigarette smoking

• Pathology

• Cells develop a pattern of clusters with intracellular bridges and keratin pearls


Squamous cell carcinoma

(A) Keratin pearl is an evidence of squamous cell differentiation. (H&E 200x )

(B) Intercellular bridges are also characteristic manifestation (H&E 400x )


Squamous Cell Carcinoma • Central lesion

• Often causing the typical symptoms of centrally located tumors • Hemoptysis

• Bronchial obstruction with atelectasis

• Dyspnea

• Pneumonia (obstructive pneumonia)

• Peripheral lesion

• Develop in a tuberculosis scar or in the wall of a bronchiectatic cavity


Central necrosis

• Air-fluid level

• Infection >> abscess formation

Mukherjee S et al 2011


Adenocarcinoma • 25 - 40% of all lung cancers

• Female > male

• Most often a peripherally based tumor

• Incidental finding on routine chest radiographs

• Symptoms

• Chest wall invasion or malignant pleural effusions


(A) Acinar adenocarcinoma consists of round to oval shaped malignant glandular structures with stromal infiltration (H&E 100x ) (B) Papillary adenocarcinoma composed of papillary proliferation along fibrovascular cores lined by malignant cuboidal to columnar tumor cells (H&E 100x )

Lung Cancer: Pathology and staging Preinvasive lesions

• Atypical adenomatous hyperplasia

• Adenocarcinoma in situ (≤ 3 cm, pure lepidic growth without invasion, formerly BAC)

• Nonmucinous

• Mucinous

• Mixed mucinous/nonmucinous

Minimally invasive adenocarcinoma

(≤ 3 cm lepidic predominant tumor with ≤ 5mm invasion)

• Nonmucinous

• Mucinous

• Mixed mucinous/nonmucinous

• Note: BAC, bronchioloalveolar carcinoma.

IASLC/ATS/ERS Classification of Lung Adenocarcinoma in Resection Specimens

Modified from Van Schil PE et al.(Van Schil et al. 2013)

Lung Cancer: Pathology and staging Invasive adenocarcinoma

Lepidic predominant (formerly nonmucinous BAC pattern, with >5mm

invasion)

Acinar predominant

Papillary predominant

Micropapillary predominant

Solid predominant with mucin production

Variants of invasive adenocarcinoma

Invasive mucinous adenocarcinoma (formerly mucinous BAC)

Colloid

Fetal (low and high grade)

Enteric Note: BAC, bronchioloalveolar carcinoma.

IASLC/ATS/ERS Classification of Lung Adenocarcinoma in Resection Specimens

Modified from Van Schil PE et al.(Van Schil et al. 2013)


Large Cell Carcinoma

• 10 - 20% of lung cancers

• Located centrally or peripherally

• cells are large, with diameters of 30 - 50 m

• Often admixed with other cell types such as squamous cells or adenocarcinoma


Neuroendocrine carcinoma (NEC)

• IHC : chromogranins, synaptophysin, CD57, and neuron-specific enolase

• 3 grade

Lung Cancer: Pathology and staging Neuroendocrine carcinoma (NEC) • Grade I NEC (classic or typical carcinoid)

• Low-grade NEC • Young patient • Central airways

• Hemoptysis with or without airway obstruction and pneumonia

• 15 % regional LN metastasis, rarely systemic metastasis • Histology

• Cells are arranged in cords and clusters with a rich vascular stroma.

Lung Cancer: Pathology and staging Neuroendocrine carcinoma (NEC) • Grade II NEC (atypical carcinoid)

• Cigarette smoking • Peripheral lesion • Histology

• Areas of necrosis, nuclear pleomorphism, and higher mitotic rates. • Much higher malignant potential

• 30 - 50% LN metastases • 25% metastases at time of diagnosis


Neuroendocrine carcinoma (NEC)

• Grade III NEC large cell–type tumors

• Heavy smokers

• Middle to peripheral lung fields

• Often large with central necrosis and a high mitotic rate

Lung Cancer: Pathology and staging Neuroendocrine carcinoma (NEC) • Grade III NEC small cell type [small cell lung carcinoma

(SCLC)] • Most malignant NEC and accounts for 25% of all lung cancers • Centrally located and consist of smaller cells with a diameter of

10 - 20 mm that have little cytoplasm and very dark nuclei. • High mitotic rate and areas of extensive necrosis • Multiple mitoses • Paraneoplastic syndromes


Salivary Gland–Type Neoplasms • Salivary-type submucosal bronchial glands at tracheobronchial tree

• Central lesion : site of origin

• 2 most common

1. Adenoid cystic carcinoma

• Slow-growing tumor : locally and systematically invasive

• Grow submucosally and infiltrate along perineural sheaths

2. Mucoepidermoid carcinoma

• Squamous and mucous cells : low or high grade, depending on the mitotic rate and degree of necrosis

Staging system : International Association for the Study of Lung Cancer (IASLC) for 2009

Sixth Edition T/M Descriptor Proposed T/M N0 N1 N2 N3

T1 (≤2 cm) T1a IA IIA IIIA IIIB

T1 (>2 to 3 cm) T1b IA IIA IIIA IIIB

T2 (≤5 cm) T2a IB IIA IIIA IIIB

T2 (>5 to 7 cm) T2b IIA IIB IIIA IIIB

T2 (>7 cm) T3 IIB IIIA IIIA IIIB

T3 invasion — IIB IIIA IIIA IIIB

T4 (same-lobe nodules) — IIB IIIA IIIA IIIB

T4 (extension) T4 IIIA IIIA IIIB IIIB

M1 (ipsilateral lung) — IIIA IIIA IIIB IIIB

T4 (pleural effusion) M1a IV IV IV IV

M1 (contralateral lung) — IV IV IV IV

M1 (distant) M1b IV IV IV IV

Lung Cancer: Pathology and staging N1 = intrapulmonary node N2 = mediastinal LN N3 = cervical LN and supraclavicular LN

Lung Cancer: Clinical Presentation

Asymptomatic >>>> life threatening conditions related to ..

1) Histologic features

2) Specific tumor location

3) Biologic features, and the production of a variety of paraneoplastic syndromes

4) Presence or absence of metastatic disease

Lung Cancer: Clinical Presentation Category Symptom Cause

Pulmonary symptoms Cough Bronchus irritation or compression

Dyspnea Airway obstruction or compression

Wheezing >50% airway obstruction

Hemoptysis Tumor erosion or irritation

Pneumonia Airway obstruction

• Central airway symptoms : squamous cell and small CA • Incidental findings or asymptomatic peripheral lesion : adenocarcinoma

Lung Cancer: Clinical Presentation Category Symptom Cause

Nonpulmonary thoracic symptoms

Pleuritic pain Parietal pleural irritation or invasion

Local chest wall pain Rib and/or muscle involvement

Radicular chest pain Intercostal nerve involvement

Pancoast's syndrome Stellate ganglion, chest wall, brachial plexus involvement

Hoarseness Recurrent laryngeal nerve involvement

Swelling of head and arms Bulky involved mediastinal lymph nodes

Medially based right upper lobe tumor

Lung Cancer: Clinical Presentation BAC (a variant of adenocarcinoma)

a) Solitary nodule b) Multifocal nodules

c) Diffuse infiltrate mimicking an infectious pneumonia (pneumonic form)

• Severe dyspnea and hypoxia • Expectoration of large volumes (over 1 L/d) of light tan fluid

–Dehydration and electrolyte imbalance. – Typical invasion, destruction, and compression of lung

architecture

–Air bronchograms.

Lung Cancer: Clinical Presentation Paraneoplastic syndrome

Endocrine

Hypercalcemia (ectopic parathyroid hormone)

Cushing's syndrome

Syndrome of inappropriate secretion of antidiuretic hormone

Carcinoid syndrome

Gynecomastia

Hypercalcitoninemia

Elevated growth hormone level

Elevated levels of prolactin, follicle-stimulating hormone, luteinizing hormone

Hypoglycemia

Hyperthyroidism

Lung Cancer: Clinical Presentation Paraneoplastic syndrome Neurologic

Encephalopathy

Subacute cerebellar degeneration

Progressive multifocal leukoencephalopathy

Peripheral neuropathy

Polymyositis

Eaton-Lambert syndrome

Optic neuritis

Lung Cancer: Clinical Presentation Paraneoplastic syndrome Skeletal

Clubbing

Pulmonary hypertrophic osteoarthropathy

Hematologic

Anemia Leukemoid reactions

Thrombocytosis Thrombocytopenia

Eosinophilia Pure red cell aplasia

Leukoerythroblastosis Disseminated intravascular coagulation

Lung Cancer: Clinical Presentation Paraneoplastic syndrome Cutaneous

Hyperkeratosis Hypertrichosis lanuginosa acquista

Dermatomyositis Hyperpigmentation

Acanthosis nigricans Erythema gyratum repens

Other

Nephrotic syndrome Hyperamylasemia

Hypouricemia Anorexia or cachexia

Secretion of vasoactive intestinal peptide with diarrhea

Lung Cancer: Diagnostic procedure Evaluation of Patients with Lung Cancer

Primary Tumor Metastatic Disease Functional Assessment

History Pulmonary Weight loss Ability to walk up two flights of stairs

Nonpulmonary thoracic

Malaise Ability to walk on a flat surface indefinitely

Paraneoplastic New bone pain Neurologic signs or

symptoms

Skin lesions


Primary Tumor

Metastatic Disease

Functional Assessment

Physical examination

Voice Supraclavicular node palpation

Accessory muscle usage

Skin examination Air flow by auscultation

Neurologic examination

Force of cough


Primary Tumor Metastatic Disease


Radiographic examination

CXR, Chest CT CXR, Chest CT, PET Chest CT: tumor anatomy, atelectasis




Tissue analysis

Bronchoscopy with biopsy, BAL, Brushing, wang procedure, EBUS, TBNA

Bone scan, head MRI, abdominal CT

Quantitative perfusion scan

Transthoracic needle aspiration and biopsy

Bronchoscopic LN FNA

Endoscopic ultrasound

Mediastinoscopy

Biopsy of suspected metastasis




Other Thoracoscopy Thoracoscopy Pulmonary function tests (FEV1, DLCO, O2 consumption)

Lung Cancer: Diagnostic procedure


CT scan with contrast

(Chest and upper abdomen)


Positron Emission Tomography • Measure metabolic activity of cell ( glucose metabolism -

uptake of 18 –flurodeoxyglucose )

• Taken up by cells in glycolysis but is bound cells (cannot enter normal glycolytic pathway )

• Most tumors have greater uptake of FDG than normal tissue

Lung Cancer: Diagnostic procedure Positron Emission Tomography • For identifying a malignancy

• Sensitivity is 96.8 % • Specificity 77.8 %

• Fasle negative: Slow growing tumor • BAC • Carcinoids • Tumor < 1 cm

Lung Cancer: Diagnostic procedure PET & CT scan


Fiberoptic bronchoscopy


Rigid bronchoscope

Transbronchial needle aspiration (TBNA)


Endobronchial ultrasound-guided fine needle aspiration (EBUS)


Mediastinoscopy



VATS (video-assisted thoracoscopic surgery)


Assessment of Functional status

• Clinician’s assessment

• Daily activity

• Smoking status

• Pulmonary function test (PFT)


Assessment of Functional status Clinician’s assessment

• Walk on a flat surface indefinitely • Likely to tolerate thoracotomy and lobectomy

• Walk up two flights of stairs (up two standard levels) • Likely tolerate pneumonectomy

• ABG : no CO2 retention : tolerate periods of single-lung ventilation and wedge resection

Lung Cancer: Diagnostic procedure Assessment of Functional status Clinician’s assessment • Smoking status and sputum production

• Current smokers : increase risk of postoperative pulmonary complications • Respiratory failure requiring ICU or reintubation • Pneumonia • Atelectasis requiring bronchoscopy • Pulmonary embolism • Discharge with oxygen supplementation



Clinician’s assessment

• Recommendation for cessation of smoking

• Ideally, at least 8 weeks preoperatively in benign cases

• 2 weeks before surgery in cancer cases



Pulmonary function test (PFT)

• FEV1 (forced expiratory volume in 1 second)

• DLCO (carbon monoxide diffusion capacity)

• VO2max (maximum oxygen consumption)

Lung Cancer: Treatment

Depend on T N M stage of disease

Surgery

Radiotherapy Chemothorapy

Target therapy


Surgery

• Lobectomy

• Combined wedge and lobectomy

• Pneumonectomy


Surgery

• Lobectomy


• Pneumonectomy

• Sleeve lobectomy


Surgery

• Lobectomy


• Pneumonectomy

• Sleeve lobectomy

• Sublobar resection

• Clinical stage I and II NSCLC with

decreased pulmonary function or comorbid

disease • Margin :

• Tumor < 2 cm • Margin > maximal tumor

diameter • Tumors > 2 cm

• At least 2 cm gross margins

3rd Edition of ACCP guideline (2013)

Lung Cancer: Treatment Systematic mediastinal LN dissection or sampling


Surgery

Approach : Open thoracotomy or VATS

Position: lateral decubitus position

Lung Cancer: Treatment Chemotherapy

• Platinum-based regimen : Cisplatin or Carboplatin

• Adjuvant

• Neoadjuvant chemotherapy

• Adjuvant chemotherapy

• Treatment

• 1st, 2nd, 3rd, 4th …. Line


Chemotherapy : Neoadjuvant and adjuvant therapy


Chemotherapy with Radiathorapy


Chemotherapy : Advanced disease


Radiotherapy Early stage(stage I)

• SABR (stereotactic ablative radiotherapy) • Medically inoperable or refuse to have surgery

Locally advanced (stage II, III)

• Resectable cases: preoperative concurrent chemoRT

• Unresectable cases : Concurrent chemoRT

Advanced or metastasis (stage IV)

• Local palliation or prevention of symptoms

http://cancer.stanford.edu/radiationoncology/treatment/stereotactic_radiotherapy.html


• Poorly differentiated

neuroendocrine tumor • Vascular invasion • Size > 4cm • Visceral pleural

invasion • Wedge resection • Incomplete LN

sampling

Long-term follow-up care

Cancer Surveillance

• H&P and chest CT ± contrast every 6-12 mo for 2 yr, then H&P and a non-contrast-enhanced chest CT annually

• Smoking cessation advice, counseling, and pharmacotherapy

Immunizations

• Annual influenza vaccine, herpes zoster vaccine

• Pneumococcal vaccination with revaccination as appropriate



Health promotion and wellness

• Maintain a healthy weight

• Regular physical activity: 30 minutes of moderate-intensity physical activity on most days of the week)

• Consume a healthy diet with emphasis on plant sources

• Limit consumption of alcohol if one consumes alcoholic beverages



Additional health monitoring

• Routine BP, cholesterol, and glucose monitoring

• Bone health: bone density testing as appropriate

• Dental health : routine dental examination

• Routine sun protection


Mediastinal mass

Mediastinal mass Usual Location of the Common Primary Tumors and Cysts of the Mediastinum

Anterior Compartment Visceral Compartment Paravertebral Sulci

Thymoma Enterogenous cyst Neurilemoma-schwannoma

Germ cell tumor Lymphoma Neurofibroma

Lymphoma Pleuropericardial cyst Malignant schwannoma

Lymphangioma Mediastinal granuloma Ganglioneuroma

Hemangioma Lymphoid hamartoma Ganglioneuroblastoma

Lipoma Mesothelial cyst Neuroblastoma

Fibroma Neuroenteric cyst Paraganglioma

Fibrosarcoma Paraganglioma Pheochromocytoma

Thymic cyst Pheochromocytoma Fibrosarcoma

Parathyroid adenoma Thoracic duct cyst Lymphoma

Mediastinal mass Mediastinal Tumors in Adults

Tumor Type Percentage of Total Location

Neurogenic tumors 21 Posterior

Cysts 20 All

Thymomas 19 Anterior

Lymphomas 13 Anterior/middle

Germ cell tumors 11 Anterior

Mesenchymal tumors 7 All

Endocrine tumors 6 Anterior/middle

Mediastinal mass Mediastinal Tumors in Children

Tumor Type Percentage of Total Location Neurogenic tumors 40 Posterior

Lymphomas 18 Anterior/middle

Cysts 18 All

Germ cell tumors 11 Anterior

Mesenchymal tumors 9 All

Thymomas Rare Anterior

Mediastinal mass Symptoms and signs

• 2/3 of mediastinal tumors in adults

• Asymptomatic abnormalities

• Incidental finding from radiologic studies

• Symptomatic : malignant

• Size, location, rate of growth, and associated inflammation

Mediastinal mass Symptoms and signs • Cough, dyspnea on exertion, or stridor

• Large, bulky tumors, expanding cysts, and teratomas • Compression of mediastinal structures : trachea

• Chest pain or dyspnea • Pleural effusion, cardiac tamponade, or phrenic nerve

involvement

• Hoarseness • Mass or LN at AP window compress LRLN

Mediastinal mass Signs and Symptoms Suggestive of Various Diagnoses in the Setting of a Mediastinal Mass

Diagnosis History and Physical Findings Compartment Location of Mass

Lymphoma Night sweats, weight loss, fatigue, extrathoracic adenopathy, elevated erythrocyte sedimentation rate or C-reactive protein level, leukocytosis

Any compartment

Mediastinal mass Signs and Symptoms Suggestive of Various Diagnoses in the Setting of a Mediastinal Mass

Diagnosis History and Physical Findings Compartment Location of Mass

Thymoma with myasthenia gravis

Fluctuating weakness, early fatigue, ptosis, diplopia

Anterior

Mediastinal granuloma

Dyspnea, wheezing, hemoptysis Visceral (middle)

Germ cell tumor Male gender, young age, testicular mass, elevated levels of human chorionic gonadotropin (B-hCG) and/or alpha-fetoprotein (AFP)

Anterior

Mediastinal mass Diagnostic Evaluation

Imaging • Contrast-enhanced CT scans

• MRI : invasion of vascular structures or spinal involvement

• PET scan : unclear, benign vs malignancy

• Single-photon emission computed tomography (SPECT) • 3D localization of some tumors of endocrine origin

Mediastinal mass Nuclear Imaging Relevant to the Mediastinum

Radiopharmaceutical, Radionuclide, or Radiochemical

Label Disease of Interest

Iodine 131I, 123I

Retrosternal goiter, thyroid cancer

Monoclonal antibodies 111In, 99mTc

NSCLC, colon and breast cancer, prostate cancer metastases

Octreotide 111In

Amine precursor uptake decarboxylation tumors: carcinoid, gastrinoma, insulinoma, small cell lung cancer, pheochromocytoma, glucagonoma, medullary thyroid carcinoma, paraganglioma

Mediastinal mass Nuclear Imaging Relevant to the Mediastinum

Radiopharmaceutical, Radionuclide, or Radiochemical

Label Disease of Interest

Sestamibi 99mTc

Medullary thyroid carcinoma, nonfunctional papillary or follicular thyroid carcinoma, Hürthle cell thyroid carcinoma, parathyroid adenoma or carcinoma

Thallium 201Tl

See sestamibi

MIBG 131I, 123I

Pheochromocytoma, neuroblastoma; see also octreotide

Fluorodeoxyglucose 18F

General oncologic imaging, breast and colon cancer, melanoma

Mediastinal mass Diagnostic Evaluation Serum markers • Alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG)

• Nonseminomatous germ cell tumors • > 90 % • > 500 ng/mL specificity close to 100% • Definite diagnosis without tissue biopsy (some center)

• Seminoma • Normal AFP • 10 % : hCH < 100 ng/mL

Mediastinal mass Diagnostic Evaluation

Serum markers

• Parathyroid hormone

• Ectopic parathyroid adenoma

Mediastinal mass Diagnostic Nonsurgical Biopsy of the Mediastinum Noninvasive imaging and history • Surgical removal in resectable disease : thymoma, substernal

goiter etc. Biopsy • Nonsurgical disease : lymphoma, germ cell tumor etc. • Limited by overlying bony thoracic cavity and the proximity to

lung tissue, the heart, and great vessels • Core-needle technique or surgery > FNA

Mediastinal mass Diagnostic Nonsurgical Biopsy of the Mediastinum

FNA (fine-needle aspiration)

• Mediastinal thyroid tissue, cancers, carcinomas, seminomas, inflammatory processes, and cysts

Virginia et al 2010

Mediastinal mass Diagnostic Nonsurgical Biopsy of the Mediastinum

Core-needle biopsy

• Nonsurgical disease : lymphoma, germ cell tumor etc.

Li Li et al 2005

Mediastinal mass Surgical Biopsy and Resection of Mediastinal Masses

• Failed to FNA or CNB

• Completely removed evaluated by CT scan

• Median sternotomy or lateral thoracotomy (gold standard)

• VATS : romoval of the thymus gland in MG cases or small encapsulated thymomas ( < 2 cm)

Mediastinal mass Surgical Biopsy and Resection of Mediastinal Masses

• Large or incompletely removed due to invade vital structure such as heart, SVC or great vessels

• Parasternal biopsy

• Mediastinoscopy

• VATS to biopsy

Mediastinal mass Neoplasms :Thymus

Thymic Hyperplasia

• Children after treating lymphoma : Diffuse thymic hyperplasia

• Adult : Rebound thymic hyperplasia

• 2-12 months (mean 9 months) after chemotherapy for lymphoma or germ cell tumors

• Requiring careful follow-up with serial CT scans

• PET scan

Mediastinal mass Neoplasms :Thymic Tumors

Thymoma

• Most common of anterior mediastinal mass

• 40-60 years of age, rare in children

• Asympthomatic

• Symptomatic : mass effect • Cough, chest pain, dyspnea, or superior vena caval syndrome


Thymoma • 10-50% of thymoma have MG or circulating antibodies to

acetylcholine receptor • < 10 % of MG are found to have a thymoma on CT • MG with thymoma

• Improvement or resolution of symptoms of MG in only approximately 25% after treated with thymectomy

• Mg without thymoma • 90 % improve and up to 50% complete remission treated with

thymectomy


Thymoma

• 5% of patients with thymomas

• Red cell aplasia, hypogammaglobulinemia, SLE, Cushing's syndrome, or syndrome of inappropriate secretion of antidiuretic hormone


Thymoma Diagnosis • CT scan and history

• CT : solitary encapsulated mass

• PET (thymic cancer vs thymoma)

• Tissue diagnosis • Surgical resection • FNA sen 87% spec 95% • Cytokeratin (thymoma vs lymphoma)


Thymoma

Mediastinal mass Staging system : Masaoka • Presence or absence of gross or microscopic invasion of the capsule and

surrounding structures, as well as on the presence or absence of metastases

Masaoka Staging System for Thymoma Stage I Encapsulated tumor with no gross or microscopic evidence of capsular

invasion

Stage II Gross capsular invasion or invasion into the mediastinal fat or pleura or microscopic capsular invasion

Stage III Gross invasion into the pericardium, great vessels, or lung

Stage IVA Pleural or pericardial dissemination

Stage IVB Lymphogenous or hematogenous metastasis

Mediastinal mass

Mediastinal mass Treatment • Definitive treatment : complete surgical removal of all resectable

tumors include all of thymus tissue and surrounding fat

• Approach • Median sternotomy with extension to hemiclamshell in more advanced cases

• VATS

• Adjuvant or neoadjuvant therapies : unclear

• Advanced cases : platinum-based chemotherapy and corticosteroids combination with radiotherapy

VATS thymectomy in MG

Mediastinal mass

Mediastinal mass Thymic carcinoma

• Low-grade tumors

• Well differentiated with squamous cell, mucoepidermoid, or basaloid features.

• High-grade thymic carcinomas

• Lymphoepithelial, small cell neuroendocrine, sarcomatoid, clear cell, and undifferentiated or anaplastic features

Mediastinal mass Thymic carcinoma

• Compared with thymomas

• More heterogeneous group of malignancies

• Early local invasion and widespread metastases

• Drop metastasis or pleural metastasis in malignant thymoma

• Complete resection is occasionally curative, but most thymic carcinomas will recur and are refractory to chemotherapy

• Poor prognosis

Mediastinal mass Thymolipoma

• Rare benign tumors that may grow to a very large size before being diagnosed

• Generally well-encapsulated, soft, and pliable masses that do not invade surrounding structures

Mediastinal mass Thymolipoma • Resection is recommended for large masses

Fat density dotted by isolated areas of soft tissue density representing islands of thymic tissue

Mediastinal mass Nerve Sheath Tumors

• 20% of all mediastinal tumors

• More than 95% of nerve sheath tumors

• Benign neurilemomas or neurofibromas

• Malignant neurosarcomas : less common

Mediastinal mass Neurilemoma or schwannoma

• Schwann cells in intercostal nerves

• Firm, well encapsulated, and generally benign

• Histologic component

• Antoni type A : compact spindle cells with twisted nuclei and nuclear palisanding

• and Antoni type B : loose and myxoid connective tissue with a haphazard cellular arrangement


Dumbbell configuration (MRI) • Cord compression and paralysis

Mediastinal mass Neurofibroma

• Up to 25 % of nerve sheath tumors

• Component : nerve sheaths and nerve cells

• Up to 40 % of patients with mediastinal fibromas have generalized neurofibromatosis (von Recklinghausen's disease)

• 70 % : benign, 25-30 % : malignancy

• Treatment : complete resection

Mediastinal mass Neurofibroma

Cervicothoracic sign

Mediastinal mass Neurofibrosarcoma

• Risk of malignancy • Advanced age

• Von Recklinghausen’s disease

• Previous exposure to radiation

• Poor prognosis : rapid growth and aggressive local invasion along nerve bundles

• Treatment : complete resection

Mediastinal mass Ganglion Cell Tumors

• Ganglioneuroma

• Ganglioneuroblastoma

• Neuroblastoma

Paraganglionic Tumors

• Chemodectomas

• Pheochromocytomas

Mediastinal mass Lymphomas

• Most common malignancy of the mediastinum

• ~ 50 % of both Hodgkin's and non-Hodgkin's lymphoma, mediastinum is primary site

• Location • Anterior compartment (most commonly involve)

• Middle compartment ( extension to hilar nodes)

• Posterior compartment :rare

Mediastinal mass Lymphomas

• Treatment : Chemotherapy and/or radiotherapy

• Cure rate of up to 90% for early-stage Hodgkin's disease and up to 60% for more advanced stages

Mediastinal mass Mediastinal Germ Cell Tumors

• Most common malignancy in young men (15-35 yrs)

• Most germ cell tumors are gonadal in origin

• Primary site are rare

• Less than 5 % of all germ cell tumors

• Less than 1 % of all mediastinal tumors


Seminomas (1/3)

• Advanced disease at time of diagnosis

• Local compressive symptoms • SVC syndrome, dyspnea, or chest discomfort

• Diagnosis • FNA or core-needle biopsy or surgical biopsy (anterior mediastinotomy

(chamerlain procedure) or thoracoscopy)

• Normal level of hCG and AFP


Seminomas (1/3)

• Treatment • Cisplatin-based chemotherapy regimens with bleomycin and either

etoposide or vinblastine

• More than 75 % : complete response

• Surgery

• Curative for small asymptomatic seminomas

• Resection of residual masses after chemotherapy


Nonseminomas

• Endodermal sinus tumors

• Embryonal cell carcinomas

• Choriocarcinoma

• Mixed types

Bulky, irregular tumors of the anterior mediastinum with areas of low attenuation on CT scan (necrosis, hemorrhage, or cyst formation)


Nonseminomas Treatment • Chemotherapy : combination therapy with cisplatin, bleomycin, and

etoposide : Survival is 67% at 2 years and 60% at 5 years • Surgical resection

• Residual masses • up to 20% of residual masses contain additional tumors; in another

40%, mature teratomas; and the remaining 40%, fibrotic tissue


Teratomas

• Most common type of mediastinal germ cell tumors (60-70%)

• Mature (benign) and immature teratomas (malignant teratomas)

• Containing two or three embryonic layers

• Ectodermal : teeth, skin, hair

• Mesodermal : cartilage and bone

• Endodermal : bronchial, intestinal, or pancreatic tissue

Mediastinal mass Mediastinal Germ Cell Tumors Teratomas • Treatment

• Mature teratoma (benign) : surgical resection , excellent prognosis • Malignant teratomas

• Locally aggression (unresectable) • Poor response to chemotherapy • Limited manner to radiotherapy • Poor prognosis Mature teratomas : benign • CT scan : multilocular cystic tumor, encapsulated with combinations of

fluid, soft tissue, calcium, and/or fat attenuation in the anterior compartment

Mediastinal mass Mediastinal Cysts

Primary Mediastinal Cyst

• Benign cysts account for up to 25% of mediastinal masses

• Most are located in the middle compartment

• CT scan showing characteristic features of near-water density in a typical location is virtually 100% diagnostic

Mediastinal mass Pericardial Cyst • Most common type of mediastinal cysts

• Asymptomatic and detected incidentally

• Contain a clear fluid

• Location : right cardiophrenic angle

• Cyst wall lining is a single layer of mesothelial cells

Mediastinal mass Pericardial Cyst • Treatment

• Observation alone for most simple, asymptomatic pericardial cysts

• Surgical resection or aspiration for complex cysts or large symptomatic cysts

• ภาพ pericardial cyst

Mediastinal mass Bronchogenic cyst

• Abnormality during embryogenesis

• Abnormal budding of the foregut of tracheobronchial tree

• Most occur in mediastinum, 15 % in lung parenchyma

• Location : just posterior to the carina or main stem bronchus

Figure 1. A, Contrast enhanced computed tomographic (CT) scan of the thorax showing a well-defined 7-cm subcarinal mass (curved arrow) of

predominantly fluid attenuation with wall enhancement.

Browne R et al. Circulation. 2002;106:e209-e210

Copyright © American Heart Association, Inc. All rights reserved.


Pathology

• Thin walled and lined with respiratory epithelium containing with a protein-rich mucoid material and varying amounts of seromucous glands, smooth muscle, and cartilage

• They may communicate with the tracheobronchial tree

Mediastinal mass Bronchogenic cyst Treatment In children : most of these are symptomatic • Large cyst may cause complications

• Airway obstruction • Infection • Rupture • Malignant transformation (rare)

In adults : incidentally asymptomatic found during work-up for an unrelated problem or during screening


Treatment

In adults : some of these (up to 67%) develop symptoms later

• Chest pain, cough, dyspnea, and fever

• Serious complications : less common

• Hemodynamic compromise, airway obstruction, pulmonary artery obstruction, hemoptysis, and malignant degeneration


Treatment

• Symptomatic bronchogenic cysts should be removed

• Complete removal of the cyst wall

• Approach

• Posterolateral thoracotomy

• VATS

• Small cysts with minimal adhesions

Enteric Cyst

• Esophageal cysts

• Prone to enlargement >> propensity for serious complications

– Hemorrhage, infection, or perforation

• Resection for both adults and children : regardless of the presence or absence of symptoms

Mediastinal mass

Mediastinal mass Enteric cyst

Thymic Cyst

• Asymptomatic , incidental finding during radiographic work-up for an unrelated problem

• Simple cysts without any consequence

• However, the occasional cystic neoplasm must be ruled out

• Cystic components occasionally are seen in patients with thymoma and Hodgkin's disease

Mediastinal mass

Ectopic Endocrine Glands : Substernal thyroid or intrathoracic goiter

• Thyroid : up to 5% of all mediastinal masses

• 3 types by location of major part of goiter

a) Small substernal extension (> 80%)

b) Partial intrathoracic goiter

c) Complete intrathoracic goiter (rare)

• Non toxic goiter, less than 2 % thyrotoxicosis

Mediastinal mass


• Age > 50 yrs (many in 70-80 yrs)

• Female > male (3-4 times)

• History of previous thyroid operation

Mediastinal mass


S&S

• Asymptomatic , incidental finding

• Cervical mass, dysphagia, dyspnea, stridor, cough or wheezing, and facial flushing

• Serious symptoms : acute tracheal obstruction with severe respiratory compromise after respiratory tract infection

Mediastinal mass


Diagnostic procedure

• CT scan neck and chest

• Radionuclide scintigraphy

Mediastinal mass

Lung cancer Signs and Symptoms

• Asymptomatic • Central lesion symptoms • Peripheral lesion symptoms

Diagnostic procedure • Non-invasive : CT, PET-CT, MRI • Invasive : bronchoscopy biopsy, EBUS, TBNA, Direct lung

tapping, mediastinoscopy, mediastinotomy, VATS

Staging : TNM system Treatment : Surgery, chemotherapy, and radiotherapy

Summary

Mediastinal mass Anatomy of mediastinum

• 3 compartment

• Disease : organ in each compartment • Anterior : thymoma, intrathoracic thyroid, teratory, lymphoma

• Middle : pericardial cyst, bronchogenic cyst

• Posterior : neurogenic tumors

Summary

Mediastinal mass • Diagnostic procedure : CT scan, FNA, CNB, serum marker,

nuclear imaging

• Treatment

• Surgery : thymoma, intrathoracic thyroid, mature teratomy

• Chemotherapy and radiotheorapy : lymphoma , malignant teratoma, seminoma, non-seminoma

Summary

Reference • Schwartz’s Principles of

Surgery, 9th Edition

• General thoracic surgery, Tomas W. Shields, 7thedition

• Staging Manual in Thoracic Oncology

• NCCN guideline 2014

apichat tantraworasin m.d., ph.d., frcs(t) general thoracic

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