Presentation and management of Lung lesion Supervised by

Presentation and management of Lung lesion Supervised by: Dr. Wassim Hajjar Presented By: Yaser Alshhab Mohammed Alkarzae Sultan Aldrees

Objectives: n n n n To identify lung lesion and how to manage. To differentiate between Benign lung lesions. Understand Solitary lung lesion and how to approach. Identify and treat Pulmonary carcinoid tumor. To have a clear picture about lung cancer. SCLC vs NSCLC. The surgical role in treating lung lesion.

Lung Lesion n A lung lesion is abnormal tissue found on or in a person’s lung. It appear as lump of mass of tissues and other matter such as hardened blood, or pus in the lungs. They may appear in the bronchi or in the air sacs. n Wherever they are found, they can cause pronounced difficulty in the respiratory system especially if they are malignant.

In some cases, lung lesions may be numerous and may form on a specific area which is known as solitary lung lesion. n In general, lung lesions may be classified as benign or malignant. Benign as : Malignant lung lesions: granulomateous lesion (TB), cyst carciniod lung tumor, n n benign tumors (hamartoma, bronchial adenoma, mucous gland adenoma) Tuberculosis creates cavities visible in x-rays like this one in the patient's right upper lobe. Lung cancer(SCLC, NSCLC) A CXR in a patient with central cancer of the right lung. Notice the white mass in the middle portion of the right lung

Benign Lung Lesion n Benign lung tumors are a heterogenous group of neoplastic lesions originating from pulmonary structures. These tumors include bronchial adenomas, hamartomas, and a group of uncommon neoplasms (eg, chondromas, fibromas, lipomas, leiomyomas, hemangiomas, teratomas) n Although benign lung tumors do not pose a significant health problem, complications can result from an obstructive lesion that could predispose the patient to pneumonia, atelectasis, and hemoptysis. n Age range is 17 -77 years. n The exact cause is unknown, because it is usually asymptomatic and discovered incidentally.

Benign lung tumors can be classified by their origin into: Mesodermal (fibroma, lipoma, leiomyoma, chondroma, granular cell tumor, sclerosing hemangioma) Other (myofibroblastic tumor, xanthoma, amyloid, mucosaassociated lymphoid tumor). Benign Lung Lesion NOTE: Adenoma and hamartomas constitute the largest group of benign lung lesion Unknown (hamartoma, clear cell, teratoma), epithelial (papilloma, polyps),

n It is clinically asymptomatic. n It may present with atelectesis , airway obstruction <<suggesting an endobronchial origin. n Majority identified incidentally finding on CXR. n CT scanning and FNA occasionally suggest a benign diagnosis n Definitive diagnosis is made by excisonal biopsy n Rigid bronchoscopy diagnostic and therapeutic in case of symptomatic lesions

Hamartomas (chondroadenomas) n n n n Most common type of benign lung tumor, slow growing lesion Mainly occur in adults. Hamartomas are peripherally located. Grossly, they have a firm marblelike consistency. Histologically, hamartomas generally consist of epithelial tissue and other tissues such as fat and cartilage. Radiologically appears as well-circumscribed single nodules, up to 2 cm , it can be localized in the lung CT scanning shows calcification and fat in up to half of the lesions. Parenchymal hamartoma of the lung. The surrounding lung falls away from the well-circumscribed mass, a typical feature of these lesions. The hamartoma shows a variegated yellow and white appearance, which corresponds respectively to fat and cartilage

Bronchial Adenomas Make up 50% of all benign pulmonary tumors. The use of the term bronchial adenoma should be discouraged because it encompasses several benign and malignant tumors. n n Mucous Gland Adenomas

Solitary lung lesion (Coin lesion) Definition: n Is a peripheral circumscribed mass in the lung less than 3 centimeters in diameter. It can be an incidental finding found in up to 0. 2% of chest Xrays and around 1% of CT scans n The nodule most commonly represents a benign tumor such as a granuloma or hamartoma, but in around 10 -20% of cases it represents a malignant cancer, (But smoker patients older than 50 years have >50% risk for lung cancer). n Usually asymptomatic but it may include {coughing, hemoptysis, chest pain, and weight loss}

Chest X-ray showing a solitary pulmonary nodule (indicated by a black box) in the left upper lobe.

Etiology

Pathophysiology n A solitary pulmonary nodule is defined as a single, discrete pulmonary opacity that is less than 3 cm in diameter, surrounded by normal lung tissue, and not associated with adenopathy or atelectasis. Lesions larger than 3 cm are considered masses and are treated as malignancies until proven otherwise. Generally, a pulmonary nodule must reach 1 cm in diameter before it can be identified on a chest radiograph.

So how to approve that it is a benign lesion: Persons younger than 35 years without other risk factors. Benign appearance on chest x-ray film. Stability of the SPN over a period of 2 years on chest x-ray film.

When it is significant: In the presence of risk factors for malignancy: Size: lesions>1 cm(have a chance for malignancy), >4 cm(very likely to be malignant) Increase age Indistinct margin(Corona radiata sign) Documented growth on follow up x ray(If no change in two years, most likely benign)

Approach We start by order the following investigation: 1 - chest x ray 2 -TB skin test 3 -sputum cultures 4 -sputum cytology(diagnostic in 5%-20%) 5 -chest CT 6 -biopsy In case of early bleeding we do bronchoscopy.

A CXR or chest CT scan differentiate between malignant and benign lesion: 1) popcorn calcification Hamartoma 2) Concentric calcification calcified granuloma. 3)Spiculated lesions, with scattered calcification Are highly suspicious of malignancy.

Management: n . Based on the results of exams and tests, persons with SPN can be divided into the following 3 groups: 1 -Persons with benign SPN: undergo chest x-ray films or CT scans every 3 -4 months in the first year, every 6 months in the second year, and once every year for up to 5 years. 2 -Persons who have been diagnosed with a malignant SPN should have the nodule surgically removed. 3 -Persons with SPN that cannot be classified as either benign or malignant{Most persons fall into this category}. However, as many as 75% of these patients have malignant nodules on further evaluation. Therefore, such persons are also advised surgical removal.

Surgical excision is the mainstay of management. Types of surgery : Lobectomy for central placed lesions Lobectomy with nodes dissection for primary cancer(if resectable by preop evaluation)

Carciniod Tumor n Carcinoid tumors are a slow-growing cancer that can arise in several places throughout your body. n Carcinoid tumors, which are one subset of tumors called neuroendocrine tumors APUD{amine-precursor uptake and decarboxylation}, known as the usually appear in the gastrointestinal tract (appendix, stomach, small intestine, colon, rectum) and in the lungs. n Metastasis to the Liver with GI symptoms.

Types of Carcinoid tumor Typical lung carcinoid Atypical lung carcinoid

Typical Carcionoid Tumor n Typical carcinoid tumors of the lung represent: n Most well differentiated and least biologically aggressive type of cardconoid tumor. n n Grow slowly and tend to metastasize infrequently (5%-15%) n Consist of polygonal cells arranged in clusters.

Atypical Carcinoid Tumor n Atypical carcinoid tumors of the lung represent: n More aggressive histologic and clinical picture. n Metastasize at a considerably higher rate than do typical carcinoid tumors(predominantly lymph node) reported in 50 -70% and, therefore, carry a worse prognosis. n Variable nuclear configuration and moderate mitotic activity.

Carcinoid Syndrome Carcinoid syndrome has been reported in association with very large bronchopulmonary carcinoid tumors or in the presence of metastatic disease. It is noted much less frequently in association with carcinoids of pulmonary origin than those originating within the gastrointestinal tract.

Frequency n The gastrointestinal tract is the most common area in which carcinoid tumors arise. n Bronchopulmonary carcinoid tumors are reported to represent about 10% of all carcinoid tumors. n One to 6% of all lung tumors are carcinoid tumors. (10% are atypical) n Carcinoid tumors occur in equal numbers of males and females. n The average is 40 -50 years, . n Atypical carcinoid tumors appear in older people than typical carcinoids do. n 90% of tumors develop within a bronchus. (10% of tumors arise in a mainstem bronchus; rarely appear in the trachea. ) n 10% of tumors are located in the pulmonary periphery. .

Clinical presenatation About 25% are asymptomatic. n In symptomatic patients, n Symptoms of bronchial obstruction: persistent cough, hemoptysis, recurrent or obstructive pneumonitis, Wheezing, chest pain, and dyspnea. n Symptoms of malignancy: Weight loss, fatigability, and generalized illness.

Investigation Chest xray: An abnormal finding on chest X-ray is present in about 75% of patients with a carcinoid lung tumor Bronchoscopy: It reveals round red-yellow -purpule mass covered by epithelium that protrudes into bronchial lumen. Carcinoid tumor is Red shiny and it’s very easy to bleed Bronchoscopic image shows a red nodule that obstructs the entrance to the lower lobe bronchus

CT scan: Some carcinoid lung tumors that are small or covered by other organs in the chest may not be seen on a chest X-ray MRI: Same as CT but it help in differentiating small tumors from adjacent blood vessels Radionuclide : 1)Octreotide scintigraphy 2) Iodine-131 meta-iodo-benzyl guanidine (MIBG) scintigraphy Biopsy: Even if a chest X-ray and/or CT scan shows a tumor, these exams cannot confirm whether the mass is a carcinoid lung tumor, a lung carcinoma, or a localized infection.

Chest radiograph (CXR) demonstrates complete collapse of the left lower lobe. The cause of collapse is not identified on the image, so we asked for a ct scan. CT scan shows a hyper attenuating nodule within the left main bronchus. This is a bronchial carcinoid tumor. And then we need to ask for biopsy to confirm the diagnosis.

Staging Stage Type of the tumor Stage 1 Typical carcinoid tumor Stage 2(bronchopulmonary lymph node involvement) Atypical carcinoid tumor Stage 3(mediastinal lymph node involvement) Atypical carcinoid tumor

Managment All pulmonary carcinoid tumors should be treated as malignancies by doing total surgical resection as long as no surgery contraindication exist.

Medical Therapy n No medical therapy exists for the primary treatment of carcinoid tumor of the lung. Chemotherapeutic agents and radiation therapy have been used in the treatment of metastatic disease(Carcinoid Syndrome)

Surgical Therapy Surgical resection is the primary mode of therapy. We have different types of surgical treatment, but anatomic lobectomy is the most commonly performed procedure at present for resection of pulmonary carcinoid tumors.

Types of surgery n n n Most tumors follow a benign course and are amenable to surgery. Surgical options range from radical resection (the tumor with a good margin of normal tissue is removed) to minimally invasive surgery. Different surgical options include the following: n Sleeve resection: Section of the airway containing the tumor is removed. In this procedure, we have to remove one part of the main bronchus containing the tumor and anastmose the bifurcation with bronchus intermmedius, instead of pneumonectomy to preserve the other tumor free lobes) n Segmental resection: Segment of the lung containing the tumor is removed. n Wedge resection: Small wedge of the lung containing the tumor is removed.

n Lobectomy: Lobe of the lung containing the tumor is removed. n Pneumonectomy: Entire lung containing the tumor is removed. (Rarely) n Endoscopic tumor ablation using laser: This technique involves removal of the tumor through the bronchoscope, using laser. It is reserved for treating bronchial obstruction caused by the tumor or reduction of the tumor mass prior to surgical resection. This procedure is rarely curative on its own. Endoscopoic tumor ablation using laser, is not curative we use only in palliative treatment

Follow Up After discharging from the hospital, we need to follow up the pt for 2 -3 months in the first year (clinically and chest x ray), then every 6 months for the following years. Prevention Unlike most lung tumors, carcinoid lung tumors have not been associated with smoking, air pollution, or other chemical exposures. Therefore, there are no known ways to prevent carcinoid lung tumors.

Prognosis n Carcinoid lung tumors generally have a better prognosis(mainly typical) than other forms of lung cancer. Typical carcinoid lung tumors: 5 -year survival rate of 78%-95% 10 -year survival rate of 77%-90%. n Atypical carcinoid lung tumors : 5 -year survival rate of 40%-60% 10 -year survival rate of 31%-60%. n

Lung cancer

Definition : n Lung cancer is a disease which consists of uncontrolled cell growth in tissues of the lung. n The vast majority of primary lung cancers are carcinomas, derived from epithelial cells.

n The incidence of lung cancer has increased significantly over the last three decades. n The most common cancer in male and the second in female ( after a breast cancer) n It is the 1 st most common cause of cancer-related death in both men and women.

Causes: n ü ü ü n n Smoking: responsible for 85% of all lung cancers. Passive smoking account for 3 % ( nitrosamines and polycyclic aromatic hydrocarbons) Environmental: Asbestos , silica , chromium, cadmium

n ü ü n • n n Dietary: cholesterol and high fat diet increases the risk. Fruit and vegetables decreases the risk Pre- existing lung lesion : COPD, IPF , TB or infarct, Viruses ( HPV , CMV) Inheritence: AD Molecular genetics.

Symptoms and signs: n n n For a primary tumor: respiratory symptoms constitute more than 70% of the presentation Cough, dyspnea , unresolved pneumonia, wheeze, hymoptysis, pain ) For a regional spread: ( pleural effusion, chest wall pain, pericardial effusion , SVS, horner syndrome, horesness, dysphagea , phrenic nerve injury.

n Distant met : adrenal, liver, bone, brain. n Paraneoplastic syndrome: ACTH, ADH, GH, calcitonin , PTH. n SCLC : ACTH( cushing’s synd), ADH (SIADH) n Sqamous cell canrcinoma : PTH > hyper calcimia n Cachexia (weight loss, fatigue, and loss of appetite

Diagnosis: n Performing a chest radiograph is the first step if a patient reports symptoms that may suggest lung cancer.

CT scanning: n Has prove useful for assessing the primary tumor in relation to size and proximity to adjacent structure and surgical approaches

n n It is only 50% accurate in diagnosing tumor invasion into structures Abdominal CT is mandatory ( adrenal and liver

MRI n Has no advantage over CT , but better in visualazing tumor incasion of nearby structures.

Broncoscopy n n n Rigid or flexible. Dx , staging and treatment. Cytology and biopsy can be taken.

The differential diagnosis: n For patients who present with abnormalities on chest radiograph includes lung cancer as well as nonmalignant diseases. n These include infectious causes such as: • • • Tuberculosis Pneumonia Inflammatory conditions such as sarcoidosis.

Types of Lung Cancer: n The main types of lung cancer are small cell lung carcinoma (SCLC ) and non-small cell lung carcinoma (NSCLC ).

Small Cell Carcinoma n Accounts for about 20% of lung cancer. n A type of highly malignant carcinoma usually associated with the lung, though it can be associated with other topographies, such as in cervical cancer or prostate cancer n When associated with the lung, it is sometimes called "oat-cell carcinoma" due to the flat cell shape and scanty cytoplasm.

n It is thought to originate from neuroendocrine cells (APUD cells) in the bronchus called Feyrter cells (named for Friedrich Feyrter). n Hence, they express a variety of neuroendocrine markers, and may lead to paraneoplastic syndromes and Cushing's syndrome. n Paraneoplastic Syndromes: Small-cell carcinomas produce ACTH or ADH, which can lead to SIADH

n n It is more metastatic than non-small-cell lung carcinoma (and hence staged differently) and is sometimes seen in combination with squamous-cell carcinomas. There is usually early involvement of the hilar and mediastinal lymph nodes. Smoking is a significant etiological factor.

n Symptoms and signs are as for other lung cancers. In addition, because of their neuroendocrine cell origin, small-cell carcinomas will often secrete substances that result in paraneoplastic syndromes. n Small-cell lung cancer is pragmatically divided into two stages: q Limited Stage and q Extensive Stage depending on the presence of metastases

Limited-stage small-cell lung carcinoma: combination chemotherapy (often consisting of a cyclophosphamide, cisplatinum, doxorubicin, etoposide, vincristine and/or paclitaxel) is administered together with concurrent chest radiotherapy. n n Thoracic irradiation improves survival in limited stage smallcell lung carcinoma.

Extensive disease: combination chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms such as dyspnen, pain from liver or bone metastases, or for the treatment of brain metastases, which, in small-cell lung n Carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy. n Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. n

n Response rates are high even in extensive disease, with up: § § 15 -30%of patients having a complete response to combination chemotherapy Vast majority of patients having at least some response to combination chemotherapy.

n In limited stage disease, median survival with treatment is 14– 20 months, and about 20% live 5 years or longer. n The prognosis is far worse in extensive stage, with treatment, median survival is just 8– 13 months, and only 1 -5% live 5 years or longer. n No role for surgery in the treatment of SCLC because they metastasize early only chemo +/- radiation.

Non-small-cell lung carcinoma n Definition: is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). n Sometimes the phrase non-small-cell lung cancer [Not Otherwise Specified, or NOS] is used generically, usually when a more specific diagnosis cannot be mad.

n The most common types of NSCLC are: q q q Adenocarcinoma Squamous-cell carcinoma Large-cell carcinoma but there are several other types that occur less frequently, and all types can occur in unusual histologic variants and as multiphasic combinations

Adenocarcinoma: n n n The most common type (45%) Tend to be in the peripheral lung parenchyma and the alveolar septa Lymph node metastasis is common

Squamous-cell lung carcinoma: n n n n Also called epidermoid carcinoma 30% of cases Men > Women. It is closely correlated with a history of tobacco smoking Tend to be centrally located ( major bronchi), may also be a Pancoast’s Tumor. Ectopic PTH secretions Invaded locally

Pancost tumor ( syndrome) Tumor at the apex of the lung or superior sulcus that may involve : n the brachial plexus § sympathetic ganglia § Vertebral bodies Leading to pain, upper extremity weakness, and Horner’s Syndrome. §

Horner’s syndrome : Injury to the cervical sympathetic chain: n 1. 2. 3. Ptosis Miosis Anhydrosis of ipsilateral face.

Large Cell Carcinoma : n n n Also non as Undifferentiated carcinoma Accounts for 5 -10% of cases Tend to be in peripheral lung Often cavitate Early metastasis

Staging: n n patients undergo staging as part of the process of considering prognosis and treatment. The American Joint Committee on Cancer (AJCC) recommends TNM staging

Primary tumor (T) TX: The primary tumor cannot be assessed, or there are malignant cells in the sputum or bronchoalveolar lavage but not seen on imaging or bronchoscopy n Tis: Carcinoma in situ T 0: No evidence of primary tumor. T 1: 3 cm or less in diameter and completely surrounded by lung parenchyma

T 2: is greater than 3 cm OR invading the visceral pleura OR within a major bronchus OR Associated with atelectasis or obstructive symptoms T 3: is a tumor of any size with direct invasion of nonvital structure such as diaphragm, chest wall or pericardium T 4: is a tumor of any size with direct invasion of vital organs such as heart , great vessels OR malignant pleural effusion or pericardial effusion

Lymph nodes (N) n n n NX: Lymph nodes cannot be assessed. N 0: No lymph nodes involved. N 1: Metastasis to ipsilateral peribronchial or ipsilateral hilar lymph nodes. N 2: Metastasis to ipsilateral mediastinal or subcarinal lymph nodes N 3: Metastasis to any of: q q q Ipsilateral supraclavicular lymph nodes. Ipsilateral scalene lymph nodes. Contralateral lymph nodes.

Distant metastasis (M) MX: Distant metastasis cannot be assessed. M 0: No distant metastasis. M 1: Distant metastasis is present.

Treatment: Early/non-metastatic NSCLC: are usually not very sensitive to chemotherapy and/or radiation, so surgery is the treatment of choice if diagnosed at an early stage, often with adjuvant (ancillary) chemotherapy involving cisplatin. n

Contraindications of surgery : 1. 2. 3. 4. 5. 6. 7. 8. 9. Superior vena cava syndrome Supraclavecular node metastasis Scalene node metastasis Tracheal carina involvement Oat cell carcinoma PFT shows FEV 1<1 Myocardial infarction Tumor elsewhere (metastatic disease ) Bilateral lung lesions Acronym ( STOP IT )

Other treatment choices are : • Chemotherapy, • Radiation therapy (radiotherapy), including radiosurgery (SRS), or targeted therapy. This means less radiation affects nearby healthy tissues. **Neoadjuvant chemotherapy is done before surgery, then reassess the pt, if the tumor is resectable do surgery, but if not treat with chemo…

Advanced/metastatic NSCLC A wide variety of chemotherapies are used. Some patients with particular mutations in the EGFR gene respond to EGFR tyrosine kinase inhibitors such as gefitinib. n

Staging Groups TNM staging Treatment of choice Occult carcinoma TX N 0 M 0 - Stage 0 Tis N 0 M 0 - Stage IA T 1 N 0 M 0 Surgical resection Stage IB T 2 N 0 M 0 Surgical resection Stage IIA T 1 N 1 M 0 Surgical resection Stage IIB T 2 N 1 M 0 T 3 N 0 M 0 Surgical resection Stage IIIA T 1 N 2 M 0 T 2 N 2 M 0 T 3 N 1 M 0 T 3 N 2 M 0 Surgical resection if early IIIA, chemotherapy with or without XRT. Stage IIIB Any T N 3 M 0 T 4 Any N M 0 Chemotherapy and XRT Stage IV Any T Any N M 1 Chemotherapy +- XRT

Prognosis. Non-small-cell lung carcinoma survival by stage(1997) n Grouping Survival rate (percents) One year Two years Three years Four years Five years IA 82% 79% 71% 67% 61% IB 72% 54% 46% 41% 38% IIA 79% 49% 38% 34% IIB 59% 41% 33% 26% 24% IIIA 50% 25% 18% 14% 13% IIIB 34% 13% 7% 6% 5% IV 19% 6% 2% 2% 1%

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