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CLASSIFICATION OF LUNG TUMORS
- 1. Classification of Lungtumors Dr Kamal Bharathi. S Department of Pulmonary Medicine Sri Manakula Vinayagar Medical college and Hospital
- 2. CLASSIFICATION OF LUNGTUMOURS Primary Epithelial –Adeno carcinoma -Squamous cell carcinoma -Adenosquamous carcinoma -Neuro endocrine tumors -Large cell carcinoma -Salivary gland tumours -Sarcomatoid carcinomas Mesenchymal • Pulmonary hamartoma • Chondroma • PEComatous tumors Lymphohistiocytic tumors Ectopic origin Metastatic
- 3. WHO Classification ofLung Tumors • Epithelial tumors – Adenocarcinoma – Lepidic adenocarcinomae – Acinar adenocarcinoma – Papillary adenocarcinoma – Micropapillary adenocarcinoma – Solid adenocarcinoma – Invasive mucinous adenocarcinoma • Mixed invasive mucinous • nonmucinous adenocarcinoma – Colloid adenocarcinoma – Fetal adenocarcinoma – Enteric adenocarcinomae – Minimally invasive adenocarcinoma • Nonmucinous • Mucinous – Preinvasive lesions • Atypical adenomatous hyperplasia • Adenocarcinoma in situe – Nonmucinous – Mucinous – Squamous cell carcinoma • Keratinizing squamous cell carcinoma • Nonkeratinizing squamous cell carcinoma • Basaloid squamous cell carcinoma • Preinvasive lesion – Squamous cell carcinoma in situ – Neuroendocrine tumors • Small cell carcinoma – Combined small cell carcinoma • Large cell neuroendocrine carcinoma – Combined large cell neuroendocrine carcinoma • Carcinoid tumors – Typical carcinoid tumor – Atypical carcinoid tumor • Preinvasive lesion – Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia -Large cell carcinoma -Adenosquamous carcinoma -Sarcomatoid carcinomas – Pleomorphic carcinoma – Spindle cell carcinoma – Giant cell carcinoma – Carcinosarcoma – Pulmonary blastoma
- 4. WHO Classification ofLung Tumors • Epithelial tumors – Salivary gland-type tumors • Mucoepidermoid carcinoma • Adenoid cystic carcinoma • Epithelial-myoepithelial carcinoma • Pleomorphic adenoma – Papillomas • Squamous cell papilloma – Exophytic – Inverted • Glandular papilloma • Mixed squamous and glandular papilloma – Adenomas • Sclerosing pneumocytoma • Alveolar adenoma • Papillary adenoma • Mucinous cystadenoma • Mucous gland adenoma – Mesenchymal tumors • Pulmonary hamartoma • Chondroma • PEComatous tumors – Lymphangioleiomyomatosis – PEComa, benign » Clear cell tumor – PEComa, malignant – Congenital peribronchial myofibroblastic tumor • Diffuse pulmonary lymphangiomatosis Inflammatory myofibroblastic tumor • Epithelioid hemangioendothelioma • Pleuropulmonary blastoma • Synovial sarcoma • Pulmonary artery intimal sarcoma • Pulmonary myxoid sarcoma – Lymphohistiocytic tumors • Extranodal marginal zone lymphomas of mucosa- associated Lymphoid tissue (MALT lymphoma) • Diffuse large cell lymphoma • Lymphomatoid granulomatosis • Intravascular large B cell lymphoma • Pulmonary Langerhans cell histiocytosis • Erdheim–Chester disease – Tumors of ectopic origin • Germ cell tumors • Teratoma, mature • Teratoma, immature • Intrapulmonary thymoma • Melanoma • Meningioma, – Metastatic tumors
- 6. Classification of LungTumors They are divided into 3 groups for clinical usage • 1. Small cell carcinoma (19-20 %) – – Chemo & Radiotherapy +/-Targeted therapy • 2. Non – small cell ca (85-95 %) – – Surgical Management +/-Targeted therapy (squamous, adeno ca, large cell ca) • 3. Combined / Mixed patterns (5 to 10 %)
- 7. Origin and characteristicsof various types of lung cancer • Squamous cell lung cancer: – commonest type in males, central origin, manifests early • Adenocarcinoma: – commonest type in females, peripheral origin, manifests late • Large cell lung cancer: – least common type, peripheral origin • Small cell lung cancer: – most aggressive type, central origin, spreads quickly
- 8. Adenocarcinoma • Most commonlung cancer in nonsmokers and females • Activating mutation of K-Ras • Associated with hypertrophic osteoarthropathy “clubbing” • Located peripherally with central scar • Early metastasis • Histological examination: • Acinar (gland forming) • Papillary • Mucinous • Solid
- 10. • Atypical adenomatoushyperplasia (AAH) > Adenocarcinoma in situ (AIS) > minimally invasive adenocarcinoma > invasive adenocarcinoma • AAH: well demarcated focus of epithelial proliftation 5 mm or less composed of cuboidal to low-columnar cells with cytological atypia. • AIS: (bronchoalveolar carcinoma) involve peripheral parts of the lung. Diameter of 3 cm or less, growth along preexisting structures & preservation of alveolar architecture. • Can be nonmucinous, mucinous or mixed.
- 12. Adenocarcinoma precursor (AAH) Atypical adenomatous hyperplasia •Focal, 5.0 mm or less with defined borders • Alveoli lined by cuboidal to low columnar cells with variable atypia • Alveolar walls may be slightly thickened • Non-mucinous
- 13. Adenocarcinoma In Situ •The 2011 classification completely discards the term BAC in favor of “adenocarcinoma in situ” (AIS). • small (≤3 cm) solitary AC with predominant lepidic growth and small foci of invasion measuring ≤0.5 cm, the term “minimally invasive adenocarcinoma” is recommended. • typically present as pure GGO without a solid component on CT scan
- 15. AAH vs AIS AtypicalAdenomatous Hyperplasia Adenocarcinoma in situ (Mucinous)
- 16. a less commontype of adenocarcinoma - bronchioloalveolar carcinoma ADENOCARCINOMA IN SITU (bronchioloalveolar carcinoma) - well- differentiated columnar cells proliferate along the framework of alveolar septae - better prognosis than other primary lung cancers
- 17. Invasive Adenocarcinomas • Lepidicpredominant, • Acinar predominant, • Papillary predominant, • Micropapillary predominant, • Solid predominant with mucin production.
- 19. Lepidic predominant adenocarcinoma •consists mainly of tumor cells growing along alveolar septa (previously referred to as a nonmucinous BAC pattern) but with greater than 5 mm invasion.
- 20. Acinar predominant adenocarcinoma •consists of irregularly contoured but nonetheless recognizable glandular structures and is often associated with a desmoplastic stroma
- 21. Papillary predominant adenocarcinoma • consistsof malignant cuboidal or columnar cells that line the surface of fibrovascular cores
- 22. Micropapillary predominant adenocarcinoma • consistsof small papillary clusters of glandular cells growing within airspaces
- 23. Solid predominant adenocarcinoma withmucin • consists of sheets of tumor cells without an acinar, papillary, or lepidic growth pattern. • Solid nests of cells with mucin
- 24. Variants of invasiveadenocarcinoma • Invasive mucinous adenocarcinoma (formerly mucinous BAC) • Colloid adenocarcinoma • Fetal adenocarcinoma (low & high grade) • Enteric adenocarcinoma
- 25.
- 27. IHC • Immunohistochemistry Positive for –TTF - 1 – Napsin - A • Differential Diagnosis • Metastatic Adenocarcinoma
- 29. • 65 yearsold female presented with breathlessness 1 week duration • Right mass lesion in the periphery of lung • Bronchial wash & Lung Biopsy done Posteroanterior radiograph of chest showing a non-cavitated opaque density in the left upper lung field
- 30. Bronchial Wash group of largepleomorphic cells with high nuclear cytoplasmic ratio and vague glandular formations
- 32. TTF -1 NUCLEAR POSITIVITYChromogranin was negative
- 33.
- 34. Squamous cell carcinoma •commonly in men, cigarette smoking. • 2/3 occur centrally. • Endobronchial growth pattern- associated with bronchial obstruction and postobstructive pneumonia. • Cavitation is seen more frequently.
- 35. Definition • Squamous cellcarcinoma is defined as a malignant epithelial tumor showing keratinization and/or intercellular bridges.
- 36. squamous cell carcinoma arisingcentrally, obstructing the right main bronchus sqamous cell carcinoma extends from hilum to pleura
- 37. •Squamous cell carcinoma inwhich a portion of the tumor demonstrates central cavitation •Probably because the tumor outgrew its blood supply. •Squamous cell carcinomas are one of the more common primary malignancies of lung
- 38. Central type (hilartype) Diffuse type Peripheral type (nodular type) Gross types
- 39. Histologically: Squamous CellCA Keratin pearls Intercellular bridges
- 40. Histologic variants • Papillary-exophytic growth pattern and papillary cores • Clear cell- clear cell cytoplasm • Small cell- lack the nuclear characteristics of small cell ca and may show focal keratinization. • Basaloid patterns- Very aggressive clinical course , peripheral palisading of cells.
- 41. SCC WITH PAPILLARYGROWTH PATTERN
- 42. Small cell variantof squamous cell carcinoma small cell variant of squamous cell carcinoma can only be distinguished from true small cell carcinomas by means of immunohistochemical markers.
- 43. Clear cell variant squamouscell carcinoma shows cells with cytoplasmic clearing as well as groups of cells with features of keratinization
- 44.
- 45. • Preinvasive lesion Squamouscell carcinoma in situ
- 46. IHC • Immunohistochemistry – Positivefor P40 P63 – CK 5/6 • Differential Diagnosis • Metastatic Squamous cell carcinoma
- 47. • 46 yearsmale • Known Smoker for past 16 years • Bronchial wash & Lung Biopsy taken Posteroanterior radiograph of chest showing large cavitated lesion in the left mid upper lung field.
- 48. Bronchial wash elongated clusterof large cells with increased nuclear cytoplasmic ratio. Necrotic debris in the background string-like arrangement of tumor cell showing very dense nuclear chromatin.
- 51. Diagnosis • Squamous cellCarcinoma
- 52. Neuroendocrine tumors • Smallcell carcinoma • Large cell neuroendocrine carcinoma • Carcinoid tumors • Sarcomatoid carcinomas • Salivary gland-type tumors
- 53. Small Cell Carcinoma •Arises from “Kulchtisky cells” • Centrally located masses , extension to lung parenchyma • Involvement of hilar & mediastinal nodes • Amplicfication of myc oncogen is common Usually respond to chemo and radiotherapy
- 54. Clinical Features Paraneoplastic syndromedue to abnormal production of: • Hormones: – ACTH (Cushing's syndrome) – ADH (hyponatremia) • Auto-antibodies: – Encephalomyelitis – Lambert-Eaton syndrome – Subacute sensory neuropathy • Main line of treatment: chemotherapy, radiation – SCLC is rarely resected – Small cell carcinoma is very aggressive tumor with early distant metastasis
- 55. Small cell anaplastic(oat cell) carcinoma small cell anaplastic (oat cell) carcinoma – small dark blue cells with minimal cytoplasm Ill defined borders salt-pepper nuclear chromatin pattern
- 56. Microscopy Crushed Blue Cells“Crush artifact” is common SCLC, especially in biopsies rather than large specimens. – “chromatin smearing or streaming” Azzopardi phenomena: • basophilic nuclear DNA from necrotic tumor cells get deposited in the walls of vessels and connective tissue • +ve for feulgen reaction • Also seen in lymphomas, seminomas
- 57. Differential diagnosis • Otherneuroendocrine tumors: – Carcinoid tumors – Large cell Neuroendocrine carcinoma
- 58. • 40 yearsold Female • Complaints of breathlessness during night • Endoscopy, bronchial wash and lung Biopsy taken Hilar and perihilar masses in continuity with mediastinal lymphadenopathy
- 59. Bronchial wash cluster ofsmall very dark cells showing scant cytoplasm and hyperchromatic nuclei.
- 62.
- 63. Diagnosis • Small cellcarcinoma
- 64. Large cell carcinoma •“an undifferentiated malignant epithelial tumor that lacks the cytologic features of small-cell carcinoma and glandular or squamous differentiation.”
- 66. • 58 yearsold male presented with Breathlessness, hemoptysis for past 3 days duration • Chest X-ray was taken • Bronchial wash & Lung Biopsy done Posteroanterior radiograph of chest showing large nodular density with relatively well- defined borders in the left upper lobe.
- 67. Bronchial Wash Dispersed tumor cellpopulation with predominance of larger cells with very dense nuclear chromatin and lack of squamous or glandular features Few lymphocytes can be seen in the background
- 68.
- 69. Diagnosis • Large cellcarcinoma
- 70. Carcinoid tumor • TypicalCarcinoid tumor- central & peripheral variants. • Mostly asymptomatic. • Central carcinoids- present with recurrent pneumonias or hemoptysis. • association with (MEN)1 syndrome in 5% ppl.
- 71. • grossly appearas yellow or fleshy, polypoid masses. • tumor can infiltrate between cartilaginous rings to extensively involve the bronchial submucosa.
- 72. • tumor cellsare uniform in appearance • low nuclear:cytoplasmic ratio • characteristic neuroendocrine tumor chromatin that is finely granular or classically described as “salt and pepper.”
- 73. • carcinoid tumorshave a generally excellent prognosis with reported 5-year survival rates of 87% to 100%
- 74. Sarcomatoid carcinomas - bydefinition poorly differentiated non–small-cell carcinomas that have a histologic appearance that suggests mesenchymal differentiation. • Pleomorphic carcinoma • Spindle cell carcinoma • Giant cell carcinoma • Carcinosarcoma • Pulmonary blastoma
- 75. Spindle cell carcinoma Subtype of Sarcomatoid carcinoma (WHO) < 1% of all primary lung carcinomas Majority of cases are diagnosed in adults over the age of 65 years Carcinoma composed exclusively of spindle-shaped tumor cells Tumor cells often obliterate vessels
- 76. Carcinosarcoma Rare, 0.1%of all lung cancers M > F, most with smoking history, average age 60 Sites - Large airways and peripheral lung Biphasic tumor consisting of a non- small cell carcinoma with heterologous sarcomatoid differentiation Rare tumor with poor prognosis mixture of well differentiated adenocarcinoma and heterologous elements of cartilage
- 77. Pulmonary Blastoma Raretumor composed of mixture of immature epithelial and mesenchymal tissue resembling fetal lung tissue – Embryoma Usually adults (mean age 43 years) Microscopy Biphasic tumor in which epithelial and mesenchymal components have a primitive, "fetal-type" appearance Well formed tubular glands surrounded by cellular stroma of "embryonal" appearance Morules with ground glass nuclei are common Positive stains PAS (glycogen in epithelial cells) Molecular Genetics CTNNB1 mutation
- 78.
- 79.
- 80. Perivascular epithelioid celltumor (PEComa) Also called- Clear cell (sugar) tumor Extremely rare, benign pulmonary tumor derived from perivascular epithelioid cells Generally older adults >40 years old No gender predilection • Microscopy : – Clear to eosinophilic, finely granular cytoplasm containing abundant PAS+ glycogen – Small, uniform, rounded nuclei with small nucleoli, variably prominent sclerotic vasculature – “Spider cells” with nuclear condensation of eosinophilic cytoplasm with extensions to the cell membrane • Positive stains – HMB45, MART1/MelanA, SMA, desmin
- 81. Synovial sarcoma • Raretumor of lung • Associated with chest pain, hemoptysis, dyspnea, cough, fever • Monophasic spindle cells or biphasic with epithelial and spindle cell component • Death due to metastases to bone, CNS, liver, or invasion of adjacent organs • Positive stains – TLE1 highly specific • Negative stains – CD117 • Molecular cytogenetics: – t(X;18)(p11.2;icq11.2) – SYT-SSX1 or SYT-SSX2 fusion genes
- 82. Salivary gland-type tumorsAdenoidcystic Carcinoma Acinic Cell Carcinoma Epithelial Myoepithelial Carcinoma Mucoepidermoid Carcinoma
- 83. LYMPHOMA Types: • Extranodalmarginal zone lymphomas of mucosa-associated Lymphoid tissue (MALT lymphoma) • Diffuse large B-cell lymphoma • Intravascular large B cell lymphoma Presents as large parenchymal solitary discrete mass, occasionally multiple nodules Median age 68 years (range 34 - 88) Monotonous population of lymphocytes with germinal centers that infiltrate overlying epithelium (lymphoepithelial lesions) and around vessels, pleura and alveolar septa 5 year survival is 50%
- 84. Tumors of EctopicOrigin
- 85. Mediastinal GERM CELLTUMOUR • Primary extragonadal germ cell tumors comprise 2% to 5% of all germ cell tumors • Approximately two thirds of these tumors occur in the mediastinum • The mediastinum is the most common site of primary extragonadal germ cell tumors in young adults • Represent 10-15% of adult antero- superior mediastinal tumors
- 86. Pulmonary meningioma • Veryrare tumour, - presents as a solitary pulmonary nodule • Age range is 41 to 75, with a mean of 52 years. • The lesions are usually asymptomatic. • The appearances are the same as those of meningioma of the central nervous system • Vimentin & EMA positive
- 87. Mediastinal Thymoma • Mostcommon primary anterior mediastinal neoplasm • Commonly ages 49-62 years • Associated with Autoimmune- mediated disorders • Gross – – 80% encapsulated - Multinodular, yellow-gray with Sharp lobulations due to fibrous bands • Microscopy: – Spindle cell histologic patterns with cytologically bland epithelial cells and non-neoplastic lymphocytes and thick capsule. No well formed Hassalls corpuscles • Positive stains – CEA, CD3, EMA, keratin, S100, PAX8 • Negative stains – Vimentin
- 88. • 58 yearsold female with past history of mastectomy for CA breast 15 years back • Presented with weight loss and dyspnoea for 1 month duration • Chest X-ray was taken • Bronchial wash & Lung Biopsy done Posteroanterior radiograph of chest showing multiple large nodular density both right and left lobe of lung.
- 89.
- 90. Biopsy small nodular aggregatesof tumor cells suggestive of a mammary origin
- 91.
- 92.
- 93. Metastatic carcinoma fromcolon Metastatic renal cell carcinoma
- 94. Metastatic melanoma Metastatic follicularcarcinoma thyroid Metastatic cholangiocarcinoma Metastatic carcinoma endometrium
- 95. Common Sites ofMetastasis of Lung Cancer 1. Lymph node (most cases) 2. Liver 30-50% 3. Adrenal >50% 4. Bone 15-20% 5. Brain 20% 6. Kidney 15% 7. Spleen 5% 95
- 96. Metastatic Tumors intothe Lungs • Prostate • Colon • Cervix • Breast • Bone • Bladder
- 97. • 68 yearsold male presented with Progressive shortness of breath for past 2 years • History of worked in Asbestos manufacturing company • Chest X-ray was taken • Biopsy done Posteroanterior radiograph of chest showing multiple large nodular density both right and left lobe of lung.
- 98.
- 99. Biopsy Enlarged nuclei withprominent nucleoli represent malignant cells that resemble mesothelial cells in the background of numerous lymphocytes
- 100.
- 101. Gross Both lungs withtumor in pleural space around right lung and parenchyma extension at diaphragm
- 102. Microscopy • Three broadhistopathological features – Epithelioid: includes tubulopapillary, deciduoid, clear cell, and small cell types – Sarcomatoid: desmoplastic and lymphohistiocytoid types – Biphasic / mixed • Stromal or fat invasion is helpful in diagnosis
- 103. Differential diagnosis • Adenocarcinoma •Atypical mesothelial hyperplasia synovial sarcoma
- 104. Mesothelioma vs Carcinoma AntigenMesothelioma % Carcinoma % WT 1 100 5 Thrombomodulin 100 8 Calretinin 90 30 104
- 105.