lung tumor

LUNG TUMORS:

LUNG TUMORS

Lung:

Lung Capillary lumen Type I pneumocyte Type I pneumocyte Type II pneumocyte Endothelium Alveolar space

Carcinoma of the Lung:

Carcinoma of the Lung 6.5 % of all deaths #1 cause of cancer deaths in males & females 31% of male cancer deaths in 2001 90,367 deaths 25% of female cancer deaths 65,506 deaths

Carcinoma of the Lung:

Carcinoma of the Lung

Carcinoma of the Lung:

Carcinoma of the Lung EPITHELIAL TUMORS : BENIGN Papilloma Adenoma MALIGNANT : Squamous cell carcinoma Small cell carcinoma Adeno carcinoma Large cell carcinoma Adeno squamous carcinoma SOFT TISSUE TUMORS : Fibroma Fibro sarcoma Leiomyoma Leiomyosarcoma Lipoma Chondroma Hemangioma Lymphangioma Granular cell myoblastoma

Carcinoma of the Lung:

Carcinoma of the Lung PLEURAL TUMORS : Benign mesothelioma Malignant mesothelioma MISCELLANEOUS : Carcinosarcoma Pulmonary blastoma Malignant melanoma Malignant lymphoma

Carcinoma of the Lung:

Carcinoma of the Lung SECONDARY TUMORS TUMOR LIKE CONDITIONS :\ Hamartomas Eosinophillic granulomas Inflammatory pseudotumor

Smoking-related diseases:

Smoking-related diseases

Causes of Lung Cancer:

Causes of Lung Cancer 85-95% smoking 1% asbestos + smoking (estimate) Rare arsenic, chromium, mustard gas, nickel, vinyl chloride, bis (chloromethyl) ether Speculation 0.3-3% passive smoking 3-14% radon

BENIGN TUMORS:

BENIGN TUMORS

BENIGN TUMORS:

BENIGN TUMORS SQUAMOUS PAPILLOMAS & PAPILLOMATOSIS CLINICAL : Upper airway – solitary; adult smoker Lower airway – multiple; papillomatosis : children & young adults

SQUAMOUS PAPILLOMAS & PAPILLOMATOSIS :

SQUAMOUS PAPILLOMAS & PAPILLOMATOSIS MACROSCOPIC : Multiple lobulated escrescences in bronchioles; distal bronchiectasis common MICROSCOPIC : Fibrovascular core with cytologically bland non keratinizing squamous epithelium Koilocytic changes are common Mucus secreting

BENIGN TUMORS:

BENIGN TUMORS PAPILLARY ADENOMA OF TYPE II CELLS CLINICAL : Asymptomatic, coin lesion MICROSCOPIC : Circumscribed lesion of branching, papillary fronds lined by cytologically bland columnar cells No mitoses, necrosis Intra nuclear cytoplasmic inclusions common

BENIGN TUMORS:

BENIGN TUMORS HAMARTOMA CLINICAL : Two locations; central endobronchial & parenchymal Only central causes symptoms

HAMARTOMA :

HAMARTOMA MACROSCOPIC : Well circumscribed white, bulging nodules of cartilagenous consistency Calcium or bone may be present MICROSCOPIC : Usually composed of cartilage;fat, smooth muscle & fibromyxoid tissue can be seen Surrounded by clefts of benign ciliated or non ciliated epithelium, probably entrapped metaplastic epithelium

CARCINOMA in SITU of BRONCHIAL MUCOSA:

CARCINOMA in SITU of BRONCHIAL MUCOSA MICROSCOPIC : Dysplasia : cytological atypia, nuclear enlargement in lower, middle & upper third of mucosa ( grades: mild, moderate, severe ): superficial surface maturation CIS : entire mucosal involvement by dysplasia; no invasion below basement membrane

MICRO INVASIVE CARCINOMA OF BRONCHIAL MUCOSA:

MICRO INVASIVE CARCINOMA OF BRONCHIAL MUCOSA

SQUAMOUS CELL CARCINOMA:

SQUAMOUS CELL CARCINOMA Frequency: 35% Smoking: X 25 (increased risk) Males > females Survival (5 years): 15 - 20% Arises in bronchial squamous metaplasia Centrally located May cavitate

INTRA LUMINAL BRONCHIAL GROWTH OF SQUAMOUS CELL CARCINOMA:

INTRA LUMINAL BRONCHIAL GROWTH OF SQUAMOUS CELL CARCINOMA

SQUAMOUS CELL CARCINOMA:

SQUAMOUS CELL CARCINOMA Definition Malignant neoplasm of the bronchopulmonary epithelium with evidence of either keratinization or intercellular bridging and graded into well, moderately and poorly differentiated on the basis of the amount of keratinization present. Clinical Features Majority in males Signs of bronchial obstruction: such as: obstructive pneumonitis atelectasis in ≈50% Most centered in segmental bronchipresent as hilar or perihilar masses in chest radiograph May be: peripheral subpleural Larger than other types at diagnosis 3

SQUAMOUS CELL CARCINOMA:

SQUAMOUS CELL CARCINOMA GROSS : Tendency to undergo central necrosis with cavitation Calcification extremely unusual Rarely intrabronchial polypoid mass with only minor extrabronchial spread

SQUAMOUS CELL CARCINOMA:

SQUAMOUS CELL CARCINOMA Diagnosis of malignancy based on: cell atypia invasiveness Diagnosis of squamous cell type based on detection of: keratin and/or intercellular bridges Keratin formation may be seen: in isolated cells: isolated necrotic cells should not be confused with keratinized cells more commonly in ‘keratin pearls’

SQUAMOUS CELL CARCINOMA:

SQUAMOUS CELL CARCINOMA Whorl formation and definite stratification of tumor cells: used by some as presumptive evidence of squamous differentiation in absence of features listed: according to WHO classification should be in undifferentiated large cell category May be: oncocytoid appearance of tumor cells: due to increased mitochondrial density giant cell foreign body reaction to keratin palisaded granulomas extensive infiltration by neutrophils and other inflammatory cells: simulating inflammatory malignant fibrous histiocytoma lepidic type of growth into air spaces at tumor periphery Bronchial mucosa adjacent to tumor: usually squamous metaplasia sometimes carcinoma in situ occasionally extending several centimeters from main mass

Special Stains and Immunohistochemistry :

Special Stains and Immunohistochemistry Reactivity for: low- and high-molecular-weight keratin involucrin precursor of cross-linked envelope protein or marginal band in stratum corneum in some cases: vimentin EMA human milk fat globule (HMFG-2) S-100 protein Leu-M1 CEA

SQUAMOUS CELL CARCINOMA:

SQUAMOUS CELL CARCINOMA Small Cell Variant Small tumor cells Only focal keratinization Distinction from small cell carcinoma (and combined small cell/squamous cell carcinoma) can be difficult: in small cell variant of squamous cell carcinoma: nuclei more vesicular and better defined nucleoli tumor nests more sharply outlined stroma more mature less necrosis

SQUAMOUS CELL CARCINOMA:

SQUAMOUS CELL CARCINOMA Clear Cell Variant Numerous clear cells: usually because of glycogen accumulation Clearcut keratinization Clear cell changes more frequent in other types of lung carcinoma, particularly adenocarcinoma

SQUAMOUS CELL CARCINOMA:

SQUAMOUS CELL CARCINOMA Well-Differentiated Papillary Variant Delicate intrabronchial papillary lesion Little or no stromal invasion Practically no necrosis Basaloid variant Important subgroup Very aggressive clinical course 13,14 Morphologic features analogous to those of homonymous tumor in upper aerodigestive tract

SQUAMOUS CELL CARCINOMA:

SQUAMOUS CELL CARCINOMA Spindle Cell Variant (Sarcomatoid)/Carcinosarcoma Predominantly composed of spindle cells but still identifiable as epithelial on morphologic, ultrastructural or immunohistochemical grounds

PULMONARY ADENOCARCINOMA:

PULMONARY ADENOCARCINOMA Frequency: 30% Smoking: X 3 (increased risk) Males < females Survival (5 years): 15 - 20% Peripheral

PULMONARY ADENOCARCINOMA:

PULMONARY ADENOCARCINOMA Definition Malignant neoplasm of respiratory epithelium with glandular differentiation and mucin production, and exhibiting acinar, papillary, bronchioloalveolar or solid growth patterns. Clinical Features ≈50% of all lung carcinomas in females <50% of all lung carcinomas in males In absolute numbers, more common in males May be becoming more prevalent than other microscopic types of lung cancer

PULMONARY ADENOCARCINOMA:

PULMONARY ADENOCARCINOMA Usually: poorly circumscribed gray–yellow lesions Single or multiple Mucoid glairy appearance if secrete abundant mucin Cavitation extremely unusual ≈65% peripheral location At excision 77% involve visceral pleura: often resulting in pleural fibrosis or ‘puckering’

PULMONARY ADENOCARCINOMA:

PULMONARY ADENOCARCINOMA Occasionally: pseudomesotheliomatous carcinoma: both pleural layers coated by a small peripheral adenocarcinoma that has spread massively into pleural space simulates diffuse mesothelioma Even rarer: presentation as large endobronchial polypoid mass High percentage associated with peripheral scar or honeycombing:

PULMONARY ADENOCARCINOMA:

PULMONARY ADENOCARCINOMA may show foci of atypical bronchiolar and alveolar proliferation in neighboring air spaces of 82 ‘scar cancers’: 72% adenocarcinomas 18% squamous cell carcinomas remainder large cell undifferentiated carcinomas no small cell carcinomas controversy about whether scar: precedes carcinoma is a desmoplastic host reaction to the tumor immunophenotyping of collagen in scar suggests desmoplastic host reaction is most prevalent

PULMONARY ADENO CARCINOMA:

PULMONARY ADENO CARCINOMA

PULMONARY ADENO CARCINOMA:

PULMONARY ADENO CARCINOMA Wide range of differentiation: one extreme blending with bronchioloalveolar carcinoma other extreme blending with undifferentiated large cell carcinoma Glandular differentiation: two morphologic signs often found together are: formation of tubules or papillae secretion of mucin

PULMONARY ADENO CARCINOMA:

PULMONARY ADENO CARCINOMA depending on relative prominence subdivided with considerable overlap into: acinar papillary: controversial relationship with bronchioloalveolar carcinoma sometimes close morphologic similarity with metastatic papillary thyroid carcinoma – both are TTF-1 immunoreactive solid (adeno)carcinomas with mucin production

PULMONARY ADENO CARCINOMA:

PULMONARY ADENO CARCINOMA Lining of tumor cells along alveolar walls: a pattern of growth of many primary or metastatic tumor types can simulate gland formation Much rarer: pagetoid spread along mucosa of large bronchi Occasionally prominent eosinophilic intracytoplasmic globules Blood vessel invasion in 86%

PULMONARY ADENOCARCINOMA with SIGNET RING appearance:

PULMONARY ADENOCARCINOMA with SIGNET RING appearance

Special Stains and Immunohistochemistry :

Special Stains and Immunohistochemistry Special Stains and Immunohistochemistry Reactivity for: low molecular weight keratins EMA CEA TTF-1 secretory components Expression of keratin 7: evidence of glandular differentiation Sometimes coexpression of keratin and vimentin S-100 protein-positive Langerhans' cells frequent in stroma Surfactant apoprotein (PE-10) positivity: ≈50% useful in differential diagnosis with: other types of primary lung carcinoma metastatic adenocarcinoma Cathepsin B and basement membrane components also encountered Consistent expression of Lewis X and Y blood group antigens: may be of some differential diagnostic value

Large Cell Carcinoma:

Large Cell Carcinoma Frequency: 10 % Synonyms: Large Cell Undifferentiated Carcinoma (LCUC), Undifferentiated Large Cell Carcinoma , Poorly Differentiated Epithelial Lung Tumor

LARGE CELL CARCINOMA:

LARGE CELL CARCINOMA Definition Aggressive tumors distinguished by absence of squamous or glandular differentiation by light microscopy and exhibiting large tumor cells arranged in monotonous fields with moderate cytoplasm, coarse peripherally clumped chromatin and prominent nucleoli. Clinical Features Variants: giant cell carcinoma lymphoepithelioma-like carcinoma large cell neuroendocrine carcinoma and non-small cell carcinoma with neuroendocrine features Giant Cell Carcinoma May be peripheral leukocytosis Usually: peripheral location quite extensive at diagnosis

LARGE CELL CARCINOMA:

LARGE CELL CARCINOMA Pleomorphic Malignant Epithelial without definite evidence of squamous or glandular differentiation Tumor cells: large compared to those of small cell carcinoma solid sheets relatively uniform

LARGE CELL CARCINOMA:

LARGE CELL CARCINOMA Giant Cell Carcinoma variant Bizarre multinucleated giant cells alternating with mononuclear forms Solid fashion Simulates sarcoma Heavy neutrophilic infiltration between and inside tumor cells: Sometimes foci of glandular differentiation and/or mucin production

LARGE CELL CARCINOMA:

LARGE CELL CARCINOMA Lymphoepithelioma-like Carcinoma variant Morphologically analogous to homonymous tumor in upper respiratory tract Seemingly syncytial pattern of growth Large vesicular nuclei Prominent eosinophilic nucleoli Heavy lymphocytic infiltration: sometimes so prominent misdiagnosed as inflammatory pseudotumor or malignant lymphoma

BRONCHO ALVEOLAR CARCINOMA:

BRONCHO ALVEOLAR CARCINOMA Frequency: 2 % Smoking: yes Males = females Survival (5 years): 25 a 40 %. Presentation: Single or multiple tumor nodules Miliary tumor “Pneumonic form”

BRONCHO ALVEOLAR CARCINOMA:

BRONCHO ALVEOLAR CARCINOMA Definition Well-differentiated adenocarcinomas displaying noninvasive, nondestructive pattern of growth along preexisting alveolar walls. Clinical Features Incidence seems to be increasing Mucinous and nonmucinous types: nonmucinous type 60–75% of cases

BRONCHO ALVEOLAR CARCINOMA diffuse lung involvement:

BRONCHO ALVEOLAR CARCINOMA diffuse lung involvement Various forms with important relationship to microscopic type and prognosis: single peripheral nodule multiple nodules: may be several lobes or bilateral diffuse pneumonic-like infiltrate may be several lobes or bilateral Mucinous type: glistening appearance usually preserved underlying lung architecture occasional distortion of air spaces by pools of mucus Nonmucinous type: gray-white foci of parenchymal consolidation sometimes central scar

BRONCHO ALVEOLAR CARCINOMA MUCINOUS TYPE:

BRONCHO ALVEOLAR CARCINOMA MUCINOUS TYPE Mucinous type: well-differentiated mucin-containing columnar cells line respiratory spaces without invading stroma tumor nodules have topographic association with bronchioles rather than bronchi continuity between tumor cells lining alveoli and epithelium of respiratory bronchioles or alveolar ducts often sharp separation between neoplastic and normal cells: useful diagnostic feature

BRONCHO ALVEOLAR CARCINOMA NO MUCIN:

BRONCHO ALVEOLAR CARCINOMA NO MUCIN Nonmucinous type: tumor cells: cuboidal rather than columnar often bright eosinophilic neoplasm greater nuclear atypia and nucleolar prominence than in mucinous type may be: apical spouts as indicators of Clara cell differentiation hobnail cells exceptionally: cilia: presence suggests alternative possibility of reactive condition commonly eosinophilic intranuclear inclusions: PAS positive useful diagnostic sign also intranuclear inclusion of similar or different appearance in adenocarcinomas of conventional types in contrast to mucinous type: various degrees of: interstitial fibrosis: when extensive referred to as ‘sclerosing variant’ chronic inflammatory cells: some S-100 protein positive psammoma bodies in

BRONCHO ALVEOLAR CARCINOMA NO MUCIN:

BRONCHO ALVEOLAR CARCINOMA NO MUCIN

Special Stains and Immunohistochemistry :

Special Stains and Immunohistochemistry Mucinous type: usually immunoreactive for CK20: unlike conventional adenocarcinoma, which is usually CK7+/CK20− (and readily distinguishable from CK7−/CK20+ metastatic colorectal adenocarcinoma) Nonmucinous type: type 2 pneumocytes: surfactant apoprotein detected with antibody PE-10 Clara cell differentiation: α-1-antitrypsin useful immunomarker Mucinous and nonmucinous types: usually TTF-1-positive. aberrant expression of MUC3 and MUC6: in contrast to ordinary type adenocarcinoma Exceptionally foci of endocrine differentiation

BRONCHO ALVEOLAR CARCINOMA IHC with PE – 10 (surfactant):

BRONCHO ALVEOLAR CARCINOMA IHC with PE – 10 (surfactant)

Small cell carcinoma:

Small cell carcinoma Frequency: 25 % Smoking: 95% of patients Males >> females Survival (5 years): 1 - 5 %.

SMALL CELL CARCINOMA:

SMALL CELL CARCINOMA Definition High grade, rapidly growing, early metastasizing, neuroendocrine carcinoma of the lung, arising predominantly in the central major airways, with a strong assocition with smoking. Clinical Features 10–20% of all lung cancers Usually male Median age 60 years >85% smokers 1

SMALL CELL CARCINOMA:

SMALL CELL CARCINOMA Subclassification has been primarily based on cytologic criteria Terminology has changed over years as follows: Kreyberg (1962): oat cell polygonal WHO (1967): lymphocyte-like polygonal fusiform WHO (1981): oat cell intermediate combined International Association for Study of Lung Cancer (IASLC) (1988): small cell (classic) mixed small cell/large cell combined currently preferred scheme No scheme is entirely satisfactory

SMALL CELL CARCINOMA:

SMALL CELL CARCINOMA Gross Pathology White-tan Soft Friable Extensively necrotic Typically central lung 13,14 usually centered in large bronchus: circumferential and/or spread widely beneath normal mucosa may be total occlusion in late stages pure or predominant endobronchial involvement highly unusual

SMALL CELL CARCINOMA:

SMALL CELL CARCINOMA Classic Form Almost exclusively in small bronchial biopsies: tumor cells usually larger and with more abundant cytoplasm in specimens from lymph node or distant metastases or from rare resection specimens of primary tumor: artifactual shrinkage may be partially responsible for ‘small cell’ phenotype Small round or oval cells resembling lymphocytes sometimes elongated (fusiform) shape

SMALL CELL CARCINOMA:

SMALL CELL CARCINOMA Nuclei: finely granular very hyperchromatic inconspicuous nucleoli frequent mitoses Cytoplasm: scanty almost unrecognizable in routine preparations Nuclear ‘molding’: elongation of nuclei with deformation, clumping, and diffusion of chromatin first described in cytologic smears also microscopic preparations common artifact prominent in small biopsy specimens if present throughout may make diagnosis impossible

SMALL CELL CARCINOMA with EXTENSIVE NECROSIS:

SMALL CELL CARCINOMA with EXTENSIVE NECROSIS AZZOPARDI’S EFFECT ( HEMATOXYPHILIC STAINING OF VESSEL WALLS ) Chromatin diffusion secondary to necrosis may spread to wall of blood vessels, which appear strongly hematoxyphilic: sometimes referred to as Azzopardi's effect positive for Feulgen reaction

SMALL CELL CARCINOMA (intermediate size):

SMALL CELL CARCINOMA (intermediate size) Mixed Small Cell/Large Cell Carcinoma Admixture of small and large tumor cells Poorly defined category with poor interobserver agreement Designation not entirely accurate: most not an admixture of two cell populations instead display tumor cells with nuclear features similar to but larger than those of classic small cell carcinoma Early claims of worse survival not substantiated

COMBINED SMALL CELL – SQUAMOUS CARCINOMA:

COMBINED SMALL CELL – SQUAMOUS CARCINOMA Overall features of small cell carcinoma but also minor (<5%) component of either: squamous cell carcinoma, or Adenocarcinoma (including bronchiolo alveolar type) 1–3% of all cases Rarely small cell carcinomas that are otherwise typical contain scattered giant tumor cells: more common after chemotherapy

Special Stains and Immunohistochemistry :

Special Stains and Immunohistochemistry Variable positivity for neural markers such as: Neurofilaments Leu7 chromogranin synaptophysin histidine decarboxylase neuron-specific enolase often elevated in serum, so useful in monitoring disease Also positivity for keratin: usually low molecular weight often simultaneous with neural markers Usually unreactive for CD99: in contrast to Ewing sarcoma/PNET Often express bcl-2 protein In contrast to non-small cell carcinomas: usually negative for 34βE12 TTF-1 positive in ≈85% of cases consistently negative for surfactant apoprotein (PE-10)

SMALL CELL CARCINOMA:

SMALL CELL CARCINOMA Ultrastructurally: few dense-core neurosecretory-type granules in at least some tumor cells in ≈80% Small cell carcinoma of lung. A few uniform, round, dense-core, membrane-bound granules are present. These granules are difficult to find and are usually present at the periphery of cells. (×41,200)

ADENO SQUAMOUS CARCINOMA:

ADENO SQUAMOUS CARCINOMA CLINICAL : 0.4 – 4.0 % of lung carcinomas Strong association with smoking MICROSCOPIC : Contains well differentiated squamous cell carcinoma & adeno carcinoma Each component must comprise at least 10 % of the tumor

ADENO SQUAMOUS CARCINOMA:

ADENO SQUAMOUS CARCINOMA SQUAMOUS component GLANDULAR component

PULMONARY BLASTOMA:

PULMONARY BLASTOMA Definition Biphasic pulmonary tumor of adults, composed of well differentiated epithelial glands resembling fetal lung and nondescript fusiform blastema-like cells. Well differentiated fetal type adenocarcinoma is a term used for tumors with only the epithelial component. Clinical Features Typically adult Metastases in close to 50% Low-grade and high-grade forms: low grade more common in elderly high grade more common in middle aged

PULMONARY BLASTOMA:

PULMONARY BLASTOMA Gross Pathology Usually: peripherally located solitary well circumscribed large Polypoid tumor nodules are seen on the cut surface, in association with extensive hemorrhage.

PULMONARY BLASTOMA:

PULMONARY BLASTOMA Well-differentiated tubular glands: glandular cells often show subnuclear and supranuclear cytoplasmic vacuoles Cellular stroma: typically undifferentiated small oval or spindle cells may show differentiation toward: skeletal muscle cartilage, or bone Overall appearance: resembles fetal lung of 10–16 weeks' gestation reminiscent of Wilms' tumor

PULMONARY BLASTOMA:

PULMONARY BLASTOMA Commonly: solid balls of cells (‘morules’) with: abundant acidophilic cytoplasm ground-glass (optically clear) nuclei: said to be due to accumulation of biotin Glycogen abundant in epithelial cells Sometimes: intestinal differentiation yolk sac differentiation component of malignant melanoma

PULMONARY ENDODERMAL TUMOR:

PULMONARY ENDODERMAL TUMOR

SQUAMOUS CELL CARCINOMA CYTOLOGY:

SQUAMOUS CELL CARCINOMA CYTOLOGY

ADENO CARCINOMA CYTOLOGY:

ADENO CARCINOMA CYTOLOGY

LARGE CELL UNDIFFERENTIATED CARCINOMA - CYTOLOGY:

LARGE CELL UNDIFFERENTIATED CARCINOMA - CYTOLOGY

SMALL CELL CARCINOMA CYTOLOGY:

SMALL CELL CARCINOMA CYTOLOGY

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