Sandbox lung cancer differential

• Differentiation of primary and secondary lun tumors is difficult due to overlapping histologic features.
• Topography, size and form of pulmonary growth pattern are important aspects for the differential diagnosis.
• Primary lung tumors are mainly localized in upper lobes as singular nodules, metastases in lower lobes as multiple lesions.
• On the contarary, endobronchial primary or secondary squamous cell carcinomas findings of severe dysplasia and CIS of the bronchial epithelium are important.
• Stroma and vascularisation pattern of primary and secondary lung tumors differ in distribution, arrangement and extracellular matrix components.
• Pulmonary vascular changes in primary tumors are characterized by vascular infiltration, destruction and occlusion whereas in secondary tumors intravascular embolisation and extravasation predominate.

Malignant lung carcnimoma
			Risk Factors	Topography	Histology	Gross	Immunohistochemistry	Imaging			Pulmonary growth pattern	Mets	Other differentiating features
								Xray	CT	PET scan
Squamous cell carcinoma	Papillary		Cigarette smokers Arsenic	Centrally in the mainstem	Exophytic and endobronchial growth. Limited amount of intraepithelial spread without invasion.	White or grey and, depending on the severity of fibrosis Firm with focal carbon pigment deposits in the centre and star-like retractions on the periphery. Cavitations. Intraluminal polypoid masses and / or infiltrate through the bronchial wall into the surrounding tissues	High molecular weight keratin (34ßE12 Cytokeratins (5/6) Carcinoembryonic antigen (CEA) Low molecular weight keratin (35ßH11) Thyroid transcription factor-1 (TTF-1) Cytokeratin 7 (CK7)	In central SCC, lobar or entire lung collapse Shift of the mediastinum to the ipsilateral side. Central, segmental or subsegmental tumours can extend into regional lymph nodes Appear as hilar, perihilar or mediastinal masses with or without lobar collapse. Peripheral tumours Presents as solitary pulmonary nodules (< 3 cm) or masses (> 3 cm). Cavitations Hilar opacities, atelectasis or peripheral masses Mediastinal enlargement Hemidiaphragmatic elevation
	Clear cell				Predominantly composed of cells with clear cytoplasm.
	Small cell				Poorly differentiated with small tumor cells Focal squamous differentiation. Lacks the characteristic nuclear features of small cell carcinoma. Focal intercellular bridges or keratinization.
	Basaloid				Prominent peripheral palisading of nuclei. Poorly differentiated Carcinomas with an extensive basaloid pattern but lacking squamous differentiation
Small cell carcinoma	Combined small cell carcinoma
Adeno carcinoma	Adenocarcinoma, mixed sub type
	Acinar adenocarcinoma
	Papillary adenocarcinoma
	Bronchio-alveolar carcinoma	Non-mucinous
		Mucinous
		Mixed non-mucinous and mucinous or indeterminate
	Solid adenocarcinoma with mucin production	Fetal adenocarcinoma
		Mucinous (“colloid”) carcinoma
		Mucinous cystadenocarcinoma
		Signet ring adenocarcinoma
		Clear cell adenocarcinoma
Large cell carcinoma	Giant-cell carcinoma of the lung
	Basaloid large cell carcinoma of the lung
	Clear cell carcinoma of the lung
	Lymphoepithelioma-like carcinoma of the lung
	Large-cell lung carcinoma with rhabdoid phenotype
	Large cell neuroendocrine carcinoma of the lung
Sarcomatoid carcinoma	Pleomorphic carcinoma
	Carcinosarcoma
	Spindle cell carcinoma
	Giant cell carcinoma
	Pulmonary blastoma
Carcinoid tumour	Typical carcinoid
	Atypical carcinoid
Salivary gland tumours	Mucoepidermoid carcinoma
	Adenoid cystic carcinoma
	Epithelial-myoepithelial carcinoma
Preinvasive lesions	Squamous carcinoma in situ
	Atypical adenomatous hyperplasia
	Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
Mesenchymal tumors	Epithelioid haemangioendothelioma
	Angiosarcoma
	Pleuropulmonary blastoma
	Chondroma
	Congenital peribronchial myofibroblastic tumor
	Diffuse pulmonary lymphangiomatosis
	Inflammatory myofibroblastic tumor
	Synovial sarcoma Monophasic Biphasic
	Pulmonary artery sarcoma
	Pulmonary vein sarcoma

Benign lung tumor
			Risk factors	Gross pathology	Histopathology	Immunohistochemistry	Topography	Spread
Papilloma	Squamous cell papilloma	Exophytic	HPV 6 and 11	Cauliflower-like tan-white soft to semifirm excrescences protruding into bronchial lumens	Loose fibrovascular core Stratified squamous epithelium Acanthosis Wrinkled nuclei Binucleate forms and perinuclear halos Koilocytosis Dyskeratotic cells Large atypical cells Occasional mitotic figures	N/A	Endobronchial
		Inverted
	Glandular papilloma
	Mixed squamous cell and glandular papilloma
Adenomas	Alveolar adenoma
	Papillary adenoma
	Adenomas of the salivary gland type	Mucous gland adenoma
		Pleomorphic adenoma
	Mucinous cystadenoma
	Lymphoproliferative tumors	Marginal zone B-cell lymphoma of the MALT type
		Diffuse large B-cell lymphoma
		Lymphomatoid granulomatosis
		Langerhans cell histiocytosis
Miscellaneous tumors	Harmatoma
	Sclerosing hemangioma
	Clear cell tumor
	Germ cell tumors	Mature tratoma
		Immature teratoma
		Other germ cell tumours
	Intrapulmonary thymoma
	Melanoma
Metastatic tumors