Uncommon Lung Tumors:
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1 4th World Congress of Thoracic Imaging Uncommon Lung Tumors: Exhibit Category: Thoracic Neoplasms 1 Tae Jung Kim, 1 Boda Nam, 2 Joungho Han, 1 Kyung Soo Lee Department of 1 Radiology and 2 Pathology Samsung Medical Center Sungkyunkwan University School of Medicine
2 Financial Disclosures for All Authors All of the authors have read and approved this manuscript No conflict of interests to disclose and industry relationship No funding for this educational exhibit
3 Learning Objective/Outcomes To review the rare lung tumors based on the 2015 World Health Organization (WHO) classification of tumors of the lungs To illustrate the radiologic features of the rare lung tumors on CT and PET/CT To correlate radiologic features of the rare lung tumors with histologic and genetic features
4 2015 WHO Classification of Lung Tumors Different approach to lung adenocarcinomas as proposed by the 2011 IASLC/ATS/ERS classification Updates on other rare histologic subtypes of lung tumors changing the term sclerosing hemangioma to sclerosing pneumocytoma adding NUT carcinoma creating a group of PEComatous tumors adding myoepithelioma and myoepithelial carcinoma Other uncommon tumors: colloid adenocarcinoma, enteric adenocarcinoma, sarcomatoid carcinoma, intravascular lymphomatosis, etc.
5 Major changes in 2015 WHO classification of lung adenocarcinomas 1) Discontinuing the terms bronchioloalveolar carcinoma and mixed subtype adenocarcinoma 2) Adding Adenocarcinoma-in-situ to the list of pre-invasive lesions 3) Introducing the concept of minimally-invasive adenocarcinoma 4) Classification of invasive adenocarcinomas based on the predominant subtype 5) Use of the term lepidic for non-invasive component in an invasive adenocarcinoma 6) Introduction of the term invasive mucinous adenocarcinoma for cases previously classified as mucinous bronchioloalveolar carcinoma; 7) Discontinuing the use of clear cell and signet ring cell adenocarcinoma subtypes 8) Discontinuing the term mucinous cystadenocarcinoma and including them in colloid adenocarcinoma.
6 Epithelial tumors CONTENTS Adenocarcinoma: colloid, fetal, enteric Sarcomatoid carcinomas: pleomorphic, spindle cell, giant cell, carcinosarcoma Unclassified: Lymphoepithelioma-like carcinoma Salivary gland type tumors: epithelial-myoepithelia carcinoma Adenomas: sclerosing pneumocytoma Papillomas: glandular papilloma Mesenchymal tumors PEComatous tumors: lymphangioleiomyomatosis, PEComa Diffuse pulmonary lymphangiomatosis Inflammatory myofibroblastic tumor Epithelioid hemangioendothelioma Synovial sarcoma Pulmonary artery intimal sarcoma Lymphohistiocytic tumors MALT lymphoma Intravascular large B cell lymphoma Pulmonary Langerhans cell histiocytosis
7 I. Epithelial tumors - Adenocarcinoma Colloid adenocarcinoma 1/2 M/74 non-smoker HU: 5 SUVmax: 1.5 Colloid adenocarcinoma has abundant extracellular mucin, which corresponds to homogeneous lowattenuation on contrast CT and low SUV on FDG-PET. Gross specimen shows soft, gelatinous, wellcircumscribed nodule (bottom left). Note floating tumor cells in the mucin (arrows in bottom center).
8 I. Epithelial tumors - Adenocarcinoma Colloid adenocarcinoma 2/2 M/55 HU: 5 SUVmax: 1.5 CT shows well-circumscribed solid mass with lobulated contour and poor contrastenhancement, which is correlated with abundant extracellular mucin. Low FDG-avidity is noted on PET/CT. Histology shows abundant extracellular mucin (arrows) with floating tumor cells WHO classification discontinues the term mucinous cystadenocarcinoma and include them in colloid adenocarcinoma.
9 I. Epithelial tumors - Adenocarcinoma F/70 Fetal adenocarcinoma Fetal adenocarcinoma with fetal pseudoglandular and canalicular period. Fetal adenocarcinoma is an adenocarcinoma resembling fetal lung (bottom right). The lesions usually present as a solitary, well-demarcated solid mass with variable contrast-enhancement on CT.
10 I. Epithelial tumors - Adenocarcinoma Enteric adenocarcinoma M/60 Enteric adenocarcinoma strongly resembles to colorectal adenocarcinomas, and the diagnosis of enteric adenocarcinoma needs exclusion of enteric primary in the GI tract. IHC profile: positive for enteric markers (CDX-2, MUC2 and CK20) as well as lung markers (CK7 and TTF-1, etc).
11 I. Epithelial tumors Pleomorphic carcinoma M/55, 50py smoker Pleomorphic carcinoma (PC) is a poorly differentiated NSCLC that contains more than 10% spindle and/or giant cells or a carcinoma consisting only spindle or giant cells. There is strong association with smoking. This tumor shows very aggressive behavior and early postoperative recurrence. Imaging: PC typically presents as a large necrotic mass (arrows) in upper lobe with chest wall invasion. Histology: Spindle cell and giant cell tumors with some adenocarcinoma components (arrowheads)
12 I. Epithelial tumors others and unclassified carcinomas Spindle cell carcinoma Spindle cell carcinoma is a subtype of sarcomatoid Preoperative carcinoma and consists Postop. of an 6 almost months pure FU populations of epithelial spindle cells, with no differentiated carcinomatous elements. Imaging: This tumor presents as a large peripheral mass, usually in upper lobes, showing central low attenuation (arrowhead), strong FDG uptake on PET, and frequently invasion to adjacent pleura. Spindle cell carcinomas are very aggressive tumors; distant metastases including unusual locations (arrow) (e.g: GI tract) are common.
13 I. Epithelial tumors others and unclassified carcinomas Lymphoepithelioma-like carcinoma M/52 Lymphoepithelioma-like carcinoma is a rare and distinctive tumor characterized by poorly differentiated HU: 5 morphology admixed with marked lymphocyte infiltrate and the presence of EBV in the nuclei of neoplastic cells. It is rare (0.9% of all lung cancer) and more common in South-East Asia. It affects non-smoking, young patients, and mostly women. Imaging and Histology: As we can see from the pushing border (arrows) of the tumor, this tumor is expected to present as a well-defined solid mass on CT. Lymphoepithelioma-like carcinoma is characterized by a syncytial growth pattern, large vesicular nuclei, and heavy lymphocyte infiltration (right bottom).
14 I. Epithelial tumors Salivary gland-type tumors Epithelial-myoepithelial carcinoma M/74 50py smoker M/57 HU: 5 Epithelial-myoepithelial carcinoma is a low-grade malignant epithelial tumor with biphasic morphology, inner layer F/63 of duct-like structures (arrowheads) and surrounding layer of myoepithelial cells. This tumor typically presents as an central endobronchial mass (arrows). Prognosis is usually excellent after curative resection.
15 I. Epithelial tumors Adenoma F/54 Sclerosing pneumocytoma HU: 5 papillary hemorrhage SUVmax: 1.5 Sclerosing pneumocytoma (SP) is a tumor of pneumocyte origin with a combination of histologic findings, including solid, papillary, sclerotic and hemorrhagic regions. It has a striking female predominance and is more common in Asian populations. Imaging and histology: SP typically presents as a solitary well-defined mass with marked contrastenhancement corresponding to the area of solid or papillary component. Sharply marginated lowattenuation corresponds to the area of hemorrhagic region (arrows). Several microscopic patterns can be seen in a single lesion. Papillary component (left) and hemorrhagic region (right) are clearly visible on both gross and low-power microscopic examination.
16 I. Epithelial tumors Papilloma Glandular papilloma Glandular papilloma (GP) is a benign papillary tumor line by ciliated or non-ciliated columnar cells, with varying numbers of M/74 cuboidal and goblet cells. GP has excellent prognosis and malignant transformation has not been reported. Imaging and Histology: Most GP present as an endobronchial lesion, but it GP may be incidentally detected as an SPN on screening CT. FDG avidity has been reported. Macroscopy shows central dilated bronchus (arrow) suggesting the bronchial origin of the tumor. Uniform columnar cells are admixed with mucinous cells. HU: 5
17 II. Mesenchymal Tumors PEComatous tumors M/72 PEComa PEComatous tumors arise from Perivascular Epithelial Cells and can present in the lungs in following forms: 1) lymphangioleiomyomatosis (LAM); 2) PEComa; 3) PEComatosis with overlapping features between LAM and PEComa. CT: Localized PEComas usually present as well circumscribed peripheral nodule/mass ranging 2-6cm. Note dense calcification (arrows) Pathology: PEComas comprise rounded or oval cells with distinct borders and abundant clear or eosinophilic cytoplasm (arrows).
18 II. Mesenchymal Tumors PEComatous tumors Lymphangioleiomyomatosis F/47 CT and histology: Multiple thin-walled cysts (LAM, red boxes) are randomly distributed in both lungs. Small solid nodules (arrows and blue box) are multifocal micronodular pneumocyte hyperplasias (MMPHs), which are often accompanied by tuberous sclerosis complex.
19 II. Mesenchymal Tumors Diffuse pulmonary lymphangiomatosis M/74 50py smoker M/19 HU: 5 Diffuse pulmonary lymphangiomatosis is a diffuse proliferation of lymphatic spaces and smooth muscle along otherwise normal lymphatic vessels of the lungs, pleura and mediastinum It is typically diagnosed shortly after birth or during childhood or young adulthood, with typically worsening dyspnea or chylous effusion. Prognosis is poor and lung transplantation is considered the last treatment. Imaging: CXR shows diffuse increased interstitial markings and pleural effusion (left). CT shows diffuse and smooth thickening of interlobular septa and peribronchovascular bundles, mediastinal soft tissue infiltration and pleural effusion.
20 II. Mesenchymal Tumors Inflammatory myofibroblastic tumor F/18 Inflammatory myofibroblastic tumor (IMT) is a distinctive lesion composed of myofibroblastic spindle cells accompanied by an inflammatory infiltrate usually composed of plasma cells and lymphocyte. ALK rearrangement is common in young adults but very uncommon in old adults. CT: IMT usually present as a peripheral well-circumscribed mass; irregular nodule or consolidation patterns are also reported. IMT shows variable FDG uptake. Histology: Microscopic examination shows spindle cells with minimal cytologic atypia admixed with inflammatory infiltrate composed of mainly lymphocytes and plasma cells (middle). ALK- IHC shows strong positivity, especially in the spindle cells (right).
21 II. Mesenchymal Tumors Epithelioid hemangioendothelioma Epithelioid hemangioendothelioma (EHE) is a low- to intermediate grade malignant vascular tumor seen most commonly in young female adults (60-80%). Lung involvement alone accounts for 12% and lung and liver involvement accounts for 18% of EHE. CT: EHE presents in the thorax Pattern in following 1: Multiple forms: nodular 1) multiple nodular; 2) reticulonodular Pattern 2: Reticulonodular (interstitial); 3) diffuse pleural thickening (mimicking malignant mesothelioma); 4) peripheral mass with diffuse pleural thickening (mimicking lung cancer with pleural seeding). Histology: It consists of polypoid or nodular aggregates of hyalinized eosinophilic stroma with a thin rim of plump endothelial cells. Pattern 3: Diffuse pleural thickening Pattern 4: Mimicking lung cancer with seeding
22 II. Mesenchymal Tumors Synovial sarcoma F/47 CT: homogeneous contrast-enhancement, often pleural based without bone destruction, chest wall invasion or calcification. Pathology: Synovial sarcoma is a soft tissue sarcoma with variable mesenchymal and epithelial differentiation. Biphasic pattern (small round cell and spindle cell) is present (middle). At least one epithelial marker and cytokeratin should be positive, with co-expression of vimentin or SMA. TLE-1 (upper right) is another specific marker for synovial sarcoma.
23 II. Mesenchymal Tumors Pulmonary artery intimal sarcoma M/64 SUVmax: 1.5 Pulmonary artery intimal sarcoma originates from the arterial intima of elastic pulmonary arteries. Imaging: PA intimal sarcoma present as a intraluminal mass with filling defects. Extravascular extension into lung or mediastinum can be a diagnostic finding from pulmonary thromboembolism. PA intimal sarcoma may present as a large necrotic mass (arrow) mimicking NSCLC. Histology: Gross and low-power specimen demonstrate large necrotic intraluminal mass. Arrow: intraluminal thrombus; Arrowheads: intraluminal mass.
24 III. Lymphohistiocytic tumors MALT lymphoma 1/2 F/52 HU: 5 SUVmax: 1.5 Pulmonary MALT lymphoma (extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, BALT lymphoma) is thought to arise in acquired MALT secondary to inflammatory or autoimmune processes. Imaging: CT: 1) single or multiple nodular or consolidative (most common); 2) bronchiectasis and bronchiolitis; 3) diffuse interstitial lung disease patterns. FDG PET: variable FDG uptake Pathology: MALY lymphoma generally appears as a diffuse infiltration of small lymphoid cells, which surround lymphoid follicles.
25 III. Lymphohistiocytic tumors MALT lymphoma 2/2 M/38 HU: 5 SUVmax: 1.5 MALT lymphoma: multi-nodular consolidation type CT: Multiple ill-defined nodular lesions with ground-glass opacity and air-bronchogram (arrow). Histology: Monotonous small lymphoid cells track along the bronchovascular bundles and interlobular septa at the periphery of the mass, with increased filling and destruction of alveolar parenchymal toward their center. Note the intact airway (arrow), which is correlated with air-bronchogram on CT.
26 III. Lymphohistiocytic tumors Intravascular lymphomatosis M/74 50py smoker M/62 SUVmax: 1.5 Intravascular lymphomatosis is a rare aggressive extranodal diffuse large B-cell lymphoma, characterized by the presence of lymphoma cells within small vessels, particularly capillaries. Dyspnea and B symptoms are almost always present. Imaging: Diffuse ground-glass opacity and centrilobular nodules are seen but CT may also be normal. Diffuse pulmonary FDG uptake on PET may be helpful if CT is normal. Pathology: Lymphoma cells are identified within the lumens of small arteries, veins and capillaries (arrows), with no involvement of the alveolar spaces.
27 III. Lymphohistiocytic tumors Pulmonary Langerhans cell histiocytosis M/32 S 100 stain PLCH is caused by a proliferation of Langerhans cells with associated interstitial changes. Smoking is a strong risk factor (95%), and 15% of PLCH have extrapulmonary involvement. CT: irregular nodules with or without cavitation, evolving into cystic change with upper lung predilection. Pathology: Cellular proliferation of Langerhans cells along small airways. As the lesions enlarge, rounded nodules develop and bronchiolocentricity is not easy to discern. In end state, the nodules undergo a natural history progression from cellular lesions to fibrotic scars.
28 SUMMARY 2015 WHO classification of lung tumors different approaches to lung adenocarcinomas as proposed by 2011 IASLC/ATS/ERS classification Updates on other rare histologic subtypes of lung tumors - changing sclerosing hemangioma to sclerosing pneumocytoma - adding NUT carcinoma, myoepithelioma and myoepithelial carcinoma - creating a group of PEComatous tumors - Other uncommon tumors: colloid, enteric, fetal adenocarcinoma, sarcomatoid carcinoma, intravascular lymphomatosis, etc. Radiologic-pathologic-genetic correlation helps to understand the pathophysiology of these rare lung tumors
29 References 1. Travis WD, Brambilla E, Nicholson A et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol 2015; 10: Travis WD, Brambilla E, Burke AP, et al. WHO Classification of Tumors of the Lung, Pleural, Thymus and Heart. 4 TH edition. Lyon, 2015, IARC 2. Lee KH, Song KS, Kwon Y, Lee I, Lee JS, Lim TH. Mesenchymal tumors of the thorax: CT findings and pathological features. Clin Radiol. 2003; 58: Giménez A, Franquet T, Prats R, Estrada P, Villalba J, Bagué S. Unusual primary lung tumors: a radiologic-pathologic overview. RadioGraphics. 2002; 22: Yoon YC, Lee KS, Kim TS, Seo JB, Han J. Benign bronchopulmonary tumors: radiologic and pathologic findings. J Comput Assist Tomogr. 2002; 26: Chong S, Lee KS, Chung MJ, Han J, Kwon OJ, Kim TS. Neuroendocrine tumors of the lung: clinical, pathologic and imaging findings. RadioGraphics 2006; 26: Im JG, Kim WH, Han MC, et al. Sclerosing hemangiomas of the lung and interlobar fissures: CT findings. J Comput Assist Tomogr 1994; 18: Kim TH, Kim SJ, Ryu YH, et al. Pleomorphic carcinoma of lung: comparison of CT features and pathologic findings. Radiology 2004; 232: Kim TS, Han J, Lee KS, et al. CT findings of surgically resected pleomorphic carcinoma of the lung in 30 patients. AJR Am J Roentgenol 2005; 185:
30 Contact information: Tae Jung Kim Department of Radiology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea Tel) FAX) )
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