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World Journal of W J R Radiology Online Submissions: http://www.wjgnet.com/1949-8470office World J Radiol 2011 December 28; 3(12): 279-288 [email protected] ISSN 1949-8470 (online) doi:10.4329/wjr.v3.i12.279 © 2011 Baishideng. All rights reserved.

EDITORIAL

Chest neoplasms with infectious etiologies

Carlos S Restrepo, Melissa M Chen, Santiago Martinez-Jimenez, Jorge Carrillo, Catalina Restrepo

Carlos S Restrepo, Melissa M Chen, Santiago Martinez- Peer reviewer: Patrick K Ha, MD, Assistant Professor, Johns Jimenez, Jorge Carrillo, Catalina Restrepo, Department of Hopkins Department of Otolaryngology, Johns Hopkins Head Radiology, The University of Texas Health Science Center at San and Neck Surgery at GBMC, 1550 Orleans Street, David H Koch Antonio, Mail Code 7800, 7703 Floyd Curl Drive, San Antonio, Cancer Research Building, Room 5M06, Baltimore, MD 21231, TX 78229, United States United States Author contributions: Chen MM, Restrep CS reviewed and summarized the literature that provided the basis of the manu- Restrepo CS, Chen MM, Martinez-Jimenez S, Carrillo J, Re- script. Martinez-Jimenez C, Carrillo J and Restrepo C contributed strepo C. Chest neoplasms with infectious etiologies. World J to the conceptual design of the manuscript and data interpretation. Radiol 2011; 3(12): 279-288 Available from: URL: http://www. Correspondence to:�� Carlos S Restrepo, M�D��, Assistant �P��ro- wjgnet.com/1949-8470/full/v3/i12/279.htm DOI: http://dx.doi. fessor, Department of Radiology, The University of Texas Health org/10.4329/wjr.v3.i12.279 Science Center at San Antonio, Mail Code 7800, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States. [email protected] Telephone: +1-210-5676488 Fax: +1-210-5676418 Received: May 4, 2011 Revised: September 19, 2011 Accepted: October 11, 2011 INTRODUCTION Published online: December 28, 2011 Approximately 12% of cancers worldwide can be linked to a viral infection[1]. Oncogenic viruses that have been identified include Epstein-Barr virus (EBV), human herpes virus 8 (HHV8), human papillomavirus (HPV), Sim- Abstract ian virus 40 (SV-40), Human T-lymphotropic virus, and A wide spectrum of thoracic tumors have known or sus- human immunodeficiency virus (HIV)[1,2]. Viruses can be pected viral etiologies. Oncogenic viruses can be classi- categorized into several families and sub-families accord- fied by the type of genomic material they contain. Neo- ing to the type of genomic material they contain (DNA plastic conditions found to have viral etiologies include or RNA), symmetry of the capsid, presence or absence post-transplant lymphoproliferative disease, lymphoid of an envelope, dimension, and the viral genome replica- granulomatosis, Kaposi’s sarcoma, Castleman’s disease, tion mechanisms. Tumor viruses belong to a number of recurrent respiratory papillomatosis, lung cancer, malig- families including the DNA virus families: Hepadnaviri- nant mesothelioma, leukemia and lymphomas. Viruses dae, Herpesviridae, and Papillomaviridae and the RNA involved in these conditions include Epstein-Barr virus, virus families: Retroviridae and Flaviviridae[3]. human herpes virus 8, human papillomavirus, Simian virus 40, human immunodeficiency virus, and Human This article focuses on thoracic tumors with viral T-lymphotropic virus. Imaging findings, epidemiology etiologies, which include post-transplant lymphoprolif- and mechanism of transmission for these diseases are erative disease, lymphomatoid granulomatosis, Kaposi’s reviewed in detail to gain a more thorough appreciation sarcoma (KS), Castleman’s disease, recurrent respiratory of disease pathophysiology for the chest radiologist. papillomatosis (RRP), lung cancer, malignant mesothelioma, leukemia and lymphomas. The participation of the © 2011 Baishideng. All rights reserved. viral infection in the pathogenesis of these tumors as well as their most common imaging findings will be discussed. Key words: Acquired immunodeficiency syndrome; Cas- tleman’s disease; Kaposi’s sarcoma; Thoracic imaging; Thoracic lymphoma; Thoracic malignancies; Malignant EBV mesothelioma EBV was first discovered in 1964 by Epstein and Barr

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Figure 1 Hodgkin’s lymphoma. A 23-year-old woman with a four-mo history of dry cough and chest pain. A: Chest X-ray shows mediastinal widening and upper lobe parenchymal opacities; B and C: Contrast-enhanced computed tomography confirms lymphadenopathy involving the mediastinum and infiltrative masses in the bilateral upper lobes; D: Photomicrograph (HE stain). Nodular sclerosing HL lymph node. Fibrous bands divide the lymphoid infiltrate into nodules and contain Hodgkin cells. from a cell line derived from Burkitt lymphoma (BL)[4]. being EBV positive. Similarly, the association between The virus is a DNA double-stranded virus which be- EBV and HL is even higher in patients with acquired longs to the γ herpesvirus subfamily. More than 95% of immunodeficiency syndrome (AIDS) in whom 95% are the healthy population worldwide carries the virus and EBV positive HL. The histology of these tumors also transmission usually occurs during childhood via saliva. has some distinctive features since HL positive for EBV Children under the age of 10 usually have an asymptom- is more often a mixed cellular type. The clinical presenta- atic primary infection. Primary infection occurring over tion also differs from that of the EBV negative counter- the age of 15 leads to the clinical syndrome of infectious part in that this form is more commonly seen in either mononucleosis in 30%-40% of cases[5]. children younger than 10 years of age or in adults older EBV infection develops when virions (the infective than 45 years old. Additionally, the prognosis of EBV form of a virus which consists of a DNA or RNA core positive HL in the elderly and immunocompromised is with a protein shell or capsid) transit across the epithelial poor, compared with that of patients with EBV negative cells in the oropharnynx to infect B cells in the mucosa. HL[8]. The virus has two phases of replication, a lytic and a la- HL is currently classified by two distinct types: nodu- tent cycle. The virus initiates a latent infection by shutting lar lymphocyte predominant HL and classical HL (CHL). down viral protein expression. It is this latent infectious The latter is further categorized into three subgroups: state that is responsible for malignant transformation[6]. nodular sclerosis, lymphocyte rich, and mixed cellularity The virus remains in the B cell memory pool, recirculat- (MCCHL)[9]. There is significant overlap in the imaging ing, and is found predominantly in the blood and pharyn- manifestations of the different types and subtypes of geal lymphoid tissue[3,7]. lymphomas, which in the chest may involve the medias- EBV is known to be associated with several different tinum, lung, pleura and chest wall, but some differences malignancies in humans, including Hodgkin’s lymphoma should be highlighted. First, primary pulmonary lym- (HL), BL, nasopharyngeal carcinoma, and post-transplant phoma is rare in Hodgkin’s disease. Pulmonary involve- proliferative disease (PTLD), in which the malignant cells ment in HL is more commonly seen either in advanced are characterized by unique viral and cellular phenotypes, stages (secondary involvement) or in recurrent disease[10]. as well as unique viral antigen expression[8]. Second, even though HL is the most common lymphoma More than 30% of HL cases are EBV-associated, with presenting with mediastinal lymphadenopathy, MCCHL, the clonal virus localized inside the malignant cells. In de- the type most commonly seen in association with EBV veloping countries this number is higher with 90% of HL involvement, typically spares the thymus gland and medi-

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Figure 2 Burkitt lymphoma in a 38-year-old male with a left axilla mass. Contrast-enhanced computed tomography, axial (A) and coronal (B) images demonstrates a bulky soft tissue mass involving the axilla, subpectoral and subscapular spaces.

also been implicated in the pathophysiology of non- HLs in AIDS, typically B-cell lymphomas. AIDS-related lymphomas remain an important cause of morbidity and mortality in HIV-infected individuals, often occurring in extranodal locations (e.g. bone marrow, brain, viscera) and have an aggressive clinical course[16]. On imaging examina- tions the extranodal location of these tumors manifest as pleural effusion, interstitial and alveolar lung disease, and pulmonary nodules[17]. PTLD is made up of a heterogeneous group of EBV diseases with malignant lymphoproliferation occurring after hematopoietic or solid organ transplantation secondary to iatrogenic suppression of T-cell function[18]. EBV- Figure 3 Post-transplant proliferative disease in a 50-year-old male post- infected B cells in the germinal centers, which should be right lung transplant. Contrast-enhanced computed tomography shows an destroyed, persist in the absence of cytotoxic T cells[6]. infiltrative right hilar mass surrounding the right lower lobe bronchus and involving the subcarinal region. Ipsilateral small pleural effusion is also noted. Approximately 2% of all allograft recipients are af- flicted with PTLD, and it is more likely to develop in patients who are seronegative for EBV before transplan- [9] astinum (Figure 1). tation. Onset of the disease can occur at variable inter- The association between EBV infection and BL var- vals with the mean at 2-5 mo after bone marrow, lung or ies depending on the subtype of the disease. The en- heart-lung transplantation and at a mean of 22-32 mo demic form (eBL) is associated with EBV infection in after kidney, or liver transplantation[19]. over 95% of cases. Only half of AIDS-related BLs are PTLD involvement of the lung is more common associated with this viral infection, while the sporadic after heart-lung transplantation than after liver or renal [11,12] form of (sBL) is rarely associated with it . Thoracic transplant. The most common intrathoracic findings of involvement in BL is less common than the more typi- PTLD include well-circumscribed, often bilateral periph- cal facial or abdominal disease, and is more commonly eral pulmonary nodules, patchy air space consolidation seen in HIV positive (10%) than in HIV negative (2%) and mediastinal and hilar lymphadenopathy[19]. Pleural- patients[13]. The most common thoracic manifestations based masses, chest wall masses, pleural and pericardial of BL include mediastinal mass and lymphadenopathy effusion, and thymic enlargement have also been report- followed by pleural and chest wall involvement. Isolated ed[20] (Figures 3 and 4). pleural effusion and pulmonary parenchymal disease are Positron Emission Tomography with Fluoro-2-deoxy- rare[14,15] (Figure 2). D-glucose (FDG-PET) has replaced gallium-67 scintig- Another infectious disease associated with BL is ma- raphy in the functional and metabolic imaging evaluation laria. It is currently thought that the association between of lymphomas. FDG-PET, in particular, is recommended malaria and BL arises from a combination of multiple before treatment in typically FDG avid lymphomas like factors including immunosuppression, B-cell activation diffuse large B cell lymphoma (DLBCL) and HL[21]. directly by the malarial parasite Plasmodium falciparum and FDG-PET has also proven useful for the diagnosis, stag- EBV, since the viral loads for EBV are higher in areas ening and therapy monitoring of PTLD both in infants demic for malaria[11]. and adult patients, revealing foci of increased uptake, not EBV and KS virus (KSV) in a complex interaction seen by other imaging techniques[22-24]. with the HIV, and the immunosuppression status have Lymphomatoid Granulomatosis is a B-cell lymphop-

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Figure 4 Post-right lung transplant post-transplant proliferative disease in a 68-year-old male with pulmonary fibrosis. Non-contrast computed tomography, axial (A) and sagittal images (B) demonstrates an irregular mass in the right lung involving the middle lobe and lower lobe extending across the major fissure.

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Figure 5 Lymphomatoid granulomatosis in a young adult male with acquired immunodeficiency syndrome. Initial chest computed tomography (CT) (A) demonstrates a round solid mass in the right lower lobe. After surgical resection follow-up CT (B) 4 mo later shows recurrent disease with new multiple nodules and cavitation in the right lower lobe. roliferative disease that is angiocentric and angiodestruc- KS patients without HIV[31]. HHV8 is a γ2-herpes virus tive. It is comprised of predominantly reactive T cells and and similar to EBV has two different life cycles: lytic and some neoplastic EBV-positive B cells. The pathogenesis latent. Viral proteins produced in both phases of viral of the disease is hypothesized to be similar to that of replication are responsible for oncogenesis[32]. PTLD, in which infected B cells proliferate in the absence The virus has been identified in association with KS, of an adequate number of cytotoxic T cells[25]. Malignant primary effusion lymphomas (PEL) and Multicentric transformation to lymphoma occurs in 12%-47% of pa- Castleman’s Disease[33]. Epidemiologically, the virus is tients with a mortality rate between 53% and 63.5%[26]. widespread in most of sub-Saharan Africa with 50% of The most common site of involvement for lympho- the population having antibodies to HHV8. It is also rela- matoid granulomatosis is the lung[27]. Imaging findings tively frequent in the Mediterranean region. In endemic include poorly marginated pulmonary nodules and lung countries, transmission of the virus occurs in childhood masses distributed along the bronchovascular bundle and from mother to child or among peers. In non-endemic interlobar septa[26]. On computed tomography (CT), the countries, HHV8 is a sexually transmitted disease[34]. nodular lesions may present with surrounding ground- PEL is a rare type of AIDS non-HL that predomi- glass density (halo sign) or central ground-glass sur- nantly grows in the pleural, pericardial and peritoneal rounded by a denser rim (the reverse halo sign)[28]. Rapid cavities. They are characterized clinically and on imaging progression, central necrosis and cavitation masquerad- examination by the presence of neoplastic effusions in ing as a lung abscess are other imaging features[29,30]. The complete absence of a contiguous solid mass, and are presence of migratory nodules in the lung parenchyma considered to develop from HHV8/KSV infection[35]. mimicking the imaging findings of pulmonary vasculitis KS is a low-grade mesenchymal tumor involving has also been reported[30] (Figure 5). blood and lymphatic vessels and is considered one of the major complications of AIDS. Four variants of KS are recognized: classic KS, endemic (African) KS, iatrogenic HHV8 (organ transplant-related) KS, and AIDS-related KS[36]. HHV8 or KS herpes virus was first isolated in a patient In two of the forms of KS (AIDS and iatrogenic), the with AIDS-associated KS and subsequently isolated in HHV8 causes a reactive polyclonal angioproliferative re-

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Figure 6 Kaposi sarcoma in a 37-year-old male with acquired immunodeficiency syndrome.Contrast enhanced computed tomography of the chest, mediastinal window (A) and lung window (B) images demonstrate innumerable peribronchovascular and peripheral pulmonary nodules throughout the bilateral lungs. Enhancing skin lesions and bilateral pleural effusion are also noted. sponse in the presence of host immunosuppression. The tures include fever, weight loss, respiratory symptoms such polyclonal cells become an oligoclonal cell population as dyspnea and cough, hepatomegaly and splenomegaly. which proliferates and undergoes a malignant transfor- Prognosis is poor with a median survival of 14 mo[40]. mation[37]. There is an increased risk of progression to large B-cell KS with pulmonary involvement is found in approxi- plasmablastic lymphoma and other lymphomas[33]. The mately 45% of patients with cutaneous AIDS-related most common location for the localized form of Castle- KS[37]. Pulmonary involvement in KS is usually secondary man’s disease, typically the hyaline vascular type, is in the to profound immunosuppression. Pulmonary KS was chest, where the characteristic imaging manifestation on found to be associated with a low CD4 cell count and CT is as a mediastinal or hilar mass, with diffuse homo- may be related to late presentation of HIV[38]. Following geneous enhancement after contrast injection[41]. Pleural, the introduction of highly active antiretroviral therapy pericardial and intrapulmonary forms of Castleman’s (HAART), thoracic disease has become less frequent[38]. disease, which are considered atypical presentations, have The most common presenting symptoms of pulmo- also been reported[42]. The multicentric type of Castle- nary KS are progressive dyspnea, non-productive cough man’s disease associated with AIDS, typically the plasma and fever. Other symptoms reported include pleural cell type, more commonly manifests as diffuse pulmonary effusion with chest pain, hypoxemia, and acute respira- involvement with acute reticular and nodular opacities tory failure requiring mechanical ventilation[37]. KS may in patients who also present mediastinal and peripheral involve the tracheobronchial tree, the lung parenchyma lymphadenopathy[43] (Figure 7). and pleura. Imaging manifestations in the chest include reticular and nodular opacities with a bronchovascular distribution, consolidation and adenopathies (Figure 6). HPV Enlarged lymph nodes in the chest and abdomen may HPV is a non-enveloped double-stranded DNA virus demonstrate significant contrast enhancement. Chest wall with more than 200 types isolated[44]. The virus infects involvement with skin lesions and subcutaneous nodules the basal layers of cutaneous and mucosal epithelium and or masses as well as osteolytic bone lesions involving the enters the cell via a receptor. E6 and E7 proteins are the sternum, ribs and spine are not uncommon[36]. portions of the viral genome that encode viral oncop- Castleman’s Disease was identified in a series of 13 roteins expressed in HPV-positive cancers. E6 interferes cases of localized mediastinal lymph node hyperplasia with p53, a tumor suppressor protein that regulates the resembling thymoma described in 1956 by Dr. Benjamin G1/S and G2/M cell cycle checkpoints. The main func- Castleman[39]. Histologically, the disease is characterized tion of E7 is the binding and degradation of the Rb fam- by expanded germinal centers with B-cell proliferation ily of proteins, which are the major regulators of the cell and vascular proliferation. Castleman’s disease can be cycle[45]. classified histologically as either hyaline-vascular or plas- RRP is a benign lesion commonly found in the larynx ma cell variant, and clinically as either localized or mul- with rare pulmonary involvement. The disease is diffi- ticentric[33]. Castleman’s disease in the HIV population is cult to treat because of frequent recurrence and spread usually of the multicentric and plasma cell variant[40]. throughout the respiratory tract. Ororespiratory exposure It is hypothesized that the active viral lytic replication during vaginal birth is thought to be the origin of the dis- cycle of HHV8 in lymphoid tissue can lead to Multicentric ease and is often associated with HPV types 6 and 11[46]. Castleman’s Disease[34]. HIV-related Multicentric Castle- HPV 11 is thought to be associated with more aggressive man’s disease is associated with Kaposi sarcoma. In fact, disease than HPV 6[47]. Pulmonary papillomatosis affect- in a clinical series, 71% of HIV positive patients with ing the bronchi and lung parenchyma occurs in 1.8% of Castleman’s Disease had Kaposi sarcoma[40]. Clinical fea- patients with RRP. Spread to the lower airways is usually

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Figure 7 Multicentric Castleman’s disease in a 40-year-old male with acquired immunodeficiency syndrome. Contrast-enhanced chest computed tomography, axial images at two different levels (A, B) reveal numerous enhancing abnormally enlarged lymph nodes in the axillae and mediastinum.

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Figure 8 Recurrent respiratory papillomatosis in a 27-year-old patient. Contrast-enhanced computed tomography, axial (A, B) and coronal (C) images. Numer- ous nodules and cystic lesion are seen in the bilateral lungs as well as a large lobulated mass partially obstructing the distal trachea (arrows). caused by tracheotomy performed in a child with laryn- It is believed that the most likely route of transmission of geal papillomatosis. Prognosis of pulmonary papilloma- SV-40 from monkey to human was through contaminated tosis is poor with a mortality rate of 57.1%[47]. Malignant polio vaccines produced between 1955 and 1978[53]. Ex- transformation in RRP can develop in 10% to 13% of pression of the oncogenes, large T antigen and small T affected patients[48,49]. antigen, causes a high rate of malignant transformation. Radiographic findings of RRP in the lungs include The large T antigen binds and inhibits p53 and pRB tu- bilateral, multiple, thin-walled cysts and nodular papillo- mor suppressor proteins. Human mesothelial cells are sus- mas with predominant lower lobe distribution. Cysts are ceptible to SV-40 infection and allow the virus to replicate usually less than 5 cm in size with air-fluid levels. Pulmo- without lysing leading to malignant transformation[2]. nary nodules are usually small, but occasionally may be Malignant mesothelioma is an aggressive tumor that as large as 3 cm in diameter (Figure 8). Chest CT can be arises from mesothelial cells lining the pleura, peritonea more sensitive in detecting small cysts and nodules. Vir- and pericardia. SV-40 DNA is found in up to 60% of tual bronchoscopy is a non-invasive technique that can mesothelioma[54]. There is solid evidence linking SV-40 be used to evaluate the tracheobronchial tree and reduces either alone or with asbestos exposure as a contributing the risk of downward spread of the virus that can occur factor in the malignant transformation of mesothelial during an endoscopic exam[46]. cells and subsequent development of malignant meso- The association of lung cancer and HPV was first theliomas[55,56]. Affected patients typically present with suggested by Syrjanen in 1979, who described epithelial pleural effusion associated with chest wall pain. Prog- changes in bronchial carcinomas similar to those of exo- nosis is poor with an average survival of just 12 mo phytic condylomas of the genital tract seen with HPV[50]. after diagnosis[54]. Characteristic imaging findings on CT It has been theorized that HPV can infect the lungs he- include unilateral pleural effusion; nodular pleural thick- matogenously from other sites such as the cervix[51]. HPV ening that may completely encase the affected lung; and types 16, 18, 31, 33 and 35 have been associated with lung pleural thickening extending into the pulmonary fissures cancer and both adenocarcinoma and squamous cell carci- (Figure 9). Given the association with asbestos exposure, noma have been seen with HPV infections[44]. HPV DNA calcified pleural plaques are seen in approximately in one has been identified in more than 20% of lung cancers[52]. fifth of affected patients[57].

SV-40 Human T-cell-lymphotropic virus 1 SV-40 is a double-stranded DNA polyoma monkey virus. Human T-cell-lymphotropic virus 1 (HTLV-1) is an RNA

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Figure 9 Malignant mesothelioma in a 60-year-old male with progressive chest pain. Contrast-enhanced computed tomography, axial (A) and sagittal (B) images show an irregular and slightly lobulated soft tissue density mass extensively involving the pleural surface of the left lung including the major fissure (arrows).

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Figure 10 Adult T cell leukemia in a 24-year-old male. Contrast-enhanced computed tomography at the level of the aortic arch (A) and mid-ventricular level (B) demonstrates a large mediastinal mass with extensive pericardial involvement and bilateral pleural effusions. virus belonging to the deltaretrovirus genus. It is the first peribronchovascular interstitium with predominant pe- human retrovirus linked to human malignancy[58]. It was ripheral distribution. Pleural effusion and enlarged lymph isolated from peripheral blood samples of a patient with nodes are less common findings[62] (Figure 10). cutaneous T-cell lymphoma in the 1980s[59]. HTLV-1 is endemic to Japan, South America, Africa and the Carib- bean[3]. Based on a number of studies, it appears that the HIV viral regulatory factors, TAX and HBZ, are the malignant Patients with HIV have an increased risk of develop- transforming factors. TAX modulates gene expression ing cancer compared to the general population. Defined and induces genomic instability. HBZ stimulates T-lym- by the Center for Disease Control (CDC, Atlanta GA, phocyte proliferation[58,60]. USA), some of the AIDS-defining malignancies include Adult T cell leukemia/lymphoma (ATLL) is a mature KS, non-HL and invasive cervical cancer. Some of the T cell neoplasm of post-thymic lymphocytes that has non-AIDS defining malignancies that patients with HIV been linked to HTLV-1. Although worldwide, 20 mil- have an increased risk of developing include: HL, leuke- lion people are infected with HTLV-1, it is estimated that mia, lung cancer, invasive anal carcinoma, and multiple only 2%-6% will develop ATLL. Patients with ATL have myeloma[63]. An increased risk of primary liver cancer atypical lymphoid cells with multilobulated nuclei[58]. ATL has also been reported[64]. The mechanisms for the de- is divided into 4 subcategories based on the diversity of velopment of these malignancies are multifactorial and clinical features and prognosis of patients: acute, lympho- include a complex interaction between the HIV and ma, chronic and smoldering. The acute form is aggressive other oncogenic viruses (e.g. EBV and HPV), immuno- with poor prognosis due to multidrug-resistant malignant suppression and dysregulation of the immune system cells. Chronic and smoldering types have an indolent and environmental factors[65]. course and do not require chemotherapy[61]. Thoracic While the incidence of KS has decreased with the ad- involvement in Adult T-cell leukemia and lymphoma is vent of HAART, HIV patients continue to be at risk for common, with abnormal imaging findings in two thirds non-HL[66]. The most common AIDS-related lymphomas of affected patients. The most common abnormalities on among patients include: DLBCL and Burkitt’s lymphoma, CT include ground-glass opacities and thickening of the representing 90% of all lymphomas. The pathogenesis of

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Figure 11 Non-Hodgkin lymphoma in two different patients with acquired immunodeficiency syndrome. A: Contrast-enhanced computed tomography (CT) at the level of the AP window demonstrates a large mediastinal mass with areas of cavitation with air-fluid levels (arrows); B: Contrast-enhanced CT reveals a large mediastinal mass with low-density foci consistent with tumoral necrosis. There is small left sided pleural effusion in both cases.

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Figure 12 Non-small cell lung cancer in a 39-year-old male with acquired immunodeficiency syndrome. Contrast enhanced chest CT. A: Mediastinum window, axial image at the level of the pulmonary arteries demonstrates a soft tissue density mass with air-bronchogram in the right lung; B: Lung window image at the same level shows the spiculated contour of the lung mass. these lymphomas include: HIV-induced immunosuppres- ity of these cancers (94%) are non-small cell lung can- sion, chronic antigenic stimulation, genetic abnormalities, cers with adenocarcinoma as the most common subtype cytokine release and dysregulation, dendritic cell impair- (34%). Mortality is high (97%) with a median survival of ment, and the role of EBV and HHV8[63]. 3 mo[70] (Figure 12). Compared to the general population with NHL, AIDS Marginal zone lymphomas, a subtype of B-cell non- patients with NHL tend to have advanced disease and Hodgkin lymphoma has also been associated with bacte- present with B symptoms. The AIDS patients also have rial infection (e.g. Helicobacter pylori, Campylobacter jejuni, extranodal disease including bone marrow involvement Borrelia burdoferi, and Chlamydia psittaci) and viral infection and have disease in unusual locations such as body cavi- (HIV, EBV and hepatitis C virus)[71]. ties, jaw, rectum, and soft tissues. In addition, patients have frequent plasmacellular differentiation and the disease is commonly associated with EBV and HHV8[63]. CONCLUSION The respiratory system is the most common extranodal A significant number of malignancies, many of which site (70%) involved in individuals with AIDS-related originate or manifest in the thoracic region, are known to NHL. Pleural effusion and mediastinal lymphadenopathy be associated with viral infections. The pathophysiology are the most common findings on CT (60%), followed by for the development of these neoplastic processes are pulmonary nodules in half of them, and lobar opacities extremely complex and in some cases not yet completely or consolidation in one fourth[67]. Cavitation of a lung understood. Multiple variables in addition to the initial vi- or mediastinal mass is not an uncommon imaging find- ral infection including immunosuppression and dysregu- ing[68,69] (Figure 11). lation of the immune system, co-infection with another Patients with HIV/AIDS also have an elevated risk virus, as well as genetic and environmental factors come for developing lung cancer. The incidence of HIV-related into play and interact. CT, with its capability for imaging lung cancer has significantly increased, independent of the lung, mediastinum, pleural and chest wall, remains the smoking history, after the introduction HAART from most common imaging modality used for the diagnosis, 0.8% (pre-HAART) to 6.7% (post-HAART). The major- staging and follow-up of these lesions.

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S- Editor Cheng JX L- Editor Webster JR E- Editor Zheng XM

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