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Lung Masses of Unusual Histologies Mimicking Malignancy: Flurodeoxyglucose Positron Emission Tomography-Computed Tomography Appearance
Address for correspondence: Dr. Nilendu C Purandare, Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra, India. E-mail: nilpurandare@gmail.com
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This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
Abstract
18F flurodeoxyglucose positron emission tomography-computed tomography (18F FDG PET-CT) is widely used in the evaluation of patients with lung mass suspicious for malignancy. In addition to malignancy, a variety of benign neoplasms and inflammatory lesions can arise in the lungs, many of which show increased FDG concentration, thereby mimicking malignancy. Awareness of the common mimics of lung cancer and a thorough understanding of their key imaging characteristics on CT as well as FDG PET is helpful in narrowing the differential diagnosis, eventually leading to appropriate therapy. In this article, we enlist these mimics and discuss their metabolic and morphologic characteristics and provide a pathophysiological basis for their FDG uptake.
Keywords
18F flurodeoxyglucose positron emission tomography-computed tomography
lung mass
mimicking malignancy
unusual histologies
Introduction
18F flurodeoxyglucose positron emission tomography-computed tomography (18F FDG PET-CT) is an established modality in the evaluation of lung masses, especially in patients with suspected carcinoma lung.[1] A variety of benign neoplasms and inflammatory lesions can arise in the lungs, many of which show increased FDG concentration, thereby mimicking malignancy. In this article, we enlist these mimics [Table 1] and discuss their metabolic and morphologic characteristics and provide a pathophysiological basis for their FDG uptake.
| FDG avid | FDG nonavid/low grade avid |
|---|---|
| Tuberculosis | Pulmonary sequestration |
| Organizing pneumonia | Schwannoma |
| Sarcoidosis | Hamartoma |
| Aspergillosis | Solitary fibrous tumor |
| Mucormycosis | Benign PEComa |
| Wegener’s granulomatosis | Pleomorphic adenoma |
| Inflammatory myofibroblastic tumor | Carcinoid |
| Malignant PEComa | |
| Castleman disease |
PEComa: Perivascular epitheliod cell tumor, FDG: Flurodeoxyglucose
Tuberculosis
Tuberculosis is a chronic granulomatous infection caused by Mycobacterium tuberculosis. Common patterns described on CT scan are tree in bud opacities, cavitatory lesions, and nodules with a central hypoenhancing necrotic area with peripheral enhancing rim of granulomatous inflammatory zone.[2] Active tuberculous lesions involving lung parenchyma usually show high FDG uptake [Figure 1]. It is due to the high glycolytic rate of a large number of activated macrophages seen in these lesions.[3] Thick-walled cavities with high FDG uptake mimicking squamous carcinoma are also seen in pulmonary tuberculosis, making a diagnosis of lung cancer difficult.
Organizing Pneumonia
Focal organizing pneumonia is considered as unresolving pneumonia or pneumonia with delayed resolution. It consists of a granulation tissue with chronic inflammatory cell infiltrate. On CT, it appears as an area of consolidation or a nodule with spindle-shaped margins and satellite nodules.[4] Sometimes, it appears as a nodule or mass with spiculated margins and central necrosis, resembling malignant lung pathology. As these lesions contain inflammatory cells with upregulated glucose metabolism, they show FDG uptake [Figure 2].[5]
Sarcoidosis
Sarcoidosis is a multisystem disease of unknown etiology which can affect any organ in the body. Mediastinal and hilar lymph node involvement is the most common finding, followed by lung parenchymal involvement. Typical CT findings of lung involvement are bilateral perihilar opacities, micronodules showing peribronchovascular distribution, and fibrotic changes. Few cases may show atypical manifestations such as miliary opacities, mass-like or alveolar opacities, honeycomb-like cysts, tracheobronchial involvement, and pleural disease.[6] On FDG PET, active sarcoid lesions show intense uptake and a nodule or mass-like opacity can resemble malignancy [Figure 3]. Noncaseating granulomas and inflammatory cells including activated macrophages, lymphocytes, and neutrophils are responsible for the accumulation of FDG.[7]
Aspergillosis
Aspergillosis is a mycotic infection caused by Aspergillus fungus. It typically affects weakened or damaged lungs or patients with immunodeficiency. Aspergillus can colonize a preexisting cavity and grow within the cavity to form an aspergilloma. The mass within the cavity is mobile and lies on the dependent part of the cavity, thus helping to distinguish from a cavitating neoplasm.[8] On CT, it appears as a nodular area or mass-like consolidation with radiolucency within (crescent sign) or surrounded by a zone of low attenuation (halo sign). These lesions contain inflammatory cells and granulation tissue with upregulated glucose metabolism and show good FDG concentration [Figure 4].[9]
Mucormycosis
Mucormycosis is an opportunistic fungal infection caused by the Rhizopus genus. Pulmonary mucormycosis is one of the common clinical manifestations of mucormycosis infection. On CT, it may appear as an area of consolidation, nodule, or mass lesion with halo sign or reverse halo sign. Central necrosis with development of air crescent sign is seen in later stages.[10] These lesions are positive on FDG PET as they contains activated inflammatory cells and granulation tissue [Figure 5].[11]
Wegener Granulomatosis
Wegener granulomatosis is an uncommon chronic granulomatous necrotizing vasculitis that involves mainly small- and medium-sized vessels. Pulmonary involvement often predominates and the common CT findings include waxing and waning parenchymal nodules and mass lesions. Other findings include consolidation, cavitary lesions, ground-glass opacities, circumferential tracheobronchial thickening, and pleural effusion.[12] Halo sign and reverse halo sign may also occur in lesions with associated hemorrhage.[13] Wegener's granulomatosis nodules and cavities may be easily mistaken for lung primary or metastases. Because it is an inflammatory condition, active lesions show increased FDG uptake as they are composed of acute and chronic inflammatory cells [Figure 6].[14]
Pulmonary Sequestration
Pulmonary sequestration (PS) is a rare congenital malformation in the group of bronchopulmonary foregut malformation. PS is an island of nonfunctioning lung tissue commonly seen on CT in posteromedial portion of lower lobes. It lacks direct connection to the normal tracheobronchial tree or pulmonary artery and has an independent systemic arterial vascular supply often identified on CT.[15] Two forms of PS are described based on their relation to pleura, namely intralobar sequestration and extralobar sequestration. CT typically shows a heterogeneous or homogeneous soft-tissue mass which shows partial or heterogeneous contrast enhancement. FDG PET shows no significant tracer uptake in the soft-tissue mass unless it is complicated by infection [Figure 7].[16]
Schwannoma
Schwannoma is a benign mesenchymal tumor arising from Schwann cells. Schwannomas most commonly affect the posterior mediastinum and present as paravertebral mass with or without bone erosion. Rarely, schwannomas can present as well-circumscribed endobronchial lesions.[17] Contrast CT shows homogeneous enhancement in small schwannomas and more heterogeneous enhancement when there is associated cystic degeneration or hemorrhage.[18] Schwannomas show variable FDG uptake and sometimes show intense uptake as the glucose transporter (GLUT) expression varies widely.[19] Because of this, it is difficult to distinguish between a schwannoma and a malignant tumor precisely by imaging alone [Figure 8].
Hamartoma
Hamartoma is a benign mesenchymal neoplasm composed of cartilage, smooth muscle, connective tissue, and fat, with areas of calcification. Hamartoma is the most common benign tumor of the lung and accounts for 77% of all cases.[20] On CT scan, it appears as a well-defined, smooth, round, or lobulated nodule or mass lesion, with areas of fatty attenuation. Popcorn calcification or central calcification is seen in about 25% of cases.[20] The presence of intralesional fat and calcification may make the diagnosis of hamartoma easy, but if not identified, it becomes difficult to distinguish from lung cancer or other benign lesions. They usually show low-grade FDG uptake which corresponds to their slow-growing behavior. The mechanism of FDG uptake in hamartomas remains unclear [Figure 9].[21]
Inflammatory Myofibroblastic Tumor
Inflammatory myofibroblastic tumor of lung is a pseudotumor composed of spindle myofibroblasts on a background of collagen and inflammatory cells. Some consider it as a locally invasive low-grade neoplasm and recommends complete surgical excision for definite diagnosis and cure.[22] On CT, it appears as an enhancing, well-defined round/lobulated/spiculated nodule or mass in the peripheral lung parenchyma or occasionally as a well-defined endobronchial lesion. On FDG PET, these tumors usually show very high uptake, which further makes their differentiation from lung cancer difficult.[23] High FDG uptake in these tumors is probably due to the associated intense inflammatory cell infiltration seen [Figure 10].
Solitary Fibrous Tumor
Solitary fibrous tumor of the lung is a benign or malignant spindle cell neoplasm of fibroblastic or myofibroblastic origin that commonly arises in the pleura. On CT, small tumors appear as hyperdense, well-defined mass lesions forming obtuse angles with the pleura and show homogeneous enhancement. Large tumors may undergo necrosis, hemorrhage, cystic degeneration, and calcification and appear heterogeneous with similar enhancement pattern.[24] On FDG PET, these tumors usually show heterogeneous and low-grade uptake similar to mediastinal blood pool [Figure 11]. Few studies have shown that the uptake patterns vary in benign and malignant fibrous tumors and thus aid in the differentiation.[25]
Perivascular Epithelioid Cell Tumor
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms composed of epithelioid or spindle cells in perivascular location. They are frequently benign and are cured with surgical resection. However, malignant cases are reported, which show local recurrence or distant metastases.[26] They are also referred as clear cell sugar tumors of the lung and usually present as a solitary peripheral lung nodule that is well defined spherically with no evidence of calcification or cavitation. These lesions have good vascular supply and enhance brilliantly on contrast administration.[27] Benign PEComas show low-grade FDG uptake. Malignant PEComas have upregulation of mTOR pathway which controls multiple cellular processes including GLUT-1, and these lesions show high FDG uptake [Figure 12].[28]
Pleomorphic Adenoma of Lung
Pleomorphic adenoma is a common benign neoplasm occurring in the salivary glands. It rarely arises in the trachea and is more uncommon to occur in lung parenchyma. Primary pulmonary pleomorphic adenoma has similar histopathologic features as salivary gland pleomorphic adenomas.[29] The imaging characteristics of primary pulmonary pleomorphic adenomas are not adequately described and on imaging, these tumors may be confused with other primary or metastatic lung tumors. On CT scan, it may appear as homogeneous, circular, soft-tissue density nodule or mass lesions with smooth margins in the peripheral lung parenchyma.[30] On FDG PET, these lesions show low-grade FDG uptake similar to other benign neoplasms [Figure 13].[29]
Carcinoid
Carcinoid tumor arises from the neuroendocrine cells of the bronchial mucosa. Endobronchial tumors are a more common presentation compared to parenchymal nodules.[31] On CT, they appear as spherical or ovoid, well-defined, homogeneous nodules or mass lesions. Narrowing or obstruction of the bronchus can occur resulting in atelectasis, bronchiectasis, or obstructive pneumonia. On contrast administration, these lesions shows good enhancement as they have abundant vascular supply. Typical carcinoids which are more commonly seen compared to the atypical variant are more indolent and have low glucose turnover and usually show less FDG uptake.[32] However, these tumors express somatostatin receptors, and radiolabeled somatostatin analog such as 68 gallium DOTANOC shows excellent concentration in these tumors, which aids in the diagnosis [Figure 14].[33]
Castleman Disease
Castleman disease (CD), also known as angiofollicular hyperplasia or giant lymph node hyperplasia, is a benign lymphoproliferative disorder. It can be clinicoradiogically classified as unicentric (unifocal) or multicentric (multifocal). Approximately 70% of CD occurs in the thorax and commonly manifests as a mediastinal or hilar mass. In unicentric disease, CT generally shows well-circumscribed homogeneous mass lesions.[34] Interleukin-6-induced inflammation is the major pathophysiological mechanism for CD and on FDG PET-CT, these lesions show moderately increased uptake.[35] A hilar soft-tissue mass with FDG uptake can mimic bronchogenic carcinoma [Figure 15].
Conclusion
Benign and low-grade malignant tumors may pose a diagnostic challenge on imaging. The morphologic and metabolic characteristics of these tumors often show significant overlap with malignant lesions. Awareness of the common mimics of lung cancer and a thorough understanding of their key imaging characteristics on CT as well as FDG PET is helpful in narrowing the differential diagnosis, eventually leading to prompt and appropriate treatment.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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