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Radiographic and Pathologic Manifestations of Uncommon and Rare Pulmonary Lesions
Canadian Association of Radiologists Journal xx (2015) 1e11 www.carjonline.org
Thoracic and Cardiac Imaging / Imagerie cardiaque et imagerie thoracique
Radiographic and Pathologic Manifestations of Uncommon and Rare Pulmonary Lesions Kyle Pfeifer, MDa,*, Ali Mian, MDa, Adeniran Adebowale, MDb, Ahmed Alomari, MDb, Vivek Kalra, MDa, Elise Krejci, MDc, Myung Soo Shin, MD, DSca a
Department of Radiology, Yale New Haven Hospital, New Haven, Connecticut, USA Department of Pathology, Yale New Haven Hospital, New Haven, Connecticut, USA c Department of Pathology, Lawrence and Memorial Hospital, New London, Connecticut, USA b
Abstract Pulmonary opacities/nodules are common findings on computed tomography examinations, which may represent an underlying infections or malignancy. However, not every pulmonary nodule or opacity represents malignancy or infection. We present a pictorial essay illustrating common as well as obscure noninfectious, nonmalignant pulmonary lesions. Lesions discussed include organizing pneumonia, Langerhans cell histiocytosis, pulmonary amyloidosis, hyalinizing granuloma, tumourlet (benign localized neuroendocrine cell proliferations), atypical alveolar hyperplasia, inflammatory myofibroblastic tumour, papillary alveolar adenoma, plasma cell granuloma, juvenile xanthogranuloma, and sclerosing hemangiomas. We discuss the clinical presentation, prevalence, radiographic clues, pathology, and diagnostic pitfalls of these rare lesions. Resume Les examens de tomodensitometrie permettent souvent de detecter les opacites ou les nodules pulmonaires, signes d’une possible infection ou tumeur sous-jacente. Toutefois, la presence d’opacites ou de nodules ne signifie pas necessairement qu’il y a tumeur ou infection. Notre essai descriptif traite des lesions pulmonaires courantes, mais aussi des lesions non infectieuses et non cancereuses difficilement decelables. Nous y abordons entre autres la pneumopathie organisee, l’histiocytose des cellules de Langerhans, l’amylose pulmonaire, le granulome hyalinisant, la tumorlet (proliferation localisee de cellules neuroendocrines non cancereuses), l’hyperplasie alveolaire atypique, la tumeur myofibroblastique inflammatoire, l’adenome alveolaire papillaire, le granulome plasmocytaire, le xanthogranulome juvenile et les hemangiomes sclerosants. Nous discutons du tableau clinique, de la prevalence, des indices radiographiques, de la pathologie et des pieges diagnostiques de ces lesions rares. Ó 2015 Canadian Association of Radiologists. All rights reserved. Key Words: Atypical alveolar hyperplasia; Computed tomography; Hyalinizing granuloma; Inflammatory myofibrolastic tumour; Juvenile xanthogranuloma; Langerhans cell histiocytosis; Organizing pneumonia; Papillary alveolar adenoma; Plasma cell granuloma; Pulmonary amyloidosis; Pulmonary nodule; Sclerosing hemangiomas; Tumourlet
Indistinct pulmonary opacities and pulmonary nodules are very common findings on computed tomography (CT) studies. Studies have estimated that pulmonary nodules are seen in up to 51% of smokers aged 50 years old or older [1]. Moreover, with the implementation of new more sophisticated of CT scanners, smaller nodules are being detected * Address for correspondence: Kyle Pfeifer, MD, Yale New Haven Hospital, Department of Radiology, 20 York St, New Haven, Connecticut, 06510. E-mail address: [email protected] (K. Pfeifer).
with a greater frequency, with identification of nodules and opacities as small as 1-2 mm. The mainstay of the radiologist is to determine the clinical importance of indistinct opacities and pulmonary nodules, and determine which represent early malignancy necessitating surgical biopsy/intervention [1]. However, not every pulmonary opacity represents a potential pulmonary malignancy. A small minority of pulmonary opacities and nodules represents distinct entities, which are separate from infection or malignancy. It is important for the diagnostic radiologist to be aware of these lesions, which may mimic underlying
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Figure 1. (A, B) Axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 158). Patient is a 60-year-old female with history of renal transplant and worsening dyspnea. Interstitial lung disease was suspected and high-resolution computed tomography was performed. An axial slice on lung windows shows peribronchial opacities with subpleural sparing, and peripheral ground-glass opacities or the reverse halo sign (red arrows). Incidental note is made of small bilateral right greater than left pleural effusions. The focal opacities resolved once additional immunosuppresion was administered, however, there were residual ground-glass opacities resembling nonspecific interstitial pneumonia, and a biopsy was performed.
neoplasm or infection. Several of these entities include more common etiologies such as organizing pneumonia, Langerhans cell histiocytosis (LCH), pulmonary amyloidosis, and rare entities such as hyalinizing granuloma, tumourlet (benign localized neuroendocrine cell proliferations), atypical alveolar hyperplasia, inflammatory myofibrolastic tumour, papillary alveolar adenoma, plasma cell granuloma, juvenile xanthogranuloma, and sclerosing hemangiomas. Diagnosis of all of these entities can be challenging and often requires a combination of clinical history, radiographic studies, pathology specimens, and advanced immunohistochemical stains. We present a radiographic and pathologic review of reactive and benign pulmonary neoplastic lesions, including the complex histopathology/immunohistochemical techniques utilised to confirm an underlying diagnosis. We discuss the clinical presentation, prevalence, radiographic clues, pathology, and diagnostic pitfalls of some relatively common pulmonary lesions that may mimic malignancy or infection such as organizing pneumonia, LCH, and
pulmonary amyloidosis. Then we focus on rare pulmonary lesions, which are distinct from underlying pulmonary malignancy and infection. Organizing Pneumonia Organizing pneumonia (formally known as cryptogenic organizing pneumonia) or bronchiolitis obliterans organizing pneumonia is increasingly recognized as a major cause of diffuse infiltrative lung disease [2]. The average age of onset is approximately 55 years old with men and women affected equally [3]. Clinically, patients present with symptoms such as shortness of breath, fever, malaise, and weight loss. Often these symptoms are preceded by a respiratory tract infection [4]. There is no known association with cigarette smoking, and studies have demonstrated that most patients do not have a smoking history [3]. Imaging findings of cryptogenic organizing pneumonia are well described. Chest radiography findings include bilateral patchy airspace consolidation predominantly in the
Figure 2. Representative hematoxylin and eosin sections from a biopsy of the same patient in Figure 1. (A) Low-power image with a patchy distribution of the inflammatory process with areas of less involved lung tissue (left). (B) Medium-power image demonstrating a chronic inflammatory process involving the distal airways (bronchioles and alveoli) and imparting a solid appearance to the lung tissue. Also noted are areas of young loose fibromyxoid connective tissue (top). (C) Lymphocytes and foamy macrophages along with fibrin plugs occupy the terminal airways and the alveolar spaces. These combined findings are characteristic of organizing pneumonia.
Radiology correlation of rare lung lesions / Canadian Association of Radiologists Journal xx (2015) 1e11
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Figure 3. Patient is a 41-year-old female smoker with a history of shortness of breath. (A) Axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 300), which demonstrates multiple bizarre shaped cysts. (B) A coronal reformat, again illustrating multiple bizarre shaped cysts. Patient underwent subsequent biopsy.
subpleural and lower lung zones. On CT, the most common imaging presentation of organizing pneumonia is bronchovascular and subpleural ground-glass opacities, which are seen in close to 90% of patients [4]. The ‘‘reverse-halo sign’’ has also been associated with organizing pneumonia and refers to central ground-glass opacities within the lung parenchyma surrounded by dense airspace consolidation [5]. Additional CT findings include perilobular opacities, which may also be seen in up to 60% of patients as well as multiple subcentimeter pulmonary nodules (Figure 1). Diagnosis and recognition often requires combining imaging characteristics with clinical presentation as well as a histological specimen. In some groups of patients, a biopsy is required for a definitive, especially if the presentation is multiple pulmonary nodules. It is important to recognize organizing pneumonia as a separate entity from malignancy or infection because the gold standard for treatment is with corticosteroids [4]. While the overall prognosis for
organizing pneumonia is good, there have been cases of relapse, as well as cases that have progressed to respiratory failure and death [4]. Histologically, organizing pneumonia is characterized by the presence of granulation tissue polyps within the small airways, alveolar ducts, and alveoli respiratory bronchioles [4]. These are referred to as Masson bodies, and extend into the alveolar ducts and alveoli. The lung parenchyma adjacent to the affected bronchioles undergoes similar fibroblastic changes within the alveolar airspaces (Figure 2) [2]. Langerhans Cell Histiocytosis Another entity that may mimic infection or malignancy is LCH. Pulmonary LCH is an isolated from of LCH that primarily affects predominantly female cigarette smokers [6]. Pathologically LCH is manifested by abnormal nonmalignant proliferation of monoclonal Langerhans cells. The most
Figure 4. (A) Representative hematoxylin and eosin section that demonstrates alveolar spaces filled with histiocytes with folded and grooved nuclei. (B) Cluster of differentiation 1a immunohistochemical stain, which demonstrates reactivity in the lesional cells consistent with Langerhans cell histiocytosis.
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Figure 5. Patient is a 50-year-old male with history of multiple myeloma was found to have numerous pulmonary nodules on routine computed tomography examination performed for minor trauma. (A) Coned down axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 350) demonstrates a peripheral pulmonary nodule (red arrow). Multiple additional cysts throughout both lungs were also incidentally noted. (B) Coronal reformate on bone windows, which demonstrates the partially calcified nodule in the right upper lobe (red arrow).
common symptoms include dyspnea, cough, chest pain, or fatigue. The exact cause of LCH is unknown, although theories range from viral infection, antigen exposure, or somatic mutation. Pulmonary LCH typically affects the upper lobes, likely secondary from inhalation of cigarette smoke. Imaging findings of pulmonary LCH vary depending on what point in the disease process the patient is imaged. Early imaging findings include multiple nonspecific pulmonary nodules, which progress to cavitate into cysts over time. (Figure 3) [6]. The radiographic cysts/nodules may regress, resolve, stabilize, or progress to fibrosis [6]. When LCH presents as a solitary pulmonary nodule, a biopsy is often indicated to exclude an underlying neoplasm [7]. Treatment for LCH is most often with corticosteroids and smoking cessation, which usually leads to symptom stabilization. However, treatment in advanced cases may involve lung
transplantation with or without chemotherapy agents [6]. Histology of LCH demonstrates a densely cellular infiltrate of histiocytes and inflammatory cells within the interstitium and alveoli (Figure 4). Pulmonary Amyloidosis Pulmonary amyloidosis includes a heterogeneous group of disorders, which are characterized by abnormal accumulation of insoluble amyloid protein. The etiology of Pulmonary amyloidosis can be idiopathic (primary) or can result from various inflammatory, hereditary, or neoplastic processes [8]. The respiratory system is involved approximately 50% of patients diagnosed with amyloidosis with a mean age of onset of approximately 55-60 years old [9]. Pulmonary amyloidosis most commonly affects the lung
Figure 6. (A) Low-power hematoxylin and eosin section from the patient in Figure 5 showing deposition of pink amorphous material in the lung parenchyma characteristic of amyloid disease. (B) Polarized microscopy of Congo red stained section of the case in Figure 5 showing the classic apple green birefringence and confirming the diagnosis of amyloid.
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Figure 7. Axial computed tomography on (A) soft tissue and (B) lung windows (kilovoltage peak: 120 milliamperes: 200). Patient is a 74-year-old man with a history of shortness of breath. (A) Axial computed tomography on soft tissue windows with a large subpleural pulmonary nodule in the right lung (red arrow) along with a moderate right-sided pleural effusion. (B) Subpleural nodule (red arrow). Due to the concern for underlying malignancy the lesion underwent subsequent biopsy.
Figure 8. (A) Low-power hematoxylin and eosin section of the patient in Figure 7 illustrating a hyalinizing granuloma with a central area of hyalinized collagen bands with scattered peripheral inflammatory cell collections. (B) Collagen bands arranged in a vague storiform pattern. (C) Inflammatory cell collections composed primarily of lymphocytes and occasional plasma cells and macrophages are also noted in between the collagen bundles. These findings are characteristic of a hyalinizing granuloma.
Figure 9. Axial and coronal computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 200). (A) Axial computed tomography demonstrating a well-circumscribed nodule (red arrow) in the right lobe adjacent to the posterior pleural surface. (B) The same lesion on a coronal computed tomography, which abuts the posterior pleural surface. Patient is a 64-year-old woman with incidentally found pulmonary nodules on computed tomography performed for unrelated reason. Due to the concern for malignancy, the patient underwent subsequent biopsy.
parenchyma but can affect any part of the respiratory tract including the larynx [8e11]. Some authors have split pulmonary amyloidosis into 3 forms based on imaging appearances: tracheobronchial, nodular parenchymal, and diffuse [12].
Presenting symptoms of pulmonary amyloidosis depend on what part of the respiratory tract is involved. For example, tracheobronchial amyloidosis may present with symptoms of airway obstruction including dyspnea, cough, or recurrent pneumonia [9]. Diffuse parenchymal pulmonary amyloidosis
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Figure 10. (A) Medium-power hematoxylin and eosin section of a tumourlet arising in a background of damaged fibrotic lung. The lesion is composed of solid nests of cells extending within the confines of airways. (B) Magnification demonstrating that solid nests are composed of small cells with little cytoplasm and no mitotic activity.
Figure 11. Coned down axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 500). Patient is a 47-year-old man with incidentally found pulmonary nodule while undergoing follow up evaluation for known ascending aortic aneurysm. (A) Coned down axial computed tomography on lung windows demonstrates a coarsely calcified pulmonary nodule in the left upper lobe at the level of the aortic arch (red arrow). (B) Reillustration of the same nodule (red arrow) on a coned down coronal computed tomography on bone windows (kilovoltage peak: 120 milliamperes: 500). (C) Coronal fused positron emission tomography computed tomography demonstrates the same nodule in the left upper lobe, which demonstrates mild fluorodeoxyglucose avidity. Due to a concern for underlying malignancy the patient underwent subsequent biopsy.
is the least common form of respiratory amyloidosis, and presents with nonspecific symptoms including dyspnea, cough, or hemoptysis. Nodular parenchymal amyloidosis is generally asymptomatic at presentation [9]. Chest radiography findings of pulmonary amyloidosis include diffuse small nodular parenchymal opacities, which can be chronic and progressive, and may mimic military tuberculosis, silicosis, or sarcoidosis [12]. CT imaging findings of pulmonary amyloidosis includes dense branching opacities and dense pulmonary subpleural or peripheral nodules at the bases, with associated basal cysts (Figure 5). In addition, calcification or ossification of the pulmonary nodules occurs in up to 50% of patients [8e11]. In most cases treatment is not needed. However, the nodular subtype of pulmonary amyloidosis may slowly progress and requires treatment, which includes surgical resection or laser ablation [8e11]. Because the clinical presentation of amyloid is nonspecific, patients often undergo biopsy for definitive diagnosis. Histological diagnosis can readily be made with
Congo red staining and demonstrates green birefringence under polarized lights (Figure 6). Hyalinizing Granuloma Pulmonary hyalinizing granulomas are best classified as fibrosing lesions of the lung from an unclear etiology. These lesions are thought to arise from an underlying autoimmune process [13]. Hylanizing granulomas classically occur in middle-aged patients, and present with nonspecific respiratory or general symptoms such as cough, chest pain, dyspnea, hemoptysis, malaise, or fatigue. Imaging findings of hyalinizing granulomas include multiple pulmonary nodules or a single large nodule (Figure 7) [13e15]. Hyalizing granulomas may demonstrate slow growth over time [15]. If the diagnosis is confirmed, patients may respond to corticosteroids. However, definitive treatment is often obtained with surgical resection [14]. Pathologic examination demonstrates classic histological findings such as distinct fibrosing lesions
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Figure 12. (A) Low-power hematoxylin and eosin section showing a well-circumscribed nonencapsulated lesion composed of a cellular proliferation admixed with inflammatory cells. (B) Medium-power image from the same patient demonstrating that the lesion is composed of bundles of spindle shaped fibroblasts with occasional trapped epithelial structures. (C) Collections of plasma cells can be easily seen between the fibroblast bundles. Other inflammatory cells including lymphocytes and occasional macrophages are also seen. (D) Anaplastic lymphoma kinase immunohistochemical stain showing focal nuclear and cytoplasmic positivity in the tumour cells.
of lung, having central whorled deposits of lamellar collagen [15] (Figure 8).
cytoplasm. These findings are identical to carcinoid lesions and microscopically are indistinguishable [16] (Figure 10).
Tumourlet (Benign Localized Neuroendocrine Cell Proliferations)
Inflammatory Myofibroblastic Tumour
Tumourlets are benign lesions, which occur, in damaged, ectatic small airways. They contain local proliferations of neuroendocrine cells. On imaging, tumourlets classically present as multiple sub-5 mm nodules (Figure 9). They are often seen in association with larger neuroendocrine lesions such as carcinoid lesions. Even though tumourlet lesions are often biopsied, there is no significant risk of malignant degeneration of the lesions themselves, despite the association with carcinoid neoplasms [16]. They are more common in women and may also be associated with a demoplastic reaction, which includes associated lung fibrosis or bronchiectasis. Histopathologic findings include small round nests of bland spindled cells with scant
Inflammatory myofibroblastic tumour is an interesting entity, which has been formerly known as plasma cell granuloma. Patients usually present with a productive cough. The lesions are felt to represent benign entities, but case reports of inflammatory myofibroblastic tumours invading local blood vessels have been reported, and thus surgical removal is recommended [17]. Inflammatory myofibroblastic tumours occur in middle-aged adults and are most commonly found in the fifth decade of life. They commonly present as a solitary pulmonary mass, which mimics malignancy (Figure 11). If multiple lesions are present, inflammatory myofibroblastic tumours may also be confused with metastatic disease [17,18]. Histopathologic images reveal a
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Figure 13. Patient is a 21-year-old male who presented with right-sided chest discomfort. (A) Coned down axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 500), which demonstrates a large peripherally calcified mass in the right middle lobe (red arrow). (B) The same lesion on an axial computed tomography on soft tissue windows (red arrow) (kilovoltage peak: 120 milliamperes: 500). (C) Axial positron emission tomography image, which demonstrates mild fluorodexoyglucose avidity. Due to the concern for underlying malignancy the patient underwent subsequent biopsy.
Figure 14. The results of the biopsy sample from the patient in Figure 13. (A) Low-power hematoxylin and eosin image illustrating broad papillae with hyalinized fibrovascular cores. (B) The same image on higher magnification, which illustrates that the papillary structures are lined by a single layer of cuboidal-columnar epithelium. (C) The lining cells are positive for thyroid transcription factor-1 immunostain supporting their proposed derivation from type II pneumocytes, and consistent with a papillary alveolar adenoma.
Figure 15. Patient is a 2-year-old male who presents with chronic cough and skin lesions. (A) Axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 250), demonstrates a pulmonary nodule (red arrow). (B) Another image demonstrating an approximately 5 mm pulmonary nodule in the posterior aspect of the right upper lobe (red arrow). Multiple additional nodules were also noted (not visualized). Due to the concern for metastatic disease with an unknown primary one of the nodules was sampled.
proliferation of spindle cells combined with inflammatory changes. A definitive diagnosis can be made with the imunohistochemical stain ALK1 (Figure 12) [18]. In addition to lung lesions, inflammatory myofibroblastic tumours may also arise in the abdominal cavity, retroperitoneum, and the extremities [17,18].
Papillary Alveolar Adenoma Papillary adenomas are extremely rare neoplasms, which typically occur in the peripheral areas of the lung [19]. They are well defined tumours with no cases of reported metastasis [20]. Papillary alveolar adenomas frequently arise from type
Radiology correlation of rare lung lesions / Canadian Association of Radiologists Journal xx (2015) 1e11
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Figure 16. A representative hematoxylin and eosin section from the case in Figure 15 demonstrating a fibrohistiocytic proliferation with mixed inflammatory cells and occasional giant cells (A). (B) Immunohistochemical staining for CD68 is positive confirming the diagnosis of juvenile xanthogranulmona.
Figure 17. Patient is a 58-year-old female with an incidentally noted pulmonary nodule. (A) Axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 220) that demonstrates a pulmonary nodule in the right lower lobe (red arrow). (B) Coronal CT (kilovoltage peak: 120 milliamperes: 220) on lung windows, which illustrates a solid pulmonary nodule in the right lower lobe. Subsequent examinations raised the concern for interval enlargement of the nodule and the patient underwent a right lower lobe wedge resection.
II pneumocytes, patients are typically asymptomatic, and the lesion is usually identified incidentally in middle to elderly females [21]. Imaging findings are nonspecific and these lesions classically present as solitary pulmonary nodules or masses (Figure 13) [21]. Histopathology shows a circumscribed lesion consisting of a papillary growth of cuboidal to low-columnar epithelial cells lining the surface of a fibrovascular stroma [21] (Figure 14). However, many patients undergo wedge resection to exclude an underlying malignancy [21].
extremities and resolve spontaneously. However, the lesions can also occur in the lungs, and involvement of the pulmonary tissues is associated with systemic disease, and has a worse prognosis. Typical presenting symptoms include dyspnea, wheezing, or hemoptysis [22]. Imaging findings in the lung are nonspecific and include multiple simple pulmonary nodules (Figure 15). Treatment is usually supportive. Histological findings include non-LCH with macrophage marker staining and no S-100 or cluster of differentiation 1a characteristic of Langerhans cells (Figure 16) [22].
Juvenile Xanthogranuloma
Sclerosing Hemangioma
A juvenile xanthogranuloma represents an extremely rare entity, which typically presents in patients younger than 2 years old. Most lesions occur within the soft tissues of the
Pulmonary sclerosing hemangioma (PSH) (also known as a pneumocytoma of the lung) is a rare benign tumour that classically presents in middle-aged adult females. While the
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Figure 18. Subsequent biopsy of the pulmonary nodule shown in Figure 17 from the patient’s wedge resection. (A) Low-power hematoxylin and eosin stain of sheets of cells admixed with scattered sclerotic areas. (B) Higher power image of the same lesion demonstrating a neoplasm composed of solid sheets of polygonal small to medium sized cells admixed with scattered blood vessels. (C) Another higher power image demonstrating angiomatous spaces filled with red blood cells admixed with hemosiderin-laden macrophages. (D) Thyroid transcription factor-1 stain showing diffuse staining of tumour cells confirming sclerosing hemangiomas.
lesion is usually asymptomatic, symptoms such as cough, pleurisy, dyspnea, and hemoptysis have been reported. On CT, the lesion presents as a well-defined subpleural nodule or mass with occasional calcifications and a lucent halo. Enhancement is usually heterogeneous (Figure 17). Histologically, there are 4 main components: solid, papillary, sclerotic, and hematogenous, with a thin fibrous pseudocapsule (Figure 18) [23]. Summary Even though pulmonary nodules are extremely common on CT examinations, it is important for the interpreting radiologist to be aware of other pulmonary lesions, which may mimic infection or malignancy. These entities demonstrate overlapping imaging features, and often a definitive diagnosis cannot be obtained without tissue sampling and unique immunohistochemical stains. In this review, we have seen that radiographic features such as scattered pulmonary
nodules, focal consolidation, subpleural or bronchovascular grand glass opacities, and various patterns of adenopathy can be common to a variety of entities. The rare entities described here form an important component of a complete differential diagnosis.
References [1] MacMahon H, Austin JH, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology 2005;237:395e400. [2] Greenberg-Wolff I, Konen E, Ben Dov I, et al. Cryptogenic organizing pneumonia: variety of radiologic findings. Isr Med Assoc J 2005;7: 568e70. [3] Mueller-Mang C, Grosse C, Schmid K, et al. What every radiologist should know about idiopathic interstitial pneumonias. Radiographics 2007;27:595e615. [4] Lee JW, Lee KS, Lee HY, et al. Cryptogenic organizing pneumonia: serial high-resolution CT findings in 22 patients. AJR Am J Roentgenol 2010;195:916e22.
Radiology correlation of rare lung lesions / Canadian Association of Radiologists Journal xx (2015) 1e11 [5] Kim SJ, Lee KS, Ryu YH, et al. Reversed halo sign on high-resolution CT of cryptogenic organizing pneumonia: diagnostic implications. AJR Am J Roentgenol 2003;180:1251e4. [6] Abbott GF, Rosado-de-Christenson ML, Franks TJ, et al. From the archives of the AFIP: pulmonary Langerhans cell histiocytosis. Radiographics 2004;24:821e41. [7] Leatherwood DL, Heitkamp DE, Emerson RE. Best cases from the AFIP: Pulmonary Langerhans cell histiocytosis. Radiographics 2007; 27:265e8. [8] Vieira IG, Marchiori E, Zanetti G, et al. Pulmonary amyloidosis with calcified nodules and masses - a six-year computed tomography followup: a case report. Cases J 2009;2:6540. [9] Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract. Thorax 1999;54:444e51. [10] Chung MJ, Lee KS, Franquet T, et al. Metabolic lung disease: imaging and histopathologic findings. Eur J Radiol 2005;54:233e45. [11] Lee AY, Godwin JD, Pipavath SN. Case 182: pulmonary amyloidosis. Radiology 2012;263:929e32. [12] Graham CM, Stern EJ, Finkbeiner WE, et al. High-resolution CT appearance of diffuse alveolar septal amyloidosis. AJR Am J Roentgenol 1992;158:265e7. [13] Rahatullah A, Waheed Z, Khan JA, et al. Pulmonary hyalinising granuloma: a rare pulmonary disorder. J Pak Med Assoc 2012;62:493e5.
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[14] Chalaoui J, Gregoire P, Sylvestre J, et al. Pulmonary hyalinizing granuloma: a cause of pulmonary nodules. Radiology 1984;152:23e6. [15] Yousem SA, Hochholzer L. Pulmonary hyalinizing granuloma. Am J Clin Pathol 1987;87:1e6. [16] Ginsberg MS, Akin O, Berger DM, et al. Pulmonary tumorlets: CT findings. AJR Am J Roentgenol 2004;183:293e6. [17] Sakurai H, Hasegawa T, Watanabe S, et al. Inflammatory myofibroblastic tumor of the lung. Eur J Cardiothorac Surg 2004;25:155e9. [18] Lai V, Wong YC, Lam WY, et al. Inflammatory myofibroblastic tumor of the nasal cavity. AJNR Am J Neuroradiol 2007;28:135e7. [19] Cornejo KM, Shi M, Akalin A, et al. Pulmonary papillary adenoma: a case report and review of the literature. J Bronchology Interv Pulmonol 2013;20:52e7. [20] Noguchi M, Kodama T, Shimosato Y, et al. Papillary adenoma of type 2 pneumocytes. Am J Surg Pathol 1986;10:134e9. [21] Glaab R, Turina M, Achermann E, et al. [Alveolar adenomaea rare pulmonary mass: case report and review of the literature]. Zentralbl Chir 2009;134:478e80. [22] Janssen D, Harms D. Juvenile xanthogranuloma in childhood and adolescence: a clinicopathologic study of 129 patients from the kiel pediatric tumor registry. Am J Surg Pathol 2005;29:21e8. [23] Keylock JB, Galvin JR, Franks TJ. Sclerosing hemangioma of the lung. Arch Pathol Lab Med 2009;133:820e5.
Thoracic and Cardiac Imaging / Imagerie cardiaque et imagerie thoracique
Radiographic and Pathologic Manifestations of Uncommon and Rare Pulmonary Lesions Kyle Pfeifer, MDa,*, Ali Mian, MDa, Adeniran Adebowale, MDb, Ahmed Alomari, MDb, Vivek Kalra, MDa, Elise Krejci, MDc, Myung Soo Shin, MD, DSca a
Department of Radiology, Yale New Haven Hospital, New Haven, Connecticut, USA Department of Pathology, Yale New Haven Hospital, New Haven, Connecticut, USA c Department of Pathology, Lawrence and Memorial Hospital, New London, Connecticut, USA b
Abstract Pulmonary opacities/nodules are common findings on computed tomography examinations, which may represent an underlying infections or malignancy. However, not every pulmonary nodule or opacity represents malignancy or infection. We present a pictorial essay illustrating common as well as obscure noninfectious, nonmalignant pulmonary lesions. Lesions discussed include organizing pneumonia, Langerhans cell histiocytosis, pulmonary amyloidosis, hyalinizing granuloma, tumourlet (benign localized neuroendocrine cell proliferations), atypical alveolar hyperplasia, inflammatory myofibroblastic tumour, papillary alveolar adenoma, plasma cell granuloma, juvenile xanthogranuloma, and sclerosing hemangiomas. We discuss the clinical presentation, prevalence, radiographic clues, pathology, and diagnostic pitfalls of these rare lesions. Resume Les examens de tomodensitometrie permettent souvent de detecter les opacites ou les nodules pulmonaires, signes d’une possible infection ou tumeur sous-jacente. Toutefois, la presence d’opacites ou de nodules ne signifie pas necessairement qu’il y a tumeur ou infection. Notre essai descriptif traite des lesions pulmonaires courantes, mais aussi des lesions non infectieuses et non cancereuses difficilement decelables. Nous y abordons entre autres la pneumopathie organisee, l’histiocytose des cellules de Langerhans, l’amylose pulmonaire, le granulome hyalinisant, la tumorlet (proliferation localisee de cellules neuroendocrines non cancereuses), l’hyperplasie alveolaire atypique, la tumeur myofibroblastique inflammatoire, l’adenome alveolaire papillaire, le granulome plasmocytaire, le xanthogranulome juvenile et les hemangiomes sclerosants. Nous discutons du tableau clinique, de la prevalence, des indices radiographiques, de la pathologie et des pieges diagnostiques de ces lesions rares. Ó 2015 Canadian Association of Radiologists. All rights reserved. Key Words: Atypical alveolar hyperplasia; Computed tomography; Hyalinizing granuloma; Inflammatory myofibrolastic tumour; Juvenile xanthogranuloma; Langerhans cell histiocytosis; Organizing pneumonia; Papillary alveolar adenoma; Plasma cell granuloma; Pulmonary amyloidosis; Pulmonary nodule; Sclerosing hemangiomas; Tumourlet
Indistinct pulmonary opacities and pulmonary nodules are very common findings on computed tomography (CT) studies. Studies have estimated that pulmonary nodules are seen in up to 51% of smokers aged 50 years old or older [1]. Moreover, with the implementation of new more sophisticated of CT scanners, smaller nodules are being detected * Address for correspondence: Kyle Pfeifer, MD, Yale New Haven Hospital, Department of Radiology, 20 York St, New Haven, Connecticut, 06510. E-mail address: [email protected] (K. Pfeifer).
with a greater frequency, with identification of nodules and opacities as small as 1-2 mm. The mainstay of the radiologist is to determine the clinical importance of indistinct opacities and pulmonary nodules, and determine which represent early malignancy necessitating surgical biopsy/intervention [1]. However, not every pulmonary opacity represents a potential pulmonary malignancy. A small minority of pulmonary opacities and nodules represents distinct entities, which are separate from infection or malignancy. It is important for the diagnostic radiologist to be aware of these lesions, which may mimic underlying
0846-5371/$ - see front matter Ó 2015 Canadian Association of Radiologists. All rights reserved. http://dx.doi.org/10.1016/j.carj.2015.07.004
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Figure 1. (A, B) Axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 158). Patient is a 60-year-old female with history of renal transplant and worsening dyspnea. Interstitial lung disease was suspected and high-resolution computed tomography was performed. An axial slice on lung windows shows peribronchial opacities with subpleural sparing, and peripheral ground-glass opacities or the reverse halo sign (red arrows). Incidental note is made of small bilateral right greater than left pleural effusions. The focal opacities resolved once additional immunosuppresion was administered, however, there were residual ground-glass opacities resembling nonspecific interstitial pneumonia, and a biopsy was performed.
neoplasm or infection. Several of these entities include more common etiologies such as organizing pneumonia, Langerhans cell histiocytosis (LCH), pulmonary amyloidosis, and rare entities such as hyalinizing granuloma, tumourlet (benign localized neuroendocrine cell proliferations), atypical alveolar hyperplasia, inflammatory myofibrolastic tumour, papillary alveolar adenoma, plasma cell granuloma, juvenile xanthogranuloma, and sclerosing hemangiomas. Diagnosis of all of these entities can be challenging and often requires a combination of clinical history, radiographic studies, pathology specimens, and advanced immunohistochemical stains. We present a radiographic and pathologic review of reactive and benign pulmonary neoplastic lesions, including the complex histopathology/immunohistochemical techniques utilised to confirm an underlying diagnosis. We discuss the clinical presentation, prevalence, radiographic clues, pathology, and diagnostic pitfalls of some relatively common pulmonary lesions that may mimic malignancy or infection such as organizing pneumonia, LCH, and
pulmonary amyloidosis. Then we focus on rare pulmonary lesions, which are distinct from underlying pulmonary malignancy and infection. Organizing Pneumonia Organizing pneumonia (formally known as cryptogenic organizing pneumonia) or bronchiolitis obliterans organizing pneumonia is increasingly recognized as a major cause of diffuse infiltrative lung disease [2]. The average age of onset is approximately 55 years old with men and women affected equally [3]. Clinically, patients present with symptoms such as shortness of breath, fever, malaise, and weight loss. Often these symptoms are preceded by a respiratory tract infection [4]. There is no known association with cigarette smoking, and studies have demonstrated that most patients do not have a smoking history [3]. Imaging findings of cryptogenic organizing pneumonia are well described. Chest radiography findings include bilateral patchy airspace consolidation predominantly in the
Figure 2. Representative hematoxylin and eosin sections from a biopsy of the same patient in Figure 1. (A) Low-power image with a patchy distribution of the inflammatory process with areas of less involved lung tissue (left). (B) Medium-power image demonstrating a chronic inflammatory process involving the distal airways (bronchioles and alveoli) and imparting a solid appearance to the lung tissue. Also noted are areas of young loose fibromyxoid connective tissue (top). (C) Lymphocytes and foamy macrophages along with fibrin plugs occupy the terminal airways and the alveolar spaces. These combined findings are characteristic of organizing pneumonia.
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Figure 3. Patient is a 41-year-old female smoker with a history of shortness of breath. (A) Axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 300), which demonstrates multiple bizarre shaped cysts. (B) A coronal reformat, again illustrating multiple bizarre shaped cysts. Patient underwent subsequent biopsy.
subpleural and lower lung zones. On CT, the most common imaging presentation of organizing pneumonia is bronchovascular and subpleural ground-glass opacities, which are seen in close to 90% of patients [4]. The ‘‘reverse-halo sign’’ has also been associated with organizing pneumonia and refers to central ground-glass opacities within the lung parenchyma surrounded by dense airspace consolidation [5]. Additional CT findings include perilobular opacities, which may also be seen in up to 60% of patients as well as multiple subcentimeter pulmonary nodules (Figure 1). Diagnosis and recognition often requires combining imaging characteristics with clinical presentation as well as a histological specimen. In some groups of patients, a biopsy is required for a definitive, especially if the presentation is multiple pulmonary nodules. It is important to recognize organizing pneumonia as a separate entity from malignancy or infection because the gold standard for treatment is with corticosteroids [4]. While the overall prognosis for
organizing pneumonia is good, there have been cases of relapse, as well as cases that have progressed to respiratory failure and death [4]. Histologically, organizing pneumonia is characterized by the presence of granulation tissue polyps within the small airways, alveolar ducts, and alveoli respiratory bronchioles [4]. These are referred to as Masson bodies, and extend into the alveolar ducts and alveoli. The lung parenchyma adjacent to the affected bronchioles undergoes similar fibroblastic changes within the alveolar airspaces (Figure 2) [2]. Langerhans Cell Histiocytosis Another entity that may mimic infection or malignancy is LCH. Pulmonary LCH is an isolated from of LCH that primarily affects predominantly female cigarette smokers [6]. Pathologically LCH is manifested by abnormal nonmalignant proliferation of monoclonal Langerhans cells. The most
Figure 4. (A) Representative hematoxylin and eosin section that demonstrates alveolar spaces filled with histiocytes with folded and grooved nuclei. (B) Cluster of differentiation 1a immunohistochemical stain, which demonstrates reactivity in the lesional cells consistent with Langerhans cell histiocytosis.
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Figure 5. Patient is a 50-year-old male with history of multiple myeloma was found to have numerous pulmonary nodules on routine computed tomography examination performed for minor trauma. (A) Coned down axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 350) demonstrates a peripheral pulmonary nodule (red arrow). Multiple additional cysts throughout both lungs were also incidentally noted. (B) Coronal reformate on bone windows, which demonstrates the partially calcified nodule in the right upper lobe (red arrow).
common symptoms include dyspnea, cough, chest pain, or fatigue. The exact cause of LCH is unknown, although theories range from viral infection, antigen exposure, or somatic mutation. Pulmonary LCH typically affects the upper lobes, likely secondary from inhalation of cigarette smoke. Imaging findings of pulmonary LCH vary depending on what point in the disease process the patient is imaged. Early imaging findings include multiple nonspecific pulmonary nodules, which progress to cavitate into cysts over time. (Figure 3) [6]. The radiographic cysts/nodules may regress, resolve, stabilize, or progress to fibrosis [6]. When LCH presents as a solitary pulmonary nodule, a biopsy is often indicated to exclude an underlying neoplasm [7]. Treatment for LCH is most often with corticosteroids and smoking cessation, which usually leads to symptom stabilization. However, treatment in advanced cases may involve lung
transplantation with or without chemotherapy agents [6]. Histology of LCH demonstrates a densely cellular infiltrate of histiocytes and inflammatory cells within the interstitium and alveoli (Figure 4). Pulmonary Amyloidosis Pulmonary amyloidosis includes a heterogeneous group of disorders, which are characterized by abnormal accumulation of insoluble amyloid protein. The etiology of Pulmonary amyloidosis can be idiopathic (primary) or can result from various inflammatory, hereditary, or neoplastic processes [8]. The respiratory system is involved approximately 50% of patients diagnosed with amyloidosis with a mean age of onset of approximately 55-60 years old [9]. Pulmonary amyloidosis most commonly affects the lung
Figure 6. (A) Low-power hematoxylin and eosin section from the patient in Figure 5 showing deposition of pink amorphous material in the lung parenchyma characteristic of amyloid disease. (B) Polarized microscopy of Congo red stained section of the case in Figure 5 showing the classic apple green birefringence and confirming the diagnosis of amyloid.
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Figure 7. Axial computed tomography on (A) soft tissue and (B) lung windows (kilovoltage peak: 120 milliamperes: 200). Patient is a 74-year-old man with a history of shortness of breath. (A) Axial computed tomography on soft tissue windows with a large subpleural pulmonary nodule in the right lung (red arrow) along with a moderate right-sided pleural effusion. (B) Subpleural nodule (red arrow). Due to the concern for underlying malignancy the lesion underwent subsequent biopsy.
Figure 8. (A) Low-power hematoxylin and eosin section of the patient in Figure 7 illustrating a hyalinizing granuloma with a central area of hyalinized collagen bands with scattered peripheral inflammatory cell collections. (B) Collagen bands arranged in a vague storiform pattern. (C) Inflammatory cell collections composed primarily of lymphocytes and occasional plasma cells and macrophages are also noted in between the collagen bundles. These findings are characteristic of a hyalinizing granuloma.
Figure 9. Axial and coronal computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 200). (A) Axial computed tomography demonstrating a well-circumscribed nodule (red arrow) in the right lobe adjacent to the posterior pleural surface. (B) The same lesion on a coronal computed tomography, which abuts the posterior pleural surface. Patient is a 64-year-old woman with incidentally found pulmonary nodules on computed tomography performed for unrelated reason. Due to the concern for malignancy, the patient underwent subsequent biopsy.
parenchyma but can affect any part of the respiratory tract including the larynx [8e11]. Some authors have split pulmonary amyloidosis into 3 forms based on imaging appearances: tracheobronchial, nodular parenchymal, and diffuse [12].
Presenting symptoms of pulmonary amyloidosis depend on what part of the respiratory tract is involved. For example, tracheobronchial amyloidosis may present with symptoms of airway obstruction including dyspnea, cough, or recurrent pneumonia [9]. Diffuse parenchymal pulmonary amyloidosis
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Figure 10. (A) Medium-power hematoxylin and eosin section of a tumourlet arising in a background of damaged fibrotic lung. The lesion is composed of solid nests of cells extending within the confines of airways. (B) Magnification demonstrating that solid nests are composed of small cells with little cytoplasm and no mitotic activity.
Figure 11. Coned down axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 500). Patient is a 47-year-old man with incidentally found pulmonary nodule while undergoing follow up evaluation for known ascending aortic aneurysm. (A) Coned down axial computed tomography on lung windows demonstrates a coarsely calcified pulmonary nodule in the left upper lobe at the level of the aortic arch (red arrow). (B) Reillustration of the same nodule (red arrow) on a coned down coronal computed tomography on bone windows (kilovoltage peak: 120 milliamperes: 500). (C) Coronal fused positron emission tomography computed tomography demonstrates the same nodule in the left upper lobe, which demonstrates mild fluorodeoxyglucose avidity. Due to a concern for underlying malignancy the patient underwent subsequent biopsy.
is the least common form of respiratory amyloidosis, and presents with nonspecific symptoms including dyspnea, cough, or hemoptysis. Nodular parenchymal amyloidosis is generally asymptomatic at presentation [9]. Chest radiography findings of pulmonary amyloidosis include diffuse small nodular parenchymal opacities, which can be chronic and progressive, and may mimic military tuberculosis, silicosis, or sarcoidosis [12]. CT imaging findings of pulmonary amyloidosis includes dense branching opacities and dense pulmonary subpleural or peripheral nodules at the bases, with associated basal cysts (Figure 5). In addition, calcification or ossification of the pulmonary nodules occurs in up to 50% of patients [8e11]. In most cases treatment is not needed. However, the nodular subtype of pulmonary amyloidosis may slowly progress and requires treatment, which includes surgical resection or laser ablation [8e11]. Because the clinical presentation of amyloid is nonspecific, patients often undergo biopsy for definitive diagnosis. Histological diagnosis can readily be made with
Congo red staining and demonstrates green birefringence under polarized lights (Figure 6). Hyalinizing Granuloma Pulmonary hyalinizing granulomas are best classified as fibrosing lesions of the lung from an unclear etiology. These lesions are thought to arise from an underlying autoimmune process [13]. Hylanizing granulomas classically occur in middle-aged patients, and present with nonspecific respiratory or general symptoms such as cough, chest pain, dyspnea, hemoptysis, malaise, or fatigue. Imaging findings of hyalinizing granulomas include multiple pulmonary nodules or a single large nodule (Figure 7) [13e15]. Hyalizing granulomas may demonstrate slow growth over time [15]. If the diagnosis is confirmed, patients may respond to corticosteroids. However, definitive treatment is often obtained with surgical resection [14]. Pathologic examination demonstrates classic histological findings such as distinct fibrosing lesions
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Figure 12. (A) Low-power hematoxylin and eosin section showing a well-circumscribed nonencapsulated lesion composed of a cellular proliferation admixed with inflammatory cells. (B) Medium-power image from the same patient demonstrating that the lesion is composed of bundles of spindle shaped fibroblasts with occasional trapped epithelial structures. (C) Collections of plasma cells can be easily seen between the fibroblast bundles. Other inflammatory cells including lymphocytes and occasional macrophages are also seen. (D) Anaplastic lymphoma kinase immunohistochemical stain showing focal nuclear and cytoplasmic positivity in the tumour cells.
of lung, having central whorled deposits of lamellar collagen [15] (Figure 8).
cytoplasm. These findings are identical to carcinoid lesions and microscopically are indistinguishable [16] (Figure 10).
Tumourlet (Benign Localized Neuroendocrine Cell Proliferations)
Inflammatory Myofibroblastic Tumour
Tumourlets are benign lesions, which occur, in damaged, ectatic small airways. They contain local proliferations of neuroendocrine cells. On imaging, tumourlets classically present as multiple sub-5 mm nodules (Figure 9). They are often seen in association with larger neuroendocrine lesions such as carcinoid lesions. Even though tumourlet lesions are often biopsied, there is no significant risk of malignant degeneration of the lesions themselves, despite the association with carcinoid neoplasms [16]. They are more common in women and may also be associated with a demoplastic reaction, which includes associated lung fibrosis or bronchiectasis. Histopathologic findings include small round nests of bland spindled cells with scant
Inflammatory myofibroblastic tumour is an interesting entity, which has been formerly known as plasma cell granuloma. Patients usually present with a productive cough. The lesions are felt to represent benign entities, but case reports of inflammatory myofibroblastic tumours invading local blood vessels have been reported, and thus surgical removal is recommended [17]. Inflammatory myofibroblastic tumours occur in middle-aged adults and are most commonly found in the fifth decade of life. They commonly present as a solitary pulmonary mass, which mimics malignancy (Figure 11). If multiple lesions are present, inflammatory myofibroblastic tumours may also be confused with metastatic disease [17,18]. Histopathologic images reveal a
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Figure 13. Patient is a 21-year-old male who presented with right-sided chest discomfort. (A) Coned down axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 500), which demonstrates a large peripherally calcified mass in the right middle lobe (red arrow). (B) The same lesion on an axial computed tomography on soft tissue windows (red arrow) (kilovoltage peak: 120 milliamperes: 500). (C) Axial positron emission tomography image, which demonstrates mild fluorodexoyglucose avidity. Due to the concern for underlying malignancy the patient underwent subsequent biopsy.
Figure 14. The results of the biopsy sample from the patient in Figure 13. (A) Low-power hematoxylin and eosin image illustrating broad papillae with hyalinized fibrovascular cores. (B) The same image on higher magnification, which illustrates that the papillary structures are lined by a single layer of cuboidal-columnar epithelium. (C) The lining cells are positive for thyroid transcription factor-1 immunostain supporting their proposed derivation from type II pneumocytes, and consistent with a papillary alveolar adenoma.
Figure 15. Patient is a 2-year-old male who presents with chronic cough and skin lesions. (A) Axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 250), demonstrates a pulmonary nodule (red arrow). (B) Another image demonstrating an approximately 5 mm pulmonary nodule in the posterior aspect of the right upper lobe (red arrow). Multiple additional nodules were also noted (not visualized). Due to the concern for metastatic disease with an unknown primary one of the nodules was sampled.
proliferation of spindle cells combined with inflammatory changes. A definitive diagnosis can be made with the imunohistochemical stain ALK1 (Figure 12) [18]. In addition to lung lesions, inflammatory myofibroblastic tumours may also arise in the abdominal cavity, retroperitoneum, and the extremities [17,18].
Papillary Alveolar Adenoma Papillary adenomas are extremely rare neoplasms, which typically occur in the peripheral areas of the lung [19]. They are well defined tumours with no cases of reported metastasis [20]. Papillary alveolar adenomas frequently arise from type
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Figure 16. A representative hematoxylin and eosin section from the case in Figure 15 demonstrating a fibrohistiocytic proliferation with mixed inflammatory cells and occasional giant cells (A). (B) Immunohistochemical staining for CD68 is positive confirming the diagnosis of juvenile xanthogranulmona.
Figure 17. Patient is a 58-year-old female with an incidentally noted pulmonary nodule. (A) Axial computed tomography on lung windows (kilovoltage peak: 120 milliamperes: 220) that demonstrates a pulmonary nodule in the right lower lobe (red arrow). (B) Coronal CT (kilovoltage peak: 120 milliamperes: 220) on lung windows, which illustrates a solid pulmonary nodule in the right lower lobe. Subsequent examinations raised the concern for interval enlargement of the nodule and the patient underwent a right lower lobe wedge resection.
II pneumocytes, patients are typically asymptomatic, and the lesion is usually identified incidentally in middle to elderly females [21]. Imaging findings are nonspecific and these lesions classically present as solitary pulmonary nodules or masses (Figure 13) [21]. Histopathology shows a circumscribed lesion consisting of a papillary growth of cuboidal to low-columnar epithelial cells lining the surface of a fibrovascular stroma [21] (Figure 14). However, many patients undergo wedge resection to exclude an underlying malignancy [21].
extremities and resolve spontaneously. However, the lesions can also occur in the lungs, and involvement of the pulmonary tissues is associated with systemic disease, and has a worse prognosis. Typical presenting symptoms include dyspnea, wheezing, or hemoptysis [22]. Imaging findings in the lung are nonspecific and include multiple simple pulmonary nodules (Figure 15). Treatment is usually supportive. Histological findings include non-LCH with macrophage marker staining and no S-100 or cluster of differentiation 1a characteristic of Langerhans cells (Figure 16) [22].
Juvenile Xanthogranuloma
Sclerosing Hemangioma
A juvenile xanthogranuloma represents an extremely rare entity, which typically presents in patients younger than 2 years old. Most lesions occur within the soft tissues of the
Pulmonary sclerosing hemangioma (PSH) (also known as a pneumocytoma of the lung) is a rare benign tumour that classically presents in middle-aged adult females. While the
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Figure 18. Subsequent biopsy of the pulmonary nodule shown in Figure 17 from the patient’s wedge resection. (A) Low-power hematoxylin and eosin stain of sheets of cells admixed with scattered sclerotic areas. (B) Higher power image of the same lesion demonstrating a neoplasm composed of solid sheets of polygonal small to medium sized cells admixed with scattered blood vessels. (C) Another higher power image demonstrating angiomatous spaces filled with red blood cells admixed with hemosiderin-laden macrophages. (D) Thyroid transcription factor-1 stain showing diffuse staining of tumour cells confirming sclerosing hemangiomas.
lesion is usually asymptomatic, symptoms such as cough, pleurisy, dyspnea, and hemoptysis have been reported. On CT, the lesion presents as a well-defined subpleural nodule or mass with occasional calcifications and a lucent halo. Enhancement is usually heterogeneous (Figure 17). Histologically, there are 4 main components: solid, papillary, sclerotic, and hematogenous, with a thin fibrous pseudocapsule (Figure 18) [23]. Summary Even though pulmonary nodules are extremely common on CT examinations, it is important for the interpreting radiologist to be aware of other pulmonary lesions, which may mimic infection or malignancy. These entities demonstrate overlapping imaging features, and often a definitive diagnosis cannot be obtained without tissue sampling and unique immunohistochemical stains. In this review, we have seen that radiographic features such as scattered pulmonary
nodules, focal consolidation, subpleural or bronchovascular grand glass opacities, and various patterns of adenopathy can be common to a variety of entities. The rare entities described here form an important component of a complete differential diagnosis.
References [1] MacMahon H, Austin JH, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology 2005;237:395e400. [2] Greenberg-Wolff I, Konen E, Ben Dov I, et al. Cryptogenic organizing pneumonia: variety of radiologic findings. Isr Med Assoc J 2005;7: 568e70. [3] Mueller-Mang C, Grosse C, Schmid K, et al. What every radiologist should know about idiopathic interstitial pneumonias. Radiographics 2007;27:595e615. [4] Lee JW, Lee KS, Lee HY, et al. Cryptogenic organizing pneumonia: serial high-resolution CT findings in 22 patients. AJR Am J Roentgenol 2010;195:916e22.
Radiology correlation of rare lung lesions / Canadian Association of Radiologists Journal xx (2015) 1e11 [5] Kim SJ, Lee KS, Ryu YH, et al. Reversed halo sign on high-resolution CT of cryptogenic organizing pneumonia: diagnostic implications. AJR Am J Roentgenol 2003;180:1251e4. [6] Abbott GF, Rosado-de-Christenson ML, Franks TJ, et al. From the archives of the AFIP: pulmonary Langerhans cell histiocytosis. Radiographics 2004;24:821e41. [7] Leatherwood DL, Heitkamp DE, Emerson RE. Best cases from the AFIP: Pulmonary Langerhans cell histiocytosis. Radiographics 2007; 27:265e8. [8] Vieira IG, Marchiori E, Zanetti G, et al. Pulmonary amyloidosis with calcified nodules and masses - a six-year computed tomography followup: a case report. Cases J 2009;2:6540. [9] Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract. Thorax 1999;54:444e51. [10] Chung MJ, Lee KS, Franquet T, et al. Metabolic lung disease: imaging and histopathologic findings. Eur J Radiol 2005;54:233e45. [11] Lee AY, Godwin JD, Pipavath SN. Case 182: pulmonary amyloidosis. Radiology 2012;263:929e32. [12] Graham CM, Stern EJ, Finkbeiner WE, et al. High-resolution CT appearance of diffuse alveolar septal amyloidosis. AJR Am J Roentgenol 1992;158:265e7. [13] Rahatullah A, Waheed Z, Khan JA, et al. Pulmonary hyalinising granuloma: a rare pulmonary disorder. J Pak Med Assoc 2012;62:493e5.
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[14] Chalaoui J, Gregoire P, Sylvestre J, et al. Pulmonary hyalinizing granuloma: a cause of pulmonary nodules. Radiology 1984;152:23e6. [15] Yousem SA, Hochholzer L. Pulmonary hyalinizing granuloma. Am J Clin Pathol 1987;87:1e6. [16] Ginsberg MS, Akin O, Berger DM, et al. Pulmonary tumorlets: CT findings. AJR Am J Roentgenol 2004;183:293e6. [17] Sakurai H, Hasegawa T, Watanabe S, et al. Inflammatory myofibroblastic tumor of the lung. Eur J Cardiothorac Surg 2004;25:155e9. [18] Lai V, Wong YC, Lam WY, et al. Inflammatory myofibroblastic tumor of the nasal cavity. AJNR Am J Neuroradiol 2007;28:135e7. [19] Cornejo KM, Shi M, Akalin A, et al. Pulmonary papillary adenoma: a case report and review of the literature. J Bronchology Interv Pulmonol 2013;20:52e7. [20] Noguchi M, Kodama T, Shimosato Y, et al. Papillary adenoma of type 2 pneumocytes. Am J Surg Pathol 1986;10:134e9. [21] Glaab R, Turina M, Achermann E, et al. [Alveolar adenomaea rare pulmonary mass: case report and review of the literature]. Zentralbl Chir 2009;134:478e80. [22] Janssen D, Harms D. Juvenile xanthogranuloma in childhood and adolescence: a clinicopathologic study of 129 patients from the kiel pediatric tumor registry. Am J Surg Pathol 2005;29:21e8. [23] Keylock JB, Galvin JR, Franks TJ. Sclerosing hemangioma of the lung. Arch Pathol Lab Med 2009;133:820e5.