Current Problems in Diagnostic Radiology ] (2015) ]]]–]]]
Current Problems in Diagnostic Radiology journal homepage: www.cpdrjournal.com
Acute Fibrinous Organizing Pneumonia: A Case Report and Literature Review Bryan A. Garcia, MDa,n, Timothy Goede, MDb, Tan-Lucien Mohammed, MDb a b
Department of Internal Medicine, University of Florida, Gainesville, FL Department of Radiology, University of Florida, Gainesville, FL
Acute ﬁbrinous organizing pneumonia (AFOP) is a distinct histopathologic pattern of lung injury with the hallmark feature of intra-alveolar ﬁbrin deposits with associated organizing pneumonia, type II pneumocyte hyperplasia, and a patchy lymphohistiocytic proliferation. We describe the case of a previously healthy 47-year-old man who presented with a 4-day history of worsening dyspnea, cough, and nocturnal fevers and miliary nodules on chest imaging. Subsequently, there was an indication of AFOP when he underwent open lung biopsy. AFOP has been associated with a variety of underlying conditions including rheumatologic diseases, medications, and infections, and several cases were idiopathic. This case highlights the importance for radiologists to be aware of this uncommon pattern of lung injury and to consider it in the differential when encountering bilateral miliary inﬁltrates on chest imaging. & 2015 Elsevier Inc. All rights reserved.
First described by Beasley et al in 2002, acute ﬁbrinous organizing pneumonia (AFOP) is a histopathologic entity with the hallmark feature of intra-alveolar ﬁbrin “balls” in the setting of organizing pneumonia in a patchy lung distribution. Given the histologic ﬁndings and clinical picture, AFOP may represent a part of a spectrum of diffuse alveolar damage (DAD) and organizing pneumonia.1 As the initial description, several sporadic cases have been described in the literature, and AFOP has been associated with a variety of underlying conditions such as rheumatologic diseases and environmental exposures including medications, infections, and transplantation, and several cases have been idiopathic.1-9 Presenting symptoms are nonspeciﬁc and commonly include cough, dyspnea, and fever. There are 2 patterns of disease progression that have been described: an acute and fulminant course with rapid progression to death and a less severe, subacute course.1 Radiographic ﬁndings are also nonspeciﬁc and not well deﬁned, though they often demonstrate bilateral basilar inﬁltrates and ground-glass opacities.10 No speciﬁc therapy exists, but case reports describe response to steroids and immunosuppressant therapy.1,11 The following is a case of AFOP in a patient who presented with nonspeciﬁc ﬂulike symptoms and rapidly progressed to respiratory failure. Chest imaging demonstrated bilateral military nodules, which in the setting of his clinical presentation encompassed a broad differential.
A 46-year-old man, with no signiﬁcant medical history, presented to the emergency room with a 4-day history of dyspnea, cough, night sweats, and fevers. The patient was hypoxic and required supplemental oxygen. Findings on physical examination were remarkable for diffuse crackles without wheezing or rhonchi. Findings on his cardiovascular examination were benign, and lack of muscle wasting suggested an acute process. Initial laboratory workup was signiﬁcant for a white blood cellcount of 12.7 with neutrophil predominance. Chest radiographs revealed a bilateral nodular interstitial pattern. Chest computed tomography was performed and demonstrated bilateral diffuse nodules in a miliary pattern with multiple small subpleural consolidations and associated hilar and mediastinal adenopathy (Figs. 1 and 2). Though tuberculosis (TB) was initially considered, his only risk factor for TB exposure was extensive travel as a medical missionary throughout South America 10 years prior. The patient was admitted to the intensive care unit and administered empiric therapy for community-acquired pneumonia. Despite initial treatment, his respiratory status continued to decline and required mechanical ventilation. Because of his worsening clinical status, the antimicrobial regimen was expanded to empirically cover TB and fungal infections. Results of autoimmune panel, viral polymerase chain reaction, bronchoalveolar lavage staining, and numerous cultures (blood, bronchoalveolar lavage, and sputum) were all negative. Given his lack of clinical improvement, an open lung biopsy was performed. Pathology demonstrated multifocal patchy areas of intra-alveolar ﬁbrin, type II pneumocyte hyperplasia, and organizing ﬁbroblasts without evidence of hyaline membranes, eosinophilic inﬁltrate, or granuloma formation (Fig. 3). Staining for Acid-Fast Bacillus and fungus were negative. These ﬁndings were most consistent with AFOP. The
n Reprint requests: Bryan A. Garcia, MD, Department of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610 E-mail address: [email protected]
http://dx.doi.org/10.1067/j.cpradiol.2015.02.006 0363-0188/& 2015 Elsevier Inc. All rights reserved.
B.A. Garcia et al. / Current Problems in Diagnostic Radiology ] (2015) ]]]–]]]
Fig 1. A CT image of the chest demonstrating bilateral diffuse, small nodules in a miliary pattern. There are several prominent hilar and mediastinal lymph nodes. CT, computed tomography.
patient was administered methylprednisolone, and his respiratory status markedly improved. He was subsequently extubated, weaned off supplemental oxygen, and discharged on a prolonged steroid taper. On follow-up he has been doing well without residual respiratory deﬁcit.
Discussion AFOP is a histopathologic diagnosis that was initially described in 2002 by Beasley et al in a case series of 17 patients. The dominant histopathologic feature is intra-alveolar ﬁbrin “balls” with type II pneumocyte hyperplasia in the setting of organizing pneumonia, typically in a patchy distribution. AFOP has been associated with a variety of disease states including infections such as human immunodeﬁciency virus, Pneumocystis jiroveci pneumonia, H1N1, and Chlamydia pneumoniae and rheumatologic disorders such as systemic lupus erythematosus, hematologic malignancy, and environmental and drug exposures.2,4-6,8,9,12-14 Despite this, several cases remain idiopathic, as was the case in our patient.1,11,15-17 There are 2 distinct clinical courses that have emerged: an acute and fulminant course typically leading to respiratory failure and death and a subacute course. No speciﬁc therapy exists, but prior cases demonstrate that patients with AFOP can beneﬁt from steroid therapy. A variety of radiographic ﬁndings have been described. Among patients with an acute presentation and rapid decline, imaging
Fig 3. Right lower lobe biopsy with multifocal patchy areas of acute and chronic interstitial and bronchiolar inﬂammation with intra-alveolar ﬁbrin deposition and type II pneumocyte hyperplasia. No evidence of hyaline membranes, eosinophilic inﬁltrate, or granuloma formation is present. (Color version of ﬁgure is available online.)
ﬁndings are similar to those of DAD, commonly including diffuse but basilar predominant consolidation and ground-glass opacities. Patients with a subacute course have imaging ﬁndings similar to those of organizing pneumonia, including both focal and diffuse parenchymal abnormalities.10 Our case is unique in that a bilateral miliary pattern was identiﬁed at presentation, giving rise to a broad differential diagnosis including tuberculosis, viral pneumonia, and metastatic disease. Postprimary TB, or reactivation TB, typically demonstrates upper lung consolidations and multiple cavitary nodules. Endobronchial spread of disease manifests as centrilobular nodules and “tree-in-bud” lesions. These ﬁndings are because of caseous necrosis and granulomatous inﬂammation ﬁlling and surrounding the respiratory bronchioles and alveoli. In immunocompromised hosts, hematogenous spread results in a miliary pattern with innumerable tiny nodules throughout both the lungs.18-20 Viral pneumonias, particularly cytomegalovirus and varicellazoster virus, may present similarly. Imaging ﬁndings of cytomegalovirus are varied and include small, poorly deﬁned nodules with patchy ground-glass attenuation, consolidation, and smooth interlobular thickening. On histologic examination, the alveoli are ﬁlled with ﬁbrinous exudates, hyaline membranes, and hemorrhage,
Fig 2. A coronal CT image of the chest demonstrating diffuse bilateral, innumerable small miliary nodules. CT, computed tomography. (Color version of ﬁgure is available online.)
B.A. Garcia et al. / Current Problems in Diagnostic Radiology ] (2015) ]]]–]]]
leading to the ground-glass or consolidative appearance. The interstitium is inﬁltrated by lymphocytes, giving the imaging ﬁndings of interlobular septal thickening. varicella-zoster virus pneumonia usually demonstrates diffuse tiny nodules (1-10 mm) throughout both the lungs. Ground-glass opacity and surrounding consolidation can be seen as well. Progressive disease leads to histologic ﬁndings of DAD.21 Though rare, metastatic disease may present with diffuse miliary nodules. This pattern of spread is found in highly vascular primary tumors such as renal cell carcinoma, choriocarcinoma, thyroid carcinoma, breast cancer, and melanoma.22 In summary, AFOP is a rare histopathologic diagnosis that is thought to represent an underdiagnosed histologic variant of DAD with the hallmark pathologic ﬁnding of intra-alveolar ﬁbrin “balls.” Imaging ﬁndings are variable, although this case demonstrates that radiologists should consider AFOP when encountering diffuse bilateral miliary inﬁltrates on chest imaging. References 1. Beasley MB, Franks TJ, Galvin JR, et al. Acute ﬁbrinous and organizing pneumonia: A histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med 2002;126:1064–70. 2. Hariri LP, Unizony S, Stone J, et al. Acute ﬁbrinous and organizing pneumonia in systemic lupus erythematosus: A case report and review of the literature. Pathol Int 2010;60:755–9. 3. Valim V, Rocha RH, Couto RB, et al. Acute ﬁbrinous and organizing pneumonia and undifferentiated connective tissue disease: A case report. Case Rep Rheumatol 2012;2012 [Article ID: 549298]. 4. Balduin R, Giacometti C, Saccarola L, et al. Acute ﬁbrinous and organizing pneumonia in a patient with collagen vascular disease “stigma”. Sarcoidosis Vasc Diffuse Lung Dis 2007;24:78–80. 5. Yokogawa N, Alcid DV. Acute ﬁbrinous and organizing pneumonia as a rare presentation of abacavir hypersensitivity reaction. AIDS 2007;21:2116–7. 6. Ribera A, Llatjos R, Casanova A, et al. Chlamydia pneumoniae infection associated to acute ﬁbrinous and organizing pneumonia. Enferme Infecc Microbiol Clin 2011;29:632–4.
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