Histopathology 2014, 65, 581–585.
Correspondence Expanding the spectrum of pulmonary histopathological manifestations of anti-synthetase syndrome: anti-EJassociated acute fibrinous and organizing pneumonia
A
DOI: 10.1111/his.12420 © 2014 John Wiley & Sons Ltd.
Sir:There are few reports of the pulmonary histopathological features of anti-synthetase (AS) syndrome. We report a case of AS syndrome with acute fibrinous and organizing pneumonia (AFOP), a pattern of interstitial lung disease (ILD) not reported previously in AS syndrome. This is an idiopathic inflammatory disorder characterized by autoantibodies against aminoacyl-tRNA synthetases and by one or more or the following: myositis, ILD and joint involvement. Although generally considered a subset of dermatomyositis/polymyositis (DM/PM), rare patients with AS antibodies have another form of collagen vascular disease (CVD).1 The most prevalent AS antibody is directed against histidyl tRNA synthetase (Jo-1). Others include anti-threonyl (PL-7), anti-alanyl (PL-12), anti-isoleucyl (OJ), anti-glycyl (EJ), anti-asparaginyl (KS), anti-phenylalanyl (Zo) and anti-tyrosyl (YRS) antibodies. Herein we describe the case of a 66-year-old female with a 20 pack-year smoking history and no occupational exposures, who presented initially with a pruritic rash involving her upper extremities and trunk. The rash resolved with topical steroids, and shortly thereafter she developed constitutional symptoms, progressive muscle aches, and a mild productive cough. Bibasilar crackles were found on physical examination and a reduced diffusing capacity was found with pulmonary function testing. Laboratory testing disclosed elevated creatine kinase and lactase dehydrogenase levels, a positive anti-neutrophil cytoplasmic antibody titre (1:640) in an atypical perinuclear pattern, and anti-EJ autoantibodies. Testing for multiple other autoantibodies was negative. Chest X-ray demonstrated multifocal airspace consolidation. High-resolution computed tomography showed patchy peripheral airspace consolidation including foci of central lucency, suggestive of cryptogenic organising pneumonia.
B
Figure 1. Patchy acute fibrinous and organizing pneumonia with minimal lymphocytic interstitial inflammation and no significant interstitial fibrosis.
Video-assisted thoracoscopic biopsies of the left lung disclosed AFOP, featuring patchy OP accompanied in some areas by alveolar fibrin with minimal lymphocytic interstitial inflammation (Figure 1). There were no hyaline membranes and no significant eosinophilic inflammation or interstitial fibrosis. Microbiological tissue cultures and histochemical stains for microorganisms were negative. The patient did not tolerate initial treatment with either azathioprine or mycophenolate, but after nearly 2 years of corticosteroid therapy her symptoms have improved to the point that a steroid taper has been initiated. The pulmonary histopathological manifestations associated with anti-EJ antibodies have only been detailed in four cases: three cases of non-specific interstitial pneumonia (NSIP) (two cellular and one fibrotic) and one case of usual interstitial pneumonia (UIP) with prominent lymphoid follicles.2 While several reported cases of AFOP have been associated with underlying collagen vascular disease, AFOP has not been recognized previously in AS syndrome.3
582
Correspondence
Although not included as a new idiopathic interstitial pneumonia (IIP) in the recently published update of the American Thoracic Society/European Respiratory Society International Multidisciplinary Classification, due to concerns over whether it exists only in association with other conditions, AFOP is now recognized as a histological pattern that can occur in the clinical spectrum of diffuse alveolar damage and OP.4 In addition to occurring in association with CVD, as in our patient, other secondary associations of AFOP include hypersensitivity pneumonitis or drug reaction.4 Recognizing this pattern of lung injury is important, as patients with abundant fibrin in association with OP may require longer courses of corticosteroid treatment than OP alone to prevent relapse.5 Interstitial lung disease may be the initial or sole manifestation of AS syndrome in 20–40% of patients.1,2 The presence of AS antibodies in patients with ILD is not uncommon, and has been detected in 6.6% of patients undergoing evaluation for possible IIP.2 Such patients should be screened for AS antibodies, as pulmonary involvement is a major cause of morbidity in patients with AS syndrome. In summary, we present a case of AFOP in the setting of AS syndrome, which expands the pulmonary histopathological spectrum of this disease. It is important to consider evaluating patients with AFOP on lung biopsy for AS antibodies to facilitate proper clinical management. Jennifer L Sauter1,2 Kelly J Butnor1,2 1
Department of Pathology, The University of Vermont, and 2Department of Pathology and Laboratory Medicine, Fletcher Allen Health Care, Burlington, VT, USA 1. Koreeda Y, Higashimoto I, Yamamoto M et al. Clinical and pathological findings of interstitial lung disease patients with anti-aminoacyl-tRNA synthetase autoantibodies. Intern. Med. Tokyo Jpn 2010; 49; 361–369. 2. Watanabe K, Handa T, Tanizawa K et al. Detection of antisynthetase syndrome in patients with idiopathic interstitial pneumonias. Respir. Med. 2011; 105; 1238–1247. 3. Hernandez-Prera J, Beasley MB. Novel patterns of interstitial lung disease. Diagn. Histopathol. 2013; 19; 276–281. 4. Travis W, Costabel U, Hansell D et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am. J. Respir. Crit. Care Med. 2013; 188; 733–748. 5. Nashino M, Mathai SK, Schoenfeld D et al. Clinicopathologic features associated with relapse in cryptogenic organizing pneumonia. Hum. Pathol. 2014; 45; 342–351.
CD99 expression in nasal lobular capillary haemangioma DOI: 10.1111/his.12430 © 2014 John Wiley & Sons Ltd.
Sir: A CD99 (p30/p32mic2) cell adhesion glycoprotein intracytoplasmic dot-like expression pattern has been reported in several tumour types, such as ependymomas, ependymoma-like pituicytomas, the PNET component of endometrial carcinomas, anaplastic T-cell lymphomas, pancreatic solid papillary tumours, colon adenomas and adenocarcinomas, Merkel cell carcinomas, lung small-cell carcinomas, and, more recently, malignant soft tissue tumours such as rhabdomyosarcomas.1,2 Here, we report a similar pattern in a benign soft tissue vascular tumour, a nasal lobular capillary haemangioma (LCH). The patient (female; 32 years of age) presented with a right nasal mass and fever for 2 days. The patient’s history revealed drug allergy (amoxicillin/ clavulanic acid and penicillin) and lung infection. Nasal inspection showed a polypoid lesion, which was resected. The specimen was composed of four tissue fragments measuring 7 mm, 8 mm, 14 mm, and 4 mm in greatest dimension, respectively, which were analysed entirely on haematoxylin and eosinstained tissue sections. The unencapsulated lesion consisted of a proliferation of small vessels with both lobular and diffuse or patternless architecture (Figure 1). Some vascular spaces were observed, several of which were dilated or pseudocystic, with rare papillary projection tufts. The endothelium was focally hyperplastic, but unistratified. One of the larger vascular structures showed extensive thrombosis. More than half of the tumour tissue, both superficially and deeply situated, showed a lack of lobular architecture, and contained a high density of mainly immature-looking, indefinite small vessels, frequently with inconspicuous vascular lumina (bud-like), or resembling vascular slits. In these zones, stroma/ interstitial tissue was almost completely absent. Focal oedema was observed in the superficial parts of the tumour, where stroma was more abundant. Ulceration with a small amount of granulation tissue and mild inflammation was seen focally. Vascular luminal cells were CD31-positive on immunohistochemistry in all vessel types (wellformed vessels, vascular slits, and cavities), whereas D2-40 staining was positive in some peripheral, submucosal vessels and vascular spaces. Vascular luminal cells were also CD34-positive. Abluminal vascular Histopathology, 65, 581–585.
Correspondence Expanding the spectrum of pulmonary histopathological manifestations of anti-synthetase syndrome: anti-EJassociated acute fibrinous and organizing pneumonia
A
DOI: 10.1111/his.12420 © 2014 John Wiley & Sons Ltd.
Sir:There are few reports of the pulmonary histopathological features of anti-synthetase (AS) syndrome. We report a case of AS syndrome with acute fibrinous and organizing pneumonia (AFOP), a pattern of interstitial lung disease (ILD) not reported previously in AS syndrome. This is an idiopathic inflammatory disorder characterized by autoantibodies against aminoacyl-tRNA synthetases and by one or more or the following: myositis, ILD and joint involvement. Although generally considered a subset of dermatomyositis/polymyositis (DM/PM), rare patients with AS antibodies have another form of collagen vascular disease (CVD).1 The most prevalent AS antibody is directed against histidyl tRNA synthetase (Jo-1). Others include anti-threonyl (PL-7), anti-alanyl (PL-12), anti-isoleucyl (OJ), anti-glycyl (EJ), anti-asparaginyl (KS), anti-phenylalanyl (Zo) and anti-tyrosyl (YRS) antibodies. Herein we describe the case of a 66-year-old female with a 20 pack-year smoking history and no occupational exposures, who presented initially with a pruritic rash involving her upper extremities and trunk. The rash resolved with topical steroids, and shortly thereafter she developed constitutional symptoms, progressive muscle aches, and a mild productive cough. Bibasilar crackles were found on physical examination and a reduced diffusing capacity was found with pulmonary function testing. Laboratory testing disclosed elevated creatine kinase and lactase dehydrogenase levels, a positive anti-neutrophil cytoplasmic antibody titre (1:640) in an atypical perinuclear pattern, and anti-EJ autoantibodies. Testing for multiple other autoantibodies was negative. Chest X-ray demonstrated multifocal airspace consolidation. High-resolution computed tomography showed patchy peripheral airspace consolidation including foci of central lucency, suggestive of cryptogenic organising pneumonia.
B
Figure 1. Patchy acute fibrinous and organizing pneumonia with minimal lymphocytic interstitial inflammation and no significant interstitial fibrosis.
Video-assisted thoracoscopic biopsies of the left lung disclosed AFOP, featuring patchy OP accompanied in some areas by alveolar fibrin with minimal lymphocytic interstitial inflammation (Figure 1). There were no hyaline membranes and no significant eosinophilic inflammation or interstitial fibrosis. Microbiological tissue cultures and histochemical stains for microorganisms were negative. The patient did not tolerate initial treatment with either azathioprine or mycophenolate, but after nearly 2 years of corticosteroid therapy her symptoms have improved to the point that a steroid taper has been initiated. The pulmonary histopathological manifestations associated with anti-EJ antibodies have only been detailed in four cases: three cases of non-specific interstitial pneumonia (NSIP) (two cellular and one fibrotic) and one case of usual interstitial pneumonia (UIP) with prominent lymphoid follicles.2 While several reported cases of AFOP have been associated with underlying collagen vascular disease, AFOP has not been recognized previously in AS syndrome.3
582
Correspondence
Although not included as a new idiopathic interstitial pneumonia (IIP) in the recently published update of the American Thoracic Society/European Respiratory Society International Multidisciplinary Classification, due to concerns over whether it exists only in association with other conditions, AFOP is now recognized as a histological pattern that can occur in the clinical spectrum of diffuse alveolar damage and OP.4 In addition to occurring in association with CVD, as in our patient, other secondary associations of AFOP include hypersensitivity pneumonitis or drug reaction.4 Recognizing this pattern of lung injury is important, as patients with abundant fibrin in association with OP may require longer courses of corticosteroid treatment than OP alone to prevent relapse.5 Interstitial lung disease may be the initial or sole manifestation of AS syndrome in 20–40% of patients.1,2 The presence of AS antibodies in patients with ILD is not uncommon, and has been detected in 6.6% of patients undergoing evaluation for possible IIP.2 Such patients should be screened for AS antibodies, as pulmonary involvement is a major cause of morbidity in patients with AS syndrome. In summary, we present a case of AFOP in the setting of AS syndrome, which expands the pulmonary histopathological spectrum of this disease. It is important to consider evaluating patients with AFOP on lung biopsy for AS antibodies to facilitate proper clinical management. Jennifer L Sauter1,2 Kelly J Butnor1,2 1
Department of Pathology, The University of Vermont, and 2Department of Pathology and Laboratory Medicine, Fletcher Allen Health Care, Burlington, VT, USA 1. Koreeda Y, Higashimoto I, Yamamoto M et al. Clinical and pathological findings of interstitial lung disease patients with anti-aminoacyl-tRNA synthetase autoantibodies. Intern. Med. Tokyo Jpn 2010; 49; 361–369. 2. Watanabe K, Handa T, Tanizawa K et al. Detection of antisynthetase syndrome in patients with idiopathic interstitial pneumonias. Respir. Med. 2011; 105; 1238–1247. 3. Hernandez-Prera J, Beasley MB. Novel patterns of interstitial lung disease. Diagn. Histopathol. 2013; 19; 276–281. 4. Travis W, Costabel U, Hansell D et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am. J. Respir. Crit. Care Med. 2013; 188; 733–748. 5. Nashino M, Mathai SK, Schoenfeld D et al. Clinicopathologic features associated with relapse in cryptogenic organizing pneumonia. Hum. Pathol. 2014; 45; 342–351.
CD99 expression in nasal lobular capillary haemangioma DOI: 10.1111/his.12430 © 2014 John Wiley & Sons Ltd.
Sir: A CD99 (p30/p32mic2) cell adhesion glycoprotein intracytoplasmic dot-like expression pattern has been reported in several tumour types, such as ependymomas, ependymoma-like pituicytomas, the PNET component of endometrial carcinomas, anaplastic T-cell lymphomas, pancreatic solid papillary tumours, colon adenomas and adenocarcinomas, Merkel cell carcinomas, lung small-cell carcinomas, and, more recently, malignant soft tissue tumours such as rhabdomyosarcomas.1,2 Here, we report a similar pattern in a benign soft tissue vascular tumour, a nasal lobular capillary haemangioma (LCH). The patient (female; 32 years of age) presented with a right nasal mass and fever for 2 days. The patient’s history revealed drug allergy (amoxicillin/ clavulanic acid and penicillin) and lung infection. Nasal inspection showed a polypoid lesion, which was resected. The specimen was composed of four tissue fragments measuring 7 mm, 8 mm, 14 mm, and 4 mm in greatest dimension, respectively, which were analysed entirely on haematoxylin and eosinstained tissue sections. The unencapsulated lesion consisted of a proliferation of small vessels with both lobular and diffuse or patternless architecture (Figure 1). Some vascular spaces were observed, several of which were dilated or pseudocystic, with rare papillary projection tufts. The endothelium was focally hyperplastic, but unistratified. One of the larger vascular structures showed extensive thrombosis. More than half of the tumour tissue, both superficially and deeply situated, showed a lack of lobular architecture, and contained a high density of mainly immature-looking, indefinite small vessels, frequently with inconspicuous vascular lumina (bud-like), or resembling vascular slits. In these zones, stroma/ interstitial tissue was almost completely absent. Focal oedema was observed in the superficial parts of the tumour, where stroma was more abundant. Ulceration with a small amount of granulation tissue and mild inflammation was seen focally. Vascular luminal cells were CD31-positive on immunohistochemistry in all vessel types (wellformed vessels, vascular slits, and cavities), whereas D2-40 staining was positive in some peripheral, submucosal vessels and vascular spaces. Vascular luminal cells were also CD34-positive. Abluminal vascular Histopathology, 65, 581–585.
