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in the setting of chronic cough with hemoptoic sputum&#46; He was a previous smoker &#40;100 pack-year of smoking&#41;&#46; Bronchoscopy showed neither signs of bleeding nor morphological anomalies and bronchoalveolar lavage &#40;BAL&#41; was negative for malignant cells and acid-fast bacilli&#46; Further investigation with positron emission tomography &#40;PET&#41; demonstrated a right upper lobe nodule with standardized uptake value &#40;SUV&#41; max of 2&#46;6&#46; Due to the high suspicion of primary lung malignancy&#44; biopsy of the nodule was performed by transthoracic needle aspiration &#40;TTNA&#41;&#44; documenting a fibrocollagenous lesion with lymphoplasmacytic infiltration and wall thickening of venous-type vessels&#46; On immunohistochemistry&#44; the number of IgG4-positive plasma cells was &#62;20 per high power field &#40;HPF&#41; and immunostaining for CD20 and CD3 was positive&#46; The serum concentrations of total IgG and IgG4 were normal&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">71-Year-old man who presented with posterior upper thoracic pain for 2 years&#46; He is an active smoker with 50 pack-year of smoking&#46; Chest CT detected a 35<span class="elsevierStyleHsp" style=""></span>mm spiculated mass in the right upper lobe&#44; which was biopsied by TTNA&#46; Histological examination demonstrated a nodular lesion with total architectural distortion due to fibrosis and lymphoplasmacytic infiltration&#46; On immunohistochemistry&#44; the number of IgG4-positive plasma cells was &#62;30 per HPF&#46; Given the suspicion of IgG4-RD further workup was performed&#44; showing elevated serum concentrations of IgG4 and normal concentrations of total IgG&#46; PET demonstrated a right upper lobe nodule with SUV max of 3&#46;1 and BAL pathological analysis was negative for malignant cells&#46; Hence&#44; in both cases the diagnosis of IgG4-RD was established based on clinico-pathological correlation&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Both patients started corticosteroid therapy with an initial prednisolone dosing of 0&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d for 4 weeks&#46; Patient 1 had a poor compliance to the treatment and presented no improvements after 2 months &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Patient 2 showed clinical improvement and a reduction of the mass&#8232;tm&#41; dimensions on CT imaging after 3 months of treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The prednisolone dose was tapered by 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d after the first and third month of therapy&#44; maintaining 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d at the present time&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Although the epidemiology of IgG4-related lung disease &#40;IgG4-RLD&#41; remains poorly described&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> it usually occurs in male adults with an average age of 69 years&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> Its clinical presentation depends on the location of the lesion&#44; nonetheless half of patients present nonspecific respiratory symptoms&#44; whereas the remaining present abnormalities on imaging studies in the absence of symptoms&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">2&#44;8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Appropriate diagnosis can be challenging&#44; as it relies upon the integration of clinical&#44; laboratorial and histopathologic findings&#46; The consensus statement on the pathology of IgG4-RD mentions that the final diagnosis requires both an appropriate histologic appearance and increased numbers of IgG4&#43; plasma cells&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> Such statement suggested &#62;50&#47;HPF and &#62;20&#47;HPF as the cut-off value for increased IgG4&#43; cells in surgical and nonsurgical biopsies&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> Additionally&#44; it underlines that diagnosis should be based primarily on morphological appearance and less importantly on tissue IgG4&#43;&#47;IgG&#43; ratio&#44; since various conditions can course with elevated IgG4&#43;&#47;IgG&#43; ratio&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1&#44;2</span></a> While pathologic findings represent the cornerstone for a definite diagnosis&#44; the interpretation of lung biopsy for any fibroinflammatory condition is challenging due to the fact that the lung tends to undergo stereotypic morphologic responses regardless of the type of injury&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> The characteristic histologic findings of IgG4-RLD are fairly common in lung samples afflicted by severe infection or organizing injury of various causes&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> highlighting the importance of a careful correlation with clinical and laboratorial data&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Elevation of IgG4 serum concentration is used to support the diagnosis of IgG4-RD&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">2</span></a> However&#44; recent studies have demonstrated that up to half of patients with biopsy-proven and clinically active IgG4-RD may have normal serum concentrations<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">9</span></a> and only a minority of patients with high IgG4 levels have IgG4-RD&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a> Thus the current trend is to deemphasize excessive reliance on serum IgG4&#44; which is neither specific nor sensitive of IgG4-RD&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">PET has been advocated as it can detect unforeseen localizations of the disease and assess the extent of systemic disease&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> In both patients&#44; PET confirmed that the disease is confined to the lung&#46; Two other case reports documented pulmonary&#44; hilar and mediastinal lesions with SUV max from 2&#46;1 to 11&#46;0&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">6&#44;12</span></a> yet there is no demonstrated range for SUV that can either gauge disease activity or guide treatment decisions&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The natural course of the disease is not completely known and there are no formal treatment guidelines&#46; However&#44; it is agreed among experts that the threshold for initiating treatment is low&#44; in order to prevent fibrosis and its irreversible damage on organs&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> The consensus statement on the treatment of IgG4-RD recommends glucocorticoids as the first-line agent for remission induction in all patients with active and untreated disease&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> Prednisolone at an initial dosage of 0&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d for 2&#8226;4 weeks is recommended&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a> which may be adjusted if the disease appears to be particularly aggressive&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> Immunossupression with rituximab is indicated in the steroid refractory disease&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">2</span></a> There is no consensus regarding the tapering regimen and maintenance therapy however&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In cases of isolated pulmonary disease&#44; it is imperative to ensure a regular follow-up with screening of multi-systemic involvement and malignancies&#46; Although the association of lung cancer with IgG4-RLD remains unclear&#44; a small number of adenocarcinoma-associated cases have been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion&#44; IgG4-RLD is a rare condition that may be diagnosed after the unexpected result of a biopsy in the setting of suspected lung malignancy&#46; Awareness of IgG4-RD is of utmost importance&#44; as the pathologist must perform a specific immunostaining and the clinician must exclude other differential diagnoses&#46; Increasing recognition and further studies will enlighten our understanding of the pathogenesis&#44; diagnostic criteria and standardized therapy for this disease&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Histological and radiological results from case 1&#58; &#40;A&#8242;&#41; hematoxylin and eosin stain&#44; &#40;B&#8242;&#41; immunohistochemistry for IgG4-positive plasma cells&#44; &#40;C&#8242;&#41; CT images at the time of diagnosis&#44; and &#40;D&#8242;&#41; CT images after 2 months of therapy with poor compliance&#46;</p>"
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