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as a non-specific sign of advanced stage disease&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Here we report the case of a patient with subclinical familial pulmonary fibrosis &#40;FPF&#41; identified during the screening program for first-degree relatives of idiopathic pulmonary fibrosis &#40;IPF&#41; cases with telomere shortness&#44; and who was finally diagnosed after a surgical lung biopsy that demonstrated DPO and usual interstitial pneumonia &#40;UIP&#41; pattern&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 63-year-old man with a history of mild cigarette smoking and no other relevant conditions was under study in our Unit of Interstitial Lung Diseases for telomere shortness as a first grade relative of a patient with IPF&#46; His brother suffered from IPF&#44; and both patients were diagnosed with telomere shortness &#40;&#60;1&#37;&#41; after genetic processing of a mouth swab specimen&#46; He had no respiratory symptoms&#46; Chest radiography showed bilateral peripheral reticulo-nodular pattern&#46; Pulmonary function tests showed a mild restrictive pattern with forced vital capacity &#40;FVC&#41; of 3&#46;83<span class="elsevierStyleHsp" style=""></span>L &#40;79&#37;&#41;&#44; total lung capacity &#40;TLC&#41; of 6&#46;43<span class="elsevierStyleHsp" style=""></span>L &#40;85&#37;&#41; and carbon monoxide transfer coefficient &#40;KCO&#41; 4&#46;82 &#40;125&#37;&#41;&#46; No oxygen desaturation was seen in the 6-minute walking test&#46; Laboratory data including hematological tests&#44; coagulation&#44; and renal and liver functions were normal&#46; Serum precipitins for different common antigens &#40;avian and fungi&#41; were negative&#44; as were immunological investigations&#44; including rheumatoid factor&#44; antinuclear antibodies and antineutrophil cytoplasmic antibodies&#46; A high-resolution CT chest scan demonstrated profuse calcification within the reticular &#40;septal&#41; lines &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; A surgical lung biopsy of the upper and lower left lobules was performed&#46; Histology showed numerous foci of branching bone tissue&#44; some of them with associated marrow elements&#44; and marked fibrosis of neighboring interstitium with abundant fibroblastic foci&#44; consistent with DPO and probable UIP pattern &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Discussion of this clinical case was made after a search of the terms dendriform pulmonary ossification and pulmonary fibrosis in PubMed as of January 6th 2016&#44; and includes citations from 2003 to 2013&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The incidence of DPO in patients with respiratory diseases has been estimated&#44; from autopsy reviews&#44; at between 0&#46;6&#37; and 1&#46;63&#37;&#44; mainly in late stages of chronic obstructive pulmonary disease and some ILD&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Familiar clustering has also been described in one case of spontaneous pneumothorax in a 29-year-old patient and his otherwise healthy father&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The incidence of DPO in fibrotic ILD seems to be higher&#44; but the clinical-pathogenic significance remains unknown&#46; Kim et al&#46; retrospectively reviewed 75 cases of UIP&#44; with an incidence of 6&#46;7&#37; of DPO seen in both CT scans and open-lung biopsy specimens&#46; However&#44; they found no cases of DPO in 44 patients with non-specific interstitial pneumonia &#40;NSIP&#41;&#44; suggesting that DPO could be useful for the differentiation between UIP and NSIP&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Nevertheless&#44; the relevance of this finding for the differential diagnosis remains controversial&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Our case demonstrates that DPO can also be found in a very early stage of fibrotic ILD&#46; Since DPO contains bone marrow mesenchymal stem cells &#40;MSCs&#41; and could be a source of different pro-fibrotic mediators&#44; it would be relevant for lung fibrosis development and&#47;or progression&#46; Although the mechanism of bone formation during normal development is clearly defined&#44; the formation of true bone in unusual sites and especially in the lungs is not well understood&#46; It is thought that these two mechanisms may not differ greatly since heterotopic bone is morphologically the same as that found in normal skeleton&#46; The association of FPF or IPF with heterotopic ossification &#40;HO&#41; supports the theory of a genetic linkage in this case&#46; This linkage has been described on the basis of homologous sequences on the transforming growth factor-&#946; &#40;TGF-&#946;&#41; and bone morphogenic protein &#40;BMP&#41; genes&#46; Another explanation could be the Wnt&#47;&#946;-catenin pathway&#44; which controls osteoblast function and bone formation and regulates differentiation of MSCs into myofibroblasts&#44; as well as osteopontin production&#44; which is involved in the induction of fibroblast migration and proliferation&#44; and also in the differentiation of MSCs into osteoblasts&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> Additionally&#44; the recently described Glast-expressing progenitor MSCs&#44; which have been identified as major contributors to HO&#44; could also play a role in the pathogenesis of pulmonary fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The requirement of lung biopsy in FPF patients&#44; mainly in subclinical cases&#44; is a current focus of debate among ILD clinicians&#46; Our case is an example of lung biopsy allowing the final diagnosis of the patient to be defined from early stages of the disease&#46; The procedure may reveal interesting histological findings providing relevant information for better understanding of pathogenic lung fibrotic process&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion&#44; this case suggests that the presence of HO could be involved in the progression of the lung fibrotic process in lung fibrosis&#44; rather than being only a consequence&#46; The heart of the matter lies&#44; therefore&#44; in understanding the heterogeneous fibrotic pathogenesis in order to identify the appropriate treatment targets for the different IPF or FPF cases&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Diez-Ferrer M&#44; Luburich P&#44; Llatj&#243;s R&#44; Xaubet A&#44; Dorca J&#44; Molina-Molina M&#46; Osificaci&#243;n pulmonar dendriforme en un caso subcl&#237;nico de fibrosis pulmonar familiar&#46; Arch Bronconeumol&#46; 2016&#59;52&#58;e9&#8211;e10&#46;</p>"
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