gemcitabine is a chemotherapy agent frequently elected to treat solid tumors , including breast , colonic , ovarian , pancreatic , and non - small cell lung cancers [ 112 ] . metastatic gallbladder cancer is a complex and uncommon event [ 1417 ] . in this report , we describe a case of gallbladder metastatic colonic adenocarcinoma associated with fatal gemcitabine - induced pulmonary toxicity and discuss the histologic appearance of this dysfunction . a 72-year - old male patient experienced an incidental diagnostic of tubular adenocarcinoma inside the gallbladder after elective laparoscopic cholecystectomy for chronic cholecystitis . four days after cholecystectomy , he was submitted to laparotomy aiming radical resection ; however , peritoneal carcinomatosis was observed . the patient was submitted to a tumor screening and a pet scan pointed out a hot - spot in the left colon . this lesion was removed by colonoscopy and a histological examination confirmed a margin - free resection of a tubular adenocarcinoma . the patient was finally scheduled to receive three sections of gemcitabine ( 1,600  mg / m ) once a week . three weeks after the completion of chemotherapy , he developed an important respiratory distress requiring ventilator support . a helicoidal ct scan showed bilateral and diffuse lung infiltrates ( fig .  1 ) . a surgical lung biopsy was done and an accelerated usual interstitial pneumonia ( uip ) ( fig . 2 ) , consistent with drug - induced toxicity , was observed . the patient presented with progressive impairment of respiratory function , coagulopathy , hypotension , and acute renal failure despite the use of methylprednisolone pulse therapy , large spectrum antimicrobial therapy , and full respiratory , hemodynamic and dialytic support . he died 1  month later . to assess the probability that the event was caused by gemcitabine we computed a naranjo et al . average point score , which is based on the direction of causality between the drug and the manifestation of adverse effects . naranjo s method estimates gemcitabine as the probable cause of pulmonary toxicity in the current report.fig . 1a coronal reformatted images demonstrate involvement of all lung zones and predominantly upper lobe distribution of the ground - glass opacities and areas of consolidation . also noted are reticulation and small cysts in the subpleural and basal regions of the lungs . b high - resolution ct image at the level of the main bronchi shows extensive bilateral ground - glass opacities and dependent areas of consolidation . 2lung surgical biopsy specimen showing accelerated usual interstitial pneumonia ( uip ) . a characteristic area of honeycomb change is shown at low magnification ( a ) . at lower left corner ( a ) higher magnification of area showed in lower left corner ( b , c ) highlights the fibroblasts and chronic inflammation within alveolar septa and shows associated hyaline membranes ( arrow ) . note also the squamous metaplasia ( arrows ) of bronchiolar epithelium from adjacent honeycomb area ( d ) . this finding is another sign of superimposed acute lung injury a coronal reformatted images demonstrate involvement of all lung zones and predominantly upper lobe distribution of the ground - glass opacities and areas of consolidation . also noted are reticulation and small cysts in the subpleural and basal regions of the lungs . b high - resolution ct image at the level of the main bronchi shows extensive bilateral ground - glass opacities and dependent areas of consolidation . some emphysema can also be seen lung surgical biopsy specimen showing accelerated usual interstitial pneumonia ( uip ) . a characteristic area of honeycomb change is shown at low magnification ( a ) . at lower left corner ( a ) higher magnification of area showed in lower left corner ( b , c ) highlights the fibroblasts and chronic inflammation within alveolar septa and shows associated hyaline membranes ( arrow ) . note also the squamous metaplasia ( arrows ) of bronchiolar epithelium from adjacent honeycomb area ( d ) . there are several papers reporting pulmonary toxicity due to gemcitabine used as a single agent [ 18 ] or in combination with other antineoplastic agents [ 913 ] . the treatment of this event includes early use of steroid therapy administered either as pulses or continuously , mainly using methylprednisolone ; nevertheless , most cases have a dramatic and fatal evolution . our patient obtained fatal evolution in spite of the use of steroids as recommended in the literature . belknap et al . , reviewed data from spontaneous reports to research on adverse drug events and reports of pharmacovigilance ( radar ) program and appraised the clinical feature of gemcitabine - associated severe acute lung injury . among 178 reports of gemcitabine - induced pulmonary injury ( 55 from clinical trials and 92 from spontaneous reports ) dyspnea , fever , and pulmonary infiltrate were the most frequent symptoms of gemcitabine - induced pulmonary injury . the median time to the diagnosis of this toxicity is 48  days ( range 1529 ) after initiation of gemcitabine . eleven phase ii or phase iii clinical trials enrolling 317 patients identified pulmonary injury rates greater than 10% . highest rates of this toxicity ( 22 and 42% ) were observed in phase iii clinical trials in which patients with hodgkin s disease were treated with gemcitabine and bleomycin . the authors concluded that high rates of gemcitabine - associated severe lung injury were observed , mainly when gemcitabine was combined with other agents that can also cause lung injury . just recently , arrieta et al . , observed that radiotherapy and gemcitabine for locally advanced non - small cell lung cancer is associated with excessive pulmonary toxicity . differently , czarnecki and voss   reviewed records of patients with pulmonary toxicity at fda freedom of information ( fda - foi ) database and observed that there was no substantial difference in pulmonary toxicity with the combination of gemcitabine and taxanes in comparison with gemcitabine alone . indeed , gemcitabine - induced pulmonary toxicity is a dramatic condition . in the current case , the patient presented with rapidly progressive respiratory failure and the lung biopsy showed an accelerated uip complicated by superimposed acute lung injury . most reported cases have occurred in patients with known uip , but the lesion can occur in patients with clinically unrecognized uip . the etiology of acute lung injury in uip is unknown , but most cases are assumed to represent an inherent part of the natural history of uip . histologically , however , the changes can not be separated from other causes of acute lung injury ( such as viral infections , aspiration , sepsis , drug reactions , or toxic inhalants ) , and it is entirely possible that some cases may represent reactions to clinically unrecognized extrinsic lung insults . pathologically , the diagnosis is not usually difficult if all microscopic changes are taken into consideration . classically , there are easily recognizable areas of uip with patchwork pattern and honeycomb change . focus of diffuse alveolar damage ( dad ) recognizable by larger and more confluent interstitial fibroblast proliferation smaller than fibroblast foci of uip are usually present . . other findings of the diagnosis include squamous metaplasia in bronchiolar epithelium lining honeycomb areas . in the current case , naranjo s method identified gemcitabine as the probable agent of pulmonary toxicity . the liver is the most common site of metastatic dissemination of a colonic tumor ; however , a tumor from this region is very rare . in fact , this is the first report of metastasize inside the gallbladder from a tumor of colon origin . the prognostic of these patients was very poor with most of them achieving < 1-year survival . in summary , physicians should suspect pulmonary toxicity in patients with respiratory distress after gemcitabine chemotherapy , mainly in elderly patients that received high doses of this drug .