A 75 - year - old man was referred to our hospital for the evaluation of dysphagia for 9 months . He had associated symptoms of nausea and vomiting but denied hematemesis , hematochezia , lethargy , and dyspnea . He was an active smoker and consumed alcohol for 30 years . Physical examination revealed no peripheral lymphadenopathy , thyromegaly , ascites , or mass in the abdomen . Laboratory data were normal : HBs - Ag negative , HIV negative , and syphilis negative . Test for serum antibody against Helicobacter pylori was negative . Chest computed tomography ( CT ) was notable for a huge well - circumscribed and homogeneous cylindrical mesenchymal neoplasm measuring 15.5×5.9×4.0 cm in lower and middle esophagus with mild contrast enhancement ( Fig.1A ) . CT revealed no abnormalities in the lungs , heart , ribs , or mediastinum . Endoscopic examination showed a submucosal lesion in the esophagus starting at 20 cm from the incisor teeth extending up to the cardia ( Fig.1B ) . Endoscopic ultrasonography ( EUS ) revealed hypoechoic lesion with a clear boundary located in the 4th layer . The mass appeared as a benign tumor and was preoperatively diagnosed as esophageal leiomyoma based on chest CT , endoscopic examination , and EUS findings . Endoscopic mucosal resection or endoscopic submucosal resection was not possible because of large size . Hence , surgical resection was planned and informed written consent was taken . The patient underwent thoracoscopic - assisted resection of the mass with gastroesophageal anastomosis , thoracic duct ligation , and jejunostomy . Postoperative course was uneventful . Grossly , a spindle shaped lump measuring 14 × 3.5 × 2.5 cm , was observed in the resected esophagus , which grew into the esophageal lumen and blocked most of lumen . This lump located in the submucosa was covered with intact mucosa , without erosion , ulcer , and hemorrhage . Its cut surface was homogenously white to grayish - white in color . Histological examination using hematoxylin and eosin staining revealed that tumor was covered with intact squamous epithelium , arising from the submucosal layer and expanding in to the muscular layer . The tumor was composed of many nodules of varying sizes separated by collagen fibers . Numerous cytoplasm - rich cells were observed in the collagenous septations with invasive growth pattern ( Fig.2A – C ) . The nodules were mainly composed of small to mid - sized centrocyte - like or monocyte - like cells arranged in diffuse pattern . These atypical lymphocytes possessed clear boundary , pale cytoplasm , irregular nucleus , and occasional nucleolus ( Fig.2D ) . Mitosis was rare . No lymphoepithelial lesion was recognized in the lesion . On immunohistochemical staining , epithelium was diffusely positive for cytokeratin ( Fig.3A ) , and the tumor cells were diffusely positive for cluster of differentiation ( CD)20 , paired box 5 ( Fig.3B ) , and B - cell lymphoma ( Bcl)-2 ( Fig.3D ) . Small deposits of tumor cells , which were distributed mainly in the collagen fibers , were positive for multiple myeloma oncogene 1 , CD138 , and CD43 . Several tumor cells were also positive for CD30 . Small lymphocytes were positive for CD3 and CD5 . Follicular dendritic cells were positive for CD21 and CD23 ( Fig.3C ) . All cells were negative for CyclinD1 , CD10 , Bcl-6 , and B lymphocyte specific activation of OCT binding protein 1 . These follicular dendritic cells were arranged in nodules in which the tumor cells were relatively evenly distributed . This pattern was suggestive of follicular colonizations seen in MALT lymphoma . In this case , gene rearragements and clonality analysis of immunoglobulin heavy chain gene , kappa light chain gene , and lambda light chain gene was performed using the IdentiCloneTM IGH / IGK / IGL Gene Clonality Assay ( InVivoScribe Technologies , CA ) . On monoclonal gene rearrangement , 1 band appeared within 150 to 175 base pairs ( bp ) in heavy chain gene , 2 discrete bands within 225 to 250 bp in kappa light chain gene , and 1 band within 125 to 150 bp in lambda light chain gene ( Fig.4 ) . In addition , no Epstein – Barr virus was observed in this lymphoma on in situ hybridization using the EB virus - encoded small RNA ( Fig.3E , F ) . Based on the clinical data , pathological , immunohistochemical , and gene rearragements analysis , final diagnosis of primary esophageal MALT lymphoma was made . After the surgical resection , no additional therapy in the form of chemotherapy or radiotherapy was administered . Over the 8 months of follow - up , no evidence of recurrence or metastases was found on CT and the patient has been asymptomatic . Ethical approval for this study was obtained from Medical Ethics Committee of the Third Affiliated Hospital , the Third Military Medical University . Written informed consent was obtained from the patient for the publication of this case report and the accompanying images .


This case report was approved by the Review Board of Shandong Power Central Hospital and the patient 's parents signed informed consent for publication of the case report and any accompanying images . A 4 - year - old female child presented at the outpatients department with slowly enlarging , painless , symmetrical swelling of both cheeks . When the girl was approximately 2 years old , the parents noticed a change in her facial symmetry , which later became more obvious . On palpation , the swellings were bony and hard in consistency . The skin over the swelling was smooth and freely movable , with no increase in temperature ( Fig.1 ) . There was no history of any trauma , pain , pus discharge , blood discharge , fever , paresthesia , anorexia , or weight loss . No significant family history was reported . Panoramic radiography revealed involvement of both the mandible and the maxilla , and showed a soap bubble - like multilocular radiolucency with thin and expanded cortices . Unerupted teeth included : 15 , 25 , 35 , 37 , 45 , and 47 was impacted ( Fig.2 ) . Multislice computed tomography showed the presence of multilocular cystic lesions filled with soft - tissue density material and dental anomalies affecting the body and the sides of the mandible . Similar lesions were also observed in the maxilla ( Fig.3 ) . A biopsy was obtained from the central area of the left rami . Histologic examination showed many large multinucleated giant cells in a loose , delicate fibrillar connective tissue stroma containing large numbers of fibroblasts and many small blood vessels ( Fig.4 ) . As the child grows older , the lesions often become static and may show regression at puberty . In the current case , no surgical intervention was under taken and the patient was followed up at regular intervals .


A 54 - year - old woman with stage IV NSCLC was treated with carboplatin and paclitaxel without disease response . Molecular analysis of tumor tissue was unavailable at that time . However , her demographic profile ( Asian , minimal smoking history , non - small cell histology ) predicted her disease would harbor EGFR TKI sensitive cells [ 2 ] . Therefore , she then initiated standard daily dosing of erlotinib ( 150 mg ) and her disease responded . Twenty - eight months later , she acquired resistance to erlotinib with progression of disease systemically . Following further progression through an experimental angiogenesis inhibitor , she initiated pemetrexed and resumed standard dose erlotinib . After initial response , 11 months later , her disease again progressed . DNA was extracted from biopsy of a progressing lung lesion and examined using established techniques for analysis of EGFR mutations [ 5 ] . Direct sequencing of exons 18–21 encoding the kinase domain of EGFR revealed the L858R mutation associated with EGFR TKI sensitivity ( Fig.1 ) [ 2 ] . It also demonstrated the T790 M mutation associated with acquired EGFR TKI resistance ( Fig.1 ) [ 2 ] . She also developed headaches and there was a high clinical suspicion of CNS metastases despite negative imaging ( not shown ) . She refused a lumbar puncture . She initiated empiric temozolomide plus standard dose erlotinib ( 150 mg daily ) for presumed CNS disease , but after one cycle her headaches worsened , and she developed nausea and vomiting concerning for CNS metastases with associated raised intracranial pressure . Magnetic resonance imaging ( MRI ) of the brain now demonstrated LM ( Fig.2 ) confirmed by CSF cytology ( not shown ) . By direct sequencing , DNA from CSF cells harbored L858R predicting EGFR TKI sensitivity ( Fig.3 , left panel ) but not the T790 M resistance mutation ( data not shown ) . Because the result for T790 M was negative in this sample , we performed a more sensitive fluorescence detection PCR - based assay that takes advantage of a PCR restriction fragment length polymorphism generated by the specific missense mutation ( Fig.3 , right panel , arrow , positive control ) [ 6 ] . That result was also negative , as only the wild type peak was detected ( Fig.3 , right panel , bottom ) . Therefore , we hypothesized that the LM remained sensitive to an EGFR TKI if sufficiently high concentrations of drug could be achieved in the CSF . The erlotinib concentration required to inhibit growth of cell lines harboring L858R by 50 % ( IC50 ) is 100 nM ( nM ) [ 2 ] . Standard dose erlotinib ( 150 mg daily ) achieves 3000 nM in plasma [ 7 ] , but CSF concentrations of EGFR TKIs are as low as 1 % plasma levels below the IC50 [ 3 , 8 ] . Increasing the daily dose of gefitinib to enhance CSF penetration has been an effective strategy [ 3 ] , but gefitinib is no longer available in the United States following failure in phase III NSCLC trials . An analogous increase of the daily erlotinib dose above 150–200 mg daily induces unacceptable toxicity . However , weekly high - dose erlotinib up to 2000 mg is tolerable [ 4 ] . Pharmacokinetic analysis of CSF from another patient with NSCLC LM ( not shown ) treated with 1500 mg erlotinib weekly demonstrated a peak plasma concentration of 11,300 nM with a concurrent CSF concentration of 130 nM. Therefore , such high dose weekly administration of erlotinib achieved a CSF concentration exceeding the IC50 . Therefore , to increase CSF penetrance over standard daily erlotinib dosing in this patient , we initiated high - dose weekly erlotinib at 1000 mg then 1200 mg ; persistent nausea precluded higher doses . Pharmacokinetic analysis was not undertaken in this patient . After 1 month there was a partial radiographic response of LM on brain MRI ( Fig.2b ) and after 2 months in the cauda equina ( not shown ) . However , hydrocephalus and persistent symptoms referable to increased intracranial pressure led to a VP shunt and whole - brain radiation therapy , after which she resumed treatment with 1500 mg weekly erlotinib . One month later , progressive intra - thoracic disease led to initiation of cetixumab and erlotinib was continued but changed to low dose ( 100 mg ) daily . She survived 14 months following the diagnosis of CNS disease .


A 53 - year - old man came to our hospital with signs and symptoms of acute heart failure after a 2 - week history of progressive breathlessness . He had a history of recurrent skin abscesses and atopic dermatitis and regularly visited a dermatologist in our hospital . On arriving at our hospital , his extremities were warm and dry . According to the New York Heart Association criteria , he had class III congestive heart failure ( CHF ) . An electrocardiogram revealed diffuse nonspecific T - wave changes , low voltage ( < 5 mm ) in the extremity leads and poor R - wave progression in the anterior chest leads . Multiple sporadic ventricular premature beats were seen ( Figure 1 ) . Chest x - ray film confirmed right pleural effusion , and mild cardiomegaly but no pulmonary congestion ( Figure 2 ) . Blood tests showed severely elevated B - type natriuretic peptide ( 901 pg / mL ) and markedly raised IgE ( 12 000 IU / mL ) without eosinophilia ( eosinophil count of 1.62×108 / L ) . Biochemical analysis revealed no significant findings : blood urea nitrogen of 14.3 mg / dL [ reference value ( RV ): 7.00–22.00 ] , creatinine of 0.90 mg / dL ( RV : 0.60–1.00 ) , C - reactive protein ( CRP ) of 0.2 mg / dL ( RV : 0.00–0.50 ) , serum amyloid A ( SAA ) of 7.0 μg / mL ( RV : 0–8.0 ) , and troponin T of 0.07 ng / mL ( RV : 0–0.1 ) . Immunology testing revealed negative perinuclear anti - neutrophil cytoplasmic antibodies and no elevation of myeloperoxidase antibodies . The distribution of albumin and globulin in the serum was normal . Serum protein immuno - electrophoresis did not reveal M - protein , and urinalysis revealed no Bence - Jones protein . Transthoracic echocardiography ( Figure 3 ) showed concentric mild left ventricular ( LV ) hypertrophy ( 12 mm ) without the characteristic granular sparkling appearance and pericardial effusion , preserved ejection fraction ( 60 % ) , and bi - atrial enlargement with normal ventricular chambers . Doppler - derived LV diastolic filling demonstrated a restrictive pattern with a trans - mitral early filling wave deceleration time of 160 ms and an elevated E / A ratio of 2.8 . A markedly elevation of E / e ’ ratio of 27.3 indicated elevated LV filling pressure . On day 1 of hospitalization , we prescribed an angiotensin - converting enzyme ( ACE ) inhibitor and low - dose diuretics . On day 3 of hospitalization , after initiating ACE inhibitor and diuretic therapy , the patient ’s symptoms resolved . The dermatologists performed a biopsy of a blue macula of the forehead skin . On day 4 , we introduced a low - dose β - blocker and performed an endomyocardial biopsy ( EMB ) , obtaining 3 fragments of the right ventricular septum because diagnostic confirmation of cardiac amyloidosis requires the demonstration of amyloid deposits . In addition , we performed right heart catheterization ( RHC ) , and coronary angiography to exclude obstructive coronary artery disease . The data obtained from the RHC indicated subset type IV according to the Forrester classification . The right ventricular pressure curve did not show a dip - and - plateau configuration . Skin biopsy revealed hyperkeratosis in the epidermis and mild inflammatory changes throughout the dermis with an infiltration of lymphocytes . The specimen exhibited apple - green birefringence with polarized light after Congo red staining ( Figure 4 ) . Histological examination of the myocardial specimen showed no signs suggesting myocarditis , eosinophilic granulomas , or cardiomyopathy with iron deposition , but Congo red staining revealed amyloid deposits ( Figure 5 ) . In addition , a strongly positive immunohistochemical reaction to immunoglobulin λ - chain in the myocardial interstitium led us to diagnose this patient ’s systemic amyloidosis as AL amyloidosis . The patient generally tolerated the low - dose β - blocker well and was discharged on day 10 with no complications . The patient is currently being followed - up at 6 - month intervals as an out - patient , with no exacerbation of the CHF thus far .


Our patient was a 7 - year - old Italian boy born after an uneventful gestation of normal duration . At the age of 16 months , he presented with a clinically evident enlarged abdomen and was referred for oncological examination . Initial tests revealed anemia , thrombocytopenia , and splenomegaly . A bone marrow biopsy revealed the presence of foam cells , which led to suspicion of lysosomal storage disease . Biochemical testing revealed elevated level of acid phosphatase ( 47.8 IU / L [ normal range 5–7 IU / L ] ) and chitotriosidase activity ( 508 nmol / mg protein [ normal range 5.9–41.0 nmol / mg protein ] ) , as well as reduced beta - glucosidase activity ( 2 nmol / mg / protein [ normal range 4.5–18.0 nmol / mg / protein ] ) . Molecular analysis showed homozygous L444P mutations in the GBA gene ( OMIM reference 606463 ) , confirming the diagnosis of chronic NGD . The patient began ERT at a dosage of 60 U / kg every 2 weeks at the age of 18 months . Thereafter , when the patient reached the age of 30 months , we decided to combine ERT with SRT with miglustat . This clinical decision was approved by our institution ’s ethics committee , and informed consent was obtained from the patient ’s parents before commencing combination therapy . The dose of miglustat was adjusted according to the patient ’s body surface area and was uptitrated during the first 4 weeks with the following scheme : one - third of target dose during weeks 1 and 2 , two - thirds of target dose during weeks 3 and 4 , and target dose ( 100 mg three times daily ) after 1 month . From 2 weeks before starting miglustat therapy , the patient also followed specific dietary modifications , avoiding high intake of carbohydrate - containing food in single meals , especially foods high in disaccharides , such as sucrose and maltose , to ensure acceptable gastrointestinal tolerability . He experienced mild episodes of diarrhea after commencing miglustat therapy , which decreased in frequency / severity over time . From the start of ERT / miglustat combination treatment , we observed a reduction in splenomegaly and a gradual normalization of hematological values and plasma angiotensin - converting enzyme activity ( Table 1 ) . Plasma chitotriosidase was evaluated at the time of diagnosis and then approximately every 6 months during follow - up . Values showed an initial reduction after the start of ERT , with a further , substantial , and sustained decrease after commencement of miglustat treatment ( Fig.1 ) . The patient has been followed according to recommended guidelines for GD , which specify a complete neurological examination , clinical evaluation of ocular movements , and psychological evaluations every 6–12 months [ 10 ] . After 5 years of combination therapy and follow - up , the patient did not show any signs of neurological impairment . As of February 2016 , he had not displayed any epileptic crises and had demonstrated clinical performance and cooperation . He showed good muscular tone and trophism , normal reflexes with a slight hyperreflexia in his legs , and a negative Romberg sign . His toe and heel deambulation was normal . In particular , ocular evaluations revealed no evidence of saccadic movement velocity reduction and normal visual evoked potentials . The patient ’s auditory brain responses were also normal . In addition , he has not demonstrated any cognitive impairment , and he has regularly attended school with good performance since the age of 5 years .


A 69 - year - old male diabetic patient was admitted with acute left ventricular ( LV ) failure and was treated with intensive decongestive therapy . He had severe peripheral edema and bilateral basal crepitations . Initial workup revealed normal levels of troponine ( < 0.01 ng / ml ) and CPK - MB ( 4.6 ng / ml ) , thereby ruling out acute coronary syndrome . The level of BNP was 1230 pg / ml confirming the diagnosis of heart failure . Echocardiographic assessment revealed LVEF of 10 % with dilated cardiac chambers , and estimated pulmonary artery systolic pressure ( PASP ) was 70 mm of Hg with features of raised LV diastolic pressure . Angiography was performed after 3 days of decongestive therapy which revealed critical triple vessel disease with left main coronary artery disease ( Fig.1 ) . He was referred for CABG . The patient was put on frusemide infusion with oral ramipril and aldactone . He was taken up for elective OPCAB 1 week after angiography . Renal function was monitored regularly to adjust diuretic dose . There was no feature of end organ dysfunction . STS risk of mortality was 2.4 % . Repeat echocardiographic assessment revealed improvement of LVEF to 15 % and decrease in PASP to 30 mm Hg and decrease in LV filling pressure . OPCAB was performed through median sternotomy . Left ITA was used for grafting left anterior descending artery ( LAD ) . After revascularizing LAD , right ITA ( RITA ) and RA composite , graft was prepared . The distal end of RITA was used for revascularizing the diagonal artery . There was significant improvement in systolic blood pressure after this distal anastomosis . After these two grafts , heart was lifted for lateral and posterior wall vessels . We make a longer skin incision , open the sternum widely , and release pericardium on the right side to displace the heart gradually . This was supplemented with headlow and lateral tilt position . Liberal doses of inotropic support were used . RA was used for sequential grafting of obtuse marginal , posterior LV branch , and posterior descending artery . All these five distal anastamoses were performed uneventfully . The patient was electively ventilated for 2 days . Echocardiography on 1st POD revealed improvement in LVEF to 20 % . He was started on low dose beta blockers after inotropic supports were weaned off . He had slow and uneventful recovery . Echocardiography on 4th POD revealed improvement in LVEF to 30 % ( Table 1 ) . He had persistent pleural drainage requiring prolonged intensive care unit stay . After pleural drainage subsided and drains were removed , he was discharged on diuretics , low dose beta blocker , and ramipril .


Our 24 - year - old non - smoking male patient presented with repeated hemoptysis in May 2008 with 4 days of concomitant right thoracic pain which intensified while breathing . During holidays in his home country , this Cuban patient suffered from a cold with fever and a strong cough . The strong dry cough persisted after recovery from the cold . The patient did not report any loss of weight . The initial CT scan of the thorax showed a 12 × 4 cm solid mass paravertebral right in the lower thorax without any signs of metastases ( Figure 1 ) . The bronchoscopy ( Figure 2 ) with non - bleeding biopsy revealed a mass of the lower right bronchus which histologically and immunohistologically provided evidence of a granular cell or Abrikossoff tumor [ 1 ] . The bronchial lavage which followed was negative for malignant cells . The patient was discharged and surgical intervention was planned . Four days after discharge a spontaneous hemothorax developed . The patient needed to be readmitted and the hemothorax was drained . No malignant cells were detected in the cytological examination of the drained liquid . After an uneventful course and decreasing of the hematoma , the tumor was excised by performing a lower right lobectomy 6 months after the initial admission . The final histological examination confirmed a peribronchial and infiltrating S100 positive tumor supporting the Schwann cell origin theory with very low growth rate of 2 % and a size of 15 mm ( Figure 3 ) .


A 25 - year - old female patient had noticed left - sided visual loss and amenorrhea 2 years prior to being seen , with right hemiparesis developing 6 months beforehand . Aggravated symptoms ( drooping at corner of right lip and bilateral temporal hemianopia ) finally prompted hospitalization . At that time , a massive ( > 5 cm ) tumor of intra- and suprasellar location , excluding mesencephalon backward , was seen on computerized tomography ( CT ) of the head ( Fig.1a ) . Further testing revealed an exceedingly high - serum level of prolactin ( PRL ) ( 4408 ng / ml ) , whereas levels of all other pituitary hormones were within reference ranges ( growth hormone ( GH ) , 0.50 ng / ml ; luteinizing hormone ( LH ) , 2.60 mIU / ml ; follicle - stimulating hormone ( FSH ) , 4.57 mIU / ml ; adrenocorticotropic hormone ( ACTH ) , 37.4 pg / ml ; thyroid - stimulating hormone ( TSH ) , 2.68 μIU / ml ) . T1 - weighted magnetic resonance ( MR ) imaging with contrast ( gadolinium ) showed homogeneous tumor enhancement , but adjacent tissue was not edematous in T2 - weighted views . The mass did not regress , despite a 4 - week course of the dopamine analog , cabergoline ( 1 mg / week ) , and serum PRL level ( 2207 ng / ml ) remained elevated . Relative to status at admission , the right lateral ventricle also had enlarged somewhat , due to obstruction at foramen of Monro ( Fig.1b ) . In light of this intransigence , surgical debulking of tumor was elected first , through craniotomy and then via transsphenoidal approach . The hardened elastic quality of the tumor and its strong attachments to neighboring structures prevented complete removal , but related mass effect was significantly reduced and serum PRL level declined ( to 250 ng / ml ) in steps at each procedural stage . But the normalization of PRL level had not been achieved with the administration of cabergoline increased up to 0.5 mg / day . The residual tumor showed no evidence of regrowth or distant metastasis 1 year after surgery . Histopathologically , hematoxylin and eosin ( H&E)-stained sections of specimens from the first and second surgical procedures similarly were composed of polygonal and spindle cells with round , oval , or elongated nuclei and eosinophilic cytoplasm ( Fig.2a – c ) . The cells formed irregular nests or short fascicles , accompanied by frequent hyaline changes in vessel walls and vacuolation ( Fig.2d ) . Some nuclear pleomorphism was prominent ; on the other hand , neither a high mitotic rate nor necrosis was evident ( Fig.2b , c ) . Conspicuous fibrous change of tumor stroma was noted focally as well ( Fig.3a ) . The chromophobic nature of tumor cells was confirmed by Pearse ’s Periodic Acid Schiff ( PAS ) stain ( Fig.3b ) . Immunostains showed strong diffuse positivity for PRL ( Fig.3c ) , chromogranin - A , and synaptophysin . No other hormones ( GH , TSH , ACTH , LH , FSH ) were expressed by tumor cells , and the other markers , including S-100 protein ( Fig.3d ) , glial fibrillary acidic protein ( GFAP ) , epithelial membrane antigen ( EMA ) , cytokeratin AE1 / AE3 ( CK AE1 / AE3 ) , vimentin , p53 , and bcl-2 , were also negative by immunostaining . Ki-67 labeling index was approximately 2 % . A final diagnosis of PRL - producing pituitary adenoma was reached after considering the immunohistochemical profile , suprasellar location , and prolactin production of the tumor , as well as the absence of metastatic foci and invasion into surrounding tissue .


A 70 – year – old female presented to the Emergency Department with palpitations , dyspnea and anterior epistaxis . She had a 3 years history of atrial fibrillation and chronic heart failure NYHA class III . She was treated with aspirin 100 mg / day . Physical examination revealed an irregular pulse of 148 beats / min , blood pressure of 130/100 mmHg , pansystolic mitral murmur of 2/6 grade , murmur of tricuspid regurgitation of 3/6 grade , lower extremities swelling . The oto - rhino - laryngology exam conclusion was of anterior epistaxis . The 12 – lead electrocardiogram revealed atrial fibrillation , inferior ischemia . Her International Normalized Ratio ( INR ) was of 1,24 . The two – dimensional transthoracic echocardiography showed the thickening of the mitral valves with a moderate mitral insufficiency and a mobile round mass in the left atrium , heterogeneous , inhomogeneous , of 18 mm in size , attached with a narrow stalk to the interatrial septum . It showed a tumor – like movement with a cardiac cycle , reaching the mitral annular plane ( Figure 1,Figure 2 ) . Also , echocardiography showed tricuspid insufficiency with a maximum gradient of 30 mmHg , intact interatrial septum , akinesia of two thirds of basal inferior wall , ejection fraction of 42 % . There was no mass in the left atrial appendage . The two – dimensional transesophageal echocardiography confirmed the presence of the intraatrial mass . Epistaxis was considered to be due to heart failure and the increased venous pressure . The patient was referred to the cardiovascular surgery clinic , but she refused surgery . Anticoagulation with fraxiparine of 0,6 ml / day was started and continued for 3 weeks , after cessation of epistaxis by nasal tamponament . After 3 weeks the echocardiography was repeated , with no remnant mass in the left atrium . The conclusion was that the mass must have been a thrombus that has melted away . In this particular case , the left intraatrial thrombus may have been due to the presence of atrial fibrillation .


A 78 - year - old previously healthy male heavy smoker presented at the Emergency Department with generalized jaundice ( sclera and skin ) , ascites , and hepatic coma . The relatives declared that he was known to have a urinary bladder carcinoma that was diagnosed at a routine control performed 3 months before but no medical papers to prove this diagnosis were shown . They also mentioned a 2 - month history of progressive jaundice , somnolence , and temporary loss of consciousness . No weight loss or other clinical signs were mentioned . No previously viral hepatitis or drug excess was reported . No family history of cancer was declared . At the present admission , the abdominal CT scan showed marked hepatomegaly with multiple small nodules ( 2–10 mm in diameter ) that was supposed to be hepatic metastases from the bladder carcinoma . The thoracic x - ray showed a bilateral bronchopneumonia without abnormal opacities . The patient died with hepatic encephalopathy at 7 hours after admission . Prior to the autopsy , signed informed consent of the relatives was obtained for the case publication . Being about a case report , no Ethical Committee approval was necessary . At autopsy , the macroscopic examination showed a huge liver ( 6.5 kg ) with widely distributed white nodules of varying sizes ( Fig.1 ) . The urinary bladder was not modified , but a 30 × 30 × 50 mm prostate nodule with infiltrative aspect was observed ( Fig.2 ) . The bilateral bronchopneumonia was confirmed , without any central tumor mass . A 10 - mm white nodule was identified encasing a small bronchus from the middle lobe of the right lung , without peripheral nodules ( Fig.3 ) . Except for moderate edema , no other brain lesions were identified . The other organs did not show modifications . The tissues were fixed in 10 % neutral formalin and embedded in paraffin together with iliac crest bone grafting . Microscopic examination of the prostate showed a 3 + 3 Gleason 's grade 2 occult adenocarcinoma ( Fig.2 ) . Clusters and sheets of small round cells were seen in the liver parenchyma ( Fig.1 ) and the lymph nodes from the hepatic hilum . Examination of the lung parenchyma showed a peribronchial SCLC with multiple tumor emboli in both veins and lymphatic vessels and multiple “ coin - shaped ” tumor nodules of 1 to 2 mm in diameter below the pleura ( Fig.3 ) . The small round tumor cells were also seen in bone marrow from the iliac crest bone ( Fig.3 ) . No brain metastases have been detected . Based on the macro- and microscopic features and clinical picture , the final diagnosis was “ peribronchial and coin - like peripheral SCLC with massive angiolymphatic invasion and metastases in the lymph nodes , liver and bone , associated with encephalopathy and synchronous occult adenocarcinoma of the prostate . ”


A 42 year - old man with chronic lymphocytic leukemia underwent allogeneic bone marrow transplant in September 2013 . The graft was mismatched at a single human leukocyte antigen allele ( DQB1 ) , and was T - cell depleted using in vivo alemtuzumab . He engrafted on day 12 after transplant . Aside from persistent lymphopenia and diarrhea from norovirus infection , his posttransplant course was unremarkable until mid - October when he developed tinnitus and rapidly progressive sensorineural deafness , resulting in subtotal hearing loss bilaterally ( > 95 dB ) over 2–3 weeks . Brain magnetic resonance imaging ( MRI ) was unremarkable , as was cerebrospinal fluid ( CSF ) analysis ( 4 leukocytes/µL with 50 % neutrophils and 50 % lymphocytes , 6 red blood cells/µL , glucose 2.4 mmol / L [ normal range , 2.2–4.7 mmol / L ] , protein 61 mg / dL [ normal range , 15–45 mg / L ] , absence of oligoclonal bands ) . Viral polymerase chain reaction ( PCR ) testing of CSF was negative for enterovirus and herpesvirus infection . The patient was treated empirically with high - dose valacyclovir , broad - spectrum antibiotics , and 2 g / kg intravenous immunoglobulin ( IVIG ) . Despite these interventions , he developed new symptoms of central dyspnea , postural hypotension , nausea , and gradually worsening balance . Repeat neurological assessment confirmed persistent vestibulocochlear dysfunction 6 weeks after symptom onset . By mid - December , the patient had become increasingly withdrawn , irritable , and intermittently agitated . He remained lymphopenic ( lymphocytes 0.54 × 106 / μL [ normal range , 1.2–3.6 × 106 / μL ] ) . MRI scans of the brain were unremarkable , as was serum testing for antineuronal antibodies ; an electroencephalogram revealed only diffuse encephalopathy . Given continued suspicion for a viral etiology , the patient was treated with high - dose glucocorticoids and again with IVIG . He began refusing fluids , food , and medication , and was detained under the UK Mental Health Act . Repeat MRI scanning showed interval development of new , nonenhancing signal abnormalities in both thalami and midbrain with cranial nerve involvement but no meningeal enhancement ( Figure 1A ) . Near the end of December , a frontal lobe biopsy was performed . Histology revealed reactive gliosis and diffuse infiltration with CD3+/8 + lymphocytes ( Figure 1B ) . Extensive microbiological testing of the biopsy tissue for an infectious etiology was negative ( Supplementary Table 1 ) . Given the absence of a diagnosis and the patient 's progressive neurological deterioration , CSF and brain biopsy tissue were analyzed in January 2014 by metagenomic next - generation sequencing ( NGS ) [ 2 ] . NGS analysis of the brain biopsy , genome assembly , and in situ hybridization revealed findings of neuroinvasive astrovirus ( AstV ) infection . Despite lack of approved therapies , the patient was treated with ribavirin and IVIG . However , he did not respond to these interventions , and remained in a minimally conscious state following withdrawal of sedation in March 2014 . He eventually died at the end of May , 4 months after the NGS diagnosis and approximately 7.5 months after onset of symptoms .


A 64 - year - old man was admitted to the Department of Gastroenterology of the Affiliated Hospital of Qingdao University Medical College ( Qingdao , China ) due to epigastric pains . Physical examination revealed no palpable mass , lymphadenopathy , or organomegaly . On endoscopy , several submucosal lesions were identified in the gastric antrum and the duodenal bulb ( Fig.1 ) . Endoscopic ultrasonography ( EUS ) ( OLYMPUS EUS EU - ME2 , Miniprobe sonography ) demonstrated that the lesions were almost 0.5 - cm homogeneously hypoechoic neoplasms originating from the submucous layer ( Fig.2 ) and the initial diagnosis was digestive neuroendocrine tumors . Computed tomography revealed enlarged lymph nodes in multiple regions ( mediastinal , retroperitoneal , mesenteric , and inguinal ) and intracavitary nodules in the duodenum . To reach a definitive diagnosis , the patient underwent repeat EUS and biopsy was performed . On endoscopy , a 2 × 1 - cm columnar uplift in the terminal ileum and multiple submucosal lesions in the rectum were identified ( Fig.3 ) . EUS revealed that the lesions in the terminal ileum were sized 1.6 × 1.2 cm and the lesions in the rectum were sized almost 0.6 × 1.0 cm , they were all homogeneously hypoechoic and originated from the muscularis mucosa layer . Pathological examination of the biopsied specimens from the lesions of the rectum showed diffuse lymphomatous proliferation and dense infiltration by monomorphic , small cleaved cells with irregularly shaped nuclei ( Fig.4 ) . On immunohistochemical analysis , the cells were positive for cyclin D1 , CD20 , CD21 , SOX-11 , and Bcl-2 , but negative for CD3 and CD10 , which was compatible with the diagnosis of MCL . Ki-67 staining revealed a proliferative index of 30 % . Based on these findings , the diagnosis of Ann Arbor stage IV MCL was confirmed . The patient was referred for combination chemotherapy with rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisone ( R - CHOP regimen ) . The patient has been in remission clinically .


In 2013 , a 50 - year - old man patient visited hospital complaining of local bone pain in the left leg . On August 14 , 2013 , the patient underwent a left distal femoral tumor en bloc resection and reconstruction with a modular femoral prosthetic system . Pathology diagnosis confirmed osteoblastic osteosarcoma ( Fig.2 ) . One cycle of neoadjuvant chemotherapy and 4 cycles of adjuvant chemotherapy with MAP regimen ( high - dose methotrexate , cisplatin , and doxorubicin ) were administered . In January 2015 , a mass was found on the left upper crus area . Tumor recurrence was confirmed by biopsy on January 23 , 2015 . However , only an upper femur amputation was carried out , as the patient refused hip joint replacement . After wound healing , the patient went back to his normal life in the help of artificial limb , but refused to receive further chemotherapy due to concerns regarding the chemotherapy toxicities such as nausea , vomiting , leucopenia , deadlimb , and headache . About half a year after the amputation , the patient got occasional cough and chest tightness . Then a thin chest computed tomography ( CT ) was performed on July 15 , 2015 . The CT results revealed multiple pulmonary nodules ( Table 1 ) , considering the possibility of metastases . The patient still rejected further chemotherapy . Immunophenotype was suggestive of CD31 + and CD34 + tumor cells ( Fig.3 ) . Furthermore , most cells showed strong positive staining for VEGFR-2 ( Fig.3 ) . Apatinib was administered at a dose of 500 mg daily . Half a month later , the symptoms disappeared , but a progressive wound necrosis appeared . A debridement surgery was finally conducted and an enlarged lymph node near iliac vessels was resected on February 24 , 2016 ( Fig.(Fig.4).4 ) . The result of pathological examination revealed an inflammatory hyperplasia lymph node . Apatinib administration was stopped during the 3 weeks of wound healing period . The thin chest CT was performed 7 and 11 months following apatinib administration . At the 7 - month follow - up time point , 2 out of 5 measurable and 9 out of 17 non - measurable lesions disappeared , but 1 new measurable nodule and 6 new non - measurable lesions were observed ( Table 1 , Fig.5 ) , which considered PD according to the Response Evaluation Criteria in Solid Tumors ( RECIST ) 1.1 standard . However , at the 11 - month follow - up time point , a total of 9 lesions disappeared , including 1 measurable nodule and 2 non - measurable lesions presented before apatinib treatment as well as 6 non - measureable lesions presented 7 months after apatinib treatment . No new lesion was raised . After target lesion measurement according to the RECIST 1.1 standard , it was narrowly considered PR . The toxicities the patient experienced included mild hand - foot syndrome and slight high blood pressure . Both were well controlled after appropriate treatment . No severe toxicities and other treatment - related adverse events were observed . The patient continued to use apatinib as maintenance therapy without major toxic effects , and went back to normal life , even driving an automatic car .


A 29 - year - old primipara presented with complaints of persistent , severe right -sided upper abdominal pain during deep inspiration , physical exercise and on local pressure . These complaints had developed gradually after giving birth one year earlier . This pregnancy had been complicated by HELLP syndrome with a subcapsular liver hematoma sized 20 cm × 5 cm , which had resolved spontaneously . At current presentation , liver function tests were normal . She assured having never experienced signs suggestive of sexually transmitted diseases or pelvic inflammatory disease ( PID ) . She had never undergone intra - abdominal interventions . An upper - abdominal magnetic resonance imaging revealed a density between liver and diaphragm at the site of the former subcapsular hematoma , suspect of perihepatic adhesions ( Figure 1 ) . She was referred to the hepatobiliary surgeon , who performed a laparoscopy and confirmed the presence of a thick adhesion between liver segment V / VIII and the diaphragm ( Figure 2 ) . Adhesiolysis was performed in the same session by monopolar diathermia and sharp dissection , followed by the instillation of 1.5 L Adept ( 4 % icodextrin solution ) into the peritoneal cavity to prevent the formation of new adhesions . On follow - up until three years post - surgery , she was free of symptoms .


A 34 - year - old Japanese woman had a diagnosis of MCTD with the presence of Raynaud 's phenomenon , pancytopenia , elevated plasma creatinine kinase , and antibodies against U1 - ribonucleoprotein in 2005 and received 10 mg of prednisolone daily . Pulmonary arterial systolic pressure estimated by echocardiography was slightly elevated ( 48 mmHg ) in 2006 . She felt progressive shortness of breath on physical effort in 2011 . Pulmonary arterial hypertension was diagnosed with 74 mmHg of mean pulmonary arterial pressure ( mPAP ) evaluated by right heart catheterization ( RHC ) in 2012 . Cyclophosphamide - based immunosuppressive therapy was proposed but refused because of possible early menopausal symptoms . Treatment with 250 mg / day of bosentan and 120 μg / day of beraprost was initiated . However , in January 2014 , her dyspnea deteriorated ( WHO functional class IV ) , and she was admitted to our hospital . A physical examination showed low systemic blood pressure ( 89/61 mmHg ) , tachycardia ( 104 / min ) , low blood oxygen level ( percutaneous oxygen saturation ( SpO2 ) 95 % ) , jugular venous distension , and severe systemic edema . Coarse crackles and loud pulmonic valve closure sounds were detected . She was unable to undergo the 6 - minute walk test due to severe dyspnea . Laboratory examinations showed elevated plasma brain natriuretic peptide ( BNP ) level ( 929.4 pg / mL ) , hypoxemia ( PaO2 62.5 mmHg , PaCO2 27.1 mmHg ) , and the presence of antibodies against U1 - ribonucleoprotein ( 97.9 U / mL ) as well as antinuclear antibodies ( 1:640 , speckled pattern ) . A chest X - ray showed enlarged pulmonary arteries and cardiomegaly ( Figure ) . Electrocardiogram showed P wave elevation in the V1 - V2 leads . RHC demonstrated elevated mPAP ( 65 mmHg ) with normal pulmonary arterial wedge pressure ( 12 mmHg ) , high pulmonary vascular resistance ( 1,547 dyne・sec・cm-5 ) , and decreased cardiac output ( cardiac index 1.69 L / min / m2 ) . A ventilation / perfusion scan showed no signs of pulmonary thromboembolism . No signs of chronic obstructive pulmonary disease or interstitial lung diseases were found with computed tomography . Her dyspnea was therefore considered to be due to MCTD - associated PAH which was refractory to bosentan and beraprost therapy . In addition to supportive therapy with oxygen supplementation and diuretics ( 40 mg / day of furosemide ) , initiation of 60 mg / day of sildenafil as well as gradual increment in the dose of beraprost was chosen as an additional treatment . However , her dyspnea remained unchanged , and her plasma BNP level increased . IVCY ( 750 mg / m2 , every 4 weeks ) was initiated , and the dose of prednisolone was increased to 60 mg daily . Her dyspnea then ameliorated , and she became able to undergo the 6 - minute walk test ( 260 m , minimum SpO2 95 % ) . Her plasma BNP level also decreased after the initiation of IVCY ( Figure ) . Six months after the admission , a follow - up RHC revealed improved mPAP ( 65 to 53 mmHg ) , pulmonary vascular resistance ( 1,547 to 1,116 dyne・sec・cm-5 ) , and cardiac index ( 1.69 to 1.83 L / min / m2 ) ( Table ) . Since she remained stable but did not obtain further improvements 18 months after the admission ( Table ) , we consider parenteral prostanoids or lung transplantation as a subsequent treatment .


A 61 - year - old Chinese woman complained of dizziness for 3 weeks and was admitted to our hospital after a bifrontal mass was found radiologically . Other than dizziness , the patient presented no signs or symptoms that are commonly associated with neurological disease , such as headache , vomiting , sensory disturbances , altered consciousness , or seizures . Except for a 20 - year history of hypertension , which was properly controlled with angiotensin - converting enzyme inhibitors , the patient was otherwise healthy . No special circumstances were identified regarding her personal or family history , and the patient was found to be normal upon neurological examination . Plain and contrast - enhanced magnetic resonance imaging ( MRI ) of the head showed a space - occupying lesion in the bifrontal lobe , mainly on the right side , clinging to the sagittal sinus and the cerebral falx . The 5.7 × 5.0 × 5.0 cm dural - based mass growing across the sagittal midline revealed isointensity on the T1 - weighted image and a slight hyperintensity on the T2 - weighted image and was homogenously enhanced with a characteristic “ dural - tail ” sign ( Fig.1 ) . Diagnosis of a parasagittal - parafalcine meningioma was made , and a craniotomic meningioma resection was chosen as treatment . The blood cell examination ; coagulation function , liver and renal function tests ; urinalysis ; chest x - rays and electrocardiogram were normal . The albumin was 36 g / L , the total bilirubin ( TBil ) was 12.2 μmol / L , and the direct bilirubin ( DBil ) was 4.1 μmol / L. Alanine transaminase ( ALT ) was 17 U / L , and the international normalized ratio ( INR ) for coagulation values was 1.02 . Because of the patient 's advanced age and history of hypertension , we performed an echocardiograph and a blood gas analysis and tested her creatine kinase levels and pulmonary functions . The results revealed no surgical contraindications . Written consent was obtained from the patient . Five hundred milligrams of VPA twice per day was initiated 3 days before the operation . The patient tolerated the administration well . A craniotomy was then performed with a radical tumor resection ( Simpson II ) . The tumor was pink and solid and had a moderate blood supply , and its texture was medium . Thirty minutes before the end of surgery , 800 mg of VPA was administered by intravenous infusion . After the operation , the patient regained consciousness within 30 minutes and scored 15 on the Glasgow coma scale ( GCS ) . Two hours later as she was being transported back to her ward , the patient underwent UGH . The vomitus ( approximately 50 mL ) was composed of coffee - colored blood . Excluding the possible etiology of endotracheal intubation damage , we diagnosed the patient as experiencing acute erosive - hemorrhagic gastritis , a reaction to the craniotomy injury . The patient was given omeprazole to inhibit gastric acid secretion , and the hematemesis ceased . The patient was administered VPA ( 1200 mg , intravenously ) during the first 2 postoperative days . Because of her stomach and intestine functional recovery , the VPA dosage was changed to 500 mg via oral administration twice a day . A brain MRI was performed on postoperative day 3 , and it revealed that the tumor was radically removed and the operative field was clean ( Fig.2A and B ) . A subsequent paraffin histological examination confirmed the diagnosis of meningioma . At 3 am on postoperative day 4 , the patient was suddenly found in a deep coma . Her pupils were dilated to 3.0 mm and round , and the light reflex was sensitive . The neurological examination was unremarkable , and her vital signs were stable ; however , her mental state gradually changed to a deep coma ( GCS = 8) , which we believed was caused by intracranial lesions . A computerized tomography ( CT ) scan of the brain was immediately performed ; however , it failed to reveal any abnormalities , such as severe brain swelling , intracranial hemorrhage , or cerebral infarction ( Fig.2C ) . Because a possible cerebral infarction could not be excluded within 24 hours , glucocorticoid , mannitol , and a vasodilator were used . The patient 's routine laboratory results for blood cell , liver , and renal functions were in relatively normal ranges . The albumin was 33 g / L , the TBil was 13.3 μmol / L , and the DBil was 4.5 μmol / L. ALT was 12 U / L , and the INR for coagulation values was 1.01 . Because of her history of UGH , we checked her blood ammonia levels and performed a fecal occult blood test and blood gas analysis . Her blood ammonia was elevated ( 181.6 μmol / L ; normal range is 11–32 μmol / L ) , whereas the fecal occult blood test was positive . Thus , considering her history and elevated blood ammonia , she was diagnosed with UGH - induced hepatic encephalopathy , and the oral administration of VPA was changed to intravenous administration to prevent seizures . Lactulose , vitamin B , and L - arginine were administered , clysis with vinegar was performed , and the patient was fasted . The patient 's blood ammonia level fluctuated ( 144.8–207.7 μmol / L ) , and she remained unconscious during the following 3 days . Because of the unremarkable progress in the patient 's mental state and blood ammonia level , we held a multidisciplinary conference to discuss diagnosis and treatment , initially considering hemodialysis or peritoneal dialysis . After the multidisciplinary discussion , a suspected diagnosis of VHE was finally made , even though the blood VPA level was within the normal range . We decided to stop VPA administration before performing any dialysis and administered levetiracetam instead of VPA . The patient 's blood VPA and ammonia levels were then routinely monitored . The patient 's mental state began to improve from the first 24 hours of VPA discontinuation , and she achieved complete consciousness within 48 hours ( GCS = 15 ) . The ammonia levels in her blood decreased dramatically and returned to normal within 4 days ( Fig.3 ) . On postoperative day 15 ( 8 days after the discontinuation of VPA ) , the patient was discharged with no complications . The follow - up interviews in postoperative month 5 witnessed her full consciousness and non - recurrence of the primary tumor ( Fig.2D ) . The patient 's GCS score was 15 , and she reported enjoying a satisfying quality of postoperative life .


A 58 - year - old white American male presented to the emergency department ( ED ) with acute onset of confusion , disorientation , inability to walk steadily , and dehydration with associated generalized weakness , polyuria , and polydipsia over the previous week . He had been diagnosed with CML six years earlier , with no hematological response to multiple chemotherapy regimens ; he was at that time on treatment with allopurinol and awaiting allogenic bone marrow transplant . Vital signs on admission to the ED included heart rate of 104 bpm , blood pressure of 122/68 mm Hg and temperature of 99.7 ° F ( 37.6 ° C ) . There were no remarkable findings on physical examination except for altered mental status and dehydration . Laboratory evaluations were : hemoglobin 13.3 g / dL , white blood cell count 18.3×109 / L ( neutrophils 79.6 % , lymphocytes 7.2 % , and monocytes 8.3 % ) , and platelet count 910×109 / L. Serum levels were : calcium 18.6 mg / dL , phosphate 4.6 mg / dL , sodium 135 mEq / L , potassium 2.7 mg / dL , albumin 4.0 g / dL , creatinine 2.2 mg / dL , total bilirubin 0.9 mg / dL , alkaline phosphatase 125 IU / L , aspartate aminotransferase 41 IU / L , and alanine aminotransferase 71 IU / L. SPEP was negative for an M spike . Hormones and vitamins levels were : PTH 8.5 pg / L ( 15–65 pg / L ) , PHTrP 1.4 pg / L ( < 2 pg / L ) , 25 - OH vitamin D 30.4 ng / mL ( 20–50 ng / mL ) and 1,25 OH vitamin D3 33.7 ng / mL ( 18–64 ) ng / mL. Chest CT scan showed diffuse lytic lesions and bone destruction throughout the visualized thoracic skeleton , concerning for diffuse bone marrow involvement . The clinical history and biochemical findings led to a diagnosis of CML - associated hypercalcemia in the context of a blast phase . Treatment with aggressive hydration with 0.9 % saline and calcitonin 400 units subcutaneous was administered . Additionally , zoledronic acid 3.3 mg intravenous , adjusted for renal insufficiency , was given . After five days of treatment , normalization of symptoms and serum calcium levels were achieved . After discharge from the hospital , the patient continued with palliative treatment with ponatinib and radiotherapy . Acceptable serum calcium levels were maintained with zoledronic acid 4 mg every eight weeks . Despite these therapies , his cancer progressed and he passed away approximately eight months after the initial admission for hypercalcemia .


A 76 - year - old woman presented to our hospital with complaints of epigastralgia since a day prior to admission . Laboratory data on admission revealed an elevation of aminotransferase , alanine aminotransferase , ɤ - guanosine triphosphate , and alkaline phosphatase . Serum total bilirubin and tumor markers , carcinoembryonic antigen ( CEA ) , carbohydrate antigen 19 - 9 ( CA19 - 9 ) , SPan-1 , and neuron - specific enolase ( NSE ) , were all within normal ranges . Abdominal computed tomography ( CT ) and magnetic resonance cholangiopancreatography ( MRCP ) showed a mass in an enlarged gallbladder and bulky hepatic lymph nodes surrounding the hepatic hilum ( Fig.1a , b ) . There were also no apparent lesions in upper and lower gastrointestinal endoscopy . Endoscopic ultrasound - guided fine - needle aspiration ( EUS - FNA ) was performed to obtain tissue from the hilar lymph node . Immunohistochemical staining of the specimen identified diffuse positivity for keratin , CD56 , and synaptophysin in the tumor cells , which is consistent with NEC . An endoscopic naso - gallbladder drainage ( ENGBD ) catheter was placed , and the bile cytology revealed class V malignant cells . Therefore , positron emission tomography / computed tomography ( PET / CT ) examination was performed to evaluate other primary or metastatic lesions . It revealed that no other accumulated lesions were identified , and the accumulation of 18F fluorodeoxyglucose ( FDG ) was in the gallbladder ( SUVmax 7.8 ) and lymph nodes ( SUVmax 13.4 ) ( Fig.1c , d ) . On the basis of these findings , the most likely diagnosis was a gallbladder NEC that was confined to the regional hepatic hilar lymph nodes metastasis . Finally , we decided to perform surgical resection prior to chemotherapy because of concerns about complications developing from mechanical obstruction of the hepatic hilum by the enlarged lymph node . She underwent cholecystectomy , hepatic hilar lymphadenectomy , extrahepatic biliary duct resection , and hepaticojejunostomy . The bulky lymph nodes were totally resected as “ en bloc ” . There were no apparent residual lesions surgically . The postoperative course was uneventful and she was discharged on the tenth day after surgery . Macroscopically , the tumor was 58 × 42 mm in size and was located in the fundus , which contained a yellowish gallstone ( Fig.2a ) . A portion of the hepatic hilar lymph nodes ( 71 × 37 mm ) was also excised separately ( Fig.2b ) . Microscopic examination of the gallbladder revealed a moderate to well differentiated tubular adenocarcinoma infiltrating from the mucosa to the muscular layer , but not the serosal surface , without any NEC components ( Fig.2c , d ) . The tumor cells in the gallbladder are slightly positive for synaptophysin and CD56 , but negative for chromogranin A ( Fig.2e – g ) . The resection margin from the liver bed was negative for tumor cells . The epithelium around the carcinoma showed intestinal metaplasia with the goblet cells ( Fig.4a ) , which area was stained by alcian blue ( Fig.4b ) . On the other hand , the hepatic hilar lymph nodes were composed of small round tumor cells with hyperchromatic nuclei and scant cytoplasm ( Fig.3a ) . Some of the tumor cells were large and had vesicular nuclei . The tumor cells were arranged in sheets , cords , or in a trabecular or rosette fashion and were interspersed with focal necrosis . They were immunohistochemically positive for CD56 , synaptophysin , and chromogranin A ( Fig.3b–3d ) . The mitotic count was 24 per 10 high - power microscopic fields , and the Ki-67 proliferation index was 70–80 % , consistent with NEC . The surgical dissection margin of the hepatic lymph nodes was microscopically cauterized within the tumor cells . There was no invasion to the extrahepatic biliary duct . As the result of thorough pathological re - evaluation by total segmentation , a negligible area of adenocarcinoma was detected in the lymph nodes ( Fig.3e , f ) . The adenocarcinoma component and the intestinal metaplastic epithelium in the gallbladder were both positive for CDX2 ( Fig.4a ) , but the neuroendocrine component in hilar lymph nodes was negative for CDX2 ( Fig.4b ) . Postoperatively , the patient received three cycles of carboplatin ( area under the curve of 5 on day 1 repeated every 21 days ) and etoposide ( 80 mg / m2 on days 1 through 3 repeated every 21 days ) . During the first course , grade 4 neutropenia occurred and it was managed with prophylactic fluoroquinolones . After 4 months , multiple recurrences in the para - aortic lymph nodes were detected , which was pathologically demonstrated via EUS - FNA to be NEC . The patient underwent second - line chemotherapy with amrubicin ( 24 mg / m2 on days 1 through 3 repeated every 21 days ) . Grade 4 neutropenia and anemia developed during the courses , and she needed to receive pegylated granulocyte colony - stimulating factor and red blood cell transfusion . However , she died of progressive disease 8 months after surgery .


A 45 - year - old woman presents to her general practitioner because of left - sided neck and shoulder pain . The pain was mild and non - specific and the patient 's history was unremarkable . She denied a history of smoking , excessive alcohol use and radiation exposure . Physical examination demonstrated mild left sided cervical lymphadenopathy . Routine blood tests revealed borderline elevated calcium of 10.5 mg / dL and subsequent work up exhibited a markedly elevated parathyroid hormone level of 286 pg / mL , so the patient was referred to otolaryngology for further evaluation . Thyroid ultrasound showed a hypoechoic nodule in the left lower lobe of the thyroid . CT scan of the neck revealed a 2 cm hypodense nodule on the posterior inferior aspect of the left lower thyroid and sestamibi scan showed increased uptake along the lower pole of the left thyroid lobe . Elevated PTH along with an aberrant parathyroid gland on imaging suggests primary hyperparathyroidism . Historically , hyperparathyroidism is associated with bone disease , renal stones and neuromuscular dysfunction , however , with the current screening modalities , most patients are caught early and often asymptomatic.3 Primary hyperparathyroidism is most commonly caused by a parathyroid adenoma . Infrequent causes include parathyroid hyperplasia , which would affect all four glands and rarely caused by parathyroid carcinoma . Markedly elevated serum PTH and calcium levels leading to severe renal and bone manifestations are helpful in the diagnosis of cancer , however , it is usually discovered operatively based on local invasion and metastases.3 The primary indication for parathyroidectomy , historically , is for symptomatic patients . Currently , since most patients are caught earlier , there are newer indications for surgery . These include an asymptomatic patient with any of the following : glomerular filtration rate < 60 mL / min , bone density T - score < −2.5 at any site and/or previous fractures , age < 50 , and serum calcium 1.0 ng / dL above the upper limit of normal.3 This patient presented with pain , markedly elevated PTH , and was younger than 50 years old , so it was decided that surgery was the best choice in management . The patient was brought to the operating room and underwent a parathyroidectomy . The surgeon found the parathyroid gland to be firm and densely adherent to the thyroid capsule and overlying strap muscle , making it difficult to dissect . There was no visible invasion into the capsule , surrounding muscle or regional lymph nodes . The resected specimen was noted to be brownish grey in colour with scattered necrotic foci , and irregular texture . On postoperative pathology , the specimen was confirmed positive for parathyroid carcinoma with capsular invasion , focal tumour necrosis , reactive fibrosis and local skeletal muscle invasion ( figures 1 and 2 ) . Margins were resected . Immunohistochemical stains showed increased Ki-67 reactivity as well as strong Bcl-1 ( cyclin D1 ) reactivity , which support the diagnosis of parathyroid carcinoma ( figure 3 ) . Additionally , P57 staining was negative . Although most reports of parathyroid carcinomas are associated with marked hypercalcaemia , non - functioning cancers in patients tend to behave more aggressively.1 Owing to the severity and uncertainty of the lesion , the patient was followed up postoperatively for repeat imaging to determine if residual tumour remained . Repeat sestamibi and positron emission tomography ( PET ) scan revealed residual activity along the surgical area so the patient subsequently underwent a second operation for a radical left neck dissection and left hemithyroidectomy . The patient recovered very well postoperatively and it has now been 3 years since the second surgery . The patient continues to do very well and is followed up every 3 months to monitor serum PTH and calcium levels . She no longer reports of neck and shoulder pain . Sometimes the patient 's blood tests show marginally elevated PTH levels , however , she remains eucalcaemic and follow - up nuclear scans and PET scans continue to be negative . The patient will continue to be monitored every 3 months indefinitely .


A 16 - year - old female suffered from an abdominal pain at right upper quadrant , lasting for more than 10 days . Shortly ahead of her medical consultation , 4 ascaris - like worms were vomited out , individually with a length of about 10 cm . She had a previous onset of ascariasis , during which low - grade fever ( 38.4 ° C ) occurred without apparent jaundice , diarrhea , or anemia . Physical examination revealed tenderness at right upper quadrant . Her total leukocyte count was 11.2 G / L consisting of 5.2 % eosinophils . Serum and urine amylase were 386 and 928 U / L , respectively . In terms of liver functionality , the level of total bilirubin rose up to 23.2 μm / L , meanwhile the hepatic enzymes were similarly elevated ( alanine aminotransferase 163 U / L ; aspartate aminotransferase 96 U / L ) . Abdominal ultrasound described the enlargement of the gallbladder , upper segment of common bile duct ( 1.5 cm in diameter ) and intrahepatic bile duct ( 1.3 cm in diameter ) . Furthermore , the intrahepatic bile duct was also discovered to be filled with echogenic and banded substances . Based on such evidences , she was clinically diagnosed as biliary ascariasis with a concomitant manifestation of biliary duct infection . Through a laparoscopic exploration , the enlarged gallbladder and common bile duct were visually confirmed , as well as the massive storage of worms within the biliary tract . Subsequently , a 1 cm incision was made on the common bile duct in order to facilitate the extraction of the pathogenic worms , which were then placed into a specimen bag laparoscopically ( Fig.1 ) . Once the contained worms were virtually cleared out under laparoscope , chodedochoscopy was employed to seek for more hidden worms inside the biliary system ( Fig.2 ) . After finishing the removal of ascarides , the biliary duct incision was well sutured , with a T - tube placed in situ ( Fig.3 ) . Eventually , a standard laparoscopic cholecystectomy was performed , followed by the removal of specimen bags and drainage tube placement ( Fig.4 ) . The total amount of worms inside the common bile duct summed up to more than 100 ( Fig.5 ) . Postoperatively , she was treated with oral antihelminthic drugs for 3 days . The T - tube was rinsed with saline every day , and during the first 3 days , 6 more worms were additionally washed out . The patient experienced a smooth postoperative recovery and was finally discharged from hospital without any complications .


A 51 - year - old man was referred to our hospital due to severe congestive heart failure and ventricular arrhythmias in March 2008 . He had been suffering from heart failure and ventricular tachycardia for years despite receiving the conventional treatment ( ie , furosemide , lisinopril hydrate , pimobendan , warfarin potassium , carvedilol , metildigoxin and amiodarone hydrochloride ) . His height was 161 cm and body weight was 83 kg . Blood pressure was 110/60 mm Hg . The fasting blood glucose was 107 mg / dl and HbA1c was 6.3 % . The chest x - ray showed cardiomegaly with a cardiothoracic ratio of 0.67 ( figure 1A ) . ECG , as shown in video 1 , revealed a diffused hypokinetic left ventricle with markedly dilated left ventricle dimension ( end - diastole : 95 mm ) and reduced EF ( 0.11 ) . The coronary angiogram was normal . A myocardial biopsy revealed that over 50 % of cardiomyocytes were replaced by fibrosis ( figure 2 ) . An implantable cardioverter - defibrillator was implanted . Due to the typical facial appearance and thickening of hands , he was referred to the endocrinology department . The plasma level of GH was 8.2 ng / ml and IGF-1 was 504 ng / ml . MRI demonstrated a macroadenoma in the pituitary . Thus , he was diagnosed as acromegaly . He was treated with octreotide long - acting - release ( LAR ) for 8 months . Thereafter , he underwent trans - sphenoidal surgery in January 2009 ( figure 3 ) . The plasma levels of GH and IGF-1 were decreased with octreotide LAR , but basal plasma levels of GH were always more than 4 ng / ml and plasma IGF-1 levels were above the appropriate age range ( figure 3 ) . After surgery , both plasma levels of GH and IGF-1 further decreased . Basal plasma levels of GH were mostly less than 0.5 ng / ml and IGF-1 levels were within normal ranges ( figure 3 ) . With the treatment of LAR , the cardiac function improved partially ( cardiothoracic ratio=0.58 ; EF=0.20 in September 2008 ) . After surgery , the cardiac function improved drastically ( cardiothoracic ratio=0.47 ; EF=0.55 in April 2009 ; figures 1B and and2B).2B ) . Frequency of ventricular arrhythmias decreased and pimobendan was tapered off .


In January 2009 , a 57 - year - old woman emergently presented with acute shortness of breath . She had a 1 - month history of progressive shortness of breath and a gradual decrease in exercise capacity secondary to mild dyspnea . She reported no additional symptoms . At age 40 , she had been diagnosed with a stage IIA , T1bN1 , left - sided breast cancer . Initial treatment had included a lumpectomy and axillary node dissection . She subsequently underwent 4 cycles of DOX therapy ( 75 mg / m2 ) , followed by 8 cycles of cyclophosphamide , methotrexate , and 5 - fluorouracil . Multigated acquisition scans before and after chemotherapy showed normal cardiac function . After chemotherapy , she underwent left whole - breast radiation with an axillary boost . Because the tumor had been estrogen receptor - positive , her subsequent medical regimen consisted only of anti - estrogen therapy . She took tamoxifen for 5 years , and , ever since , the aromatase inhibitor letrozole . In the 17 years after chemotherapy , she had been active and in relatively good health . In addition to her other symptoms , she now presented with tachycardia , tachypnea , and hypertension . She had marked jugular venous distention , an S3 , pulmonary rales , and trace peripheral edema . Initial laboratory values were within normal limits except for an elevated level of N - terminal pro - brain natriuretic peptide ( > 2,000 pg / mL ) . Results of investigation into the new - onset cardiomyopathy included normal cardiac enzyme levels , an electrocardiogram ( ECG ) that revealed no ischemic changes , and a coronary angiogram of normal appearance . The ECG showed sinus tachycardia with frequent premature ventricular complexes , left - axis deviation , left atrial enlargement , and low - voltage QRS complexes with nonspecific ST changes ( Fig.1 ) . A 2 - dimensional echocardiogram revealed a left ventricular ejection fraction ( LVEF ) of 0.20 , severe diffuse left ventricular ( LV ) hypokinesis , and a mildly dilated left atrium . To better define the cause of the LV systolic dysfunction , cardiovascular magnetic resonance ( CMR ) was performed . It confirmed the LVEF of 0.20 . The T2 - weighted sequence showed slow flow secondary to LV dysfunction , and no myocardial edema ( Fig.2A ) . Late gadolinium enhancement disclosed diffuse myocardial thinning and no scarring ( Fig.2B ) . The patient was treated medically . Her symptoms progressively improved during therapy , which consisted of a β - blocker , an angiotensin - converting enzyme inhibitor , digoxin , and a diuretic . The therapy was slowly tapered , and her LVEF increased from 0.20 to 0.55 during an 8 - month period . All medications except for low - dose metoprolol were discontinued after 1 year , and she remained asymptomatic .


A 61 - year - old male patient had a history of chronic obstructive pulmonary disease under regular bronchodilator treatment . In 2014 , he suffered from severe productive cough with mucus sputum for several months and unintentional body weight loss 6 kg within 6 months . After sputum analysis and chest imaging examinations in May 2014 , he was diagnosed of squamous cell carcinoma in right upper lobe lung ( cT3N2M0 , stage IIIa ) . Then he received neoadjuvant chemoradiotherapy ( etoposide 70 mg [ 45 mg / m2 ] + cisplatin 79 mg [ 50 mg / m2 ] ; 4500 cGY in 25 fractions ) from June to July 2014 . In October 2014 , surgical intervention was arranged . Because the tumor was located at right hilum and invaded main bronchus and major vessels , video - assisted thoracoscopic surgery with right side intrapericardial pneumonectomy was performed . Postoperatively , pathological exams revealed squamous cell carcinoma , T3N0M0 , stage IIB . The postoperative course was smooth but he suffered from severe cough and right chest pain one month later . Laboratory exams revealed leukocytosis ( white blood cells = 21,860 μL ) and elevated C - reactive protein to 23.94 mg / dL. Chest X - ray showed cavitary lesion and computed tomography showed pleural effusion and fluid collection with mottled gas appearance in the dependent portion of right hemithorax ( Fig.1A ) . According to the patient 's history , results of laboratory exams , and imaging findings , postpneumonectomy empyema was diagnosed and bronchopleural fistula was highly suspected . After admission , chest tube drainage was inserted and bronchoscopic tissue glue sealing was performed . However , persistent air leakage was presented and we decided to repair the bronchial stump with flap coverage . Because the patient just received neoadjuvant chemoradiotherapy a few months ago , the flaps harvested from chest area were not appropriate because the pedicle arteries might have been injured by irradiation . After discussing with the plastic surgeon , we decided to repair the bronchial stump by a TRAM flap . Intraoperatively , the patient was placed in supine . Right side exploratory thoracotomy was performed and the bronchial stump was located . The superior epigastric vascular artery and right rectus abdominis muscle was identified and the location of the TRAM flap was marked on the skin ( Fig.2A ) . Then the TRAM flap was harvested from right rectus abdominis ( Fig.2B ) and was deepithelialized ( Fig.2C ) . Through a subcutaneous tunnel , the TRAM flap was moved toward the right thoracic space with no tension or kinking on the pedicle ( Fig.2D ) . Then the TRAM flap was fixed to posterior chest wall to cover the bronchial stump ( Fig.2E ) and the tissue glue was also applied to the bronchial stump under bronchoscope . The donor site of flap was closed with mesh repair . The postoperative course was smooth and the air leak was diminished gradually . Then the patient was discharge under stable condition and was free from air leak after following for 12 months ( Fig.1B ) . The patient provided written informed consent for publication of this report and all accompanying images .


A 36 - yr - old previously healthy Sri Lankan male who takes care of a horse presented to the medical casualty ward with fever , arthralgia and myalgia for one day . He complained of mild dysuria but had normal urine output . He did not have chest pain or shortness of breath . Further inquiry revealed that he was treated for leptospirosis during a febrile illness in the past . On examination , patient was afebrile , anicteric . His blood pressure was 90/60 mmHg and pulse rate 76 bpm . Rest of the examination was unremarkable . Initial investigations performed on the day of admission revealed neutrophil leukocytosis , mild thrombocytopaenia and microscopic haematuria ( Table 1 ) . Renal function and liver enzymes were within normal limits . Urine analysis revealed pus cells 05 – 06 /hpf , red cells 30 – 35 /hpf . CRP ( C - reactive protein ) was 75 mg / dl . A clinical diagnosis of leptospirosis was made and he was started on intravenous penicillin in addition to adequate hydration . On the second day of illness , he developed hypotension with tachycardia and dyspnoea . ECG revealed sinus tachycardia with ST depression in leads V4 – V6 [ Figure 1 ] . His CXR ( chest x ray ) showed gross cardiomegaly and bilateral pulmonary shadows [ Figure 2 ] . CVP ( central venous pressure ) was 16 cmH2O and 2D echocardiogram revealed dilatation of all four chambers , severe global hypokinesia and ejection fraction of 20 % . Troponin I was 12.77 ng / ml ( normal range < 0.40 ) . He was diagnosed to have early and severe myocarditis . Patient was transferred to ICU ( intensive care unit ) as he needed inotropic support . Intravenous antibiotics including penicillin , meropenem and levofloxacin were continued . Patient was electively ventilated on the 3rd day of illness due to severe respiratory distress . On the same day , he developed rapid atrial fibrillation [ Figure 3 ] unresponsive to digoxin and intravenous amiodarone . Platelet count dropped to 10 × 103 μ / L and he was given platelet transfusions to prevent bleeding [ Table 1 ] . We started intravenous methylprednisolone based on previous studies showing a mortality benefit in severe leptospirosis complicated with myocarditis [ 11 ] . His serum creatinine increased to 362 μ mol / L by the 5th day of illness and ALT ( alanine transaminase ) and AST ( aspartate transaminase ) were markedly elevated up to 2726 U / l and 7438 U / l respectively . Dengue and Mycoplasma infections were excluded . Blood cultures were negative . Leptospira IgM antibody performed on the 5th day of illness was positive ( IgG negative ) . Patient developed refractory shock and died of persistent ventricular tachycardia despite optimal treatment in the ICU .


A 71 - year - old woman with known diastolic congestive heart failure ( CHF ) presented to the ER with exacerbation of CHF and a decreased level of consciousness . Brachial blood pressure ( BP ) was measured at 55/40 mmHg . The patient had four recent admissions with exacerbation of CHF . Her medical history was also significant for autoimmune hepatitis , but preserved liver function ; esophageal varices with a bleeding episode ; and long - term corticosteroid therapy complicated by adrenal insufficiency , type 2 diabetes mellitus and osteoporosis . Recent echocardiography had revealed moderate concentric left ventricular hypertrophy with diastolic dysfunction , and mild to moderate mitral regurgitation . Cardiac catheterization in a recent admission demonstrated 50 % stenosis in the second diagonal artery , with mild diffuse disease in the other coronary arteries . Right ventricular endomyocardial biopsy had ruled out myocarditis and infiltrative cardiomyopathies , but healing ischemic microinfarcts with atheroemboli were observed . Previous BP values were also low ; systolic BP was between 60 mmHg and 65 mmHg , and diastolic BP was between 40 mmHg and 45 mmHg . Following intubation , dopamine was started for hypotension management and was later replaced with noradrenaline . The patient developed atrial flutter but successfully converted to sinus rhythm with two direct current electric shocks . Cardiology consultation resulted in admission to the coronary care unit ( CCU ) . On admission to the CCU , BP was measured at 56/36 mmHg in the left arm but was not detectable in the right arm . An arterial line was inserted via the femoral artery , and BP was measured at 191/92 mmHg . BP values were consistently much higher through the femoral arterial line than the cuff on the arms , and was higher in the left arm than in the right arm . For instance , on the first day post - CCU admission , BP at one point was measured at 170/80 mmHg through the arterial line , while cuff readings on the arms were 83/74 mmHg on the left and 60/39 mmHg on the right arm . To investigate the inconsistency between brachial and femoral BP values , a computed tomography ( CT ) scan of the thorax was obtained using 1.25 mm slices , both before and after intravenous contrast injection with sagittal and coronal planar reformatting of maximum - intensity projection images . Analysis of the initial unenhanced CT images showed densely calcified plaque or thrombus at the origins of both subclavian arteries and the right common carotid artery . The CT angiogram showed absence of flow in the right subclavian artery , a very tight stenosis at the origin of the left subclavian artery and a tight stenosis at the origin of the right common carotid artery . Both vertebral arteries showed normal calibre and flow ( Figure 1 ) . Further management following the insertion of the femoral arterial line was based on femoral BP readings with diuretics and BP - lowering agents . The patient was eventually discharged in stable condition . She remained stable during the eight months between discharge and the time the present report was written , without further exacerbation of CHF or related ER visits .


A 61 - year - old male was referred to the emergency department by his general practitioner in April 2010 for investigation of loose bowel motions and an episode of black stool . The patient had a history of insulin - dependent type II diabetes mellitus , hypertension , ischaemic heart disease with two previous ischaemic events , obstructive sleep apnoea , depression , schizophrenia and a previous incisional hernia repair . On examination , he was morbidly obese ( BMI 45 ) and was noted to have marked hepatomegaly . This was not associated with any recent weight loss , haematemesis , jaundice or abdominal pain . The patient denied previous blood transfusions , usage of intravenous drugs and did not drink alcohol . A faecal occult blood test was negative , and the patient ’s last colonoscopy 2 years prior was unremarkable . He was referred to our tertiary centre for further management after an ultrasound scan ( USS ) displayed an ovoid mass of mixed echogenicity arising from the liver , measuring 12 × 9 cm . A computed tomography ( CT ) scan confirmed a malignant appearing , pedunculated lesion attached to segment IV ( Fig.1 ) . A subsequent magnetic resonance imaging ( MRI ) confirmed that on T2 weighted imaging ( WI ) , the lesion was isointense to the liver peripherally with central branching hyperintensities ( Fig.2a ) which corresponded to the hypointensities seen on T1WI ( Fig.2b ) . Enhancement of the lesion was noted in arterial phase ( Fig.3a ) , during portal venous phase ( Fig.3b ) and at 2 min ( Fig.3c ) , with some central areas of non - enhancement . The lesion becomes slightly hypointense on delayed images at 10 ( Fig.3d ) and 20 min compared to the surrounding liver . Laboratory investigations revealed a mildly elevated gamma - glutamyl transpeptidase of 137 IU / L ( normal 5–50 IU / L ) . Hepatitis screen , alpha - fetoprotein , carcinoembryonic antigen and cancer antigen 19–9 were all unremarkable . The patient underwent a subsegmental resection of the 15 cm segment IVb mass in June 2010 . There was severe hepatic steatosis , but no cirrhosis . The patient was discharged postoperative day seven without complications . Pathology of the resection specimen confirmed SFTL . The specimen displayed a pale tan nodular appearance with a firm and rubbery cut surface . Histological examination revealed fascicles of spindle cells in storiform arrangement with a pushing margin . There was evidence of extracellular collagen deposition , areas of myxoid stroma and branching vessels with hyalinisation . The specimen displayed a high mitotic rate of up to 9 per 10 high - power fields ( HPF ) with no necrotic or haemorrhagic features . Immunohistochemistry showed positive staining for CD34 , CD99 and BCL-2 . The tumour was negative for c - Kit , CD31 , SMA , desmin , cytokeratins ( AE1 / AE3 , MNF116 and Cam 5.2 ) , EMA and S100 . The margins were clear . The non - neoplastic remainder of the liver displayed pericellular fibrosis indicative of steatohepatitis . The patient was followed - up regularly every 4 to 6 months with CT scans by the local general practitioner who liaised with the consultant surgeon . There were two episodes of re - admissions for further investigation of recurrent right upper quadrant pain between 2011 and 2013 . Multiple MRI scans performed during this period revealed expected postsurgical changes with no tumour recurrence . However , in May 2016 , the patient presented to his local emergency department with progressively worsening right upper quadrant pain and increasing dyspnoea with an oxygen demand . CT of his chest , abdomen and pelvis revealed extensive tumour recurrence adjacent to the previous resection site ( Fig.4 ) . In addition , there was a clinically significant right - sided pleural effusion and a pleural mass at the right lung base measuring 3.8 cm ( Fig.5 ) . Pleurocentesis was performed , draining 1400 ml of serosanguineous fluid . Cytology was negative for malignant cells . The case was discussed extensively in a multi - disciplinary setting , and it was decided given the patient ’s two sites of disease and significant perioperative risk that he was not a candidate for radical reoperation . There were also no suitable chemo- or radiotherapeutic therapies available . The patient was subsequently referred to the palliative team for management of his symptoms and discharged back to the community . He was still alive 1 month after discharge .


A 41 - year - old man with weight loss , nausea , vomiting , and abdominal pain was referred for an abdominal CT scan to rule out intraabdominal pathology . A dedicated CT of the abdomen was performed at our institution according to our standard venous phase protocol . Following ingestion of positive oral contrast material ( barium sulfate suspension 2.1 % w / v , Mallinckrodt ) and injection of 125 ml of iopromide , 300 mg I / mL ( Ultravist , Bayer HealthCare ) , helical CT was obtained with a 65 - s delays using a 64 - slice GE Lightspeed VCT scanner ( GE Medical Systems ; Milwaukee , WI ) . Axial sections of the abdomen showed a large ( 18×22×22 cm ) heterogeneous retroperitoneal mass probably arising from the left adrenal gland containing multiple areas of macroscopic fat ( Fig.1 ) . The patient had no documented clinical or laboratory evidence of adrenal hormonal excess . On the basis of the clinical history and CT findings , the patient underwent surgical resection of the left adrenal mass , which was found on pathologic examination to represent a low - grade adrenocortical carcinoma .


A 76 - year old woman presented with a 24 - month history of enlarging mass involving the back history of trauma . Physical examination showed a mass of an 3x4 cm in diameter , localized in the right inter - scapular region . The mass was ulcerative helophytic , grayish in colour , hard in consistency and easily bleeding on manipulation . The remainder of the examination was unremarkable ; no lymphadenopathy and no abdominal masses were felt . After resection , the histological examinations of the specimens have concluded for basal cell carcinoma . A local recurrence was observed 18 months later ; the patient was admitted to our institution for Lumpectomy ( Figure 1 ) . Histopathological examination revealed a syringomatous pattern infiltrating the dermis ( Figure 2 , Figure 3 ) , subcutis and skeletal muscle . The neoplastic epithelial cells were arranged in interconnecting cords with microcystic areas . Nests , cords , and tubules of the tumour extended into the dermis and into the adjacent muscle . Many lobules showed squamous differentiation . Sclerosis of stroma around the cords was present . Tumour cells were not connected to the epidermis . The immunohistochemical analysis showed positivity for anti - CK7 ( Figure 4 ) , AE1 / AE3 and negativity for anti CEA and anti CK20 . Based upon her histological and immunohistochemical presentation , the diagnosis of syringomatous eccrine carcinoma was established . Radiotherapy of the involved area was performed ( 70 Gy , 35 sessions )


The patient was a 34 - yr - old man who presented with complaints of fever and a chronic cough . He was a smoker and had a history of pulmonary tuberculosis that had been treated and cured . A computed tomographic ( CT ) scan revealed multiple tiny nodules in both lungs . A thoracoscopic lung biopsy was taken from the right upper lobe . The microscopic examination revealed a typical LCH . The tumor cells had vesicular and grooved nuclei , and they formed small aggregations around the bronchioles ( Fig.1 ) . The tumor cells were strongly positive for S-100 protein , vimentin , CD68 and CD1a . There were infiltrations of lymphocytes and eosinophils around the tumor cells . With performing additional radiologic examinations , no other organs were thought to be involved . He quit smoking , but he received no other specific treatment . He was well for the following one year . After this , a follow - up CT scan was performed and it showed a 4 cm - sized mass in the left lower lobe , in addition to the multiple tiny nodules in both lungs ( Fig.2 ) . A needle biopsy specimen revealed the possibility of a sarcoma ; therefore , a lobectomy was performed . Grossly , a 4 cm - sized poorly - circumscribed lobulated gray - white mass was found ( Fig.3 ) , and there were a few small satellite nodules around the main mass . Microscopically , the tumor cells were aggregated in large sheets and they showed an infiltrative growth . The cytologic features of some of the tumor cells were similar to those seen in a typical LCH . However , many tumor cells showed overtly malignant cytologic features such as pleomorphic / hyperchromatic nuclei and prominent nucleoli ( Fig.4 ) , and multinucleated tumor giant cells were also found . There were numerous mitotic figures ranging from 30 to 60 per 10 high power fields , and some of them were abnormal . A few foci of typical LCH remained around the main tumor mass . Immunohistochemically , the tumor cells were strongly positive for S-100 protein ( Fig.5 ) and vimentin ; they were also positive for CD68 ( Dako N1577 , Clone KPI ) , and focally positive for CD1a ( Fig.6 ) , and they were negative for cytokeratin , epithelial membrane antigen , CD3 , CD20 and HMB45 . The ultrastructural analysis failed to demonstrate any Birbeck granules in the cytoplasm of the tumor cells . Now , at five months after lobectomy , the patient is doing well with no significant change in the radiologic findings .


A 37 - year - old African American female with a past medical history significant for stage 1 sarcoidosis presented to our facility with a chief complaint of shortness of breath . Ten years prior , she presented with bilateral uveitis and lupus pernio ( LP ) on her right ear and was subsequently diagnosed with sarcoidosis . She was successfully treated for these conditions and her sarcoidosis remained quiescent until three years ago , when , at an outside institution , she was discovered to have laryngeal involvement . She was treated with prednisone 60 mg daily for several months and eventually tapered to 10 mg daily . Her sarcoidosis remained well - controlled on this maintenance dose of prednisone until six months prior , at which time she self - discontinued her prednisone in favor of the homeopathic treatment Nopalea cactus juice , which unsubstantially claimed to have anti - inflammatory properties [ 4 ] . Subsequently , she developed dyspnea on exertion progressing to dyspnea at rest . During this time her voice became increasingly hoarse and she experienced frequent episodes of difficulty swallowing . In our emergency department , her physical examination was concerning for respiratory distress as she presented with inspiratory stridor and hoarseness . She also had chronic - appearing , indurated lesions on her right ear . Given that she had signs of upper airway disease for impending respiratory failure , an emergent bedside laryngoscopy was performed , revealing an obstructed airway with the epiglottis retroflexed over the glottis and significant edema in the arytenoids and aryepiglottic folds . She was immediately treated with high - dose intravenous dexamethasone and taken emergently to the operating room ( OR ) to secure her airway for concern for complete upper airway obstruction , which was confirmed with direct visualization of her larynx in the OR . She was intubated for a surgical airway , and after taking biopsies from the lingual surface of her epiglottis , a # 4 cuffed Shiley ™ tracheostomy was placed . Her respiratory status immediately stabilized , was extubated , and transferred to our medical intensive care unit . Her tracheostomy was exchanged to a # 4 cuffless Shiley on postoperative day 5 . During this time she was transitioned from intravenous dexamethasone to prednisone 60 mg daily . Biopsies ultimately revealed non - necrotizing epithelioid granulomas consistent with sarcoidosis ( Figure 1 ) . She was prescribed this high - dose prednisone for three months , and after receiving education for self - tracheostomy care , she was discharged home . At her subsequent one - month and three - month follow - up visits , she denied any further respiratory issues . Repeat laryngoscopies showed significant improvement in the edema in the arytenoids and aryepiglottic folds , but the epiglottis continued to obscure the glottis despite therapy with high - dose prednisone . Methotrexate was initiated while prednisone was tapered to 10 mg daily ; however , this regimen failed and her prednisone dosage was increased to 20 mg daily to reduce edema . Because she declined surgical treatment , she will continue with medical management with immunosuppressive therapy to facilitate eventual de - cannulation .


A 71 - year - old African - American woman presented to the hospital with worsening exertional dyspnoea associated with orthopnoea and lower extremity oedema for 3 weeks . She had a long - standing history of hypertension and documented G6PD deficiency with prior episodes of haemolysis . She was a former cigarette smoker and had family members with G6PD deficiency , hypertension and diabetes mellitus . Vital signs measurement revealed a blood pressure of 150/73 mm Hg , pulse rate of 70 bpm , respiratory rate of 24 breaths / min , temperature of 36.6 ° C and 97 % saturation on room air . She was comfortable at rest . Her physical examination showed distended jugular veins , inspiratory crackles in bilateral lung bases , a laterally displaced apical impulse and bipedal oedema . The ECG showed left ventricular hypertrophy and inferolateral T - wave inversions . Chest radiography revealed cardiomegaly and mild pulmonary oedema . The metabolic panel and troponin levels were normal but the B - type natriuretic peptide was increased at 826.5 pg / mL. Echocardiography showed a dilated left ventricle with an ejection fraction ( EF ) of 30 % and mild right ventricular systolic dysfunction . Coronary artery catheterisation revealed normal coronary circulation . Ethacrynic acid at 50 mg daily was chosen for diuresis . She improved after a day but still had dyspnoea , so we added spironolactone . Subsequently , metoprolol succinate and losartan were included in the regimen . Repeat chest radiography showed resolution of pulmonary oedema . The patient 's laboratory results during her hospital stay did not show signs of haemolysis nor worsening kidney function . She did not develop ototoxicity and was discharged home asymptomatic .


A 36 - year - old female presented at the emergency department with aggravating right upper abdominal pain for 2 hours . The patient was diagnosed hepatitis B virus ( HBV ) carrier for several years and non - alcoholics . No other specific personal and familial medical history was noted . Initial blood pressure was 100/60 mmHg , pulse rate 70 / min , respiration rate 20 / min , body temperature 37.5 ℃ . The laboratory findings were white blood cell 12,000 / mm3 ( poly : 70 % ) , hemoglobin 12.8 g / dL , platelet 198,000 / mm3 , prothrombin time 14.3 seconds , international normalized ratio 1.11 , aspartate aminotransferase 22 IU / L , alanine aminotransferase 12 IU / L , total bilirubin 0.5 mg / dL , alkaline phosphatase 134 IU / L , lactate dehydrogenase 295 IU / L , gamma - glutamyl transpeptidase 26 IU / L , protein / albumin 6.4/4.0 g / dL , uric acid 5.0 mg / dL , blood urea nitrogen / creatinine 16.6/0.7 mg / dL. And serum viral markers were HBsAg ( + ) , anti - HBs ( - ) , anti - HBc ( + ) , HBeAg ( - ) , anti - HBe ( + ) , HBV - DNA < 20 IU / mL , anti - HCV ( - ) and anti - HIV ( - ) . The patient 's serum α - fetoprotein ( AFP ) was 676.5 ng / mL and carbohydrate antigen 19 - 9 ( CA19 - 9 ) < 0.6 U / mL. She took an abdominal CT scan , which showed a 9 cm sized necrotic mass with internal hemorrhage at the right hepatic lobe and ruptured to peritoneum ( Fig.1A ) , so an emergency hepatic central bisectionectomy was done ( Fig.2A ) . The initial histological diagnosis was cHCC - CC with spindle cell metaplasia of cholangiocarcinoma element ( Fig.2B ) . The serum AFP was decreased to 7.67 ng / mL at time of discharge . Regarding as cHCC - CC , postoperative adjuvant chemotherapy with tegafur / uracil ( UFT ) was administrated for 3 months . 3 months later , follow - up abdominal CT scanning showed previously unseen a 5.5 cm sized left subphrenic mass with mild enhancement in delayed image ( Fig.3A , B ) and AFP was increased to 312.06 ng / mL. She underwent laparoscopic splenectomy with mass excision . On histologic examination , mesenchymal elements consisted of a proliferation of primitive - appearing mesenchymal spindle - shaped cells , intimately admixed with the epithelial elements in a highly cellular pattern . Cytoplasm was more abundant than that of mature fibroblasts , and the nucleus was elongated and plump . These cells blended progressively with areas of less intense cellular mesenchymal proliferation , and with relatively acellular , fibrous septa . Osteoid was present either within the primitive mesenchyme , near the fibrous septa or pseudocapsule , or admixed within the epithelial elements . Osteoid foci contained cells morphologically identical to osteoblasts ( Fig.4A ) . The immunohistochemistry stains showed expression of hepatocyte , β - HCG , AFP , vimentin , CK7 , CK19 , CD56 and β - catenin and negativity for CEA.(Fig.4B , C , D , E , F , G ) . Metastatic hepatoblastoma was confirmed by histologic examination with immunohistochemistry stains , so immunohistochemistrically re - examination of previous surgical specimens was also confirmed as hepatoblastoma . Follow - up abdominal CT scan performed 1 month after reoperation showed a newly onset 1.7 cm sized subtle enhancing soft tissue mass in splenic bed , and positron emission tomography ( PET ) showed multiple FDG uptake(max SUV > 3.80 ) in left upper and lower quadrant area of abdomen , paralumbar area including right subphrenic area ( Fig.5A , B , C ) . Follow - up AFP was 162.69 ng / mL. Systemic chemotherapy started with cisplatin ( 60 mg / m2 ) , 5 - fluorourasil ( 5 - FU ) ( 600 mg / m2 ) , vincristine ( 1.5 mg / m2 ) and total 3 cycles of chemotherapy were done every 4 week . Entecavir 0.5 mg was also started for chemoprophylaxis of CHB . After the 3rd chemotherapy cycle , follow - up abdominal CT and PET scan showed progression of multiple intraperitoneal metastasis with large amount of intraperitoneal fluid ( Fig.6A , B ) and follow - up AFP was further increased to 254 ng / mL. So chemotherapy regimen was changed to carboplatin ( 350 mg / m2 ) with doxorubicin ( 30 mg / m2 ) every 3 weeks . The patient experienced neutropenia after the new regimen , but recovered shortly after treatment with granulocyte colony - stimulating factor ( G - CSF ) . After second carboplatin with doxorubicin chemotherapy , follow - up AFP was increased 1510.19 ng / mL , but abdominal CT scan showed that amount of ascites was decreased ( Fig.7 ) . Because of radiologic improvements , third and fourth chemotherapy were performed . After 4th chemotherapy , follow - up abdominal CT revealed progression of multiple intraperitoneal metastatic masses , newly developed hepatic metastasis and large amount of intraperitoneal fluid ( Fig.8 ) . A diagnostic paracentesis was performed and showed white blood cell 310 / mm3 ( poly 20 % , lymph 80 % ) , protein 3.6 g / dL and albumin 2.3 g / dL on ascitic fluid analysis . The serum albumin was 3.1 g / dL and serum - ascites albumin gradient ( SAAG ) was 0.8 g / dL. The AFB stain and culture were all negative in ascitic fluid . The AFP was 6881.93 ng / mL on serum . Regarded as peritoneal carcinomatosis , the patient underwent conservative treatments including the use of repeated therapeutic paracentesis for 1 month before death .