A 58-year-old woman presented with loss of appetite and general fatigue. Blood examination revealed marked leukocytosis (37.6 × 109/L) with 81.5% lymphoblasts. Bone marrow aspiration showed that 95% lymphoblastic cells were positive for B-cell markers, including CD10, CD19, CD34, and human leukocyte antigen (HLA)-DR, while cytogenetic analysis reported a complex karyotype including t(9;22) (q34;q11). Real-time quantitative polymerase chain reaction (RT-qPCR) detected 3.1 × 105 copies/μg of RNA p210 bcr-abl transcripts in the marrow specimen. The patient was diagnosed with Ph-positive precursor B-cell ALL in April 2005, when imatinib-combined induction therapy was initiated (Yanada et al.
).
She exhibited complete hematological and cytogenetic responses, and bcr-abl transcripts were negative according to RT-qPCR. In July 2005, after receiving high-dose methotrexate (MTX) therapy as CNS prophylaxis, she underwent bone marrow transplantation (BMT) using an allogeneic bone marrow graft from an HLA-matched sibling donor after a conditioning regimen with fludarabine (25 mg/m2/day for 5 days), busulfan (2mg/kg/day for 2 days), and melphalan (80 mg/m2/day for 1 day). Cyclosporine A and short-term MTX were used as prophylaxis against graft-versus-host disease (GVHD). The patient exhibited rapid and sustained engraftment, with a neutrophil count higher than 0.5 × 109/L and a platelet count higher than 50 × 109/L on day +16. However, 3 months after BMT, she relapsed with meningeal leukemia, despite being treated with prophylactic intrathecal chemotherapy before BMT. She was subsequently administered high-dose MTX therapy and 6 cycles of MTX-based intrathecal chemotherapy. This regimen eliminated lymphoblastic cells from her CSF, but 1.6 × 105 copies/μg of RNA p210 bcr-abl transcripts were still detected in her marrow blood. In July 2006, she underwent allogeneic cord blood transplantation (CBT) after a conditioning regimen that included fludarabine (30 mg/m2/day for 5 days), cytarabine (1.5 g/m2/day for 4 days), melphalan (80 mg/m2/day for 1 day), and total body irradiation with 4 Gy. Prophylaxis against GVHD was performed with continuous infusion of tacrolimus.
Neutrophil engraftment was observed on day +18, but acute GVHD was not observed. The patient developed a limited type of chronic GVHD on day +165; nevertheless, she responded well to treatment with prednisolone. However, 7 months after CBT, she relapsed again, developing meningeal leukemia accompanied by headache. Imatinib and intrathecal chemotherapies were initiated again, and whole-brain irradiation (24 Gy in total) was added to her treatment regimen. She achieved remission, and imatinib therapy was continued to prevent CNS relapse. In April 2009, she again complained of headache, and cranial magnetic resonance imaging revealed an extramedullary mass on the right side of the temporal region (Figure
a).
The clinical course of the patient after relapse is shown in Figure
. Because of molecular resistance against imatinib, the patient was treated with 100 mg of dasatinib daily and was administered 2 cycles of intrathecal chemotherapy. While on dasatinib therapy, the patient, despite receiving adequate supportive therapy, experienced grade 2 pleural effusion and grade 2 hematemesis according to the National Cancer Institute Common Terminology Criteria (NCI-CTC). Dasatinib was discontinued because of these adverse events and reinitiated at a daily dose of 40 mg once she recovered. The extramedullary mass in her temporal region disappeared (Figure
b), and meningeal leukemia was ameliorated almost immediately. During the course of treatment, we investigated the dasatinib concentrations in the patient’s plasma and CSF using high-performance liquid chromatography coupled with electrospray mass spectrometry (HPLC-MS) as described previously (De Francia et al.
), albeit with some modifications. The trough level and CSF concentration of dasatinib administered at a daily dose of 40 mg were 32 ng/mL and below the sensitivity threshold of 1 ng/mL, respectively. Two months after the initiation of dasatinib treatment, large granular lymphocytosis was observed in the peripheral blood. These large granular lymphocytes were CD3, CD8, CD56, and CD57 positive, and PCR revealed an oligoclonal pattern of T-cell receptor gene rearrangement (data not shown). Until April 2011, the patient remained in complete remission while taking 40 mg of dasatinib once daily; however, meningeal relapse was revealed after close investigation of vertigo. Bone marrow examination showed the presence of 73 copies/μg of RNA p210 bcr-abl transcripts that were detected by RT-qPCR. In addition, the lymphoblasts in her CSF harbored an E255K ABL tyrosine kinase domain mutation, which is known to be moderately resistant to both dasatinib and nilotinib. On the basis of these results, we increased the dose of dasatinib to 100 mg once daily and administered one cycle of intrathecal chemotherapy. Three weeks after the initiation of this treatment, the patient achieved complete molecular remission in the bone marrow, and lymphoblasts were undetectable in the CSF. Seven years after the initial diagnosis of Ph-ALL, the patient died of pneumonia. Until the time of her death, no evidence of ALL recurrence was observed.


The patient was a forty-three year old male, with evolving malaise and progressive weakness over a four year period in all 4 limbs with episodes of partial improvement and frequent relapse. He was evaluated at our institution for exacerbation of symptoms. History of Guillain-Barre dating to 16 years prior, controlled hypertension, chronic renal insufficiency, stage IV, and chronic anemia syndrome. There was a history of a firearm wound to a foot 24 years earlier with orthopedic management. When examined he presented with muscular weakness predominantly in the upper limbs and hyporeflexia without involvement of the cranial nerves. Blood profile: Hemoglobin: 8.3 g/L, Hematocrit: 25. Microcytosis. Na: 135 K: 5.1. C3-C4: normal, VDRL: No reagent.
Blood smear (-). HIV (-). Rated by Internal Medicine and Neurology with a diagnostic impression of: Viral myelopathy, Guillain-Barré sequelae. Radiographs show presence of multiple fragments of lead in the sidebar of the foot with partial destruction of the Cuboids ().
We considered the possibility of lead poisoning. Blood lead levels were taken and reported as 62 ug / dL (Normal: 0-9.9). Starting chelation therapy with EDTA: administered 50 mg/kg/day.
After chelation therapy, the patient was taken to surgery for removal of the bullet material and midfoot reconstruction ().


The patient was a 38 year old male with a 3-year history of evolving paroxysmal abdominal pain, postprandial emesis and weight loss. Medical management with partial improvement reported. Progress accompanied by exacerbation of symptoms, bizarre behavior, aggression and seizures. The patient was initially wounded 15 years ago with a shot to the foot. Smoking and drinking to intoxication was reported. Physical examination showed decreased muscle strength with predominantly at C5 -T1 levels. Achilles hyporeflexia. The blood count and peripheral blood smear showed hypochromic microcytic anemia. Lead Levels were: 90.3 µg/dL. Radiograph of foot evidences multiple metal fragments at the midfoot joints. Osteoarthritis of the calcaneocuboid joint, Talo-navicular and subtalar (). Diagnosis of blood poisoning, starting chelation with EDTA (50 mg/kg/day) for 7 days ago. It is taken to surgery for removal of projectiles lodged and hindfoot arthrodesis ().


Herein, we present a case of a 56-year-old female with a pigmented and painful nodule with progressive growth in the abdominal region with 15-year evolution, which presented easy bleeding in the last months prior to consultation. Upon physical exam, a hyperpigmented and angiomatous pedunculated nodule was found with hyperkeratotic surface . The following were considered as presumptive diagnoses: irritated seborrheic keratosis, epithelialized pyogenic granuloma, inflamed intradermal nevus, and nodular melanoma. A skin excision biopsy was carried out, whose report was a dermal tumor mass from the lower portion of the epidermis, well defined, formed by small cuboidal cells without atypia, arranged in well-defined bands that anastomose without barricade, with pigmented areas and few dilated ducts, which are in contact with the resection margins, compatible with eccrine poroma () Immunohistochemistry was also performed, highlighting Carcinoembryonic Antigen (CEA) with elongated cells that line the cavities that support glandular differentiation. S100 staining was observed in the dendritic cells and melanocytes in the thickness of the cell proliferation ().
The patient attended clinical controls post intervention, without lesion recurrence found until now.


A 46 year old man with the history of drug abuse for the last 15 years without any systemic disease was referred to our office by a general practitioner. The dentist stated that he was doing a root canal treatment (RCT) for upper central and lateral incisors and canine without being aware of the occurrence of a perforation during access cavity preparation on lateral teeth. He prepared and obturated the canals. After providing the final radiography he decided to extirpate the GP from PDL space without anesthesia, by means of Chloroform, again being unaware of its leakage through the perforation site. The patient did not feel any pain neither unpleasant feeling which was believed to be due to his addiction. He was dismissed and the following morning he came up with a large missing zone in his buccal gingiva. He was immediately referred by his dentist to an endodontist for problem solving.
A large necrotic area in the gingival areas surrounding upper lateral incisor was obvious during clinical examination (). Lateral incisor had a large longitudinal perforation on mesial wall of the root. The patient reported history of drug abuse and that he had felt no pain or irritation during the retreatment. He also reported that he has experienced a medical surgery without anesthesia years before. After consulting with a periodontist, nonsurgical retreatment of upper central incisor and canine was performed by the endodontist (). Before treatment, the patient was referred for Cone Beam Computed Tomography (CBCT) for more evaluation that showed a long perforation on coronal half of mesial wall of maxillary left lateral incisor ().
The lateral incisor was extracted and during a flap surgery the area was re-contoured. The extracted tooth showed a longitudinal perforation (). After the time needed for gingival healing, the patient treatment was completed with fixed partial denture between central incisor and the canine. shows the six-month follow-up.


A 32 weeks pregnant, 23-year-old known asthmatic woman presented to a peripheral hospital with acute respiratory failure during winter. Cold air was a known precipitant for her asthma. She was intubated and ventilated for presumed severe acute asthma with refractory bronchospasm. Following intubation she was found to be extremely difficult to ventilate and was retrieved to our intensive care unit for further management.
She had widespread, faint, prolonged monophonic wheeze on auscultation with no evidence of pneumothorax. Mechanical ventilation in volume control mode was commenced with an inspired oxygen fraction of 1.0, external Positive End Expiratory Pressure (PEEP) 0 cmH2O, respiratory rate six breaths per minute, a tidal volume of 300 ml, and inspiratory flow rate of 30 L/min. However, high peak airway pressures truncated each breath. Intrinsic PEEP was measured as 30 cmH2O, with evidence of dynamic hyperinflation and accompanying hemodynamic instability despite inspiratory to expiratory ratio of close to 1:16. An arterial blood gas sample revealed severe respiratory acidosis (pH of 6.92, PaO2 116 mmHg, and PaCO2 143 mmHg). There was evidence of foetal distress on Cardiotocograph (CTG). Bronchoscopy demonstrated a pedunculated tumour arising from the posterior tracheal wall, extending from the tip of the Endotracheal Tube (ET) and measuring approximately 4 cm by 2 cm. The tumour acted as a ball valve to cause severe expiratory airflow obstruction (Figure ; Additional file : Video 1). The bronchoscope was advanced beyond the lesion and the ET advanced over the bronchoscope to bridge the lesion, resulting in dramatic improvements in lung mechanics and haemodynamics. Urgent Caesarean section was performed due to persistent decelerations on CTG, with birth of a healthy baby. Access to her previous records revealed that she previously presented with haemoptysis at 16 weeks of the current gestation. At this time she had a small polyp (~0.5 cm) in the same tracheal location, which had been excised and diagnosed as LCH.
The following day, tumour debulking was attempted. In view of the high risk of major haemorrhage and hypoxemia, precautionary cannulation for veno-venous Extra-Corporeal Membrane Oxygenation (ECMO) was established via a bi-femoral approach. Surgical debulking was complicated by significant haemorrhage causing desaturation (SpO2 < 80%). She was promptly commenced on ECMO with recovery of arterial oxygen saturation and minimal disruption to surgery. A small bolus of heparin (2000 units) was given intravenously just prior to connection of the ECMO circuit, but no further heparin was administered until after surgery. On return to the ICU, a low dose heparin infusion (10 units/kg/hour) was used to maintain ECMO circuit patency. The histopathology revealed recurrent LCH (Figure ), with intact overlying epithelium (Arrow) and lobular arrangements (*) of proliferating capillaries (horizontal arrow) in an edematous fibro-myxoid stroma, containing extravasated red blood cells (vertical arrow). There was intense staining with CD31 Immunohistochemical staining highlighting proliferating endothelial cells and vascular origin of tumor. Her trachea was subsequently stented and ECMO was discontinued. She made a full recovery.


A 26-year-old man presenting with an episode of dysarthria and dizziness 3 weeks prior to admission was referred to our center to be evaluated for transient ischemic attack (TIA). His past medical history showed no evidence of previous illness. On admission, physical examination showed that he was in sinus rhythm, had a pulse rate of 75 bpm, and a blood pressure of 100/60 mm Hg. On auscultation, he had no murmur or carotid bruit. Laboratory tests were normal. He had a normal electrocardiogram and chest X-ray. Initial cardiac evaluation was also normal. The patient had been previously admitted to a different hospital which had performed transthoracic echocardiogram and reported it as normal. The patient was referred for transesophageal echocardiography (TEE) to rule out of patent foramen ovale (PFO). We performed another transthoracic echocardiogram (TTE), but mobile strand-like masses in left ventricular (LV) were detected (). TEE also revealed two distinct highly mobile filamentous LV masses, suggesting papillary fibroelastoma (Figures and ). One mass measuring 5 × 0.6 cm originated from the posterior wall, near the apex, and another mass measuring 3 × 0.6 cm originated from the mitral valve (MV) annulus just beside the posterior MV leaflet. Both of the masses extended toward LV outflow tract. Both aortic and mitral valve were spare, but chordae tendina was suspected to be involved. CT angiography confirmed the diagnosis. The patient was given anticoagulant therapy and referred for surgery. At operation, two large beading tumors were found in the LV (). One of the tumors was attached to posterior leaflet of the MV and the other one was attached to the posterior papillary muscle adjacent to the chordae tendina. The tumors were successfully excised via mitral valve approach. Chordae reconstruction and MV annuloplasty were performed for the patient. The postoperative recovery was uneventful. Follow-up TEE revealed no residual tumor.


A 76-year-old woman with a history of hypertension and hyperlipidemia was admitted to our emergency department with typical angina pectoris ongoing for 30 minutes. On admission, her arterial blood pressure was 160/95 mmHg; pulse rate was 72 bpm. Her physical examination was normal. The 12-lead electrocardiogram revealed normal sinus rhythm, left ventricular hypertrophy (27 mm R wave V6), and T wave inversion in leads II, III, aVF, I, aVL, and V3–V6. The chest X-ray showed no cardiomegaly or pulmonary congestion. Cardiac enzymes were not raised throughout the admission. Echocardiography revealed normal ventricular function without wall motion abnormality and left ventricular hypertrophy.
Figures , , and show the fistula from the first diagonal artery to the ventricle. There was no stenosis in the coronary arteries (Figures , , and ). Left ventriculography demonstrated good systolic function (EF = 60%) without wall motion abnormality.


A 77-year-old woman presented complaining from the sudden onset of acute retrosternal pain radiating to the left arm. Three months earlier, the patient was referred to our laboratory for a giant, calcified, aneurism of proximal LAD and coronary subocclusion immediately proximal to the sac () and percutaneous coronary intervention (PCI) was performed using a 3.5 × 14 mm bare metal stent (BMS) (Figures and ).
During the current hospitalization, she had severe hypotension (70/50 mmHg) with heart rate of 63 beats/min. The ECG showed diffuse ST segment depression and elevation in lead aVR, suggesting an acute myocardial infarction (AMI) due to possible occlusion of the left main coronary artery (LMCA). Anteroposterior chest X-rays showed no significant widening of the mediastinum. The patient was under double antiplatelet therapy with aspirin 100 mg and clopidogrel 75 mg. Transferred to the laboratory for primary PCI, there was the evidence of subocclusion of the LMCA with patency of the BMS previously implanted in the LAD and closure of the coronary aneurism (). LMCA was then stented using a 3.5 × 9 mm BMS (). Because of recurrent episodes of ventricular tachycardia, a control angiogram soon after the procedure showed a significant length reduction of LMCA, just prior the implanted stent (). Thus, in overlap with the first stent, a second one (BMS 4.5 × 13 mm) was applied in the proximal tract of LMCA ().
Back in the ward, the patient underwent transthoracic echocardiography whereby a double outline was seen at the level of ascending aorta. A successive CT scan clearly showed dissection of the ascending aorta starting near the LMCA (Figures and ). The patient suddenly died before surgery could be undertaken. No autopsy was performed.


A 50-years old woman with no relevant medical history and no underlying liver disease was referred to our Division for acute abdominal pain but no other abdominal or systemic symptom. Palpation of the right upper quadrant showed tenderness but Murphy’s sign was negative. Lab tests showed slightly increased serum CRP (53 mg/L), normal white cell count, undisturbed coagulation blood tests, and liver function remained unremarkable. Tumor markers CA 19–9 and CEA were also normal, 3 kU/L and 1.1 ug/L, respectively. A CT showed portal vein aneurysm measuring 88 × 65 mm with complete thrombosis extending to superior mesenteric (SMV) and splenic (SV) veins (Figure ). The risk of rupture being low, we decided to treat conservatively with anticoagulation therapy. We completed our investigations with an upper GI endoscopy and thrombophilia workup; the former did not show any esophageal varices indicating portal hypertension, and any coagulation disorder could be detected. The patient was released after two weeks and followed on an outpatient basis. At two months, she reported decreased pain, and a control CT demonstrated the decreasing of the thrombosis, measuring 80 × 55 mm, associated with a diminished extension to superior mesenteric and splenic veins (Figure ).


A 42-year-old African-American male presented to our hospital with a 2-week history of rapidly progressive exertional dyspnea. He had no significant past medical history, did not take any medications, had no allergies, occasional cigarette smoking, drank an average of six-pack of beer a week, and his parents had hypertension and diabetes.
Cardiac enzymes were negative, BNP level was 843, and D-dimer was elevated at 3.7. A urine drug screen, HIV 1/HIV 2 antibodies, and hepatitis viral panel were negative. Rheumatoid factor was normal, ANA titer was mildly positive with a speckled pattern, angiotensin converting enzyme level was high at 70 U/L (normal 7 to 46), histoplasma antigen was negative, parvovirus B-19 IgM antibody was negative, and parvovirus IgG antibody was positive suggesting a past infection. Patient's EKG showed sinus rhythm, low voltage, and poor R-waves in inferior and anterior leads. CXR showed pulmonary edema and cardiomegaly, with nodular pattern in the periphery. CT chest with contrast showed no evidence of pulmonary embolism, significant degree of mediastinal, hilar, right peridiaphragmatic lymphadenopathy, small pleural effusion, small pericardial effusion, and bilateral multifocal consolidation.
TTE showed severe global hypokinesis with regional variation, mostly sparing the apex.
Tc-99 tetrofosmin with adenosine stress testing showed a medium to large, severe, fixed anterior perfusion defect with sparing of the apex, suggesting an anterior infarct, although the distribution was atypical for a proximal LAD occlusion. Severe global LV systolic dysfunction was also noted.
Left and right heart catheterization showed normal coronary arteries, elevated right atrial pressures, moderate pulmonary hypertension, elevated pulmonary capillary wedge pressure, elevated LVEDP, decreased cardiac output and index, no intra- or extracardiac shunts were noted. Patient was anticoagulated and placed on intra-aortic balloon pump for afterload reduction.
Cardiovascular magnetic resonance imaging (CMR) was done for further evaluation of fulminant myocarditis. CMR showed top normal left ventricular size, mildly dilated by 3D, LVEF of 27%, with severe regional wall dysfunction, worse at base and sparing the apex (see Video 1 in Supplementary Material available on line at doi:10.1155/2011/647041). First-pass perfusion demonstrated nonspecific subtle subendocardial hypoperfusion defect, not following any coronary distribution (). Delayed hyperenhancement imaging (DHE) showed an extremely heterogeneous, dense, and patchy, near complete enhancement of the myocardium, with increased T1 signal by gadolinium imaging. Late imaging after the postedema washout period reveals a marked patchy signal consistent with a severe inflammatory or infiltrative process (). Right ventricular segmental dysfunction exactly colocalized with the transmural RV signal. Right paratracheal and perihilar lymphadenopathy was also noted. The official CMR report suggested that this pattern was most consistent with GCM.
Based on the CMR findings and the clinical presentation EMB was done. The EMB showed noncaseating granulomatous inflammation with many multinucleated giant cells, histiocytes, and mild chronic inflammation (Figures and ). Special stains were negative for organisms. No viral cytopathic effect was seen. Iron stain was negative. Thioflavin-T stain and congo red stain for amyloid were negative. Sarcoidosis/granulomatous myocarditis was favored over idiopathic giant cell myocarditis because of the presence of well-formed granulomas and granulomatous inflammation. Interestingly, the first official pathology read was signed out as GCM. Thus, the patient was initiated on prednisone and cyclosporine 50 mg PO BID which was later increased to 75 mg PO BID in 6 days, in specific treatment of GCM.
With rapid clinical improvement from CHF, the IABP was removed. After clinical stabilization, the patient was discharged home on carvedilol, aspirin, lisinopril, prednisone slow taper over 5 weeks, cyclosporine at 75 mg PO BID, and Bactrim SS for prophylaxis while on cyclosporine.
Repeat CMR 7 weeks after the initial CMR showed improved LVEF to 40% (Video 2). The first-pass perfusion imaging showed hypoperfused subendocardial defects remained generalized (). DHE showed moderate improvement and coalescence of previously seen LV myocardial enhancement with mild to moderate improvement in RV signal as well (). Also noted was the interval improvement in the mediastinal lymphadenopathy.
Repeat CMR 9 months later showed the LVEF stabilized at 40% and RVEF at 45% (Video 3). First-pass perfusion by gadolinium revealed an unchanged generalized subendocardial, near circumferential hypoperfusion defect (). The DHE pattern had mildly improved as well (). Also noted was the interval improvement of the pulmonary sarcoidosis pattern since the second CMR.


A 53-year-old woman presented with abdominal cramping pain and bloody diarrhea for 3 days. She was robust prior to this event, with no known relevant medical history. She denied fever or chills. Physical examination revealed increased bowel sounds and tenderness in the lower abdomen. Laboratory tests demonstrated minimal leukocytosis (10,300 cells/μL) without left shift and elevated C-reactive protein. Intravenous ciprofloxacin 400 mg q12 h was prescribed to treat the suspected infectious diarrhea. No specific finding was reported on enterogastroduodenoscopy. Due to suspicion of an infectious or inflammatory process of the lower gastrointestinal tract, colonoscopy was arranged after 3 days of colonic preparation. Hyoscine 20 mg was prescribed via a slow intravenous drip as a premedication for colonoscopy. Unfortunately, loss of consciousness and cyanosis of all 4 limbs developed 1-2 minutes later. The patient's blood pressure was 55/28 mmHg, and her heart rate was 58 beats per minute. After fluid resuscitation, epinephrine injection, and continuous dopamine infusion, the patient regained consciousness and her blood pressure recovered. However, electrocardiography revealed ST-segment elevation over the V3–V6 lead (). Troponin I was elevated to 5.49 μg/L.
Emergent percutaneous coronary intervention was performed for ST elevation myocardial infarction. No obvious stenosis or obstruction was noted (). Balloon angioplasty or stenting was not applied. Fluid hydration, heparinization, ticlopidine, and continuous dopamine were prescribed. On echocardiography, the ejection fraction and aortic wall motion remained normal. The dosage of dopamine and diuretics were tapered down, and the antiplatelet and anticoagulation agents were discontinued. Under conservative treatment with fluid hydration and antibiotics, the patient recovered gradually. The bloody diarrhea subsided, and no angina or heart failure signs were observed. The patient was discharged within 2 weeks.


A previously healthy 28-year-old non-smoking woman was admitted to the hospital because of cough, mild dyspnoea, and fever of 38°C. The blood pressure, heart rate, and respiration rate of the patient were 103.0/63.0 mmHg, 100 beats/min, and 25 beats/min, respectively. During physical examination, she presented tachycardia, cyanosis, and diffusely reduced breath sounds but no vesicular murmur, crackles, or wheezing. Blood gas analysis revealed the following findings: pH 7.47; pCO2, 40 mmHg; pO2, 53 mmHg; HCO3-, 29.1 mmol/L; and Lac, 0.6 mmol/L. These findings indicate hypoxemia. High-resolution computed tomography (HRCT) of the chest revealed bilateral diffuse airspace opacification (Figure A). Levofloxacin was administered intravenously for 4 d. Her condition deteriorated with acute onset of dyspnoea and rapidly progressive respiratory failure, and the patient required intubation and mechanical ventilation. Blood gas analysis indicated hypoxemia; pH 7.19; pO2, 32 mmHg; and pCO2, 35 mmHg. HRCT revealed the deterioration of diffuse ground-glass opacification (Figure B). Fiberoptic bronchoscopy was performed on the same day after the patient was transferred to an intensive care unit. The bronchial tubes were normal with little sputum. Microbiologic investigations were negative. Transbronchial lung biopsies were performed on the same lobe (left upper lobe) on the fifth day of hospitalization. The first lung specimen exhibited edema, hyaline membrane formation, and acute interstitial inflammation, which all suggest an exudative phase of AIP (Figure A). High doses of intravenous methylprednisolone (500 mg for 3 d and 160 mg for 2 d) were administered based on presumptive diagnosis of interstitial lung disease. After 5 d, HRCT revealed diffuse ground-glass attenuation (Figure C). However, the patient still had acute hypoxic respiratory failure and could not be extubated after the procedure. Despite initiating intravenous with normal dose of methylprednisolone (80 mg per day) and high concentrations of oxygen, the patient remained intubated for eight weeks. Chest X-ray analysis indicated that her lung deteriorated did not improve even when high-dose glucocorticoid was re-administered. Her oxygen saturation was only 30% when the fraction of inspired oxygen was 100%. The patient eventually expired after 62 d of hospitalization. The patient underwent autopsy, and the slides showed diffusely thickened alveolar septal interstitium by hyaline membrane remnants, pulmonary interstitial and alveolar edema, type II pneumocyte hyperplasia (Figure B), and significant amount of myofibroblasts (Figure ). These results indicate organized DAD. Transmission electron microscopy revealed that the epithelial cells, which are characterized by their basement membrane and specialized cell-cell junction structures, contained bundles of filament in the cytoplasm (Figure ). The presence of filaments in these cells suggested the occurrence of EMT. We then determined the changes in EMT-related proteins, such as surfactant associated protein (SPC), α-smooth muscle actin (α-SMA), and Snail. (Santa Cruz Biotechnology Inc. Dallas, Texas, USA). The results of the double immunostaining of the lungs showed mesenchymal specific protein α-SMA in the alveolar epithelial cells (SPC-positive cells). The double positive cells were evidently increased in the lung tissue from the 62 d autopsy compared with that from the 5 d biopsy (Figure ). The zinc finger transcription factor Snail was evidently expressed in the lung tissue, especially in the lung tissue from the 62 d autopsy (Figure ).


A 9-year-old girl was referred for assessment of a 1 year history of episodic abdominal pain and non-bilious vomiting. The pain was described as dull, localized to the periumbilical area and unassociated with food. A breath test was consistent with lactose malabsorption. However, lactose restriction only transiently improved symptoms. The review of systems and past medical history were unremarkable. She denied the use medications including nonsteroidal anti-inflammatory drugs (NSAIDS). There was no family history of celiac disease, pancreatitis, inflammatory bowel disease, or autoimmune disorders other than multiple sclerosis (paternal grandmother). Her physical exam was within normal limits with satisfactory weight and growth parameters.
Initial laboratory investigations revealed a normal hemoglobin and white blood cell count, erythrocyte sedimentation rate and serum albumin. Her tTG was discretely elevated (10 U/ml; normal < 5). However, her total serum IgA was low (<0.06 g/L; normal 0.63-3.49), whereas her IgE was elevated (986 ug/L; normal <240).
An initial upper endoscopy revealed small apthous ulcerations in the duodenal bulb. The second portion of the duodenum appeared normal. One duodenal biopsy revealed mild villous blunting and acute duodenitis, without an increased IEL count. No giardia or other parasites were seen. Two other duodenal biopsies revealed normal villi, with moderate eosinophlic infiltration involving the glands (40–50 eosinophils per high power field (HPF)). The pathology report concluded that the findings were insufficient for a diagnosis of celiac disease and that the focal eosinophilic infiltrates were consistent with infectious, allergic or eosinophilic gastroenteropathies. A colonoscopy revealed mild inflammatory changes in the terminal ileum and ileocecal valve as well as hyperemia of the mucosa in the rectosigmoid area. Histological analysis showed focal active ileitis, and foci of mild active colitis with intraepithelial eosinophils. No granulomas, crypt abscesses, or chronic inflammatory changes were seen. She was given a tentative diagnosis of eosinophilic gastroenteritis and was treated with once daily oral montelukast sodium. No sustained benefit was achieved.
In view of persistent symptoms, further investigations were pursued, which revealed positive EMA and HLA DQ2 typing. CE of the small bowel showed patchy villous atrophy with delayed appearance of villi until the proximal to mid jejunum, as well as areas with slight mucosal scalloping. Moreover, fibrin covered actively bleeding mucosal ulcerations were observed in the jejunum (Figure ). Her tTG remained slightly elevated (7 U/ml; normal < 5). Push enteroscopy performed 7 months following her initial upper endoscopy, confirmed ulcerative jejunitis. Biopsies revealed subtotal villous atrophy, crypt hyperplasia and an IEL count of 58 lymphocytes/100 enterocytes in the second stage of the duodenum (Marsh classification III B). Changes in the jejunum varied from preserved villous architecture with 82 IEL/100 enterocytes (Marsh I at 65 cm) to partial villous atrophy and crypt hyperplasia with an IEL count of 89/100 enterocytes (Marsh III B at 95 cm), consistent with a diagnosis of celiac disease (Figure ).
Institution of a strict GFD for 6 months led to clinical improvement, with considerably less pain and cessation of vomiting. Moreover, her serum tTG normalized (<3 U/ml). However, a repeat CE again revealed delayed appearance of villi until the mid jejunum and mucosal ulcerations in the proximal jejunum without active bleeding, consistent with persistent ulcerative jejunitis. Biopsies obtained by repeat push enteroscopy after 6 months on a GFD showed normal villous architecture in the duodenum and jejunum down to 150 cm, with an IEL count of 12/100 enterocytes per HPF in the duodenum (Marsh 0) and 40-46/100 per HPF in the jejunum at 130 cm and 150 cm respectively (Marsh I). The biopsies were subsequently sent for lymphocytic identification and PCR amplification studies for T cell rearrangement on fresh tissue. PCR amplification studies were also done on paraffin embedded tissue from the samples at diagnosis. On the sample from initial diagnosis prior to GFD, a T-cell clonal population was observed although it stained positive for surface expression of both CD3 and CD8 (Figure ). The specimen obtained after 6 months on a GFD showed oligoclonal T-cell populations and still stained positive for surface expression of both CD3 and CD8 (Figure ). Since there was definite improvement histologically, a decision was made to continue the strict GFD and to re-evaluate by CE and histology after another 6 months.
A third CE after 12 months on a GFD was unremarkable, with early appearance of normal villi in the duodenum and no evidence of ulcerative jejunitis. A duodenal biopsy now showed well preserved villous morphology and a normal IEL count (25 lymphocytes/100 enterocytes; CD3/CD8 positive), consistent with celiac disease in remission. A recent capsule, done 4 years after diagnosis, was unremarkable and multiple duodenal biopsies were completely normal as well. Her tTG remained normal (<3 U/ml), her EMA normalized and her total serum IgA remained low (0.4gL; normal 0.82-4.57).


A 54-year-old Caucasian man underwent right pleural biopsy in December 2005 for recurrent pleural effusion and locally advanced malignant mesothelioma was diagnosed. Subsequently, he was treated with chemotherapy containing cisplatin and pemetrexed for seven cycles; CT scan showed a partial response. In December 2006, he underwent surgery involving total right pleuro-pneumonectomy plus partial resection of the pericardium and diaphragm. The histological features showed epithelioid malignant mesothelioma involving the parietal and the visceral pleurae, the lung, the pericardium and the diaphragm.
Subsequent radiotherapy to the right chest was administered using 50.4 Gy, 28 fractions.
The patient remained disease-free until June 2009 when an isoechogenic and hypodense nodule of 35 × 16 mm was discovered on US and CT scan in the right side of the anterior abdominal wall. An ultrasound-guided biopsy showed metastasis of mesothelioma. In August 2009, the nodule was surgically removed, and radiotherapy was then administered to this site using 45 Gy, 15 fractions.
In September 2011, a relapse in the mediastinum (lymph nodes) was found by CT scan and Positron Emission Tomography (PET), so six cycles of chemotherapy with cisplatin and pemetrexed were started which lasted until January 2012. Complete response at PET examination in February 2012 was demonstrated.
In November 2012, a right submandibular salivary gland tumefaction was recorded. US examination showed right submandibular gland hypertrophy (Figure ), confirmed on CT scan and with neither US nor CT signs of metastasis; a diagnosis of inflammation of the gland was made. Anti-inflammatory therapy was administered; the patient also received antibiotic therapy but without improvement. An US-guided FNAB of the right submandibular salivary gland was then performed using a 22-gauge needle and showed atypical mesothelial cells, with nuclear enlargement and increased chromatin representation (Figure ). Immunocytochemistry showed positivity for calretinin (Figure ) and nuclear, weak and focal positivity for WT-1 (Figure ). Based on the previous history of malignant mesothelioma and the morphologic features of the cells, immunocytochemistry allowed confirmation of the diagnosis of right submandibular involvement from epithelioid mesothelioma. The subsequent PET scan was positive for the right submandibular salivary gland. The patient was treated with radiotherapy to this site.
A computerized literature search through MEDLINE, Cancerlit and Embase was performed, in order to make a comparison with our case, applying the words: ‘mesothelioma', ‘metastasis', ‘oral cavity', ‘mouth', ‘buccal', ‘tongue', ‘head and neck area’. Articles and abstracts were also identified by back-referencing from original and relevant papers. Selected for the present review were papers published in English before April 2013.


In 1990, a 7-year-old white female suffered a trauma in a swimming pool and fractured the crown of her maxillary left central incisor. Her parents found the fragment, and a pediatric dentist placed a crown with the autogenous fragment. The fractured line of the left maxillary central incisor was below the buccal gingival margins, restricted to the crown. Radiographic examinations showed no abnormality; the tooth was followed up for a few months (clinical and radiographic controls) and showed no signs or symptoms that could lead to suspicion of pulp necrosis.
At eleven years old, while on a school trip, the patient developed swelling and drainage in her anterior maxilla, and she was immediately referred to an endodontist for root canal treatment of the maxillary left central incisor. The treatment was limited regarding pulp calcification; the obturator material did not fill in to complete the canal in the apical region (). At sixteen years old, the maxillary left central incisor darkened, and the patient underwent intracanal whitening. Eleven years later, at 27 years old, the patient was referred to a dental clinic for orthodontic treatment, with the chief complaint related to an accentuated deep bite, and a professional started orthodontic treatment. At this time, the patient presented a Class I occlusal relationship in the right side, a Class II full occlusion on the left side (Figures
), an overbite and opened interincisor angle, a history of clenching, and TMD signs (click at both ATMs). At this stage, a periapical radiograph showed no significant changes in comparison to X-rays taken immediately after the root canal of the maxillary left central incisor (Figures
).
After sixteen months of orthodontic treatment, the maxillary left central incisor fractured. The fracture was confirmed by means of Cone Beam Computed Tomography (Figures and ). The patient did not agree with the treatment plan of this professional, which involved immediate extraction of maxillary left central incisor with implant placement, and she sought another professional opinion. At this time, our team evaluated the patient, and the prognosis at this stage was good for compensatory treatment (interincisor angle closure) and questionable for the maxillary left central incisor, requiring mechanical extrusion to expose the fracture line and reassessment to maintain the root or removal for implant placement. It is important to emphasize that the patient is a dentist, and she wanted to participate in the elaboration of treatment plan. She did not agree to have the tooth extracted—despite of the tooth presenting periapical lesions—without an attempt to keep the tooth and to undergo endodontic surgery at a later time for lesion removal. Thus, the conservative treatment plan included orthodontic treatment, including forced orthodontic extrusion of the maxillary left central incisor until exposure of the fracture line to allow for the fabrication of a crown.
At this time, endodontic retreatment was performed, with installation of an intracanal pin (Figures and ). The purpose of the pin was only to strengthen the tooth to allow for orthodontic extrusion and consequently to gain bone. Subsequently, forced orthodontic extrusion of the central incisor was undertaken (Figures and ) to restore the physiological periodontal attachment, according to de H. Salama and M. Salama []. The maxillary and mandibular arch were leveled using a stainless steel .018” arch wire, combined with bending for the extrusion of tooth 21, and each return was pronounced to achieve tooth extrusion.
Concomitant to the tooth traction, Class II asymmetric mechanics were performed with elastics for the correction of the sagittal relationship, corroborating interincisor angle closure and lower midline and overbite correction. The orthodontic extrusion was completed after 8 months, and the maxillary left central incisor was repositioned and fixed with an orthodontic appliance in the cervix, with the intention of stabilizing the carried motion. At this stage, with the goal of orthodontic treatment achieving an end, orthodontic documentation was requested, and the lower braces were removed (Figures
).
Computed tomography (CT) was obtained to reevaluate the response of tooth 21 after orthodontic extrusion, and a perforation in the root was observed, likely a consequence of successive attempts at endodontic retreatment (). At this time, the team decided on implant placement with bone grafting, connective tissue grafting, and prosthesis.
The implant procedure was planned considering the bone gain obtained with mechanical extrusion and the level of exposure during smiling. The surgical procedure was initiated by incision of the buccal and lingual soft tissues around the tooth to be extracted, as well as on the contralateral aspect of each adjacent tooth (). Full-thickness flaps were elevated, and a minimally invasive surgery was performed to preserve the alveolar bone, using a periotome (Hu-Friedy, Chicago, IL, USA), associated with curettage of the periapical lesion. The treatment succeeded with implant placement (). shows the implant position (). After implant placement, an exact universal abutment (Morse Taper) was installed (Neodent, Curitiba, PR, Brazil). The provisional abutment was realigned and was adapted on the sleeve prior to cementing, and the gap between the bone and the implant labial plate was filled with Bio-Oss (Geistlich, Wolhusen, Switzerland) (). A subepithelial connective tissue graft () was inserted to improve the periodontal tissue biotype [], thus increasing the range of keratinized gingiva, favoring the red aesthetics, and avoiding recession. After implant installation, a provisional crown was performed in infraocclusion (Figures
).
Four months later, the provisional crown was removed to evaluate the gingival tissue (Figures and ). The gingival color, texture, and contour appeared similar to the adjacent soft tissues of the teeth (Figures and ). The definitive prosthesis was created eight months after the implant surgery, with implant and peri-implant tissue impressions obtained to create a custom abutment in zirconia with a CAD/CAM system (Figures and ). This case has been followed up, and the clinical and radiographic examinations have shown excellent aesthetic results (Figures
) and satisfaction of the patient. Clinical success was achieved in this case with multidisciplinary treatment after 1-year follow-up (Figures
).


A 32-year-old male, known case of neurofibromatosis type 2, presented with insidiously increasing painless swelling over left side of the neck over one year. On examination, a soft, spherical, nonpulsatile, nontransilluminant, and nontender swelling free from overlying skin and underlying structures was found in left anterior triangle of the neck. Computed tomography (CT) scan revealed well-defined isodense, nonenhancing mass in the left lateral aspect of the neck, medially abutting the left lateral wall of trachea and the oesophagus, laterally abutting the carotid sheath, and posteriorly abutting the vertebral body. However, no vertebral bony defect was noted in the spine (Figures and ). For further characterisation of the lesion, magnetic resonance scan (MRI) of neck was done which showed the lesion to be hyperintense on T1, T2, and fat saturation sequences, suggesting a lesion with predominant proteinaceous or hemorrhagic component (Figures –). On T2 weighted axial image, the lesion had a small beak-like extension (arrow in ) towards the esophagus pointing to the radiaological diagnosis of esophageal duplication cyst. During surgery, the cyst was found to be free from all structures including esophagus and it contained mucoid viscous secretion. Total excision was done. His postoperative course was uneventful. Histopathological examination revealed the cyst wall to be lined by pseudostratified ciliated columnar epithelium with underlying smooth muscle bundle fibres arranged in two layers and lymphocytes in perivascular distribution. (Figures
). These findings are consistent with enterogenous cyst. At follow-up of 1 year, the patient has no recurrence.


A 45-year-old African American male with a past medical history of hypertension, HCV infection, and polysubstance abuse was admitted with epigastric and right upper quadrant abdominal pain, pruritus, and itching for two days. Symptoms are associated with nonbilious vomiting, fatigue, and a 9 kg unintentional weight loss over three months. He denied any history of Hepatitis B in the past. Ten months before, he had a similar complaint where evaluation at an outside facility showed a hepatic mass. A liver biopsy at that time showed acute inflammation suggestive of an abscess with extensive chronic inflammation and fibrosis adjacent to the necrosis, moderate to severe acute and chronic periportal inflammation with portal lymphoid aggregates. Cultures from the biopsy were negative for any organisms but the patient was treated with an empiric course of vancomycin and piperacillin/tazobactam for four weeks. His social history was significant for cigarette smoking, alcohol, and intravenous illicit drug use of heroin and cocaine. The family history was significant for a brother with gastric lymphoma, now in remission. Physical exam was significant for skin excoriations, scleral icterus without any lymphadenopathy, hepatomegaly, and tenderness along the epigastrium and right upper quadrant areas.
Initial laboratory values showed a hemoglobin of 13.0 gm/dL, hematocrit of 37.7%, white blood cell count of 4.4 × 103, and platelet count of 240 × 103. His metabolic panel showed normal renal function tests with a calcium of 9.4 mg/dL. His comprehensive metabolic panel revealed a total bilirubin of 6.1 mg/dL, direct bilirubin of 4.1 mg/dL, aspartate aminotransferase (AST) of 150 U/L, alanine aminotransferase (ALT) of 142 U/L, alkaline phosphatase (ALP) of 282 IU/L, gamma-glutamyl transferase (GGT) of 385 IU/L, total protein of 7.4 g/dL, and albumin of 3.6 g/dL. His prothrombin time was 13.7 seconds with an International Normal Ratio (INR) of 1.04. Amylase and lipase levels were within normal limits. Hepatitis B panel showed immunity to Hepatitis B. His HCV RNA viral load was 422131 IU/mL (5.63 log). HCV genotype is 1b. HIV by ELISA was negative. His alpha-fetoprotein levels (AFP) were 2.2 ng/mL. Blood cultures were negative. Triphasic computed tomography (CT) of the abdomen and pelvis with contrast showed multiple masses in the liver (largest being 8.8 cm) without any cholelithiasis or extrahepatic bile duct dilatation (). There was no significant enhancement of the hepatic lesions on arterial phase, while on portal venous phase the lesions showed slight enhancement. The spleen, pancreas, gallbladder, kidneys, and adrenals appeared within normal limits. Over his hospital course, his bilirubin levels increased to 23.3 mg/dL on eleventh day along with aspartate transaminase (AST) of 277 U/L, alanine aminotransferase (ALT) of 197 U/L, and alkaline phosphatase (ALP) of 199 IU/L (). In spite of high bilirubin levels, the patient maintained normal coagulation parameters and showed no evidence of hepatic encephalopathy. CT chest with contrast was within normal limits. Meanwhile, both upper endoscopy and colonoscopy were negative for occult malignancy. The biopsy of the liver mass done under fluoroscopic guidance was consistent with diffuse large B cell lymphoma (DLBCL). By immunohistochemistry, the cells were positive for CD 20, CD 10, and BCL-6. The Ki-67 proliferative index was 100% (). FISH for c-myc rearrangement was negative. Bone marrow biopsy was negative for lymphoma.
With stage IVB DLBCL and elevated bilirubin levels, there was a concern for giving full dose chemotherapy, since the liver metabolizes most of the chemotherapy agents. A decision was made to do local irradiation to the liver and reevaluate his bilirubin level to determine if chemotherapy could be administered. The patient's liver received a total dose of 6 Gy in 4 fractions of 1.5 Gy each using a 2-field 3D conformal technique with 10 MV photon beam therapy on days 1, 2, 9, and 12. Initial staging positron emission tomography- (PET-) CT showed decreased metabolic activity compared with normal adjacent liver parenchyma, suggesting a positive response to treatment and no extranodal disease. Meanwhile, total bilirubin levels fell to 3.4 mg/dL () and allowed the first dose of R-CHOP (rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone) chemotherapy to be administered at a 50% dose reduction. The patient subsequently received six cycles of R-CHOP. After completion, beside neutropenia, no other significant adverse effects were noted. Restaging PET-CT showed no hypermetabolic activity in the liver.


A 66-year-old Caucasian woman with type 2 diabetes presented to our emergency department with a three-week history of generalized malaise, associated poor oral intake, and some diarrhea. Her enteric symptoms were vague and unquantifiable. She was obese and had a past medical history of poorly controlled type 2 diabetes for 15 years, hypertension, asthma, and depression. Her regular medication comprised metformin 3g daily, modified-release gliclazide 60mg daily, aspirin 100mg daily, atorvastatin 40mg daily, ramipril 10mg daily, and hydrochlorothiazide 25mg daily. Our patient was brought into hospital by ambulance; her pre-hospital observations were as follows: Glasgow Coma Scale score, 15; blood sugar level, 2.8mmol/L; blood pressure, 90/40mmHg; pulse, 54 beats per minute; respiratory rate, 32 breaths per minute; and peripheral oxygen saturation, 98% on 8L oxygen via a variable oxygen delivery mask. On arrival to our emergency department, she was confused with a Glasgow Coma Scale score of 14 out of 15 (E4V4M6), with the rest of her physiological parameters similar to her pre-hospital observations.
Her initial investigations were as follows: serum sodium, 140mmol/L (normal range: 137 to 145mmol/L); serum potassium, 7.3mmol/L (normal range: 3.5 to 4.9mmol/L); serum chloride, 91mmol/L (normal range: 100 to 109mmol/L); serum bicarbonate, 1mmol/L (normal range: 22 to 32mmol/L); anion gap, 55mmol/L (normal range: 7 to 17mmol/L); serum glucose, 2.3mmol/L; urea, 30.8mmol/L (normal range: 2.7 to 8.0mmol/L); and serum creatinine, 768umol/L (normal range: 50 to 100umol/L). Results from liver function tests were normal. Her troponin level was 50ng/L (normal range: <30ng/L). Venous blood gas measurements revealed a profound metabolic acidemia: pH, 6.58; partial pressure of CO2, 38.6mmHg; HCO3, 3.6mmol/L; glucose, 2.0mmol/L; and lactate, 16.7mmol/L. Her initial resuscitation strategy included 2000mL of 0.9% sodium chloride solution, 10mL of 10% calcium gluconate, 15 units insulin (Actrapid) in 50mL 50% dextrose, and 1mL/kg of 8.4% sodium bicarbonate solution.
Minutes after these initial investigations, our patient experienced a pulseless electrical activity cardiac arrest and was managed as per advanced life support protocol. She had a total downtime of 25 minutes. During cardiopulmonary resuscitation she was intubated and ventilated. Following return of spontaneous circulation, she required an infusion of adrenaline for blood pressure support. She had an unremarkable chest radiograph, electrocardiogram, and toxicology screen.
With a presumed diagnosis of ischemic bowel based on vague abdominal features and profound lactatemia, our patient was admitted to our intensive care unit (ICU) for preoperative optimization. In our ICU, she was sedated and ventilated on an inspired oxygen concentration of 40% and on modest ventilator paramters (peak inspiratory pressure <25cmH2O). To treat her severe circulatory shock, she was fluid-resuscitated with a total of 10,000mL crystalloid from a central venous pressure of 8cmH2O to 16cmH2O. In addition, she required very high doses of noradrenaline and adrenaline. Continuous veno-venous hemodiafiltration was commenced at exchange rates of 50mL/kg/h using Hemosol B0 solution. She was empirically started on vancomycin and piperacillin and tazobactam (Tazocin) as broad-spectrum antimicrobial cover.
Our patient went to theater 26 hours post admission for an exploratory laparotomy, which revealed no significant findings. We continued her broad-spectrum antimicrobial cover despite negative microbiological cultures. Renal replacement therapy continued and our patient’s acid-base balance slowly normalized over three days. Having excluded all causes of a high anion gap lactic acidosis, including negative red blood cell transketolase activity for thiamine deficiency, we presumed our patient to have had a severe MALA ‘triggered’ by an acute kidney injury from dehydration. This was supported by a serum metformin level of 4mg/L. Her renal function slowly improved with continuous veno-venous hemodiafiltration and she slowly recovered with a total of 35 days stay in ICU.


A 17-year-old male was referred for urologic evaluation of a right paratesticular mass noted on routine physical examination by his pediatrician. The patient had a history of congenital adrenal hyperplasia, treated with dexamethasone. He had not noticed any scrotal masses and denied any scrotal pain, swelling, or discomfort. The patient denied any history of dysuria, hematuria, urinary tract infection, or sexually transmitted diseases. No history of trauma, fevers, or any other constitutional symptoms was elicited.
Physical examination revealed Tanner stage 5 genitalia with a circumcised phallus and normal urethral meatus. Both testes were descended and were symmetric and nontender, with no intratesticular masses. A nontender, firm 0.8 cm mobile mass was palpated superior to the right testicle and was noted to be completely separate from the testis. Scrotal examination was otherwise normal. The patient had no inguinal lymphadenopathy bilaterally, and his abdominal examination was normal.
Scrotal sonography confirmed a 0.7 × 0.8 × 0.6 cm hypoechoic, vascular, slightly heterogeneous lesion superior to the right testicle (). The testes and epididymides were normal bilaterally. Quantitative serum beta-human chorionic gonadotropin, alpha-fetoprotein, and lactate dehydrogenase were within normal limits.
Despite a low suspicion for malignancy, surgical exploration was performed through a right inguinal approach with proximal control of the spermatic cord. The lesion was identified superior to the right epididymis and was noted to be mobile and completely separate from the epididymis, vas deferens, and testis (). A moderate amount of fat surrounded the lesion. The mass was removed intact along with a rim of fat circumferentially. Frozen section analysis revealed an encapsulated lesion with a predominance of spindle cell proliferation and lymphocytic aggregates, with no malignant features. Given the absence of indication for immediate radical orchiectomy, the spermatic cord was unclamped, and the testis was replaced into the scrotum.
Final gross pathologic analysis revealed a white, smooth nodule measuring 1.3 × 0.6 × 0.3 cm (). Microscopically, the mass demonstrated benign fibrous proliferation with lymphoplasmacytic infiltrate, consistent with IMT. No cytologic atypia, mitotic activity, or necrosis was present (). The mass was noted to be completely excised. Immunohistochemistry revealed negative staining for myogenin, cytokeratin MNF116, calretinin, mast cell tryptase, and anaplastic lymphoma kinase (ALK). Immunohistochemical stains for IgG and IgG4 showed only scattered IgG4-positive plasma cells. Staining for kappa and lambda light chains confirmed the absence of monoclonality in the plasma cells.
The patient recovered uneventfully. Physical examination three months postoperatively revealed a well-healed incision and no evidence of recurrence.


A 56-year-old man presented to our hospital complaining of osphyalgia, dorsalgia, and melosalgia for 2 months, and bloodstained sputum for 2 weeks. He had been a drinker and smoker for more than 30 years, but denied personal or family history of cancer. Physical examination on admission disclosed vertebral tenderness. Routine blood examination revealed slightly decreased hemoglobin (HGB, 10.5 g/dL) and platelets (PLT, 87,000/mm3). On chest computed tomography (CT), we observed two lobulated masses measuring 30 to 40 mm in diameter in the left inferior lobar bronchus (Figure A) and peripheral tissue of the lower lobe of the left lung (Figure B), respectively. We also observed left hilar lymph nodes enlargement. Magnetic resonance imaging confirmed multiple sites of bone destruction of the lumbar spine, and bone scans revealed systemic multiple abnormal hypermetabolic lesions (Figure ). Based on the clinical and auxiliary examination findings, the presumptive diagnosis was lung cancer with multiple bone metastases.
On his third day in hospital, the patient underwent CT-guided percutaneous puncture biopsy of the lung and received palliative radiotherapy for the areas with severe bone destruction. The pathological findings of the lung biopsy were poorly differentiated mucoepidermoid carcinoma (Figure A). Ki-67 expression was about 70%. Immunohistochemical examination revealed tumor cells were positive for cytokeratin (CK) 7, CK5/6, and thyroid transcription factor-1 (TTF-1) (Figure B-D), which allowed us to determine that his condition was primary lung cancer. On the sixth day of admission, he presented with mild hemoptysis; routine blood examination revealed clearly decreased HGB and PLT, which were 6.2 g/dL and 56,000/mm3, respectively. As we suspected bone marrow infiltration by the cancer cells, we stopped radiotherapy and suggested that he undergo bone marrow aspiration and biopsy. However, he continued to deteriorate. Eight days later, we repeated the laboratory tests; Table lists the results. We did not find skin petechiae or ecchymosis, or other evidence of bleeding. To carry out further examinations and prevent the risk of severe bleeding, we started supportive treatment comprising drug hemostasis and transfusion of platelet, fresh frozen plasma, and red blood cell suspension. However, the patient presented with upper gastrointestinal bleeding without any obvious cause the following day, which we suspected was stress ulceration bleeding. Thus, we administered gastrointestinal decompression and gastric acid inhibition.
Eleven days later, his PLT count rose to 63,000/mm3. Bone marrow aspiration and biopsy revealed malignant cells and necrosis (Figure A-D). We informed the patient of the diagnosis of bone marrow metastasis with bronchial mucoepidermoid carcinoma. Unfortunately, on the day he was scheduled to receive systemic chemotherapy, the patient presented with severe respiratory tract hemorrhage. Following rapid deterioration from the disease, he died on the 16th day of admission.


A 68-year-old male patient presented to The First Affiliated Hospital of Zhejiang University School of Medicine with a previous history of hypertension and diabetes. A 2.5×2.5-cm space-occupying lesion in the center of the lower pole of the right kidney parenchyma was identified during the physical examination (). The results of the preoperative CT angiography indicated that the bilateral renal arteries had only one main trunk and no abnormal feeding arteries of the lesion. The results of the preoperative laboratory tests (liver function, kidney function, routine blood test and clotting time) were all within normal ranges. Laparoscopic surgery was performed as previously described. The warm ischemia time of the right kidney was 28 min and postoperative recovery of the patient was good. The pathological examination was performed to confirm renal cell carcinoma (clear cell type) and the negative margins.
On day 23 following surgery, the patient complained of gross total hematuria. The enhanced CT scan found a 6-cm hematoma on the edge of the right kidney and a 2.2-cm cystic shadow bound to the surgical area of the right kidney with enhancement. These results suggested the formation of a RAP (). On day 25 following surgery, the selective embolization of the right renal artery branches failed. Thus, on day 29, the embolization was performed again and was successful. The hematuria was controlled and the results of the CT scan performed two weeks following the embolization indicated that the RAP had contracted ().


A 47-year-old male patient presented to The First Affiliated Hospital of Zhejiang University School of Medicine with a previous history of diabetes. A 2.5×3-cm space-occupying lesion in the center of the upper pole of the left kidney parenchyma was identified during a physical examination (). The results of the preoperative CT angiography indicated that the bilateral renal arteries had only one main trunk and no abnormal feeding arteries of the lesion. The results of the preoperative laboratory tests (liver function, kidney function, routine blood test and clotting time) were all within normal ranges. Laparoscopic surgery was performed as previously described. The warm ischemia time of the left kidney was 31 min and postoperative recovery of the patient was good. The pathological examination was performed to confirm the angiomyolipoma.
On day 31 following surgery, the patient complained of gross total hematuria and left lumbago, and received symptomatic hemostasis at Xinchang Renmin Hospital (Xinchang, China), but the symptoms were not controlled. On day 36 following surgery, the patient was admitted to The First Affiliated Hospital of Zhejiang University School of Medicine. A contrast-enhanced CT scan revealed a ~3-cm cystic shadow bound to the center of the upper pole of the left kidney, with enhancement similar to that of the surrounding renal arteries, which suggested the formation of a RAP (). On day 37 following surgery, the patient underwent selective embolization of the left renal artery branches. This procedure was successful and the patient’s hematuria was controlled. The results of the CT scan performed one week following the embolization indicated that the RAP had contracted ().


In August 2012, a 32-year-old male was admitted to the Department of Hematology (Beijing Chaoyang Hospital, Beijing, China) with asthenia, nausea, vomiting, spontaneous ecchymosis, a cough and a fever. The patient’s hemoglobin level was 7.2 g/dl, platelet count was 13×109/liter and white blood cell count was 2.44×109/liter. Bone marrow smears were hypercellular containing 61.5% myeloblasts, 7% promonocytes and 2.5% monoblasts. In addition, the blasts in the bone marrow were positive for peroxidase staining. Immunophenotypic analysis revealed that the blasts were positive for cluster of differentiation (CD)117, CD33 and CD64, weakly positive for CD15, human leukocyte antigen-DR, myeloperoxidase and CD13, and negative for CD22, CD56, cCD3, CD11b, CD14, CD19, CD34 and CD7. The patient had been well prior to the development of these symptoms, had no history of exposure to organic solvents or dye, and had never received irradiation or anticancer agents.
The diagnosis was determined as AML with maturation (French-American-British classification of M2). The patient commenced a standard 7+3 schedule with cytarabine and daunorubicin as an induction therapy. Following the achievement of complete remission (CR), the patient underwent consolidation chemotherapy followed by a medium dose of cytarabine. The patient relapsed following three cycles of medium-dose cytarabine and subsequently received salvage therapy, however, the patient succumbed to a cerebral hemorrhage in March 2013.
A bone marrow sample was processed following short-term culture (24 h) according to the standard procedures. The chromosomes were stained by G-banding and the karyotype was determined according to recommendations from the International System for Human Cytogenetic Nomenclature (2009) ().
Fluorescent in situ hybridization (FISH) was performed on 200 interphase cells using the Vysis LSI MLL dual color break apart translocation probes (Abbott Molecular, Inc., Des Plaines, IL, USA).
RNA was extracted from the patient’s peripheral blood cells using the Whole Blood RNA isolation kit (BioChain Institute, Inc., Newark, CA, USA). In total, 1–2 μg of RNA was reverse transcribed to cDNA using the Thermo Scientific Maxima First-Strand cDNA synthesis kit (Thermo Fisher Scientific, Waltham, MA, USA). cDNA solution (2 μl) was amplified by polymerase chain reaction (PCR) to a total volume of 20 μl with 0.5 μM of each primer and 10 μl master mix. The primers used for the first reverse transcription (RT)-PCR were as follows: Sense, TACAGGACCGCCAAGAA for MLL-5S; and antisense, TTGGGCAGCTTCACGAAGTC for SEPT-5A. The nucleotide sequences of the PCR products were determined by a BigDye Terminator v3.1 cycle sequencing kit (Invitrogen Life Technologies, Paisley, UK).
The karyotype of the bone marrow cells from the patient was identified as 46,XY,t(11;22)(q23;q11.2)[13]/46,X, −Y,+10,t(11;22)(q23;q11.2)[7]/47,XY,+10,t(11;22)(q23;q11.2)[1]/46,XY[1] in the 22 cells that were examined (). FISH analysis using an MLL-specific probe showed a split in the MLL gene (). This result indicated that the gene was involved in this translocation.
To demonstrate an MLL-septin 5 (SEPT5) fusion transcript in the current t(11;22)-AML patient, RT-PCR analysis was performed using the MLL-5S primer and an antisense primer, SEPT-5A (). Nucleotide sequencing analysis of the PCR product demonstrated the fusion between MLL exon 9 and SEPT5 exon 3, and the product was 521 bp in length ().


The current study presents the case of a 41-year-old female who underwent modified radical mastectomy due to left breast infiltrating ductal cancer (pathological stage, IIA; pT1aN1M0) on May 30, 2010 at the General Hospital of Shenyang Military Region (Shenyang, China). The patient was negative for estrogen and progesterone receptors. In addition, the human epidermal growth factor 2 (HER-2) immunohistochemical analysis showed ++/+++ staining and fluorescence in situ hybridization (FISH) indicated HER-2 gene amplification. Following the surgery, six cycles of adjuvant chemotherapy (docetaxel plus epirubicin regimen) in combination with sequential adjuvant radiotherapy were conducted. In May 2011, the patient felt pain at multiple sites on the body and subsequent positron emission tomography/computed tomography (CT) examination indicated the following: Left cervical, left supraclavicular, mediastinal, retroperitoneal and pelvic lymph node metastases; superior lobe metastasis of the left lung; peritoneal metastasis; multiple osseous metastases; and tumors in the right appendix region. The patient had an Eastern Cooperative Oncology Group (ECOG) performance status score of 3 and numeric rating scale (NRS) pain score of 8. The results of the routine blood test showed that the lowest peripheral blood cell counts were 1.6×109 cells/l for white blood cells (WBCs), 54 g/l for hemoglobin (Hb) and 26×109 cells/l for platelets (PLTs). In addition, a bone marrow smear test revealed the presence of metastatic cancer cells (). Trastuzumab monotherapy was subsequently initiated on June 1, 2011, at a loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg every three weeks. During the night following administration of the initial dose of trastuzumab, the patient experienced fever (body temperature of 39.0°C) and more severe pain, which were alleviated by symptomatic treatment. Following trastuzumab treatment, the patient’s PLT count markedly increased (), while the WBC count and Hb concentration increased gradually. Furthermore, following four doses of trastuzumab treatment, the patient’s performance status score (ECOG) decreased to 1 and pain score (NRS) decreased to 2. On August 17, 2011, taxol chemotherapy was initiated at a dose of 75 mg/m2 on days two and nine, and was administered on the basis of trastuzumab. In total, seven cycles, each lasting 21 days, were completed. No cancer cells were identified in the subsequent bone marrow smear test (). CT demonstrated metastatic foci in the left lung, however, the enlarged lymph nodes had subsided, and the tumor in the right appendix region had decreased in size by 50%. In April 2012, the trastuzumab treatment was withdrawn due to brain metastasis and in May 2012, the patient succumbed to disease progression.


A 66-year-old woman was referred to the Sichuan Cancer Hospital and Institute (Chengdu, China) presenting with a soft palatal mass that was discovered following oral examination for sudden pharyngeal discomfort 20 days previously. Physical examination was unremarkable, with the exception of the mass, and the laboratory results showed no obvious abnormalities.
A plain CT scan confirmed a well-circumscribed, round soft tissue mass measuring ~2 cm in diameter at the soft palate. The tumor showed marked and homogeneous enhancement following intravenous injection of contrast material, no evidence of bone invasion and enlarged cervical nodes were found (). A benign lesion of pleomorphic adenoma was suspected and the tumor was excised with considerable local resection. The surgical specimen was oval shaped and encapsulated by relatively dense fibrous tissue; microscopic examination revealed a storiform or fascicular pattern () that was consistent with the diagnosis of an SFT. The patient was well and free of disease 20 months after surgery.


A 27-year-old woman presented with an asymptomatic submucosal mass involving the right soft palate. A soft tissue nodule measuring ~1.5 cm in diameter was detected in the right side of the soft palate on a plain CT scan. The lesion showed marked and homogeneous enhancement following intravenous injection of contrast material, and no evidence of bone invasion and enlarged cervical nodes was found (). The patient underwent wide local excision. Microscopic examination () revealed hypercellular, haphazard spindle cell proliferation with a small amount of nuclear atypia, abundant capillary vessels and invasion of mucinous gland. Immunohistochemically, the specimen was diffuse and showed intense positive staining for cluster of differentiation (CD)34 () and vimentin (), partial positive staining for B-cell lymphoma 2 (Bcl-2), CD99, epithelial membrane antigen (EMA) and smooth muscle actin (SMA), weak positive staining for S-100, but negative for desmin. The patient was diagnosed with an SFT with malignant characteristics. The patient was free of disease 16 months after surgery.


A 9-year-old boy was treated and followed since being diagnosed at the age of 4 years. He had a significant impairment in social skills, including reduced eye contact, lack of imaginative play, and absence of joint attention. He also had autistic regression. He had apparently normal language development when he aged 1 year; however, he lost acquired language abilities at the age of 2.5 years. He had a heavy acoustic hypersensitivity from childhood. He let out a strange noise and would panic, particularly on rainy days. He was diagnosed with autistic disorder according to the criteria in the DSM-IV-TR []. Background and clinical data are given in . At the age of 7 years, he had interfering behaviors consisting of hyperactivity, restless activities, and significant insomnia, including a delay in sleep onset of 2-3 h. Risperidone (0.5 mg/day) was started for sedating hyperactivity and restless activities. It was effective for approximately 1 year; however, restless activities and insomnia gradually relapsed. In addition, self-injury, such as knocking his head, appeared. Sodium valproate (200 mg/day) was added; however, he continued to exhibit self-injury. He could not keep regular sleep hours nor maintain a regular sleep-wake rhythm. As a result, he was not able to attend school. Ramelteon (2 mg/day) was started orally at 9:00 pm to advance the sleep phase, and other drugs were discontinued. Four weeks after starting ramelteon, he began to sleep before 11:00 pm and was able to maintain sleep throughout the night (). Adverse effects were not observed. He could wake up in a better mood in the morning than before. As he acquired the ability to maintain a regular sleep-wake rhythm, he was able to go outside and start attending school (). His acoustic hypersensitivity became mildly improved and the frequency of panic attacks had been reduced two to three times weekly.


An 11-year-old-boy was diagnosed with pervasive developmental disorders in another hospital at the age of 3 years. He was absent from most morning classes because he slept late at night and was unable to wake up until noon. His full intelligence quotient was 51, measured with the Wechsler Intelligence Scale for Children, Fourth Edition. He was diagnosed with autistic disorder and mental retardation according to criteria in the DSM-IV-TR. He was also observed to be hyperactive and impulsive. To treat the sleep-wake disturbance, ramelteon (2 mg/day) was administered at 10:00 pm. After 1 week, his sleep-wake phase had advanced and he was able to sleep from 12:00 pm to 9:00 am. He became able to keep regular sleep-wake rhythm both on weekdays and got up more comfortably. He started to go to school in the midmorning. In addition the symptom of hyperactivity at school and home was reduced. This beneficial effect of ramelteon has been maintained for over 50 weeks. No adverse effects, such as residual daytime sleepiness, were present during treatment with ramelteon.


A 12-year-old-girl was followed since the age of 6 years. At the initial visit, she exhibited a delay in language development, hyperactivity, stereotyped movements, and perseverative behavior. She had autistic regression. She had apparently normal language development until she was aged 1 year but lost acquired language abilities at the age of 1.5 years. Her developmental quotient was 30. She was diagnosed with autistic disorder according to criteria in the DSM-IV-TR. When she was 9 years old, she suffered from an irregular sleep-wake pattern and midnight awakening with beating and kicking her mother. For sedation, risperidone (0.5 mg/day) was administered. Although her agitated mood improved, difficulty in initiating and maintaining sleep remained. Flunitrazepam (2 mg/day) and brotizolam (0.25 mg/day) were administered. However, her sleep disturbance did not improve. She suffered from partial convulsive seizures at the ages of 5, 10, and 13 years. Carbamazepine (100 mg/day) and lamotrigine (50 mg/day) were administered at the age of 12 years. She began to wake up at midnight, associated with repeated overeating, which caused a rapid weight gain. As sleep duration shortened to 6 h, from 10:00 pm to 4:00 am, ramelteon (4 mg/day) was administered orally at 9:00 pm. After 2 weeks, the dose was titrated to 8 mg/day. One week later, she was able to sleep from 10:00 pm to 6:00 am (). The intermittent awakenings were reduced, and overeating at midnight disappeared although overeating before going to bed still continued. Ramelteon was effective for bedtime resistance for more than 1 year, and risperidone was discontinued.


A 71-year-old female with a 2-year history of esophageal squamous cell carcinoma was referred to the Cancer Center of Daping Hospital (Chongqing, China). The patient had severe grade III dyspnea for 6 days and required a semi-liquid diet for 2 years. The performance status (PS) upon admission was 4 points according to the Eastern Cooperative Oncology Group scale. The medical history of the patient included COPD, diagnosed in 1999, and diabetes, diagnosed in 2008, with no history of smoking or drinking. The patient had undergone surgery 2 years prior, followed by four cycles of cisplatin plus 5-fluorouracil as a post-operative adjuvant therapy. At the time of the initial surgery, the cancer was classified as T2N0M0 stage. A computed tomography (CT) of the chest () prior to admission revealed the presence of a paratracheal lymph node metastasis, measuring 4.5×3.5×2.5 cm, that was squeezing the trachea and esophagus. No other metastasis in the abdominal organs or lymph nodes were detected by CT.
Upon referral, the airway of the patient was so narrow that endotracheal intubation was unsuccessful and, consequently, the patient was unsuitable for tracheotomy due to the location of the stenosis. For similar reasons, the patient was also unsuitable for surgical resection. In addition, dyspnea is a contraindication for radiotherapy, as radiation edema may aggravate the condition. As the life of the patient was in danger, methylprednisolone acetate was administered at 80 mg per day for temporary relief of the dyspnea, and this was followed by initial treatment with chemotherapy combined with endostar. As the PS of the patient was 4, the chemotherapy regimen, which included intravenous (IV) administration of docetaxel (40 mg/m2; days 1 and 8), 5-fluorouracil (400 mg/m2; days 1–5 and 8–12), nedaplatin (40 mg/m2; days 1 and 8) and endostar (3 mg; days 1–14), was divided into 2 weeks. The dyspnea of the patient was downgraded to grade II after 1 week, and the methylprednisolone acetate dose was reduced to 40 mg per day. One month following chemotherapy, the dyspnea of the patient was alleviated. The dyspnea was downgraded to grade I and a CT scan showed that the lesions were 3.0×2.5×1.5 cm (). Objective efficacy evaluation indicated partial remission.
The patient was then administered SBRT treatment combined with methylprednisolone acetate at 40 mg per day until the end of radiotherapy. The stereotactic γ-ray whole-body therapeutic system (body γ-knife radiosurgery) with 30 rotary conical-surface Co (60) sources was focused on the target volume. Low-speed CT simulation was conducted, followed by three-dimensional conformal radiotherapy (3D-CRT) planning. A total dose of 33 Gy was delivered at 3.3 Gy/fraction to the 60% isodose line covering the planning target volume. The biological equivalent dose (BED) was 43.89 Gy. The radiotherapy course was delivered in 2 weeks. During the radiotherapy, the patient experienced grade II esophagitis. One month following radiotherapy, the patient showed rapid improvement in dyspnea and dysphagia, and CT revealed that the paratracheal lymph node lesions had disappeared (). Objective efficacy evaluation indicated almost complete remission.
The patient then received another three cycles (separated by a 3-week interval) of IV systemic chemotherapy combined with endostar (docetaxel: 75 mg/m2, day 1; 5-fluorouracil: 800 mg/m2, days 1–5; nedaplatin: 75 mg/m2, day 1; and endostar: 3 mg; days 1–14). Four months following radiotherapy, CT imaging revealed that the cancer was in complete remission (). The patient was virtually asymptomatic following this treatment, and was able to breathe, eat normally and gain weight. Significantly, radiation-induced esophageal perforation and stenosis was not observed. The patient continued to exhibit no symptoms of dyspnea and dysphagia and has had no evidence of metastatic disease, with a progression-free survival of >8 months at the time of writing.


A 59-year-old female patient presented with complaints of recurrent palpitations over the past three years. Paroxysmal supraventricular tachycardia (SVT) was diagnosed on several emergency department visits. A 12-lead surface electrogram and physical examination were normal. The SVT had a narrow QRS-complex during the attacks (230 bpm). After informed consent was obtained, the patient received an electrophysiologic study (EPS) and catheter ablation. Multipolar electrode catheters (Biosense Webster, USA) were positioned in the His-bundle region, right ventricular apex, and coronary sinus (CS). Prior to EPS, blood pressure was 121/67 mm Hg and pulse was 72 bpm. Programmed atrial stimulation indicated that sinus and atrioventricular (AV) nodal functions were normal. CS1,2 proceeded during ventricular extrastimulus testing and a basic drive (S1S1) cycle length of 400 ms of ventricular pacing induced AV re-entrant tachycardia (AVRT). The ventriculoatrial (VA) conduction during ventricular pacing was consistent with inducible AVRT. A concealed left free wall accessory pathway was confirmed and selected for mapping and ablation via a transaortic approach. The target site was obtained above the mitral annulus during AVRT and RF energy was delivered (60°C; 30 W) using a temperature-controlled catheter (Biosense Webster). Tachycardia terminated after a 2-sec ablation and ablation was continued for 25 sec more. At 22 sec after the onset of energy delivery, sudden cardiac asystole lasted for 13.2 sec followed by profound sinus rate slowing though ablation was aborted 2 sec after asystole emerged (Figure ). No escape rhythm emerged. Moreover, AV interval was not changed before and after asystole. After sinus rhythm was rescued, blood pressure was 165/97 mm Hg and ventricular pacing indicated VA disassociation. Multiple ventricular pacing and programmed electrical stimuli for a subsequent 30 min revealed VA disassociation and no induction of tachycardia. Sinus node function AV conduction was normal. The patient no longer experienced tachycardia and syncope 9 months post-ablation.
Here, we describe a rare complication during RF ablation above the mitral annulus during a retrograde aortic approach to ablate a left free wall accessory pathway, characterized by prolonged asystole which resolved on its own. Prolonged asystole has been reported to occur not only occurred during SVT ablation [-], but atrial fibrillation ablation [-].
Based on prior case reports and this case, prolonged asystole induced by ablation can be described as depicted in Table . These have occurred in individuals with no apparent structural heart disease. Prolonged asystole can occur during slow pathway ablation, at the pulmonary vein, the intra-coronary sinus and around the mitral annulus. Asystole is prone to be reproducible under ablation procedures and Table depicts the duration of each asystolic event (mean = 9.6 ± 3.9 sec) as well as other symptoms patients experienced seemed to resolve on its own and not affect success of ablation. Asystole that does not influence the ablation procedure but may require pacing or atropine. Among the current 10 cases, only one patient failed because the patient requested to complete the process due to anxiety after the second asystole [].
Cardiac asystole has been observed during ablation of various arrhythmias and some intra-cardiac procedures and no clear mechanistic explanation for these events is available. A Bezold–Jarisch-like reflex was a putative mechanism because this is thought to be a cardiovascular decompressor reflex originating in sensory receptors with vagal efferent discharge to the heart []. RF current delivery may acutely stimulate the unmyelinated vagal C-fibers which are predominantly distributed within the right atrium lateral wall, the left atrium roof, around the four pulmonary veins, and in the posterior left ventricle. These fibers reflexively increase parasympathetic tone, decrease sympathetic activity, mediate bradycardia-hypotension, and then cause prolonged asystole.
However, bradycardia only lasts 1 to 2 sec after cessation of direct efferent vagal fiber stimulation [] which is unlike prolonged asystole which persisted for up to 3 sec after cessation of RF current in the series case. Another potential mechanism is the ganglionated plexus (GP) response. GPs embed within epicardial fat pads and the ligament of Marshall, receiving input from the extrinsic cardiac nervous system. This response includes afferent neurons, post-ganglionic efferent parasympathetic and sympathetic neurons, and numerous interconnecting neurons that provide communication within and between the GPs []. Capulzini and co-workers reported that targeting the area corresponding to the left superior GP provoked induction of atrial fibrillation and a 12.5-sec asystole []. Mathuria and his colleagues speculated that attempted slow-pathway ablation might stimulate nearby GPs and induce cardiac asystole []. Whether the GP response is a plausible mechanism that causes reflexive cardio-inhibition is uncertain, evidences suggest that prolonged asystole can be induced by direct GP stimulation. First, targeted GP high-frequency stimulation (HFS) produced a notable vagal response including prolonged asystole. GP ablation has been found to be effective in the treatment of AF and HFS is commonly used to verify localization and ablation of GP via evoked vagal reflexes []. HFS of GPs elicited 3.1 sec ventricular asystole via an endocardial approach [] and a 7.85 sec AV block in the left atrial epicardium prior to RF ablation in patients with AF []. Secondly, GPs are composed of sympathetic and parasympathetic nerves, the majority of which are cholinergic []. Stimulation of GPs predominantly elicited more vagal effects, as seen in targeted GP ablation. Thirdly, ablation sites are close to the GP area (Table ). Slow pathway ablation most likely corresponded with the interatrial septal GP formed by the two posterior atrial GPs that are fused and extend anteriorly into the interatrial septum. Ablation of the coronary sinus and left superior pulmonary (LSPV) occurs in areas adjacent to the posterolateral left atrial GP and the superior left atrial GP respectively. Moreover, asystole may occur more commonly in the left atrium and the interatrial septum, which has abundant GPs (60%, 3/5). Tsai et al. [] reported that 15% (6/40) of patients developed bradycardia-hypotension syndrome during energy delivery to the superior pulmonary veins for treatment of paroxysmal atrial fibrillation. The present case may be caused by stimulation of GP or its adjacent area which facilitated sudden cardiac asystole during attempted ablation in the region of left free wall accessory pathway. Moreover, pain and other factors (nausea, sedation and anxiety) may also be associated with the response. In these collected cases, 3 patients (3/10, 30%) showed chest pain. Clinically, RF induced pain was common and slight. And asystole still emerged repeatedly though the patient was familiar with the procedure and pain []. The causal mechanism is sometimes implicated in clinical situations and study should be furthered to disclose the intrinsic mechanism.


A 27-year-old African-American female presented to our hospital with a 3-day history of generalized cramping abdominal pain and nausea with vomiting. She denied any fevers, night sweats, weight changes, or urinary complaints. Her past medical history was significant for chronic paranoid schizophrenia, cocaine abuse, and HIV infection. She was not on highly active antiretroviral therapy (HAART) at the time of admission. Her vital signs included a heart rate of 120 beats/min and a blood pressure of 160/110 mmHg. Physical examination was remarkable for the presence of coarse crackles at the lung bases, periorbital and lower extremity edema, and mild abdominal distension. Laboratory studies revealed an elevated serum creatinine of 14.6 mg/dL, an elevated serum urea nitrogen of 86 mg/dL, and an elevated serum potassium of 6.9 mmol/L. Of significance, her renal function 4 months prior to this admission was normal with a creatinine of 0.8 mg/dL at that time. Urinalysis showed 2000 mg of protein per dL and urine microscopy revealed 6 red blood cells per high-power field and 22 white blood cells per high-power field but no dysmorphic red blood cells or casts. Other abnormal laboratory values on admission included a low serum albumin of 1.8 g/dL and a spot urine protein-to-creatinine ratio of 33.7 consistent with nephrotic range proteinuria. An ultrasound revealed enlarged kidneys with diffuse increased echogenicity and a computed tomography (CT) scan of the abdomen/pelvis without contrast revealed bilateral enlarged and edematous kidneys, scattered abdominal and pelvic ascites, and moderate soft tissue anasarca ().
During the course of admission, the patient became tachypneic, had worsening oxygen saturations, and had to be intubated and mechanically ventilated for respiratory distress. Hemodialysis was emergently implemented after she became anuric and her renal function continued to deteriorate.
The patient's CD4 count at the time of admission was 350 cells/ul with a HIV RNA viral load of 1,790,000 copies/mL. Given the finding of nephrotic range proteinuria accompanied by a precipitous decline in renal function, a presumptive diagnosis of HIVAN was made and a serological workup was initiated to exclude other possible underlying etiologies. Serum protein electrophoresis, urine protein electrophoresis, anti-nuclear antibody, anti-double stranded DNA (anti-dsDNA) antibody, anti-streptolysin O, hepatitis serology, serum cryoglobulins, complement levels (C3, C4), and rapid plasma reagin tests were all negative. Her HbA1C was within normal limits at 5.8%. Serum testing was negative for cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA) and perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA). However, the serum was positive for anti-glomerular basement antibody (anti-GBM Ab) with a value of 91 units (normal: 0–20 units).
Although chest CT and bronchoscopy did not reveal diffuse alveolar hemorrhage that can be seen in anti-glomerular basement membrane antibody disease, the finding of an elevated anti-GBM antibody precluded a definitive diagnosis of HIVAN based on clinical context alone. A decision was therefore made to perform a CT-guided renal biopsy at this point.
Light microscopy of the renal cortical tissue showed marked diffuse tubular degenerative and regenerative changes with interstitial fibrosis, focal microcystic tubular dilatation, and hyaline casts (Figures , , and ). Electron microscopy showed glomerular basement membrane thickening without disruption or electron dense deposits. Endothelial tubuloreticular inclusions most consistent with HIVAN were also visualized (Figures , , and ). The glomeruli showed focal segmental sclerosis with no evidence of crescentic glomerulonephritis and immunofluorescence revealed no specific immunoglobulin or complement deposits (). Based on these pathologic findings, the final diagnosis was therefore HIVAN.
The patient continued to improve clinically and biochemically while receiving hemodialysis three times a week. She was eventually weaned from the ventilator and extubated. However, due to the patient's persistent dependence on hemodialysis throughout admission, it was concluded that the patient had end-stage renal disease (ESRD) and that she would require lifelong hemodialysis. She was also started on HAART therapy prior to discharge. At a 6-month follow-up visit, the patient remained compliant with HAART therapy and dialysis dependent.


The patient is a 32-year-old G4P2012 admitted at 23 6/7 weeks of gestation for fetal tachycardia. The fetal heart rate was noted to be persistently between 180 and 190 beats per minute, which is shown in . Fetal ECHO revealed a structurally normal heart, with an isolated pericardial effusion which is demonstrated in . The patient's past medical history was significant for Graves' disease for which she underwent radioactive iodine ablation 2 years earlier. She became hypothyroid soon thereafter and has been maintained on thyroid replacement. Her current dose is 150 mcg daily. She had two prior full term vaginal deliveries without complication and one first trimester elective abortion. Her past surgical history was significant for a laparoscopic appendectomy. She denied tobacco, alcohol, or illicit drug use. On arrival to labor and delivery, the fetal tachycardia was again noted. Laboratory studies revealed a normal metabolic and thyroid profile. Stimulating thyroid antibodies were drawn but not yet available. The patient had a normal EKG. Because of the persistence of the fetal tachycardia and the pericardial effusion, the decision was made to treat the fetal tachycardia with maternally administered digoxin. Although there was suspicion that the tachycardia may be secondary to thyroid stimulating immunoglobulins (TSIs), the decision was made to start with our usual first-line drug for SVT in the absence of confirmatory results. The patient was loaded with IV digoxin and subsequently placed on an oral maintenance dose of 0.375 mg daily. She was discharged home with close follow-up.
Despite having a maternal digoxin level as high as 2.5 ng/mL, the tachycardia persisted. Over the following week, she complained of increasing nausea. A maternal EKG showed nonspecific changes. The thyroid stimulating antibodies returned significantly elevated at 195% of basal activity. The digoxin was discontinued, and Sotalol 80 mg PO bid was begun. There was no significant improvement over the following few days with the fetal heart rate between 170 and 190 bpm. The Sotalol was increased to 120 mg bid. A few days later the patient complained of decreased fetal movement. A maternal EKG showed a HR of 62. The decision was then made to begin maternal PTU 100 mg three times a day for presumed fetal hyperthyroidism secondary to the transplacental crossing of maternal thyroid stimulating immunoglobulins. Within 48 hours, the fetus had a normal sinus rhythm of 150 bpm. The Sotalol was decreased to 80 mg bid and discontinued the following visit when the FHR was noted to be 140 bpm.
The pericardial effusion resolved over the next few weeks, and the fetal heart rate remained normal for the remainder of the pregnancy. She was maintained on the same dose of PTU, and her thyroid function testing remained normal.
An induction of labor was undertaken at 37 weeks of gestation for presumed fetal hyperthyroidism, which resulted in a vaginal delivery of a live born female infant, with Apgar scores of 9 and 9 after 1 and 5 minutes. The neonate appeared well and in sinus rhythm of 164 bpm. Initial thyroid labs revealed a suppressed TSH of 0.013, a normal free T4 of 1.4 ng/dL, and an elevated free T3 of 5.1 pg/mL. Although the neonate appeared clinically stable, thyroid function tests redrawn at 2 days of age were markedly abnormal, with a TSH of 0.008, free T4 > 8, free T3 > 20, and thyroid stimulating IG 372. By days 4-5 of life she was noted to be tachycardic, jittery, and with loose stools. Methimazole was started at 0.35 mcg every 8 hours. Propranolol 0.5 mg/kg/dose three times a day while being in the hospital for a HR of 180–200, which improved to a baseline of 150 bpm. The neonate was discharged home in stable condition at 1 week of age, with close follow-up. The methimazole was gradually lowered over the following few weeks based on thyroid function testing every 7–10 days. The medication was discontinued at 6 weeks of age.


A 20-year-old female patient reported to the Department of Periodontics, Kannur Dental College, Kerala, with a chief complaint of a white patch on her gums which was present for the past 2 years. The lesion was asymptomatic and increased in size gradually during the course of the first year and has remained stable since then. The patient was otherwise healthy and was not under any medication. There was no history of alcohol consumption, smoking, and areca nut chewing habits. Neither was there a familial history of similar disease nor a history of trauma in the concerned site. The patient was concerned about the sudden change in the colour of her gingiva and reported to the hospital to find out the underlying cause.
On physical examination, the patient was moderately built and nourished and had a moderate brown skin colour (TYPE IV according to Fitzpatrick scale) []. Extra oral examination revealed no abnormal findings. There was no abnormality present anywhere else on the body.
Intraorally, in the maxillary arch, there was a diffused white patch of 1.5 cm × 1 cm involving the gingiva extending from the middle of the right central incisor (8) to the distal aspect of canine (6) posteriorly, from the attached gingiva to the mucogingival junction (). A similar diffused white patch of 1 × 0.5 cm was present on the gingiva in the left side of the maxilla extending from the distal half of the central incisor (9) to the canine region (11) but was less pronounced compared to the right side.
On inspection of gingiva in the mandible, a similar white patch of 0.5 cm × 0.5 cm was observed in the attached gingiva of the mandibular right central incisor (25). There was no other abnormality detected intraorally.