A 65 year-old Japanese man attended for the first time to Sapporo Medical University Hospital, and was admitted because of gait disturbance and amyotrophy of lower limbs. No perinatal abnormalities were observed, except that he had been enable to walk until three years old. He was clumsy in running since childhood and walking became gradually more difficult with age. He had attended to other neurological hospital in his 40s having given no reasonable diagnosis, stopped seeing doctors. He began to use a walker two years before admission. He had a history of atrial fibrillation at 43 years of age and complete atrioventricular block at 45 years, after which a pacemaker was implanted at other hospital. He had hypertension since the age of 57, and had two attacks of cerebral embolism in the last decade.
The pedigree of his family is shown in Figure . His mother (I-3), two uncles (I-6, 8) and sister (II-2) had gait disturbance, and his sister (II-2) also had a pacemaker implanted due to atrioventricular block. However, no detailed information on disease onset and progression was available in their medical records. His sister also had gait disturbance since childhood and atrioventricular block was detected in early adulthood. She had more severe muscle weakness than the patient, and was unable to get up by herself. She could not come to our hospital because of her physical condition, and rejected to get a genetic analysis. His mother and sister had hypertension and ischemic stroke. His children were in their 30’s and remained healthy with no gait disturbance and cardiac disease. Our investigation found no consanguineous marriage.
On admission, his heart rate was 60 rpm (pacemaker rhythm), and blood pressure was 119/75 mmHg while on antihypertensive drugs. Whereas transthoracic echocardiography showed diffuse cardiac hypofunction with ejection fraction 42%, no ventricular and atrial dilatations were observed. According to his medical record, his ejection fraction was 62% in his 50’s and had deteriorated gradually.
A neurological examination revealed significant muscle weakness in lower limbs with pes cavus. The extent of muscle weakness was the same in the proximal and distal parts of lower limbs (Table ). Muscle weakness in upper limbs and swallowing impairment were mild (Table ). Mild joint contracture was observed in his right knee joint. Muscle weakness was more prominent on the left side because of ischemic stroke (Table ). Fasciculation was observed in both legs. His tendon reflexes were absent. There were no abnormalities in sensory and autonomic systems. Evaluation of cognitive function showed mild cognitive impairment, with Mini-Mental State Examination score of 23/30 and Frontal Assessment Battery score of 12/18.
Examinations of blood and cerebrospinal fluid showed no remarkable abnormalities, and creatine kinase was slightly high (179 IU/L: normal value 45–160 IU/L). The patient refused a muscle biopsy. A brain computed tomography scan revealed multiple old cerebral infractions, but hippocampal atrophy was not indicated.
A motor conduction study of the tibial nerve showed low amplitude compound muscle action potential with no decrease in conduction velocity. F wave studies showed repeater F waves in median and tibial nerves, with low persistence. However, sensory nerve conduction studies of median, ulnar and sural nerves were normal. Needle electromyogram showed chronic neurogenic changes especially in the lower limbs (Table , Figure ). These results strongly suggested degeneration of lower motor neurons.
With a presumptive diagnosis of SMA type 3, we conducted gene analysis. Exon 7 and 8 deletions of SMN1 were not found. Early-onset muscular atrophy combined with cardiomyopathy made us to consider the possibility of inherited Charcot-Marie-Tooth disease (CMT) as a differential diagnosis. Some familial cases of SMA phenotypes with cardiac involvement were reported in some parts of Japan [], and, within the responsible genes of CMT, LMNA mutations were reported to cause SMA phenotype with cardiac involvement in Germany []. For those reasons we added sequence analysis of LMNA gene, and a novel nonsense mutation p.Q353X (c.1057C > T) in exon 6 of LMNA was detected (Figure a). Exon 6 encodes the rod domain of lamin A and lamin C, which results in truncated lamin A protein lacking tail domain including nuclear localization signal (NLS) site (Figure b). The genetic analysis was limited to the proband, as we could not get a permission from other family members.
The molecular mechanisms of autosomal dominant SMA are largely unknown. However, Rudnik-Schöneborn et al. [] reported adult-onset autosomal dominant proximal SMA phenotype with LMNA mutations in two families; one family with a novel nonsense mutation Q493X (c.1477C > T) and the other with missense mutation R377H (c.1130G > T) previously described in Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy 1B []. Their report indicates that LMNA mutations can mimic SMA and some patients have cardiac diseases such as atrioventricular block and DCM. The patients in the two families had onset of gait disturbance from early adulthood to maturity, with cardiac diseases diagnosed at the same time or several decades later. In one family, two of five cousins died from heart attack in their 40’s-50’s.
Our case is the second report of SMA phenotype with LMNA mutation. The patient showed muscle weakness of lower limbs since early childhood, and had cardiac diseases including atrial fibrillation, atrioventricular block and cardiac dysfunction in maturity. Amyotrophy was severe in proximal lower limbs and the trunk. This distribution of amyotrophy and findings of nerve conduction study are consistent with proximal SMA phenotype. Their clinical presentations were similar to previous cases family especially in cardiopathy, however, the gait disturbance were shown in different age. He had a novel nonsense mutation p.Q353X (c.1057C > T) in exon 6 of LMNA (Figure ). In general, nonsense mutation in coding exon results in a significant molecular functional defect even with heterogeneity. The patient’s uncle (I-4, Figure ) showed no muscular weakness, but died suddenly in his 20’s. According to a meta-analysis of carriers of LMNA mutations, sudden death was reported in 46% in both patients with cardiac diseases and those with neuromuscular diseases []. Electrocardiographic findings indicated cardiac dysrhythmias in 92% of the patients after the age of 30 years, while heart failure was reported in 64% after the age of 50 years. Furthermore, 28% of carriers of LMNA mutations were implanted a pacemaker [].
LMNA spans 12 exons and is located on chromosome 1q21-22. It encodes lamin A and lamin C via alternative splicing. These lamins belong to the family of type V intermediate filaments. The protein consists of an N-terminal head domain, a central α-helical coiled coil rod domain, and a C-terminal tail domain (Figure b) []. Lamins are expressed exclusively in the nucleus of differentiated cells, and are the major constituents of the nuclear lamina and distributed in the nucleoplasm forming a part of the skeleton-type structure. Lamins also show high affinity to DNA, chromatin and histone for regulating gene expression.
LMNA mutations have been associated with several genetic disorders with different phenotypes and hereditary modes. These disorders are called laminopathies, and they include autosomal dominant Emery-Dreifuss muscular dystrophy (EMDM), autosomal repressive EMDM, Limb-girdle muscular dystrophy 1B (LGMD1B), Dilated cardiomyopathy with conduction defects (CMD1A), and CMT type 2B1 (CMT2B1). Laminopathies involving the muscular system and the peripheral nervous system both of which have mutations mainly at the N-terminal side of the NLS (Figure b). These diseases are suspected to result from abnormalities of the nuclear laminar structure. On the other hand, abnormality in genes encoding lamin-associated proteins such as emerin also caused EMDM [], and the pathogenic mechanisms of laminopathies are not clarified. Several phenotypes of laminopathies were reported within the same family [], and the interactions with other laminar factors might make part of the differences.
Distal hereditary motor neuropathies (dHMN), also referred to as distal SMA, manifest motor-dominant axonal neuropathy. This group shares several gene mutations with CMT2 [,]. Nevertheless there is no pathological evidence to differentiate whether our case is proximal SMA or dHMN, although electrophysiological findings and the distribution of amyotrophy suggest proximal SMA phenotype.
Two missense mutations of LMNA; E33D and R298C, have been reported in CMT2B1 [,]. They are associated with abolished deep tendon reflex and amyotrophy mainly affecting lower limbs. A combined phenotype with cardiac complications such as arrhythmia and cardiomyopathy is possible []. Interestingly, some cases of CMT2B1 due to LMNA mutations show amyotrophy in proximal limbs []. In these cases, degeneration of neurons in the anterior horn of spinal cord is suspected. The mechanisms underlying neuropathy and neuronopathy of lower motor neurons may be different.


A 57-year-old male presented with a 6-month history of blisters and painful erosions on the right buccal mucosa. His medical history was relevant for hypertension and hypothyroidism. He had been taking valsartan and levothyroxine for years and denied the use of topical drugs and previous dental procedures. On physical examination, the patient was found to have few bullae, erosions, and pseudomembrane-covered erosions on the right buccal mucosa ().
No skin or other mucosal involvement was seen. He had fragmented teeth with sharp edges adjacent to the lesions. Laboratory evaluation was unremarkable. Histopathological examination of bullous lesion revealed a subepithelial blister with a mostly lymphocytic infiltrate in the upper corion ().
Direct immunofluorescence of peribullous mucosa showed a linear band of IgG, IgA, and complement component 3 (C3) at the epithelial BMZ ().
ELISA was negative for antibodies against bullous pemphigoid antigens 180 and 230 and desmogleins 1 and 3. Correlation between these features allowed the diagnosis of MMP. Application of dipropionate betamethasone cream, twice daily, was started. After one year the patient had persistent bullae and erosions on the right buccal mucosa that healed without scarring. Oral prednisolone (0.5 mg/kg/d) was started for six months, and as no response was achieved, treatment with dapsone (100 mg/d) was administered during one year. Further involvement of the right hard palate mucosa occurred, erosions were extremely painful, and the patient had difficulty in eating and depression ().
Intravenous immunoglobulin (IVIg) at a dose of 2 g/kg/cycle was started and repeated every three weeks. Complete remission was achieved after three cycles. IVIg therapy was maintained for six additional months. No recurrence was seen after three years of follow-up ().


Our patient was a 44-year-old woman who underwent proximal gastrectomy and bilateral truncal vagotomy for a gastric neuroendocrine tumor. Her immediate postoperative course was uneventful, and no surgical complications, such as anastomotic fistula, were observed. On the third postoperative day, she presented with abdominal discomfort and bloating, nausea and vomiting (Figure ). On the fourth postoperative day, the patient developed severe, watery diarrhea. Her blood pressure suddenly decreased to 60/38 mmHg for unknown reason. An examination revealed that her body temperature was 37.2°C, her pulse was increased at 126 beats/minute, her respiratory rate was 28 breaths/minute and her blood oxygen saturation was 86%. A complete blood count was obtained, and the results revealed a white blood cell count of 2.9 × 109/L with 83% neutrophils and 13% lymphocytes. Analysis of blood gas showed that the patient’s blood lactate level was 8.2 mmol/L and base excess was −9.2. Serum level of C-reactive protein (CRP) was 143.4 mg/L. Blood and urine were collected for bacterial culture, and both test results were negative. The patient was urgently transferred to the ICU. On the fifth postoperative day, her temperature rose to 39.6°C and her pulse rate was 145 beats/minute, and she developed respiratory distress (Additional file ). Endotracheal intubation was performed to allow mechanical ventilation (Figure ). Her degree of diarrhea was aggravated, with a passage of greenish, watery liquid exceeding 1,800 ml. Her white blood cell count had increased to 7.9 × 109/L, and the proportion of neutrophils had risen to 98%. Her platelet count had decreased, and a coagulation test showed a prolonged time to coagulation. Sulbactam, ornidazole, vecuronium, norepinephrine, hydrocortisone and intensive intravenous fluids were administered, owing to concern about septic shock []. The patient was then treated with venovenous extracorporeal membrane oxygenation (VV-ECMO) via percutaneous access and continuous renal replacement therapy (CRRT). During the following days, the patient’s vital signs and clinical condition gradually stabilized. VV-ECMO and CRRT were stopped on the 12th postoperative day, but the patient’s diarrhea did not shown any improvement. On the next day, her fever reoccurred, with a peak temperature of 38.7°C (Additional file ). Her white blood cell count rose further to 18.0 × 109/L with 89% neutrophils and 10% lymphocytes. Her blood cultures now yielded Acinetobacter baumannii and Enterococcus faecalis, revealing a polymicrobial sepsis. Multiple antibiotics, including imipenem, caspofungin, penicillin and/or linezolid, and even probiotic bifidobacteria, were administered. Abdominal computed tomography (CT) was performed on days 15 and 22 postsurgery, and no intraabdominal free fluid or abscesses was noted (Additional file and Additional file ). The therapeutic strategies with antibiotics and probiotic were continued until 28 days, when the patient still had a fever (38.3°C) and the volume of watery stools reached 2,855 ml. On that day, the patient’s blood culture grew Propionibacterium acnes. Her white blood cell count returned to normal, but her CRP level remained as high as 103.3 mg/L. The timeline shown in Figure depicts the temporal course of our patient’s treatment.


A 60-year-old postmenopausal woman was referred to our hospital with massive vaginal bleeding. Before menopause at age 43, she had a history of 2 cesarean deliveries. She also had a history of hydatidiform mole, 4 years prior to her first viable pregnancy, for which dilatation and curettage was performed and chemotherapy administered. The patient had a medical history of idiopathic portal hypertension and portal thrombosis and a surgical history of esophageal transection and splenectomy. She was on anticoagulation therapy.
Three years prior to the current presentation, she was seen in another prefecture and found to have dilated vessels around the uterus. There was no further follow-up by gynecology. On the day of her current presentation, she went to a local hospital complaining of sudden-onset continuous vaginal bleeding; she was transported to our hospital by helicopter. Speculum examination revealed continuous bleeding from the cervical os. On bimanual examination, the uterus was the size of a man’s fist, soft and spongy, and non-tender. A urine hCG test was negative. She was anemic, with a hemoglobin of 7.6 g/dL, but no tumor markers were elevated (CA 19–9, CEA, CA 125, SCC).
Transvaginal sonography showed several 2-cm low-echoic cystic lesions in the anterior uterine body. Color-flow Doppler revealed a mosaic pattern of blood flow within these cystic spaces (Figure ). Computed tomography (CT) and magnetic resonance imaging (MRI) showed multiple tortuous vessels surrounding the uterus and in the anterior uterine wall (Figure ). The patient underwent CT angiography which suggested multiple expanded vessels around the uterus (Figure ). Based on these findings, a uterine AVM was suspected. Given the large vessels supplying the uterus, we anticipated a significant intraoperative blood loss and decided against immediate hysterectomy. We decided to perform UAE.
Pelvic angiography showed that this patient’s AVM was supplied by many arteries, including the right uterine artery, right internal iliac artery, right external iliac artery, and left uterine artery (Figure ). We performed UAE in the conventional fashion, using coils and gelatin sponges, and found no significant flow to the AVM after the procedure (Figure ). Eight days after embolization, we repeated pelvic angiography and unfortunately found newly established arteries and collateral vessels feeding the uterus (Figure ). A second embolization was performed using coils, with n-butyl-2-cyanoacrylate (NBCA) for residual blood flow, but the abundance of feeding and collateral arteries made it difficult to thrombose every vessel. Finally, we concluded that hysterectomy was the better choice and asked the patient for her consent to attempt it as elective surgery. However, 3 days later, a sudden onset of massive vaginal bleeding indicated rupture of the patient’s uterine AVM and we performed an emergency hysterectomy. There were numerous dilated vessels surrounding the uterine corpus. Surprisingly, it was not difficult to ligate and cut the dilated vessels and we were able to perform the hysterectomy with little bleeding in the operative field. The intraoperative blood loss was 2670 mL, but most of this was transvaginal bleeding from the AVM.
The location of the rupture in the AVM could not be identified, either on macroscopic (Figure ) or microscopic examination (Figure ). Microscopy revealed many dilated thick-walled vessels of varying caliber in the myometrium, extending into the endometrium. The final diagnosis of uterine AVM was established. The patient has had no further episodes of atypical vaginal bleeding and no evidence of intraperitoneal hemorrhage 1 year after surgery.


A 26 year old South-Asian female, having irregular menstrual cycles but was otherwise healthy presented with fever to the accident & emergency unit with severe generalized myalgia and arthralgia. Clinical assessment revealed a tachycardia with a pulse rate of 108 b.p.m and an initial blood pressure of 90/50 mmHg, indicating shock. Clinical picture favored dengue fever with the classic repertoire of symptoms. Since the patient had taken mefenamic acid, a non steroidal anti-inflammatory agent (NSAID) for myalgia for a few days, her complaint of fever for only one day at presentation suggested an erroneous timeline and a late presentation. Rest of the systemic examination was normal and clinically there was no evidence of leakage of fluid in the chest and abdomen on presentation. She was started immediately on an intravenous infusion of 0.9% saline. Preliminary whole blood analysis demonstrated a low haematocrit of 32% with a reduced haemoglobin of 10.4 g/dL (11–17) and a platelet count of 173 × 10 9/L (150–450). Despite fluid replacement her blood pressure declined to 80/40 mmHg with development of shock together with a reduction of the haematocrit to 29%. At this stage haemorrhagic shock was suspected on a background of NSAID usage. She was transfused with cross matched packed red cells urgently and stabilization of the haemodynamic parameters were noted with a borderline but stable blood pressure of 100/60 mmHg. Haematocrit also stabilized at 35%. An ultra sound scan failed to reveal either leakage of fluid into pleural cavity or the presence of ascitic fluid and intra-abdominal heaemorrhage. However the patient suffered heavy per vaginal bleeding which continued. She was observed in a high dependency setting and 8 hours after admission and clinical stabilization, she developed bradycardia, which was confirmed on electrocardiogram (ECG). In addition to sinus bradycardia, the ECG showed T wave inversions from V2- V5 (Figure ). Cardiac insult due to dengue virus infection was suspected, although creatine kinase-MB was normal and Troponin I remained negative. ECG was done serially to monitor the progression and on the second day of hospitalization revealed the occurrence of complete heart block with atrio-ventricular dissociation and a junctional rhythm with a short P-R interval (Figure ). Despite this, the blood pressure remained within acceptable safe limits. In view of satisfactory peripheral perfusion a clinical decision was made not to insert a temporary pacemaker, but to continue close observation for possible haemodynamic compromise occurring due to arrhythmia or worsening due to its presence.
Primary dengue virus infection was confirmed by the presence of positive IgM antibodies with negative IgG antibodies on day 2 of hospitalization. Platelet counts on day 2 of hospitalsation was 157 ×109/L(150–450), but haematocrit value started to rise to 42 and then 45 within a few hours, and clinical examination revealed a right sided pleural effusion which was confirmed on sonographic imaging with the presence of pleural fluid and additionally fluid in the hepatorenal pouch. Fluid resuscitation and replacement was carried out in accordance with the national guidelines on dengue management. Serum magnesium levels were within reference range, with a value of 2.07 mg/dL (1.58-2.55). Serum sodium and potassium values were within reference throughout her stay. Initial serum ionized calcium levels were found to be low normal with a value of 1.14 mmol/L(1.12-1.32) Subsequent ionized calcium levels were found reduced to a value of 1 mmol/L (1.12-1.32). In the background of ECG changes, hypocalcemia was corrected cautiously with intravenous calcium gluconate and the electrolytes were monitored regularly, though the cardiac rhythm remained unchanged. Post correction serum ionized calcium was 1.17 mmol/L and later 1.22 mmol/L (1.12-1.32). Two dimensional echocardiogram revealed an ejection fraction of 50% with normal valves, normal sized atria and ventricles with no systolic wall motion abnormalities though myocardial depression was observed. Liver function tests revealed elevated enzymes. Aspartate transaminase and alanine transaminase were 141U/L (<40) and 119 U/L (<40) respectively and later rose to the highest recorded value of 320 U/L(<40) and 187U/L (<40) respectively. Gamma GT was also elevated at 347.5 U/L (7–50). Total protein was normal with a value of 62.4 g/L (60–85) but albumin was marginally reduced to 30.9 g/L (35–54). The patient remained clinically stable but the persistence of bleeding prompted a blood picture analysis to identify and exclude features of disseminated intravascular coagulation (DIC). Blood picture revealed moderately low platelets and reactive lymphocytes but no features of DIC. However thromboelastography revealed hypocoagulation, platelet deficiency and fibrinogen deficiency. In light of low platelets (lowest nadir of 10x109/L) and continuous per vaginal bleeding 4 units of factor VII complex was given. Normal sinus rhythm was noted on day 5 of admission, though she remained bradycardic till the time of discharge from hospital.
The bleeding ceased and platelet counts rose gradually. The patient made good clinical recovery with the pleural effusion subsiding and vaginal bleeding ceasing. ECG showed resolution upon review two weeks later.


A 44-year-old male with the past medical history of essential hypertension and tuberculosis presented to the emergency room (ER) with the complaints of high grade fever, fatigue, and shortness of breath. According to patient, he developed high grade fever 1 week ago that was accompanied by myalgias, frontal headache, and generalized weakness. Fever was followed by shortness of breath and exercise intolerance which started 3 days ago and worsened with time. History was positive for mild paroxysmal nocturnal dyspnea and orthopnea though he denied any chest pain, palpitations, cough, or syncope. He also had frequent light headedness and got 1 episode of coffee ground emesis after which he was brought to ER. There was no history of blood in stools or urine. The patient denied any history of diabetes, ischemic heart disease, or hyperlipidemia. The patient was only taking HCTZ for hypertension and did not have any allergies. He was an active smoker with a history of one pack of cigarettes daily but denied use of alcohol or illicit drugs. The family history was positive for myocardial infarction in father at the age of 77. The patient did have a history of recent sick contact with one of his brothers who had dengue fever 3 weeks ago.
Review of patient's past medical records indicated that patient had dengue fever 1 year ago for which he was admitted on the floor but fever got resolved on its own with no complications. At that time patient developed vague chest discomfort for which EKG was done which showed widespread T wave inversions. Cardiac enzymes were mildly elevated and echocardiography showed normal wall thickness and ejection fraction of 58%. Taking into account above findings, a tentative diagnosis of mild dengue myocarditis was made. CXR was normal and patient was discharged. Endomyocardial biopsy and cardiac MRI were not done as the patient had mild myocarditis with normal myocardial functions. Follow-up CXR, Echo, and EKGs were normal and patient remained healthy other than having slight fatigue.
In ER patient was lethargic and seemed anxious due to generalised body aches and headache. On physical examination, vital signs were as follows: blood pressure of 89/52 mmHg, temperature of 103 F, heart rate of 116/min, and respiratory rate of 19. Chest examination revealed reduced breath sounds at lung bases bilaterally with scattered fine crackles in both lungs; no rhonchi or wheeze was heard. Examination of heart was remarkable for normal S1 and S2 with no murmur or clicks; an S3 gallop sound was audible. There was no pallor, scleral icterus, cyanosis, clubbing, or peripheral edema. The rest of the physical examination was unremarkable.
Patient was suspected to have dengue shock syndrome and was immediately admitted on floor and resuscitated with IV fluids. Antiemetics and Tylenol was also given. Routine EKG was done which showed sinus rhythm and frequent premature ventricular contractions (PVC) with no ST or T wave ischemic changes (). CXR showed bilateral interstitial edema, cardiomegaly, and pleural effusion in both lungs (). The X-ray findings were suggestive of acute congestive heart failure. Elevated BNP (1040) supported the X-ray findings His haematological investigations revealed slight thrombocytopenia (127000), leucopenia (3100), and haemoglobin of 12. Cardiac enzymes were initially slightly elevated but remained stable over the course of hospital stay (). Urgent transthoracic echocardiography was done which showed ejection fraction of 10% and left ventricle dilation without focal wall motion defect and or focal thinning (). Cardiac catheterization revealed EF of 13% and normal coronary arteries (). Patient was started on dobutamine infusion along with ACEIs, spironolactone, and Lasix. Blood cultures, ESR, hepatitis panel, thyroid profile, and urine drug screen were all within normal limits. Malarial antigen test and typhoid serology were also negative. Anti-dengue IGM by ELISA was negative at the time of admission but was positive for IGG antibodies at that time. Repeat testing on day 3 showed positive IGM antibodies for dengue. The diagnosis was confirmed with reverse transcriptase polymerised chain reaction (RT-PCR) which was positive for dengue virus serotype 3 (DEN-3). In view of above clinical scenario with positive dengue serology, history of myocarditis during primary dengue infection 1 year ago, and echocardiographic findings, diagnosis of dengue virus induced dilated cardiomyopathy (DCM) was made. Fulminant myocarditis with acute myocardial failure was ruled out as cardiac enzymes were almost normal in the setting of dilated cardiac chambers on Echo.
Patient condition worsened gradually and he developed acute hypoxic respiratory failure for which he was intubated on day 4. Patent developed severe thrombocytopenia and despite platelet transfusions he developed massive lower GI bleed leading to refractory shock. Patient was transfused 2 units of PRBC and platelets, but despite aggressive resuscitation and intensive care, patient died on day 5.


A 23 year-old female was referred to our private clinic with a chief complaint of hypersensitivity, fear of tooth loss and gingival recession in the mandibular anterior tooth. She was in good general health and non smoker. Intraoral examination showed a good oral hygiene status with a full-moth plaque score equal to 17% []. A deep class II Miller recession with the lack of attached gingiva, and narrow band of keratinized tissue was observed (Figure ). Probing depths (PD) and clinical attachment level (CAL) measurements and registrations of marginal gingival recession (MGR) were obtained using a periodontal probe (UNC 15, Hu-Friedy Mfg. Inc, Chicago, IL, USA). The measurements were rounded up to the nearest millimeter. Tooth mobility was assessed and graded 0-2 and tooth hypersensitivity calculated via visual analysis scale (VAS). Measurements were done by an examiner with more than 10 years of clinical experience. Bone mapping revealed that it was complete lack of buccal bone plate over involved tooth. The suggested treatment plan comprised root coverage combined with xenograft bone particles. Initial therapies, including supra-gingival plaque removal, polishing, occlusal adjustment, and oral hygiene instruction with proper tooth brushing method were performed. Surgical procedures were performed by one of the authors who was not involved with clinical measurements. The clinical measurements were done by other experienced and calibrated investigators who were not informed about the surgical method. In case of controversy in the measurements by the examiners, they were asked to repeat the evaluation to reach a consensus. Another experienced and blinded operator was responsible for the radiographic examination. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The design of CPF was similar to that described previously by Langer and Langer []. After local anesthesia of the recipient site using 2% articainewithepinephrine1:100 000 (Septanest®, Septodont, Spain), an intra crevicular incision was made from right to left mandibular canines. Two verticalreleasing incisions were made along neighboring teeth. A partial thickness flap was elevated with a No.15c surgical blade beyond the mucogingival junction. Thus, it was extended until it could be passively positioned coronally over the defect without tension (Figure ). The exposedroot surface was debrided completely with a curette (3/4 Gracey curette, Hu-Friedy Mfg. Inc, Chicago, IL, USA) and conditioned with tetracycline powder. Pedicle flaps were sutured to make a single flap. The connective tissue was harvested from palate by trap door technique. In the palate, the distance between the horizontal incision and gingival margin had to be more than 2 mm. By using no.15 scalpel, the epithelium was elevated and then a 1.5- 2.0 mm thickness connective tissue graft was obtained []. The epithelium was laid back and sutured with sutures (Silk 4-0, SUPA Co, Tehran, Iran).
Dehiscence bone defects over exposed root surfaces were overfilled with a mixture of deproteinized bovine bone (Bio-Oss Collagen, Geistlich AG, Wolhusen, Switzerland) and blood obtained froma peripheral vein. CTG was trimmed and sutured over the defect with a 5–0 bio-absorbable suture (Vicryl®, ETHICON, Johnson & Johnson, Livingston, Scotland) at the level of CEJs. Previously reflectedpartial-thickness flap was sutured as double papillary technique described by Harris [], and then coronally positioned to cover the entire graft without tension []. The flap was sutured in place with sling sutures (Figure ).
The patient was instructed to discontinue tooth brushing for 3 weeks and to avoidtrauma at the surgical site. A 0.2% Chlorhexidine digluconate mouthwash (CHX mouthwash, Daroupakhsh Co, Iran) was prescribed twice daily. Professional cleaning was done by a hygienist every day until the sutures were removedon day14. The patients were recalled for prophylaxisat every month, postoperatively. The clinical measurements were recorded at baseline and every 3 months till the final recall visit at six years.
Wound healing was uneventful. The grafted area healed well and complete coverage was achieved at 12-monthfollow-up visit (Figure ). Complete root coverage was achievedwith a minimum of 6 mm gain in keratinized tissue. There was also no change in probing depthcompared to the valuebefore thesurgery (Figure ). The general color and volume match were satisfactory. The clinical and patient-centered outcomes were excellent. No scars resulting in esthetically displeasingappearance were observed. Clinically, the grafted tissues seemed to be attached to the root surfaces.
After six years of regular follow up, patient needed to a 3D imaging for implantation in posterior sites. Cross sectional views that were obtained revealed a clear maintained space over denuded roots which were covered with CTG in clinic. The remnant particles of xenograft were still present on the root surfaces (Figure ).


A 66-year-old male was admitted to the Department of Dermatology of the Sir Run Run Shaw Hospital (Zhejiang University School of Medicine, Hangzhou, Zhejiang, China) in October 2007 with a four-month history of scalp masses. Upon physical examination, two masses without ulcers or tenderness were noted in the right temporoparietal area, measuring 3.0×3.0 cm and 1.5×1.5 cm, respectively. No superficial lymph nodes were palpable, and the rest of the physical exam was unremarkable. Brain magnetic resonance imaging (MRI) showed a subcutaneous soft-tissue mass with irregular margins in the right temporoparietal area, which was moderately enhanced upon enhanced scanning. Serum tumor marker levels were normal. Chest and abdominal computed tomography (CT) scans did not indicate distant metastases.
Surgical excision was performed on October 31, 2007, following a pre-operative evaluation in the Department of Neurosurgery. The resection range was as large as 8.0×10.0 cm, so skin grafting with a free flap taken from the outer side of the right thigh was performed. The tumor did not invade the galea aponeurosis, and complete resection was achieved. The post-operative pathology revealed an infiltrative, irregularly configured vascular channel tumor. The tumor formed a pattern of vascular channels which were interlacing and anastamosing, which were lined with hyperchromatic endothelial cells, which exhibited mitotic activity. The pathological diagnosis was angiosarcoma of the scalp, with negative peripheral margins (). Adjuvant radiotherapy of the right parietal area was started at two months post-surgery, with a β-line dosage of 5,800 cGy/29 fractions for six weeks. Adjuvant chemotherapy was refused by the patient for personal reasons.
In June 2008, more than seven months after the surgery, the patient was readmitted to the Department of Neurosurgery presenting with multiple scalp masses (). This was diagnosed as a post-operative recurrence of the scalp angiosarcoma. No evident distant metastasis was documented by chest and abdominal CT scans. The patient underwent an extended resection of the frontal and occipital scalp masses, measuring 6.0×2.5 cm and 1.0×1.0 cm, respectively, and a bilateral neck nodal dissection. The post-operative histopathological examination showed two scalp angiosarcomas with negative resection margins, and two out of eight lymph nodes were metastatic. Again, the patient refused post-operative chemotherapy.
Three months later in September 2008, a mass measuring 3×4 cm was found close to the left pulmonary hilum in a routine chest X-ray. A chest CT scan revealed a lobulated hilar mass of 2.5×2.5 cm in size in the left upper lobe, with enlargement of the mediastinal lymph nodes. A subsequent CT-guided core needle biopsy of the lung mass indicated metastatic angiosarcoma. The patient experienced no discomfort, such as coughing, dyspnea or chest distress. Following a diagnosis of post-operative lung metastasis of the scalp angiosarcoma, the patient received six cycles of first-line palliative chemotherapy consisting of 750 mg/m2 cyclophosphamide on day 1, 60 mg/m2 epirubicin on day 1, 1.4 mg/m2 vincristine on day 1 and 250 mg/m2 dacarbazine from day 1–5, repeated every three weeks. Chest CT showed disappearance of the lung mass, which indicated a complete response (CR) according to to the Response Evaluation Criteria in Solid Tumors (). The progression-free survival (PFS) time following first-line chemotherapy was eight months, and the patient tolerated the chemotherapy extremely well. Grade 2 nausea and leucopenia were observed according to Common Terminology Criteria for Adverse Events (). No severe adverse reactions, such as febrile neutropenia, or cardiac and renal dysfunction, were documented during the treatment process.
In April 2009, four months after the end of first-line chemotherapy, the patient presented with waist ache and numbness of the lower limbs. Brain MRI revealed a mass in the left parietal lobe. Whole-body bone single-photon emission CT showed abnormally enhanced metabolism in the vertebral joint of the 8th left rib, the 8th thoracic vertebra and the 1st lumbar vertebra. Further spinal MRI indicated signal changes in these bones, which were considered metastases. Chest CT showed no lesions. Consequently, a clinical diagnosis of post-operative recurrence of scalp angiosarcoma, with lung, brain and bone metastases, was established. The patient was referred to a radiation oncologist to receive brain, thoracic and lumbar vertebrae radiotherapy, with an X-ray dosage of 6 MV, 4,000 cGy/20 fractions for four weeks. The symptoms of waist ache and numbness of the lower limbs were greatly relieved upon the conclusion of radiotherapy. However, during the radiotherapy, a scalp nodule of 2 cm in diameter was found at the edge of the previous surgery area and a mass of 1.0×1.0 cm in size was found in the left parotid gland area, both without tenderness. The disease was considered as having progressed, so second-line chemotherapy was administered with a regimen of 75 mg/m2 docetaxel and 75 mg/m2 cisplatin on day 1, repeated every three weeks. Severe myelosuppression and liver dysfunction occurred following the first cycle of treatment. Therefore, the regimen was changed to 60 mg/m2 docetaxel on day 1 plus 30 mg/m2 cisplatin from day 1–2. The patient tolerated this well and received another five cycles of chemotherapy. In addition, twice daily administration of 100 mg oral thalidomide was prescribed throughout the treatment process and chemotherapy intervals. The scalp nodule and left parotid mass significantly reduced in size following the chemotherapy, and was considered to be a partial response (PR). The patient again obtained a PFS time of eight months for the second-line chemotherapy.
In March 2010, half a year after stopping the chemotherapy, an abdominal CT scan revealed multiple liver metastases during a routine follow-up. Chemotherapy was administered again with a regimen of 1.0 g/m2 gemcitabine on days 1 and 8, 75 mg/m2 cisplatin on day 1 and 15 mg endostatin on days 1–14, repeated every three weeks. Following six cycles of chemotherapy, the liver metastases were greatly reduced in size, which was again considered to be a PR. The patient continued to use endostatin as maintenance therapy. A PFS time of nine months was obtained for this third-line chemotherapy.
In December 2010, the disease progressed again. Best supportive care was provided, and the patient finally succumbed in February 2011, with an overall survival time of 38 months following initial diagnosis. Written informed consent was obtained from the patient’s family for publication of this case study and the accompanying images.


In April 2006, an abdominal computed tomography (CT) scan revealed multiple solid hypodense lesions with a size of 18×18 mm in a 56-year-old male undergoing a routine physical examination at The Affiliated Cancer Hospital of Zhengzhou University (Zhengzhou, China). After four months, further CT scans detected an irregular nodular mass with a size of at least 125×100 mm. The patient did not present any symptoms, such as fever, respiratory problems, weakness, anorexia or weight loss. The patient had a 20-year history of hepatitis B virus infection and had been receiving treatment with lamivudine.
Clinical examination detected hepatomegaly (45 mm) below the right costal margin, while no other abnormalities were observed. The liver was nontender, with an irregular surface on the right side. Viral markers were found to be positive for hepatitis B and negative for hepatitis C. Fluorescence in situ hybridization revealed EBV-DNA levels of 5×106 copies/ml. The results of further examinations, including a baseline electrocardiogram, chest CT scan, complete blood count, liver function test and kidney function test, were found to be normal. In addition, the levels of lactase dehydrogenase, uric acid, calcium, α-fetoprotein, β-2-microglobulin and carcinoma embryonic antigen were normal. An abdominal and pelvic CT scan revealed an irregular nodular mass in the right lobe of the liver with a size of at least 125×100 mm (). No other abnormal findings were detected at the abdomen and pelvis. Furthermore, a chest and neck CT scan demonstrated normal lung fields and no mediastinal or paratracheal lymphadenopathy. Bone marrow biopsy identified no evidence of tumor involvement. Ultimately, a diagnostic liver biopsy was performed, which revealed sheets and nests of round cells, surrounded by mature lymphoid cells at the periphery. These cells were positive for the CD20 and leukocyte common antigen markers (). The findings were consistent with non-Hodgkin’s lymphoma (NHL) of diffuse large B-cell type. Therefore, the final diagnosis of the patient in the present study was PHL of diffuse large B-cell type at stage IE, according to the Ann Arbor staging system, since a single extranodal site was involved ().
The patient received R-CHOP chemotherapy, which involved administration of the following: 375 mg/m2 rituximab [intravenously (IV)] over 6 h on day –1; 750 mg/m2 cyclophosphamide over 3 h, 2 mg vincristine and 50 mg/m2 doxorubicin (IV) on day 1; and 40 mg/m2 prednisolone (orally) on days 1–5, every 21-day cycle. An abdominal CT scan was performed following two cycles of chemotherapy, which revealed a marked regression of the lesion to 58×58 mm in the right lobe of the liver (). Following two further cycles of R-CHOP, an abdominal CT scan detected that the mass was slightly enlarged, having a size of 62×59 mm ().
Subsequently, the right liver of the patient was treated with radiotherapy at a dose of 40 Gy over 28 days (2 Gy fractions, days 1–5). CT scans revealed further regression of the liver lesion to 26×32 mm following radiotherapy (). In addition, the patient received treatment with the R-Hyper-CVAD/R-HD MTX-ara-C regimen, following radiotherapy. The regimen consisted of two cycles of dose-intensive therapy courses with rituximab and Hyper-CVAD (R-Hyper-CVAD) therapy alternating with rituximab and high-dose methotrexate (MTX) and cytosine arabinoside (ara-C) therapy (R-HD MTX-ara-C). The R-Hyper-CVAD regimen involved administration of the following: 375 mg/m2 rituximab (IV) on day –1; 300 mg/m2 cyclophosphamide (IV) over 3 h every 12 h for six doses on days 1–3; 300 mg/m2 mesna by continuous infusion initiated along with cyclophosphamide administration and ending 6 h after the last dose of cyclophosphamide; 2 mg vincristine (IV) on days 4 and 11; 50 mg/m2 doxorubicin (IV) on day 4; and 40 mg dexamethasone daily on days 1–4 and 11–14. The R-HD MTX-ara-C regimen involved administration of the following: 375 mg/m2 rituximab on day 1; 200 mg/m2 MTX (IV) over 2 h, followed by 800 mg/m2 IV over 24 h on day 1; 15 mg citrovorum factor rescue every 6 h, initiated 24 h after completion of MTX infusion and increased to 50 mg every 6 h when MTX levels were >20 mmol/l at the end of the infusion, >1 mmol/l at 24 h after infusion or >0.1 mmol/l at 48 h after infusion, until MTX levels were <0.1 mM; 3 g/m2 ara-C over 2 h every 12 h on days 2 and 3; and 50 mg methylprednisolone (IV) twice daily on days 1 through 3. After three cycles of the R-Hyper-CVAD/R-HD MTX-ara-C regimen, abdominal CT scans revealed that the liver lesion disappeared and the patient achieved complete remission (). Following complete remission, the patient was subjected to maintenance therapy by administration of 375 mg/m2 rituximab on day 1 and every three months thereafter for a total of seven doses. The patient remained in a stable and healthy condition, with regular follow-ups for >3 years.


A 40-year-old man presented with a history of liver failure and sudden onset of abdominal pain. He was hospitalized at the department of general surgery. The patient's medical history was unremarkable. On physical examination, he had absence of signs of peritonism. Thus, an exploratory laparotomy was not necessitated. Laboratory data revealed leukocytosis (23900 × 103
μL−1) and elevated levels of amylase (124 U/L), aspartate aminotransferase (3145 IU/L), alanine aminotransferase (2945 IU/L), creatinine kinase (1561 IU/L), total bilirubin (1.2 mg/dL), international normalised ratio (2.1), and activated partial thromboplastin time (25 sec). An urgent computed tomography angiography revealed CA occlusion (). Superior and inferior mesenteric arteries were intact. Surgeons requested an aortogram and recanalization, if applicable.
Anterioposterior and lateral aortograms were performed via the transfemoral approach. The aortogram demonstrated total occlusion of the CA with a visual stump (). Retrograde and antegrade opacification of superior mesenteric artery and antegrade flow in inferior mesenteric artery were imagined (). A bolus of 10.000 IU intravenous heparin and 600 mg loading dose of clopidogrel were administered immediately after the decision was taken for recanalization.
A 7-French (Fr) sheath from the right femoral artery was inserted. A 7-Fr Judkins right guiding catheter (JR3.5, Medtronic, MN, USA) was used to select the origin of the CA. The total occlusion could not be crossed with a 0.014-inch floppy guidewire (Asahi Soft, Asahi Intecc, Aichi, Japan) at first attempt. Then a 0.014-inch stiff guidewire (Asahi Standart, Asahi Intecc, Aichi, Japan) was employed to cross the lesion. The occlusion could be crossed towards splenic artery (SA). A faint antegrade flow was observed beyond the occlusion, with incomplete filling of the distal bed. Median arcuate ligament syndrome was excluded.
The artery was predilated with 3 × 15 and 4 × 20 mm monorail balloons (Invader PTCA balloon, Alvimedica, Assen, Netherlands). A 4 × 24 mm balloon-expandable stent (Liberte Monorail Stent, Boston Scientific, MA, USA) was placed across the occlusion covering the ostium of the CA. An arteriogram confirmed an adequate flow to the splenic territory. A second 0.014-inch stiff guidewire (Asahi Standart, Asahi Intecc, Aichi, Japan) was able to cross the hepatic artery (HA) through stent struts. A 3 × 15 mm monorail balloon (Invader) was used to predilate the HA and expand the stent struts. Balloon dilatation did not establish an adequate flow within the hepatic artery. Therefore a stent implantation by utilizing TAP-stenting technique was decided in the CA bifurcation. Subsequently, the HA stent (Liberte Monorail 4 × 24 mm) was placed with minimal protruding into CA with an uninflated SA stent balloon for final kissing (). After HA stent deployment, the balloon of the HA stent was slightly pulled into the CA and final kissing was performed. Final angiogram showed excellent flow within the CA, SA, and HA (). Patient was transferred back to intensive care unit of surgery. For prevention of stent thrombosis aspirin (100 mg/d) and clopidogrel (75 mg/d) were initiated. Laparotomy was not performed because the patient did not develop clinical signs of bowel ischemia after endovascular procedure. A follow-up angiogram was not planned as a result of improvement in his condition.


A 51-year-old male patient, smoker, known to have diabetes insipidus type II, presented with a large deforming right hemifacial mass growing progressively over a period of 10 years, measuring 11 × 14 × 6 cm extending from the level of the right temporalis muscle above the zygomatic arch superiorly, down to the level of the mandible inferiorly, medially extending to the right lateral epicanthal fold, and laterally abutting the right external auditory meatus. The mass was firm, fixed but not tender, rubbery consistent with no overlying skin changes. Weakness was noted over the right eyebrow and right lower lip. No trismus or respiratory distress was present. Oral exam was unremarkable and a fiberoptic flexible laryngoscopy showed no narrowing of the nasopharyngeal, oropharyngeal, or hypopharyngeal walls. Narrowing of the right external auditory canal was evident on otoscopic exam. To note that the patient underwent a previous surgery in an outside hospital in attempt of removing the tumor bulk but the resection was minimal and a small portion of the tumor was removed, no pathological studies were taken at the time.
CT scan of the brain and neck showed 11 × 6.2 × 14.5 cm heterogeneously enhancing right parotid mass with areas of necrosis, involving the deep lobe of the parotid gland. It is invading the lateral aspect of the masticator space, right temporomandibular joint, and external auditory canal causing narrowing of the latter and extending superiorly into the temporalis muscle and involving the masseter muscle (). The parapharyngeal space appears normal. There is erosion of the right zygomatic arch and a few subcentimetric lymph nodes surrounding the parotid mass posteriorly.
A fine needle aspirate was done showing a picture suggestive of pleomorphic adenoma.
The decision was made to surgically excise the mass.
An extended right radical parotidectomy with excision of a portion of temporalis muscle, part of the masseter muscle, and zygomatic arch was made. Intraoperatively, the facial nerve was disappearing into tumor and was completely encased and invaded by tumor; a frozen section biopsy taken intraoperatively demonstrated high suspicion of malignancy, so the decision was made to sacrifice the facial nerve.
Patient was scheduled for postoperative radiation.
Mass is composed of multiple components, with epithelial-myoepithelial carcinoma being dominant (80% of the tumor mass) with a minor component of solid variant of adenoid cystic carcinoma and basal cell adenocarcinoma (). The diagnosis of a hybrid carcinoma was made, in the presence of perineural invasion and absence of lymphovascular invasion. The surgical margins were negative for malignancy.


A 64-year-old man was referred to our hospital with bulging of the sternal manubrium. He was otherwise asymptomatic. There was no antecedent history of Gardner syndrome, trauma or surgery. Physical examination revealed a firm, 3× 3 cm palpable sternal mass. The contrasted computed tomography (CT) scan of the chest showed a 4× 4 cm mass based on the sternal manubrium, with no apparent involvement of the mediastinal structures (Figure A and B). 18F-fluorodeoxyglucose–positron emission tomography (FDG-PET) revealed metabolically active areas around the manubrium, both sternoclavicular joints, and bilateral first sternocostal joints, which was suggestive of malignant tumor of the sternal manubrium. The patient refused to undergo preoperative fine-needle aspiration of the lesion. Thus the patient underwent a radical en bloc resection of the tumor and sternal reconstruction with autogenous rib grafts. At surgery, an expansile lesion involving the entire manubrium, both sternoclavicular joints, and bilateral first sternocostal joints was found. En bloc radical manubriectomy was performed including portions of the bilateral clavicles and first ribs. The specimen was removed 4 cm beyond the margin of the lesion. Then through a left anterior lateral incision, about 10 cm of the left fifth rib was harvested from the subperiosteum and carved into two parts with preservation of intact periosteum and pleura. Slots were cut into the ends of the two rib clips, bilateral clavicles, and the edge of the sternum using an electric drill. The two rib grafts were placed to form a T shape between the edges of the residual sternum and bilateral clavicles using rib nails, and then fixed with stainless steel wires. Histopathological examination revealed long fascicles of spindle-shaped cells with slight atypia arranged in a collagenous stroma, indicating a diagnosis of desmoid tumor (Figure A and B). The resection margins did not show any signs of neoplastic infiltration. Postoperative recovery was unremarkable and there were no complications. Three months postoperatively, computed tomography scan of the reconstructed chest showed neither instability of the chest wall nor evidence of tumor recurrence (Figure C). The patient has been free of disease for 46 months after surgery without any other treatment.


Seventeen year old boy with mass lesion in the right neck and weight loss attended to the hospital. He had a family history of malignancy in his sister. He had bilateral exophtalmos, cervical lymphadenopathy approximately 3 cm in diameter, icterus and ulcers in the scalp in physical examination.
Computed Tomography
The computed tomography images were obtained by a 64 channel multidetector CT device (Aquilion 64, Toshiba Medical Systems, Japan) with intravenous contrast medium administration and with slice thickness of 0.5 mm. The images were reconstructed in axial, coronal and sagittal planes and interpreted in soft tissue and bone windows.
Computed tomography examination revealed multiple cervical, anterior mediastinal conglomerated lymph nodes and bilateral pulmonary nodules. Additionally lytic lesions in the corpus of T7, T10 and destruction of T2 vertebra by a soft tissue mass were reported in the diagnostic CT ().
Bone Scintigraphy
The bone scintigraphy was performed by a double head single photon emission tomography (SPECT) gamma camera (GE, Infinia II, Israel) equipped with low energy high resolution parallel hole collimator. After intravenous administration of 20 mCi (740 MBq) (according to the body weight) Tc-99m methylene diphosphonate (MDP) and waiting period of 2-3 hours, routine whole body, and additional spot images were obtained. Asymmetrical increased tracer accumulation in unexpected sites without history of previous trauma or surgery was accepted as disease extent.
Bone scintigraphy showed multiple increased activity in predominantly cranium, bilateral ribs and pelvic region () however, there was no sign of vertebral involvement; neither decreased nor increased activity accumulation.
PET/CT Imaging
The patient fasted for 12 hours before PET/CT examination and his blood glucose concentration was 124 mg/dL. Imaging was performed by a PET/CT scanner (Siemens Biograph, 6 slice spiral CT integrated PET/CT, Siemens Medical System) after injection of 10 mCi (370 MBq) 18F-FDG and 60 minutes waiting interval. CT was performed from head to thigh with a slice thickness of 5.0 mm. For semi-quantitative assessment, regions of interests (ROIs) were produced. The maximum SUV (SUVmax) value was measured from ROI according to the standard formula. PET and CT datasets and fusion images were interpreted by an experienced nuclear medicine physician.
In the PET/CT images there were multiple hypermetabolic areas bilaterally in cervical region, mediastinal, abdominal and pelvic lymph nodes, anterior mediastinal mass () and in all the bone lesions identified in bone scintigraphy and CT , ). Additionally orbital involvement of the LCH is observed as increased FDG accumulation in the left orbita and the soft tissue component in CT (). Excisional biopsy of cervical lymph node revealed Langerhans cell histiocytosis. In the biopsy specimen there were atypical histiocytes infiltrating the whole lymph node, giant cells and microabcesses were present. Immunohistochemical analysis revealed positivity of CD3, CD8, CD5, CD20, CD15, CD68, S-100, Vimentin, LCA and CD1a and negativity of CD10, Pan CK, EMA, Fascin, CD38 and CD138.
Literature Review and Discussion
Langerhans cell histiocytosis might cause death especially in the infants with pulmonary involvement (). Bone is the most frequently affected site in 90% of patients which is the only site in one-third of the patients (). Especially in childhood the bone lesions (50-57%) is the most frequent manifestation of the disease however in adult age the frequency varies (). The incidence of vertebral involvement in LCH has been documented to be 12-35%, however a single lesion in the spine is relatively rare (). LCH is characterized with lytic bone involvement which might cause predisposition to fractures in especially vertebral column. PET/CT shows lytic bone lesions more clearly than other types thus the diagnostic efficiency of PET/CT is superior to the other imaging methods in LCH. Aoki et al. have demonstrated that LCH lesions could have FDG uptake as high as osteosarcoma lesions (). Coincidence FDG PET even has higher specificity than bone scintigraphy and radiography (). Additionally PET/CT might show the treatment response of the LCH patients according to the previous studies (). The presented patient had a critical lesion beneath the T2 vertebra which was identified in PET/CT. PET/CT identified a hypermetabolic lesion at second thoracic vertebra which had an apparent destruction on diagnostic CT in the presented patient. Although the lesion was more than 15 mm in diameter, the bone scintigraphy, secondary to a possible lytic nature of the lesion, was negative for this vertebral lesion. In the absence of a PET/CT the disease could be underestimated and treated inadequately.
Although Philips et al. have reported that bone scintigraphy identified approximately 75% of vertebral lesions in their series of 44 cases () bone scintigraphy was insufficient to show lytic vertebral involvement of LCH in our case. There is need for future prospective studies related to the diagnostic efficiency of bone scintigraphy in LCH. A previous study comparing FDG-PET to radiography and bone scintigraphy also have concluded that PET imaging is helpful in skull, limb, pelvis, scapula and clavicle lesions, however, not sensitive in spine which is attributed to complete collapse of vertebra or smaller diameter of lesions as shown by MRI (). We in fact did not observe an underestimation of vertebral involvement of LCH in PET/CT, however, we did not observe the paravertebral effect of lesion to the adjacent structures to the T2 vertebra. This conclusion supports the idea of Azouz et al. that the lesions of LCH adjacent to the vital structures should be additionally evaluated by diagnostic CT (). MRI has been also introduced as a suitable method for delineating the bone marrow extent and soft tissue involvement in LCH of the bone. Additionally MRI have found be superior in not only locating more skeletal lesions but also extraskeletal lesions (,).
Langerhans Cell Histiocytosis accounts for less than 1% of orbital tumors (,). In our patient one of the striking physical examination finding and one of the first finding of the disease was left sided exophtalmos which was a consequence of a mass lesion approximately 4 cm in maximum diameter, invading the globe with intracranial projection and infiltrating the bone tissue. This orbital lesion was also FDG avid and demonstrated increased osteoblastic activity in the bone scintigraphy.
Pulmonary LCH is also a rare entity which is presented as interstitial lung disease. It is approximately 5% of interstitial lung disease however isolated lung disease in LCH is rare (). The presented patient also had lung involvement with multiple lung nodules without FDG uptake with diameter of ≤1 cm.
We presented a case of LCH with exophtalmos and disseminated disease in especially bone tissues. Comparison of bone scintigraphy and F-18 FDG PET/CT scan findings in our patient revealed that the sensitivity of the bone scintigraphy was inferior to F-18 FDG PET/CT scan in vertebral lesions.


The patient is a 37 year-old man. His medical history was characterized by surgery for frequent shoulder dislocations at the age of 24, a traumatic injury with rupture of anterior cruciate ligament in his left knee and chicken pox at the age of 30. He is a cigarette smoker and has familial history of arterial hypertension and dyslipidemia.In 2010 he started complaining of weakness in his upper limbs and shoulder girdles (Figure
) and an abnormal posture with cervical hyperlordosis. In a few months he developed progressive hypostenia at upper extremities with involvement of lower extremities and marked inability to perform daily activities (like dressing, driving, climbing stairs). On September 2011 he was admitted to hospital for medical investigations.
At admission, resting heart rate (HR) and blood pressure were 92 beats per minute (bpm) and 100/70 mmHg, respectively. His body surface area (BSA) was 1.64 mq.
Thoracic and heart auscultation of the heart were unremarkable and no signs of pulmonary or systemic congestion were detected. Neurologic findings included severe weakness and hypotonia of upper extremities, mild weakness of lower extremities with slight reduction of deep tendon reflexes, mild weakness of the neck extensor muscles, inability to reach Mingazzini position (I and II) without help and waddling gait. No facial weakness nor ophthalmoplegia were detected.Electromyography highlighted bilateral myogenic suffering of the shoulder girdle with signs of secondary reorganizations of motor units. Muscle biopsy of biceps brachii showed marked variation in muscle fiber size, atrophic type I fiber predominance and marked disarray of contractile proteins and Z-disks; multiple cytoplasmic nemaline rods were visible in atrophic fibers with Gomori trichrome staining. Electron microscopy (Figure
) revealed numerous sarcoplasmic inclusions with the typical ultrastructural features of nemaline bodies. Nemaline myopathy was diagnosed. No familiarity for NM was proven. The analysis of gene mutations is still in progress.
Electrocardiography (ECG) showed sinus rhythm, with a resting HR of 92 bpm and diffuse non-specific ST-T wave changes. Echocardiography showed left ventricular systolic dysfunction due to diffuse hypokinesia with a moderate reduction of left ventricular ejection fraction (LVEF = 42%), normal dimensions of cardiac chambers, moderate pericardial effusion with initial systolic collapse of the right atrium and no signs of pulmonary hypertension.
Spirometry revealed the presence of a moderate restrictive syndrome. He also underwent a cardiopulmonary test (VO2 max: 16.7 ml/kg/min) resulting in a moderate-severe reduction of functional capacity.
Blood test findings were normal except for a mild increase in liver function tests without organic evidence of liver abnormality at abdomen echography and computed tomography (CT) scan. Autoanticorpal screening, viral hepatitis and Human Immunodeficiency Virus (HIV) serology were negative. A monoclonal gammopathy of undetermined significance was found.
Pericardiocentesis was performed because of increasing pericardial effusion. No signs of infection or malignancy were noted on pericardial effusion on thoraco-abdominal CT scan.
The patient was treated with enalapril (2.5 mg b.i.d.), carvedilol (6.25 mg b.i.d.) and spironolactone (50 mg/die). Target HF doses of beta-blocker wasn't reached because of symptomatic hypotension. LVEF at discharge was 50%.
In the following months the patient started a program of intensive rehabilitation with a mild improvement in posture and gait although a worsening dysphagia was noted.
After an initial improvement of clinical conditions, increasing signs of systemic congestion occurred [progressive positive fluid balance, tender hepatomegaly, jugular distension, bilateral perimalleolar pitting edema, pleural effusion, New York Heart Association (NYHA) Class III-IV], together with dyspnea during speech, requiring admission to Intensive Care Unit (ICU). At admission, ECG showed sinus rhythm with resting HR 105 bpm; blood pressure was 90/60 mmHg. Echocardiogram revealed worsened biventricular systolic function [LVEF = 20%; Tricuspid Annular Plane Systolic Excursion (TAPSE) 13 mm], with signs of initial eccentric remodeling (End Diastolic Volume/BSA = 99 ml/mq) and mild pericardial effusion. Treatment with dobutamine and furosemide infusion improved hemodynamics but after few days three cardio-circulatory arrests occurred due to ventricular fibrillation and ventricular tachycardia requiring external defibrillation. An implantable cardioverter defibrillator (ICD) was then implanted for secondary prevention. Therapy was added with digossin, amiodarone and furosemide but patient's resting HR at discharge was still >70 bpm due to the aforementioned limitation in beta-blocker titration.On November 2011 a new rehabilitation program was started at our institution. Ivabradine (5 mg b.i.d.) was initiated with successful reduction of resting HR from 90 bpm to 55 bpm at 1 month follow up, also confirmed at sixth month follow up (Figure
). Echocardiogram showed amelioration of left ventricular function at 3 month follow up (LVEF = 45%) (Figure
). At 2,5 year follow up Echocardiogram revealed recovered biventricular function and significant reverse remodeling (LVEF = 55%; End Diastolic Volume = 41 ml/mq, TAPSE = 21 mm).
The patient is now able to carry on the rehabilitation program, achieving net improvement in neuromotor control of the limbs and trunk and less limitations in daily activities. No more hospitalizations for HF occurred since optimization of medical therapy with ivabradine was started with reduction of HR. However a single hospitalization occurred for aspiration pneumonia; because of persistent dysphagia, a tracheostomy tube was inserted to protect airways from further aspiration. At clinical follow up ivabradine was well tolerated, the compliance was satisfactory and no side effects occurred. The patient is regularly doing chest physiotherapy.


A 60-year-old man was referred to the Ophthalmology Department for assessment of progressive blurred vision in both eyes, in the past two years. He had a liver transplantation 3 years before, due to liver failure after hepatitis C. He developed chronic arterial hypertension and mild renal insufficiency as collateral effects of transplant medication. There were no medical records of transplant rejection. The medication in use was acetylsalicylic acid (100 mg), anlodipine (5 mg), furosemide (40 mg), tacrolimus (1 mg), and mycophenolate mofetil (360 mg), all for three years. He also had a past history of corticosteroid use (5 to 10 mg) for 6 months after the transplant.
In the ophthalmological examination, he presented a corrected visual acuity of 20/200 in both eyes. There was no pupillary reflex defect. The biomicroscopy was unremarkable. The fundoscopy () showed mild hypertensive retinopathy and mottled pigmentary changes in posterior pole. The Spectralis SD-OCT (Heildelberg Engineering, Heildelberg, Germany) evidenced a serous macular detachment with protein-enriched fluid, without RPE detachment (). The EDI evidenced a thickened choroid (450 μ, measured subfoveal, from the outer border of RPE to the inner border sclera) with hyperreflective dots (). FA (Visucam 500, Zeiss, Germany) showed a distinct pattern of multiple small (100 μ), round hypofluorescent dots, and a diffuse hyperfluorescent fundus due to pooling, especially around the fovea (). The FAF (Visucam 500, Zeiss, Germany) showed round granular hyperautofluorescence lesions corresponding to the hypofluorescent areas on the FA, with a granular hypoautofluorescent fundus in posterior pole (). The ICG (TRC 50-X retinal camera and Imaginet 50X Imaginet Systems, Topcon Inc., Tokyo, Japan) presented with multifocal areas of choroidal vascular hyperpermeability, without focal leakage ().
Although our patient did not show prominent RPE changes in the fundus examination, the FA findings were similar to the “leopard skin” pattern. We could also observe dye pooling around the fovea consistent with serous macular detachment, without specific points of leakage. This fact is important in order to distinguish this condition from idiopathic chronic CSC or CSC after solid organ transplantation, since IOTC does not present with focal leakage []. Moreover, it is also distinct from DRPE, characterized by widespread distribution of small pigment epithelial detachments (PEDs), a few RPE changes, and the presence of more extensive pigmentary alterations with variable leakage on the FA [].
The use of FAF among several retinal conditions has been well established []. This patient presented with granular and confluent hyperautofluorescent lesions, associated with granular hypoautofluorescent areas. Additionally, hypofluorescent spots on the FA were correlated with hyperautofluorescence areas on FAF, showing a RPE distress, with lipofuscin deposition. These mottled RPE changes were not fully observed with ocular fundi. It suggests that FAF might better assess early RPE changes with the additional advantage of being a noninvasive tool, considering that patients in the setting of kidney or liver transplantation may have contraindication to dye injection. Spaide and Klancnik Jr. reported diverse findings of FAF in CSC. In chronic stages, hyperautofluorescent lesions with material seemed to gravitate inferiorly or to collect in deposits in the border of the detachment. In the absence of subretinal fluid, decreased autofluorescence lesions were seen, associated with geographic atrophy and fluid descending tracts []. Our patient showed a very distinct pattern, suggesting that the FAF may play a role in the differential diagnosis of IOTC.
The ICG is an adjunct diagnosis tool to assess diseases affecting the choroid. In this case, the ICG presented with multifocal areas of choroidal vascular hyperpermeability, similar to CSC []. These similar ICG findings arise questions about similarity in pathogenesis with CSC.
The advance of OCT provided a better understanding of serous detachments, especially those located in the macular region. Our patient presented with a serous macular detachment, rich in protein exudation (hyperreflective dots) and no pigment epithelial detachments (PED). In a recent study about CSC after renal transplantation (RT), the OCT images revealed subretinal fluid and multiple small PEDs []. Patients with organ transplant are indeed subject to neurosensory macular detachment or CSC probably due to corticosteroid use. However, patients with IOTC present with serous detachment with the particularity of absence of PEDs []. Thus, besides the pigmentary changes, the pattern of macular detachment is distinct from idiopathic and isolated CSC after solid organ transplant.
Another aspect was the presence of a thickened subfoveal choroid (575 μ) associated with hyperreflective points, assessed by EDI. The average normal choroidal thickness is 275–300 μ, although a correlation of choroidal thickness with age, axial length, and refraction has been found. Increasing age and myopia are associated with choroidal thinning []. Choroidal thickening in patients with CSC has been reported in the literature []. Jirarattanasopa et al. also recently described choroidal thickening in CSC subtypes, in agreement with vascular hyperpermeability seen in ICG []. Considering that IOTC and CSC may have similar pathogenesis with regard to choroidal function, the EDI may be an alternative and noninvasive tool to evaluate the choroid in these patients.


A 48-year-old female patient with history of skull fracture suffered in a traffic accident 25 years ago presented in mid-January 2014 in the infectology clinic of her local hospital for facial, neck and ear erythema; butterfly-shaped rash; pain in the upper arm muscles; stiffness of hands and dysphagia. Considering the sedimentation (SE) 30 creatine kinase (CK) 308 result, as well as leukocyte (L) 11.4 (white blood cells (WBC) differential percent neutrophils (% neu) 87, percent lymphocytes (% lymphs) 7.2, percent monocytes (% monos) 5.9, percent eosinophils (% eos) 0), the patient was referred to immunology tests (anti-antinuclear antibodies verified by indirect immunofluorescence (ANA IIF) slightly positive and anti-double-strained DNA (anti-dsDNA), anti-Ro/SSA antibodies (anti-SS-A52), anti-Ro/SSA antibodies (anti-SS-A60), SSB/La antibody (anti-SSB), anti-Sm antibodies directed against 7 proteins (anti-Sm), autoantibodies directed against the RNP/Sm ribonucleoprotein complex (anti-Sm/RNP), anti-DNA topoisomerase 1 antibody (anti-DNA-topo 1), antibody directed against Jo-1 protein (anti-Jo-1), CENP-B specific anti-centromere autoantibodies (anti-CENP-B), autoantibodies to ribosomal P (anti-RIBO P) negative). Since the administered corticosteroid treatment yielded no improvement, a multi-slice computed tomography (MSCT) of the abdomen (Figure ) was performed, showing a pronounced thickening of the cholecyst wall ranging from 11 to 17 millimeters (mm), scattered and eccentric in appearance; two intraluminally present choleliths, one within the fundus 18 × 16 mm and the other infundibular 22 × 16 mm; and no evident pericholecystic edema. The tumour markers are carcinoembryonic antigen (CEA) 0.7 μg/l and carbohydrate antigen 19-9 (CA 19-9) 964 U/ml. Laparoscopically visualized gallbladder showed malign alterations. Urgent cytological analysis showed malign cells, after which the procedure was reverted to laparotomy which verified omentum carcinomatosis, as well as infiltration of the fifth liver segment. Palpable lymph nodes were in the direction of the hepatoduodenal ligament. The procedure was finished with exploration. Final histopathology report of the omentum was adenocarcinoma (diffuse solid clusters of polymorphous atypical hyperchromatic tumour cells and gland formations with atypical mucous-cylindrical epithelium).
Oncologist suggested treatment with cisplatin 25 mg/m2 (per square meter of body-surface area) and gemcitabine 1,000 mg/m2, each administered on days 1 and 8 and repeated every 21 days for up to 6 cycles, unless disease progression or unacceptable toxicity occurs. Prior to starting chemotherapy in March 2014, the dermatologist increased the corticosteroid dosage (methylprednisolone 60 mg/day) due to newly manifested periorbital edema and macular exanthem in the regions of the trunk, neck and dorsum of the hand (Figures and ). The patient refused the recommended skin biopsy. Still, there was some improvement in muscular strength.
Prior to the first cycle of chemotherapy, the patient was given two doses of erythrocyte concentrate for normocytic anaemia (haemoglobin (Hgb) 95 g/l, haematocrit (Ht) 0.345 l/l, mean corpuscular volume (MCV) 82.8 fl). After 10 days of high-dose corticosteroid therapy, the skin eruptions faded. During and after the second cycle of chemotherapy, the patient complained of general weariness and fatigue.
After 3 cycles of chemotherapy, new skin changes developed on the right upper arm and both thighs, with periorbital edema more pronounced on the left side, despite the 32 mg/day maintenance dose of methylprednisolone. A follow-up MSCT of the abdomen showed a 12-mm thickening of the cholecyst wall - a regression, compared to the initial MSCT result - and increased tumour marker levels (CEA 1.6 μg/l, CA 19-9 2,525 U/ml). During the next three chemotherapy cycles, additional skin changes manifested in the armpit and on the scalp; some marker levels also increased (CA 19-9 3,259 U/ml; the gamma-glutamyl transferase (GGT) doubled). Final MSCT of the thorax, abdomen and pelvis was performed after treatment completion in August 2014, showing a progression of hepatic changes and ascites, after which the patient was referred to palliative care.
The patient presented in the case report was treated using the standard care of gall bladder carcinoma. The Helsinki Declaration was obeyed. Ethical board of Hospital Sisters of Charity gave the approval.
Gallbladder carcinoma is the most common and the most malignant tumour of the biliary tract. It occurs mostly between the ages of 60 and 70 and is 2 to 6 times more common in women. Histologically, 95% of gallbladder carcinoma patients have adenocarcinoma; this was also the case with my patient, as the final histopathology report of the omentum showed. Interestingly, the patient was not aware of her long-standing cholelithiasis and had no pathological condition connected to increased risk.
Gallbladder carcinoma has an extremely bleak prognosis; only 5% to 10% of patients who undergo surgery are likely to survive the following 5 years []. Also, one third of patients whose surgery is finished with exploration show peritoneal and liver metastases that were not visible on MSCT or MRI. In cases of suspected disseminated malignant disease, diagnostic laparoscopy is recommended []. My patient’s preoperative CT of the thorax, abdomen and pelvis showed no sign of liver or peritoneal metastases.
Although skin biopsy was not performed on my patient and although she did not test positive for autoantibodies usually present in patients suffering from dermatomyositis, it is my opinion that her clinical presentation is consistent with paraneoplastic dermatomyositis. The patient underwent chemotherapy with cisplatin and gemcitabine, which was in accordance with the results of the study of phase III of patients with advanced or metastatic carcinoma. Adding cisplatin to gemcitabine, that is its interaction between gemcitabine and cisplatin afforded significant progression-free survival (median, 8.4 versus 6.5 months; hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.57 to 0.90; p = .003) and overall survival benefits (median, 11.7 versus 8.3 months; HR, 0.70; 95% CI, 0.54 to 0.89; p = .002). The most common side effects include decreased WBC count and fatigue []. My patient never exhibited decreased WBC count, which was partly due to the effects of corticosteroid therapy. Since receiving the second cycle of chemotherapy, she complained of increased general weariness and fatigue, which could be due to the chemotherapy treatment.
In January 2015, I searched PubMed for terms gallbladder cancer, gallbladder carcinoma and dermatomyositis and found a total of six case reports in English describing dermatomyositis in patients suffering from gallbladder carcinoma [-]. All of the cases featured female patients over 44 years of age, some with present risk factors (previously verified gallstones). The time interval between the appearance of dermatomyositis and malignant disease ranged from 2 weeks to 2 years. Considering the patient was initially treated in a relatively small facility and the administered treatment did not lead to improvement of her condition, it was soon suspected she had a malignant disease.
In the cases I studied, malignant disease was diagnosed within 2 to 7 months.
My patient initially had elevated CK, slightly positive ANA IIF and negative anti-Jo-1, as described in other patients. The tumour markers were initially determined to be CEA and CA 19-9. CEA was within range, whereas CA 19-9 was 24 times above normal. Elevated serum CEA and CA 19-9 levels could be suggestive of gallbladder cancer, bearing in mind that CA 19-9 has higher specificity, and CEA a higher sensitivity []. Although some authors describe a complete regression of skin changes following adequate treatment, in the case of my patient, the dermatomyositis and the malignant disease progressed independently of one another []. Following high-dose corticosteroid therapy, the skin changes faded within the same period as described in the case report of another patient; however, after 3 cycles of maintenance therapy, they progressed, although the radiology report verified the regression of the disease.


A 43-year-old Caucasian unemployed man presented with lifelong symptoms of depression, anxiety, and impulsive behavior. He reported struggling with intense depressed mood, substantial life stress including a divorce in progress, and the inability to hold a job due to the impairment and distress associated with his symptoms. He had received psychopharmacological and psychotherapeutic treatment for the previous six years, but reported that he had not experienced any clinically meaningful gains as a result of those treatments. His medication history included fluoxetine, sertraline, paroxetine, escitalopram, desvenlafaxine, duloxetine, levetiracetam, valproic acid, oxcarbazepine, ezogabine, aripiprazole, quetiapine fumarate, chlorpromazine, mesoridazine, and lithium. At his initial assessment, his medications included sertraline, valproic acid, and lisdexamfetamine dimesylate (this medication was not approved by our team, but rather was prescribed by his previous physician who believed his diagnosis to be attention deficit hyperactivity disorder). On the Thase and Rush Staging Model, he was at Stage III of treatment resistance, indicating failure of more than two adequate trials of distinct classes of antidepressants, as well as failure of an adequate trial with a tricyclic antidepressant.
He was given a primary diagnosis of bipolar II disorder, currently in a mixed state, based on a psychometric assessment conducted by an independent licensed clinical psychologist prior to the beginning of treatment. His assessment included the administration of a valid Personality Assessment Inventory (PAI) and the Beck Depression Inventory (BDI)-II. These measures showed severe depressive (PAI Depression (DEP) T score=79, BDI-II=36) and manic (PAI Mania (MAN) T score=74, PAI Aggression (AGG) T score=72) symptoms. Elevations in his life stress were also apparent (PAI Stress (STR) T score=86).
He was also assessed at baseline using brain single-photon emission computer tomography (SPECT) with 99mTechnetium-hexamethylpropyleneamineoxime (HMPAO). SPECT is a neuroimaging technique that shows the functional status of gray mater areas via the measurement of relative perfusion [-]. Results from this assessment revealed significant relative underperfusion bilaterally in multiple hemispheric areas, more accentuated in his frontal lobes, anterior cingulate and extensive underperfusion in his orbitofrontal and apico-mesial temporal areas. Marked hyperperfusion was seen in his right caudate head, cerebellar vermis, and retro-splenial posterior cingulate. Moderate hyperperfusion was apparent in his left caudate head, dorsal aspect of his posterior cingulate, and in an asymmetric thalamus. This combination of underperfused areas is compatible with multiple dysfunctions related to attention, memory, executive function, impulse control, and social interaction, while the hyperperfused areas are often found in anxiety and depression [,].
After informing him of the possible risks and benefits of the combined ketamine and TMS treatment, the new technique was used to treat his bipolar II disorder. He was first given two days of TMS pretreatment, which consisted of four treatments of 30 minutes each day, with 45-minute resting intervals between each treatment. Based on 14 years of observational evidence from our clinic, the TMS consisted of 40 minutes of 1 hertz continuous TMS administered at 115% of the motor threshold. The combined protocol treatment added the intravenous ketamine infusion (Ketalar®, manufactured by Par Sterile Products LLC, Parsippany, NJ, USA), which was administered concurrent to, and bracketed within, the middle 30 minutes of TMS; there were five minutes of TMS pre- and post-infusion. The TMS head coil (manufactured by Neotonus, Inc., Marietta, GA, USA) was positioned at the midline of his scalp to maximally stimulate the medial prefrontal area that overlays the anterior cingulate region. This area was targeted based on evidence that it is implicated in depression [].
The protocol described above was repeated a total of 24 times over five months, at approximately one-week intervals. All stimulation levels were within published safety guidelines, and a certified registered nurse anesthetist personally managed the anesthesia aspects of this treatment at all times. The dosage of infused ketamine was gradually increased from 50mg at the first treatment (approximately 0.5mg/kg) to 600mg by the last treatment. The dose increases were based on his tolerance to higher doses and to symptom reduction, as well as on the clinical evaluation that was performed a few days after each treatment. The ketamine dose adjustment was previously described []. Institutional review board exemption was obtained for this report from an independent accredited agency (Sterling IRB) because the ketamine dose adjustment used in our current study has been previously described and approved.
Beginning after the second combined treatment, he reported substantial improvements in his symptoms and related functioning, eventually including the ability to maintain a full-time job. Five and a half months after his initial assessment, he again underwent a psychometric assessment. Results from a valid PAI and BDI-II showed substantial decreases in his symptoms related to both depression (PAI DEP T score=65, BDI-II=13) and mania (PAI MAN T score=61, PAI AGG T score=56). Remarkably, these improvements occurred even though he continued to experience elevated life stress over the duration of the treatment (PAI STR T score=82). Moreover, his follow-up brain SPECT scan showed increased relative perfusion in all previously underperfused areas (see Figure ), thus documenting a specific functional substrate for the treatment effect.


A confused 41-year-old male was found in a park and brought to emergency department by the paramedics. During transit he had two generalized seizures. On the admission the patient appeared confused but conscious with a Glasgow Coma Scale of 13. He behaved aggressively and spoke neither English nor a local language. An interpreter was consulted, but the patient showed aggressive behaviour, therefore making it impossible to take a history. The physical examination was unremarkable except for a tongue bite and several bruises and scratches over the whole body. The pupils were moderately dilated and sluggishly reactive. All vital signs were stable (heart rate: 108 beats per minute, blood pressure: 123/80 mmHg, oxygen saturation: 98% at room air with a normal respiratory rate, and a body core temperature of 37.2°C). Laboratory tests revealed a leukocytosis of 25.1 G/L, elevated values for C-reactive protein (12 mg/L), creatinine kinase (2185 U/L), myoglobin (618 μg/L), creatinine (143 mmol/L), and uric acid (1344 mmol/L) suggesting renal insufficiency. Electrolytes, liver enzymes, troponin I, coagulation, and haematology were in the normal range. An electrocardiogram showed a sinus tachycardia. Neurology service was consulted because of ongoing confusion and for assessment of epilepsy. A cranial CT scan ruled out haemorrhage or other focal lesions. Lorazepam (2 mg, IV) was administered twice with no effect on his neurological status. The patient started to sweat and became hypertensive (systolic blood pressure of 180 mmHg) and more tachycardic (heart rate of 140/min). A drug screening (Triage 8) was performed, which was positive for cocaine. Finally he admitted the cocaine consumption but refused to give further information. Benzodiazepines as well as phentolamine were given. In order to further investigate the drug intoxication a plain abdominal dual-energy CT scan was requested. Four round, hyperdense, foreign bodies were found in the transverse colon ().
An emergency laparotomy was indicated and carried out immediately. Following colotomy four packages () were removed. Thorough exploration revealed no further packages. The procedure took 60 minutes and postoperatively the patient was on observation for 24 h in the intensive care unit. The neurological signs as well as the renal insufficiency improved rapidly under conservative therapy. The further clinical course was unremarkable, and the patient was discharged six days after surgery.


A 32-year-old healthy male weighting 72 kg was stung by a scorpion on his right thumb while collecting these animals (Figure ). The accident occurred in a savanna in the Tapari community, Santarém city, Pará state, Brazil (02° 26’ 54” S; 54° 53’ 25” W) on October 17, 2013 (Figure ). Previously, the species was identified as R. amazonicus by the arachnologist who originally described it, Dr Wilson R. Lourenço [].
The victim described local pain similar to a bee or wasp sting immediately after the scorpion sting, which rapidly spread throughout his arm, together with paresthesia, remarkably numbness and tingly sensations, 30 minutes after. Subsequently, he had a slight swelling that started in the thumb and spread to the arm during the first 12 hours along with severe itching that consisted of a crawling sensation on his skin from the hand to the arm. Hence, treatment with antivenom was not necessary. Approximately 56 hours after the accident, local and systemic symptoms disappeared.


A 33-year-old Caucasian woman with a BMI of 30.5 and a documented penicillin allergy () was prepped with chlorhexidine gluconate and the following sutures were utilized: silk for drains, deep polyglactin 910, subcuticular poliglecaprone 25, and poliglecaprone 25 for the nipple. Six days later, bilateral breast swelling, blisters, and eczematous, erythematous patches near the DERMABOND PRINEO Skin Closure System were noted. Diphenhydramine did not relieve the pruritus. An oral steroid taper pack and hydroxyzine were prescribed. Although the dermatitis was not consistent with a drug rash, the cephalexin was stopped due to the risk for cross reactivity. Steroid taper was discontinued after five days due to gastrointestinal intolerance. At this time, the rash had intensified and spread from chest to arms, neck, and face. All drains and residual DERMABOND PRINEO Skin Closure System were removed; the skin was washed with saline and covered with sterile mesh gauze impregnated with petrolatum 3% bismuth tribromophenate (Xeroform) and petrolatum ointment. A steroid taper was restarted and dermatology consult was made. Two days later, the rash had greatly improved. After six additional days, there was no trace of the rash ().


A 31-year-old Caucasian woman with a BMI of 24.2 with no history of allergic contact dermatitis or drug allergy () was prepped with chlorhexidine gluconate and the following sutures were utilized: deep polyglactin 910, subcuticular poliglecaprone 25, polyglactin 910, and rapidly absorbing plain gut for the nipple. Five days later, there was no rash. Twenty-three days later, a pruritic, erythematous rash along the intramammary incision was noted. Diphenhydramine did not alleviate symptoms. The remaining DERMABOND PRINEO Skin Closure System was removed. The patient was given prednisone and scheduled with dermatology. One month later, the rash had resolved.


A 38-year-old African American woman with a BMI of 28.13 and an allergy to codeine and iodine () was prepped with chlorhexidine gluconate and the following sutures were utilized: deep polyglactin 910, deep poliglecaprone 25, and intracuticular poliglecaprone 25. The patient presented eight days later with numerous erythematous papules on the upper poles of the breasts that had presented that morning. Over-the-counter hydrocortisone cream had not alleviated symptoms. She was instructed to continue hydrocortisone. Ten days later, the rash had spread to her flexor forearms. She began a methylprednisone taper pack and the rash resolved within two days.


A 61-year-old gentleman presented to our urology outpatient department with complaints of painless progressive swelling in the perineal area for the past 2 years. The swelling was around 3 cm in size to begin with and progressively increased in size to the present size of 10 cm over the last 2 years. Patient reported difficulty in sitting due to swelling. He also developed LUTS in the form of straining at urine, poor stream, intermittency, incomplete emptying, and increased daytime frequency for the past 2 months. He also complained of increasing constipation for the past 2 months. There was no history suggestive of neurofibromatosis type 1 or type 2. His general physical examination was unremarkable. Abdominal examination revealed a palpable firm swelling in the suprapubic area of size 10 × 5 cm. Examination of the perineum showed a firm immobile nontender 12 × 10 cm lump behind the scrotum with extension towards right gluteal area (). Posteriorly the perineal lump was going up to 2 cm beyond the anal verge. On digital rectal examination (DRE), the lump had occluded majority of the rectal lumen. However, the rectal mucosa was free over the lump. Superior limit of the lump could not be felt on DRE. Prostate was not felt separately from the lump. His investigations revealed normal blood workup, with blood urea 27 mg%, serum creatinine of 0.7 mg%, and serum PSA of 0.940 ng/mL. USG pelvis and abdomen showed 12 × 10.9 cm heterogenous mass inferior to bladder with internal vascularity with anechoic areas suggestive of necrosis. Bladder was pushed anteriorly and superiorly by the mass. There were no upper tract changes. MRI abdomen showed a heterogenous solid pelvic mass on T1 image, 25 × 15 cm, which was probably arising from prostate, as prostate was not visualized separately (). Mass had central hyperintense areas on T2 image likely necrosis with increased perilesional vascularity. The mass was seen extending up to pelvic inlet superiorly and abutting the lateral pelvic wall, compressing the sigmoid colon and bladder with ill-defined planes between them (Figures and ). The fat planes with iliac vessels were well defined. Uroflowmetry showed mild obstructive pattern. Patient underwent a TRUS guided biopsy (12 cores) from the mass, which suggested a diagnosis of benign schwannoma. Thus, with a working diagnosis of giant abdominoperineal benign schwannoma, the patient was taken up for laparotomy with tumor excision. Using meticulous dissection, it was possible to safely separate the mass from iliac vessel, sacrum, small bowels, and pelvic side walls. The pelvic plexus was also well preserved. Due to very large size of the tumor and its dumbbell shape, it could not be extracted from the abdomen itself, so a perineal incision was made and the perineal part of dissection completed from below (Figures and ). But the tumor was densely adhered to the middle third of rectum and to bulbar urethra. In view of suspicious nature of the mass, the involved rectal wall and urethral wall were removed. The large gut continuity was restored using anal pull through and coloanal anastomosis. The urethral defect was repaired primarily. Suprapubic and perurethral catheters were placed and a diversion loop ileostomy to protect the anastomosis was also fashioned. Postoperative recovery of the patient was uneventful. The stoma started functioning from 2nd postoperative day and the patient was orally allowed. Per urethral catheter was removed on 7th postoperative day and suprapubic catheter was clamped. Patient voided well per urethrally and suprapubic catheter was also removed on postoperative day nine. Patient was discharged home on post op day ten with advice to follow up regularly. Subsequently final histopathology report was suggestive of low grade malignant peripheral nerve sheath tumor in view of presence of spindle shaped nuclei, occasional verocay bodies with mitotic counts of 2 to 3 per 10 HPF, and areas of infarction (Figures and ). IHC was positive for vimentin and S-100 (). All margins of specimen were free of tumor. Patient is currently doing well and is under followup in our outpatient department. He is planned for ileostomy closure.


A 46-year-old Caucasian male presented to his primary care physician with a painless neck mass. A computerized tomography (CT) scan of the neck and chest was obtained which revealed a left supraclavicular soft tissue lymph node mass. A fine needle aspiration biopsy demonstrated amyloid deposits suggesting amyloidoma. The patient was observed for a year when he noticed a slight increase in the size of the mass concurrent with an upper respiratory illness. He was referred to a hematologist at our center. The amyloidoma was subject to mass spectrometry-based proteomic analysis, which revealed this to be of AL (kappa) subtype. There was no evidence of a monoclonal protein on serum and 24-hour urine protein electrophoresis, immunofixation electrophoresis, and serum-free light chain analysis. He underwent a bone marrow aspiration/biopsy and a fat pad aspirate, both of which were unremarkable and showed no evidence of amyloidosis by Congo red staining. There was no evidence of solid organ amyloidosis based on clinical and focused laboratory and imaging studies. A CT scan of his chest, abdomen, and pelvis did not reveal any evidence of a lymphoproliferative disorder. Comparison of his previous imaging demonstrated stable 3.5 cm amyloidoma in the left supraclavicular fossa (). Because of his local symptoms, he was referred to a head and neck surgeon and underwent a complete excision of this mass which histologically showed predominant fibroadipose tissue with extensive amyloid deposition (). No evidence of an underlying clonal B cell or plasma cell population was found. No specific therapy was indicated or offered after the resection of the mass. The patient continues to remain asymptomatic with no evidence of lymphadenopathy, mass lesion, or any other systemic evidence of amyloidosis.