A 73-year-old man was seen by his primary care provider for routine follow-up of hypertension, hyperlipidemia, esophageal reflux, and generalized anxiety disorder. The patient complained of neuropathic pain in his lower extremities and right hand but denied chest discomfort, dyspnea, lightheadedness, or palpitations. He reported taking aspirin, bisoprolol, bupropion, hydrochlorothiazide, ibuprofen, omeprazole, simvastatin, tamsulosin, and valsartan. Vital signs were blood pressure of 111/69 mmHg, heart rate of 86 bpm, respiratory rate of 20, and oxygen saturation of 96%. On physical exam, he was in no apparent distress but was noted to have an irregularly irregular heart rate and rhythm, no murmurs or rales were detected, and peripheral pulses were strong and symmetrical. An electrocardiogram showed atrial fibrillation (AF) with a ventricular rate of 118 bpm without ST segment or T wave changes suggestive of ischemia (). Lab values including complete blood count, thyroid stimulating hormone, basic metabolic panel, liver panel, and fasting lipid panel were unremarkable. The patient was transferred to the emergency department (ED) for further evaluation where he remained stable except for a heart rate varying between 90 and 120 bpm. Rate control was achieved in the ED with several doses of intravenous metoprolol. Given his low risk for complications, the patient was discharged with oral metoprolol and outpatient follow-up. Subsequently, a cardiologist interviewed the patient and ordered a transthoracic echocardiogram (TTE) to evaluate for structural heart disease and a cardiac stress test to evaluate for ischemia as a possible cause for the new onset AF. The cardiac nuclear scan was negative for ischemia. However, the TTE showed normal left ventricular size and systolic function (57% EF by 2D biplane), a severely enlarged left atrium (LA volume index of 57 mL/m2), aortic sclerosis without stenosis, mild mitral regurgitation, trace tricuspid regurgitation, and left atrium with an echogenic linear structure suggestive of cor triatriatum (). Estimated right ventricular pressure or pulmonary arterial pressure was 35 mmHg. The gradient across the membrane was minimal, estimated at 3 mmHg. A transesophageal echocardiogram (TEE) was obtained in order to further evaluate the possible diagnosis of CTS, evaluate for atrial septal defect (ASD), fenestration of the fibromuscular membrane, identify the location of the pulmonary veins, and distinguish the membrane from a possible supramitral valvular ring.
A TEE with color flow and pulse wave Doppler analysis revealed cor triatriatum with a large communication between the accessory left atrium and the true left atrium (). All 4 pulmonary veins entered the accessory left atrium. There was no evidence of atrial septal defect. The left atrial appendage (LAA) was shown to be in the distal chamber, LAA opening measured 1.42 cm in width and 3.1 cm in length, and there was no evidence of thrombi in either the LAA or the left atrium. The mitral valve was structurally normal with central mild regurgitation (). The left ventricle was normal in size with preserved systolic function. Given the severely enlarged left atrium, the low-normal left atrium appendage velocities, and a CHA2DS2-VASc score of 2, the patient was asked to stop taking aspirin and was placed on rivaroxaban for stroke prevention. Given the asymptomatic nature of atrial fibrillation, low gradient across the membrane orifice (nonobstructive), and the patient's unwillingness to undergo further invasive procedures, medical management with rate control was pursued.


A 24-hour-old male was referred to the department of otolaryngology for tracheostomy due to respiratory distress and impending respiratory failure. He was born at term by elective cesarean section for prenatally diagnosed ventriculomegaly. At birth, he weighed 3.66 kg and was given APGAR scores of 7 and 8 at 1 and 5 minutes, respectively. He did require oxygen and bag mask ventilation. He was then maintained on nasal CPAP of 7 mm H2O and a FiO2 of 30%. A prenatal MRI showed he had vermian hypoplasia with associated cisterna magna and severe symmetrical ventriculomegaly with enlarged third ventricle. There were no other abnormalities related to the cardiorespiratory system or craniofacial structure.
He presented to the operating room with respiratory distress consisting of tachypnea and retractions despite the above mentioned ventilatory support. On physical exam he had severe microstomia and retrognathia (). He also had a cleft of the second palate. His lungs were clear to auscultation but as mentioned previously he was tachypneic. After placement of standard monitors, he underwent mask induction with oxygen and sevoflurane. Mask ventilation was a challenge, even performed by an experienced anesthesiology attending, due to the retrognathia without any translocation of his mandible to aid in lifting soft tissue. The patient was mask ventilated with an endoscopy mask, which allows for continued positive pressure mask ventilation while providing a site for flexible fiberoptic intubation. The mask has a flexible membrane that a fiberoptic scope can pass through while still maintaining a seal on the patient's face. After instillation of oxymetazoline HCl into the nares, flexible nasolaryngoscopy was performed to evaluate the anatomy, which showed significant tongue base prolapse causing retroflexion of the epiglottis. No other airway abnormalities were noted further in the larynx or trachea. The scope was then removed from the patient and a 3.0 mm ID uncuffed endotracheal tube was then placed over the flexible scope. The scope loaded with the endotracheal tube was maneuvered back into the trachea. Once the appropriate tracheal anatomy was identified the endotracheal tube was advanced into the trachea over the flexible scope. After confirmation of end-tidal CO2 and adequate ventilation in both lungs the endotracheal tube was secured. The case then continued with an uneventful tracheostomy and return to the NICU.


On December 25, 2012, a 51-year-old female presented with intermittent chest pain that had been apparent for one year. The physical examination was unremarkable. The patient’s performance status was 1 according to an Eastern Cooperative Oncology Group (ECOG) evaluation ().
Laboratory investigations revealed a normal complete blood cell count, coagulation routine and serum biochemical profile. The thoracic computed tomography (CT) scan revealed a huge mass in the posterior mediastinum, with invasion of the esophagus, descending aorta and right pulmonary artery (). On December 31, 2012, a biopsy of the mediastinal mass was performed by thoracoscopy, during which an irregular posterior mediastinal mass measuring ~8×8 cm was located under the arch of the azygos vein. The final pathology showed a malignancy of small round cells, which was consistent with an Ewing’s sarcoma/PNET (). The immunohistochemical results demonstrated a Ki-67 of 20% (), positivity for cluster of differentiation (CD)99 () and synaptophysin (), partial positivity for CD56, neuron-specific enolase and S-100, and negativity for CD1a, Wilms tumor 1 protein, octamer-binding transcription factor 3/4, vimentin, epithelial membrane antigen, cytokeratin (CK)5/6, desmin, thyroid transcription factor-1, inhibin A, CD34, terminal deoxynucleotidyl transferase, CK and leukocyte common antigen. The following abdominal CT, brain magnetic resonance imaging and bone scan excluded the possibility of metastasis.
The patient was administered four cycles of dacarbazine and pirarubicin chemotherapy. One cycle consisted of 300 mg dacarbazine on days 1–5 and 40 mg pirarubicin on days 1–2, for 21 days (patient’s body surface area, ~1.6 m2). Following one cycle of chemotherapy, the tumor rapidly decreased in size () and the patient’s discomfort disappeared. The thoracic CT revealed that the tumor became even smaller after three cycles compared with one cycle (). Minimal residual tumor remained subsequent to four cycles of chemotherapy (). Radiotherapy was then administered to the tumor bed at a total dose of 54 Gy/30 fractions over 42 days (between May 10, 2013, and June 21, 2013) and the recorded side-effects, such as esophagitis and leukopenia, were mild.


The present study reports the case of a 34-year-old female (gravida 1, para 0, aborta 1) who underwent laparoscopic myomectomy for uterine fibroids at the Second Hospital of Jilin University in August 2009. During the surgery, a myoma that was 5 cm in diameter was identified in the posterior uterine wall and was removed using a morcellator. The post-operative pathology report determined that the uterus was rich in leiomyoma cells.
In May 2012, the patient underwent an exploratory laparotomy due to relapse of the uterine fibroid. During the surgery, a myoma that was 10 cm in diameter was identified at the uterine bladder peritoneal reflection, numerous unequally sized leiomyoma tubercles were identified on the uterine surface and a leiomyoma tubercle that was 2 cm in diameter was identified on the surface of the right fallopian tube. The mass was removed from the uterine bladder peritoneal reflection and frozen section analysis determined a diagnosis of uterine leiomyoma, therefore, a myomectomy was performed. Post-operative pathology determined that the lesion was a leiomyoma and immunohistochemical staining resulted in positivity for α-smooth muscle antibody (α-SMA), h-caldesmon and desmin, with a Ki-67 labeling index of 5%.
In September 2013, a gynecological ultrasound revealed a 5.0×5.0-cm mass in the left lower abdomen. As the patient presented with no specific symptoms, the patient decided to continue with follow-up examinations only. The patient was hospitalized again on 6 June, 2014, following identification of a bilateral adnexal cyst in a patient review. A gynecological ultrasound determined that the endometrium measured 0.5 cm and that the uterus and ovaries were of normal size. However, a heterogeneous hypoechoic mass was identified on each ovary, measuring 5.2×4.3 cm and 3.7×2.3 cm, respectively, and exhibiting a regular form with clear boundaries. Furthermore, color Doppler flow imaging revealed no abnormal blood flow signals and the mass activity was good under gynecological examination, demonstrating no tenderness. No abnormalities were identified in the liver, gall bladder or spleen ultrasound examinations, heart and lung assessments or gastrointestinal endoscopy. In addition, a cancer antigen 125 level of 9 U/ml (normal range, <35 U/ml), a human epididymis protein 4 level of 60.36 pM (normal range, <150 pM) and an α-fetoprotein level of 3.27 IU/ml (normal range, <10 IU/ml) were recorded.
Based on the clinical manifestation and auxiliary examinations, ovarian neoplasm was considered as a possible diagnosis, therefore, an exploratory laparotomy was performed. During the surgery, concentrated myoma tubercle-like cysts were identified on the surface of the intestine and mesentery, with sizes ranging from 0.4×0.3×0.3 cm to 5.0×4.0×3.0 cm (). Additionally, a 1.5-cm diameter endometriotic cyst was identified on left ovary and a 1-cm endometriosis lesion was identified on the left posterior uterosacral ligaments. The cysts on the surface were partially removed. The frozen section indicated a diagnosis of mesenchymal tumors, however, intestinal leiomyoma could not be excluded. During the surgery, the following diagnoses were made: Intestinal leiomyoma, endometriotic cysts on the left ovary and pelvic endometriosis. The majority of the leiomyoma on the intestine and mesentery was removed, however, the myomas were compact and therefore, not all of them could be removed. The endometriotic cysts on the left ovary and the pelvic endometriosis lesion were removed concurrently. Post-operative pathology determined a diagnosis of leiomyomatosis peritonealis disseminate, with occasional mitosis and no necrosis (). Immunohistochemical staining revealed the resected tissues to be positive for h-caldesmon, α-SMA, desmin, estrogen receptor and progesterone receptor (PR) (), and negative for cluster of differentiation (CD)117, discovered on gastrointestinal stromal tumor-1, CD34, neuron-specific enolase and S-100, with a Ki-67 labeling index of 1%. The post-operative procedure was successful and the patient was monitored by follow-up every six months. Follow-up is scheduled for five years, after which gynecological sonography examination will be performed annually. In October 2014, a gynecological sonography examination revealed no abnormalities and at the time of writing, the patient remains alive and well.


A young man aged 18 years was referred to our center for laterocervical lymphadenopathy and anemia. Peripheral blood smears analysis showed the presence of blast cells (19%). Bone marrow aspirate and biopsy confirmed diffuse blast infiltration (90%), characterized by a mixed-cell population of large and small blasts (Figure A-C). Immunophenotype analysis showed that blast cells were HLA-DR+, CD4+ CD5+, CD7+, cyCD3+, CD13+, CD33+, CD34+, MPO+, CD117+, CD56+. Conventional cytogenetic analysis of G-banded BM metaphase cells showed the following karyotype: 46,XY,?t(5;14)(q11;q11),?inv(6)(p11;p21)[9]/46,XY,idem,del(11q)[8]/46,XY[3]. Molecular analysis showed the occurrence of the FLT3 internal tandem mutation and the absence of the NPM1 mutation and BCR-ABL1 fusion gene. A diagnosis of T/My MPAL NOS was made according to the 2008 WHO criteria. The patient was treated with chemotherapy according to the Medical Research Council (UKALL XII)/ Eastern Cooperative Oncology Group (E2993) chemotherapy regimen []. After induction treatment the patient obtained complete hematological remission, which persisted during the consolidation and maintenance therapy. At these time points bone marrow immunophenotype analysis did not show the presence of blast cells. After sixteen months from the diagnosis, the patient is doing well and is still in hematologic, cytogenetic and molecular remission, defined by the ADAMTS2 gene expression analysis.
To confirm the conventional cytogenetic data regarding the t(5;14)(q11;q11) rearrangement, reiterative Fluorescence in situ hybridization (FISH) experiments with specific bacterial artificial chromosome (BAC) clones were carried out. FISH analyses were performed on BM samples, using BAC selected according to the University of California Santa Cruz database (UCSC ; Feb. 2009 release). Chromosome preparations were hybridized in situ with probes labeled by nick translation, as previously described []. FISH cohybridizations were done by chromosome walking, employing a total of 10 and 8 selected clones belonging to chromosomes 5 and 14, respectively (Table ). According to the FISH pattern, a complex mechanism of double insertion with a concomitant duplication of the chromosome 5q pericentromeric region was hypothesized (Figure ). In detail, chromosome 14 showed three different breakpoints: BAC clone RP11-990 K12 (chr14:22,860,409-23,039,541) was the insertion site of the chromosome 5 segment as it produced a signal on normal chromosome 14 and a splitting signal on der(14) (Figures and A), whereas the region included between BAC clones RP11-696 J16 (chr14:23687161–23889944) and RP11-634B2 (chr14:99,566,527-99,778,328) was inserted in chromosome 5, as both clones showed a signal on normal chromosome 14 and a splitting signal on der(14) and der(5) (Figure ). As for the chromosome 5 breakpoints, the region included between BAC clones RP11-641 M21 (chr5:178,525,062-178,697,496) (Figure A) and RP11-1150B10 (chr5:49406372–49441108) was inserted on der(14) as both clones hybridized on chromosomes 5, der(5) and der(14). Moreover, a duplicated region spanning from BAC RP11-1079 J18 (chr5:54403379–54555179) up to the centromere was identified on der(5). The insertion breakpoint of the chromosome 14 segment into chromosome 5 was mapped next to the chromosome 5 telomeric region between BAC clones RP11-834P23 (chr5:180585112–180782496) and RP11-242C5 (chr5:180720141–180862796) (Figure ).
After the achievement of complete hematologic remission, FISH analysis no longer revealed the presence of the chromosomal rearrangement. The lack of material precluded the possibility of investigating the other chromosomal abnormalities pointed out by the karyotypic analysis.
According to the UCSC database, the ADAMTS2 and TRD genes were mapped in correspondence with the chromosomes 5 and 14 breakpoints, respectively. Therefore, as a consequence of the complex chromosomal rearrangement, the ADAMTS2 gene was juxtaposed to the TRD locus on the der(14) chromosome. In particular, the FISH pattern data suggested that the breakpoint inside the ADAMTS2 gene probably maps between exons 3 and 4 (Figure B). Bioinformatic analysis was performed by querying the Conserved Domain Database ( ) for the annotation of functional domain proteins encoded by the coding sequence of the ADAMTS2 gene. This analysis clarified that the exons 1–3, retained on der(5), code for the N-terminal propeptide domain of the metallopeptidase ADAMTS2; moreover, exons 4–22, transferred on der(14), encode for catalytic, disintegrin-like, cysteine-rich, spacer, 4 thrombospondin and procollagen N propeptidase domains (Figure B).
To verify the dysregulated expression of the ADAMTS2 gene portion juxtaposed to the TRD locus on der(14), quantitative real-time PCR (qRT-PCR) analysis was carried out on the sample at diagnosis. Total RNA derived from BM cells was reverse transcribed into cDNA using the QuantiTect reverse transcription kit (Qiagen, Chatsworth, CA, USA). qRT-PCR experiments were carried out by using the LightCycler 480 SYBR Green I Master mix on the LightCycler 480II (Roche Diagnostics, Indianapolis, IN, USA). All samples were run in triplicate as technical replicates. The β-glucuronidase (β-GUS) gene was employed as endogenous control and a commercial pool of cDNA derived from healthy individuals BM cells (Clontech, US) was used as calibrator. Gene expression level was also compared to two pools of three normal karyotype (NK) AML and acute lymphoblastic leukemia (ALL) cases, respectively. Bone marrow samples from these patients were retrospectively obtained from the hospital archive. For ADAMTS2 gene expression analysis, primers specific for exons 6 and 7 were selected according to the Primer3 software () (forward primer: GCCACGATGAATACCACGAT, reverse primer: GGTGACAGGAGCATAGCCTTG). qRT-PCR experiments showed a higher expression level (61-fold change) compared to that of healthy bone marrow, NK-AML, and NK-ALL pools. qRT-PCR analysis was later performed at the time of complete hematologic and cytogenetic response and during the follow-up, revealing that by that time the ADAMTS2 gene expression was not different from that observed in control sample (Figure ).


In March 2003, a 23-year-old Arab ethnicity Kuwaiti male with a strong family history of dilated cardiomyopathy presented to a specialized neurology hospital with dizzy spells and feet parasthesia. He was given intravenous methylprednisolone for 3 days for probable multiple sclerosis and was booked electively for a magnetic resonance imaging (MRI) of the brain. On March 23rd 2003, he had a witnessed sudden cardiac arrest and suddenly collapsed when he was at an automated banking teller machine. The paramedic personnel were at the scene within 5 minutes of the call, endotracheal intubation was carried out as well as an intra-tracheal atropine and adrenalin was given at the scene. A cardiac monitor was attached and revealed ventricular fibrillation (Figure
), and thus was electrically cardioverted 3 times (200 J, 300 J and 360 J) until reverted to sinus rhythm. The resuscitation procedure including the transit time to hospital was around 30 minutes. On arrival to intensive care unit (ICU), he had a heart rate of 150 beats per minute and a blood pressure of 110/70 mm/Hg. Electrocardiography (ECG) revealed sinus rhythm with incomplete Left bundle branch block (LBBB) and non-specific ST-T wave changes (Figure
). A transthoracic echocardiography showed a mildly dilated left ventricular (LV) with severe global LV systolic dysfunction with an estimated Left Ventricular Ejection Fraction (LVEF) of 20 to 25% (Figure
). An echocardiogram was done 6 months prior to the hospital admission and LV systolic function reported to be normal. During his ICU stay, he had recurrent convulsions, which were controlled with epanutin and clonazepam. Computed tomography scan (CTS) of the head showed a small infarct (probably embolic) in the right centrum semiovale adjacent to the body of the right lateral ventricle. An electroencephalograph (EEG) was performed and this revealed diffuse cortical dysfunction with no epileptic discharge. He had a battery of laboratory investigations including liver function test, renal function test, complete blood count and thyroid function test and these were all within normal limits. Later on, he had a transient rise in liver enzymes and this was found to be secondary to hepatic hypo-perfusion (hepatitis viral screening, auto-immune screening and serum copper tests were all normal). Eventually a tracheostomy was performed and a nasogastric tube fed him. His neurological condition showed a slow but steady improvement over a course of 3 months and regained consciousness, with spontaneous breathing and thus the tracheostomy was closed. However, he was left mentally handicapped with sphincteric incontinence and was referred to the rehabilitation hospital for aggressive physiotherapy. During his follow up, he was treated medically with anti-failure and antiepileptic drugs (digoxin, revotril, epanutin, zestril, lasix, zantac and amiodarone). However, he continued to show non-sustained ventricular tachycardia on a 24-hour holter monitor (Figure
). Eventually, he had an automated implantable cardioverter-defibrillator (AICD) inserted in 2004 and his functional status significantly improved and he is still alive. He developed amiodarone induced thyroiditis with hyperthyroidism, Thyroid test, FT4 = 15.29 (Normal = 5.69-13.44) and Thyroid stimulating hormone, TSH = 0.03 (Normal = 0.43-4.1) which was proven by a positive thyroid scan. His thyroid function normalized following the discontinuation of amiodarone. Investigations of his family history revealed that his father was known to have dilated cardiomyopathy (DCM) and was treated with AICD, but had a sudden cardiac death a few years ago while he was waiting for cardiac transplantation. In addition, two of his sisters had pacemakers inserted, and one of his paternal uncles died suddenly at the age of 25 years. Family pedigree is shown in (Figure
).


A 58-year-old Native American female presented to the emergency department with a 3-month history of progressive shortness of breath, orthopnea, and dyspnea upon exertion. Initially, the patient experienced only mild exercise intolerance but by the time of her presentation to the emergency department (ED), she noted that she was becoming winded after only a few steps. The patient's orthopnea had become so intolerable that she now slept upright in a recliner every night. Associated symptoms included paroxysmal nocturnal dyspnea and a non-productive cough. The patient denied chest pain, lower extremity edema, weight loss, or episodes of syncope. The patient had seen her primary care physician several times for these symptoms. Her doctor had performed a chest x-ray, diagnosed bronchitis, and arranged a sleep study that had not yet been performed. The patient's only known medical problem was gastroesophageal reflux disease for which she was taking omeprazole. The patient had no surgical history, medication allergies, and drank no alcohol and did not smoke or use illicit substances.
Upon examination, the patient was not in acute distress. Vital signs including blood pressure, temperature, heart rate, respiratory rate, and pulse oximetry were all within normal limits. The cardiovascular exam demonstrated a regular rate and rhythm with no audible murmurs, gallops, or rubs. There was no jugular venous distension. There was trace lower extremity edema at the right pretibial region. Lung sounds were clear bilaterally, and there was no respiratory distress. The remainder of the physical exam was normal. Bedside echocardiogram showed a grossly dilated right ventricle, non-collapsibility of the right ventricle throughout the cardiac cycle, and bowing of the intraventricular septum into the left ventricle (Figure ).
Laboratory workup included a metabolic panel and a complete blood count that were unremarkable, as well as a D-dimer which was elevated at 1,345 ng/ml. The patient's electrocardiogram revealed T wave inversions in leads V1 through V3 with extreme axis deviation. Chest x-ray demonstrated a small right pleural effusion. Computed tomography angiogram (CTA) of the chest was ordered to rule out pulmonary embolism (Figure ). CTA was negative for pulmonary embolism but did demonstrate a 6.3 × 4.3 cm filling defect of the entire left atrium that was suspicious for cardiac tumor. A right pleural effusion was also confirmed.


A 49-year-old Caucasian woman with a 26-year history of HIV-HCV co-infection was admitted to an Infectious and Tropical Diseases Department in Marseille, France in February 2014 for significant influenza-like syndrome in a context of repetitive exacerbations of chronic obstructive pulmonary disease. Pulmonary auscultation found diffuse wheezing. Significant biological parameters included a C-reactive protein level of 57mg/L, lymphocytes of 1.6G/L including 237/mm3 T4 lymphocytes, a HIV viral load of 1.6 log and a HCV viral load of 6 log. Her chest radiography was normal. Reverse-transcriptase polymerase chain reaction (PCR) of her nasopharyngeal aspiration confirmed influenza A H1N1. At a 6-month follow-up, her clinical outcome was favorable with initial supportive treatment only. Three sputum specimens lacked acid-fast bacilli (AFB) after Ziehl–Neelsen staining and microscopic observation but one grew AFB after 21-day incubation in MGIT (Becton Dickinson, Le Pont-de-Claix, France) at 37°C in a 5% carbon dioxide atmosphere. After subculture on Coletsos (bioMérieux, La-Balme-les-Grottes, France), the isolate was deposited in our collection (CSUR P1344) and tentatively identified by using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF-MS), the bioMérieux extraction protocol, a MicroFlex™ mass spectrometer (Bruker Daltonics, Bremen, Germany) and the Bruker MALDI Biotyper procedures as previously described []. A reproducible profile (Figure A) yielded a 1.56 log score with M. europaeum DSM 45397T listed in the Bruker Mycobacterium Library 1.0 and 2.0 databases. A 1,482-bp 16S ribosomal ribonucleic acid (rRNA) gene sequence (GenBank LN680852) yielded 99% similarity with both Mycobacterium parascrofulaceum ATCC BAA-614 (GenBank GQ153273) and M. europaeum DSM 45397T (GenBank HM022196), two species known to share almost identical 16S rRNA gene sequence []. Partial rpoB PCR-sequencing [] yielded a 725-bp sequence (GenBank LK021335) exhibiting 100% similarity with M. europaeum strain DSM 45397T (GenBank HM022215; Figure B).
Here, one M. europaeum isolate was made from broth culture whereas the eight previous isolates have been made from agar or egg-based solid medium [, ], illustrating the capability of automatons routinely used in laboratories, to detect the growth of M. europaeum. Starting from colonies, this isolate was identified by MALDI-TOF-MS and its profile made freely available at Méditerranée Infection Foundation URMS Database [] in order to complement the sole profile (M. europaeum DSM 45397T) commercially available.


In 2010, a 26-year-old Moroccan man was referred to our oncology and radiotherapy center for management of recurrent tumor of his right subscapularis. No pathological medical or surgical history was reported and no alcohol or tobacco habits. One year before, he had presented to his surgeon with a subscapularis tumor which had appeared gradually and increased in size during 6 months without associated pain or other symptoms. A physical examination reported a mass size 10cm, palpated in his right subscapularis region. A first resection was realized. Histopathological analysis demonstrated spindle-shaped cells with no identifiable nuclear pleomorphism or mitotic activity. There was no necrosis. A benign tumor with spindle-shaped cells is suspected. On immunohistochemical analysis, the cells stained positive for anti-smooth muscle actin, favoring a smooth muscle origin. The diagnostic of AF was retained. Unfortunately, the mass recurred within a period of 10 months and continued to increase in size reaching 13cm on a computed tomography scan and magnetic resonance imaging (MRI; Figure ) without regional structures involved (bone, muscle or vascular). A second tumor and lymph nodes resection were performed by another surgeon who reported “a very hard resection without cleavage plane”. Histological analysis regarding two fragments size 4×3cm and 14×10×8cm led to a conclusion of AF tumor; hormonal receptor was not found. The resections of margins were narrowed and lymph node resections regarding four nodes were not involved. At assessment in our oncology and radiotherapy center after this second resection, his World Health Organization performance status was zero, weight 84kg, height 177cm. There was no induration or palpable mass. A MRI performed after the repeat surgery was normal. During follow up, a recurrence was suspected 1 year after the second resection. An axillary MRI (Figure A and B) was performed and a large mass was found in the last tumor site, measuring 12.6cm involving deltoid muscles and extending to axillary area. A third resection was realized and a histopathological examination showed the same AF tumor with a low positivity of c-KIT. Margins were narrowed. Post-surgery MRI (Figure C and D) was performed and showed a right axillary residual tumor measuring 2.1cm. Diagnosis of recurrent AF tumor with positive c-KIT and without hormonal receptor was retained. The decision to administrate imatinib 400mg daily by mouth was taken. His follow up was performed by clinical examination and was normal during 6 months. When we stopped imatinib administration during 1 month, the tumor grew to a size of 4cm. Retreatment with imatinib was decided. Clinical and MRI evaluation were performed regularly and they reported a stable tumor. The last MRI (Figure A) was performed in January 2014; it showed a stabilized tumor and many intratumoral calcifications. We reported no side effects regarding Common Terminology Criteria for Adverse Events. Currently he is feeling well but he continues to have ankylosis (90°) in his right upper limb due to the particular localization of AF and surgery (Figure B).


A 50-year-old man with a history of hypertension, hyperlipidemia, crack-cocaine abuse, and two prior ischemic strokes (2004, 2011) characterized by right-sided weakness with no residual deficits presented to a large urban hospital with left-sided arm weakness, left-sided leg weakness, and mild slurring of speech. Patient had received tPA when he presented with his stroke symptoms in 2011, without any adverse events. He was last seen normal four hours prior to arrival. On presentation he had a National Institute of Health Stroke Scale (NIHSS) of 5, left-sided facial droop, drift and ataxia in both his left arm and left leg. His blood pressure was 175/103mmHg, a pulse of 94beats/minute, a temperature of 37.2°C and a right atrium oxygen saturation of 98%. A computed tomography of the head was negative for any acute hemorrhage. Patient was supposed to be on an angiotensin- converting enzyme (ACE) inhibitor but had been non compliant with his medications for the last three months.
Per protocol he was evaluated by a neurologist and received intravenous (IV) tPA 90mg, 10% as bolus and the remainder as an IV drip over the following hour. His weakness began to improve. As the tPA infusion was ending, the patient started complaining of tongue swelling and his voice was noticed to be altered. He did not have any shortness of breath. On examination the patient had a significant amount of left-sided dorsal and ventral tongue swelling, which abruptly ended at the midline (). The posterior pharynx, uvula, soft palate, floor of mouth did not have any swelling. Otolaryngology was consulted and performed a bedside flexible laryngoscopy. He did have some mild interarytenoid, arytenoid, and superior aspect of esophageal inlet swelling. The vallecula and epiglottis were within normal range. He was started on 10mg of dexamethasone IV, 20mg of famotidine IV, and 50mg of diphenhydramine IV. He remained non-intubated and was transferred to the neurologic intensive care unit. Magnetic resonance imaging/angiography demonstrated restricted diffusion in genu and posterior limb of right internal capsule with some extension into the right cerebral peduncle, mild intracranial atherosclerosis of posterior cerebral arteries and a hypoplastic right vertebral artery. His swelling and dysphonia resolved completely within 48 hours (). Afterwards, his hospital course was uncomplicated and he was discharged after five days total to acute rehabilitation on aspirin and pravastatin. His NIHSS remained five; however, his left-sided strength had improved. At follow up one month later he was improved, subjectively reporting to be at 60% of his baseline. On examination his speech was fluent with no dysarthria or aphasia, no tongue swelling, strength was 5/5 in all four extremities, although he did have mild dysmetria on the left during finger-to-nose.


An 84 year-old female presented to the ED with shortness of breath for the past two days. She was dyspneic on arrival, with noted use of accessory muscles and difficulty answering questions. Her presenting vitals were blood pressure 76/59, respiratory rate 36, oxygen saturation 75% on a non-rebreather mask, a temperature of 100.2°F, and a pulse of 65. Due to her severe respiratory distress and hypoxemia, she underwent endotracheal intubation as she became progressively unresponsive. The working diagnosis was septic shock, so the patient was started on intravenous antibiotics and underwent aggressive fluid resuscitation. A vasopressor, norepinephrine, was empirically initiated.
Despite the vasopressor, the patient continued to deteriorate. A bedside abdominal ultrasound performed by the emergency physician demonstrated a dilated inferior vena cava (IVC) with minimal respiratory variation. Bedside echocardiography showed no evidence of pericardial effusion, however, a free-floating clot was visualized in the right atrium and ventricle (). The right ventricle was dilated and the left ventricle displayed wall hypertrophy and poor contractility ( and ). A presumptive diagnosis of massive pulmonary embolism was made based upon these findings.
Due to the patient’s hemodynamic instability, t-PA was administered after consultation with her family. Subsequent to t-PA administration, the patient’s condition began to improve. She was admitted to the ICU, continued on heparin, and bridged to Coumadin. Her post-t-PA echocardiogram showed complete resolution of the clots, however, right ventricular dilation persisted. The patient continued to improve and was discharged to a skilled nursing facility on hospital day 17.


Patient 1 is a 28-year-old right-handed woman with a long history of complex partial seizures secondary to temporal lobe epilepsy (TLE). Attacks were often precipitated by vigorous exertion, particularly on the exercise bicycle at the gym. The severity of events would range from isolated auras of déjà vu and gustatory hallucination to loss of contact with manual and oral automatisms. Although seizures were not exclusive to exercise, the events were reliably induced with exertion. This was recorded during video-EEG monitoring (see and the attached video online). As seizures were quite refractory to antiepileptic drugs (AEDs), and EEG, MRI, and PET scan all corresponded to right anterior temporal seizures, the patient underwent a right temporal lobectomy. Unfortunately, the postoperative outcome was not favorable, and she continued to have seizures including exercise-induced events. Seizure freedom was achieved, however, when lacosamide was added to her medication regime, which included topiramate and oxcarbazepine. This included seizure freedom during high levels of exercise.


Patient 2 is a 49-year-old right-handed man with focal seizures secondary to cortical dysplasia of the left superior temporal gyrus. Seizures would most frequently occur during exercise, particularly running, when most of his secondarily generalized seizures would occur. Seizures would only occur in the latter part of his runs, after several kilometers, when he was especially exerting himself. As the patient's seizures were refractory to four AEDs, with several other agents trialed in the past, surgery was discussed but not performed because of concerns regarding speech areas in the brain being affected. He stopped running entirely five years ago up to the present. This resulted in a marked reduction in seizures, with only one convulsive episode annually at the most and infrequent minor seizures. Although it was against medical advice, the patient started swimming to maintain some form of exercise. Interestingly, this did not precipitate any increase in seizures as was noted with his running.


Patient 3 is a 63-year-old right-handed man, formerly a professional footballer, who was referred to our epilepsy clinic with a history of left hippocampal sclerosis, which was surgically resected 15 years earlier. Although seizure frequency decreased as a result, the patient's epilepsy remained quite refractory to treatment with four AEDs. Although some seizures would occur from sleep, the patient identified physical exertion as another clear precipitant. This was fairly reproducible, and seizure control improved dramatically when he avoided any vigorous exercise. Gentle walking was not associated with any issues. Retrospectively, the patient felt that exercise had been a part of the pattern for years, even prior to his surgery. Interestingly, in addition to his typical seizures, exercise could induce a bout of severe depressive feelings. He also found that there was a family history of depressive symptoms provoked by exercise. On review by a neuropsychiatrist, it was felt that these latter symptoms actually represented part of a postictal psychosis, and some improvement was made with the introduction of olanzapine.


Patient 4 is a 48-year-old right-handed woman with temporal lobe epilepsy with bitemporal independent seizures documented on video-EEG monitoring. Events followed an encephalitic illness of unclear etiology several years prior and were resistant to polytherapy with four AEDs, with seizures occurring at least weekly. The patient noted that they were much more likely to occur while playing her weekly game of netball in the evenings.


Patient 5 is a 50-year-old right-handed woman with Rasmussen's encephalitis, with progressive speech disturbance and deafferent right hand, as well as focal seizures involving the right hand and face. Brain MRI showed marked focal atrophy of the left frontal and temporal lobes. Simple partial seizures were noted by the patient to occur predictably whenever she went line dancing. After a trial of low-dose clonazepam prior to dancing showed no significant improvement and resulted in excessive sedation, the patient was forced to cease this activity.


Patient 6 is a 74-year-old right-handed man with long-standing temporal lobe epilepsy with PET scan showing bitemporal hypometabolism and video-EEG monitoring showing bitemporal seizure origin but more frequent on the left. Seizures would more often than not occur while riding his bicycle, and despite being advised not to cycle, the patient continued to do so with several accidents as a result.


Patient 7 is a 44-year-old right-handed man with intractable complex partial seizures with frequent secondary generalization due to left hippocampal sclerosis. This was refractory to medical and surgical treatment. Major seizures occurred weekly, most often with exercise, particularly at the gym when lifting heavy weights. Thankfully, he would get a prolonged warning of rising epigastric sensation, which would prompt him to stop what he was doing and avoid injury. A small dose of clonazepam was trialed to be taken prior to physical exertion with some effect.


Patient 8 is a 27-year-old right-handed woman with long-standing focal seizures, which began during an admission with an encephalitic illness in childhood. Events were stereotyped, with nausea followed by right arm tingling and occasional secondary generalization. Symptoms were noted to be more frequent during intensive physical exertion, particularly during martial arts training. Brain MRI showed extensive left temporal lobe atrophy with involvement of mesial temporal structures, and PET imaging showed corresponding hypometabolism. Depth electrodes confirmed that seizures originated from the left hippocampus, and temporal lobectomy was performed. Unfortunately, there was no improvement in her symptoms, and she remains on five antiepileptic agents.


Patient 9 is a 31-year-old right-handed man with ten years of focal seizures that would rapidly generalize, with the majority of events noted to occur while cycling. Video-EEG monitoring revealed a left temporal focus, but MRI was unremarkable. Positron emission tomography evaluation showed hypometabolism in the left anterior and mesial temporal cortex, and the patient proceeded with temporal lobectomy. Similar to the previous patients in this case series, this provided little improvement in seizure control.


Patient 10 is a 45-year-old right-handed man with seizures that occurred soon after a diagnosis of a venous sinus thrombosis a few years earlier. The events consisted of a feeling of déjà vu and then global dysphasia with retained awareness. On rare occasions, they would secondarily generalize. The patient noted that his seizures were more likely to occur during intense aerobic exercise. This included both running and cycling, and his seizures would occur at the end of his training or in the first few seconds after stopping. He also noted that events could be induced even when only thinking about exercise. Routine EEG was unremarkable. Magnetic resonance imaging did not show any intracerebral injuries that could relate to the previous sinus thrombosis but did show mild volume reduction of the left anterior temporal lobe structures. Positron emission tomography showed corresponding left anteromesial temporal hypometabolism. Some control was achieved on a combination of lamotrigine and levetiracetam, but exercise and thinking about exercise would still provoke seizures.


A 31-year-old multigravid woman with a history of a prior low transverse cesarean delivery presented to a family planning clinic at 16 weeks gestation for elective termination of pregnancy. Her obstetric history was significant for a prior cesarean section performed six years prior. Her past medical and surgical history was otherwise unremarkable. A transabdominal ultrasound performed on the day of admission confirmed a fetus of 16 week gestation with an anterior placenta. In order to further delineate the relationship between the uterine scar and the placenta, an abdominal MRI was performed. The MRI demonstrated an unclear uterine scar near the placental implantation site. The patient was counseled on risks associated with abnormal placentation and was offered uterine artery embolization, dilation and evacuation and hysterotomy. The patient, however, decided to proceed with induction of labor for termination. The termination of her pregnancy was approved by the ethics committee of Zhejiang Provincial People’s Hospital. A written informed consent was obtained from this patient before the procedure.
Termination was performed with a loading dose of 50 mg of oral mifepristone (RU486) followed by 25 mg administered every 12 hours until a total of 300 mg had been administered. Following completion of mifepristone, misoprostol was administered at a dose of 200 ug orally every hour. The patient received a total of 1200 ug of misoprostol. She had an unremarkable vaginal delivery with spontaneous delivery of the placenta. Vaginal bleeding was minimal. Four hours after the procedure the patient developed a fever of 38.5°C, but denied further symptoms. The patient’s temperature resolved spontaneously by the next morning without intervention. On post procedure day 1, the patient complained of abdominal distention and dysuria. A urethral catheter was inserted and 800 ml of clear urine was drained. A pelvic ultrasound was performed and demonstrated a 32 x 25 mm abnormal radiodensity at the anterior uterine wall with an unclear boundary at the anterior cervical wall, concerning for retained products of conception versus placenta accreta. Methotrexate was administered. Given the idiopathic urinary retention and abnormal findings on ultrasound, laparoscopic exploration was performed to evaluate for placental growth into in bladder.
At the time of diagnostic laparoscopy, no hemoperitoneum was noted; however, there were significant adhesions between the omentum and anterior abdominal wall. Unexpectedly, a uterine rupture at the lower uterine segment was observed when the pelvic organs were restored to their normal anatomy. There was a 1.5 cm length anterior wall uterine rupture along the left portion of the previous scar (Figure ). Moreover, a portion of the placenta was found to be adherent to the uterus at the site of the rupture when the omentum was removed (Figure ). The bladder was firmly adherent to the uterine scar and rupture, and urology was consulted to assist in separating the bladder from the uterus. Dilatation and curettage was performed under direct laparoscopic visualization and the specimens were confirmed to be placenta by postoperative pathology examination (Figure ). An ultrasound was performed to ensure no residual placental tissue was present. The uterine dehiscence was repaired laparoscopically. The entire procedure was performed using minimally invasive techniques.


The patient is a 58-year-old obese male whose past medical history is significant for laparoscopic cholecystectomy in 2012, nephrolithiasis, spinal osteoarthritis, and exploratory laparotomy for a gunshot wound and bullet fragments who presented with right flank pain since cholecystectomy. The pain was continuous but waxed and waned, reaching levels the patient described at times as eight out of ten on a ten-point Likert scale. He had no prior episodes of such pain. He received some relief from naproxen and hydrocodone/acetaminophen that he takes for osteoarthritis. He denied that the pain interferes with daily life but has been on leave from his job as a construction worker due to chronic osteoarthritic back pain. He denied nausea, vomiting, diarrhea, dysuria, hematuria, dyschezia, and bloody or tarry stool.
The patient's medical history includes hypercholesterolemia, hyperlipidemia, heart palpitations, anxiety, and headaches. His regular medications are aspirin, fenofibrate, gabapentin, and esomeprazole. He denies alcohol use but smokes twenty small cigars per week and marijuana regularly.
His physical examination was notable for right flank tenderness without rebound. Additionally, he had a painless, reducible bulge in his left flank suggestive of a port site hernia from his prior laparoscopy.
Laboratory studies showed bilirubin, liver function tests, and alkaline phosphatase levels within normal limits. Urinalysis showed no hematuria or abnormalities. Computed tomography scanning from an outside institution revealed hyperintensities between the liver and right abdominal wall with surrounding streakiness suggestive of inflammation. Ultrasound of the biliary tree showed no distension or retained gallstones.
Diagnostic considerations included irritation from dropped gallstones in the perihepatic space, nephrolithiasis, and somatization ().
Hypothesizing that the stones were the cause of the patient's pain, we performed an explorative laparoscopy to retrieve the stones and a left flank incisional hernia repair. The patient had extensive omental adhesions to the abdominal wall. Exposure of the lateral edge of the right liver revealed several yellow gallstones. We removed every stone that was visualized intraoperatively; they were 4.4 cubic cm in aggregate volume. The patient reported reduction of right upper quadrant pain in the immediate postoperative period and at a postoperative visit three weeks later stated that his pain had almost completely resolved.


Patient is a 64-year-old Caucasian male presented to the emergency room at the end of December at our facility with worsening left arm swelling. Two weeks ago, he was initially admitted for the right arm swelling and tenderness. He, at baseline, has been on leflunomide for three years for treatment of rheumatoid arthritis and previously was on prednisone for the same reason. Patient reported that, in mid-November, he started to experience significant pain in both wrists and was evaluated at the rheumatologist office for possible rheumatoid arthritis flare. He had received steroid injections in bilateral wrists. During his first admission two weeks prior, he was diagnosed with deep abscesses of right upper extremity (RUE) which has later gotten incision and drainage. At that time, only bacterial cultures were sent, which grew methicillin-sensitive Staphylococcus aureus. Patient was discharged home on trimethoprim/sulfamethoxazole oral tablets but readmitted seven days later with pain and pustules now mainly on all of the fingers of the left forearm ().
He again underwent drainage and bacterial and acid fast bacilli smear and cultures were sent. M. marinum was identified phenotypically in our lab when the culture grew at 30 degrees Celsius. The sample was also sent out for biochemical sequence and further identified as M. marinum (Nichols Institute, Chantilly, VA). He was empirically treated with intravenous imipenem, linezolid, and azithromycin. During this second admission, magnetic resonance imaging (MRI) of the left arm was done which showed multiple ulcerations extending from the skin surface into the subcutaneous fat with the largest visualized at the palmar aspect of the wrist, extending deep to the level of the carpal tunnel/hook of the hamate, at the dorsal and ulnar aspects of the mid- and distal forearm at two sites and at the ulnar aspect of the distal forearm suggesting tenosynovitis with necrotizing fasciitis. He recovered well from the surgery and was discharged on doxycycline and azithromycin while waiting for susceptibility. Despite being adherent to this regimen for four weeks, he was ultimately readmitted a third time with new abscess formation on medial aspect of his proximal LUE and repeated MRI showing osteomyelitis of the left distal ulna (). Susceptibility test with minimal inhibitor concentration (MIC) (Focus Diagnostics, Inc., Cypress, CA) came back with M. marinum resistant to doxycycline and rifampin (). He underwent the third incision and drainage with the skin graft for his LUE. Therapy was then changed to azithromycin and trimethoprim/sulfamethoxazole based on the susceptibility result (). Because of extensive disease and slow improvement on therapy, our patient received nine months of antibiotics therapy with good response (). He is still being followed by infectious diseases and plastic surgery.


A 60-year-old male was admitted to The First Hospital, Jilin University (Changchun, China) in October 2012 complaining of redness on the hands and face that had been apparent for three months. The patient exhibited no feelings of discomfort, and reported that the skin problems appeared to be insidious. A review of the medical history revealed that the patient had experienced a lacunar infarct eight years previously, and had suffered with hypertension for >30 years, for which antihypertensive drugs had been taken for ~20 years. The patient did not smoke or regularly consume alcohol. Immediate family members exhibited no history of any neurological or hematological diseases.
A physical examination revealed that the patient was afebrile, with an Eastern Cooperative Oncology Group score of 0 (), a normal heart rate and a blood pressure of 145/90 mmHg. The face, neck and hands appeared red, but no pain was reported. There was no evidence of edema or blistering of the skin. Lymphadenopathy, hepatosplenomegaly or an abnormal physical mass in the abdomen were not apparent. Digital rectal examination did not reveal any masses or enlargement of the prostate.
Hematological analysis revealed slightly elevated readings for hemoglobin (Hb; 20.4 g/dl; normal range, 12.0–16.0 g/dl) and the hematocrit (Hct; 0.610 l/l; normal range, 0.400–0.500 l/l), and also evidence of leukocytosis [white blood cell (WBC) count, 12.89×109/l; normal range, 4.0–10.0×109/l]. The WBC count consisted of 80% neutrophils (normal range, 50–70%), but normal levels of platelets (253×109/l; normal range, 100–300×109/l). The concentration of alkaline phosphatase (ALP) was slightly high (115.0 U/l; normal range, 15.0–112.0 U/l), but liver function tests appeared normal. The serum total prostate-specific antigen (TPSA) level was 10.94 ng/ml (normal range, 0–4 ng/ml), and the serum free PSA (FPSA) level was 0.98 ng/ml. As a result, the percentage of FPSA in TPSA was 9%, which was less than the normal value of 19%.
MRI of the prostate () revealed a small nodule measuring 5×5 mm, which exhibited abnormal intensity signals in the right prostatic peripheral zone. The capsule of the prostate gland was continuous and complete, and no evidently enlarged surrounding lymph nodes were observed. The signal intensity of the pelvic bone marrow was diffusely inhomogeneous, but the structure of the cortical region was intact. A bone scan indicated slightly elevated radioactivity within the left ankle and right knee, but without any other abnormalities. A computed tomography scan of the lung appeared normal. A transrectal ultrasound-guided biopsy of the prostate initially revealed a well-differentiated adenocarcinoma measuring <0.5×0.1 cm, with a Gleason score of 3+3 (). The bone marrow aspiration and biopsy revealed erythrocytosis and leukocytosis consisting of 12% eosinophils (normal range, 0–8%). The genetic chromosome analysis indicated the presence of a JAK2-V617F mutation, but no other abnormalities.
A diagnosis of stage IIA prostate adenocarcinoma (TNM stage, cT1aN0M0) and PV was established (). The patient was subjected to phlebotomy procedures to remove 400 ml of blood twice weekly for two weeks, and was treated with 100 mg aspirin daily. Prior to surgery, the blood Hb level dropped to 14.1 g/dl, and the Hct to 0.47 l/l. In November 2012, a radical prostatectomy was performed by laparoscopy. Pathological examination of the surgical specimen revealed an adenocarcinoma with negative margins, but with no evidence of seminal vesicle invasion or extra-capsular extension. The tumor volume occupied ~3% of the total prostate volume. The patient was discharged seven days after the surgery. Following surgery, the Hb level and Hct values gradually increased. The patient was therefore continually treated with 300×104 units of interferon-α2b (Beijing Kawin Bio-Tech Co., Ltd., Beijing, China) twice-weekly, and 100 mg aspirin daily.
The patient was continually followed up, and the serum TPSA levels were monitored every three months. Abnormal levels of serum TPSA were not reported during the one-year follow-up period. At six months post-surgery, MRI analysis of the prostate indicated no evident abnormalities. However, there was no marked change in the atypical signal intensity of the pelvic bone marrow that was detected during the initial MRI scan. At present, the blood Hb, Hct, platelet and WBC counts remain within the normal ranges.


A 66-year-old Chinese male presented to the Deaprtment of Pathology, The Third Affiliated Hospital of Soochow University (Changzhou, China) in May 2009 with complaints of a 2-cm asymptomatic, smooth and firm nodule in the left inguinal region. There was no discoloration or other visible abnormality of the overlying skin. Surgical excision of the lesion was performed and a diagnosis of malignant lymphoma was formed at the Changzhou No.2 People’s Hospital (Changzhou, China). The patient’s medical history revealed a previous resection of a similar painless nodule in the subcutaneous region of the left knee 6 months previously, but a pathological examination had not been performed. The nodule in the left groin was suspected to be a metastatic lesion.
Upon review of 4-μm sections of the lesion by light microscopy, the entire thickness of the dermis was observed to be widely infiltrated by small round monomorphic cells, with minimal cytoplasm, hyperchromatic nuclei and small nucleoli (). Apparent nuclear atypia and multiple mitotic figures were observed. These neoplastic cells showed diffuse distribution and infiltrated into the deep mesenchyme, where blood vessels were plentiful (). Immunohistochemical staining was performed on 4-μm thick, formalin-fixed, paraffin-embedded tissue sections provided by the external hospital. The results demonstrated that the tumor cells were strongly positive for neuroendocrine markers, including chromogranin A (CgA) and synaptophysin (Syn), and epithelial markers cytokeratin (CK) 20, CK8/18 and epithelial membrane antigen (EMA) (), but negative for leukocyte common antigens (LCA), thyroid transcription factor-1 (TTF-1), Melan-A, human melanoma black 45 (HMB45), vimentin (Vim), S-100, cluster of differentiation (CD)34, CD57 and CD99. These histopathological and immunohistochemical features were consistent with a diagnosis of MCC. Therefore, a corrected diagnosis of MCC was made for this patient.


The patient was a 44-year-old male who presented in March 2009 with palpitations, dyspnea and lymphadenectasis in the neck. The patient was treated with antibiotics for one week, during which time the symptoms were not alleviated. A subsequent ultrasonic examination showed several low echo-level masses in the bilateral axillary, submaxillary regions, neck and supraclavicular fossa. The largest mass was 3.0×2.2 cm in size and the blood supply was abundant. An enlarged spleen and liver were also detected. A complete blood count (CBC) test obtained the following results: hemoglobin 10.2 g/dl, leukocyte count 169.87×109 cells/l, (neutrophils, 84.93×109 cells/l; lymphocytes, 1.70×109 cells/l; monocytes, 5.07×109 cells/l; eosinophils, 0.84×109 cells/l; basophils, 2.55×109 cells/l) and platelet count 129×109 cells/l. Bone marrow analysis revealed a myeloproliferative disorder with hyperactivity in the medullary system (). The fluorescence in situ hybridization (FISH) test for BCR/ABL was positive (). The patient was diagnosed with CML in the chronic phase, and hydroxyurea was then administered from March 5, 2009. Informed consent was obtained from the patient prior to this study.
When the ultrasonic examination was performed, the patient underwent a left cervical lymph node biopsy. Immunohistochemical staining showed that the lymphoblastic cells expressed CD7, CD3, PAX5, Bcl-2, terminal deoxynucleotidyl transferase (TdT) and, to a lesser extent, CD20. By contrast, staining for CD10 and CD21 was negative. The Ki-67/MIB-1 labeling index was 70% (). A preliminary diagnosis of a precursor T-lymphoblastic lymphoma (T-LBL) was made. A week later, the FISH test for BCR/ABL was positive in lymph node section (), and the final diagnosis of EBC of CML was made.
The initial chemotherapy regimen CHOP was administered from March 21, 2009 and, after the first course of chemotherapy, the patient’s lymphadenectasis disappeared. Two further courses of the chemotherapy regimen followed between April and May 2009. Hematopoietic stem cell transplantation (HSCT) from a matched relative donor had been considered, but no donor was identified. While the patient’s sister was revealed to be HLA-mismatched donor, only HLA-DQ was mismatched. The allo-HSCT was administered from May 27, 2009 with the conditioning regimen: Bu/CY/Ara-c/CCNU (BU, busulfan; CY, cyclophosphamide; Ara-c, aracytidine; CCNU, lomustine). On June 3, 2009 peripheral blood stem cells were collected from the donor and infused into the patient. The following day, bone marrow was collected from the donor and administered to the patient by infusion. During the transplantation period, anti-graft-versus-host disease (anti-GVHD) medications, including CsA, MTX, mycophenolate mofetil and anti-thymocyte globulin (ATG) were administered to the patient. Four weeks later, hematopoietic reconstitution was definite. Accompanied by the chemotherapy, the patient received lumbar puncture and intrathecal chemotherapy eight times, and the cerebrospinal fluid was continuously normal.
Two months after transplantation, the patient received a repeated ultrasonic examination and the results showed that lymphadenectasis had disappeared and the sizes of spleen and liver were normal. FISH detection demonstrated changes in the patient’s sex chromosomes from XY to XX and the test for BCR/ABL was negative. Until now (September 2013)the patient obtained continuous remission for 51 months and recent ultrasonic examination, FISH detection, bone marrow smear and biopsy results were normal.


A 9-year-old girl was referred to the Department of Oral and Maxillofacial Surgery, Pusan National University Hospital, Pusan, Republic of Korea, for the evaluation and treatment of a facial deformity. Clinical findings were as follows: micrognathia, lower incisor midline deviation towards the left side, hypoplasia of the mandibular condyle and coronoid process, deficiency in ramus height and length of the left mandibular body, and canting of the occlusal plane (Figure ). Clinical and radiographic examinations indicated that she had HFM anomaly.
Preoperative orthodontic treatment was administered at the age of 10 years to correct posterior openbite at the Department of Orthodontics. DO was initiated when the patient was 12 years old. The amount of horizontal and vertical DO was measured on an RP model prior to the procedure (Figure ). From the model analysis, the required horizontal and vertical bony lengths measured were 3 mm and 16 mm, respectively. The estimated vector angle for DO was 12° from the mandibular angle. The operation included an incision on the left mandibular posterior vestibule; the lateral surface of the left mandibular body and ramus were also exposed. Furthermore, a lateral and medial corticotomy was performed at the lateral angle of the mandible, in order to create a complete greenstick fracture. An extraoral mandibular distraction device was also installed on both segments of the ramus, with the aid of screws (Leibinger, Multi-guide 2®, Switzerland) (Figure ).
Seven days after the surgical procedure, DO, in an anteroposterior (A–P) direction, was initiated at a rate of 1 mm/day (two half–turns per day). Ten days after the surgery, total A–P DO (3 mm) was completed and a vertical DO, at a rate of 1 mm per a day, was resumed. The final vertical DO length was determined by multiplying the original estimated vertical DO (16 mm) by 120% in order to apply a conventional DO with stimulatory compression forces for callus molding, thereby accelerating new bone quality. Moreover, the total vertical DO length obtained was 19 mm. In the present study, DO with compression force was applied, as previously described [,]. After a pre-compression latency period of 3 days, compression, by reverse turning of the device, resulting in a counter force at a rate of 1 mm per a day, was initiated for 3 days. The final length of vertical DO achieved was 16 mm, similar to the original DO length (Figure ). The distraction device was left in place for 6 weeks and was removed after the radiological evidence of mineralization was detected (Figure ).
Subsequent to the DO procedure, orthodontic treatment was continued and periodic follow-up was conducted till the end of pubertal growth. An additional operation for the correction of facial asymmetry was performed when the patient was 18 years old. A second operation for advancement genioplasty was designed at 19 years of age, wherein the left mandibular body was augmented with a porous polyethylene implant (PPE, Medpor®, Porex) to correct the chin retrusion and mild left facial deficiency. The clinical findings of the patient at this stage were as follows: microgenia, left condyle hypoplasia, deficiency of the left mandibular body, and midline deviation of the chin to the left side (Figure ). Advanced midline corrected genioplasty and insertion of a 5-mm thick PPE in the left ramus that was fixed with metal screws (Figure ). Thus, the second corrective surgical procedure was completed (Figure ).


26-year old female patient underwent surgery of a cleft palate at the age of 5 years, later she had no significant health issue. Melorheostosis was diagnosed incidentally by X-ray after shoulder injury in sport.
Clinical examination showed reduced joint abduction 60 degress in the shoulder, further movement was possible only in scapula, movement range in the elbow was limited to 20 degrees, in radiocarpal joint was volar flexion up to 40 degrees, dorsal flexion 0, pronation and supination was also 0. The patient reported pain in the whole upper limb at rest. Osteopoikilotic islands were identified in the body of third cervical vertebra and also in the right collar bone and sternum manubrium. CT of the upper limbs and upper chest was performed without contrast tracer. There was no family history of melorheostosis found.
Diffuse thickening and sclerotisation was identified on index finger, II. metacarp shaft on the left hand, the lesion was less aparent at the I. metacarp of the left hand and on some carpal bones (Figure ). There was diffusely enlarged sclerotic radius, humerus and the scapula on the left side. The cavities on affected bones were completely filled with the sclerotic bone. Small sclerotic focus was in the ventral part of C3 vertebral body - size 7 mm (Figure ), there was also a small island in the left manubrium sternum and in the sternal part of the left collarbone. The finding corresponded to melorheostosis Léri. Thickness of patient’s left scapula was up to 31 mm, the contralateral scapula was unaffected with thickness of 2–3 mm. The cortex of both collarbone and ribs had slightly higher bone density. The skull was without pathological finding.
Bone scintigraphy showed normal level of overall metabolic activity in the skeleton. Significant, locally inhomogeneous increase of activity was evident in most of the scapula, humerus, radius and in II. shaft on the left, the highest intensity of changes was in the scapula, which showed 7-times higher activity compared to the contra lateral parts. Activity increase in the I. shaft left was more modest and slight accumulation was present in the left medial clavicle (Figure ). The rest of skeleton was without significant pathological changes.
DXA examination of the whole skeleton showed osteopenia in the lumbar spine: T score −1.2 SD, in both hips T-score was same and within the normal range. There was no abnormality found in the laboratory tests including bone markers except for increased level of osteocalcin and C-terminal telopeptide.
The published cases reported good experience with bisphosphonate in terms of disease progression []. The patient was treated with weekly alendronate and COX-2 inhibitor (celecoxib). In connection with the development of sleep disorders and increased skin sensitivity sensitivity on affected site naftidrofuryl in high doses (600 mg daily) was added, which led to symptoms relieve. The patient is currently without pain and is able to perform normal daily activities with non-progressive restriction for 5 years after the diagnosis. Pharmacological treatment in described combination could delay surgery solution and eventually could prevent an excessive dosage of analgetics. Questionable is further development of patient performance status and sustainability of conservative treatment in the long term follow up.


A 35-year-old Caucasian man presented with a complaint of facial asymmetry for a mass in his right midcheek area, which had increased in size over 4 months (Figure a). In January 2011, he was admitted to our Department of Maxillofacial Surgery complaining of right cheek discomfort and pain, refractory to analgesics, in his right maxilla area and radiating to the right zygoma. Two weeks before the onset of pain, he underwent an examination by his dentist. When he came to our observation, an apparent swelling of the right side of his face was observed, with anesthesia, in the area of his face innervated by the second branch of the trigeminal nerve, and he had pain on palpation. An intraoral examination revealed an expansion of his upper right gums and the vestibular portion, and the mucosa appeared reddened, and his teeth were movable with the presence of a widespread periodontitis. No lymphadenopathy was apparent at neck examination. Computed tomography revealed a hyperdense mass lesion, measuring 83 × 55mm in its greatest dimension, arising from the pterygopalatine fossa, and extending to the soft tissue of his midcheek area (Figure b). An open biopsy was conducted for the diagnosis. The biopsy specimen was histologically examined; it was found to be composed of fibroma and exhibited myxomatous changes as well as abundant collagen fibers. The tumor was characterized by spindle-cell proliferation with moderate cellular density in the fibromyxoid stroma. On immunohistochemical examination, the tumor cells were positive for vimentin, Ki-67, smooth muscle actin, but negative for S-100 (Figure a,b).
A total right maxillectomy was accomplished by means of Weber-Ferguson approach, preserving the orbital floor. On macroscopic examination the anterior and the posterior maxillary walls were totally reabsorbed and the tumor was removed from the pterygopalatine fossa (Figure ). In the right midcheek area, the tumor was detached from the subcutaneous tissues with safe margins preserving the skin. The excised portion was reconstructed using the free rectus abdominis myocutaneous flap. The size of the excised tumor was approximately 84 × 56 × 58mm; it was well circumscribed, elastic, and homogeneously whitish in color. The final diagnosis was low-grade MFS. Postoperative radiotherapy was given to the area adjacent to the lesion, with a total dose of 60Gy. No relapse occurred in 27-month postoperative follow-up.


A 66-year-old Japanese man undergoing hemodialysis for chronic renal failure was referred to our hospital with suspected duodenal cancer. On physical examination, his abdomen was soft and flat without symptoms. Tumor markers were within normal limits, and laboratory findings were normal except for renal dysfunction due to chronic renal failure. Upper gastric endoscopy revealed a giant polypoid-type tumor extending from the duodenum bulb to the pyloric ring; its main location was thought to be the duodenum bulb (). The surface of the tumor was rough, but its outline was clear. A biopsy of the tumor showed atypical papillous epithelium containing goblet cells, and nuclei in the epithelium were p53-positive. An endoscopic ultrasound test suggested that the tumor might invade the muscular tunic (). A computed tomography scan revealed a slightly enhanced lobular tumor (54 mm × 34 mm) protruding into the duodenum bulb, although serosal invasion was not detected (). Positron emission tomography showed an accumulation of 18F-fluorodeoxyglucose (60 mm × 34 mm, maximum standardized uptake value = 5.6) in the area extending from the antrum of the stomach to the duodenum bulb (). Because indications of endoscopic mucosal resection were not favored, the giant polypoid-type early gastric cancer that was expressed on the pyloric ring and confined within the mucosal layer was curatively removed via abdominal surgery. We performed a submucosal resection via an incision in the gastric anterior wall. The resected tumor was localized in the anterior wall of pyrolic ring. Intraoperative histopathological diagnosis with a frozen section suggested that the tumor contained adenocarcinoma components; therefore, we performed distal gastrectomy followed by Billroth II reconstruction. The extent of resection was from the lesser curvature of stomach, which was 5 cm from the pyrolic ring, to the duodenum, which was 4 cm from the pyrolic ring. The resected lymph nodes were number 3b, number 4d, number 5, and number 6. The histopathological diagnosis was papillary adenocarcinoma, and the invasion depth was the mucosal layer without vascular invasion (Figures and ). There are no metastases in the removed lymph nodes and the numbers of resected lymph nodes were number 3b (0/1), number 4d (0/3), number 5 (0/1), and number 6 (0/4). The pathological stage was T1aN0M0- pStage IA. The postoperative course was uneventful, and the patient was free from recurrence 1 year after the surgery.


A 53-year-old male with seven months of crampy abdominal pain, melena, and weight loss of 22 kg was experiencing worsening pain with nausea and vomiting. During the duration of these symptoms he had been evaluated at two different hospitals. Escalating symptoms brought him to seek care from our institution.
The patient had multiple repeat endoscopies at these separate institutions as well as a small bowel enteroscopy and CT and MRI scans in the weeks and months prior to the MRE. All of these tests were unable to uncover the etiology for the patient's symptoms. MRE was then pursued, revealing a mass in the small bowel mesentery that was consistent with a carcinoid tumor (). The patient was able to proceed to the operating room four days later to have a laparotomy with a small bowel resection and an appendectomy. The finding at the time of surgery was a carcinoid tumor in the distal ileum with invasion into the mesentery.
The patient was diagnosed with a small bowel carcinoid tumor with nodal metastasis. Pathology confirmed that the tumor invaded through the muscularis propria with the suspicion of penetration into the peritoneal space (). The final pathologic diagnosis was stage IIIB, T4N1M0, small bowel carcinoid tumor. He was sent home on postoperative day eight. Patient did well postoperatively and is alive at the time of this paper's preparation.


A 34-year-old HIV positive male was seen urgently in our colorectal surgery clinic after a colonoscopy showed an inflamed mucosa and polypoid rectal mass that was partially obstructing. The patient's symptoms had begun as rectal pain six months prior to his visit to the surgery clinic that was soon associated with mucous drainage from his rectum every several days with normal bowel movements in between those. In the months preceding the surgical visit, the patient had been seen by two gastroenterologists and underwent two colonoscopies, the first of which showed inflammation and ulceration of the sigmoid mucosa and the second was the one previously mentioned. He had been started on steroids and narcotics in addition to his other meds, including a clinical trial medication for his HIV diagnosis. His viral load was undetectable and he had a CD4 count in the 200 s.
Prior to the patient's clinic visit, he had undergone a colonoscopy, which showed an area of ulceration in the sigmoid colon. Pathologic evaluation of that lesion revealed a benign, nonspecific inflammatory process. In the colorectal surgery clinic the patient underwent anoscopy and rigid sigmoidoscopy, which revealed a nodular and inflamed mucosa but patent rectal lumen. The patient was then scheduled for an MRE.
The MRE showed significant submucosal inflammation, suggestive of rectal lymphoma with severe, but nonobstructing, lumenal narrowing (). The tumor measured 4.3 cm in its maximal diameter and showed evidence of extension through the mesorectal fat to the mesorectal fascia posteriorly. The patient eventually went on to receive chemotherapy after his oncologist obtained confirmatory biopsies () done by the colorectal surgery service via a transanal approach. To this date, the patient has received a full course of chemotherapy and is asymptomatic. He is to have a follow-up imaging in the near future.


A 70-year-old female with Peutz-Jeghers Syndrome (PJS) and a history of familial adenomatous polyposis had developed anemia and hematochezia. Eight years prior to this presentation the patient had undergone laparotomy for small bowel polypectomies when her surveillance endoscopies and imaging had demonstrated the presence of the polyps.
The patient's semiannual enteroscopies and flexible sigmoidoscopies had not demonstrated any new polyps or other etiology for this new anemia. A capsule study was read as negative three months prior to when the MRE was done. The MRE was able to demonstrate at least seven small bowel polyps; the largest was measured at 25 mm while the smallest ones were less than 10 mm (). The patient proceeded to laparotomy where four polyps were removed through two enterotomies in the proximal and midjejunum ().
The patient had recurrent Peutz-Jeghers polyps. The pathologist confirmed that the specimens were hamartomatous polyps consistent with PJS (). The patient is currently at home on cycled TPN due to chronic abdominal pain caused by intermittent partial small bowel obstructions. These intermittent partial small bowel obstructions are due to the fact that patient had multiple laparotomies and therefore has thick intra-abdominal adhesions.


A 64-year-old female with a history of left upper extremity melanoma had undergone wide local excision without sentinel lymph node biopsy one year prior to presentation to our institution. This patient then presented with 3 weeks of worsening abdominal pain with diarrhea, nausea, and vomiting.
The patient had a CT of abdomen and pelvis, which showed a distal ileal intussusception and incomplete high-grade small bowel obstruction. The MRE then demonstrated similar findings in addition to identifying a leading point mass that was consistent with an edematous polyp (). The patient subsequently had an exploratory laparotomy with small bowel resection and primary anastomosis.
The patient had an inflammatory and edematous fibroepithelial polyp on final pathology (Figures and ). At the time of paper preparation, the patient is doing well with no complaints.


The index patient is a 9 year old boy with autism spectrum disorder diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). He suffered from generalized tonic-clonic epilepsy from age 4. He had taken multiple different medications such as phenobarbital, sodium valporate, and carbamazepine with sufficient dosages and durations without favorable control of his epilepsy. According to his parents’ reports, the patient took cefixime 200mg/day to control diarrhea about 2 years ago. The seizure episodes were dramatically decreased 3 days after starting the medication while the there was no change in his anti-epileptic medication regime. The seizure episodes were controlled for about 5 months, after which the number of seizure episodes again increased. His highly educated parents administered cefixime 200mg/day to control seizure again. They reported that seizure attacks were controlled markedly after taking cefixime for three days. The patient was not febrile while the medication trials were administered. Both parents reported that they repeated this trial for several times to control the seizure episodes in the recent years. The epilepsy was controlled in all of the trials after taking cefixime for 3 to 5 days. Then, they discontinued cefixime after 7 days. They reported that there was a marked decreased in the number of seizure attacks as well as aggressive behaviors. Physical examination did not show any remarkable finding such as fever, headache, or photophobia. Brain MRI did not illustrate any abnormal finding. No remarkable finding was found on laboratory examinations. This is a retrospective case report, and caution needs to be used in interpreting case reports. His parents provided their consent for publication of this report.


This is a 71-year-old male with a notable medical history of EMPD, hypertension, and end-stage renal disease (ESRD) on hemodialysis who presented to our office for evaluation of a left neck mass.
His EMPD was initially diagnosed in 2011 when he noticed scrotal and perianal skin lesions. This was biopsied and pathology revealed EMPD with lymphovascular invasion and lateral margins positive for Paget's disease. Immunostaining was positive for CAM5.2, CK7, focally positive for BRST-2, negative for CK20, MART-1, and S100 (). He was treated with surgical resection and reconstruction with a local flap. He then received adjuvant radiation to the affected area and did well for two years.
In 2013 he was referred to our institution following a work-up of an enlarged left neck mass which was biopsied and reported as metastatic adenocarcinoma of unknown primary with a broad differential diagnosis. The slides were examined in our institution which revealed that the lymph node tissue was entirely replaced by metastatic poorly differentiated adenocarcinoma associated with necrosis (). A screening colonoscopy and upper endoscopy did not demonstrate any malignancy. The tumor cells by immunohistochemical stains were positive for CK7, CK17, CK19, CA19.9, CK5/6 (focal), PSMA (focal), and Ber-EP4 (focal) while they were negative for CDX2, CK20, p63, TTF-1, PSAP, and PSA. Tumor cells were also positive for BRST-2 (GCDFP). The morphological and immunohistochemical findings were consistent with metastatic EMPD.
Further immunohistochemistry revealed complete membranous positive HER2/neu staining (moderate to strong) in 90% of tumor cells. According to HER2 test guideline recommendations for breast cancer, this HER2 result would be considered to be positive (3+) (). Next generation sequencing (NGS) on limited remaining lymph node tissue (FoundationOne) was performed, revealing two genomic alterations: DNMT3A R882H and SLIT2 rearrangement exon 37.
The patient underwent a diagnostic CT of the chest, abdomen, and pelvis which showed left cervical and axillary lymphadenopathy as well as a pathologic fracture through a lytic lesion of the left 7th rib and lytic lesion in the T10 vertebra (representative images of Figures and ).
Since he was on hemodialysis, it was decided to attempt to treat him with trastuzumab monotherapy rather than initiating cytotoxic chemotherapy, with a loading dose of 8 mg/kg followed by every third week treatment with 6 mg/kg, a standard dosing regimen for breast cancer. The patient tolerated therapy without any significant side effects, experiencing only mild fatigue for some days following each dose. Following the second treatment with trastuzumab, he had complete resolution of back pain that had been attributed to the T10 metastasis. Restaging CT after 4 doses or 3 months (Figures and ) revealed left axillary and left supraclavicular lymphadenopathy that had resolved, returning to normal size, consistent with treatment effect, and no new measurable disease in the chest, abdomen, or pelvis, and noted previously lytic bone metastases in the left seventh rib and spine now sclerotic, consistent with treatment effect. Almost 12 months after initiation of therapy, while undergoing periodic cardiac function analysis, the patient continues to receive trastuzumab therapy without significant side effects. Of note, he was diagnosed with squamous cell carcinoma under the right index nail bed in the midst of his treatment, approximately 3 months into treatment, and this was resected.


A 76-year-old woman with RVF was referred to our hospital. She suffered from RVF over 30 years after the third childbirth. A fistula was found at the level of dentate line by the anoscope examination. Similarly, colonoscopy also showed a fistula at the same level (Figure ). She underwent ERAF under the diagnosis of RVF (Figure a). She was placed at the jack-knife position. The procedure of ERAF was same as previously mentioned (Rothenberger et al. ). In short, a four-centimeter-long flap which consisted of mucosa, submucosa, and circular muscle was outlined around the fistula (Figure b). The base was two times as wide as the apex of the flap for adequate blood supply. After the resection of the fistula, circular muscle was sutured by horizontal mattress manner (Figure c). The flap was advanced over the repaired area (Figure d). She had a good postoperative course and was discharged from hospital on the 7th postoperative day. She had a nighttime soiling once a month, but it disappeared one year after surgery.


A 23-year-old woman with RVF was referred to our department during the second pregnancy. She suffered from RVF after the first childbirth. After the second childbirth via Caesarean section, contrast radiography showed the discharge from anal canal to vagina (Figure ). She underwent ERAF and had a good postoperative course. She was discharged from hospital on the 7th postoperative day. She did not have any complications.


In December 2006, a 72-year-old female was admitted to our hospital presenting with general malaise and dyspnea. A physical examination revealed anemic palpebral conjunctiva and purpura of the extremities. The complete blood count indicated severe anemia and thrombocytopenia as well as mild leukocytosis with 22.5% blast cells (Additional file ). A bone marrow examination showed a total nucleated cell count of 41,000/μL with 67.0% blasts (Additional file : Figure S1A). A cytogenetic analysis of the bone marrow cells with G-banding showed 46,XX,inv(16)(p13.1q22) in all 20 dividing cells (Additional file : Figure S1B). Based on these findings, the patient was diagnosed as having AML with inv(16)(p13.1q22).
The patient achieved complete remission (CR) after one course of induction chemotherapy comprising behenoyl cytarabine and daunorubicin according to a study protocol [] (Table ). However, the AML relapsed four months after the completion of the last cycle of consolidation therapy. Re-induction chemotherapy using the same regimen as the first induction induced a second CR. Thereafter, the patient suffered four further episodes of relapse with temporary remission (Figure ). The failure to achieve durable remission even with high-dose consolidation therapy and its toxicities prompted us to select palliative care with LDAC at the third relapse. After achieving the sixth CR, the patient declined further treatment with LDAC due to toxicity. Therefore, oral cytarabine ocfosfate hydrate (SPAC) was started in order to maintain remission in November 2011. The SPAC therapy was not associated with any significant toxicity. The CBFB-MYH11 fusion mRNA in the peripheral blood became negative after twelve courses of SPAC therapy, which was terminated in October 2013. The patient has since remained in molecular remission without chemotherapy (Figure ).


A 10-year-old boy with no past medical history presented with a 2-day history of central abdominal pain which subsequently migrated to the right iliac fossa. A diagnosis of acute appendicitis was made and an open appendicectomy was performed. There were no immediate postoperative complications and he was discharged on day 2 postoperatively. The patient represented to hospital 4 days later with increasingly severe left leg pain and inability to weight-bear. The leg was enlarged and erythematous. He denied any history of trauma. The patient was initially admitted under the medical team without consultation of the orthopaedic service, with a presumed diagnosis of a left sided below knee deep venous thrombosis.
Initial investigations revealed white cell count, C-reactive protein, and erythrocyte sedimentation rate within the normal range with a normal prothrombin and partial prothrombin time. Doppler ultrasonography of the lower leg arranged by the medical team revealed no evidence of deep venous thrombosis. The pain increased in intensity despite increasing dosage of opiate analgesia. The patient was referred to our orthopaedic service one day after admission. At this point the child had severe, unrelenting pain of his left lower leg. On examination his leg was hard throughout all compartments with hyperaesthesia of the anterior aspect of the leg. Severe pain was elicited on passive ankle plantar flexion, inversion, and dorsiflexion. Dorsalis pedis and posterior tibial artery pulses were palpable; however the leg was cold.
A diagnosis of acute compartment syndrome was made and he underwent emergent fasciotomy.
Immediate preoperative compartment pressure was measured using the Intracompartmental Pressure Monitor (Stryker). All four lower leg compartments had delta pressure readings (defined as diastolic blood pressure − intracompartmental pressure) less than 30 mmHg, which was diagnostic of compartment syndrome. A standard two-incision (medial and lateral) fasciotomy was performed decompressing all four compartments (Figures and ). The muscle tissue appeared viable at the initial fasciotomy and subsequent wound reviews revealed no evidence of necrotic tissue. The patient underwent three partial closure procedures before the fasciotomy wounds were definitively closed on day 12.
The patient made a slow recovery and had ongoing hyperalgesia in the affected area, despite thorough decompression of all four compartments. Repeated compartmental pressure monitoring over a one-week period revealed no evidence of residual compartment syndrome. The pain persisted for a further two months postoperatively and a diagnosis of chronic regional pain syndrome was made. He was treated by a multidisciplinary team (MDT) involving the orthopaedic team, physiotherapists, pain specialists, and psychologists. The pain improved with MDT management and he is now pain-free at 18-month follow-up with no residual functional or neurovascular deficit.


A 70-year-old man was referred to our institution with bilateral continuous painless swelling of the parotid glands (PGs) and submandibular glands (SMGs) in March 2013. He had previously attended another hospital with chief complaints of dry mouth and bilateral swelling of SMGs, which were diagnosed as chronic sialoadenitis by computed tomography (CT) in January 2013. However, he did not receive any treatment at that time and ignored the swelling. He had no medical history of allergic diseases such as bronchial asthma, atopic dermatitis, or allergic rhinitis.
Physical findings showed no fever (body temperature, 36.6°C), a blood pressure of 124/68 mmHg, a pulse rate of 64 beats per min, and arterial oxygen saturation of 98% in room air. He had a dry mouth and stomatitis with reduced unstimulated salivary flow rate (0.9 ml/15 min). Bilateral PGs, SMGs, and sublingual glands were elastic, hard, and swollen, but not painful. Several cervical lymph nodes were enlarged. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated abnormal multiple accumulations in the SMGs (SUVmax, 4.63) and in several systemic lymph nodes (SUVmax, 3.23–4.12) (Figure A). CT and magnetic resonance imaging showed remarkable swelling of bilateral PGs, SMGs, and generalized lymph nodes, including in the neck (Figure b). On ultrasonograms, SMGs showed bilateral nodal hypoechoic areas with high vascularization, whereas PGs showed normal or slight change (Figure C).
Laboratory findings are indicated in Table . He had an increased erythrocyte sedimentation rate (15 mm/h), hemoglobin concentration of 12.6 g/dl, white blood cell count of 4,680/mm3 (neutrophils 40.7%, lymphocytes 49.8%, monocytes 8.5%, eosinophils 0.4%, basophils 0.6%), and platelet count of 12.6 × 104/mm3. Serum chemistry data were all within normal limits. His C-reactive protein concentration was 0.07 mg/dl. Immunological tests were negative for anti-nuclear antibody, anti-SS-A antibody, and rheumatoid factor. Serum levels of IgG, IgA, IgM, and IgE were within normal limits (1,177 mg/dl, 179 mg/ml, 91 mg/dl, and 15 IU/ml, respectively), but his serum IgG4 concentration was elevated (215 mg/dl). The proportion of total IgG molecules that were subclass IgG4 was 18%. The serum soluble interelukin-2 receptor (sIL-2R) concentration was abnormally high (1,566.2 U/ml).
IgG4-DS was initially suspected because of the enlarged glandular tissues and high serum IgG4 concentration. Open biopsies of the cervical lymph node and a portion of the left SMG were therefore performed for definitive diagnosis. Histologically, all sections showed severe lymphoplasmacytic infiltration with hyperplastic lymphoid follicles, so-called follicular colonization. Furthermore, the plasmacytoid cells showed nuclear pleomorphism. Immunohistochemical staining showed mild infiltration of IgG4-positive plasma cells (IgG4-positive/IgG-positive plasma cell ratio, 10%) and monotypic predominance of kappa-light chain. The infiltrating lymphocytes were positive for B cell markers (CD20 and CD79a) and bcl-2, but negative for T-cell markers (CD3, CD5, CD8, and CD45RO), CD10 and cyclinD1 (Figure ).
These histopathological findings and clinical features confirmed a diagnosis of MZL. The patient was treated with 600 mg rituximab for six times as currently recommended regimen [-]. Swelling of the SMGs diminished slightly, and there was no metastatic spread. PGs and LNs showed no remarkably change on all images, whereas SMGs had ill-defined borders of nodal hypoechoic areas (Figure ). Laboratory findings after treatment still revealed high concentrations of serum IgG4 (195 mg/dl) and sIL-2R (752.0 U/ml) (Table ).


A 19-year-old male patient, injured as a result of a single vehicle motorcycle accident, was accepted as a trauma transfer to our Level I trauma center for definitive evaluation and management of an open femur fracture with significant segmental bone loss (). The patient had lost control of his motorcycle while performing “wheelies” and struck a concrete highway divider. His resultant injuries included multiple minor orthopedic fractures and ligament disruptions, including a Gustilo III-B open fracture to the distal left femur. All injuries were evaluated and treated by the initial treating hospital, including external fixation stabilization and two rounds of irrigation and debridement of the open femur fracture.
A thorough history and physical examination revealed that the young patient was in otherwise good health aside from his orthopedic injuries. Distal vascular function to the leg below the level of the open fracture was uninterrupted, and no deficit existed either in the motor or in sensory function of the distal lower extremity. New radiographs and a repeat serial irrigation and debridement upon arrival at our hospital revealed absence of the distal 17 centimeters of metadiaphyseal bone of the left femur. The distal end of the femur was fractured, including extension into the articular surface, but was retained with significant soft tissue attachments. The segment of missing bone included a modest amount of the lateral femoral trochlear articular surface.
The decision on how to best proceed was made after numerous and detailed discussions with both the patient and his family regarding the surgical options of primary amputation of the severely injured leg, or limb salvage. The superior short-term results of primary amputation, as well as a lack of published support for superiority of either technique at two years, were thoroughly discussed []. Despite the probability of multiple surgeries over the course of approximately the next year, the attendant risks of each surgery, and the very real possibility of enduring pain and challenging control measures, the patient opted for the limb salvage option. We then set about formulating a surgical plan to provide the best possible outcome to that end.


A 41-year-old woman, undergoing her second cycle of IVF treatment, presented to the ED with acute chest pain. The chest pain was central, was worse on inspiration, and was not induced or exacerbated by exercise. The patient had associated dyspnea and observations revealed oxygen saturations to be 90% on air. Her thrombogenic risk factors included reduced immobility due to back pain and recent IVF []. Past medical history included one failed cycle of IVF and a recent embryo implantation in her second IVF cycle. Examination revealed a woman in substantial pain, with associated tachypnea, tachycardia, and bilateral reduction in air entry to the lung bases.
The presence of thrombogenic risk factors and the clinical presentation gave the patient a modified Wells score of six, rendering pulmonary embolus a likely diagnosis []. Consequently, the patient was placed on high flow oxygen and routine bloods, a d-dimer, and a clotting profile were requested. The d-dimer returned as mildly raised (430 mg/L, upper limit of normal in our laboratory was 250 mg/L) and the patient was sent to the medical admissions unit (MAU) for further clerking and therapeutic thromboembolic treatment.
In the MAU, two important inconsistencies with the original assessment were established. Firstly, the chest pain appeared to be epigastric and was associated with new onset abdominal bloating. Secondly, a thorough drug history highlighted that the patient had been taking a low molecular weight heparin following her previous IVF failure. These findings significantly reduced the likelihood of a pulmonary embolus. Consequently, beta-human chorionic gonadotropin (beta-hCG) levels and abdominal ultrasound scan were requested. The beta-hCG returned as raised and the scan revealed bilateral ovarian enlargement, ascites, and a right-sided pleural effusion, uniting the symptoms and thus confirming the diagnosis of severe OHSS.
Subsequently, the patient was transferred to gynecology where she was closely monitored. During her stay, the ascites reduced, the shortness of breath improved and the following week, she was discharged home with no symptoms.