A 54-year-old male with end-stage renal failure secondary to IgA nephropathy received a deceased donor renal transplant in 1999. He had received peritoneal dialysis for six years prior to transplantation. The posttransplant course was uneventful and graft function was excellent (serum creatinine concentration 90–100 μmol/L). Maintenance immunosuppressive therapy was cyclosporine, prednisone, and azathioprine. Fifteen years after transplantation, the patient presented to the outpatient clinic for routine follow-up complaining of discomfort over his allograft. The serum creatinine concentration had increased to 120 μmol/L. Urinalysis was normal.
Transabdominal ultrasonography revealed an 8 cm solid vascular mass arising from the midpole of the transplanted kidney. It was partially obstructing the collecting system (). Further characterisation with CT did not reveal local or distant disease (). Sections from a core biopsy showed a spindle cell neoplasm composed of bundles of bland-looking spindle cells with eosinophilic cytoplasm without mitoses, necrosis, or nuclear pleomorphism (). Immunohistochemical studies of the neoplastic cells were positive for SMA and desmin but negative for CD34, CD117, S100, and HMB45 (Figures and ). They were also positive for EBV RNA (). The overall features were those of EBV-positive leiomyoma, a benign smooth muscle tumour.
Given the benign nature of the tumour, the relatively stable renal function, and the difficulty of total excision due to size and location, surveillance was deemed to be the most appropriate management. Treatment with cyclosporine and azathioprine was ceased and immunosuppression therapy was changed to everolimus. There was ongoing monitoring of renal function and graft morphology at three-monthly intervals. At the time of writing, 12 months following diagnosis, the patient's kidney transplant function was stable (serum creatinine concentration 108 μmol/L). The tumour size was unchanged.


A 68-year-old man presented to our institution with acute kidney injury, two months following an induction course of intravesical Bacillus Calmette-Guerin (BCG) for high-grade T1 urothelial cell carcinoma (UCC). His serum creatinine level was 12.1 mg/dL. Computed tomography (CT) demonstrated bilateral hydronephrosis with dilated ureters to the level of the posterior bladder wall. Bilateral percutaneous nephrostomy tubes were inserted with resultant improvement in his renal function. Subsequent cystourethroscopy demonstrated a large tumor burden at the trigone, which was resected and confirmed to be recurrent high-grade UCC.
The patient had no prior surgical history. Medical comorbidities included obesity, hypertension, gastroesophageal reflux disease, and benign prostate hyperplasia. He reported a 25-pack-year smoking history. On physical examination, the patient was obese but otherwise well-appearing. His BMI was 38.5 kg/m2 and abdominal exam revealed a large pannus draping over the groin (). Staging CT of the chest, abdomen, and pelvis demonstrated no evidence of metastatic disease. The patient elected to proceed with immediate radical cystectomy, ileal conduit urinary diversion, and concomitant panniculectomy, as his renal function precluded the use of cisplatin-based neoadjuvant chemotherapy.
The patient was reexamined preoperatively. In the supine position, the height of the inferior abdominal incision was marked six centimeters cephalad to the base of the penis. Care was taken to err on the side of leaving too much distance between the inferior incision and the base of the penis, in order to avoid pulling the escutcheon and penile skin upwards or place undue tension on the abdominoplasty. In the standing position, the lateral extent of the pannus was marked bilaterally. A line was drawn connecting the lateral border of the pannus to the previously described inferior abdominal incision marking. With the patient still standing, the pannus was lifted to assess the planned incision for symmetry and minor alterations were made.
Following the induction of anesthesia, the patient was positioned supinely and prepped widely from the upper thigh to the nipple line. A solution of 1 : 100,000 epinephrine was instilled in the subdermal and subcutaneous layer at the planned inferior pannus and periumbilical incision sites. Ten minutes was permitted to pass prior to incision. The lower incision was made and carried deep towards the abdominal wall. An abdominal flap was raised towards the umbilicus using towel clamps for retraction. Care was taken to leave a layer of subscarpal fat on the superficial investing fascia in order to preserve lymphatics and reduce the risk of postoperative seroma. The umbilicus was circumscribed with sharp dissection. Once the abdominal flap was sufficiently raised, the bed was flexed into a “beach chair” position and the site of the superior abdominal incision was verified by retracting the flap cephalad. The pannus was excised with a superior transverse abdominal wall incision. Undermining the superior resection margin was minimized. A total of 3.9 kg of abdominal wall tissue was resected as the panniculectomy specimen ().
A vertical, lower midline fascial incision was made. Radical cystoprostatectomy, bilateral pelvic lymph node dissection, and construction of an ileal conduit urinary diversion proceeded without complication. The superior and inferior panniculectomy margins were approximated with towel clamps. Sites for the stoma and neoumbilicus were marked in the right upper quadrant and superior flap, respectively. A cone of tissue was removed from the stoma site and a Turnbull loop stoma was matured cephalad to the undermined portion of the superior flap []. Fascia was closed with a running #1 polydioxanone suture. The umbilicus was secured with 3–0 absorbable monofilament suture. Two round, fluted drains were passed through separate stab incisions and placed between superficial investing fascia and the superior flap. The superficial abdominal wall was approximated with 2–0 polypropylene vertical mattress sutures followed by a staple closure of the skin. Total operative time was six hours. Estimated blood loss was 600 cc, with 200 cc being returned via cell salvage. Approximately one hour of operative time and 100 cc of blood loss were contributed by the panniculectomy portion of the case.
The postoperative course was uncomplicated. An abdominal binder was applied and worn at all time. Length of stay was seven days. Jackson Pratt drains were removed at two-week follow-up, as the daily output was less than 30 cc each. The abdominal binder was discontinued at 6 weeks. Final pathology revealed a six-centimeter tumor with squamous features invading the perivesical fat and one positive pelvic lymph node, staged pT3N1Mx. The patient is currently doing well after completing adjuvant gemcitabine with cisplatin. At six-month follow-up, the patient had good urostomy function, protuberant and healthy stoma, and no issues with stomal appliance fit ().


A 78-year-old man was admitted to our Internal Medicine Department because of asthaenia, anorexia, unexplained weight loss (6 kg in the last four months), and high fever spikes lasting for two weeks. His past medical history includes hypertension, type 2 diabetes, hypercholesterolemia, and a transient ischemic attack. Two months before admission he underwent stent placement in the right coronary and circumflex arteries because of ischemic heart disease.
On admission, his blood pressure was 100/60 mmHg and his temperature 38.2°C. There were no enlarged lymph nodes, hepatosplenomegaly, or other positive physical examination findings. A full blood count was normal and the erythrocyte sedimentation rate was 23 mm/hour. A biochemical profile showed potassium 8.1 mEq/L, sodium 128 mEq/L, serum creatinine 2.3 mg/dL, C-reactive protein 11.2 mg/dL, LDH 1383 IU/L, and ferritin 7275 mg/dL.
With the suspicion of adrenal insufficiency, he was started on hydrocortisone and fludrocortisone, with progressive clinical improvement and correction of hyponatremia, hyperkalemia, and renal function. During admission he continued to be febrile with spikes of up to 39°C, which resolved with oral naproxen. Baseline serum cortisol levels were 13 mg/dl, with no response to ACTH stimulation. Serum ACTH levels were 217 pg/mL (normal <50 pg/mL), and 24-hour urinary free cortisol was 13 μg (normal, 20–90 μg). An abdominal CT-scan () showed a heterogeneous mass of about 6 cm in diameter in each adrenal gland without other structural abnormalities or lymph node enlargement. F18FDG PET/CT-scan confirmed these findings, and showed high metabolic activity in both tumours, highly suggestive of malignancy.
A percutaneous Tru-cut needle biopsy of the left adrenal gland was performed. The histological examination revealed diffuse large B-cell lymphoma positive for CD20, BCL-2, BCL-6, and Ki-67 stain, showing a proliferative index >90%. Immunostains for cyclin D-1, CD10, S-100, chromogranin A, pankeratin, and calretinin were negative. Staging was completed with a bone marrow biopsy, in which no neoplastic invasion was observed. Finally, a diagnosis of large B cell extranodal lymphoma (bilateral adrenal, which determines functional impairment) IIEB stage with an international prognostic score of 3 was made.
Five cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP) and one cycle with cyclophosphamide, vincristine, prednisone, and rituximab (R-CVP) were administered reaching complete response ().
The patient remained in complete remission for two years, until his death because of brain metastasis of an epidermoid lung cancer diagnosed after PAL.


A 22-year-old man, of South Asian ethnicity, with a known diagnosis of Stage IIIA (pT1, cN2, and cM1a) nonseminomatous germ cell tumour was undergoing multiagent cytotoxic chemotherapy with curative intent. He had no significant medical comorbidity but was a cigarette smoker and moderately overweight. He had undergone right inguinal orchidectomy which revealed predominant (99%) embryonal carcinoma (immunohistochemistry positive for placental alkaline phosphatase, cytokeratins, and CD30) with a minor (1%) malignant teratoma intermediate component. Staging CT scan showed lymphadenopathy in the retroperitoneum, pelvis (right external iliac), superior mediastinum, and left axilla. Four days after the first dose of intramuscular bleomycin as part of the bleomycin, cisplatin, and etoposide (BEP) chemotherapy regimen, he complained of recent onset headache over a 7–10-day period. He described it as a generalised, moderately severe constant “pressure” headache that was worse on waking in the morning and exacerbated by coughing and straining. There were no other neurologic symptoms. He had also vomited on two occasions in the first 5 days following cisplatin and had several episodes of loose stools. On examination, there was no focal neurologic deficit and he was alert and orientated. Laboratory investigations showed mild hyponatraemia (133 mM), raised serum urea (7.8 mM), and profound leucopaenia (0.7 × 109/L) and neutropaenia (0.0 × 109/L), and moderate thrombocytopaenia (53 × 109/L) in keeping with recent chemotherapy administration. On the second day of admission he had a brief and self-terminating episode of loss-of-consciousness. Unenhanced CT scan of the head showed hyperdensity in the distal aspect of the superior sagittal sinus close to the torcula () and a subsequent CT intracranial venogram confirmed acute sagittal venous sinus thrombosis close to the torcula with complete occlusion and partial nonacute occlusion of the right transverse and sigmoid sinuses. There was no evidence of cerebral metastases. He was treated with low-molecular-weight heparin (enoxaparin 1.5 mg/kg once daily) administered subcutaneously and there was a rapid improvement in the headache over a week. Following three months of therapeutic anticoagulation without any haemorrhagic complications, repeat imaging confirmed recanalisation of the cerebral dural venous sinuses with disappearance of the hyperdense thrombus () and anticoagulation was discontinued. Currently, the patient is in complete remission from his metastatic testicular cancer with regression of all sites of lymphadenopathy having completed all 3 scheduled cycles of BEP chemotherapy.


A 23-year-old woman with a history of IPAH presented to our service with malignant catatonia. She was diagnosed with IPAH at the age of 8 due to her high mean pulmonary arterial pressure (PAP) of 50 mmHg (a diagnosis of IPAH is made if PAP is >25 mmHg according to the World Symposium on Primary Pulmonary Hypertension 1998). Because her IPAH progressed despite treatment with beraprost and home oxygen therapy, she began to receive 24-hour infusions of epoprostenol (prostaglandin I2) at the age of 12. Epoprostenol was temporarily effective to improve pulmonary circulation, but when she was 23 years old, her heart function deteriorated to the New York Heart Association (NYHA) class III []. At age 16, the patient was also diagnosed with insulin-resistant diabetes mellitus (DM) and was started on insulin injections.
The patient’s significant medical history also included her psychiatric illnesses. She was hospitalized at the ages of 20 and 21 because of attempted suicide under depressed mood with psychomotor excitement and psychosis. Therefore, she had been treated with antidepressants and antipsychotics for psychotic depression, but she was later re-diagnosed with schizophrenia during the present hospitalization.
At the age of 23 years, the patient became non-compliant with psychiatric medications. One month later, she became agitated and began muttering and then was gradually rendered mute and cataleptic. Subsequently, she was hospitalized at our psychiatric ward because of a substuporous state. Despite continuing her cardiovascular drugs, she was physically unstable with tachycardia, hypertension, a fluctuating blood glucose level ranging from 50 to 400 mg/dL, and hyperthermia (up to 40.0 °C). The findings of cardiac examination on admission are shown in Table . The medications used to treat these somatic problems were oral digitalis (0.125 mg/d), spironolactone (25 mg/d), warfarin (2 mg/d), furosemide (40 mg/d), epoprostenol, and subcutaneous insulin injections.
Head magnetic resonance imaging (MRI), electroencephalography (EEG), and cerebrospinal fluid (CSF) analysis were unremarkable. We determined that the most likely diagnosis for her condition, including delirium, mutism, catalepsy, hyperpyrexia, posturing, and autonomic instability, was malignant catatonia according to the criteria of Fink []. The score on the Bush-Francis Catatonia Rating Scale [] was 23 on admission (Fig. ). Lorazepam (given orally, 3 mg per day) alleviated the substuporous state, but she developed Capgras’ syndrome and persecutory delusions and exhibited agitation. Levomepromazine (50 mg/day) and aripiprazole (24 mg/day) were not effective for these symptoms. Because her autonomous and hemodynamic instability was potentially life threatening, we decided to introduce ECT using a square wave-generating instrument (Thymatron System IV; Somatics, LLC, Lake Bluff, IL, USA) after obtaining informed consent from her family. To monitor for potential pulmonary hypertensive (PH) crisis, which is the most serious complication of ECT, a pediatric cardiologist and medical engineer carefully observed her cardiopulmonary status during all ECT sessions. Endotracheal intubation was performed, and standby nitric oxide (NO) inhalation was prepared in case of PH crisis secondary to dilating pulmonary arteries. Moreover, during each ECT procedure, epoprostenol was continuously infused to prevent PH, and a combination of propofol and remifentanil was used to induce anesthesia. Remifentanil was chosen because it is a short acting opioid with strong anti-nociceptive features and was expected to stabilize blood pressure. Propofol was injected intravenously using a target-controlled infusion (TCI) at blood concentrations between 3 and 4 mcg/mL, which can keep most patients unconscious, and remifentanil was infused at 0.5-1.0 mg/h, followed by rocuronium (0.8 mg/kg) to relax the muscles. TCI is a drug infusion technique that combines a real-time pharmacokinetic model with an infusion pump and allows the administration and maintenance of a constant blood concentration of drug.
The ECT electrodes were positioned bilaterally through all sessions. For the first ECT session, a stimulus dose of 25 % was administered, and seizures were observed for 59 s by electromyography (EMG) and 69 s by EEG. Though the patient was expectedly tachycardic during the intubation procedure and after convulsion, her blood pressure was kept within the expected range. Therefore, we speculated that pulmonary artery constriction did not occur and that NO was not needed. Because she complained of intense throat pain, we used a laryngeal mask instead of intubation for subsequent ECT sessions. This was determined after discussing with the anesthesiologists who assured a laryngeal mask would be sufficient for NO inhalation and oxygenation. Moreover, we speculated she would need more than 10 ECT sessions but were concerned she would not tolerate repeated intubation. As the ECT sessions were repeated, the symptoms of malignant catatonia, such as tachycardia, hypertension, fluctuating blood glucose and hyperthermia, were gradually alleviated, and these parameters were generally within the normal ranges after the ninth session. Eventually, we completed 14 ECT sessions with an average stimulus dose of 56.6 %, which is equivalent to 285 mC. The average seizure durations were 35.9 s on EMG and 39.3 s on EEG. The Bush-Francis Catatonia Rating Scale score decreased to zero after the last ECT session (Fig. ). Upon completion of the ECT, her mental state returned to her baseline. She was discharged from the hospital 93 days after admission. Follow-up was continued on an outpatient basis with the patient in remission with the oral administration of aripiprazole (30 mg/day), valproic acid (600 mg/day), lorazepam (1 mg/day), zotepine (150 mg/day), digitalis (0.125 mg/day), spironolactone (25 mg/day), warfarin (2 mg/day), and furosemide (40 mg/day) in addition to epoprostenol and insulin therapies.
The patient and/or her family had shared their perspectives on the treatments she received. In particular, when the patient was considered to be not competent in terms of understanding her medical condition, the treatment team gave her family a full explanation regarding her condition and treatment options, including ECT and medication treatments. Then, when the patient recovered well enough to be competent, the same process was repeated to obtain her informed consent.


A 64-year-old woman presents to the Emergency Room with palpebral edema as well as various erythematous plaques in supraciliary and malar areas that appeared and have gradually worsened a couple of days prior to presentation (). Initially the patient did not share having changed her daily facial hygiene, making any diet changes, getting any animal bites, or taking any new medication.
On exanimation, the patient had facial swelling, pain on palpation, and flushing.
A full blood count was performed with no alterations of the blood formula, neither leucocytes nor the eosinophils, and no inflammatory markers or IgE elevated.
Still suspecting an allergic reaction, she was given treatment with corticosteroids and antihistaminic medication, both intramuscularly and with a unique dose.
Four days later, the patient returned to the Primary Care consultation due to recurrence of her symptoms and was referred once again to the Emergency Room where she was clinically diagnosed with cellulitis and received antibiotic treatment (amoxicillin with clavulanic acid) along with corticosteroids and antihistaminic medication once again.
Although she referred a short period of improvement of the symptoms, the swelling and rash reappeared when the treatment was suspended along with another two nodules of hard consistency localized on the cheekbone of the right facial side ().
During the fourth Primary Care consultation, the patient was interrogated more thoroughly and only then she mentioned that she was visiting, for about four months, an Esthetic Private Clinic, where she was injected in various sessions with Metacrill, as a facial lift, for beauty purpose. Apparently no other patient suffered the same symptoms.
Due to suspecting an allergic reaction to the Metacrill and the failure of the initial treatments, she was referred to the dermatologist.
During the dermatology consultation, a biopsy of one of the granulomas was performed, being diagnosed as Chronic Edematous Panniculitis to a foreign body and probably caused by a polymeric material in the context of an iatrogenic infiltration of esthetic filler ().
The patient received a new treatment with corticosteroids, in a decreasing dose associated with antibiotics (doxycycline orally).
When trying to lower the dose of corticoid, the patient suffers a new episode of edema and as a consequence the dose of oral corticoid is raised and is associated with a corticoid topic cream.
Due to the bad evolution, the patient is sent to the autoimmunity consultation at the hospital where she receives an immunosuppressive treatment with Tacrolimus and was not presenting new symptoms ever since. Every three months, the levels of the immune response are being tested to avoid toxicity ().


A 37 year-old male with a history of chronic ear infections throughout childhood, and childhood asthma and rhinitis was referred to immunology clinic for an evaluation. Since the age of 15 years, he is having 2–3 episodes of bronchitis per year, developed recurrent otitis media requiring myringotomy tubes, and suffered six image-proven sinus infections in the previous 2 years. In 2013, he was hospitalized twice for pneumonia. He has no history of receiving prior blood or blood product transfusions. In 8/2014, a diagnosis of common variable immunodeficiency (CVID) was confirmed. His laboratory findings are shown in Table . Gammagard 10 % IV infusion was started at the rate of 30 cc/h. Within 5 min of starting IGIV, patient reported tightness of chest, difficulty in breathing, facial flushing, bilateral wheezes, pulse rate of 126/min, severe rigor, and oxygen saturation drop to 86 %. Patient was given IV famotidine, IV meperidine, IV hydrocortisone, IV Benadryl, and Oxygen at 6 L. Patient was skin tested for various IGIV and subcutaneous Ig preparations along with purified IgA and normal saline. On 2/11/2015, Patient was given graded dosage of IgA-depleted IGIV (Gammagard SD) preparation (5, 10, 30 ml) to which skin test was negative, with premedication of prednisone, Benadryl, and acetaminophen orally an hour prior to infusion. He tolerated the infusion without any side effects. Patient tolerated infusion at 80 ml/h rate. Patient has no history of allergies to pollen, food, or drugs.


A 54-year-old right-handed woman presented 12-year history of progressive memory decline. She was a university educated woman. At the age of 42 years, her main symptoms were that she forgot names and needed to make notes. She had poorer recall of information than the others at her school of hotel management. In contrast, she was independent in all activities of daily living but her mood was depressed. At initial consultation, when she was 45 years old, general neurological exam was unremarkable. Attention, language and visuospatial function and frontal executive function were normal. Apraxia, dyscalculia and Gerstmann syndrome were not shown. However, Hopkin’s verbal learning test showed that free-recall score was 21 (5-8-8) and 20 min delayed-recall was 2. Its recognition score presented that true positive was 8 and false positive was 3. Delayed recall of Rey figure score was 5.5. Mini-Mental State Examination (MMSE) was 27/30, time orientation 4/5 and three word recall 2/3. Magnetic Resonance Imaging (MRI) scan are shown in Fig. . The upper axial and coronal FLAIR images showed that medial temporal lobe atrophy was not prominent but bilateral parietal atrophy was on. Her APOE genotype was homozygous for ε3. Her mother had dementia at the age of 40s and died before 60s. No specific diagnosis was made in her mother. Her father and only brother did not show dementia. She has two daughters, 29 and 26 years old. The initial clinical impression was mild cognitive impairment with depression. However, AD could not be ruled out. She showed progressive deterioration in verbal and visual memory. At the age of 53, her MMSE was 2/30 and clinical dementia rate (CDR) was 3. She was able to respond only to her name and distinguish her daughter from unfamiliar people. She needed personal care. Her brain MRI (Fig. , lower) demonstrated that global cortical atrophy, more prominent in medial temporal and parietal lobes. FDG-PET (fludeoxyglucose- positron emission tomography) of the patient reveals the bilateral temporal, parietal, precuneal and frontal hypometabolism (Fig. ). They consent to perform genetic sequencing on her and her 2 daughters. We screened the APP, PSEN1, PSEN2 and PRNP (prion protein) gene.
White blood cells (or buffy coat) were separated by centrifugation at 800 g (30 minutes). Genomic DNA was extracted by GeneAll blood kit (Seoul Korea) as described in the protocol. We performed a polymerase chain reaction (PCR)-based genetic analysis. We used PCR primers for APP exon 16 [] and 17 [], PSEN1 exon 4, 5, 6, 7, 8 and 11 [, ], PSEN2 exon 4, 5, 6, 7 and 12 [] and PRNP genes []. Single-strand conformation polymorphism (SSCP, Fig. a) analysis was performed with the PCR products. Denaturation buffer was added to the amplicons (50:50), which was composed of 95 % formamide, 18mMol EDTA and 0.025 % xylene cyanol, and bromophenol blue. These mixes were incubated on 98 °C for 10 minutes, resulting in the denaturation of double stranded DNA bands []. The single stranded DNA bands were separated in non-denaturing polyacrylamide gel electrophoresis (PAGE) (10-12 %) for 18–21 hours (BioRAD, Seoul, Korea). Depending on the mutations, single stranded DNAs could have different mobility in the gel. SYBR Gold staining (Invitrogen, USA) was used for staining DNA bands, which visualized under UV light. To confirm and identify the mutation, sequencing was performed for all PCR products at both directions by the BioNeer Inc. (Dajeon, Korea). Prior to sequencing, we purified the PCR products by GeneAll PCR protocol kit (Seoul, Korea), as described in the protocol. For the sequencing reactions, Big Dye Terminator Cyclic sequencing was performed on ABI 3730XL DNA Analyzer (, Bioneer Inc., Dajeon, Korea) was used (Fig. b and c). We aligned the sequenceing results by NCBI Blast (), and the chromatograms were analyzed by DNA BASER () software. Mutations and sequence variants were identified by using the NCBI Gene () and UniProt () databases.
Mutations were analyzed by an online software, the Polymorphism Phenotyping v2 (PolyPhen 2, ), which could make in silico predictions on the putative damaging properties of mutations. This software made a comparison on the wild-type and mutant alleles of proteins by homology searching and multiple sequence alignment. Identity- and structure-based searches, such as accessible surface area and hydrophobicity features, were also performed. These predictions might define the potential role of amino acid exchanges in the proteins. Three categorized of mutations could be available: probably, possibly damaging or benign variants. PolyPhen2 could also provide a multiple sequence alignment, by comparing the homologous sequences from different vertebrate and non-vertebrate species. Two types of datasets could be available: the HumDiv and HumVar scores. HumDiv should be used for the prediction of putative pathogenic nature of rare alleles. In HumDiv scores, the alleles with mildly damaging properties should be categorized as possibly damaging. HumVar should be used in case of diagnosis of Mendelian disorders. Here, the highly damaging phenotypes should be distinguished from the alleles with less damaging phenotypes [].
Sorting Intolerant from Tolerant or SIFT algorithm () is an online software, which estimates the potential effects of missense mutations substitution on the protein function. SIFT uses several protein databases, including SWISS-PROT, SWISS-PROT/TrEMBL, or protein databases of NCBI, and calculates the possibility on the damaging nature of mutations by the comparison of the mutant and normal proteins. It scores the amino acid substitutions, and under and over the score of 0.05, mutations could be defined as deleterious or tolerated, respectively diction [].
3D structures of PS1 with mutation(s) were analyzed by an online software, the Raptor X (, Fig. ). Server of protein structure prediction used the full amino acid sequence of PS1 (1–467 amino acids). Discovery Studio 3.5 Visualizer from Accelrys was used to display the images after superimposition [].
Alternative mobility was found in the SSCP (Fig. a) for exon 7 of PSEN1 gene. Sequencing revealed a G → C exchange at codon 209, resulting in a glycine (GGA) → Alanine (GCA) exchange (Fig. b and c). This mutation was not found in neither in the AD and FTD mutation database nor in the Alzgene database, which suggested that it might be a novel mutation in PSEN1. Mutation was checked in the Exome Aggregation Consortium (ExAC) database, which screened 60,706 unrelated individuals for the different disease causing genes (). PSEN1 G209A was not found in this database.
PolyPhen-2 scores were high, both HumDiv and HumVar was 1.000 (sensitivity: 0.00; specificity: 1.00 at both scores) suggesting G209A as a probably damaging variant. Multiple sequence alignment suggested that glycine 209 might be a conservative residue among vertebrates. Several mammalian (such as dogs, pigs) and non-mammalian (such as chicken, frog, zebrafish) showed glycine at the same position in their presenilin or presenilin-like proteins. SIFT prediction also confirmed the probably damaging nature of mutation, with the score of 0.
3D prediction (Fig. ) revealed significant differences in the N-terminal region of normal PS1 protein. The c-terminal region of normal PS1 and PS1 with G209A were overlapped. These findings suggest that even glycine and alanine are both small sized, hydrophobic amino acids, but one extra –CH3 group on alanine could result significant differences in the protein structure. Since alanine is more hydrophobic than glycine, it could result extra stress inside the helix.
We reported a novel mutation in PSEN1, the G209A in a female patient in her early 50s. Even though we could not find any affected family members, one of her daughters is a mutation carrier and deceased mother had an undiagnosed case of dementia. Our finding suggested that this mutation could be a novel probably pathogenic variant, involved in EOAD.
Glycine 209 is located in the transmembrane –IV region of PS1 protein, and it was suggested as a conservative residue. For codon 209, three additional mutations were found, G209R, G209E and G209V (Table ), which also suggested that Glycine 209 might be an important residue in PS1. G209R was found in a Japanese family. The proband was a male patient, the disease progression started at the age of 46. Additional affected family members were found, since his sister and mother also showed clinical symptoms. All of these patients showed rapid progression of dementia, with memory impairment, amnesia, aphasia, disorientation and personality changes. Parietal focal symptoms such as apraxia or agnosia were not apparent in the patients []. G209V was found in a German family, where the age of onset ranged between 30–48 years. Clinical symptoms included myoclonus, seizures, language loss and apraxia and agnosia [, ]. G209E was reported in one AD patient by Rogaeva. No detailed information was found on the disease age of onset or clinical phenotype of disease, associated with G209E [].
In silico modeling and the previously described mutations for G209 could support that PSEN1 G209A could be a novel causative mutation for AD. Glycine and alanine are similar, both of them are small sized hydrophobic amino acids. 3D prediction suggested that in this mutation, a single extra –CH3 group could result disturbances inside the PS1 protein. Since alanine is more hydrophobic than glycine, it could enhance the stress inside the PS1 TM domain or between PS1 and its binding partners.
As conclusion, we suggest that G209A can be a novel, probably pathogenic variant in PSEN1. Guerrio et al. published an algorithm for the novel mutations in PSEN1 and PSEN2. Several criteria were analyzed: such as whether the mutation is segregates with the disorder segregation; whether there are additional affected family members; and whether additional mutations were described for the screened residue []. PSEN1 G209A was not found in the ExAC database, which could be a strong evidence on its pathogenic nature. The additional three, probably pathogenic mutations for the glycine at position 209 (G209R, G209V and G209E) can also enhance the importance of residue 209 in PSEN1 and the probably damaging nature of G209A. However, the family history of patient could not be well-defined. Her mother was a dementia patient, but it remained undiagnosed, so it is unclear whether she is the carrier of mutation. One of her daughter carried the mutation, who might be in the pre-symptomatic stage of disorder. Online predictions were suggested that PSEN1 G209A mutation could be a probably deleterious variant. Additional studies are needed on for this variant since its pathogenic nature can’t rely on the in silico predictions only.


A 30-year-old lady presented with complaints of progressive ascending weakness of both lower limbs for a week for which a diagnosis of GBS was made elsewhere. After few days she also developed incontinence of urine and stools. A Magnetic Resonance Imaging (MRI) done then revealed myelitis of the spine at junction of the medulla and cervical spine. Owing to the diagnostic quandary, she was referred to our centre for further evaluation. Review of her history revealed a course consistent with the diagnosis of GBS but lack of any prodrome or viral illness prior to the onset of the weakness. Past history revealed occurrence of pain with minimal swelling affecting the small joints of hands, wrists, knees, and ankles, associated with Raynaud's phenomenon. These symptoms had been occurring for 2-3 months every winter for the last three years and always subsided with onset of summers. Only this time, the resolution of symptoms was not complete. She had been treated intermittently with nonsteroidal anti-inflammatory drugs (NSAIDs) and low dose corticosteroids by her general practitioner (GP). She had two healthy children, was a teetotaler, never suffered from tuberculosis, was not a known diabetic or hypertensive, and did not give any history of abortions. Family history was insignificant. General examination was unremarkable except for pallor. Central nervous system (CNS) examination revealed a conscious oriented lady with flaccid quadriparesis, areflexia, and unresponsive plantar reflexes. Cardiovascular, respiratory, and abdominal examinations were normal. Musculoskeletal examination revealed minimal to mild synovitis in few metacarpophalangeal (MCP) and interphalangeal (IP) joints of both hands and wrists. Laboratory investigations revealed haemoglobin (Hb) 9.2 g/dL, total leucocyte count (TLC) 7800/mm3, total platelet count of 120000/mm3, a normocytic normochromic blood picture, serum sodium (Na+) 142 mEq/dL, serum potassium (K+) of 4.6 mEq/dL, and normal liver and kidney function tests. Chest radiograph was reported to be normal. Serology for Human Immunodeficiency Viruses (HIV) types 1 and 2, Hepatitis B Virus Surface Antigen (HBsAg), Hepatitis C Virus (HCV), Herpes Simplex Virus (HSV) types 1 and 2, and Cytomegalovirus (CMV) was negative. Cerebrospinal fluid (CSF) analysis showed albuminocytological dissociation with sugar 85 mg/dL and proteins 110 mg/dL and no cells. MRI of brain and spinal cord reviewed showed hyperintensities in T2 weighted images in cervicomedullary junction (Figures and ). Nerve conduction study (NCS) showed pure motor involvement with increased distal latencies, decreased conduction velocities, normal amplitude, and absent F-waves with no affection of sensory nerves, features which in the background of rapidly progressive ascending areflexic quadriplegia suggested the diagnosis of the Acute Inflammatory Demyelinating Polyneuropathy (AIDP) subtype of GBS. Anti-Nuclear Antibody (ANA) was positive in 1 : 640 dilution and homogeneous in pattern by indirect immunofluorescence (IIF), and anti-smith antibody (anti-Sm) was positive with intensity of 65 by EUROLine scan. Levels of complement component C3 were low (76.2 mg/dL, normal 90–180 mg/dL) while component C4 levels were towards the lower limits of normal (10.5 mg/dL, normal 10–40 mg/dL). Direct Coombs test (DCT), rheumatoid factor (RF), and cyclic citrullinated peptide antibodies (anti-CCP) were negative. A provisional diagnosis of SLE with CNS involvement was kept in view of arthritis, CNS involvement, positive ANA, and low complements. Treatment was instituted immediately with intravenous methyl prednisolone 1 g once a day for three days followed by oral prednisolone at 1 mg/kg body weight daily, hydroxychloroquine 200 mg twice a day, and cyclophosphamide 750 mg infusion. Her neurologic status improved and a repeat neurological examination after 3 days showed improved power of 2/5 in both upper limbs. After two weeks her muscle power improved to 2/5 around hip joints and 3/5 around shoulders, elbows, knees, and ankle joints. Her bladder and bowel functions also improved and she could be decatheterised. Subsequent MRI screen of spine repeated after 3 weeks was normal.
The patient was put on monthly pulses of cyclophosphamide, and steroids were continued at 1 mg/kg body weight for 6 weeks and then tapered by 10% of the dose every two weeks. After 12 weeks, she had grade 4− (4 minus) muscle power around hips. Power around shoulders, elbows, wrists, knees, and ankles was grade 4. Grip was normal. She is able to carry out most of her activities of daily living.


Case 1. A 2- days old male infant, weighing 3.5 kilograms, was noted to have bluish discoloration over the lips and periphery, with percutaneous oxygen saturation of 75%. The baby was born in Madrid from parents refugees from Kosovo during the war 1999. He required intubation following one apneic episode. Despite being ventilated on 100 % oxygen, pulse oximetry could not be raised above 80 %. Hence, a prostaglandin infusion was commenced. Physical examination showed a short neck, low hairline at the back of the head, and particularly restricted mobility of the upper spine. Cardiovascular and respiratory examination was normal.
An electrocardiogram showed tight atrial and ventricular hypertrophy. Chest X-ray showed cardiomegaly. Transthoracic echocardiography showed confluence of the all pulmonary veins above left atrium and draining together to the right atrium. The diagnosis of total anomalous venous return to the right atrium was confirmed. In the region of fosa ovale restrictive secundum atrial septal defect was presented with a predominantly right-to-left shunt.
Suspicion for KFS was indication for cervical radiography and multiple developmental anomalies of the upper cervical spine, consistent with Klippel-Feil syndrome. Antero posterior (AP) as well as lateral neutral, flexion, extension radiographs of the cervical spine demonstrate abnormal development of the upper cervical spine described as follows: There is at least a partial fusion of C2 and C3, the ossified portion of the dens is noted to be inferiorly displaced relative to the anterior arch of C1, the posterior elements of C1, C2 and likely C3 are hypoplastic/absent, and there is a defect in the lamina of the superior – most vertebral body which contains formed posterior elements. The fused vertebral bodies are small and also have an abnormal anterior convex configuration. On the flexion and extension radiographs and atlanto-axial, instability is identified. The skull projects over most of the cervical spine on the AP views so evaluation for vertebral bodies is limited. The posterior skull is noted to have a “beaten copper” appearance. A cervical rib is present on the right. The paravertebral soft tissues have normal appearance. The nasopharynx, oropharynx, and laryngopharynx are patent and clear.
Family history was normal for congenital heart disease, clefts, MR/DD, seizures, hearing loss, eye, Dx, diabetes, other birth defects, and pregnancy losses. Consanguinity is denied. Genetics examination confirmed new mutations in the GDF6
At the 7th day of birth, at the “Hospital Universitario La Paz” in Madrid surgical repair of the anomalous pulmonary venous return was done successfully and in the next day, in stable condition, was extubated. At the 15th day of life he was discharged on the only Captopril, 0.5mg/kg three times daily. Control echocardiography showed normal pulmonary venous return without obstruction and normal heart function.


Case 2. A 28-month-old girl, as the fourth child, from normal pregnancy and absolutely health parents, weighing 16.3 kg, during the routine pediatric examination systolic murmur was noted and for cardiological examination at tertiary level was referred. The child’s growth and development was completely normal. There was no sweating or fatigue during feeding or normal activities. Complete clinical and cardiological examination was obtained. Objective examination of other children is in normal limits.
During routine examination a short neck, low hairline at the back of the head and restricted mobility of the upper spine was noted. Anteroposterior (AP) and lateral in extension radiographs of the cervical spine demonstrate abnormal development of the upper cervical spine as a partial fusion of C2 and C3 and hypoplastic C1 spine. The fused vertebral bodies manifested an abnormal anterior convex configuration. Arterial blood gas was within normal limits. Clinical examination demonstrated: a quite precordium, normal first heart sound, short midsystolic murmur 2-3/6 degree on the apex and left sternal border, and single second heart sound. Electrocardiogram showed: normal sinus rhythm, left axis deviation, and incomplete bundle branch block. A chest radiogram revealed a normal cardiac silhouette.
The pulmonary vasculature was normal in appearance, and there were no infiltrates seen. Cross-sectional echocardiography demonstrated: normal systemic and pulmonary vein connection, big hole, diameter 12 mm, in the middle part of interatrial septum with nonrestrictive left to right flow. There was normal atrio-ventricular and ventriculo-arterial connection. By continuous Doppler waves and color Doppler trivial tricuspid regurgitation and hyperdynamic flow through the pulmonary, artery was noted. Family history for consanguinity and congenital heart disease is denied. At age of 18 month, in the absence of cardiac services in Kosovo, child was sent in the Santa Rosa Children’s Hospital (USA) and surgical correction of atrial septal defect has been successfully done. Also genetics examination confirmed new mutations in the GDF6 and GDF3 genes.


Case 3. A 2-day-old male infant, weighing 2890 g., from the first and normal pregnancy, from both healthy parents, born in regional hospital, at the second day of life is presented with respiratory distress. Despite being ventilated on 100 % oxygen, pulse oximetry could not be raised above 85 %. Baby was transferred at tertiary level and a complete history and careful physical examination was obtained. Objectively a short, webbed neck, decreased range of motion in the cervical spine and a low hairline was noted and suspicion for KFS awakened. Anteroposterior (AP) and lateral radiographs of the cervical spine demonstrate abnormal development of vertebra C1, C2 and C3 with massive fusion of the cervical spine.
Echocardiography revealed situs solitus, levocardia, atrioventricular concordance and transposition of the great arteries with patent ductus arteriosus. At the third day of life balloon atrioseptostomy was performed and 7- 8 mm communication between atria was achieved. In the lack of cardio surgery services in Kosovo and financial impossibility of family to cover surgery abroad Kosovo, baby dies after 2 months as a consequence of congestive heart failure and respiratory infection.


Case 4. An asymptomatic girl, aged 12 years, born to non-consanguineous parents and from normal pregnancy, so far with normal development, was referred for assessment of a recently discovered systolic cardiac murmur, grade at 2 from 6, and a best heard along the left parasternal border. During the clinical examination a very short neck, reduced bilateral neck movements, and a low hairline at the back of the head was noted. Radiographic examination showed fusion of C1 and C2 and C5-7 vertebrae. Transthoracic echocardiographic exami-nation, using Acuson Sequoia 256 machine, showed usual arrangement of the atrial appendages and thoraco-abdominal organs, with concordant atrio-ventricular and ventriculo-arterial connections. There was a slight enlargement of the right heart side. In the parasternal short-axis view thick pulmonary valve cusp with restricted systolic motion was noted. The main pulmonary artery was dilated. By Doppler and color Doppler turbulent flow through the pulmonary, artery was noted with max pressure of 68 mm of mercury.


A 24-year-old man developed lower limbs edema and exertion dyspnea in the past 3 years. When he first came to our institution, he was already receiving high doses of furosemide, hydrochlorothiazide and spironolactone, without an established diagnosis.
On physical examination, lower limb edema and stasis dermatitis were observed. The apical impulse was normally placed, and jugular venous distention was not present. Upon cardiac auscultation, wide inspiratory splitting of the second heart sound, and no other sounds or murmurs.
The electrocardiogram was normal. Chest radiography showed a normal cardiac silhouette, without calcifications or signs of pulmonary congestion. The brain natriuretic peptide (BNP) level was 69pg/mL (reference range <100pg/mL). Echocardiogram revealed normal function of right and left ventricles, biatrial enlargement, and an estimated pulmonary artery systolic pressure of 25mmHg. The pericardium was described as normal. Coronary arteries were dilated, and the left main coronary artery measured 7.6mm and the right coronary artery (RCA), 10mm.
The diagnosis of constrictive pericarditis was considered due to the presence of symptoms and signs of HF with normal morphology and function of both ventricles. Magnetic resonance imaging of the heart showed a diffusely thickened pericardium and interventricular septal bounce during systole (). Coronary computed tomography angiogram was performed to evaluate the unexpected coronary dilation observed on echocardiogram. An anomalous RCA arising from the pulmonary artery was diagnosed ().
Surgical resection of the diseased pericardium was performed along with coronary revascularization, by performing a right internal thoracic artery graft to the RCA and occlusion of the anomalous origin of this vessel at the pulmonary artery. Pathological assessment of the pericardium demonstrated a nonspecific chronic pericarditis of low intensity. Polymerase chain reaction used to detect Mycobacterium tuberculosis was negative. The patient was discharged home with marked improvement of symptoms.


A 68-year-old man had undergone low anterior resection and regional lymph node dissection for rectal cancer (Fig. ). The pathological examination showed the tumor to be a moderately differentiated adenocarcinoma with invasion to the subserosa (T3) and regional lymph node metastasis (N1). No distant metastases were found at the time of operation (M0), and the pathological staging of the tumor was stage IIIB, according to the seventh edition of the International Union Against Cancer TNM classification. He was treated with oral uracil and tegafur plus leucovorin for 5 cycles as adjuvant chemotherapy. Eight months after the initial surgery, follow-up computed tomography (CT) showed an enlarged retroperitoneal lymph node located below the aortic bifurcation, which would be considered one of the aortic bifurcation nodes (Fig. ), a tumor in the head of the pancreas (Fig. ), and dilation of the common bile duct and main pancreatic duct. Positron emission tomography (PET) showed abnormal uptakes of 18F-fluorodeoxyglucose (18FDG) in these two lesions (Fig. ). Biopsy of the narrowed section of the pancreatic duct showed an adenocarcinoma. However, it was difficult to identify whether the pancreatic tumor was primary or metastatic disease. Clinical examination was unremarkable. Blood tests showed continued elevation of serum bilirubin (>2.0 mg/dL). The serum carcinoembryonic antigen level was within normal limits (4.1 ng/mL), while the serum carbohydrate antigen 19-9 level was increased to 127 U/mL. Based on these findings, a diagnosis of retroperitoneal lymph node metastasis from the previously resected rectal cancer and primary pancreatic head cancer or pancreatic metastasis from rectal cancer was made. For these lesions, resection of the enlarged retroperitoneal lymph node and pancreaticoduodenectomy were performed. The pathological examination of the resected specimen showed that the histological type of both the retroperitoneal lymph node and the pancreatic head tumor was adenocarcinoma. Moreover, they were identical to the primary rectal cancer (Fig. –), and immunohistochemical study of the pancreatic tumor showed positive immunoreactivity for CDX-2 staining (Fig. ). Based on these findings, these lesions were diagnosed as metastases from the primary rectal cancer. These specimens had negative resection margins. The patient’s postoperative course was uneventful. After the second surgery, he was given 5-fluorouracil, leucovorin, and oxaliplatin (modified FOLFOX6) as adjuvant chemotherapy. However, the chemotherapy was discontinued after only 5 cycles due to an adverse event. He was then routinely followed up without any medication. Sixty-nine months after the metastasectomy, there has been no indication of recurrence.


A 16-month-old female Caucasian child was admitted to our hospital for recurrent and postprandial vomiting episodes, which started at 11 months of age. A history of gastroesophageal reflux, unresponsive to drug therapy, was present until she was 1 year old, in association with recurrent respiratory infections. On physical examination, her weight was 9.97 kg (less than the fiftieth percentile) and height 82.5 cm (less than the ninety-fifth percentile). Her general condition at admission was good, with abdominal bloating in the absence of organomegaly. A routine basic metabolic panel was performed, along with general functional tests, complete blood count, and C-reactive protein test. All results were normal, in association with plasma amino acids, celiac serology, urinalysis, cytomegalovirus serology, stool test, and parasitological examination of stools. A neurological examination with electroencephalogram and fundus oculi was normal. A barium study showed stomach rotation along a horizontal plane of the stomach, with partial rotation of the greater curvature toward the diaphragmatic side; the stomach was markedly dilated with delayed gastric emptying (Fig. ). Esophagogastroduodenoscopy was negative for mucosal alterations. A diagnosis of chronic organoaxial GV was advanced with evidence of increasing difficulty in feeding. Due to the persistence of episodes of vomiting, in combination with progressive failure to thrive, gastropexy and Nissen fundoplication were performed. At the 6-month follow-up, the child demonstrated catch-up growth with regular calorie intake.


A 9-month-old male Caucasian baby was admitted to our hospital for chronic, recurrent, postprandial vomiting, which started at 7 months of age. He was a term-born baby, at birth his weight was 2.070 kg and during the first days support was required for respiratory distress. Since birth, he was formula fed, underwent gluten-free weaning at 5 months, and was regularly vaccinated. A history of gastroesophageal reflux was reported with regular growth. His symptomatology began at 7 months of age and was characterized by recurrent episodes of postprandial vomiting associated with progressive failure to thrive. On admission, his weight and height were respectively 7.28 kg and 67 cm. A routine basic metabolic panel was performed. Aminoacidemia and aminoaciduria determination was negative. Results of celiac serology tests, thyroid functionality tests, cytomegalovirus serology tests, urinalysis and culture, stool test, and parasitological examination of stools were negative. An electroencephalogram showed normal electrical activity and brain magnetic resonance imaging (MRI) was negative. An ultrasound (US) examination showed gastrectasia and gaseous distension of the large intestine. A radiological study of transit on barium swallow detected an organoaxial volvulus, with the greater curvature lying to the right of the lesser curvature and above it. There was no obstruction to the passage of the contrast agent into the small bowel. On lateral projection, a marked thinning of the pylorus was present (Fig. ). Also for this patient, after a short attempt of enteral nutrition by nasogastric tube, an anterior gastropexy was performed in association with Nissen fundoplication. The surgical finding reported only one important gastrectasia and a temporary gastrostomy tube was placed. At 30-day follow-up, a significant improvement in his growth was highlighted and after 1 year there was a complete resolution of his symptoms.


A 23 year-old pregnant woman was referred to the department of Clinical Genetics due to isolated ID and a familial interstitial duplication on chromosome 6 characterized by karyotyping in the past. This duplication was discovered in 1983 in a family member that was known to suffer from ID, developmental delay (DD) and seizures. The observed ID in this family varied from very mild (low degrees and learning problems) to more severe (accompanied by DD and seizures).
The partner of the pregnant patient was known to have ID as well. He was an adopted child. His biological brother was said to have ID as well. Neither further family history, nor parental samples were available. Because of the pregnancy, our patient and her partner were investigated with genomic SNP array (Illumina HumanCytoSNP-12) to study their chromosomal constitution.
The pregnant patient carried an interstitial ~16.1 Mb 6q duplication and the array testing additionally revealed a susceptibility locus (SL) for neurodevelopmental disorders: a ~580 kb 16p11.2 microduplication (arr[hg19] 6q22.1q23.2(116,411,005-132,541,408)x3,16p11.2(29,595,483-30,174,926)x3). The partner of the pregnant patient was shown to carry another SL for neurodevelopmental disorders, a ~806 kb 16p11.2 microdeletion (arr[hg19] 16p11.2(28,475,873-29,282,147)x1).
Because both partners had abnormal array results, prenatal diagnosis was advised. Amniocentesis was performed at 15 5/7 weeks of gestation and diagnostic array testing on uncultured amniotic fluid cells showed only the interstitial 6q duplication (Fig. ). In order to enable clinical interpretation of this result, 4 other family members of the pregnant woman, two healthy and two affected (one mild and the other severe (the one that was karyotyped in 1983, see above)), were tested with SNP array. Two healthy relatives turned out to carry only the 6q duplication, whereas the two affected relatives carried both the 6q duplication and the 16p11.2 microduplication.
As the fetus inherited only the 6q duplication, in the absence of SL, the prognosis of the fetal phenotype may be favorable. The second trimester fetal ultrasound investigations showed no structural anomalies. A healthy baby boy without any dysmorphic features was born and there were no developmental abnormalities noted so far (follow up at the age of 1 year).
A 34 year-old pregnant woman was referred to a clinical geneticist after suspicion of fetal esophageal atresia at third trimester ultrasound investigations, based on polyhydramnios and lack of visualization of the stomach. This was the first pregnancy of non-consanguineous parents. Fetal karyotype (amniotic fluid) revealed an interstitial duplication on chromosome 6. SNP-array (Affymetrix CytoScan HD) was performed, showing a 15.3 Mb duplication (arr[hg19]6q21q22.33(113,465,762-128,774,807)x3) (Fig. ). Given the combination of the duplication along with fetal structural abnormalities, the parents opted for termination of pregnancy at 33 weeks gestational age. The male fetus had normal biometry: weight 2593 g, height 49 cm, occipitofrontal circumference (OFC) 29 cm. Dysmorphic facial features were noted: short nose with anteverted nares and long eyelashes. Fetal autopsy confirmed the esophageal atresia and revealed additional structural abnormalities: an abnormal pulmonary lobulation (2 lobes on right lung and 1 lobe on left lung), a Meckel’s diverticulum, bilateral hydronephrosis, pancreatic ectopia, and neuronal heterotopia of the cerebellum located on the dentate nuclei.
Familial studies revealed that the mother was carrier of the same interstitial duplication on chromosome 6 (karyotyping and Oligo aCGH Agilent 60 K), while her parents had normal karyotypes. No additional copy number variation was found in both the mother and the fetus. The mother had previously experienced learning difficulties, dyslexia and was known with a scoliosis. Cardiac ultrasound showed no abnormalities. No cerebral or abdominal imaging was performed. She works as a nurse assistant in a hospital.


A 63-year-old woman was re-admitted to our hospital because of fever, diarrhea and disturbance of consciousness with polymorphic VT. She had been first admitted to our hospital five years ago because of polymorphic VT (Fig. ). Serum concentrations of cortisol, luteinizing hormone, follicle stimulating hormone, and prolactin had been very low with relatively low concentrations of corticotropin, while those of thyroid hormone and serum electrolytes levels had been almost normal. She had had a history of large bleeding by extrauterine pregnancy and her brain MRI had shown atrophy of pituitary, suggesting that her hypopituitarism was due to Sheehan’s syndrome []. She has no family history of VT and sudden deaths. On admission of this time, she had fever (38.0 ℃) with slightly lower blood pressure (92/60 mmHg). Her ECG showed prolongation of the QT interval (QTc 567 ms) (Fig. a) and ECG monitor recorded various arrhythmias such as sinus bradycardia, atrial flutter, paroxysmal atrial fibrillation, and polymorphic VT. Routine blood examination revealed normal levels of sodium (137 mEq/L), potassium (3.8 mEq/L), and calcium (9.9 mg/dl), and slightly high levels of magnesium (2.75 mg/dl). C-reactive protein and white blood cell counts were elevated 6.9 mg/dl and 11 × 103 μl, respectively. The rapid test of influenza type A was positive. Ultrasound echocardiography (UCG) showed normal cardiac size and function of the left ventricle. We intravenously administered hydrocortisone with large volume of physiological saline and started rapid ventricular pacing at the rate of 120 bpm. In the second day of the treatments, arrhythmias were not observed and the QT interval was normalized (QTc 394 ms) (Fig. b).
Although she has been treated with hydrocortisone for secondary adrenal insufficiency due to hypopituitarism, adrenal crisis might be induced by infection of influenza. When she arrived at our hospital, the QT interval was remarkably prolonged, however, it became normal within 12 h with replacement of glucocorticoids.


A 75-year-old woman was admitted to the emergency department with vomit, diarrhea, confusion and epigastric pain. She had a diagnosis of chronic renal insufficiency for several months, and she recently suffered several episodes of urinary tract infection and acute renal failure due to severe dehydration consequent to diarrhea. Furthermore, she reported consistent weight loss in the last period. She had hypertension, cardiac insufficiency, chronic pulmonary obstructive disease, hiatal hernia and an history of cardiac arrhythmias. On admission, blood pressure was 140/85 mmHg and pulse rate was 95. On physical examination, abdomen was nontender. Abdominal ultrasound was negative. An electrocardiograph was normal. Laboratory analysis were significant for hyponatriemia (124 mmol/L, normal range: 135–145 mmol/L), hypokalemia (3.1 mmol/L, normal range: 3.5–5.0 mmol/L), high creatininemia (318.24 μmol/L, normal range: 53–106 μmol/l), hyperazotemia (188 mg/dl, normal range: 10–50 mg/dl), leukocytosis (10.810 x 10^9/L, normal range 4.0–10.0 x 10^9/L), and proteinuria (2.5 g/day, normal value: <0.15 g/day). After adequate rehydration and PPI infusion epigastric pain subsided. She was admitted to the nephrology department, where she was treated with intravenous 0.9 % saline and potassium infusion. A complete normalization of her biochemistry, followed by normalization of her creatinine values, occurred only after 10 days of intravenous therapy. In light of her persistent, mucous diarrhea a digital examination was performed, documenting a circumferential lesion of the rectum, with mucosal involvement of the anal canal up to 1 cm from the anal verge, and a colonoscopy was ordered.
The colonoscopy showed sigmoid diverticula and a giant polyp of the rectum, occupying three quarters of the luminal circumference, with a cranial-caudal extension of 8–9 cm and (Fig. ). Considering the typical clinical presentation, McKittrick-Wheelock syndrome was diagnosed.
A biopsy was performed on the polyp, and pathology showed a villous adenoma with focal high-grade dysplasia. Subsequently, the patient underwent a contrast-enhanced CT scan of the thorax and abdomen for staging of the disease. The CT scan did not show any signs of mural involvement, nor sphincterial or mesorectal involvement or signs of distant metastases (Fig. ). She was finally transferred to our department and referred to surgery.
Given the dimension and the extension of the polyp transanal surgery was excluded, and considering the good general conditions and continence status of the patient a low anterior rectal resection with mucosectomy of the anal canal had initially been planned. However, an intra-operative frozen section pathological examination showed involvement of the distal margin by intramucosal adenocarcinoma, and a conventional abdomino-perineal resection with end-colostomy was performed (Fig. ).
Pathological examination on the whole specimen showed a villous adenoma with areas of intramucosal adenocarcinoma and high grade dysplasia (TisN0).
After surgery, the patient showed persistent normalization of physical and serological parameters and full recovery of her renal function. She did not have any medical or surgical postoperative complication. At 10 months follow-up, she was in good general conditions, without signs of local recurrence, with a regular GI function and no signs of renal insufficiency or electrolyte disturbance.


A 33 year-old Moroccan male presented with left sided laterocervical mass, which had persisted for four months. No personal or family history was noted. He had no previous history of smoking, alcohol use, or irradiation. The mass had slowly grown with occasional pain. He had no fever, chills, or weight loss. Upon physical examination, the left parotid gland was enlarged, firm, with cervical lymphadenopathy, no skin lesions were found. Ultrasonography and computed tomography revealed a solid mass involving the parotid gland. A biopsy revealed a poorly differentiated carcinoma.
The patient underwent tumor excision. The excised mass measuring 21,5 × 9 × 6 cm, with skin tag measuring 11 × 10 cm. The cut surface of the tumor was firm tan-gray, lobulated, measuring 6 × 5,5 × 5 cm, with, apparently normal looking, salivary gland tissue at the peripheral margin (Fig. ). Meticulous and extensive sampling of the tumor was done.
Histopathological examination revealed a lobulated tumor with expansive growth within parotid parenchyma (Fig. ). It was composed of nests of two cell populations : large foamy cells with centrally located nuclei and vacuolated clear cytoplasm, surrounded by closely packed smaller basaloid cells with scanty cytoplasm (Fig. ). Large tumor cells showed sebaceous differentiation (Fig. ), with cellular pleomorphism, high mitotic activity (Fig. ) and necrosis. Some areas showed squamous islands with keratin pearl formation. Periodic acid–Schiff (PAS) was negative in the foamy, large cells.
Immunohistochemical staining of the tumor showed expression of epithelial membrane antigen (EMA) (Fig. ), pancytokeratin, and p63 in all neoplastic cells, and focaly B-Catenin. They lacked expression of CK5/6, CEA, S100, CD10, Vimentin, melan A, and CD45. The diagnosis of Sebaceous carcinoma of the parotid gland was made.
Since a recent literature review report a relation between sebaceous carcinoma and MSH2 mutation, we evaluated by immunohistochemistry MLH1 and MSH2 protein expression. Strong nuclear expression of both proteins was found (Figs. and ). All surgical margins were microscopically negative. A staging computerised tomography (CT), gastrointestinal endoscopy and colonoscopy were preformed and no tumor was found. Thus, the Muir-Torre syndrome was excluded. Adjuvant radiotherapy was decided. The patient is alive without signs of tumor recurrence after 1 year of follow-up.


A 67-year-old male, originally from Southeastern Europe, was admitted to hospital in 2011 after a 12 × 6 × 8 cm perirenal abdominal aortic aneurysm (AAA) was found on ultrasound during workup for acute lower back and abdominal pain. The patient had a previous AAA open repair 5 years earlier with no complications. He also had chronic renal disease secondary to hypertension (baseline serum creatinine 140–180 μmol/L), past history of heavy smoking (quit 5 years earlier, total pack years unknown), and chronic mechanical low back pain managed medically for the last four years. He had immigrated to Canada from Southeastern Europe in 2009 and was living in Southern Alberta. He had previously worked as a mechanical technician. He denied any recent or past exposures to farm animals or unpasteurized dairy products. The patient denied fatigue, weight loss, night sweats, fevers, or chills. Vital signs were normal and the patient was afebrile. Physical exam demonstrated poor distal pulses and a palpable aorta with the remainder of the exam being normal. Laboratory workup revealed a longstanding normocytic anemia (Hgb 125 g/L) and elevated creatinine (174 μmol/L). Liver enzymes and function were within normal limits. C-reactive protein was elevated at 156.8 mg/L.
Computed tomography (CT) angiogram demonstrated an 11.8 × 14.3 cm perirenal saccular abdominal pseudoaneurysm arising from the posterior aspect of the proximal anastomosis of his abdominal aortic graft repair (). The sac extended posteriorly with extensive destruction of L1, L2, and L3 vertebral bodies (). Follow-up magnetic resonance imaging revealed L2-L3 disk space destruction that caused a moderate degree of spinal stenosis and severe left neural foraminal compromise at the L2-L3 level. It was noted that a smaller (11.4 × 7.3 cm) aortic mass with L1–L3 destruction was observed on noncontrast CT 1 year prior to his presentation, though no interventions were taken at that time. Based on the CT and MRI findings, it was felt that the pseudoaneurysm was most likely a complication from the patient's previous AAA repair (anastomotic pseudoaneurysm). Infection was not suspected.
The patient underwent an open, redo repair of his abdominal aortic aneurysm and bilateral renal artery reconstruction. The operation revealed a contained AAA rupture with large amounts of purulence and massive erosion of the patient's adjacent lumbar spine with exposure to anterior elements but no visible dura. Pathology demonstrated normal appearing atherosclerotic plaque with no signs of infection or granulomas.
One day after operation the patient developed respiratory distress as a result of renal failure from prerenal acute tubular necrosis. He was transferred to the intensive care unit for mechanical ventilation. During his stay he had recurrent fevers (Tmax 39.2) despite prolonged (approximately 1 month) treatment of piperacillin/tazobactam and vancomycin for presumed mycotic aneurysm. Aerobic and anaerobic bacterial and fungal cultures of blood and infected vascular tissue were negative, including cultures specific for Mycoplasma, Brucella, and Mycobacteria. Screening for human immunodeficiency virus, hepatitis B, hepatitis C, and syphilis was negative. After 1 month, Q fever serology results returned positive with phase I IgG serological titer of 1 : 2048 and phase II 1 : 1024, consistent with a diagnosis of chronic Q fever. Coxiella burnetii IgM was negative. PCR on the vascular tissue, completed postmortem, was positive for C. burnetii.
The patient was treated for chronic Q fever with doxycycline 100 mg twice daily and hydroxychloroquine 200 mg daily, with plan for reassessment once fully recuperated. Response to treatment was verified by repeat Q fever serology 20 months later revealing decreased titers of 1 : 512 (phase I) and 1 : 256 (phase II).
Though the patient had multiple complications during his 3-month hospital stay, the patient was successfully discharged to another centre for ongoing rehabilitation and shortly thereafter returned home with his family. He died 18 months later (22 months since admission) from hypoxia and multiorgan failure secondary to an acute pulmonary embolism (PE) confirmed on CT angiography. The PE was not thought to be related to Q fever since the patient had previously improved from his hospital stay and had decreasing phase I and II serological titers.


A 55-year-old female presented to the emergency department with acute intermittent unsteadiness worsening with mobility. Her initial workup including brain computed tomography (CT) scan was interpreted as normal and she was discharged home. Three days later, her unsteadiness progressed and she developed a new onset of right ear pain and diplopia. She returned to the emergency department and neurological examination revealed right ear erythematous vesicular lesions, gait ataxia, limb dysmetria, right-sided facial palsy, and fluctuating horizontal diplopia. She denied fever, headache, nuchal rigidity, altered level of consciousness, vertigo, weakness, or any other neurological complaints.
Her medical history included well-controlled type 2 diabetes, hypertension, and hyperlipidemia. Medications included metformin, ramipril, metoprolol, atorvastatin, and acetylsalicylic acid.
Due to the new onset of neurological signs and symptoms, a repeat brain CT scan was performed followed by lumbar puncture (LP). Brain CT was interpreted as normal. Cerebrospinal fluid (CSF) revealed elevation in glucose, nucleated cells (lymphocyte-dominant), and protein ().
The patient was initially treated empirically with intravenous broad-spectrum antimicrobial therapy including ceftriaxone 2 g every 12 hours, vancomycin 15 mg/kg every 12 hours, and acyclovir 10 mg/kg every 8 hours. Subsequently, varicella zoster virus (VZV) was detected in CSF by polymerase chain reaction (PCR) and antibiotics were discontinued. She had no history of chicken pox or vaccination against VZV. One day after presentation, follow-up contrast brain magnetic resonance imaging (MRI) showed nonspecific cerebral deep white matter hyperintensities likely due to chronic small vessel changes.
The facial palsy completely resolved within 48 hours of starting intravenous acyclovir and the right ear edema improved dramatically; however, she continued to have gait ataxia, dysmetria, fluctuating diplopia, mild right ear hearing deficiency, and vesicular lesions. She remained in the hospital for 7 days and was discharged on intravenous acyclovir to complete a total 21-day course at a dose of 10 mg/kg every 8 hours.
Upon follow-up, the patient was found to have ongoing cerebellar findings, including dysarthria, dysmetria, gait ataxia, and inability to perform the tandem walk test. The remainder of her neurologic examination including cognitive testing was normal. Laboratory results revealed a normal C-reactive protein (CRP) of 2.5 mg/L and white blood cell count (WBC) of 8.9 X 109/L, but the erythrocyte sedimentation rate (ESR) was mildly elevated at 33 mm/h. A tapering course of high dose prednisone (60 mg initially and 10 mg taper weekly for a total of 6 weeks) was added to the treatment regimen due to her ongoing neurological signs.
Her neurological examination 6 weeks later showed a significant improvement (); however, she had recurrence of right ear vesicular lesions without central nervous system (CNS) involvement; therefore, oral acyclovir 800 mg three times a day was prescribed for five additional days.


A 10-year-old girl had crusts and persistent wounds on the nose and in the internal mucosal layer for six months. She also had progressive nasal stuffiness. She had not received any medication. There were no known diseases in her previous history. Her father was treated for pulmonary tuberculosis 20 years before this presentation; however, there were no active complaints in his clinical follow-up, and no other family members had any history of tuberculosis. There were also no close blood-relatives who had been diagnosed with tuberculosis. It was learned from the family that a bacille Calmette-Guerin (BCG) vaccination was given at 2 months of age based on the vaccination schedule in Turkey.
On physical examination, her body weight was 25 kg (25–50th percentile), and her height was 115 cm (50th percentile). There were erythematous, edematous, yellow-brown colored, and thick-crusted plaques on her nose (Figures and ). There were no systemic symptoms.
The patient was hospitalized for investigation. Her laboratory tests, which included a complete blood count, peripheral smear, and tests for kidney and liver function, were within normal limits. The erythrocyte sedimentation rate was 57 mm/h (0–20), and the C-reactive protein was 0.41 mg/dL (0–0.8). The Venereal Disease Research Laboratory (VDRL) and Human Immunodeficiency Virus (HIV) antibody tests were negative. Imaging studies were taken of the patient's lungs with no abnormality found. The purified protein derivative (Mantoux test) was strongly positive, with a maximum diameter of 24 mm of induration. A punch biopsy of the lesion was performed: histology revealed pseudoepitheliomatous hyperplasia, as well as a subepithelial lymphocytic reaction of histocytes and giant cells with a granulomatous reaction in the epidermis (). No specific agent was shown on acid-resistant bacilli (ARB) or Giemsa and Gomori's Methenamine Silver (GMS) stains. M. tuberculosis was isolated from the tissue culture. The isolate was resistant to streptomycin and ethambutol and sensitive to isoniazid and rifampicin. The patient was assessed to have primary tuberculosis with nasal involvement. The induration diameters of PPD were detected to be 4 mm and 3 mm in the mother and sister, respectively. A chest radiograph was normal. Additional images from a contrast-enhanced computerized tomography (CT) scan of the head demonstrated that the nasal septum was normal. Isoniazid (10 mg/kg/day), rifampicin (10 mg/kg/day), and pyrazinamide (30 mg/kg/day) treatments were started. A primary immunologic workup of serum quantitative immunoglobulin, lymphocyte subsets, and nitroblue tetrazolium (NBT) levels was normal.
The patient was discharged after 15 days of hospitalization. Two months later, she came for an outpatient clinic visit with signs of improvement. At the end of the second month, pyrazinamide was discontinued. Six months later, isoniazid and rifampicin treatments were also discontinued. There were no interruptions in drug administration during the treatment period, and no drug complications were observed. The total treatment plan was completed in 6 months. The skin lesion had almost completely resolved 24 months after her first admission to our department (Figures and ).


A two-day-old male neonate, first birth by order born out of a nonconsanguineous marriage, was admitted in NICU with petechial rashes all over the body. Baby was born full term and healthy and there was no history of birth trauma present. There were no history of fever, respiratory distress, or signs of sepsis and no maternal history of preeclampsia, thrombocytopenia, or bleeding tendency. Patient's examination was unremarkable except for petechial lesions. Complete hemogram showed Hb of 15.3 g/dL, WBC of 19 × 109/L, PLT of 18 × 109/L, and MPV of 8.5 fL with shift to the left and presence of NRBCs ().
Mother's hemogram, transfusion transmitted disease workup, and tests detecting antibodies against platelet antigens (antiplatelet antibodies) were not contributory. Baseline immunoglobulin levels were normal (IgG Levels 317 mg/dL, IgA 14 mg/dL, and IgM 87 mg/dL). A diagnosis of neonatal alloimmune thrombocytopenia was considered and IVIG 1 gm/kg was given along with platelets transfusion. Human platelet antigen genotyping of parents was done but no incompatibility was found. Baby's platelet increased up to 183 × 109/L on day 3 of IVIG and he was discharged.
On day 25 of life, baby was again admitted with similar symptoms along with bloody stools. Patient's examination revealed pallor, petechial lesions and spleen was palpable 2 cm below left costal margin, and the rest of history and examination was unremarkable. Complete hemogram showed Hb of 11.2 g/dL, WBC of 22.8 × 109/L, PLT of 20 × 109/L, MPV of 8.3 fL, and NRBCS of 8/100 WBCs, and platelet morphology was normal () ().
Workup for infections and sepsis was negative. Baby's FISH for BCR-ABL was negative. In view of pallor, splenomegaly, persistent leukocytosis, monocytosis, and myeloid and erythroid precursors in the peripheral blood, a diagnosis of JMML was considered (see the following).
Minimal diagnostic criteria for JMML (adopted by the International JMML Working Group and by EWOG-MDS) are described as follows.
(i) Suggestive clinical features are as follows:Hepatosplenomegaly. Lymphadenopathy. Pallor. Fever. Skin rash.
(ii) Laboratory criteria (all three must be met) are as follows:Persistent peripheral blood monocytosis (>1 × 109/L). No Philadelphia chromosome or BCR-ABL fusion gene. <20% myeloblasts or monoblasts in the marrow.
(iii) Further criteria to be met (need to fulfill at least two) are as follows:Increased hemoglobin F (corrected for age). Immature myeloid precursors on the peripheral blood smear. Peripheral blood white blood cell count >1 × 1010/L. Clonal cytogenetic abnormalities (including monosomy 7). GM-CSF hypersensitivity of myeloid progenitors (in vitro test).
Bone marrow examination showed normocellular marrow with eosinophilia and adequate megakaryocytes. Cytogenetics and FISH for monosomy 7/Del 7 revealed no abnormality. HbF level was in normal range (HbF 34.7%). Patient's lymphocyte subset analysis and repeat immunoglobulin levels were also normal and no mutation was detected on RAS pathway PCR analysis. Due to inconclusive reports and unavailability of other specific JMML diagnostic workup such as spontaneous colony assay, GM-CSF hypersensitivity and diagnostic dilemma persisted. Meanwhile, patients had received a repeat course of IVIG and platelets transfusion, and platelet count increased to 150 × 109/L on day 3 of IVIG.
For the next 2 months of follow-up, patient was intermittently symptomatic for petechial lesions with platelet count within range of 20–30 × 109/L. High WBC count with shift to the left and eosinophilia were persistent. At 4 months of life, on routine OPD visit maculopapular rash was noted on baby's forehead and cheek ().
These spots prompted us to reconsider diagnosis of Wiskott-Aldrich syndrome in the baby. Hence baby's complete gene sequencing for WAS gene was done, and it showed known pathogenic mutation c.37C>T (p.R13X) in WAS gene confirming diagnosis of Wiskott-Aldrich syndrome.


On further investigation, the patient's mother revealed history of consanguineous marriage and that her younger daughter (Case 2), who is 7 years old, also showed similar features.
General examination revealed the height and weight as 23 inches and 10 kgs, which are less when compared with average height and weight of an age-matched Indian girl (average height: 47.4 inches, average weight: 21.8 kgs). Further examination revealed the clinical characteristics of base diagnosis given: There was bowing of legs () and enlargement at the wrist () and ankle joints (). The presence of rachitic rosary () and Harrison's groove () was also noted.
On intraoral examination, incompetent lips, macroglossia (), and caries-free mixed dentition were present with missing maxillary centrals, canines, and mandibular lateral incisors with fair oral hygiene ().
Radiographic Findings. Chest radiograph, radiograph of hip with femur and tibia, wrist radiograph, and intraoral periapical (IOPA'S) radiographs were advised.Chest radiograph () revealed (a) mild scoliosis, (b) both humeral metaphyses showing fraying of bones with resorption in their proximal ends, and (c) ribs being broadened and anterior ends of ribs appearing to be widened which is the classical feature of rickets. Radiograph of hip with femur and tibia () revealed (a) cupping/fraying in both lower end of femur and upper end of tibia in both hips, (b) cortical thinning, (c) bowing of legs, (d) growth arrest lines, (e) epiphyseal widening, and (f) femoral ossific nuclei not fully developed and appearing to be superiorly migrated. Wrist radiograph () revealed (a) widening and cupping/fraying of metaphysis in the lower ends of radius and ulna, (b) significant osteoporosis, (c) epiphysis for radius visible but epiphysis for ulna not yet visualised, (d) evidence of periostitis in metacarpals, (e) resorption of bones seen, and (f) skeletal age found to be 2 yrs. IOPA'S () shows the presence of deciduous teeth 52, 54, 55, 62, 65, 74, and 84 and all the permanent teeth.
Laboratory investigations of both Cases 1 and 2 are presented in . The ultrasound report of kidneys revealed early renal disease and complete blood picture revealed leucocytosis and thrombocytosis in both siblings.


A 68-year-old woman presented with a 3-month history of recurrent, multiple, subcutaneous nodules on the right ankle. Seven months previously, she had undergone complete excision of similar lesions at nearly the same sites at another hospital. Pathological examination had shown multiple abscesses with many fungal hyphae, but antifungal therapy was not prescribed. For the previous 7 years, she had been on medication for type 2 diabetes mellitus and hypertension, and for the previous 5 years, she had additionally been taking a daily dose of 10 mg prednisolone to treat psoriasis.
On the first visit to the orthopedic outpatient clinic, the patient’s vital signs were stable, with a blood pressure of 130/70 mmHg, pulse rate of 86 beats per minute, and body temperature of 36.2 °C. Physical examination showed multiple nodules located on the lateral peri-malleolar area and posterior aspect of the right ankle (Fig. ). They were round, well-demarcated, and firmly palpable with fluctuation. The sizes varied from 0.5 cm to 4 cm in diameter. The patient did not report any itching, tenderness, or paresthesia on the lesion sites. There was no abnormal change in the skin and nails. Laboratory tests revealed the following: white blood cell count, 8,800/mm3 with 69.6 % segment neutrophils (normal, 4,000–9,900/mm3 with 39–72 % segment neutrophils); hemoglobin level, 13.8 g/dL (normal, 12–15 g/dL); platelet count, 231,000/mm3 (normal, 140,000–400,000/mm3); fasting glucose level, 147 mg/dL (normal, 75–115 mg/dL); and C-reactive protein level, 3.61 mg/L (normal, 0–5 mg/L). None of the blood chemistry data were significantly abnormal. Magnetic resonance imaging of the right ankle showed multiple, well-demarcated, cystic lesions around the lateral malleolus, located in the subcutaneous or dermal layers. The lesions had an intermediate signal intensity on T1-weighted images (Fig. ) and a high signal intensity on T2-weighted images (Fig. ), and showed rim enhancement after contrast medium injection on fat-suppressed T1-weighted images (Fig. ). The thick, purulent, exudative fluid obtained from the lesions by direct needle aspiration was examined by Gram staining, bacterial and fungal culture, acid-fast bacilli staining, mycobacterial culture, and real-time polymerase chain reaction assay to detect Mycobacterium tuberculosis and non-tuberculous mycobacteria. The patient was treated empirically with oral cefixime 100 mg twice daily for 14 days, but the lesions did not improve. After 18 days of incubation, the microbiology laboratory reported a slight growth of Trichophyton rubrum on Sabouraud dextrose agar. Results of other tests were all negative.
The patient was admitted to the hospital for complete excision and biopsy of the lesions. The operative findings were multiple, well-defined, multilobular nodules filled with pus, which were completely excised (Fig. ). Bacterial and fungal culture of the pus and histopathology of the tissue samples were performed to discriminate true fungal infection from contamination. Histopathology showed organizing abscesses with degenerated fungal hyphae identified by Grocott's methenamine silver stain and periodic acid-Schiff stain (Fig. ). Bacterial culture of the pus was negative and fungal culture yielded Trichophyton rubrum.
The patient was diagnosed with recurrent dermatophyte abscesses caused by Trichophyton rubrum, and oral itraconazole 200 mg once daily was started. Oral prednisolone slowly tapered and stopped 3 weeks after operation. She was discharged without any postoperative complications and prescribed continued oral itraconazole. After the 12-week oral itraconazole treatment course, the surgical wound remained clean and there was no evidence of the development of new lesions. A follow-up magnetic resonance imaging of the same site also showed no remnant abscess or any sign of recurrence. The patient did not show any recurrence at the 2.5 years follow-up.


A 4-year-old Caucasian boy was referred from a private office to our pediatric dentistry clinic with a complaint of swelling in left anterior maxillary canine and lateral incisor teeth area. It was started about five months previously bilaterally in a smaller dimension. The right lesion subsided without any intervention but the left lesion has been enlarging with parents and child manipulation. The central and lateral primary incisors were extracted 3 months ago by a general dentist with the diagnosis of periapical abscess but the lesion did not heal and has been progressively growing. The lesion was painless and with no associated spontaneous bleeding except for occasional interference of the swelling with mastication. His medical history includes no complication.
On clinical examination, he had slight extraoral facial swelling of his left anterior maxilla, without any palpable regional lymph nodes. An intraoral examination showed a 20 × 15 × 12 mm pedunculated, lobular soft tissue mass of his left anterior maxillary gingiva related to his incisors (). On palpation, the lesion had a firm consistency. The mucosal covering of the lesion exhibited surface tan, red, and bluish areas with a focal area of ulceration. A periapical radiograph of this area revealed superficial erosion of the alveolar bone with no other significant findings ().
These clinical and radiographic findings indicated a benign lesion, and the following differential diagnoses were considered: parulis, pyogenic granuloma, peripheral ossifying fibroma, PGCG, and peripheral odontogenic fibroma. Malignant entities such as squamous cell carcinoma, other primary malignant lesions, and metastatic lesions, although thought to be unlikely, were also considered.
The patient was scheduled for surgical excision. Under local anaesthesia, the lesion was excised down to the periosteum (). After complete excision of the lesion, the exposed surface was cauterized to control the bleeding and the entire specimen submitted for histopathologic examination.
Microscopic examination shows multinucleated giant cell proliferation within a background of spindle-shaped and ovoid mesenchymal cells. Areas of haemorrhage and acute and chronic inflammatory cells are frequently present. A zone of dense fibrous connective tissue separates giant cell proliferation from mucosal surface. Areas of dystrophic calcifications and reactive bone formation are seen around (). This histopathology confirmed the entity of PGCG.
Follow-up visits were scheduled at three week intervals. No signs of recurrence of the lesion have been observed during nine months after the excision.


A 30 year old female with a history of recurrent febrile UTIs since her childhood was incidentally diagnosed during an obstetric ultrasound with a horseshoe kidney and bilateral double collecting systems and duplication of ureters. She had a past medical history of left sided ureterocele treated 9 months ago with laparoscopic decompression. After a 3-month period of recurrent UTIs, the patient was referred to the nuclear medicine department for a 99mTc-MAG3 (mercaptoac-etyltriglycine) renal scan for the assessment of renal function and to rule out obstruction and VUR.
Structural imaging included abdominal ultrasound, CT urogram, MRI and IVU (intravenous urography) which revealed a horseshoe kidney with bilateral duplex collecting systems, bilateral duplication of the ureters, duplicated renal arteries, bilateral tiny calculi, moderate left upper moiety hydronephrosis and significant hydroureter (Figures -).
MCUG (micturating cystouretherogram) showed left-sided grade IV VUR. The MAG3 renogram with Lasix washout and indirect cystography, showed a normally functioning right kidney with no evidence of obstruction or VUR; however, both moieties on the left had relatively reduced function without any evidence of obstruction, with significant VUR seen in the upper moiety of this kidney ().


A 38-year-old female patient (height: 153cm, weight: 55kg) was scheduled for kidney transplantation from cadaveric donor. She had been diagnosed with chronic kidney disease about two years ago and on hemodialysis for one year.
Anesthesia was induced with propofol 100mg and atracurium 25mg with equipment of monitoring including BIS, invasive arterial pressure, pulse oximeter and electrocardiogram. After tracheal intubation, the anesthesia was maintained by 6% desflurane, 0.1μg/kg·min remifentanil and intermittent atracurium. Triple lumen venous catheter was placed in the right internal jugular vein with fluid infusion and central venous pressure monitor. Esophageal probe was inserted to record body temperature. Warming blanket with convective air warming system covered chest, both arms and head to keep body temperature normal (). BIS value maintained from 35 to 50 and electromyography (EMG) was almost fixed at 27 during one and half hour of operation. BIS Signal Quality Index (BIS-SQI) and Suppression Ratio (SR) was 100 and 0, respectively. Blood pressure was 131 over 72 mmHg, and heart rate was 69 beats per minute. WarmTouch™ was operated for body heating because esophageal temperature dropped from 36.3 to 36.0ºC. BIS and EMG increased to 74 and 37, respectively. BIS-SQI and SR was 100 and 0, unchanged. Hemodynamics was steady state. The anesthesiologist added up desflurane to 8% concentration and inject atracurium 5mg. However, BIS was over 70 and EMG was 37. After turning off WarmTouch™, BIS and EMG returned to 45 and 27. BIS and EMG was raised again to same numerical value after switch on WarmTouch™. Heated and humidified breathing circuit (Heated Circuit Kit®, Ace Medical, South Korea) was applied for normothermia without activation of WarmTouch™. Esophageal temperature was maintained at 36.0 ºC to recovery of anesthesia. Total operation time was four hours and the patient did not recall any intraoperative event. The patient was discharged without any symptom or complication on postoperative 22 days.


A 65 year old non diabetic, non-alcoholic gentleman presented with a 2 day history of right sided severe abdominal pain with no prior trauma, surgery, urinary retention or calculus disease.
Clinically, he was vitally stable, apart from mild tachycardia (pulse rate 92 beats/min). On local examination, there was no abdominal or costo-vertebral tenderness and rest of his abdomen was unremarkable, however his pain was seemingly out of proportion to these examination findings. His serum urea/creatinine, liver function tests, serum amylase/lipase as well as all other biochemical tests were within normal limits.
His ultrasound whole-abdomen was suggestive of increased liver echogenicity, with no evidence of any abnormality to the kidneys, ureters, bladder as well as no intra or retroperitoneal fluid collection, and he was being evaluated along the lines of a liver abscess.
However, a CECT scan when done, reported a ureteric rupture with leakage of contrast from the upper ureter, well away from the renal pelvis, at the level of the 2nd lumbar vertebra (Fig. ).
He was promptly taken up for cysto-ureteroscopy, retrograde pyelography (RGP) and DJ stenting. Intraoperative RGP demonstrated the upper ureteric rupture at a fair distance from the pelvis without cystoscopic evidence of any calculus or obstructive uropathy (Fig. ).
He was managed via cystoscopy and placement of a DJ Stent (5Fr, No 26). His post operative course was uneventful and he was discharged on the second post operative day, without event.
At 6 weeks of follow up, there was no contrast extravasation as confirmed via an RGP done during stent removal (Fig. ).
The patient was discharged without event and advised to remain on 6 monthly follow ups, with imaging to be done as per his subsequent symptoms.