A 38-year-old Saudi male, a known case of ventricular septal defect (VSD) diagnosed at age 11 years, was admitted at the Prince Sultan Cardiac Center in Riyadh, Saudi Arabia. He underwent a diagnostic right heart catheterization to characterize his hemodynamics before surgical repair, which showed severe and non-reactive PAH. He was labeled inoperable and was kept on regular outpatient follow up. Five years prior to his current presentation, he became more cyanosed with a significant activity restriction and his serial echocardiographic assessment showed chronic PE.
In September 2012, he visited the outpatient clinic complaining of severe shortness of breath with activity limitation. On examination, he was tachypneic and tachycardiac at rest, deeply cyanosed with oxygen saturation of 65 -70% and showing signs of congestive heart failure. Electrocardiogram showed sinus rhythm with right axis deviation and P pulmonale. The initial chest x-ray (CXR) showed cardiomegaly, oligemic lung fields with chronic hypoxic changes. Echocardiogram revealed large unrestrictive peri-membranous VSD with biventricular hypertrophy, mild tricuspid regurgitation with supra-systemic right ventricular pressure and a moderate PE with no signs of tamponade. The overall picture was compatible with Eisenmenger’s syndrome. Left ventricular systolic function was normal. A baseline 6 minutes walk test (6MWT) was carried out and the patient could only walk for 2 minutes with a maximum distance of 120 meters and Borg dyspnea scale of 4. He was on oral furosemide, captopril, and sildenafil (50 mg TID) as a chronic treatment. He was hospitalized for the management of his hypoxia, PE, and right-sided congestive heart failure. He was started on oxygen, inotropes and aggressive diuresis with fluid restriction, aside from his previous medication. He stayed for 24 hours in the adult congenital heart disease ward, but he did not show any improvement despite the aggressive management. On the discussion of patient’s case with the pulmonary hypertension team, it was suggested to start a course of intensive inhaled iloprost therapy (intravenous prostacyclin was not available) at a dose of 5 micrograms every 2 hours along with intravenous furosemide and oral sildenafil. There was also a careful follow up of patient’s daily CXR, echocardiography, and laboratory work. He showed a dramatic response to this regimen and at the end of the first week, his oxygen saturation was above 90% on 1L oxygen, and the signs and symptoms of heart failure were controlled. The heart shadow on the CXR became smaller, and echocardiogram showed improvement of right ventricular contractility with minimal residual PE. Inhaled iloprost was reduced gradually to the final dose of 5 micrograms every 4 hours with no documented side effects. He was discharged from the hospital after 3 weeks in excellent condition on inhaled Iloprost 5 micrograms every 4 hours, aside from his usual medications. He was still in good condition with oxygen saturation ranging from 85-90% in room air and no symptoms or signs of heart failure during the follow up visits at week 3 and 6. His daily activities improved, and he could manage to walk 360 meters on 6MWT. His echocardiogram showed a complete resolution of PE. At 3-months, he was asymptomatic [modified NYHA functional class I] and could walk 408 meters on 6MWT. illustrates the improvement in clinical and physiological parameters. He was advised to continue the same treatment with regular follow up at the clinic.


A 49-year-old-woman was found at home presenting neurological distress with a Glasgow score of 11 caused by mepronizine and lormetazepam (supposed ingested doses: 12 g and 32 mg, respectively) poisonings and was brought to our intensive care unit. She already tried to kill herself by voluntary drug intoxication (chronic depression) and was known to have a factor V Leiden mutation.
Her initial physical examination at admission showed tachycardia (143 bpm) and tachypnea (respiratory rate 30 cycles/min) with an oxygen saturation of 75% in room air. A worsened Glasgow score of 5 was observed at that time. Due to those respiratory and neurological failures, the patient was intubated, but her respiratory parameters did not improve. The transthoracic echocardiography revealed enlarged right cardiac chambers and an elevated pulmonary artery pressure (sPAP 50mmHg). Considering the severity of respiratory failure and normality of chest X-ray, a spiral computed tomography (CT) was performed revealing a massive bilateral proximal pulmonary embolism.
Increased neurological distress was suggested by anisocoria with areactive left mydriasis and body-part pyramidal syndrome. A cerebral CT scan showed left sylvian and cerebellar infarctions. Those infarctions were complicated by a perilesional edema which caused an under falcorial engagement. No hemorrhagic part was found. Association of stroke and pulmonary embolism led us to suspect a PFO responsible for a cerebral paradoxical embolism.
This diagnosis was confirmed by transesophageal echocardiography with an entrapped thrombus (supplementary video) and positive agitated saline contrast injection. Both pulmonary embolism and brain infarction were treated by unfractioned heparin due to the probable embolic origin of the stroke. The cerebral edema was treated by injection of mannitol.
The further care took place in a neurosurgery unit, but she unfortunately died 2 days after admission.
Despite the confirmation of etiological diagnosis, we were unable to reconstruct the natural history of events: Did the suicide attempt lead to a coma with prolonged immobility favoring thromboembolic complications? Was an embolic complication (stroke) or pulmonary embolism the first event, leading to feeling unwell which triggered the suicide attempt? Were embolic complications and suicide attempt completely independent?"
We described here a rare but potentially life-threatening event. PFO is present in more than 25% of adults[] and is the cause of about 95% of the right-to-left shunts. Several previous reports described a straddling thrombus within a PFO with pulmonary and coronary[] or cerebral embolism.[] Cryptogenic strokes represent about 40% of strokes and paradoxical embolism via a PFO seems to be responsible of 50% of them leading to 40,000-160,000 such cerebral accidents per year in the United States.[]
The principal cause of elevated right cardiac chambers pressure is pulmonary embolism and presence of a PFO in patients with clinically apparent pulmonary embolism increases systemic embolism from 2% to 28% (P < 0.02).[] Size of the PFO might also affect the embolic risk.[] On the contrary, venous thrombosis, oral contraceptives, or recent surgery can increase the risk of paradoxical embolism through PFO as factor V Leiden mutation (known in our case) and prothrombin G20210A mutation that seems to play a critical role[] increased about fivefold the risk of stroke in these patients.[] Those findings show that estimation of paradoxical embolism risk level should simultaneously take into account both the presence of PFO and risk factors for right cardiac chambers pressure elevation.
Despite therapeutic interventions, mortality vary from 14% to 33% during the hospital stay[], impending paradoxical embolism being associated with a 30-day mortality rate is 18.4%. There is no modification of mortality between thromboembolectomy, anticoagulation, or thrombolysis.[] High level evidence for impending paradoxical embolism treatment need has to be investigated and treatment has to be adapted to the characteristics of the patients and care center resources and expertise.
The first PFO treatment was cardiac surgery, but it is no longer indicated as an isolated procedure. Guidelines remain ambiguous concerning secondary prevention of complications. No prospective randomized long-term study has ever proved a benefit from closing the PFO. PFO can be treated by percutaneous therapy with low morbidity and mortality rates[] and recurrent neurological or peripheral embolic event in 0%-3.8% per year. Nonetheless, the interest of a PFO closure after a stroke remains debatable as a recent study did not show a significant benefit, using a composite end-point mixing mortality and stroke recurrence in a 2 years follow-up period.[] Two more recent trials confirmed these observations.[] Nonetheless, per-protocol and as-treated analysis showed significant improvement in the risk of recurrent stroke.[] Pooling these data suggesta probable benefit of the percutaneous closure of PFO. These works confirmed a previous propensity score-matched comparison showing a mortality reduction.[] Local radiofrequency application and percutaneous intracardiac suture are still being evaluated clinically.[] At last, medical strategy by lifelong anticoagulants such as warfarin is preferable to acetylsalicylic acid as it reduces the risk of recurrent ischemic events.[]
A risk stratification at the base of treatment strategy was proposed as a compromise.[]


A 33-year-old primigravida and nullipara woman in preterm labor at 32 weeks of gestation was referred to our hospital. Upon presentation, she had a temperature of 37.3°C, a pulse rate of 108 beats per minute, and leukocytosis (white blood cells count >22,000 mm2 ). Vaginal examination revealed no pooling of fluid. She gave birth to a 2,000 g female infant by vaginal delivery, with Apgar scores of 7 and 9 at 1 and 5 minutes, respectively.
Grossly, the placenta was 18×14×2.5 cm and 510 g. The attached cord measured 30 cm in length and 2 cm and 1.3 cm in maximal and minimal diameters, respectively. The middle portion of the umbilical cord was focally enlarged, measuring 2 cm in length and 2 cm in diameter. The cut surface showed an ill-defined white to brown horseshoe-shaped area surrounding the umbilical vessels, measuring 2 cm in length and 0.2 cm in thickness (). The chorionic plate had a patchy appearance and was covered by a purulent exudate.
Microscopically, there was a horseshoe-shaped calcified area located within the Wharton’s jelly. The calcified area consisted of multiple, small, round to oval, and calcified bodies (calcospherites), which were both intra- and extracellular. Many of the inclusions were confirmed to be within macrophages on CD68 immunohistochemical stain. The majority of the lesion was necrotic and contained an inflammatory infiltrate composed mainly of neutrophils and macrophages. The macrophages had abundant eosinophilic cytoplasm with eccentric, hyperchromatic, and round nuclei (). Concentrically laminated, roundovoid, and basophilic calcified bodies, which are referred to as Michaelis-Gutmann bodies, were also seen (, ). These bodies stained positive for von-Kossa and periodic acid–Schiff. Acute inflammation of the choriodecidua, amnion, and chorionic plate was noted. Based on the above findings, the diagnosis of malakoplakia of the umbilical cord, acute chorioamnionitis, and funisitis was made. Unfortunately, intracellular and extracellular bacterial organisms were not revealed on special stains.


A 24-year-old female without a history of familial DCM was admitted with a progressive heart failure (HF). Clinical signs of HF (NYHA III) developed within 12 weeks of the initial development of dyspnea on both walking and bending forward, a feeling of palpitations, weakness and unexplained syncope.
On examination, the patient was asthenic. The patient was in slow atrial fibrillation (AF) with an intermittent complete right bundle branch block, incomplete left bundle branch block (alternating left fascicular posterior and left fascicular anterior block), mean heart rate of 52 b.p.m. and blood pressure 105/65 mmHg. Echocardiographic study revealed biventricular global dysfunction and dilatation: low left ventricular ejection fraction (LVEF) of 27%, hypokinesis of all segments, mean global strain (GS) LV −8.8%, LV end-diastolic volume (EDV) 171 ml, LV end-systolic volume (ESV) 124 ml, right ventricular (RV) EDV 122 ml, RV ESV 74 ml, right ventricular ejection fraction (RVEF) 39%, mean GS RV −9.8%. Left ventricular thickness of the posterior wall was at the upper limit of normal (10 mm). There were biatrial dilatation (left atrial volume 78 ml, right atrial volume 200 ml), mitral and tricuspid regurgitation (II degree MR, III degree TR) with the estimated mean pulmonary artery pressure (PAP) 18 mmHg.
Coronary angiography revealed no major abnormalities; however, cardiopulmonary exercise testing evaluated VO2 peak 15,5 ml/kg/min (normal score range 29–40 ml/kg/min considering age and sex). Blood serum creatine kinase concentration was 279 U/l (normal values 24–190 U/l) and the brain natriuretic peptide level was 676 pg/ml (normal range 0–50 pg/ml).
Neurological examination revealed mild hypotrophy of quadriceps muscles, hypertrophy of calf muscles but without reduced limb strength. Reflexes and nerve conduction studies were normal.
The 24 h ECG Holter monitoring detected a slow AF (mean HR 45 b.p.m., max HR 72 b.p.m.), intermittent complete heart block with HR 27 b.p.m., episodes of non-sustained ventricular tachycardia (n = 42), polymorphic ventricular extrasystoles (VEs >300/h). Patient's ECG Holter showed ventricular tachyarrhythmia which is presented in Fig. a and b.
The patient underwent implantation of a biventricular pacemaker with cardioverter-defibrillator (CRT-D) as a preventive measure prior to confirmation of the genetic lesion. After CRT-D implantation, the patient was treated with beta-blocker, ACE inhibitor, aldosterone antagonist and diuretic (daily doses: bisoprolol 3,75 mg; ramipril 5 mg; spironolactone 50 mg; torasemide 5–10 mg). After 6 months, the patient showed no evidence of cardiac remodeling (LVESV increased up to 140 ml, LVEDV up to 180 ml, LVEF decreased up to 22%, mean LV GS up to −5.2%; RVESV enlarged up to 93 ml, RVEDV up to 131 ml, RV EF reduced up to 29%, RV GS up to −4.9%). Owing to progression of HF symptoms (development of ascites, hydropericardium and pulmonary hypertension to PAP mean 39 mmHg), a successful orthotropic cardiac transplantation was performed.
In the removed heart, the findings were non-specific with diffuse alteration in myocytes including variation in size, nuclear variation, and interstitial fibrosis.
DNA mutations were detected using a single-stranded conformational polymorphism method and direct sequencing of the amplified LMNA exons. We detected the mutation c.569G>C in the third exon of the gene.


A 65-year-old Japanese man was diagnosed with HIV infection in October 2005. There were no comorbidities, including hypertension, diabetes mellitus and dyslipidemia. cART, comprising lamivudine, abacavir and atazanavir/ritonavir (300 mg of atazanavir boosted by 100 mg of ritonavir), was started to treat his low CD4+ T-cell count (205 cells/μL) and high HIV-RNA (230 000 copies/mL) in June 2006. Soon after the initiation of cART, both proteinuria and hematuria emerged (1+ and 1+ on dipstick test, respectively) and his renal function started to decline slowly, yet there were no crystalline precipitates in the urine. Serum creatinine (Cr) increased from 0.6 to 1.0 mg/dL in June 2009, and to 1.4 mg/dL in February 2012, with persistent proteinuria (1+) and occult hematuria (2+) on a dipstick test. As serum Cr increased to 1.7 mg/dL, he was admitted to the Department of Nephrology in April 2012. The cART regimen remained unchanged, since the control of HIV infection was good at the time.
On admission, his blood pressure was 102/78 mmHg and pulse rate 98 beats per minute. His height was 154 cm and his weight was 35.4 kg (body mass index, 14.9 kg/m2). There were no particular abnormalities on physical examination. The blood data were as follows: white blood cell count 6400/μL; red blood cell count 387 × 104/μL; hemoglobin 12.5 g/dL; platelet count 27.0 × 104/μL; serum urea nitrogen 21 mg/dL; serum Cr 1.7 mg/dL; serum sodium 139 mEq/L; serum potassium 4.5 mEq/L; serum chloride 103 mEq/L and serum C-reactive protein 0.49 mg/dL. Urine dipstick test showed pH 6.0, proteinuria (1+), and occult blood (3+). The urinary concentrations of biomarkers for tubular damage, which was corrected for urinary Cr concentrations, were as follows: N-acetyl-β-d-glucosaminidase (NAG), 12.0 IU/gCr (normal level of NAG concentration, 0.0–7.0 IU/L) and β2M, 391 μg/gCr (normal level of β2M concentration, 27–265 μg/L), respectively. The daily amount of urinary protein was 250 mg. Urinary sediments included 50–99 red blood cells/high power field (HPF), 20–29 white blood cells/HPF and small amounts of crystalline precipitation (no detail for its shape). Infrared spectroscopic analysis was implemented to test whether the urinary crystalline precipitation included atazanavir crystals. In brief, the patient's urine was stored for 24 h, and some of the urine was centrifuged for 2 min at 2000 rpm. The supernatant was used for infrared spectroscopic analysis, and the spectrum of the infrared absorbance was compared with that of the standard for atazanavir analysis (Santa Cruz Biotechnology, Inc., Dallas, TX, USA). This analysis strongly indicated that the urinary crystalline precipitation of the patient included atazanavir crystals (Figure ). The first renal biopsy was performed in May 2012. The kidney tissue contained eight glomeruli, one of which (12.5%) was globally sclerotic. The remaining glomeruli showed no convincing histological changes indicating renal failure. In contrast, interstitial nephritis, accompanied by diffuse inflammatory infiltrates consisting of lymphocytes and plasma cells, was noted (Figure A). Moreover, needle-shaped crystalline precipitation, likely in the epithelia of the tubule, surrounded by multinuclear giant cells, was very characteristic (Figure B). Immunohistochemistry was negative. Electron microscopy showed no electron-dense deposits in the glomeruli; however, crystalline precipitation was confirmed within the tubular epithelial cells (Figure C). In June 2012, atazanavir was replaced by raltegravir, but renal function did not improve. From November 2012, 6 months after the first renal biopsy, oral prednisolone was started at the initial dose of 0.75 mg/kg daily for 4 weeks, and was slowly decreased in the subsequent 5 months. However, serum Cr remained constant at 1.5 mg/dL. In August 2013 (1 year and 3 months after the first renal biopsy), a second renal biopsy contained 28 glomeruli, 5 of which (17.9%) were globally sclerotic. The remaining 23 glomeruli had unremarkable changes. Needle-shaped crystals surrounded by lymphocytes and multinuclear giant cells in the tubulointerstitial compartment were completely removed. Sclerotic findings of glomeruli and intrarenal arterioles including interlobular arteries were more prominent than those observed in the first renal biopsy. Additionally, tubular atrophy and interstitial-fibrosis developed further, although the severe interstitial inflammation was almost cured (Figure D). Immunohistochemistry and electron microscopy showed no characteristic findings.


A 55-year-old male patient presented to our rheumatology clinic with cutaneous nodular lesions and a necrotic distal phalangeal lesion, which had developed over the last month. In his medical history, he had been diagnosed with tuberculosis 23 years ago and had been treated with anti-tuberculosis therapy. He smoked 40 packets-years. There were no fever, weight loss, and night sweats. His physical examination revealed multiple cutaneous lesions on the skin of the face, limbs, neck, scalp, dorsal side, fingers, subungual side, right leg, and feet. The lesions were painless, fragile, dark purple colored, measuring 1-3 cm, arising from the subcutaneous tissue, and with a tendency to bleed, one of them caused distal finger auto-necrosis []. His complete blood count and serum biochemistry was unremarkable. Erythrocyte sedimentation rate was 51 mm/h (↑), C-reactive protein: 105 mg/L (↑), lactate dehydrogenase: 212 IU/L (↑), carcinoembryogenic antigen: 3.69 ng/ml, (N), anti-microsomal antibody: 220.54 IU/ml (↑) (N < 5.61), and anti-thyroglobulin antibody: 29,25 IU/ml (↑), (N < 4.11). Necrotic and nodular skin lesions were thought to be symptomatic of vasculitis. Rheumatologist evaluated the patient and clinical and laboratory findings of the patient were not consistent with vasculitis. A punch biopsy from the skin lesion was performed. Histopathological examination of the biopsy specimen revealed a cutaneous metastasis, probably from squamous cell carcinoma of the lung. Biopsy material was immunohistologically negative for surfactant and TTF-1, and positive for P 63. On thorax computerized tomography (CT), a left hilar mass with 5.5 × 3.5 × 6 cm dimensions was detected. He was diagnosed with squamous cell lung cancer after bronchoscopic biopsy. Staging work-up including abdominal CT and Tc-99m bone scan revealed liver and bone metastasis. The patient received palliative radiotherapy to the metastatic bones. Then, he was treated with combination chemotherapy regimen consisted of docetaxel (75 mg/m2/day for every 3 weeks) and cisplatin (75 mg/m2/day for every 3 weeks) with support granulocyte stimulating factor. After 3 chemotherapy courses, his skin lesions tended to disappear with scar tissue []. But his liver metastasis progressed and a new lesion on surrenal gland was detected. Therefore, a second-line chemotherapy protocol was given 6 courses, but only partial response was obtained. The patient died 10 months after the initial diagnosis due to disease progression.


A 71-year-old male presented with multiple subcutaneous soft tissue mass lesions in the postero medial aspect of mid right thigh region since 2 weeks. Local examination revealed multiple firm to hard mass with skin over the swelling being unremarkable []. CT of the right thigh showed a heterogeneous lesion with infiltrative margins in the thigh. Clinically soft tissue sarcoma was considered. Routine hematological and biochemical investigations were unremarkable. HIV and HBs Ag tests were nonreactive. Diagnostic FNAC was performed showing numerous mature and immature sporangias with giant cell reaction [Figure and ]. Intraoperatively, the mass was irregular and nodular grey white []. An excision biopsy showed multiple grey white masses with cystic and mucoid areas []. Histopathology confirmed the rhinosporidiosis with numerous mature and immature sporangia surrounded by dense inflammatory response []. Complete ENT examination revealed no obvious rhinosporidial lesion. The patient is under regular follow up since 1 year without any evidence of recurrence.


A 71-year-old man with a tremor in both hands visited our clinic. His hands had started shaking since 1990 and the action tremor was worse than the postural or resting tremor. The tremor aggravated gradually, and recently his voice too had started trembling especially when he was nervous. He received numerous medications at other hospitals, but the tremor could not be controlled effectively. His initial TRS score checked before GKT was 80. He refused to undergo invasive surgical treatment and preferred GKT. A maximal dose of 130 Gy was applied to the left VIM nucleus (). The drawing of a helical figure and the address written by the patient before GKT are shown in .
At two months after GKT, the follow-up TRS score was 65 (81% of that at baseline). At 10 months after GKT, the TRS score was improved to 23 (29% of that at baseline). MRI scan with contrast enhancement was performed after 4 months of GKT. A peripheral enhancing rim-like lesion at the intended target site was noted on MRI (). His right hand tremor was nearly arrested and voice tremor was also reduced. The drawing of a helical figure and the address written by the patient at the last follow-up visit are shown in .


A 12-month-old girl visited the emergency room with a high fever and progressive paraparesis. The patient had normal development and began to walk at approximately 10 months of age. She had developed a fever of up to 39.5℃ 15 days prior to the visit. While visiting a local clinic, she was diagnosed with pharyngitis and received antibiotics and antipyretics. Her fever subsided but repetitive vomiting started 10 days prior. Five days ago, her high fever returned again. From then, she intermittently showed lethargic symptoms and was unwilling to walk. She received additional examinations for infectious disease and supportive treatment for days, and finally, the local physician decided to transfer her to our hospital, when she showed overt paraparesis.
Upon arrival at the emergency room, she was acutely ill-looking and lethargic. Her vital signs were as follows : heart rate 137 beats/min; blood pressure 123/56 mm Hg; respiratory rate 28 breaths/min; body temperature 38.6℃. She was alert but exhibited quadriparesis. Her motor grade was I/I for upper extremities and 0/0 for lower extremities. She also exhibited profound hypesthesia below the C4 dermatome. Bilateral biceps jerks were weak, and bilateral knee and ankle jerks were absent. No meningeal irritation sign was observed. A palpable mass was found in her abdomen, which was determined to be a distended bladder. There was a tiny dimple in the midline of the upper sacral area (). It was located above the gluteal folds, approximately 6 cm away from the anus. A small amount of whitish thick discharge was squeezed from the dimple by manual pressure. A laboratory examination revealed blood leukocytosis (15500/µL), decreased hemoglobin (10.9 g/dL), decreased hematocrit (31.6%), and elevated C-reactive protein (5.83 mg/dL).
The febrile illness and rapidly ascending quadriparesis indicated an infectious disease of the central nervous system involving the spinal cord. The high-lying midline skin dimple with discharge added suspicion of an underlying infected dermoid. A detailed history was collected and revealed that her parents had found the skin dimple during her neonatal period, but they thought it was an innocent lesion that did not require further investigation.
Spinal magnetic resonance imaging (MRI) was immediately obtained (). The MRI revealed diffuse high signal intensity along the spinal cord up to the medulla oblongata. There was a low-lying conus down to the S3 level. An enlarged central canal and thick gadolinium-enhancement of the lining up to the T1 level was observed. There were multiple cystic dilatations with rim enhancement in the lumbosacral cord. A dermal sinus tract ran obliquely upward from the conus at the S3 level to the skin. An infected CDS with massive holocord pyomyelia was diagnosed.
An emergency operation for abscess evacuation and untethering was performed. The sinus tract was followed from the skin ostium. There were multiple dermoid cysts along the sinus tract entering the dural sac through the fascial and bone defect (). After a multi-level laminectomy, the dural sac was opened and a thickened spinal cord was observed. A dorsal midline myelotomy was made and noxious green-colored pus was discharged from the abscess. The abscess cavity and syrinx were flushed with saline. Finally, the sinus tract was resected just distal to the last root.
Multiple pathogens were suspected and the patient received vancomycin and cefotaxime for empirical therapy. Later, Peptoniphilus asaccharolyticus and an unidentified anaerobic rod were isolated from the pus and we added metronidazole to the drug regimen. She received the triple antibiotics for 6 weeks following the operation. Her fever subsided quickly, but profound neurological deficits remained. The lower extremity weakness improved only slightly, and spasticity ensued. She had weakness in both hands (C8-T1 level). Horner syndrome in the left side with ptosis and anhydrosis of face was observed. Sensory function in the trunk and lower extremities improved slightly but incompletely. She had a neurogenic bladder and clean intermittent catheterization (CIC) was required. She was followed post-surgery for 2 years. Serial spinal MRIs showed gradual shrinkage of the residual T2 high signal intensity and enhancement in the spinal cord. In this time period, she never developed another bout of the febrile episode. She regained grasp function in both hands, particularly in the right hand. She can move her legs slightly, but she is still wheelchair-bound and needs CIC for bladder care.


A 23-year-old male patient visited the Department of Periodontology, complaining of dark gums. History revealed that it was present since childhood suggestive of physiological melanin pigmentation []. Patient was systemically healthy without any habits. Patient's oral hygiene was good. Patient was explained about the treatment options available and the possibility of repigmentation after certain period. Phase I therapy was carried out during the initial visit. A split mouth approach comparing scalpel technique with that of cryosurgery was planned. Local infiltration of lignocaine was administered. At the maxillary left anterior region from central incisor to canine (anterior esthetic segment), a conventional/traditional technique was used, wherein a #15 blade is used for depigmentation [Figure –].
At the right counterpart, cryosurgery technique was used for depigmentation [Figure –]. There was absolutely no bleeding during the procedure. Postoperative instructions were given to the patient, nonsteroidal anti-inflammatory in the form of diclofenac sodium was given thrice daily for 3 days. Patient was recalled after 1-week for re-evaluation. Wound healed uneventfully on both the sides.
Patient experienced pain on the scalpel treated site for 3 days postoperatively.
After 1-week, the pack was removed, and the surgical area was examined. On 1-month postoperative follow-up, the healing was uneventful without any postsurgical complications. The gingiva appeared pink, healthy, and firm giving a normal appearance []. The patient was very impressed with such a pleasing esthetic outcome. Depigmentation was not carried out for mandibular anterior region because they were of no esthetic concern for the patient.


An 18-year-old female had a chief complaint of black gingiva []. The procedures were performed with the same method as described in the previous case. The wound healed well after 2 weeks. No pain or bleeding complications were found. The gingiva became pink and healthy within 4 weeks [].


A 21-year-old female had a chief complaint of black gingiva []. The procedures were performed with the same method as in the previous case. The wound healed well after 4 weeks. No pain or bleeding complications were found. The gingiva became pink and healthy within 4 weeks [].


A 43-year-old female referred at our polyclinic with complaints of pain in her distal area of the left thigh, which had been ongoing for approximately 6 months. She was admitted to a state hospital in Yozgat, Turkey in February 2014. The patient had a history of a dog bite in the lateral distal left thigh 15 years ago. On physical examination, there was pain on deep palpation of the distal area of the left thigh. No pathological lymph node was determined on palpation of surface lymph nodes.
In the laboratory tests, apart from erythrocyte sedimentation rate of 67 and high C-reactive protein (5.7 mg/L), no pathology was determined in routine haemogram and biochemical tests. In the radiographic examination, there was a left femur distal diaphyseal-metaphyseal radio dense area.
On computerized tomography (CT), a hypo dense 20cm cystic lesion was observed located medullary from the left femur at the intertrochanteric level extending to the distal metaphysis, and the width of the medullar segment with slight lobular contours caused by cortical thinning ().
In the magnetic resonance (MRI) examination, an evident hypo intense mass lesion was observed on T1-weighted images, localized in the femur distal metaphyseal-diaphyseal area involving the entire bone medulla and accompanying soft tissue components visualized as evident heterogeneous hyper intensity on the T2-weighted series ().
Characteristic of our specific case is a rare involvement of cystic lesion located medullary from the left femur intertrochanteric level extending to the distal metaphysis.
The patient underwent surgery and following intraoperative left femur medullar cyst excision, the histopathological examination determined hyalinized membranous fragments within calcified areas consistent with hydatid cyst (). The microbiological examination determined positive titer > 1/1280.
Immobilization was applied for 1 month postoperatively. For a period of 6 months, mebendazole 400 mg orally was administered. No recurrence was determined clinically or radiologically in the 6-month follow-up period. Negative results were obtained from serological examinations ().


A 12 year-old female patient with a history of ventriculoperitoneal shunt placement at the age of 6 months due to hydrocephaly, was evaluated for bilateral decrease in visual acuity of 4 months of evolution. She had previously been administered oral prednisone because of a presumptive diagnosis of bilateral optic neuritis at another institution.
On examination, her right eye visual acuity was limited to hand movements and the left eye was 2/200. Torch light examination revealed pupillary mydriasis with equal pupillary size, and bilateral abnormal light and consensual reflexes. No cranial nerve palsies were evident in the ocular movements exam.
Both eye fundi had generalized paleness (4+), elevated and blurred borders of both optic discs; from their emergence there was sheathing of the central blood vessels, were tortuous, with gliosis and lacking of a venous pulse. The macula had scattered hard exudates, Paton lines, retinal folds and no lesions at the peripheral retina (Fig. ).
Retinal fluorescein angiography obtained in another institution, revealed early hyperfluorescence due to papillary leakage.
Goldmann visual fields revealed a concentric decrease of the peripheral visual fields with a right eye 25-30 degree remaining central field on IV/E3 stimulation, and a 20-30 central field in the left eye, also on IV/E3 stimulation (Fig. ).
Brain magnetic resonance imaging showed the ventricular system in the midline mild bilateral ventricular dilation, an increase in supratentorial volume with no associated sub-ependymal edema, slightly decreased overall encephalic volume for the patient’s age and no causes of intracranial hypertension like tumors or hematomas (Fig. ).
The patient never developed other systemic manifestations of increased intracranial pressure such as headache, vomiting, nausea or lethargy other than the reported progressive visual deterioration and late-stage pupillary abnormalities with bilateral papilledema. An extensive laboratory work-up was conducted that excluded other inflammatory or infectious processes. She was then referred for pediatric neurologic evaluation with the diagnosis of ventriculoperitoneal shunt dysfunction with ophthalmologic manifestations, with subsequent confirmation of the diagnosis by the referral institution.


A 35-year-old unregistered poorly communicative primigravida from a low socioeconomic, tribal community with an obstructed labour presented for an emergency caesarean section. She had a dysmorphic scarred face, short, weak body and limb contractures []. The attender gave a history of some swelling on the face in childhood followed by facial and limb deformities.
Examination of her face revealed nasal cartilage atrophy, absent nasal bridge and a fistula over the area, single nasal cavity, absent nasal tip, columella and septum. The nasal floor had a midline cleft up to the soft palate such that the hard palate appeared nearly absent. The soft palate appeared contracted. The upper central, lateral incisors and canines were absent []. The lower jaw appeared protruded. Mouth opening and neck movements were normal. Purulent discharge was seen from the right ear. The forehead appeared prominent. There was anterior bowing of both tibia. Right wrist was fixed in palmar flexion. Right foot had equino-varus deformity. Height and weight could not be measured. Remaining systems and spine appeared unremarkable. Her blood pressure (BP) was 126/84 mm of Hg, pulse rate was 110/min and haemoglobin was 12 g/dL. Electrocardiography revealed sinus tachycardia. Human immunodeficiency virus and venereal diseases research laboratory tests were negative. It was decided to administer subarachnoid block to the patient.
Equipment for tackling a difficult airway was kept ready. After intravenous preloading, subarachnoid block was administered with 1.2 ml of 0.5% hyperbaric bupivacaine and the patient in left lateral position. An upper level of sensory block up to T3 dermatome was achieved. A stillborn baby was extracted and oxytocin infusion was started. BP decreased to 70/50 mm of Hg. Intravenous fluids and increments of intravenous ephedrine were ineffective in improving the BP and dopamine drip was started. The approximate blood loss was 800 ml. She was Shifted to the (ICU) with a pulse rate of 130/min, BP 80/56 mm of Hg on dopamine support. Echocardiography was normal. The patient stabilized over the next 3 hours and dopamine was tapered off.
Post-operatively, ophthalmological examination revealed small corneal opacities in left eye. Examination of ears revealed right ear chronic suppurative otitis media with conductive deafness and bilateral sensorineural deafness. Rapid plasma reagin test was negative. Fluorescent treponemal antibody absorption (FTA-ABS) test could not be done due to non-availability.


A 62-year-old woman was admitted for suspected pneumonia and nephrotic syndrome in June 2012. She had suffered from cough and sputum from 2 weeks prior to admission. On admission, her blood pressure was 111/58 mmHg, temperature 36.5°C and pulse 63 bpm. A physical examination revealed pale conjunctiva and slight bilateral pretibial edema. No abnormal sign was observed in the lungs, heart or abdomen.
Urinalysis showed heavy proteinuria (4.3 g/day) with hematuria (5–10/HPF). White blood cell count was 8300/μL with normal distribution, hemoglobin 9.9 g/dL, hematocrit 29.1% and a platelet count of 230 000/μL. Serum total protein was 5.8 g/dL, albumin 2.5 g/dL, blood urea nitrogen 23.8 mg/dL, creatinine 1.56 mg/dL, alanine aminotransferase 23 U/L, aspartate aminotransferase 15 U/L, lactate dehydrogenase 172 U/L and total cholesterol 138 mg/dL. Serum IgG was 1255 mg/dL, IgG1 746 mg/dL, IgG2 446 mg/dL, IgG3 86.1 mg/dL and IgG4 35.9 mg/dL. IgA was 250 mg/dL, IgM 128 mg/dL, C3 86 mg/dL and C4 32 mg/dL. Anti-nuclear antibodies were 40-fold with speckled pattern. Both MPO- and PR3-antineutrophil cytoplasmic antibodies were negative. Chest X-ray revealed a right lower lobe infiltrate.
A renal biopsy was performed. Light microscopy showed 13 global scleroses, 15 cellular and 2 fibrotic crescents within 38 glomeruli, with bubbling and spike appearance of the glomerular basement membrane (GBM) in the functioning glomeruli (Figures and ). In the tubulointerstitium, severe lymphocyte infiltration, mild tubular atrophy and interstitial fibrosis were observed (Figure ). Immunofluorescence studies showed granular staining 3+ for γ heavy chain, 2+ for κ-light chain and trace staining for C3, along with the GBM, but no significant staining for λ-light chain or C1q. Immunofluorescence staining for γ-heavy chain subclasses showed a dominant 3+ granular staining for IgG4, trace staining for IgG2, negative for IgG1 or IgG3 (Figure ). Immunofluorescence staining for antibodies to M-type phospholipase A2 receptor (PLA2R) (Sigma-Aldrich, USA) was performed. The specimen had negative glomerular staining for anti-PLA2R. Immunohistochemistry study revealed IgG1 dominant and minor IgG4 staining of the infiltrate plasma cells in the tubulointerstitium, and normal ratio of κ/λ light chain positive plasma cells. Electron microscopy revealed granular electron-dense deposits without organized structures in the subepithelial space and in the mesangial area (Figure ). Bone marrow aspiration was performed because of the presence of monoclonal immunoglobulin deposition in the glomeruli. The smears were normocellular with no morphological abnormality, and 1.8% of the cells were plasma cells. Serum M-protein and urine Bence-Jones protein were not detected by immunofixation electrophoresis. The serum free κ/λ light chain ratio was 1.06, which is within the normal range. By the above results, multiple myeloma or underlying plasma cell dyscrasia was denied.
Computed tomography of the chest revealed a tumor-like mass of 2.3 cm in diameter in the base of the right lung. Partial resection of the lung was performed by video-assisted thracoscopic surgery. Microscopic examination of the section revealed fibrotic changes of the lung interstitium, proliferation of lymphocytes and plasma cells, with no malignant changes. Immunohistochemical study showed positive IgG4 staining in half of the proliferated plasma cells (Figure ). Light chain restriction was not detected by κ and λ light chain immunostains. No abnormal expression of CD56 or cyclin D1 was observed.
From these findings, she was diagnosed with PGNMID (membranous features) complicated with IgG4-related lung disease, according to the criteria for IgG4-related disease []. Steroid therapy was initiated by 3 days of intravenous methyl-prednisolone of 250 mg, followed by 30 mg/day of prednisolone. Following the treatment, proteinuria improved gradually, while serum creatinine level showed little change. At the 1-year follow-up, the patient was found to be well with 10 mg/day of prednisolone. The urinary protein was 0.9 g/g creatinine, serum total protein 5.8 g/dL, albumin 3.8 g/dL and creatinine 3.23 mg/dL. No abnormality in the chest X-ray was found during the follow-up period.


A 42-year-old female presented with acute, severe continuous pain in the upper abdomen for 3 days. It was associated with multiple episodes of coffee colored vomiting and swelling in the left hypochondrium. Patient had similar complaints 1-year earlier for which she was hospitalized and was managed conservatively. She had open cholecystectomy 10 years earlier for cholelithiasis and some upper abdominal surgery 20 years ago, details of previous surgery were not available. She was poorly built and anemic. Patient had mild tachycardia, but blood pressure, and respiration rate was within normal limits. On abdominal examination, there were two well healed surgical scars, one in the upper midline and another in right the subcostal region. The abdomen was not distended, and there was a diffuse mass about 8 cm × 5 cm in the left hypochondruim. There was no tenderness and guarding. Bowel sounds were normal.
Abdominal X-ray showed dilated stomach with dilated small bowel loops on the left side of the abdomen. Ultrasound revealed hypoechoeic intragastric mass having irregular margins []. Contrast-enhanced computed tomography of the patient showed serrated intragastric mass of about 8.4 cm with intra gastric contrast around it giving a “claw sign” suggestive of the retrograde intussusception. The serrated margins were due to thickened mucosal folds of intussuscepted jejunal loops. The coronal view showed efferent jejunal loop with areas of central fat attenuation (−42 HU) suggestive of jejunal mesenteric fat along with vessels intussuscepting into stomach and dilated afferent jejunal loop. The sagittal view showed a “target type” intragastric lesion due to jejuno-gastric intussusception [Figures -].
At laparotomy, there was retro colic, posterior gastrojejunostomy. The efferent jejunal loop was intussuscepting into the stomach, and afferent jejunal loop was dilated. The intussuscepted efferent loop was manipulated back to its normal position. The efferent loop was edematous, thick walled and viable having circumferential hyperemic ring on its serosa. The efferent loop was sutured to the anterior abdominal wall and transverse mesocolon to prevent recurrence. Postoperative course was uneventful. On follow-up after 3 months, patient is asymptomatic and doing well.


A 34-year-old African American female presented with excessive sweating, tremors, sore throat, and neck pain that was followed by aches and weakness in her lower limbs. Patient's past medical history was significant for Graves' disease diagnosed about a decade ago, when she had declined surgical options and radioiodine ablation, but continued medical therapy for maintenance of a euthyroid state. She denied any precipitating events for her weakness, such as physical exertion, heavy carbohydrate meals, or alcohol intake preceding the weakness. Physical examination revealed a tender goiter. Motor strength in the lower extremities was 3/5. Serum potassium was 3.6 mmol/L (lab reference range 3.5-5) and thyroid function tests showed hyperthyroidism. She was diagnosed with TPP precipitated by subacute thyroiditis (SAT). The patient was given propanolol, methimazole, potassium chloride, and nonsteroidal anti-inflammatory analgesics. The patient's weakness improved and pain diminished. She had a similar episode of weakness few days later with similar borderline serum potassium levels. She was started on low-dose oral potassium supplementation to maintain high normal serum potassium levels and continues to need this till date to prevent recurrent attacks.


A 5-year-old boy with a good mentality had a fracture of his left femur scheduled to do plate in the left femur in the prince sultan military medical city, the patient known to have pycodysostosis.
The patient was underweight to his age (12 kg), had a blue sclera and short stature for his age (101 cm), frontal bushing, micrognathia, Mallampati grade II, prominent nose, and osteosclerosis and chest deformities in the form of pectusexcavatum [Figures –].
There is also a history of delayed sagittal stenosis, craniosynostosis involving the superior sagittal, which was corrected surgically at age of 2 years.
Furthermore, the patient had a history of gastro esophageal reflux, sleep apnea syndrome and trachiomalacia with an improving course.
There was history of anesthesia 1-week before where a laryngeal mask was tried first but with no satisfactory ventilation and the patient experienced severe desaturation and bradycardia, resuscitation was done, patient was awaken, shifted to the Intensive Care Unit (ICU) and the surgery was postponed.
The labs were normal; imaging regarding the cervical skeleton was also unremarkable.
Regarding his family history; there was a parental consanguinity and pycodysostosis in his both brothers.
The parents were clearly notified and agreed to sign about the case of their child, the risk possibility, the method of anesthesia and its complications, a pediatric ICU bed was ready.
In the operating room there was no previous premedication or an intravenous access, full routine monitoring was connected.
The anesthesia started by an inhalational technique using sevoflurane and 100% O2, there was good ventilation, and intravenous access was inserted and secured.
0.15 mg/kg of cisatracurium, fentanyl 3 μg/kg, dexameshtasone 0.15 mg/kg and granistron 40 μg/kg were given and intubation was tried 2 times using different blades sizes of Macintosh laryngoscope with an impossible intubation, the view was Cormack and Lehane grade IV, rapidly the patient airway was suctioned and ventilated, then Glidescope® blade size 2 was used and it facilitated the view greatly, endotrachial tube size 4.5 was inserted, checked, confirmed, secured and lung mechanically ventilated.
The glidescope showed a left and up deviation of the laryngeal opening but with normal anatomy [Figures and ].
Anesthesia was maintained with sevoflurane, oxygen, and air and accompanied by caudal block that was easy.


A 78-year-old right-handed Caucasian woman was at a friend's house when she had difficulty speaking followed by right arm and right leg weakness. On evaluation in the emergency room she was found to have profound expressive aphasia. Her vascular risk factors included hypertension, but she was not taking any medications. She had no known allergies and she did not drink alcohol, smoke tobacco, or use recreational drugs. Vitals on admission were significant only for systolic hypertension (170/80 mmHg). She was awake with sustained eye opening; she had expressive aphasia and could follow simple commands, such as raising her left hand or nodding yes and no appropriately. She had a right facial droop and hemiplegia involving both proximal and distal muscles of the right upper and lower extremities. Routine labs complete blood count (CBC), comprehensive metabolic panel (CMP) and coagulation profile were unremarkable. MRI of patient's brain showed large area of left sided intra-axial parenchymal hemorrhage with mass effect and midline shift to the right []. The patients static pupillary sizes were imaged under conditions to steady background illumination after light adaptation of 5 minutes, for bright light conditions (~1035 Lux) and dim light conditions (~1 Lux).


A 75-year-old man presented with hemoptysis in our outpatient clinic. He had recurrent episodes of blood tinged sputum and minor hemoptysis during the past year. He had a history of smoking an average of 55 pack-year of cigarettes and had bronchial asthma. Recently, he had also been diagnosed with smear-negative pulmonary tuberculosis (TB) in the public health center and was treated with anti-TB drugs. The results of hematologic and chemical laboratory tests were unremarkable. Chest radiography showed small nodules with linear opacities in the left upper lung zones. Low dose chest computed tomography (CT) scans without contrast enhancement showed small calcified nodules with linear opacities in the left upper lobe. The opacities in the left upper lobe were unchanged in comparison with low dose chest CT scans examined 10 months ago. Occasional hemoptysis persisted despite the ongoing anti-TB therapy and oral tranexamic acid administered for about a month. Flexible bronchoscopy performed under local anesthesia, revealed an approximately 6 mm-sized, well-circumscribed, reddish hypervascular, multiloculated, polypoid lesion found on the ventral wall of the tracheal midline, 5 mm below the vocal cords (). The other parts of the trachea and bronchi were unremarkable. Bleeding from the polypoid lesion occurred on intra-procedural coughing. The bleeding stopped after endobronchial instillation of 1:10,000 diluted epinephrine. However, forcep biopsy without laser coagulation equipment was not attempted due to the possibility of profuse intra-procedural bleeding.
The patient was admitted and treated with intravenous tranexamic acid. Subsequently, no further hemoptysis was found until 1-week postbronchoscopy. Chest CT scans with contrast enhancement showed a focal enhancement <5 mm in the midline of the anterior tracheal wall (, arrow). The polypoid lesion was diagnosed as a presumptive tracheal hemangioma. We referred the patient to a tertiary referral hospital for therapeutic bronchoscopic laser ablation. The hospital staff recommended a wait-and-see policy; however, 3 days later he was admitted to our hospital for recurrent episodes of massive hemoptysis. During the follow-up bronchoscopy, approximately 500 mL of blood was suctioned from the tracheal polypoid lesion (). A consult was arranged with the otorhinolaryngology department. The patient underwent an emergency operation for the tracheal lesion, under general anesthesia on the 10th day of hospitalization. A 4-mm-sized, hemorrhagic and polypoid lesion was found about 5 mm below the glottis. The lesion was removed by CO2 laser (2 watt, super-pulse, continuous mode) under rigid laryngoscopy. After removal, bleeding from tracheal mucosa was controlled by coagulation with a suction Bovie. The patient had no further episodes of hemoptysis during the 12 months postoperative follow-up period. Histopathology showed several dilated spaces generally with degenerated lining cells; the dilated spaces lined by flattened cells focally, contained few red blood cells (). A diagnosis of tracheal cavernous hemangioma was made. One-week follow-up flexible bronchoscopy showed healing and scarring of the lesion with no evidence of bleeding (). The tracheal nodular lesion had disappeared in the 6-month follow-up chest CT scans ().


A 29-year-old male visited our center complaining of cough, sputum and coryza. These respiratory symptoms developed about 20 days prior to visit, and the patient has been prescribed oral medications including cefditoren and azithromycin within the preceding 10 days at local clinic. The patient was admitted to our center by the end of December 2013, as respiratory symptoms persisted despite medications. He had no significant past medical history, except a history of pneumonia during neonatal period, receiving treatment including mechanical ventilation. He was never-smoker and is working in office. He had no regular medications and only took recently prescribed medications for respiratory symptoms.
At the time of admission, the patient's vital signs, including body temperature, pulse rate, blood pressure, respiratory rate were 36.6℃, 108 per minute, 148/84 mm Hg, and 20 per minute, respectively. On a physical examination, he showed a symmetric expansion of the thorax related to respiration, with slight crackle on the right middle lung field. On a routine blood test, white blood cell count was 8,640/µL (neutrophil 62.5%, lymphocyte 26.2%), and C-related petide level was 0.17 mg/dL. There was no significant abnormality otherwise, except mild elevation of alanine transaminase (ALT) (aspartate transaminase/ALT level, 39/70 IU/L). After admission, patient's pulmonary function test (PFT) was performed. It showed forced vital capacity (FVC) of 3.87 L, forced expiratory volume in 1 second (FEV1) of 3.26 L, which were 74%, 76% of predicted value, respectively. Diffusing capacity for carbon monoxide was 17.7 mL/mm Hg/min, 57% of predictive value. A reversible bronchodilator response was not seen at this time. His forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) was 3.78 L, and it was 86% of the predicted value.
The patient's chest posteroanterior radiograph showed symmetrically increased peribronchovascular opacities in both lungs. He underwent a low-dose CT scan (120 kVp and 30 mAs; 2-mm slice thickness) of the thorax, and CT images showed mixed areas of ground-glass and reticular opacities in both lungs, predominantly along central and peribronchovascular areas (). The patient was admitted for diagnosis and treatment as the chest CT findings suggested the possibility of interstitial lung disease. For definitive diagnosis, VATS wedge resection for tissue confirm was scheduled and several serologic tests for viral and atypical pathogens were also performed. Additionally, antibiotics were switched to intravenous piperacillin-tazobactam, and steroid therapy with methylprednisolone (32.5 mg intravenous Q12hr) was also administrated to improve respiratory symptoms and radiologic findings. VATS was performed on fourth day of admission. The superior segment of left lower lobe was resected with visual identification of the consolidation.
Pathological examination of the lung specimen showed accentuated bronchioles due to bronchiolar hyperplasia with cystic dilatation of bronchiolar lumens, reminiscent of congenital pulmonary airway malformation. Also, peribronchiolar fibrosis was present, as well as smooth muscle hyperplasia. Alveolar structures were relatively intact except for focal emphysematous change. These pathologic findings were similar pattern to classic BPD. Some bronchiolar lumens were filled with necro-inflammatory mucoid material, suggestive of superimposed recent bronchiolitis (). These findings suggest previous small airway damage, accompanied by recent bronchiolitis. The possibility of cryptogenic organizing pneumonia or other atypical pneumonia could be ruled out by pathologic findings.
For the follow-up evaluation, low dose chest CT follow-up was performed on 12th day of admission, but it showed no significant interval change after medical treatment with antibiotics and steroid. PFT was also followed up on the same day, and FVC and FEV1 equally showed 36% of predicted value but post-bronchodilator FEV1 was 47% of predicted value, increasing about 31% after bronchodilator inhalation. He complained a chest pain which could be explained the result of his lower FEV1 compared with preoperative basal FEV1 but the reversibility after bronchodilator inhalation may also suggest his potential asthmatic component. With the results of radiology, pathology and the patient's past medical history, the patient's damaged lung lesions might be assumed to be sequelae of BPD. As the patient's symptoms had subsided, he was discharged on 17th day of hospitalization, and planned to follow-up on out-patient department for asthma evaluation and treatment.
Meanwhile, 29-year-old male, the twin brother of the abovementioned patient, visited our hospital for further evaluation after his brother discharge, concerning about abnormal findings found in his sibling. A low-dose chest CT was performed on an out-patient department, and the chest CT showed peribronchovascular mixed ground-glass and reticular opacities in both lungs, nearly identical lesions to the chest CT findings of the patient's twin brother ().


A 24-year-old Caucasian male, without a significant past medical history, presented with a 2-week history of hematuria and occasional expectoration of blood-tinged sputum. He reported a smoking history of ∼1 pack per day for the past 5 years. Physical examination revealed the following vital signs: temperature of 36.5°C, heart rate of 78 bpm, blood pressure of 131/82 mmHg and respiratory rate of 18 per minute with 99% saturation on room air. He had clear lung fields, no peripheral edema and had no rash.
Laboratory evaluation showed the following values: hemoglobin 1.7 mmol/L (11.0 g/dL), hematocrit 32.4%, WBC 10.5 K/μL, platelets 227 K/µL, sodium 138 mmol/L, potassium 4.3 mmol/L, chloride 100 mmol/L, serum creatinine (SCr) 247.35 µmol/L (2.8 mg/dL) and a glucose level of 5.49 mmol/L (99 mg/dL). The SCr rose to 379.86 µmol/L (4.3 mg/dL) over 4 days despite volume expansion with intravenous fluids. A chest radiograph, obtained on admission, was interpreted as within normal limits. The examination of the urine sediment disclosed red blood cell casts. His initial urine albumin-to-creatinine ratio (ACR) was 1004 mg/g. He had normal complement levels with C3 and C4 levels of 160 mg/dL (normal range, 90–230) and 29 mg/dL (normal range, 10–51), respectively. His erythrocyte sedimentation rate was elevated at 53 mm/h. Other negative tests included the following: antinuclear antibody, anti-neutrophilic cytoplasmic antibody, anti-DNA antibody, rheumatoid factor, human immunodeficiency virus antibody, hepatitis C antibody and hepatitis B surface antigen. Anti-GBM titers were pending at the time of kidney biopsy.
The kidney biopsy () revealed a crescentic glomerulonephritis with 54% of 13 glomeruli demonstrating cellular crescents and linear IgG staining of the glomerular capillary basement membrane characteristic of anti-GBM disease, along with faint capillary loop granular staining. Electron microscopy confirmed the presence of occasional small epimembranous and intramembranous electron dense deposits characteristic of membranous nephropathy.
Daily apheresis treatments were initiated and were reduced to a thrice-weekly regimen after three consecutive treatments. Initial anti-GBM titer was 161 units (normal < 21). He was transitioned to prednisone 60 mg daily by mouth, after 3 intravenous pulse doses of 1 g methylprednisolone and oral, daily cyclophosphamide (CYC) 250 mg (2.5 mg/kg) that was soon reduced to 150 mg daily after adjustment for renal function. Approximately 2 weeks after admission, he was discharged on prednisone 60 mg daily, CYC 150 mg daily and thrice-weekly apheresis treatments. At discharge, the SCr was 459.36 µmol/L (5.2 mg/dL) and the anti-GBM titer was 86 units.
Following two apheresis treatments, the patient's kidney function deteriorated. His SCr increased to 644.88 µmol/L (7.3 mg/dL) and his anti-GBM titer rose to 132 units. The patient also became volume overloaded. This led to readmission for initiation of hemodialysis, along with daily apheresis. He received 17 apheresis treatments during his second hospitalization, on a near daily basis. He also received four hemodialysis treatments that were eventually stopped due to substantial improvement in his kidney function. His SCr stabilized around 397.53 µmol/L (4.5 mg/dL) with a creatinine clearance of 26 mL/min/1.73 m2 determined by a 24-h urine collection. He was discharged again on a thrice-weekly apheresis schedule. He was maintained on CYC 150 mg daily and prednisone 60 mg daily. His last anti-GBM titer before discharge was 59 units. Although the SCr declined to 362.19 µmol/L (4.1 mg/dL), the anti-GBM titer was persistently elevated. The patient remained apheresis-dependent and attributable to the lack of response to conventional therapy, B-cell depletion with rituximab was attempted to eliminate antibody production. Approximately 2 months after his initial presentation, the patient received a single, 1000 mg dose of rituximab. Subsequently, the patient's anti-GBM titer normalized (), and the patient was maintained on CYC and prednisone. The apheresis treatment frequency was slowly decreased and then stopped. The last treatment was administered 3 months after his initial presentation. CYC was stopped after 6 months at 21.7 g for a total cumulative dose. Prednisone was slowly reduced and ultimately discontinued over a 6-month time period. Presently, his SCr is 181.98 µmol/L (2.06 mg/dL) and the ACR is 366 mg/g on maximal dose lisinopril therapy. The patient's course is summarized in .


A 52-year-old Caucasian man presented to our emergency department with severe asthenia and muscle cramps. Several days before admission he noticed muscle weakness in his limbs. This gradually progressed, resulting in a fall and inability to stand. He denied nausea, vomiting, diarrhoea or use of laxatives. There were no respiratory or cardiac complaints. His daily nutritional intake predominantly consisted of soup and bread and he had abstained from consuming alcohol a few months previously.
Relevant medical history included hypercholesterolaemia and hypertension, treated with lisinopril 20 mg per day, hydrochlorothiazide 12.5 mg per day and amlodipine 5 mg per day, but with questionable therapeutic adherence. He ceased the statin therapy 1 year before admission.
Clinical examination revealed severe paraparesis with preserved sensory input and low reflexes: he was unable to lift his limbs against gravitational force. He was cachectic, with a total body weight of 44 kg at admission, a length of 166 cm and a body mass index of 16.0 kg/m2. He had mild hypertension with a blood pressure of 156/103 mmHg. All other physical findings were normal.
Laboratory investigations at admission revealed metabolic alkalosis (pH: 7.54; pCO2: 46.4 mm Hg; HCO3−: 39 mmol/L) and severe hypokalaemia (1.6 mmol/L). Nine hours later, a control sample showed further decrease of the kalaemia to 1.5 mmol/L, despite intravenous potassium and magnesium substitution. Urine collection revealed a high urinary potassium: 188.6 mmol/24 h (reference range (RR): 26.0–123.0). The transtubular potassium gradient (TTKG) was 10.2, indicating marked renal potassium wasting.
In addition there were arguments for rhabdomyolysis: CK levels were 118.87 μkat/L (RR: 0.83–2.84) [7118 U/L (RR: 50–170)] at admission and increased to 925.48 μkat/L (55 418 U/L) few days after admission; urinary myoglobin was 930.37 nmol/L (RR: <0) [16 300 μg/L (RR: <0)]. The kidney function remained normal during his stay.
In the endocrine investigations the suppression of renin and aldosterone and the elevated urinary free cortisol are most noticeable (Table ). We also noted a marked polyuria (up to 5 L/24 h in the first few days) inconsistent with the amount of intravenous fluid administration.
The key abnormalities of our case were an extreme hypokalaemia, accompanied by metabolic alkalosis, moderate hypertension, rhabdomyolysis and polyuria. Diuretic abuse was excluded through urinary sampling and our patient denied laxative abuse. Bartter and Gitelman syndrome, Liddle syndrome, congenital adrenal hyperplasia and other congenital or genetic disorders were highly unlikely in view of his age and since previous potassium levels were normal. The suppressed renin and aldosterone and normal morning cortisol suggested an apparent mineralocortoid excess-like disorder. Other endocrinopathies, such as Cushing syndrome and ectopic corticotrophin syndrome, could be excluded through laboratory findings (Table ). Through a careful medication and dietary history our patient disclosed the consumption of two centimetres of liquorice root a day for the last 2 months, an equivalent of 1.5 g liquorice daily.
All oral medication and liquorice ingestion was ceased. Up to 15 mmol potassium chloride per hour was needed to correct the hypokalaemia, which took about 3 days. Due to persistent hypertension an ACE-inhibitor was started.
At discharge alkalosis was still present, but the kalaemia remained within the normal range without further need for substitution. One month after permanent cessation of the liquorice ingestion, all ion, metabolic and endocrine disorders returned to normal. This confirmed our diagnosis of liquorice-induced apparent mineralocorticoid excess syndrome with hypokalaemic paraparesis, rhabdomyolysis and nephrogenic diabetes insipidus.


A 68-year-old male presented with longstanding, left sided nasal obstruction and serosanguinous nasal discharge. He had been experiencing nasal obstruction and intermittent epistaxis for one year already. His past medical history was otherwise unremarkable. The patient complained of the recent onset of left cheek fullness. On anterior rhinoscopy, a bulge was detected, arising from the left nasal wall and impinging on the septum. The computed tomography (CT) examination was performed on a spiral scanner (Light Speed VCT, GE Medical Systems, Milwaukee, WI, USA). The CT scan obtained following intravenous contrast administration revealed a large, inhomogeneously enhancing mass in the left maxillary sinus and nasal cavity ( and ). The nasal turbinates and the medial wall of the maxillary sinus had been eroded by the mass. There was also a bony remodeling in the anterior wall of the maxillary sinus. For further evaluation, magnetic resonance imaging (MRI) was performed on a 1.5 T scanner (Gyroscan NT; Philips, Eindhoven, Netherlands) to produce pre- and post-contrast T1-weighted spin-echo images and T2-weighted fast spin-echo images, with or without fat saturation. The MR images were obtained in at least two planes with 5 mm section thickness and 0.5 - 1.5 mm intersection gap. The MRI showed a heterogeneous high-signal intensity mass on the T2-weighted images (). When enhanced with gadolinium (our institute’s routine MRI protocol of our institute includes fat suppression for axial enhanced T1-weighted image), it seemed to arise from the antrum of the maxillary sinus and extended into the left nasal cavity, through the ostiomeatal complex (). Because of the suspicion of sinonasal cancer, a biopsy was taken to obtain tissue from the nasal cavity and maxillary sinus. However, the biopsy revealed only stromal sclerosis and chronic necrotizing inflammation. The tumor was completely excised by performing endoscopic sinus surgery with the patient under general anesthesia. No significant hemorrhage occurred during the surgery, and the surgical findings were well correlated with the CT imaging. However, the uncinate processes as well as the medial wall of the maxillary sinus were found to have been destroyed by the mass. The microscopic examination showed dilated sinusoidal vascular channels in the stroma lining with an interconnecting fibrous wall covered with flat endothelium. The lumina of these spaces were filled with blood. The histologic features were most compatible with cavernous hemangioma (). On follow up after 1 year, the patient was asymptomatic, without any sign of recurrence.


A 22-year-old primigravida presented to the emergency room at 10 weeks gestation with acute onset left iliac fossa pain of 1 day duration. The Pain was colicky in nature and radiated to the left loin. It was associated with nausea. The patient was rolling in pain and there was tachycardia, but the temperature and blood pressure were normal. Abdominal examination revealed a vague mass in the left iliac fossa with marked tenderness. Her hemoglobin was 12.6 g/dL, white cell count 7.7 × 109/L and C-reactive protein (CRP) 26 mg/dL.
Ultrasound examination showed a single live intra-uterine fetus of 10 weeks gestation, an enlarged and edematous left ovary with a clear cyst of 76 mm × 63 mm with flow to the ovary []. The right ovary appeared normal.
With a provisional diagnosis of left adnexal torsion in pregnancy, she was taken up for emergency surgery. Mini-laparotomy was performed through a suprapubic transverse incision; straw colored fluid was noticed in the peritoneal cavity, the left adnexa was delivered through the abdominal incision to improve the access and it was twisted twice on its pedicle, the left ovary and tube were blackish, edematous and congested []. The cyst had ruptured during manipulation, and it drained blood stained fluid. The uterus was 10 weeks in size, and the right adnexa was grossly normal.
On detorting the twisted adnexa, the tube regained its color and became pink, the ovary also began to regain its color slowly. Ovarian cystectomy with reconstruction and conservation of the left fallopian tube and ovary was performed. Postoperatively the patient received 17 alpha hydroxy progesterone caproate 250 mg intramuscularly weekly × 4 weeks (Proluton depot) as progestogen support for the pregnancy. The pregnancy progressed normally, and the patient had a spontaneous vaginal delivery at term of a live baby girl that weighed 2700 g. Follow-up ultrasound scans and Doppler studies showed flow to the ovary and developing follicles indicating normal functioning ovary.


A 62-year-old man with type 2 diabetes mellitus and hypertension presented with generalized weakness. The patient had undergone partial penectomy 5 months earlier for a mass, which was diagnosed histologically as squamous cell carcinoma, moderately to well differentiated, condylomatous subtype. The neoplasm involved the entire glans and distal part of the urethra, with up to 1.5 cm depth of invasion (Stage T3). No lymph node dissection was performed at the time of surgery. Physical examination showed the trace edema of lower extremities but was otherwise unremarkable. Laboratory data on admission were significant for hypercalcemia with a serum calcium of 13.4 mg/dL (3.35 mmol/L) and increased serum creatinine at 2.3 mg/dL (203.3 μmol/L). Urinalysis showed pH 5, 2+ proteinuria and granular casts (2–4/low-power field). A computed tomographic scan revealed lymphadenopathy in mediastinum, inguinal regions and external iliac lymph nodes. Bone scintigraphy showed increased uptake in the skull, ribs, shoulders, vertebral bones and left sacroiliac joint, consistent with metastasis. The hypercalcemia was treated with intravenous fluid and bisphosphonate, with significant improvement. However, the patient's serum creatinine rapidly increased to 8.1 mg/dL (716 μmol/L) in 2 weeks. Nephrology was consulted and a kidney biopsy was performed.
Microscopic examination showed acute interstitial nephritis characterized by diffuse interstitial edema and infiltration by mononuclear and polymorphonuclear leukocytes including neutrophils. The interstitial inflammatory changes were associated with widespread acute tubular injury. The glomeruli showed features of diabetic nephropathy including nodular mesangial sclerosis. One of the glomeruli was partially obliterated by a proliferative epithelial lesion with crescent-like features involving the capillary tuft and adjacent urinary space (A and B). Epithelial cells comprising this lesion were cytologically atypical and showed feature suggestive of squamous differentiation including the eosinophilic cytoplasm, distinct cell borders and occasional intercellular bridges. Many of these cells had large irregular nuclei, and prominent eosinophilic nucleoli (A and B). Occasional mitotic figures and apoptotic bodies were also identified (A). The glomerular capillary involved with this lesion was markedly distended and completely filled by atypical epithelial cells. A few of these cells were also identified in the adjacent proximal tubules. A review of the partial penectomy specimen, previously diagnosed as squamous cell carcinoma, showed a strong similarity between the cancer cells of the primary neoplasm and the atypical epithelial cells found in the kidney biopsy (data not shown). Taken together with the squamous features of the intraglomerular epithelial cells, this finding was most suggestive of glomerular involvement by metastatic squamous cell carcinoma of the penile origin.
Immunohistochemical studies were performed to confirm the squamous differentiation and neoplastic nature of the intraglomerular proliferative epithelial lesion. The atypical intraglomerular epithelial cells were positive for cytokeratin (CK) 5 (EP1601Y, Cell Marque; C) and p63 (BC4A4, Cell Marque; D), markers of squamous cell carcinoma [, ], and negative for WT1 (6F-H2, Dako, podocyte marker), CK8 (35bH11, Cell Marque, parietal epithelial cell marker) and CD31 (JC/70A, Dako, endothelial marker) (data not shown). Atypical cells with similar cytologic and immunoreactive features were identified within the urinary space of an additional glomerulus (data not shown).
Based on the histologic and immunohistochemical findings, the lesion was diagnosed as intraglomerular metastatic squamous cell carcinoma of penile origin. The patient's clinical condition deteriorated despite supportive care, including dialysis, to the extent that systemic chemotherapy could not be administered. The patient was kept on palliative care until his demise 3 weeks after the kidney biopsy. No autopsy was performed.


A 42-year-old male presented with malaise, cough, myalgia and a reduced urine output in November 2011. He was a known previous intravenous drug user who was currently on a methadone programme. He had also been diagnosed with pulmonary tuberculosis in early October 2011 and was being treated with directly observed therapy of isoniazid (750 mg), pyridoxine, pyrazinamide (2.5 mg) and rifampicin (750 mg) three times per week.
On admission, the patient looked cachectic. Clinical examination was largely unremarkable except for some mid-abdominal tenderness. Laboratory results revealed acute kidney injury (AKI) with urea 36.3 mmol/L and serum creatinine 579 μmol/L. Creatinine had been normal 3 weeks earlier. Serum amylase was 900 U/L. A renal ultrasound scan was unremarkable. Serum albumin was 33 g/L and the urine protein creatinine ratio was 144 mg/mmol. Autoimmune screen was negative. Renal function deteriorated and haemodialysis was begun. A renal biopsy was performed.


A 30-year-old right-handed Nigerian woman was admitted to the University of Calabar Teaching Hospital, Nigeria, with a 1-week history of inability to move the left upper and lower limbs of acute onset. There was a history of headache, but no seizures, vomiting or loss of consciousness. She was not known to be hypertensive or diabetic, and she does not drink alcohol nor does she smoke. The patient was diagnosed to be HIV positive about 2 years prior to this admission and commenced on antiretroviral drugs (ARV) but defaulted on therapy for about 1 year prior to the current presentation. Her latest CD4+ count was not known.
On neurologic examination, she showed left upper motor neuron facial nerve palsy and increased tone and brisk reflexes in both left upper and lower limbs. Power was grade 0/5 and grade 1/5 in the left upper and lower limbs, respectively, on the Medical Research Council scale, with a positive Babinski sign on the left. A brain CT scan revealed a rounded ring-enhancing hypodense lesion in the parafalcine region of the right parietal cortex (fig. ). A complete blood count revealed low haemoglobin (8 g/dl), ESR 80 mm in the first hour, and CD4+ count 18 cells/mm3. Toxoplasma IgM was 0.14 IU/l and toxoplasma IgG was 202.0 IU/l, both markedly raised.
A diagnosis of stroke-like syndrome due to cerebral toxoplasmosis in the background of HIV infection was made and the patient was commenced on pyrimethamine (200 mg at start, then 50 mg daily), clindamycin (600 mg every 6 h), folic acid (10 mg daily), septrin (960 mg b.i.d.), amoxicillin/clavulanic acid (625 mg t.d.s.), and haematinics. Two weeks after treatment, the patient resumed ARV therapy with Truvada and Lopinavir/Ritonavir. Power gradually improved to 4/5 in both limbs, and she started ambulating and was discharged to follow-up as an outpatient.


A 35-year-old female was referred to the University of Calabar Teaching Hospital, Nigeria, with a 2-day history of left-sided weakness affecting her leg and arm and focal seizures involving her left upper limb. She had headaches but no vomiting or alteration of consciousness. She had a history of HIV infection, diagnosed 4 years prior to the current presentation and treated with ARV drugs. Her last CD4+ count (6 months before) was 28 cells/mm3.
On neurologic examination, there was left hemiparesis (grade 3:5 on the Medical Research Council scale for both left upper and lower limbs) with increased tone and brisk reflexes and upgoing plantar reflexes (Babinski sign). An urgent brain CT showed a rounded marginally enhancing hyperdense lesion with perilesional oedema in the right thalamus (fig. ). There was obliteration of the posterior horn of the ipsilateral lateral ventricle by the aforementioned mass. A similar but ill-defined lesion with more extensive perilesional oedema was also noted within the ipsilateral parietal lobe.
Blood tests showed haemoglobin 10 g/dl, ESR 106 mm in the first hour, CD4+ count 24 cells/mm3 and toxoplasma IgG antibody 300 IU/l. Based on these findings, a diagnosis of cerebral toxoplasmosis presenting with a stroke-like syndrome, on the background of HIV treatment failure, was made. The patient was commenced on appropriate treatment and her muscle power gradually improved. She then started ambulating, while focal seizures ceased. The patient was discharged home to continue follow-up at the medical outpatient department.


Patient 1 was a 70-year-old asthmatic woman who had no history of a drug allergy. Cefotetan had been administered several times previously with no adverse reaction. On this occasion, she was admitted because of aggravated cough, dyspnea, and fever, and cefotetan was administered intravenously under the impression of pneumonia. A few minutes later, she developed chest tightness, wheezing, urticaria, and decreased blood pressure. Systemic corticosteroids were administered along with intramuscular injection of epinephrine, and she subsequently recovered. One week later, a skin prick test (SPT) and an intradermal test were performed using cefotetan at concentrations of 0.1-10 mg/mL in 0.9% NaCl. Skin tests were considered positive when a wheal larger than 3 mm with surrounding erythema was present 15 minutes after exposure. She showed negative responses to all common inhalant allergens on SPT. A positive response was noted on the intradermal test with 10 mg/mL cefotetan, but there was no response on SPT.


Patient 2 was a 63-year-old woman diagnosed with reactive airway dysfunction syndrome, due to 2,2-dichlorovinyl dimethyl phosphate 11 years ago. She was non-atopic and had no history of allergic disease. She visited the emergency room due to pneumonia and cefotetan was administered intravenously. Immediately, she complained of aggravated dyspnea and chest tightness, followed by a significant fall in blood pressure and loss of consciousness. The patient was intubated and resuscitated with the administration of intravenous fluid, epinephrine, and inotropes.
The diagnosis in both cases was cefotetan-induced anaphylaxis. To investigate the underlying pathogenic mechanisms, we prepared cefotetan-human serum albumin (HSA) conjugate and detected serum-specific IgE and IgG antibodies to cefotetan-HSA conjugate using ELISA as described previously., When the positive cut-off value was determined from the mean + 3 SD of non-atopic healthy controls, patient 1 showed high serum-specific IgE to cefotetan-HSA conjugate (), whereas serum-specific IgG1 (data not shown) and IgG4 antibodies to cefotetan-HSA conjugate were not detected ().
By contrast, serum-specific IgE to cefotetan-HSA conjugate was not detected in patient 2 (), whereas high serum-specific IgG1 (data not shown) and IgG4 antibodies were noted (), compared with controls. To evaluate a possible mechanism of IgG4-mediated basophil activation, we performed a basophil activation test (BAT) with cefotetan and anti-IgG4 antibody using peripheral basophils from patient 2, as described previously. The patient's basophils were incubated for 30 minutes with various concentrations of cefotetan and anti-IgG4. Anti-IgE antibody (1 µg/mL; Sigma-Aldrich, St. Louis, MO, USA) and no drug incubations were used in positive and negative control treatments, respectively. A significant up-regulation of CD63, a marker of activated basophils, was noted upon serial addition of cefotetan (from 10% to 57.6%) and anti-IgG4 antibody (from 12.6% to 27.7%) compared with that in healthy controls (). However, no significant response was noted when the anti-IgG1 antibody was added (data not shown).


A 31-year-old male consulted from the neurology department to evaluate the cardioembolic source of multifocal cerebral infarctions () and progressive dyspnea. He had been treated for CSS with eosinophilic pneumonia, bronchial asthma, and paranasal sinusitis for last ten years from the department of allergic disease. His blood pressure was 120/70 mm Hg, heart rate was 96/min, body temperature was 96.7℃. And, his electrocardiogram (ECG) on admission showed normal sinus rhythm (). Crackles on both lung fields, jugular venous distention, and pitting edema of both legs were noted on physical examination.
Blood chemistries showed marked elevation of liver enzymes with mild hyperbilirubinemia, hypereosinophilia (1500/mm3), the increased level of C-reactive protein (19.5 mg/dL), and normal ranged troponin I. N-terminal-pro-B-type natriuretic peptide was also markedly increased (5135 pg/mL).
Chest X-ray showed cardiomegaly and bilateral pulmonary opacities (). Echocardiography revealed dilated all cardiac chambers, global hypokinesia with severe biventricular dysfunction (ejection fraction: 20%) (), moderate degree of functional mitral and tricuspid regurgitation with severe pulmonary hypertension (estimated pulmonary artery systolic pressure = 78.8 mm Hg). Restrictive filling pattern of mitral inflow was noted on diastolic functional evaluation (). Two mobile and hyperechoic thrombi were also observed within the left ventricular (LV) apex (). To evaluate the underlying cause of DCMP and cardiac involvement of CSS, cardiac magnetic resonance imaging (MRI) was performed. Cardiac MRI revealed multiple high signal intensity spots in the LV myocardium with multifocal delayed enhancement, mainly subendocardial area, suggesting the multifocal myocarditis due to the small vessel vasculitis associated with CSS. Consolidative lesions with high signal intensity in right middle lobe, suggesting pulmonary involvement of CSS, were also noted ().
With the diagnosis of acute decompensated heart failure due to DCMP complicated by LV thrombosis and subsequent acute embolic cerebral infarctions in CSS, anticoagulation therapy, treatments for heart failure, and immunosuppressive therapy including oral steroids (Methylon, Kunwha Pharm, Seoul, Korea, methylprednisolon 24 mg for one month) and parenteral cyclophosphamide (Endoxan, Bukwang Pharm, Seoul, Korea, cyclophosphamide 1000 mg for 1 day) to control the disease activity of CSS were done. The symptoms and signs of heart failure, and neurologic deficits were gradually disappeared. His electrocardiogram at discharge was shown in . After 3 months of medical therapy, cardiomegaly and pulmonary infiltrates were disappeared on follow-up chest X-ray (). Follow-up echocardiography showed improved wall motion and function of both ventricles with the normalization of the cardiac chamber size, and the LV thrombi were also disappeared ().


A 67-year-old man was transferred to our department from the urology department of our hospital. He complained of nocturia and frequent urination. During evaluation, an approximately 3 cm mass in the spinal canal was detected incidentally on abdominal computed tomography (CT) imaging. Abdominal CT imaging showed a fat-containing mass with mural calcification at the L2 level (). The patient looked ill and had experienced aplastic anemia 2 years previously. On neurologic examination, an approximately grade 4 weakness was noted in both lower extremities. He could not walk without support since the last 2 months. Lumbar magnetic resonance (MR) imaging showed a hyperintense intradural mass on a T1-weighted image. After gadolinium enhancement, there was no significant enhancement of the mass in the conus medullaris and focal enhancement of the distal soft tissue component (). He underwent total laminectomy and tumor resection. During the operation, the cystic portion of the intradural mass was ruptured. After surgery, his lower-extremity weakness did not improve, and he could not walk without assistance. Histopathologically, a mature teratoma was confirmed (). After surgery, his general condition worsened gradually. Two weeks after surgery, his mental status also deteriorated. Preoperative CT imaging showed low density lesion in both lateral ventricle and cistern. At that time, he didn't complain any symptom. Postoperative brain MR imaging showed hyperintense lesion on a T1-weighted image on both the lateral ventricle and as well as slightly enlarged ventricles (). We performed extra ventricular drainage (EVD), and his mental status recovered temporarily. However, his mental status again declined; EVD was performed on the other side after 7 days but, we could not retrieve tissue from the mass. During treatment, his general condition and mental status worsened further. Finally, he died of pneumonia and sepsis.


A 35-year-old female presented with partial complex seizures in January 2007, increasing in frequency after the delivery of her second child in September 2007 (Figure A). MRI carried out in June 2008, revealed a right temporal mass (6 × 6.7 × 4.5 cm) with slight contrast enhancement. She underwent complete removal of the tumour on 3 July 2008 and the diagnosis of WHO grade IV astrocytoma (GBM) was established (the tumour consisted of a grade II and grade IV histological components). She received concomitant treatment with irradiation (60 Gy in 30 fractions) and TMZ, followed by 6 monthly cycles of TMZ (200 mg/m2 D1–D5) until March 2009. She was free of symptoms for 2 years but partial seizures reappeared in early 2011. A further MRI showed a multi-focal recurrence in the right temporal area extending to the thalamus and the corpus callosum. Considering the long disease-free interval (3 years) between first treatment and recurrence, TMZ at a similar dose and schedule was prescribed again.
In March 2012, she presented with acute headache and intra-cranial hypertension. MRI showed massive progression mainly in the right frontal area with risk of herniation. She underwent partial removal of the tumour on 29 March 2012. The histology confirmed grade IV astrocytoma with MGMT gene promoter methylation. She received bevacizumab and TMZ; after transient clinical improvement, her clinical condition deteriorated and TMZ was replaced by 800 mg imatinib daily, guided by the WGS data, sequenced and reported within 7 days by Illumina, indicating amplification of KIT and PDGFRA. The tumour progressed rapidly on therapy and she died 3 months after the second surgical debulking procedure.


A 19-year-old female patient reported to the Department with a complaint of mobile teeth along with a history of pus discharge since three months. The history revealed that the patient had a painful swelling in the upper front region of the face three months back, which later subsided due to formation of multiple draining sinuses. The medical history revealed that the patient had generalized weakness, weight loss, and episodic fever for the last one month. On general examination, the patient was poorly nourished and thin built. On extra oral examination a diffuse swelling was present in the middle third of the upper left and right side of the face, which extended from the right to the left mid pupillary line mediolaterally and from the ala tragus line, 4 cm inferior to the infraorbital margin. Superoinferiorly the swelling was slightly tender on palpation []. On intraoral examination, multiple draining sinuses were present with reference to the 23, 26 and 14, 15 extraction socket region; there was discharge of pus from all the sinuses and from the extraction socket [Figures -]. On digital palpation (using index finger and thumb) a very unusual finding was found, the maxillary teeth and maxillary arch in their entirety were movable, like a paper-thin bone []. There was no carious tooth associated with the sinuses, so on the basis of the above-mentioned history and clinical presentation a provisional diagnosis of multiple periodontal abscesses was made. Routine hematological, radiological, and histopathogical investigations were carried out. On the hematological investigation, the erythrocyte sedimentation rate (ESR) was seen to be very high, which indicated a deep-seated infection. On a panoramic examination, diffuse bone loss in the maxilla, involving all the maxillary teeth, was seen []. A sputum examination for acid fast bacilli (AFB) was inconclusive. A chest x-ray showed that the bronchovascular markings were accentuated and in the left upper zone Pulmonary Koch's was found []. A Montoux test was advised, which came positive (>10 mm). A cytological smear taken from the sinus drainage was stained with Ziehl-Neelsen and Periodic acid–Schiff (PAS), but revealed only polymorphonuclear leucocytes and few lymphocytes. Fine needle aspiration cytology (FNAC) showed no granulomatous lesion. A serological examination for M. tuberculosis antibody was performed, which showed a raised level of IgG and IgM antibodies. Finally, an incisional biopsy, which is considered the gold standard, was performed in the extraction socket 14, 15 region []. It showed granulomas of varying sizes and shapes, consisting of central Langhan's giant cells, epitheloid cells, surrounded by lymphocytes, and few plasma cells []. The above-mentioned features are consistent with a tuberculous granuloma, a chronic granulomatous lesion. Therefore, a final diagnosis of pulmonary tuberculosis as a primary lesion, with a secondary lesion in the maxilla, was made. The standard anti-tubercular therapy for bone tuberculosis was started. At the four-week follow up, a marked improvement in the overall health was noticed, with an overall reduction in the mobility of the maxillary bone and teeth [ and ].


A 40-year-old male patient reported in 2012, with a complaint of TMJ ankylosis since last nine years. The patient had sustained a road traffic accident in May 1990. He was treated conservatively for head injury and suspected condylar fracture. One year after trauma, the patient experienced gradual reduction in mouth opening. It became 0 mm in next seven years. In 1998, 1999, 2000, and 2003, the patient underwent surgical operations for the treatment of TMJ ankylosis []. After every surgical intervention he did achieve some mouth opening, but it quickly reverted to 0 mm in three to six months’ time, in spite of good compliance with physiotherapy.
In 2012, his mouth opening was 0 mm. A computed tomography (CT) scan examination showed a huge new bone in the previous 1.5 cm arthroplasty area []. The mediolateral dimension of ankylotic mass on the left side was 3.2 cm and the anteroposterior dimension was 3.5 cm. On right side, there was relatively less amount of bone. His sequential radiographs showed adequate bone removal in the previous surgeries.
The patient was operated via preauricular with extended temporal and submandibular approaches. To avoid two broad cut bone surfaces facing each other, a lower osteotomy cut was planned below the mid-ramus region. To maintain the ramus height a titanium mandibular condylar plate with 2.4 mm diameter screws was used. Buccal fat pad was interposed between the metal condyle and sclerosed temporal bone. On the right side, gap arthroplasty and coronoidectomy was performed. Intraoperative passive and active mouth openings were 30 mm and 35 mm, respectively. Exercises were started within 24 hours. The patient was started on oral indomethacin 25 mg thrice a day for six weeks, along with pantoprazole 40 mg once a day. He was advised to continue mouth-opening exercises as per the unit's protocol.[]
There were no complications other than gastritis six weeks postoperatively. Pantoprazole 40 mg and antacid syrups controlled this. Two years postoperatively, his passive mouth opening was 30 mm, with no signs of heterotopic bone formation [].


A 19-year-old male, presented to us in June 2013, with less than a finger-width mouth opening. History revealed that he fell from the roof of his house and hit his chin at four years of age. Over one year following the trauma his parents noticed gradual reduction in the mouth opening. He was operated at the ages of five, nine, and sixteen years, but his mouth opening always reduced to nil in one to nine months’ time []. In 2011, with nil mouth opening and an extremely short ramus and body, due to repeated operations, he had to be taken up for distraction osteogenesis prior to osteoarthrectomy of the bilateral TMJs []. In four to six months’ time he again experienced reduced mouth opening.
CT scan examination showed extensive new bone in the previous osteoarthrectomy area causing a recurrence of left TMJ ankylosis. Medio-lateral dimension of the new bone was 1.5 cm, and antero-posterior dimension was 2.0 cm []. Left gap arthroplasty and coronoidectomy were done using a preauricular with extended temporal approach. Adequate mouth opening was achieved. Exercises and indomethacin in the same regimen were started within 24 hours.
A postoperative period of eighteen months has shown no recurrence [].


A 64-year-old female was referred to Gachon University Gil Medical Center for further evaluation of incidentally detected bilateral renal masses. She had a history of a partial thyroidectomy due to a thyroid mass, which was diagnosed as benign, and she was taking levothyroxine. A physical examination showed symmetrically swollen lacrimal and submandibular glands but no abnormal tenderness. Quite well-demarcated, nodular, and movable swollen eyes were noted, but no visual field defects or limitations in ocular movement were detected. Palpable, nodular, and movable submandibular gland masses without tenderness were also present.
Her laboratory data showed a white blood cell count of 7.24×103/mm3, a hemoglobin level of 12.0 g/dL, a platelet count of 349×103/mm3, a serum blood urea nitrogen level of 17.0 mg/dL, a creatinine level of 0.7 mg/dL, an erythrocyte sedimentation rate of 39 mm/h, and a high-sensitivity C-reactive protein level of 0.05 mg/dL. A white blood cell count of 11 to 20 and a red blood cell count of 3 to 5 were shown in her urinalysis, but the results of a urine gram stain were negative.
Her serum IgG level was increased to 2,052 mg/dL, and the serum IgG4 level was 1,281 mg/dL (). In addition, her serum total IgE level was also increased to 1,050 U/mL. Other serum Ig levels were normal, including those of IgA and IgM. Serum C3 (78 mg/dL) and C4 (25 mg/dL) levels were within the normal range.
A computed tomography (CT) scan of the orbit and chest demonstrated enlarged bilateral lacrimal glands with enhancement (), a low-density nodule in the left lobe of the thyroid gland and right lobectomy status (), but no evidence of a mass lesion in either submandibular gland. We consulted ophthalmology and otolaryngology because of concern over a neoplasm. Lacrimal and submandibular gland biopsies were recommended but the patient refused owing to the low overall estimated risk of malignancy. An abdominal CT scan showed renal pelvic, calyx, and left pelvic masses extending into the upper ureter, suggesting urothelial cell carcinoma (). The results of urine cytology were negative for malignancy. A bladder mass was detected on cystoscopy at the trigone, suggesting a bladder tumor. No filling defect was found on ureteroscopy. Because a malignancy could not be ruled out, an ultrasonogram-guided biopsy was performed on the pelvocalyceal masses. A histopathological examination was negative for malignancy () but showed dense lymphoplasmacytic infiltration with an increased number of IgG4-positive plasma cells. IgG4 immunostaining revealed >25 IgG4-positive cells per high-power field (HPF) (). However, kidney biopsy showed relatively well-preserved glomeruli and tubulointerstitium ().
We initially prescribed 30 mg oral prednisolone daily for 4 weeks with a subsequent decrease in dosage by 10 mg every 4 weeks. The patient was maintained on low-dose steroid therapy with serum IgG4 level monitoring. A follow-up CT scan and IgG4 level test were performed at the appropriate time. The sizes of the lacrimal gland, the submandibular gland (), and the parapelvic masses in both kidneys slowly diminished (). The IgG4 level also decreased with systemic steroid treatment, which has been maintained with no recurrence.