A 35-year-old woman of Turkish origin presented to our outpatient clinic with increasing gait and stance disturbances of 2 or 3 years’ duration. She reported tingling pain in the feet and lower legs as well as an impairment in detecting cold temperatures as a sign of small fiber involvement. In addition, the patient had recurrent shortness of breath. She had previously been diagnosed with a severe polyneuropathy of unknown origin. Besides the neuropathy, her medical history was empty. She denied gastrointestinal or visual disturbances.
She was a daughter of nonconsanguineous parents from Turkey. Her family history was empty regarding neuromuscular disorders. She has four brothers and two sisters. She is the mother of two healthy children (ages 5 and 7 years).
Her clinical examination revealed a distal as well as left pronounced tetraparesis, hyporeflexia with absence of Achilles tendon reflexes, hypesthesia of the lower legs reaching the patellae and pallanesthesia at the medial malleoli. No compound motor unit potential could be measured on her lower extremities of the tibial or peroneal nerves bilaterally. Motor conduction studies of her upper extremities, including investigation of both the median and ulnar nerves, were unremarkable. No sensory nerve action potentials could be obtained on the upper or lower extremities. Signs of denervation in the distal muscles of the lower extremities, as well as signs of chronic neurogenic reorganization, were detected by electromyography. The extensive polyneuropathy work-up and rheumatology assessments did not produce any pathological results. No indication for a paraneoplastic origin of the disease was discovered. Standard screening methods did not reveal an associated monoclonal gammopathy of undetermined significance or diabetes. However, proteinuria was discovered in the 24-hour urine collection, indicating renal involvement. Because she had dyspnea, a cardiac work-up was performed. In this clinical examination, minor signs of chronic heart failure were found, and we classified her as New York Heart Association functional class II. Magnetic resonance imaging of her heart revealed early left ventricular hypertrophy with a normal ejection fraction of 60%. Echocardiography showed an increased thickness of the interventricular septum of 15mm and a slightly impaired longitudinal left ventricular function. The general weakness might also have been associated with an involvement of the autonomic nervous system with low systolic blood pressure (generally 90mmHg or lower). The patient did not complain about visual disturbances. However, upon examination, opacity of the vitreous body with signs of visual loss was detected in both eyes.
A sural nerve biopsy was performed and processed using standard protocols
[]. Paraffin-embedded nerve tissue was processed for Congo red staining. The stain depicted small but distinct endoneural deposits of amyloid (Figure
A) with a bright green birefringence under polarizing filters (data not shown). These deposits stained positive with antibodies against transthyretin (TTR) (Figure
B). Elastica van Gieson staining allowed visualization of collagen fibers and showed a strong endoneural fibrosis (data not shown). Immunohistochemistry against neurofilament and p-phenylenediamine-stained semithin sections revealed peripheral nerve fascicles with severe loss of myelinated fibers (about 95% compared to healthy controls) and only few remaining myelinated fibers (Figures
C and
D). Single fibers with acute myelin degradation could be observed. Electron microscopy confirmed the severe axonal neuropathy with few remaining myelinated fibers with signs of axonal atrophy, few myelin debris and denervated Schwann cell bands (Figures
E and
F). Additionally, a severe loss of unmyelinated fibers could be detected. Single amyloid deposits were demonstrated by ultrastructural analysis. There were no signs of axonal regeneration.
In the genetic analyses of the TTR gene, we found a heterozygous missense mutation: c.221A>G (GAG>GGG; p.Glu74Gly). The four coding exons of TTR, corresponding to coding cDNA nucleotides c.1 to c.444, including flanking sequences, were amplified by PCR and screened for mutations by direct sequencing (reference sequence: TTR ENSG00000118271 with transcript ENST00000237014). Mutation designation according to standard naming conventions of the Human Genome Variation Society
[], which uses numbering beginning at the Met initiation codon, includes a 20–amino acid signal sequence and may be different from that reported in the literature. The alternative mutation designation for the mutation detected in our patient is p.Glu54Gly.
Treatment with tafamidis was initiated after TTR-FAP was diagnosed
[], but our patient’s neuropathy was aggravated nonetheless. An orthotopic liver transplant was performed 10 months later, but the patient died as a result of intra-operative complications. Three of her four brothers and three sisters have since presented to our outpatient clinic. A 36-year-old brother tested positive for amyloid in a subcutaneous fat aspiration test. Further family members in Turkey have been evaluated for the mutation. One cousin was found to be a mutation carrier; unfortunately, we have no further information on his health condition.


A 47-year-old man presented with acute pulmonary edema with severe progressive dyspnea and orthopnea. He had a 10 pack-year history of cigarette smoking, but no other medical or familial conditions. Chest radiograph showed a small right-sided pleural effusion. Electrocardiogram revealed sinus tachycardia without any conduction abnormalities. Transthoracic echocardiography and cardiac magnetic resonance imaging (CRMI) showed a tumor (4 × 5 cm) occupying the side wall of the right atrium budding into the lumen (Figure
).
Through a median sternotomy, a radical excision of the neoplasm was performed; the atrial wall was reconstructed using a bovine pericardial patch. The post-operative course was unremarkable and the anatomical pathology analysis revealed fusiform cells with considerable nuclear pleomorphism and mitotic activity. The immunohistochemical study was positive to vimentin, desmin, actin, and HHF-35, and negative for PS-100, cytokeratin, and hormone receptors. The final diagnosis was cardiac leiomyosarcoma. Adjuvant chemotherapy with doxorubicin (60 mg/m2 day 1) and ifosfamide (3 g/m2 day 1 and 2) were realized and MRI after the four cycles did not show any sign of local or distant relapse.
Seven years after the first operation, local recurrence with a metastatic paravertebral soft tissue mass was revealed by magnetic resonance imaging. There was no lung metastasis. The patient received antalgic vertebral radiotherapy with systemic palliative chemotherapy consisting of oral cyclophosphamide. One year later, he died of progressive disease and multiorgan failure.


A 29/12 years old male patient had been admitted to the emergency department with complaints of headache, vomiting and gait disorder which had developed within the past month. In brain magnetic resonance imaging (MRI), a lobulated contoured and contrast-enhancing suprasellar mass was detected. The mass was 30x40 mm in size, consisted of solid and cystic components and had led to hydrocephalus (). After incomplete surgical resection of the tumor, the histopathological findings were reported to be compatible with neuronal hamartoma ().
The patient was referred to the pediatric endocrinology clinic for evaluation of probable anterior and posterior pituitary hormone deficiencies. On physical examination, his weight was 16 kg (75-90p) [+1.28 standard deviation score (SDS)] and height was 98 cm (90-95p) (+1.36 SDS). Clinical findings were normal and puberty was compatible with Tanner stage 1. Determination of hormone levels in a morning plasma specimen revealed an adrenocorticotropic hormone level of 46 pg/mL (normal, 0-46), a serum cortisol level of 19.7 µg/dL (normal, 0.8-1.9), a prolactin level of 3.19 ng/mL (normal, 2.5-17). Thyroid-stimulating hormone level was 3.98 mIU/mL (normal, 0.4-5) and free thyroxine level was 1.05 ng/dL (normal, 0.8-1.9). In view of the location of the mass, it was decided that the patient needed to be followed up for the possible development of hypothalamo-pituitary disorders such as CPP and growth failure. He was also being followed up clinically and radiologically for his giant intracranial mass.
At the age of five years and six months, the patients’ weight was 23 kg (75-90p) (+1.23 SDS), his height was 116 cm (75-90p) (+0.98 SDS) and his testicular volumes were 5 mL and 6 mL. He had no pubic hair. During the physical examination, aggressive behavior and mental retardation were noted. However, he had no history of any type of epilepsy. Biochemical measurements revealed a basal follicle-stimulating hormone level of 2.48 mIU/mL (normal, 0.7-11.1), luteinizing hormone (LH) level of 1.45 mIU/mL (normal, 0.8-7.6) and a total testosterone level of 50 ng/dL (normal, 3-30). Scrotal USG revealed age-inappropriate enlargement of the testicles with normal echotexture - the right testicle was 22x15x35 mm and the left testicle was 21x16x34 mm in diameter. The bone age was compatible with the chronological age. In LH-releasing hormone test, a peak LH value of 15 mlU/mL (>5) was detected by direct chemiluminometric technique. The patient was diagnosed with CPP and started on gonadotropin-releasing hormone (GnRH) agonist treatment (triptorelin acetate 3.75 mg every 4 weeks). A normal electroencephalogram ruled out subclinical epileptic activity. Until the third year after the surgery, the patient was clinically and radiologically stable with no evidence of tumor growth. However, at the age of six years and three months, the patient was referred with neurological deficit due to the rapid growth of the suprasellar mass. After the second surgery, he died because of brain herniation. Histopathological examination of the biopsy specimen revealed the lesion to be a juvenile PA ().


A 60-year-old male presented for an annual skin examination. Physical exam incidentally revealed two large, well-delineated patches on the bilateral forearms comprised of hyperpigmented, hypopigmented, telangiectatic, and slightly atrophic macules (Figures and ). Superficial telangiectasias were also present on the neck and anterior chest. The patient was unsure as to when the forearm lesions first appeared but reported a gradual onset and progressive course over several years. On further questioning he denied any associated symptoms. The patient reported a 25-year history of chronic sun exposure secondary to his profession as a fleet service agent handling aircraft cargo transport outdoors. He denied using any consistent form of photoprotection in the form of sunscreen or physical barriers.
The patient is Fitzpatrick skin type III. Past medical history included hypertension, hyperlipidemia, type 2 diabetes mellitus, asthma, and a history of basal cell carcinoma. Current medications include amlodipine/benazepril, which the patient had been taking since his diagnosis of hypertension six years earlier, chlorthalidone, rosuvastatin, metformin, and inhaled mometasone.
Potassium hydroxide (KOH) preparation on lesion scrapings, performed to rule out underlying fungal infection, was negative. A punch biopsy was obtained from a representative patch on the forearm. Biopsy of the lesion revealed epidermal atrophy with blunting of the rete ridges. There was increased pigmentation of the basal layer without melanin incontinence. There were prominent superficial blood vessels ().


An 8-month-old Caucasian baby boy with heterotaxy syndrome was admitted to our general pediatric ward after presenting to a scheduled clinic visit with fever, hypoxemia and cyanosis. His history was significant for dextrocardia, polysplenia, interrupted inferior vena cava, biliary atresia status post-Kasai procedure, and malrotation status post-Ladd’s procedure. He was febrile on presentation, and was started on oxygen via nasal cannula for oxyhemoglobin saturations as low as 70%. His chest radiograph on admission showed a patchy right lower lobe opacity, and he was started on antibiotics out of concern for pneumonia. He was subsequently transferred to our pediatric intensive care unit (PICU) for refractory hypoxemia requiring high flow oxygen therapy.
Throughout his PICU admission, he continued to require high flow oxygen up to 9L per minute and fraction of inspired oxygen (FiO2) of 1 to maintain oxyhemoglobin saturation greater than 75%, with persistent desaturations while upset. Early in his admission, he developed increased work of breathing requiring positive pressure ventilation with bilevel positive airway pressure. A chest radiograph revealed pulmonary edema, and brain natriuretic peptide (BNP) at that time was elevated at 1130pg/mL. His pulmonary edema improved with diuresis, resulting in de-escalation of therapy with return to standard nasal cannula. He required blood pressure support with a dopamine infusion during aggressive diuresis, which was subsequently weaned off without complication. Multiple echocardiograms revealed no clear cardiac etiology of his hypoxemia.
A chest CT angiogram with high resolution reconstruction of the lung parenchyma was performed on the recommendation of our Radiology department to further evaluate the pulmonary vasculature and lung parenchyma. CT imaging showed dilatation of the pulmonary vasculature bilaterally without significant abnormalities of the lung parenchyma (Figure ). Pulmonary arterial hypertension was felt to be an unlikely cause of his dilated pulmonary vasculature as right ventricular pressures were measured as less than half of systemic pressures on echocardiogram. Given his history of biliary atresia and constellation of symptoms, HPS was included on the differential diagnosis. He underwent agitated saline contrast study, which showed bubbles entering the right-sided atrium (systemic atrium in the setting of dextrocardia) through a right pulmonary vein approximately 3 cardiac beats after opacification of the left-sided chambers (Figure ), consistent with clinically significant intrapulmonary shunting.
Abdominal magnetic resonance imaging (MRI) was performed to evaluate for the presence of a congenital portosystemic shunt given the strong association of Abernethy malformation and heterotaxy syndrome and the possibility of reversal of HPS with shunt occlusion. MRI did not reveal portosystemic shunting. The patient subsequently underwent evaluation for liver transplantation. His liver enzymes and coagulation studies were normal. His bilirubin levels were also normal and given normal bile ducts on abdominal ultrasound, a hepatobiliary iminodiacetic acid scan was not performed. Abdominal ultrasound also demonstrated diffuse liver disease, patent portal vein with hepatopetal flow, and no ascites. He did have polysplenia with splenomegaly. He had no signs of collateral circulation on examination. No abnormalities were noted in his stools. His partial pressure of oxygen in arterial blood (PaO2) was measured at 29mmHg while on FiO2 of 0.5. He was listed for transplant with a pediatric end-stage liver disease score of 28, which was further increased to 35 following petition to UNOS for worsening clinical status.
Prior to diagnosis of HPS, the patient was initiated on a milrinone infusion for suspicion of diastolic heart failure. Following the diagnosis, he was trialed off milrinone with the rationale that further pulmonary vasodilation actually may be deleterious given the diagnosis of HPS. However, he responded poorly with subsequent oxyhemoglobin desaturations requiring reinitiation of the infusion. His oxygenation stabilized on a milrinone infusion of 0.5μg/kg/minute. Inhaled nitric oxide was also trialed without significant improvement in oxygen requirement and was subsequently weaned off. Oxygen requirements ultimately stabilized on a diuretic regimen including spironolactone and furosemide.
He underwent OLT 2 months after initial presentation. His postoperative period was complicated by hypercarbic and hypoxemic respiratory failure requiring mechanical ventilation. He underwent tracheostomy for chronic ventilator-dependent respiratory failure. He was transferred out of the PICU 2 months after OLT and subsequently weaned off mechanical ventilation during the daytime. He was discharged home 4 months following OLT on FiO2 of 0.21 through a tracheostomy mask with nighttime ventilator support. He continues to do well. Please see Figure for a timeline of the patient’s clinical course.


Patient: A 65-year-old man.
Presenting complaint: difficulty in swallowing.
In 2002, the patient underwent right nephrectomy for renal cancer at another hospital. Histopathological examination revealed clear cell carcinoma (G2 > G3, pT3a, pN0, M0, and pStage III). Postoperative adjuvant therapy was performed with natural interferon alpha (Dainippon Sumitomo Pharma, Osaka, Japan) at a dose of 6 million units 3 times a week from 2002 to 2005, with no evidence of recurrence.
Present illness: in March 2012, the patient complained of dysphagia. Because upper gastrointestinal endoscopy detected a pedunculated polypoid tumor in the mid-esophagus and biopsy revealed clear cell carcinoma, he was referred to our hospital with a diagnosis of esophageal metastasis of renal cancer.
Findings on admission: the patient was 159 cm tall and weighed 51.8 kg. His temperature was 36.6 °C, blood pressure was 108/60 mmHg, and pulse rate was 77/min (regular). There was an upper abdominal scar from the transverse incision for his old right nephrectomy.
Hematology and biochemistry tests: there were no abnormal findings (Table ).
Upper gastrointestinal endoscopy: a pedunculated polypoid tumor was noted on the anterior wall of the esophagus at 29–35 cm from the incisors (Fig. ). Biopsy revealed clear cell carcinoma. The tumor showed invasion for submucosal layer on endoscopic ultrasonography.
Thoracoabdominal CT: A a tumor was seen in the mid-thoracic esophagus, and a lymph node adjacent to the right main bronchus was enlarged (Fig. ).
Upper gastrointestinal contrast radiography: a pedunculated polypoid tumor was identified in the mid-thoracic esophagus (Fig. ).
Positron emission tomography/CT: uptake was noted at the mid-thoracic esophagus and in a lymph node adjacent to the right main bronchus.
Based on these findings, a diagnosis of esophageal metastasis and mediastinal lymph node metastasis of renal cancer was made, and esophagectomy via right thoracotomy was performed with reconstruction using a posterior mediastinal stomach tube. Endoscopic treatment was not indicated for the esophageal metastasis because of its invasion of the submucosal layer and associated obstruction.
Surgery was performed under general anesthesia plus epidural anesthesia. A midline incision was made in the upper abdomen and a thin stomach tube was fashioned on the side of the greater curvature. The patient was then placed in the left lateral decubitus position, and thoracotomy was performed at the right 5th intercostal space. The thoracic duct was preserved. After dissecting the azygos vein and right bronchial artery, the esophagus was dissected free and cut at the level of the aortic arch. An enlarged lymph node (right main bronchus lymph node) was adherent to the cartilage of the right main bronchus, so this node was dissected free. Reconstruction was performed by high intramediastinal anastomosis and the operation was completed. The operating time was 6 h and 59 min and the blood loss was 234 ml.
Histopathological findings: small alveolar proliferations of atypical cells with clear cytoplasm were noted (Fig. ). The diagnosis was clear cell carcinoma. Because histopathological examination at the time of right nephrectomy in 2002 also revealed proliferation of tumor cells with clear cytoplasm (Fig. ), metastasis of renal cancer to the esophagus was suggested.
Postoperative course: although suture dehiscence occurred, the patient’s condition improved with conservative treatment (enteral and central venous hyperalimentation) and he was discharged from hospital 27 days postoperatively.


A 25-year-old gravida 4 para 3 at 8-week gestation presented to the emergency department with sudden onset of generalised abdominal pain and vomiting. There was no per vaginal bleeding, hematemesis, diarrhea or constipation, syncopal attack, or fever. She did not have any medical illness except for gastritis which occurred intermittently but was treated effectively with antacids and H2 antagonists by her family doctor.
On admission, she was conscious and in pain. She was normotensive and afebrile. There was tachycardia with pulse rate of 118 bpm. She had mild pallor but no jaundice. There was tenderness at the lower half of the abdomen with rebound tenderness but no guarding. No other significant findings were noted on physical examination.
Ultrasound examination showed a doubtful, very small intrauterine gestational sac with no fetal echo or yolk sac. There was significant amount of free fluids in the pelvic cavity; however, no adnexal mass was seen. A provisional diagnosis of ruptured ectopic pregnancy was made with ruptured corpus luteal cyst as the differential diagnosis. An emergency laparotomy was done and, intraoperatively, there was about 500 mL serosanguinous fluid in the peritoneal cavity and presence of ruptured corpus luteal cyst without any active bleeding.
Postoperatively, she was initially stable. However there were persistent abdominal pain and tachycardia of 130–150 bpm four hours after the laparotomy. Further investigations were done to look for other causes of her illness. Hemoglobin was still within normal range, from 16.6 to 15.5 g/dL (reference range: 12–15 g/dL), white cell count was raised at 19.7 × 109/L (reference range: 4.0–11.0 × 109/L), platelet count was normal (205 × 109/L reference range: 110–450 × 109/L), and hematocrit was normal (39.2% reference range: 37–47%). However, serum amylase, urine diastase, and lactate dehydrogenase were all raised. Serum amylase was 1273 U/L (reference range: 25–125), urine diastase was 3054 U/L (reference range: 1–17), and lactate dehydrogenase was 827 U/L (reference range: 125–220 U/L). Corrected calcium was 2.16 mmol/L (reference range: 2.1–2.55 mmol/L), and random blood sugar was 12.4 mmol/L (6.7–11.1 mmol/L). Serum albumin was low at 24 g/L (reference range: 35–50 g/L); bilirubin was raised at 46.8 μmol/L (reference range: 3.4–20.5 μmol/L). Other parameters of liver function test were normal. Additional tests including lipid profile, D dimer, thyroid function test, renal profile, coagulation screening, and electrocardiogram (ECG) were normal.
Ultrasound of the abdomen showed bulky pancreas with peripancreatic fluid suggestive of acute pancreatitis (see ). Therefore diagnosis of acute pancreatitis was made. Modified Glasgow Score was 3 at day 1 of admission.
Despite hydration and supportive management, tachycardia persisted and subsequently she developed Adult Respiratory Distress Syndrome (ARDS). Chest radiograph showed bilateral lower lobe haziness. She then required ventilation with CPAP and was nursed in ICU. Surgical team decided to perform a diagnostic laparoscopy to rule out any concomitant perforated gastric ulcer or perforated bowel. Intraoperatively, there was hemorrhagic fluid about 500 cc with saponification seen on the omentum with inflammation seen around the retroperitoneum region seen. The whole length of the bowel was normal. Peritoneal washout was done. Thus a diagnosis of acute hemorrhagic pancreatitis was made.
She was managed by a multidisciplinary team involving the intensivist, surgeon, gynaecologist, dietitian, and physiotherapist. She required assisted ventilation for five days. Her blood pressure remained stable without any inotrope. She was given intravenous morphine as painkiller. Reassessed after 48 hours later, the Modified Glasgow Score was 2. She also developed ileus, which required Ryle's tube and subsequently endoscopic nasoenteral tube (ENET) before it resolved. Postpyloric enteral feeding was commenced initially. Intravenous pantoprazole was also given. Intravenous Tazocin was given for 14 days.
Her general wellbeing and the blood test parameters improved remarkably. She was asymptomatic and the last blood test results prior to discharge were as follows: serum amylase dropped to 147 U/L (reference range: 25–125), serum LDH was 557 U/L (125–220 U/L), serum albumin was 37 g/L (35–50 g/L), and random blood sugar was normal.
She had complete miscarriage after a week of admission.
After 16 days staying in the hospital, she was well and was discharged home with further follow-up with the surgical team.


82-year-old male patient was admitted to hospital with the complaint of altered mental status in July 2014. In April 2014, he was taken to hospital because of traffic accident. Computerized tomography (CT) was performed and it revealed subarachnoid hemorrhage. He was followed up at neurosurgery clinic. He was operated on because of left tibia fracture and discharged with full recovery two weeks later. He was admitted to neurosurgery clinic again with the complaints of vertigo, nausea, and vomiting in June 2014. CT revealed chronic subdural hematoma and subdural hygroma. At the same day, he was immediately operated on and haematoma was evacuated. He was discharged ten days later. Then he was admitted to neurosurgery clinic again with altered mental status in June 23, 2014. Physical examination revealed no pathological findings except disorientation. Laboratory tests revealed leucocyte 7.8 K/μL, hemoglobin 10.8 g/dL, platelet 252 K/μL, procalcitonin 0.26 ng/mL, and CRP 8.18 mg/dL. Urine tests revealed pyuria and urine culture was performed. Brain CT was performed and bilateral subdural hematoma was noted. On the second day of admission dyspnea occurred, and he was intubated and transferred to neurosurgery intensive care unit. Thorax CT was performed; an air cyst in right lobe, bronchiectasis, and a consolidated area in left lobe were noted. Piperacillin/tazobactam therapy was initiated empirically. On the third day, transtracheal aspirate sample was sent to microbiology laboratory. Antimicrobial therapy was modified to ertapenem after urine culture yielded ESBL (+).
E. coli and C. indologenes were isolated from transtracheal aspirate sample. Antimicrobial susceptibility test revealed resistance to carbapenems and sensitivity to levofloxacin. Levofloxacin was added to antimicrobial therapy on the 6th day of admission. On follow-up, after the second day of therapy modification, improvement on blood gas parameters was observed and the patient was extubated. He was transferred to neurosurgery clinic and antimicrobial therapy continued. He was discharged on the 15th day of admission with cure.


A 58-year-old Japanese man fell from a ladder and sustained a left acetabular fracture. His injury was managed conservatively by a previous physician and he was able to walk without pain. He developed left coxalgia six months after the injury, and was unable to walk when he visited our institution, one year after the onset of pain. He had a past history of hepatic cirrhosis due to hepatitis C and had undergone a living liver transplantation 12 years prior to the current admission. He had consumed no alcohol since the liver transplantation and had no history of corticosteroid therapy.
Plain radiography and computed tomography (CT) images obtained at his first visit to our institution showed a fused acetabular fracture and collapsed left femoral head (Figure ). Magnetic resonance (MR) imaging demonstrated a low-intensity area on T1-weighted images consistent with the collapsed area (Figure ). Fat-suppressed T2-weighted images demonstrated a diffuse region of high intensity in the proximal and medial portions of his femoral head. The initial images obtained at the time of injury showed fractures in the acetabular roof and inner wall of his acetabulum without hip dislocation, and an approximate 2mm step-off was observed on the articular surface of the acetabular roof (Figure ). The acetabular fracture was classified as an anterior column-posterior hemitransverse fracture according to the Judet-Letournel classification system []. There was also a fracture on the medial articular surface of his femoral head.
Retrospective revaluation of the plain radiographs and CT images revealed that the weight-bearing area of his femoral head had progressively collapsed, with residual displacement of the acetabular fracture (Figure ). Dual X-ray absorptiometry showed that our patient’s bone mineral density was 0.657g/cm2 in the unaffected right femoral neck, which was 76% of the young adult mean, indicating the presence of osteopenia. Our patient underwent left total hip arthroplasty for advanced osteoarthritis associated with the collapse of his femoral head. The resected femoral head exhibited a flattened widespread surface with a flap of articular cartilage and subchondral bone, and the cut section demonstrated a subchondral fracture line parallel to the articular surface (Figure A). Histological examination demonstrated repair tissue consisting of marked fracture callus and vascular rich granulation tissue on both sides of the fracture line (Figure B). There was no evidence of antecedent osteonecrosis. Based on these histopathologic findings, we determined that the collapsed lesion was caused by a subchondral fracture of his femoral head resulting from acetabular fracture.


A 38 year old female presented to the Clinic of General Surgery, Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University (Xiamen, China), after experiencing backache for three months previously. The patient was diagnosed with a retroperitoneal mass following computed tomography (CT) and ultrasonic tests ( and ), which was removed surgically. Postoperative magnetic resonance imaging () and pathology revealed an inflammatory myofibroblastic tumor, borderline type, according to the World Health Organization Classification of Tumors ().
Following surgery, the patient was treated with reduced glutathione (300 mg/day) and phosphatidylcholine (200 mg/day) for a month. A liver function test one month after surgery revealed total bilirubin (TBIL) levels of 13.8 μmol/l (normal range, 0–20.5 μmol/l), alanine aminotransferase (ALT) levels of 78 μ/l (normal range, 0–45 U/l), aspartate aminotransferase (AST) levels of 105 μ/l (normal range, 0–35 U/l), alkaline phosphatase (ALP) levels of 458 μ/l (normal range, 40–150 U/l), and gamma glutamyltransferase (GGT) levels of 225 μ/l (normal range, 0–50 U/l). The patient exhibited no symptoms of fever, jaundice, nausea, loss of appetite, fatigue or diarrhea, however, no significant improvement in liver function was observed when compared with that prior to surgery. Three months following surgery, the patient’s liver function was evaluated, which revealed TBIL levels of 16.1 μmol/l, ALT levels of 165 μ/l, AST levels of 127 μ/l, GGT levels of 438 μ/l and ALP levels of 1426 μ/l. The patient was transferred from surgical clinic to our department (the Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University), and was admitted with a diagnosis of liver damage of unknown origin.
Physical examination on admission to our department revealed that the patient showed no mental or intellectual abnormalities, with no jaundice of the skin or sclera and no liver palm or spider angiomas. Lung sounds were clear, with no dry or moist rales. The patient’s heart rhythm was regular and no murmurs were heard. The abdomen was flat and soft and a diagonal surgical incision 20 cm in length was identified on the abdomen. No tenderness or rebound tenderness was identified. The liver was palpable under the inferior margin of the rib. However, xiphoid bone and the spleen were not palpable under the left rib. The patient was negative for Murphy syndrome and no shifting dullness of the abdomen or swelling of the lower extremities was identified. Levels of α-fetoprotein (AFP) were <1.0 ng/ml (normal range, 0–9 ng/ml). Levels of AFP glycosylation heterogeneity were normal (<10%). Tests for viral markers of hepatitis A, B, C, D and E were negative. Furthermore, antibody profiles of autoimmune liver disease and auto-antibodies were negative: IgG, 22.200 g/l; IgA, 3.8200 g/l; IgM, 2.4200 g/l; and IgG2, 11.0 g/l. Color ultrasound of the upper abdomen showed diffuse disease of the hepatic parenchyma (). Plain and enhanced CT scans of the liver revealed a marginal reduction in volume and cavernous hemangioma in the right posterior liver (). Liver biopsy was performed to clarify the nature of the lesion (). Pathological observation revealed widespread infiltration of spindle-shaped cells, with abundant and eosinophilic cytoplasm, unclear cell borders and low and moderate range atypia of the nuclei. A small number of lymphocytes and eosinophilic granulocytes were also observed in the liver tissue. In the surrounding liver tissue lesions, the dividing lines of liver lobules were clear, and edema and spotted and focal necrosis was present in a small number of liver cells. The portal area had marginally expanded and the infiltration of lymphocytes and eosinophilic granulocytes was identified. Immunohistochemical analysis revealed positivity for smooth muscle actin, CD99, Bcl-2, P53, calponin and vimentin and negativity for cytokeratin (CK), CK8, glypican-3, Hep, myoglobin, myosin, desmin, S100, HMB45, CD117, CD34 and anaplastic lymphoma kinase. MASSON + reticular fiber staining revealed a mesh stent in the hepatic lobule, with a clear structure and slight hyperplasia of fibrous tissue in the portal area. Pathological diagnosis indicated infiltration of low grade MS in the liver. After diagnosis was confirmed, the patient was transferred to the Department of Surgical Oncology, The First Affiliated Hospital of Xiamen University for further treatment. The patient refused further treatment and was lost to follow-up three months after discharge from the hospital.


A 71-year-old Caucasian man with osteoarthritis underwent an elective total right hip joint replacement. He had a history of ischemic heart disease with a drug-eluting stent deployed to an 80% lesion in his left anterior descending artery in 2007; the indication was stable angina. At this stage there was a residual 50% to 60% lesion in his right coronary artery. Stress echocardiography one year prior to the hip replacement was negative for ischemia at 90% of maximum predicted heart rate. Other co-morbidities included hypertension, dyslipidemia, type 2 diabetes and epilepsy.
His intra-operative course was uncomplicated. A posterior approach was taken. A 52mm acetabular component with a ceramic liner was press-fitted in place; the stem was also press-fitted and a ceramic femoral head used. Immediately after the operation, however, our patient experienced chest pain and was hypotensive with a blood pressure of 90/70mmHg with associated tachycardia and hypoxia. A cardiorespiratory examination was unremarkable and there were no neurological or dermatological changes seen at this time. Results of an electrocardiogram were normal; chest radiography showed a possible left lung base opacity. A high-sensitive troponin-T assay detected a rise in troponin T from 29ng/L to 528ng/L. Therapy for acute coronary syndrome was instituted and our patient recovered. A subsequent in-patient coronary angiography revealed a patent left anterior descending artery stent, minor left circumflex artery disease, and a 60% lesion in his right coronary artery. This was felt to be the culprit lesion and a drug-eluting stent was deployed. His subsequent post-operative recovery was unremarkable.
Our patient attended a routine review at two months. He was asymptomatic at this time. A treadmill stress echocardiography was performed. At peak exercise, an extensive shower of small echodense bubbles in his right heart was seen, consistent with fat emboli (Additional file : Video 1, Figure ). Our patient remained asymptomatic. Directly after this, repeat stress echocardiography was undertaken on a supine exercise bicycle, allowing isolated exercise of each leg. Small bubbles were reproduced with exercise of his right leg but not his left (Additional file : Video 2, Figure ). A technetium-99m colloid scan [] confirmed pulmonary fat emboli (Figure ). Computed tomography pulmonary angiography showed no thromboemboli. Similar findings were found on stress echocardiography at four months, although diminished, with resolution at six months.
Our patient has recovered fully and has subsequently undergone elective left total hip joint replacement with a cemented prosthesis. There were no further clinical events or echocardiographic findings to suggest fat embolism after this second operation. Our patient remains well.


Case 2 (Index case’s daughter, Figure ), a 24-year-old female with no underlying diseases, developed a throat sore and cough on January 20, the day her father died. She initially consulted the healthcare clinic in hospital A1 due to constant fever on January 22, where she was treated with antibiotics (amoxicillin) and then transferred to hospital D1 for further examination, where sputum and throat swab samples were taken. RT-PCR was conducted on the samples of sputum and throat swabs on the January 23, and the influenza A/H7N9 specific RNA (Ct value 34) was positive. Afterwards, Case 2 was admitted directly to an isolation room at the hospital D1 and commenced on oral Oseltamivir (75 mg, twice daily), and intravenous Peramivir (300 mg, once daily). On admission her peripheral blood count, serum blood biochemistry, and chest CT scan were normal (Table ). She was given supplemental oxygen via nasal cannula with a flow rate of 1–3 L/min, whereas her oxygen saturation was 99%. Her condition remained stable, and symptoms were improved during hospitalization. Later, she was completely recovered and was discharged on February 2 after sputum samples tested negative for H7N9 RNA by RT-PCR on January 30 and February 1 (Table , Figure ).


Case 3 (Index case’s wife and Case 2’s mother), a 43-year-old female farmer, with no underlying diseases, developed an acute cough with expectoration on January 23. She attended the hospital D1 where a throat swab was collected and an RT-PCR assessment was conducted on the throat swab sample, which was positive for H7N9 (Ct value of 37). She was admitted to the hospital D1 on January 23. Although chest radiography was normal, she was treated empirically with oral Oseltamivir (75 mg, twice daily) and intravenous Peramivir (300 mg, once daily). Results of peripheral blood cell count, serum electrolytes, renal and liver function, and coagulation profiles were normal. Arterial blood gas results were normal while the patient was breathing room air. The case remained stable during her admission and then she was discharged on February 5 after sputum tested H7N9 negative by RT-PCR on February 4 (Table , Figure ). The husband of Case 2, who had been in close contact with the Index case and Case 2, had no respiratory symptoms, and throat swabs and paired serum samples were negative (Figure ).


The patient was a woman in her 70s. Her screening mammography showed scattered fibroglandular densities in both breasts and a mass lesion in her right breast (fibroadenoma). The prone cranial-caudal mammogram of the right breast showed a 2 cm, sharply marginated mass with coarse lobulations of a soft-tissue mass (Figure A). The fibroadenoma region was clearly seen in the VA images, taken at a depth of 25 mm below the skin (Figure B and C), denoted by arrows. The VA images could show the gentle coarse lobulation in the mass, a classic finding in fibroadenoma, and the margin very well. The mammogram additionally showed a well-circumscribed 3 mm calcification near the mass, but it was out of focus in the VA image, due to its different depth (Figure ). This case demonstrates that VA can identify fibroadenomas.


The patient, a woman in her 40s, presented with a palpable mass in the right breast. Targeted US showed a 29 × 19 × 13 mm well-defined lobulated and mildly hypoechoic mass. Her diagnostic mammography showed heterogeneous dense parenchyma in both breasts, but was not able to detect the palpable mass on right breast. A marker was placed on the skin to identify the approximate location of palpable mass as seen in the ultrasound (Figure A and B). The VA images indicated a round mass with a defined border and some lobulation inside denoted by arrows (Figure C and D). The pathology result revealed the mass to be a fibroadenoma. This case demonstrates that VA can identify mass lesions not seen on mammograms.


A 19-year-old unbooked primigravida at 15 week period of amenorrhea presented with lower abdominal pain and giddiness. The present pregnancy was a result of spontaneous conception with married life of 8 months. She had a history of slight bleeding per vaginum and lower abdomen pain at 12 weeks when a transabdominal ultrasound was done by a technician and reported normal, for which the report was not available now. On examination, she had a pulse rate of 116 beats per minute and blood pressure of 90/60 mmHg of right upper limb. The abdomen was tender and uterus was deviated to left side corresponding to the size of a 20 week pregnancy. The cervix was firm, 2.5 cm long, posterior and the cervical os was closed. A speculum examination did not reveal any cervical or vaginal pathology. No vaginal bleeding was noted.
A transabdominal ultrasound scan was done and revealed two live fetuses, one live fetus with placenta was surrounded by momentum and the other live fetus with no surrounding myometrium and placenta was seen. Gestational age corresponded to about 16 weeks and free fluid was seen in the pelvis and Morrison’s pouch. Her haemoglobin was 9.0 g/dl, platelet count was 220x109 L, and the clotting profile was normal. Ruptured tubal (cornual) ectopic pregnancy with an intrauterine pregnancy, twin pregnancy in bicornuate uterus and twin pregnancy occupying the unicornuate uterus and its associated rudimentary horn were considered as differential diagnosis.
An emergency laparotomy was performed immediately with simultaneous ongoing resuscitation. Intraoperative findings revealed a unicornuate uterus of 16 weeks gestation with intact left rudimentary horn pregnancy of around 16 weeks. A vessel running superficially over the rudimentary horn had been torn, probably due to expansion of the horn (). Around 1L of haemoperitoneum was drained. Non communicating rudimentary horn was attached to the main uterus with a fibro muscular band which was then excised. Both the ovaries and the Fallopian tubes were normal. The intrauterine pregnancy was left untouched.
Three units of packed cell blood transfusion were given intraoperatively. The intrauterine pregnancy was supported with progesterone and uterine relaxants given intraoperatively and progesterone was continued up to 4 weeks postoperatively. The postoperative period was uneventful. The patient went into spontaneous labor at 37 weeks of gestation and delivered a healthy baby boy weighing 2.8 kg. There were no postnatal maternal and neonatal complications. On histopathological examination sectioning showed a fetus with a crown-rump length of 122 mm. Microscopy Sections showed normal villi within a thickened smooth muscle cavity. Few endometrial glands and stroma were seen within the muscle layer. The findings were consistent with rudimentary horn pregnancy (). Consent from the patient was taken for publication of case report.
Differential diagnosis
• Ruptured tubal (cornual) ectopic pregnancy with an intrauterine pregnancy
• Twin pregnancy in bicornuate uterus
• Twin pregnancy occupying the unicornuate uterus and its associated rudimentary horn.


A 43-year-old woman with noncontributory medical, social, and cultural records was referred to the Oral and Maxillofacial Surgery Service, Department of Dentistry, Pontifícia Universidade Católica de Minas Gerais in Belo Horizonte, Brazil, to evaluate a nodule in her mouth. The patient reported that the lesion had been presenting a slow progressive growth for 3 years. Through clinical examination, a swelling of the left paranasal area with asymmetry could be observed extraorally. Intraorally, a swelling of the left maxilla associated with teeth 21, 22, and 25 could be identified. Teeth 23 and 24 were not presented. The lesion was painless, uneventful, well-defined, firm consistency, covered by normal color and texture of mucosa, and measured 32 x 30 mm. The cone-beam computed tomography (CBCT) of the maxilla showed a well-defined mixed hyperdense/hypodense lesion (Fig. a,c). Expansion of the buccal cortical bone (Fig. a,d), as well as root resorption on teeth 21 and 22 (Fig. b), could be observed. Additionally, expansion of the lateral wall, associated with invasion of the nasal cavity, could be identified by CBCT imagery (Fig. a,c). Ossifying fibroma, calcifying epithelial odontogenic tumor, calcifying cystic odontogenic tumor, complex odontoma, dentinogenic ghost cell tumor, and adenomatoid odontogenic tumor were proposed as differential clinical-radiographic diagnoses. An incisional biopsy was performed and a suggestive histopathological diagnosis of the ossifying fibroma was proposed. Enucleation of the lesion was performed by intraoral approach. An important surgical finding was the easy detachment of the lesion from the healthy bone. Microscopical analysis of surgical piece demonstrated a lesion with fibroosseous features, comprised of composed by mature collagenous fibers and spindle-shaped fibroblasts, with numerous islands and cords of odontogenic epithelium (Fig. a,c). This component was intimately admixed with calcified tissue characterized by trabeculae of bone and round shaped structures (Fig. b). Immunohistochemical study was performed by employing anti-CK antibodies. Positivity to CK 14 and 19, as well as negativity to CK 7, 8, and 18, could be observed (Fig. d). The diagnosis of ossifying OF was therefore established. The postoperative period proved to be uneventful. The patient is currently undergoing routine follow-up with no signs of recurrence after 12 months.


A 53-year-old male developed weakness of the lower limbs, numbness and stabbing pains below the ankle and wrist joints, accompanied by a low fever and night sweating. One month later, the patient developed a red, full-body rash and noticed gradually worsening instability when walking. A rapidly proliferative painless lymph node on the left side of the neck was also noted. As a consequence, the patient was admitted to the Xiangya Second Hospital of Center South University (Changsha, Hunan, China). A physical examination revealed lower limb paresis (grade 4/5 according to the manual muscle testing) (), a high fever, a red rash and swelling of the left neck lymph nodes to a size of 2.0×1.5 cm2. Blood analysis revealed the following results: White blood cell count, 14.6×109/l (normal range, 3.0–10.0×109/l) [87.6% neutrophils (normal range, 50–70%) and 5.6% lymphocytes (normal range, 20–40%)]; hemoglobin, 88 g/l (normal range, 20–160 g/l); platelet count, 462×109/l (normal range, 100–300×109/l); sodium, 133 mmol/l (normal range, 136–146 mmol/l); calcium, 1.96 mmol/l (normal range, 2.08–2.80 mmol/l); albumin, 22.8 g/l (normal range, 35–50 g/l); lactate dehydrogenase, 290 IU/l (normal range, 100–300 IU/l); rheumatoid factors, 23.7 IU/ml (normal range, 0.0–20.0 IU/l); erythrocyte sedimentation rate, 65 mm/h (normal range, 0–15 mm/h); and C-reactive protein, 15 mg/dl (normal range, 0–10 mg/dl). Endocrine investigations revealed reduced levels of neo-hombreol F (130 ng/dl; normal range, 250–836 ng/dl). The serum immunoglobulin (Ig)G (31.5 g/l), IgA (8.55 g/l) and IgM (3.12 g/l) levels were all high (normal ranges, 7.6–166 g/l, 0.71–3.35 g/l and 0.48–2.12 g/l, respectively), and immunoelectrophoresis revealed monoclonal gammopathy (γ globulin, 51.5 g/l; normal range, 20.0–30.0 g/l). Bence-Jones protein was not detected in the urine. The electromyography test showed a motor-dominant polyneuropathy with demyelinating features in the lower limbs. An ultrasonic cardiogram revealed that the interventricular septal and left ventricular posterior walls were thickened. A biopsy of the left neck lymph nodes revealed that the normal architecture was lost, except for the presence of occasional depleted follicles with concentrically arranged follicular dendritic cells, and that the architecture was effaced by polymorphic infiltrate with marked vascular proliferation (). Immunohistochemistry revealed the following results: CD21 (++), CD3 (+), CD4 (+), CD45RO (++), CD8 (+), Ki-67 (++; 60%), CD79a (−), anaplastic lymphoma kinase (−) and CD20 (−). The staining scores were defined as follows: −, negative (<3% cells positively stained); +, weakly positive (3–24% cells positively stained); ++, moderately positive (25–49% cells positively stained); +++, strongly positive (≥50% cells positively stained). Computed tomography scans () revealed swelling of the axillary, mediastinal and retroperitoneal lymph nodes, and hepatosplenomegaly. Magnetic resonance imaging of the head was normal. Abnormal cells were confirmed by bone marrow punctures. These findings were consistent with a diagnosis of stage IV AITL, according to the World Health Organization classification (). The patient was also diagnosed with POEMS syndrome, as determined by the criteria defined by Dispenzieri et al (). Following two courses of gemcitabine (1,600 mg, days 1 and 8), oxaliplatin (150 mg, day 1), DXM (10 mg, days 1–5) and L-asparaginasum (1,000 IU, days 1–5) therapy, in a 21-day cycle, the lymphadenopathy was reduced, and the skin changes and limb neurological symptoms improved markedly.


A 71-year old male was referred to our Hematological Department in January 2013 suspected for MDS. He had an acute myocardial infarction (AMI) in 1999 and recovered from this without complications except for dyspnea. He has been on anti-thrombotic medication with Warfarin and Aspirin since. At the time of referral to our department he had had thrombocytopenia since 2008 with values between 87–124 × 109/L and developed additionally moderate anemia (hemoglobin 7.4 mM) in December 2012. His white blood cell counts were in the years 2008–2013 within normal range whereas he had a moderate increase in LDH with values between 264–398 U/L. Physical examination revealed areas with bruising of his skin. He has epistaxis once every second month. He had been smoking until approximately 6 months prior to referral with a calculated 10 pack years.
As part of the diagnostic work-up in January 2013 a bone marrow examination was performed including morphology and cytogenetic analyses. The morphological examination was normal whereas the cytogenetics analysis revealed a pericentric inversion of chromosome 2 in 23 out of 25 analyzed metaphases. Watchful waiting was decided with additional cytogenetic work-up (se below for further description). Eighteen month after referral a follow-up examination of his bone marrow cells included morphology, flow cytometry and cytogenetic analyses. Morphology examination was still without dysplastic signs or increased blasts whereas flow cytometry could not exclude myelodysplasia. Biochemistry at one-year follow-up was without progression and showed continued thrombocytopenia (platelets, 92 × 109/L) with moderate anemia (hemoglobin, 7.2 mM). He is continuously well and without development in symptoms, and visits our hospital for regular follow-ups.


A 50-year-old Caucasian male with a history of alcohol and injection-drug abuse, chronic HCV infection, coronary heart disease, and idiopathic renal function impairment (creatinine clearance < 60 mL/min) for preceding four months attended in the emergency department with uremic symptomatology. He was dysphonic (O2 saturation, 85%) and hypertensive (blood pressure, 185/90 mmHg) and had prominent hepatosplenomegaly with mild peripheral edema; he had no palpable lymph nodes, skin rash, or other manifestations of systemic diseases. Laboratory analyses results were as follows: metabolic acidosis (pH, 7.123; and HCO3-, 8.6 mmol/L); mild hyperkalemia (K+, 5.7 mmol/L); hyperphosphatemia (PO43-, 10 mg/dL); hypoalbuminemia (albumin, 2.8g/L); anemia (hematocrit, 21.2%; and hemoglobin, 6.8 g/dL); thrombocytopenia (platelet, 72 × 10³/μL); lactate dehydrogenase,185 U/L; and severe renal failure (serum creatinine, 9.9 mg/dL; and urea, 199 mg/dL) with signs of glomerular involvement (urine red blood cells, 40 to 60/HPF; and 24-hour urine proteins, 3.06 g).
The clinical and laboratory findings on admission necessitated the immediate start of hemodialysis. Subsequent ultrasound studies revealed hepatosplenomegaly, two kidneys of normal size (right kidney, 11.7 cm; and left kidney, 11.5 cm), and parenchymal thickness (right kidney, 10 mm; and left kidney, 9.9 mm). There was no clinical or radiological sign of lymph nodes involvement. Further laboratory testing by immunological assay (ANA, anti-dsDNA, ASMA, AMA, C-ANCA, P-ANCA, and C3 complement levels) had negative results except for serum proteins electrophoresis, which showed a monoclonal gammopathy of IgM. At the same time, urine immunofixation revealed the presence of albumin, IgM, and kappa light chains, type I cryoglobulinemia, and low C4 complement levels. Considering the history of the patient and after excluding and treating all other causes of renal function deterioration, our diagnostic approach pointed towards an HCV-related renal offence in the context of cryoglobulinemia. However, the rapid decline of renal function and the absence of mixed cryoglobulinemia suggested performing the renal biopsy. While the histopathological examination of the specimen was consistent with the initial suspicion, indicating MPGN (), the immunofluorescence study revealed two unusual findings: dominant monoclonal IgMκ deposits in glomerular basement membrane and infiltration of the interstitium by abundant strongly IgM-positive lymphoid cells (). The presence of CD20 cell marker was distinctive while CD5 was absent. According to these findings, a bone marrow biopsy was performed. The histopathological examination revealed plasmacytic differentiation of small B cells and the immunophenotyping results were positive for CD20 and negative for CD5. These findings were consistent with SMZL. The patient became hemodialysis dependent and received no treatment for the lymphoproliferative disease and was monitored regularly for possible transformation to a high-differentiated lymphoma.


A 54-year-old male was admitted to the gastroenterology clinic with epigastric pain, weight loss of 6 kg, night sweats, and high fever that started a month prior to admission. He reported no severe allergic reactions in medical history; however, he described flushing and flu-like symptoms during gardening. In his physical examination, we detected nonmobile pathologically lymphadenopathies in bilateral cervical, axillary and inguinal regions, and splenomegaly. His routine laboratory results were as follows: lactate dehydrogenase: 133 U/L, Beta2 microglobulin: 4.246 mg/dL, leucocytes: 5.6 × 109/L, erythrocytes: 3.92 × 1012/L, platelets: 137 × 109/L, and hemoglobin: 12.6 g/dL. In his cervical and inguinal ultrasonography and thoracoabdominal computed tomography (CT) scan, bilateral axillary, mediastinal, hilar, paraceliac, peripancreatic, portal hepatogastric, and inguinal pathological lymphadenopathies were detected. His right axillary region lymph node biopsy and bone marrow biopsy results indicated low-grade B cell (follicular) NHL. We diagnosed him with Stage 4 disease and prescribed 6 cycles of an R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, adriamycin 50 mg/m2, vincristine 1.4 mg/m2 (max: 2 mg), and prednisone 100 mg/day) protocol. Prior to the first dose of rituximab, 45.5 mg of pheniramine (intravenous) and 500 mg of acetaminophen (peroral) were administered. The patient developed flushing within 5 minutes following administration. The infusion was then interrupted, and 45.5 mg of pheniramine was administered. The infusion was slowly restarted. Ten minutes following readministration, generalized urticaria, dyspnea, and nausea developed. His physical examination revealed the following: 38.2°C body temperature, arterial blood pressure of 100/60 mmHg (initial arterial blood pressure of 120/80 mmHg), arterial O2 saturation: 92%, 120 beats/min tachycardia, and bilateral rhonchi with no stridor or pharynx edema. The infusion was stopped and the reaction was treated with the administration of 100 mg methylprednisolone and pheniramine. The tryptase level was 24.60 μg/L (n: <11 μg/L) at four hours after the hypersensitivity reaction. Next day, the patient received CHOP only protocol (no rituximab) uneventfully. We referred the patient to the Immunology and Allergy Clinic to continue rituximab treatment.
In the Immunology and Allergy Clinic, his reaction was defined as Grade 3 according to the Brown Classification, which indicates a severe systemic hypersensitivity reaction []. A 12-step rapid drug desensitization protocol was planned for the patient. He was premedicated with H1 and H2 blockers with systemic steroids and was desensitized by an experienced allergist and nurses according to established protocols (). The rituximab dosage was not decreased throughout the following cycles. The basal tryptase level was 8.89 μg/L. At the twelfth step of the protocol, he developed urticaria in his face and body; thus, desensitization was interrupted and treatment was administered. The infusion was restarted without adverse effects. He had a positive skin prick test result for rituximab before second course. During further cycles, the same dose rituximab was administered with minimal urticaria in his face and body so desensitization protocols were completed with increased premedications. The patient is followed by complete response after 6 cycles of R-CHOP; the bone marrow involvement was disappeared. The patient's desensitization protocol is currently ongoing during maintenance therapy.


A 75-year-old man was referred to our institution after being diagnosed incidentally with a 3.0 cm, solid, right renal mass on computed tomography (CT) performed to assess thoracic trauma. He had no specific symptoms. The results of laboratory investigations were within normal limits. On abdominal CT, a renal mass was identified in the upper portion of the right kidney (). The mass measuring approximately 3.0 cm × 2.0 cm was well defined, and it consisted of a partial cystic mass within a mainly solid renal mass. The cystic component contained calcifications. No definite hydronephrosis or caliectasis was detected. The patient had no other abnormal findings, such as suspected distant metastasis or lymph node metastasis. At that time, we considered cystic renal cell carcinoma (RCC), oncocytoma, and adult-type cystic nephroma as the differential diagnosis of this mixed cystic and solid renal tumor. In May 2012, we planned an open partial right nephrectomy; however, during the operation, we noticed that the tumor had invaded the renal capsule. Therefore, we performed open right nephrectomy. After histopathological evaluation, the lesion was diagnosed as a primary renal carcinoid tumor (neuroendocrine tumor). The tumor met both the histological and immunochemical criteria for designation as a carcinoid tumor. Grossly, the resected tumor included a white-yellow soft mass attached to a cystic lesion (). On microscopic examination, the tumor consisted of a ribbon-like, trabecular, or rosette like pattern of cells with a high nucleus: cytoplasm ratio (). Immunohistologically, the tumor cells were positive for antibodies for the neuroendocrine markers, chromogranin A (), neural cell adhesion molecule (NCAM) (), and somatostatin receptor type 2 (SSTR2) (). The tumor cells had a mitotic count of 4 mitoses/10 high-power fields and the level of proliferation marker Ki-67 was 5%. The microscopic and immunohistological findings were compatible with the diagnosis of a primary renal neuroendocrine tumor (grade 2). No local recurrence or systemic metastasis was detected during the 18-month follow-up period.


A 17-year-old otherwise healthy male with noncontributory past medical history presented to his orthopedic surgeon for evaluation of chronic unremitting right foot pain that had been bothering him for six months. He finally decided to visit his orthopedic surgeon after noting swelling along the medial aspect of his foot while playing lacrosse. The patient graded the pain as an 8/10 with nothing making the pain better or worse. No inciting event could be recalled by the patient that started the pain six months earlier. On physical exam, the patient was tender over the tarsonavicular region without any appreciable swelling. Range of motion around the foot was normal and the patient could bear weight. Blood results such as complete blood count, erythrocyte sedimentation rate, and C-reactive protein values were all within normal limits.
The orthopedic surgeon decided to order radiographs of the foot that initially were read as negative for fracture or any significant abnormality by the radiologist. In retrospect, the posterior medial aspect of the cuboid articulated abnormally with the plantar lateral aspect of the navicular (). Importantly, no talar beak was visualized on radiography. The orthopedic surgeon then ordered magnetic resonance imaging (MRI) of the right foot without intravenous contrast to further elucidate the etiology of the patient's symptoms. MRI revealed abnormal articulation between the cuboid and navicular as well as marrow edema on both sides of the coalition with cystic change along the cuboid (Figures , , , , and ), consistent with fibrocartilaginous coalition as no osseous connection was seen between the cuboid and navicular. The patient was treated conservatively with physical therapy that helped for three months and is scheduled to receive a cortisone injection into the coalition if necessary for further alleviation of symptoms. However, to date, the patient has not reported pain recurrence and cortisone injection has been deferred until the patient presents again with pain. The orthopedic surgeon never ordered computed tomography (CT) examination since surgical planning was not needed in this case. No further imaging has been performed on this patient after his baseline MRI foot examination.


On 6 November 2008, a 53-year-old man presented to a nearby hospital with the chief complaints of epigastric pain and black stool. Upper gastrointestinal endoscopy revealed a large deep ulceration in the gastric antrum. Enhanced abdominal computed tomography (CT) scan showed multiple enlarged para-aortic lymph nodes. The other lymph nodes were not enlarged. Positron emission tomography/CT showed abnormal accumulations of fluorodeoxyglucose in the gastric angle, para-aortic lymph nodes, pelvic lymph nodes, and prostate. They suspected malignant lymphoma or prostate cancer. The prostate biopsy showed prostate cancer, and a definitive diagnosis of gastric malignant lymphoma could not be made despite gastric biopsies that were performed every 6 months. There were no abnormal findings in the bone marrow biopsy. Because of the high-serum level of prostate-specific antigen (833 ng/ml) and prostate capsular invasion on magnetic resonance imaging (MRI), they made the diagnosis of metastasis of prostate cancer to the para-aortic and pelvic lymph nodes (cT3aN1M1). Treatment was initiated for the prostate cancer rather than the gastric malignant lymphoma. They started medical therapy for prostate cancer (bicalutamide and leuprorelin acetate). After medical therapy, enhanced abdominal CT showed that the para-aortic and pelvic lymph nodes had become progressively smaller and the level of prostate specific antigen had decreased. On the other hand, upper gastroscopy showed that the gastric tumor had enlarged gradually. Once control of prostate cancer was achieved, they had planned to start medical treatment for the gastric tumor. The presence of Helicobacter pylori infection was demonstrated by the positive results of histologic examination, rapid urease test, and serology. They performed H. pylori eradication therapy.
In November 2013, the patient visited the authors’ hospital with acute abdominal pain. He had severe epigastralgia that had started after breakfast. He was 58 years old, 166-cm tall and weighed 62 kg, with a body temperature of 35.9°C, a pulse rate of 81 beats/min, and a blood pressure of 127/82 mmHg. On physical examination, abdominal distension and severe tenderness were present. Blood tests showed normal results for the white blood cell count (4,900/μl), C-reactive protein (0.1 mg/dl), lactate dehydrogenase (200 IU/l), and interleukin-2 receptor (264 U/ml). Abdominal CT scan showed a large amount of intraperitoneal free gas and a fluid collection around the stomach, liver, and spleen. Also, the site of gastric perforation at the anterior wall of the body of the stomach was identified (Figure ). A diagnosis of perforation of gastric ulcer and pan-peritonitis was made, but details of the gastric lymphoma were unknown because it was his first visit to the authors’ hospital. The results of imaging studies indicated a perforated gastric ulcer, and an emergency operation was performed. At first, a laparoscopic omental implantation repair was planned. On laparoscopic visualization of the abdominal cavity, purulent ascites and food residue were observed. There was a large perforation about 50 mm in diameter in the anterior wall of the middle part of the stomach body (Figure ). Because a large amount of food residue had escaped through the large perforation, removal of the food residue around and within the stomach was attempted but it was unsuccessful. Therefore, an emergency laparotomy was performed. A distal subtotal gastrectomy with Roux-en-Y anastomosis and lymph node dissection was performed. Macroscopically, the gastric ulcer was 4.2 × 1.5 cm in size, and the perforation was 4.0 × 1.3 cm in size and located on the anterior wall of the gastric antrum (Figure a, b). It was ulcerative and infiltrative and was the excavated type according to Sano’s classification []. Microscopically, a population of large atypical lymphoid cells diffusely infiltrated the full thickness of the gastric wall. Tumor cells were mainly centroblasts. Tumor cells diffusely infiltrated the muscle and subserosal layers (Figure ). Tumor cells and necrotic matter were detected around the perforation and ulcer floor. The lymphoid nature of these cells was confirmed by the strong positive immunohistochemical staining for CD20, CD38, and CD10; the slightly positive staining for Bcl-6; and partial positivity for MUM-1 (Figure ). On the other hand, the results for CD3, CD5, Bcl-2, and EBER ISH were negative. The MIB-1 labeling index was about 80%. These findings confirmed the diagnosis of germinal center B-cell-like type of DLBCL. There was no evidence of a low-grade MALT lymphoma. The number of metastatic lymph nodes was 3/31. Based on the Lugano International Classification, the stage was II1E (perforation and pan-peritonitis) since lymph node metastasis was present around the left gastric artery and greater curvature of the stomach and distant metastasis was absent.
He recovered from the operation uneventfully and was discharged from hospital 16 days postoperatively. He was administered rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy at the previous hospital.


A 68 years old female of Afghan descent with a past medical history significant for controlled type 2 diabetes mellitus, spinal stenosis due to which she was bed ridden and recent upper respiratory tract infection presented to the emergency department with progressively worsening shortness of breath, high grade continuous fever associated with rigors and chills, and a cough productive of thick whitish sputum for 2 weeks. She had received 2 courses of antibiotics from a general practitioner without relief.
She did not smoke and had no respiratory or cardiac disease. She had a family history of ischemic heart disease and her sister had recently been treated for pulmonary tuberculosis.
On examination, she was an elderly lady in distress. Her pulse rate was 110/minute, blood pressure 110/70 mm hg, temperature 102 degrees Fahrenheit (°F) and respiratory rate 30/minute. Her oxygen saturation was 92% on room air. The percussion note was dull over the right lower lung zone. On auscultation, air entry was decreased in the right lower lung zone with bilateral coarse pan inspiratory crepitations and increased vocal resonance audible up to the middle lung zones.
Arterial Blood gases revealed a pH of 7.44, partial pressure of oxygen (pO2) 88 mm hg, partial pressure of carbon dioxide (pCO2) 33 mm hg, bicarbonate 22 meq/L and oxygen saturation 93%.
A chest X-ray revealed an inhomogeneous opacification in the right basal lung with slight volume loss accompanied by alveolar and interstitial infiltrates (Figure A). The white blood cell count was 30,900 cells/mm3 (differentials 90% neutrophils), C reactive protein (CRP) level 294 mg/dL and the Erythrocyte Sedimentation Rate (ESR) was 65 mm/hr. The blood cultures revealed no growth while sputum grew the normal respiratory tract flora. Three consecutive samples for Acid Fast Bacilli (AFB) were also negative. There was no other identifiable source of infection in the body.
Autoimmune work up including anti nuetrophil antibody (ANA), anti nuetrophil cytoplasmic antibody (ANCA), and rheumatoid factor (RF) were all negative.
The patient scored 2/5 on the CURB65 scoring system for community acquired pneumonia and needed hospital admission. She was initially treated with moxifloxacin 400 mg intravenously once daily and intravenous fluids. Serial White cell counts and CRP levels showed resolution with antibiotic therapy; however the patient’s complaints improved minimally. Serial Chest X rays showed no significant resolution of the right lower lung zone opacity (Figure B).
A High resolution computed tomography scan (HRCT) was performed 4 days after antibiotic therapy. It revealed soft tissue nodular infiltrates and dense consolidation in the lower lobe of the right lung. There was ground glass opacification and haze bilaterally with more prominenence in the right lower lobe (Figure ). Atelactatic changes were also present right middle lobe, ligular segment and left lower lobe. There was pleural thickening bilaterally and calcified pleural plaques were noted along the diaphragmatic pleura on the left. Our experienced radiologist described these changes were most probably due to chronic infective/granulomatous disease, most probably tuberculosis (TB). In high suspicion of tuberculosis, especially since the patient was not recovering, had a family history of treated TB in the past one year and since TB is extremely common in our country, anti tuberculous therapy (ATT) was begun empirically.
Despite ATT, patient did not improve. A bronchospcopy was refused by the patient’s family. Thus finally a CT guided biopsy of the right lower lung lobe was planned on the 8th hospital admission day. Histopathology revealed multiple organizing “fibrin balls” within alveolar spaces without associated hyaline membrane formation. Variable areas of spindle cells fibroblastic proliferation were also seen with focal type II pneumocyte hyperplasia. Special stains for fungus, Acid Fast Bacilli (AFB) and gram staining were all negative. There was no growth on culture of the biopsied tissue. These changes are well depicted in Figure .
Thus, finally with a diagnosis of acute fibrinous and organizing pneumonia we started methyl prednisolone 60 mg/kg intravenously every six hours. There was a dramatic and excellent response. Patient was discharged after 10 days on oral prednisolone 40 mg daily; at this point she was clinically much better, and very high doses of steroids were avoided due to already severe osteoporosis. Figure C shows the interval improvement of the chest x ray findings with this treatment.
One month later she presented again with shortness of breath and non productive cough. She admitted to have stopped taking steroids for the past 10 days. After readmission she was discharged on the same dose of prednisolone with strict advice of adherence to steroids. Her chest radiographs on this admission and discharge are shown in Figure . On the next follow up 1 month later, she was completely symptom free. Currently she is on a tapering dose of steroids and is being evaluated by a neurosurgeon for correction of her spinal stenosis. Over all she tolerated the treatment well and complied well after her first exacerbation.


A previously healthy 22-year-old African American woman presented with progressive vision loss and headache. She denied any trauma, pain, pain with eye movements, flashes, or floaters but complained of lethargy. A head CT showed a subacute infarct of the posteroparietal and occipital lobes. The patient was hospitalized and a hypercoagulability work-up was ordered. Initial laboratory testing showed anemia, thrombocytopenia, elevated creatinine, and positive antiphospholipid antibodies. Echocardiography revealed valvular vegetations.
Ophthalmic evaluation demonstrated best corrected visual acuity of hand motions in the right eye and 20/200 in the left eye. An afferent pupillary defect was appreciated in the right eye. Extraocular movements were full. Confrontational visual fields showed global depression in the right eye and inferior hemifield depression in the left. Tonometry was 15 and 11 by applanation in the right and left eyes, respectively. Slit-lamp examination of the right eye was remarkable for anterior vitreous red cells while the left eye was quiet. Dilated fundus exam revealed pale optic nerves, disc hemorrhages, disc neovascularization, arterial attenuation, and arterial “boxcarring.” Multiple retinal hemorrhages, retinal whitening, and a cherry red spot were noted in both eyes ().
Fluorescein angiography showed extensive retinal nonperfusion bilaterally (). Macular optical coherence tomography showed bilateral cystoid macular edema with distortion of the foveal contour ().
Review of systems revealed a recent 30-pound weight gain, difficulty focusing, hair loss, skin changes, and constipation. Rheumatological work-up was significant for positive ANA, anti-Smith antibodies, cardiolipin antibodies, lupus anticoagulant test, and RPR. Given the clinical presentation, laboratory work-up, and imaging, the patient was diagnosed with SLE, antiphospholipid antibody syndrome, and catastrophic antiphospholipid syndrome (Tables , , and ).
The patient was given IV methylprednisolone followed by an oral prednisone taper. She was later initiated on mycophenolate mofetil. She underwent panretinal photocoagulation. Her kidney failure recovered while in the hospital and she later required a mitral valve replacement.


A 35-year-old woman presented with a 1-day history of a right central scotoma and metamorphopsia which was preceded by viral exanthem and a macular rash over the hand and in the mouth. On examination, the dermatological findings were characteristic of HFMD, and there was an associated history of contact with the virus from the patient's daughter. Visual acuity was 20/20 in both eyes with right central scotoma. Fundus examination revealed right macular intraretinal haemorrhage, intraretinal thickening and retinal pigmentary changes temporal to the fovea (Figure A). No signs of vasculitis or chorioretinitis were seen peripherally. The left eye revealed no abnormalities. The following day the Snellen visual acuity had dropped to 20/80 in the right eye. Infrared imaging showed the presence of a figure of eight or dumb-bell-shaped lesion with abnormalities of the inner segment-outer segment (IS-OS) junction and hyperreflective debris along the retinal pigment epithelium (RPE) on the corresponding spectral domain ocular coherence tomography (SD-OCT), (Figure B). Fundus fluorescein angiography (FFA) showed significant macular leakage (Figure C) with no extra-macular abnormalities and no vasculitis. Indocyanine green angiography (ICGA) demonstrated blocked fluorescence in the corresponding area (Figure D). Oral prednisolone treatment was commenced with 60 mg/day once daily dose in the morning after breakfast (1 mg/kg body weight/day). Over the next few days, the scotoma became well defined and constricted. Corticosteroid therapy was tapered by 10 mg/day every week till 20 mg/day dose and subsequently tapered by 5 mg/day every week and stopped over 2 months. Visual acuity continued to improve over successive weeks to 20/20. Dermatological lesions subsided within 2 weeks of presentation. Follow-up FFA and ICGA did not reveal the presence of active disease (Figure A,B). ICGA showed irregular moth-eaten appearance of the choroidal vasculature with no areas of abnormal hypercyanescence. Residual scar remained in the right macula with intraretinal pigmentary change and resolution of subretinal fluid with a subretinal fibrotic scar on SD-OCT (Figure C). This correlated with subjective improvement in vision and scotoma. Autofluorescence revealed a hypofluorescent lesion at base line (Figure A), which over the next 4 days became morphologically similar to a dumb-bell-shaped maculopathy (Figure B). The autofluorescence lesion started constricting on subsequent follow-up (Figure C,D,E).


A 31-year-old Korean male presented to our hospital with anal discomfort for more than one month due to a protruding mass. He had a history of BCR-ABL-positive acute lymphoblastic leukemia (ALL) and had undergone an allogenic stem cell transplantation from a human leukocyte antigen (HLA) 1 locus-mismatched unrelated donor approximately 70 days prior. The conditioning regimen was busulfan, fludarabine, antithymocyte globulin (BU-FLU-ATG), and he had been tapered on cyclosporine for prophylaxis of graft versus host disease (GVHD). He was at an especially high risk of GVHD, therefore we used total 9mg/kg of ATG for strong immunosuppression. On post-transplant day 69, he complained of discomfort due to an anal mass, which gradually grew over the course of one month.Gross findings revealed a large perianal cauliflower-like mass over 7cm in size with invasion of the anal orifice (Figure -A). He was not married and did not have a history of anal intercourse, furthermore he had not any intercourse within one year due to induction and consolidative chemotherapy for ALL. He tested negative for HIV and venereal disease research laboratories test (VDRL). Based on the data, he was diagnosed with giant anal condyloma of anus occurring after an allogeneic bone marrow transplantation.He was initially treated with podophyllin and cryotherapy under the care of a dermatologist. Because of the unusual size of the mass, he was treated a total of six times per week (Figure B, C, D). After treatment, the mass markedly decreased and was only present in the anal canal (Figure A). The mass was removed by surgical excision using scissors and electrocautery under general anesthesia. Postoperative histopathologic examination confirmed a condyloma without malignant transformation or dysplasia (Figure ). He tested positive for HPV 6 and negative for HPV 11, 16, and 18. Following removal of the condyloma mass, thereafter followed a bleomycin local injection into the small remnant lesion. We performed the irrigation twice with bleomycin mixed with 0.9% normal saline, at a final concentration of 1.0U/mL (Figure B). On post-transplant day 90, cyclosporine treatment was stopped. After seven months, there was no mass present in the perianal and anal orifices, and there were no problems in defecation. He continues to have normal anal function. (Figure C).
Successful treatment included a combination of topical podophyllin and cryotherapy and transanal surgical excision, followed by bleomycin irrigation.


Case 1: an 83-year-old man was admitted to the ICU in order to manage postoperative respiratory failure with AKI. He had previously undergone resection of rectal cancer and ileal conduit replacement. Clinical data from his ICU stay are shown in Table (case 1). On his 1st day in the ICU, Escherichia coli (E. coli) was isolated by urine culture and normal florae were isolated by oral culture (Table (case 1)). PSP measured on the 2nd day was 2,745 without PCT or CRP elevation. However, on the 6th day, severe sepsis set in and E. coli was isolated by blood culture. PSP was elevated to 3,977, and PCT and CRP had also increased. The patient’s kidney function recovered gradually with continuous hemodiafiltration; however, PSP rose to 6,051 on the 9th day, along with high SIRS and APACHE II values. The patient did not survive on the 13th day due to multiple organ failure.


Case 2: a 78-year-old woman with CKD on hemodialysis (HD) was admitted to the ICU after a coronary artery bypass graft under cardiopulmonary pump. Continuous HD was undergone postoperatively, and PSP ranged from 1,473–1,870 without sepsis symptoms. Clinical data from her ICU stay are presented in Table (case 2). Temporary elevation of CRP or PCT was observed; however, SIRS and APACHE II values gradually decreased postoperatively. Bacteria were not isolated in blood culture, and normal florae were isolated in oral culture (Table (case 2)). Postoperative complications were not observed, and the patient’s clinical prognosis was good.


Case 3: a 74-year-old woman with CKD on HD was admitted to the ICU after surgical clipping for intracranial arterial aneurysm. Intermittent HD was undergone postoperatively, and PSP ranged from 1,240–1,935 without sepsis symptoms. Clinical data from her ICU stay are listed in Table (case 3). Temporary elevation of CRP or PCT was also observed, while SIRS and APACHE II values did not change postoperatively (Table (case 3)). Bacteria were not isolated in blood culture, and normal florae were isolated in oral culture (Table (case 3)). Postoperative complications were not observed, and the patient’s clinical prognosis was good.


Case 4: a 62-year-old man with CKD was admitted to the ICU in order to control gastrointestinal bleeding. Initial PSP was 606 without infection. Clinical data on his 1st day in the ICU are presented in Table (case 4). His CRP was not elevated and PCT was elevated only slightly, while low SIRS and APACHE II values were observed. Bacteria were not isolated in blood culture, and normal florae were isolated in oral culture (Table (case 4)). No signs of infection were observed, and the patient’s clinical prognosis was good.


A 48-year-old woman was admitted to the emergency department of a community hospital for an unusual thunderclap occipital headache associated with nausea, phonophobia, and photophobia, reaching peak intensity within one minute. Headache occurred during an emotional stress (while crying after having been informed of the death of a friend). She had never experienced such a brutal and painful headache. There was no prior history of headaches. Brain computed tomography (CT) and CT-angiography performed at the emergency department were unremarkable. On day four, the patient came back to the emergency department, because of the persistence of her headache. She was reassured and was rapidly discharged home without any further brain imaging. On day 11, she presented a sudden left hemianopsia and she was thus hospitalized. A brain magnetic resonance imaging (MRI) with diffusion-weighted imaging was performed the day of admission and showed hyperintense lesions in the right frontal lobe in the territory of anterior cerebral artery and in the right occipital lobe in the territory of posterior cerebral artery indicative of cytotoxic oedema. The same lesions were visible on fluid-attenuated inversion recovery imaging sequence. Images compatible with a cSAH were localised to the cortical sulcus in the right superior frontal lobe (). Magnetic resonance angiography demonstrated diffuse severe arterial narrowing in the anterior and posterior circulations bilaterally. Injection of cervical vessels with gadolinium and fat saturation sequences excluded the presence of cervical dissections. On day 12, the patient experimented sudden weakness of the left upper and lower extremity and was immediately referred to our stroke unit. On admission, her blood pressure was 120/70 mmHg, her pulse 64 beats per minute, and her temperature 36°C. The neurologic examination showed left hemiparesis predominant to the lower extremity, dysarthria, and spatial neglect. The National Institute of Health Stroke Score was 11. A second MRI was performed and showed an extension of ischemic lesions in frontal and occipital lobes and diffuse cSAH. Magnetic resonance angiography showed poor vascularisation of bilateral anterior and posterior circulations. A CT did not show recent cSAH and CT-angiography image showed vasoconstriction of the right anterior cerebral artery and stenosis of bilateral middle cerebral arteries, as well as vasoconstriction of the bilateral posterior cerebral arteries and vertebral arteries. A bedside transcranial Doppler ultrasonography revealed bilateral and asymmetrical elevated mean middle cerebral arteries velocities (right middle cerebral artery: 240 cm/s; left middle cerebral artery: 150 cm/s) and elevated mean anterior cerebral arteries velocities (right anterior cerebral artery: 102 cm/s; left anterior cerebral artery: 190 cm/s). Oral nimodipine (120 mg/day) and intravenous hydration were initiated and the patient was referred to the resuscitation department. Digital subtraction angiography performed on day 13 showed typical segmental vasoconstriction in the anterior and posterior circulation (). There was neither sinus thrombosis nor arteriovenous malformation. A control of the digital subtraction angiography on day 16 showed complete regression of vasoconstriction. A MRI performed on day 24 did not evidence new ischemic lesions and showed a regression of vasospasm. The patient had no neurological residual impairments.
We diagnosed her as having RCVS complicated by cSAH and ischemic lesions, on the basis of reversibility of the vasoconstriction and brain imaging findings.


Our patient was a 57-year-old Caucasian male diagnosed in 2004 with ankylosing spondylitis. Since 2007, he was under stable treatment with adalimumab monotherapy (40 mg every other week).
The patient came to our observation during a routine follow-up visit in March 2013. In that occasion he presented with multiple nodular lesions arranged in a linear fashion along the left hand and forearm (). The nodules appeared reddish in color, not painful, and not ulcerated, with the maximum diameter of 2.2 cm (). The patient was afebrile and his general condition was good.
The clinical presentation suggested S. schenckii infection, and we have been able to identify the probable site of fungus inoculation, represented by a small ulcer on the fingertip of the third digit (). The patient was not able to remember exactly how and when this injury had arisen. However, the most likely hypothesis is that of an unnoticed puncture with rose thorn, because these flowers are abundant in the home garden of the patient.
Laboratory testing was immediately performed, showing only a mild elevation of alanine aminotransferase (59 IU/L), aspartate aminotransferase (40 IU/L), and creatine phosphokinase (313 IU/L). Complete blood count, erythrocyte sedimentation rate, C-reactive protein, and procalcitonin were in the normal range.
In the following days, an ultrasound evaluation of subcutaneous nodules was performed. The lesions appeared as well-defined hypoanechoic subcutaneous nodules with internal debris. Finally, diagnostic needle aspiration of the biggest nodule was performed. Sporothrix schenckii was isolated from culture of the collected material.
The final diagnosis was of cutaneous sporotrichosis with nodular lymphangitic spread. Adalimumab was discontinued and appropriate treatment with oral itraconazole 200 mg/daily was subsequently started. After 3 months of treatment the patient improved significantly but after 9 months sequelae of the lesions were still present.


A 34-year-old healthy Caucasian male complained of progressive nasal obstruction for several years. Clinically there was a severe narrowing of the nasal inlet due to three tumors in the soft tissue. One was located in the anterior part of the nasal septum; the other two were symmetrically located in both lateral nasal walls. The bulk of the lesions were in the vestibulum. A CT scan showed a thickening of the soft tissues at the nasal inlet without erosion of bony structures. The sinuses were clear. The tumors were removed surgically. At the first examination (2009) we were not aware of IgG4-related disease. The patient had no other respiratory symptoms or signs. Three years later there was a recurrence of all lesions dorsally involving the inferior conchae. The pseudotumors were resected relieving the obstruction. Serum IgG4 level was 1.630 g/L (normal value 0.030–2.010). The haematological values and the other serum IgG subclasses were within normal limits. The histology was identical to case number 2. During the ensuing nine months there has been no apparent recurrence of the manifestations.


A 34-year-old woman originally from Sri Lanka complained of increasing nasal obstruction for two years. There was no history of trauma, infection, or surgery. Clinically, the soft tissues of the caudal end of the nasal septum, the inferior conchae, and the vestibuli were enlarged in size and created a swelling on the external nasal wall (). A CT scan showed normal sinuses and a wide caudal septum with a narrow airspace in the vestibulum and a widening of the lateral nasal walls (). There was no sign of bony erosion. A PET scan showed no other location of the disease. She had a history of acute pancreatitis eight years ago which spontaneously resolved. She has iron deficiency anaemia. The SR was 28 mm and the serum IgG4 level was 2.080 g/L. The other IgG subclasses, the white cell count, and ANCA were normal. Fibrous tumors were dissected free from the surrounding soft tissue in the caudal septum and in the anterior part of the inferior conchae. The nasal symptoms (obstruction and local pain) were not completely resolved and she was started on a low oral dose of corticosteroid therapy as she suffered from diabetes. This had limited effect, so supplementary treatment with rituximab was initiated. This eliminated the pain but had limited effect on the obstruction. The serum IgG4 level decreased to normal level (1.355 g/L). The histological description of the biopsies is given below.