Case 2. A 61-year-old woman with progressive leukocytosis and splenomegaly () was diagnosed with ET 20 years ago. Additionally, she was diagnosed with post-ET MF 5 years ago. Although she was treated with hydroxyurea, her spleen had progressively enlarged and extended 10 cm below the left costal margin. She exhibited MF-related symptoms such as fatigue, abdominal pain, and transfusion-dependent anemia. Laboratory blood tests showed pancytopenia (WBC, 3.0 × 103/L; Hb, 7.0 g/dL; platelets, 7.1 × 1010/L) and leukoerythroblastosis. A bone marrow biopsy showed hypocellular marrow with severe fibrosis (). We detected the JAK2 V617F mutation in the peripheral blood. The disease was classified as “intermediate-2 risk” according to the prognostic classification of the DIPSS, and she was evaluated as a candidate for HCT. After written informed consent was obtained, she was treated with 4 Gy splenic irradiation on day −9 to day −8 prior to HCT. During splenic irradiation, her splenomegaly decreased, and the abdominal pain gradually improved. The conditioning regimen consisted of Flu 30 mg/m2 × 5 (day −6 to day −2), Bu 3.2 mg/m2 × 2 (day −6 to day −5), and 4 Gy of TBI on day −6 to day −5. The patient underwent HCT from an HLA-matched unrelated donor. The infused bone marrow contained 2.3 × 108/kg nucleated cells. Neutrophil engraftment occurred on day 30. Grade III acute GVHD of the gut occurred on day 76 along with chronic GVHD of the liver. There was no GI toxicity as a result of the splenic irradiation. The chimerisms in the bone marrow and peripheral blood were 100% donor. A bone marrow aspiration and biopsy showed complete remission, and fibrosis regressed on day 340 (). The JAK2 V617F mutation was not detected since the neutrophil engraftment. The patient's spleen gradually decreased in size until it was not palpable, and computed tomography showed that the splenomegaly was reduced (Figures and ).


A 54-year-old Japanese man who had been diagnosed as ulcerative colitis 28 years ago and had been treated with conventional medications, including corticosteroids, presented to our hospital. Eighteen years ago, his colitis had become refractory to conventional medication, and J-shaped ileal pouch-anal anastomosis with a double-staple technique was performed. In the postoperative period, diarrhea and blood in the stool were observed, and a diagnosis of pouchitis was made. The patient was treated with metronidazole. Thereafter, he had repeated recurrence episodes of pouchitis. Endoscopic surveillance was regularly performed to rule out dysplasia or cancer. Upon presentation to our hospital, 18 years after the operation, he was admitted with complaints of faintness and fresh blood in the stool of 2 days’ duration.
The patient’s vital signs were stable after an intravenous saline drip, with blood pressure of 90/56 mmHg, heart rate of 86 beats/minute, and body temperature of 36.3 °C. His laboratory data revealed a decreased hemoglobin level of 11.2 g/dl, a normal white blood cell count of 5.8 × 103/μl, a normal C-reactive protein level at 0.04 mg/dl, and a normal erythrocyte sedimentation rate at 6 mm/h. A digital rectal examination revealed a large amount of blood in the pouch. Lower endoscopy was performed to confirm the origin of the hemorrhage, which revealed the hemorrhage to be from an area of neovascularization close to the site of the patient’s ileal pouch-anal anastomosis (Fig. ) but no evidence of pouchitis, although a biopsy was not taken, to avoid promoting the bleeding. Cap-assisted APC was carried out with a clear cap over the tip of the colonoscope for hemostasis. Two sessions of brief pulse APC at a power setting of 50 W and an argon flow rate of 1.4 L/minute were performed (Fig. ). The APC probe was moved close to the lesion site, and cauterization was performed carefully to avoid contact with the stapled ileal pouch-anal anastomosis. APC cauterization was performed several times to enable stoppage of bleeding, and complete hemostasis was achieved without causing pain or complications. Three months later, the patient was admitted to our hospital with a small amount of fresh blood in the stool again. Although lower endoscopy revealed no active hemorrhage, electrocoagulation was carried out in the most suspicious area, where there was an area of neovascularization close to the site of previous cauterization. After that, the patient returned for a follow-up visit, and he reported being without bleeding for 8 months.


A 32-year-old Vietnamese man weighing 55 kg presented to our Department of Neurosurgery, 108 Military Central Hospital, Hanoi, Vietnam, in 2015 with CSF rhinorrhea as sequelae of traumatic brain injury after a traffic accident 3 years earlier. On admission, a computed tomography (CT) scan of his skull was indicated to verify any fractures and brain injury at the right frontal lobe and left occipital lobe. He underwent a craniectomy to cover a shunt identified with muscular fascia. In addition, postoperative antibiotic chemoprophylaxis was applied with 3 g cefotaxime plus 160 mg tobramycin per day (Table ).
One week after surgery, he had fever, but no chills, headache, vomiting, stiffness of the neck or localized paralysis. The Kernig’s sign of meningitis was absent. Treatment with antibiotics was indicated with 3 g ceftizoxime plus 400 mg ciprofloxacin per day. However, fever (38 °C) persisted without further symptoms of meningitis; CSF was still leaking though his nose. The CSF was clear, with a white blood cell (WBC) count of 21,000 cells/ml, glucose concentration of 3.1 mmol/l, protein 620 mg/dl, and serum procalcitonin of 0.2 ng/ml. At that time, an external lumbar drainage was inserted to release his CSF and antibiotic treatment was changed to 3 g ceftriaxone plus 0.5 g levofloxacin daily. After 9 days at day 28 of hospitalization, he had no fever, no headache, and CSF rhinorrhea discontinued.
His normal condition lasted for 1 week only. At day 35 of his hospitalization he developed meningitis. A physical examination showed fever of 39 °C, chills, headache, vomiting, neck stiffness, impaired consciousness, and a positive Kernig’s sign. A laboratory examination revealed a WBC count of 25×106 cells/ml with 95 % of neutrophils, serum procalcitonin of 2.25 ng/ml, and CSF findings of 1800 leukocytes/μl, a protein level of 7 g/ml, and a glucose level of 0.1 mmol/l. A CSF culture did not yield any microorganism (Table ) and he was treated with 4 g meropenem plus 2 g vancomycin per day despite unconfirmed microbiological diagnosis.
One week later at day 42 of his hospitalization he still had a severe meningitis syndrome with chills, headache, vomiting, neck stiffness, reduced consciousness, positive Kernig’s sign, fever peaking at 39 °C, a WBC count of 18×106/mL with 85 % neutrophils, procalcitonin of 6.95 ng/mL, and CSF containing 2540 leukocytes/μl (Table ). The CSF culture was still negative for any microorganism. Therefore, in-house molecular assays were indicated [], which led to the identification of genetic fragments of A. baumannii. Furthermore, the beta-lactam carbapenem resistance genes Vietnamese extended-spectrum beta-lactamase (VEB), OXA-58, New Delhi metallo-beta-lactamase-1 (NDM-1), and Imipenemase (IMP), respectively, were detected (Fig. ). Thus, his diagnosis was established as meningitis due to infection with multidrug-resistant A. baumannii.
Following initiation of antibiotic treatment at day 45 of hospitalization with 4 g meropenem plus colistin 3 MIU per day as indicated, his clinical condition improved considerably. Fever and headache discontinued, Kernig’s sign was negative, CSF rhinorrhea halted, and the laboratory parameters (measured at day 52 of hospitalization) were WBC count 13×106/mL, procalcitonin 0.1 ng/mL, CSF with 85 leukocytes/ml, and protein level 1.96 g/L. However, after 12 days of colistin-based therapy, he relapsed with typical symptoms of meningitis, including renewed fever peaks of 38 °C, headache, neck stiffness, impaired consciousness, and a positive Kernig’s sign; PCR assays of CSF samples were again positive for A. baumannii. Most likely, 4 g meropenem plus colistin 3 MIU per day were not effective enough to eliminate the pathogens. We decided to increase the dosage to 6 g meropenem plus colistin 6 MIU per day, which was maintained for 2 weeks. Following this increase, he recovered, and laboratory parameters were normal. A CSF PCR assay was negative for A. baumannii. The antibiotic treatment was continued for 3 weeks. At the last 3 weeks of hospitalization, antibiotics were no longer indicated and he did not develop any clinical signs and symptoms. He was discharged but underwent control examination every 2 weeks for a period of 3 months without a diagnosis of relapse.


A 63-year-old man, who had undergone total gastrectomy and Roux-en-Y reconstruction for early gastric cancer 10 years previously, was transferred to our institution from a local hospital with complaints of intermittent abdominal pain, palpable abdominal tumor, and hematemesis. On arrival, he was hemodynamically stable, the abdominal tenderness was improving, and the abdominal tumor was not felt on physical examination. Mild inflammatory reaction and anemia were noted on blood examination. All other laboratory values were unremarkable and there was no evidence of acidosis.
Abdominal computed tomography (CT) revealed a tumor with a layered structure in the left abdomen (Fig. ). Endoscopy revealed a bulky, rounded, congested mass that occupied the lumen beyond the esophagojejunal anastomosis (Fig. ) and showed a small amount of oozing from the mucosal surface caused by disruption to the blood flow resulting from intussusception. These findings led to the diagnosis of intestinal obstruction caused by jejunal intussusception. Although we observed retrograde jejunal intussusception, endoscopic reduction was not attempted and surgical repair was performed by laparotomy.
Surgery revealed retrograde jejunal intussusception in the elevated jejunum through the Y anastomosis (Fig. ). We reduced the intussusception using the Hutchinson procedure. The involved bowel was dilated, edematous, and congested, but there was no evidence of ischemia (Fig. ), and therefore, we performed only manual reduction and adhesiotomy without intestinal resection. The patient’s postoperative recovery was free of complications, and he was discharged 12 days postoperatively. He has been alive without symptoms of bowel obstruction for 2 years after operation.


A 29-year-old male, with a history of excessive alcohol intake and chronic pancreatitis, presented to the emergency department at The Chrissie Tomlinson Memorial Hospital, Cayman Islands. He exhibited a 24-hour history of abdominal pain, which was increasing in intensity, without a history of significant trauma. He also had associated vomiting. An abdominal examination revealed upper abdominal tenderness but no signs of peritonism.
The patient was investigated with ultrasound scan (USS) that revealed a PP (). A computed tomography (CT) scan of the abdomen confirmed the presence of a PP in direct contact with the inferior pole of the spleen (). The patient was not known to have a PP prior to admission. A heterogenous hypodense area of the splenic hilum was noted and there was a grossly enlarged liver with a normal gall bladder (). Fat stranding was identified at the tip of the pancreatic tail with a thickened lateral conal fascia. A small fluid collection was seen between the upper pole of the spleen and the left liver. His serial serum amylase throughout this period remained within normal range, making acute pancreatitis less unlikely [].
Over the following 24 hours, the patient became haemodynamically unstable and showed signs of peritonism. An USS revealed intra-abdominal haemorrhage (), which was confirmed by CT as a result of a splenic rupture (). The patient was transfused and underwent an emergency laparotomy with splenectomy and distal pancreatectomy. The spleen was completely disintegrated and the parenchyma had shelled out of the capsule. The tail of the pancreas was densely adherent to the hilum of the spleen. The histology report did not demonstrate acute pancreatitis but identified variable inflammation, reactive changes, and focal necrosis, consistent with chronic fibrosing pancreatitis. Following surgery, the patient went on to make a full recovery. We believe that the PP directly contributed to atraumatic splenic rupture within this individual (ASR).


A 30-year-old Sinhalese man was presented to us with history of high fever, head ache, generalized myalgia, arthralgia, loss of appetite, and nausea on the fourth day of the illness. He gave a history of digging a well a week before onset of fever and working at a rice paddy (exposure to leptospirosis). Leptospirosis was endemic, and a dengue epidemic was going on in his locality at that time. Six weeks ago, he developed a purpuric skin rash affecting all limbs with pruritus. After investigations including a bone marrow biopsy, a consultant hematologist has diagnosed ITP and started oral prednisolone and omeprazole. At the onset of his present illness, he has been on those drugs. He was also on topical clobetasol cream from a dermatology clinic for a patch of hypertrophic lichen planus at his left wrist. Apart from those, he was healthy.
On examination, he was not icteric or pale and had no skin rashes other than lichen planus rash. His pulse rate was 88/min, and blood pressure was 100/70 mmHg without a postural drop. Auscultation of lungs and abdominal examination was unremarkable. His oxygen saturation was 97 %.
Two most probable differential diagnoses were dengue and leptospirosis. Standard dengue fever management [, ] started, and in addition, intravenous crystalline penicillin was prescribed to cover leptospirosis. His skin sensitivity test for crystalline penicillin became positive. Hence, it was substituted with oral doxycycline, and prednisolone and omeprazole were continued.
Since his myalgia and arthralgia did not respond to oral paracetamol (acetaminophen) given pro re nata, a regular dose of oral tramadol was added. Oral calcium lactate was given from day 5 of the illness. On the seventh day of the illness, both dengue IgM and IgG were positive. Doxycycline was discontinued thereafter.
Table summarizes his laboratory investigation results.
His fever subsided after the sixth day of illness and never recurred. He developed marked flushing of the skin and conjunctival injection after the fifth day of illness that improved by the tenth day but never had any purpura or other bleeding manifestations; daily tourniquet tests were also negative during his hospital stay. He was sent home after 8 days and reassessed once and advised to continue to attend his hematology clinic. One week after discharge, his white cell count was 7.68 × 109/l (neutrophils 72.7 % and lymphocytes 23.4 %), hemoglobin level was 14.9 g/dl with a hematocrit of 43.9 %, and the platelet count has risen to 97 × 109/l. We did fasting blood sugar level test as well as he has been on steroids and it was also normal (4.1 mmol/l).
We discussed the relevant issues under four subheadings.
A dengue epidemic was going on in his locality when he presented. His symptoms and signs were compatible with dengue. His laboratory reports also favor diagnosis of dengue (leucocytopenia, invertion of neutrophils to lymphocyte ratio on the seventh day of illness and again reversing, serial changes of his platelet count, serial changes of his hematocrit). Finally, positive dengue IgM and IgG tests confirmed the diagnosis. Infection with other flavoviruses can give false positives in IgM and IgG tests. Japanese encephalitis (JE) is the other flavovirus disease in Sri Lanka, and it is rare. JE is very rare in the central hill country where the patient lives and he has never traveled abroad and never got vaccinated against JE. Considering all, we can conclude this as a dengue case.
Past studies from Sri Lanka and other countries show that in children with dengue, there is little correlation between platelet count and bleeding manifestations [, , ]. One study involving adult dengue patients demonstrated platelet counts <5 × 109/l and hematocrit >50 % were significantly associated with bleeding manifestations. Another study suggested that bleeding occurred more often when platelet counts <20 × 109/l that necessitate platelet transfusion []. However, one study done on adult dengue patients demonstrated no correlation between clinical bleeding and platelet count, and one third of their nonbleeding patients had counts <20 × 109/l []. Before starting prednisolone, our patient had a purpuric rash although his platelet counts were higher. His platelet count did not drop below those risky levels, and the lowest was 20 × 109/l in the morning of the eighth day of illness but quickly improved without any bleeding manifestations. The above evidences explain why he did not bleed.
We wondered what prevented his platelet count dropping too low. The most likely possibility is he got a less severe form of dengue hemorrhagic fever (DHF). We speculate whether prednisolone he was on also might have helped him. Some of us and many other doctors known to us have used prednisolone, hydrocortisone, and methyl prednisolone to manage severe dengue, and in fact, some of us were treated with steroids as dengue patients in the past. There was a debate within the Sri Lankan medical fraternity of the use of steroids in dengue, and present dominant view is steroids are not beneficial. Complying with the latest national guidelines [], we also have stopped using them except for especial cases like in this patient. Thrombocytopenia and capillary leakage (the corner stone of severe dengue), both are mainly resulting due to immune mechanisms. Temporary reversible disruption of the surface glycocalyx, a lining in the vascular endothelium that regulates microvascular filtration, is attributed to transient capillary leakage in dengue []. Immune mechanisms play a role in increased peripheral destruction of platelets and impairment of platelet functions in dengue []. Steroids blunt both innate and acquired immunity mechanisms responsible for these changes. There are evidences indicating that steroids modulate the function of the endothelial glycocalyx and may prevent damage to this layer []. We generally expect steroids to compromise immunity and favor viral replication. Viral load was correlated to severity of dengue in the past studies []. However, a laboratory study has shown that corticosteroids do not increase dengue viral replication in cell culture []. A randomized, placebo-controlled, blinded trial also showed that both low-dose and high-dose prednisolone therapy during viremic phase of dengue is not associated with prolongation of viremia or other adverse effects []. Nevertheless, this study did not show any benefits of prednisolone in preventing severe thrombocytopenia, shock or other complication of dengue as well []. Another placebo-controlled study employing sealed envelope randomization done in Sri Lanka showed low-dose intravenous dexamethasone was not effective in achieving a higher rise of platelet count in dengue infection []. According to the Cochrane review, there is insufficient evidence to evaluate the effects of corticosteroids in dengue at present []. However, the only other similar reported case who was also on steroids at the onset of fever and continued to receive steroids like our patient recovered after only having petechial hemorrhages []. His platelet count also did not fall <20 × 109/l, and those authors mention that they contemplated to increase steroid dose in the case of bleeding or platelet counts dropping below that level []. Hence, steroids may be beneficial, at least unlikely to be harmful in treating dengue in diagnosed ITP patients when we consider above evidences. However, available evidences on the subject are inadequate to come to a reasonable conclusion.
An Indian boy who was also on steroids at the onset of dengue and continued to receive steroids like our patient recovered after only having petechial hemorrhages []. Other reported cases are from Americas. They were managed in different ways such as high doses of corticosteroids [, ], intravenous immunoglobulins (IVIG) [], IVIG with steroids and platelet transfusion [], and platelet and other blood product transfusion []. One 11-year-old Brazilian girl died []. Others recovered, and unlike our patient, most of them have previously undergone splenectomy. Some past studies indicate patients undergone splenectomy may be less susceptible to development of severe forms of dengue []. However, all of them had bleeding manifestations unlike our patient. Innate immunity and both humoral and cell-mediated immune processes are known to contribute to the pathogenesis of dengue hemorrhagic fever []. Unlike IVIG, steroids blunt all those immune processes. That might be a reason for no bleeding of our patient and minimal bleeding manifestations of the Indian boy. Nevertheless, some other reported patients received steroids also had bleeding, but steroids were started late in them [].
It is interesting to note one Cuban patient was treated symptomatically, and there was a steep transient rise of platelet count much above her baseline level on the 15th day after onset of fever []. Our patient’s platelet count did not show such a rise. Persistence of thrombocytopenia (or onset of ITP) after dengue infections were also reported []. In contrast, our patient’s platelet count improved in days.


A 48-year-old female with complaints of gastrointestinal symptoms such as abdominal pain, fatigue, vomiting, nausea, and weight loss was admitted to the gastroenterology clinic in order to perform an endoscopy. The endoscopy revealed multiple polypoid lesions with a diameter of 1-2 mm. The histopathology examination showed grade 1 neuroendocrine tumor and incomplete metaplasia. After polypectomy, since the symptoms of the patient did not relieve completely, she was referred to magnetic resonance imaging (MRI) for detection of possible metastasis or any other etiology. MRI showed multiple linear hypointense lesions in the liver (). A PET/CT scan was performed for differential diagnosis, which showed high FDG uptake in these lesions (). However, the findings in FDG-PET/CT were not thought to be related to metastasis since it is known that grade 1 neuroendocrine tumor does not have FDG avidity. Thus, this uptake was thought to be associated with either a primary liver malignancy or infectious process. The patient was evaluated in detail with clinical and laboratory analysis. Indirect hemagglutination test for Fasciola hepatica was positive at 1/320. The eosinophil count has elevated to 3x103 (normal range: 0-0.4x103) and the EO% was 34.6% (normal range: 0-5%). All other laboratory test results were within normal range. Laboratory analysis indicated Fasciola hepatica. The imaging features of this case is presented to aid in differentiating this infectious disease from malignancy and avoid misdiagnosis on FDG-PET/CT.


The proband of this study was a 13-year-old boy. When he was 2 years old, his parents accidentally discovered hard masses with slight tenderness on his right hip and feet. With increasing age, the masses increased in size. Several operations were performed to remove the masses on his feet and right hip.
The patient’s sister also had similar masses on her hip () and feet; these masses were excised but recurred post-operatively. No ectopic calcification foci were identified in their parents. The serum phosphate concentrations of the father and mother were normal (). Both parents were healthy and did not have a history of autoimmune diseases or similar disorders. There was no consanguineous marriage or white or black genetic admixture in this family for the past three generations.
Upon physical examination, the proband was conscious and cooperative. Claudication of the right leg was observed. A large, hard mass with slight tenderness was found on the right hip (). The serum phosphate level for this patient was as high as 2.88 mmol·L−1 (normal range: 0.8–1.6 mmol·L−1). His serum levels of parathyroid hormone (PTH) and 25-hydroxyvitamin D3 were normal.
A plain X-ray of the pelvis revealed calcification of a soft tissue mass in the right hip. No cortical hyperostosis, diaphysitis, or periosteal apposition was observed at the femur () or ankle joints. Magnetic resonance imaging of the pelvis confirmed the findings of the plain radiography ().
An operation to remove the mass on the right hip of the proband was performed in our hospital. The tumor size was ~16×3×5 cm3 with multiple lobes and gray allantoic fluid (). The size of the cyst within the tumor was 1.5×2.5 cm2, and the cyst was encapsulated by a 0.5 cm thick, smooth wall and contained a lime-like material. The histopathological examination of the tumor mass revealed fibrous tissue hyperplasia within the cyst wall with calcification and giant cell reaction ().


A 67-year-old, 85 kg man with a prior history of left anterior descending artery (LAD) stent placement was brought by emergency medical services (EMS) to the emergency department (ED) of an academic, community-based hospital. He complained of numbness in his left arm that radiated into his chest. He took 325 mg of aspirin 20 minutes prior to EMS arrival, and EMS gave a single 0.4 mg sublingual nitroglycerin while in transport with full relief of pain. Electrocardiogram (ECG) performed by EMS showed normal sinus rhythm. As the patient was undergoing his initial nursing assessment, he reported that he “felt funny;” his upper extremities began to shake, and then he became unresponsive with agonal respirations, followed by apnea. At this point, no pulse was present and the monitor displayed VF. Chest compressions were started and he received biphasic defibrillation at a dose of 200 J. The first attempt at intubation was esophageal, so the endotracheal tube was promptly removed and ventilation resumed via bag-valve mask (BVM) with excellent chest wall rise. The resuscitation continued with administration of epinephrine 1 mg intravenous bolus approximately every three minutes with four total doses given. In addition, he received a total of 450 mg of amiodarone. The patient received a total of five defibrillation shocks, the first four at 200 J and the fifth at 300 J, biphasic.
After failing to successfully terminate the VF in the first 15 minutes, it was decided to attempt dual axis defibrillation and esmolol administration, so a second defibrillator was brought to the room. A STAT request was made for pharmacy to send esmolol. The paddles of the second defibrillator were placed in an anterior – posterior central position (). Coordination of dual discharge using the original pads and the additional second device and pads occurred “on the count of 3,” and 300 J were simultaneously delivered from each device in the 15th minute of resuscitation. There was no change from VF with this intervention, so CPR continued. While cardiopulmonary resuscitation (CPR) was performed, the patient received a bolus of 80 mg of esmolol IV push and an infusion of 0.1 mg/kg/hr was initiated at the 18th minute of the resuscitation attempt. After allowing time for the esmolol to circulate with CPR, there was persistent VF, and a second simultaneous dual defibrillatory shock was delivered after 21 minutes of resuscitation in the same manner as the first. With that attempt, there was return of spontaneous circulation with a room air pulse oximetry of greater than 90%.
A second attempt at intubation was initiated at the 23rd minute of the resuscitation attempt, but was aborted when the patient became more alert with the insertion of the laryngoscope. Following resuscitation, the ECG demonstrated atrial fibrillation with 2–5 mm ST elevations in leads I, AVL, and V2–V6 consistent with an ST-segment elevation myocardial infarction (STEMI). Laboratory analysis showed a mild hypokalemia, mild elevation in Troponin I, and mild anemia. A repeat ECG approximately 30 minutes after the resuscitation, and just prior to going to the catheterization laboratory, was still consistent with a STEMI (). At this time the patient was awake, speaking in full sentences, and was breathing room air with stable vital signs. He received a heparin bolus and drip and was successfully transferred to the catheterization laboratory where, with minimal sedation, he was found to have a mid-left anterior descending (LAD) lesion. A drug-eluting stent was placed.
The patient had an otherwise uneventful inpatient stay and was discharged on hospital day 4. He was seen again one week later in the outpatient cardiology clinic. He complained of some chest wall soreness, and mild dyspnea on exertion, but otherwise felt well. At follow up with the patient after completion of cardiac rehabilitation, he had no known long-term sequela and was riding his bicycle over eight miles a day. He provided permission for this case report.


A 53-year-old female with a remote history of melanoma of the left arm had recurrence to the chest wall and brain. She presented for routine restaging positron emission tomography/computed tomography (PET/CT) (Figures and –) which showed an F(18) fluorodeoxyglucose (FDG) avid focus in the lower superior vena cava (SVC) just above the cavoatrial junction adjacent to the catheter tip of her right chest wall port. Maximum standard uptake value (SUV max) was 8.8. Due to poor vascular access, the patient's port was utilized to administer the FDG dose of 11.9 mCi for the exam. The patient had no clinical signs of catheter related infection. Figures and show the FDG avid focus on coronal fused PET/CT and the port catheter on frontal chest radiograph, respectively. Although catheter-related thrombus was initially suspected, the patient had a recent history of hemorrhagic brain metastases with an increased risk for anticoagulation. In addition, the SUV max of 8.8 was relatively higher than previous reports of bland thrombus. Cardiac magnetic resonance (CMR) was recommended for imaging confirmation. CMR demonstrated a hypointense lesion along the medial superior vena cava wall just above the catheter tip. The lesion demonstrated hypointense T1- and iso- to hypointense T2-weighted signal (Figures and –). No appreciable enhancement was noted on postcontrast (gadobutrol, 0.15 mmol/kg) or delayed gadolinium images. CMR findings were consistent with bland catheter-related thrombus.


A 49 year old, male construction worker with no prior intraocular surgeries first presented to the emergency department after accidentally being struck in the left eye with a utility knife while at work. Upon examination, visual acuity (VA) of the right eye and left eye (OS) were 20/30 and hand movements (HM), respectively. Slit lamp examination showed a penetrating corneal laceration inferiorly with prolapsed iris and 270 degree iridodialysis. The patient was taken to the operating room for surgical repair of the open globe. Post-surgically, the patient was noted to have traumatic aniridia with remnants of iris superiorly and nasally only (see Fig. ). At follow-up appointments, the patient complained of occasional mild pain in the OS, but there were no signs of acute infection.
Three months after initial injury, a pars plana vitrectomy, lysis of iridocorneal adhesions, and lensectomy were performed due to chronic vitreous hemorrhage, post-surgical or inflammatory adhesions, and a traumatic cataract, respectively. The posterior capsule was removed and the anterior capsule opened. There were no acute complications (see Fig. ). At a two-week post-surgical follow-up appointment, the patient’s OS had a VA of 20/200 and an intraocular pressure of 10 mmHg. Slit lamp examination findings including diffuse conjunctival injection, mild corneal edema, and a deep anterior chamber were noted.
Because of the patient’s light sensitivity, aniridia, and aphakia, it was decided to implant an iris prosthesis with lens, the Ophtec 311. Implantation surgery took place two months after the prior surgery, five months since initial injury. For implantation, the Ophtec 311 was sutured into two scleral flaps made nasally and temporally 180 degrees away from each other and then centered onto the remaining anterior lens capsule and ciliary sulcus. The procedure was without acute complications and the patient was discharged with a prescription of dexamethasone drops every 2 hours and ofloxacin four times daily (see Fig. ).
On post-operative day 1 the VA was HM, IOP 7 mmHg, and there was 4 + cells and flare in the anterior chamber. These findings were unchanged after 2 weeks. At post-operative week 5, VA improved to 4/200, pain and photophobia were said to be improving, but 1+ cell and 2+ flare were noted. At post-operative week 6 and 8, the OS had a VA of 4/200, 6 mmHg IOP, and 2+ flare in the anterior chamber. Conjunctival injection and a hazy view through the Ophtec 311 lens were noted. The patient was offered a sub-Tenon’s capsule injection of triamcinolone, but declined.
By post-implant month 4, a retrocorneal fibrous membrane and 1+ corneal edema was seen in addition to persistent 1+ cell, 2+ flare, and a decline of VA to 1/200. Consequently, dexamethasone drops were increased from 3 to 4 times daily. At post-implant month 6, the patient complained of increasing frequency of pain and tearing, and examination findings included a VA of HM, 4 mmHg IOP, persistent corneal edema, and anterior chamber inflammation. A Sub-Tenon’s triamcinolone injection was performed for what was thought to be chronic uveitis secondary to implantation and trauma. By 3 months post-injection (9 months post-operative) the patient felt well, and the anterior chamber was clear on examination. Consequently, a slow taper of the dexamethasone drops was begun.
At post-implant month 14, the patient came to the emergency department because of a week of worsening redness, pain, and photophobia in the OS. On examination there was marked episcleral and conjunctival injection, diffuse corneal edema with deep and superficial vascularization, and as previously noted, a retrocorneal fibrous membrane and stable fibrous deposits on the Ophtec lens. There was a hazy view of the anterior chamber to assess for cells. The patient was given another sub-Tenon’s capsule triamcinolone injection, restarted dexamethasone drops four times daily, and started erythromycin ointment four times daily. Symptoms began to improve within a week, but the patient endorsed intermittent pain beginning a couple months later.
At post-implant month 21, the patient presented again in the emergency department because of a new foreign body sensation on the surface of his OS in addition to several weeks of intermittent pain and irritation of his OS. A slightly protruding suture from the iris prosthesis was found and trimmed. Consequently the foreign body sensation and pain improved, but intermittent pain, irritation, and mild conjunctival injection of the left eye continued through post-implant month 24 (see Fig. ). The patient was given another sub-Tenon’s capsule triamcinolone injection and explantation surgery was planned because of the patient’s chronic, intraocular inflammation.
At post-implant month 26, a penetrating keratoplasty, pars plana vitrectomy, and Ophtec 311 explantation surgery was performed. A penetrating keratoplasty was also performed due to the progressively worsening corneal edema and growth of a retrocorneal membrane. A Gram stain, aerobic, anaerobic, and fungal cultures were taken from vitreous. Aerobic, anaerobic, and fungal cultures of the cornea were also ordered. The patient tolerated the procedure well and there were no acute complications.
On day 5 of intravitreal culture, Gram positive bacilli were seen on the anaerobic vitreous culture medium and identified as Propionibacterium acnes. No organisms and rare white blood cells were seen on vitreous gram stain, and no growth was seen on cornea cultures. Pathologic examination of the cornea showed moderate endothelial cell loss, bullous keratopathy, inflammatory pannus, with stromal scarring and neovascularization.
The patient was treated with a 10 day course of levofloxacin, 750 mg daily, and intravitreal injections of 4.5 mg of ceftazidime and 2 mg of vancomycin. Two weeks after surgery, VA was stable at HM, there was 2+ flare and cells, and the patient was experiencing mild pain in the OS. By post-operative week 4, there were rare cells in the anterior chamber on examination and only occasional mild irritation reported by the patient.
Most recently, at post-operative month 10, the corneal transplant was noted to have become edematous and failed, most likely due to keratoplasty performed in the setting of CPOE, so a good examination of the anterior chamber to completely rule out inflammation was not possible. However, the eye was quiet with no signs of recurrent inflammation, ultrasound showed an attached retina with no vitreous debris, and the patient reported complete resolution of ocular pain (Fig. ).


A 67-year-old female being followed up for an extensive pulmonary and oncologic history had a PET scan done for follow-up of splenic lymphoma that revealed an FDG avid 6.3 x 2.5 cm paramediastinal mass with an standardized uptake value (SUV) of 12.4 (Figure ). The patient was an ex-smoker with a 30-pack-year history of smoking. The patient’s history went back to 2009 when she had a chest-CT scan which showed three nodules, 10 x 4.9 mm, 7.7 x 6.9 mm and 6.8 x 6.1 mm, in the right upper lobe. This was followed by a PET-CT, a month later, which showed mild FDG uptake in all three nodules (maximum SUV of 2.9) with no change in size. The patient continued having surveillance scans until November 2011 when her CT-chest showed a new 9 mm solid nodule in the posterior left lower lobe (Figure ), with an SUV of 3.0 on a PET-CT that followed.
In January 2012, the patient underwent left lower lobe wedge resection with mediastinal lymph node sampling. The pathologic examination was consistent with well to moderately differentiated adenocarcinoma with all lymph nodes negative for tumor, hence staged as IA (T1a, N0, M0). She continued periodic follow-up, and a CT-chest scan in March 2013 showed an increase in the size of the right upper lobe nodule to 2.0 x 1.0 cm, solid in appearance (Figure ). The lesion was FDG-avid on PET scan with a maximum SUV of 5.2 (Figure ). Following this, in April 2013, the patient underwent right upper lobectomy, with the pathologic examination consistent with well-differentiated adenocarcinoma. As the patient had stage IIb (T3 N0 M0) disease, it was recommended that the patient must receive an adjuvant chemotherapy, which the patient declined.
The patient had a repeat imaging in August 2013 and January 2015 that did not show any evidence of disease. In October 2015, the patient presented to the hospital with an acute onset of abdominal pain. A CT scan of the abdomen showed two hypodense masses within the spleen measuring 8.5 x 8.1 x 8.8 cm along the superior aspect and 5.5 x 4.8 x 6.9 cm along the inferior aspect (Figure ). Several enlarged sub-centimeter lymph nodes were noted within the splenic hilum. A CT scan of the chest done during the same hospitalization showed postsurgical changes with no new nodules. On PET-CT, the splenic masses were FDG-avid with a maximum SUV of 26. An ultrasound-guided biopsy of the spleen was consistent with diffuse large B cell lymphoma with c-myc and bcl-6 positive by FISH. Her lactate dehydrogenase (LDH) was 750 U/L, ESR 65 mm/hr and C-reactive protein (CRP) 4.29 mg/dl. The patient was started on chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. After five cycles, the patient had significant fatigue requiring a 10% reduction in the cyclophosphamide dose of her last cycle. A PET-CT scan post-chemotherapy showed resolution of the previously FDG-avid splenic masses. However, pathologic uptake was seen within the enlarged right paramediastinal soft tissue mass along the right upper lobectomy suture line (Figure ).
The mass was concerning for lung cancer recurrence prompting a CT-guided needle biopsy with pathology consistent with non-caseating granulomas, negative for lymphoma or other malignancy and negative for AFB and fungal stains. Following this, the patient underwent a right middle lobe transbronchial biopsy that on histologic exam showed mild acute and chronic inflammation, and necrotizing caseating granulomas (Figure ). The acid-fast culture of the bronchoalveolar lavage fluid showed growth of acid-fast bacilli (AFB). The patient was started on four-drug anti-tubercular therapy i.e. isoniazid, rifampin, ethambutol, and pyrazinamide. The AFB were identified by DNA probe as Mycobacterium avium complex, and the patient was thereafter treated for MAC with clarithromycin 500 mg twice daily, ethambutol 1000 mg once daily and rifampin 600 mg once daily. Two months into diagnosis, the patient remains in remission for her lymphoma and does not have any overt signs or symptoms of infection with the pulmonary lesion stable in size and appearance on follow-up CT scan of the chest.


A 26-year-old African American man with AIDS presented with complaints of pleuritic chest pain, exertional shortness of breath, and hemoptysis of 3-week duration. He reported 10-pound weight loss in 6 months, drenching night sweats, and fever. He denied tobacco use but admitted using marijuana in the past. He denied neurological, gastrointestinal, or dermatological symptoms and had no recent travel. He was being treated with dapsone and elvitegravir/cobicistat/emtricitabine/tenofovir but was poorly compliant.
Of note, he was admitted 3 months earlier for similar complaints and was diagnosed with atypical pneumonia. A CT scan of the chest done on that admission showed diffuse fine noncalcified nodular densities in both lungs and small to moderate bilateral axillary, mediastinal, and hilar adenopathy. Bronchoscopy was unrevealing for endobronchial lesions. Bronchoalveolar lavage was negative for Pneumocystis jirovecii, acid fast bacilli, or fungal infection.
On index presentation, he had bilateral axillary and supraclavicular lymphadenopathy with signs of right lower lung zone consolidation on chest examination. There were no lesions on the skin or mucosa. Complete blood count was significant for normocytic anemia and metabolic panel was within normal limits. Absolute CD4 cell count is of 102 cells μ/L (17%). A repeat CT scan of the chest showed significant worsening of fibronodular infiltrates with consolidation in the right middle and lower lobes and left upper and lower lobes with bilateral axillary, supraclavicular, mediastinal, and hilar lymphadenopathy (). Subsequent bronchoscopy revealed erythematous lesions on the proximal and distal part of the trachea and right middle lobe (). Left main stem had vascular markings with dilated veins. These findings were consistent with endobronchial KS. Transbronchial biopsy was done and pathology was positive for atypical spindle cell proliferation with slit-like vascular spaces, lymphoplasmacytic infiltrate, and extravasated red blood cells (). Nuclear HHV8 immunostain was expressed in atypical cells consistent with Kaposi Sarcoma.
He was started on a different HAART regimen: abacavir/dolutegravir/lamivudine after consultation with the infectious disease team. The patient tolerated the new medication and was discharged with appropriate follow-up. However he was readmitted twice: once with Immune Reconstitution Syndrome and the second time with massive hemoptysis. He developed acute respiratory failure, which unfortunately led to his death.


A 9-year-old boy presented to our hospital complaining of a foreign body feeling in the throat of a few months' duration, causing him a nonproductive cough, mild dysphagia, and sleep disturbance. His medical and surgical history were unremarkable. The examination of the oral cavity revealed a large, oval, pale mass protruding from the lower pole of the right tonsil, which was partially obstructing the airway (). It was nontender, nonfriable and did not bleed on touch. It was attached to the lower pole of the right tonsil by a narrow elongated stalk. The patient underwent a bilateral tonsillectomy under general anesthesia. The right tonsil and the pedunculated mass were removed by dissection, and hemostasis was performed by ligation. The recovery was uneventful and the patient was discharged the following day. A postoperative follow-up after one month revealed no evidence of any residual or recurrent polypoid disease.
The histopathological examination showed macroscopically a tonsil of 3.2 × 2 × 0.8 cm in size with an exophytic polypoid nodule measuring 1.8 × 1.2 × 1.2 cm (). Under the microscope, the examination of the mass showed strong cellular proliferation without suspicion of malignancy, consistent with lymphangioma of the tonsil. Abnormal lymphatics did not involve the deep tissues of the tonsil and the tumor was removed in its entirety. The adjacent tonsil showed no significant abnormalities (Figures and ).


A 59-year-old man with hypertension and a family history that included two brothers who died of an aortic aneurysm was brought to the Emergency Department after falling from his bicycle. He reported abdominal pain since one day. On examination, he was pale and had a pulse rate of 64/min, a blood pressure of 70/50 mmHg, a body temperature of 36°C, and a respiratory rate of 16 breaths/min. He had abdominal tenderness with muscular rigidity, especially in the upper abdominal region. A full blood count showed a haemoglobin level of 6,4 mmol/L, while all other laboratory tests were within the normal range. A chest X-ray showed normal lung fields and no pneumoperitoneum. As a vascular incident was feared, an abdominal ultrasound revealed free abdominal fluid around the liver and spleen without an aortic aneurysm. An abdominal computed tomographic (CT) demonstrated fluids in the omental bursa with a normal aspect of the pancreas but was unable to point to the origin of the free fluid. After resuscitation using standard techniques, the patient was transferred to the operating room under the diagnosis of intra-abdominal haemorrhage of unknown origin. During laparotomy, three litres of blood were obtained from the abdominal cavity but no active bleeding was found. Inspection of the omental bursa revealed a hematoma surrounding the pancreas. The patient was packed using several large volume gauzes and admitted to the intensive care unit. The next day, these gauzes were removed and again no active bleeding was seen. The next four days were uneventful. However, on the fifth day, the patient developed acute severe abdominal pain. An abdominal computed tomographic angiography (CTA) revealed a 14 mm splenic artery aneurysm () as well as a 12 mm aneurysm of the coeliac trunk. In retrospect, on the first CT, a 9 mm focal contrast-filled dilatation of the splenic artery could already have been identified in a large hematoma (). This was initially missed.
A ruptured splenic aneurysm was now considered the source of the abdominal bleeding and the patient underwent a coil embolisation of the proximal splenic artery using a femoral approach (). The splenic artery appeared very delicate and reacted with intense vasospasm following minimal movement of the endovascular catheter tip. Fear of arterial dissection together with the tortuous aspect of the distal splenic artery urged the interventionalist to refrain from coil embolisation at the distal end of the aneurysm. Flow in the distal part of the splenic artery was absent after placement of 8 coils proximal to the aneurysm. During the endovascular procedure, it was noted that the aneurysm had grown further to 18 mm. Although initially stable, some 24 hours after the embolisation, the patient again experienced severe abdominal pain and became hemodynamically instable. After cardiopulmonary resuscitation, a CTA was repeated and revealed recanalization of the splenic artery without migration of the coils. An urgent laparotomy was performed with removal of the spleen and the tail of the pancreas, encountering the ruptured aneurysm. The patient recovered uneventfully and was discharged from the hospital 7 days later. He will undergo vaccination and follow-up for his coeliac trunk aneurysm.


A 78-year-old man who presented with epigastric pain and elevated liver functional enzymes was referred to our clinic for further examination. Endoscopic retrograde cholangiography (ERC) revealed biliary obstruction at the confluence of the left and right anterior bile ducts, resulting in the diagnosis of Bismuth type II hilar cholangiocarcinoma (Fig. ). An arteriogram generated by multidetector-row computed tomography (MDCT) showed that the proper hepatic artery ran transversely and right laterally to the right side of the hepatoduodenal ligament, which then branched towards the left hepatic artery (Fig. ). Invasion of the hepatic artery was highly suspected. Four weeks after right portal vein embolization, right hepatectomy and caudate lobectomy combined with left hepatic artery resection were performed. The hepatic artery was reconstructed by direct end-to-end anastomosis (Fig. , ). The tumor was a moderately differentiated adenocarcinoma with microscopic invasion of the resected hepatic artery but without any lymph node metastasis. The patient was discharged from the hospital on day 24 without major complications and has since enjoyed a normal social life without any recurrence for 26 months.
The second patient was a 76-year-old woman who presented with jaundice. MDCT and ERC with biopsy confirmed the diagnosis of Bismuth type II hilar cholangiocarcinoma (Fig. ). The reconstructed arteriogram showed the proper hepatic artery ran transversely and bifurcated into the right and left hepatic arteries just behind the perihilar tumor, and the left hepatic artery ran right lateral to the left portal vein (Fig. ). MDCT showed possible invasion of both the hepatic artery and the portal bifurcation. Three weeks after right portal vein embolization, right hemihepatectomy and caudate lobectomy combined with simultaneous resection of the hepatic artery and portal vein were performed. The left hepatic artery was reconstructed using an interposition radial artery graft (Fig. , ). The left portal vein was reconstructed with direct end-to-end anastomosis. The tumor was a poorly differentiated adenocarcinoma without lymph node metastasis; however, microscopic invasion of the resected hepatic artery and portal vein was found. After control of the biliary fistula, the patient was discharged from the hospital on day 46 and is alive without any recurrence 7 months after surgery. Our practice and surgery followed the guidelines of the Japanese Hepato-Biliary-Pancreatic Association. Written consent forms for publication of this manuscript are available from both patients.


A 38-year-old Japanese man was admitted to our hospital because of muscle weakness in his lower extremities. His and his family’s histories were unremarkable. Fifteen days before admission, he had a mild fever with fatigue. Simultaneously, itchy skin rashes emerge on his foot and face, particularly around his mouth. The patient was tentatively diagnosed as having hand, foot, and mouth disease. Prior to admission, his fever, fatigue, and skin rash began to resolve, but the lower limb weakness progressively worsened within a few days. On admission, his general condition was unremarkable. A neurological examination showed that he was alert and oriented. His higher cerebral functions and cranial nerves were intact. The patient showed spastic paraparesis, with weakness of both lower extremities at approximately 4/5 strength. Deep tendon reflexes were brisk in all extremities, with ankle clonus in both legs. Babinski sings were bilaterally positive. He had paresthesia below the level of the T7-8 dermatome. Difficulty in micturition was noted. The patient had no sign of meningeal irritation. The results of his laboratory tests showed that his complete blood cell count, chemistry, immunoglobulin levels, C-reactive protein, erythrocyte sedimentation rate, and urinalysis were all within reference values. In particular, alterations in the liver function test results, suggestive of infectious mononucleosis, were not observed. Serological tests for syphilis, hepatitis B and C, HIV, and human T-lymphotropic virus type 1 were negative. The test results were also negative for anti-nuclear antibodies, anti-double stranded DNA, and cytoplasmic and perinuclear types of antineutrophil cytoplasmic antibodies, antiphospholipid antibodies, and anti-aquaporin-4 antibody. Antibody titers were not elevated for herpes simplex virus immunoglobulin M (IgM), varicella zoster virus IgM, Epstein–Barr virus IgM, and CMV IgM. CMV IgG was found elevated significantly. Additionally, the tests for coxsackie A16 and enterovirus were not significantly elevated, although we could not perform a serodiagnosis with paired serum samples. A malignancy survey, in which contrast-enhanced CTs of the chest, abdomen, and pelvis were included, was conducted in the present patient, and no cancer was identified. Additionally, tumor markers (alpha-fetoprotein, CEA, CA19-9, and soluble interleukin-2 antigen) were all within normal ranges. Examination of CSF showed elevated white blood cells, although protein (34 mg/dl) and glucose (57 mg/dl) levels were within normal ranges. The CSF IgG index 0.8 was found to be mildly elevated. The myelin basic protein (40.0 pg/ml) levels were not increased, and there were no oligoclonal IgG bands in the CSF sample. Nerve conduction velocity studies of the peripheral nerves indicated that they were intact. Sensory evoked potentials obtained by tibial nerve stimulation demonstrated no reproducible waves. Both brain and spinal cord magnetic resonance images (MRI) obtained at admission appeared normal (Figs. , , and ). Brain and spinal cord MRI examinations with gadolinium-enhancement were also performed, although no significant enhancement was demonstrated. After admission, the patient’s weakness and deep sensation disturbance of the lower extremities progressively worsened. He was tentatively diagnosed with transverse myelitis, and treatment was started with intravenous methylprednisolone at a dose of 1000 mg/day for 3 days, followed by oral prednisolone (PSL) (60 mg/day). After 7 days, the muscle weakness in his lower extremities continued to worsen, and we added intravenous immunoglobulin therapy (IVIG) at a dose of 0.4 mg/kg for 5 days. Ten days after admission, intravenous administration of ganciclovir (600 mg/day, 19 days) was initiated because CMV DNA was found in his CSF following polymerase chain reaction analysis (PCR) performed at admission. The deterioration of his symptoms ceased, and the weakness in his lower extremities gradually recovered. Other findings in his CSF also improved, including the results for white blood cells (13/mm3; all cells were lymphocytes), protein (23 mg/dL), and glucose (62 mg/dL). The CSF samples were also negative for CMV. However, MRI performed again on day 26 after admission demonstrated a spinal cord lesion of high signal intensity at cervical levels C2–C6, suggesting that the spinal cord was involved and may have been responsible for the paraplegia, although his paraplegia continued to improve with treatment (Fig. ). Additionally, a hyperintense signal was observed in the right frontal subcortical white matter (Figs. and ). On day 40 after admission, the weakness and numbness of his lower extremities again worsened, and myoclonic movements appeared in his lower legs. Subsequently, a loss of finger dexterity appeared bilaterally. In addition, the patient developed dysarthria and truncal ataxia, the latter of which resulted in his inability to maintain a sitting position. Brain MR images demonstrated faint, irregular-shaped lesions involving cerebral white matter with dense T2-weighted and fluid attenuated inversion recovery (FLAIR) hyperintensities in the internal capsules, suggesting that extensive disseminated demyelination was actively ongoing (Figs. and ). The CSF examination results showed re-elevation of protein (39 mg/dL), and MBP (58.9 pg/mL) was also increased compared with results from the initial CSF study, although both levels were within normal ranges. The white blood cell count in the CSF did not increase (7/mm3). We considered the possibility that the patient had ADEM, and intravenous methylprednisolone (1000 mg/day, 3 days) was administered again, followed by IVIG (0.4 mg/kg, 5 days). After this treatment, his neurological deterioration ceased, but he had residual neurological sequelae. Time course of clinical symptoms, CSF results, treatment, and MRI findings in the present patient are schematically shown (Fig. ).


A 71-year-old man was referred to our hospital for investigation of hypoglycemia. Two years before, he had attended the emergency department with acute-onset loss of consciousness after a traffic accident. Hypoglycemia was identified as the cause; however, because his condition had quickly improved, he was not extensively investigated and was discharged without a definitive diagnosis. Since then, he had recurrent hypoglycemia associated with impaired consciousness. In the four preceding months, his serum glucose concentrations had been less than 67 mg/dL and he had been given intravenous glucose, which resulted in gradual resolution of symptoms.
On this presentation, his serum glucose, immunoreactive insulin and C peptide concentrations were 45 mg/dL, 17.2 μIU/mL, and 4.1 ng/mL, respectively. MEN-1 syndrome was excluded by normal serum intact parathyroid hormone, calcium, and prolactin concentrations. He thus had Whipple’s triad (symptoms known or likely to be caused by hypoglycemia, low serum glucose at the time of the symptoms, relief of symptoms when the glucose has increased to normal). To confirm the diagnosis of endogenous hyperinsulinemia caused by insulinoma, the patient underwent a supervised overnight fast during which he developed symptomatic hypoglycemia with serum glucose of 50 mg/dL.
Dynamic magnetic resonance imaging showed a 13.5 cm × 12 cm × 8 cm hypervascular tumor containing necrotic areas in the pancreatic head (Fig. a). Magnetic resonance cholangiopancreatography showed no involvement of the pancreatobiliary systems (Fig. b). Computed tomography scan demonstrated a heterogenous, enhancing, partly necrotic mass partially replacing the head of the pancreas (Fig. a). There was no evidence of hepatic metastasis; however, local invasion of the surrounding adipose tissues and duodenum and lymph node involvement were identified (Fig. b). This patient’s pancreatic body and tail were slender, measuring 2 cm × 1.5 cm × 5 cm; no other tumors were identified in them (Fig. c). No distant metastases having been identified; extended pancreatic resection was performed.
Intraoperatively, one bulky tumor and two additional undiagnosed tumors were identified in the head of the pancreas. Manual palpation by an experienced surgeon revealed no tumor in the pancreatic body and tail. One 3.5-cm diameter pedunculated lesion was suspended from the surface of the uncinate process of the pancreas, and another 2-cm diameter tumor was attached to the duodenum. The patient underwent a subtotal stomach-preserving pancreaticoduodenectomy.
Macroscopically, the largest tumor measured 15 × 9 × 9 cm and was firmly adherent to the retroperitoneum (Fig. a). Cut sections showed a solid lesion with evidence of hemorrhage (Fig. b). All three tumors were composed of uniform bland cuboidal cells with granular eosinophilic cytoplasm and round nuclei. Most of the largest mass comprised well-differentiated tumor cells (Fig. a); however, poorly differentiated tumor cells were identified in a small part of it (Fig. b). The retroperitoneal fat tissues and duodenum were involved, and metastases were identified in two of four peripancreatic lymph nodes. Immunohistochemically, the tumor showed strong diffuse expression of chromogranin A, insulin, and glucagon and weak expression of somatostatin. The Ki-67 index was 2–5% in most of the largest tumor (Fig. c) but over 20% in the poorly differentiated areas (Fig. d). This tumor was classified as a NEC in accordance with the 2010 World Health Organization (WHO) classification of pancreatic endocrine neoplasms.
Postoperatively, a moderate pancreatic fistula developed. This resolved with conservative treatment and he was discharged on postoperative day 35. At a routine follow-up visit 3 months postoperatively, he reported no hypoglycemic symptoms, and he remains free of evidence of recurrence 2 years and 3 months after surgery.
Because it has been difficult to differentiate between benign and malignant insulinomas on the basis of histologic findings, malignant insulinomas have been diagnosed based on metastasis to liver, lymph nodes, or other organs []. However, the new 2010 “WHO Classification of Tumors of the Digestive System” considers all insulinomas of 0.5 cm or greater malignant tumors []. According to the 2010 European Neuroendocrine Tumor Society guidelines, the most critical prognostic factors are the proliferative rate (mitotic index or Ki-67 labeling index) and the presence of distant metastases [].
Surgery is the only potentially curative treatment for malignant insulinoma diagnosed at a locally advanced stage []. The median disease-free survival after curative resection is 5 years; recurrence occurs in more than 60% of patients at a median interval of 2.5–3 years []. Patients with distant metastases from insulinomas to the liver, bone, and lymph nodes have a median survival of <2 years [].
Callacondo et al. [] reviewed 35 cases of giant insulinoma and reported that they are more likely to be malignant than non-giant insulinomas; however, the relationship between clinical features, pNETs grading, and G1/G2/NECs has not been elucidated. In all, we reviewed 45 cases of giant insulinoma comprising the 35 cases of Callacondo et al., an additional 9 cases [, , –] and the present case (Table ). We also investigated the relationship between recurrence rates and grade in reported cases (Table ). We performed a PubMed search and Japanese MEDLINE databases (during the period of 1975–2015) using the keywords: “giant insulinoma,” “malignant insulinoma,” and “pancreatic neuroendocrine tumor” and limited our review to reports in English- and Japanese-language publications, including case reports.
The mean age at presentation of the 45 patients with giant insulinoma was 57 years (range, 15–83 years), and there was a slight male preponderance (male/female ratio, 1.14:1). Those patterns are similar to those of non-giant insulinomas.
Tumor location within the pancreas was available for 42 patients. Tumors in a single segment of the pancreas had a predilection for the tail (n = 22); involvement of both the body and tail was seen in 12 patients. Giant tumors occur more frequently in the body and tail of the pancreas because they can grow freely there without causing mass effects or mechanical obstruction []. Even huge masses in the head of the pancreas rarely present with gastric outlet obstruction or obstructive jaundice because insulinomas generally enlarge slowly and do not massively invade adjacent vital organs.
Surgical resection had been performed in 36 (81.8%) of all cases studied; the procedures comprising distal pancreatectomy (combined with resection or ablation of hepatic metastases) in 23 (4) cases, pancreaticoduodenectomy in 3, tumor resection in 5, and total pancreatectomy in 1 case. No patient had undergone combined resection and reconstruction of the portal vein or hepatic artery. Complete resection should be performed; however, removing 90% of the tumor is acceptable. Surgery is justified for functional advanced neuroendocrine tumors, the aims being to control symptoms, improve quality of life, and extend survival rate compared with conservative treatment []. Seven of 19 patients with metastases or recurrence had received sequential multimodal therapy (systemic chemotherapy, chemoembolization, ablation, and resection of liver metastases). These aggressive therapies can prolong the survival of patients with malignant insulinoma, even in the presence of liver metastases [].
The diameter of these patient’s tumors ranged between 9 and 21 cm (median, 12 cm). Most insulinomas become symptomatic when very small, allowing early detection and prompt surgical treatment, possibly before they can metastasize. The severity of hypoglycemia varies from patient to patient and has no direct relationship with tumor burden []. Sugiyama et al. [] suggested that giant insulinoma initially diagnosed as non-functioning pNETs may secondarily become functioning.
Twenty-five (55.6%) of the cases of giant insulinoma reviewed had metastases at presentation, this percentage being higher than the 10% reported in most insulinoma series []. At the first surgery, six patients had involvement of the multiple organs, seven had liver metastases only, and 12 had locally advanced disease such as invasion of the surrounding adipose tissues or/and lymph node involvement. Eight cases had developed recurrences, the major site of metastases being the liver.
Follow-up data were available for 41 of the published cases. Duration of follow-up of 24 cases who had no recurrences ranged between 3 months and 23 years (median 18 months). Seven cases of the 11 fatal cases were reported before 1980. The overall survival of all patients who died with disease ranged between 1 month and 13 years (median, 2 years), whereas patients of non-giant malignant insulinoma with distant metastases had a median survival of <2 years []. Six cases alive with disease had been followed-up for 15 months to 17 years (median, 4 years).
Since 2001, the mitotic activity, Ki-67 index, and grade have been reported for 17 patients with giant insulinomas (Table ) [–, –, –, ]. We compared the grade, the rate of metastases and duration of follow-up of 18 cases, including the present case. The Ki-67 index was <2% in eight cases; the only three cases with a Ki-67 index of ≥20% were diagnosed as having NECs. Four, three, and one patient had no metastases from G1/G2/NEC at surgery, respectively, whereas four, four, and one had synchronous metastases, respectively. Unexpectedly, there was no difference in proportion of G1/G2/NEC in patients with versus without synchronous metastases. The median durations of follow-up by grade were as follows: 12 months (G1), 12 months (G2), and 31 months (NEC); the duration of follow-up for NECs being longer than expected. We anticipated that patients with giant insulinoma and higher Ki-67 indexes would have worse prognoses; however, we identified no relationship between grade and survival. In our small case series, we were unable to identify any correlation between grade and biological behavior of giant insulinomas.


A one-day-old female newborn was admitted to the neonatal intensive care unit (NICU) of Suez Canal University, Ismailia, Egypt, after uneventful prolonged vaginal delivery ended with urgent cesarean section (CS). At admission the neonate suffered from depressed activity and grade IV respiratory distress with the need for mechanical ventilation.
The prenatal history was insignificant apart from premature rupture of membranes 12 hours before the delivery. There is no history of maternal urinary tract infection, asthma, or diabetes mellitus. The trial of the vaginal delivery lasted for 10 hours with failure to progress and fetal distress on the recording cardiotocography that urged CS delivery. The APGAR score at 1 minute was 2, at 5 minutes was 4, and at 10 min was 4.
By the end of the 2nd day the basic laboratory investigations were withdrawn showing no abnormal findings with C-reactive protein (CRP) value 2 mg/dL. The chest X-ray (CXR) showed only increased bronchovascular markings (). On the next day the Glasgow Coma Scale (GCS) of the patient started to improve with progressive lowering the settings of the mechanical ventilator. LUS screening was done after the arterial blood gases (ABGs) showed impaired oxygenation and ventilation and the new CXR was free (). The LUS showed multiple large consolidations with thickened irregular pleural line, absent A-lines, and coalescent B-lines around the consolidations suggesting the possibility of ventilator associated pneumonia (VAP) (Figures , , and ). A new CRP at this point also was negative (3 mg/dL) with leucocytic count 5,600/cmm and negative cultures.
One day later the settings of the mechanical ventilator became higher, and the follow-up CXR showed right lower pneumonic consolidation associated with collapse. Lung auscultation did not reveal any fine or coarse crepitations but only slightly diminished air entry over the right side. The CRP started to rise a day later (56 mg/dL) with increased leucocytic count (18,600/cmm) with absolute neutrophilia. Three days later the blood culture was positive. The diagnosis of VAP was made and the antibiotics were changed according to the culture and sensitivity results.
The 7th day witnessed deterioration of the general condition with markedly impaired aeration of the right lung. A new plain CXR was done () showing large opacity developed on the right lower lung zone with air-bronchogram and obliteration of the right costophrenic and cardiophrenic angles, suggesting consolidation collapse.
The following 3 days showed no improvement in either the chest condition or the ventilator settings guided by the ABGs. So the antibiotics were changed to Vancomycin, Imipenem/Cilastatin, and Diflucan according to the local NICU protocols of antibiotics' usage.
By the 11th day, there was progressive deterioration with inadequate response to the medical and ventilatory support. A new plain CXR () which showed complete opacification of the right lung is seen causing opaque right hemithorax. Also small consolidation patches are seen in the left para-cardiac region in middle and lower left lung zones with obliteration of the left cardiac border.
The failure of ventilation and oxygenation on high ventilator settings showed the need to transfer the neonate to a center with high frequency oscillatory ventilation (HFOV) or extracorporal membrane oxygenation (ECMO). However, there was no available place for transfer at that time. Respiratory failure then developed with eventual cardiac arrest.


A 71-year-old previous healthy man was referred to cardiac evaluation due to symptoms of dyspnea, orthostatic dizziness, and episodes of postural related syncope during a period of 2 months.
Electrocardiogram revealed low-voltage limb leads and first degree of AV-block (). Echocardiogram revealed thickened left ventricle (LV) walls with a septal thickness of 18 mm and posterior wall of 16 mm (). The LV cavity was small with end-diastolic diameter of 34 mm and end-systolic diameter of 21 mm. The mitral valve was thickened and mild systolic anterior motion (SAM) was noted. However, left ventricular outflow track (LVOT) velocity was normal at 1.3 m/s both at rest and during the Valsalva maneuver. Ejection fraction was 70% but long-axis function severely reduced with global longitudinal strain at −10.1%. Apical sparing was noted. Coronary flow reserve was measured by Doppler echocardiography. CFR was severely reduced at 1.2 (normal range >2.5–4.5). Cardiac amyloidosis (CA) was suspected and the patient was referred for endomyocardial biopsy. This revealed extensive amyloid infiltration (). Immunohistochemistry was positive for λ-light chains and negative for transthyretin, amyloid A, and κ-light chains.
Pacemaker implantation was considered due to the previous syncopes and the findings of first degree of AV-block. However, we decided to evaluate the hemodynamics of the patient during a semisupine bicycle exercise-stress test with simultaneous echocardiography. At rest, blood pressure (BP) was 108/68 mmHg and heart rate (HR) was 90 beats/min. At 10 Watts BP was 98/61 mmHg, HR was 94 beats/min, and LVOT velocity was still normal at 1.5 m/s. At 30 Watts BP declined to 88/51 mmHg, HR was 98 beats/min, and LVOT velocity was between 2.0 and 3.5 m/s with a shark fin pattern. At peak exercise (40 Watts), BP was 74/45 mmHg and HR 106 beats/min. Severe SAM was noted at this point and the patients felt dizziness and dyspnea. The LVOT velocity was between 2.5 and 3.6 m/s ().
The present case illustrates that mitral leaflet SAM should be suspected in CA patients with dizziness and syncopes, especially if echocardiography shows involvement of both the myocardium and mitral valve. This is important as CA patients with syncopes traditionally receive prophylactic pacemaker implantation. Previous case reports have demonstrated obstruction of the left ventricular outflow tract in CA patients [–]. The underlying mechanism of SAM in CA patients is unclear. It could involve a Venturi effect due to increased outlet tract flow mediated by increased septal thickness. This effect may be enlarged in CA patients due to the small LV cavities and increased heart rate. Furthermore, the amyloid deposit-induced increased leaflet thickness and papillary muscle displacement may also be involved. In the present case, symptoms and SAM were not present during resting conditions or during the Valsalva maneuver. However, we noted a stepwise drop in BP with the exercise induced SAM progression, which clearly illustrates the hemodynamic significance of the SAM. Therefore, exercise-stress echocardiography should be considered in the clinically evaluation of CA patients prior to prophylactic pacemaker implantation. Other causal symptom mechanisms such as conduction disturbances, ventricular arrhythmias, orthostatic hypotension, or vasovagal effects could be involved in the present case. However, Holter monitoring revealed no arrhythmias and no pacemaker was implanted in the patient.
Optimal treatment of left ventricular outflow tract obstruction in CA patients is difficult. The risk of surgical myectomy or mitral valve plasty is considered to be significantly increased []. The effect of alcohol septal ablation in CA patients is unknown. However, the patient was found unlikely to benefit alcohol septal ablation due to the severely reduced CFR, the pronounced SAM, and the small LV cavity. Hypertrophic obstructive cardiomyopathy patients often have near normal CFR [] and slightly dilated LV cavity, which may be important for the effect of alcohol septal ablation. Disopyramide may reduce the left ventricular outflow tract obstruction in CA patients, but the negative inotropic effect may lead to further decrease of long-axis function []. We initiated treatment with Midodrine 5 mg × 3 and Metoprolol-Succinate 25 mg × 1. Furthermore, Dexamethasone and Melphalan therapy was initiated with satisfying hematological response. At three weeks of control the patient described no further syncopes. However, he suffered continuously from dizziness. The long-term Midodrine and Metoprolol-Succinate effect on SAM in CA patients is unknown.
In conclusion, mitral leaflet SAM should be ruled out prior to pacemaker implantation in CA patients. Furthermore, exercise-stress echocardiography may prove benefit in the clinical surveillance of CA patients.


A 63-year-old female with past medical history of diabetes mellitus and hypertension presented to emergency department for abdominal distention for 2 weeks associated with poor appetite and weight loss. She denied current fever, chills, rigors, night sweat, cough, abdominal pain, leg edema, facial swelling, bowel problems, headache, vomiting, nausea, dizziness, blurry vision, chest pain, palpitations, paroxysmal nocturnal dyspnea, orthopnea, or similar illness in the past. The patient does not have any family history of rheumatologic diseases, and she denied any rash, joint pain, morning stiffness, and muscle weakness. She is a nonsmoker. She lives in central Africa and travelled to the United States to visit her daughter.
Initial vital signs included temperature 97°F (36.1°C), pulse rate 103 beats/minute, respiratory rate 18 breaths/minute, blood pressure 137/97 mm Hg, and oxygen saturation 96% on room air. Physical examination showed markedly distended abdomen, soft, nontender without palpable mass. There was fluid thrill with shifting dullness. Bowel sounds were normoactive. Respiratory exam was unremarkable except for mildly reduced air entry in lung bases.
Laboratory tests showed white blood cells 6.4 × 109/L, hemoglobin 11 g/dL, platelet counts 367 000/µL, bilirubin 0.5 mg/dL, aspartate transaminase 36 IU/L, alanine transaminase 22 IU/L, alkaline phosphatase 67 IU/L, and albumin 2.9 g/dL. Tumor marker α-fetoprotein level, carcinoembryonic antigen, cancer antigen 19-9, coagulation profile, lipase, hepatitis A, B, and C panels, B-type natriuretic peptide, antinuclear antibody, kidney function tests, and thyroid function tests were within normal limits. Blood test revealed CA 125 antigen level 390.9 (normal = 0-38 U/mL) and rheumatoid factor level 41.6 IU/mL (normal = 0-13.9 IU/mL). Anti–cyclic citrullinated proteins test was not done. Purified protein derivative test was positive with 20 mm; however, 3 sets of sputum for acid-fast bacilli were negative.
Chest X-ray showed atelectasis in lung bases. Abdomen ultrasound computed tomography scan of abdomen and pelvic with intravenous contrast showed large amount of ascites without masses. Transvaginal ultrasound revealed large pelvic ascites and nonvisualization of both ovaries. Diagnostic and therapeutic paracentesis showed yellow, cloudy fluid, white blood cells 910 cells/µL, neutrophils 13 cells/µL, lymphocytes 89 cells/µL, red blood cells 395 cells/µL, total protein 6.1 g/dL, and albumin 2.5 g/dL. Serum-ascites albumin gradient was 0.4.
The patient underwent peritoneal laparoscopy, which showed straw colored ascitic fluid with whitish tuberculous peritoneal nodules (-). Four liters of fluid was drained. Both ovaries were not enlarged and looked grossly normal. Biopsy of peritoneum revealed multiple nonnecrotizing and necrotizing granulomas with Langham type of giant cell and acid-fast bacilli seen on special stain, consistent with mycobacterial infection and negative for malignant cells.
The patient was started on anti-TB drugs (rifampin, isoniazid, pyrazinamide, and ethambutol) with resolution of ascites 2 weeks later.


A 35-year-old HIV- (human immunodeficiency virus-) negative male presented with three weeks of right lower extremity paresthesias and right upper extremity apraxia. His history was significant for Ann Arbor stage IV follicular lymphoma, in remission after initial Bendamustine and Rituximab, followed by maintenance Rituximab completed four months earlier. Physical exam revealed right upper extremity apraxia and weakness. Head CT revealed new bifrontal multifocal white matter hypoattenuation, while MRI brain (see ) revealed bilateral peripherally enhancing white matter lesions and signs of demyelination. Cerebrospinal Fluid (CSF) PCR was positive for the JC virus. Subsequent bone marrow biopsy and PET scan were negative for lymphoma. Flow cytometry revealed a CD4 count of 322/mcL. His presentation was consistent with inflammatory PML during immune reconstitution. Plasma exchange was deferred given the patient had not received Rituximab for over 4 months. Initial treatment with Mirtazapine 15 mg was started. However, the patient continued to develop enlarging lesions on imaging and worsening neurologic status including new onset aphasia. After expert consultation, he was then given Maraviroc, a small molecule CCR5 antagonist used to treat HIV, 300 mg twice daily without improvement, as well as a trial of methylprednisolone 1000 mg IV for three days without improvement. His clinical course was further complicated by bilateral retinal hemorrhages, and papilledema was thought secondary to IRIS. Due to the progression of disease, the Maraviroc was discontinued. He proceeded to intensive neurologic rehabilitation for patients with traumatic brain injury. He continued to dramatically improve neurologically; however he did not return to his premorbid baseline. Remarkably, he has since cleared the CSF of the JC virus on follow-up labs and shown substantial interval imaging improvement on recent MRI ().


A 55-year-old male presented to the ENT outpatient clinic complaining of right nasal blockage during the last six months. Endoscopy revealed a polypoid mass that filled the right nasal cavity and caused deviation of the lateral nasal wall. The patient’s medical history and laboratory studies were unremarkable.
A computed tomography (CT) scan showed a well-defined, sharply enhancing mass lesion in the right nasal cavity extending into the posterior ethmoid air cells with minimum projection to the nasopharynx. The medial wall of the orbit was preserved, and there was no intracranial extension. The mass measured 4 x 3 x 1.5 cm. Retained secretions and inflammatory changes to the sphenoid and maxillary sinuses were also seen. No lymphadenopathy was identified ().
Magnetic Resonance Imaging (MRI) revealed an ovoid encapsulated mass occupying the right nasal cavity extending into the ethmoid air cells and nasopharynx. Enhancement of the mass was heterogeneous on T1-weighted images following intravenous administration of gadolinium. The signal was heterogeneous on T2-weighted images ().
A biopsy was performed after preparation for any possible bleeding including nasal vasoconstrictors and general hypotensive anaesthesia, and this showed glomangiopericytoma. Histological examination of the biopsy specimen showed sheets of benign spindled cells arranged in a syncytium separated by prominent vessels. Pleomorphism, necrosis, and increased mitoses were not present. Immunohistochemistry showed positivity to vimentin, SMA, with few cells positive with CD34 and negative reactions with S-100 protein, desmin, and myogenin ().
Because of the bleeding propensity of the tumour, preoperative embolisation was planned. Under general anesthesia and systemic heparinisation, the right common femoral artery was punctured and a 5F diagnostic catheter was used to selectively catheterise both external carotid arteries. The angiographic control demonstrated arterial supply to the mass by both internal maxillary arteries (). Although the tumour blush was mild, it was decided to perform the embolisation with the aim of diminishing perioperative blood loss and facilitating complete removal.
With a coaxial technique, both internal maxillary arteries were sequentially catheterised with a microcatheter (Progreat, Terumo, and Tokyo, Japan). The vessels were embolised with microparticles measuring 350–500 μm in size (Embospheres, Boston Scientific, Massachusetts, USA ). The final angiographic control showed complete devascularisation of the tumour (). Immediately after embolisation, the patient was transferred to the operating theatre. The patient underwent an endoscopic right middle meatal antrostomy followed by a ‘powered’ reduction of middle turbinate using microdebrider, anterior’, and posterior ethmoidectomy and a sphenoidotomy. The axilla of middle turbinate was left intact to guide as landmark for future surgery. The lesion arose from the middle turbinate and extended to the anterior wall of the sphenoid sinus (). Complete resection of the tumour mass was achieved. Histological examination of the surgical specimen confirmed the former biopsy. The postoperative course was uneventful, and the patient was discharged a week later. The patient is under regular follow-up, and one year later he remains disease-free.


A 65-year-old man of Kashmiri origin with a history of essential hypertension and type II diabetes mellitus was referred to our out-patient department with a diagnosis of obstructive jaundice. He had been already evaluated with a whole body positron emission tomography-computed tomography (PET-CT) scan. The PET-CT scan documented a fluorodeoxyglucose (FDG) avid space-occupying lesion in segments IV and II of his liver that measured approximately 7.2×5.2 cm, maximum standardized uptake value (SUVmax) of 15.6, compressing his left hepatic duct (Fig. ), along with a metabolically active thyroid nodule (SUVmax 32.0; Fig. ). In addition, a 2.9×2.3 cm periportal lymph node with SUVmax 7.6 was also noted (Fig. ). The above findings were confirmed by magnetic resonance cholangiopancreatography (MRCP) which showed an ill-defined heterogeneous signal intensity mass lesion (hyperintense on T2-weighted image and hypointense on T1-weighted image), predominantly occupying segments II, III, IV, VI, and VIII and measuring approximately 7.5×8.5 cm (Fig. ). The lesion was shown to predominantly involve the left ductal system causing upstream dilatation. Multiple heterogeneous lymph nodes (hyperintense on T2 and diffusion-weighted imaging) were seen in his periportal region. A physical examination of our patient revealed icterus and mild hepatomegaly; palpation of his neck was unremarkable. He had altered liver function tests (LFTs) with grossly elevated bilirubin (total bilirubin 10.1 mg/dl, direct bilirubin 7.2 mg/dl, indirect bilirubin 2.90 mg/dl) and alkaline phosphatase levels. The results of a complete blood count (CBC), coagulation assay, and kidney function tests (KFTs) were normal.
Ultrasonography (USG)-guided fine needle aspiration cytology (FNAC) of the liver lesion was reported as papillary adenocarcinoma. FNAC from his thyroid was labelled as follicular neoplasm (Bethesda IV category; Fig. ). An USG-guided core-cut biopsy of the liver lesion was carried out and hematoxylin and eosin examination of this revealed metastatic deposits of follicular carcinoma with surrounding areas of necrosis (Figs. and ). Immunohistochemical staining of the liver biopsy was positive for thyroid transcription factor 1 (TTF-1), cytokeratin (CK) 19 and CK20, and negative for mucin (MUC) 1 (Fig. ), establishing his thyroid as the primary source of the liver lesion.
In view of PET-CT and pathological findings he was finally diagnosed to have follicular carcinoma of the thyroid with isolated hepatic metastasis with obstructive jaundice and was scheduled for total thyroidectomy followed by radioactive I131 ablation (RIA). In view of his altered LFTs, it was decided to subject him to preoperative biliary drainage by biliary stenting. However, unfortunately, post-procedure he developed acute cholangitis and severe sepsis which proved fatal for him.


A 57-year-old woman applied to our gastroenterology outpatient-clinics with intermittent nausea and vomiting in August 1994. A sessile polypoid mass of 15 X 15 mm dimension was observed in prepyloric region during the endoscopic examination (). The patient refused polyp resection or biopsy at that time and 6 years later she had applied to the gastroenterology department for control. Later on she had four follow-up endoscopies between 2-year intervals. The polyp in prepyloric region persisted without any progression during this period. In the second biopsy the polyp was exulcerated under endoscopy and this finding was confirmed by histopathology.
Totally, 12 biopsies were evaluated from the target lesion (3 biopsies from first, 4 biopsies from second, 2 biopsies from third, 3 biopsies from fourth endoscopy). In order to evaluate the progress of this polyp, we calculated the percentage of intestinal metaplastic component, the serrated component and also the intensity of mucin expression profile of each biopsy and took an average for each endoscopic biopsy set. Percentage of identifiable intestinal metaplastic component and serrated component for each biopsy material were calculated, so we were able to take an average for each biopsy. Goblet cells were accepted as the hallmarks of intestinal metaplasia. For immunohistochemical evaluation we calculated the percentage of immunoreactive mucosal component and took an average percentage for each biopsy.
An appropriate paraffin block was selected from four follow-up biopsies for immunohistochemical examination and a panel of MUC1 (E29 Neomarkers Fremont CA, USA), MUC2 (M53 Neomarkers Fremont CA, USA), MUC5AC (45M1 Neomarkers Fremont CA, USA), and MUC6 (MCN6.01 Neomarkers Fremont CA, USA) was applied. Histochemical stain of PAS-Alcian Blue Ph:2,5 was also applied to slides.
In microscopic examination, the first biopsy was composed of distorted and hyperplastic glandular structures with fibrovascular stroma. Intestinal metaplasia and a few glands composed of eosinophylic high columnar cells with slightly enlarged nucleus were observed and therefore lesion was diagnosed as hyperplastic polyp with intestinal metaplasia. Later in the second and third biopsy sets the glandular distortion and cellularity increased. In the last biopsy the polypoid mass had short villous proliferations composed of high columnar eosinophilic cells on the mucosal surface. The stroma was fibrotic and a few inflammatory cells were observed (). The component composed of crowded glands with large and oval nuclei, eosinophylic cytoplasm with distorted starry shaped glands increased progressively during the follow up biopsies () (). Mild cellular atypia was observed in a few cells in the third and fourth biopsy set. We counted goblet cells in ten-high power fields in their most frequently observed localizations. The number of goblet cells also decreased during the follow up. Surrounding gastric mucosa was detected in only 1 biopsy from the third endoscopy and there was chronic antral gastritis without Helicobacter Pylori colonization.
In PAS-Alcian Blue stain, eosinophilic columnar cells were stained purple and goblet cells were stained deep blue. PAS positive cells were decreased in surface epithelium during the follow-up. MUC1 immunoreactivity was observed in all cells. MUC 2 was observed commonly in goblet cells but also in non-goblet cells (), MUC5AC was observed more strongly in surface epithelium, but weakly in eosinophilic and goblet cells (). MUC6 was observed in all cell types. Co-expression of MUC1, 2, 5AC and 6 was observed frequently.
The number of biopsies, percentage of identifiable intestinal metaplastic component, serrated component and the immunoreactivity with MUC1, MUC2, MUC5AC and MUC6 are summarized in .


A 35 years old male, a known case of hypothyroidism for the past 3 years presented to the emergency department with upper abdominal pain of 16 hours duration. He was on thyroid hormone therapy for 2 years, which he discontinued and switched over to Ayurvedic (alternative medicine) treatment since one year. He gave a history of chronic constipation which worsened since the last four months. He was also on treatment for acid peptic disease. On examination he was tachycardic (pulse rate: 100/min), blood pressure was 110/70 mm Hg. The abdomen was distended with maximal guarding and tenderness in the epigastrium. Bowel sounds were diminished. Laboratory investigations showed a total count of 14,900/mm3. Thyroid hormone profile was T3 = 55 ng/dl (normal range 97 - 169), T4 = 3.5 ugm% (normal range 5.5 - 11), TSH = 22µ IU/ml (normal range 0.462 - 4.68). Plain abdominal X-ray revealed free intraperitoneal air under the right hemi diaphragm. Hence based on a provisional diagnosis of hollow viscus perforation, an emergency exploratory laparotomy was performed. At laparotomy the upper abdomen appeared relatively normal; however there was purulent fluid and multiple small fecoliths in the pelvis. A thorough search revealed a small circular perforation of about 1 cm diameter over the antimesenteric border of recto-sigmoid. The sigmoid colon was found to be thinned out and dilated with hard faecal matter within it. No other gross abnormality could be detected. The mesenteric artery pulsations were well felt. Hence a Hartmann’s procedure was performed using a linear stapling device, and a segment of about 10 cm of thinned out distal colon including the ulcer was resected. The post operative period was uneventful. Manual faecal evacuation and multiple enemas were given through the colostomy to evacuate impacted faeces. He was started on thyroid hormones 200 ug/day. Histopathology report was suggestive of a non specific ulcer with focal mucosal and sub mucosal neutrophilic infiltration ().


A 74-year-old Caucasian man with history of CLL (del 17p, del 13q) was initiated on ibrutinib therapy after experiencing an adverse reaction to the first cycle of R-CHOP. One month later, he presented to his primary care clinic with the complaint of a tender, discolored lesion of the glans penis. He was initially treated with acyclovir due to concern for Herpes Simplex Virus; however the lesion continued to worsen, which led to difficulty with urination. He was admitted to the hospital for further evaluation and management. The patient denied any history of sexually transmitted infection, condom catheter use, trauma to the penis, or unretractable foreskin. Past medical history was significant for type II diabetes mellitus and hypertension, but negative for known atherosclerotic disease. On examination, he was found to have an uncircumcised penis with a necrotic lesion of the glans penis with minimal sensation (). There was no evidence of phimosis or paraphimosis.
At the time of presentation, white blood cell count was found to be 9,300/microliter. Penile ultrasound revealed no appreciable arterial flow in the penile arteries (). Pelvic MRI showed minimal enhancement of the skin overlying the glans penis consistent with necrosis; there was no evidence of mass lesions of the penis (). HSV serologies were negative. A workup for vasculitis was initiated; however ANCA, rheumatoid factor, cryoglobulins, and anticardiolipins were all negative. Workup for atherosclerotic disease was carried out with arterial Doppler of bilateral lower extremities which did not show evidence of arterial insufficiency. A CT scan of the abdomen/pelvis was negative for narrowing of the abdominal aorta (which could predispose to penile necrosis), as its narrowest point was 15.6 mm ().
In this case, onset of symptoms after the initiation of ibrutinib supported a potential association. Moreover, he did not have any underlying risk factors for penile infection, trauma, or a history of phimosis or paraphimosis. Ibrutinib was discontinued as an alternative etiology was not discovered. Despite a comprehensive workup, no alternate etiology was found to explain penile necrosis, suggesting likely ibrutinib related adverse effect. Our urology colleagues were involved in the patient care and recommended allowing for autoamputation of the glans penis. A suprapubic catheter was placed to allow for bladder drainage during this process. After stabilization, the patient was discharged home. He did not experience any bleeding episodes on ibrutinib. Upon follow-up in the clinic, the gangrene had not progressed further.