The patient was a 7-year-old boy, born in Belgium from two parents of Burundi origin, who suffered from sickle-cell disease that was diagnosed during the neonatal period. He was undergoing manual recurrent partial exchange transfusion (roughly once a month since the age of four) in combination with medical treatment (hydroxyurea). Despite suitable therapy, he presented with some complications that mainly consisted of neurovascular malformations (Moyamoya disease). A look-back procedure, launched soon after an infected donor was detected through the new screening program implemented in Belgium in September 2013, revealed that this child had received contaminated RBCs eight months earlier. Subsequent serological investigations showed that the child’s serum was reactive in the three tests used in the national reference laboratory (). The diagnosis of T. cruzi infection was finally confirmed in another blood sample, collected three weeks later, by the demonstration of T. cruzi DNA by PCR ( and ). Since a pre-transfusion sample tested retrospectively was proven to be non-reactive against T. cruzi, the imputability of the Chagas contamination to the incriminated blood donation could be definitively established in this young patient who had never travelled to South America. No symptom suggestive of acute Chagas disease could be retrospectively noticed in the period of time elapsing from blood donation to infection diagnosis. An antiparasitic treatment (benznidazole), obtained through the donation program from the World Health Organization in Geneva, was administered at a dosage of 5 mg/kg twice daily, for a duration of eight weeks. As no formal information was available about interactions between benznidazole and hydroxyurea—two drugs that are potentially hematotoxic [,]—the latter drug was suspended during the first two weeks of antiparasitic therapy but was resumed later without any inconvenience. Tolerance was markedly good, with no clinical or biological adverse reaction observed throughout the whole treatment. Only the neurosurgery that was planned for his significant neurovascular lesions had to be delayed during the medical treatment. Unfortunately, a cerebrovascular ischemic event, as commonly observed in Moyamoya disease, occurred in the meanwhile but was of short duration and recovery was spontaneously complete. T. cruzi DNA remained detectable by PCR in the patient’s blood two and three months after the antiparasitic treatment was started, but intensity of amplicon bands was markedly decreased compared to that observed at the time of infection diagnosis (). The PCR became negative three months after completion of therapy; this result, however, does not guarantee a complete cure of the child since PCR might be falsely negative in the case of very low parasite burden. Extended follow-up with repeated testing is therefore planned to sustain long-term resolution of infection and absence of chronic complications. At present, more than two years after the contaminated transfusion occurred and one year after treatment completion, the child remained asymptomatic, and parasite DNA was undetectable in blood samples by PCR (as assessed in June 2015). He was still regularly receiving blood transfusion/manual partial exchanges, which are the only option in sickle-cell patients waiting for curative bone marrow transplant.
The contaminating donor was a 47-year-old male born in an endemic rural area near Santa Vitoria in Brazil, where he lived until the age of 23 before moving to São Paulo and then to Belgium when he was about forty. Shortly after implementation of T. cruzi blood screening in Belgium, he was found to be positive with four different serological assays that all remained reactive in another sample obtained three months later (). A positive T cruzi PCR confirmed the possible disease activity and infectivity (). The donor was fully asymptomatic, had no clinical sign of chronic Chagas disease, and did not report any history of Chagas disease in his family, though he was aware of the risk of infection because of insecticide spraying performed annually in his home in Santa Vitoria. Despite repeated requests by the blood bank services that he see an infectious disease specialist, the infected donor has been unfortunately lost to follow-up. The look-back procedure revealed that two other patients had received blood products from the same infected donor. The first one was a 43-year-old woman who received RBC within the care of extensive burns. She died one month later from the underlying pathology, and no further evaluation of the Chagas status could be performed. The other recipient was a 40-year-old man with HIV infection, a herpes virus 8-associated lymphoma, and Kaposi’s sarcoma. He received a pool of platelet concentrates prepared from six leuko-reduced whole blood samples (one of which was from the infected donor) and was treated for pathogen reduction with amotosalen and UVA (INTERCEPT, Cerus Europe BV, Netherlands). Such treatment has been shown to efficiently inactivate T. cruzi [], which is important because, without treatment, parasites remain detectable at low level in platelet concentrates []. No evidence of T. cruzi infection was found in this patient.


A 43-year-old woman presented to the emergency room (ER) with palpitations, dizziness, and shortness of breath. The patient did not have chest pain or syncope. She had a 2-year history of palpitations. An ECG and an echocardiogram performed six years prior to her presentation were normal accordingly. She denied family history of premature sudden death and coronary artery disease. An ECG done in the ER showed a sustained ventricular tachycardia (VT) with a rate of 218 bpm. The QRS pattern was in left bundle branch block (LBBB) morphology with inferior axis (). Retrograde 1 : 1 P waves were present. Adenosine temporarily interrupted the tachycardia. However, multiple runs of nonsustained VT, all in LBBB morphology, were recorded on telemetry. After intravenous administration of amiodarone all ventricular arrhythmias were abolished. The ECG while on amiodarone showed sinus rhythm, low QRS amplitudes in limb leads, T wave inversion in V1–V3, and QTc prolongation. In the following days the inverted T waves in the right precordial leads gradually became upright after the discontinuation of amiodarone, but VTs reappeared. Flecainide failed to abolish VT. The patient was finally started on atenolol with good results. Cardiac angiography revealed patent coronary arteries, normal right ventricle, and a left ventricular diverticulum (LVD) with a distinct morphology (). LVD was also confirmed by cardiac magnetic resonance imaging (CMRI). Signal averaged ECG study was negative. An electrophysiology study was performed which showed a normal endocardial voltage mapping. However, the epicardial mapping divulged a small area of fibrotic tissue at the anterior RVOT and a large area of fibrotic tissue in the inferolateral portion of the RV (). Activation mapping demonstrated that the earliest tachycardia exit point was in the endocardial RVOT, while the best pace-mapping was in the facing epicardial surface. VT ablation was successfully performed with combined epicardial and endocardial approaches. After the ablation, this patient has been event-free for the last ten months without any drug therapy. Since there is a large area of fibrotic tissue formation on the epicardial surface of the right ventricle, long-term follow-up was advised.


We report a case of a 24-year-old Japanese woman, gravida 0, who had no relevant past medical history or family history when she became ill. She complained of prolonged menstruation and was examined with Cusco’s speculum. The patient presented with a uterine cervical tumor and was diagnosed with uterine leiomyoma. She underwent her first transvaginal resection of the tumor with a myomectomy and endometrial curettage. The pathological diagnosis was leiomyoma and endometrium, no malignancy, as a benign tumor. She underwent four additional tumor resections: polypectomy, two myoma resections, and a submucosal leiomyoma resection via hysteroscopy. The resections were performed at intervals of 10 months, 9 months, 9 months, and 6 months, respectively. After these resections, she gave birth to a 3396g boy via cesarean section at age 28 years. During her pregnancy, she was diagnosed with oligoamnios. The birth took place at the 39th week of pregnancy. At age 30 years, the patient developed a sixth tumor (a fibroid in statu nascendi), which was removed by exeresis at age 30 years. Four subsequent tumor resections were performed, at intervals of 23 months, 4 months, 12 months, and 3 months, respectively. When the seventh tumor was resected by polypectomy at age 32 years, the pathology report revealed for the first time the high density of the stroma and the necessity of careful follow-up. At the time these ten tumor resections were performed (five before and five after childbirth), the tumors were not diagnosed as malignant. The correct diagnosis was obtained by analysis of advanced-stage surgical specimens. The discovery of minimal elements of LGESS by a retrospective study of the transvaginally resected tumors led to a correct diagnosis of early-stage LGESS.
The patient visited our hospital, complaining of lower abdominal pain at age 34 years and was found to have a tumor 10cm in diameter behind the uterus (Fig. ), which was diagnosed as an advanced malignant ovarian tumor before surgery. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, and resection of peritoneal dissemination were performed. The tumor was classified as International Federation of Gynecology and Obstetrics 1982 stage VIb for uterine corpus cancer and Union for International Cancer Control 1990 tumor, node, metastasis stage pT4NxM1 on the basis of the finding of tumor spreading in the peritoneal cavity. The histological result revealed LGESS of the uterine corpus. A great amount of bulky, disseminated tumor lingered in the abdominal cavity, particularly on the serosa of the rectum and descending colon. After the operation, gemcitabine (800mg/body surface area, Day 1 and 8) and docetaxel (60mg/body surface area, Day 8) combination chemotherapy (GD) was started with informed consent. A subcommittee of our institutional review board reviewed the case and gave approval to treat this patient with GD chemotherapy. Six cycles of GD were administered every 3 weeks, followed by six cycles every 3 months (age 36 years). After nine cycles of chemotherapy, the patient developed ileus and underwent surgery. She had a complete response to chemotherapy, and no visible tumor remained in the abdominal cavity. No recurrent tumor was detected for the next 4 years, and the patient did not undergo any treatment during that time.
When the patient reached the age of 40 years, a new tumor was detected in the pelvic cavity. She underwent surgery to remove the recurrent tumor. The tumor, 2.5cm in diameter disseminated on the ileum, was resected. Numerous small disseminations remained. Five cycles of GD every 3 weeks were administered after surgery. The sixth cycle of GD was discontinued because the patient’s neutropenia worsened to a grade 4 adverse event as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 3, even after granulocyte colony-stimulating factor was administered. No recurrent tumor was detected for the next 18 months.
A small accumulation of fluid was detected in the pouch of Douglas when the patient was age 42 years. Computed tomography (CT) revealed recurrence of the tumor in the form of many disseminations in the right pleura, peritoneum, right diaphragm pleural and peritoneal surface, and liver surface (Fig. ). Although three cycles of GD at the initial dose were administered, the disease progressed and shock was induced by abdominal cavity bleeding (Fig. ). Infusion and blood transfusion were started with hospitalization to treat bleeding shock. Medroxyprogesterone acetate (MPA) was administered at a daily dose of 600mg. Although the bleeding in the patient’s abdominal cavity stopped, her pleural effusion and ascites did not decrease. Because the effect of MPA was not enough, a gonadotropin-releasing hormone analogue (leuprorelin acetate) at a dose of 3.75mg/body surface area once every 28 days was administered in addition to MPA. The increase in both the pleural effusion and ascites accelerated, and thoracic bleeding induced shock and dyspnea on the 18th day after leuprorelin acetate was first administered (Fig. ). The pleural effusion began to decrease at 1 month after leuprorelin acetate was first administered. Because the patient’s ascites were not decreasing, an aromatase inhibitor (anastrozole) 1mg/day was administered in addition to MPA and leuprorelin acetate. After beginning treatment with anastrozole, the patient’s ascites decreased. She was discharged from the hospital after 116 days.
Three months later, the tumor had enlarged between the liver and diaphragm and had spread to the right pleura (Fig. ). Paclitaxel at a dose of 170mg/m2 and carboplatin (area under the curve =4) combination chemotherapy (TC) was started with MPA, leuprorelin acetate, and anastrozole. The dose of TC was reduced because during the time five cycles of GD were administered after the recurrent tumor on the ileum was resected the patient’s neutropenia gradually worsened to CTCAE grade 4. The tumor size and state were confirmed by CT after every three cycles of chemotherapy. The tumor gradually reduced, and the liver returned to the normal position. Chemotherapy was stopped after 18 cycles (Fig. ). The patient is currently alive and being treated with MPA, leuprorelin acetate, and anastrozole (age 45 years at the time of this report).
The first, sixth, and ninth tumors transvaginally resected in the early stage showed similar histopathological findings. The tumors had a polypoid appearance with various degrees of surface erosion (Fig. ). The surfaces were covered by non-atypical columnar epithelium of endocervical or endometrial type. The stroma was edematous, loosely fibrous, and paucicellular, often containing capillaries and small vessels recapitulating inflammatory granulation tissue (Fig. ). There were a few foci of mild stromal hypercellularity, where small, short spindle stromal cells surrounded the blood vessels (Fig. ). The seventh, eighth, and tenth transvaginally resected tumors were clinically diagnosed as endocervical or endometrial polyps, and they had wide areas of stromal hypercellularity, which is unusual for conventional endocervical or endometrial polyps (Fig. ). Although several suspicious findings were present, it was difficult to diagnose LGESS on the basis of only transvaginal resection of the tumors.
The surgically resected uterus in the advanced stage had multiple polypoid excrescences in the lower uterine segment. Examination of cut sections revealed multiple nodular lesions in the muscular layer of the uterine corpus and paraovarian connective tissue. The cut surfaces of these tumors were whitish yellow and had a monotonous solid appearance. Multiple peritoneal tumors ranging from 20mm to 60mm in diameter had similar macroscopic findings.
Histologically, the polypoid endometrial lesions invaded the muscle layer with pushing margins and multiple tongue-like projections (Fig. ). Prominent intralymphatic tumor extensions were noted, especially in the paraovarian connective tissue (Fig. ). The tumor consisted of a monotonous proliferation of oval to short spindle cells with indistinct cytoplasm (Fig. ). The spindle cells often surrounded small arterioles in a concentric pattern. Some cells had abundant clear cytoplasm (Fig. ). In some areas, the stroma was edematous and cellularity was low (Fig. ). Such areas were similar to the pathological findings of the first, sixth, and ninth transvaginal polypectomy specimens.
Immunohistochemically, the tumor cells of the surgically resected specimens were diffusely positive for estrogen receptor, progesterone receptor, and cluster of differentiation 10 (CD10) (Fig. ). The staining intensity of progesterone receptor and CD10 was strong, and that of estrogen receptor was weak to moderate. CD10 was also positive in the spindle cell of the pre-operative specimens of the transvaginal resections (Fig. ). The series of lesions, including those from the ten transvaginal resections and hysterectomy, were finally diagnosed as LGESS. Focal stromal hypercellularity surrounding small blood vessels seen in the first ten resected tumors was retrospectively considered the characteristic finding of LGESS. The recurrent intestinal serosal, peritoneal, and hepatic lesions showed essentially the same histological findings.


A 43-year-old homeless male presented with several weeks of weight loss, bilateral burning foot pain, and overall weakness that had progressed to an inability to walk. The past medical history was largely unknown but included admission to a different hospital two years prior with acute kidney injury secondary to rhabdomyolysis, with a serum creatinine of 1.5 mg/dL on discharge. The social history was significant for crack-cocaine use. On admission, he appeared cachectic and had a temperature of 38.7°C. On the neurological exam, he had impaired soft touch sensation bilaterally up to the ankles and diffuse weakness. There were no skin abnormalities seen.
The creatinine on admission was 3.93 mg/dL, and the BUN was 55 mg/dL (upper limit of normal is 1.0 mg/dL and 25 mg/dL, resp.). A globulin gap was present with a total protein of 6.7 g/dL and albumin of 1.4 g/dL. Urinalysis demonstrated moderate protein and blood, with a spot protein-creatinine ratio of 1 : 55 mg/mg (upper limit of normal is 0.11 mg/mg). There was no peripheral eosinophilia. Microscopic urinalysis showed granular casts but no red blood cell casts. His urine tested positive for eosinophils. Cocaine metabolites were found on urine toxicology. HIV, anti-nuclear and anti-glomerular basement membrane antibodies, RPR, and hepatitis B and C serologies were negative. There were no abnormal bands on serum or urine protein electrophoresis. ANCA were strongly positive at 1 : 5120 (upper limit of normal is less than 1 : 20) with a perinuclear staining pattern and myeloperoxidase reactivity at 76 AU/mls (upper limit of normal is less than 19 AU/mls). Kidney biopsy specimen had a total of 21 glomeruli, out of which only two were globally sclerotic. The majority of glomeruli showed pauci-immune necrotizing crescentic glomerulonephritis (). A prominent plasma cell-rich tubulointerstitial nephritis was also present.
Based on his laboratory findings and renal biopsy, a diagnosis of microscopic polyangiitis was considered, but levamisole-induced ANCA vasculitis remained a likely possibility given his history of cocaine use. The presence of interstitial nephritis on biopsy was felt to explain the eosinophils in his urine, a finding previously reported in cocaine users []. He was treated with pulse methylprednisolone 1000 mg for three days and 600 mg of IV cyclophosphamide. His creatinine peaked to 7.21 mg/dL during hospitalization but stabilized at 6.25 mg/dL after treatment. The patient was counseled on abstaining from cocaine and was discharged on 40 mg of prednisone per day with instructions to follow-up for monthly cyclophosphamide injections at renal clinic.
The patient was readmitted one month later with increasing lower extremity swelling and pain. He had been off prednisone since discharge and had ongoing crack-cocaine use. Renal function had declined, reaching serum creatinine of 8.8 mg/dL. He was treated with cyclophosphamide and prednisone, and his fluid status and electrolyte abnormalities were corrected. Renal function did not improve with treatment, and hemodialysis was initiated.


We report the case of a 58-year-old male that presented to our Emergency Department with complaints of acute interscapular back pain and bilateral lower extremities weakness.
Patient's medical history was significant for diabetes mellitus type II, hypertension, dyslipidemia, and atrial fibrillation. His surgical history consisted of umbilical hernia repair and left hip arthroplasty. Patient had no allergies and had stopped smoking many years ago. He was diagnosed with atrial fibrillation 30 days prior to admission, for which he was started on rivaroxaban 20 mg once daily. The rest of his medications included atorvastatin, fish oil, sitagliptin, quinapril, and triamterene-hydrochlorothiazide.
On the day of admission, the patient admitted waking up at 3:00 am with sudden onset, sharp, interscapular back pain. He denied any similar pain in the past. The patient first presented to another institution, where he started having bilateral lower extremities numbness, which progressed rapidly to bilateral weakness. At this point, he was still able to walk but with difficulty. He was then transferred to our institution, where his weakness became more pronounced. Patient denied any other neurologic symptoms. There was no history of trauma. Prior to this, he had a left hip arthroplasty three weeks earlier, which was performed under spinal (lumbar) anesthesia, without complications. Rivaroxaban was stopped three days before the surgery. Postoperatively he did not receive nonsteroidal anti-inflammatory drugs and was restarted on the OAC few days later. Moreover, he reported driving for almost 7 hours from Elmira (New York) to Staten Island (New York) one day prior to presentation.
Initial physical examination revealed an alert and oriented patient in no acute distress, with a Glasgow Coma Scale score of 15. His blood pressure was 148/98 mmHg; heart rate was 82 beats/min and irregular; body temperature was 98.7°F; respiratory rate was 18 breaths/min. Cardiopulmonary and abdominal exams were within normal limits. Tenderness was elicited over the upper thoracic spine. There were no neurological deficits in the cranial nerves or upper limbs. The motor strength in both lower limbs was of Medical Research Council grade 0/5. A sensory level was evident at the level of T2 with positive bilateral Babinski reflexes.
Initial laboratory assays included a hemoglobin concentration of 11 g/dL, a platelet count of 176 × 109/L, an activated partial thromboplastin time (aPTT) of 36.6 seconds, a prothrombin time (PT) of 18.4 seconds, and an international normalized ratio (INR) of 1.6. Kidney function and liver enzymes were normal. Electrocardiogram and chest radiograph were unremarkable. A noncontrast computerized tomography (CT) of the brain was negative for bleed, and a CT of the chest was also negative for dissection.
The clinical presentation combined with findings on the neurological exam pointed towards a spinal pathology. Moreover, a spinal bleed was strongly suspected given the history of recent spinal anesthesia in addition to the rivaroxaban use. An emergent cervical and thoracic magnetic resonance imaging (MRI) demonstrated an acute 6.3 × 0.6 × 1.6 cm intradural hematoma from C7 to T2, with spinal cord edema (). Neurosurgical intervention was not deemed an option at this point given that the increased risk of rivaroxaban-induced bleeding outweighed the benefits. Therefore, a conservative management was adopted, including close neurological monitoring in the intensive care unit along with high dose intravenous dexamethasone (100 mg once followed by 10 mg every 6 hrs). Patient was also offered prothrombin complex concentrate (PCC), but he declined to proceed with this therapeutic option given its potential side effects, such as prothrombotic state, as well as its uncertain efficacy in similar spinal bleed. He was started instead on aminocaproic acid.
The following day, patient's neurological exam had improved. Sensory level was down to T4-T5, and motor strength was 4/5 in the right lower extremity while it remained 1/5 on the left lower extremity. Given the increased risk of bleeding, especially taking into account the minor improvement in the patient's condition, surgical intervention was delayed for three days, to allow complete elimination of rivaroxaban. On hospital day 4, patient underwent a successful and uneventful anterior C7 corpectomy with resection of a large intradural hematoma. Postoperatively, his neurological exam continued to improve slowly, and he was discharged for intensive rehabilitation 5 days after the surgery. A repeat MRI done 6 weeks later showed almost complete resolution of the spinal hemorrhage ().


We report the case of a 65-year-old woman with a history of hysterectomy at age 35, who presented generalized osteoporosis, severe bone pain and risk of bone fractures. The patient was referred from trauma management after failure of prior treatments for osteoporosis (bisphosphonates, alendronate and risedronic acid) after major side effects: gastrointestinal erosion with biphosphonates and alendronate, and severe gastrointestinal bleeding, severe muscle and joint pain, fever, flu symptoms, conjunctivitis, episcleritis and uveitis with risedronic acid. All symptoms were intense and persistent. On the day after the first administration of denosumab the patient developed a generalized urticarial rash (thighs, abdomen, bilateral breast area, back) accompanied by bilateral facial angioedema and pruriginous injuries in the area of drug administration (the abdomen) (Fig. ). The symptoms started 2 h after the first administration and resolved completely after 15 days with the administration of antihistamines and oral corticoids and the application of local corticoids.
Informed consent was obtained from the patient to perform an allergy test. Skin prick test (SPT) with denosumab was performed 8 weeks after the initial adverse reaction in order to minimize the risk of false negative results. A commercial preparation of Prolia (Amgen Europe B.V., Breda, Netherlands; GlaxoSmithKline) was used, containing 60 mg of denosumab in each preloaded 1 ml syringe (60 mg/ml). Histamine prick (10 mg/ml) and saline solution were used as positive and negative controls. A positive reaction was defined as a wheal with a diameter at least 3 mm larger than that obtained by a negative control. For SPT, a drop of denosumab (60 mg/ml) was applied and pricked to the volar surface of the forearm, eliciting a negative response. For intradermal testing, denosumab was diluted in normal saline. We proceeded with intradermal injections of 0.03 ml of 1/100 and 1:10 dilution of the denosumab strength solution, which obtained negative results. These concentrations proved to be non-irritating in ten control subjects who had never been treated with denosumab. The patch test with undiluted drug was applied at both the upper back and the previous local injection site, and also produced negative results. Skin prick test to house dust mites, cat and dog dander, olive, grass pollen and latex were negative, as was serum specific IgE to latex dander.
Given the risk of bone fracture and the numerous side effects of the conventional therapies for the treatment of osteoporosis, the patient agreed to denosumab treatment using a desensitization protocol. After informed consent was given, the desensitization procedure was performed. Blood pressure and heart rate were monitored during the test. The patient was pre-medicated with methylprednisolone (40 mg IV), ranitidine (50 mg IV) and dextrochloropheniramine (5 mg IV) 1 h before drug administration. A desensitization protocol was begun with an initial subcutaneous dose of 0.005 mg which was gradually increased in an eight-step cycle until a cumulative dose of 60 mg was reached (Table ). The interval between doses was 15 min and the process was completed in 2 h. No local or systemic reactions were observed, either immediate or delayed. Since then, the patient has tolerated other two cycles of denosumab desensitization using only antihistamines for premedication, and her osteoporosis has evolved favourably.
In order to demonstrate the efficacy of our desensitization procedure, a denosumab provocation was performed 6 months after the third desensitization protocol. After 3 h the patient presented bilateral angioedema, which had not occurred in the previous cycles of denosumab desensitization. On the next day, the patient had a very pronounced angioedema of the eyelids and cheekbones. Tryptase levels were 2.3 ng/ml (negative up to 15 ng/ml) before the challenge test, 2.1 ng/ml after the challenge test, and finally 2.2 ng/ml after desensitization. Applying our desensitization procedure once again using only antihistamines as premedication, the drug was perfectly tolerated.


Case 1 was a 28-year-old patient with primary male factor infertility. Her husband had a history of varicocelectomy which had not improved the sperm parameters. Two embryos were subjected to cosmetic micromanipulation and seven embryos were cryopreserved. The cryopreserved embryos also had the same fragmentation percent and pattern. The patient had the history of four implantation failures and one fresh ET and three frozen-thawed ET cycles. There were no multinucleated blastomeres in embryos. Each embryo had circular shape and moderately even blastomeres on day three. Efforts were made to defragment the embryos as timely as possible to avoid long stay of embryo out of the incubator. The percent of fragmentations in first embryo and second embryo subjected to cosmetic micromanipulation were 15% and 20% with pattern of localized and scattered fragmentation, respectively. One embryo was implanted and the clinical pregnancy outcome was positive.


This was a 36-year-old patient with primary male factor infertility. Seven eggs were retrieved and five mature oocytes underwent ICSI. Two embryos developed from three normally fertilized eggs. Two embryos were subjected to micromanipulation with two and four cells on day two with no blastomere multinucleation. Both embryos had circular shape, while one embryo had uneven blastomeres. The embryos had 20% and 40% fragmentation with localized and distributed patterns, respectively. The patient had the history of three ICSI fertilization failures and two implantation failures. The quality of embryos developed in this cycle was the same as her previous cycles. Coarse granulation removal was performed for this case. One embryo was implanted and the clinical pregnancy outcome was positive.


A 45-year-old African American female presented for evaluation of a left renal mass. She did not complain of any urinary symptoms such as flank pain or hematuria, and her past medical history was significant for type 2 diabetes mellitus, gastric bypass surgery, and thyroid cancer diagnosed at an outside hospital 20 years previously, which was treated by total thyroidectomy. However, the histologic type of the thyroid tumor was unknown, and neither the outside medical records nor histologic sections of the thyroid tumor were available for review. The patient's primary care physician had told her that imaging studies of her left kidney were suspicious for renal cell carcinoma and had suggested that she undergo nephrectomy. A CT of the abdomen and pelvis revealed a 7.5 × 6.8 cm, exophytic, homogeneously enhancing mass in the inferior pole of the left kidney. There was no evidence of hydronephrosis or nephrolithiasis, and the urinary bladder, ureters, and adrenal glands were all unremarkable. A percutaneous CT-guided core biopsy of the mass was performed (), and imprints and histologic sections of the biopsy specimen were evaluated and deemed positive for metastatic FTC.
Nine months following biopsy, the patient underwent left radical nephrectomy, and examination of histologic sections of the resection specimen confirmed the cytologic diagnosis made on the core biopsy specimen. She did well in the immediate postoperative period, with no evidence of wound infection, and was discharged. Three years later, she was admitted for malnutrition and dehydration due to an anastomotic leak from her previous gastric bypass surgery. She was discharged after a 2-month inpatient stay, during which she underwent gastrostomy tube placement, and has not been hospitalized since. A repeat CT at that time showed several hypodense lesions in the right kidney, as well as one of intermediate density measuring up to 1 cm in greatest dimension that had remained stable since the previous CT, 3 years earlier. The patient was subsequently lost to follow-up.


A 55-year-old male patient presented to the emergency department after sustaining a fall from 4-meter height. Patient attempted to break his fall and landed on his outstretched left hand. After the fall, the patient had severe pain and deformity of his left forearm. Initial assessment revealed a hemodynamically stable and cooperative patient but in distress due to severe pain. His left upper extremity had an obvious deformity in the forearm, with swelling and restricted range of motion due to pain. The patient also had a 3 cm wound on the dorsolateral side of his elbow.
Roentgenograms showed a comminuted fracture of the ulnar shaft at the proximal and middle third junction with 35° of angulation along with a posteriorly dislocated nonfractured radial head and a fractured lateral humeral epicondyle (). Furthermore due to the presence of the wound the fracture was classified as an open fracture. Computed topographic scan with 3D reconstruction was done to understand the injury more ().
Patient was transferred the same day to the operative room for treatment. The wound was copiously irrigated with minimal debridement needed. Traction was first applied and it was sufficient to reduce the radial head and align the ulnar fracture. Open reduction of the ulnar fracture helped attain a better reduction and the fracture was fixed using a laterally applied 3.5 mm locked compressive plate (LCP) and ensuring a fixation of at least 6 cortices both proximally and distally. The fractured lateral humeral epicondyle was then reduced and fixed using 2 cannulated 3.5 mm partially threaded screws. The radial head stability was then evaluated and was found to be stable.
The postoperative period was uneventful and the patient was discharged home on day 3 postoperatively with a clean noninfected wound. The elbow was immobilized with a long posterior arm splint for 7 days. The elbow was then held in an articulated elbow brace and physical therapy was started. Active and passive range of motion exercises were started and at 6-week follow-up visit the patient was pain-free and showed full elbow extension, flexion to 140, supination to 90, and pronation to 80 degrees.
Radiographs done at 3-month follow-up visit revealed a healing ulnar and humeral fracture with a radial head in its adequate position (). Patient at 6-month follow-up had full extension, flexion to 130°, supination to 90°, and pronation to 80° (). Based on Broberg and Morrey scale [], the end result was excellent.


A 86-years-old woman, whose smoking habits are not known, noted, in September 2013, the appearance of a small lesion on the left cheek mucosa. She was followed at the department of Oral and Maxillofacial Surgery. The physical examination revealed the presence of an ulcerated lesion, 2 cm of diameter, lightly painful on palpation, with hard/elastic consistence. The histological picture of an incisional biopsy of the lesion, revealed a poorly differentiated, invasive squamous cell carcinoma. The diagnosis was confirmed on the whole excision of the lesion. Three months later, the clinical examination revealed the presence of a node swelling in the left laterocervical region of about 3 cm in diameter, firm, fix and painful on palpation, which showed a rounded morphology at US, ranging in size between 20 and 23 mm of maximum diameter. A PET-CT scan showed tracer hyperaccumulation restricted to the retromandibular and left parapharyngeal regions (SUV 17.4) (Fig. and ). A left laterocervical lymphadenectomy was then performed, and the sample was sent to the institutional Pathology Unit. The surgical specimen was composed of a salivary gland, 12 single lymph nodes and a single mass of few fused lymph nodes (maximum diameter: 3 cm). At microscopic examination, the lymph-node mass showed massive necrosis lined by granulomatous inflammation with palisading epithelioid and Langhans’ giant histiocytes, in close association with metastatic sheets from a squamous cell carcinoma (Fig. ). The immunohistochemistry clearly evidenced the tumor nests (pan-cytokeratin positive) and the granulomatous reaction area (CD68 immunoreactive) (Fig. and ). On the basis of morphological and immunohistochemical findings, we posed diagnosis of metastatic squamous cell carcinoma associated with necrotizing granuloma, strongly suggestive of mycobacterial infection/tuberculosis. Requestioning the patient about her previous pathological history, we finally found out that she had an episode of tuberculosis in the 1960s. The patient was redirected to the department of infectious diseases for further investigation; at x-chest rays there was no evidence of pulmonary activity of the disease, as reported for most patients with tuberculosis of the head and neck lymph nodes [].
Mycobacterium tuberculosis (MTB) infects one third of the world’s population and is the second leading cause of death from an infectious disease after HIV. The association between cancer and tuberculosis infection was already described [, , ], some authors suggest that the onset of these chronic disease is favored by a state of immunosuppression. Lymphadenitis is the most frequent manifestation of extrapulmonary tuberculosis and neck swelling is the commonest presentation (multiple lymph node widening without constitutional signs). Some authors have reported the presence of tuberculous lymphadenitis in a patient with breast cancer [] and in a patient with a history of sovraglottic carcinoma [] who were misdiagnosed as malignant lymph node based on the imaging. Cancer can be associated with a granulomatous response in the draining lymph node []; in particular, squamous cell carcinoma can elicit this reaction, being tumor keratins the reaction target []. The simultaneous presence of tuberculosis infection and metastasis in the same lymph node is a rare event, described mostly in patients with breast cancer [–] and less in patient with a history of head and neck squamous cell carcinoma [, ]. Here we describe an unexpected, rare case of node metastasis from oral squamous cell carcinoma coexisting with tuberculosis; to our knowledge, our case represents the first involving the oral cavity as the source of the primary tumor. Wang at al reported two cases of OSCC with node metastasis and TB infection, being the two pathological entities found separately in different lymph-nodes [].


This female infant was born to a 29 year old G2P1 mother at term via an emergency C-section due to fetal distress. During the prenatal period, an echogenic intracardiac focus and nuchal thickening (6-7 mm) were identified at 21 weeks gestation. The family received genetic counseling and further investigations were declined. Apgar scores were 8 at 1 minute and 8 at 5 minutes and the infant fed well shortly after birth. Postnatal exam showed a healthy appearing infant with bilateral type B postaxial polydactyly of the hands (postminimus). She did well in this immediate post-natal period and, after removal of the polydactyly, was discharged from the hospital. At home she was fed breast milk but, even with adequate volumes grew poorly. She was admitted to our hospital at 26 days of age with severe failure to thrive and a history of diarrhea and occasional emesis. Serum albumin levels during this admission ranged from 13 – 17 g/L (normal range 32 – 48 g/L). When she was switched to a hypo-allergenic formula, she started gaining weight and was discharged with a provisional diagnosis of cow’s milk protein allergy. She presented again at 51 days of age with significant ascites, generalized edema and severe hypoalbuminemia with a serum albumin level of 10 g/L. The remainder of her examination was unremarkable. Large volume, non-bloody diarrhea had continued to be a problem throughout the time at home despite the change in formula.
Her investigations included a normal CBC with normal lymphocytic count, normal liver enzymes, normal bilirubin, low serum transferrin, low serum immunoglobulins and normal thyroglobulin. Her stools were negative for fat globules and reducing substances. However, 24 hour-stool collection had a markedly elevated alpha-1-antitrypsin level of 576 mg/g (normal <54 mg/g) indicative of protein losing enteropathy. Esophagogastroduodenoscopy and sigmoidoscopy were performed and did not reveal any obvious abnormalities. Biopsies taken at the same time were also unremarkable by both light and electron microscopy. A small bowel contrast study showed thickening and nodularity in several segments of the small bowel suggestive of segmental intestinal lymphangiectasia. Treatment during her admission included multiple albumin infusions and eventually a switch to a medium chain triglyceride (MCT) containing formula. She responded very well with resolution of vomiting and diarrhea. At discharge, the ascites had resolved as had most of the edema and she was gaining weight appropriately. At her last clinical assessment she was 27 months of age and her albumin levels were maintained at 25-30 g/L on a MCT rich-diet. With the resolution of the facial edema evident in hospital she was non-dysmorphic based on the assessments of two experienced dysmorphologists (B.C. and C.R.G) and there was absence of distichiasis. Her height, weight, and occipitofrontal circumference were all between the 50th and 75th percentiles. Her hands and feet continued to be mildly edematous despite control of her albumin levels. Her development was considered normal with age appropriate verbal and motor skills and no social concerns or abnormal behaviors. Her development was assessed on the Bayley scales of infant and toddler development, 3rd edition (Bayley III) and showed a Cognitive Composite at the 25th centile, a Language Composite at the 34th centile and a Motor Composite at the 50th centile.
Her family history was significant for consanguinity with her parents being first cousins of Pakistani descent. There was an older healthy male sibling. A maternal aunt had an undiagnosed disorder which included corneal clouding and she died at 13 years of age. Genetic investigations in our patient were initiated early on in the course of her hospitalization and included a normal transferrin isoelectric focusing, normal plasma amino acids, normal urine organic acids and normal urine mucopolysaccharides. Her karyotype was 46,XX and an array CGH was done which identified an ~100 kb deletion on chromosome 15q11.2 that encompasses exon u1b of SNRPN (within the Prader-Willi / Angelman critical region). This was felt to be an incidental finding as it was inherited from her normal father and there was no overlap of her symptoms with classic Prader-Willi syndrome.
An autosomal recessive lymphatic dysplasia was strongly suspected given the consanguinity. In order to identify the causative mutation, we used a combination of SNP genotyping and exome sequencing. The nuclear family was genotyped using Illumina Human Omni 2.5 SNP arrays at the Centre for Applied Genomics, Toronto, Canada. Twenty-seven regions of homozygosity containing >1000 SNPs were evident in the patient sample and ranged in size from 0.9-37.5 Mb. Segregation analysis was used to rule out some of these regions, leaving ~183 Mb of sequence that appeared to be identical by descent (IBD) but not present in the unaffected brother. Exome sequencing was performed on the affected patient as described for previous FORGE projects []. Mean Consensus Coding Sequence (CCDS) coverage was 132X with 93% of bases covered by at least 20 reads. Approximately 180,000 moderate to high quality variants were identified in the sample. Using the regions of IBD and other filters consistent with our genetic model, we were able to narrow the candidates down to 5 possibilities (Fig. ). The most likely candidate, based on previous functional data, was a homozygous missense variant in CCBE1 (c.294 T > G, p.C98W [NM_133459]). This variant segregates in the family with both parents being carriers (Fig. ). This variant is rare (not found in dbSNP or the NHBLI exome server) and affects a highly conserved amino acid found within the EGF calcium-binding domain. Orthologs from 38/39 species, ranging from placental mammals to fish, show conservation of this residue suggesting functional importance (Fig. ).
Collagen- and calcium-binding domain 1 (CCBE1) is a signaling molecule essential for lymphangiogenesis in humans and model organisms. Initial description of CCBE1 function came from a zebrafish mutant, full of fluid (fof), identified on a forward genetic screen []. These fish had an absence of truncal lymphatic vessels, including the thoracic duct, and developed significant edema. The cause for this zebrafish mutant was determined to be a missense mutation within the CCBE1 EGF domain (p.D162E) suggesting this protein was essential for appropriate lymphangiogenesis. Creation of a knockout mouse allowed further elucidation of the function of CCBE1 []. CCBE1 knockout mice died prenatally with progressive edema beginning at E13.5 onward and lacked all detectable lymphatic vessels. The protein was found to be excreted and bound to the extracellular matrix, acting as a potentiating factor of VEGF-C in lymphatic budding and outgrowth.
Mutations in the CCBE1 gene have been found in patients with Hennekam syndrome of varying severity. Our patient appears to represent the mildest of this phenotypic spectrum. Certainly, the mutation identified in her (p.C98W) is similar to missense mutations that have been identified in other Hennekam patients (eg. p.C47F, p.C75S, p.C102S, p.R158C, p.C174R, and p.C174Y) [, ]. All of these mutations affect cysteine residues within the EGF domain and given the disulfide linkages within EGF domains, it is reasonable to assume all of them will disrupt the tertiary structure of the domain to a certain degree. Three of these previously reported mutations (p.C75S, p.C102S, and p.C174R) were studied further and had reduced ability to rescue zebrafish ccbe1 knockdown morphants, confirming their pathogenicity []. Further functional work is needed to determine if the p.C98W allele is the reason for her milder phenotype or whether there are alternate genetic or environmental factors at play.
The outstanding issue in this case is the preaxial polydactyly of her hands. No other individuals in the family have polydactyly (either currently or treated at birth like our patient). This anomaly has never been seen in CCBE1-related disease nor has it been associated with the clinical entity of Hennekam syndrome to our knowledge. Postaxial polydactyly has been reported to be associated with intestinal lymphangiectasia in Urioste syndrome, however, this clinical entity also includes hepatic failure, persistence of the Mullerian ducts in males and all reported patients have died within 1 year of age [–]. The underlying cause of Urioste syndrome remains unknown but it does seem unlikely to be associated with mutation in CCBE1 given the lack of any Mullerian abnormalities or hepatic failure in the known CCBE1 patients []. It is possible that the polydactyly in our patient is unrelated to the lymphatic disorder. We did review her molecular data for other variants that could independently cause polydactyly via a candidate gene approach but we were unsuccessful. At this point it is unclear whether this feature is related to her CCBE1 mutation or not.


The patient is a 58 year-old Japanese male presented with a rapidly progressive history of a swelling on his left cheek and restricted mouth opening. He had no history of HIV infection, multiple myeloma or underlying immunosuppression. Physical examination showed a bleeding tumor of the oral cavity. The laboratory findings on admission were: hemoglobin 10.9 g/dL, white blood cell count 11.4×109/L, platelet 197×109/L serum lactate dehydrogenase (LDH) 2232 U/L (normal value: 119–229), serum creatinine 1.68 mg/dL (normal value: 0.6–1.1), serum uric acid 12.7 mg/dL (normal value: 3.6–8.0), serum potassium 4.9 mg/dL (normal value: 3.6–4.9), serum phosphorus 6.2 mg/dL (normal value: 2.5–4.7), serum calcium 11.3 mg/dL (normal value: 8.7–10.3). Serum IgG, IgM, and IgA levels were within the normal range. Serum protein electrophoresis had no M-spike. Serology for HIV was negative. There were no osteolytic lesions on bone survey. A computed tomography (CT) demonstrated a bulky tumor localized in the mucosa of the oral cavity (Fig. ), without enlargement of the systemic lymph nodes. Biopsy of the oral mass showed diffuse proliferation of large lymphoid cells (Fig. ) with centroblastic morphology, which were positive for CD138 (Fig. ), CD38 (Fig. ), CD56, and MUM-1 (Fig. ) and negative for CD20 (Fig. ), CD79a (Fig. ), CD3 and BCL-6. EBV-encoded RNA in situ hybridization (EBER-ISH) (Fig. ) and HHV8 (Fig. ) were negative. The Ki-67 proliferation index was almost 100 % (Fig. ). No apparent plasmacytic differentiation of the tumor cells was observed. G-banding analysis of the tumor showed abnormal karyotypes: 46, X, −Y, dup(1)(q42q21), −6, +7, +7, −8, add(14)(q32), add(20)(p11.2), +mar/ 82<3n>, XX,-Y, dup(1)×2, −4, +5, +6, +6, +7, +7, +7, +7, +7, −8, −8, +9, +9, +11, add(14)×2, +15, +5mar. Although no lymphoma cells were found in his peripheral blood, bone marrow examination showed infiltration of large atypical lymphoid cells, suggesting bone marrow involvement. The patient was diagnosed with stage IVA PBL.
Immediately after diagnosis, the patient was treated with THP-COP composed of pirarubicin, cyclophosphamide, vincristine and prednisolone. Since pirarubicin (THP) has been reported to have comparable efficacy to doxorubicin with a lower incidence of cardiac toxicity in aggressive non-Hodgkin lymphoma treatment, THP-COP therapy was used []. Intravenous hydration and allopurinol also started.
Despite the prompt treatment, the oral tumor continued to enlarge, with increasing risk of suffocation. Therefore, bortezomib was started on day 9 of admission. Bortezomib was given at a dose of 1.3 mg/m2 on days 1, 8 and 15 without dexamethasone in the first cycle. In the second cycle, the patient was treated with bortezomib in combination with dexamethasone. One week after the initiation of bortezomib, a marked regression of the oral tumor was observed, and one month after its initiation, no significant swelling of the oral cavity was detected (Fig. ). Serum LDH levels also rapidly improved. However, since resistance to bortezomib developed after the third cycle of bortezomib, the patient was salvaged with EPOCH and irradiation. He had disease-progression and died five months post-diagnosis.


We report a case of 30-year-old fit and well Asian (Indian ethnicity) woman in her second pregnancy, with a BMI of 26. The couple were nonconsanguineous.
In the current pregnancy, her 11–14 weeks' scan revealed no major structural abnormalities in the fetus and the risk for Down syndrome was low (1 : 50000) on combined screening. A routine anomaly scan at 20 weeks was also reported as normal. She was diagnosed with gestational diabetes at 16 weeks that was diet controlled and was offered serial growth scans from 28 weeks. A growth scan at 29 weeks showed reduced growth, and in view of this the woman was referred to the Fetal Medicine Unit. Scan performed by the fetal medicine specialist showed borderline bilateral ventriculomegaly, absent corpus callosum, and absent cavum septum pellucidum. The amniotic fluid volume was mildly reduced. All the other systems appeared normal (). The couple were counselled regarding the possibility of genetic or chromosomal causes, and they opted for an amniocentesis. A fetal MRI was also organised for further assessment of the brain. Microarray result indicated a copy number loss for the short arm of chromosome 11 with break points between 11p12 and 11p14.1. Deletion of this region indicates WAGR 11p13 deletion syndrome.
Another detailed ultrasound scan was performed before the late termination. In addition to the above findings, large kidneys visualised. Measurements of both kidneys' volumes were above the 97th centile for gestational age. There was no evidence of hydronephrosis ().


An African American male in his 50s presented with increased shortness of breath, dyspnea on exertion, and orthopnea. He has a past medical history of coronary artery disease with multiple myocardial infarctions and two coronary stents placed in 2003 and two additional coronary stents placed two months prior to his admission. He had a history of systolic heart failure with a left ventricle ejection fraction of 20%. In the emergency department atrial fibrillation with rapid ventricular rate was noted with a heart rate of 140. A diltiazem infusion was started and he was admitted to the Cardiac Intensive Care Unit. Repeat echocardiogram several days later showed progressive worsening of his ischemic cardiomyopathy with an ejection fraction of 18%. He was started on inotropic support and underwent placement of an intra-aortic balloon pump (IABP) to assist with hemodynamic stability. Approximately 24 hours later the patient had an episode of melena associated with a drop in his hemoglobin from 10.1 to 7.7. He was started on proton pump inhibitor infusion. He underwent emergent esophagogastroduodenoscopy which showed erythema and erosions in the gastric fundus compatible with gastritis as well as grade 1 reflux esophagitis but no evidence of active bleeding. A Helicobacter pylori stool antigen was found to be negative. A colonoscopy was performed after hemodynamic stabilization for further evaluation of melena and pretransplant screen. This was positive for abnormal vascularity, congestion, nodularity, erosions, erythema, and ulceration in the cecum and ascending colon suggestive of ischemic colitis which was later confirmed by biopsy (). Given the unusual involvement of nonwatershed areas such as the cecum and ascending colon, a CT of the abdomen and pelvis with contrast was performed to evaluate the celiac and mesenteric vasculature. There was no significant narrowing of either vessel noted on the CT; however the inferior metallic marker of the IABP was found to be inferior to the origin of the superior mesenteric artery (). Findings were consistent with ischemic colitis of the cecum and ascending colon as visualized on colonoscopy from occlusion caused by the IABP. The IABP was repositioned and the patient's melena resolved.


An 83-year-old woman visits our hospital with complaint of a one-week history of worsening lower back pain. She felt lower back pain 3 months ago, occasionally radiating along right leg. She had taken medication for hypertension, diabetes mellitus, and dyslipidemia for several years. She underwent abdominal ultrasonography in our hospital 8 and 3 years ago, and she was suspected to have mild and moderate fatty liver, respectively. She denied alcohol drinking and cigarettes smoking for her entire life. Her family history was uneventful. She admitted for further evaluation.
On admission, her blood pressure was 140/90 mmHg. Height and body weight were 149 cm and 47.3 kg, respectively. Body mass index was 25.8 kg/m2. In physical examination, there was direct tenderness on sternum, right ribs, and thoracic and lumbar spine. Hypoesthesia on L4/5 dermatome was noted. At left occiput, a 3 cm-sized, fixed, and round mass was palpated without tenderness. She said that it seemed to be felt about 3 months ago. Breath sound was clear without adventitious sound, and heart beat was regular without murmur. There were no abnormal findings in abdomen. There was no palpable lymph node. The remaining examinations are unremarkable.
In laboratory examinations, total leukocyte count was 7,440/mm3, the level of hemoglobin was 11.3 g/dL, and platelet count was 245,000/mm3. In chemistry battery, creatinine was 1.2 mg/dL, uric acid was 5.5 mg/dL, total protein was 7.0 g/dL, albumin was 3.9 g/dL, AST was 38 IU/L, AST was 26 IU/L, total bilirubin was 0.2 mg/dL, alkaline phosphatase was 135 IU/L, and serum total calcium was 9.0 mg/dL. In lipid battery, total cholesterol was 130 mg/dL, triglyceride was 75 mg/dL, HDL cholesterol was 40 mg/dL, LDL cholesterol was 82 mg/dL, and HbA1c was 6.2%. In serologic test, hepatitis B surface antigen, hepatitis B core antibody, and hepatitis C antibody were negative; and hepatitis B surface antibody was positive. Serology for HIV and syphilis were negative.
In whole spine magnetic resonance image (MRI), 3 cm-sized metastatic lesions were revealed in T12 and L5 body to right pedicle, respectively. Also, small nodular lesions at T3, 9, 10, and 3 cm-sized occipital lesion were observed. To find primary cancer, chest computed tomography (chest CT) and abdominopelvic CT (AP-CT) were performed. In chest CT, multiple bone metastases were shown in sternum, right clavicle, right 11th rib, and thoracic spines. However, there was no abnormal finding to suspect primary cancer. In AP-CT, small round nodule was observed in liver segment 8, which was measured by 2.5 cm, showing faint arterial enhancement and delayed washout (). Also, moderate degree of fatty liver was suspected concordantly with her previous findings in ultrasonography. However, there were no features of cirrhosis such as surface nodularity, ascites, or splenomegaly. Also, there was right ovarian cystic tumor without mural nodules or calcification. It was measured by 3 cm compared to 1.4 cm 8 years ago. Liver MRI and α-fetoprotein (AFP) were checked due to the typical enhancing pattern observed in AP-CT. Carbohydrate antigen 125 (CA-125) also was checked due to right ovarian cystic tumor despite the fact that it did not show hot-uptake in PET-CT. In liver MRI, hepatic mass (<3 cm) showed low signal intensity on T1WI, high signal intensity on T2WI, diffusion restriction positive, arterial enhancement, delay washout, and defect on hepatobiliary phase in segment 8 (). The level of AFP was elevated to 12230 ng/mL, and the level of CA-125 was in normal range. HCC was identified; however, it was a small solitary HCC with T2 intrahepatic stage in modified International Union Against Cancer (UICC) staging system. There was no other intrahepatic metastasis. Because the liver lesion or ovarian lesion was too small to conclude it as the primary cancer of the disseminated bone metastases, further evaluation with positron emission tomography-computed tomography (PET-CT) was planned. PET-CT image showed fluorodeoxyglucose (18F-FDG) hot-uptakes in hepatic segment 8 (max standardized uptake value: 3.7), multiple bone metastases at right scapula, sternum, cervix—thoracic—lumbar vertebrae, bilateral ribs, left occipital bone, and right mandible. However, no other abnormal 18F-FDG uptakes were shown except liver and bone lesions. No lung metastasis and lymph node metastasis were suspected.
Because it is very unusual clinical finding that the diffuse and extensive musculoskeletal metastases were derived from small solitary HCC or ovarian cystic mass, we planned tissue biopsy at bone metastatic site to confirm the primary cancer. Brain MRI was taken to biopsy at occipital mass; brain MRI showed lobulating, enhancing skull mass in left occiput (3.5 × 2.5 cm), with destruction of bone and intracranial extension (). Incisional biopsy from occiput mass was done, and it revealed metastatic HCC with Edmondson Steiner grade 4/4 (). Finally, HCC with multiple bone metastases, modified UICC T2N0M1, IV-B stage was diagnosed. The patient needs two times of resuture due to the wound dehiscence at the incision site.
After diagnosis, the cause of HCC was searched again. However, antinuclear antibody, anti-neutrophil cytoplasmic antibody, anti-liver kidney microsomal antibody, anti-mitochondrial antibody, anti-smooth muscle antibody were all negative findings. Immunoglobulin G was in normal range (1461 mg/dL), serum ceruloplasmin was 32.7 mg/dL, and ferritin was 79.24 ng/mL. Although there was a suspicion of fatty liver and associated NAFLD, we did not perform liver biopsy because the patient would not have additional benefit from it.
With regard to the advanced stage and patient's poor performance status, conservative treatment with radiation therapy on L5 (39 Gy in 13 fractions) was done. After 1 month from the completion of radiotherapy, she complained of right chest pain and increased occipital mass, additional radiotherapy on metastatic lesion of left occiput and right 11th rib was done. After 3 months from then, PET-CT was reevaluated due to the aggravating lower back pain. Although there was little change in primary cancer in hepatic segment 8, the previous bone metastases were aggravated significantly and multiple new bone metastatic lesions were developed. She wanted supportive care and was transferred to hospice.


A 50-year-old man presented in 2008 with a backache. X-rays and MRI showed multiple lytic bone lesions of the spine and pelvis. He also had renal involvement and anemia while calcemia and LDH were within the reference ranges (see ).
Serum electrophoresis revealed a monoclonal protein, which was identified by immunofixation electrophoresis (IFE) as IgD lambda associated with monoclonal lambda FLC. IgD was quantified at 7600 mg/L (radial immunodiffusion, Bindarid IgD, The Binding Site) and FLCs were measured at 3590 mg/L (Freelite assay, Immunonephelometer Immage 800, Beckman Coulter). Urinary IFE revealed monoclonal lambda FLCs. A bone marrow aspirate showed the presence of 35% dysmorphic plasma cells. Therefore the diagnosis of IgD multiple myeloma (MM) was made (ISS stage III). FISH analysis did not reveal 13q14 nor 17p deletions. The search for translocation t(4;14) was inconclusive.
The patient was enrolled in the clinical trial IFM 2007-02 (). A 4-cycle treatment associating Bortezomib and Dexamethasone was initiated followed by high dose therapy with Melphalan 200 mg/m2 followed by autologous stem cell transplantation in February 2009.
The patient achieved a very good partial response (VGPR) with a serum M-protein undetectable on IFE but monoclonal lambda FLCs were still detectable on urinary IFE. During this period, serum lambda FLC and IgD were within the normal range ( and ).
The patient relapsed in December 2010 as he presented with a skull vault tumor. IgD was quantified at 204 mg/L and FLCs were measured at 779 mg/L. Patient started on radiotherapy plus high dose Dexamethasone. In May 2011, while on therapy, the patient presented with epiduritis and spinal cord compression. IFE identified monoclonal lambda FLC, which was quantified at 6330 mg/L (). A treatment associating methylprednisolone, radiotherapy followed by 3 cycles of dexamethasone cyclophosphamide etoposide cisplatin was initiated. The patient died in August 2011 of MM progression.


An 80-year-old female presented with a pT1c (1.3 cm) pN0 (two negative sentinel nodes), Grade 2, lobular carcinoma of the upper inner quadrant of the left breast detected incidentally on a CT scan for follow-up of colitis. Estrogen receptor status were 6/8, progesterone receptors 6/8 (both using the Allred scale), and the HER-2 gene was not over-expressed [-]. The lateral and posterior margins were < 1 mm. Co-morbidities included a 25-year history of colitis not associated with inflammatory bowel disease, hypertension, hypothyroidism, and osteopenia. Our patient had a diagnostic CT scan of the chest six months before RT with no radiographic evidence of pre-existing lung disease.
Informed patient consent was obtained prior to treatment. No reference to the patient's identity is present in this paper.
She declined endocrine therapy and was treated with RT to the left breast using a deep inspiration breath hold technique (DIBH) commencing 10 weeks after surgery. The radiation dose was 42.5 Gy in 16 fractions using a mixed 6 and 15 MV photon tangent pair, followed by a boost of 10 Gy in four fractions using 6 MeV electrons. The mean lung dose (MLD) was 4.32 Gy and the volumes of ipsilateral lung receiving ≥ 5 Gy, ≥ 20 Gy, and ≥ 30 Gy were 17%, 7%, and 6%, respectively (Figure ). She developed brisk erythema of the skin overlying the axillary tail, but otherwise, the treatment course was uneventful. She started 3 mg of budesonide (an orally administered corticosteroid) daily for colitis seven weeks following completion of RT. She discontinued the corticosteroid after 4.5 weeks without a tapering schedule.
Commencing 11.5 weeks after completion of RT (15 weeks from the start of RT) she noticed increasing fatigue, exertional dyspnea, fever, and cough. Two chest x-rays at 13.5 and 15.5 weeks from the completion of RT both confirmed left-sided consolidation favouring either pneumonia or a radiation reaction (Figure ). Treatment with appropriate antibiotics failed to resolve her symptoms, which progressed over the next two weeks. On examination, moist rales were appreciated over the anterior left chest. She was not short of breath at rest. A repeat CT simulation scan using DIBH was performed in the treatment position to compare the consolidation location with the original treatment plan. The repeat CT scan was merged with the treatment planning CT, and the dosimetry and treatment fields were imported onto the new CT scan. The CT demonstrated consolidation in the anterolateral aspect of the left lung, which extended slightly above where the radiation volume projected onto the chest wall and terminated inferiorly at the lower field edge (Figure ).
Two certified medical physicists independently reviewed the treatment plan and delivery parameters and confirmed that treatment delivery was as intended. The radiographic appearance, along the tangential irradiated fields and the time interval from RT, favoured RP rather than cryptogenic organizing pneumonia (COP). She started 40 mg of prednisone daily with prompt improvement in symptoms over one week. The dose of prednisone was tapered by 5 mg every six days. A chest x-ray completed four weeks after commencing prednisone showed significant improvement with some persistent airspace consolidation (Figure ).


This patient was a 17-year-old boy who developed facial erythema and calcinosis around the left knee and femoral region at the age of 15 in 2001. He had undergone extensive resection of subcutaneous calcinosis within the year. In January 2003, he was referred to our hospital because of pain in the right knee and femoral region and skin rash on the face, the anterior chest, and the upper limbs. Physical examination revealed erythema of the forehead and buccal region, a V sign, a shawl sign, nail bed angiitis, and Gottron's papules. Although limb muscle weakness and elevation of muscle enzymes were slight, juvenile dermatomyositis was diagnosed because plain and contrast-enhanced MRI of the right femoral region revealed muscular atrophy, increased signal intensity on fat-suppression T2-weighted images, and enhancement by Gd-DTPA. There was prominent induration due to subcutaneous calcinosis around the right knee and femoral region, and the range of knee joint motion was limited.
To treat juvenile dermatomyositis, administration of prednisolone was started at a dose of 20 mg/day. Then azathioprine was added at a dose of 100 mg/day for skin ulcers that developed during prednisolone treatment. Cimetidine was also administered for his subcutaneous calcinosis. Although his erythema, skin ulcers, and muscular symptoms tended to improve with these medications, the range of knee joint motion was still restricted and this interfered with his daily activities. In September 2009, CT scans of the lower limbs revealed extensive tumorous/nodular and diffuse lesions of calcinosis in the subcutaneous tissue and muscles extending from the thigh to the knee joint in both lower limbs ().
Accordingly, intermittent, high-dose treatment with etidronate was added for the calcinosis. Etidronate was administered at a dose of 800 mg/day for 3 months and then was discontinued for 6 months, with this intermittent treatment schedule being continued over 5 years. As a result, induration of the lower limb due to calcinosis resolved gradually, and the range of knee joint motion also increased. In August 2014, repeat CT of the lower limbs revealed a dramatic decrease of subcutaneous and muscular calcinosis ().
At present (March 2015), the patient has no disturbance of daily activities. There have been no appreciable adverse reactions to etidronate therapy. The dose of prednisolone has been decreased to 5 mg/day and azathioprine has been discontinued without aggravation of skin or muscular symptoms.


Tibial lateral plateau fracture was detected after the results of anteroposterior and lateral direct radiographs of the 20-year-old male patient admitted to our emergency department with the complaints of pain and not being able to weigh on his right knee after falling down the stairs. Then, surgical treatment was planned on the case after seeing an isolated fracture in his tibial lateral plateau posterior and a step-off of about 7 mm in the examination of his computed tomography (CT) scan ().
As the second case, a lateral tibial plateau fracture was detected after radiological examinations in a 26-year-old female patient admitted with complaints of pain and not being able to weigh on her left knee after falling down the stairs. It is seen in the CT examination that the fracture extends in both the sagittal and coronal plane and a collapse occurs in posterior ().
Following spinal anesthesia, prophylactic antibiotics were administered in both cases. Following the pneumatic tourniquet application, while in the prone position, an approximately 8 cm incision was applied lateral to the midline longitudinally. Lateral head of the gastrocnemius muscle was passed as a split with blunt dissection. Removing the popliteus muscle, posterior plateau was reached. Collapsed articular surface is removed with the help of the osteotome and step-off was corrected. Then, posterior cortex which was lifted like a cover was reduced and fixed with temporary K-wire. After scopy control, the 3.5 mm titanium locking the posteromedial plate (Truemed, Istanbul, Turkey) has been fixed to posterior (). In the second case, additionally, the fracture in the sagittal plane was fixed with a screw from lateral to medial. Posterior capsule and lateral meniscus posterior were repaired. Layers were closed in anatomic plan by one hemovac drain.
After being held in a long leg plaster splint for a week postoperatively, the articular was allowed to be moved at the beginning of the second week. Partial weight onto the leg was allowed in 10 weeks postoperatively and in 12 weeks, full weigh was allowed. The unions maintained were seen in the follow-up of the patients (Figures and ). Any complications were not observed.
In the final examination, it was observed that the first patient in 18 months and the second patient in 12 months could be able to walk unsupported and without hitching, with the absence of pain and stabile knees. In both cases, it was detected that the extension was full (0°) and the flexion was 140° in the first case and 130° in the second case ().


Case 10 was a 4-year-old boy who presented with laceration at lip commissure (). Suturing was done under local anesthesia at the initial appointment. Wound gaped on the 2nd postoperative day. Cyanoacrylate was then used to glue the lacerated margin (), but again wound gaping was seen the next day. Cyanoacrylate was reapplied to the lacerated margins and dressing was given to protect the lacerated site. Wound later healed () without complications.
Summary. Marginal seal/wound seal was acceptable as the incised margins were in close apposition with each other. Inflammation and edema were not present in maximum number of cases at the 15th postoperative day. One case of pus discharge was recorded after 15 days of surgery and one case of wound dehiscence was noted and gluing of the collagen membrane to the surgical site was not successful.


A 69-year-old man visited our hospital because of persistent melena and hematuria. Thirty years before, he had undergone radical cystectomy with bilateral ureterosigmoidostomy for high-grade urothelial carcinoma of the urinary bladder. Colonoscopy showed a tumor at the site of the right ureter-colon anastomosis, which was managed by endoscopic mucosal resection and histologically confirmed as adenocarcinoma. He had no known genetic predisposition for colorectal and urothelial carcinoma.
Seven years later, follow-up colonoscopy detected a tumor of the left ureterocolonic anastomosis. Computed tomography (CT) demonstrated invasive colonic cancer and left hydronephrosis. He underwent temporal left percutaneous nephrostomy followed by sigmoidectomy and left ureterocutaneostomy. The tumor was located around the anastomotic site, and it was undetermined whether the tumor had originated from either the colon or the ureter ().
Eighteen months after the operation, the patient complained of pain and induration in his left back. CT showed a 2 cm mass in the left renal pelvis and a soft tissue mass posterior to the kidney along the former nephrostomy tract without distant metastasis (). We performed left nephroureterectomy and resection of the nephrostomy tract tumor with reconstructive latissimus dorsi musculocutaneous flap. Both the renal pelvic tumor and nephrostomy tract tumor were diagnosed as adenocarcinoma. The ureter was also involved by adenocarcinoma as multiple exophytic lesions as well as adenocarcinoma in situ. The tumors of both ureterocolonic anastomotic sites, the left renal pelvis, nephrostomy tract, and the left ureter were of indistinguishable histological appearance. All these tumors showed a similar immunophenotype: positive for cytokeratin 7, negative for cytokeratin 20, partially positive for CDX-2, positive for p53, and negative for β-catenin nuclear accumulation (). Three months later, metastasis in lung, paraaortic nodes, and local recurrence were identified on CT. The patient died six months after the operation.


An 18-year-old man was referred to our hospital with acute onset of painless obstructive jaundice, nausea, fatigue, loss of appetite, and icterus but no fever or past history of similar complaints.
Laboratory tests revealed the following results (values in parentheses indicate normal range): white blood cell count 5270/mm3 (3500–9700/mm3), hemoglobin 14.5 g/dL (13.6–18.3 g/dL), hematocrit 43.2 % (40.4–51.9 %), platelet count 295,000/mm3 (140,000–379,000/mm3), aspartate aminotransferase 214 IU/L (0–40 IU/L), alanine aminotransferase 314 IU/L (5–45 IU/L), alkaline phosphatase 2367 IU/L (104–338 IU/L), total bilirubin 8.1 mg/dL (0.3–1.2 mg/dL), direct bilirubin 6.0 mg/dL (0–0.4 mg/dL), amylase 74 U/L (39–134 U/L), total protein 8.1 g/dL (6.5–8.2 g/dL), albumin 4.4 g/dL (3.7–5.5 g/dL), and urine bilirubin 3+ (negative). Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) levels were within normal limits as was the serum IgG4 (40 mg/dL; range, 4–108 mg/dL) and IgG (1055 mg/dL; range, 820–1740 mg/dL) levels.
Contrast-enhanced computed tomography (CT) revealed abnormal thickening of the gallbladder wall, which appeared to invade the adjacent portion of the liver. Other imaging findings included an infiltrative low-density mass (30 mm; with mild enhancement in the arterial and delayed phases) involving the gallbladder neck, upper biliary tract, and hilar bile duct as well as intrahepatic bile duct dilatation. The pancreas was not enlarged (Fig. ). Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) revealed an infiltrative mass involving the gallbladder neck, upper biliary tract, and hilar bile duct with high-signal intensity on diffusion-weighted imaging. Furthermore, there was a sharp-beaked stenosis with an upstream dilatation of the hilar bile duct. The main pancreatic duct appeared normal without any malfusion of pancreaticobiliary ducts (Fig. ). Endoscopic retrograde cholangiopancreatography (ERCP) revealed a bile duct stricture similar to that observed on MRI; for this, both the intrahepatic bile ducts were dilated and a plastic stent was placed (Fig. ). An endoscopic ultrasound revealed a heterogeneous hypoechoic tumor measuring 9.3 × 7.3 mm2. Doppler ultrasonography of the abdomen revealed a hypoechoic lesion of the gallbladder that showed good vascularity and direct hepatic invasion as well as intrahepatic bile duct dilatation. Exfoliative cytology of the bile duct revealed inflammatory cells without atypia. Positron emission tomography (PET)-CT was not performed. As a malignancy could not be ruled out, surgical resection was proposed. First, we decided to perform right hemihepatectomy with caudate lobectomy. However, we chose extended cholecystectomy and intrahepatic cholangiojejunostomy because we found a benign region for intraoperative consultation. We had to resect the common bile duct because the inflammation of the gallbladder was severe and had spread to the common bile duct.
Gross pathologic examination of the surgical specimen (a 4.5-cm mass) revealed invasion of the gallbladder and hilum of the liver; the liver was depressed by the mass but not invaded (Fig. ). Histopathological examination revealed diffuse lymphoplasmacytic infiltration and dense fibrosis and a diffuse fibrohistiocytic inflammatory pseudotumor of the gallbladder (Fig. ). Obliterative phlebitis, eosinophilic and neutrophilic infiltration, and some xanthogranulomatous inflammation were also observed (Fig. ). No histologic signs of malignancy were detected; however, storiform fibrosis and lymphoplasmacytic infiltration were present. Immunohistochemical staining for IgG4 showed the IgG4/plasma cell ratio was 10–40 % and many IgG4-positive plasma cells (maximum density, 50 per high-power field) (Fig. ). The mucous membrane of the common bile duct was normal. As the histological findings were highly suggestive of IgG4-related disease, the patient was diagnosed with IgG4-related cholecystitis.
The postoperative course was uneventful, there was no added steroid therapy, and the patient was discharged 17 days after the surgery without any additional treatment. At the 1-year follow-up, the patient had no symptoms or signs of the disease.
In recent years, IgG4-related sclerosing disease has become an increasingly intriguing clinicopathologic entity. The pathology involves diffuse or focal organ enlargement and mass-forming or thickening lesions, caused by heavy infiltration of IgG4-positive plasma cells and lymphocytes with fibrosis [–], in various organs, with resultant autoimmune pancreatitis, sclerosing cholangitis, cholecystitis, sialadenitis, retroperitoneal fibrosis, inflammatory aortic aneurysm, or inflammatory pseudotumors. However, the exact pathogenesis and pathophysiology of IgG4-related sclerosing disease remains unclear. As a malignancy is frequently suspected on the basis of clinical symptoms and radiologic findings in such cases, IgG4-related sclerosing disease should be included as a differential diagnosis. In the present case, diseases contributing to stenosis of the bile duct included cholangiocarcinoma, infiltration of the bile duct by gallbladder cancer, PSC, IgG4-related sclerosing disease, ischemic bile duct stenosis, and an amputation neuroma. In most cases, the diagnosis is easily established; however, a preoperative diagnosis is difficult to establish in a few patients.
Diagnostic criteria for IgG4-related sclerosing disease were published by Deshpande et al. [] wherein the three major histopathological features reported to be associated with IgG4-related sclerosing disease are dense lymphoplasmacytic infiltration and fibrosis, arranged at least focally in a storiform pattern, and obliterative phlebitis. Other histopathological features associated with IgG4-related sclerosing disease include phlebitis without obliteration of the lumen and eosinophilia. Minimal criteria for IgG4-related sclerosing disease in a new organ/site are characteristic histopathological findings with elevated IgG4 plasma cell numbers, increased IgG4/IgG ratio that is considered characteristic [], high serum IgG4 levels, quick response to steroid therapy, and reports of multiorgan involvement consistent with IgG4-related sclerosing disease (Table ). On histopathology of surgical specimen, 50 or more IgG4 plasma cells per high-power field and an IgG4/IgG plasma cell ratio greater than 40 % are highly suggestive of IgG4-related sclerosing disease [].
Most IgG4-related sclerosing diseases are associated with autoimmune pancreatitis (AIP) [], which was not the case in our patient. This case was unique in that the patient was considerably younger and had IgG4-related cholecystitis mimicking gallbladder cancer with a normal IgG4 concentration. Normal serum IgG4 levels in IgG4-related sclerosing disease have been reported only in a few articles [, , ], and the sensitivity and specificity of serum IgG4 for IgG4-related SC is reported to be 50 and 60 %, respectively []. In cases with suspected IgG4-related cholecystitis, other benign gallbladder diseases such as xanthogranulomatous cholecystitis etc., gallbladder cancer should be a differential diagnosis. Therefore, serum IgG4 should be assessed. However, serum IgG4 and the IgG4/IgG ratio were normal in this case, and without the associated AIP, a preoperative diagnosis was very difficult and a histopathological diagnosis was necessary for a definitive diagnosis. Bile cytology indicated no malignancy in this patient. However, bile cytology is often normal in cholangiocarcinoma. We tried endoscopic ultrasonography fine-needle aspiration (EUS-FNA). However, we did not succeed. EUS-FNA was useful for diagnosing IgG4-related sclerosing disease. In AIP, EUS-FNA provided tissue samples adequate for histopathological evaluation and greatly contributed to the histological diagnosis []. We did not perform other pathological examinations because the patient was developing worse obstructive jaundice rapidly in a short time. In general, other diagnostic approaches include biopsies of the gallbladder, bile duct, and liver. A previous study suggested that biopsies of the gallbladder, bile duct, and liver are useful for diagnosing IgG4-related cholecystitis [–]. Biopsies of the bile duct and gallbladder, although technically difficult, could provide the full spectrum of morphologic changes. In general, fibroinflammatory involvement is mainly observed in the submucosa of the gallbladder and bile duct wall, whereas the epithelium of these structures was intact in the present case. Cytological examinations were often useful in establishing a differential diagnosis of gallbladder cancer, although it was difficult to obtain biopsy samples adequate for establishing characteristic histopathological findings of IgG4-related cholecystitis []. Liver biopsies have the lowest diagnostic potential, although sometimes useful in the diagnosis of IgG4-related cholecystitis in cases of intrahepatic bile duct involvement []. Therefore, we thought EUS-FNA or biopsy was useful for a differential diagnosis between gallbladder cancer and IgG4-related cholecystitis. We did not conduct other pathologic examinations in the present case because of the technical difficulty involved in performing a biopsy as well as the inadequacy of the tumor mass required for a biopsy. The quality of biopsy samples depends on the experience of the endoscopists undertaking the procedure; moreover, biopsy samples were sometimes small or had artificial degeneration. We did not perform PET in the present case as a report of PET that revealed an elevated standardized uptake value, associated with malignant tumor, has been published previously [] and was not considered beneficial to establish a differential diagnosis.
In view of all of these aspects, establishing a preoperative diagnosis of IgG4-related cholecystitis was possible but highly challenging and it was too difficult to determine whether surgical intervention was actually necessary in this case. This patient was developing worse obstructive jaundice rapidly in a short time. We did not perform both PET and EUS-FNA. In this case, a preoperative diagnosis was difficult. We could not assess the benign region (xanthogranulomatous cholecystitis or IgG4-related cholecystitis) or cancer; therefore, we decided to perform operation and intraoperative consultation. Although there is much to be understood with regard to IgG4-related cholecystitis, it is conceivable that a trial of steroid therapy may be warranted if this disease entity is suspected before surgery. A poor response to steroid therapy should indicate the possibility of a diagnosis of gallbladder cancer with a need for re-evaluating the diagnosis. Thus far, there are several reasons why a definitive preoperative diagnosis cannot be established in such a case. Moreover, because malignant tumors were frequently suspected under these conditions, surgical intervention should be undertaken after due deliberation.
At present in Japan, there are no reports describing a presentation of IgG4-related cholecystitis without AIP. Herein, we report the first case in the literature of a young man with only IgG4-related cholecystitis and normal serum IgG4 concentrations.
In 2010, Leise et al. reported a case of an ill-defined tumor (6 cm) in the liver hilum that appeared to surround the gallbladder, which was established to be IgG4-related cholecystitis on examination of the surgical specimen []. In 2005, Gumbs et al. reported the appearance of synchronous tumors in the pancreatic head and gallbladder that were preoperatively diagnosed as pancreatic ductal adenocarcinoma and gallbladder cancer []. Postoperative histopathological examination established AIP with IgG4-related cholecystitis. Some other cases reported IgG4-related cholecystitis mimicking gallbladder cancer [–, , ] (Table ). A few cases of synchronous autoimmune pancreatitis and pancreatic ductal adenocarcinoma have also been reported [, ]. In addition, one report describes epithelial atypia in the common bile duct in the presence of bile duct involvement in autoimmune pancreatocholangitis []. Previous reports have reported IgG4-SC occurring with cholangiocarcinoma, but no reports of IgG4-related cholecystitis with gallbladder cancer exist so far. We intend to continue the follow-up of the present case in the outpatient setting.
In conclusion, we reported the case of a young man with only IgG4-related cholecystitis and normal serum IgG4 concentrations. It was important for preoperative differential diagnosis of IgG4-related cholecystitis from other benign diseases and gallbladder cancer. When we could not diagnose IgG4-related cholecystitis by usual examination, we performed additional examinations. Although we did not succeed, we concluded that EUS-FNA was useful for differential diagnosis. Nevertheless, preoperative diagnosis may be difficult. In that case, operation and intraoperative consultation should be considered.


A 68-year-old lady with End Stage Kidney Disease (ESKD) secondary to IgA nephropathy had been established on maintenance hemodialysis for three years via a tunneled central venous dialysis catheter. She presented with fever after a routine dialysis session having had a change of tunneled dialysis catheter due to a split in the catheter 6 weeks before. She had no focal symptoms such as dysuria or productive cough to indicate an alternative source of infection. Other medical history included type 2 diabetes mellitus, hypothyroidism, and an aortic tissue valve replacement for severe aortic stenosis two months previously. This was complicated by complete heart block and a pacemaker inserted. She was a nonsmoker and did not drink alcohol. Medications were simvastatin and levothyroxine. On physical examination, the patient was febrile with temperature 38.2°C, blood pressure 112/72 mmHg, heart rate 105 beats/min, respiratory rate 20 breaths/min, and oxygen saturations 99% on air. Her chest was clear on auscultation, jugular venous pressure was not raised, and cardiac heart sounds were heard with a grade 2 apical pansystolic murmur. She had pitting sacral edema, but no splinter hemorrhages, Roth's spots, or Janeway lesions.
Laboratory tests showed albumin 3 g/dL, hemoglobin 8.4 g/dL, white blood cell count 3.7 × 103/μL, platelets 86 × 103/μL, and C-reactive protein 126 mg/L. Urine culture displayed mixed growth without pyuria. An electrocardiogram showed sinus rhythm, and a plain chest radiograph confirmed a right tunnelled central venous dialysis catheter and left pacemaker wire in situ, but no other abnormalities. Central and peripheral blood cultures were positive with Staphylococcus aureus sensitive to vancomycin, gentamicin, and rifampicin.
Dialysis catheter associated infection with possible infective endocarditis was the presumed diagnosis and therefore the central venous dialysis catheter was removed under local anesthetic. The patient then underwent a 2D transesophageal echocardiogram that demonstrated normal heart valves but showed a large thrombus at the superior vena cava/right atrial junction with some protrusion into the right atrial cavity and in proximity to her pacing wire. It was not possible to delineate the spatial relationship of the thrombus to the pacemaker wire because the ultrasound image can only depict a sector, originating from the rotation axis of the transducer (). It was therefore not clear whether the infection and/or thrombus was caused by or involved the pacing wire. This is a vital consideration as there would be increased technical difficulty and risk of thrombus dislodgement for pacemaker removal if the thrombus was entangled with the pacemaker wire. Therefore, using the same echocardiography machine and with selection of the 3D function (echocardiography machine, Philips IE 33 x MATRIX; Transducer: X5-1; 3D analysis software: QLAB 9), 3D images were acquired (). These images clearly demonstrated the tracts of the pacemaker wires (2 pacing leads: right atrial and right ventricular leads) and showed that the venous thrombosis was separate from the wires.
A diagnosis of infected venous thrombosis without involvement of pacemaker wire was therefore reliably made. This meant that there was no need for further invasive investigation and also that no inappropriate, high-risk attempts to remove and replace the pacing wire were undertaken.
The patient received sensitivity-specific antibiotics for 4 weeks and was commenced on peritoneal dialysis. She was warfarinized to an international normalized ratio target of 2.5 intended for lifelong treatment. Her fever settled and she was discharged without the need for pacemaker removal.


This 39-year-old achondroplastic dwarf man was admitted with a 9-month history of progressive weakness of all his extremities following an insignificant fall from the stairs. Before this event, his developmental landmarks and intelligence had been normal. On examination, an incontinent and bedridden dwarf even dependent in feeding was noticed. His general weakness was graded 1/5 on the right and 0/5 on the left. His tendon reflexes were increased with bilateral extensor planter responses. MRI which was done as the first diagnostic method showed an os odontoideum with marked forward displacement of C1 in relation to C2 resulting in severe stenosis at cervicomedullary junction, accompanied with a hyperintense signal in T2-weighted images indicating myelopathy (). Lateral dynamic cervical radiographs taken two months after the fall revealed atlantoaxial dislocation with marked instability, a large head with small posterior fossa also noted (). Axial and reconstructed CT images demonstrated dysplastic os odontoideum accompanied with anterior dislocation of C1 on C2. Forward extension of the posterior edge of foramen magnum and mild hypertrophy of the opisthion were also noted (Figures and ).
Surgery with atlantoaxial posterior instrumentation was decided. Subsequent to placement of screws in lateral mass of atlas, C2 pedicle was inserted on the right side. But on the left side, because of overriding vertebral artery translaminar screw was done. Later, after C1 arch laminectomy, the rods were placed and the nuts were tightened in extension. Optimal alignment could be achieved confirmed with fluoroscopy (). However, because of the faint dural pulsation at the scene and constriction of the dura by the posterior lip of occiput as well as the presence of several dense fibrous bands, a limited suboccipital craniectomy and division of the fibrous bands were accomplished. This additional procedure was followed with significant expansion of the dura and good pulsation ().
Postoperative course was uneventful and was followed by steady neurological recovery of the patient. Plain radiographs revealed proper reduction of atlantoaxial dislocation (Figures , , and ). Reconstructed CT angiography revealed optimal alignment of the atlas on axis, accuracy of decompression, and hopefully the integrity of the arteries of posterior circulation which we were worried about (). MR images done two months after surgery revealed successful alignment and decompression of the cervicomedullary region (). Now 18 months postoperatively, the patient has shown fair recovery. Now, the force on the right side is 3/5 and 1/5 on the left. He can feed himself with a spoon and is able to stand and walk a few steps with walker.


A 65-year-old man presented with escalating dull pain to the left flank and lower back for 2 days. In addition, he experienced abdominal pain just before the admission. Surgical history included a mechanical aortic valve replacement 6 months ago. The patient was taking a vitamin K antagonist. He reported no history of trauma for several months prior to admission. There was no familial tendency toward bleeding. On admission, his heart rate was 110 beats per minute with sinus rhythm and blood pressure was 110/70 mmHg.
Ecchymotic lesion was noted on his left flank and he experienced tenderness of the left flank and left lower quadrant of the abdomen. There was no rebound tenderness though the patient expressed that the pain worsened when bending over. The results of laboratory test revealed decreased hematocrit level at 23.8 % and prolonged international normalized ratio of prothrombin time at 5.25. The platelet count was within normal range.
Abdominal computed tomography (CT) was performed to evaluate the abdominal and left flank pain and revealed a large hematoma of the left iliopsoas muscle and extravasation of contrast material. Hemoperitoneum was also revealed though the amount was minimal (Fig. ). The patient continued to have abdominal pain and follow-up hematocrit level dropped to 21.5 %. Fresh frozen plasma was infused and an emergent lumbar arterial angiogram was performed for hemostasis. There was active bleeding on the left 5th lumbar arterial branch. Transarterial embolization (TAE) was successfully performed (Fig. ).
On day 5 of hospitalization, follow-up abdominal CT was performed. It revealed decrease in the size of the hematoma in the left iliopsoas muscle. However, a new small hematoma was detected in the right iliopsoas muscle (Fig. ). Close observation was the plan of care for this finding as it was not large enough to cause symptoms. Furthermore, there was no extravasation of contrast media in the right iliopsoas hematoma. Follow-up abdominal CT was performed on day 12 of hospitalization and showed decrease in the size of two retroperitoneal hematomas that had become more liquefied. The hemoperitoneum was no longer evident (Fig. ). Fortunately, the patient did not experience worsening symptoms associated with the hematoma and the hematocrit concentration was constant without the need for additional transfusion during hospitalization.
We adjusted prothrombin time international normalized ratio from 2.0 to 2.5 and he was discharged without complications.
Iliopsoas hematoma has been reported to occur mainly in relation to trauma; however, spontaneous iliopsoas hematoma has been reported in patients with coagulation problems, such as hemophilia, liver cirrhosis, and anticoagulants-related incidents [–].
The mechanism of spontaneous iliopsoas hematoma is unclear, but tearing of muscle fibers, small vessel atherosclerosis, heparin-induced immune microangiopathy, and unrecognized minor trauma are generally accepted etiologies [, ]. The exact mechanism of the bilateral iliopsoas hematoma is more difficult to determine, as in this case, it could be assumed that the unilateral hematoma occurs first and the opposite later. Although it is unlikely that muscle tearing would occur at the same time, if the patient were to use the contralateral leg to relieve ipsilateral leg pain, muscle tearing is a possible explanation for the etiology of spontaneous bilateral iliopsoas hematoma.
Iliopsoas hematoma has a variety of clinical manifestations. The most common symptom is sudden onset of lower back and flank pain. Patients also describe using leg flexion to try to relieve pain on the involved side (psoas sign). They may also present with ecchymotic lesions on the affected flank, the so-called Grey Turner’s sign, which is a result of massive retroperitoneal hematomas, as with our patient. A large amount bleeding may cause hypovolemic shock and abdominal compartment syndrome []. Iliopsoas hematomas have also been associated with compressive femoral neuropathy, because the nerve can be compressed anywhere along its course. Femoral neuropathy and motor weakness of the lower extremity, develops in almost all patients [, , ].
There is no clear strategy for treatment of iliopsoas hematoma yet, and a variable treatment plan may be used according to the patient’s condition. Close monitoring is required when administering anticoagulants to prevent the possibility of complications occurring as a result of anticoagulant overuse []. However, despite conservative management, if fatal complications occur—such as femoral neuropathy, hypovolemic symptom or abdominal compartment syndrome—aggressive surgical intervention should be considered [, ].
Although TAE is safer, faster, and less invasive than surgical intervention for controlling active bleeding, the hematoma cannot be evacuated in this manner. Therefore, surgical intervention should be considered preferentially when femoral neuropathy or abdominal compartment syndrome develops due to mass effect of the large hematoma [, , ]. Our patient underwent TAE for two reasons. First, he needed immediate hemostasis because he was exhibiting hypovolemic signs that led to the development of femoral neuropathy or abdominal compartment syndrome. Second, the bleeding had to be controlled in order to reinitiate the anticoagulant therapy for preventing prosthetic valvular thrombi. The newly developed right iliopsoas hematoma that occurred during the hospital stay was managed with conservative treatment because it was small and the patient was asymptomatic.