A 33-year-old Asian pregnant woman para 2, gravida 3, gestational age of 25 weeks, was hospitalized with fever, chills, shortness of breath, and myalgia. She had her first baby delivered by vaginal delivery 5 years ago and her second by cesarean section 2 years ago. The patient had no underlying diseases and did not have direct contact with COVID-19 cases. Vital signs of the patient were recorded as follows: respiratory rate (RR) 26 breaths per minute, blood pressure (BP) 110/70 mmHg, temperature (T) 39.5 °C, heart rate (HR) 110 beats per minute, and oxygen saturation (SpO2) 94%. The laboratory results showed that lymphocyte count was lower than normal (lymphocyte count 1 × 109/L). While platelet count, hepatic enzymes, and creatinine levels were within the normal range, C-reactive protein level (CRP) was significantly increased. Coagulation function and blood biochemistry were normal (Table). A GeneXpert SARS-CoV-2 RNA polymerase chain reaction (PCR) test was performed, and the result was positive. The patient had no complaints about uterine contractions, hemorrhage, and symptoms of amniorrhexis. Bilateral involvement was detected on chest computed tomography (CT), and on lung auscultation, diminished breath sound was detected. A day after the hospitalization, the patient was transferred to the intensive care unit (ICU) because of the shortness of breath (RR 32 breaths per minute) and low oxygen saturation (SpO2 88%). CT chest on the second day of hospitalization revealed an exacerbation of pulmonary involvement. The patient was intubated 1 week after hospitalization owing to a reduction in the oxygen saturation to 80% and exacerbation of respiratory distress. Chest CT on the eighth day of hospitalization showed extensive bilateral diffuse infiltrates and deterioration of lung involvement (Fig. ). From the beginning of hospitalization, despite the use of broad-spectrum antibiotic coverage, the patient’s fever was intermittent.
One week after transferring to the ICU and due to the patient’s deteriorating condition, plasmapheresis was performed twice with 10 units of fresh frozen plasma (FFP) for the patient, which did not improve her condition. Also, due to a decrease in hemoglobin (HB 8.1 g/dl), two units of packed cells were transfused twice. Three weeks after hospitalization, ultrasounds were performed several times to assess fetal growth, and a sharp decrease in the amniotic fluid (amniotic fluid index 2.5 cm) and fetal growth retardation were observed. To rule out the possibility of a preterm ruptured membrane, an AmniSure test was performed twice, which was negative both times. Due to the condition of the fetus and the exacerbation of the patient’s respiratory condition, it was decided in the committee constituting of specialists in the special care and departments of lung and perinatology that the pregnancy should be terminated to improve the patient’s respiratory condition. Therefore, to induce cervical ripening, an intracervical Foley catheter was placed and extra-amniotic saline infusion was performed. After receiving three doses of vaginal misoprostol at doses of 50, 100, and 200 μg every 6 hours, a 600 g baby was born with a 1-minute Apgar score of 2 and a 5-minute Apgar score of 4, and the fetal heart rate was 145 beats per minute. The newborn was intubated and transferred to the neonatal intensive care unit (NICU) and died after 12 hours.
One week after the termination of pregnancy, due to the observation of bilateral pleural effusion on the chest CT, a chest tube was installed on both sides. Since no improvement in lung condition was observed and complete destruction of lung tissue was detected, the patient died 1 month after hospitalization.


A 63-year-old Caucasian male patient was referred to hematological investigation because of eosinophilia.
His medical history was unremarkable except for post-infectious glomerulonephritis in childhood and flushing episodes that started one year before the hematological evaluation. No pathological findings were reported at physical examination. Previous blood tests revealed a gradual increase of absolute eosinophils count over two years. Recent laboratory examinations showed white blood count (WBC) 8.2x109/L with absolute eosinophil count 2.2x109/L (27%), serum tryptase level 26 ng/mL (normal level <5 ng/mL), normal serum lactate dehydrogenase (LDH), and normal liver and renal function.
A bone marrow biopsy detected 60% of cellularity, with myeloid hyperplasia, increased eosinophils and reticulin, and the presence of multifocal clusters of spindle-shaped MCs co-expressing CD25 and CD2 (>15 cells). Karyotype analysis was normal. Polymerase chain reaction (PCR) detected the D816V KIT mutation on bone marrow (variant allele frequency – VAF - 0.01%), while the FIP1L1-PDGFRA fusion transcript was absent.
Overall, these findings were consistent with a diagnosis of SM for the presence of the major criterion (BM MCs infiltrates) and 3 minor criteria (aberrant MCs, KIT D816V mutation, tryptase level >20 ng/mL). Abdominal ultrasound showed normal liver and spleen dimensions and an absence of lymphadenopathy. Dual-energy X-ray absorptiometry scan detected osteoporosis (lumbar T score -3.3, lumbar Z-score -2.6, femoral neck T-score -1.5, femoral neck Z-score -0.5).
In the absence of ‘B’ and ‘C’ findings, we concluded with an indolent form of SM. The patient did not receive specific therapy other than osteoporosis treatment.
Two years later the patient complained of a worsening of flushing and a recurrent headache. Blood examinations revealed an increase of WBC (13x109/L) with an absolute eosinophil count of 5.1 x 109/L. Suspecting a myeloid neoplasm with eosinophilia, a new bone marrow evaluation was performed. The histological analysis confirmed myeloid hyperplasia with a marked increase of eosinophils and 3% of MCs in rare aggregates. Aspirate smear revealed 36% of eosinophils and 6% of MCs. No aberrant MCs were detected with flow cytometry. Cytogenetic analysis showed normal male karyotype and a digital PCR was negative for KIT D816V mutation. Real-time PCR performed on peripheral blood detected the FIP1L1-PDGFRA fusion transcript and serum tryptase was 20 ng/ml. Thus, the final diagnosis was myeloid neoplasm with PDGFRA rearrangement.
Imatinib 100 mg daily was started, and after 3 months all symptoms resolved and blood tests showed WBC 5.96x109/L with normal eosinophil count (0.09x109/L).
BM analysis revealed the absence of eosinophils and the presence of rare MCs with normal morphology, corresponding to 4% of cellularity at the aspirate smear. Flow cytometry showed a normal MCs phenotype. FIP1L1-PDGFRA and KIT D816V mutations were negative on BM and peripheral blood.
A subsequent BM analysis, performed after 12 months of imatinib treatment, confirmed complete remission of the myeloid neoplasm, absence of aberrant MCs, and negative FIP1L1-PDGFRA and KIT D816V mutations.
and report the main hematological findings at diagnosis of SM, diagnosis of myeloid neoplasm with PDGFRA rearrangement, and after 3, 6, and 12 months of imatinib treatment.


A 44-year-old woman presented to another hospital with a few hours’ history of severe epigastric pain radiating to the back, accompanied by nausea. Her past medical history was significant for psoriatic arthritis treated with infliximab biosimilar (Inflectra®) for the past two years. The last infliximab biosimilar (Inflectra®) infusion had been 15 days prior to presentation. At that time, due to a severe arthritis flare, the patient also received a single dose 500 mg of IV methylprednisolone, with instructions to complete a 10-day course of oral prednisolone, 30 mg per day with gradual decrease of the dose.
Her vital signs were normal. Abdominal examination revealed tenderness to deep palpation in the epigastrium, without guarding or rebound. The remainder of the clinical examination, including skin and nervous system, was unremarkable. Laboratory tests showed lymphopenia (1,000/μL) and mild anemia (13.6 g/dL). The rest of the blood tests, including liver enzymes and serum and urine amylase, were within normal range. A chest radiograph was normal. Abdominal computed tomography (CT) reported periarterial fat stranding and possible dissection of the superior mesenteric artery (SMA) () and the patient was transferred to our hospital for further evaluation and treatment.
On presentation, CT images were reviewed, findings were considered equivocal, and a new contrast-enhanced abdominal CT scan with an angiographic arterial phase was performed. Perivascular fat stranding was noted as the single abnormal finding while the arteries were found patent without evidence of dissection (). Due to isolated periarterial fat stranding, the possible diagnosis of visceral VZ was raised and the patient was admitted to hospital for further evaluation. On a subsequent further review of patient’s medical history, it was found that she had been diagnosed with varicella during her childhood. On the second day of hospitalization, a skin eruption without blistering emerged on the patient’s back (). Varicella-zoster virus DNA was detected by polymerase chain reaction (PCR) in the serum and the diagnosis of visceral HZ was established. The patient received 4 days of intravenous acyclovir and was discharged with an additional 10-day course of oral valacyclovir. On her follow-up visits, two and ten weeks later, the pain and the rash had subsided, and the patient was in a good health condition in general.


A 58-year-old female, 22 months after resection of giant cell tumor of the left distal radius and allogeneic bone transplantation. 22 months ago, due to a giant cell tumor of the distal radius on the left side (Fig. A), the patient underwent giant cell tumor resection and allogeneic bone transplantation (Fig. B) in the department of oncology. 5 months later, fractures and collapses of the distal radius and dislocation of the radiocarpal joint occurred (Fig. C); 6 months after the operation, another operation was performed with the ulna shortened, the radiocarpal joint reduced, and the external fixator and Kirschner wires were fixed (Fig. D); 22 months after the operation, further fracture collapsed and radio-carpal joint dislocated again, which made her to our department. The patient presented with severe deformity, accompanied by moderate pain, and extremely poor grip and pinching power of the affected limb (Fig. A, 2B, 2C).
X-rays showed that the distal radius was absorbed and collapsed, the palm of the wrist was dislocated to the radial side, and the distal ulna was protruding, close to the skin (Fig. E).
The patient was treated with surgery under brachial plexus anesthesia. During the surgery, the allograft bone and the lunate were removed and the capitate was trimmed with a groove, the cartilage surface and subchondral bone of the distal ulna were resected, matching with the groove of the capitate, and fixed by a straight plate and screws (Wrist fusion plate- straight, RFP-STR, TriMed, Inc) (Fig. F).
The follow-up was 15 months. Bone healing was achieved at 4 months after surgery, and the wrist dorsal extension angle was fixed 10°. At the last follow-up, the patient's pain symptoms were basically relieved, and the grip and pinch strength of the affected limb were significantly restored (Fig. D, 2E, 2F). The patient was satisfied with the improvement in appearance and function (Tables and ).
Informed consent was obtained from the patient for the purpose of publication.


An 18-year-old male, 6 months after resection of the left distal radius osteosarcoma and implantation of the artificial prosthesis. 6 months ago, due to osteosarcoma of the left distal radius, the patient underwent osteosarcoma resection and three-dimensional printed prosthesis implantation in the department of oncology. Radio-carpal joint dislocation began 3 months later, and life was seriously affected 6 months after surgery. The patient had severe radial palmar flexion deformity, accompanied by mild pain, and extremely poor grip and pinching power (Fig. A).
X-rays showed that the radiocarpal joint was completely dislocated, the distal end shifted to the radio-volar side. The joints had completely lost their involute relationship (Fig. B).
The operation was performed in the same way, and the follow-up was 13 months. Bone healing was achieved 3 months after the operation, and the wrist dorsal extension angle was fixed 10°. At the last follow-up, there was no discomfort in the affected limb, and the grip and pinch strength were significantly restored (Fig. C, 3D). The patient was also satisfied with the improvement in appearance and function (Tables and ).
Informed consent was obtained from the patient as well for the purpose of publication. This study was approved by our institutional ethics board (Beijing Jishuitan Hospital Institutional Review Board


A 40-year-old gentleman presented with a history of progressive lower back pain and circumferential right leg pain. Over a period of one week, the pain developed into higher low back pain along with bilateral lower extremity weakness and increasing difficulty with balance. Previously, a magnetic resonance imaging (MRI) of his thoracolumbar spine demonstrated an intradural, extramedullary mass in the T11 to T12 intradural region.
A repeat MRI was performed due to the new onset bladder incontinence. Upon further review of his most recent imaging, the lesion was located at T12-L1, no longer as high as T11 (Figure ).
Informed consent was acquired for the study. The patient was then taken to the operating room for surgical excision of the lesion. An intraoperative ultrasound confirmed the intradural location and the resection went without untoward events (Figure ).
Pathology was consistent with a schwannoma. Ultimately, the patient had an unremarkable hospital stay and was discharged to an acute rehabilitation facility.


The patient was a 63-year-old man with HS, idiopathic aortic bileaflet, and subaortic aneurysm (SAA) caused by infective endocarditis. The SAA was incidentally discovered during a clinical evaluation for aortic regurgitation (AR); this was due to idiopathic aortic bileaflet and infective endocarditis that were diagnosed 10 years ago. Because of the patient’s HS history and severe anemia, a cardiologist conducted the medical follow-up. The patient’s LV systolic function worsened gradually and he had frequent episodes of dyspnea. Moreover, transapical echocardiography showed a decrease in the AR grading. On admission, the hemoglobin level was 8.7 mg/dL, hematocrit was 23.8 %, platelet count was 18.2 × 104/μL, blood urea nitrogen was 15.1 mg/dL, and creatinine was 0.93 mg/dL. The physical examination revealed an anemic and icteric conjunctiva, and his skin appeared jaundiced. The laboratory findings of the patient’s blood smear revealed a type 1 + polychromasia.
The transthoracic echocardiogram showed a bicuspid aortic valve (adhesions on the left and right coronary cusps), a 10-mm SAA prolapsing at the atrio-ventricular continuity, an ascending aorta measuring 38 mm, and a grade IV central AR (Fig. ). The left ventricular ejection fraction was preserved. The computer tomography angiography revealed a right coronary sinus aneurysm in the sagittal and axial plane.
A surgical intervention was indicated because of severe AR due to the bicuspid aortic valve, moderate dilation of ascending aorta, and SAA. The procedure was performed through a median sternotomy. A CPB was instituted by ascending aortic cannulation and bicaval drainage. Left atrial venting was carried out from the right upper pulmonary vein. Cardioplegia was performed by selective antegrade and retrograde perfusion with blood Frem’s solution and cold blood. Before initiating the CPB, we transfused four units of RBCs (hemoglobin of 12.1 mg/dL). Furthermore, human haptoglobin was also transfused.
At the time of the CPB, the centrifuge pump was selected rather than the roller pump, and perfusion index was 2.5 L/m2/min. First, the epicardial membrane was used for the repair of the SAA (Figs. and ). Second, aortic valve replacement was performed by using the biological valve (Magna EASE 21 mm, Carpentier-Edwards, Japan). Third, an ascending aorta replacement was performed under moderate hypothermia and cross-clamping condition. The aortic cross-clamp time was 182 min, and CPB time was 234 min. The urine remained clear throughout and after CPB, indicating that no significant hemolysis had occurred during the procedure. The patient was extubated on day 1, and all the vasoactive infusions were discontinued on day 3 postoperatively.
Despite the 1.5 L RBC transfusion during the operation, the immediate postoperative blood smear did not show any spherocytes and other abnormal RBC morphologies. Postoperative bleeding was minimal, and further RBC transfusions were performed on day 4 and 14 postoperatively.
The echocardiography showed no residual AR, and the patient was discharged from the hospital on day 18 without any hemolysis. At the 6-month follow-up, he was doing well. Recent echocardiography showed no residual AR, and good left ventricular function. Hematogenic investigation showed the hemoglobin level to be maintained at 10.6 g/dL without any transfusion. The total bilirubin and lactate dehydrogenase levels were 3.9 mg/dL, and 303 IU/L, respectively (Table ).


A 43-year-old woman presented with severe anaemia secondary to menorrhagia. She was symptomatic of dizziness, shortness of breath on exertion, and worsening fatigue. She reported having increasingly heavy and painful periods for 2 years, requiring 5-6 pads per day. She had regular 30-day cycles, and her periods lasted 5-6 days. She had previously tried oral contraceptive pills (OCP) but had experienced headaches with their use and hence had ceased them. She was a nonsmoker and had had one vaginal delivery 16 years ago.
On examination, she was found to be tachycardic but normotensive. She had a soft nontender abdomen. Her uterus was enlarged and palpable and corresponded to 16 weeks' gestation. On vaginal examination, there was a mass felt in the pouch of Douglas. Her cervix appeared normal.
Her haemoglobin was 55 g/L. Pelvic ultrasound showed an intramural posterior fundal fibroid measuring 9.3 × 9.1 × 10.8 cm. Endometrial thickness was 3 mm.
After initial resuscitation with IV fluids and 3 units of packed red blood cells, she underwent a hysteroscopy, which showed the fibroid distorting the endometrial cavity, precluding endometrial biopsy and Mirena® device placement. As she was initially hesitant to have a hysterectomy, medical management was instituted with tranexamic acid and a different OCP than that used previously, with good effect.
Fifteen months later, she presented again on day 2 of her periods after a syncopal episode at home. She had a postural drop in her blood pressure (99 mmHg to 76 mmHg systolic from lying to standing). She was admitted for observation and given tranexamic acid to stop her bleeding. Her haemoglobin dropped from 89 g/L to 65 g/L during that admission. She was again counselled regarding permanent methods of management of menorrhagia and consented to a hysterectomy.
While awaiting her hysterectomy, she went on a long road trip and presented again with left leg swelling and tightness. She denied chest pain or shortness of breath. Circumferential measurements of her legs supported the diagnosis of a deep vein thrombosis (DVT) ().
Doppler ultrasound of the left limb showed an extensive deep vein thrombosis involving the iliac, femoral, popliteal, posterior tibial, and gastrocnemius veins (). The uterine fibroid was found to be compressing the left common iliac vein.
She was commenced on warfarin for anticoagulation but presented again with menorrhagia and was found to be severely anaemic and overanticoagulated. Her haemoglobin was 54 g/L and INR 6.6. She was stabilized with multiple blood transfusions and reversal of anticoagulation. After consultation with a haematologist, her warfarin was ceased in favour of enoxaparin. She underwent fluoroscopy-guided inferior vena cava (IVC) filter insertion () prior to a total abdominal hysterectomy and bilateral salpingectomy. Significant endometriosis was an unexpected incidental intraoperative finding.
Histology confirmed a benign leiomyoma measuring 14 × 9 cm with foci of red degeneration and minor adenomyosis (). The uterus weighed 1490 g.
The patient was restarted on enoxaparin 6 hours postoperatively and underwent removal of the IVC filter a few weeks after the hysterectomy.


The patient is a 54-year-old female who presented in September 2014 with headache, visual disturbance and right-sided facial weakness. There were no associated fevers or weight loss. Her past medical history included MG diagnosed in 1998 when she presented with ptosis and dysarthria. A thymoma was diagnosed and resected in 2003 but she subsequently developed pulmonary metastasis in 2011 and was treated with radiotherapy and chemotherapy including adriamycin, cisplatin and cyclophosphamide. Her past history also included hypertension, dyslipidaemia and a previous history of smoking. Of relevance, our patient contracted primary varicella zoster at the age of three months and had three episodes of herpes zoster (shingles) in her fifth decade. Medications on admission were: mycophenolate mofetil (MMF) 1 g PO BD, pyridostigmine 90 mg PO BD, prednisolone 12 mg PO OD, monthly intravenous immunoglobulin (IVIG) at a dose of 0.4 mg/kg for MG, atorvastatin 40 mg PO nocte, telmisartan 20 mg PO OD, multivitamin, calcium and cholecalciferol 1000 IU PO OD.
Blood tests on admission are shown in Table . Of note there was a normal leukocyte count of 7.9 × 109 with low lymphocytes 0.7 × 109/L and monocytes 0.1 × 109/L. A CT brain showed an irregular contrast enhancing lesion within the left frontal lobe with moderate associated vasogenic odema. A subsequent MRI confirmed the solitary solid/cystic rim-enhancing lesion in the left posterior frontal lobe with moderate vasogenic odema resulting in a 3.5 cm midline shift (Fig. ). In the setting of known metastatic thymoma this was thought to be most consistent with an intracranial metastasis. The patient underwent stereotactic left frontal craniotomy and excisional biopsy which showed toxoplasmosis on the basis of histopathology and polymerase chain reaction.
The patient commenced induction therapy for toxoplasmosis with sulfadiazine 1 g PO QID, pyrimethamine 75 mg PO OD and calcium folinate 15 mg OD according to local guidelines []. Her prednisone was increased to 25 mg PO OD and nystatin 1 ml PO QID was prescribed for oral candidiasis. She was discharged with a plan for 6 weeks induction course of anti-toxoplasma treatment and outpatient appointments with Neurology, Infectious Diseases and Neurosurgery. At review 3 weeks post-discharge, she complained of nausea, thought to be secondary to the sulfadiazine. Her medications were reduced to sulfadiazine 500 mg PO QID and pyrimethamine 50 mg PO OD.
Four weeks after initial presentation she underwent an MRI brain for post-neurosurgical follow-up. This revealed multiple new miliary lesions in the cerebral hemispheres bilaterally, which were predominantly cortical but with involvement of central grey structures including the right lentiform nucleus and thalamus (Fig. ). These lesions were not present on the initial MRI and were thought to represent disseminated toxoplasma. The patient was recommenced on sulfadiazine 1 g PO QID and pyrimethamine was maintained on 50 mg PO OD. Immunological review followed.
Further immunological investigations included flow cytometric evaluation of lymphocyte subsets which showed a CD4+ T-cell lymphopenia and complete absence of B-cells (see Table ). Serum immunoglobulin levels showed normal IgG levels (consistent with replacement IVIG), low IgM and undetectable IgE and IgD. Although complicated by immunosuppression with MMF and treatment with IVIG, it was concluded that the lack of B-cells, serum immunoglobulins suggestive of an underlying hypogammaglobulinemia, and T-cell immunodeficiency as demonstrated by toxoplasma infection were all consistent with a diagnosis of TWI/Good’s Syndrome. The patient received a total of 12 weeks at induction level therapy for cerebral toxoplasmosis with sulfadiazine 1 g PO QID and pyrimethamine 50 mg PO OD. Following this the treatment was reduced to maintenance phase with sulfadiazine 1 g PO BD and pyrimethamine 25 mg OD.
In February 2014, four and a half months after the initial presentation and 4 weeks after the second reduction in medications, the patient presented with acute onset nausea, headache and loss of consciousness. A CT of the brain showed a new ring-enhancing lesion in the right temporal lobe. An MRI of the brain confirmed the ring enhancing lesion in the right temporal lobe and the diffuse miliary nodules present in the previous MRI (Fig. ). These signs were considered to be consistent with persistent and progressive cerebral toxoplasmosis. She was recommenced on the induction dose of sulfadiazine 1 g PO QID and pyrimethamine 75 mg in addition to treatment intensification with atovaquone 750 mg PO BD. A cryptococcal antigen was negative as was HIV antigen/antibody screening. A CT of the chest showed stable anterior mediastinal and right sided pleural disease extending to the thoracic vertebrae exit foramen at the 9/10 level, with no evidence of new metastases (Fig. ).
Two weeks following discharge a decision was made to withhold the MMF in order to promote cell-mediated immunity to the toxoplasma. Lymphocyte subsets repeated on multiple occasions consistently showed a complete absence of B-cells with fluctuating levels of CD4+ T-cells with a range 280–1100 × 109/L. At the time of writing the patient remains stable on induction-dose sulfadiazine and pyrimethamine together with atovaquone therapy for toxoplasmosis, with MMF being withheld. The measureable cerebral lesions have reduced in size on MRI assessment and the miliary lesions have resolved. Her MG is stable and there have been no signs of progression of her metastatic thymoma. She is receiving localised radiotherapy to prevent nerve root and/or spinal cord compression at the thoracic 9/10 level, and continues to attend regular Neurology, Infectious Disease and Immunology outpatient clinics.


A 44-year-old Japanese man was referred to our hospital complaining of a large tumor that had been accidentally pointed out in a medical examination as being an esophageal submucosal tumor. Relevant family history brought to light that his father had been diagnosed as having MEN1. Our patient had undergone total parathyroidectomy and autologous transplantation for primary hyperparathyroidism at the age of 18. His height and weight were 187 cm and 120 kg, respectively, with a body mass index of 34 kg/m2 on admission. He also complained of sleep apnea and bilateral nipple discharge. He was not aware of the hypoglycemic symptoms before the admission, but he frequently encountered the symptoms under nutritional management after the admission. Laboratory data of blood chemistry were normal as well as the tumor markers, such as carcinoembryonic antigen and carbohydrate antigen 19-9, whereas neuron specific γ-enolase was high (19.1 ng/ml). Hormonal examinations revealed a hypoglycemia, a hyperinsulinemia (fasting serum glucose, insulin levels, and hemoglobin A1c, 76 mg/dl, 134.5 μU/ml, and 4.5 %, respectively), a hyperprolactinemia (serum prolactin level 871.2 ng/ml), and elevated urinary catecholamines. On an enhanced thin-slice abdominal computed tomography (CT), a large tumor was detected in the pancreatic tail, showing heterogeneous enhancement with partial calcification and cystic components. Its maximum diameter was about 18 cm (Fig., ). Other than a pancreatic tail tumor, six enhanced liver tumors, a right adrenal tumor (3.9 cm in diameter), and a left adrenal tumor (2.6 cm in diameter) were found (Fig. , ). The right adrenal tumor was heterogeneously enhanced. An endoscopic ultrasonography (EUS) revealed four tumors in the body and tail of the pancreas, except for the giant tumor, and abundant blood flow in all these tumors. Immunohistochemical examinations of a EUS-guided fine-needle aspiration biopsy showed that the giant pancreatic tumor and liver tumors were positive for chromogranin A, synaptophysin, and CD56; thus, the tumors were diagnosed as being a pancreatic neuroendocrine tumor (NET) and its liver metastases. They were NET G1 as the labeling index of Ki67 was 1.8 %. A calcium gluconate injection into the distal splenic artery during a selective intra-arterial calcium injection test resulted in a marked increase in serum insulin and C-peptide. Both 123I-metaiodobenzylguanidine scintigraphy and 131I-adosterol scintigraphy showed high radioactivity in the right adrenal tumor and no radioactivity in the left one. The left adrenal tumor was therefore diagnosed as having a non-functional adenoma. A magnetic resonance imaging (MRI) identified a heterogeneous pituitary adenoma, 3.1 cm in diameter.
His pedigree diagram is shown in Fig. . Five patients with MEN1, including our patient who has an MEN1 gene mutation, were identified within his family. Furthermore, the genetic examination revealed a deletion mutation (g.249_252delGTCT) at codons 83–84 in exon 2. He underwent distal pancreatectomy, splenectomy, cholecystectomy, right adrenalectomy, abdominal subcutaneous tumor excision, and cutaneous tumor biopsy for the purpose of tumor volume reduction. Six tumors in the resected pancreas were diagnosed as being pancreatic NETs. The giant tumor in the pancreatic tail was insulinoma, and NET G2 as the Ki67 labeling index was 4.2 % (Fig. ). Of the other five lesions, two tumors consisted of the insulin-positive tumor cells with less than 0.1 % of the Ki67 index, and three tumors consisted of the glucagon-positive tumor cells with less than 0.1 % of the Ki67 index. These tumors were diagnosed as being non-functional NET G1 because no symptom due to a glucagon excess was encountered. A non-functional adrenal cortical adenoma, measuring 1.3 cm in maximum diameter, and a pheochromocytoma, measuring 4.7 cm in maximum diameter, coexisted in the right adrenal gland (Fig. ). The abdominal subcutaneous tumor was found to be a neurofibroma, and the cutaneous tumor was a fibroma.
During the postoperative outpatient follow-up, he developed diabetes mellitus and required treatment with an oral antidiabetic drug. For the treatment of his pituitary prolactinoma, cabergoline was administered. Octreotide therapy for the multiple liver metastases of the NETs began 2 months after the operation. After the ninth administration of the octreotide, three new lesions were detected in the liver on a CT scan. His general condition was judged to be tolerable to undergo liver resection, and the radiological examinations showed that there was no recurrence except the liver. Complete surgical resection of liver metastases was therefore achieved by an extended right posterior segmentectomy with partial hepatectomy of S2, S3, and S8. Immunohistochemical examination revealed that liver metastases were derived from a glucagon-positive tumor of the pancreatic NET. The Ki67 labeling index of these lesions ranged from 1.5 to 5.4 %.
Nineteen months after the hepatectomy, a CT scan revealed a small nodule in the S4 of the liver. Twenty-three months after the hepatectomy, gadoxetic acid- or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI demonstrated multiple liver tumors. We started everolimus therapy following a diagnosis of unresectable pancreatic NET recurrence. He is still alive after 4 years and 4 months after the initial surgery, although he is suffering from worsened diabetes mellitus, a pituitary prolactinoma that led to a hemorrhage into the pituitary tumor, and an increasing size of the left nonfunctional adrenal tumor.
MEN1 is an autosomal-dominant hereditary syndrome caused by germline mutations of the MENIN gene that predisposes the development of endocrine and non-endocrine tumors with variable penetrance [–, ]. The most frequent tumors in MEN1 patients arise in the parathyroid glands, the pancreas, and the pituitary gland [, , ]. The incidence of pancreatic NETs is reported to be from 50 to 70 %. Insulinoma is one of the pancreatic NETs arising in the setting of MEN1. In Japan, the mean tumor size of pancreatic NETs was reported to be 3.03 cm at the time of diagnosis [], whereas that of insulinoma was smaller than 2 cm in approximately 70 % of insulinoma patients, probably because insulinoma is a symptomatic disorder []. There are some previous reports on a giant insulinoma [–], and the insulinoma with a diameter of 18 cm in the present case is the second largest by referring to the previous reports. Moreover, only the present case did not complain of hypoglycemic symptoms, whereas all other patients with giant insulinoma presented such symptoms. The reasons why the present case showed no hypoglycemic symptoms were unclear; however, we can propose some hypotheses for this: pheochromocytoma might reduce hypoglycemia due to insulinoma; at the time of hypoglycemia, our patient overate unconsciously; and glucagon secreted from glucagon-positive tumor cells compensates hypoglycemia.
More than a half of the patients with a giant insulinoma reportedly had a liver metastasis at the time of diagnosis. Liver metastases of the present case were estimated to be derived from the glucagon-positive cells of the pancreatic NET. This was consistent with the consensus that non-functional tumor have a higher incidence of liver metastases than insulinoma []. On the other hand, the fact that the Ki67 labeling index of metastatic tumors was higher than that of the primary tumors suggested that highly proliferative components had more potential to form metastatic lesions.
An incidence of adrenal involvement in patients with MEN1 is about 20 % [], most of which lesions are derived from the adrenal cortex. Concomitant pheochromocytoma is rare [, ]. Corticomedullary mixed tumor is a single adrenal tumor mass composed of an intimately admixed population of both adrenal cortical cells and pheochromocytes []. However, in our case, adrenal cortical adenoma and pheochromocytoma separately coexisted in the same adrenal gland, which is extremely rare [–], and even more so in the setting of the MEN1.


A 50-year-old African American male with a past medical history significant for Insulin Independent Diabetes Mellitus and a 20-year history of DLE presented to the dermatology clinic with a rapidly enlarging left cheek and ear mass. He underwent two shave biopsies, initially nondiagnostic followed by a subsequent biopsy revealing poorly differentiated SCC. He was then referred for surgery. Preoperative imaging revealed a left facial mass with adjacent ear canal invasion with metastatic adenopathy (Figures and ). After informed consent, he successfully underwent a radical excision of left ear and face, left total parotidectomy, left modified neck dissection, left lateral temporal bone resection, and anterolateral thigh free flap for reconstruction. Final pathology revealed a well-differentiated Squamous Cell Carcinoma with multiple levels of neck adenopathy. There was direct invasion from the skin into the parotid, ear cartilage, and bone but no perineural or vascular invasion identified. Postoperatively the patient healed without any major complications and was referred for adjuvant radiation therapy. Unfortunately, the patient developed recurrence in the ipsilateral axilla and contralateral neck lymph nodes and the patient was referred to palliative care.


A 51-year-old male was admitted to the hospital on April 2011 complaining of epigastric pain, jaundice, fever, chills, and billinuria. The lab results revealed increased levels of liver function test (AST, ALT, γGT, and ALP). With the diagnosis of cholangitis the patient underwent ERCP which revealed biliary gallstones which were removed after sphincterotomy as well as abnormal tissue surrounding the papilla of Vater. Biopsy revealed an adenoma with moderate-to-high grade dysplasia where the possibility of infiltrative development could not be definitely excluded. Tumor markers (CEA, CA 19-9, and AFP) were within normal levels. On May 2011 a CT scan of the abdomen was conducted and revealed a compact homogenous tumor 1.5 × 1 × 1.4 cm invading the lumen of the 2nd section of the duodenum. Subsequently, the patient underwent pancreatoduodenectomy. Due to a superficial surgical site infection the hospitalization of the patient was prolonged until the 17th postoperative day. Histological examination of the specimen revealed a mixed neoplasm consisting of a part with histological characteristics of a well differentiated adenocarcinoma (), neoplastic blasts of which were extending focally to the submucosa without invading the muscular layer (Figures and ). In the region of submucosa, there was low differentiation carcinoma consisting of solid clusters and pagetoid formations. The neoplastic cells of the former tumor were homogenous without obvious cytoplasm and they present a large number of mitoses (). Immunohistochemical staining showed that the latter tumor was Cytokeratin 7(−), Cytokeratin 20(−), CEA(−), Cytokeratin MNF 116(+), CD56(+) (), NSE(+), Synaptophysin(+), and Chromogranin(−). In contrast, the region of the well differentiated carcinoma was Cytokeratin 7(+), Cytokeratin 20(+), and CEA(+). Carcinomatous lymph embolus was obvious as well, but all 18 lymph nodes of the specimen were free of neoplastic disease and the surgical margins of the specimen were tumor-free.
Four months after the operation the patient developed liver metastasis. The CT scan showed 4 hypodense lesions in the liver segments V, VI, and VIII with respective maximum diameter of 13 mm, 2.5 cm, and 13 cm and hypodense lesion at the level of the hepatic vein ramification. FNA cytology of the hepatic lesions revealed low grade carcinoma with neuroendocrine characteristics and the patients received 1st-line chemotherapy treatment with VP and CDD: D1–D3 VP 100 mg/m2 and D2 CDDP 80 mg/m2. After 2 months, CT of the abdomen revealed progressive disease (PD) with 3.5 cm maximum lesion and received 2nd-line chemotherapy with paclitaxel, ifosfamide, Mesna, and CDDP (D1 paclitaxel 175 mg/m2, D1-D2 ifosfamide 2.5 g/m2, D1-D2 Mesna 1 gr/m2 before ifosfamide, 1 g/m2 3 hrs after the ifosfamide dose, and 1 g/m2, 6 hrs later, and D1-D2 CDDP 40 mg/m2). Three months later due to PD (with the largest lesion being 3.7 cm) the patient received 3rd-line treatment with Folfox and Avastin (D1 Avastin 5 mg/kg, D1 LOHP 85 mg/kg, D1-D2 LV 200 mg/m2, D1-D2 STUp 400 mg/m2, and D1-D2 STUi 600 mg/m2). Two months later due to PD (with the largest lesion being 4.2 cm and appearance of new hepatic lesion as well) the patient received 4th-line chemotherapy with Folfiri and Avastin (D1 SFUbolus 400 mg/m2, D1 CPT 150 mg/m2, D1 LV 200 mg/m2, and D1-D2 SFUinf 600 mg/m2). Octreoscan revealed a region with moderate scintillation in the left hepatic lobe. Four months later the patient had PD (multiple hepatic lesions, with the largest one being 5.7 cm) and received 5th-line treatment with CAV: D1 Endoxan 1000 mg/m2, D1 Doxorubicin 40 mg/m2, and D1 Oncovin 1 mg/m2. In December 2012 the patient presented to the emergency department due to worsening general condition, malaise, weakness, and anemia. He was transfused with 3 blood units. A new CT scan of the abdomen revealed PD with multiple liver metastatic lesions with the largest one having 9.5 cm diameter. The patient experienced grade IV myelotoxicity without evidence of any response to chemotherapy and denied further treatment. He was discharged from the hospital and succumbed to his disease 13 months after the operation.


A 58-year-old woman was referred to us from a private facility with a 6-day history of altered sensorium and high-grade fever. She has history of systemic hypertension for 8 years with poor medication adherence. She was diagnosed with high-parasitemia falciparum malaria (blood slide for malaria parasite >1000/200 white blood cells), and the sequestered red cells contained the mature forms of the parasite (trophozoites and meronts). She was started on intravenous artesunate 240 mg at 0, 12, 24, and 48 hours, and intravenous clindamycin 600 mg twice daily for 3 days was also administered as per the current local guidelines for the management of severe falciparum malaria. However, due to clinical deterioration, she was referred to us on the fourth day of hospitalization in the private facility for expert management. There was no prior history of head injury or fall from a height, convulsions, or anticoagulant use. Furthermore, there was no history suggestive of recent sinusitis, rhinitis, or mastoiditis.
On admission, she was febrile (39.2°C) with a Glasgow Coma Score (GCS) of 9/15 (E4V2M3). Her blood pressure was 156/109 mm Hg, pulse rate was 116 beats/minute, random blood glucose was 12.2 mmol/L, and she weighed 90.3 kg. She had a reduced urine output (300 mL/24 hours) with elevation of urea (33.2 mmol/L; range = 1.8-7.1 mmol/L) and creatinine (442.3 µmol/L; range = 46-92 µmol/L). On her blood count, leukocyte concentration was 15.4 × 109/L (range = 4.5-10.5 × 109/L) with neutrophilia (75%), hemoglobin was 9.5g/dL (range = 12-16 g/dL), and she had thrombocytopenia (platelets 62.7 × 109/L; range = 150-450 × 109). In liver panel, she had elevated aspartate transaminase (203 IU/L; range = <20 IU/L) but normal alanine transaminase (38 IU/L), and both direct (26.0 µmol/L; range = <7 µmol/L) and total bilirubin (44.3 µmol/L; range = 5-17 µmol/L) were elevated. She tested negative for HIV and had normal electrolytes. Electrocardiogram revealed sinus tachycardia (rate 124) and ECHO showed mild left ventricular hypertrophy with good systolic function (ejection fraction 62%). Intravenous artesunate 240 mg was reinstated, and she received 3 units of platelet concentrate and was resumed on her antihypertensives (amlodipine, hydralazine, and furosemide). Hemodialysis was also started, and after 5 sessions, her renal functions returned to normal (creatinine 76.8 µmol/L; urine output 950 mL/24 hours); however, her altered mentation did not improve.
A brain magnetic resonance imaging (MRI) was then ordered, which revealed a bilaterally thin but widely spread subdural collection in the frontoparietal region ( and ). A diagnosis of SDE was then reached and neurosurgeons were consulted promptly. The patient was started on intravenous meropenem, antiepileptic prophylaxis, and underwent a frontotemporal osteoplastic flap craniotomy in which thick pus was removed on dura mater opening. Analysis of the purulent fluid revealed pus cells with no organism. Twenty-four hours postoperative, GCS started improving, and she was afebrile (37.1°C) and had a fasting blood glucose of 3.9 mmol/L. On the fifth day postoperative, she started speaking comprehensively, and her postsurgery MRI and renal and liver functions were normal. Her postoperative blood slide for malaria parasite was negative. She was discharged home after a total of 21 days of hospitalization.


‘Mr. C’ is a 58-year-old Navy veteran with a history of substance use disorder in sustained remission, traumatic brain injury (TBI), mild neurocognitive impairment, and a 15-year diagnosis of schizophrenia. Importantly, his sister indicated that Mr. C suffered his first psychiatric break during adolescence. He was prescribed medication, but his parents, who indicated their preference for treating his condition with prayer, refused these. He has been living with his sister for the past 20 years and participates in all activities of daily living. He is a widower and is currently unemployed. His TBI history includes a single episode approximately 25 years ago when he fell off a moving train, requiring extended hospitalization. Mr. C was brought in to our Veterans Affairs (VA) hospital by his sister after calling the Veterans’ Crisis Line with SI. One week earlier there was an altercation with his brother-in-law resulting in Mr. C attacking him with a crowbar and the sister intervening. On admission, the family reported that Mr. C was taking venlafaxine and quetiapine.
Upon initial interview, Mr. C was grossly oriented, with psychomotor agitation, mildly pressured speech, anxious mood, and restricted affect. Thought process was tangential, and his cooperation was poor due to his preoccupation with delusions that he was dead, that nothing existed. He felt his body was being energized by demons: “These demons are my energy, I am dead, how can I have any energy?” He perseverated on this content despite attempts to engage him: “How can you help me, I am dead.” When asked about suicidal ideation (SI) he indicated, “I am dead, how can I be suicidal?” When providers commented on the novelty of speaking with a dead person, he replied, “Maybe you are dead too.” Importantly, his nihilistic beliefs included strong religiously mediated content not shared by his family. Mr. C. made the comments: “That physical God is alive because he has a physical body, but the demons inside me keep me dead, keep me from being alive.” “It is not nice meeting the devil, all the demonic spirits are tormenting me and raping me.” He believed his insides were being corroded by demons and indicated that he had repeatedly sodomized himself to try and purge himself of the demons. Mr. C’s sister indicated that the onset of his religiously themed delusional symptoms began after his TBI when he became convinced that a miracle had occurred during the accident and he became aware of his “dead nature.”
Magnetic resonance imaging (MRI) performed in April 2015 revealed mild global volume loss for age with widening of the Sylvian fissure bilaterally. Neither evidence of past acute TBI or white matter abnormalities were noted on fluid-attenuated inversion recovery (FLAIR) imaging (Figure ). Neuropsychological testing administered during the index hospitalization was significant for impairment on tasks of processing speed, simple attention, verbal learning and memory, aspects of executive functioning (set-shifting, verbal fluency), facial recognition, and affect naming and recognition. Aspects of visuospatial discrimination and construction, confrontation naming, and visual memory were intact (Table ).
Upon initial presentation, given the patient’s aggressive and activated behavior as well as sleep difficulties, venlafaxine was discontinued and quetiapine was titrated to 700 mg. Divalproex was added during the admission for mood stabilization and titrated to 750 mg. During his 2 weeks on the inpatient ward repeated inquiry about his religious experience and his relationship to God led to changes in the content of Mr. C’s delusion from literal and concrete beliefs that he was physically dead to more abstract and metaphorical descriptions of spiritual death. His belief that only God was physically alive remained, and his belief that demons possessed his body persisted. Continued probing about the patient’s existence demonstrated further amelioration of the nihilistic content. A month into his admission when asked if his daily activities (eating, drinking, showering) were evidence that he was in fact physically alive, he indicated that he was ‘probably alive.’
Mr. C continued to be alert and oriented to person, place, and time, with evidence of increased insight into his preoccupation with his belief that he was dead. Approximately 1 month into his admission he recognized when the content of his speech began to focus on death, demons, and self-negation, at which point he would stop and remark, ‘There I go again talking about all that dead stuff.’ He was ultimately discharged after 5 weeks of hospitalization. On discharge, the patient’s brother noted that he was less delusional and more linear than at baseline.


A 17-year-old male from southwestern China with epilepsy presented with a painless ulcer on his right leg which was clinically suspected as being dry gangrene. The lesion started 2 months earlier when he was injured during an epileptic insult by a wooden bench. Initial lesions were in the form of small, painless papules which quickly progressed to a painless ulcer with a black eschar over a period of 2 weeks. All laboratory investigations were within normal ranges, and in particular, no immune deficiency was apparent. However, the patient had a history of epilepsy for which he was on carbamazepine for 7 years. Examination of the skin lesion showed a 5 × 13 cm skin ulcer with black eschar, i.e., the ulcer edge appeared to “roll over” and took the shape of a tough, erythematous and fibrous ring. The black eschar adhered tightly without discharge of pus or granules (a1, a2). Upon first visit, the case was diagnosed as EG (Fig. ).


A 5-year-old Moroccan boy presented with a 2 months history of torticollis with radiation of the pain to the left upper limb. The patient had no medical history. Physical examination revealed hypoesthesia of the upper limbs, evidence of bilateral lower extremity weakness with motor power 4/5 in distal muscular group, and hypoactive reflexes in four extremities. There was no bowel or bladder dysfunction.
Cervical CT-scan and MR imaging demonstrated the presence of a 75 × 36 × 24 mm extradural mass, with extra-spinal extension at the left C1–C6 level (Fig. ). This dumbbell-shaped mass had heterogeneous signal intensity, calcifications and homogeneous intermediate post-contrast enhancement following gadolinium administration.
No other cord lesion and no osseous abnormality of the spine were found. A biopsy was done. Microscopic sections showed a highly cellular neoplasm composed of diffuse sheets of tumor cells having monomorphic, round to oval, finely vesicular nuclei, occasional nucleoli, and scanty cytoplasm. Large areas of necrosis were seen (Fig. ). Immunohistochemical analysis showed positivity for CD99 (Fig. ) and S-100 protein, and negativity for synaptophysin, chromogranin, desmin, myogenin and CD56; favoring the diagnosis of PNET. After six courses of chemotherapy, cervical CT scan demonstrated complete regression of the mass. Our patient has remained in remission at 8 months follow-up.


A 39-year-old male presented with painless progressive diminution of vision in the right eye (RE) of 5 years and in the left eye (LE) of 6 months duration. There was no history of chronic drug use, specifically, use of steroid in any form. The visual acuity was 1/60 (RE) and 6/18 (LE). There was no anterior chamber or retrolental cells in both eyes and intraocular pressures were normal. The RE had a bullous inferior RD involving the macula with a smooth surface and shifting fluid. There was whitish subretinal exudation inferior to the macula (fibrin, Fig. ). The LE showed pigmentary changes at the posterior pole and multiple pigment epithelial detachments (PEDs) (Fig. ). No mass lesion or peripheral break was detected in either eye. Fluorescein angiography (FA) of the RE showed window defects at the posterior pole with leaks at the nasal part of the window defect and inferonasal to the optic disc (Fig. ). There was no disc leak or vasculitis. The LE revealed window defects with multiple PEDs. Optical coherence tomography (OCT) of the RE revealed subfoveal fluid with some underlying hyperreflective material suggestive of fibrin and a serous PED (Fig. ). OCT of the LE revealed multiple serous PEDs. The sclero-chorioretinal thickness was 2 mm (RE) and 2.01 mm (LE). Axial lengths were 21.06 mm (RE) and 21 mm (LE). Serum cortisol level, blood pressure, and kidney functions tests were normal. A diagnosis of bilateral chronic CSCR with an exudative RD in the RE was made. Some cases of CSR can undergo spontaneous resolution. Thus at the first presentation, the patient was advised to follow-up.
At 1 month, there was no change. Then a 2 month trial of oral rifampicin 300 mg twice daily [] was tried without success. Laser was not considered as the trans-retinal pigment epithelial leakage was not well defined. Though photodynamic therapy (PDT) [] has been studied extensively for chronic CSCR [], its role in chronic CSCR complicated by retinal detachment needs evaluation. Our patient was given the option of PDT, but he declined the therapy due to financial constraints. As the exudative RD was not responding and the eye was small in size, we felt that similar to nanophthalmic eyes, the sclera may be the culprit by not allowing the resolution of the subretinal fluid. Thus, we planned partial thickness scleral resection in the RE as the eye was small with increased thickness of the ocular coats like in nanophthalmos. A proper informed consent for the procedure was obtained. Surgically, an area of 4 mm by 3 mm was marked on the sclera, 4 mm posterior to the insertion of recti in inferotemporal and inferonasal quadrants. Using a blade and crescent knife, a partial thickness (more than 50 %) square of sclera was excised from the marked areas. Mitomycin C 0.02 % was placed on the scleral bed for 2 min after which a thorough wash with the balanced salt solution was performed.
At 2 months, the vision of the right eye had improved to 3/60 and the exudative detachment had started regressing. At 4 months, the vision was 6/60 and the exudative detachment had totally resolved (Fig. ). OCT revealed resolution of subretinal fluid and marked reduction in the height of the PED with persistence of some of the hyperreflective subretinal fibrin (Fig. ).
After 2 years of surgery, the right eye had achieved a best-corrected visual acuity of 6/36. The right eye had attached retina with a focal elevated pigmented area at the fovea surrounded by hypopigmentation (Fig. ). OCT showed the absence of subretinal fluid. Few intraretinal cystoid spaces and a subretinal mound presumably due to fibrin were visible (Fig. ). The FFA revealed the absence of any active leak and leopard spot like fluorescence in the inferior retina reminiscent of previous retinal detachment (Fig. ). The mid-phase indocyanine green angiogram (ICGA) of the right eye was suggestive of DRPE. The foveal center appeared dark, likely due to blocked fluorescence by the focal retinal pigment epithelial hyperplasia as seen on the fundus image. Small pinpoint leaks were visible superior to the disc (Fig. ).
The left eye had retained 6/18 vision and showed RPE changes and subretinal yellowish deposits (Fig. ). The OCT showed PEDs temporal to the fovea; and nasal intraretinal cystoid spaces (Fig. ). The FFA of the left eye revealed areas of mottled hyper and hypofluorescence with broad areas of staining, but no definitive focal leak could be identified (Fig. ). ICGA (early phase) of the left eye showed patchy granular fluorescence at the posterior pole, and dilated large choroidal vessels inferior to the fovea (Fig. ). Diffusely increased choroidal hyperfluorescence around this region at the posterior pole persisting in the late phase, suggestive of increased choroidal permeability was also seen. In the mid phase, few active pin point leaks were also evident (black arrowhead, Fig. ).


A fifty-year-old male from Dhahran, Nepal presented to the surgical outpatient clinic with a vague symptom of abdominal discomfort. He had no history of trauma, persistent vomiting, altered bowel habits, change in the color of the stool or abdominal distension. There were no significant past medical or surgical illnesses. Family history of similar symptoms was also absent. Examination of the abdomen was normal except for slight discomfort during palpation in his left upper quadrant. Ultrasound examination of the abdomen revealed a huge left suprarenal mass. Computerised tomogram (CT) of the abdomen confirmed a giant mass of approximately 12×8 cm
2 in the left suprarenal region showing rim enhancement and areas of low attenuation within it. The left renal vein was normal and the lesion was slightly abutting the spleen (
).
The patient denied attacks of headache, cheat pain, palpitation and sweating. The serum and urinary catecholamine levels were within normal range. The patient was kept for observation with 24 hour electrocardiography (ECG) and blood pressure monitoring (BP) which was normal.
The patient and his relatives were explained of the disease entity and were advised for surgery. With written consent, he was prepared for surgery. The anesthesiologists prepared medication (Intravenous (i.v.) Phentolamine (1 mg injection), Nitroprusside (4 mg drip) and Esmolol (30 mg injection) for potential intra-operative crisis pertaining to catecholamine surge during surgical manipulation. Vasoactive agents were also made available for combating sudden loss of peripheral vascular resistance following tumor removal. Early vascular control was secured. There was a well demarcated plane to dissect the tumor from the surrounding structures (
).
The patient was extubated and was kept in the intensive care unit (ICU) for 48 hours. There were no untoward events in the post-operative period and the patient was discharged home on the 10
th day. Histopathological study revealed zellballen nests of chromaffin cells with no invasion of the capsule (
), which is highly suggestive of a benign pheochromocytoma.
The patient is asymptomatic 4 years following surgery, and has been advised to follow up periodically in order to rule out early recurrence.


A 48-year-old Caucasian woman was referred to our hospital to exclude an unrecognized infection as the cause of three episodes of fever associated with splenomegaly. Her past medical history was unremarkable up to 4 years previously, when by routine mammography and subsequent biopsy an intraductal carcinoma was diagnosed. She underwent a skin-sparing mastectomy of her right breast combined with reconstruction and implantation of a silicone prosthesis (Polytech 445 g). No adjuvant chemotherapy or radiotherapy was provided or indicated. Three years later she underwent a reduction operation of her left breast combined with lipofilling of both breasts. She had experienced fever 8 and 5 months prior to hospitalization that lasted for about 3 weeks. She was treated at home with levofloxacin because of a known allergy to penicillin.
When fever appeared again together with sore throat, fatigue, sweating, cough (she smokes about 10 cigarettes daily), and an involuntary weight loss of 10 kg in the last year, she was hospitalized for 2 weeks in a peripheral hospital. Abnormal results from laboratory investigations included: hemoglobin 10.4 g/dL, leukocytes 3.6 × 109/L, serum total protein 5.3 g/dL, lactate dehydrogenase (LDH) 638 U/L, and ferritin 398 ng/mL. An abdominal ultrasound examination demonstrated her spleen was enlarged, with a diameter of 15 cm. X-ray examination of her chest showed bilateral apical pleural scarring, which was confirmed by computed tomography (CT). CT also revealed subpleural densities of uncertain significance, an enlarged liver and spleen, ovarian cysts, and a 2.3 cm large layer of fluid in the Douglas space. There was no evidence of enlarged mediastinal, abdominal, or retroperitoneal lymph nodes. A histologic examination of a bone marrow biopsy specimen was of no diagnostic help. 18FDG-PET/CT evidenced hypermetabolism of both adrenal glands. She was given azithromycin and her fever subsided but profound weakness remained. Extensive laboratory examinations did not indicate any infectious, autoimmune, or malignant diseases. She was referred to our Division of Infectious Diseases for a search for an unrecognized infectious disease.
On physical examination our patient was pale and weak. Her body temperature was 37.3 °C, blood pressure 110/90 mmHg, heart frequency 92 beats/minute, arterial blood oxygen saturation 98 %, body weight 59 kg, and high 168 cm. She complained of memory deficits and an unexplainable unstable gait. There were no signs of meningeal irritation. Since her breast operation 4 years previously she had needed sleeping tablets. During her first 6 days in hospital without any treatment her body temperature rose progressively from 37.3 to 39 °C. Because of the pleural scars and subpleural densities seen in the CT images, and the hypermetabolic adrenal glands shown by 18FDG-PET/CT [adrenocorticotropic hormone (ACTH) and cortisol concentrations were within the normal range], a tuberculosis (TB) infection was considered. Results from a repeated search by microscopy, culture and PCR analysis of Mycobacterium tuberculosis in her sputum and bronchial aspirate were unremarkable. A Mantoux skin test and QuantiFERON-TB assay were negative too. Leishmania infection was excluded by serology and microscopy of her bone marrow aspirate.
Despite repeated negative blood, urine, and stool cultures for pathogenic bacteria, among the many laboratory examinations, titers of 1:160 anti-Salmonella O and 1:2560 anti-Salmonella H antibodies were detected by Widal Wright’s reaction (Table ). Thus empiric antibiotic therapy with ceftriaxone 2 g daily was started. There was no response to treatment and her high fever persisted. Therefore, indomethacin 50 mg three times daily was administered. This was followed by prompt defervescence; however, it lasted only for 3 days (Fig. ). On the fourth day of indomethacin treatment, her fever of 39 °C recurred and was associated with increased weakness, malaise, and confusion. That night, two episodes of right hemiparesis with aphasia of about 30 min duration were observed. No areas of ischemia or hemorrhage were seen by magnetic resonance imaging (MRI)-angiography of her brain. An analysis of her cerebrospinal fluid found 282 mg/dL of protein, but there was no increase in cell number (Table ). At this point, her symptoms were treated with dexamethasone 16 mg daily for 2 days followed by methylprednisolone 1 g daily for the next 4 days and then again dexamethasone 16 mg daily. Ceftriaxone was substituted by meropenem, and empiric anti-TB treatment and treatment with fluconazole were added. Corticosteroid therapy was followed by an impressive clinical improvement, including defervescence, regaining orientation, and regaining her ability to stand and to eat. However, on the fourth day of corticosteroid treatment, her high fever recurred together with extreme weakness, anorexia, and episodes of confusion.
The criteria for HLH/MAS were fulfilled (Table ), but no underlying cause was evident. Because eight cases of AOSD associated with SBIs have been reported (see below), the silicone breast prosthesis of our patient was considered to have possibly contributed to her hyperinflammatory state, and consequently was explanted on the 22nd hospital day. A more detailed medical history revealed that the breast prosthesis had caused our patient many problems. Because of painful inflammation, the first prosthesis had to be explanted after 6 weeks and necrotic inflammatory tissue surrounding the prosthesis removed. Because an infection was suspected, the prosthesis was cleaned with antiseptics and then re-implanted, but no infectious agent could be isolated. Two months later, the prosthesis had to be removed definitively. Again, necrotic inflammatory tissue had to be removed and no infectious agent could be isolated. One year prior to her current hospitalization, a new silicone breast prosthesis was implanted. An inflammatory reaction with swelling of her breast was treated locally with infiltration of corticosteroids. Thereafter, our patient could tolerate the prosthesis and a mild pain was felt only when touching the prosthesis.
Significant worsening occurred after removal of the intact prosthesis. Her fever rose up to 40.4 °C, she became icteric (Table ) and for the first time she experienced severe low back pain that radiated to her lower legs and required analgesic treatment with opium derivates. She complained of perianal anesthesia and fecal incontinence. The day of implant removal, 25 g of endovenous immunoglobulin was started and given daily for 3 days to treat the MAS. Finally, cyclosporine 100 mg twice daily was administered without any benefit. On the 29th hospital day, the results of the histologic examination of the tissue taken at implant removal were available and showed (a) normal pectoralis muscle with absence of neoplastic infiltration; (b) cutis and subcutis with dilated vessels showing an intraluminal proliferation of atypical large lymphocytes with a vesiculosus nucleus with several nucleoli (Fig. ). A immunohistochemical analysis of the neoplastic cells revealed positivity for cluster of differentiation (CD) 20, B-cell lymphoma (BCL)-6, BCL-2, multiple myeloma oncogene 1 (MUM-1), and weaker staining for CD5. The proliferation index Ki-67 was over 90 %. Results for terminal deoxynucleotidyl transferase (TdT), CD10, CD34, CD3, and cytokeratin-CAM were negative. These results are consistent with the diagnosis of IVLBCL. The remaining parenchyma showed an extensive giant cell-lymphohistiocytic foreign body reaction, but no carcinomatous infiltration. Her familial medical history was notable for an uncle who has died from acute lymphatic leukemia at 43 years of age.
Our patient was transferred to our Hematology Ward where she was treated with six cycles of R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine, prednisone] chemotherapy. Intrathecal prophylaxis with methotrexate was also given. After 6 months her white blood cell count, platelet count, hemoglobin level, LDH level, and liver function tests were again within the reference ranges. After 2 years our patient’s clinical status is good, but sequelae of the cauda equina syndrome are still present, including low back pain, saddle anesthesia, difficulties in voiding the bladder and intestine, loss of sexual sensation, right plantar numbness, and gait instability. She continues to undergo 3-monthly follow-up visits (see Additional file for supporting data).


A 73 y/o male presented with stage IIA cutaneous melanoma of the left shoulder and underwent surgical resection in 2003. In November 2012, he developed bilateral lung nodules with no other metastatic sites. A right lung biopsy at this time confirmed metastatic melanoma. He initiated therapy with ipilimumab at 3 mg/kg IV every three weeks. After his second treatment dose, he developed an intensely pruritic, papulovesicular rash over his chest, bilateral upper extremities, and back. Prior to this, the patient had no history of skin rashes. He received methylprednisolone (40 mg IV initially, then 20 mg IV 1 month later without topical therapy) with significant pruritus improvement; however, the rash persisted. His outside physician then discontinued ipilimumab in March 2013 because of persistent rash symptoms and transitioned the patient to close observation. Remarkably, his lung nodules remained stable based on CT imaging performed every six months.
In July 2014, we evaluated the patient for progressive lung and liver metastases. He underwent a liver biopsy that confirmed metastatic melanoma with mutations in BRAF G466A and RET W917. Interestingly, he continued to have an extensive, erythematous, papular rash over his chest, arms, and back that was asymptomatic and had persisted since his previous ipilimumab therapy. He had no other oral ulcers or skin lesions. A skin biopsy was performed and histopathologic examination revealed suprabasal acantholysis with associated overlying dyskeratosis, consistent with Grover’s disease (Fig. ). The acantholysis extended to the spinous layer of the epidermis with some keratinocytes retaining partial attachment to one another. In addition, there was a superficial dermal mononuclear inflammatory infiltrate. Immunohistochemical (IHC) studies demonstrated a predominance of CD3+ T-cells with a predominance of CD4+ over CD8+ T-cells (Fig. ). Because anti-PD-1 therapy had not been FDA-approved at the time, he received systemic chemotherapy with disease progression. Considering his BRAF G466A mutation, we subsequently initiated single agent trametinib but his disease again progressed. Both chemotherapy and trametinib were initiated after the patient’s repeat skin biopsy.
Thereafter, we started pembrolizumab at 2 mg/kg IV every three weeks. He tolerated therapy without significant toxicities. His previous rash symptoms remained stable during therapy with pembrolizumab. Unfortunately, after two cycles he continued to have rapid, progressive disease, and we discontinued therapy. Given the previous favorable response with ipilimumab, we re-initiated this therapy, but after one ipilimumab dose, he experienced grade 2 rash exacerbation with an intensely pruritic, papulovescular skin eruption on his upper back. A repeat biopsy confirmed Grover’s disease exacerbation. We started topical steroids and oral antihistamines with minimal symptom improvement. Thereafter, he received one additional ipilimumab dose but transitioned to hospice after demonstrating terminal, progressive disease. A treatment course timeline is included as Fig. .


A 53-year-old man with no previous cardiac history was admitted for exertional chest pain and dyspnea for few days. His medical history was significant for a poorly controlled type II diabetes mellitus and long-standing RA. Few weeks before, the patients was hospitalized in a Rheumatologic Unit for disease reactivation, and immunosuppressive therapy was started (high-dose subcutaneous methotrexate plus leflunomide) (Tables and ). Current medications also included metformin and glibenclamide. The body mass index (BMI) was 31.1 (class I obesity). The ECG on admission showed T-wave inversion in peripheral and precordial left leads and QTc prolongation (520 ms), as well as frequent polymorphic ventricular ectopic beats (Figure A). Laboratory investigation revealed elevation in cardiac enzymes (troponin I 5.07 ng/mL, r.v. <0.07) and brain natriuretic peptide (1,091 ng/L; r.v. <100), increased A1c (glycated hemoglobin) (9.3%, r.v. 4.3–5.9), and moderate hypocalcemia (7.9 mg/dL, r.v. 8.8–10.5). Potassium and magnesium were normal. Inflammatory markers were elevated [C-reactive protein (CRP) 5.55 mg/dL, r.v. <0.5; erythrocyte sedimentation rate (ESR) 67 mm/h, r.v. <25; fibrinogen 508 mg/dL, r.n. 170–410], and both rheumatoid factor and anti-Ro/SSA antibodies tests were positive (Tables and ). A complete blood count showed neutrophilia (white blood cell count: 9,500 × 103/μL, neutrophils 78%), with normal values of hemoglobin (12.0 g/dL; mean corpuscular volume 91 fL) and platelets (277 × 103/μL). Echocardiography documented severe left ventricular dysfunction [ejection fraction (EF) ~20%], and coronary angiography demonstrated critical three vessel disease. The patient was treated with diuretics and vasodilators, and then underwent triple coronary artery bypass grafting surgery. Although the immediate postoperative period was uneventful, 3 days later, he suddenly presented with two episodes of TdP, the second one rapidly degenerating to VF (Figures B,C) that was reversed by DC-shock. Intravenous magnesium sulfate and calcium gluconate were started, and coronary angiography was repeated. Since normal function of coronary grafts was demonstrated, a residual critical stenosis of the right coronary artery was treated by angioplasty and stenting. Nevertheless, a few hours later, further episodes of TdP with VF degeneration occurred, and the patient underwent temporary ventricular pacing. In the next days, although ventricular arrhythmias did not recur, a permanent implantable cardioverter defibrillator was implanted. Notably, the recently introduced immunosuppressive treatment was maintained during hospitalization, and the patient showed a progressive normalization of the inflammatory activation, as demonstrated by the serial assessment of fibrinogen levels (500, 448, and then 415 mg/dL before discharge). Long-term follow-up demonstrated the improvement of left ventricular function with recurrence of neither life-threatening arrhythmias nor ischemic events. Moreover, RA treatment maintained the disease in remission, and QTc stably remained near-normal/slightly prolonged (450–460 ms) (Figure in Supplementary Material).


An 87-year-old woman developed an out-of-hospital cardiac arrest during the nighttime and was successfully treated by defibrillation. The medical history included hypertension, heart failure, complete atrioventricular block, paroxysmal atrial fibrillation, previous single-chamber pacemaker (PM) VVI implantation (Vitatron C10 S), cerebrovascular disease, chronic kidney disease, and hypothyroidism. Moreover, she had a history of RA that was poorly controlled by steroid treatment. Current medications were warfarin, furosemide, amlodipine, atenolol, l-thyroxine, and prednisone. The ECG on admission demonstrated atrioventricular dissociation with low-rate PM-induced ventricular beats (45 bpm), alternating with narrow beats from a junctional escape revealing significant QTc prolongation (550 ms, Figures A,B). Bradycardia was due to activation of “sleep-function,” an algorithm aimed to reduce ventricular pacing by lowering nocturnal pacing rate. Laboratory values were remarkable for inflammatory activation (CRP 1.21 mg/dL, ESR, 82 mm/h, fibrinogen 722 mg/dL) (Table ) and positive rheumatoid factor, while anti-Ro/SSA antibodies were negative and electrolytes were normal. A complete blood count showed increased white blood cell count (15,900 × 103/μL) with neutrophilia (neutrophils 88%), low hemoglobin values (11.6 g/dL; mean corpuscular volume 91 fL), and normal platelet count (268 × 103/μL). Echocardiography revealed left ventricular hypertrophy (LVH) and moderate systolic dysfunction (EF~40%) with PM-induced ventricular septum dyssynchrony. Shortly after admission, ECG monitoring showed repeated episodes of TdP (Figure C) treated with DC-shock. Intravenous magnesium sulfate was started, and PM was reprogramed with a stimulation rate of 110 bpm. As a result, electric storm ceased, and the patient’s clinical condition rapidly improved. In the next days, no further arrhythmic events were recorded. Upgrading to dual-chamber PM was performed, and the patient was discharged with the recommendation to follow-up with a rheumatologist to optimize the immunosuppressive therapy for the underlying RA.


An 82-year-old woman was admitted for palpitations and dizziness. Moreover, it was reported that out-of-hospital ECG monitoring showed runs of ventricular tachycardia (no documentation available). Her medical history included hypertension, Alzheimer’s disease, diabetes mellitus (type II), chronic kidney disease, glaucoma, and breast cancer. She also had a history of psoriatic arthritis (PsA) for several years that was effectively controlled with corticosteroids, methotrexate, and TNF-inhibitors. However, for several months, she was undertreated for renal, ocular, and oncologic conditions. Current medications included ramipril, hydrochlorothiazide, metformin, letrozole, lansoprazole, methylprednisolone, and, among potentially QT-prolonging drugs, quetiapine, escitalopram, rivastigmnine, and trazodone (Table ). The BMI was 29.6 (overweight). On admission, ECG demonstrated sinus rhythm with sporadic ventricular ectopic beats, diffuse T-wave inversion with T-wave alternans, and marked QTc prolongation (690–870 ms; Figure ). Blood tests were significant for elevated troponin T levels (227 ng/mL; r.v. <15) and electrolytes imbalance (low levels of potassium, calcium, and magnesium), and high levels of inflammatory markers (CRP 5.53 mg/dL, fibrinogen 600 mg/dL) (Table ). A1c (glycated hemoglobin) was 7.0%. A complete blood count showed neutrophilia (white blood cell count: 4,100 × 103/μL, neutrophils 76%), low hemoglobin values (9.1 g/dL; mean corpuscular volume 92 fL), with increased platelet count (428 × 103/μL). Echocardiography revealed LVH, regional contraction abnormalities (mid and apical septum) with moderate EF reduction (~40%). No TdP events at ECG monitoring were observed. The patient was treated with aspirin, low molecular weight heparin, diuretics, magnesium sulfate, potassium chloride, and calcium gluconate, while all concomitant QT-prolonging drugs were stopped. In the next days, the patient’s clinical condition progressively improved, and troponin and electrolyte levels normalized. A parallel shortening of the QTc was documented, although it remained significantly prolonged (>550 ms). Since inflammatory marker elevation persisted, corticosteroids and methotrexate were restarted, and at discharge, CRP levels began to reduce (2.39 mg/dL). Notably, at this time also QTc was shortened to ~500 ms (Figure in Supplementary Material).


A five and half-year-old girl accompanied by her mother reported to our department with the chief complaint of multiple decayed teeth. Her oral hygiene status was poor. Medical history was unremarkable. Behavioral history revealed that the child was anxious and reluctant to sit in the dental chair at her first visit. Mother was instructed to fill the 7 days diet record to assess the dietary status of her child. She was asked to fill all that the child takes during the day, between meals and the frequency of their intake. Dietary evaluation revealed that the child was on high cariogenic diet with frequent intake of in between meal, snacks and soft drinks.
Intraoral examination revealed multiple carious teeth involving maxillary (54, 55, 64, 65) and mandibular (74, 75, 84, 85) molars, canines (53, 63, 73, 83) and maxillary laterals (52, 62). White spot lesions and brownish discol-orations were seen in mandibular incisors (71, 72, 81, 82). Root stumps were present in relation to maxillary centrals (51, 61) (). Orthopantamogarm (OPG) confirmed the above clinical findings. Diagnosis was made based on history, clinical and radiographic findings as S-ECC.
At first visit, parents were counseled to modify their child’s diet by including the food groups from the basic diet. Reducing the frequency of cariogenic food and supplementing cariogenic food with noncariogenic items like cheese and peanut. Mother was instructed to follow oral hygiene measures. Preappointment behavior modification was performed by modeling and treatment which was initiated with the help of audiovisual aids and tell-show-do (TSD) technique.
During the second visit, dentin stabilization/ tempori-zation was done for all the molars to reduce their caries progression. Fluoride varnish application was initiated.
At third visit, all the molars were restored with miracle mix and anterior teeth with glass ionomer cement (GIC). Maxillary right first molar (54) was extracted as it could not be saved, and band and loop space maintainer was given. Pulpectomy was done in maxillary central incisors (51, 61) and sealed with GIC.
After 3 months, molars with extensive caries (74, 84, 85) restored with miracle mix were further reinforced with stainless steel crowns (SSC).
Six months follow-up revealed exfoliation of maxillary right central incisor (51) with the partial eruption of permanent maxillary right central incisor (11), which was in developing crossbite with the mandibular incisors (). Therefore, tongue blade therapy was planned, wherein the patient was instructed to place an ice cream stick on the palatal aspect of the tooth in crossbite. The blade was made to rest on the mandibular tooth (fulcrum) in crossbite, and the patient was asked to move the oral part of the blade upwards and forwards for 1 to 2 hours for about 2 weeks. Second round of fluoride varnish applications were done ().
Eighteen months follow-up showed complete eruption of permanent maxillary centrals (11, 21) with the correction of anterior crossbite. With the eruption of permanent maxillary first molar (16, 26) band and loop space maintainer was replaced by Nance palatal arch appliance ().
Recall visits were planned every 3 months initially followed by biannual visits, during which we observed improvement in the patient’s oral health. Dietary and behavioral changes were satisfactory (). The oral rehabilitations, including preventive and curative measures were found to be successful in our patient at the end of 18 months follow-up period.


A 67-year-old male patient was referred to a private dental practice, complaining of acute, pulsating pain in the mandibular left first molar (#36). In the case history, the patient reported episodes of acute pain, exacerbated during the night and temporarily alleviated with common painkillers. Pain intensifications were also diminished by rinsing with cold liquids in the affected molar region. The clinical oral examination revealed a deep carious lesion on the distal aspect of the crown, close to the cementum-enamel junction, and also a mesial decay lesion was observed at #37. Decayed dentin was present throughout the entire cavity, including the axial wall of both molars. For the first molar (#36), removing the decayed dentin led to an opening in the axial wall, with the occurrence of a puss droplet, followed by an abundant hemorrhage. The pain gradually subsided later and the tooth remained tender to percussion. Acute purulent pulpitis was established as positive diagnosis. In addition, a retroalveolar X-ray was performed ().
The root canal treatment was conducted in two appointments for both molars. In the first session, under local anesthesia, pulp extirpation was performed under 2.5% Sodium Hypochlorite irrigation, and a sterile cotton pellet was left in the pulp chamber. The cavity was sealed with temporary filling. In the second session, chemomechanical root shaping was performed using the manual nickel-titanium (Ni-Ti) ProTaper system according to the technique indicated by manufacturer (Dentsply-Maillefer, Ballaigues, Switzerland), in association with Sodium Hypochlorite and Ethylene Diamine Tetraacetic Acid (EDTA) irrigations. The root canals were dried using paper points. At this time, a discrete blood stain on the paper point between the cervical and middle thirds of the mesial root of tooth #36 was noted. Root canals were sealed with ProTaper gutta-percha and sealing cement. In the same session, the filling of the crown cavity with composite material was performed. Postsurgical retroalveolar X-ray performed showed an incomplete and incorrect root canal filling, associated with changes of the initial curvature of the canal () for tooth #36 and a correct endodontic treatment for tooth #37. A light tenderness to percussion was recorded at the first molar, while the second molar was asymptomatic. Despite the fact that he was informed about all risks and treatment options (including tooth extraction or #36 tooth retreatment and MTA sealing under microscope), the patient's final decision was to keep the tooth under observation without any additional treatment.


A 52-year-old male patient was referred to a private dental practice for endodontic advice and treatment. The patient was complaining about discomfort in the mandibular right molar region and the case history revealed spontaneous acute pain exacerbated by cold drinks, occurring a couple of months before. Intake of common painkillers helped to alleviate the pain, which disappeared later. Intraoral clinical examination revealed two metallic crowns on the right first and second molars. In addition, a retroalveolar X-ray of the tooth was performed showing a canal wall already thinned by a preexistent external distal root resorption, caused by an inflammatory lesion. After tooth opening through the metal crown, decayed dentin was noticed, including the axial wall. The opening of the pulp chamber occurred while removing the decayed dentin. Pain was not present at the opening time. The root canal probing revealed sensitivity and hemorrhage, while the tenderness to percussion test was negative. The positive diagnosis of chronic pulpitis was set. The root canal treatment was conducted in two sessions. In the first session, under local infiltration anesthesia, pulp extirpation was performed, irrigations with 2.5% Sodium Hypochlorite were carried out, a cotton pellet with a mixture of antibiotic and steroidal anti-inflammatory (Ledermix, Riemser Pharma GmbH, Greifswald, Germany) was introduced in the pulp chamber, and the cavity was sealed with temporary filling.
During the second appointment, a rigorous chemomechanical root shaping was performed. Manual K-files, size 15–40, were used just to avoid a potentially dangerous enlargement of the distal and mesial canals. However, because of the initial curvature of the canal, a relocation of the canal orifice to mesial became obvious even during the mechanical preparation and a retroalveolar X-ray with manual K-file was performed. Irrigations with 2.5% Sodium Hypochlorite and EDTA were also performed. While drying the canal, blood impregnation of the paper point was observed at the middle third level of the distal root. In the same appointment, the root canals were filled using the lateral cold condensation technique. Endomethasone (Septodont, Saint-Maur-des-Fosses, France) was used as sealer. Temporary coronal filling was performed. The postoperative retroalveolar X-ray showed a slight overfilling of the distal root canal, a thinned distal wall of the mesial root, and a nonhomogenous radioopaque mass protruding in the periodontal space at the mid-level of the root canal (). Patient was informed about the event and advised about the treatment options, including tooth extraction or using MTA applied under a surgical microscope. The second option was preferred by the patient. Due to incorrect root canal filling of tooth #47 as well, both molars were retreated after referral to an endodontist specialist.


An 18-year-old Brazilian man developed dyspnea and fever of one week’s duration and was then diagnosed with right lower lobe pneumonia. Before this incident, he had not experienced any medical complications, lived in full sanitary conditions, denied previous symptoms related to disease, did not have any pets, and denied eating raw meat. He then began hospital inpatient treatment with intravenous antibiotics, and third-generation cephalosporin (Ceftriaxone) and a macrolide (Clarithromycin) were prescribed for 8 days. Laboratory tests from the patient’s admittance showed mild anemia with a hemoglobin (Hb) level of 11.7 g/dL, with normal mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Other biochemical results were as follows: creatinine 0.9 mg/dL, urea 32 mg/dL, total bilirubin 0.2 mg/dL, glucose 90 mg/dL, sodium 134 mEq/L, potassium 3.7 mEq/L, and C-reactive protein 138.2 mg/L. Leucocytes levels were a little low, with 2700 cells/μL. Blood and urine cultures were negative for infection and serological tests for human immunodeficiency virus (HIV), hepatitis B and C, and syphilis were all negative.
On the fourth day of this related treatment, our patient developed abdominal distension and pain in his lower right abdominal quadrant. Acute appendicitis was confirmed by ultrasound examination, and he underwent laparoscopic surgery the same day. Our patient was then taken to our intensive care unit for worsening of his clinical condition. On the fourth postoperative day, our patient developed fever associated with right pleural effusion, which was a lymphocytic exudate with an adenosine deaminase concentration of 17.99 U/L and negative culture (Fig. ). Thus, the attending physicians requested a bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. The transbronchial fluid had negative cultures for infection. At that time, the antibiotic spectrum was extended for treatment of the sepsis, including piperacillin/tazobactam for 10 days.
Anatomopathological examination of the transbronchial biopsy specimen showed a small fragment of lung parenchyma with discrete septal thickening and a rounded structure suggestive of a pseudocyst containing Toxoplasma gondii bradyzoites (Fig. ).
Our patient showed progressive improvement after antibiotic therapy with piperacillin/tazobactam, and was discharged on the 14th day after surgery. A chest radiograph showed significant improvement in lung opacification (Fig. ) and serological tests for toxoplasmosis were negative for immunoglobulin G and immunoglobulin M.
Our patient was followed up on an outpatient basis for 2 years without any signs of recurrence of lung infections or other comorbidities. Serology for toxoplasmosis were repeated and remained negative.


A 59-year-old Iranian woman presented to the orthopedic department complaining of acute pain, swelling and erythema of her left knee 18 days after undergoing cemented TKA due to left osteoarthritis. Body temperature was 39ºC; blood culture for fungus and bacteria were negative. Laboratory investigations revealed a normal white cell count of 4200 cells/mcl and a C-reactive protein (CRP) of 0.8 mg/L. Synovial fluid collected before antibiotic therapy was mildly cloudy and yellow. Microscopic images of the synovial fluid after Gram-staining revealed some leukocytes and yeast cells with broad pseudohyphae and the morphological appearance of Malassezia (Figure 1 ). The patient was suspected of having had a skin disease on all lower body parts for the past several years. The synovial fluid sample did exhibit bacterial growth on blood agar and MacConkey agar, and it remained negative after 48 h of incubation. The patient started antifungal therapy with amphotericin B (500 mg) and fluconazole (400 mg daily).
After one dose antifungal therapy (on the third day of hospitalization) with amphotericin B and fluconazole, the CRP changed from 0.8 to 2.33 mg/L. Furthermore, the patient complained of dysuria, with urine cultures revealing Klebsiella pneumoniae. The isolates were susceptible to amikacin and cefepime only, and resistant to ceftazidime, ciprofloxacin, gentamicin, imipenem, nitrofurantion, and piperacillin by the disc-diffusion method. Due to urinary tract infection (UTI) and increasing CRP, amphotericin B and fluconazole were discontinued, and cefepime (2 g IV q8hr for 7 days) with voriconazole (200 mg orally every 12 hours) was administered. The UTI improved with the antibiotics. The patient is presently receiving oral voriconazole treatment, and is reporting relief of her symptoms. Her symptoms in the left knee have disappeared; she is still under regular follow-up and in terms of her left knee is presently completely asymptomatic.


A-59-year-old woman presented to the hospital with fever, generalized weakness, and decreased appetite started from one week ago.
She was known case of end-stage renal disease due to autosomal dominant polycystic kidney disease that has underwent renal transplantation from a living unrelated donor six months ago in another center. Her medications including prednisolone, cyclosporine, and mycophenolate mofetil (MMF).
She had a history of raised serum creatinine and Candida pyelonephritis in her allograft kidney, one month after transplantation that had been confirmed by kidney biopsy and was treated with caspofungin and her immunosuppressive drugs was discontinued. At that time, she was discharged from hospital with good general condition and normal kidney function while she was receiving voriconazole and low dose corticosteroid. After two months, MMF 250 mg two times per day was added to her drugs. Her serum creatinine was between 1.1 mg/dL to 1.4 mg/dL. She came again with weakness and fever.
On physical examination, she was febrile with a pulse rate of 100 beat/min and blood pressure of 110/70 mm Hg. General physical examination did not reveal any abnormality. Her laboratory data revealed increased leukocyte count with majority of neutrophils, blood urea nitrogen; 92 mg/dL, serum creatinine; 7 mg/dL, hemoglobin level; 9.6 g/dL. Abdominopelvic sonography showed 50×48×35 mm3 heterogeneous splenic mass.
Antifungal therapy was begun and patient underwent splenectomy on third day of her admission.
Spleen biopsy showed abscess formation, including numerous fungal element suggestive for candida infection (). Unfortunately, she died after splenectomy because of fungal septicemia.


A six-year-old female, 192 g, reticulated Pac-Man frog (Ceratophrys ornata) was presented to the Texas A&M University Veterinary Medical Teaching Hospital (College Station, TX, USA) in February 2010 for depression, anorexia, weight loss, and a history of ingestion of foreign bodies (animal ID: 191570).
Five months prior to presentation, the frog ingested small glass beads that were part of the decorations in her enclosure, and was then moved to a different enclosure that contained a moss substrate. The following month, the frog ate an adult mouse and passed normal feces. Subsequently, the frog did not eat, despite the multiple attempts to feed her, and did not pass feces. The owner reported that the live prey used to feed the frog traumatized its digits and back. Prior to ingesting the foreign bodies, the frog had no history of illness. This pet was fed with a diet of live mice and received no additional nutritional supplements. A natural sunlight lamp was used to illuminate the frog's enclosure, and it was covered at night with a towel. The ambient temperature of the enclosure was maintained between 21–24°C.
On presentation, the frog was unresponsive with fixed and dilated pupils. No pupillary light response was noted. Three to five, glass beads were palpable within the coelomic cavity. The distal phalanges of digits 3 and 4 of the right rear leg were missing, and skin over the back was eroded. The frog was determined to be 5–10% dehydrated. No other apparent abnormalities were noted on physical exam. The frog had a body condition score of 1 out of 5. Because of a poor prognosis for recovery, and after informed consent of the owner, the frog was humanely euthanized by first anesthetizing it with a tricaine methanesulfonate (MS-222) bath followed by intracoelomic, pentobarbital sodium injection. Euthanasia was confirmed via Doppler ultrasound.
At necropsy, the liver was tan and friable, and the coelomic cavity of the frog had numerous strands of fibrin and firm adhesions adhering the coelomic organs to each other and to the body wall indicating subacute to chronic peritonitis. The stomach contained six, 2 × 1 cm, elliptical, smooth-surfaced glass beads, but grossly, they did not appear to have affected the stomach. No evidence of metabolic bone disease was observed. No significant lesions were observed in the other body systems. Histologic examination of the liver indicated severe, diffuse, vacuolar degeneration with intrahistiocytic pigment. The final diagnosis was severe, chronic peritonitis. Samples of the liver and peritoneum were submitted for bacterial culture.


A 56-year-old female living in Louisiana presented with a two-month history of diarrhea and abdominal pain which worsened one week prior to presentation. She had undergone orthotopic heart transplantation in 1989 for post-partum cardiomyopathy during which time she was infected with hepatitis C. The patient received a second heart transplant in 2011 due to graft failure. She was on prednisone, tacrolimus and mycophenolate mofetil. She had no history of travel outside of the United States. Her family members engaged in deer hunting.
At the time she was seen in our clinic, she was tachycardic and hypotensive with a heart rate of 109 beats/min and a blood pressure of 89/56 mmHg. Laboratory studies at the time included a total bilirubin 9.4 mg/dL, alanine aminotransferase (ALT) 82 U/L and aspartate aminotransferase (AST) 60 U/L. Stool studies for Clostridium difficile, ova and parasites, Campylobacter jejuni, Cryptococcus, Shigella and Salmonella were negative. PCR RNA for Cytomegalovirus (CMV) and epstein-barr virus (EBV) were unremarkable. Hepatitis E IgM and IgG antibodies were positive at the time of presentation. HEV RNA by PCR assayed six weeks after presentation was undetectable.
Despite supportive management, the diarrhea persisted. Colonoscopy showed only diverticulosis. Random biopsies of endoscopically unremarkable mucosa showed no colitis. MRI of the abdomen showed no mass or biliary ductal dilation. Transjugular liver biopsy showed an active hepatitis with stage 1-2 fibrosis (). The hepatitic changes were felt to be related to hepatitis E given the absence of portal lymphoid aggregates typically seen in chronic hepatitis C.
Immunosuppressive therapy with tacrolimus was reduced from 2 mg to 1.5 mg daily. In addition, she was treated with oral ribavirin 600 mg twice daily for two months. At follow-up, the diarrhea and abdominal pain had resolved. Laboratory values included total bilirubin 1.9 mg/dL, AST 82 U/L and ALT 82 U/L. Follow-up liver biopsy obtained three months after the initial biopsy showed stage 3 fibrosis and marked perisinusoidal fibrosis ().


A 76-year-old Vietnamese female living in Texas presented with a three-week history of generalized weakness, subjective fevers, right upper quadrant abdominal pain, nausea, vomiting, loss of appetite and yellowing of her skin. The patient had moved to the United States 20 years earlier. Her last travel outside of the US was to Vietnam ten months prior to presentation. She had no significant past medical history. On dietary history, it was found that the patient ate pig liver and had been exposed to deer meat.
On physical examination, she was noted to have hepatomegaly without splenomegaly. Serum creatinine was 5.6 mg/dL, AST 122 U/L, ALT 204 U/L, alkaline phosphatase 1,159 U/L and total bilirubin 17 mg/dL. WBC was 11.48 × 103/µL, hemoglobin 8.1 g/dL, MCV 80.9, platelets 163 × 103/µL, INR 1.2 and albumin 2.8 g/dL. MRI of the abdomen and abdominal ultrasound with Doppler were unremarkable. HIV antibody was negative. Acute panel for hepatitis A, B, C and D was also negative. Hepatitis E IgM and IgG antibodies were positive. Hepatitis E PCR was assayed two weeks after admission and was undetectable. CMV IgM and IgG were positive, with serum CMV PCR assay 351 copies/mL. One week later, repeat CMV PCR was unremarkable. Autoimmune panel that included anti-smooth muscle and anti-mitochondrial antibodies, ANA, p-ANCA and c-ANCA were all unremarkable.
The initial renal biopsy showed a small focus of interstitial lymphohistiocytic infiltration (). A follow-up renal biopsy obtained seven weeks later () showed evidence of severe interstitial lymphohistiocytic inflammation with extensive tubular injury and rare eosinophils. No immune deposits or vasculitis were seen. Direct immunofluorescence for IgG4 was negative.
Bone marrow biopsy showed no lymphoma, and flow cytometric immunophenotyping demonstrated no clonal cells or aberrant T cell antigen expression. Alkaline phosphatase isoenzyme assay demonstrated a liver fraction of 83% and bone fraction of 17%.
Transjugular liver biopsy showed very focal mild portal lymphocytic infiltration with rare eosinophils, a small focus of apoptotic hepatocytes, scattered tiny foci of individual hepatocyte dropout and focal minimal intracellular cholestasis (). No granuloma, CMV inclusion, significant steatosis, or fibrosis was seen. Immunohistochemical stain for CMV antigen was negative.
The patient was treated supportively for hepatitis E complicated by acute renal failure. She required intermittent blood transfusions and dialysis throughout her hospital admission. She eventually developed hospital-acquired pneumonia with acute respiratory insufficiency, ST-elevation myocardial infarction and cardiogenic shock, and died five weeks after her initial presentation.