A 42-year-old Caucasian man (twin A) presented to our clinic complaining of lower extremity edema and dyspnea beginning several weeks prior. His past medical history included chronic pancreatitis and insufficiency, diabetes mellitus type one, and former alcohol and cocaine abuse with last use 10 years prior. He also suffered from uncontrolled hypertension despite compliance with his medication. His medications included amlodipine 10 mg daily, lisinopril 40 mg daily, hydralazine 25 mg twice daily, and hydrochlorothiazide 25 mg daily. His family history was significant for a monozygotic twin brother (twin B) who suffered a fatal myocardial infarction (MI) at the age of 40; there was no evidence of premature CAD in any other close relative. Twin B had similar symptoms prior to MI that prompted twin A to present. The decision was made to proceed with ischemic evaluation for twin A given the family history and presenting symptoms.
2-D echocardiogram revealed normal ejection fraction, normal wall motion, moderate left ventricular hypertrophy, grade one diastolic dysfunction, and mild mitral regurgitation. Regadenoson stress testing revealed a large area of moderate ischemia involving the entire inferior wall and inferoseptal wall with associated moderate hypokinesis of the inferior and inferoseptal walls. This was followed by diagnostic coronary angiography which revealed a left dominant circulation and severe triple vessel CAD. There was 50% stenosis of the proximal segment and 80% focal stenosis of the distal segment of the dominant left circumflex artery (LCX), 90% mid-segment stenosis of the posterior descending artery (PDA), and 100% mid-segment occlusion of the right coronary artery (RCA). Finally, the procedure revealed ostial and proximal 40% stenosis and 90% mid-segment stenosis of the left anterior descending artery (LAD). Twin B’s coronary angiography (performed two years prior to twin A’s presentation) revealed 99% stenosis in the left PDA of the dominant LCX, 90% mid-segment stenosis of the RCA, and a prior stent occluded with thrombus in the LAD (Figures -).
Twin A was referred for cardiothoracic surgery evaluation. He underwent coronary artery bypass grafting with grafts including left internal mammary artery to LAD and independent reversed saphenous vein grafts from aorta to diagonal branch and obtuse marginal branches. Eight weeks into recovery, his presenting complaints of dyspnea and lower extremity edema had completely resolved.


A 43-year-old Caucasian male was brought to the emergency department (ED) after he was found lying on the floor for more than 24 hours because of an inability to move his extremities due to profound weakness. Reportedly, the patient did not experience loss of consciousness, seizures, or focal weakness. His past medical history was most significant for anxiety, depression, and polysubstance abuse. Two days prior to the ED arrival, the patient took a bag of cocaine and six tablets of alprazolam. In the ED, his vital signs were unremarkable. On physical examination, profound motor weakness in all four extremities was noted (power: 1/5). Sensory examination and deep tendon reflexes were normal. The patient was awake and alert. On electrocardiogram (ECG), he was noted to have widespread ST depressions and U waves (Figure ).
In his labs, he was noted to have a potassium level of 1.3 mEq/L, magnesium 2.7 mg/dL, bicarbonate 15 mEq/L, creatine kinase 911 U/L, blood urea nitrogen 16 mg/dL, and creatinine 1.27 mg/dL. Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction was negative. Magnetic resonance imaging of the brain and cervical spine were unremarkable. The serum drug screen was also unremarkable. The urine drug screen was positive for benzodiazepines and cocaine. He was admitted to the medical intensive care unit for aggressive potassium and magnesium repletion and frequent electrolyte monitoring. Additional laboratory investigations were requested. Thyroid-stimulating hormone and cortisol levels were normal. The plasma renin-to-aldosterone ratio was slightly below normal. A spot urine potassium-to-creatinine ratio was not suggestive of urinary potassium wasting. After aggressive electrolyte repletion, the potassium started to improve (2.4 to 2.7 to 3.0). He initially got 60 mEq of potassium chloride in the emergency department. Later, in the intensive care unit, he was given additional doses of 40 mEq based on the repeated basic metabolic profile checks. His motor strength gradually improved. By day three of the hospitalization, no motor weakness was observed. The patient was discharged from the hospital and asked to have a close follow-up with his primary care physician. Unfortunately, the patient did not follow up with any healthcare providers after discharge.


A 57-year-old female with multiple melanic bowel movements for one day presented in the emergency department (ED). Her past medical history was significant for systemic lupus erythematosus (SLE), antiphospholipid syndrome, lacunar infarct, hypertension, and osteoarthritis of both knees’ status post arthroplasty. She denied any abdominal pain, nausea, vomiting, or hematemesis. Due to the subtherapeutic international normalized ratio (INR), low molecular weight heparin (LMWH) was added to her anticoagulation regimen for three days. She was also taking meloxicam chronically for her arthritis and prednisone for SLE. The previous history of gastrointestinal bleed or ulcers was negative. Her basic labs revealed hemoglobin of 5 g/dL, INR 2.5, and platelet count within normal limits. While in the ED, she had ongoing melena but was hemodynamically stable. Her warfarin and LMWH were held, and her INR was reversed with fresh frozen plasma. She also received multiple packed red blood cells for a goal of hemoglobin of 7-9 g/dL. Emergent endoscopy revealed a clot in the duodenum extending into the antrum overlying a large 12 mm gastric ulcer with a visible vessel within the pyloric channel extending into the proximal bulb not amenable to endoscopic clipping (Figure ).
Interventional radiology was consulted, and on the pancreaticoduodenal arteriogram, active extravasation was demonstrated (Figure ).
Following coil and surgifoam embolization of the gastroduodenal artery (GDA), the post-embolization arteriogram revealed occlusion of this vessel; and the patient underwent successful embolization of the GDA and main pancreaticoduodenal artery supplying the ulcer. She was later started back on her anticoagulation with heparin bridging and discharged with outpatient follow-up.


A 5-year-old non-castrated male Shetland Sheepdog with DRE was referred to Azabu University Veterinary Teaching Hospital (AUVTH) to evaluate the indication for VNS surgery. Frequent recurrent focal seizures (FS) and FS evolving into generalized tonic–clonic seizures (FS-GTCS) had occurred for 4 years. FS started with bilateral facial twitching or eyelid blinking, mastication, running without purpose, and immobilization and typically lasted for a few seconds to 1 min. FS evolving into GTCS started with the same motor activity before immediately developing into GTCS, which generally lasted 1–2 min. FS evolving into GTCS never continued for more than 5 min. The dog had been treated with various antiseizure drugs (ASDs), including zonisamide for 4 years, potassium bromide (KBr) for 3 years, phenobarbital for 2 years, levetiracetam for 6 months, and gabapentin for 5 months, with adequate dosing and serum concentrations (zonisamide, KBr, and phenobarbital) without good seizure control. The current ASD regimen consisted of zonisamide (8 mg/kg, BID, serum concentration: 56.8 μg/ml), gabapentin (15 mg/kg, TID), levetiracetam (40 mg/kg, TID), and KBr (20 mg/kg, BID, serum concentration: 1.2 mg/ml). Ursodeoxycholic acid and glycyrrhizinic acid were also administered due to slightly elevated liver enzymes. Despite strenuous attempts, seizure frequency progressively increased with countless FS every day and FS-GTCS clusters five to 14 times monthly for the last 6 months.
On presentation to AUVTH, the dog was alert and responsive, but restless. Physical and neurological examinations revealed no abnormalities. A complete blood count and serum biochemistry were unremarkable with the exception of a slight elevation of liver enzymes. X-ray showed microhepatica, and abdominal ultrasound revealed gallbladder mucocele. Fasting and postprandial total serum bile acid concentrations were 3.9 and 119 μmol/L, respectively. Computed tomography (CT) by the referring veterinarian showed no evidence of a portosystemic shunt or nodular lesions in the liver.
The Veterinary Medical Teaching Hospital of Nippon Veterinary and Life Science University diagnosed idiopathic epilepsy based on the Tier III level of the International Veterinary Epilepsy Task Force (IVETF) consensus proposal () 3 months prior to presentation to AUVTH. Magnetic resonance imaging (MRI) of the brain [3T, IVETF recommended protocol ()] and a cerebrospinal fluid (CSF) analysis (proteins, cell counts, and cytology) revealed no abnormalities. Scalp electroencephalogram (EEG) under dexmedetomidine sedation was recorded using the recommended method (). Despite semiology indicating FS, generally synchronized spike or spike-wave complexes were frequently observed in inter-ictal EEG (). During EEG recordings, generalized electroencephalographic seizure activities without convulsions, that is, subclinical ictal EEG, were also noted (). Based on EEG findings, the irritative zone remained unclear.
DRE was diagnosed based on these results and history, and liver cirrhosis was suspected to be caused by multiple ASD treatments, including phenobarbital. VNS was selected as adjunctive therapy because the epileptogenic zone was not identified, and less invasive surgery was preferable due to suspected cirrhosis. The owner also requested VNS therapy.
A VNS device was implanted at AUVTH following ultrasound-guided Tru-Cut liver biopsy. The dog was premedicated with butorphanol and atropine. Anesthesia was induced with propofol and maintained with isoflurane. The VNS device comprised a pulse generator (Demipulse™ Model 103; LivaNova USA, Inc., Houston, TX, USA) and electrode lead with two helical electrodes at the tip (VNS lead M304, LivaNova USA, Inc., Houston, TX, USA) (). The method to implant the VNS device was previously described (). Briefly, the two helical electrodes and anchor tether were wrapped around the left vagosympathetic trunk in the cervical area (), and the electrode lead was connected to the pulse generator implanted in the subcutaneous space cranial to the left scapula. Surgery was uneventful. After confirmation by system diagnostics of proper functioning, the device was maintained at 0 current.
A bandage for cast padding and a self-adherent bandage were applied around the neck to prevent postoperative seroma. During hospitalization, bile peritonitis occurred due to gallbladder rupture, and cholecystectomy was performed 6 days after VNS implantation. Recovery was uneventful. The liver and gallbladder were histologically diagnosed with chronic hepatitis progressing to cirrhosis and mucocele, respectively. The dog was hospitalized for 9 days. Ampicillin sodium/sulbactam sodium was intravenously administered during VNS surgery. Amoxicillin/clavulanate potassium was orally administered for 18 days after VNS implantation.
The device was activated after the neck wound had healed, in accordance with the manufacturer's instructions (). The owner continued to record the number of FS, FS-GTCS, and any other seizures daily in the diary. The owner answered a visual analog scale (VAS) created for epilepsy surgery () in the day the dog was discharged. The VAS was completed again at the end of the 1-year follow-up. This survey was performed to investigate a subjective assessment of the owner to the treatment outcome of VNS therapy such as the QOL of both the dog and the owner.
Nine days after discharge, the dog presented to AUVTH for the first evaluation after VNS implantation. Physical and neurological examinations revealed no abnormalities. There was no seroma, and the wound had healed (). The device was activated using an external programming system with stimulation parameters output current 0.25 mA, pulse width 250 μs, frequency 20 Hz, on-time 30 s, and off-time 5 min, which are initial settings commonly recommended for the treatment of epilepsy in humans (, ) (). There was no cough, voice change, bradycardia, or Horner's syndrome. The dog did not seem to take notice of the region around the left side of the neck where the vagosympathetic trunk was stimulated. The ASD regimen was unchanged from 3 months before VNS implantation to the 1-year follow-up.
Reevaluations were conducted approximately every 2 weeks in the initial post-implant period until the maximum tolerated stimulus current was reached and then every 4 weeks until the 1-year follow-up to screen for any adverse effects, check device function, and assess VNS efficacy. The output current was gradually increased by 0.25 in each visit based on tolerability and treatment efficacy (). Other VNS parameters were adjusted to optimize and minimize adverse effects when required.
The owner was provided with a VNS external magnet, which may be used to stop seizures by swiping over the pulse generator to instantaneously provide an extra temporary stimulation. The output current of the magnet-induced stimulation (i.e., magnet mode) was configured at 0.25 mA above the cycling stimulation (i.e., normal mode). The other parameters of the magnet mode included a pulse width of 250 μs, frequency of 20 Hz, and on-time of 60 s.
In the second reevaluation after implantation (day 14 after VNS initiation), the general condition of the dog as well as seizure frequency and intensity remained unchanged. When the output current increased from 0.25 to 0.50 mA, the dog began to cough during a 30-s cycle of stimulation. Therefore, the pulse width was decreased to 130 μs, which prevented coughing while maintaining the output current.
During the 1-year follow-up, stimulation parameters were adjusted in each visit based on the dog's responses (). FS evolving into GTCS frequency began to decrease after day 14 but increased between days 42 and 63. There are strong fumes from exterior wall painting at a nearby apartment on days 53–62, and the dog became very nervous during this period. There was also a typhoon, which typically induced seizures in the dog, on days 46, 47, 54, and 55. During days 53–62, seizure frequency increased. A routine reevaluation was performed on day 63. It was then difficult to increase the output current without coughing. Therefore, to increase the stimulation intensity and not the output current, we increased the pulse width and decreased the output current while avoiding coughing.
After the output current was set to 0.5 mA and pulse width to 250 μs on day 63, it was not possible to increase the current to more than 0.5 mA without coughing. Since seizure frequency remained reduced and the owner was satisfied with the dog's condition, initial optimal dosing (i.e., highest efficient parameter setting without adverse effects) was attained on day 63, and a reevaluation was re-scheduled for every 4 weeks after day 84. The owner reported that the dog had regained his original character and slept well on day 112. The output current was not increased further due to coughing; therefore, the stimulation off-time was shortened at 3 and 1.8 min on days 112 and 287, respectively, according to a method described for humans (, ). On days 243 and 377, X-ray showed neither twisting of the electrode lead nor subcutaneous migration of the pulse generator ().
Throughout the 1-year follow-up, an 87% reduction was observed in the frequency of FS-GTCS (373 seizures for 6 months before VNS vs. 97 seizures in 1 year after VNS initiation). An 89% reduction in the frequency of FS-GTCS clusters was also achieved (55 clusters for 6 months vs. 12 clusters in 1 year) (). The number of FS-GTCS days also had 76% reduction (93 seizure days for 6 months vs. 45 seizure days in 1 year) (). Due to their very high frequency, the number of FS was not counted before VNS therapy, and, thus, there were no baseline data. The owner was instructed to count the number of FS after VNS initiation, and no decreases were noted during the 1-year follow-up (). However, VAS showed that the duration of FS shortened with measurement decreases from 100 to 15 mm. VAS also showed improvements in the QOL of the dog and owner with measurement decreases from 100 to 17 mm and from 93 to 13 mm, respectively (). Status epilepticus was not observed in the 6-month pretreatment or 1-year VNS treatment period.
The owner used the handheld magnet at the onset of FS or the development of GTCS from FS. When the magnet was used during FS, subsequent GTCS did not occur; however, ongoing GTCS was not stopped. Once the duration of FS shortened, it was difficult to effectively use the magnet because FS had already stopped before the magnet was used.
The only adverse effect of VNS was a cough when the stimulation intensity increased. The owner reported that the dog tolerated VNS. There were no complications of surgery to implant the VNS device.


A 60-year-old female presented to the emergency department in our hospital with acute bilateral eye vision loss. Her past medical history included an undocumented splenectomy, diabetes mellitus, and hypothyroidism. Two weeks prior to the onset of visual symptoms, she reported flu symptoms, including fever, myalgia, and dry cough. The patient neglected these symptoms and did not benefit from any treatment. Fifteen days later, the patient presented with a sudden drop in visual acuity in the left eye without pain, eye redness, or headache which became blinding after 24 hours with involvement of the contralateral eye after four days, associated with right hemibody weakness. Her admission parameters were as follows: pulse 94 beats per minute (bpm), blood pressure 135/88 mmHg, temperature 38.2°C, and oxygen saturations were 85% on room air.
Her neurological examination on admission revealed complete bilateral blindness with no perception of light. Pupil responses to light were abolished with horizontal nystagmus and unremarkable fundoscopic findings. No other obvious abnormal findings in cognitive function, cranial nerves, or neck rigidity were demonstrated. Motor system examination revealed normal bulk in all four limbs. There was hypotonia, most marked on the right side. Power was grade 4/5 in the right hemibody and 5/5 in the left side. There was no involuntary movement or seizures. Plantar reflexes showed bilaterally Babinski signs. All modalities of sensation were conserved. Clinical examination of other systems revealed no abnormalities She presented with breathlessness a few hours after her admission to the neurology department. She was then transferred to the intensive care unit following clinical deterioration and continued increasing oxygen requirements where she was started on non-invasive ventilation.
The patient had magnetic resonance imaging (MRI) (1.5 Tesla) of the brain and orbits with and without contrast, which revealed right parietal nodular signal abnormality in the posterior limb of the internal capsule (Figures -)". No intramedullary abnormal signal or enhancement was present.
Biochemical and cytological studies of the cerebrospinal fluid (CSF) showed an elevated protein count (1.41 g/L) and normal glucose without pleocytosis. No oligoclonal band was found in the CSF analysis. Blood and CSF cultures were negative. SARS-CoV-2 ribonucleic acid (RNA) in the CSF was not detected. She tested negative for myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) and serum aquaporin-4 IgG antibodies. The serum paraneoplastic panel was assessed at the Mayo Clinic, and the serum angiotensin-converting enzyme (ACE) levels were normal. Blood tests showed a highly elevated C-reactive protein (CRP) at 300 mg/L with marked hyperleukocytosis (15,510/μl). Other laboratory results, such as copper, B12, and zinc levels, were checked and were within the reference range. Her nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) was negative for SARS-CoV-2. COVID serology was positive for immunoglobulin M (IgM) and IgG antibodies. Other serological tests for syphilis, human immunodeficiency virus (HIV), human T-cell leukemia virus, types 1 and 2 (HTLV I/II), Epstein-Barr virus, cytomegalovirus, and hepatitis B and C were all negative. Serum ferritin (42.92 μ/L) and interleukin-6 levels (7.8 pg/mL) were normal. They were only measured on Day 5 of her admission (15 days after symptom onset). The patient reported no family history of cancer. Computed tomography (CT) imaging of the thorax, abdomen, and pelvis was done to assess possible malignancy, which was negative. The patient received seven sessions of plasmapheresis and motor physiotherapy sessions, with the prevention of thromboembolic complications by anticoagulant therapy. Her clinical evolution was stationary. A second control by encephalic and medullar MRI was performed and showed stability of the lesion load with disappearance of contrast enhancement with optic atrophy (Figure ).
During her stay in intensive care, she benefited from an immunoglobulin cure (0.40 g/kg per day for five days) associated with corticosteroids. The evolution was marked by the remission of the respiratory discomfort, an improvement in the motor deficits on the right side (5/5 proximal, 4/5 distal), and the persistence of blindness. The patient was then discharged with regular neurology follow-up.


A 61-year-old male presented to his primary care physician (PCP) complaining of intermittent chills, fever, and sweats. The patient had undergone a left axillary-bifemoral bypass graft surgery to repair an abdominal aneurysm 6 years prior. This procedure was complicated by a spinal cord infarction and paraplegia. The results of a complete blood count (CBC), a comprehensive metabolic panel (CMP), a thyroid stimulating hormone, and a urinalysis were within normal limits. Blood cultures were not obtained. His symptoms resolved within a few days and further work up was deferred. However, within 2 weeks, the fevers and sweats recurred. The symptoms continued to recur every 2–3 weeks, and each episode lasted 3–4 days. During the episodes, he had fever as high as 39.8 °C, chills, and sweats. Over the next 3 months, his CBC and CMP remained within normal limits, but his C-reactive protein and erythrocyte sedimentation rate increased from 2.4 mg/dL and 33 mm/Hr, respectively, to 4.8 mg/dL and 39 mm/Hr. Two blood cultures were negative, and a chest radiograph did not find evidence of infection. Three months after symptom onset, an Indium-111-labeled white blood cell scan with single emission positron computed tomography (SPECT-CT) found focal increased radio-tracer uptake in the axillary-bifemoral graft suggestive of focal infection (A and B).
He was referred to the infectious disease clinic for further evaluation. He denied headaches, respiratory symptoms, abdominal pain, skin rash, gastrointestinal symptoms, and urinary symptoms. He lived in a small town in southeast Iowa and he denied recent travel and contact with sick people, including those with tuberculosis. He had no direct animal exposure although there were several farms within a few miles of his house. He worked as an insurance agent and was indoors most of the day. His blood pressure was 121/75 mmHg, his pulse rate was 109 beats per minute, and he was afebrile. Physical examination was unremarkable except for muscular atrophy and decreased strength in both legs. Repeated CBC and CMP tests were all within normal range. Repeated bacterial, fungal, and mycobacterial blood cultures were negative. CT angiography demonstrated a patent left axillary to femoral artery bypass with fat stranding and a small surrounding rim enhancing fluid collection extending from the level of the diaphragm to the iliac crest (A and B). C. burnetii phase I and phase II IgG antibody titers were > 1:32,768. Phase I and phase II IgM antibody titers were 1:64 and 1:32, respectively. A transesophageal echocardiogram did not show evidence of endocarditis. He was diagnosed with C. burnetii vascular graft infection and started on oral doxycycline 100 mg twice and hydroxychloroquine 200 mg three times a day. He underwent explantation of the axillary-bifemoral bypass graft with reimplantation of a cryopreserved artery graft. Cultures obtained during the procedure were negative but C. burnetii polymerase chain reaction (PCR) performed on explanted vascular graft was positive. Three weeks later, he returned to clinic for new onset of orthopnea and leg edema. Fluid retention, possibly due to hydroxychloroquine, was suspected and his treatment was changed to doxycycline and ciprofloxacin, with a plan to continue treatment for at least 18 months.


An 82-year-old man with a past medical history of hypertension and a remote history of cigarette smoking presented to his otolaryngologist with a primary concern of a palpable mass on the right side of his neck. CT of the neck without intravenous (IV) contrast demonstrated no discernible abnormalities within the right parotid gland, though the right retromandibular vein was slightly larger than the left. A follow-up ultrasound demonstrated a focal mass-like abnormality in the deep parotid gland extending around the angle of the right mandible, measuring 2.6 cm by 1.8 cm. There was also a re-demonstration of the prominent retromandibular vein. Repeat ultrasound demonstrated no discernible mass, and the abnormality within the right parotid gland was thought to represent a thrombosed retromandibular facial vein. Magnetic resonance angiography (MRA) of the brain with and without gadolinium revealed an ill-defined region of enhancement measuring 3.0 cm by 1.7 cm in the deep right parotid gland extending medially adjacent to the carotid space and right masticator space. Ultrasound-guided fine-needle aspiration of the parotid mass demonstrated a myoepithelial neoplasm. Additional imaging studies, surgical resection of the parotid tumor, and pathology evaluation were performed.
MRI of the neck with and without gadolinium demonstrated a 3.5 cm by 2.8 cm by 5.2 cm lobulated mass within the deep and superficial portions of the right parotid gland. Interestingly, there was an abrupt cut-off of the asymmetrically enlarged right EJV and compression of the right internal jugular vein (IJV) at the level of the mass, which was concerning for segmental venous occlusion (Figure ). Positron emission tomography with CT (PET-CT) demonstrated the right parotid mass to have a standard uptake value of 10.1. There were no additional fluorodeoxyglucose (FDG)-avid foci to suggest regional or metastatic spread or synchronous cancers.
The patient underwent a right parotidectomy with facial nerve monitoring and a right selective neck dissection of levels II-IV. Intraoperatively, a large, dilated vein was appreciated grossly within the mass that appeared to contain the tumor. Final pathology demonstrated a 5.5-cm poorly differentiated MC involving the parotid gland and surrounding soft tissue with perineural invasion and extensive angiolymphatic invasion. There was also gross invasion into vessels forming nodules and tumor thrombus. Tumor cells were present 1 mm from the superior margin and <1 mm from the medial margin. Nine lymph nodes were dissected from the right neck (levels 2, 3, and 4), all of which were negative for evidence of malignancy.
The tumor was positive for cytokeratin 5/6 (CK5/6), p16, p40, sex-determining region Y-box transcription factor 10 (SOX10), smooth muscle actin, myosin, and synaptophysin, but negative for insulinoma-associated protein 1 (INSM1), nuclear carcinoma of the testis (NUT), S100, erythroblast transformation-specific-related gene (ERG), and uroplakin. However, the screen for human papillomavirus was negative on subsequent ribonucleic acid in situ hybridization study. Tumor positivity for nuclear p40 encompassed the differential diagnoses of squamous cell carcinoma versus MC of the parotid gland. However, subsequent positivity for nuclear SOX10 and focal positive staining for myosin favored the diagnosis of MC []. Figure depicts the basaloid features of this poorly differentiated carcinoma that immunohistochemically stained positively for nuclear p40 and SOX10, consistent with MC of the parotid gland and the positive nuclear ERG staining for endothelial cells, confirming vascular invasion in our patient.
The patient subsequently underwent adjuvant radiation therapy to the right parotid bed, base of the skull, and the right side of levels II through IV. A volumetric arc modulated therapy plan with 6 MV photons was used to deliver a dose of 70 Gy in 35 daily fractions prescribed as a minimal peripheral dose to the planning target volume. No concurrent systemic chemotherapy was administered.
He tolerated treatment well with minimal dysgeusia and xerostomia. He had a restaging PET-CT three months later, which demonstrated innumerable bilateral pulmonary nodules suspicious for pulmonary metastasis. There was no local or regional relapse. A chest CT without IV contrast confirmed numerous bilateral pulmonary nodules measuring up to 1 cm. CT-guided biopsy of a left lower lobe nodule was completed, with pathology demonstrating poorly differentiated MC consistent with metastasis from the patient’s previous primary lesion. He was started on pembrolizumab and was alive at the time of this writing.


A 50-year-old female patient was referred to the department of thoracic surgery, Gazi University for a solitary pulmonary nodule in the left upper lobe detected on computed tomography (CT) of the thorax, which was performed for suspected coronavirus disease 2019 (COVID-19)-related pneumonia. She did not have a history of smoking or any other cardiopulmonary symptoms; the physical examination and routine laboratory tests were non-remarkable. A solitary pulmonary nodule located in the left upper zone and dextrocardia were detected on the initial chest X-ray, following which CT-thorax was done, which revealed SIT and an irregularly shaped pulmonary nodule (15 x 14 mm in diameter) in the left upper lobe (Figures -). On positron emission tomography-computed tomography (PET-CT) scan, the 18f-FDG uptake in the nodule showed a pathological increase (SUV max: 10).
A decision for surgical wedge resection of the nodule, followed by examination of its frozen section, was made; additionally, if required, a lobectomy with mediastinal lymph node dissection was also planned. Informed consent for the procedure, including publication of the radiological images, intraoperative photographs, and videos, was obtained from the patient, and she was taken to the operating room. Following the double-lumen intubation, her left hemithorax was explored in the lateral decubitus position using the bi-portal VATS method. We detected a mirror image of the right hemithorax in the left hemithorax, i.e., the right-sided anatomical structures, such as the three-lobed lung, superior vena cava, and azygos vein, were present on the left side. Additionally, the fissure of the superior segment of the left lower lobe was separate. The pulmonary artery branches of the left upper lobe included a two-branched truncus anterior (apical-posterior), a two-branched posterior artery, and a separate single-branched anterior segmental artery. Likewise, the superior pulmonary vein was formed from the upper and middle lobe veins. IIn addition, there were accessory pulmonary vein branches arising from the lower lobe vein and draining the upper lobe (Figures -).
After identifying the relevant anatomical structures, the nodule was excised by wedge resection, and a frozen section was prepared for examination. The frozen section examination reported the nodule to be NSCLC; consequently, a left upper lobectomy with mediastinal lymph node dissection (intralobar, hilar, paratracheal, and subcarinal) was done. During hilar dissection, the azygos vein was injured, so it was divided with a vascular stapler to facilitate exposure of the upper lobe bronchus and control bleeding. Her postoperative follow-up was uneventful, and she was discharged on the fifth postoperative day. The final histopathological report described the nodule as acinar-type adenocarcinoma, and the pathological stage of the tumor was classified as T1aN0M0/Stage-IA1 according to the 8th TNM classification.


A 22 yr old multigravida (G3P2L1A1) from Jumla, Nepal was brought to the emergency department of Karnali Academy of Health Sciences (KAHS) and admitted with the concerns of multiple erythematous papular rashes with fluid-filled vesicles that had erupted over her face, then on her neck, arms, thorax and back regions. The patient was the first in her family to develop such eruptions and she has no known history of allergies.
Thorough history revealed that the patient is a diagnosed case of epilepsy for which she has been taking sodium valproate since she was 13 years of age. Eighteen days before the admission, the patient had gone for her antenatal care (ANC) visit where she was switched to carbamazepine due to its low teratogenicity compared to sodium valproate. On the 8th day of use of carbamazepine, she developed a cough, sore throat, malaise, fever, and loss of appetite followed by irritation over the eyes. Then, on the 12th day of exposure, in addition to all the above symptoms, she developed erythematous rashes and fluid-filled vesicles that firstly appeared on her face, then spread to the neck, arms, thorax, and back regions.
The patient was brought to the hospital on the 19th day of exposure, before that she visited faith healers. At this time we noticed that she had multiple erythematous papular lesions with fluid-filled vesicles/bullae over her face, then on her neck, arms, thorax, and back regions. She had areas of denuded skin with BSA involvement of 21 % (face: 9 %, right and left upper arm: 2 % + 2 %, back: 2 %, chest and abdomen: 2 % + 2 %, right and left lower limb: 2 %). Nikolsky's sign was positive. Also, ocular examination revealed matted cilia with blepharitis and congested conjunctiva with normal findings in the fundus. Whereas oral mucosa and vermillion border showed painful hemorrhagic erosions, and also, the tongue was edematous. The patient was in pain and couldn't swallow for which a nasogastric tube was introduced.
On the 2nd day of admission, in her 8 weeks and 3 days of gestation, she had per-vaginal bleeding and fleshy clot were passed which was suggestive of spontaneous abortion. So, suction and evacuation were carried out (, , , ).
First sign of ADR was seen on the 8th day of exposure and the worst with 21 % BSA involvement was seen on the 19th of exposure to carbamazepine ()
At the time of presentation, body temperature was 37.33° Celsius, blood pressure was 100/70 mm Hg, pulse rate was 128/min and respiratory rate was 22/min. Test of C-reactive protein came positive and erythrocyte sedimentation rate (ESR) was 50mm/hr. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) measured 44.5 u/l and 50.3 u/l respectively. Other parameters were not deranged and serological tests to rule out infections (human immunodeficiency virus, hepatitis B virus, and Treponema pallidum) came out negative. Considering the history of exposure to carbamazepine, prodromal symptoms, nature of the lesions, and laboratory reports, diagnosis of SJS/TEN overlapping was made.
Carbamazepine was stopped immediately and sodium valproate (200mg, per-oral, once a day) was reinstated. The patient was put on chlorpheniramine (20mg for 7 days), ceftriaxone (1 gm for 14 days), dexamethasone (6mg for 10 days), metronidazole (500mg for 10 days), and paracetamol (500mg for 14 days), all intravenously once in a day. Intravenous fluid was given by maintaining a strict in/out chart. Eye care was done for fourteen days through the administration of eye drops of carboxymethylcellulose (0.5 %) and eye drops having a combination of chloramphenicol (4 mg/ml), polymyxin B (5000 IU/ml), and dexamethasone (1 mg/ml). For oral care chlorhexidine (0.2 %) gargle and topical gel having a combination of lidocaine (2 %), chlorhexidine gluconate (1 %), and metronidazole (1 %) were used. Mupirocin (2 %) ointment was applied in skin lesions after dressing for two weeks. As prophylaxis enoxaparin (40mg, subcutaneously, for 10 days) and ranitidine (30mg, intravenously, in two divided doses for 2 weeks) were used. Abstinence to carbamazepine and supportive measures have worked well for the patient. The patient is recovering well with no trace of new issues and adverse reactions ().
The patient and her family were well counseled about her clinical state and the medications she was put under. Discharge is being planned for the patient with sodium valproate tablets (200mg), chlorhexidine(0.2 %) gargle, mupirocin(2 %) ointment and pantoprazole tablets (40mg for 10 days). She will be asked to visit for a follow-up after two weeks for assessments.


A 56-year-old menopausal female complained with intermittent chest pain for 1 day. The pain was significantly aggravated for 1 h during her shoulder massage. No medication was taken throughout the whole episode. After admission in ER, immediate ECG indicated ST-segment elevation in II/III/AVF and V2-V6 leads and elevated cardiac troponin-I, with sinus rhythm (Fig. ). 30 min later, emergent coronary angiogram was performed, which showed no obstructive lesions in coronary arteries. Afterwards, she was admitted to cardiac care unit with a primary diagnosis of myopericarditis. Physical examination was remarkable for extremely slender habitus and transient pericardial friction rub, with no obvious crackles. Soon after admission, she presented a new-onset moderate fever (38.6 °C) and atrial fibrillation. Auxiliary examination on the admission day: CRP 55.49 mg/L, ESR 96 mm/h, WBC 18.36 × 109/L, Hb 86 g/L, PLT 192 × 109/L, CK-MB 14.74 ng/mL, MYO 304.80 ng/mL, CK 602U/L, TnT-T 0.215 ng/mL, NT-proBNP 1532.0 pg/mL. Echocardiogram indicated minor pericardial effusion. Up to then, we further confirmed diagnosis of myopericarditis possibly induced by infection. Therefore, the patient was treated with oseltamivir 75 mg twice daily for 6 days, piperacillin tamzotan 4.5 g three times daily for 3 days for anti-infection; intravenous immunoglobulin (IVIg) 20 g once daily for 5 days, coenzyme Q10 and phosphocreatine for myopericarditis; diuretic therapy for heart failure; amiodarone and low molecular heparin for atrial fibrillation. 2 days after admission, ECG showed obvious recession of ST-segment, with alleviated fever and chest pain. Furthermore, the cardiac enzymes including TnT-T, CK, CK-MB gradually declined. However, 10 days after admission, the patient suffered again from a fever with the maximum temperature of 39℃ accompanied with weakness and fatigue. Without positive findings of infection, the patient was empirically treated with meropenem and levofloxacin. However, the fever recurred and the thermal spike remained still. Echocardiogram indicated no neoplasm in valves but enlargement of left ventricle (LVEDD 52 mm) and atria (31 mm * 56 mm * 44 mm) with normal ejection fraction of 54%. Cardiac MR at 3 T (Prisma, Siemens Healthcare, Erlangenm Germany) during this episode indicated diffuse swelling and gadolinium enhancement of the pericardium, as well as pericardial effusion, which was consistent with pericarditis, while elevation of global native T1- and T2-mapping value suggested myocardial edema (Fig. ). Based on the unusual therapeutic response, we assumed that this patient was not simply myopericarditis due to infection.
Importantly, we noticed the mismatched elevation of cardiac enzymes after the episode of fever: CK elevated most (maximum 693U/L, reference range 25–200 U/L), CK-MB (maximum 39 U/L, reference range 0.1–4.94 U/L) and no elevation of TnT-T. Furthermore, we noticed that the ratio of CK/CK-MB in this patient was higher than 10, maximum 67.69. The alteration of CK/CK-MB ratio was not parallel to the alteration of TnT-T. These phenotypes of cardiac enzymes strongly indicated the damage of muscle rather than myocardium. Tracing back, the patient recalled an intermittent pain in her left shoulder-back, accompanied with weakness in upper limbs in the recent 6 months. Myositis was highly suspected based on myodynia and elevated CK. We then explored the evidence of myositis. MRI of bilateral upper arms and shoulder joints indicated degeneration and damage of left supraspinatus, left subscapularis tendon and right supraspinatus tendon, characterized by high signal in T2WI. Abnormal spontaneous activities were discovered in electromyography, indicating myopathic damage. Left arm muscle biopsy showed muscular dystrophy with lymphocytes infiltration (Fig. ). Based on the above, the patient met the diagnostic criteria of PM according to the Bohan and Peter Criteria []. However, the etiology of myositis required further explorations. Negative discovery in PET-CT excluded tumors as the common cause of myositis. Finally, autoantibodies analysis (Table ) indicated positive anti-Ku IgG (+ + +), anti-Ro-52 IgG (+) and ANA (1:3000). No proteinuria, negative findings in skins and mucosa, negative anti-SS-A, anti-SS-B, anti-Scl-70 etc. excluded myositis secondary to lupus erythematosus, sicca syndrome, systemic sclerosis (SSc), etc. Considering that the myocardium injury in CMR was adjacent to the epicardium, endomyocardial biopsy might not provide positive findings, not to mention its invasiveness. We can conclude the diagnosis of this patient was PM as well as anti-Ku syndrome with myopericarditis as cardiac involvement.
Afterwards, the patient was administrated with methylprednisolone (1 mg/kg/day) 22 days after the initial episode. Fever and fatigue were finally released. 4 days after methylprednisolone administration, CK and CK-MB was reduced to 131U/L and 11.57 U/L, respectively; NT-proBNP returned to normal. The patient was finally discharged. After discharge, the patient was followed up by both cardiologist and rheumatologist. The patient was administrated with continued glucocorticoid and mycophenolate mofetil (MMF) titrated by rheumatologist. The patient complained no upper limb weakness and fever. ESR, CRP, CK, CK-MB levels were gradually decreased and finally normal 4 months after the first glucocorticoid administration. Two months later, a follow-up CMR was performed and demonstrated diminished pericardial effusion, significantly reduced swelling and enhancement of the pericardium. The global native T1- and T2-mapping value were also decreased (global native T1 mapping: from 1300.9 to 1258.5; global native T2 mapping: from 41.7 to 39.3).


A Hispanic 58-year-old female with a past medical history of gastritis arrived into the emergency room (ER) with acute onset severe pain on the left leg associated with discoloration of the leg. According to the patient, approximately three hours prior to her arrival to the ER, she was walking when, suddenly, she started experiencing sharp pain in her left leg which rapidly progressed. The physical examination was remarkable for left lower extremity pain, discoloration, edema, associated with tenderness to touch, diminished distal pulses, and reduce sensation and mobility throughout the leg, which can be appreciated below (Figure ).
Within the first 30 min after her arrival to the hospital, a pressure Doppler was performed where extensive deep vein thrombosis (DVT) (left femoral-popliteal venous thrombosis) (Figure ) diagnosis was made and within the subsequent 60 min, a computed tomography angiography (CTA) aorto-ilio-femoral runoff with delayed phase was performed, showing delayed opacification of arterial segments below the knee level (Figure ), confirming the diagnosis. A bolus of heparin was given, followed by an infusion. Thrombolysis was offered to the patient, however, she refused due to concern for side effects.
After one hour of starting heparin infusion, blood flow to the leg was regained and the patient recovered full sensation and movement in the leg; coloration returned to normal in the affected leg. The patient was admitted for continued observation and discharged later on direct oral anticoagulants (DOACs) without any recurrence of DVT so far.
The patient denied recent flights, a sedentary lifestyle, surgery, trauma, alcohol, tobacco, and drug use. There was neither a previous episode nor a family history of similar symptoms to her knowledge. Age-appropriate oncology screening was negative; mammogram from June 2020 was normal; colonoscopy four years before the presentation was also negative; Pap smears as well. Thrombophilia workup done by the Hematology/Oncology service was unrevealing, leading to a diagnosis of unprovoked DVT.
The curious part of the case is that even though thrombolysis and thrombectomy are considered the gold standard in the treatment of PCD, this patient had a spontaneous recovery only with heparin which serves as the only purpose to prevent the propagation of the thrombus. This specific patient according to Rutherford limb ischemia classification [] was a IIb which granted surgical intervention. Still, it remains unclear how such an extensive DVT improved in so quick fashion without thrombectomy/thrombolysis but seems that early use of heparin might have played an important role in the evolution of this patient's case and that early use of heparin might decrease the need for surgical intervention in some patients.


A 60-year-old male non-smoker, non-diabetic, and normotensive patient was referred to our center with a history of retrosternal chest pain and dyspnea [New York Heart Association (NYHA) class IV] for two days. The patient had a history of exertional dyspnea and angina (NYHA class II) for the past year, but he was neither on any sort of medication and nor had consulted any physician for the same. The patient denied any past history of fever, joint pain, limb claudication, trauma to the chest. He was a farmer by occupation, and prior to this visit, there was no history of any medication or procedure done on him. On physical examination, his blood pressure was 100/70 mmHg, pulse was 100/minute, and regular in rhythm. The rest of the cardiovascular examination was unremarkable. An electrocardiogram at admission showed sinus rhythm with ST elevation in inferior leads (lead III/aVF) along with reciprocal ST depression in lead I, aVL, and V5-V6 (Figure ). The cardiac biomarkers were significantly elevated. Initial imaging with chest X-ray revealed cardiomegaly with enlarged right heart border (Figure ), and 2D-echocardiogram demonstrated inferior wall hypokinesia with mildly reduced left ventricular systolic fraction and a well-circumscribed cystic mass adjacent to the right ventricle (Figures , ). The routine biochemistry findings are provided in Table .
Angiogram of the left coronary system (Figures -; Videos , ) showed significant left main stenosis with a GCA arising from proximal LAD (Figures -) with Thrombolysis in Myocardial Infarction (TIMI) grade II flow distal to the aneurysm. Diffuse significant lesions in the proximal left circumflex artery and its major branches were also observed.
The ostium of RCA could not be engaged selectively despite several attempts, and a nonselective angiogram revealed occlusion of RCA from the ostium with mild disease in the conal branch of RCA arising from a separate ostium (Figure , Video ).
Subsequently, contrast-enhanced CT (CECT) of the thorax and coronary CT revealed a partially thrombosed giant aneurysm (80 x 60 mm) arising from the proximal RCA (Figure ), compressing the proximal segment of RCA against the aortic wall and causing occlusion from the ostium and a giant saccular coronary aneurysm (30 x 30 mm) arising from the proximal segment of LAD. No other abnormality was noted in the aorta and other major vessels, nor any signs of vasculitis were detected.
The patient was counseled on the need for surgical intervention for his treatment, but he opted for medical management only. He was treated with guideline-directed medical therapy including anticoagulation and was discharged in a hemodynamically stable condition. The follow-up data was not available at the time of writing this case report.


A 23-day-old girl was referred to our department for brain imaging. She was the second child of a nonconsanguineous couple and born at full term by caesarian section. Birth weight was 2400 g (<3rd percentile), length was 47 cm (15th percentile), head circumference was 32 cm (3rd percentile), and her Apgar score was 8/10 at one minute and 10/10 at 5 minutes. The infant had multiple cutaneous finger-like appendages on the right side of her face. There also was a fleshy mobile, skin-colored mass measuring about 12 mm over her right cheek ().
Her sister was about 5 years old without any anomalies or developmental delay. The parents had no medical problems, including no history of abortion or miscarriage. During the pregnancy, the mother was properly under midwifery-led care and there were no antenatal or maternal problems. Also, the mother denied any teratogenic exposure during pregnancy. Physical examination revealed three finger-like, firmed, and skin-colored cutaneous appendages on her right cheek and the right periauricular and mandibular area. Ophthalmologic examination showed a fleshy mass in the place of the right orbit. The right eye was completely blind, and the left eye seemed to have a normal vision. Her echocardiogram showed no structural abnormalities. Her abdominopelvic ultrasound study was unremarkable. The extremities and genitalia were normal. Also, no report of seizure had been documented since birth.
The patient was referred to the department of radiology for imaging work-up. Brain and orbit MRI was performed which showed colpocephaly and agenesis of the corpus callosum. Also, there were nodular subependymal heterotopias, adjacent to the right lateral ventricle. Aplasia of the vermis, hypoplasia of the right cerebellar hemisphere, and widening of the CSF space in the posterior fossa were some other findings in her brain MRI. There were also some skin lesions with exophytic appearance in the face up to 13 × 12 mm in the infraorbital area. In the orbital MRI, there was a mixed cystic solid mass measuring about 25 × 20 mm in her right orbital cavity. The orbital content was abnormal and suggestive of rudimentary orbit. The left orbit was completely normal ().
Finally, based on the findings, diagnosis of oculocerebrocutaneous syndrome (Delleman syndrome) was established for the patient.


In November 2016, a 70-year-old Russian female patient with metrorrhagia was diagnosed with a moderately differentiated cervical carcinoma in a Russian hospital. Her previous family and medical history was negative. In that period, no metastases were found. In December, she underwent chemoembolization with cisplatin of the cervical neoformation. In January 2017, she underwent both hysterectoannexectomy and pelvic lymphadenectomy for local recurrence. The scheduled radiochemotherapy was not performed due to the development of a vesicovaginal fistula as a post-surgical complication. After her arrival in Italy in July 2017, the PET/CT scans detected liver and para-aortic and iliac lymph node metastases as well as dubious lung lesions that a subsequent CT total body better defined as pulmonary consolidations of a probable inflammatory nature.
In September, the patient started chemotherapy with bevacizumab, cisplatin, and paclitaxel (six cycles every 3 weeks) with both good tolerance profile and clinical outcome. In fact, in December her CT scan showed a prominent reduction of liver, para-aortic, and iliac lymph node metastases. After the 6th cycle of chemotherapy, the patient had to continue with bevacizumab maintenance therapy but after two administrations of the drug (February 21 and March 14, 2018) she began to experience mild weakness in the right arm and show signs of cognitive impairment.


A 32-year-old female was referred to our urology clinic and presented with persistent, painless gross hematuria and intermittent, blunt lumbago for 15 days. She did not report any fever, fatigue, edema, dysuria, urgent or frequent urination. Physical examination findings and all laboratory values, including complete blood count, renal and liver functions, and coagulation profile were unremarkable, except for urine erythrocyte at 343.5 /ul (normal range within 0–26 /ul). Urinary cytology and fluorescent in situ hybridization of exfoliated cells were both negative. However, contrast-enhanced abdominal MRI revealed an irregular mass, approximately 5.7 × 3.5 × 1.9 cm in size, in the right renal pelvis (Fig. A), with hypointensity on the T1 weighted image (Fig. B) and slight hyperintensity on the T2 weighted image (Fig. C). Meanwhile, the enhancement of the mass was markedly increased during the arterial phase (Fig. D) and decreased during the portal and delayed phases (Fig. E, F) with multiple enlarged lymph nodes (mild lymphadenectasis) in the right renal hilum. Based on the symptoms and imaging characteristics, a tentative diagnosis of carcinoma of the right renal pelvis was made.
Therefore, the patient underwent laparoscopic right radical nephroureterectomy with partial cystectomy and lymph node clearance around the renal pedicle. Intraoperatively, an elliptic solid tumor, approximately 6 × 4 cm in size, with unclear boundary, was located in the right renal pelvis. The cut surface appeared grayish-white in color, and sectioning showed hard texture without hemorrhage and necrosis. Grossly, the mass partially invaded the adipose tissue of the renal sinus, excluding the perirenal fat (Fig. A). Postoperative pathology reported lymphoid tissue hyperplasia in the specimen and eosinophilic deposits were observed in the follicle centers with numerous plasma cells infiltrating the paracortex zone and lymphatic sinus (Fig. B-D). Immunohistochemical staining indicated CD38 (+), CD138 (+) in the interfollicular plasma cells (Fig. E, F). In summary, the pathology and immunohistochemistry supported the diagnosis of PC type CD.
Subsequently, the patient visited the hematology department for further treatment of CD. A bone marrow biopsy was performed, which excluded hematological malignancies. Serology testing for human herpesvirus-8 (HHV-8) and human immunodeficiency virus (HIV) were both negative. A positron emission tomography with computed tomography (PET/CT) scan revealed slightly elevated metabolism of the operative region (SUVmax 2.7) and in multiple enlarged lymph nodes (SUVmax 2.4–3.3) including the parotid, neck, axilla, hilar and mediastinal nodes. Thereafter, she was treated with R-COP (rituximab 600 mg day1 + cyclophosphamide 1.2 g day2 + vindesine 4 mg day2 + prednisone 50 mg day2-day6) chemotherapy. Six courses later, the patient recovered, and symptoms disappeared. A follow-up PET/CT showed shrinkage and normal metabolism in the lymph nodes mentioned above with no recurrence.


A 45-year-old male with a history of hyperuricemia was brought to the local hospital with chief complaint of anuria for 2 days, with no occurrence of fever, edema, lumbago, hematuria, pyuria, or lower abdominal pain. CT of the abdomen indicated bilateral hydronephrosis and tumors in the renal pelvis and serum creatinine rose to 400 μmol/L (normal range within 32–116 μmol/L). Consequently, percutaneous ultrasound-guided nephrostomy was performed to relieve obstruction and an ultrasound-guided renal biopsy performed on both sides indicated lymphoma.
A few days later he presented to our hospital for further treatment. The antegrade urography demonstrated bilateral hydronephrosis and ureteropelvic junction obstruction with prominent filling defect of the renal pelvis (Fig. A, B). Meanwhile, physical examination revealed no significant abnormalities. His laboratories were notable for low hemoglobin (113 g/L, with normal range within 130–175 g/L), high eosinophil count (0.67 * 109/L, with normal range within 0.02–0.52 * 109/L), high creatinine (146 μmol/L, with normal range within 32–116 μmol/L), and high uric acid (606 μmol/L, with normal range within 90–420 μmol/L). The glomerular filtration rate (GFR) of the left kidney was 14.5 ml/min, and that of the right was 22.2 ml/min. The subsequent contrast-enhanced CT urography (CTU) yielded soft-tissue density masses with an irregular border and mild-to-moderate homogeneous enhancement around the bilateral renal pelvis, measuring approximately 64 × 48 × 73 mm (right) and 74 × 50 × 74 mm (left). And the renal pelvis was compressed with a smooth surface. Obstruction at the ureteropelvic transition, with moderate dilatation and effusion of the renal pelvis and calyces was noticed. Multiple enlarged lymph nodes were observed in the lesser omental sac, hilum of liver and spleen, perirenal and paraaortic regions (Fig. C-F). Urine cytology did not reveal any cancer cells. Based on the above results, the patient was tentatively diagnosed with lymphoma preoperatively.
Intraoperative excisional biopsy and frozen section examination performed to identify the precise nature of the mass indicated a diagnosis of mixed-type CD and ruled out malignancy. To clinically remove the obstruction and rapidly improve renal function, the patient underwent partial resection of the renal hilum masses on both sides. On gross examination, the specimen was composed of a solid mass of gray-yellow and gray-red tissue measuring roughly 5 × 4 × 3 cm. Sectioning of the tissue revealed hard texture (Fig. A). Histopathological examination revealed increased degree of fibrosis and dense infiltration of plasma cells and lymphocytes, with storiform-type fibrosis and obliterative phlebitis (Fig. B-D). Immunohistochemistry demonstrated that many of the plasma cells were IgG (+) and IgG4 (+). More than 40% of the plasma cells were IgG4 (+) with more than 10 IgG4 (+) plasma cells per high powered field (HPF) of specimen (Fig. E, F). Serum IgG4 level was 27.40 g/L (normal range within 0.03–2.01 g/L). Thus, the diagnosis of IgG4-RD was finally confirmed, at which time treatment with methylprednisolone (40 mg/day) and cyclophosphamide (0.2 g every other day) was initiated, followed by a gradual decrease of the dose. Repeat CT scan 3 months later revealed no hydronephrosis, with significant reductions in the size of renal lesions and enlarged lymph nodes. Follow-up studies performed 9 months after the diagnosis confirmed a decrease in serum IgG4 and creatinine to 2.21 g/L and 118 μmol/L, respectively. No recurrence was observed as the patient was prescribed low dose methylprednisolone.


Patient A is a 59-year-old, healthy man from the south of the Netherlands. He was struck in the right eye with an unknown object while cycling along an oak forest, known to be infested with oak processionary caterpillars. At the emergency department, only a small erosion was noticed and a bandage with antibiotics was applied. Due to persisting pain a day later, the patient was referred to a general ophthalmologist.
The main complaints were itching and photophobia in the right eye. Visual acuity was normal. On slit-lamp examination, more than 30 small hairs were seen in the cornea on the inferonasal side (Fig. ). The processionary setae were already lodged in the corneal stroma and could not easily be removed. Therefore, patient was prophylactically treated for possible pathogens on the hairs, including fungi; topical ofloxacin and chlorhexidine were given four times a day.
Two weeks later, the patient was free of complaints. The setae had remained in their exact same position. There was no aqueous reaction, nor had limbal nodules developed. Topical medication was stopped hereafter.


Patient B is a 46-year-old man with complaints of red and itchy eyes. Interestingly, he had red, itching bumps all over his body as well. This happened after he walked through the forest a day prior to presentation at the outpatient clinic. Our patient had normal visual acuity. Nasal hyperaemia in the left eye was the only pathological finding that could be assessed on slit-lamp examination, for which he was treated with topical ofloxacin and chlorhexidine, both six times a day. After a week, there were no complaints and the drops were discontinued.


Patient C is a 56-year-old man that presented with a red right eye with good visual acuity and multiple red spots on his arms. The day before presentation, he biked through a forest known to be invaded by oak processionary caterpillars. Slit-lamp examination showed hyperaemia and chemosis of the conjunctiva with several setae lodged in the cornea. The setae in the epithelium were removed by a hockey-stick knife. As before, topical ofloxacin and chlorhexidine, both six times a day, were given. In 3 days, the clinical state had improved and after 2 weeks there were no complaints and the drops could be discontinued.


Patient D is a 70-year-old man that was referred with progressive decline of visual acuity in his left eye since 2 months. He was treated with anti-VEGF because of exudative age-related macular degeneration. Six weeks after injection, he noted a decline in visual acuity, which was 0.05 (Snellen) at presentation. On slit-lamp examination, hyperaemia of the conjunctiva, 2+ cells in the anterior segment, no flare and 4+ cell in the vitreous were found. Also, three thin, hair-like structures were seen floating in the vitreous. Fundoscopy only showed a red reflex.
During subsequent pars plana vitrectomy, around ten hairs were seen in the vitreous, with haze and lots of inflammatory cells (Fig. ). Intravitreal antibiotics and subconjunctival steroids were given. Additional anterior chamber tap and culture of the vitreous showed no pathogens.
The vitreous was sent for pathological examination, and oak processionary setae were collected from a nest in an oak tree near the hospital by a brave pathology resident for comparison. Typical processionary setae could not be identified in the vitreous, due to the lack of the characteristic barbs (Maier et al. ). This could be the result of the hairs being in vitreous inflammation for 2 months (Steele et al. ; Fraser et al. ).
With all other diagnoses excluded and the ongoing outbreak of oak processionary caterpillars, this case of endophthalmitis was concluded to be caused by a reactive uveitis to processionary setae (RUPS). On follow-up, visual acuity remained low (0.1), possibly because of other ocular morbidity.


A 7-year-old girl, born to non-consanguineous parents, was referred to our department for the evaluation of numerous soft brownish papules on her face, trunk and back resembling skin tags. On clinical evaluation we also observed translucent pearly papules, mainly localized on the limbs, and on the dorsum of the feet and toes. Her parents reported that the lesions had appeared after birth. One of the skin tag-like lesions and one of the translucent papules were surgically removed, with a histological diagnosis of infundibulo-cystic BCC and BFH, respectively. On careful examination, peculiar facial anomalies such as macrocephaly, broad nasal ridges, heavy and fused eyebrows, mild hypertelorism with down-slanting eyes and micrognathia were noted. Also, mandibular odontogenic keratocysts had been surgically removed at the age of 5 years. Genetic analysis of the PTCH1 gene showed c.878_904delTTA de novo mutation in a heterozygote state, confirming our suspicion of sporadic BCNS. Family history was negative for BCNS.


A 6-year-old Caucasian girl, born to non-consanguineous parents, was referred to our center with a suspicion of BCNS. She had undergone surgical removal of a medulloblastoma followed by chemotherapy and stem cell transplant at the age of one year and presented a history of BCNS on her father's side. On physical examination numerous erythematous skin tag-like lesions were observed on her neck and two were removed, with a histological diagnosis of infundibulocystic BCCs. Pearly translucent papules ranging from 1 to 2 mm in diameter on the trunk and the dorsum of foot and toes were also present. On anamnesis, the onset was at the age of six months, with a progressive growth in diameter over the years. Four of these lesions were removed, with a diagnosis of BFHs. Analysis of the PTCH1 gene confirmed the c.886delT mutation in a heterozygote state of PTCH1 gene, also present in her father.


A 5-year-old Caucasian boy, born to non-consanguineous parents, presented at birth a triventricular hydrocephalus, treated with ventriculoperitoneal repositioning. At the age of 4 years, the patient presented a head circumference in the 97th percentile, mild frontal bossing and synophrys. Radiographic examination revealed odontogenic cysts adjacent to the left mandibular canal. Small hyperpigmented papules, present at birth, were detected on the sole of the right foot. The lesion was removed and the histological diagnosis was BFH. In the next six months, another two similar lesions were removed, with the same histological diagnosis. The child underwent further investigations due to a strong clinical suspicion of sporadic BCNS and the diagnosis was confirmed by the analysis of the PTCH1 gene, which highlighted a c.2795_2795delT de novo mutation in a heterozygote state. Family history was negative for BCNS.


A 35-year-old G2P1 with history of previous cesarean section attended the Out Patient Department (OPD) of Kathmandu Medical College with history of amenorrhea for one and half months, and non-specific periumbilical pain with no other alarming symptoms. On examination her general condition was fair, her vitals were within normal limits. Per abdominal examination and per speculum failed to reveal any abnormality.
She however produced two transvaginal sonography (TVS) reports, one report revealed a single gestational sac of 6 weeks 1 day in the anterior myometrium with subtle echogenicity in the adjacent wall suggestive of scar pregnancy (). The other TVS done a couple of days apart showed an intrauterine gestational sac corresponding to 6 weeks 5 days in the uterine endocervix which suggested a cervical pregnancy ().
She was admitted and planned for an Magnetic Resonance Imaging (MRI) of pelvis due to the diagnostic dilemma. MRI conclusively showed a well-defined cystic lesion of (21x19)mm2 in the anterior aspect of the lower uterine segment embedded within the previous cesarean scar evocative of cesarean scar pregnancy ().
With the provisional diagnosis of cesarean scar pregnancy, laparotomy was performed. Laparotomy unveiled uterus around 6 weeks size, bilateral ovaries and fallopian tubes were normal. However a (3x3)cm bulge was noted at the lower uterine segment at the site of previous cesarean scar (). Previous scar was intact and a small incision was given over the bulge and the gestational sac was removed following which the uterine incision was closed with 2-0 polyglactin suture ().
She had an uneventful postoperative period and was discharged on the 4th postoperative day on oral antibiotics.


A 31-year-old incarcerated male with schizophrenia and untreated chronic hepatitis C was transferred to our facility for the evaluation of altered mental status and agitation. During the week preceding admission, the penitentiary staff reported that he was uncharacteristically digging through trash cans and had become increasingly agitated. Upon transfer to our hospital, the patient was already intubated and deeply sedated. As sedation was weaned, he demonstrated repetitive, involuntary, non-fatigable choreiform movements with associated hemiballismus of the right upper and lower extremities (Video ).
He did not have any focal weakness or any other focal neurological signs on examination. Relevant findings on laboratory evaluation were white blood cells 17.2 x 109/L (3.5-10.5 x 109/L) and creatine phosphokinase 6950 unit/L (30-200 unit/L). The remainder of his complete blood count, basic metabolic, hepatic, and coagulation profiles were unremarkable. HIV testing was negative and the hepatitis C viral load was 153,767 IU/ml. Urine drug screen was positive for benzodiazepines only. MRI of the brain demonstrated abnormal restricted diffusion and T2-weighted-fluid-attenuated inversion recovery (T2-FLAIR) hyperintense signal with associated enhancement in the globus pallidus, internal capsule, and cerebral peduncles bilaterally, representing multiple small areas of cerebritis and abscess formation within the basal ganglia (Figures -). A lumbar puncture was performed and had an opening pressure of 27 centimeters of water with 36 red blood cells/microliter, 89 nucleated cells/microliter (69% lymphocytes, 15% neutrophils, and 11% monocytes), 32 mg/dL of glucose (45-75 mg/dL), and 118 mg/dL of protein (15-50 mg/dL) in the cerebrospinal fluid (CSF). The CSF cryptococcal antigen was positive with a 1:320 titer and fungal culture grew Cryptococcus neoformans (grubii subtype by molecular typing). The patient was initiated on intravenous amphotericin, dexamethasone, and oral flucytosine.
Despite successful extubation, the patient remained confined to the intensive care unit for over 50 days due to the need for analgosedation to control the violent flailing of his leg. Tetrabenazine, haloperidol, olanzapine, lorazepam, amantadine, valproic acid, and gabapentin were unsuccessfully titrated to the maximal tolerated dose. He underwent six lumbar punctures for the management of raised intracranial pressure. The CSF protein and glucose both normalized on hospital day 15 and CSF pleocytosis declined to 1 white blood cell/mcL on hospital day 26. His cryptococcus antigen titers sequentially decreased to a final titer of 1:10 and the last opening pressure was recorded at 13 centimeters of water. Repeat MRI on hospital day 30 showed improvement in restrictive diffusion, T2-FLAIR hyperintensities, and resolution of the enhancement in the basal ganglia and cerebellum.
After completing six weeks of induction antifungal therapy, the patient’s distressing hemichorea-hemiballismus was not controlled despite normalization of CSF parameters and radiologic improvement noted on repeat MRI. As the pharmacologic options had been exhausted for his movement disorder, he underwent a unilateral left pallidotomy on hospital day 56. Using standard stereotactic methodology, the posterior-ventral pallidum was targeted and intraoperative test stimulation was used to avoid capsular lesioning. Three lesions (60 seconds at 80°C) were delivered to posteroventral globus pallidus interna (anterior commissure-posterior commissure {AC-PC}: anterior-posterior {AP} = +2.1 mm, mediolateral {ML} = -19.0 mm, superior-inferior (SI) = -3.2, -6.2, -9.2mm). His choreiform movements dramatically improved within 48 hours, and he was discharged from the hospital. Six weeks later, he was able to walk during his follow-up appointment and his hemichorea-hemiballismus had not recurred (Video ).


A 64-year-old male was brought to the emergency department (ED) by helicopter after sustaining an injury falling over a fence. The patient reported injuring his “stomach” and feeling a pop followed by severe back pain. On scene, the prehospital paramedics reported no pulses in the bilateral lower extremities. Prior to arrival, the patient had been given 250 micrograms fentanyl, 20 milligrams (mg) labetalol, and 4 mg of midazolam by medics for concern of possible aortic dissection. Vital signs upon arrival included a blood pressure of 166/102 millimeters of mercury, heart rate of 92 beats per minute, 16 respirations per minute, an oxygen saturation of 96% on room air, and a temperature of 99.2ºF. Physical examination was notable for 2+ carotid and radial pulses bilaterally, and absent dorsalis pedis and popliteal pulses bilaterally. Point-of-care ultrasound identified a large infrarenal abdominal aortic aneurysm (AAA) of approximately 7 centimeters (cm) in size with contained thrombus within the lumen. ( and ).
Computed tomography angiography of the chest, abdomen, and pelvis reaffirmed the presence of an acutely ulcerated thrombus contained within the lumen of the aorta and no evidence of extraluminal contrast extravasation. This information, combined with vascular duplex ultrasound of the lower extremity confirming extensive clot burden down to the level of the dorsalis pedis, was presented to our vascular surgeon and therapeutic interventional radiologist on call. In shared decision-making with the patient, this multidisciplinary team initiated anticoagulation with unfractionated heparin and transferred the patient to the operating room for emergent embolectomy and intra-arterial tissue plasminogen activator.


A 23-day-old, female, term newborn (birth date: September 03, 2020) was admitted to a district general hospital in Belo Horizonte, Brazil. The infant was hypothermic, dehydrated, and hypoactive, with diarrhea, vomiting, and poor peripheral perfusion. There was no relevant obstetric or developmental history. The infant's birth weight was 3.250 g, and their height was 48 cm. The infant was immediately referred to the intensive care facility for appropriate monitoring and investigations, including X-rays, blood tests, and a lumbar puncture (LP). These investigations demonstrated no significant abnormalities ().
The patient developed significant apnea episodes and requiringoral intubation with mechanical ventilation. A chest CT scan was conducted, which demonstrated bilateral pneumothoraxes. A drain was inserted to treat the pneumothoraxes, resolving the infant's respiratory distress. The initial chest X-ray had a normal cardiac size, and the CT scan showed no signs of frosted glass. A COVID-19 PCR test was conducted and was positive. The parents were not positive for COVID-19, albeit one of the caregivers (the father) worked as a physician and had contact with COVID-19 patients. An echocardiogram (ECHO) showed an ejection fraction (EF) of 49% (moderately reduced) with no other significant abnormalities ().
It was considered that the patient had viral myocarditis and was treated with a fluid infusion, dobutamine, epinephrine, and antibiotics for 10 days (cephalosporins, beta-lactam antibiotics, and aminoglycosides). The infant was weaned from mechanical ventilation and discharged from the hospital for outpatient follow-up at 18 days with furosemide and an angiotensin enzyme inhibitor (ACEi).
At 55 days of life (on October 27, 2020), the infant returned to the hospital, presenting with tachypnea, tachycardia, lethargy, diarrhea, vomiting, and difficulty in breast feeding (). Their symptoms were similar to their last admission to the hospital. The infant required intubation with mechanical ventilation and developed clinical signs of decompensated heart failure with worsening left ventricle function, by ECHO. The patient received dobutamine, epinephrine, and levosimendan. Given that the provisional diagnosis was a post-viral cardiomyopathy, immunoglobulin was administered. In total, the child was hospitalized for 55 days, being discharged at 3 months of age with spironolactone, ACEi, carvedilol, furosemide, and hydralazine.
On December 30, 2020 (age: 3 months), the infant presented with signs of low output (which included emesis, cold and sticky skin, drowsiness, tachypnea, and tachycardia). During an attempt to pass a PICC line, the child became increasingly agitated with apneic episodes. A COVID PCR was negative for COVID-19. The infant was intubated with mechanical ventilation for 2 days, and CPAP for a further day. During this period, the infant received vasoactive drugs (milrinone, dobutamine, and epinephrine). An ECHO showed severe DCM with mitral valve insufficiency, pulmonary hypertension, and an EF of 35%.
Given the concerning emerging features, the infant was transferred to a tertiary cardiac center in São Paulo on February 12, 2021. On transfer, the patient was receiving mechanical ventilation, with epinephrine 0.06 mcg/kg/min and milrinone 1 mcg/kg/min. A prompt cardiac work-up was conducted, including two ECHO scans:
The first was conducted on February 12, 2021, on admission. This demonstrated DCM with pulmonary hypertension and left ventricular systolic dysfunction (LVEF) of 28%.
The second ECHO was conducted on April 29, 2021. This demonstrated worsening systolic function, LVEF 17%.
A CXR demonstrated significant cardiomegaly (). The patient was negative for Coxsackie virus and Parvovirus. A gallium-67 scintigraphy was negative for an active cardiac inflammatory process. An abdominal ultrasound was unremarkable. A Holter demonstrated normal sinus rhythm (max: 195, min: 86, average: 129, EEVV: 27 EEAA: 21). A thorough evaluation excluded innate errors of metabolism as well as major genetic causes, with whole-genome sequencing demonstrating a variant of uncertain significance which was not known to cause ventricular dysfunction. There was no family history of cardiomyopathy, arrhythmia, or sudden cardiac death. Finally, a cardiac MRI demonstrated left ventricle DCM without late enhancement or edema and a discrete pericardial effusion (EF 21%, left ventricle end diastolic diameter: 40 mm, left ventricle end systolic diameter: 36 mm). Serologies for myocarditis were negative. With difficulties in weaning the infant from inotropic drug therapy, the patient was promptly referred for pediatric cardiac transplantation.


A 38-year-old woman presented to the maxillofacial surgery clinic of the Department of Neurosciences at ASST Ovest Milanese complaining of mild proptosis of the right eye and minimal binocular diplopia in the right gaze, which had appeared a few months earlier.
MRI of the orbits showed an enhanced, T2-hyperintense, T1-isointense, intraconic lesion in the inferior lateral part of the right orbit just behind the ocular globe ().
Preoperatively, the patient underwent contrast-enhanced MRI with volumetric acquisition (1–1.20-mm slice thickness) for 3D reconstruction. The woman underwent surgery to remove the lesion with a transpalpebral approach through the right inferior eyelid. The surgical procedure was performed by the second author (S.P.), who has substantial experience in transpalpebral approaches for orbital tumors and orbital reconstruction.
The patient was placed in a supine position, with the head slightly rotated to the left side.
The entire surgical procedure, starting from the skin incision, was performed under 4K-3D exoscopic vision. After the skin incision of the lower eyelid, a blunt dissection to expose the inferior orbital rim up to the lateral canthus was performed, and then gently dissecting the periorbit from the lateral wall.
Minimally-invasive removal of the lesion was aided by the use of intraoperative navigation (electromagnetic StealthStation S8, Medtronic) and ultrasound (BK 5000®, BK Medical) in order to limit retraction on the ocular globe, and to reduce the incision of the periorbita and manipulation of intraconic structures within the periorbital fat (). The main steps of the surgical procedure are clearly visible in the attached Video as well as summarized in .
There were no complications during the procedure.
The surgical time was comparable to that of the same procedures previously performed by the same surgeon with loupes.
Postoperative MRI showed complete removal of the lesion (). The esthetic result for the patient was optimal (). Histological examination returned a diagnosis of cavernous hemangioma.


A 44-year-old Saudi male, was referred to our clinic from Dammam Medical Centre (DMC) for a scalp lesion suspicious for basal cell carcinoma. The patient initially noticed a mass on his scalp that appeared one year ago, gradually increasing in size. Not associated with pain, discharge, headache or itching. Patient denied any systemic features such as, fever, abdominal pain, nausea or vomiting. He presented to DMC for evaluation as the size was starting to bother him. On examination, there was a scalp lesion 1x2cm in size, regular borders, no signs of inflammation or infection. The patient's past medical history is significant for hypertension and diabetes mellitus. Past surgical history involved a hemorrhoidectomy ten years ago. The patient is on antihypertensive and anti-diabetic medications with no known allergies. No significant family history was noted. The patient subsequently underwent excision of the lesion and subcutaneous tissue under local anaesthesia in DMC. He was discharged on ibuprofen 400 BID PO for five days and omeprazole 40 mg OD PO for seven days. Ten days later, when he represented to the clinic for suture removal, there was a small area of wound dehiscence in the upper edge of the wound. The histopathology report at the time was consistent with basal cell carcinoma, nodular type with deep surgical margins involved by tumour cells. The patient was then referred to our surgical oncology clinic in King Fahad Specialist Hospital (KFSH) for re-excision of positive margins and further management. A slide review () was done in our hospital which showed skin adnexal tumour with trichilemmal differentiation favouring trichoblastoma with small tiny foci of tumour cells present in the inferior margin (1 mm). The slide was sent to an expert dermatohistopathologist for a final report which confirmed our findings and a final diagnosis of Trichoblastoma with benign features was made. A computed tomography (CT) scan was done of the head and neck which showed subcentimetric lymph nodes with suspicious morphology involving the posterior aspect of the neck, the post auricular and sub-occipital region. The patient underwent wide local excision under general anaesthesia which was performed by a breast and endocrine surgery consultant. The patient was then discharged home on analgesia and followed up in clinic 10 days later for removal of superficial sutures and alternating removal of deep sutures. He was seen again seven days later for the removal of the remaining sutures.


A 37-year-old African American female with a history of two unprovoked deep venous thromboses (DVT) treated with apixaban was evaluated for a pruritic rash of two weeks' duration. She had started apixaban two months prior to the rash onset; there were otherwise no changes in her medication regimen. The exam showed hyperpigmented brown scaly plaques with central atrophic patches on the conchal bowl of the ears (Figure ), violaceous nodules, and indurated plaques with scattered flaccid vesicles on the medial thighs, knees, and antecubital fossae (Figures , ), and eroded plaques with dry, serosanguinous crust on the elbows. Vesicles were not appreciated on non-lesional skin and there was no mucosal involvement. She endorsed hematuria and weight loss but denied lesion photosensitivity. Laboratory analysis was significant for leukopenia (WBC of 3.4 thousands/μL), anemia (hemoglobin of 5.6 g/dL), and proteinuria. Serology was positive for antinuclear antibodies (ANA) (>1:160), anti-double-stranded DNA (anti-dsDNA), anti-Smith, anti-Ro/SSA, cardiolipin antibody, beta2 glycoprotein antibody, and low C3 and C4 complement.
A 4-mm punch biopsy of a representative lesion from the medial knee was performed. Histopathologic findings suggested early SCLE and consisted of basilar vacuolar degeneration with scant dermal perivascular lymphocytic infiltrate (Figure ). Colloidal iron staining highlighted mucin deposition throughout the superficial and deep dermis (Figure ). Apixaban was discontinued and warfarin initiated. Triamcinolone 0.01% was used as needed for her skin. She remains in remission at her three-month follow-up, treated with hydroxychloroquine (200 mg BID), mycophenolate mofetil (1 gm BID), and prednisone (40 mg daily) for her SLE and lupus nephritis, respectively.


An 80-year-old Hispanic male with known medical problems of hypertension, type II diabetes mellitus, hyperlipidemia, gout, and iron deficiency anemia (baseline hemoglobin [Hb] of 11.1 g/dl) presented to the ER with complaints of generalized weakness and malaise for the past two days. The patient endorsed that he took his second dose of Pfizer-BioNTech COVID-19 vaccine two weeks before his presentation to the ER. The patient denied any fever, nausea, vomiting, diarrhea, chest pain, dyspnea, recent travel, sick contacts, drug abuse, and pedal edema.
On examination, the patient was in no acute distress. The patient's vitals were blood pressure of 154/84, heart rate of 88, respiratory rate of 22, saturating 99% on room air with a temperature of 37 degrees Celsius. He was pale and icteric. Oral examination showed purpura spots in the buccal mucosa. No cervical lymphadenopathy was noted. The abdomen was soft, non-tender, not distended, and no hepatosplenomegaly was noted. Respiratory and cardiovascular system examinations were normal. No focal neurological deficits were noted, power was 5/5 in all four extremities. Bilateral lower extremities were positive for purpuric spots.
Laboratory evaluation showed normocytic normochromic severe anemia with Hb of 4.8 g/dl, hematocrit was 14.2%, and thrombocytopenia with a platelet count of 48 x 10^3/mcL. His blood urea nitrogen was elevated at 75 mg/dl and creatinine of 2.4 mg/dL (baseline was 1 mg/dL). Liver function test showed total bilirubin of 3.3 mg/dL with direct bilirubin at 0.6 mg/dL and indirect bilirubin at 2.7 mg/dL. Prothrombin time was 12.2 and the international normalized ratio (INR) was 1.2. Lactate dehydrogenase (LDH) was elevated at 1118 U/L and haptoglobin was less than 10 mg/dL. Troponin was elevated at 3.810 ng/ml (Table ). Peripheral blood smear showed 3+ schistocytes in each high-power field (Figure ). All these findings raised concern for MAHA. The ADAMTS13 antibody inhibitor titer was 182%, and ADAMTS13 activity was less than 2%, which confirmed the diagnosis of TTP. Work up for anti-nuclear antibodies (ANA), anti-Smith antibodies, anti-double-stranded DNA (anti-dsDNA) antibodies, Scl-70 scleroderma antibodies, and anti-centromere antibodies were negative ruling out systemic lupus erythematosus, antiphospholipid syndrome, and systemic sclerosis as the cause for MAHA and thrombocytopenia. The stool culture was negative, and the patient did not have abdominal pain and diarrhea, ruling out Shiga toxin-mediated HUS as the cause for MAHA and thrombocytopenia. For the initial management of TTP, the patient received a transfusion with two units of packed RBCs and two units of platelets. The treatment was followed by prednisone 80 mg per oral daily and plasmapheresis. Over the subsequent 10 days, the patient recovered symptomatically, with laboratory data showing complete resolution of TTP. The patient was started on rituximab as an outpatient therapy to prevent relapse.


An 86-year-old male was referred to Saitama Medical University Hospital (Moroyama, Saitama, Japan) from a local dentist in July 2015 due to the presence of an intraoral mass. The patient had not noticed the mass until the dentist brought it to his attention. His previous history included transitional cell cancer of the bladder, but his family history was unremarkable. The round mass, measuring 12 mm in diameter, was located in the left buccal mucosa (). The mass was soft, nontender, and nonadherent to the surrounding tissue, and the surface exhibited normal mucosa. Magnetic resonance imaging (MRI) of the left buccal region showed a mass with intensity lower than that of skeletal muscle tissue on T1-weighted imaging () and with intensity higher than that of adipose tissue on T2-weighted imaging (). This was diagnosed as a benign buccal tumor and was subsequently resected under local anesthesia. The tumor was easily dissected from the surrounding tissue and appeared to be covered with a thin fibrotic capsule. The resected specimen measured 2 cm at its largest diameter () and was filled with glossy, mucoid, and milky white materials (). Microscopically, the tumor cells in the sparse mucoid matrix () exhibited a spindle or stellate shape without nuclear atypia (data not shown). The tumor matrix had abundant collagen fibers and was strongly stained with alcian blue, indicating the presence of acidic polysaccharides (data not shown). On immunohistochemistry, the tumor cells were negative for S-100 protein, ASMA, and CD3 (data not shown). The final histopathological diagnosis was a myxoma. The tumor was completely resected, and five years later, the patient exhibited no recurrence or distant metastasis.


A 48-year-old female with a past medical history of low-risk JAK2 positive PV presented to the emergency department with a chief complaint of right eye pain for eight days. Her pain started after she had an accidental low-impact trauma inflicted by her child. She described non-pulsatile, dull pain with increasing intensity overlying her right eye. She had no visual changes in her right eye and unchanged chronic left eye myopia. To attenuate the pain, the patient consumed 12 tablets of 81 mg aspirin every day for three days at the onset of pain. She took preparations of ginseng and other unspecified Chinese herbs and prepared a herbal poultice to place over her right eye.
Her PV was diagnosed in China more than 15 years ago. She was compliant with therapeutic phlebotomies every two months for treatment of her PV, however recently she was not able to get to the clinic due to novel coronavirus restrictions. She was treated in the past with Hydroxyurea but was discontinued due to severe mucositis. Three years before presentation to our institution, she had been having heavy menstrual bleeding. Ristocetin-induced platelet aggregation assay showed decreased Von Willebrand factor (VWF) activity. Therefore, scheduled 81 mg of aspirin daily was stopped. Abdominal ultrasound, performed for the indication of abdominal swelling, revealed splenomegaly with 19.4 cm spleen in maximal dimension as well as a fully distinct 2 cm splenule.
At the time of presentation to our institution, she had no skin or eyelid wounds, mucosal bleeding, menorrhagia, joint swelling, rash, bruises, or neurological deficits. She has no family history of coagulopathy. Her vital signs were within normal limits. Her neurological exam revealed normal extraocular muscle movement, normal visual fields, decreased left eye visual acuity that remains unchanged from previous encounters. The rest of her neurological examination was unremarkable.
CT head without contrast was significant for right-sided subdural hematoma with a 6 mm right-to-left subfalcine shift and mass effect noted in the right ventricle without evidence of hydrocephalus (Figure ). CTA scan of the head and neck showed a 4-mm cortically based vascular malformation or suspected aneurysm observed within the right parieto-occipital region (Figure ). At the time of admission, her hemoglobin was 14.8 gm/dL, hematocrit was 53.6%, mean corpuscular volume was 68 fL, platelet count was 1,029,000/µL, and white blood cell count was 24,800/µL. Peripheral blood smear showed microcytosis, hypochromia, and polychromasia. Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) were within normal laboratory limits. VWF activity was reduced to 26%. She had a normal factor VIII assay. Platelet mapping revealed no inhibition to arachidonic acid (AA), but significant inhibition to adenosine diphosphate (ADP) (60% inhibited) was observed with a significant reduction in the mean amplitude of clot.
Magnetic resonance angiography (MRA) revealed a possible saccular aneurysm, measuring up to 0.7 cm, along the lateral aspect of the right parietal lobe associated with a distal branch of the right middle cerebral artery (MCA). Apparent clotted blood material surrounding this aneurysm was observed. Direct angiographic imaging of the right internal carotid artery was then performed which showed an inferolaterally projecting aneurysm arising from the mid aspect of M4 right MCA branch, specifically the angular artery. The aneurysm in question measured 3.6 x 3.9 mm. The neck of the aneurysm was relatively wide, measuring 3.2 mm (Figure ). The right anterior and remaining right middle cerebral artery branches were normal in appearance without significant stenosis or major branch vessel occlusion.
Neurosurgical intervention was recommended as the distal position of the aneurysm made endovascular access difficult and the wide-necked morphology of the aneurysm was not amenable to vascular intervention. The patient was given 1-deamino-8-D-arginine vasopressin (DDAVP) prior to the surgery to reduce the risk of bleeding. She underwent right craniotomy and intra-op examination revealed that directly underneath the dura, there was a very thick membrane of fibrinous material as well as hemorrhage. There was a large grape-like membrane that was attached to the pia-arachnoid. There was some bleeding noted from one of the pial arterial branches on the surface. This thickened grape-like membrane was then detached from the underside of the dura and sent off to pathology. Intraoperative microscopic evaluation of the angular artery of the middle cerebral artery revealed no evidence of an aneurysm. This aneurysm-like structure was in fact a small grape-like structure of the fibrinous part of the subdural membrane that had formed from the subdural hematoma that was being fed by a pial branch of the middle cerebral artery through a parasitized process. The pathological examination of the excised specimen was consistent with a subdural membrane showing organized hematoma with highly vascularized granulation tissue. In the post craniotomy diagnostic cerebral angiogram, the aneurysm was no longer visualized. (Figure ). The patient recovered well postoperatively with no clinical evidence of rebleeding. She was discharged home one day later.


Case 2: A 45-year-old male patient with stage IV melanoma who had received four doses of ipilimumab and nivolumab followed by two doses of nivolumab for bipulmonary metastases presented with severe heartburn, lack of appetite, nausea, and weight loss of approximately 10 kg over 3 weeks. Because the patient was no longer able to achieve adequate food intake, he was admitted to hospital for further evaluation. Subsequent gastroscopy revealed pronounced erythematous pangastritis with marked diffuse, patchy-to-streaky and edematous mucosa with prominent fibrinous deposits throughout the stomach (). Sample biopsies taken during the gastroscopy histologically showed ulcerative high-florid pangastritis (). CPI-assGastritis was suspected, and the patient therefore received i.v. methylprednisolone (1 mg/kg/day), i.v. pantoprazole (40 mg twice per day), and—because intake of solid food was no longer possible—a liquid diet. After 5 days there was a noticeable improvement, and the patient was able to eat solid food again. After 9 days in hospital, the patient could be discharged. Follow-up gastroscopy performed 3 months later revealed an overall improvement but ongoing presence of chronic pangastritis with marked diffuse, patchy reddened and edematous mucosa throughout the stomach (). Specimen biopsies histologically showed moderate to severe chronic gastritis with predominantly lymphoplasmacytic cells and occasional neutrophils (). Subsequent staging showed progressive disease, and the patient received pembrolizumab in combination with the histone deacetylase inhibitor domatinostat (NCT03278665) without further recurrence of CPI-assGastritis. Three months later the patient died from his progressive disease.