A previously well male infant born to nonconsanguineous Irish parents presented at 9 months old with a two-day history of fever, vomiting, nonbloody diarrhea, irritability, and poor feeding. This was preceded by an upper respiratory tract infection (URTI) a week prior to presentation. He received a second dose of H1N1 vaccine two weeks previously. At presentation, he was pale and irritable with petechial rash, had microscopic hematuria and proteinuria, and was hypertensive (systolic blood pressure of 140 mmHg). He developed hypertensive encephalopathy with seizures requiring labetalol, sodium nitroprusside, and phenytoin infusions.
Investigations at presentation revealed thrombotic microangiopathy (hemoglobin, 105 g/L; platelets 77 × 109/L; lactate dehydrogenase (LDH) 4795 U/L, blood film showed numerous red cell fragments) and impaired renal function (urea 8.5 mmol/L, creatinine 90 μmol/L). Stools were positive for rotavirus but negative for E. coli 0157 and verotoxin. Urinary protein/creatinine ratio (PCR) was 2851 mg/mmol. The patient's ADAMTS13 activity, complement C3 and C4 were normal. A diagnosis of aHUS was suspected, direct sequencing of the entire coding regions for CFH, CFI, CD46, DGKε, and C3 did not reveal any disease causing variant and multiplex ligation-dependant probe amplification analysis for deletions, and duplications of CFH, CFHR1, and CFHR3 exons were negative. Sequencing of CFB identified a missense heterozygous variant of c.724A>C (Chr 6:31915584 (p.lle242Leu, rs144812066)), a benign variant as it was identified in his phenotypically normal mother, common in ExAC control database and predicted to be benign by in silico programs.
He received eight daily sessions of plasma exchanges (PE) with clinical improvement and subsequently relapsed on day 15 leading to resumption of daily PE. He required at least twice weekly PE but was gradually weaned over the course of 6 months, until eventual discontinuation at 15 months old (total 64 sessions of PE). Although LDH remained persistently elevated (620–925 U/L), full blood count (FBC), plasma creatinine, and haptoglobin levels normalised. Urinary PCR fell to <50 mg/mmol. He remained in clinical remission for 18 months.
The first clinical relapse of aHUS occurred at 33 months of age, preceded by an URTI (hemoglobin 102 g/L, platelets 39 × 109/L, LDH 1785 U/L, haptoglobin 0.06 g/L, and creatinine 35 μmol/L). He received the first dose of eculizumab 600 mg, which led to clinical, haematological, and biochemical improvement within two days, and was maintained on fortnightly doses (300 mg) thereafter. On fortnightly eculizumab regimen, he presented with three relapses, in the setting of immunological challenges (vaccination and URTI). Clinical, haematological, and biochemical improvement occurred within 2-3 days of eculizumab infusion with each relapse ().
Since the first relapse, he remained hypertensive requiring captopril, amlodipine, and carvedilol. On fortnightly eculizumab, FBC, plasma creatinine, haptoglobin, and C3/C4 levels remained within normal limits, with persistently elevated LDH (630–881 U/L). The alternative and classical complement pathways were suppressed confirming drug action (CH50 and AP50 hemolytic assays < 10%). Although clinically in remission (Hb 122 g/L, platelets 380 × 109/L, LDH 707 U/L, haptoglobin 1.16 g/L, and creatinine 26 μmol/L), plasma sC5b-9 concentrations measured 14 days after eculizumab dose were high at 240 ng/ml. The high sC5b-9 was interpreted as ongoing dysregulated complement activation and his maintenance eculizumab dose was changed to 300 mg every 10 days. Eight weeks after decreasing the interdose interval, sC5b-9 concentration remained elevated at 227 ng/ml (10 days after eculizumab dose) despite clinical remission (Hb 125 g/L, platelet 309 × 109/L, LDH 756 U/L, haptoglobin 0.51 g/L, and creatinine 27 μmol/L) and adequate trough eculizumab levels (>600 μg/ml) with levels >99 μg/ml considered to be therapeutic.
During follow-up, it became evident that he had global developmental delay. Careful review of his history demonstrated subtle gross and fine motor delays were present prior to his initial presentation with aHUS (sat with support at 9 months, not reaching for objects/transferring). He made slow developmental progress, without regression. At 4 years, he could stand with support, had palmar but no pincer grip, and only two words with meaning. He had good understanding, could follow 4-step commands, and was sociable and interactive. Examination at 4 years showed occipitofrontal circumference less than the 0.2nd centile, bilateral optic nerve pallor, hypodontia, truncal ataxia, upper limb tremor, and hypotonia. Therefore, an alternate pathology to the aHUS and associated hypertensive encephalopathy was required to explain the preexisting developmental delay and neurological deficits.
A MRI brain performed at 10 months following initial presentation showed subtle changes in the basal ganglia. He underwent extensive genetic and metabolic work-up including karyotype, microarray, PLP gene, very long chain fatty acids, paired serum and CSF glucose and amino acids, CSF neurotransmitters, urinary organic acids, and skin and muscle biopsy, all of which were negative. Two subsequent MRI brain scans at 2.25 and 3.5 years showed very delayed myelination with no progression since the original scan showing hypomyelination, increased T2 signal in the basal ganglia with volume loss, and cerebellar atrophy. Based upon these findings, he was diagnosed with 4H syndrome with subsequent confirmation of compound heterozygous mutation of POL3B (c.1568T>A, p. Val523Glu and c. 1464+1 G>A), reported previously [].
Eculizumab treatment was discontinued after careful consideration with his parents due to ongoing relapses and the diagnosis of a progressive severe neurological condition.


A 59-year-old African American male with alcohol-related dementia presented with scaly lesions. His asymptomatic rash had progressively worsened during the prior three months. No one else in his group home had a similar skin condition.
The cutaneous examination showed scaly papules and annular plaques on his back, buttocks, flanks, and the abdomen, many of them were distributed along the lines of Langer (Figure ). Similar lesions were absent on his face, neck, arms, forearms, and legs. However, closer examination revealed burrows on his finger webs (Figure ). Separate mineral oil preparations of the skin scrapings taken from several areas including his chest, finger webs, and umbilicus, each showed mites, ova, and scybala (Figure ).
The correlation of the clinical presentation and mineral oil preparations confirmed the diagnosis of scabies masquerading as pityriasis rosea. The patient was treated topically with permethrin 5% cream and also received oral ivermectin 15 mg on days one and eight.
The patient returned for follow-up examination four weeks later. There was complete resolution of the skin lesions. In addition, separate mineral oil skin preparations taken from multiple sites were each negative for mites, ova, and scybala.


A 67-year-old female presented with malignant hypertension on four medications for which investigation by an endocrinologist showed positive metaiodobenzylguanidine scan (MIBG), elevated catecholamines levels, and CT with contrast showed intravesical tumor with a tentative diagnosis of bladder paraganglioma of size 3.5 × 3 cm as seen in and .
She was admitted and was prepared for surgery. Laparoscopic partial cystectomy was conducted (she was placed in low lithotomy position and laparoscopic procedure was started by mobilizing the bladder in combination with flexible cystoscopy that showed a mucosal bulge located in anterior bladder wall with a wide base near the bladder neck. The light of the endoscope guided the start of resection with a safety margin and then we excised the mass completely with a good safety margin as shown in , and bladder was closed in one layer laparoscopically. During surgery, she developed one attack of hypertension and was managed by anesthesia with no intraoperative or immediate postoperative complications. She had a smooth postoperative course and was discharged home, then the catheter was removed after cystogram. Histopathology confirmed the diagnosis of bladder paraganglioma (). As well, a follow-up at 1 year postoperation, the patient was asymptomatic with controlled blood pressure and normalized catecholamines level with no evidence of recurrence.


A 43-year-old male with a history of decompensated cirrhosis secondary to refractory autoimmune hepatitis with hepatocellular carcinoma on triple therapy, with budesonide 3 mg, prednisone 5 mg, and azathioprine 50 mg, was transferred from an outside hospital for septic shock secondary to a complicated enterococcus urinary tract infection (UTI). On admission, the patient’s model for end-stage liver disease (MELD)-Na was 32 (creatinine: 1.3 mg/dL, total bilirubin: 21.2 mg/dL, international normalized ratio (INR): 1.7, and Na: 123 mmol/L). Initial vital signs were temperature: 35.1℃, heart rate: 89 beats per minute (BPM), respiratory rate: 18 BPM, blood pressure: 96/48 mmHg, and peripheral capillary oxygen saturation (SpO2): 98% on room air. The physical exam was significant for a chronically ill-appearing obese male in no acute distress. The patient was alert, oriented, and had bilateral asterixis. His skin was visibly jaundiced. A fluid wave and shifting dullness were appreciated on the abdominal exam; however, the patient was without tense ascites, tenderness, or peritoneal signs. The patient demonstrated 2+ lower extremities edema to knees bilaterally. Initial paracentesis on the day prior to transfer was negative for SP (white blood cells (WBC): 80 cells/cmm), as was a subsequent paracentesis (WBC 64 cells/cmm with 42% polymorphonuclear cells (PMNs)) performed 12 days later, following the completion of antibiotics for his complicated UTI. On hospital day 13, the patient became hypotensive and complained of severe abdominal pain. He was transferred to the intensive care unit (ICU) for the escalation of care. Given the chronic immunosuppression, both bacterial and fungal pathogens were investigated. Fungitell B-D-Glucan returned positive (255 pg/mL). Serum cryptococcal antigen (CrAg) returned positive (titer: 1:20). Subsequently, the ascitic fluid culture from the previous day grew yeast, which eventually speciated into Cryptococcus neoformans. Broad-spectrum antibiotics (vancomycin, cefepime, and metronidazole) were initiated along with fluconazole for antifungal coverage. The lumbar puncture was negative (WBC: 4 cells/cmm, protein: 46 mg/dL, glucose: 70 mg/dL, and cerebral spinal fluid (CrAg) was negative). Computed tomography (CT) thorax was negative for lung involvement. The urinary bladder pressure (UBP) measurement was 29 mmHg, which was consistent with intra-abdominal hypertension (IAH) as well as abdominal compartment syndrome (ACS) (defined as UBP > 20 mmHg). The patient underwent a therapeutic paracentesis with the removal of 6.5 L of fluid with an improvement in UBP to 10 mmHg. The ascitic fluid analysis was consistent with spontaneous peritonitis (WBC: 654 cells/cmm; PMNs: 61%). Fluconazole was switched to liposomal amphotericin B and flucytosine.
Subsequently, the patient developed acute oliguric renal failure, which was felt to be due to poor renal perfusion in the setting of abdominal compartment syndrome. He was briefly intubated due to respiratory failure from volume overload at which point continuous renal replacement therapy was initiated. He required repeat paracentesis every two to four days due to abdominal pain and concern for worsening IAH. Unfortunately, 15 days after being transferred to the ICU, the patient developed severe abdominal pain out of proportion to the physical exam and became hypotensive, requiring sequential reinitiation of three vasopressors. A CT abdomen was performed, demonstrating extensive venous mesenteric gas, concerning for bowel ischemia (Figure ). General surgery was consulted, who felt the intraoperative risks were too high to offer surgical intervention. The patient was transitioned to comfort care and expired shortly after.


An 84-year old right-handed male presented to hospital with dysarthria, dysphagia, right-sided facial drop, a history of generalized weakness and multiple falls.
The patient had a past history of a transient ischemic attack (TIA) 8-years prior to presentation, manifesting as speech disturbance and weakness, type 2 diabetes mellitus, hypertension, and glaucoma. His medications on presentation included: perindopril 8 mg daily, amlodipine 5 mg daily, clopidogrel 75 mg daily, metformin 500 mg b.i.d., amitriptyline 25 mg qHS and timolol ophthalmic drops 0.5% - 1 drop each eye b.i.d.
He was a retired electrician and had quit smoking 35 years ago. He did not drink alcohol. He lived alone, independently in his own home. He usually walked using a cane. He received meals delivery services and his niece assisted him by driving him to where he needed to go.
The patient had an unwitnessed fall in his home and subsequently activated his emergency response device. He was brought to the Emergency Department by the emergency medical services. He was alert on arrival and was noted to have speech difficulties. His vital signs showed a low-grade fever of 38.5 °C oral and an elevated heart rate of 105 beats per minute. His clinical exam showed that he was alert, with new dysarthric speech, a pronator drift of his right arm and a fine tremor of his left hand. Ausculation of his chest was clear. Initial laboratory results are shown in Table . Remarkable results include an elevated erythrocyte sedimentation rate (ESR) of 112 mm/h (normal 0–6) and a C-reactive protein (CRP) of 110 mg/L (normal less than 10). A chest radiograph was reported as showing ill-defined left lower lobe airspace disease, possibly representing a pneumonia. A plain computed tomography (CT) of his head showed moderate cerebral parenchymal atrophy and chronic periventricular microvascular ischemic changes. The patient was hospitalized and admitted to the Geriatric Medicine service. He was given intravenous azithromycin followed by oral cefuroxime for a presumed community-acquired pneumonia. The neurology service suggested additional brain imaging with magnetic resonance scan (MRI) and a CT angiogram of his head and neck to further clarify the etiology of this man’s possible stroke syndrome. At no point during this person’s multiple clinical evaluations did he report headache, visual problems, or jaw claudication. The CT angiogram of the neck and circle of Willis showed mild atherosclerotic changes of the aortic arch and proximal great vessels without significant stenosis. There was a pseudoaneurysm of the mid-cervical portion of the right internal carotid artery and mild luminal irregularity of the vertebral arteries bilaterally at the level between the 1st and 2nd cervical vertebrae. The radiologist was unable to differentiate between vasculitic or atherosclerotic changes in the vertebral arteries and suggested further imaging. Magnetic resonance arteriography was unable to be performed due to the presence of a metallic foreign body embedded in his left eye. An echocardiogram showed normal cardiac function and normal valve anatomy and function. A 48 h Holter recording showed sinus rhythm, with very rare premature atrial and ventricular beats. Atrial fibrillation was not detected. His repeat inflammatory markers 5-days after admission were: ESR 90 mm/h, CRP 47.7 mg/L. In view of a possible cerebral vasculitis the patient was started on prednisone 60 mg daily. Bilateral temporal artery biopsies were done on the 7th hospital day. A contrast-enhanced CT of the thorax, abdomen and pelvis was done to investigate the possibility of diffuse vasculitis and these studies were reported to show no evidence of aortitis or medium and large artery vasculitis.
The biopsy results (right artery specimen length 1.9 cm, left 2.0 cm) were reported on the 10th hospital day and was positive for GCA showing transmural inflammation and the presence of multi-nucleated giant cells in the arterial wall (Figs. and ). The prednisone dose was maintained at 60 mg daily. After 2-weeks methotrexate 10 mg weekly was added, with the plan to slowly taper down the prednisone dose and increase the weekly methotrexate dose. The patient’s dysarthria, dysphagia and right arm weakness progressively improved. He was able to swallow normally and his speech became clear. He regained safe independent mobility using a 4-wheeled walker and was discharged to a seniors home with services on the 29th hospital day.
Table shows the serial results of his serum inflammatory markers.


Our patient is a 44-year-old male who was brought in by ambulance for altered mental status. As per the patient's wife, the week prior to admission he began staring off in space and responding to internal stimuli. His mentation deteriorated, and he began hallucinating and became aggressive, at which point she brought him to the emergency department. Six months prior to admission, he was diagnosed with metastatic renal cell carcinoma and underwent primary cancer removal with subsequent right nephrectomy. He was found to have multiple leiomyomas and was referred to the National Cancer Institute in Maryland. Genetic testing showed autosomal dominant Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC). Follow-up L-spine MRI for back pain showed extensive metastasis to the lumbar spine, sacrum, and right and left ilium. He was started on targeted immunotherapy of nivolumab and given a single dose of 240 mg two weeks prior to admission. On presentation, he was febrile and unable to communicate. He was acutely encephalopathic and responding to internal stimuli. During the interview, he was experiencing and responding to auditory, visual, and tactile hallucinations. On admission, his blood pressure was 122/86 with a pulse of 118 and temperature of 100.8°F. Chest X-ray showed no signs of pneumonia or metastases. Brain MRI showed no evidence of metastases or lymphoreticular disorder. Blood work showed an elevated white blood cell count of 16.61, unchanged from a previous admission due to home medication of Decadron. Serum Na was 132 with AST/ALT 36/72, TBili 0.5, alkaline phosphatase 246, and a creatinine of 2.0 at his baseline. Urinalysis performed in the ED showed packed hyaline casts without superimposed urinary tract infection. Blood cultures were drawn, and he was started on normal saline and oxygen. His home medications included methadone, naproxen, omeprazole, oxycodone, risperidone, hydromorphone, trazodone, benzonate, dexamethasone, buproprion, cyclobenzaprine, and ondansetron. Given the nature of the patient's pain and the severity of his illness, all of his home medications were continued. He was started on Haldol for agitation and transferred to the medical intensive care unit for treatment of encephalopathy. On examination, he exhibited garbled speech and continued encephalopathy. Initial attempts to sedate the patient using ketamine were effective and resulted in increased lucidity. He eventually became hypertensive and required treatment with Precedex while in the MICU. After 5 days in the MICU, the patient was found to be speaking in short sentences and was alert, awake, and oriented to person, place, and time with no signs of encephalopathy. Blood cultures throughout the stay showed no growth. Given the patient's lack of metabolic abnormalities, acute infection, continuation of all home medication throughout the hospital stay, and temporal resolution of symptoms after removal of nivolumab, he was diagnosed with nivolumab-induced encephalitis. The patient was discharged home on his home medications and scheduled for outpatient radiation therapy with discontinuation of nivolumab. After a short stay at home, patient was advanced to hospice and soon after passed away from metastatic renal cell carcinoma.


A 53 year old man, with personal and family history of hypertension, was diagnosed with a 4 cm tumoral mass at costovertebral D6–D7 with a 21 max SUV, during a routine check-up in March 2010. The only manifestation of disease was elevated blood pressure. He was being treated at this time with irbesartan/hydrochlorothiazide (1250mg/12.5mg, respectively). After surgery, the pathology diagnosis was of PGL with a Ki67 around 5-8%, and synaptophysin and chromogranin positive. Genetic analysis found a mutation in the
SDHA gene, leading to a heterozygous missense
p.Ser445Leu change, defined as pathogenic
. The patient remained without treatment and symptom-free until August 2014, when a back pain appeared around the D10 region, with progressive worsening. In October, as the pain persisted, he underwent MRI and 18F-DG-PET scan and was diagnosed with several metastasis at: D6–D7, right acetabulum (3cm); vertebral hemi-body D10 (3cm); vertebral body of D12 (2cm); and left iliac crest (1cm). A scintigraphy with Indium-111 pentetreotide suggested metastatic disease of probably neuroendocrine origin. D10 lesion biopsy confirmed the diagnosis of PGL metastasis with a Ki67 around 15–20% (
). The patient was treated with doxazosin (8 mg/day) and bisoprolol (10 mg/day).
In November 2014, the patient started on systemic treatment with denosumab (120 mg every 28 days) and lanreotide (120 mg every 14 days). After 4 months, a PET-TAC showed a metabolic stabilization of the disease, but with a slight growth of lesions according to MRI (
). D6 and D10 lesions were then treated by radiotherapy (Cyberknife). To this purpose, in March/April 2015 the patient underwent SBRT with CiberKnife (24 Gy in D10, 15 Gy in D12 and 35 Gy in D6–7), and the pain disappeared. After 6 months, the D7 and D12 lesions were also irradiated and completed SBRT with CiberKnife (24 Gy in left iliac bone and 24 Gy to right acetabulum).
Response to radiotherapy was good, showing stability of lesions and decrease of max SUV. No new lesions appeared. In June 2015, a thermoablation and right acetabulum metastasis cementation was performed with good results.
At this moment, the anti-hypertensive bisoprolol was changed to propranolol(120mg/day), due to preliminary reports of propranolol’s good results in VHL tumors
. During the following 11 months, the patient remained stable without disease progression (
). Lanreotide dose was decreased to 120 mg every 3 weeks, due to side effects. Side effects included nausea, vomits, diarrhea and hyperglycaemia.
In May 2016, metanephrines and chromogranin were raised above normal levels, as follows: Chromogranin A, 106 ng/mL (normal level, <93); urine fractionated Norepinephrine, 196 mcg/24h (normal levels, 15–80); urine fractionated normetanephrine, 1316 mcg/24 h (normal levels, 128-484); urine total metanephephrine, 1394 mcg/24h (normal levels, 220-680). A 18FDG-PET-TAC revealed an important metastatic dissemination all over the skeleton, showing more than 40 small new lesions less than 2 cm, and with scarce or null Octreoscan and
123I-MIBG uptake (
).
From this moment on, a combined treatment of temozolomide (75 mg/m² for 21 days every 28 days) and an increase of propranolol up to 3 mg/kg/day (240 mg/day) was prescribed. After the first cycle of temozolomide, results were evaluated in August 2016 at National Institutes of Health, where the previously detected metastatic dissemination was confirmed, although catecholamines and chromogranin levels were decreasing compared with the previous measures. Treatment was kept the same for 6 cycles of temozolomide. In December 2016, most of lesions had disappeared according to PET-TAC (
). The two remaining lesions had maximum SUV significantly decreased. In January 2017, lanreotide was retired due to adverse side effects (as before).
In July 2017, a new PET supported the previous results, showing the remaining two lesions but with maximum SUV lower (
). Temozolomide was withdrawn because of side effects (lymphopenia and thrombopenia). In October 2017, 4 months since the last dose of temozolomide, and propranolol as the only treatment (240mg/day), the disease remains controlled according to the last PET-TAC (F18-FDG) (
). This imaging study suggests the presence of two neoplastic bone lesions in the dorsal spine and right acetabulum; regarding the previous examination (July 2017), the lesions described in D6 and acetabulum persist without major changes, whereas that of vertebra D10 has disappeared.


The patient's history was provided by a reliable historian. A 69-year-old female presented to the emergency department (ED) with chief complaints of experiencing difficulty maintaining balance, along with dry mouth and decreased appetite of one day duration. She recalled having increased urinary frequency from the past one month. The patient reported having a history of type II diabetes mellitus and being noncompliant with medication use. Her vital signs in the ED revealed a blood pressure of 113/76 mmHg, a respiratory rate of 14 per min, a heart rate of 86 beats per min and a temperature of 36.2°C. On physical examination, she exhibited severe choreiform movements affecting the extremities, more pronounced in the upper extremities and in the orolingual region. She denied using any antipsychotic medications. However, she admitted to using crack cocaine two days prior to presentation in light of some life stressors. Laboratory investigation showed a blood glucose level of 660 mg/dl and an anion gap of 17. A working diagnosis of nonketotic hyperosmolar hyperglycemia was established, and she was admitted to the intensive care unit (ICU). A computed tomography (CT) head scan showed an area of hyperlucency around the putamen (Figure ).
The patient received 1500 ml of normal saline, 10 units of regular insulin followed by insulin drip, 1 gm of intravenous (IV) Keppra and 5 mg of IV Diazepam. Subsequently, her metabolic condition improved and she was downgraded to the neurology floor. However, she continued having involuntary choreiform movements involving bilateral extremities affecting the left more than the right. On day two of the admission, a 12-items anchored Abnormal Involuntary Movement Scale (AIMS) [] was performed to assess the severity of the patient’s movement disorder which pointed towards moderate to severe involuntary movement disorder. Complete blood count (CBC), basic metabolic panel (BMP), salicylate levels, acetaminophen levels, serum copper, and ceruloplasmin levels came back as negative. The urine toxicology screen was positive for cocaine. After ruling out all possible neurological diagnoses, the only pertinent information remaining was the patient’s recent history of crack cocaine use. Given the similar instances reported in literature, a diagnosis of cocaine-induced choreoathetosis was established. The involuntary movements gradually improved over the next few days without any medical intervention, with the lower extremities improving first, followed by the upper extremities. The patient was discharged after 12 days of hospital stay.


A 37-year-old woman visited our hospital complaining of abdominal pain. She had no past or familial history of neoplasms. A computed tomography (CT) scan showed a 5 cm abnormal mass in the pancreas head. She was suspected for pancreatoblastoma by CT-guided biopsy (Figure ) and was sent for a pancreaticoduodenectomy.
The postoperative pathological findings showed squamoid nests, some with keratinization (Figure ). Immunohistological analysis indicated an abnormal nuclear accumulation of β-catenin proteins and the expression of Bcl-10, a pancreatic acinar cell marker, in the tumor tissues (Figures ). A pathological diagnosis of pancreatoblastoma depends on its acinar differentiation and on the existence of squamoid nests; therefore, this tumor was finally diagnosed as pancreatoblastoma according to these findings.
A CT scan taken three months postoperatively showed metastatic recurrence in the liver (Figure ). She received one course of adriamycin and gemcitabine chemotherapy, with no response. We treated her with cisplatin and S-1 as a second line chemotherapy. Although the tumor temporarily exhibited no change in size, after six cycles of cisplatin and S-1 chemotherapy her liver metastatic pancreatoblastoma increased in size (Figure ). We were unable to achieve any response via salvage treatment, and she ultimately died of pancreatoblastoma progression 13 months after diagnosis.


The patient is a 29-year-old G2P1001 Hispanic woman with uncertain last menstrual period and no previous prenatal care who presented to Labor and Delivery for evaluation of preterm labor. She complained of nausea, vomiting, and acid reflux, which she had experienced throughout this pregnancy. Obstetric history included a prior full term Cesarean delivery without complications. Medical history revealed a history of kidney stones and pancreatitis. Surgical history was remarkable for cholecystectomy, appendectomy, and ureteral stone removal. All previous medical and surgical care took place in Honduras and no records were available.
Ultrasound established an estimated gestational age of 34 weeks with bilateral echogenic fetal kidneys. Amniotic fluid was normal with an amniotic fluid index (AFI) of 15.4. She was found to have contractions and her cervical exam changed from closed to 1 cm dilated. Given concern for preterm delivery, she was given a dose of betamethasone in accordance with recently published Antenatal Late Preterm Steroids trial demonstrating benefit between 34 and 36 weeks and 6 days' gestation []. Her contractions subsequently decreased and a repeat cervical exam was unchanged. She was discharged home with instructions to return in 24 hours for her second dose of betamethasone, but she did not return the following day.
Seven days later, the patient returned to Labor and Delivery with contractions and diffuse abdominal pain. She reported vague and worsening discomfort across the entirety of her abdomen. She also complained of nausea, vomiting, and worsening acid reflux. She denied sharp or radiating epigastric pain, flank pain, or dysuria but noted polyuria, fatigue, and weakness. Her vital signs were within normal limits. Tocodynamometry demonstrated uterine irritability and contractions; however, her cervical exam remained unchanged from her evaluation one week before. Fetal heart tracing had moderate variability without acceleration. Ultrasound showed new polyhydramnios with an AFI of 41.3 with a biophysical profile of 8/10.
Despite thorough and repeat history and physical exams, no focal signs or symptoms concerning for a specific etiology of her discomfort were elucidated. Her diffuse discomfort was attributed to significant uterine distension from polyhydramnios and GERD.
However, labs demonstrated severe hypercalcemia, pancreatitis, and acute kidney injury: a corrected serum calcium of 16.9 mg/dL (ionized calcium 2.05), hyponatremia, hypochloremia, creatinine 1.4 mg/dL, BUN 41 mg/dL, amylase 334 U/L, lipase > 3000 U/L, WBC 15.8 K/mm3, and Hgb 9.7 g/dL. AST and ALT were within normal limits. An EKG was performed that showed ST elevations consistent with hypercalcemia. Troponins were negative. Focused physical exam was remarkable for a palpable thyroid gland (bilateral lobes) without rubor, calor, dolor, or bruits. Neurologic exam showed no focal deficits and full strength in bilateral upper and lower extremities. The patient remained alert and oriented × 3. Additional labs were drawn and were significant for low TSH (0.02 ng/dL), elevated free T4 (1.9 ng/dL), and significantly elevated PTH (937 pg/mL).
Thyroid ultrasound showed bilateral subcentimeter nodules and a 2.7 cm hypoechoic noncalcified solid lobulated nodule in the right thyroid lobe. A smaller, 0.7 cm nodule was also seen in the lower pole of the left thyroid lobe. A 0.6 cm predominantly cystic nodule was seen in the junction of the isthmus and right thyroid lobe. Abdominal ultrasound showed no dilatation of the intrahepatic biliary tree with a normal common bile duct. Florid bilateral nephrocalcinosis was present, consistent with longstanding hypercalcemia. Biliary etiology of her pancreatitis was deemed unlikely.
Fetal status remained reassuring with continuous monitoring. Aggressive IV fluid hydration was initiated with immediate improvement in pancreatitis but with minimal improvement in calcium levels. Given the patient's young age, severe hypercalcemia, very high PTH levels, and neck mass, there was concern for parathyroid cancer, not just parathyroid adenoma, for which the surgical treatment would be en bloc resection of the parathyroid gland as well as the thyroid gland, adjoining fatty tissue, lymph nodes, and surrounding muscles in order to achieve the best chance for surgical cure. A tissue biopsy of the thyroid nodule was obtained. Rushed pathology of a fine needle aspiration of the 2.7 cm thyroid nodule was concerning for parathyroid carcinoma.
Calcitonin, cinacalcet, and zoledronic acid were added in succession, each with minimal improvement in hypercalcemia. For concurrent hyperthyroidism, she was also started on methimazole and propranolol in order to help prevent thyroid storm during possible surgical resection. Given incomplete administration of betamethasone one week before, the decision was made to administer a complete 2-dose course of betamethasone due to risk of premature delivery. Throughout the hospital course, continuous fetal monitoring showed reassuring fetal status. However, on the third day of medical management, the patient continued to have severe hypercalcemia refractory to medical management and fetal status began to deteriorate.
Failing medical management, and in the setting of worsening fetal status, the endocrine surgery team provided emergent surgical management. Unexpectedly, intraoperative frozen section of one of two pretracheal lymph nodes was consistent with metastatic papillary thyroid cancer. She underwent bilateral exploration of parathyroid glands, total thyroidectomy, right central neck dissection, and right cervical thymectomy. After completion of the procedure, intraoperative PTH level decreased to 53, consistent with complete removal of the parathyroid lesion. Final pathology showed a parathyroid adenoma with atypia as well as occult papillary thyroid carcinoma with metastasis to a single lymph node.
The patient tolerated the procedure well and was transported to an ICU bed for close monitoring. She was closely monitored and started on calcium carbonate, calcitriol, and levothyroxine. Her calcium normalized within 12 hours and her pancreatitis resolved. Fetal status was reassuring following the procedure.
On postoperative day 2, at 36 weeks and 2 days' gestation, the patient began to contract painfully. She declined trial of labor and underwent an uncomplicated repeat C-section. She delivered a female infant weighing 3400 g with APGARS 7 and 8. The infant's calcium levels were elevated immediately following delivery with an ionized calcium of 1.66, but 24 hours later she was hypocalcemic and required calcium supplementation. The infant's hypocalcemia improved and stabilized with improved feeding and she was discharged home at 5 weeks of age with vitamin D3 supplementation. The infant also received an ultrasound that was consistent with neonatal nephrocalcinosis likely secondary to longstanding intrauterine hypercalcemia that may take months or years to resolve. A follow-up renal ultrasound is planned at 6 months of age.
The patient, now status postsurgical removal of thyroid and parathyroid glands, was discharged home on lifelong calcitriol, calcium supplementation, and levothyroxine with close outpatient follow-up with endocrinology. She will also follow up with endocrinology for further monitoring and evaluation of her thyroid function and for discussion of radioiodine therapy versus surveillance for thyroid cancer surveillance.


A 43-year-old man was rushed into the Emergency Department (ED) whilst undergoing cardiopulmonary resuscitation (CPR). Witnessed cardiac arrest had occurred during transportation to the hospital for sudden onset of shortness of breath. His initial cardiac rhythm on ED arrival was recorded as pulseless electrical activity (PEA). After confirming correct endotracheal tube placement, he was noted to have significant swelling of his entire right lower limb (). A right sided iliofemoral DVT and dilatation of the right ventricle were demonstrated on point of care ultrasound assessment that had been performed in the ED. Thrombolytic therapy with alteplase (Actilase®, Boehringer Ingelheim Pharma GmbH & Co, Germany), 100 mg (10 mg over 1 minute and then 90 mg over 2 hours), was promptly initiated whilst high quality CPR was continued. A return of spontaneous circulation (ROSC) was achieved approximately 30 minutes later. The patient remained haemodynamically stable and was sent to the radiology department for a computed tomography pulmonary angiogram (CTPA) after completion of the alteplase infusion. The diagnosis of PE was confirmed on CTPA, which demonstrated multiple large filling defects in both main pulmonary arteries as well as regions of pulmonary oligaemia. An area of hyperdensity in the posterior right lung region, suggestive of an intra-alveolar haemorrhage, was also noted on CTPA as well as on the post-thrombolysis but not the pre-thrombolysis chest X-ray films (Figures and ). Since this did not result in any haemodynamic or ventilatory instability, it was decided to manage the intra-alveolar haemorrhage conservatively. Continuous monitoring of vital signs, including temperature, was maintained in the ICU to ensure that core body temperature remained below 37°C. There was no need to initiate any active cooling measures. On day 3 after admission, a repeat in cardiac echocardiography demonstrated that the right ventricle had normalized in size. Further diagnostic investigations led to the conclusion that enlargement of regional inguinal lymph nodes secondary to active venereal disease precipitated the development of the lower limb DVT. Seven days after thrombolysis and treatment of his underlying pathology, the patient had completely recovered and was discharged home neurologically intact.


The patient is a 70-year-old male with a past medical history of hypertension and dyslipidemia, who presented in September 2009 with progressive fatigue. He was noted to have a white blood cell count of 3.3 thousand/ul, with 22% circulating blasts. His staging bone marrow biopsy showed a hypercellular marrow, 95% cellularity with complete replacement by lymphoid blasts, with flow study detecting 84% blasts expressing dim CD45 with dim TdT, CD19, CD10, CD79A, CD22, HLA-DR, and variable intensity for CD20, and CD34. The diagnosis was consistent with pre-B acute lymphoblastic leukemia, and the FISH study was negative for BCR-ABL, as well as 11Q23 translocation. His initial cytogenetic study showed a normal male karyotype. Incidentally, he was noted to have a small subacute frontoparietal subdural hematoma. Initial CSF evaluation was negative for leukemic blasts.
Our patient began induction therapy on CALGB-9111 protocol. He was noted to have persistent disease after the initial induction therapy and was transitioned to Hyper-CVAD part B with rituximab. He received intrathecal chemotherapy with methotrexate and was noted to have CNS leukemia involvement in November 2009. A recovery bone marrow biopsy in December 2009 showed complete remission, with adequate cellularity and normal trilineage hematopoiesis without residual leukemia, and normal male karyotype. He began four weekly intrathecal therapy sessions for CNS leukemia. Repeat CSF cytology studies were negative. He was deemed a poor candidate for allogeneic stem cell transplantation secondary to his age and comorbidities. In January 2010, the patient began an R-CHOP regimen, as he experienced significant complications from the Hyper-CVAD therapy (Stenotrophomonas maltophilia bacteremia with neutropenic fevers). A bone marrow biopsy after four cycles of R-CHOP showed a regenerative marrow with no evidence of residual leukemia and normal male karyotype. He then received one year of maintenance treatment with R-POMP and intrathecal chemotherapy, at which point a bone marrow biopsy in April 2011 showed no evidence of leukemia.
CSF studies at that time showed no leukemia. He then was started on maintenance therapy with rituximab therapy every two months for six cycles and intrathecal therapy every four months. He completed the course of treatment in February 2012. He had stable peripheral blood counts with no evidence of relapsed disease noted with ongoing CR1 status. In March 2013, he experienced proximal muscle weakness. MRI of his cervical, thoracic, and lumbar spine revealed no evidence of disease involvement. A diagnostic lumbar puncture for evaluation of CNS leukemia confirmed relapsed CNS disease, where the CSF fluid demonstrated a glucose level of less than 2 mg/with over 2700 nucleated cells, the majority of which were blasts consistent with pre-B acute lymphoblastic leukemia, expressing CD19, CD20, CD10, TDT, and CD34. A subset of the cells appeared to express dim CD2 with no other apparent antigen expression noted. The flow study detected 98% of the cells were blasts. An MRI showed no leptomeningeal involvement, and a bone marrow biopsy was negative. He had an Ommaya reservoir placed in preparation for long-term intrathecal treatments.
A complete history of the patient's intrathecal treatments is listed in . He began serial intrathecal chemotherapy alternating with methotrexate and cytarabine weekly followed by every two weeks. The patient was noted to have clearance of leukemia blasts, so the interval of intrathecal treatment was extended to every 2-3 months with alternating methotrexate and cytarabine. Repeat CSF cytology was negative throughout the sessions until April 2015, when an isolated CNS relapse was noted with no clinical signs or symptoms of systemic relapse. At that point, the patient's intrathecal chemotherapy interval was shortened to weekly therapy. CSF studies revealed no disease involvement. However, as treatment was prolonged to monthly administration, recurrent isolated CNS relapses were observed. The patient once again cleared the CSF cytology with more frequent intrathecal chemotherapy. An MRI of the brain in December 2015 showed no leptomeningeal disease. In September 2016, CSF cytology confirmed relapsed disease, but peripheral counts remained normal. His chemotherapy at that time remained with cytarabine and alternating methotrexate. He was transitioned to thiotepa in March 2017 following positive cytology. His repeat CSF studies were negative for leukemia, but in April 2017, the patient experienced another episode of isolated CNS relapse. He was then switched to triple therapy with intrathecal hydrocortisone, methotrexate, and cytarabine. He thereafter also received intrathecal rituximab. During these courses of treatment, CSF studies were intermittently positive for disease recurrence without signs or symptoms of systemic disease, and interval peripheral flow cytometry has demonstrated no diagnostic evidence of circulating B-cell lymphoblastic leukemia. Clinically, the patient is maintaining his quality of life eight years after his initial diagnosis, with no focal neurologic symptoms or side effects from the intrathecal treatments and no evidence of systemic relapse to date.


An 8-year-old female French Bulldog weighing 12.4 kg was referred to the Department of Clinical Sciences of Companion Animals at Utrecht University with a history of intermittent faecal incontinence and progressive abnormal gait in the hind limbs since 3 months. Conservative treatment with corticosteroids initially showed improvement but after tapering the dosage, clinical signs recurred. The owners felt that the dog was in pain because they found the dog progressively more depressed/lethargic. On general examination, the dog showed signs related to brachycephalic obstructive airway syndrome. Orthopaedic examination elicited pain on palpation and extension of the L6 to S3 region. Neurological examination identified hind limb ataxia and ambulatory paraparesis and postural deficits in the hind limbs, more severe on the left side. Spinal reflexes were normal in all limbs. The neuroanatomic localization based on the neurological deficits included T3–L3 and based on the lumbosacral pain on palpation and faecal incontinence it was extended until S3. Magnetic resonance imaging (MRI, type Ingenia 1.5T, Philips, Eindhoven, The Netherlands) was performed under general anaesthesia of the thoracolumbar, lumbar and lumbosacral spine extending from T6 to Cd3 with sagittal and/or transverse T1-weigted, T2-weighted, T2*-weighted, fluid attenuation inversion recovery (FLAIR) and short tau inversion recovery (STIR) sequences (Fig. ). At the level of L6–L7 an oval cyst-like structure was seen with dorsal compression of the cauda equina. The content of this structure was isointense with CSF. An ill-defined T2W hyperintensity was present within the spinal cord at the level of T12, most likely consistent with oedema and less likely fibrocartilaginous embolism due to the insidious onset and progressive ataxia. Kyphosis and multiple thoracic hemivertebrae were noted, consistent with breed related vertebral column deformities, without evidence of spinal cord compression. The radiological diagnosis was a cyst-like structure with dorsal compression of the cauda equina. In addition, all visible intervertebral discs showed decreased hypointense signal compatible with intervertebral disc degeneration. Mild disc protrusion was found at multiple levels, but there was no disc-associated compression of the spinal cord or cauda equina.
Since the dog was not responsive to medication, the owners opted for surgery. The dog received premedication with dexmedetomidine (4 µg/kg, IV) and butorphanol (0.1 mg/kg, IV). Propofol (2 mg/kg, IV) was used to induce anaesthesia. General anaesthesia was maintained with isoflurane, ketamine (10 µg/kg/min, IV) and dexmedetomidine (1 µg/kg/h, IV). Medication included cefazolin (20 mg/kg, IV), buprenorphine (10 µg/kg, IV), and dexamethasone (0.2 mg/kg, IV). A standard dorsal laminectomy from the midpoint of L6 extending over L7 to S1 was performed as described previously [], using a high speed burr and Kerrison rongeurs. After removal of the ligamentum flavum with a beaver scalpel knife, the cystic structure was exposed (Fig. a). The cyst was carefully freed with a ball-tipped probe, the cranial side of the cyst was attached to the dural sac and the caudal side of the cyst was attached to one of the smaller caudal nerves of the cauda equina (Fig. b). The appearance of this caudal nerve was similar to the other nerves. The cyst was sharply dissected from the caudal nerve and the dural sac (Fig. c). The lumen of the cyst was not continuous with the dural sac and therefore the cyst could be removed completely without collapse (Fig. d). Before routine closure, a morphine splash-block was deposited in the surgical field and an autologous free fat graft was transplanted over the neural tissue to prevent dural adhesions [].
The entire cyst was fixed in 10% neutral buffered formalin, processed by routine methods in toto, embedded in paraffin, sliced and stained with haematoxylin and eosin (HE) and periodic acid Schiff (PAS). Macroscopically, the cyst was stalked, thin-walled, measured 1.3 × 0.5 cm and filled with clear fluid. Histologically, several optically empty slit-like spaces were lined with cuboidal epithelium and embedded in connective tissue adjacent to a peripheral nerve that showed minor degenerative changes (Fig. ). There was sporadic perineural and perivascular lymphoplasmacellular infiltrations. After PAS staining, cilia were not detected in the epithelial lining. Thus, the histological findings were compatible with a meningeal cyst type Ib of the classification scheme proposed by Lowrie et al. [].
The dog was discharged 1 day after surgery with the following oral medication: tramadol (2–5 mg/kg, q6–8 h), gabapentin (10 mg/kg, q12 h) and prednisolone was tapered down and stopped over a period of a few weeks. The owners were advised to keep the dog quiet and on leash walks for at least 6 weeks. Physical therapy was started at 2 weeks after surgery to support rehabilitation.
At 3 months follow-up examination, the dog was without medication and the owners had noted progressive improvement in the clinical signs. The hind limb ataxia was still noticeable, but less severe and the same was true for the faecal incontinence. The dog no longer showed signs of depression/lethargy, ambulatory paraparesis was no longer present, and no pain could be elicited during palpation and/or extension of the lower back. MRI of the thoracic, lumbar and lumbosacral spine was performed, including sagittal and transverse T1W and T2W sequences, transverse T2 * W and sagittal STIR sequences (Fig. ). The rounded cystic structure, as described in the preoperative MRI examination, was no longer visible. Dorsal to the cauda equina there was hyperintensity visible at the level of L6–L7 and the LS-junction over a length of 19.6 mm (at both T1W and T2W sequences) consistent with the fat graft which slight displaced the cauda equina ventrally []. The soft tissue on the dorsal side of the L6–L7–S1 spine showed irregularity and the muscles were heterogeneously hyperintense, consistent with changes secondary to surgery (Fig. ).


A 5-year-old male French Bulldog weighing 10.3 kg was referred to the Department of Clinical Sciences of Companion Animals at Utrecht University with a 3-year history of hind limb ataxia and ambulatory paraparesis without clinical signs of pain. MRI of the cervical and thoracolumbar spine performed 1 year previously in another institution showed intervertebral disc degeneration at multiple levels and mild disc protrusion at T12–T13 but without compression of neural structures. The dog was treated conservatively with corticosteroids without clinical improvement. Ambulatory paraparesis persisted and in addition to the motor deficits, passive urine incontinence developed not related to overflow. Results of initial physical examination were unremarkable; however, a complete neurological examination revealed ataxia with dysmetria and hypermetria of both hind limbs, as well as muscle atrophy and hypotony. The dog had proprioceptive deficits in both hind limbs, but spinal reflexes were normal in all limbs. Based on the neurological deficits, the urinary incontinence, and the results of neurological examination, the neuroanatomic localization was determined as T3–S3.
Magnetic resonance imaging was repeated from C1 to S1, including sagittal and transverse T1-weigted and T2-weighted sequences, and a transverse FLAIR sequence of the lumbar spine. Multiple intervertebral discs showed decreased hypointense signal compatible with intervertebral disc degeneration. At the level of C2–C3, T12–T13, T13–L1 and L1–L2 mild disc protrusion was found with visible compression of the ventral subarachnoid space, but without compression or dislocation of the spinal cord. A fusiform cystic lesion dorsal to the cauda equina at the level of L6–L7 was found with an ill-defined cranial and caudal border. The cystic structure was isointense to CSF and compressed the cauda equina (Fig. ). Based on these imaging characteristics a SAD was suspected. There was mild dilation of the central canal from T12 to L5.
Anaesthesia and medication for the surgical procedure were identical to Case 1 except that this dog received carprofen (4 mg/kg, IV) instead of corticosteroids in the postoperative period. The surgical technique was the same as for Case 1. After dorsal laminectomy from halfway L6 over L7 to S1, a dilated dural sac was exposed which was macroscopically identified as SAD. A durotomy was performed over a length of approximately 3 cm, which resulted in free flow of CSF into the spinal canal and collapse of the diverticula. No tissue was available for histological examination. Marsupialization of the SAD was performed by placing interrupted sutures with polydioxanone 5-0 attaching the dural sac to the lateral wall of the laminectomy. Before closure the laminectomy was covered with an autologous fat graft to prevent adhesions.
The dog was discharged 1 day after surgery with the following oral medication: amoxicillin/clavulanic acid (12.5 mg/kg, q12 h), tramadol (2–5 mg/kg, q6–8 h), and carprofen (2 mg/kg q12 h). The owners were advised to keep the dog quiet and on leash walks for 6 weeks.
The dog was re-examined at 2 weeks after surgery. The dog showed moderate ataxia and postural reaction deficits in the hind limbs. The dog was both urinary and faecal continent. All spinal reflexes including perineal reflex were normal. Physical therapy and hydrotherapy was started to support rehabilitation. At 6 weeks postoperatively, the motor function of the dog had recovered significantly. Although, the dog was still ataxic, the dog was evidently less paretic in the hind limbs. Postural deficits were improved in both hind limbs and all spinal reflexes were normal. Also, the muscle mass over the hind limbs had progressively increased.


A 71-year-old woman was diagnosed as having breast cancer (left breast, invasive lobular carcinoma, T4cN3cM1, Stage IV) in September 2014 and was treated with endocrine therapy (exemestane 25 mg/day). Gross hematuria was pointed out in January 2015, and hematuria was detected by urinalysis. Her past history included hypertension and diabetes mellitus but no history of smoking. Urinary cytology was Class III (Papanicolaou classification) []. Blood tests showed a hemoglobin of 12.0 g/dL, serum creatinine of 0.87 mg/dL, lactate dehydrogenase of 251 U/L, aspartate aminotransferase of 18 U/L, and alanine aminotransferase of 6 U/L. Computed tomography (CT) showed a hypovascular mass 25 mm diameter in the right renal pelvis and a hypervascular mass of 22 mm in diameter in the upper pole of the right kidney. The hypervascular mass showed a contrast effect in the early phase. There were no signs of metastasis in the lung, liver, or abdominal lymph nodes. A retrograde pyelogram showed a filling defect in the right renal pelvis, and catheterized urine cytology was class III (Papanicolaou classification). No obvious findings were observed on radiographic imaging of the ureter.
We diagnosed her as having right renal pelvic cancer (cT3N0M0) and right renal cell cancer (cT1aN0M0). Because her metastatic breast cancer prognosis was expected to be relatively good, she thus underwent right laparoscopic radical nephroureterectomy via a retroperitoneal approach. As described below, we diagnosed right pelvic cancer and renal capsule metastasis.
Macroscopically, the renal pelvic tumor was 4 cm in diameter, yellowish white, and soft. It was located in the right renal pelvis and infiltrated into the parenchyma. The other renal tumor was 2.5 cm in diameter, well-circumscribed, yellowish white, and hard (Fig. ). It was coated with renal capsular tissue and was easily decapsulated from the renal parenchyma. This tumor was considered to be a renal capsule tumor. The ureteral wall was thickened, but its mucosa was normal.
Microscopically, the renal pelvic tumor invaded the parenchyma but not the capsule beyond the parenchyma. The renal capsule tumor was circumscribed by the renal capsule and did not invade neighboring tissue. Both tumor cells were similar and had eosinophilic cytoplasm, round nuclei, and an alveolar pattern of growth, and they were concordant with urothelial carcinoma. Tumor cells of the ureter had eosinophilic cytoplasm, round nuclei, and a trabecular pattern of growth similar to those of the breast cancer cells.
Immunohistochemically, the cancer cells of the renal pelvis were similar to those of the renal capsule (Fig. ), whereas the cancer cells of the ureter were similar to those of the breast cancer (Table ). We concluded that the renal capsule cancer was derived from the renal pelvic cancer, and the ureter cancer was derived from the breast cancer.
We thus diagnosed right pelvic cancer (urothelial carcinoma, G2 > G3, pT3) and renal capsule metastasis. We explained the necessity of adjuvant chemotherapy for the metastatic renal pelvic cancer to the patient, but she rejected chemotherapy and continued only with endocrine therapy. She then developed bilateral pleural effusions, mediastinal lymph node metastasis, para-aortic lymph node metastasis, and liver metastasis. She underwent a thoracentesis in October 2015, and the pleural effusion cytology was class V (Papanicolaou classification), compatible with breast cancer. Endocrine therapy was changed to letrozole 2.5 mg, but she died of breast cancer progression in January 2016.


A 71-year-old Caucasian female presented with a superficially located 2.5 cm palpable mass in the right breast. This lesion had been present for at least five years and was noted to be slowly enlarging in size. The patient had a personal past history of previously resected pT2 pN1 colonic adenocarcinoma, previously resected pT1 pNX renal cell carcinoma, and previously resected basal cell carcinoma of the skin of the right clavicle. By imaging, the right breast mass was located at 12 o'clock and was described as rounded in contour without associated calcifications. A differential diagnosis of sebaceous cyst versus another well-circumscribed lesion was given (). The lesion was completely excised one month after the time of mammography.
The specimen received in pathology was labeled as “skin, right breast, excision.” It consisted of an oriented segment of skin and underlying tissue measuring 4.6 × 2.5 × 1.9 cm. The specimen was differentially inked and serially sectioned revealing a centrally located 2.5 × 2.3 × 1.6 cm pink-tan, circumscribed, and elevated nodule that appeared to be dermally based and was grossly completely excised. The specimen was entirely submitted for microscopic analysis in ten cassettes. Histologically, an epithelial neoplasm was confirmed to be centered within the dermis and had a domed appearance. The neoplastic proliferation did not directly communicate with the epidermis, and the epidermis was intact throughout without ulceration. The tumor was comprised of nests of basaloid cells arranged in a “jigsaw” pattern. It was not encapsulated and showed a pushing border with some of the deeper nests of cells extending into the subcutaneous adipose tissue (). The epithelial nests were separated from one another by mildly hypercellular bands of intervening spindled fibroblasts. Most of the nests of lesional epithelium appeared intimately surrounded by a layer of homogenous eosinophilic basement membrane-like material, and some nests also showed small cylindrical accumulations of similar intrinsic material. Some tumor cell nests appeared to be comprised entirely of cells with a basaloid phenotype and a suggestion of peripheral palisading, while other nests appeared somewhat morphologically biphenotypic with slightly smaller and darker peripheral myoepithelial-like cells as well as a second population of central cells with more abundant and eosinophilic cytoplasm and a tendency toward spindling or whorling (). A histologic diagnosis of cylindroma was rendered based upon examination of routine hematoxylin and eosin (H&E) stained histologic sections and a supplemental periodic acid-Schiff (PAS) stain. The patient's surgical site healed quickly and without incident.
For reasons of academic interest, a battery of immunohistochemical studies was pursued on a representative formalin-fixed and paraffin-embedded cylindroma tissue block. All of these tests were performed using standard protocols in the Cleveland Clinic clinical immunohistochemistry laboratory. These studies showed the neoplasm to be immunoreactive (positive) with various cytokeratins including AE1/3, CK5/6, and CK7. The AE1/3 and CK7 patterns of immunoreactivity were similar with staining of the center of some basaloid tumor cell nests in a mixed membranous and cytoplasmic pattern of positivity (). The CK5/6 slide showed diffuse cytoplasmic positivity in the lesional cells with some sparing of the extreme peripheral palisading myoepithelial-like layers. The tumor cells were also noted to show diffuse nuclear immunoreactivity with p63 and SOX10 (). In addition, mammaglobin, GATA3, and E-cadherin were found to be immunoreactive in the majority of tumor cells (). Other immunohistochemical marker studies including CAM5.2, CK20, CK19, calponin, EMA, DOG-1, HER-2, estrogen receptor, and progesterone receptor showed nonreactive (negative) results. A CD117 study was nonreactive (negative) in the tumor but confirmed increased numbers of mast cells scattered exterior to the neoplastic epithelial nests within the intratumoral fibrous stroma.


We report the case of a 59-year-old lady who was referred to our thyroid clinic for a known nodule of the right lobe, which provoked a progressive difficulty in swallowing and breathing. The patient said that she was euthyroid, was diagnosed with a large thyroid cystic nodule of the right lobe since a long time, and underwent periodic fluid drainage of the cyst in another hospital and that the cyst regularly returned back to the original size. The patient always refused surgery.
Our first ultrasound examination in January 2016 revealed a thyroid nodule of the right lobe that measured 5.9 × 3.8 × 8.0 cm (volume 94.75 ml); the nodule had a cystic component that measured 3.6 × 2.5 × 5.0 cm (volume 24 ml) (); the isthmus and left lobe were normal.
Thyroid function tests were as follows: TSH, 1.79 mIU/L (0.3–3.6); FT4, 1.0 ng/dl (0.8–1.7); thyroglobulin, 305.8 ng/ml (0.2–70); TPOAb and TgAb, negative; and calcitonin, <1.0 pcg/ml (<10). FNA of the peripheral portion of the nodule was obtained with a negative cytologic result. From January to June 2016, the patient underwent 6 drainages of the cystic fluid (about once a month) with percutaneous ethanol injection (PEI) that obtained complete disappearance of the liquid component. At this time, a spongiform nodule measuring 4.0 × 3.0 × 6.0 cm (volume: 38 ml) was documented, with a 60% reduction with respect to baseline (). At the end of June, the patient underwent laser ablation (LA) of the thyroid nodule. In a single session, two fibers were placed within the nodule, and, following the pull-back technique, 15,000 joules were delivered [].
Six months after LA, the nodule measured 3.0 × 2.4 × 4.6 cm (volume: 17 ml, 82% reduction compared to baseline) (); the patient was completely asymptomatic and was still euthyroid.
The above-mentioned clinical case represented the largest cystic nodule we have treated with PEI + LA. The use of LA in thyroid cyst is not a novelty. Døssing et al. demonstrated in a prospective randomized trial that aspiration of the cystic fluid followed by LA obtained a successful outcome (cyst volume ≤ 1 ml) in 68% of patients versus 18% of cases when aspiration was not followed by LA []. The largest cystic nodule treated in this study measured 26.8 ml, less than one-third of the one treated in our patient. The combined use of PEI followed by LA allowed firstly removing the liquid component and secondly shrinking the volume of the solid nodule. LA has been successfully used to reduce the volume of thyroid nodules and has been proven to be superior to levothyroxine suppressive treatment; then, for several years, many patients, especially those suffering from spongiform nodules, benefited from LA and were spared to surgery [–]. Moreover, an unexpected chance of success of LA has also been demonstrated when used in combination with radioactive therapy for large single and multiple autonomous functioning nodules [, ].
The successful outcome of our patient demonstrates that the use of LA in combination with other techniques (PEI in this case) opens new perspectives in the treatment of thyroid disease, which were exclusively prerogative of surgical treatment. Perhaps it is premature to consider such nonsurgical treatments as standard of care, but for sure they can be utilized by skilled physicians for many cases in which until few years ago the surgical choice was the only option.
The short follow-up time (6 months) represents a major limitation in this case report. In this view, some points may be considered: LA usually obtains the greatest effect in volume reduction within 6 months; the volume reduction has been demonstrated to be stable over the time; when necessary, the residual nodule may be submitted to further LA sessions to obtain even more significant shrinkage [, ]. On the other hand, it should be noted that studies demonstrating persistent nodules reduction for a very long time and in a sizeable sample of patients are lacking.


A 76-year-old Caucasian female presented with a history of methicillin-resistant Staphylococcus aureus necrotizing pneumonia and empyema of the right lower lung. She underwent a lobectomy with a prolonged hospital course in the medical intensive care unit eventually complicated by a prolonged, generalized tonic-clonic seizure requiring intubation. Her seizures were refractory to three antiepileptic medications (levetiracetam, lacosamide, and fosphenytoin) and continuous midazolam infusion (maximum rate of 40 mg/h). A computed tomography (CT) scan of the head showed extensive vasogenic edema in the bilateral hemispheres, indicating posterior reversible encephalopathy syndrome (PRES), as shown in Figure and Figure .
Continuous electroencephalographic monitoring (CEEG) showed left occipital lateralized periodic discharges (LPDs; Figure ), evolving into subclinical electrographic seizures (Figure ).
Her seizures remained refractory, requiring an escalation of the treatment to a medically induced coma with pentobarbital. After 24 hours of burst suppression, the patient’s left pupil became nonreactive to brief penlight stimulation as well as pupillometry (Neuroptics, Irvine, CA, USA; Table ).
Her right pupil was sluggishly reactive. Mydriasis was noted to be elicited with noxious stimulation to the ipsilateral neck and resolved after 23 seconds of prolonged penlight stimulation (Figure to Figure ).
A repeat CT head was initially deferred. A CT head three days after the initial CT (24 hours after the noted pupillary changes) showed evolving changes of the known PRES (Figure and Figure ) but no progression of cerebral herniation.
She was eventually weaned off pentobarbital over the next few days. Her bedside pupillary function normalized. Unfortunately, the patient developed multisystem organ failure, and after a goals of care discussion, the family transitioned the patient to comfort care.


Patient #1
A 78-year-old female first presented to our department in 2014 with BRAF mutation-positive melanoma metastatic to the brain, left adrenal gland, and spleen. Prior to this, she was in excellent health managing her household pets until she noticed an enlarging mass in the right neck behind her ear. After she hit her head on the bus she was driving, she was incidentally found to have scalp lesions as well. Both the mass and lesions were biopsied and the patient was found to have metastatic melanoma. During workup for a clinical trial, she underwent a positron emission tomography-computed tomography (PET-CT) scan in November 2013, which revealed hypermetabolic areas in the adrenal gland and spleen, in addition to bilateral scalp and neck. A magnetic resonance imaging (MRI) of the brain the same month revealed two small enhancing metastatic lesions. On the day of treatment initiation, she was found to have eight lesions and was thus treated with Gamma Knife (GK) in 2013 by the outside institution, in addition to three cycles of ipilimumab.
On interim scanning in 2014, she was found to have at least five new lesions. She was motivated to pursue further treatment with GK. On the day of her GK procedure in April 2014, imaging and evaluation by our service showed 16 lesions in the brain (Figure ). Since she lived four hours away from our center and WBRT would be logistically difficult for the patient, the decision was made to proceed with GK. All 16 lesions were contoured and prescribed a highly conformal treatment plan receiving 18 Gy to various isodose lines in one to three shots. The patient tolerated the treatment well, but subsequent imaging in 2015 showed a right frontal lobe lesion concerning for disease progression. The patient therefore underwent a right frontal craniotomy and received postoperative GK to the lesion two months later. Since then, the patient has been on pembrolizumab maintenance treatment.
At the last follow-up in August 2017, the patient was asymptomatic and in good spirits, having recently traveled across the country and on a cruise trip to Alaska. Other than vitiligo from pembrolizumab treatment, the patient had tolerated treatment well and MRI demonstrated stable lesions. Her performance status was excellent and she had a normal neurological exam with no deficits on mini-mental status exam (MMSE). She continues to drive for multiple ridesharing companies, with aspirations for a commercial license to drive buses. The patient also cares for chickens, dogs, and a parrot on her home property, which requires performing tasks such as carrying a 50-pound bag of feed.
Patient #2
A 44-year-old previously healthy, very active female presented to the ER with a seizure while bike riding in 2013, and she was subsequently found to have metastatic BRAF-mutated melanoma to the brain and lungs. She underwent resection of her dominant left frontal lobe metastasis, followed by SRS to the resection cavity as well as four other lesions. Afterwards, she was started on ipilimumab and was asymptomatic neurologically, continuing to work regularly and bike 100 to 150 miles a week. However, later that year, she developed two more metastases that were then treated with GK, and her systemic therapy was switched to trametinib.
Unfortunately, in 2014, surveillance imaging showed multiple recurrent asymptomatic brain metastases. She also underwent lobectomy of her dominant lung lesion in August 2014 and received an interim scan while she was in the hospital and was found to have new brain metastases. During treatment, which occurred while she was still hospitalized in September 2014, nine lesions were identified. These lesions were contoured and prescribed a highly conformal treatment plan, receiving 20 Gy to various isodose lines, with two brainstem lesions receiving 18 Gy. By the end of the year, she was successfully treated for a total of 24 brain metastases, and she was switched to pembrolizumab with good response. In April 2015, she became increasingly symptomatic and was noted to have increasing edema surrounding her right posterior frontal lobe lesion, which was treated five months prior and required high dose steroids and eventually neurosurgical resection. A pathology report at this time demonstrated persistent/residual disease.
Since then, she has had only one further intracranial recurrence, which was treated with GK in the beginning of 2016. She achieved complete response on immunotherapy, which was discontinued during the summer of 2016 due to therapy-related pancreatitis and arthritis. In sum, she was treated for 37 lesions over nine GK sessions in the span of two years (Figure ). During her last follow-up in 2017, the patient had no evidence of disease and has been free of intracranial failure for the past two years. She continues to lead a very active life, having recently returned from a vacation in Europe, and she maintains an active lifestyle biking and doing yoga.


A 59-year-old female presented to the ophthalmology clinic with four months history of daily headache, double vision, and droopy eyes. Her ophthalmological examination revealed bilateral ptosis (Right: 3 mm, Left: 2 mm), more pronounced in the right eye, dysconjugate gaze and double vision most appreciable on lateral gaze bilaterally (Figure ).
Ice pack test was performed on the right eye for three minutes, which showed significant improvement in ptosis (>2 mm improvement) (Figure ).
Acetylcholine binding/blocking and modulating receptor antibodies were negative on investigation. A working diagnosis of seronegative ocular myasthenia was established and she was referred to neurology for further evaluation. On neurological examination, her motor and sensory exam was normal. Deep tendon reflexes (DTR) were 2+ and symmetrical bilaterally. Electromyography (EMG) and nerve conduction studies (NCS) were ordered for further evaluation. On NCS of her left ulnar motor nerve, a reduced compound muscle action potential (CMAP) of 4.5 mV (Normal > 5) was noted. There was no slowing across the elbow on ulnar motor studies and ulnar sensory nerve conduction was normal. Slow repetitive nerve stimulation (at 2 Hz) of left ulnar nerve showed more than 20% decrement in CMAP amplitude (Figure ).
On performing short exercise testing for 10 seconds her left ulnar CMAP increased to 10 mV (more than 100% increment) (Figure ).
This finding raised the suspicion of LEMS given her long-standing history of smoking. Computed tomography (CT) chest scan was ordered, which revealed precarinal/left lower para-tracheal mass with central necrosis (Figure ).
On biopsy of the mass, small cell carcinoma was identified. On further evaluation, her P/Q antibody titer came out to be 3.62 nmol/L (normal <= 0.02, Mayo clinic), which confirmed the diagnosis of LEMS.


A 52-year-old female patient with a BMI of 25 (1.5 m, 56 kg) and a 30A bra cup size was diagnosed with extensive intermediate- to high-grade ductal carcinoma in situ (DCIS). The breasts exhibited a degree of ptosis (a and c). Her back tissue was evaluated as borderline adequate for an autologous LD flap. The mastectomy weight was 192 g. Her reconstruction was successful with excellent cosmetic results (b, d, and f). She did not require postoperative adjuvant therapy.


A 40-year-old woman with multifocal DCIS (one focus grade II measuring 10 mm, and the other 30 mm and of a high grade) in her A cup-sized left breast (BMI = 20 kg/m2) opted for the TALD procedure. There was insufficient tissue on the buttocks and thighs, and abdominal skin closure would have been too tight for an abdominal flap. The cosmetic results (b, d, and f) were assessed as acceptable, and she suffered no complications from the mastectomy (91 g of breast tissue removed) or the simultaneous sentinel lymph node biopsy.


A 54-year-old woman (BMI 26; bra cup size of 36A/B) presented with a multifocal invasive ductal carcinoma (15-mm grade III focus and another at 6-mm grade II) with associated DCIS; bringing the total tumor size to 85 mm. Ten years earlier, she had undergone a skin-sparing mastectomy and reconstruction with pediceled TRAM flap for a contralateral cancer (a, c, and e). Therefore, the abdominal tissue was no longer available for the reconstruction and there was inadequate tissue on the inner thigh, upper buttock, and lower buttock. Furthermore, considering the size and shape of her TRAM-reconstructed breast, it was deemed that reconstruction with an implant would not produce a good enough cosmetic result to match it. She underwent TALD flap reconstruction (which during surgery was successfully converted to a free flap after accidental avulsion of the vascular pedicel during flap transposition). The mastectomy weight was 601 g. She was very pleased with the cosmetic outcome, which was assessed as acceptable (b, d, and f).


A 45-year-old nulliparous woman with a BMI of 27 and bra cup size of B was scheduled to have a mastectomy and axillary clearance surgery of the apical nodes after being diagnosed with a 40-mm grade III invasive ductal carcinoma. Considering her small breast size, the DIEP flap was considered too large a procedure while her planned adjuvant RT made implants a less favorable option. Adequate skin and fat were present on the back and inner thighs. When presented with the options of a TALD or TUG (transverse upper gracilis) flap reconstruction, the patient opted to have the former. Her mastectomy weight was 140 g. The cosmetic results were excellent (b, d, and f), and there were no postoperative complications.


A 35-year-old nulliparous woman with a BMI of 23 and bra cup size of 34C had been diagnosed with a multifocal grade III NST left breast cancer (with tumors measuring 23, 12, and 6 mm). She also requested a risk-reducing mastectomy. Several viable bilateral reconstructive options were fully discussed with the patient during her neoadjuvant chemotherapy, including an expandable implant combined with ADM support (despite future planned RT), extended DIEP flap (DIEP + DCIA fat), and bilateral LD flaps. The mastectomy weights were 244 and 206 g (left and right, respectively). She developed minor (superficial) donor site wound dehiscence, which was successfully treated with dressings and direct closure under local anesthetic. The postoperative cosmetic results were excellent.


A 41-year-old Chinese male visited our hospital in 2013, with a 4-month history of bloody purulent rhinorrhea with a peculiar smell in the right nasal cavity. We reviewed the patient's medical history. The patient had been referred to a hospital in Guangzhou in 2008 for a 3-year history of bloody rhinorrhea and nasal obstruction in the right nasal cavity. At that time, physical examination revealed congested mucous, enlarged inferior turbinate, enlarged middle nasal meatus, and markedly impaired sense of smell on the right side. Surgical resection was performed under general anesthesia. The lesion was histopathologically diagnosed as CGMS.
In 2012, nearly 4 years after the first treatment, the patient began to show nasal obstruction again and complained of no alleviation of bloody rhinorrhea since the first operation. The patient went to a hospital in Tianmen for help. According to his medical history and the results of radiological examinations, the patient underwent a radical operation. The pathologic diagnosis was CEOT.
In 2013, 1 year after the second operation, the patient came to another hospital in Guangdong with a 4-month symptom of bloody purulent rhinorrhea accompanied by a peculiar smell in the right nasal cavity. It was proved pathologically to be keratinizing squamous cell carcinoma after biopsy. Without any further treatment, the patient came to our hospital in May 14, 2013. Magnetic resonance (MR) imaging revealed a soft tissue mass measuring 3.5 × 2.5 × 2.9 cm located in the right maxillary sinus, which presented mixed, slightly high signal intensity on a T1-weighted image and slightly high signal intensity on a T2-weighted image. This was surrounded by the liquid, high signal intensity on a T2-weighted image, and the lesion invaded all walls of the right maxillary sinus and adjacent zygoma, extending into the nasal cavity and ethmoidal sinus on the right side at the same time. The contrast- enhanced MR showed significant heterogeneous density (Fig. ). Upon inspection of the emission computed tomography (CT) and lung CT, no evidence supported metastasis. Considering his medical history, we reviewed his hematoxylin and eosin stain slices in 2012. We revised the previous pathologic diagnosis as GCOC. Histopathologically, we observed the neoplastic nests. Parts of the tumor were calcified. The tumor also infiltrated the surrounding connective tissue and bone (Fig. A). It was surrounded by the deeply stained small round cells, typical ghost cells in clusters or isolated with pale swollen homogeneous eosinophilic cytoplasm, which had lost their nuclei (Fig. B).
Under general anesthesia, a radical surgery was performed. Systemic chemotherapy by intravenous administration of docetaxel (75 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1) was carried out on May 31, 2013. After 2 cycles of chemotherapy, the patient received concurrent chemoradiotherapy (planning target volume [PTV1] 60 Gy/27F, PTV2 54 Gy/27F, PTV3 50 Gy/27F during weeks 1–5) using a 3-dimensional conformal radiation therapy technique together with 4 weekly docetaxel (40 mg). The adverse effects were decreased appetite, pigmentation of skin in radiation field, and bone marrow suppression, especially thrombocytopenia. At the end of the combined modality therapy, the patient showed good results without any residual neoplasm in radiography. The patient showed a good therapeutic result after the combined modality therapy. No evidence of recurrence or metastasis was observed after the 20-month follow-up, which lasted until May 2015. We will continue to focus on the patient's follow-up.


A 60-year-old Japanese woman was brought to the emergency department of our hospital, complaining of left flank pain. The pain had started the previous day and had gradually increased in severity. On examination, she was found to be alert, with a blood pressure of 173/101 mmHg, heart rate of 110 beats/minute, oxygen saturation of 95% (on room air), and respiratory rate of 20/minute. Her past medical history included myelodysplastic syndrome (MDS), hypertension, and cerebral infarction, leading to left hemiplegia. She had no history of pancreatitis and abdominal surgery. She was taking antihypertensive and acid-reducing medications, but no antiplatelet or anticoagulant medication. Her abdomen was flat, but there was moderate tenderness in her left flank. Her laboratory findings included hemoglobin level of 7 g/dL, hematocrit level of 20.8%, platelet count of 118,000/microL, prothrombin time of 13.3 seconds, activated prothrombin time of 31.9 seconds, and fibrinogen level of 209.4 mg/dL. Her normal hemoglobin level was approximately 8 g/dL. Blood chemistry findings were almost within normal limits. A computed tomography (CT) scan of her abdomen with intravenously administered contrast agent showed a solid mass of 5 × 5 × 8 cm in the left middle abdominal quadrant (Fig. ). The mass was found to be fed by a branch of the superior mesenteric artery (SMA). The contrast agent leaked in the mass. An orally administered contrast agent was not used because she had nausea. On completion of CT, the working diagnosis was an impending rupture of an aneurysm located in a branch of SMA. We decided to perform a transcatheter arterial embolization (TAE); however, angiography of SMA and inferior mesenteric artery (IMA) did not indicate extravasation of the contrast agent. Her blood pressure remained stable, but her pulse rate was still fast. We decided to perform surgery in line with the diagnosis of an impending rupture of the visceral artery aneurysm. Her peritoneal cavity was entered with a midline incision, and there were no ascites. The mass was attached to the antrum of her stomach. There was a smooth surfaced mass at the greater curvature of the antrum. We suspected intra-tumor bleeding of the gastric submucosal tumor. We performed a wedge resection of her stomach including the mass with a 1 cm margin. The surgical specimen was opened and it revealed a large amount of clots (Fig. ). There were no tumoral lesions.
Subsequently, pathological findings indicated that the mass had not included tumor cells and was simply filled with a large amount of clots. The etiology of the hematoma was not proven by pathological findings. She was admitted to the general surgical ward after surgery, and she was transfused with six units of packed red blood cells postoperatively. She was discharged from our hospital to a nursing home on day 63 after rehabilitation.


This 31-year-old woman, with documented HIV infection for 8 years, presented with a four-day history of intermittent episodes of confusion associated with headache, fever, productive cough, and dyspnoea. Of note, the patient had declined treatment for HIV following her initial diagnosis and had not attended the outpatient department for several years.
On admission, she was moderately confused but had no focal neurological deficits or altered consciousness levels. Baseline laboratory tests revealed a very low CD4 cell count (14 cells/mm3 at 4%) and an HIV viral load of 206,548 copies/mL, indicating that the patient was significantly immunosuppressed and at risk for opportunistic infection. Other routine blood tests showed moderately raised inflammatory markers (CRP and ESR) with normal white cells and neutrophils. The patient's initial chest X-ray demonstrated patchy lower lobe infiltrates and she was commenced on treatment with trimethoprim-sulfamethoxazole for suspected pneumocystis pneumonia. Subsequent bronchoscopy with bronchoalveolar lavage (BAL) was negative for pneumocystis jirovecii and treatment for this infection was stopped with the patient receiving seven-day antibiotic treatment.
Computerised tomography (CT) brain scan was performed on admission to investigate the cause of acute confusion and revealed a left basal ganglia lesion with mass effect. Differentials included toxoplasmosis and primary CNS lymphoma. MRI of brain confirmed a single left basal ganglia mass measuring 2.5 cm with alternating concentric T2 hypointense and hyperintense rims () and postcontrast focal eccentric enhancing nodule that measured 1 cm (). These are considered both the “concentric” and “eccentric” target signs, which demonstrate specificity in the setting of cerebral toxoplasmosis. Biopsy of the lesion was performed and histopathological analysis confirmed toxoplasma cysts () confirmed on immunohistochemistry (). There was no histological evidence of lymphoma. Further diagnostic testing such as serology and lumbar puncture was not required following detection of toxoplasmosis on biopsy.
The patient was commenced on treatment for toxoplasmosis, which involves a six-week course of antimicrobial therapy including sulfadiazine, pyrimethamine, and folinic acid. She responded well to treatment and her confusion resolved. Of note, while awaiting BAL results, the patient also completed a seven-day course of trimethoprim-sulfamethoxazole for suspected pneumocystis pneumonia, which is an alternative treatment choice for CNS toxoplasmosis. She was commenced on highly active antiretroviral therapy (HAART) and was counselled by the genitourinary service regarding the importance of compliance to her HIV treatment in the future.
CT brain scan was performed two days after biopsy and showed stable focal lesion with decreased vasogenic oedema. Repeat chest X-ray after two weeks showed complete resolution of infiltrate. She was eventually discharged from hospital four weeks after her initial presentation with outpatient follow-up arranged in the HIV clinic, at which point her CD4 count was noted to have risen to 129 cells/mm3 and 10% and her HIV viral load had reduced to 129 copies/mL.


A 31-year-old male fell from an unknown height at the scene of a crime. Injuries diagnosed in the primary survey included severe brain trauma, facial fractures, serial rib fractures, bilateral lung contusions, a right-sided hemopneumothorax, bilateral pelvic fractures, intraperitoneal bladder rupture with urethral rupture of the membranous urethra, a distal femoral fracture, and a fracture of the right 5th metatarsal, resulting in an ISS of 41. During the primary survey, the pancreatic lesion was not detectable. During the first 5 days of the clinical course, acute respiratory failure occurred. The condition of the patient required cannulation for venovenous extracorporeal membrane oxygenation (VV-ECMO). Weaning from VV-ECMO and from the invasive ventilation was subsequently successful, indicative of pulmonary recovery. Then, clinical findings of deterioration arose, including increased inflammatory markers. CT scan showed massive pancreatitis with formation of a 6 cm pseudocyst at the transition from the body to the head and extensive fatty tissue necrosis in the tail of the pancreas (). The ductal injury was presumed in this case, but it was not detected on CT scan. We tried to minimize the interventions to this patient after he suffered severe ARDS treated with ECMO. For this reason, surgical decision-making indicated CT-guided drainage as first therapy attempt.
The cyst in the pancreas was successfully drained using guided CT (). Despite successful CT-guided drainage of the cyst, a new cyst developed, along with ascites and elevated laboratory markers, indicative of infection. Operative treatment was indicated at that time due to the failure of interventional drainage treatment. Exploratory laparotomy and intraperitoneal lavage were performed, and a drainage remained in situ. Intraoperatively, inflammation of the whole small intestine was discovered, likely caused by rupture of a pancreatic pseudocyst with leakage of pancreatic secretions into the peritoneum.
Subsequently the pancreatic injury was classified during the surgery as a grade III laceration due to the AAST-OIS. The drain was removed six weeks postoperatively. No recurrent symptoms appeared (). The patient was discharged from the hospital four months after the accident with disabilities due to the injury of the lower extremity.


A 50-year-old male fell approximately 20 meters from the basket of a hot air balloon. The following injuries were diagnosed in the primary survey: fractures of the sixth through eighth and eleventh thoracic vertebrae, complete paraplegia below T7, a fracture of the first lumbar vertebra, serial rib fractures, a lung contusion, a right-sided hemopneumothorax, and pancreatic injury. The ISS was 25. The pancreatic lesion was detected in the primary survey and classified according to the AAST-OIS as a grade II laceration. The initial treatment intervention was CT-guided drainage, which was performed at a referral hospital (). ERCP showed no leakage or rupture of the pancreatic duct. Two weeks after the trauma, the patient was stable for transport and was admitted to the study ICU, which specializes in the early rehabilitation of spinal cord injuries. Increased inflammatory markers were seen at the beginning of the third week after admission. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the abdominal secretions. CT scan showed a pancreatic fistula, and the pancreas showed altered signal with a hypointense formation found in the pancreatic body, indicating pancreatic injury. There was a blockage of peripancreatic fluid despite the in situ drain (). Because nonoperative treatment failed, an exploratory laparotomy was performed. During surgery, most of the pancreas was found to be necrotic; necrosectomy with partial pancreatectomy and abdominal lavage and drain placement were performed. The drain was removed seven weeks postoperatively.
Further treatment was complicated by a massive pulmonary embolism, which was lysed successfully. The patient was discharged from the hospital after completing rehabilitation for his spinal cord injury.


A 25-year-old female attempted suicide and fell from approximately 7 meters. The following injuries were diagnosed in the primary survey: fractures of the first and second lumbar vertebrae, incomplete paraplegia below L2, a type III open fracture of the right lower extremity, a fracture of the left calcaneus and a pancreatic contusion. These injuries resulted in an ISS of 26. Pancreas contusion was detected in the primary survey trauma scan. Within the first three days of hospitalization, the patient developed an acute abdomen due to peritonitis. Urgent laparotomy, lavage and abdominal drain placement were conducted. Intraoperatively, the head of the pancreas was considerably rotated, causing significant bleeding, and the lesser sac was filled with small vessel bleeding. Macroscopic rupture was not present. The injury was classified using the AAST-OIS as a grade IV laceration. Postoperatively, CT findings showed indistinguishable pancreatic tissue. Recurrent clinical deterioration occurred with symptoms including abdominal pain and increased inflammatory markers (). The infection was treated successfully with eight weeks of antibiotic therapy and consistent flushing of the drain. The patient was discharged from the hospital with paraplegia after 3 months of rehabilitation for her spinal cord injury.


A 39-year-old man presented with a 3-month history of skin lesions involving the face, neck and extremities. The patient was diagnosed as being HIV-positive a month earlier and was commenced on antiretroviral treatment abacavir 300 mg bd, lamivudine 300 mg bd and efavirenz 600 mg once daily, because of impaired renal function or pre-renal failure. The patient was hydrated with an improvement in the renal function. Two weeks after the development of the skin lesions, the patient complained of a sore throat and hoarseness of his voice.
On clinical examination, the patient had multiple translucent, clustered, umbilicated papules and nodules in the centrofacial region and neck with necrotic centres. In addition, there were verrucous plaques and nodules on the ears and upper limbs ( and ). Chest X-ray was normal with no lung, hilar or mediastinal lymph nodes. A fibre-optic laryngoscopy revealed a supraglottitis with ulceration on the lingual surface of the epiglottis ().
Routine blood investigations demonstrated elevation of the liver enzymes with an infiltrative pattern (AST-63/ALT 70/ALP -219/Gamma GT-291). Abdominal ultrasound revealed an enlarged liver with abnormal parenchyma. The kidneys and the rest of the abdomen were normal. The initial CD4 count performed prior to the commencement of antiretrovirals was 2 cells/µL with a viral load greater than one million copies/mL. A repeat test (eight weeks later) showed a CD4 count of 124 cells/µL with a viral load of less than 20 copies/mL. Urinalysis and urine histoplasma antigen test were negative. Histology of the liver, larynx and sections of the skin demonstrated pandermal necrotising granulomatous inflammation. Grocott-Gomori methenamine silver and PAS stains revealed a relative paucity of intracellular oval, narrow-neck budding fungal organisms morphologically in keeping with Histoplasma capsulatum var. capsulatum ( and ). Fungal culture of liver, epiglottis ulcer and skin confirmed the diagnosis of histoplasmosis.
On the basis of the clinical presentation, initial worsening of the disease and rapid elevation of the CD4+ T-cell count with lowering of the HIV viral load, the patient most likely has histoplasmosis associated IRIS. The patient was commenced on intravenous amphotericin B (0.8 mg/kg/day) for two weeks and continued with his antiretroviral treatment. He had an excellent response to this treatment and was discharged on itraconazole 100 mg twice a day.