A 52-year-old man presented to the emergency department with 3-day history of fatigue, dizziness, dark stools, and mild generalized abdominal pain. There was no history of hematemesis, hematochezia, bleeding from any other site, or any similar prior episodes. There was no history of liver disease or NSAIDs. Patient was taking oral rivaroxaban 20 mg/day. His past medical history was significant for extensive portomesenteric thrombosis involving superior mesenteric, splenic, main portal, and right portal veins which was diagnosed 2 years ago. Extensive workup done for the cause revealed heterozygous mutation of factor V Leiden. Another workup showed normal protein C, protein S, and antithrombin III levels. Autoimmune workup, hepatitis B, hepatitis C, and HIV serology were all negative. The patient has no family history of any venous thromboembolism or other bleeding disorders.
On clinical examination he was hemodynamically stable and not in distress. Physical examination revealed marked pallor and normal abdominal examination. Digital rectal examination showed green stool with no evidence of melena at the time of examination.
Laboratory tests revealed a hemoglobin level of 7.5 g/dl, platelet count 210,000/ul, INR 1.1, urea 6.6 mmol/l, creatinine 90 umol/l, and normal liver function tests. He was admitted as a case of probable GI bleeding. His rivaroxaban was stopped. He received transfusion of packed red blood cells for symptomatic anemia. Urgent esophagogastroduodenoscopy (EGD) was done and revealed normal esophagus and stomach; however, a suspicious area distal to 3rd part of the duodenum was seen but could not be reached by the normal EGD scope. Subsequently, push enteroscopy was attempted in the same setting and revealed multiple varices in the proximal jejunum affecting a short segment with red wale signs and submucosal feeding veins (Figures –)
CT abdomen with contrast was sought. It demonstrated total occlusion of superior mesenteric and splenic veins with well-established collateral venous circulation and reestablishment of the portal circulation at the region of porta hepatis (Figures , , and ).
He was started on IV pantoprazole infusion and then given IV terlipressin for 3 days along with ceftriaxone 1 g/day for 5 days after the enteroscopy findings. His anticoagulation with rivaroxaban was stopped. A multidisciplinary team (MDT) meeting between general surgeon, interventional radiologist, internist, and gastroenterologist was arranged. The agreement was to surgically resect the affected small bowel segment for definitive therapy. Patient was observed in the hospital for few days and did not have any further bleeding or drop in his hemoglobin. After explaining all the benefits and risks of surgery to the patient, he decided on conservative therapy. After discussion with the hematologist, patient was kept off anticoagulation considering his high risk of GI bleeding as he did not opt for surgery. Patient was discharged home with follow-up appointment in general surgery, hematology, and gastroenterology clinics. Patient was restarted on anticoagulation with Dabigatran 110 mg twice daily by the hematologist after 4 months of bleeding event. Reduced dose was chosen due to risk of GI bleeding and the drug was chosen due to availability of the antidote idarucizumab. There was no evidence of bleeding again after resumption of the anticoagulation. Patient was doing well after eight months of follow-up, and his hemoglobin level normalized.


A 48-year-old man with diabetes mellitus who had failed to adhere to his treatment presented to the emergency department with complaints of a right-sided headache and toothache for two weeks, with nausea and vomiting for two days prior to presentation. The patient was managed for septic shock secondary to dental abscesses. Non-contrast brain computed tomography (CT) was performed. The CT scan showed no significant intracranial abnormality other than pansinusitis, without obvious retro-orbital fat streakiness (Figure ). Four days later, tooth number 17 and 18 in the left mandibular region, both of which had abscesses, were extracted. The patient noted progressive painless blurring of the vision in his right eye post-extraction of the abscessed teeth and was referred to the ophthalmology team two days later. At this time, the patient was receiving day five of treatment with intravenous (IV) amoxicillin-clavulanate, (1.2 g three times a day), with the addition of IV metronidazole (400 mg twice a day).
The visual acuity (VA) in his right eye was 4/60, with no improvement in the pinhole test. A relative afferent pupillary defect was present, with an associated decrease in the optic nerve function, in addition to ophthalmoplegia and restrictions in the superior and lateral gaze. No proptosis, ptosis or lid swelling was present, and all other anterior segment findings were normal. A fundus examination of the right eye showed only proliferative diabetic retinopathy. The VA in the patient’s left eye was 6/18 and 6/9 in the pinhole test. An examination of the anterior segment was unremarkable. Moderate non-proliferative diabetic retinopathy was detected in the posterior segment. Dental caries were present in the upper molars, with mucopurulent discharge from the right sphenoid sinus region. The clinical diagnosis was OAS, and emergency functional endoscopic sinus surgery and septoplasty were performed by the ear, nose and throat (ENT) team. Intra-operatively, pus (6cc) was drained from the right sphenoid sinus. The pus breached the anterior sphenoid wall, tracked down to the septum polypoidal mucosa over the right maxillary sinus and right anterior and posterior ethmoid sinuses.
Empirical treatment with IV ceftriaxone (1 g twice a day) and IV fluconazole (400 mg once a day) was started. Despite the commencement of IV antibiotic and antifungal treatment, the patient’s condition deteriorated, and the VA in this right eye was classified as no perception of light (NPL) and almost total ophthalmoplegia four days post-presentation (Figure ). Treatment with IV methylprednisolone was not started in view of the infective nature of the disease and the possibility of a fungal infection, which could worsen his condition.
Methicillin-resistant Staphylococcus aureus was isolated from the pus and from a nasal swab. IV vancomycin (1 g twice a day) and IV metronidazole (400 mg twice a day) were added. An urgent non-contrast CT brain scan was repeated and revealed features suggestive of fungal pansinusitis, with the involvement of the right orbital apex and right orbital contents (Figure ). No suspicious intracranial lesion was seen. The patient underwent emergency nasal debridement for the second time and septotomy. A bony dehiscence was noted over the right posterior ethmoid supralaterally, exposing the orbital apex.
On day 13 after the first surgical drainage, tissue culture from the septal wall yielded S. apiospermum. IV amphotericin B (35 mg once a day) was commenced. However, the patient’s renal profile deteriorated following the amphotericin B treatment. Thus, the antifungal regime was changed to oral voriconazole (200 mg twice a day), but the patient failed to respond to the treatment. Forty days after the initial presentation, he developed invasive pansinusitis, with disease progression involving the base of the skull (both orbits) and intracranial extension.
At this stage, the VA in the patient’s right eye was classified as NPL in all four quadrants, with almost total ophthalmoplegia. The VA in his left eye was 6/12, with full extraocular movement. The neurosurgical team decided against any surgical intervention. Functional endoscopic sinus surgery was performed for the third time, with nasal toileting. Intra-operatively, minimal crusting was observed over the right nasal cavity. The right sphenoid, pterygoid, maxillary sinuses and the frontal sinuses were clear, with no pus. The mucosa was healthy, with minimal bleeding. The left maxillary sinus was also clear.
IV amphotericin B was restarted, but the patient developed gastrointestinal intolerance. The antifungal treatment was again changed to oral voriconazole (200 mg twice a day). Fifty-seven days after the initial presentation, the VA in the patient’s left eye decreased suddenly to 6/30 (reduced Snellen chart), and his colour vision decreased. A plain and contrast-enhanced CT scan of the brain, orbit and the paranasal sinuses showed invasive pansinusitis, with bilateral orbital apex involvement (Figure ). It also showed an increasing intracranial extension involving the right cavernous sinus anteriorly, the roof of the sphenoid sinus, the floor of the anterior cranial fossa and right medial cranial fossa anteriorly, as well as osteomyelitis changes at the base of the skull. In view of the acute progression of the infection, surgical intervention was considered. However, the area of the lesion was too extensive and was beyond ophthalmology coverage. Following a reassessment by the neurosurgical team, a decision was made to continue medical treatment rather than perform a surgical intervention.
SIxty-seven days after the initial presentation, the patient’s VA decreased to NPL in both eyes. Although his Glasgow coma scale was full, his general condition worsened, with lethargy, irritability and dizziness, accompanied by nausea and vomiting. The patient decided to discharge himself from the hospital (at own risk discharge) and subsequently failed to attend an appointment in the ophthalmology clinic.


A 73-year-old man was admitted in Urology ward on 30th September 2017 with a chief complaint of nocturia, frequency, dribbling, and urinary retention since last month. Ultrasound examination revealed left renal mass. In past history diabetes mellitus, hypertension, and ischemic heart disease was noted. He stopped cigarette smoking 20 years ago. His drug history was Enalapril, ASA, Metformin, and Metoral. The lab data including complete blood count, Blood Urea Nitrogen (BUN), creatinine, Na, K, Arterial Blood Gas (ABG), Prostatic Specific Antigen (PSA), and free PSA were within normal limits except for mild anemia (Hemoglobin: 10.6 gr/dl). Blood sugar (BS) was 159 mg/dl. Urine analysis showed 10-15 white blood cells (WBC) in high power field with a negative urine culture. In digital rectal examination prostate was nodular (2-3+) and symmetric. Ultrasound examination on 7th October 2017 demonstrated mild bilateral hydroureteronephrosis with the over distended urinary bladder. Prostatic volume was 25 cc with the retained urine of 950 cc. A well-defined hypoechoic exophytic mass without calcification measuring 60 × 38 mm in left renal pole with vascular areas was noted. Computer tomography scanning on 10th October 2017 revealed 44 × 38 mm hypo attenuated mass in the lower pole of the left kidney with arterial and portal enhancement and delay washout in favor of infiltrative process such as RCC close to left psoas muscle. Mild bilateral hydronephrosis due to enlarged prostate was seen. No lymphade- nopathy in pelvis and abdomen was seen. He referred to surgery department of the hospital for nephrectomy. The specimen was referred to the pathology department. The frozen section microscopic evaluation revealed oncocytic feature in favor of oncocytoma. In permanent diagnosis, a portion of renal tissue measuring 6.5 × 5.5 × 3.5 cm with perirenal fatty tissue measuring 3 × 2 × 1 cm was evaluated. In cut section, creamy brown solid mass measuring up to 5.5 cm at 1.5 cm distance from renal resected margin was noted. The pathologist reported chromophobe RCC () with vascular and renal capsule invasion but with no necrosis or margin involvement. The IHC was done and tumor cells were positive for cytokeratin (CK) 7, CK8, CK20 (weakly +), the Epithelial Membrane Antigen (EMA), Cluster of Differentiation (CD) 10, E-Cadherin and High Molecular Weight Keratin (HMWK, focally positive). Inhibin and vimentin markers were negative in tumor cells (–). The findings were in favor of chromophobe RCC. We followed- up the patient for 5 months after surgery. No recurrence or metastasis was diagnosed.


A 79-year-old Caucasian woman came to our attention complaining of dull, diffuse abdominal pain and high body temperature (38 °C). She had high blood pressure and type 2 diabetes, for which she was receiving oral ramipril 5 mg twice daily and metformin 500 mg three times daily, respectively. She was a housewife. Her parents had died of cardiovascular diseases in advanced age. She denied tobacco or illicit drug use and rarely drank a glass of wine. The patient reported a history of bile stones in her gallbladder and her common bile duct. She stated that she had undergone endoscopic bile stone extraction (endoscopic retrograde cholangiopancreatography with papillotomy) and laparoscopic cholecystectomy 3 years before. Cholecystectomy was completed with choledochotomy in order to extract further bile stones and for the positioning of a Kehr’s T tube. Postoperatively, a single daily dose of prulifloxacin 600 mg was taken for 5 days.
Two months later, the Kehr’s T tube was removed, and a new antibiotic therapy (always with single oral intake of prulifloxacin 600 mg for 5 days) was established. At reevaluation with abdominal computed tomography (CT), no bile leakage or biliary obstruction was detected.
Six months later, the patient returned to the hospital with a 4-day history of high body temperature (> 38 °C), right upper abdominal quadrant dull pain, and dyspnea. Her bowel sounds were normal; at palpation, abdomen was globally painful, with a mild tenderness at the right upper quadrant. Chest examination showed bilateral lower diaphragmatic excursion, decreased vocal fremitus, and attenuated sounds at pulmonary bases. The patient was oriented, and her language was fluent with good comprehension. Her neurological examination result was normal: Her pupils were equal, round, and reactive to light; visual fields were intact to confrontation; fundi were normal; ocular movements were intact; muscle bulk and tone were normal; sensation was intact to light touch, pinprick, vibration, and proprioception throughout; Romberg test result was negative; reflexes were normal throughout, and plantar response was flexor bilaterally; no dysmetria was observed on finger-nose-finger or heel-knee-shin; normal rapid alternating movements; and fast finger tapping with normal amplitude and speed. The patient’s blood pressure was 110/70 mmHg, and her heart rate was 97 beats per minute. Blood laboratory parameters showed severe leukocytosis (19,000 white blood cells/mm3). The patient was promptly started on broad-spectrum antibiotic therapy with endogenous piperacillin-tazobactam 4.5 mg twice daily and endovenous levofloxacin 500 mg once daily. An x-ray showed a homogeneous opacification of the right pulmonary lower zone and a slight elevation of the homolateral hemidiaphragm; the left costophrenic angle was obliterated with a meniscus. The findings were suggestive of a bilateral pleural effusion most relevant in the right side. Abdominal ultrasonography (US) showed multiple hypoechoic, loculated fluid collections within the liver parenchyma consistent with HA and confirmed pleural effusion. The subsequent contrast-enhanced chest and abdominal CT scan confirmed the presence of the HA (a 13-cm hypodense circular mass at hepatic segments VI, VII, and VIII) and marked the presence of a mild bilateral pleural effusion. Then, the patient underwent CT-guided drainage of the HA; at the same time, a 7-F multipurpose drainage catheter was positioned. In this case, the collected fluid was not examined. The chest and abdominal CT scanning performed 5 days later showed a severe right pleural effusion, whereas the left one remained superimposable to that shown 5 days before; the multipurpose drainage catheter was in the right position (close to the hepatic bare area), surrounded by plenty of retroperitoneal fluid.
The patient was discharged with oral antibiotics (levofloxacin 500 mg once daily and ceftriaxone 400 mg once daily for 15 days), and a control contrast-enhanced CT scan was scheduled for 1 month later. In this case, the examination showed a mild right pleural effusion and a well-circumscribed 9.5 × 4.5 × 9-cm fluid collection in the back of the thoracic cavity, pushing against the lower lobe of the right lung; abdominal slices showed a small 15-mm formation, laying on the posterior surface of the liver and imprinting the VIth segment, resulting from the drained abscess.
The subsequent control chest and abdominal CT scan, obtained 4 months later at the same hospital, showed an improved picture with a slight residual right pleural effusion and no signs of thoracic abscess or HA.
At the time of admission to our hospital 3 years after the last event, the patient complained of high body temperature and abdominal pain. Her body temperature was 38 °C, and she felt very weak. Her blood pressure was 100/60 mmHg, and her heart rate was 110 beats per minute. Her abdomen was slightly globose, but her bowel movements were present. She complained of an intense pain in her hypogastrium when a deep palpation was applied. Chest and neurological examination results were normal. Complete blood count showed only a mild leukocytosis (14,700 white blood cells/mm3), and her C-reactive protein level was 6.9 mg/dl. A chest x-ray was taken, but it was not clinically relevant. Abdominal US revealed a remarkable fluid collection in the patient’s pelvis. Upon admission, a single daily oral dose of Levofloxacin 500 mg + intravenous Ceftriaxone 2 g once daily were prescribed. A progressive improvement of clinical condition was observed, also confirmed by laboratory tests (see Table ). At day 19 after admission, a contrast-enhanced chest and abdomen CT scan was repeated; interestingly, the CT scan showed presence of a large, irregular, loculated fluid-density formation, of about 18 cm in diameter, with rim enhancement and internal septation. The collection was located posteriorly to the right kidney, displacing it anteriorly. The VIth and VIIth liver segments were compressed, and the abscess extended to the retroperitoneal space; furthermore, it spread to the right lateral wall of the abdomen, extending across the muscular wall to the subcutaneous layer. The fluid collection also involved the right pleural cavity, forming an empyema of about 14 cm in major diameter (Fig. ). CT-guided aspiration of the fluid collection was performed. The needle was inserted into the right lumbar region, and an 8-French multipurpose drainage catheter was positioned. Immediately, 450 ml of a grayish smelly fluid came out. Eight milliliters of the fluid were collected in an anaerobic vial (ambient temperature) and quickly sent to the Microbiology Laboratory of Palermo University Hospital. The fluid was analyzed using Grocott and periodic acid-Schiff stains for cytology, which demonstrated the presence of granulocytes, histiocytes, and bacterial debris (suspicious for Actinomyces). The aspirate material was also submitted to Gram staining and culture (aerobic, anaerobic, Mycobacterium tuberculosis, and fungi), but the results did not show any kind of bacterial or fungal growth. Culture media and techniques were carried out according to international standards for the research of the specific microorganisms. A few days later, a multipurpose drainage catheter was positioned. A CT scan showed a timely reduction of the abdominal and thoracic collections. A blood culture was not obtained. The patient was discharged 70 days after admission in good clinical condition. Before discharge, whole-body CT was performed, which showed a complete reabsorption of fluid collections. Of note, during her hospital stay, the patient’s indirect bilirubin level was raised. Owing to Coombs test positivity, this was likely caused by an immunologic response to long-term antibiotic therapy.
Fourteen months later, the patient came back to our care after 1 month of a dull pain in her right lumbar region. A few days before admission, she complained of high body temperature (> 38.5 °C) and a huge swelling with reddened skin in the same area hit by pain. At admission, her blood pressure and heart rate were normal (120/80 mmHg and 75 beats per minute, respectively), but her body temperature was high (38 °C). The result of her abdominal examination was globally normal. Laboratory blood tests did not show any relevant alteration, apart from mild leukocytosis (10,000 white blood cells/mm3). The patient was promptly started on broad-spectrum antibiotic therapy with endovenous piperacillin-tazobactam 4.5 mg twice daily and endovenous levofloxacin 500 mg once daily. A chest/abdominal CT scan showed a new retroperitoneal fluid collection extending beyond muscular layers toward the skin of the lumbar region. A few days later, a 14-French drainage catheter was positioned, and the patient was discharged in good clinical condition. One week thereafter, the abscess was no longer present.
Three months after the last follow-up, the patient came back to our attention with an evident swelling of her right lumbar region. Her skin was slightly reddish but not dystrophic. She did not report any symptom related to the neoformation. Her blood pressure, heart rate, and body temperature were normal (120/80 mmHg, 75 beats per minute, and 36.5 °C, respectively). Her blood test did not show particular alterations. The right lumbar region showed reddened skin with a 10 × 10-cm swelling. Upon palpation, it was globular in shape and soft in consistency with smooth surface and well-defined borders. It was expansive on coughing and straining. No pulsations were felt over the swelling. Suspecting a new relapse of the disease, we obtained a CT scan, and a right inferior lumbar hernia (Petit hernia) containing adipose tissue and the right kidney was detected (Fig. ). To better understand the case, a visual timeline was provided. A surgical intervention was recommended to the patient, but, owing to her poor general health, she refused any invasive approach. To date, the patient is alive and continues her life with her lumbar hernia. No further abscesses have been detected. The timeline in Fig. summarizes the sequence of events during the patient’s clinical course.


A 65-year-old female presented to the Department of Neurosurgery with an unruptured right middle cerebral artery (MCA) aneurysm (Figure ). Other than a left facial droop and subsequent left hemifacial spasm (which is incidental to an aneurysm), the patient had no relevant past medical or surgical history. The patient was admitted to the hospital for a right-sided craniotomy for clipping of a right MCA aneurysm. A pterional craniotomy was performed under general anesthesia.
Intraoperative neurophysiological monitoring methods
Median, ulnar, and posterior tibial nerve somatosensory evoked potentials (SSEP) were used in standard fashion. TCMEP and DCMEP were used for functional monitoring of the motor pathways. For TCMEP, a multi-pulse train of six was used with a pulse width of 50 µsec and an interstimulus interval (ISI) of 2 ms (500 Hz). Voltage stimulation between 100 and 300 volts was applied (controlling for the inhibition of the “crossover” response). Stimulation parameters for DCMEP included a multi-pulse train of five delivered at a constant current of 15 mA with a pulse width of 500 µsec and an ISI of 2 ms (500 Hz). Upper extremity and lower extremity muscles were used as target acquisition sites using standard intraoperative electromyography (EMG) needle electrodes for TCMEP and DCMEP.
Transcranial motor evoked potential methods
TCMEP data was collected before incision. The stimulus was delivered and optimized to inhibit a “crossover” recording from the ipsilateral hand muscles. Three sets of stimulation electrodes were affixed to the patient’s scalp using corkscrew needle electrodes, providing three channels of motor stimulation to switch between using a TCS 4 constant voltage stimulator unit (Cadwell, Kennewick, WA). This technique (involving the use of multiple stimulation channels) allowed for better optimization of the TCMEP recordings (Figure ). Scalp electrodes for TCMEP stimulation were placed so as not to disturb the surgical site.
Direct cortical motor evoked potential methods
Once the dura mater was open and the aneurysm located, a 1 x 6 strip electrode was slid under the dura and skull towards the precentral gyrus for DCMEP stimulation. Before DC stimulation was initiated, the left median nerve was stimulated at 25 mA, and somatosensory evoked responses were recorded directly from the cortical surface to ensure that the strip electrode was adequately placed over the motor area. All six contacts from the strip electrode demonstrated adequate placement over the motor cortex. Next, all six contacts from the strip electrode were plugged into six different positive output channels of an ES-IX constant current stimulator unit (Cadwell, Kennewick, WA) to allow for anodal stimulation. Six off-site returns (corkscrew electrodes placed on the scalp) were used as cathodes (negative) for each stimulation channel. Using multiple stimulation channels allowed the neurophysiologist to switch between each electrode contact from the strip electrode to find optimal DCMEP recordings. Stimulation at contact 2 from the strip electrode yielded the most reliable and robust DCMEP recordings from the targeted upper and lower extremity muscle groups (Figure ).
Once reliable and reproducible recordings from DC stimulation were obtained, the DCMEP was prioritized over other neuromonitoring modalities for the remainder of the procedure. The DCMEP recordings attenuated from all upper extremity muscle groups during the temporary occlusion of the parent vessel. The lower extremity DCMEP recordings did not deviate from their established baseline. At this point, the surgeon removed the temporary clip which yielded an immediate return of the upper extremity DCMEP recordings. Once blood flow was restored to the MCA and maintained, temporary occlusion of the parent vessel was performed for a second time. Again, the DCMEP upper extremity recordings attenuated in amplitude and were eventually not obtainable (Figure ). At this point, TCMEP stimulation was conducted and there was no diminution noted compared to the baseline recordings (Figure ). All upper extremity TCMEP recordings remained within established baseline limits, whereas the DCMEP upper extremity recordings were absent. The permanent clip was placed across the neck of the aneurysm and the temporary clip was immediately removed. The DCMEP upper extremity recordings returned almost immediately after the temporary vessel occlusion was released, and the signals remained within baseline limits for the remainder of the procedure. Hemostasis was achieved, and closure was performed in standard fashion. The patient awoke neurologically intact. SSEPs were not conducted during the time of the DCMEP deterioration, which is a limitation to the case study.


A 67-year-old woman presented to our hospital with dyspnea. She developed general fatigue 5 years ago and numbness of the right body 3 years ago. She presented to an orthopedic surgeon and was diagnosed as having OPLL of the cervical spine. The neuropathy had been getting worse, and she began to feel numbness up to the extremities and had trouble walking. One year ago, she developed dyspnea on exertion. Her body weight had fallen from 46 to 41 kg over the 5 years. Spirometry conducted by a local physician revealed restrictive ventilation impairment, but the diagnosis remained unclear and she presented to our hospital for further evaluation.
She had no medical, family, or social history of note. She had never smoked. Her vital signs included a body temperature of 36.2°C, pulse rate of 71 beats/min with a regular rhythm, and blood pressure of 103/56 mm Hg. A physical examination revealed decreased thoracic motion, muscle weakness of the right upper limb, numbness of the extremities, and claudication. No rales were audible although breath sounds were decreased in both lungs. Her Japanese Orthopaedic Association Score (JOA score) was 14 points. The JOA questionnaire grades the status of patients suffering from cervical myelopathy. A JOA score of 14 points means that cervical myelopathy is mild, and there is no indication for surgery. Chest X-ray (Figure A,B) and chest computed tomography (CT) did not show any abnormal shadows in either lung field, but the movement of her diaphragm was decreased when comparing the inspiratory X-ray with the expiratory image. Cervical X-ray (Figure ) revealed ossification of the posterior longitudinal ligament (OPLL) of the cervical spine runs longitudinally across the vertebral body. Sagittal T2-weighted magnetic resonance imaging (MRI) showed a thickened posterior longitudinal ligament that was severely compressing her cervical cord at C3/4. Spinal cord MRI showed atrophic change, and an intramedullary T2-weighted high-intensity area was seen at the C3/4 level (Figure ). There was no abnormality in the thoracic cord.
Her blood gasses under ambient air showed a pH of 7.36, PaO2 of 64.8 Torr, PaCO2 of 61.3 Torr, HCO3
- of 33.6 mmol/L, and alveolar-arterial oxygen pressure difference of 1.18 Torr. No other remarkable changes were seen in the biochemical examination of her blood and urine. Pulmonary function test results (% predicted) showed restrictive ventilatory impairment: vital capacity (VC) of 1.09 L (39.4%), FEV1 of 0.99 L (62.7%), and FEV1/FVC of 98%. Polysomnography showed obstructive sleep apnea (OSA) with an apnea-hypopnea index (AHI) of 20.7 and minimum oxygen saturation of 86%. From these findings, we considered that cervical myelopathy due to OPLL was causing her respiratory muscle paralysis and that OSA might also be affecting its course.
First of all, we started continuous positive airway pressure (CPAP) only at night, and her AHI and minimum saturation with CPAP improved to 13.9% and 88%, respectively, but her daytime hypercapnia and dyspnea on exertion did not improve. In addition, the neuropathy of her extremities was worsening, and C3-7 laminoplasty was performed.
Although her pulmonary function did not improve immediately after surgery, it began to gradually and steadily improve over the first postoperative year. The mobility of her diaphragm increased during inspiration/expiration (Figure C,D), and her blood gasses also improved (Figure ). One year after laminoplasty, her PaO2 improved from 64.8 to 85.4 and PaCO2 from 61.3 to 40.9 Torr, and they have been maintained without deterioration for 6 years after surgery. Pulmonary function testing also showed improvement in her %VC postoperatively, from 39.4% to 57.3% 3 years after surgery. Although it has declined somewhat since the 4th year, it is still maintained at a value that is 15% higher than that before surgery. Her AHI by polysomnography without CPAP also improved from 20.7 to 9.0, so the CPAP treatment was stopped. With the improved pulmonary function, her chief complaints of dyspnea on exertion and general fatigue also disappeared. She has regained her daily life and is able to exercise lightly at a fitness club.


An 18-year-old male Caucasian referred to plastic surgery clinic from dermatology department as a case of extensive skin folding on the forehead and depressed nasolabial fold. He also complained of bilateral knee joint pain and swelling. These symptoms were first noted at 16 years of age. No history of similar condition in family and consanguinity. No history of trauma and fractures.
On examination, he had pronounced folds in the area of forehead, between the eyes, in the nasolabial grooves and on the chin, furrowing on his forehead skin and first one inch of the scalp posterior to hairline, and bilateral partial ptosis (Figure ). The development of the patient's skin folds was insidious and progressive. Clubbing of his fingers and toes (Figure ) was noticed. Patient has swollen knee joints (Figure ). Patient has profuse sweating and seborrhea in his axillae, hands, and feet.
Examination of the cardiovascular, respiratory, and gastrointestinal systems revealed no significant abnormalities.
Laboratory analysis showed a mild increase in ESR (18 mm/first h; normal < 15) and significant increase in C-reactive protein (31.5 mg/L; normal < 5). The following parameters were normal: random blood sugar, serum calcium, growth hormone, and thyroid function tests.
Radiographic investigations were done to look for skeletal abnormalities. Plain X-rays revealed thickening of the bone indicating increased bone formation, symmetric shaggy sub-periosteal bone formation with the involvement of epiphyseal regions, acro-osteolysis of the tufts of distal phalanges, irregularity in the superiolateral borders of both scapulae, and diffuse soft tissue thickening (Figure ).
According to the data available from history, examination, and investigation, the patient was diagnosed with complete primary form of PDP.
Two weeks after diagnosis, the patient underwent frontal rhytidectomy to remove excess skin in the forehead and to decrease the prominent nasolabial folds. A frontal rhytidectomy was performed through a brow lift incision, with dissection into forehead in the subgaleal and subfrontalis planes (Figure ). Excision of 2 inches of excess forehead skin was achieved and sent for histopathological examination. Closure of skin with 3-0 Nylon was done without tension.
Autologous dermal-fat graft from the lower abdomen was placed in the nasolabial fold bilaterally through a small nasolabial incision, due to lack of enough fat available for liposuctioning and grafting. Postoperative recovery was unremarkable.
Hyaluronic acid (1.6 mL of Juvederm® filler) was injected in the forehead area 1 week after the operation, and Botulinum toxin type A (120 IU of Dysport®) was injected in the forehead muscles 4 weeks postoperatively (Figure ).
He was satisfied with the operation cosmetic outcome. Future interventions might be needed with further progression of the disease.
Microscopic evaluation of the excised skin revealed unremarkable epidermis and thickening of the dermis with fibrous bands extending into subcutaneous tissue surrounded by thick collagenous bundles with increased amount of ground substance. Well-controlled alcian blue and colloidal iron special stains highlight dermal per adnexal mucin deposition. Features of skin with deep dermal fibrosis, increased fibroblasts, and neuronal hyperplasia were consistent with the clinical diagnosis of Pachydermoperiostosis (Figure ).


A 24-year-old Caucasian male with a history that includes Addison's disease, developmental delay, hypogammaglobulinemia, PNH complicated by lower extremity thrombosis, minimal change disease (MCD), and end-stage renal disease (ESRD) presented with headaches, fevers, and neck stiffness for several days after a tunneled dialysis catheter was placed for hemodialysis.
The patient was diagnosed with Addison's disease at the age of 14 years following a workup for ongoing fatigue. At that time, he was also found to have macrocytic anemia (hemoglobin 9.3 G/dL, hematocrit 26.9 G/dL, and mean cell volume 114 FL), thrombocytopenia (platelets 16,000 U/L), elevated lactate dehydrogenase (1261 U/L), and reticulocytosis (3.6%). His direct antiglobulin test, platelet antibodies, and HIV antibodies were negative, and the ADAMTS13 activity level was normal. Hemoglobin electrophoresis was not suggestive of hemoglobinopathy. His peripheral blood smear reported anisopoikilocytosis, mild to moderate schistocytes, and Howell–Jolly bodies. Splenic ultrasound with Doppler studies were normal. Slightly increased osmotic fragility was present, and bone marrow biopsy reported a hypercellular marrow with predominance of erythroid precursors. Further evaluation including bone marrow biopsies, cytogenetic analysis, and autoimmune panels failed to confirm a cause for this patient's hemolytic anemia. After returning to the clinic with progressive fatigue and hematuria, the diagnosis of PNH was made when flow cytometry indicated PNH clonal populations in 38% of red blood cells (RBCs), 68% granulocytes, and 71% monocytes. Since the patient's anemia was transfusion independent and without evidence of thromboembolic disease, treatment with eculizumab was not offered until two years after the confirmed diagnosis which the patient refused. His renal function declined over time, and initial renal biopsies reported hemosiderosis due to PNH. His renal function continued to worsen over the next three years, and he eventually developed significant proteinuria (20 g/24 h) prompting repeat kidney biopsy. The results indicated significant hemosiderosis due to PNH as well as effacement of podocyte foot processes consistent with MCD. He was treated with prednisone and later rituximab for MCD. Rituximab was later discontinued after the patient developed new onset hypogammaglobulinemia after starting rituximab. His proteinuria resolved with continued steroid therapy, but his renal function did not improve, requiring initiation of hemodialysis. After the diagnosis of ESRD, the patient was agreeable to eculizumab and started therapy. The patient's clinical course was further complicated by recurrent catheter-associated infection.
Over the past two years, the patient has been treated for frequent episodes of sepsis due to coagulase-negative Staphylococcus aureus bacteremia, methicillin-sensitive and resistant Staphylococcus aureus bacteremia, Enterococcus faecalis meningitis, and Streptococcus pneumoniae bacteremia and pneumonia. It was thought that the patient's recurrent infections were from poor tunneled dialysis catheter hygiene and maintenance.
On the current admission, peripheral blood smear demonstrated the presence of numerous Howell–Jolly bodies (), Pappenheimer bodies, acanthocytes, and target cells. Splenic sonogram now showed multifocal scarring and splenic atrophy, measuring 7.9 × 3.9 × 3.3 cm, suggestive of recurrent infarctions (). Liver-splenic scintigraphy with 99mTc-labelled colloid did not show splenic uptake, consistent with AS (). The patient continued to have recurrent episodes of staphylococcus bacteremia, leading to tunneled dialysis catheter removal and transition to peritoneal dialysis.


A 66-year-old woman presented at a hospital with chest pain. Her history included diabetes, hypertension, and hyperlipidemia. On examination, the patient had a pulse of 100 beats/minute and blood pressure of 150/80 mmHg. Her electrocardiogram, echocardiogram, and blood test results were normal. Multislice computed tomography (CT) showed a saccular LMCA aneurysm and significant stenosis in the LAD artery (Fig. ). Coronary angiography revealed a saccular LMCA aneurysm measuring 9.8 × 7.5 mm with 75% stenosis in the proximal portion of the LAD artery. The operation was performed under general anesthesia. A median sternotomy was performed, and after a longitudinal pericardial opening was made, the heart was inspected. The LITA was removed from the inner chest wall in a skeletonized fashion using electric cautery. A distal segment of 1.5–2 cm was procured and reserved for use as a patch repair. Before aortic cannulation, the ascending aorta was dissected from the pulmonary artery. Under cardiopulmonary bypass, coronary artery bypasses of the left internal thoracic artery to the LAD artery were constructed in the beating heart. After aortic cross-clamping, the LMCA saccular aneurysm was exposed without main pulmonary artery transection. The saccular LMCA aneurysm was carefully dissected and completely excised. There was no thrombus in the lumen. Then, the LITA was longitudinally divided and trimmed to fit the incised LMCA. The small internal thoracic artery patch was sutured to the normal and firm lateral coronary arterial wall with a continuous 7–0 Polypropylene suture. Resection of the saccular aneurysm and closure using a small internal thoracic artery patch was then complete. The aortic cross-clamp time was 120 min, and the CPB time was 147 min. The patient had an uneventful hospitalization and was discharged on aspirin therapy. Follow-up multislice CT 10 days after the operation revealed the complete disappearance of the aneurysm and a successful repair with no luminal stenosis by the internal thoracic artery patch. The LITA graft was also found to be patent (Fig. ). The patient has been followed up yearly since 2009. Fortunately, at the 9-year follow-up, the patient was still asymptomatic, and there were no changes in the ECG and UCG. The patient included in the follow-up had preserved preoperative left ventricular function, and there was no coronary incompetence. Pathology of the aneurysm revealed that the aneurysm wall was very thin due to a lack of trilaminar arterial structure from the remarkable atherosclerotic changes (Fig. ).


A 4-year-old boy, born in Zhejiang Province of China, was admitted to Yuying Children's Hospital affiliated to Wenzhou Medical University in June 2014 with complaints of productive cough accompanied with high fever for 5 days. He was the first-born child to unrelated healthy parents, born at 38 weeks of gestation after an unremarkable pregnancy. His birth weight was 3.5 kg, and meconium was passed on the first day of life. The patient had no history of meconium ileus or diabetes mellitus and lacked family history of CF. Tracing back his medical history, the patient was formula feeding but failure to thrive with a weight of 6.8 kg at the age of 8 months and had intermittent diarrhea. For further evaluation of the condition of growth and development, the patient was taken to a local hospital at the age of 8 months, and received complete blood count and liver function tests. And the results indicated liver involvement with slightly elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with values of 78 and 82 U/L, respectively. The patient suffered from recurrently and slightly elevated ALT levels ranging from 70 to 92 U/L and AST levels ranging from 80 to 90 U/L. In addition, the common etiologies that easily lead to increased levels of ALT and AST were also excluded, such as cytomegalovirus and hepatitis B virus infection. Initially, these symptoms were not paid enough attention by the physicians or parents because the elevated levels of ALT and AST can recover to normal levels automatically without treatment or through the injection of magnesium isoglycyrrhizinate before four years of age.
Physical examination for the patient at the age of 4 years showed a weigh of 16.5 kg with a height of 104 cm. The patient had a BMI of 15.3, which was in the 50th percentile for his age. The physical examination also revealed tachypnea and a barrel-shaped chest. The liver was palpable ~2 cm below the right costal margin, and the spleen was palpable about 1 cm below the left costal margin. Clubbed fingers were absent. Laboratory examination indicated increased ALT and AST values of 93 and 92 U/L, respectively, whereas other markers such as γ-glutamyl transferase (GGT), bilirubin, bile acid, fasting blood glucose, albumin, and globulin were within normal limits. Other laboratory investigations including of complete blood count, serum electrolytes, urine, arterial blood gas, amylase, and lipase were normal. The sputum and bronchoalveolar lavage fluid cultures tested positive for Pseudomonas aeruginosa. The Sudan III dye test of fecal matter indicated fat droplet positivity. Pulmonary function tests failed to be performed because of the difficulty at this young age for the child. Additionally, the lack of laboratory facilities caused impracticability of the sweat chloride test. Utilizing computed tomography (CT), we identified severe bilateral paranasal sinusitis () and diffuse fatty infiltration of the liver () in the patient. In addition, the chest CT scan verified the presence of bilateral bronchiectasis and marked peribronchial thickening, especially in the middle and lower lobes (). Extensive sticky and purulent secretion were observed in the lungs by bronchoscopy (). Based on the aforementioned pathological findings, the patient was primarily diagnosed with CF.
Genetic testing of the patient revealed a homozygous nonsense mutation from a C-to-T substitution (c.1657C > T) in the CFTR gene, which was inherited from both his father and mother (). This single-nucleotide variant changed an arginine at position 553 into a premature termination codon (p.R553X). Notably, CF screening using amniotic fluid of the mother during her second pregnancy also indicated the fetus (sibling) to be a p.R553X carrier.
Other than hypertonic saline nebulization, high-frequency chest wall oscillation, expectorant administration, pancreatic enzyme replacement therapy, and supplementation with vitamins A, D, E, and K, the child was prescribed intravenous ceftriaxone to address the P. aeruginosa. Respiratory symptoms gradually improved after 7 days of treatment, and he was discharged on the 15th day after admission. Ursodeoxycholic acid was prescribed after confirmation of genetic diagnosis, but taken irregularly by the patient. Therefore, the medicine failed to bring about the desired effect. Remarkably, the patient was later re-hospitalized two times because of pulmonary infections and liver involvement. Liver function test showed that the levels of both ALT and AST ranged from 90 to 120 U/L. Further examination of abdominal CT and ultrasound have suggested the progression of hepatic cirrhosis. The final hospital admission in August 2016 was due to complaint of a stomachache for 3 days.
Abdominal CT showed a wave-like margin of the liver and many areas of multifocal hypoattenuation in the liver, which indicated the occurrence of hepatic cirrhosis on the basis of diffuse hepatic steatosis (). Simultaneously, the patient presented with pancreatic atrophy and splenomegaly (). In addition, both chest CT scan and bronchoscopy showed the characteristics of bilateral bronchiectasis, marked peribronchial thickening, and extensive sticky and purulent secretion, similar to that observed in 2014 (). The abnormal prothrombin time (PT) and activated partial thromboplastin time were 20.2 s (normal control: 13 s) and 52.6 s (normal control: 36 s), respectively. The international normalized ratio (INR) was 1.85, which confirmed the diagnosis of liver failure.


A 50-year-old man presented with a 2-year history of abdominal distension. He also had lower urinary symptoms such as the sensation of incomplete voiding and increased frequency. He had no symptoms of bowel obstruction. Physical examination revealed a palpable mass occupying the lower abdomen up to the level of the navel, but there was no tenderness. Digital rectal examination revealed an elastic hard mass on the anterior side of the rectum without palpable intraluminal mass. Total colonoscopy showed no masses or stenosis in the rectum. We evaluated the urinary symptoms were due to the compression of the bladder by the tumor.
The results of laboratory tests were normal. Serum prostate-specific antigen (PSA) was not available preoperatively. Urinalysis was normal, with no evidence of hematuria. Enhanced CT showed a large retroperitoneal mass measuring 30 cm in size with multiple septations surrounding the rectum and displacing the bladder, prostate, and seminal vesicle to the right anterior side (Fig. ). MRI showed a mass composed of cysts of various sizes ranging from smaller than 1 up to 6 cm and solid components. Whereas most cysts had simple fluid appearance (very high intensity on T2-weighted images), some showed the presence of layering which suggests the likelihood of either fat or blood in content (Fig. a, b). Several solid components which showed isointensity on T2-weighted images were enhanced on gadolinium-enhanced fat-saturated T1-weighted images (Fig. c–f). From these radiological findings, preoperative diagnosis was leiomyoma with cystic degeneration or perivascular epithelioid cell tumor (Fig. ). Biopsy of the mass was performed under CT guidance, and histology showed a spindle cell tumor. Immunohistochemically, preoperative biopsy of the tumor showed positive staining for SMA, desmin, and caldesmon while negative for S-100, HMB-45, and MDM2, indicating smooth muscle differentiation. Differential diagnosis of leiomyoma, low-grade leiomyosarcoma, and perivascular epithelioid cell tumor was made. We suspected the tumor originated from the smooth muscle of the bladder or deep soft tissue in the retroperitoneal space.
As the biopsy findings did not reveal obvious evidence of malignancy and because the outer wall of the tumor was relatively smooth, we chose to forego total pelvic exenteration and instead attempt complete macroscopic resection of the tumor with minimal combined resection of adjacent organs.
Laparotomy was performed through a midline incision, which revealed a huge mass from the pelvic floor up to the level of the navel (Fig. ). During exploration, the bilateral ureter was preserved but the vas deferens was resected. Because the plane of the interface between the bladder and tumor was unrecognizable, we injected air into the bladder and identified the border of the mass. We dissected the tumor, preserving the bladder and prostate with partial resection of the prostate. The tumor was not attached to the sacrum or levator ani and was mobilized from the pelvic floor. Because the tumor extended into the left pelvic sidewall and surrounded the rectum, we sacrificed the rectum as well as the left hypogastric nerve and left pelvic plexus. Finally, we performed a complete resection of the tumor with low anterior resection. Intraoperatively, the border between the tumor and normal prostate was not so clear.
The gross pathologic specimen was a 33 × 23 × 10 cm solid mass containing multilocular cavities. Sectioning revealed a multicystic cut surface (Fig. ), and blackish-brown intratumoral fluid was drained from the tumor. Histologically, the tumor was composed of variously sized dilated glandular structures lined by prostatic epithelia surrounded by fibromuscular stroma (Fig. a). Lesions of the well-developed, dilated prostate glands resembling prostatic hyperplasia were also evident (Fig. b). The cysts were lined by cuboidal to columnar secretory cells and basally located nuclei (Fig. c). Cytologically, we observed no atypical features or mitosis. Epithelial cells of the cysts and stromal glands were positive for PSA on immunohistochemical staining (Fig. d). The epithelium cells of the tumor were also positive for AR and NKX3.1 staining, indicating that the tumor originated from the prostate. The spindle cells seen on preoperative biopsy were thought to be stromal components of the tumor.
Final histology indicated a giant multilocular prostatic cystadenoma.
Postoperatively, whereas the patient developed a pelvic abscess due to urine leakage from the prostatic urethra, he recovered conservatively and was discharged on postoperative day 37. Since there is no positive evidence of adjuvant therapy of this prostatic cystadenoma, the patient is now under follow-up by blood tests and CT scan every 3–6 months.
At 2 months after surgery, the patient had a PSA of 0.365 ng/ml, which was within the normal ranges. Since then, we have observed no signs of tumor recurrence. The patient was completely asymptomatic at the 6-month follow-up visit and made a full recovery, with no complaints of any urinary disorders or sexual dysfunction.


A lung tumor was accidentally discovered in a 54-year-old Chinese man with a 20-year history of smoking when he underwent computed tomography (CT). The patient underwent upper right lobectomy in September 2011. Immunohistochemistry indicated low squamous cell differentiation, and he was diagnosed with stage IIB disease (T2N1M0) according to the Union for International Cancer Control (7th edition). He received 4 cycles of chemotherapy with gemcitabine and cisplatin, and subsequently he was followed up every 3 months. In March 2013, follow-up CT revealed recurrent disease in the hilum of the right lung (Fig. A). He received 2 cycles of salvage chemotherapy with docetaxel and cisplatin, but follow-up CT showed disease progression. The patient received intensity-modulated radiotherapy (IMRT) at a dose of 64 Gy in 32 fractions at the locoregionally recurrent lesion (Fig. A1–3). Partial response was observed by the end of radiotherapy based on CT (Fig. B).
In March 2015, the patient presented with chest distress and shortness of breath, malaise, fatigue, cough, and an enlarged tumor in the hilum of the right lung and atelectasis of almost the right lung based on CT (Fig. C). The patient refused chemotherapy and so was treated instead with salvage IMRT for local failure at a dose of 60 Gy in 30 fractions (Fig. B1–3) with the following dosimetry: left lung V5, 21%; left lung V20, 6%; maximum heart dose, 61.1 Gy; V40, 30%; V30, 39%; and maximum spinal cord dose in the dose overlap region, 23.2 Gy. The patient's respiratory symptoms improved noticeably during radiotherapy. CT revealed that the enlarged tumor in the right lung had shrunk significantly, and that the atelectasis had nearly disappeared (Fig. D).
One month after this repeat radiotherapy, the patient experienced fever (37.6°C), cough, chest distress, and shortness of breath. The patient's laboratory results at that time are shown in Table . We performed serologic tests, laboratory tests for procalcitonin, and C-reactive protein, as well as sputum and blood cultures to rule out bacterial infection. Chest CT showed consolidation with air bronchogram in the hilum of the right lung and ground-glass densities in the right lower lobe and left upper lobe (Fig. A). These radiographic signs are typical of RP. As the patient required oxygen, he was diagnosed with grade III RP. The patient was immediately prescribed oxygen, anti-infectives for prophylaxis, treatments to facilitate expectoration andprevent asthma, and most importantly, intravenous methylprednisone at an initial dose of 60 mg/day. After 1 week, the patient's respiratory symptoms improved obviously, and the patchy shadow on the chest radiograph disappeared almostly (Fig. B). At this point, we cut the steroid dose in half. After another week, the steroid dose was halved again. Then the patient was switched to an equivalent dose of oral prednisolone, which was tapered and discontinued after 8 weeks. During systemic prednisolone therapy, the patient experienced systemic side effects of weight gain, hyperglycaemia, and sleep disturbance.
One month after the end of oral prednisolone therapy, the patient again developed a productive cough with a low fever, chest distress, and shortness of breath. Chest CT again showed a consolidated shadow inside the irradiated volume (Fig. C), and the patient was diagnosed with recurrent RP. We administered intravenous methylprednisolone at an initial dose of 60 mg/day for 1 week, then we halved the dose for another week. The patient's symptoms improved obviously, and the patchy shadow on the chest radiograph nearly disappeared. As the patient had a history of COPD associated with chronic bronchitis, which was brought under control in 2006 using Seretide (FP 500 μg and Salm 50 μg), and as the patient had reacted adversely to previous systemic steroid therapy, we decided to give him FP (500 mg)/Salm (50 mg) twice daily for 2 months. Then the dose was halved for an additional 2 months. The patient showed no signs of tumor or RP relapse by the last follow-up in March 2018 (Fig. D).


A 10-month-old female presented with an oedema in the left zygomatic and retroauricular region without other inflammation sites. She was afebrile and in good clinical condition with otoscopic findings, characteristic of acute otitis media and concomitant oedema in the external auditory meatus of the left ear. Due to otorrhoea on the left side 4 days ago, the child started receiving antibiotic treatment per os with amoxicillin and clavulanic acid 457 mg/5 ml (90 mg/kg) every 12 h. Family history showed that the mother died 7 months ago at the age of 34 due to melanoma recurrence during pregnancy. She was diagnosed with melanoma at the age of 25, for which she was treated with chemotherapy with complete regression of the disease. During her pregnancy, she presented with a recurrence of melanoma with metastases in the liver, bones, lungs, and brain. She died 3 months after delivery. The child was initially treated as an acute mastoiditis on the left side according to our clinic's protocol, and a double intravenous antibiotic scheme of cefotaxime + clindamycin and dexamethasone was administered. Subsequently, a myringotomy was performed on both sides under general anaesthesia, and ventilation tubes were placed. A purulent fluid was drained from the left side, which was sent for culture. The child showed an immediate improvement in her clinical picture, showing reduced otorrhoea on the left and reduced oedema in the left zygomatic and retroauricular region after the following 24 hours. After the antibiogram results (Pseudomonas aeruginosa), the treatment was changed to ceftazidime and amikacin. Due to recurrence of the retroauricular oedema on the left after 7 days, a CT of the temporal bone with contrast was performed. An invasive lesion of the mastoid cavity on the left with widespread corrosion of the trabeculae of the bone was found, expanding intracranially (towards the cranial bones and the underlying meninx) (). A drilling of the mastoid on the left followed. During the retroauricular incision, an infiltration was observed, with multiple friable fragments of dark-coloured subcutaneous tissue of the underlying corroded bone cortex and of the whole mastoid cavity, which had been submitted to “automated trephination.” Characteristically, the mastoid cavity was infused with a material similar to cuttlefish ink in colour (). Moreover, corrosion was observed on the posterior wall of the external auditory meatus, on the apex of the mastoid, and on the bony wall of the meninx, which was uncovered especially in the area of the meninx-sigmoid corner. Furthermore, the wall of the sigmoid sinus was corroded. No thrombosis was observed of the sigmoid sinus. Neuromonitoring of the facial nerve was performed, and an urgent neurosurgical assessment was requested. Debridement and removal of the corroded bone fragments was performed.
Multiple fragments of dark-coloured tissue were sent for an immediate histological examination. The history (individual and family), the clinical picture, the radiological and surgical findings, and the immunophenotype showed an intermediate level malignity of a melanocytic tumour in the mastoid, with areas of a high level of malignity (). Oncologists were consulted, and we came into communication with the international “rare tumours” protocol in order to choose the right therapy. Using the real-time PCR-HRM analysis technique, a mutation was detected in exon 15 of the ΒRAF (p.V600E) gene. A full radiological examination was followed by an MRI of the brain, an MRI of the visceral cranium, and an MRI of the vertebral column; a thorax-CT; a cervical/parotid/axillary/groin U/S; and an upper-lower abdomen U/S.
The visceral cranium MRI showed an invasive lesion of a pathological magnetic signal with mild enhancement by contrast administration and areas of necrosis, occupying all cavities of the left temporal bone (). Whether this lesion corresponds to a residual disease or postoperative lesions remains a question.
The rest of the radiological examination was normal. The child remained in good clinical condition without treatment.
One month later, due to the appearance of asymmetry on the cheek and the right preauricular region, second visceral cranium MRI was performed, which was negative for activation of the disease. Compared to the previous ΜRI, we distinguished a clear reduction in the area of the pathological signal and of the intake of the paramagnetic substance in and around the left temporal bone (). Complete regression of the metastatic bone lesion has been confirmed by follow-up; now, the child is 4 years old, alive, and without evidence of disease.


A 21-year-old black woman, with no prior psychiatric history, presented at the Emergency Department of our hospital with an acute onset of psychotic symptoms.
These symptoms included paranoid delusion (she was convinced that her sister had made witchcraft against her and her boyfriend was cheating on her), psychomotor agitation, and initial insomnia.
The symptoms appeared four days after she was started on antituberculous therapy including isoniazid 300 mg/day, rifampicin 600 mg/day, ethambutol 1200 mg/day, and pyrazinamide 1500 mg/day, for pleural tuberculosis. She was also on pyridoxine 200 mg/day and thiamine 100 mg/day for prophylaxis against neuropathy associated with isoniazid.
In addition to the recently diagnosed pleural tuberculosis, the patient had no previous medical history and no history of substance abuse.
At mental state examination, she was poorly cooperative and suspicious, displayed psychomotor agitation, moving around constantly and had anxious humour and paranoid delusions. No errors of perception were detected and judgement regarding the morbid nature of her condition was impaired.
On examination, vital signs were stable and the physical signs, including neurological examination, were unremarkable. Testing including a complete blood count, chemistry panel, liver and thyroid function tests, and a urine toxicology screen was normal. A computed tomography scan of the head was obtained and showed no abnormality.
An initial diagnosis of drug-induced psychosis was made, once we considered the possibility that her psychotic symptoms could have been secondary to isoniazid, and the patient was admitted to our inpatient unit. All antituberculous therapy was discontinued and she was started on olanzapine 15mg/day.
By the seventh day, the psychotic symptoms had remitted, and the patient presented full insight into her clinical condition. The antituberculous therapy was reintroduced by the following order: rifampicin 600 mg/day at day 10, pyrazinamide 1500 mg/day at day 12, and ethambutol 1200 mg/day at day 17. Since these three antibacterial agents have efficacy in the treatment of pleural tuberculosis, it was decided not to introduce isoniazid.
At day 10, the antipsychotic started to be progressively reduced and by the time the patient was discharged (after 21 days of hospitalization) she was only taking olanzapine 5 mg/day and the antituberculous therapy.
The patient stopped taking olanzapine one week after discharge and at the four-week follow-up in outpatient consultation; she remained stable, with no recurrence of psychotic symptoms. The fast remission of symptoms and the good clinical outcome further supported our diagnosis of drug-induced psychosis.


A 58-year-old man with Grade IV bilateral avascular necrosis underwent a single-stage THA (metal on polyethylene; Duraloc, Johnson & Johnson, USA). The left side was operated upon first through a modified Hardinge approach and, owing to greater trochanter partial avulsion, a tension band wiring was undertaken. On the right side, the THA was uneventful. The post-reduction stability and range of movements were checked and the wound was closed. A bedside X-ray showed a proud head and a non-centric reduction on the left THA (Figure ).
We undertook an urgent computed tomography (CT) to identify the cause, presumed to be an intra-articular obstacle. The axial cuts of CT showed a piece of bone inside the joint that leads to an increase in joint space (Figures , , ).
The patient was taken up for surgical re-exploration, and the obstructive bone piece (an osteophyte) was removed. A fluoroscopy then confirmed concentric reduction (Figure ).
Postoperatively, the patient followed a non-weight-bearing protocol for three weeks, followed by gradual mobilization with walker. At the 1.5-year follow-up, the patient’s Harris hip score is 91 and findings on X-ray are satisfactory (Figure ).


An 11-year-old female presented with an incidental left-sided neck mass. Computed tomography (CT) scan revealed a 6.0 cm mass that was biopsied and found to be a PGL. At age 12, 123I-MIBG SPECT/CT scintigraphy showed lack of tracer avidity of the described mass. She had surgical resection at this age and was found to have a vagal PGL and a solitary lymph node involvement. Monitoring with whole body magnetic resonance imaging (MRI) scan for the next 3 years showed no recurrence or metastases. At the age of 15 however, her CT scan revealed a recurrent 1.0 cm left-sided neck mass, multiple subcentimeter bilateral lung lesions and, 1.0 and 0.8 cm pancreatic body and tail masses, respectively. A 123I-MIBG SPECT/CT scintigraphy remained negative. All biochemical tests remained normal. No treatment was initiated. Periodic surveillance for the next 3 years showed stable disease until she was lost to follow-up. Although asymptomatic, progressive disease was found at the age of 21, involving 2 left cervical lymph nodes measuring 2.0 and 0.9 cm, and left 2nd rib and left iliac bone lesions all positive on CT, MRI, 68Ga-DOTATATE, and 18F-FDG PET/CT scans. She underwent modified radical left neck dissection. Pathology revealed multiple cervical lymph node metastases, with the largest measuring 2.7 cm. One year later, the patient was found to be stable on CT, MRI, and 68Ga-DOTATATE PET/CT scans and biochemical tests remained normal. No further treatment was initiated.


A 53-year-old female presented with metastatic retroperitoneal PGL. Her initial biochemical tests revealed elevated urine norepinephrine (NE), dopamine (DA), and plasma normetanephrine (NMN). CT and MRI scans revealed a 6.0 cm retroperitoneal mass encircling the aorta. Although her 68Ga-DOTATATE, 18F-FDG, and 18F-FDOPA PET/CT scans revealed varied detection rates of multiple bone/bone marrow lesions and a right lung lesion, her 123I-MIBG SPECT/CT scintigraphy demonstrated only the retroperitoneal mass.
Due to the invasion of the retroperitoneal mass into the left aortic wall, it could only be partially resected. Histopathology confirmed the presence of PGL measuring 9.0 cm. Short-acting octreotide administered subcutaneously (sc) at 25 micrograms twice daily was initiated post-operatively with no relief of symptoms and little reduction in the level of catecholamines. Three months after surgery, disease progression was noted on MRI scan, with re-demonstration of the partially resected retroperitoneal PGL measuring 3.0 cm. There was an interval appearance of several lymph node and bone metastases. She underwent peptide receptor radionuclide therapy (PRRT) with 160 mCi of [90Y-DOTA]0-D-Phe1-Tyr3-Octreotide (90Y-DOTATOC) and 2 doses of 200 mCi of [177Lu-DOTA]0-D-Phe1-Tyr3-Octreotide (177Lu-DOTATOC) over a duration of 5-months. There were significant decreases in chromogranin A (CgA), urine DA, and plasma and urine NMN and NE. Her plasma metanephrine (MN) level was elevated, which was thought to be partly “stress” related. CT and MRI scans showed mixed results: a significant decrease in size of the retroperitoneal PGL from 3.0 cm pre-PRRT therapy to 1.8 cm post- PRRT therapy, decrease in size of the cervical and abdominal lymph nodes, and unchanged thoracic lymph node and lung lesions. There was interval appearance of new metastatic bone lesions and both enlargement and regression of previous bone lesions. 18F-FDG PET/CT scan showed a decrease in metabolic activity of the retroperitoneal PGL, cervical, thoracic, and abdominal lymph node lesions. 18F-FDG PET/CT scan likewise demonstrated decreased activity and disappearance of some of the bone lesions but increased activity of one bone lesion.
Eight months after her PRRT, she developed progressive disease, elevated CgA, methoxytyramine (MTY), plasma DA, plasma, and urine NMN and NE and extensive bone metastases on imaging. CT, MRI, and 18F-FDG PET/CT scans revealed a residual retroperitoneal mass, stable cervical lymph node lesions, increase in the size of one of the abdominal lymph node lesions, and both interval progression and development of new bone lesions. Chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) was started and resulted in a mixed response with a decrease in the size and activity of the abdominal lymph node lesions, stability in the size of the thoracic lymph node and lung lesions, and both stability and increase in the number and size of bone lesions as demonstrated by CT, MRI, and 18F-FDG PET/CT scans. Chemotherapy was discontinued after 10 cycles due to pancytopenia, which could have been caused by PRRT. She then had further disease progression. Bortezomib and clofarabine experimental therapy was subsequently tried but had further disease progression and hence, patient was started on combination capecitabine and temozolomide. However, the patient expired the following year.


A 14-year-old male was diagnosed with metastatic abdominal PGL. Biochemical tests at that time showed elevated CgA, urine NMN and NE. CT and MRI scans showed an abdominal PGL measuring 9.1 cm with invasion of the inferior vena cava (IVC) and bone metastases. Resection of the abdominal PGL was performed. Histopathology revealed a PGL measuring 9.0 cm. Two months after surgery, CT angiography revealed a 2.5 cm recurrent abdominal mass. 18F-FDG PET/CT scan confirmed this mass with several additional bone metastases. 123I-MIBG SPECT/CT scintigraphy did not show avidity for the aforementioned lesions.
One year later, MRI scan showed an interval increase in the size of the abdominal PGL to 3.0 cm, a thoracic soft tissue lesion, and multiple lymph node and bone metastases. 18F-FDG PET/CT scan demonstrated recurrent abdominal PGL and bone metastases. Only close monitoring was done due to the slow disease progression, limited chemotherapeutic options, and absence of alarming symptoms.
Four months later, MRI, 68Ga-DOTATATE, and 18F-FDG PET/CT scans again demonstrated slowly progressive metastatic disease. He received 3 cycles of PRRT with 100 mCi each of 90Y-DOTATOC. Eight months later, CT and [68Ga-DOTA]0-D-Phe1-Tyr3-Octreotide (68Ga-DOTATOC) PET/CT scans showed stable disease. However, 6 months later, the CT scan demonstrated an interval increase in size of the abdominal PGL to 4.3 cm without any evidence of new lesions on 18F-FDG PET/CT scan. Hence, he was started on lanreotide 120 mg/sc every 28 days and experimental therapy with ONC201 625 mg/weekly and demonstrated stable disease on 18F-FDG PET/CT and CT scan after 3 and 6 months, respectively, along with a decrease in plasma CgA at both time points.


A 57-year-old male was diagnosed with metastatic para-aortic abdominal PGL. During work-up for hypertension, CT scan revealed a 5.1 cm retroperitoneal para-aortic mass, a 2.5 cm right renal superior pole mass, and a 2.5 cm left adrenal mass, which was later found to be a non-functioning adenoma. The 123I-MIBG SPECT/CT scintigraphy was positive only for the para-aortic mass. 18F-FDG PET/CT scan showed avidity for the para-aortic mass and mild uptake for the gastric cardia. Initial biochemical tests were normal. Resection of the para-aortic and gastric lesion masses, and right partial nephrectomy were performed. Histopathology confirmed a 4.2 cm para-aortic PGL, RCC, and GIST. Immunohistochemical staining (IHC) for GIST demonstrated loss of SDHB staining without loss of SDHA staining, whereas RCC demonstrated loss of neither SDHB nor SDHA staining.
Seven months later, 18F-FDOPA and 68Ga-DOTATATE PET/CT showed recurrence of the retroperitoneal PGL with a subcentimetric soft tissue lesion in the left neck, considered another primary head and neck PGL, which along with mediastinal lymph node metastasis could not be localized by neck MRI scan retrospectively.
Two years later, MRI scan showed stable left adrenal mass, vertebral hemangiomas, liver and renal cysts, elevated plasma epinephrine (EPI) and DA, and significant uptake on 68Ga-DOTATATE and 18F-FDOPA PET/CT on the post-operative site, cervical, and thoracic area. No treatment was initiated.
Two years later, MRI, 68Ga-DOTATATE, and 18F-FDG PET/CT scans demonstrated stable disease and no treatment was initiated.


A 53-year-old male presented with a 4.0 cm right posterior mediastinal mass which was incidentally discovered on his chest radiograph, and subsequently by 18F-FDG PET/CT scan. Urine NMN and NE were elevated. Excision of the mass was done, and histopathology confirmed the PGL.
Three years and 2 months later, he showed recurrence of the mediastinal mass on MRI scan and a year and a half later, he developed painful bone metastases which were minimally avid on 123I-MIBG planar scintigraphy. 111In-pentetreotide scintigraphy had findings suggestive of metastatic disease. At this time, urine MN and CgA were elevated. He was started on lanreotide 120 mg/sc every 14 days which resulted in pain control, stabilization of bone metastases, and reduction and normalization of urine MN and CgA, respectively. This was followed by radiation therapy to bone metastases. Seven months later, the lanreotide dose was tapered to 120 mg/sc every 21 days due to development of side effects and antihypertensive management was switched from bisoprolol to propranolol 120 mg/day.
A year and a half later, the patient developed progressive bone metastases. He was started on metronomic doses of temozolomide (TMZ) 75 mg/m2 for 21 days every 4 weeks in addition to lanreotide therapy and the dose of propranolol was increased to 240 mg/day resulting in stable disease 3 months later on CT, MRI, 18F-FDG, and 68Ga-DOTATATE PET/CT scans. At that time, CgA, plasma DA, urine NE, and urine NMN were elevated. Five months later,18F-FDG PET/CT scan showed stable disease and at that time lanreotide was withdrawn due to development of nausea, vomiting, diarrhea, and hyperglycemia. Repeat 18F-FDG PET/CT scan 6 months later showed stable disease and subsequently, TMZ was withdrawn due to long standing grade 2 lymphopenia and the patient continued only on propranolol 240 mg. However, 12 months later, he developed progressive disease on 18F-FDG PET/CT scan and a combination of metronomic doses of TMZ (75 mg/m2 for 21 days every 4 weeks) and lanreotide 120 mg/sc every 21 days was resumed.


A 20-year-old male was diagnosed with metastatic retroperitoneal PGL. Biochemical testing showed elevated urine NMN. CT and 18F-FDG PET/CT scans showed a retroperitoneal mass anterior to the IVC and a periaortic lymph node metastasis. The retroperitoneal mass on biopsy revealed PGL. Two months later, the periaortic lymph node and retroperitoneal PGL were excised. Histopathology confirmed a 4.4 cm PGL and one metastatic lymph node. 18F-FDOPA and 18F-FDG PET/CT scans performed 7 months after surgery revealed a right acetabulum metastatic lesion with normal biochemical tests.
Two years and 7 months after surgery, a recurrent retroperitoneal lesion with metastatic lymph nodes and other soft tissues were seen on 18F-FDG and 18F-FDOPA PET/CT scans in addition to the acetabular lesion. 68Ga-DOTATATE PET/CT scan was positive only for the acetabular lesion. Biochemical tests were normal. One year later, 18F-FDG, 68Ga-DOTATATE, and 18F-FDOPA PET/CT scans and biochemical tests showed stable disease. To date, no treatment for metastatic disease has been initiated.


A 52-year-old male initially presented with hypertension and palpitations. Four years later, during work-up for left flank pain, a large retroperitoneal tumor was incidentally discovered. Presumably arising from the kidney, he underwent left nephrectomy with left adrenalectomy. Histopathology confirmed PHEO in the resected 4.9 cm retroperitoneal mass and in a metastatic lymph node, however, there was no renal involvement.
Ten years after the surgery, a left upper back mass was discovered. MRI scan revealed a 5.0 cm T3 vertebral body lesion extending into the epidural space with resultant cord compression. 18F-FDG PET/CT scan demonstrated metastatic bone disease involving C2-C3, T3, L5, and right iliac bone. Biochemical testing revealed elevated urine NE. He underwent T3 spinal tumor resection. Histopathology confirmed a 5.7 cm PGL with positive margins. Two months later, the patient received radiation therapy with a total of 30 gray divided into 10 fractions along C6 through T5. At that time, 123I-MIBG SPECT/CT scintigraphy showed uptake in T3 and S1 bone lesions.
Three months after external radiation therapy, he received 319 mCi of 131I-MIBG therapy. Post-therapy whole-body 131I-MIBG SPECT/CT scintigraphy showed uptake in the thoracic vertebrae and other axial bone lesions with a new bone lesion in the right femur. Three months after 131I-MIBG therapy, he underwent shave biopsy of new skin lesions in left lower shin and right-hand dorsum, which were found to be well-differentiated squamous cell carcinoma.
After 6 months of 131I-MIBG therapy, the 123I-MIBG SPECT/CT scintigraphy showed decreased uptake in the index lesions at T3 and S1 as compared to pre-therapy 123I-MIBG SPECT/CT scintigraphy without any new foci of increased radiotracer uptake from post-therapy 131I-MIBG SPECT/CT scintigraphy. However, 123I-MIBG SPECT/CT scintigraphy after 12 months of 131I-MIBG therapy revealed disease progression with extensive metastatic bone disease involving most of the spine, pelvis, and patchy areas of uptake in the scapulae, proximal humeri, proximal femurs, sternum, and multiple bilateral ribs. A year after initiation of 131I-MIBG therapy, metastatic disease involving the bones, bone marrow, lungs, and liver were found on 68Ga-DOTATATE and 18F-FDG PET/CT. During this time, plasma, and urine DA, NE, and NMN, and plasma MN and MTY were elevated. CVD chemotherapy was started on a 21-day cycle. The patient progressed 4 months later on 18F-FDG PET/CT with appearance of new lesions in the lungs. He was evaluated for pembrolizumab experimental therapy, however, he expired 4 months later due to suspected leptomeningeal disease.


A 29-year-old female initially presented with epigastric pain and weakness. CT scan showed a large 10.4 cm vascular mass in the porta hepatis, possibly obliterating the right adrenal gland, thought to be an arteriovenous malformation for which she received 4 cycles of coil embolization therapy. Subsequently, she developed lower limb weakness and difficulty in walking. A year and a half later, MRI spine showed a T7 bone lesion with extradural extension and soft tissue swelling with severe spinal cord compression, which was treated with endovascular embolization. However, 2 months later, due to worsening symptoms, she underwent vertebrae body stabilization and excision of the tumor, which was confirmed to be a metastatic PGL on histopathology. Biochemical testing revealed elevated plasma NE and CgA.
Within a year, she again developed high-grade spinal cord compression from a recurrent T7 vertebral body bone lesion, which was visible on 68Ga-DOTATOC PET/CT along with lesions in the skull base, cervical spine, right first rib, right iliac bone, both lungs, and the right adrenal bed. She underwent emergent surgical decompression of the T7 lesion and 1 month later received post-operative radiation of 54 grays divided over 30 fractions from T5 through T9. She remained stable without any disease progression for the following 14 months.
However, at 33, there was again recurrence in the T7 vertebral body and the lesion in the right adrenal bed, along with scattered metastatic bone and lung lesions which were visible on both 18F-FDG and 68Ga-DOTATATE PET/CT scans. The 18F-FDOPA and 123I-MIBG SPECT/CT scans demonstrated a much lower number of metastatic lesions and were found to be inferior in comparison to 68Ga-DOTATATE PET/CT (). At that time, her plasma NMN and CgA were elevated. Surgical intervention was deemed high-risk, therefore, she received four cycles of PRRT treatment with 200 mCi of 177Lu-DOTATATE without any adverse events and was found to be stable on CT, 18F-FDG, and 68Ga-DOTATATE PET/CT scans 1-month after completion of PRRT. At that time, there was significant decrease in her plasma NMN and CgA.


A 46-year-old woman presented with abdominal pain and her CT scan revealed a large retroperitoneal tumor, which was surgically resected and found to be a 6.8 cm PGL on histopathology. She remained disease free for the following 6 years.
At age 53, the patient reported left shoulder pain which on MRI scan revealed a lytic lesion in the coracoid process and received 2.5 gray of external beam radiotherapy over 13 fractions. Subsequent CT and 68Ga-DOTATATE PET/CT scans additionally showed liver lesions ranging from 3.9 to 5.9 cm in size, bilateral lung lesions, multiple metastatic neck, mediastinal, retroperitoneal lymph nodes, and a left inferior pubic ramus bone metastasis. However, on 123I-MIBG SPECT/CT scintigraphy, only the left coracoid process and left inferior pubic ramus bone metastases were visible. An ultrasound guided liver biopsy was performed, and pathology revealed a metastatic PGL. Biochemical tests revealed elevated plasma NMN, MTY, and CgA. A follow up CT scan after 2 months revealed an interval increase in the size of the liver lesions and recurrence of the retroperitoneal PGL. Subsequent imaging with 68Ga-DOTATATE, 18F-FDG, and 18F-FDOPA PET/CT scans re-demonstrated the aforementioned lesions. One of the liver lesions located in the left hepatic lobe did not show any DOTATATE avidity so she underwent embolization of this lesion in anticipation of starting PRRT with 177Lu-DOTATATE. She subsequently received external beam radiotherapy to the pubic bone then underwent 2 of the 4 cycles of 177Lu-DOTATATE therapy without any complications. However, she showed progression on CT, 18F-FDG, and 68Ga-DOTATATE PET/CT scans and hence, 177Lu-DOTATATE therapy was stopped. At that time, her plasma CgA and MTY were elevated and had increased in comparison to pre-PRRT levels, whereas plasma NMN had normalized. Following the progression of her disease, she was recommended to undergo CVD chemotherapy.


A 44-year-old male developed neck pain and was subsequently found to have a 3.0 cm C2 vertebral body lesion on CT spine. He developed new onset dysphagia and further imaging work up revealed a lesion anterior to C5-T1, which appeared to be displacing the esophagus along with a heterogenous 7.7 cm retroperitoneal tumor in the right peri-adrenal region which was biopsied and revealed PGL on histopathology. The scan also revealed a right fifth rib, T11, S1, and bilateral lung metastases. The biochemistry tests showed slight elevation of urine NMN, DA, and EPI as well as plasma NE and CgA. He underwent 123I-MIBG SPECT scintigraphy 1 month later which revealed uptake in C2 lesion, right anterior and inferior lateral rib cage, anterior first rib, S1, and retroperitoneal tumor. The patient underwent cervical spine decompression and fusion surgery, with subsequent radiation to the cervical spine, and then received three cycles of 131I-MIBG treatment. The 6-month post-MIBG therapy restaging 123I-MIBG SPECT scintigraphy demonstrated disease progression. The CT scan showed an increase in the number of lung lesions and an increase in the size of the retroperitoneal mass and retroperitoneal lymph nodes. A tumor vs. bland thrombus was also observed in the IVC and the patient was put on anticoagulant therapy. He was started on TMZ (150–200 mg/m2 for 5 days every 4 weeks) chemotherapy. Three months later, following 2 cycles of TMZ, the patient progressed per imaging on CT, 68Ga-DOTATATE, 18F-FDG, and 18F-FDOPA PET/CT scans, revealing an increase in size of the retroperitoneal tumor along with bilateral lung lesions and extensive bone metastases (). Biochemical tests at that time were normal except for elevated plasma CgA. For treatment of his metastatic disease, the patient was recommended a chemoswitch from standard to metronomic doses of TMZ (75 mg/m2 for 21 days every 4 weeks) and is awaiting follow up evaluation.


A 44 year-old male presented to the emergency department with a 5-day history of fever and malaise. He had recently returned to Ireland (his country of residence for 10 years) from Nigeria (his native country) after visiting friends and relatives, without taking malaria prophylaxis. He had a history of hypertension, for which he took ramipril, amlodipine and bendroflumethiazide throughout the previous year. There was no family history of renal disease. He reported having taken over the counter paracetamol during the 5 days prior to presentation, and a single 400 mg dose of ibuprofen on the day of presentation. Consumption of non-steroidal anti-inflammatory drugs (NSAIDs) beyond the day of presentation was repeatedly denied. He had not taken any other medications commonly associated with AIN such as beta-lactams, fluoroquinolones, sulfonamides or proton pump inhibitors prior to presentation.
On examination, he was euvolaemic, his blood pressure was 169/77 mmHg and he produced 1580 mls of dark urine during the first 24 h. Urinalysis revealed 4+ protein and 3+ blood. He did not have a rash and had no peripheral oedema.
Initial routine blood tests included creatinine 616 µmol/L (baseline 89 µmol/L, 5 months before presentation), haemoglobin 11.2 g/dL, platelet count 70 × 109/L, eosinophil count 0.1 × 109/L, serum albumin 26 g/L, total serum bilirubin 15 μmol/L and lactate dehydrogenase 960 U/L. A blood film was positive for P. falciparum with 0.4% parasitaemia. Initial urine protein–creatinine ratio was 346 mg/mmol (absolute proteinuria = 4448 mg/L).
Tests for HIV, HBV, HCV, ANA and ANCA were all negative. C3 was normal and C4 was low (0.09 g/L). His haptoglobin was low (0.24 g/L) and G6PD enzyme activity was normal. A renal ultrasound described diffusely echogenic kidneys with the right kidney measuring 130 mm and the left kidney measuring 143 mm.
A renal biopsy performed 10 days after presentation demonstrated acute interstitial nephritis with numerous eosinophils, particularly at the cortico-medullary junction (Fig. a). There was an absence of neutrophils or granulomas. Immunofluorescence staining showed no specific pattern of antibody deposition for standard antisera (anti-IgG, anti-IgA, anti-IgM, anti-C3, anti-kappa, anti-lambda, anti-fibrin were all negative). Interstitial fibrosis was minimal. Electron microscopy revealed podocyte foot-process fusion involving the majority of capillaries, and the majority of the surface of affected capillaries, with microvillous transformation of the podocyte cytoplasm (Fig. b).
The patient was treated for severe malaria with intravenous artesunate on day 1, followed by a further 3 days of artesunate and a further 7 days of oral doxycycline. He was also covered empirically with ceftriaxone. Intermittent haemodialysis was started on hospital-day 3, as renal function was not recovering and the patient developed symptoms of uraemia. He received five sessions of intermittent haemodialysis before regaining independent renal function (Fig. ). At 1 year follow up his creatinine had plateaued around 120 µmol/L, with persistent proteinuria (protein:creatinine ratio 172 mg/mmol) after restarting ramipril, amlodipine and bendroflumethiazide.


A 20-year-old woman who recently emigrated from Mexico with limited prior medical care initially presented to an outside hospital with a facial rash thought to be herpes zoster with bacterial suprainfection. She was begun on a course of cephalexin and valacyclovir. Over the following week, she developed new-onset headache, emesis, and photophobia. After returning to the emergency department, she was found to have altered mental status which deteriorated further following a tonic-clonic seizure. A computed tomography scan of the head was unremarkable. Lumbar puncture demonstrated budding yeast and a cryptococcal antigen titer, performed by latex agglutination, that was greater than 1 : 256. During her hospitalization, she was found to be HIV-positive with a CD4 count of 10 cells/µL, a CD4/CD8 ratio of 7%, and an HIV viral load of 37,479 copies/mL.
The cryptococcal infection was initially treated with intravenous liposomal amphotericin 5 mg/kg daily and oral flucytosine 100 mg four times per day upon transfer. After fourteen days, the dose of liposomal amphotericin B was reduced to 4 mg/kg daily due to the onset of acute renal failure (creatinine 1.15 mg/dL from 0.60 mg/dL on admission). Antiretroviral therapy (ART) for HIV was withheld until completion of treatment of cryptococcal meningitis due to risk for immune reconstitution syndrome.
The patient clinically improved on this regimen, with complete resolution of meningeal symptoms within about one week of starting the antifungal regimen. However, soon afterwards, she developed worsening pancytopenia with prominent thrombocytopenia. Platelets were initially 144 k/µL and dropped to a nadir of 46 k/µL. Her white blood cell count decreased to a nadir of 1.8 k/µL (absolute neutrophil count 1100 cells/µL) from 3.4 k/µL and hemoglobin to a nadir of 6.5 g/dL from 9.3 g/dL. During this time, flucytosine was switched to fluconazole due to concern for precipitating worsening thrombocytopenia. Hematology consultation was obtained, and bone marrow aspirate and biopsy showed silver stain positive for disseminated Cryptococcus neoformans () with findings of focal phagocytosis, mildly hypocellular bone marrow for age (60% cellularity), and otherwise normal hematopoietic maturation with no evidence of malignancy. Additional negative studies of the bone marrow included acid-fast bacilli (AFB) stain and polymerase chain reaction (PCR) for Toxoplasma gondii, Cytomegalovirus (CMV), Parvovirus B19, and Bartonella. Histoplasma was not directly noted on histopathologic analysis of the bone marrow. The patient tested negative for CMV in the bone marrow but was positive for <1000 copies/mL of CMV in the peripheral blood. No treatment for CMV was administered.
Liposomal amphotericin B and fluconazole 800 mg daily were continued for a total of four weeks of induction therapy in the setting of Cryptococcus in the bone marrow and associated pancytopenia. Pancytopenia improved with continuation of this regimen. At the time of discharge to a long-term care facility, her white blood cell count was 2.4 k/µL, hemoglobin was 8.6 g/dL, and platelets had improved to 80 k/µL. The patient was started on abacavir/dolutegravir/lamivudine after two negative lumbar punctures. Given persistently elevated serum Cryptococcus Ag > 1 : 256, the patient was continued on suppressive fluconazole (200 mg daily) therapy for the next two years.


A 51-year-old man presented to our hospital due to symptoms of myelopathy. He had been undergoing hemodialysis due to chronic kidney failure associated with nephrotic syndrome for over 10 years. He complained of numbness in the extremities and clumsy hands, and he was unable to walk without assistance. Spastic gait disturbance associated with increased muscle tonus was observed, and his serum CK level remained slightly high (315 U/l). Cervical laminoplasty was performed for cervical myelopathy related to cervical DSA (). The postoperative course was uneventful. His numbness and clumsy hands improved, and he became ambulatory.
Two months after the initial surgery, however, his condition started to deteriorate. He developed unusual intractable pain throughout his whole body, and cramp-like muscle pain was observed paroxysmally and frequently with severe spasticity. Regarding the pain intensity, the numerical rating scale (NRS) score (wherein 0 = no pain and 10 = the worst pain), painDETECT score [], and neuropathic pain symptom inventory (NPSI) [] were 10, 28, and 79, respectively.
While his pain was partially relieved by the administration of ketamine, his symptoms were disabling and not sufficiently managed by conservative treatment. Plain radiographs showed the progression of destructive changes at the C4/5 and C5/6 levels. A marked progression of kyphosis of the subaxial spine was noted with a C2-7 angle of -53° (). A laboratory examination revealed that his serum level of CK was extremely high (999 U/l). With a marked elevation of CK, we first consulted neurologists and nephrologists regarding the possible underlying pathology. The differential diagnosis included myopathy, an electrolyte imbalance, and an adverse drug reaction; however, the cause of the patient's condition remained unclear. Therefore, we performed additional surgery to resolve the deteriorated destructive changes in the cervical spine, which we assumed to be potentially responsible for his symptoms. In the first stage of surgery, cervicothoracic posterior spinal fusion was performed from C2 to T2 using pedicle screws at the C2, C3, C7, T1, and T2 vertebral levels. In the second stage of surgery (10 days after the first stage), anterior spinal fusion was performed from C3 to C7 with an autologous iliac bone graft and a titanium plate ().
The patient's intractable pain disappeared within 2 weeks after surgery. On comparing the pain intensity between before and after the two-stage surgery, the NRS score improved from 10 to 1, the painDETECT score changed from 28 to 10, and the NPSI score changed from 79 to 10. The serum level of CK was also normalized after the two-stage surgery (). At 10 months after surgery, he was able to walk without any support. The patient and his family were informed that data from the case would be submitted for publication and gave their informed consent.


A 74-year-old man presented with a chief complaint of a right-sided sore throat with odynophagia. He was febrile and had decreased his oral intake due to difficulty and pain swallowing. He was admitted from the emergency room to the ENT service due to concerns of airway edema, right oropharyngeal swelling, and right parotid tenderness. Edema and swelling involving the mucosa of the right palatine tonsil, oropharynx, uvula, base of tongue, and epiglottis with additional edema in the right masticator space were noted on flexible laryngoscopy. The significant oropharyngeal swelling caused leftward deviation of the uvula as well as trismus that was initially worrisome for a peritonsillar infection.
Ampicillin and steroids were given; however, he continued to have oropharyngeal prominence. Subsequently, an interval CT scan of the neck was obtained, revealing a hypodense deep parotid lobe sialocele measuring approximately 5.0 × 0.9 cm extending to the parapharyngeal space and exerting mass effect on the oropharyngeal airway. No prominent sialolith was noted. Several deep jugular chain lymph nodes in level II were also mildly prominent. The fluid collection was drained transorally via an incision lateral to the palatine tonsil along the anterior tonsillar pillar. Approximately 20 cc of frank purulence was drained. A swab of the oropharynx revealed Gram-positive and Gram-negative rods consistent with normal oral flora. No anaerobes were isolated. After drainage, the patient showed significant clinical improvement immediately without need for drain placement. He was discharged on a two-week course of amoxicillin with a steroid taper, warm compress, sialogogues, and pain control (Figures –).


A 37-year-old Caucasian female with a past medical history significant for spina bifida complicated by paraplegia and neurogenic bladder, kyphoscoliosis with multiple spine surgeries, hypertension, sinus tachycardia, depression, and multiple episodes of right lower leg cellulitis presented as a transfer to our tertiary medical center for further management of a left popliteal artery occlusion and right lower extremity cellulitis. Her daily medications were trazodone, Celexa, tolterodine, propranolol, Wellbutrin, and hydrochlorothiazide.
On physical examination, she was calm, cooperative, and in no acute distress. She weighed 65 kg and was 134 cm tall. Her blood pressure was 119/85 mm Hg, heart rate 101 per minute, temperature 98.8°F, respiratory rate 18 per minute, and arterial oxygen saturation of 96% on 2 liters nasal cannula. Head and neck examination was normal, and she had moist oral mucosa with no oral thrush or ulcers noted. There were no abnormal lung or heart sounds. The abdomen was soft, non-distended, non-tender with no rebound or guarding, and normal bowel sounds. Physical examination revealed kyphoscoliosis of the back, underdeveloped paraplegic lower extremities with bilateral sensory loss, and intact distal pulses in the left foot with warm pink toes. The right lower leg and foot were swollen, erythematous, and non-tender with bullae of serosanguinous fluid. Her laboratory tests were normal, except for hypokalemia, with a potassium level of 2.4 mmol/L and lactic acid of 1.6 mmol/L.
The vascular surgery team was consulted. She was started on a heparin drip for left popliteal artery thromboembolism and the recommendation was made for transthoracic echocardiography (TTE) and antiphospholipid syndrome screening.
The TTE showed a cardiac mass in the right atrium extending into the inferior vena cava (IVC) (Figure ). For further identification of the mass, cardiac magnetic resonance imaging (MRI) was done which showed a normal left ventricular ejection fraction of 57%, right ventricular dilatation with moderately reduced systolic function of 36%, and a mass-like structure projecting over the right atrium with the appearance most suspicious for a diaphragmatic caval foramen herniation of liver parenchyma encroaching on the right atrium (Figure ). A sulfur colloid nuclear single-photon emission computed tomography (SPECT) study also confirmed this finding (Figure ). She continued inpatient treatment with anticoagulation and antibiotics during which she was seen by cardiology who recommended outpatient follow-up with cardiothoracic surgery for evaluation for potential surgical excision of the right atrial mass that was found to be herniated liver tissue.