A 69 year-old male patient was admitted with difficulty urinating and nocturia for 3 months. The digital rectal examination did not indicate any hardness or nodules of the prostate, and an abdominal ultrasound revealed an enlarged prostate and the prostate specific antigen (PSA) value was normal. Fourteen months prior to this admission, he had undergone video-assisted thoracic surgery for the wedge resection of left upper lung lobe due to the left upper lung mass found in chest CT scan (), and pathology revealed infiltrating lung adenocarcinoma with T2N0M0 staging (). Re-examination of chest CT on this admission indicated no evidence of disease recurrence after lung lesion resection (). Then the patient was diagnosed with benign prostatic hyperplasia (BPH) and received holmium laser enucleation of the prostate, an effective transurethral procedure to treat bladder outflow obstruction due to BPH. The pathology revealed benign prostate hyperplasia as expected. Four months after surgery for BPH, the patient had no improvement in symptoms and continued to complain of dysuria and perineum pain. Urinalysis was negative for infection and PSA was not elevated, however an MRI of the pelvis indicated posterior urethral mass without any regional lymphadenopathy or other sites of lesion. Urethrocystoscopy under general anesthesia found the mass in the membranous urethra near the verumontanum (), and transurethral loop electrosurgical excision was conducted to remove the mass. Due to the infiltration of tumor into normal urethral tissue, the transurethral operation aimed to resect as much tumor tissue as possible, so as to facilitate pathological diagnosis, but it was difficult to guarantee negative margins. Routine hematoxylin and eosin stained sections indicated adenocarcinoma () and further immunohistochemical staining showed negative PSA, positive thyroid transcription factor 1 (TTF1) and Napsin A, confirming the urethral metastasis of lung adenocarcinoma. To identify the latent metastases to other sites and recurrence from primary lung adenocarcinoma, the patient underwent brain MRI, chest CT, abdominal ultrasound and emission computed tomography for whole-body bone scan and received negative results, suggesting isolated urethral metastases. The patient was restaged as T2N0M1 of lung adenocarcinoma, and chose 6 courses of systematic chemotherapy (pemetrexed combined with nedaplatin) plus bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor at 3 weeks intervals. The therapeutic regimen was well-tolerated, and obviously relieved the patient from dysuria and perineum pain.


A 59-year-old African American male with known chronic Stanford type B aortic
dissection with extension into a thoracoabdominal aneurysm was admitted for elective
repair. Pre-operatively, an epidural catheter was placed by and for anaesthesia on
the first attempt without any complication. Upon further investigation, patient
admitted to continued tobacco use leading up to the surgery and demonstrated poor
performance on pre-operative pulmonary function tests. In light of these findings,
his surgery was delayed until a later time, the epidural catheter was removed
3–4 h after initial placement, and the patient was discharged with
follow up within 1 month. The patient reported no immediate symptoms
after catheter removal.
11 days later, the patient presented to the emergency department with a 5-day history
of constant, global, 10/10 headache that was significantly worse when standing. He
also noted accompanying severe, constant lumbar spine pain with bilateral lower
extremity weakness but denied numbness or tingling. Additional pertinent medical
history included coronary artery disease status post-bare metal stent,
chronic obstructive pulmonary disease, Stage II chronic kidney disease,
hypertension, and ongoing tobacco use.
On physical examination, the patient was alert, oriented, and demonstrated no
focal neurological deficits, but did display tenderness to palpation over the lumbar
spine at the site where the epidural catheter had been placed and subsequently
removed.
CT of the head without contrast performed in the Emergency Department was
unremarkable. CT of the lumbar spine without contrast showed layering hyperdensity
extending from the mid L2 vertebral body to the mid L3 level as well as a second
hyperdense collection layering dependently from L4-S1 ().
MRI of the lumbar spine later that day redemonstrated a stable intrathecal
haemorrhage and an epidural haematoma with anteromedial displacement of the cauda
equina, most notably from the mid L2 to upper L3 vertebral bodies ().


A 44- year-old Caucasoid male, apparently healthy, apart from the occurrence of very rare “epileptic-like attacks”, died at work, while performing a minor effort task. His heart weighed 380.0 g and measured 14.7 cm × 12.0 cm, with global dilatation and congenitally malformed tricuspid valve, including downward ventricular insertion of the ring – “atrialization of the right ventricle” – as in the Ebstein Disease ().


A 17-year-old Caucasoid male, with no relevant personal or familial pathologic antecedents or known risk factors, dropped dead at the platform, while waiting for the underground. His heart revealed nothing abnormal but a congenitally malformed Quadricuspid Pulmonary Valve ().


A 48-year-old Caucasoid male, with no relevant personal or familial pathologic antecedents or known risk factors, was found dead at his house courtyard. His heart weighed 440.0 g, with hypertrophy and severe degenerative alterations of a congenitally malformed Bicuspid Aortic Valve ().


A 39-year-old Caucasoid female, with personal pathologic antecedents of syncope, died suddenly. Her heart weighed 362.5 g and measured 14.5 cm × 11.0 cm, with dilatation and prominent ballonization of the mitral valve leaflets, as in Myxomatous Mitral Valve Prolapse ().


A 45-year-old Caucasoid male was found dead at home. The heart weighed 1 140.0 g, was dilated and presented a Papillary Fibroelastoma of the Pulmonary Valve ().


A 64-year-old Caucasoid male, with no relevant personal or familial pathologic antecedents or known risk factors, was found dead at home. The heart weighed 580.3 g, was hypertrophic and showed perforated, bi-valvular (mitral and aortic), Infectious (Gram+ bacteria) Acute Endocarditis ().


A 70-year-old Caucasoid female, with personal medical history of Rheumatic Fever, was found fallen in the street. Cardiopulmonary resuscitation was performed while the victim was being transported to the hospital, where she died. The heart weighed 393.7 g, with hypertrophy and stenotic aortic-mitral valves, the latter displaying a “smiling face” or “fish mouth” pattern, suggesting Post-inflammatory Valvular Cardiopathy, of Rheumatic nature ().


A 69-year-old Caucasoid male, with alcoholic and smoking habits and a previous stroke, was found at home, in advanced putrefaction state. The heart revealed severe mitro-aortic Degenerative Valvular Cardiopathy ().


A 72-year-old Caucasoid female, with a previous (5 years before) surgery, due to ascending aorta aneurysm, replacing the aorta by a synthetic conduit and the aortic valve by a bi-disc, metallic prothesis. She was found dead at home. The heart weighed 637.5 g, presenting ventricular hypertrophy and aortic valve prothesis closing and opening malfunction due to Pannus ().


After 1 month of antibiotics for repeated pneumonia, a 2-year-old boy with a history of polyendocrinopathy, enteropathy, X-linked syndrome presented with watery diarrhea (type VII according to the Bristol Stool Scale) for longer than 4 months. Stool culture results were normal. Clostridium difficile antigen and the toxin B gene of stool were negative. This patient was treated with smectite powder, racecadotril granules, Lactobacillus probiotics, and rehydration. There was no significant improvement in the child, and his weight was reduced from 12 to 8 kg throughout this period. He also suffered from hypokalemia, acidosis, and severe malnutrition. Electrolyte replacement, total parenteral nutrition (TPN), and immunoglobulin were then administered. Because of ongoing diarrhea that was unresponsive to conventional treatment, the patient finally underwent two times of FMT via a jejunal tube under the guidance of gastroduodenoscopy. During a 7-day follow-up after the first FMT, the frequency of bowel movement decreased from 10 times to four times per day and the shape of the stool was obviously improved. TPN was stopped 1 week after FMT. However, on the 9th day after transplantation, urinary tract infection was confirmed by a swollen urethra opening with intermittent pus discharge. The white blood cell count was more than 50 in each high-power field as shown by a routine urine test. Cefuroxime was initially used as an empirical antibiotic, and then piperacillin/ tazobacta and meropenem were administered successively according to urine culture and drug sensitive test result. The stool mass was increased again on the 16th day after the first FMT. A second FMT was performed in the same manner on the 20th day after the first FMT. The FMT procedures were well tolerated with no adverse events, such as vomiting, abdominal distention, and fever. Four weeks after the second FMT, his stool was observed once a day, and the shape of the feces was type III according to the Bristol Stool Scale. His weight increased to 10 kg 1 month after FMT, and it was 11.4 kg in the second month and 12.4 kg in the third month. Allogeneic hematopoietic stem cell transplantation was successfully performed at 3 months after FMT.


A 5-year-old boy was diagnosed with Wiskott–Aldrich syndrome (WAS) in October 2016. He received graft form 9/10 HLA-matched peripheral blood stem cells of his mother on 4 May 2017. He presented with a 2-month history of recurrent diarrhea after hematopoietic stem cell transplantation. Cyclosporin, mycophenolate mofetil, and methotrexate were initially used for graft-versus-host disease (GVHD) prophylaxis. A rash occurred on day + 4 after transplantation and watery stool occurred on day + 6. Smectite powder and racecadotril powder were then applied to reduce the symptoms. Intravenous methylprednisolone (2 mg/kg/d) was administered on day + 10. GVHD grade was evaluated as III and then basiliximab, tacrolimus, and sirolimus were successively used to reduce acute GVHD. However, the patient did not respond to these strategies. The patient developed abdominal pain, abdominal tenderness, and worsened diarrhea when the stool volume reached 1500 mL/d on day + 35, and infliximab was then administered. He had intermittent fever and anti-infective therapy (meropenem, vancomycin, micafungin sodium, amikacin, fluconazole, sulfamethoxazole) was administered. Abdominal ultrasound and an X-ray showed the presence of intestinal obstruction. Multiple fluid levels were observed in the upper abdomen. Non-surgical therapy was then applied, including fasting, gastrointestinal decompression, maintenance of water–electrolyte balance, blood transfusion, TPN, and effective antibiotics. Bloody stool occurred on day + 37. Pelvic computed tomography showed edema and thickening of the intestinal wall, and pelvic intestinal effusion accompanied by some intraluminal high-density lesions. The patient then had surgical consultation. The surgeon suggested continuing the medical treatment without surgery because of intestinal rejection, the wide range of lesions, and the complex condition of the patient. Although the abdominal pain was relieved, the color of the stool turned yellow-green on day + 49, but diarrhea was not alleviated. Stool screening showed no CDI. Because the diarrhea persisted for longer than 2 months with traditional methods to relieve GVHD, we attempted to use FMT to treat diarrhea.
Fecal suspension was administered via a jejunal tube with the help of gastroduodenoscopy on day + 75. Consequently, the procedure of a second FMT was repeated 2 days later. The patient had no adverse reactions. Stool volumes were deceased from 1500 to 200 mL/d after FMT and TPN was stopped on day + 90. The patient’s stool returned to normal on day + 103 and he was maintained on tacrolimus and cyclosporine. The patient did not have diarrhea at 3 months of follow-up.


A 77-year-old, gravida 4, para 4004, post-menopausal female presented with brown vaginal discharge. Her gynecologic history had been essentially unremarkable, with negative Pap Tests, and negative testing for high-risk human Papillomavirus. Physical examination revealed atrophic external genitalia. A mobile, 4 to 5-cm nodule was palpated along the rectovaginal septum, with a muscle-like consistency and texture. Pelvic ultrasound showed a uterus and ovaries with measurements as expected for a post-menopausal state. In addition to a 2.5-cm calcified uterine fibroid, a 4.8-cm solid mass with internal blood flow was identified posterior and inferior to the cervix (Figure ).
At subsequent laparoscopy, no intrapelvic abnormalities were seen. The previously identified mass occupying the rectovaginal space remained palpable; an enucleation of this mass was performed, yielding a 4.2 x 4.0 x 3.0-cm red-tan, circumscribed nodule with tan, whorled cut surfaces. Histologic examination demonstrated the proliferation of bland-appearing, spindled cells with a fascicular architectural configuration (Figures , ). Few mitotic figures were identified, estimated at 3-4 per 5 mm2; a rare focus of necrosis was observed (Figure ).
In an attempt to further characterize the lesion, a panel of immunohistochemical preparations was performed. Neoplastic cells showed diffuse reactivity for vimentin, c-Kit (Figure ), and DOG1 (Figure ). Immunohistochemistry for pan-cytokeratin, desmin, S-100 protein, and SOX10 was interpreted as negative; smooth muscle actin accentuated background vascular endothelium. The global morphologic features, in correlation with immunophenotype, were diagnostic of GISTs. Further molecular testing elucidated a mutation in exon 9 of the Kit gene.
The patient presented with various management options, including imatinib versus sunitinib therapy, rectal resection, and active surveillance. She chose to pursue close active surveillance, with pelvic MRI every three months over an interval of two years. At approximately one year following surgical enucleation and close surveillance, there is no clinical or radiographic evidence of recurrence.


A 70-year-old man had history of thyroid enlargement for 10 years presented to the surgical private clinic complaining from palpitation and weight loss.


A 26-year old male, index patient (II1), with ESRD at age 24 was evaluated for LRKTx. The patient presented with microhematuria and proteinuria since age three. For progressive proteinuria, a renal biopsy was performed 10 years later demonstrating irregular thinning, thickening, and GBM-lamellation upon electron microscopy, allowing for histological diagnosis of AS (Fig. a). Screening for extra-renal manifestations revealed bilateral sensorineural hearing loss for high frequencies (Fig. b). Ocular lesions were excluded by ophthalmological examination. At age 24, his kidney function gradually worsened requiring hemodialysis followed by peritoneal dialysis over 12 months. Based on a negative family history, X-linked mode of transmission was assumed and the father (I2) was evaluated as potential kidney donor. Laboratory results including serum creatinine and urinalysis presented normal, as well as a 24 h-ambulatory blood pressure monitoring. In addition, donor kidney biopsy showed unremarkable light microscopy, and no obvious ultrastructural irregularities (Fig. a). In absence of other available living donors, the father was accepted as donor in an AB0-incompatible LRKTx to his son. Blood group antibody elimination was performed according to standard protocol, including administration of rituximab, repeated immunoadsorption, and pre-transplant initiation of standard oral immunosuppression by tacrolimus, mycophenolate mofetil, and prednisolone. Surgical procedure and postoperative period were unremarkable. Initial graft function was satisfactory with immediate diuresis. Both donor (I2) and recipient (II1) were discharged from hospital with eGFR values of 65 ml/min/1.73 m2 (I2) and 50 ml/min/1.73 m2 (II1) 10 days after LRKTx (Fig. ).
Two to three years later, satisfactory clinical outcome was illustrated by the recipient (II1) participating in the World Transplant Games (WTG) and the European Transplant and Dialysis Sports Championship (ETDSC). Taken together, he won two gold medals, two silver medals, and a bronze medal in five different disciplines (Fig. ).
Seven years after LRKTx, both donor and recipient show moderate renal function at CKD-stage 3a (Fig. ). While the donor (I2) displays stable eGFR of 60 ml/min/1.73 m2 with modest microalbuminuria, the recipient (II1) exhibits a stable baseline eGFR of 48 ml/min/1.73 m2, however with persistent proteinuria of 0.5–1 g/d, due to biopsy-proven chronic transplant glomerulopathy.
In a retrospective analysis, we performed targeted NGS of COL4A3, COL4A4, and COL4A5 in the index patient and his family and identified compound-heterozygous variants in COL4A3 (NM_000091.4) at c.1909G > A (p.Gly637Arg) and c.4421 T > C (p.Leu1474Pro) in the index patient. Segregation analysis revealed paternal transmission of c.1909G > A and maternal inheritance of c.4421 T > C (Fig. c-d). Upon examination of the 38-year-old index brother (II2), we found him to carry the paternal c.1909G > A variant without any signs of renal dysfunction (normal eGFR, normal urinalysis), ocular abnormalities, or hearing impairment at his current age (Fig. b-d). The variant c.1909G > A (p.Gly637Arg) has not been previously described and is absent from SNP databases (gnomAD/ExAc). Variant interpretation according to the American College of Medical Genetics and Genomics (ACMG) [] classifies this change as likely pathogenic. On the contrary, the maternal variant c.4421 T > C (p.Leu1474Pro) has been previously reported in AS with compound-heterozygosity []. Due to its relatively high allele frequency in the general population (0.49%, gnomAD), this genetic alteration was classified as variant of uncertain significance (VUS). Unlike the index brother, both parents showed sensorineural hearing impairment for high frequencies at the age of 62 and 65, respectively. None of the family members had any findings of ocular pathology. To further evaluate for mild renal GBM-irregularities, we retroactively reevaluated pre-donation ultrastructural findings and performed immune histochemical staining for COL4A5 in the donor biopsy specimen from the father. While upon reevaluation, electron microscopy showed mildest GBM-thinning, COL4A5-staining revealed a so-called mosaic pattern with partial COL4A5 deficits in the father’s kidney supporting the histopathological diagnosis of non-progressive TBMN compatible with light ADAS (Fig. a). In contrast, the initial kidney biopsy of the index patient showed both severe ultrastructural GBM-alterations and marked COL4A5 deficits corroborating progressive renal manifestation of ARAS (Fig. a).
Written informed consent was obtained from the index patient and all tested family members.


A 4-year-old male castrated Samoyed (13 kg) was referred with a radiographic diagnosis of spontaneous pneumothorax. On presentation the dog was moderately dyspneic. Pneumothorax was confirmed with three-view thoracic radiographs, thoracentesis was performed, and bilateral small-bore chest tubes (MILA thoracostomy tube, MILA International, Inc., Erlanger, KY.) were placed with manual suctioning every 4 h. Twenty-four hours after arrival, computed tomography (CT) confirmed the diagnosis of bilateral pneumothorax. The dog underwent a median sternotomy and a partial left lung lobectomy. Post-surgical chest tubes were maintained. Eight hours after surgery, the dog was tachypneic (72 bpm) and mildly dyspneic. Lung ultrasound, performed in a standing position, identified a normal synchronous curtain sign ventrally on both sides of the thorax and both an asynchronous curtain sign and a double curtain sign in the mid-to-dorsal caudal lung regions bilaterally. A glide sign was absent dorsally and a lung point was identified bilaterally. Following lung ultrasound, 11 and 9 mL/kg of air was removed from each chest tube. The dog was eventually discharged.


A 5-year-old female spayed Collie cross (25 kg) was referred with a radiographic diagnosis of spontaneous pneumothorax. On presentation the dog was tachypneic (56 bpm) and mildly dyspneic. Bilateral pneumothorax was confirmed with three-view thoracic radiographs and CT. The right accessory lung lobe and caudal portion of left cranial lung lobe were removed during exploratory median sternotomy. Bilateral post-surgical small-bore chest tubes were placed. The day after surgery, the dog was tachypneic (80 bpm) and mildly dyspneic. Lung ultrasound, performed in sternal recumbency, identified bilateral normal synchronous curtain signs ventrally and an asynchronous curtain sign and a double curtain sign in the mid-to-dorsal caudal lung regions bilaterally. A glide sign was absent dorsally and a lung point was identified bilaterally. Following lung ultrasound, 8 and 18 mL/kg of air was removed from each chest tube. The dog was eventually discharged.


An 8-year-old female spayed Husky cross (18 kg) was referred with a radiographic diagnosis of spontaneous pneumothorax. On presentation, the dog was eupnic (28 bpm). Lung ultrasound, performed in a standing position, identified bilateral normal synchronous curtain signs ventrally and an asynchronous curtain sign and a double curtain sign in the mid-to-dorsal caudal lung regions bilaterally. A glide sign was absent dorsally and a lung point was identified bilaterally. Immediately following lung ultrasound, three-view thoracic radiographs confirmed a mild to moderate pneumothorax. Sixty hours after arrival, a CT revealed moderate bilateral pneumothorax. A median sternotomy was performed, and a single bulla was removed via partial left lung lobectomy. The dog was eventually discharged.


A 10-month-old male mixed breed dog (38 kg) was referred with pelvic fractures and a radiographic diagnosis of pneumothorax following motor vehicle trauma. On presentation the dog was tachypneic (100 bpm) and moderately dyspneic. Eighteen milliliters per kilogram of air was removed from the left hemithorax with thoracentesis. Eight hours later, the dog was mildly tachypneic and dyspneic. Lung ultrasound, performed in sternal recumbency, identified bilateral normal synchronous curtain signs ventrally and an asynchronous curtain sign and a double curtain sign in the mid-to-dorsal caudal lung regions bilaterally. The glide sign was difficult to assess bilaterally and considered equivocal. On the right hemithorax, a lung point was present in the mid caudal region and there were increased B lines at and below the lung point. On the left hemithorax, a lung point and B lines were not observed. With the probe oriented parallel to the ribs, a scant amount of pleural effusion was noted bilaterally in the most ventral regions of the pleural space abutting the diaphragm. Following lung ultrasound, three-view thoracic radiographs revealed a mild pneumomediastinum, mild pneumothorax, and a small volume of pleural effusion. Concurrent injuries included right caudal acetabular fracture and multiple sacral fractures. The dog was eventually discharged.


An 18-month-old female spayed Great Pyrenees (38 kg) was referred with right humeral fracture and a radiographic diagnosis of pneumothorax following motor vehicle trauma. On presentation the dog was tachypneic (84 bpm) and moderately dyspneic. Thoracentesis was performed (54 mL/kg of air removed from right hemithorax and 40 mL/kg from left hemithorax). A right sided small-bore chest tube with continuous suction was placed. Twelve hours post-presentation, continuous suction was discontinued and lung ultrasound was performed in left lateral recumbency to assess the right hemithorax and partial sternal recumbency to assess the left hemithorax (the humeral fracture prevented sternal positioning due to patient discomfort). A bilateral normal synchronous curtain sign was observed ventrally and an asynchronous curtain sign and a double curtain sign were present in the mid-to-dorsal caudal lung regions bilaterally. A glide sign was absent dorsally and a lung point was identified bilaterally. Increased numbers of B lines were observed in the ventral lung regions at and below the lung point bilaterally. With the probe oriented parallel to the ribs, a scant amount of pleural effusion was noted bilaterally in the most ventral regions of the pleural space. Following lung ultrasound, 8 mL/kg of air was removed through the chest tube and three-view thoracic radiographs showed mild pneumothorax bilaterally, a small volume of pleural effusion, and increased soft tissue opacity bilaterally consistent with pulmonary contusions. A left brachial plexus avulsion was also diagnosed 12 h following admission. The owner elected euthanasia.


A 2-year-old male neutered mixed breed dog (18 kg) was evaluated following motor vehicle trauma. The dog was tachypneic (68 bpm) and moderately dyspneic. Lung ultrasound, performed in sternal recumbency, identified bilateral normal synchronous curtain signs ventrally. On the left hemithorax, both an asynchronous curtain sign and a double curtain sign were present in the mid-to-dorsal caudal lung regions, the glide sign was absent dorsally, a lung point was identified, and increased numbers of B lines were observed in the ventral lung regions at and below the lung point. On the right hemithorax, a normal synchronous curtain sign was present along the entire caudal border of the thorax, a glide sign was present at the most caudal dorsal regions, and diffuse B lines were observed in the mid to ventral lung regions. Following lung ultrasound, thoracentesis was performed only on the left hemithorax (28 mL/kg of air removed). Following thoracentesis, three-view thoracic radiographs confirmed a moderate left-sided pneumothorax, multiple left-sided rib fractures, and increased soft tissue opacity bilaterally consistent with pulmonary contusions. Concurrent injuries included a degloving tail injury and a left coxofemoral luxation. The dog was eventually discharged.


A 78-year-old woman with a medical history of congestive heart failure, pacemaker implantation due to iatrogenic atrioventricular block after heart surgery, anticoagulant therapy with warfarin for a mechanical aortic and mitral valve, chronic kidney disease stage III, arterial hypertension, and with no history of abdominal surgery was admitted due to hematochezia that had started a few hours earlier. Three days previously, she had a colonoscopy for a further diagnostic workup of microcytic anemia. The endoscopic procedure was difficult due to a redundant sigmoid colon. As a result, increased external abdominal pressure was applied to reach the cecum. The procedure was prolonged; the total procedural time was 75 minutes. CO2 was used for insufflation.
During the withdrawal, 2 sessile polyps 8 and 3 mm in the cecum were resected with a cold snare. Histology revealed low-grade dysplasia adenomas. On physical examination, she appeared in mild distress. Digital rectal examination revealed hematochezia, and she was hypotensive. On examination, her abdomen was soft and non-tender. Hemoglobin was 7.9 g/dL, platelets were 255,000 μ/L, and the international normalized ratio was 1.05. Baseline hemoglobin was 9.6 g/dL. The patient received the last dose of low–molecular-weight heparin (LMWH) dalteparin 16 hours before diagnostic colonoscopy, which was reintroduced in the same evening after the procedure and continued in full dose until she was admitted to the hospital.
On arrival, post-polypectomy bleeding was suspected and an emergent colonoscopy was performed (Figure ). She received 1 unit of packed red blood cells before the endoscopy, and 0.9% saline was started before the procedure. During the colonoscopy, a dark-red lumen-occupying mass was observed approximately 10 cm from the anal verge. The procedure was halted at 40 cm because of inadequate visualization of the lumen. She was admitted to the intensive care unit where she received an additional unit of packed red blood cells. After the transfusions, the patient was hemodynamically stable. We performed abdominal contrast-enhanced computed tomography (Figure ). An elongated sigmoid colon filled with hemorrhagic content and a hypodense mass in the wall of the sigmoid colon consistent with the appearance of hematoma were identified. No proximal dilatation of the colon was present. Anticoagulation therapy was temporarily halted and was reintroduced 3 days after the emergent colonoscopy.
During the hospitalization, the patient had several minor self-limiting episodes of hematochezia. After 9 days, we performed a control sigmoidoscopy (Figure ). Erythema and ulcerations of the mucosa with no signs of hematoma were noted at the site of the previously seen hematoma. Ulcerations were noted 10 cm from the anal verge and extended up to 45 cm. Because of the stable clinical picture and low-risk histology of completely resected adenomas, only the left colon was examined. Our patient received 5 transfusions in total and was discharged home.


A 36-year-old woman with past medical history (PMH) of “cysts in her ovaries” presented to the emergency department with the triage complaint of left lower quadrant pain starting an hour and a half prior to arrival. This pain is associated with nausea and vomiting. The nurse noted the patient’s pain to be 10/10 and described it as “terrible pain to the left lower quadrant of the abdomen”. Patient’s last menstrual period was noted as at the end of the September. Her initial vital signs were as follows: blood pressure 159/100 mmHg, pulse 81, respiratory rate 22, and oxygen saturation 98% on room air. Physical exam revealed the patient was in severe pain and distress. Her heart and lung sounds were normal. Her abdominal exam was described as soft, nonperitoneal, severe left lower quadrant tenderness was noted on exam. Genitourinary exam was deferred. The patient received one liter intravenous fluids, and 6 mg of intravenous morphine. The patient still appeared in pain. The attending physician requested a bedside ultrasound from the emergency medicine ultrasound team. The image below shows the “double bladder sign” (Video ). Obstetrics and Gynecology was consulted. An additional radiology ultrasound was not performed and the patient was taken to the operating room. She was found to have a left adnexal torsion and two left paratubal cysts, the largest measuring 7.5 cm x 7.5 cm x 0.2 cm. Pathology report showed a fallopian tube with hemorrhage and edema. The patient tolerated the procedure well with no complications and was discharged.


A 23-year-old female presented with one day history of constant left lower pelvic pain with two episodes of vomiting. Her last menstrual period was three weeks ago. She had a prior history of ovarian cyst that had been followed by her gynecologist and had resolved. She had mild dysuria but no fever, chills, hematuria. Her initial vital signs included a temperature of 97.9°F, pulse of 83, respiratory rate of 18, blood pressure of 112/57, and oxygen saturation of 100% on room air. On exam, the patient appeared in extreme discomfort, and her cardiovascular and pulmonary exams were normal. Her abdomen was soft with tenderness to left lower quadrant but without rebound or guarding. She had localized pain to the left adnexa on bimanual exam without cervical motion tenderness or vaginal bleeding. She received 1 L normal saline and 4 mg of morphine intravenously. Due to her severe pain, a bedside ultrasound was performed showing the following video. The bedside ultrasound showed a “double bladder sign” on pelvic transabdominal sagittal view with the large anechoic ovarian cyst anterior to the uterus and posterior to the bladder (Video ). Radiology ultrasound showed a left adnexal cyst measuring 6.6 cm x 6.5 cm x 8.1 cm with peripheral follicles and without internal flow. Gynecology was contacted and the patient was taken to the operating room. On laparoscopy there was a left 6-cm paratubal simple cyst, and the left ovary and pedicle was torsed and dusky in appearance. After detorsion of the ovary, the appearance improved and the patient underwent left salpingectomy and removal of the paratubal cyst. The patient tolerated the procedure well and was discharged.


A 32-year-old female with no significant PMH presented with one day history of acute left lower quadrant abdominal pain starting at 8 am with 10 episodes of vomiting. Pain was severe at 10/10. She denied fever, dysuria, or hematuria. She reported she had a left ovarian cyst during her previous pregnancy which did not need any intervention. Her initial vital signs included a temperature of 97.4°F, pulse of 62, respiratory rate of 20, blood pressure of 91/54, and oxygen saturation of 108% on room air. The patient had tenderness to left lower quadrant and suprapubic area without rebound or guarding. She received 1 L NS, Toradol 15 mg and morphine sulfate 5 mg IV. Bedside US shows double bladder sign (Video ). Ob/gyn was consulted and radiology US was performed showing 9.2 cm x 8.2 cm x 5.5 cm left adnexal cyst without vascular flow. The patient was taken to the operating room and through percutaneous endoscopic approach, the left ovary was enlarged, hemorrhagic, dusky, mottled and blue in appearance. After detorsion there was no return of color and she underwent left salpingo-oophorectomy. The patient tolerated the procedure well and was discharged. She was seen on two-week follow-up without complications.


In December 2017, a 57 year-old male was referred to the Oral Medicine Department of Dental Faculty of Babol University of Medical Sciences. The chief complaint was a massive and rapidly growing swelling in his left maxillary alveolar ridge after tooth extraction a month before. The lesion was a sessile exophytic mass with lobular surface which was erythematous in some areas. He also complained from spontaneous bleeding and tenderness. The whole lesion measurements were approximately 5cm x 5cm. The involved teeth including left maxillary canine and lateral incisor had mobility grade III ().
Based on his own statements, the patient was considered as a heavy smoker who had been smoking for a long time and reported a history of having a lung malignancy since December 2016. A complete evaluation of his medical history was performed by exploring the documents of his previous hospitalization. First, after consulting with a lung specialist, a core needle biopsy from right lung mass was done and microscopic examination of sections revealed harboring neoplastic proliferation of epithelial cells with sheet and alveolar pattern. Neoplastic cells had large hyperchromatic nuclei, clear to granular eosinophilic cytoplasm and prominent nucleoli. Inflammatory cell infiltration and multifocal necrosis were observed (). Immunohistochemistry showed strong positive reaction to CK7 and there was no response to CK20, TTF1 and CDX2. The pathologist determined it as non-small-cell carcinoma, probably TTF1 negative lung carcinoma.
No remarkable finding was shown by brain MRI taken in January 2017. Whole body bone scan was performed which showed abnormal increased uptake in the right first rib. The scan pattern suggested either a lung tumoral mass with the involvement of the first rib or radiotracer uptake by the soft tissue tumoral mass only (without bone involvement), therefore CT scan was recommended. The rest of skeleton was unremarkable. In February 2017, spiral CT of chest without contrast showed a mass lesion with ill-defined margins in the right lung apex with a maximum diameter of 62x30 millimeters in favor of a malignant process. Diffuse bilateral patchy nodular densities were noted in both lungs. There was no evidence of pleural effusion and chest wall was normal. According to all of those diagnostic procedures, the final diagnosis was unresectable Pancoast tumor. Therefore, the patient was referred to oncology service where appropriate treatment was commenced utilizing chemo-radiotherapy followed by adjuvant chemotherapy with cisplatin. Exploring the panoramic view disclosed an ill-defined radiolucency in the left maxillary area extending superiorly to the orbital floor together with cortical perforation of the alveolar ridge ipsilaterally. Left maxillary canine showed floating in air appearance, and widening of periodontal ligament was obvious in left incisors ().
Numerous specimens were taken from different parts of the lesion for histopathologic examination. Microscopic slides showed malignant neoplastic proliferation of polygonal cells in sheets and islands pattern. Most of tumoral cells had atypical hyperchromatic nuclei, and many clear cells were observed within tumoral sheets. Cellular and nuclear pleomorphism, abundant atypical mitoses, vascular invasion and large multifocal necrosis were seen ().
According to patient’s medical history, metastatic nature of the lesion was almost decisive, but because of existing undifferentiated malignant cells, immunohistochemistry staining was recommended to confirm the origin of metastasis. Since there was no reaction to HMB45 and S100 protein, melanoma and neural crest tumors were excluded. The response to CK 5/6 was strongly positive and also positive reaction to CK7 was noticed but no response to P63, CK20, CD5, CD117, WT1 and EBV were observed ().Considering the whole findings, the metastatic lesion was designated as a squamous cell carcinoma with pulmonary origin. The consultant maxillofacial surgeon determined on not performing a surgical intervention not only because the jaw lesion did not seem to be operable due to its enormous size, but basically for the primary site of tumor which had not been eradicated appropriately. Therefore the patient was referred back to oncologist to give his advice concerning the proptitious options of chemotherapy. As the tumor was in stage IV, it was declared that chemotherapy might exacerbate the patient’s general condition. So symptomatic treatment was opted just for relieving the probable excruciating pain. Three months after commencing the case evaluation, the patient was still alive and no progression of the disease was noted.


The patient was a 35-year-old male who originally presented features of CMT at the age of 8 years. Peripheral blood was collected in EDTA tubes after giving informed consent. The protocol was in accordance with French ethics legislation.


A 50-year-old female was referred to us as a case of primary acute angle closure attack in the right eye and for laser PI. She had redness, watering, and severe ocular pain in her right eye (RE) for 1 day. The visual acuity was 6/18 in the right eye (RE) and 6/6 in the left eye (LE). LE had a deep anterior chamber (AC) and a normal fundus. Slit lamp examination of RE revealed conjunctival chemosis, circumcorneal congestion, shallow AC, and no AC cells (Figure 1a,b ). Intraocular pressure (IOP) was 38 mmHg in RE and 12 mmHg in LE by applanation. A diagnosis of acute primary ACG due to pupillary block mechanism in RE was considered. However, additional findings included swelling of the upper eyelid, scleral tenderness, clear cornea, reactive round pupil, fine choroidal folds (Figure 1e ), shallow peripheral annular choroidal detachment, and limitation of ocular movement with pain in RE. She had a history of such an episode three years back. Due to these factors, a suspicion of scleritis with secondary ACG was also kept as a differential diagnosis. An ultrasonogram (USG) B-scan of RE showed fluid accumulation in the subtenon space with thickening of the ocular coats (Figure 1c ). Ultrasound biomicroscopy (UBM) revealed thickening of the sclera and supraciliary effusion along with some anterior rotation of the ciliary body (Figure 1d ). Fundus fluorescein angiography made the choroidal folds obvious (Figure 1f ). She was diagnosed to have diffuse anterior scleritis and posterior scleritis (panscleritis) with secondary ciliochoroidal effusion and ACG in RE. She was started on topical atropine sulfate drop 1% thrice a day, brimonidine tartrate drop 0.15% twice a day, prednisolone acetate 1% 4 times a day in RE, tablet acetazolamide 250 mg twice daily, and intravenous methylprednisolone 1 mg once daily for three consecutive days. At day two, there was an improvement in lid swelling, ocular pain, ocular motility, conjunctival chemosis, and congestion, and the vision improved to 6/9 in RE. The anterior chamber deepened and the IOP was 8 mmHg in RE. Oral acetazolamide were stopped. After three days of pulse steroid, she was shifted to oral prednisolone 1 mg/kg/day and atropine/prednisolone drops were continued. At 1 week, the UBM showed resolved ciliary effusion. She was negative for antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibody (P-ANCA, and C-ANCA), anti-citrullinated cyclopeptide (anti-CCP), and VDRL (venereal disease research laboratory). Angiotensin converting enzyme, chest X-ray, and Mantoux were unremarkable. Erythrocyte sedimentation rate was 28 (normal 0–20) mm in the first hour, and C-reactive protein was 21 (normal <10) mg/L. There was no history of tick bite or herpes zoster ophthalmicus. The oral and topical steroid was tapered and atropine/antiglaucoma drops were stopped. At 1 month, her best-corrected visual acuity was 6/6 in either eye, the eyes were quiet, and the choroidal folds in the right eye had disappeared (Figure 2a ). The eye remained stable till the last follow-up at 8 months, and the anterior chamber remained deep (Figure 2b ).


This is a case of 25-year-old G4P1021 diagnosed with an in utero fetal stroke at 26 weeks gestation. She had ultrasounds at 19 weeks and 23 weeks, which showed no anatomic abnormalities (see Figures and ). She presented to labor and delivery at 26 weeks complaining of vaginal spotting. Labor and rupture of membranes were ruled out; however she had a Category II tracing with minimal to absent variability. Ultrasound exam revealed severe ventriculomegaly, a left-sided frontal porencephalic cyst, enlarged 4th ventricle, mild abdominal ascites, open hands, and echogenic bowel (see Figures and ). A thrombophilia panel, antiphospholipid panel, cytomegalovirus and toxoplasmosis antibodies, and neonatal alloimmune thrombocytopenia panel were ordered and were negative. She went into spontaneous preterm labor at 26 weeks 4 days' gestation and delivered a female infant, weighing 895g with APGARS of 1, 1, and 1, at 1, 5, and 10 minutes of life. Heart rate was in the 60s and abnormal rigid tone was noted. Intubation did not improve saturations (never over 60% despite correct placement confirmed), and chest x-ray showed bilateral whited out lungs. Compressions and chest tube placement did not yield improvement. Umbilical vein catheterization was unsuccessful and surfactant and epinephrine were given via the endotracheal tube. Despite extensive resuscitative efforts, there was no improvement in the clinical status, and the mother opted to switch to comfort care. Vesicular lesions were noted on the infant, which were positive for HSV2 by PCR (see ). A postmortum ventricular tap was performed and cerebral spinal fluid was also positive for HSV 2.
Her first clinically documented HSV outbreak was immediately prior to pregnancy and she was treated with acyclovir. She became pregnant approximately 5 weeks later. A 6-week ultrasound confirmed those dates. She was seen for her initial prenatal exam at 11 weeks, which confirmed a positive HSV-2 IgG. She had no further outbreaks during pregnancy, and her pregnancy was otherwise uncomplicated. She was not on suppression during her pregnancy, though it was planned for 36 weeks.


The informed consent was provided by the patient, and ethical approval was warranted by the First People's Hospital of Huaihua.
A 49-year-old man presented with a 5-month history of back pain who was diagnosed with fourth thoracic vertebral body fracture caused by tumor cells based on pathology results. The tumor cells in the fourth thoracic vertebral body originated from hepatocellular carcinoma. The preoperative thoracic magnetic resonance imaging (MRI) showed a minor intraspinal space-occupying lesion in the fourth thoracic vertebra canal and found pathological fractures of the fourth vertebrae (). Back pain as the only clinical symptom without any weakness, numbness, or other symptoms of spinal cord injury in both lower extremities was reported to the physician. And then, he accepted the percutaneous vertebroplasty (PVP) plus interstitial implantation of 125I particles (10 particles) at a local county hospital (). Back pain was relieved postoperatively, 3 days after he received PVP combined with interstitial implantation of 125I seeds. However, back pain, bilateral lower extremity weakness, and loss of bladder control reoccurred on day 3 after surgery and got worse. A general physical examination and central nervous system examination upon patient admission revealed abnormal findings. The majority of symptoms encompassed pain and hypoesthesia below the processus xiphoideus. The abdominal reflex, the crissum and cremasteric reflex, and the knee and ankle reflex could not be induced. No pathological reflection of Babinski's sign was induced. The strengths of the major muscle of both lower limbs were 3 grades and progressively decreased in the postoperative period. The opiate drugs were used to control pain originating from the surgical site. He was admitted to our hospital after 44 postoperative days because of serious back pain. The postoperative transverse computed tomography (CT) revealed bone cements and metallic implants in T4 without any bone cement leakage, but the MRI showed the left intraspinal space-occupying lesion in the T4 vertebral body (). And the enhanced CT indicated the possibility of tissue tumor, which was also confirmed by thoracic vertebra magnetic resonance imaging (). However, no powerful evidences could be used to confirm that the intraspinal space-occupying lesion was a tissue tumor (). In fact, the results of MRI showed the high signal intensity in T2-weighted and fat-suppression images in the T5 body level (). Notably, there are several particles located in the vertebral posterior wall without appropriate distribution (). The above clinical symptoms may be caused by delayed radiation-induced myelopathy or spinal cord compression. This patient died after 5 months of surgery because of multiple organ failure.


A 44-year-old male was admitted to our hospital in September 2015 with the chief complaint of vomiting blood. His medical history included long-term use of medications (diazepam and sodium valproate tablets) for epilepsy. Laboratory testing revealed mild anemia (hemoglobin level 103 g/L). The serum levels of carcinoembryonic antigen, carbohydrate antigen 199, carbohydrate antigen 125, and alpha-fetoprotein were in the normal ranges. A gastroduodenoscopy identified a protruding lesion with an ulcerated surface in the cardia. A biopsy specimen suggested chronic superficial gastritis. Endoscopic ultrasound (EUS) revealed a solid submucosal mass 2.2 × 3.0 cm in size (Fig. ) located 40 cm from the incisors. The mass had a mixed echo pattern with an intact muscularis layer.
Based on the above findings, ESD was performed (Fig. ). First, the lesion area was marked, and the submucosal layer of the lesion was injected with a mixture of glycerin fructose, epinephrine, and indigo carmine. Next, en bloc resection was performed using a hook knife (KD-620LR). During the procedure, cauterization for bleeding on the resected surface was accomplished by argon plasma coagulation. The postoperative course was unremarkable.
Microscopic examination showed that the tumor had invaded the submucosal layer. Histologically, the tumor was predominantly composed of ductal epithelial and myoepithelial cells, and the tumor cells were arranged mostly in a tubular pattern and partly in a cribriform pattern (Fig. ). Immunohistochemically, the tumor cells expressed cytokeratin, cluster of differentiation 117, p63, and calponin. Based on these findings, a diagnosis of ACC at the gastroesophageal junction was established. Because part of the basal resection margin was positive, radical resection was suggested. Subsequently, the patient underwent total gastrectomy with D2 lymphadenectomy and Roux-en-Y esophagojejunostomy. The resected specimen showed an ulcer at the gastroesophageal junction. The ulcer was composed of inflammatory granulation tissue that invaded the superficial muscular layer. However, there was neither residual tumor nor lymphatic metastasis (total of 25 lymph nodes collected) in the surgical specimens. Finally, the pathological staging of this case was considered as pT1bN0M0 (stage IA) according to the “American Joint Committee on Cancer (AJCC) 8th edition”. Postoperative assessments were unremarkable, and the patient was discharged. Follow-up was performed every 3 to 6 months and involved a complete blood count, chemistry profile, tumor markers, and multidetector-row computed tomography. A gastroduodenoscopy examination was performed annually. No sign of recurrence has been detected during 36 months of follow-up as of October 2018.
The patient has permitted and provided informed consent for the publication of his medical data.


54-year-old white male presented with three weeks of fatigue, dyspnea, and cough productive of white sputum. Past medical history was notable for burn injury at age 7 involving 90% total body surface, hypertension, hypertrophic cardiomyopathy, and mitral regurgitation. Nine months prior to this presentation, he sought medical care for 10 x 12 cm left flank burn scar ulcer, and multiple punch biopsies confirmed poorly differentiated cSCC. He was treated by surgical excision with 2 cm margin and split-thickness skin grafting. Lateral surgical margins were positive, and adjuvant radiotherapy of 6000 cGy in 30 fractions was delivered.
On examination, the patient was alert and oriented, afebrile, tachycardiac, tachypenic and requiring supplemental oxygen. Skin examination was notable for overt signs of burn scars throughout his whole body with significant scarring and decreased air-entry on the left lower chest. Cardiovascular, abdominal, and neurological examinations were normal. Laboratory tests were significant for leukocytosis and hypercalcemia of malignancy with suppressed parathyroid hormone levels.
Chest X-ray (CXR) showed left-sided pleural effusion (Figure ). Computed tomography (CT) of chest, abdomen, and pelvis showed marked thickening of left posterolateral chest wall skin with soft tissue extension, ribs destruction and bulging into left retroperitoneum and left lower pleura, large left-sided pleural effusion with pleural thickening, left lower lobe pneumonia, and new bilateral lung nodules concerning for metastasis (Figure ).
Pleural fluid cytology showed malignant cells in small clusters and separately. The cells displayed a high nucleocytoplasmic ratio, prominent nucleoli and relatively dense cytoplasm (Figure ). A battery of immunocytochemical stains was performed to further characterize the cells. The malignant cells were negative for TTF1, CK7, and B72.3 excluding a poorly differentiated adenocarcinoma. The cells were also negative for Melan A and Calretinin excluding malignant melanoma and mesothelioma, respectively. The malignant cells showed strong cytoplasmic immunoreactivity to keratin as well as strong nuclear staining with P40, diagnostic of poorly differentiated squamous cell carcinoma (Figure ). The patient deteriorated in the following weeks and passed away from progressive disease.


A 71-year-old male patient with a past medical history of hypertension and coronary artery bypass surgery (CABG) presented to the neurology clinic with weakness in both lower extremities, progressively worsening tingling and numbness, and difficulty in getting up from the chair. He had a history of having laxity in both ankles since his 20s. He also had a tendency of his feet to turn inwards, trip, and subsequently sprain his ankles. Also, the patient reported that his balance and gait had worsened in the last few years leading him to use orthotics for one to two years. The patient denied any significant alcohol intake. Family history also reported having hammer toes in immediate family members involving his mother, sibling, and daughter.
Physical exam was remarkable for bilateral high arched feet, pes cavus deformity with Achilles contracture, wasting of distal legs and feet, and weakness in bilateral toe flexors and scoliosis. Sensations were decreased to pinprick bilaterally just below the knee in the lower limbs and at the wrist crease in the upper limbs. Proprioception was impaired in toes (great toe) and fingers (index finger) bilaterally. The vibration was absent at the feet, ankle, and the hand. Hip flexion and knee flexion were 4/5 bilaterally. Foot dorsiflexion was 3/5 bilaterally and foot plantar flexion was 4/5 bilaterally. The patient could not stand on his heels and could not do tandem gait. Romberg’s sign was positive.
The initial lab studies were remarkable for mildly elevated creatinine phosphokinase (CPK) at 295 U/L, normal complete blood count (CBC), complete metabolic profile, HbA1C, Vitamin B12, serum protein electrophoresis (SPEP), kappa/lambda ratio, and TSH levels. Antidromic sensory nerve conduction study (NCS) of bilateral sural nerve showed reduced sensory nerve action potential amplitude (right = 0.5 uV and left = 0.6 uV, normal >5 uV). NCS of the right peroneal motor nerve showed significantly reduced compound muscle action potential amplitude (0.6 mV), and NCS of the right tibial nerve was absent. Right median motor NCS showed reduced CMAP amplitude (4 mV, normal >5 mV) with slowed conduction velocity of 25 m/s (normal >40 m/s). Hereditary neuropathy panel through GeneDx was sent, which reported the presence of a novel heterozygous mutation of the PRX gene with K1062N (s1062Asn).


A 78-year-old male presented with chief complaint of chronic and worsening left hip pain. Relevant history included an intertrochanteric hip fracture that had been treated one year prior with a cephalomedullary nail. Prior to hip fracture, the patient could walk without any assistive devices and was a high-functioning community ambulatory. Following the injury, the patient was limited to ambulation with the assistance of a walker. On physical examination, the left leg was significantly shorter than the right leg. Range of motion revealed an extremely limited range of the hip and impingement testing was positive. Infectious workup was negative for an infectious source. Neurological testing was unremarkable. Radiographs of the pelvis were obtained and demonstrated a hip fracture with a non-union of the intertrochanteric region of the femur, as well as penetration of the head screw through the femoral head. There was also screw penetration into the acetabulum and an LLD radiographically measured at 45 mm (Table ).
The preoperative plan included left hip THA. During surgery, computer-assisted navigation was used to assist with component placement and monitoring of changes in leg length. Intraoperative navigation measurements indicated a lengthening of 35 mm, which was confirmed on post-operative radiographs. Surgery was successful and the patient progressed well, experiencing significant pain relief and satisfaction with his surgery. He was discharged to home with a walker and within six weeks of follow-up, the patient had transitioned to walking with only a cane. At three months the patient was no longer using any assistive walking devices and at one year follow-up the patient was pain free and returned to his previous level of function prior to the hip fracture. Radiographs revealed that the left hip was well-aligned, with the left leg lengthened by 35 mm for a significantly improved post-operative LLD of 10 mm (Table , Figure ).


A 63-year-old female presented with a chief complaint of right hip pain. She reported a fall six months previously, which resulted in a displaced femoral neck fracture and was treated surgically with a cemented hemiarthroplasty. She described no relief from this procedure and had pursued relief through other conservative treatments without success. On physical examination, the right leg was substantially shorter, with a distinguishable LLD present. Neurological testing revealed that the index surgery was complicated by a sciatic nerve injury and the patient had a foot drop on the operative side. This had developed into significant heterotopic ossification. Radiographic examination of the pelvis revealed a substantial LLD of 37 mm. Infectious workup on the right hip was negative.
Following consultation with the patient, the preoperative plan included a revision of the hemiarthroplasty and conversion to a right hip THA. During surgery, computer-assisted navigation was again used to assist with component placement and monitoring of changes in leg length. Surgery was successful and the patient did well post-operatively. She reported significant pain relief and was satisfied with the outcome of her surgery. Radiographs revealed equalized leg lengths and implants were well aligned. The patient was able to ambulate by three months post-procedure without any assistive devices. Her foot drop from the index surgery remained stable and improved slightly over the next year. A leg lengthening of 35 mm was confirmed on post-operative radiographs, resulting in a post-operative LLD of 2 mm. At one year the patient was back to her normal functional status prior to her hip fracture (Figure ).


A 76-year-old female presented with right hip pain. Relevant history included a prior intertrochanteric hip fracture treated with a cephalomedullary nail with subsequent non-union and failure, occurring four months previously. Prior to her first hip fracture the patient was able to ambulate without any assistive devices and was a high functioning. Following hip fracture, the patient was limited to minimal ambulation with a walker and used a wheelchair for distances. On physical examination, the right leg was significantly shorter, with the LLD discrepancy measured grossly at approximately 30 mm. Range of motion was extremely limited and impingement testing was positive. Infectious workup was negative for an infectious source. Neurological examination was unremarkable. Radiographs revealed the patient had penetration of the head screw through the femoral head and penetrating the acetabulum. The radiographs also showed that the LLD was at 30 mm preoperatively.
Following consultation with the patient, the perioperative plan consisted of a conversion of the previous surgery and intertrochanteric mal-union to a THA, with soft tissue release and removal of the previous heterotopic bone. An imageless navigation system was used in order to help restore leg length and set the cup abduction and version given the large leg length discrepancy, massive heterotopic ossification, and destruction of the native acetabular anatomy. Surgery was successful and the patient was discharged to a rehabilitation facility with the assistance of only a walker. She described meaningful pain relief and was content with the outcome of her surgery. Within six weeks of follow-up, the patient had transitioned to a walker from the wheelchair and at three months follow-up the patient was walking without pain in the right hip. The right leg was lengthened by 30 mm, resulting in equalized leg lengths and well-aligned hips (Figure ).


A 64-year-old immunocompetent woman was referred to hospital for cerebral hemorrhage in left temporal-parietal region. CT angiography detected an aneurysm in the distal segment of left middle cerebral artery. Tiny fragments of brain tissue together with partially organized thrombus were surgically removed. Histologically, it was identified an artery, with an interrupted wall, occluded by thrombotic material (Fig. ). Small foci of large atypical lymphoid cells (Fig. , inset; Fig. ) were disclosed within thrombus. The cells were positive for PAX5 (Fig. , inset left), CD30 and MUM1 (Fig. , inset right) with partial expression of CD79α and CD20. The proliferative index (Fig. a) was high (Ki67 about 90%). The cells expressed LMP-1 and were diffusely positive for EBV by in situ hybridization for EBV-encoded RNA (EBER) (Fig. , b). Clonal immunoglobulin heavy chain (IGH) rearrangement was detected. A fibrin-associated diffuse large B-cell lymphoma was diagnosed. Staging procedures (CT scan and bone marrow biopsy) were negative. Three months later, CT scan showed an almost complete hemorrhage resorption. No further treatment was given. The patient is alive, free of disease at 8 months from diagnosis.


A 55-year-old male with a past medical history of paroxysmal atrial fibrillation, hypertension, hyperlipidemia, and gastritis, presented to our emergency department via ambulance with a chief complaint of lightheadedness, associated with nausea and vomiting. The patient reported feeling lightheaded two hours prior to arrival, along with nausea and three episodes of non-bloody emesis. The patient underwent cardiac ablation one month prior for his paroxysmal atrial fibrillation. He denied chest pain, shortness of breath, abdominal pain, syncope, weakness, numbness, or tingling. He received 324 mg of aspirin en route. On physical exam, his heart rate was significantly elevated at 191 beats per minute, and he was hypotensive with a blood pressure of 61/57 mmHg. His pulse oximetry was 98% on room air, and he was afebrile.
The patient's electrocardiogram (EKG) showed wide complex tachycardia (WCT) (Figure ). Since the patient was hypotensive, and therefore hemodynamically unstable, the decision was made to cardiovert the patient with informed consent. The patient was successfully cardioverted with 100 joules (J) of electricity on a biphasic device.
The patient’s heart rate improved to 89 beats per minute following the cardioversion, and his blood pressure normalized (Figure ). The patient was no longer lightheaded and nauseated. The patient’s troponin came back at 0.01 ng/mL (normal), he did not have any electrolyte abnormalities or anemia. His thyroid-stimulating hormone level was also normal.
The patient was admitted for cardiac workup, and started on flecainide and nebivolol (a beta1 selective blocker) by the cardiologist then discharged home. The patient remained in normal sinus rhythm throughout his hospital stay.


An 18-month-old male presented to the emergency department with five days of high-grade fever (T
max 102.3°F), cough, congestion, rhinorrhea, and dyspnea. The patient's mother also noted swelling and decreased movements of the right upper extremity the day before admission. He had no contributory past medical history. The mother had an uncomplicated pregnancy and good prenatal care. Birth history was uneventful with cesarean section at 41-weeks gestation.
The infant had poor follow-up with his pediatrician and had missed several vaccinations. Since birth, his diet was poor consisting of cow's milk and sparse solid foods. His motor and language development were delayed. He began crawling at 8 months, pulled to stand at 15 months, and had never walked at the time of admission. The only words he spoke were “mama” and “papa.” Family history was significant for childhood strokes in his maternal grandmother and maternal grandaunt.
Upon admission, the patient was mildly tachycardic at 148 beats per minute, but all other vital signs were within normal limits. On physical examination, he appeared somnolent, pale, and malnourished (weight, 10.52 kg-11th percentile and length, 80 cm-15th percentile). Cardiovascular examination was normal. On pulmonary examination, subcostal retractions were present, and rales were heard in the base of the left lower lobe. Abdominal examination was normal.
On neurological examination, cranial nerves II-XII and gross sensation in all extremities were intact. Deep tendon reflexes were 2+ in all extremities. Plantar reflexes were upgoing bilaterally. The left upper and bilateral lower extremities showed full range of motion. There was no active movement of the right upper extremity even after painful stimulation of the right hand. The right upper extremity was hypotonic, but tone was normal and symmetrical in all other extremities. There were no abnormal movements or tremor.
A comprehensive metabolic panel showed a serum chloride of 113 mmol/L, calcium of 7.8 mg/dL, phosphorus of 3.0 mg/dL, total protein of 4.8 g/dL, albumin of 1.9 g/dL, and a total bilirubin of 0.4 mg/dL. Lactate dehydrogenase was 340 IU/L.
A complete blood count showed platelet count of 177 × 103/µL, red blood cell count of 2.2 × 106 cells/µL, hemoglobin of 2.4 g/dL, hematocrit of 10.0%, mean cellular volume of 46.1 fL, mean corpuscular hemoglobin concentration of 23.8 g/dL, and red blood cell distribution width of 26.3%. An iron panel showed serum iron of 8 µg/dL, ferritin of 8 ng/dL, iron saturation of 2%, and total iron binding capacity of 351 µg/dL.
The patient was immediately transfused three units of packed red blood cells and given ferrous sulfate. With concern for pneumonia, a chest X-ray was performed revealing left lower lobe infiltrates. Broad-spectrum treatment was started with ampicillin. Blood and urine cultures were negative.
Suspicion for stroke led to magnetic resonance imaging of the brain which exhibited restricted diffusion in the left middle cerebral artery (ie, left cortical) and watershed distribution (Figure ). A four-extremity venous Doppler did not identify any deep vein thrombosis or other potential source of embolus. Magnetic resonance venography of the brain showed patent venous sinuses throughout. A computed tomography angiogram of the head and neck demonstrated a luminal irregularity and possible filling defect in the cavernous segments of the left internal carotid artery (Figure ). Magnetic resonance imaging on day 12 of hospitalization showed resolution or changes of the ischemia (Figure ).
Thrombophilia studies showed a prothrombin time of 14.7 seconds, international normalized ratio of 1.13 partial thromboplastin time of 16.5 seconds, protein C of 41%, protein S of 74%, homocysteine of 3.4 µmol/L, and negative prothrombin and factor V mutations. The patient developed a rash after acetylsalicylic acid administration so he was given clopidogrel instead.
Right bundle branch block and signs of right ventricular hypertrophy evident on electrocardiogram necessitated further cardiology workup. A transthoracic echocardiogram found no evidence of right heart strain, systolic dysfunction, or intracardiac vegetations or thrombi. A small patent foramen ovale with left to right shunting was found.
His pneumonia eventually resolved, and on day 14 of hospitalization, he was discharged on iron supplementation and clopidogrel. Following discharge home, he began to drink less cow's milk and eat regular foods. Over time, he regained strength and tone of his right arm. However, his development continued to be delayed. At 24 months, he still did not say more than a few words and was only able to take a few steps. Follow-up laboratory tests 7 months after his hospitalization were normal except for persistently low protein C of 47%. Whole exome sequencing is still pending.


An 83-year-old woman diagnosed with primary open angle glaucoma was referred to Tsukazaki Hospital due to uncontrolled ocular pressure in December 2015. At the first visit, the IOP was 28 mmHg in both eyes under maximum anti-glaucoma eyedrop treatment. The mean deviation given by Humphrey Visual Field Analyzer (30–2 program) was −23.86 dB in the right eye and −16.31 dB in the left eye. We performed an EXPRESS shunt surgery on both eyes in the superotemporal area in January 2016 and a needling procedure on the left eye in May 2017. Thereafter, IOP in her left eye remained high (22 mmHg with the use of 2 types of anti-glaucoma eyedrops). Therefore, we performed Baerveldt 350-mm2 implantation at her inferotemporal area, placing the tube at the sulcus on December 3, 2017. The next day, 4Δ hypertropia (HT) was detected in alternate cover testing (APCT) with prism measurement in primary gaze, and significant ocular motility disturbance caused diplopia in gaze to the quadrant direction from inferior to temporal in which the Baerveldt 350-mm2 was implanted. Although the IOP was controlled well between 15 and 20 mmHg in her left eye, diplopia did not improve for 3 weeks. The Hess chart suggested persistent motor disturbance of both inferotemporal and superonasal directions (Fig. A), which could be attributed to the following reasons: motor disturbance in the inferotemporal direction due to the large size of the Baerveldt implant and motor disturbance in the superonasal direction due to muscle contraction of the rectus muscles under which the Baerveldt implant was placed. On December 23, 2017, we performed a plate reduction surgery for the Baerveldt 350-mm2 glaucoma implant. In this procedure, we first confirmed the resistance to both inferotemporal and superonasal directions and the absence of apparent adhesions and scar tissues. Then, we cut and removed the plates placed beneath the lateral rectus muscle and inferior rectus muscle, which were thought to be responsible for diplopia (Fig. A–E). After the procedure, diplopia improved subjectively, but there was no drastic objective change with remaining 4Δ HT in APCT in primary gaze. We prescribed prism glasses (3Δ base down [BD] for the left eye) for remaining mild diplopia for this patient. Thereafter, IOP was controlled well between 13 and 15 mmHg in her left eye with only topical Dorzolamide 2%. On January 21, 2019, 1 year after the operation, significant objective improvement (2Δ HT in APCT with less ocular motor dysfunction demonstrated in the Hess chart (Fig. B)) was finally observed.


A 70-year-old male patient with the past medical history of end-stage renal disease (ESRD) presented with complaints of right-hand weakness, clumsiness, and pain which developed after one month of brachiocephalic vascular graft surgery. He also experienced a similar kind of a pain in the right hand immediately after the surgery, but it was thought to be secondary to the post-surgical pain at that time. He denied any similar symptoms in the left hand. On the neurological examination, he was noted to have weakness and sensory loss in the right hand, which predominantly involves both median and ulnar nerve distribution (Figure ).
Nerve conduction studies (NCS) of the right upper extremitity showed reduced motor amplitudes in the median and ulnar nerve. NCS also showed absent sensory amplitudes in the median and ulnar nerves and reduced sensory amplitude in the radial nerve as well. The needle EMG (electromyography) of the right hand showed denervation affecting multiple intrinsic hand muscles supplied by median and ulnar nerves with sparing of more proximal muscles (Table ).
The Doppler ultrasound studies showed low arterial pressure in the affected hand but with no evidence of vascular steal phenomenon. However, immediately after the vascular access was ligated, his grip strength, involving radial half of digits and thumb was improved, but flexion of the ulnar half of digits continued to show impairment. (Poster: Shah, S, Govindarajan, R. Ischemic Monomelic Neuropathy after Arteriovenous Fistula Surgery: Clinical Features, Electrodiagnostic Findings, and Medicolegal Issues. American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting; 09/14/2016).


A 25-year-old male without significant past medical history presented to the neurosurgery clinic with worsening left shoulder and neck pain. Magnetic resonance imaging (MRI) revealed a 2.6 x 1.1 cm intradural extramedullary mass within the left C2-3 neural foramen consistent with schwannoma. The patient underwent left C2-3 hemilaminectomy with complete resection of the tumor. The 2 x 1 cm dural defect was repaired in a water-tight fashion with suturable collagen matrix (DuraGen®, Integra LifeSciences, Plainsboro, NJ, USA) and covered by fibrin sealant (Tisseel®, Baxter Healthcare, Deerfield, IL, USA). There were no complications, and he was sent home four days later. On postoperative day eight, the patient returned to the emergency room with symptoms of nausea, vomiting, headache, and photophobia that worsened when he was upright. MRI showed a large pseudomeningocele at the surgical site (Figure ) for which lumbar drain was placed. The patient’s symptoms returned after the drain was removed five days later. Therefore, the decision was made to proceed with surgical exploration and repair.
A lumbar drain was inserted at the beginning of surgery. The posterior cervical incision was opened and explored. The 2 x 1 cm dural defect was localized, and suturable DuraGen® was used to repair the defect completely. A piece of fascia and fat graft were laid over the dura and covered by Tisseel®. The 2 x 2 cm absorbable sponge from the extra-small BMP kit was soaked with 1.4 cc rhBMP-2 and laid over the top. The suction drain (Hemovac®, Zimmer Biomet, Warsaw, IN, USA) was inserted, and the wound closed in a standard anatomical layer fashion without any complications.
The lumbar drain remained in place and was open to drain for five days. The patient was discharged home on postoperative day six. He was followed clinically for 15 months after surgery. The MRI at 16 months post-surgery showed no evidence of recurrent tumor, CSF leak, infection, extraneous bony growth, excessive inflammation, or neoplasm (Figure ).


A 72-year old female presented to her family physician in February 2017 with severe post-prandial epigastric and lower sternal pain. The diagnosis of cholecystitis was made, and the patient was started on antibiotics, which alleviated her abdominal pain. An abdominal ultrasound in April 2017 showed multiple calculi in the gallbladder, the largest of which measuring 1.9 cm, as well as echogenic sludge bile. In July 2017, she had a laparoscopic cholecystectomy. Intraoperatively, there was significant distension and inflammation of the gallbladder, and there were two large lymph nodes below Hartmann’s pouch in a pericaval position. One of these nodes was biopsied. Post-operative pathology showed a > 2 cm adenocarcinoma of the gallbladder, which arose from a segment of the corpus in continuity with the hepatic bed. A 3 mm margin was obtained. Although there was no identifiable lymphovascular invasion or perineural invasion, pericaval lymph node histopathology was positive for metastasis. Final pathologic staging was pT2 N2.
A computed tomography (CT) scan of the chest, abdomen, and pelvis in July 2017 (Figure ) identified multiple mesenteric and retroperitoneal lymph nodes: a right periaortic lymph node measuring 11 x 9 mm and a left mesenteric node measuring 11 x 8 mm. A positron emission tomography (PET) scan in August 2017 (Figure ) showed multiple fluorodeoxyglucose (FDG) avid para-aortic and aortocaval lymph nodes, the largest measuring 1.3cm with a standardized uptake value (SUV) max of 6.3. There was also a sub-centimeter FDG avid peri-portal lymph node. Uptake in the uterus and adnexal regions were physiologic at that time. The patient was assessed at the provincial pancreas tumor rounds, and the group consensus was for adjuvant systemic therapy. She was started on gemcitabine and cisplatin combination in October 2017 and completed eight cycles in total by March 2018. A CT scan in March 2018 (Figure ) showed a resolution of the previously observed porta hepatis and aortocaval lymph nodes, with no new lymphadenopathies. Given the promising scan, she elected to continue and eventually completed 13 cycles of chemotherapy.
She was well in follow-up, and a CT scan in January 2019 showed a mildly heterogeneous uterus at the fundus. The pelvic US showed a 2 cm mass in the left side of the uterus and a fluid-filled space on the right side of the uterus measuring at least 2.8 cm x 1.2 cm. During an exam by a local gynecologist, a large and irregular cervix was noted. Background hysteroscopy showed a 1.5 cm fibroid in the left posterior wall. She was referred to a multidisciplinary gynecologic oncology clinic for diagnosis and workup of cervical cancer. She denied any abdominal pain, bloating, or per vaginal bleeding. She had hypothyroidism but was otherwise healthy. She had an unremarkable gynecologic history, was Gravida 1 Para 1, had no history of hormonal replacement, but she did not have regular pap smears. On physical exam, there was an exophytic, vascular mass replacing the entire cervix, measuring 5 cm AP, 5.5 cm LR, and 4cm SI. There was left parametrium involvement, but no sidewall involvement or right-sided parametrium involvement. The pelvis-rectal exam was normal.
A biopsy of the cervix and endometrial curettage were performed. Pathologic review of the biopsy specimens was remarkable for an infiltrating adenocarcinoma with high-grade nuclear features, readily identifiable atypical mitotic figures, mucin production, and a prominent desmoplastic stromal response. While consideration was given to an endometrioid endometrial carcinoma, the histomorphology was remarkably similar to that of the patient’s previous gallbladder adenocarcinoma. The tumor infiltration pattern was also in keeping with metastasis, given the regular intermixing of resident normal/reactive endometrial and endocervical glands (Figure ) with the tumor. Downstream immunohistochemical workup was performed on the endometrial curetting sample, which showed that the lesional cells were immunopositive for CK7, CK20, and CDX2 (Figure ) and were immunonegative for PAX8, ER, PR (Figure ), p16, with a wild type p53 staining pattern. This immunohistochemical profile evidenced intestinal-type pancreaticobiliary differentiation and was supportive of the morphological impression that this endometrial/cervical lesion represented a metastatic adenocarcinoma compatible with the patient's known primary gallbladder adenocarcinoma.
The PET scan in March 2019 showed a new 1 cm, moderately FDG-avid focus in the pancreatic head (SUV max 4.9), a 1.1 cm aortocaval node SUV max of 6.3, and new SUV max 20 uterine mass measuring 8.4 cm. Low-grade FDG uptake in the left external iliac node SUV max 3.4 was also observed. Magnetic resonance imaging (MRI) showed a similar finding of a large uterine mass extending down and involving the entire cervix, with potential involvement of the left parametrium. In the provincial gynecologic tumor rounds, the consensus was that the patient should consider further palliative chemotherapy with gemcitabine and cisplatin.


A 29-year-old woman was treated in 2013 for ACC of the parotid (T3N0M0). She had
parotidectomy of the left parotid gland with ipsilateral selective lymph node
dissection level II to IV preserving the facial nerve. The treatment was followed by
external beam irradiation to the parotid area and the neck. Afterward, she was
regularly followed-up in our consultation. Five years after primary surgery, the
patient consulted with pain in the right hypochondrium. In the clinical examination,
the patient was anicteric, and abdominal examination found an irregular mobile
considerable tumefaction of the left liver. There was no recurrence in the surgical
site and neck.
A computed tomography (CT) scan revealed a single liver lesion that was suspicious of
metastasis (). The
CT scan of the brain, head, neck, and chest did not reveal other distant
metastasis.
Magnetic resonance imaging of the liver affirmed a solitary liver lesion. It was a
heterogeneous, large mass measuring 21 × 9 cm with a contrast agent enhancement of
the left lobe of the liver that was suspicious of metastasis. A CT-guided needle
biopsy of the mass was done and revealed a metastatic ACC of the parotid. A
multidisciplinary staff decision was made to perform chemotherapy to down-size the
lesions, followed by hepatic metastasectomy. The young age and the presence of a
single metastatic localization were the arguments justifying the hepatic surgery on
our patient.
After 3 cycles of Navelbine-CDDP-based chemotherapy and in view of the stability of
the lesion objectified on the CT scan, we decided to do a chemo-embolization, which
failed due to extensive vascularization and of the technical difficulties.
After an evaluation of liver function, calculated at 40% by volumetric CT, the
patient had a laparotomy and we found a voluminous exophytic tumor. It was white
grayish color measuring 21 × 19 × 12 cm. The mass was appended to the liver segment
(III, IV) surface. Wedge resection of the tumor while keeping sufficient liver
parenchyma was done. Intraoperative ultrasound was performed and revealed no more
lesions.
The patient had no postoperative complications. There was no liver dysfunction, and
she left the hospital on the 15th postoperative day in good health condition.
A histologic examination showed that the tumor measured 21 × 19 × 12 cm with
disease-free surgical margins. The microscopic appearance showed that the tumor mass
is pushing out toward the hepatic tissue. The tumor was organized in cribriform
growth pattern displaying several prominent pseudocysts surrounded by basaloid cells
with hyperchromatic-angulated nuclei. These pathological findings are suggestive of
metastases from the ACC ( and ).
At the 6-month postoperative follow-up examination, magnetic resonance imaging of the
abdomen showed that the patient is currently disease-free. One year after the
surgery, she has regularly been followed-up at the consultation and has no signs of
recurrence.


A 67 year-old Caucasian female with no prior oncologic history presented to a local hospital with a multi-week history of right lower extremity edema and pain. CT abdomen/pelvis identified a 17.5 × 8.8 × 5.2 cm lobulated retroperitoneal soft tissue mass extending into the right pelvis without evidence of metastases (). CT-guided core needle biopsy demonstrated a high-grade, poorly differentiated neoplasm (). Given concern for primary RPS she was referred to our institution for further workup.
She was evaluated by surgical oncology and discussed at a multidisciplinary sarcoma tumor board that recommended primary resection if staging scans were negative for metastatic disease. CT chest/abdomen/pelvis identified primary mass progression to 20.5 × 10.3 × 7.1 cm and new right common iliac lymphadenopathy without metastases (). CT-guided re-biopsy and immunohistochemistry (IHC) demonstrated unclassified round cell sarcoma with INI1 loss (). Unfortunately, the patient progressed during work-up, and on reevaluation resection was not recommended due to symptomatic progression rendering resection highly morbid.
PET/CT identified a bulky centrally necrotic right retroperitoneal soft tissue mass (SUVmax 21.4; liver SUVmean 2.3) extending into the right hemipelvis, a soft tissue nodule medial to the right psoas muscle (SUVmax 16.4), several non-enlarged FDG-avid paracaval lymph nodes (SUVmax 13.5), and faintly metabolic right external iliac and inguinal lymph nodes (). A single FDG-avid, non-enlarged left supraclavicular lymph node (SUVmax 8.6) was identified but not amenable to biopsy (stage IV: cT4N1M1; ). Systemic first-line chemotherapy was recommended. No EWSR1 fusion gene was identified by FISH (Abbott Molecular, Des Plaines, IL). Next-generation sequencing (NGS) of the primary tumor biopsy was negative for common gene fusions (EWSR1, CIC, or BCOR; ).
Due to rapidly progressing symptomatic disease the patient was referred to radiation oncology. Palliative proton radiotherapy was recommended to the primary mass and adjacent FDG-contiguous lymphadenopathy [50 Cobalt Gray Equivalents (CGE)/25 fractions, 2 CGE/fraction; Mevion S250, Mevion Medical Systems, Inc., Littleton, MA] due to the tumor location, size, and close proximity to the right kidney and small bowel (). The patient was informed that adjuvant systemic therapy was needed to treat the metastatic disease. Radiotherapy was delivered over 38 days without complications. Peripheral blood counts remained stable throughout treatment (absolute lymphocyte counts: 0.9–1.1 k/mm3, lower limit of normal: 1 k/mm3); the patient had mild, asymptomatic Grade 1 lymphopenia before and after radiotherapy ().
PET/CT 1 month after radiation demonstrated disease progression at multiple sites outside of the radiotherapy field including the left supraclavicular lymph node (2.7 cm, previously 1 cm; SUVmax 18.1; liver SUVmean 2.6), T12-L1-adjacent retroperitoneal mass (1.4 cm; SUVmax 21.9, prior SUVmax 10.9), and new FDG-avid nodal metastases (RECIST 1.1; ) (). The primary RPS decreased in size and FDG-avidity (20.5 × 10.3 cm to 8.7 × 4.5 cm; SUVmax 20 to 7.1; ). The patient reported significant improvement in right lower extremity edema, pain, range of motion, and performance status.
CT-guided needle biopsy of the left supraclavicular lymph node revealed metastatic disease from primary RPS (). The patient was offered palliative chemotherapy for disease progression on a clinical trial. NGS of the primary tumor re-biopsy identified a nonsense mutation in SMARCB1 encoding INI1, confirmed by IHC loss of INI1 expression; no actionable mutation(s) outside of clinical trials were identified (FoundationOne CDx™, Foundation Medicine, Cambridge, MA; ). Tumor mutational burden and microsatellite stability were low, suggesting a lower probability of response to ICB ().
The patient refused additional treatment and continued on close surveillance. PET/CT performed 5 months after radiation demonstrated near complete metabolic response of the biopsy-proven left supraclavicular metastasis (SUVmax 3.2, previously 18.1; liver SUVmean 2.5), and size reduction to <10 mm, with residual focal FDG avidity in the right retroperitoneum (SUVmax 4.4, previously 6.5) consistent with post-radiation changes vs. residual disease without other abnormal metabolic activity ().
The patient continued to improve, with interval imaging at 6, 10, 13, and 17 months post-radiotherapy demonstrating residual RPS/scar tissue and resolved metastases (). Given the prolonged disease-free period without adjuvant therapy the patient agreed to PD-L1 assessment for ICB using nivolumab (28-8 pharmDx, PhenoPath; Seattle, Washington). PD-L1 expression was >/=1% for the primary RPS [tumor proportion score (TPS) 1–5] and metastatic left supraclavicular lymph node (TPS 1–10). CD4 and CD8 IHC on the pre-radiation RPS biopsy demonstrated TILs (CD4 10% positive, CD8 2% positive; 5:1 ratio) arranged in scattered nodules with patchy single-cell infiltration throughout, with similar results found for the non-irradiated left supraclavicular lymph node biopsied 1 month after completing radiation (CD4 10% positive, CD8 2% positive; 5:1 ratio; , ).
The patient remains without evidence of new metastatic disease, completely regressed metastatic lesions, and nearly resolved primary RPS with residual scar tissue. She is nearly 2 years from initial diagnosis and ~1.5 years following proton radiotherapy. If her disease progresses she may receive chemotherapy or ICB based PD-L1 expression ().


A 65-year-old man was admitted due to dizziness, diplopia, and gait imbalance for 3 days. He had been a heavy drinker for more than 10 years with daily consumption of about 400 ml of the Korean liquor, Soju. Soju is the most popular liquor in Korea which is a clear, colorless distilled beverage made from rice with 17% ~ 53% alcohol content (alcohol by volume, ABV). Neurologic examination revealed an alert mentality but frequent inattentiveness and disorientation, dysarthria, and severe truncal ataxia with dysmetria in his upper arms. Spontaneous downbeat nystagmus was observed during with and without fixation, and horizontal and vertical gaze-evoked nystagmus were also detected. On saccadic commands, extraocular movement in all directions was markedly limited which did not improve with oculocephalic maneuvers. The video head-impulse test (vHIT) revealed decreased gain with bilateral catch-up saccades for both horizontal semi-circular canals (, P-1). A bithermal caloric test revealed a severely decreased caloric response bilaterally (<5 deg/sec), and the patient had almost no response in the rotation chair test (time constant <3 s) (). Visuospatial memory was assessed during the acute period within a week after symptom onset but clear mentality, with block number, block design, and Corsi block tests, with results shown in . Blood thiamine level was 51 μg/ml (normal range 59–213 μg/ml) at admission. T2-weighted and FLAIR MRIs showed hyperintense lesions at the periaqueductal gray matter, medial thalami, and dorsal medulla (, P-1′). Follow-up ocular examination and vHIT a week after thiamine supplementation (100 mg intravenously daily) showed normalized and visuospatial memory improvement ().


A 38-year-old woman presented with a 1-month history of progressive vertigo, severe ataxia, oscillopsia, apathy, and psychomotor slowing. She was abstaining from food for religious reasons. Examination showed alert mentality but slight disorientation, perceptual disturbance, and impaired memory. Spontaneous upbeating nystagmus and horizontal gaze-evoked nystagmus were observed. Horizontal saccades were slow and limited (~30°) in both directions. The saccadic limitation did not improve with oculocephalic maneuvers. Horizontal vHIT revealed bilateral catch-up saccades (, P-2), and perverted catch-up saccades, i.e., upward deviation of both eyes followed by downward movement. She showed bilateral limb dysmetria and severe truncal ataxia, and she could not stand unaided. Bithermal caloric irrigation revealed no response, and the sinusoidal rotation chair test showed significantly reduced gain and an increased VOR lead phase. Time constants for pre- and post-rotatory nystagmus decreased markedly (2.5 s, normal 14.6 ± 3.7 s) (). Visuospatial memory decreased during the acute phase of the disease and improved after treatment (). Brain MRI revealed signal intensities in the medial thalami and periaqueductal gray matter (, P-2′). A week after thiamine treatment, follow-up vHIT normalized, and mental status, ocular signs, and ataxia recovered slowly.


A previously healthy 44-year-old man was admitted for mental change and ataxia. He had been a heavy drinker for several years, and recently, he had been fasting and drinking Soju for more than 10 days. Examination showed drowsy mentality with impaired orientation, increased deep tendon reflexes in both knees, bilateral dysmetria, and truncal ataxia. Horizontal saccades were slow and limited in both directions, and horizontal gaze-evoked nystagmus was observed. Horizontal vHIT revealed decreased gain and corrective saccades (, P-3). Caloric response was reduced bilaterally, and pre- and post-rotatory nystagmus on rotation chair tests had short time constants (). On brain MRI, a high signal intensity in the periaqueductal gray and medial thalami was observed (, P-3′). Three days after thiamine treatment, follow-up vHIT had normalized, and mental status, ocular signs, and ataxia recovered slowly. Visuospatial memory perception also improved after treatment ().


A 58-year-old man was admitted for vertigo, ataxia, and behavior change. He had been a heavy drinker consuming 600–1,000 ml of Soju daily. Neurological examination revealed impaired attention and truncal ataxia. He had no spontaneous nystagmus, but horizontal gaze-evoked nystagmus was observed. vHIT (, P-4), bithermal caloric test, and sinusoidal rotation chair test showed significantly reduced horizontal VOR gain. Brain MRI showed high signal intensity in the dorsal medulla and pons (, P-4′). A week after thiamine treatment, follow-up vHIT had normalized, and mental status, ocular signs, and ataxia recovered.


A 62-year-old man visited the hospital for severe ataxia and dizziness after consuming 1,000 ml of Soju daily for several months with no meal. Neurologic examination revealed gaze-evoked nystagmus, bilateral catch-up saccades on vHIT, dysmetria in both limbs, and severe truncal ataxia. On brain MRI, high signal intensity in the medial thalami and periaqueductal gray matter was observed (, P-5′).


The patient was a 3-year-old girl, the only child of Lebanese parents without direct consanguinity, with early onset of severe, recurrent pulmonary infections. Her first clinical manifestation occurred at 3 months of life, when she presented with fever without localizing signs. At that time, she was treated with intramuscular ceftriaxone for 3 days until she was admitted at an Intensive Care Unit due to bilateral pneumonia and pleural effusion. Then, she was submitted to pleural drainage and treatment with polymyxin, meropenem, vancomycin, and linezolid for 14 days. No etiological agents were identified in blood cultures and pleural fluids. At discharge, cefuroxime was prescribed for 10 days due to the persistent infection that was identified by radiological images.
At 4 months of age, she presented with oral moniliasis and Bacillus Calmette-Guérin (BCG) scar suppuration with slow healing. She was hospitalized for the second time at 6 months of age when she was diagnosed with bronchiolitis, with identification of Haemophilus parainfluenzae biotype I. She developed bilateral pneumonia, which did not respond adequately to ceftriaxone treatment and evolved to necrotizing pneumonia (). At that time, the patient was transferred to our hospital for evaluation by pulmonologists and immunologists. The patient was diagnosed with necrotizing pneumonia; left lung abscess; anemia, most likely secondary to infection; and stomatitis. She received a transfusion of red blood cell concentrate and was treated with ceftriaxone and linezolid and subsequently treated with meropenem and amphotericin B. Culture of material collected from bronchoscopy and bronchoalveolar lavage showed no growth of aerobic or anaerobic bacteria.
At this time, the patient was submitted to an immunological investigation, which revealed normal immunoglobulin levels, lymphocyte subset numbers, and complement system. Nevertheless, a dihydrorhodamine (DHR) test showed that the patient's stimulated granulocytes presented abnormal ROS production, a characteristic of CGD patients (). Thus, CGD prophylaxis was initiated with the administration of Bactrim, itraconazole, and IFNγ.
Despite prophylactic treatment, the patient continued to need hospitalization for pneumonia at 8 and 11 months of age that required systemic antibiotics. The first genetic analysis was performed on one of these occasions, although Sanger sequencing revealed no mutations in the NCF1 gene (data not shown). At this time, the patient's mother reported that one of the patient's female cousin had received two transplants for an unidentified immunological problem.
At 23 months of age, the patient presented with adenitis and cervical abscess, which were treated with ceftriaxone, clindamycin, and surgical drainage. She was discharged with cefuroxima treatment; however, 1 week later, she required medical assistance after developing right lobe pneumonia and atelectasis. These last conditions were treated with cefepime and prednisolone.
Whole-exome sequencing was performed to confirm or discard a CGD diagnosis, and sequence analysis revealed a mutation (c.256_257+2delAAGT NM_000433) in the NCF2 gene that leads to a K86Ifs*2 residue change in the p67−phox protein, which was confirmed by Sanger sequencing (). Sanger analysis also showed that the parents were heterozygous for the mutation. The sequence data were analyzed using the National Center for Biotechnology Information (NCBI) () and Ensembl SNP () databases, confirming this novel mutation in NCF2.
Prophylactic medications were maintained during patient follow-up. However, at 2 years and 7 months of age, she was readmitted with pneumonia that was treated with ceftazidima. Thorax computed tomography revealed pulmonary consolidation in the upper segment of the right lower lobe and areas of retractable stretch marks, with a bilateral sparse sequential aspect that was more evident in the posterior segment of the right upper lobe, the middle lobe, and the lingula (). Bronchoscopy showed non-purulent laryngotracheobronchitis, with negative results for acid-alcohol resistant bacilli, fungi, cytomegalovirus or Pneumocystis jirovecii, as well as normal serum galactomannan levels.
At 3 years and 5 months of age, the child was hospitalized with jugal abscess arising from a dental procedure. The abscess was drained, and she received ceftriaxone, clindamycin and oral steroids for 5 days. Once she presented an anaphylactic reaction to ceftriaxone, the patient received epinephrine and continued treatment with clindamycin and steroids for an additional 3 days. Thereafter, she was discharged under treatment with sulfamethoxazole and trimethoprim.