A 52-year-old female presented to her local ENT department in 2014 with progressive dyspnoea and biphasic stridor. She was a never-smoker with no prior medical problems or intubation episodes. Flexible nasendoscopy (FNE) revealed marked supraglottic stenosis and interarytenoid fibrosis with normal mobile vocal cords. IgG serology at presentation was normal. Over 3 years she underwent quarterly microlaryngobronchoscopy, steroid injection and balloon dilatation (MLB&D) and laser excision of interarytenoid fibrosis with transient symptomatic relief. Biopsies of sclerotic tissue demonstrated inflammation with fibrosis, plasma cell infiltrates, and increased IgG4 plasma cells consistent with a diagnosis of IgG4-RD. She was commenced on oral prednisolone and azathioprine, later switched to methotrexate, however her relapses continued to increase in frequency and severity, she was referred to our tertiary service in 2017 for further management.
At presentation to us, she underwent MLB&D, during which amorphous supraglottic scarring was noted and re-biopsied. Histologic analysis revealed moderate lymphoplasmocytic infiltrate and prominent stromal fibrosis with associated IgG4 plasma cells and an IgG4:IgG ratio of 80% in keeping with IgG4-RD. Serum IgG levels were normal. Ongoing medical optimisation was planned prior to laryngotracheal reconstruction, however she presented with acute worsening of symptoms from complete glottic obstruction before this could be completed. A surgical tracheostomy was performed following awake fibreoptic intubation, and she underwent endoscopic laryngotracheal reconstruction shortly after this acute episode (). Following division and excision of interarytenoid and supraglottic scarring and balloon dilatation, an Eliacher stent covered with a split skin graft was inserted. The stent was removed at 2 weeks with a much-improved calibre of supraglottic airway. She was systemically well post operatively, although she struggled to maintain adequate oral intake with evidence of aspiration on fibreoptic endoscopic evaluation of swallow (FEES) and underwent insertion of a radiologically inserted gastrostomy (RIG) for feeding. She has had one further MLB which demonstrated a clear supraglottic airway, healthy glottis, and minor posterior interarytenoid granulations which were injected with steroid. Following an intensive course of voice and swallowing rehabilitation, she reverted back to normal oral intake, the RIG tube was removed and she returned to full time employment. She remains under annual follow up.


A previously fit and well 15-year-old female presented via the emergency department in 2011 with a very short history of dyspnoea and biphasic stridor following unsuccessful treatment for presumed asthma. FNE revealed subglottic stenosis with mobile vocal cords and an urgent CT scan confirmed concentric soft tissue narrowing of the subglottis to 4 mm. She subsequently underwent emergency tracheostomy and laser MLB&D with symptomatic relief. Histology from the initial procedure had demonstrated chronic inflammation without underlying granulomatous disease, and an autoimmune screen at the time was negative.
Despite oral prednisolone, repeated MLB&D every 6 to 8 weeks provided only transient relief from restenosis, and a decision was made to perform a laryngotracheal reconstruction with posterior rib graft augmentation. Airway diameter augmentation was achieved using autologous rib graft posteriorly and a sternohyoid flap with split skin graft. This significantly improved her airway and she was discharged on prednisolone with the tracheostomy in situ. A postoperative baseline CT was performed which demonstrated extension of disease to involve the right hemilarynx, perilaryngeal fat and arytenoid cartilage. Histology from surgical specimens demonstrated inflammation with marked plasmacytosis and polyclonality on immunostaining, although immunocytochemistry for IgG4 was within normal limits (IgG:IgG4 less than 25%, 27 IgG4+ cells/high power field). Serological IgG and IgM levels were noted to be raised although IgG4 subclass have been within normal limits. With a presumptive diagnosis of IgG4-RD, she was managed with azathioprine and courses of rituximab by co-author AS.
Surveillance in ENT clinic has demonstrated stable appearances in her airway reconstruction, with a partial return of right vocal cord mobility, and she was decannulated the following year. Over the last 5 years peristomal tracheal scarring has warranted laser resection and the insertion of serial tracheal stents with adjuvant sirolimus therapy. Histologically, this recurrent stenosis has been demonstrated to be granulation and scar tissue unrelated to the previous IgG4-RD. She remains well with a good voice, receiving intermittent stent changes, and is presently studying medicine.


A 76-year-old male non-smoker was referred to our ENT department from Gastroenterology colleagues in 2014 with dysphagia and dysphonia following an oesophagogastroscopy, which had demonstrated laryngeal swelling in addition to gastritis and Helicobacter pylori infection. He is a retired carpenter with historic asbestos exposure and hypothyroidism, but no recent intubation episodes. FNE demonstrated supraglottic swelling, which was also seen as nonspecific oedema on CT imaging. He underwent MLB&D with laser debulking and steroid injection. Histology demonstrated florid subepithelial lymphoid infiltrate including numerous polyclonal plasma cells, 20% of which were positive for IgG4 (50 IgG+ cells/high power field). His serum IgG4 levels have always remained within the normal range, whist his autoimmune screen is consistently positive for P3 only.
Following a diagnosis of IgG4-RD, the patient was repeatedly offered immunomodulatory treatment and further surgery for restenosis. However, he has declined almost all medical intervention over a 30-month period due to a combination of personal bereavement and high level of fear regarding the risks of medication-associated side effects. He consented to a single MLB&D with steroid injection and laser pepperpotting of the supraglottis in July 2017, with histological findings consistent once again with IgG4-RD. Discussion within the Airway multidisciplinary team in December 2018 decided that, with the untreated progression of the disease, further surgery would likely need to be an extensive reconstruction with likely compromise of voice and swallow. Although his symptoms have continued to deteriorate, he continues to decline all treatment and we continue with a ‘watch-and-wait’ approach to his care.


A 49-year-old male non-smoker presented to us from his local ENT department in 2015 with a 2-year history of progressive hoarseness and inspiratory stridor unresponsive to a first locally-performed MLB and laser epiglottoplasty in 2016. An autoimmune serology screen at this time was negative and his past medical history consisted of gastroesophageal reflux and allergic rhinitis only. He had undergone a single intubation episode around the time of symptom onset for revision septoplasty. FNE demonstrated supraglottic scarring and an anterior web with restricted arytenoid movement bilaterally. He underwent MLB&D with laser pepperpotting of the supraglottis (). He developed recurrent supraglottic stenosis 1 year later requiring repeated MLB&D every 4 to 6 months, but histology demonstrated only chronic inflammation and fibrosis despite repeated staining including for IgG4. However, IgG4 positive staining was finally confirmed on biopsies sent in February 2019, showing that most infiltrating of plasma cells expressed IgG4.
Following this, a diagnosis of IgG4-RD was made and the patient was commenced on oral Prednisolone and reviewed by AS, but no further systemic site of disease has yet been identified. His IgG serology has remained within range at 0.9 throughout with a negative ANCA screen.


A 73-year-old male patient presented with complaints of pain in the right upper abdomen for 3 months, which was dull aching in nature and relieved with medication, only to recur again. He also noticed gradually progressive jaundice with cholestatic features and low-grade fever for 5 days. On examination, he was icteric, and on abdominal examination, there was no abnormality.
Biochemical investigation revealed elevated serum bilirubin (2.17 mg/dl) and alkaline phosphatase (630 IU/L). Ultrasound evaluation showed cholelithiasis with choledocholithiasis causing dilatation of biliary tree till intrahepatic biliary radicals. He underwent ERC, but during the procedure, while pulling the dormia basket with engaged stones, dormia basket got impacted at the ampulla and wires snapped close to handle []. Then, he was referred to our centre for further management. A contrast-enhanced computed tomography scan was performed which showed retained dormia basket with a dilated biliary system with no other injury [-].
In view of cholangitis with an impacted basket, he was taken up for emergency surgery and laparoscopic cholecystectomy with CBD exploration was planned. Longitudinal choledochotomy was performed in the supraduodenal part of the CBD, and choledochoscopy was performed through the epigastric port which showed a dormia basket with impacted stone in the lower CBD. The initial attempt to remove it with laparoscopic grasper was not successful. Then, another dormia basket was introduced through the choledochoscope and the tip of the broken dormia was engaged in it and pulled out of the CBD [-]. Impacted dormia basket with its broken wire along with all CBD stones delivered out. The basket along with stones was placed in an endobag and brought out through the epigastric port. Check choledochoscopy ascertained clearance of the bile duct both distally as well as proximally. CBD was then closed primarily with interrupted 3-0 polyglactin and the procedure was completed by performing cholecystectomy.
His post-operative period was uneventful and shifted to the ward. He was allowed orally on the 2nd post-operative day (POD) and his abdominal drain was removed on the 3rd POD and discharged on the 5th POD. At the end of 1-year follow-up, he was doing well with a normal liver function test.


Eighty one year old female with a past medical history of breast cancer with metastasis to the lung and pleura. She had radiation to the lung lesion 10 months ago and was started on gemcitabine every 2 weeks one month ago. She had finished 2 cycles of the chemotherapy and developed fever and shortness of breath, ten days after her second cycle. On presentation, she was hemodynamically stable but hypoxic with saturations at 88% on room air, which improved to 96% on two litres nasal cannula. Physical exam revealed decreased breath sounds bilaterally and moderate rales throughout, especially on the left side but no wheezing. Her initial work up included chest x ray which showed left upper lobe opacity. A CT scan chest was done which ruled out pulmonary embolism (PE) but revealed bilateral diffuse multifocal pneumonia, which was worse in the left upper lobe (). She was started on treatment with broad spectrum antibiotics and supplemental oxygen through a nasal cannula.
On Day 3 of her hospital admission, she became more hypoxic leading to increased oxygen requirements. A repeat chest x ray demonstrated bilateral airspace consolidations and interstitial markings which had worsened in comparison to the prior study. Blood cultures and sputum cultures still revealed no infection. Because of her worsening clinical condition, an alternative diagnosis such as gemcitabine induced pneumonitis was pursued and the patient was started on intravenous (IV) methylprednisolone 40 mg twice daily. She underwent flexible bronchoscopy with bronchoalveolar lavage (BAL) because of minimal improvement on steroids which was ultimately negative for infection and malignant cells. Despite her initially worsening picture, she gradually started to show improvement and was able to be off oxygen. Her IV steroids were switched to per oral (PO) prednisone 60 mg once daily with gradual tapering by 10 mg every 5 days. A repeat CT scan chest 2 months later showed complete resolution of pneumonitis ().


A 61-year-old woman visited the outpatient clinic for the treatment of a cardiac mass discovered during the workup performed prior to knee arthroplasty surgery. Transthoracic echocardiography showed a 0.8×0.9-cm mobile mass on the ventricular surface of the noncoronary cusp of the aortic valve without valvular dysfunction (, ). Computed tomography also revealed a mass-like lesion between the left ventricular outflow tract and the aortic valve (). Based on these reports, a PFE was suspected. Surgery was planned immediately because of the hypermobility of the mass at the aortic valve that could potentially cause a fatal cerebral infarction.
The aortic valve was morphologically normal in appearance (, ), and the tumor was removed using the slicing excision technique. After tumor removal, the aortic valve showed normal coaptation without leaflet injury, while postoperative transthoracic echocardiography showed normal function of the aortic valve. The pathologic examination showed findings typical of PFE (). After being discharged from the hospital in a stable condition, the patient was followed up at the outpatient clinic for 1 year without tumor recurrence.


A 65-year-old man was referred for aortic stenosis with a mass in the right ventricle discovered during the preoperative workup for a right humeral fracture. Transthoracic echocardiography showed severe aortic stenosis with a bicuspid aortic valve and a 1.5-cm hypermobile mass attached to the apex of the right ventricle (, ). Computed tomography showed an aneurysmal change of the ascending aorta (4.7 cm) and a mass lesion in the right ventricle ().
The tumor was removed concomitantly with replacement of the aortic valve and ascending aorta. The tumor was attached to the myocardial wall at the apex of the right ventricle (). Immersion of the tumor in water after resection revealed the typical sea anemone appearance (). After being discharged without complications, the patient was followed up at the outpatient clinic for 18 months without tumor recurrence.


A 79-year-old female visited our hospital presenting with gait disturbance and bilateral lower extremity weakness. She also experienced radiating pain at both the C5 and T1 dermatomes and clumsiness in both hands. These symptoms began 6 months prior and worsened progressively. Her medical history included hypertension and dyslipidemia. In addition, she had been treated in the Endocrinology Department for several months because of steroid-induced diabetes mellitus and adrenal insufficiency.
The laboratory results on admission showed elevated erythrocyte sedimentation rate (45 mm/hr), C-reactive protein (20.4 mg/L), and rheumatoid factor (149.9 IU/mL) levels, which suggests inflammation. Laboratory results further confirmed that she did not have syphilis, fungal infection, neoplasm, or other systemic autoimmune disorders. On a neurological examination, her motor power in the lower extremities was grade IV/IV, upper extremity grasping power was grade IV/IV, and she had an ataxic gait. Her deep tendon reflex and ankle clonus were normal. Based on these findings, a diagnosis of progressive low cervical radiculomyelopathy was made and the patient's condition was investigated further.
On MRI of the patient's cervical spine, we found diffuse low signal intensity at C3/4 to T4/5, causing central canal stenosis at C3/4 to T4/5 and compressive myelopathy at C6/7 to C7/T1 on the T2-weighted images ( & ). Because of the patient's progressing paraplegia and compressive myelopathy on the preoperative cervical MRI, a treatment plan was established that included immediate decompressive surgery. The main compressive lesion was C6-7 and we considered about thoracic spine MRI sagittal image and the patient's old age (), so she underwent posterior decompressive laminectomy at C4 to T1 total (T2 subtotal) and cervicothoracic screw fixation (C4 to T2 pedicle screw insertion, bilaterally) with allograft and autograft bone grafts. During surgery, we found severe adhesion of the posterior longitudinal ligament and ligamentum flavum to the dura mater. During the procedure to remove the thickened dura mater, there were multiple incidental dural tears. Consequently, the durotomy site was primarily repaired intra-operatively. The intraoperative neurophysiological monitoring (IONM) was placed and observed about the motor evoked potentials (MEPs). There was temporary MEPs decreasing when we did laminectomy, but recovered in final MEPs ().
Chronic active inflammation with fibrosis and lymphoplasmacytic infiltration was found on the pathology report ().
The postoperative cervical MRI obtained the day after surgery showed that the decompression was sufficient. However, a new, subtle change was observed in the spinal cord, specifically high signal intensity at the C3/4 (right), C4/5 (left), C5/6 (bilateral) level on the T2-weighted images () After surgery, her motor weakness became more severe bilaterally. Her motor power in the lower extremities was grade II/III immediately after surgery, but it was reduced to grade I/II the next day. One week after surgery, her motor power was grade II/III. The cervical MRI showed no significant changes to the new high signal intensity change at C3/4 to C5/6. Steroid treatment included dexamethasone administration beginning immediately after surgery (20 mg for 3 days, followed by half-dose tapering for 2 days). However, despite the steroid treatment, her symptom severity fluctuated.
One month after surgery, her lower motor power remained at grade I/II. Cervical MRI revealed a newly developed cerebrospinal fluid (CSF) collection (approximately 3.5×1.5×10 cm) along the dorsal aspect of central canal, at the operative site of C3/4 to the T1/2 level on the T2-weighted images (). We suspected dural injury during surgery or a chronic inflammatory course of ISP, but because she experienced no other progressing symptoms, we decided to observe the CSF collection. The patient's next outpatient clinic follow-up occurred 2 months postoperation, and her lower power motor was grade III/IV. Follow-up MRI was performed 3 months postoperation. The CSF collection was almost completely resolved, but high signal intensity was observed at C5 to the T2 level on the T2-weighted images, which likely indicates aggravated compressive myelopathy (). At this visit, the patient's lower motor power had worsened to grade 0/I. During the 3 months after the surgery, she developed pulmonary and infective complications.
This research is about an individual case without the approval of an ethical research. We obtained informed consent from the patient.


A 67-year-old female visited our hospital with a history of ongoing dyspnea with right chest pain for 7 days. She had spinal surgery (L4–5 lumbar interbody fusion and percutaneous pedicle screw fixation with bone cement augmentation) 7 days ago for degenerative spondylolisthesis (). Right chest pain was observed from the day after surgery. The foreign body was shown in right atrium on X-ray (), but the clinician didn’t find it. She was treated with diuretics at the hospital for 5 days, but her symptoms did not improve. She was transferred to our hospital 7 days after the spine surgery. When she arrived at our hospital, her vital signs were normal. The chest computed tomography (CT) was performed, and a linear material that perforated the right atrium and the right middle lobe of the lung was detected (). It also showed that there was a linear high-density material in the right atrium on echocardiography (). We decided to remove them by emergency surgery.
Anterolateral thoracotomy was performed at the fifth intercostal space under one-lung ventilation. We found 4.5-cm-sized needle-shaped bone cement that perforating the right atrium (). After removal of the bone cement, we confirmed there is no remnant material in the right atrium or other abnormalities in the heart by using transesophageal echocardiography. The patient was discharged from the hospital 9 days after the cardiac surgery.
We obtained informed consent from the patient and approval from the Institutional Review Board of Hospital.


A 66-year-old man was admitted because of gait disturbance and weakness of both legs. The gait disturbance had gradually worsened for a month, and the patient was only able to walk slowly with cane assistance. General physical examination results were normal. On neurological examination, motor power of both upper and lower extremities was grade 4. Sensory examination was normal, and no pathologic reflex was found. At admission, magnetic resonance imaging (MRI) of the brain showed enlarged ventricles (). CSF drainage by LP was planned to diagnose NPH.
LP was performed uneventfully at the L3–4 intervertebral space. Three hours after CSF drainage, the patient suddenly developed loss of sensation of both legs and weakness of both arms and legs. Five hours after LP, pain and temperature sensation was decreased below the T3 dermatome. Motor power was grade 1 for both hands and grade 0 for both legs. Anal tone was decreased. Cervical spine MRI showed a large herniated intervertebral disc at the C5–6 level and severe spinal cord compression with high signal intensity on T2-weighted images ().
C5–6 spinal cord decompression was performed from the posterior approach for rapid decompression after a definite event. The thecal sac was swollen and thinned with an epidural hematoma (). Lateral mass screw fixation and fusion were performed (), followed by corpectomy of C6 and anterior cervical spinal fusion of C5–7 (). The operative field showed sequestration of the ruptured intervertebral disc at C5–6 with an epidural hematoma (). After surgery, the patient's motor grade recovered to grade 3 in both arms and legs, and hypoesthesia below the T3 dermatome recovered up to 70% compared to that before LP. The patient underwent rehabilitation therapy after discharge. The patient's motor power recovered to grade 4, and was able to walk with assistance.


A 70-year-old male patient complained of severe left-side arm pain (NRS 9) despite 6 months of medication treatment. Preoperative MRI and CT scan show left parallel-shaped FS at C5-6 and C6-7 levels (). Patients underwent posterior facetectomy with fusion using a pedicle screw at C5-6 and C6-7 levels. After operation, arm VAS was improved from 9 to 3 postoperatively and 0 at the final follow-up. NDI also improved from 48 to 22. Post-operative 1-year CT scan shows correct screw position and extensive decompression on the same levels consistent with the successful surgical outcome ().


On November 26, 2015, a 59-year-old female patient was hospitalized because of a month-long
history of coughing and expectoration. A routine preoperative chest CT examination revealed
a patchy ground-glass density in the right upper lobe that measured about
2 × 1.8 cm2, suggesting the possibility of lung cancer (). A bone scan and brain CT detected no
abnormalities. On November 30, 2015, the patient underwent a thoracoscopic lobectomy
(right). During intraoperative examination, a mass in the anterior segment of the right
upper lobe was detected. The mass measured approximately 2.4 × 1.5 × 1.9 cm3, the
image was of medium texture, and the tumor’s position was fixed. There was no obvious
swelling of the hilar lymph nodes, and no other lumps were detected in the rest of the
lungs. Samples of the lung lesions were taken for pathological examination.
Histological samples were assessed. Grossly, the tumor contained gray-red cystic nodules,
measuring approximately 7.4 × 5.5 × 4.9 cm3 (), the image was of medium texture, the tumor
had no capsule, and the boundary between the mass and the surrounding lung tissue was
unclear. Microscopically, after hematoxylin and eosin (HE) staining, the lesions were
identified as polycystic. The capsule walls were covered with flat epithelium and cubic
epithelium (type II alveolar epithelial cells), and eosinophilic granular material could be
seen in the capsules. The cystic dilatation was similar to that of the alveoli, and part of
the wall was damaged because of the formation of larger cystic expansion. Inter-wall cells
containing thicker spindle cells were visible between the terminal pulmonary artery and
vein. There was also a small amount of lymphoid and macrophage infiltration. No hemorrhagic
or necrotic areas were seen in the lesion tissues. In addition, no lepidic growth was seen
in the histiocytes and infiltrating inflammatory cells (). Immunohistochemical examination was
performed (), and the
results were positive for pan-cyto-keratin (CK), thyroid transcription factor-1 (TTF-1), and
naspinA, but the results were negative for S-100 and Ki-67 (5%). Interstitial cells tested
positive, while epithelial cells tested negative, for VIM. The final pathological diagnosis
was alveolar adenoma.


A previously healthy 45-year-old female visited Emergency Department because of severe facial edema, generalized urticaria, itching, and dyspnea 3 hours after eating a broth made of L. tanakae. On arrival to the Emergency Department, she presented with loss of consciousness. Physical examination revealed a blood pressure of 41/29 mmHg, a pulse rate of 90/min, a respiratory rate of 22/min, oxygen saturation of 98%. She was immediately treated with epinephrine (0.4 mg, intramuscular), methylprednisolone (125 mg, intravenous), chlorpheniramine (4 mg, intravenous). Symptoms resolved gradually for 1 hour, with restoration of normal vital signs and physical examination findings.
Seven weeks later, she experienced generalized urticaria again after tasting only a spoon of L. tanakae broth.
The patient was referred to our allergy clinic for the long-term management of anaphylaxis. She had suffered seasonal allergic rhinitis for several years. History of food allergy and current medication were denied by the patient. There was no family history of food or respiratory allergy and she was working as a school teacher. Skin prick test with common 55 food allergens showed positive responses to cod and sweet potato (wheal size of 4.0 × 4.0 mm and 3.0 × 3.0 mm, respectively, and 3.5 × 3.5 mm to histamine). However, these foods never induced any symptoms by oral ingestion. For skin prick test and measurement of specific IgE against L. tanakae in serum, frozen L. tanakae were obtained from the restaurant and the extract of this fish was prepared by a method described previously []. The result of skin prick test was positive to the extracts which were made of the flesh of L. tanakae (wheal size 4.0 × 3.5 mm). The serum specific IgE antibodies to L. tanakae were measured using an enzyme-linked immunosorbent assay (ELISA), which showed marked elevation in the patient compared to 5 healthy controls never exposed to L. tanakae previously (). Competitive ELISA inhibition test was performed by cod extract which induced positive response on skin prick test with common food allergens. The inhibition tests showed dose-dependent partial inhibition of specific IgE binding to L. tanakae extract by the addition of cod extract (). To identify IgE-producing components in L. tanakae and cod extract, serum protein was separated by 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (). Immunoblot analysis revealed 2 specific IgE binding components in L. tanakae extract. While a very weak band was observed at 40 kDa, a band found at 75 kDa was strong and considered as a main allergen. In cod extract, 2 protein components were bound to IgE at 17 and 40 kDa. Oral challenge test with cod was performed to rule out allergic reaction to cod but cod did not induce any symptoms in the patient. The diagnosis of L. tanakae induced anaphylaxis was made and the patient was advised life-long complete avoidance of L. tanakae.


A 55-year-old male patient presented with the gradual painful loss of vision in the left eye for 4 months associated with rapidly progressive proptosis. Best corrected visual acuity in right eye was 20/40 and no perception of light in left eye. Left eye pupil was dilated and not reacting to light, cataractous lens with proptosis of 4 mm. Single well-defined yellow-red, elevated partially spherical, firm mass with diameter 1.5 cm in superonasal quadrant without any conjunctival and episcleral adhesion was noted []. The anterior border was 4 mm superior to the limbus and the posterior edge could not be visualized. B-scan ultrasonography of the left eye revealed hyperechoic lesion superiorly, sub-Tenon's fluid, hemorrhagic choroidal detachment. The right eye was within normal limits. The patient was a diagnosed case of laryngeal carcinoma with a history of laryngectomy 1.5 years back followed by three cycles of chemoradiation. The patient had no other significant past medical or surgical history.
Computerized tomography showed a well-defined homogeneous isodense mass in the superior part of orbit extending till optic nerve base; complete infiltration of the sclera was seen along with ill-defined heterogeneous mass in vitreous cavity s/o left eye vitreous or choroidal hemorrhage. No bony erosion was noted [].
Positron emission tomography (PET) scan showed the left eye scleral hyperplastic lesion along with weekly metabolic thoracic node with no other systemic lesions. In view of a single metastatic focus after consultation with a medical oncologist plan for the left eye, enucleation was made. The patient underwent left eye enucleation. Histopathological examination (HPE) revealed an invasive poorly differentiated malignant tumor of squamous differentiation with full-thickness choroidal and scleral invasion and conjunctiva free of tumor [Fig. and ]. The optic nerve was free of tumor. Immunohistochemistry was positive for CK5/6 (specific for squamous epithelial differentiation) and negative for Vimentin. HPE of incision biopsy laryngeal mass (poorly differentiated squamous cell carcinoma) was compared and diagnosis of metastasis was confirmed.
The patient underwent repeat chemotherapy with cisplatin and external beam radiation for left eye orbit of 54 Gy in 27 divided fractions. He developed multiple systemic metastasis 6 months posttreatment and expired a year after diagnosis of orbital metastasis.


In December 2016, a 63-year-old male underwent a magnetic resonance cholangiography as an assessment for cholecystectomy surgery. A possible cholangiocarcinoma was reported, appearing as a 20 mm hypodense intrahepatic mass at the right liver lobe. Confluence of the hepatic ducts was observed (Figure ).
In August 2018, a significant elevation of CA19-9 (294.4 IU/mL, Figure ) was reported, although no relapse was observed in the computed tomography (CT) scan. The patient was asymptomatic, and the liver blood test results were similar to those presented after surgery [aspartate aminotransferase (AST) 56 U/L, alanine aminotransferase (ALT) 97 U/L, gamma-glutamyltransferase (GGT) 455 U/L, alkaline phosphatase (FA) 187 U/L]. Close monitoring was implemented.
In September 2018, CA19-9 continued to increase (513.2 IU/mL, Figure ). However, the CT scan did not reveal disease relapse. In January 2019, the patient was admitted for cholangitis. A magnetic resonance cholangiography was performed, and no changes were observed in the liver. After discharge in February 2019, close follow-up was continued.
During the following months, the patient experienced clinical deterioration, which included stomach-ache, dyspepsia, and loss of 4 kg of weight. A slight deterioration in the liver blood test was seen (AST 83 U/L, ALT 125 U/L, GGT 1580 U/L, FA 308 U/L) and a progressive rise in CA19-9 was also observed (from 671.3 IU/mL in February 2019 to 3220.9 IU/mL at the end of April 2019, Figure ). A thorax-abdomen-pelvis computerized tomography (TAP-CT) scan was requested, and no disease relapse was observed. Given the high suspicion of relapse, a positron emission tomography-CT was performed in April 2019. Multiple supraclavicular, mediastinal, and bilateral hilar lymphadenopathies, as well as segment IVa liver nodes and increased soft tissue in the celiac trunk region; all showed increased metabolic activity (Figure ).
After 25 mo without signs of radiological disease, a relapse of stage IV intrahepatic cholangiocarcinoma was diagnosed. We recommended that the patient begin a first-line chemotherapy with cisplatin and gemcitabine at the usual doses. However, since a poor tolerance to gemcitabine was previously presented, we decided to instead begin with the FOLFOX6 treatment scheme.
The FOLFOX6 treatment began in April 2019. Initial clinical improvement in cancer-related asthenia was observed, as well as a significant decrease in CA19-9 blood levels (from 3592 IU/mL in May 2019, after two cycles of FOLFOX, to 1138.8 IU/mL in August 2019, after eight cycles of FOLFOX, Figure ). Grade 1 neurotoxicity and grade 1 rectal bleeding from hemorrhoids were the principal clinical chemotherapy-related toxicities that occurred. After cycle 4, grade 1 thrombopenia was presented, and cycles 5, 6, and 7 were scheduled without a 5-fluorouracil bolus. Grade 2 thrombopenia was then observed, and the administration of cycle 8 was delayed for 1 wk. In July 2019, CT scans were performed (prior to cycle 8) and segment IV liver nodes were not identified, as reported in the previous study (Figure ). However, a small amount of free fluid in the pelvis, as well as a thickening of the peritoneal leaves, appeared. A mixed response was also considered. Given the improving clinical status of the patient, the same treatment was continued, and cycle 8 was administered with a 10% decrease in oxaliplatin dose.
The patient was referred to our center for surgical evaluation. A TAP-CT scan and blood tests were performed. Distant metastases were not observed, and CA19-9 tumor markers were found to be elevated (3494 IU/mL, Figure ).
In March 2017, after a right portal embolization was performed that caused compensatory hypertrophy in the left liver lobe, the patient underwent surgery. A hilar tumor with right portal involvement was found. Resection of the extrahepatic bile duct with right trisegmentectomy extended to segment 1 and portal resection were both performed.
The pathology report revealed a moderately differentiated intrahepatic hilar cholangiocarcinoma infiltrating the liver parenchyma, perihilar adipose tissue, cystic duct, and gallbladder neck. Frequent perineural infiltration and vascular invasion were also observed. The tumor had metastasized in one of the four lymph nodes that were isolated from the hilum, which affected the resection margin of the surgical piece.
Stage III B (pT3N1M0) intrahepatic cholangiocarcinoma, a R1 resection, was diagnosed and the patient was referred to the Medical Oncology Department. Adjuvant chemotherapy treatment with capecitabine 1660 mg/m2 on days 1 to 21 and gemcitabine 1000 mg/m2 on days 1, 8 and 15 every 28 d, given for six cycles, was started. The patient received this treatment between May and November 2017. However, gemcitabine was suspended in July 2017 due to an allergic reaction. After completion of the adjuvant treatment, the follow-up period began.
Despite initial clinical improvement, a progressive clinical deterioration was then presented, with an increase in asthenia. Grade 2 diarrhea (Table ) and minimal effort dyspnea also appeared. Abdominal examination was normal, and hypoventilation in the right lower lung lobe was auscultated. Cycle 9 was not prescribed, due to grade 1 thrombopenia and persistent grade 2 neutropenia.
Serological progression was observed: CA19-9 blood levels rose to 2023 IU/mL (with a previous rise in August 2019 of 1138.8 IU/mL, Figure ) and carcinoembryonic antigen (CEA) blood levels also rose to 5 IU/mL (high CEA levels had not previously occurred). Regarding liver blood testing, AST levels were 74 U/L, ALT levels were 70 U/L, GGT levels were 849 U/L, and FA levels were 440 U/L. The remaining biochemistry parameters were normal, with the exception of grade 1 hypoalbuminemia.
Given the suspicion of disease progression, a new CT scan was performed in early September 2019. Both peritoneal carcinomatosis (Figure ) and pleural involvement were confirmed by one last cytological study (Table ).
Massive genetic analysis of the tumor using next-generation sequencing (NGS) was requested. Several alterations could be identified in some genes, such as RNF43, PTCH1, ATM and ARID1A, as well as in variants of unknown significance. Microsatellite instability was not found. Given the clinical deterioration, we decided to begin chemotherapy prior to obtaining these test results.


An 81-year-old Caucasian female presented to the hospital with a three-month history of worsening right-sided weakness, decreased coordination with acute onset word-finding difficulty. She carried a six-year diagnosis of EGPA (with initial symptoms of adult-onset asthma, chronic sinusitis, and nasal polyps). She was maintained on long term immunosuppressive therapy due to cardiac involvement requiring mitral valve replacement (eosinophilic infiltration of valve with subsequent fibrosis). Patient had been initially treated with steroids and azathioprine, but was later transitioned to MMF one-gram twice daily due to liver dysfunction from azathioprine. Induction therapy with cyclophosphamide was considered, however, her five factor score [] at the time was only one with no neurological, renal or GI involvement. Therefore, azathioprine and MMF were only used as steroid sparing agents in order to try to decrease the dose of steroids and not as induction agents. For the past six years, she had a good control of her symptoms related to EGPA while on MMF.
At this presentation, her right lower extremity weakness and incoordination had necessitated the use of a walker for 1 month. Additionally, she had acutely developed word-finding difficulties. Patient otherwise denied other neurological complaints or history of fever, chills, weight loss, and changes in appetite.
Physical exam demonstrated alert and oriented female, with vitals within normal limits. Neurological examination revealed symmetrical facial expression, a midline tongue protrusion, and an intact shoulder shrug. A mild weakness in right foot dorsiflexion and right-hand grasp was noted with otherwise intact muscle strength and reflexes. Gait assessment showed right-sided foot drop and difficulty with balance. Finger-to-nose test showed some mild dysmetria and right-sided dysdiadochokinesia.
Magnetic resonance imaging (MRI) was done which revealed three solid enhancing lesions in the right parietal lobe, left insular lobe, and left midbrain extending into the left thalamus (,)). An inflammatory process related to patient’s EGPA was thought to be possible although the parenchymal lesions appeared more concerning for a neoplastic process. Computed tomography scan of the chest, abdomen, and pelvis did not show any acute findings. A spinal MRI followed by bone scan of spine showed degenerative disease without any discrete masses. Serologic testing for HIV was negative. ANCA serologies were negative. CRP was 0.22 mg/dL and eosinophil count was 0.29 × 10 3/µL. These findings made EGPA relapse less likely.
Patient further underwent craniotomy with biopsy of right parietal brain mass. The biopsy specimen () demonstrated a patchy but focally dense lymphoid infiltrate predominantly composed of small lymphocytes with admixed large atypical cells showing frequent multinucleation. These atypical cells resembled Hodgkin/Reed-Sternberg (H/RS) cells with abundant cytoplasm, large nuclei, and prominent nucleoli. Immunohistochemistry demonstrated positive CD30 staining, some CD15 staining, and dim Pax-5 and occasional dim CD20 expression. CD45 and CD10 staining were negative. The lymphoid infiltrate contained a mixture of CD3/CD5-positive T-cells and CD20-positive B-cells, with T-cells predominating. Background T-cells were negative for CD30. An in-situ hybridization (ISH) for EBV-encoded RNA (EBER) was positive in the H/RS cells and scattered small cells. The Ki-67 proliferation index was overall low, but significantly increased in the H/RS cells.
MMF was discontinued following the biopsy due to concern for Primary CNS Immunodeficiency-associated lymphoproliferative disease (IALD). The patient was then started on rituximab therapy as the reversibility of this lymphoproliferation on discontinuation of immunosuppressants is very poorly defined. This therapy was selected as alternative therapies including methotrexate would be more toxic, and there was a concern for cognitive dysfunction with radiation therapy. Additionally, rituximab had a concomitant benefit in treating EGPA. Rituximab 375 mg/m2 weekly for 4 weeks of induction therapy lymphoma dose was used []. This was planned to be continued for a total of 6–8 doses (for management of both EGPA and lymphoma) with interval clinical and radiologic monitoring.
Following 8-weeks completion of rituximab therapy, repeat MRI showed near-total resolution of the enhancing intracranial lesions with minimal enhancement still evident within the heterogenous area involving lateral aspect of right occipital lobe (). Patient reported resolution of right-sided weakness and word-finding difficulties with significant improvement with her coordination. She remains on low dose prednisone and is in close follow-up with Rheumatology.


Our patient was a 34-year-old gentleman with a history of a wound in the right leg for 2 weeks following trivial trauma. He was a diagnosed with type 2 diabetes for 4 months, for which he was treated with irregular oral hypoglycemic agent. He had no other comorbidities.
On presentation, he had a wound of size 10 × 6 cm in the heel of the right foot extending to the dorsum approximately 2 cm below the medial malleolus []. Calcaneum was exposed and periosteum was intact and slough was present. The wound base was filled with pale pink granulation tissue. There was another ulcer at the level of lateral malleolus, the bone was not exposed and was filled with pale pink granulation tissue.
Evaluation showed that the patient had uncontrolled diabetes, which was managed with the help of an endocrinologist, and he was started on insulin. On X-ray and magnetic resonance imaging of the foot, there was no evidence of osteomyelitis. Wound tissue culture–specific antibiotics were started. Anemia was corrected with blood transfusions. Other workup for diabetes was also carried out. Assessment of wound was performed by Bates–Jenson wound scoring system.
After serial debridement, injection phenytoin was sprayed on top of the wound and secondary dressing was carried out []. Injection phenytoin (50 mg/mL) solution was diluted using normal saline (0.9% NaCl) to prepare a phenytoin solution (5 mg/mL). This dressing was changed once in 3 days, and the phenytoin instillation was repeated at the time of dressing change. Serum phenytoin concentration was monitored regularly in the Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India, and it was always below 0.4 µg/mL, indicating only minimal absorption of phenytoin systemically. The patient did not have any pain while instillation. After five dressings, his wound had drastically improved, with the wound bed granulating well with pink healthy granulation tissue []. Bone had been covered with granulation tissue and the wound bed was now ready for cover.


Male patient, 40 years old, dyslipidemic, presented with a right carotid territory transient ischemic attack 7 months prior. At the time, he underwent diagnostic investigation during which there was found evidence of moderate stenosis (about 60%) in the right carotid bulb associated with an ulcerated plaque. Double antiplatelet aggregation therapy was then prescribed with aspirin and clopidogrel and the use of statins, in addition to angioplasty with a 7 × 40 mm carotid wall stent. He progressed without complications and was discharged after 3 days without sequelae.
The patient had been involved in an automobile accident (a collision between a car and a pole) and was referred to the emergency room, with no neurological deficit at the time of admission. Tomography and angiotomography scans of both the neck and skull were performed and revealed signs of thrombosis/occlusion of the bifurcation of the right internal carotid artery, close to the origin of the middle cerebral artery.
Subsequently, he underwent cerebral angiography that showed multiple fractures in the stent and a small metallic image in the topography of a branch of the right lingual artery, which is suggestive of a fragment thereof []. The study of intracranial vessels showed the presence of a negative image in the bifurcation of the right internal carotid artery, which was compatible with a thrombus and thus determined a subocclusive stenosis (about 95%) at the site. That observation was also associated with an increasing slowing down in the opacification process of the right middle cerebral artery []. This artery was rechanneled from pial anastomoses originating from the right anterior and posterior cerebral arteries. Two small metallic images were evident in the topography of branches of the right middle cerebral artery as well, which was also suggestive of stent fragments [].
As he was an asymptomatic patient (NIHSS 0, Rankin zero), we opted for a conservative treatment with oral anticoagulant and a target international normalized ratio (INR) between 2.0 and 3.0.


An 84-year-old Caucasian female presented to the local emergency department with a recent history of severe headaches, myalgia and shoulder and calf muscle pain. She had been recently diagnosed with polymyalgia rheumatic in the context of a three-month history of fatigue, weakness and fluctuating fever and was already on tapered dose of corticosteroids. The patient was otherwise known for atrial fibrillation on anticoagulation, atherosclerotic coronary heart disease, hypertension, and dyslipidemia. Past ocular history was unremarkable except for remote bilateral phacoemulsification cataract surgery.
On presentation at the ER, the patient was afebrile. There was no temporal artery tenderness or jaw pain, and C-reactive protein was mildly elevated at 52 mg/L. Platelets count was 313 x 109, white blood cells count was 19.9 x 109. No erythrocyte sedimentation was done. The tests were otherwise unremarkable.
The patient was prescribed oral prednisone 50 mg once daily and admitted. Twenty-four hours later, solumedrol 1g IV was prescribed once daily for 48 hours for a presumed diagnosis of polymyalgia rheumatica and atypical temporal arteritis as the symptoms worsen and C-reactive protein increased to 197 mg\L. At this point, the patient had no ocular symptoms.
Despite initial improvement, the patient relapsed after three days with worsening of symptoms and a new retro-orbital pain of the right eye. On examination by the ophthalmologist, the patient had 20/20 vision bilaterally, with normal adnexal structures and extraocular movements. Intraocular pressure was within normal limits and the visual field exam showed a superonasal quadranopsia. Anterior segment examination showed no sign of inflammation and fundus examination of the right eye showed a white, vascularized chorioretinal mass in the inferotemporal quadrant. The examination was unremarkable for the left eye. The diagnosis given by the general ophthalmologist was a possible malignant tumor and the patient was referred to a retinal specialist for further evaluation.
Investigations by an infectious disease specialist led to a concomitant diagnosis of emphysematous cystitis. Piperacillin tazobactam 3.3 g IV q 6 hours was prescribed to the patient and given the partial response to antibiotics, the corticosteroids were gradually eliminated. Piperacillin tazobactam was changed for ampicillin 2 g IV q 6 hours.
One day later, a PET scan was performed with results suggesting an inflammatory or infectious etiology. It showed two pulmonary opacities of unknown etiology and hypermetabolism in the right calf muscle, thought to be a hematoma. Large vessel arteritis was absent.
Three days later at follow-up, the patient’s vision in the right eye was significantly decreased from 20/20 to counting fingers. Panuveitis was present with a stage 4 vitreal haze on fundus exam. A B-scan was performed and revealed that the mass had increased in size and was extending into the vitreous. A diagnosis of endogenous endophthalmitis with a probable fungal etiology was made. A vitrectomy with a chorioretinal biopsy of the lesion was performed the next day. Intravitreal amphotericin B 5 mg/0.1 mL, vancomycin 1 mg/0.1 mL and ceftazidime 2.25 mg/0.1 mL were administered during the procedure. A biopsy of the left calf mass was made by needle biopsy.
The culture of the vitreous () and biopsy of the left calf mass () showed high quantities of Nocardia nova. Disseminated Nocardiosis was therefore the final diagnosis.
Ampicillin was stopped and changed for meropenem 2 g IV q 8h and TMP-SMX 400 mg IV q8h for 4 doses. A dose of 2 mg of intravitreal ceftriaxone was also planned. After the intraocular injection and the parenteral antibiotics, a regression of the intraocular mass, right calf mass and two pulmonary opacities was observed. A considerable improvement of the patient’s general condition was also noted. However, the patient decided to cease treatment given her age and other comorbidities. She was transferred to palliative care and died 18 days later.


A 33-year-old Caucasian female presented to her ophthalmologist with the complaints of progressively worsening eye pain, redness and loss of vision in the right eye of 1-day duration. She gave a history of being bitten on the right eye by her domestic cat 4 days earlier. She was prescribed a course of oral amoxicillin-clavulanate potassium (Augmentin®) after being seen in the emergency department on the day of the injury. Rabies prophylaxis was not indicated according to the Centers for Disease Control and Prevention (CDC) guidelines []. Her past ocular history was significant for mild myopia. Her medical history was significant for an anxiety disorder which was being treated with oral paroxetine (Paxil®).
Her best-corrected visual acuity at presentation was hand motion in the right eye and 20/20 in the left. External examination showed healing abrasions on the nasal aspect of the left lower lid. Slit-lamp examination of the right eye showed 2+ conjunctival congestion, a healing conjunctival laceration nasally, clear cornea, 1 mm hypopyon and 3+ cells and flare in the anterior chamber, irregular pupil due to posterior synechiae, and a clear lens. The left eye was normal. The intraocular pressures were 10 mm Hg OD and 15 mm Hg OS by applanation tonometry. Dilated fundus examination of the right showed dense vitritis without any view of the nerve or retinal details. The left eye was normal.
The patient was taken to the operating room for exploration of the globe which revealed a puncture wound 3 mm behind the limbus in the inferonasal quadrant (Zone 2 injury) []. A vitreous strand presenting through the wound was excised with scissors, and the puncture wound was repaired with two interrupted 8-O nylon sutures. Anterior chamber and vitreous tap were performed, and the specimens were sent for culture and sensitivity. Intravitreal injections of vancomycin 1 mg/0.1 mL and ceftazidime 2.25 mg/0.1 mL were administered with separate 30-g needles through the pars plana. She also received intravenous vancomycin 1 gm every 12 h and intravenous gentamicin 100 mg loading dose followed by 50 mg every 8 h for 24 h. In addition, she was started on 1% prednisolone acetate eye drops every hour, 0.3% moxifloxacin eye drops every 2 h, and 1% atropine eye drops every 12 h in the right eye. The culture from the anterior chamber was sterile but the vitreous tap grew alpha hemolytic Streptococcus.
The patient was examined by a retina specialist 24 h after the initial repair. The corrected visual acuity in the right eye was hand motion and 20/20 in the left. The right eye showed a subconjunctival hemorrhage and interrupted polyglactin 910 (Vicryl®) sutures over the nasal bulbar conjunctiva. The cornea was clear (Fig. ). The anterior chamber showed mild cells and flare. The pupil was pharmacologically dilated with a few posterior synechiae. The lens appeared clear. Dense exudates were seen in the vitreous cavity (Fig. ). B scan ultrasonography showed the retina to be attached. The intraocular pressures were 15- and 18-mm Hg in OD and OS, respectively, by Goldmann applanation tonometry. The left eye was normal.
A 25-gauge vitrectomy was performed on the following day, approximately 48 h after initial repair. Approximately 1.5 mL of undiluted vitreous sample was obtained by activating the cutter in the midvitreous cavity under wide-field visualization and manual aspiration by an assistant with a 3-mL syringe under air infusion. The specimen was sent for gram stain, as well as aerobic, anaerobic, bacterial and fungal cultures. The infusion was switched to fluid and a thorough vitrectomy was performed including removal of as much peripheral vitreous as possible using a 500-mL BSS Plus® (Alcon, Fort Worth, TX, USA) bottle to which 2 mg gentamicin (4 μg/mL concentration), 32 mg dexamethasone (64 μg/mL concentration), and 1 mg epinephrine had been added. The lens was clear and was not removed.
After completion of vitrectomy, vancomycin (1 mg/0.1 mL), ceftazidime (2.25 mg/0.1 mL) and dexamethasone (400 μg/0.1 mL) were injected into the vitreous cavity via separate syringes. Subconjunctival cefazolin and dexamethasone injections were also given.
Topical prednisolone acetate, moxifloxacin and atropine drops were resumed after vitrectomy and slowly tapered off over the next 3 weeks. Aerobic cultures from the vitreous demonstrated heavy growth of Bacillus species. Anaerobic and fungal cultures were negative.
Her endophthalmitis resolved but she developed a dense posterior subcapsular cataract which was removed by an uncomplicated phacoemulsification and in-the-bag placement of a posterior chamber intraocular lens (PCIOL) 3 months after injury. Postoperatively, her vision improved to 20/20 and has remained at that level for more than 3 years of follow-up.


An 81-year-old Japanese woman presented to our hospital with dark purple nodules with erythema on her left breast (Fig. ). She had a history of left breast cancer and had undergone breast-conserving surgery 9 years previously at our institution. Histologically, her breast cancer was secretory carcinoma and was classified as pT2N0M0 pStage IIA. Her tumor was immunohistochemically estrogen receptor positive, progesterone receptor negative, and HER2 negative.
Adjuvant radiotherapy (50 Gy/25 fractions) was performed for the conserved breast, followed by chemotherapy (FEC, 4 cycles) and endocrine therapy (anastrozole, 1 mg daily for 5 years). She also had a history of pancreatic cysts and had undergone laparoscopic caudal pancreatectomy 2 years prior to the diagnosis of RIAS. Her pancreatic cysts were serous cystadenoma histologically. Her family history included her mother and sister having had gastric and pancreatic cancers, respectively. However, no one had a history of breast or ovarian cancer. Ultrasound revealed 2 superficial masses in her left breast, which were irregular in shape. These masses were hypoechoic and measured 17 mm in diameter in the upper area and 10 mm in the lower area, suggesting skin involvement (Fig. ). Doppler signaling indicated that both tumors were hypervascular. Punch biopsy was performed for one of the dark purple nodules and the pathological diagnosis was angiosarcoma. MRI (magnetic resonance imaging) revealed 4 irregular masses with heterogeneous enhancement (Fig. ). On a positron emission tomography-computed tomography scan, high fluorodeoxyglucose uptake (SUVmax 7.83) in the left breast was observed, but there were no hotspots in other organs.
Based on the imaging findings, we judged her disease to be resectable and performed total mastectomy with a wide skin resection (1 cm from the edge of the tumor and the skin discoloration). After we had confirmed all surgical margins to be negative intraoperatively, skin collected from her left thigh was grafted onto the site.
Pathologically, there were multiple lesions, with a maximum size of 13 mm, but none were continuous. Atypical endothelial cells, creating irregular vessels in subcutaneous tissue, were confirmed (Fig. ). On immunohistochemical staining, the tumor cells were positive for markers of angiosarcoma such as CD31, CD34, von Willebrand factor (focally), and vimentin (Fig. ). The surgical margin was negative. We also investigated microsatellite instability (MSI), following the approval of MSI determination as a companion diagnostic test in Japan. The MSI testing was outsourced to SRL Inc. (Tokyo, Japan). Using a kit by FALCO, the MSI status was examined and judged to be microsatellite stable; all markers (BAT-25, BAT-26, NR-32, NR-24, and MONO-27) were negative. Considering her advanced age, the patient has remained under careful observation without systemic treatment and/or adjuvant radiation and has been free of recurrence for 6 months to date.


A 59-year-old male with extensive smoking history presented to our hospital with progressive bilateral hearing loss and right-sided peripheral facial nerve palsy (Fig. ). Brain MRI showed contrast-enhancing parenchymal nodules as well as leptomeningeal and multiple cranial nerve enhancement (Fig. ). Serum Lyme IgG and IgM were positive. Cerebrospinal fluid analysis from 2 separate lumbar punctures showed lymphocytic predominance with negative PCR for Lyme, normal flow cytometry, and no malignant cells by cytology. He received 4 weeks of intravenous ceftriaxone for suspected neuroborreliosis without symptom improvement during which time he experienced a 20-pound weight loss, cough, and progressive dysphagia.
Chest CT revealed bilateral hilar and mediastinal lymphadenopathy, multiple pulmonary nodules, and bilateral upper lobe cavitary lesions (Fig. ). Infectious workup, including bronchiolar lavage with AFB staining, bacterial and fungal cultures, was unrevealing. Endobronchial ultrasound-guided biopsy of enlarged mediastinal lymph nodes revealed poorly differentiated lung adenocarcinoma. PD-L1 tumor proportion score was low/intermediate (1–49%), and next-generation sequencing for targeted driver mutation analysis revealed the presence of BRAF V600E mutation with an allelic frequency of 36%. Given rapidly progressive neurological deficits, steroids and whole-brain radiotherapy were initiated with minimal improvement. Due to pre-existing cardiomyopathy, BRAF V600E mutation-targeted therapy with dabrafenib/trametinib was deferred and he was started on ipilimumab and nivolumab. Treatment is currently on-going with clinical stability.


A 64-year-old Japanese female presented with epigastralgia and underwent esophagogastroduodenoscopy (EGD) at a nearby hospital. Several erosions and small ulcers were found at the anterior wall and the lesser curvature of the gastric corpus (Fig. ), and a biopsy was performed to exclude gastric cancer. At that time, the patient was histopathologically diagnosed with “chronic active gastritis associated with H. pylori infection” and underwent HPE treatment. Subsequently, her hospital visits were discontinued.
The results of reviewing the first pathology slide are shown. Large CD20-positive atypical lymphocytes were diffusely infiltrated (Fig. ). The Ki-67 labeling index was 30–40% (Fig. ). She was diagnosed with DLBCL instead of chronic active gastritis.
Eight months after HPE treatment, the patient presented with epigastralgia again and underwent EGD at the same hospital. Multiple ulcerative lesions were found in the anterior wall and the lesser curvature of the gastric corpus, which were deeper and more spread out than the primary lesions (Fig. ). A biopsy was performed, the patient was histopathologically diagnosed with DLBCL without H. pylori infection. Following this diagnosis, the patient was referred to our department and hospitalized. Through positron emission tomography (PET)/computed tomography (CT), it was found that the lymphoma lesions were restricted to the stomach (Lugano stage I). The patient underwent 3 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, and complete remission (CR) was achieved. Consecutively, involved-field radiation therapy (30 gray/15 fractions) was performed. Since then, the patient has maintained CR for more than 3 years without recurrence.


A 70-year-old Japanese male presented with epigastralgia and underwent EGD at a nearby clinic. Two ulcerative lesions were detected in the antrum and around the pylorus of the stomach (Fig. ). A biopsy was performed. H. pylori was confirmed to be positive, and the patient was histopathologically diagnosed with “MALT lymphoma partially combined with DLBCL components.” Subsequently, HPE was conducted. Three months later, both lymphoma lesions regressed (not shown). Histopathological confirmation was not obtained by biopsy, but the patient was endoscopically evaluated as being in remission.
The results of reviewing the first pathology slide are shown. The growth of CD20-positive atypical large lymphoid cells was observed without any evidence of MALT lymphoma, such as centrocyte-like cells or lymphoepithelial lesions (Fig. ). The Ki-67 labeling index was 40–50% (Fig. ). These observations were consistent with de novo findings of DLBCL without MALT lymphoma.
Ten months after HPE treatment, the patient presented with epigastralgia again, and an EGD was conducted. It was found that the initial lymphoma lesions were still in remission (Fig. ); however, a new ulcerative lesion, wider and deeper than the initial lesions, was found at the angulus, which had shown no abnormalities at the initial diagnosis (Fig. ). The biopsy revealed that the patient was pathologically diagnosed with DLBCL without H. pylori infection. The patient was then referred to our department and hospitalized. Through contrast CT and PET/CT, in addition to the primary gastric lymphoma, lesions spreading to the para-inferior vena cava lymph node (1 cm diameter) were observed. He was evaluated to have Lugano stage II2 disease and received 6 cycles of chemotherapy: R-THP-COP (rituximab, pirarubicin, cyclophosphamide, vincristine and prednisone). CR was achieved, and the patient remained in CR for more than 3 years without recurrence.


A 49-year-old male presented to our clinic for establishment of care. He had a
history of hypertension and diabetes mellitus. His examination was remarkable for a
systolic murmur on the left lower sternal boarder and a healed left leg ulcer and
trace lower extremity edema. Relevant history included chronic venous stasis with
stent placement to the left iliac vein (Boston Scientific, Wallstent 16 × 60 mm)
done in a different facility 10 months prior to presentation. Two days after the
procedure, he went to an outside hospital complaining of chest pain. Transesophageal
echocardiography was performed at the other institution and showed an “unclear echo
density in the right atrium, which was suspected to be an artifact.” A coronary
angiogram showed nonobstructive coronary artery disease.
Based on the previous report, we ordered a transthoracic echocardiography that showed
a foreign body in the right atrial cavity extending across the tricuspid valve (TV;
Supplemental Videos 1 and 2).
A transesophageal echocardiography was performed, which showed a dislodged vascular
stent in the right atrium measuring 5.5 × 1.6 cm (Supplemental Videos 3-5). The
stent was impinging on the TV, causing severe tricuspid regurgitation. The patient
was admitted to our cardiology service and placed on heparin for anticoagulation.
Computed tomography of the chest reported a tubular radiopaque density, in the right
atrium, partially extending into the right ventricle ().
Following a multidisciplinary meeting involving interventional cardiology, vascular
surgery, and cardiothoracic surgery, percutaneous extraction of the stent was
attempted under transesophageal echocardiography guidance; however, it was firmly
adhered to the TV and opposing the right atrial wall. Consequently, the patient
underwent open stent extraction, during which the stent was found to be adherent to
the TV and the right atrial wall ( and ). He required TV replacement and was discharged in a stable condition.


A 72-year-old man was referred to the hospital of the Ludwig-Maximilians-University (Munich, Germany) to address an isolated complaint of abdominal pain.
The patient reported that the abdominal pain had appeared that day and denied chronicity or any other symptoms.
There was no history of past illness.
The physical examination revealed a biologically unremarkable patient in good condition, with only diffuse abdominal pain during palpation.
Routine laboratory tests were unremarkable, except for serum lipase, which was elevated (5580 U/L) and prompted suspicion of ACC.
Initial imaging examination with computed tomography (CT) detected tumoral growth of the pancreatic head (Figure ) and synchronous liver metastases (Figure ).


There were no chief complaints.
A 54-year-old woman underwent abdominal ultrasound during a medical checkup, which revealed liver lesions. Abdominal ultrasonography revealed well-defined hypoechoic lesions in liver segments 1 and 2.
She had no history of persistent viral infection, autoimmune disease, inflammatory bowel disease or malignant tumors. She had a medical history of polyp in the pharynx and maxillary osteomyelitis.
There were no physical findings to note.
Blood tests revealed normal liver function and were negative for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and antinuclear antibody. Her tumor marker levels were as follows: alpha-fetoprotein, 2.1 ng/mL; PIVKA-2, 21 mAU/mL; carbohydrate antigen 19-9, 4.1 U/mL; and carcinoembryonic antigen, 2.3 ng/mL. All markers were in the normal range.
Precontrast CT showed three liver nodules with slight low attenuation relative to the liver parenchyma at segments 1, 2 and 8 (Figure ). There was perinodular enhancement (PNE) in the arterial phase in the nodules (Figure ) with washout of contrast medium in the portal and equilibrium phase (Figure and ). On precontrast MRI, the nodules showed hypointensity on T1-weighted image and hyperintensity on fat-saturated T2-weighted image (Figure and ). There was no fat component. The nodule showed obvious hyperintensity on DWI (b = 800 m2/s) and strongly restricted diffusion on apparent diffusion coefficient (ADC) mapping (ADC of the lesion: 0.54 × 10-3 mm2/s, ADC of the spleen: 1.03 × 10-3 mm2/s). There was linear hyperintensity along the portal tract consecutive to the liver lesions on DWI (Figures and ). However, that of the S2 lesion was faint because of heart beating heart and susceptibility artifact. On gadoxetic acid-dynamic enhanced MRI, the nodule showed PNE in the arterial phase (Figure ), washout of contrast medium in the portal and transitional phase and low signal intensity in the hepatobiliary phase (Figure and ).


At 8 wk gestation, a pregnant woman presented with low progesterone level.
A 30-year-old woman had a normal prenatal ultrasound examination at 7 wk gestation. The patient did not have any other discomfort.
The patient is G4P1. She delivered her first child vaginally.
The patient has no special family history.
The patient’s physical examination was normal.
Laboratory testing had revealed a low progesterone level.
The first prenatal transvaginal ultrasound was performed by CD-6 (Mindray, Shenzhen, China) at 7 wk gestation. Two-dimensional ultrasound images showed that the embryo was normal with crown-rump length of 12 mm (Figure ).
After 7 d, the prenatal ultrasound was performed again using a Volusion E8 (GE Healthcare, Milwaukee, WI, United States). Two-dimensional ultrasound images showed a single yolk and two embryos in the gestational sac. The lengths of the two embryos were 18 mm and 20 mm. The embryos were connected without distinct boundaries, and there was no fluid between them. The two embryos shared one heart. Color Doppler flow imaging showed that pulsating blood flow signals existed at the junction of the two embryos (Figure ).


A 26-year-old man with a 2-year history of schizoaffective disorder (depressed type
with catatonia) presented with catatonia, delirium, and seizures. He was taking
olanzapine 10 mg, venlafaxine 300 mg, and trazodone 100 mg on a daily basis for at
least a year. About a year prior to admission, he fell at work and sustained a
concussion, but he was never diagnosed with seizures/epilepsy. He had several
hospital visits for catatonia in the past. During his last visit, he was prescribed
lorazepam 2 mg bid, which rendered him free of catatonia for 6 months. He ran out of
lorazepam 10 days prior to admission. Three days later, he became increasingly
withdrawn and less active. After another 3 days, he appeared stiff and assumed
abnormal postures. He was brought to the emergency room (ER) after he was found
down, face toward the ground, moaning, and soaked with urine. Informants thought he
had a convulsion.
On arrival, he was hypotensive (80/50 mm Hg), tachycardic (142-160/min), and
diaphoretic, but normothermic (37 °C). Intravenous (IV) fluids increased his blood
pressure (132-142/74-90 mm Hg) and decreased his heart rate (118-132/min). He
exhibited psychomotor retardation, catalepsy, and waxy flexibility. Response to
verbal instructions and noxious stimulation was minimal. He uttered 2 words at
most—“hospital” when asked where he was, and “no” when asked if he felt anything
unusual. Formal testing of attention and other cognitive function was not done
because he did not follow instructions. He kept his eyes closed. When pried open to
check his pupils, he shut them tightly. Neurological examination was limited on
account of catatonia. Cranial nerve functions were intact. All limbs were rigid and
deep tendon reflexes were accentuated (3+). There was bilateral ankle clonus, but
Babinski sign was absent. Blood and urine toxicology was negative for substances of
abuse, including benzodiazepines. Blood tests were normal, except for elevated
creatine kinase (19 370 U/L) and mild hyperammonemia (42 µmol/L). Cerebrospinal
fluid analysis was normal, except for mildly increased protein (71.5 mg/dL).
Computed tomography of the head and magnetic resonance imaging of the brain were
normal. His home medications were put on hold because neuroleptic malignant syndrome
(NMS) and toxic serotonin syndrome (TSS) could not be excluded.
Electroencephalography (EEG) was performed in the ER (). During EEG acquisition, the
patient maintained a fixed rigid posture with hands fisted, forearms pronated and
slightly flexed, and legs and ankles slightly extended. When his arm was raised
against gravity, he maintained the posture, consistent with waxy flexibility ( and B). EEG showed
25- to 115-second episodes of high-voltage generalized rhythmic delta activity
(GRDA) alternating with 12- to 72-second episodes of non-GRDA background activity
with low-voltage beta, alpha, and theta rhythms and rare delta waves. Minor
fluctuations in GRDA amplitude and frequency was noted with 2.5 Hz as average
frequency. Lorazepam 2 mg was injected IV, and within 10 minutes, GRDA was replaced
by low-voltage semirhythmic theta and intermittent rhythmic beta activity (). Moreover,
catalepsy and waxy flexibility vanished and the patient opened his eyes, answered
simple questions (eg, full name, location) and followed simple commands (count 1-10,
close your eyes). Altogether, these findings convinced us that the patient was in
NCSE (this is explained in greater detail under Discussion).
In the ER, the patient also had 10- to 20-second episodes of rhythmic right leg
jerking, consistent with focal clonic seizures. Several episodes were witnessed by
the medical staff, but all occurred after the EEG was recorded. Levetiracetam 4000
mg IV was loaded followed by 1500 mg IV q12h. Catatonia recurred prompting
administration of lorazepam 2 mg IV q8h PRN. Catatonia resolved after he received a
total of 8 mg of lorazepam. Focal clonic seizures still occurred but were less
frequent. Because of fluctuations in mental status, with periods of deep somnolence
and stupor, the patient was intubated for airway protection. Propofol IV infusion
was started at 5 µg/kg/min. He was admitted to the intensive care unit where
continuous video-EEG monitoring was performed over 3 days.
Continuous EEG monitoring with video and compressed spectral array trending initially
showed long periods of GRDA (2-42 minutes) punctuated by shorter non-GRDA periods
(0.5-11 minutes; ).
As a rule, GRDA was not associated with any clinical change (). However, the onset of a few GRDA
episodes coincided with right lower limb jerking or focal motor seizure (). Even though GRDA
persisted for several minutes, limb jerking (when present) occurred only within the
first 10 to 20 seconds of GRDA. There was no change in the EEG, such as appearance
of focal epileptiform discharges, during leg jerking. The same GRDA was seen whether
the patient was not moving or his leg was jerking. GRDA showed some fluctuation in
amplitude, sharpness, and frequency from 1.5 to 2.5 Hz (). Propofol was gradually titrated
toward a maximum rate of 50 µg/kg/min. Lacosamide was also started: 400 mg IV load,
then 200 mg q12h. The duration of GRDA and non-GRDA episodes progressively increased
and decreased, respectively (). GRDA completely disappeared after 4 days of levetiracetam,
lacosamide, and propofol therapy. Propofol was tapered and discontinued on day 4.
There was no recurrence of GRDA, seizures, and catatonia. Serum creatine kinase
levels showed a downward trend from day 1 (19 370 U/L) to day 6 (617 U/L). On day 6,
mental status examination was normal and the patient was discharged on levetiracetam
1500 mg bid and lacosamide 200 mg bid. He was seen in clinic 4 weeks later. He
remained free of catatonia symptoms but continued experiencing focal motor seizures
of the right leg 3 to 4 times a week. At that point, extended-release valproate 500
mg bid was added to his regimen. We learned via phone call, 4 weeks later, that the
focal motor seizures stopped completely.


In July 2019, a 51-year-old female was injured in a traffic accident and subsequently sent to a local emergency department. She complained of intense pain in her severely injured ankle, which has the obvious deformity and severe soft-tissue swelling with a minor wound bleeding on the anteromedial region. Luckily, vascular and neurologic impairment and compartment syndrome were not observed. The initial plain film radiographs on anteroposterior (AP) showed obvious separation of the lower tibiofibular syndesmosis, widened medial joint space of the ankle, and oblique fibular fracture in the proximal third part of the shaft. The lateral view of radiographs showed posterior displacement of the intact distal fibula with no fracture and posterior dislocation of the talus (). Next, the manually closed reduction under sedatives condition was conducted. Unfortunately, the distal fibula was unchanged and still fixed in the original displaced position, and could not be reduced. Meanwhile, the talus was observed with posterior subluxation. After dressing the anteromedial ankle open wound and applying a long-leg cast, the patient was admitted to the ward of the local hospital for further routine treatment.
Six days after the injury, the patient was shifted to our institution. However, the operation was postponed due to the infection in the wound and the ankle joint was completely swollen. Next, we gave antibiotics, changed the dressing of the infectious wound, and gave necessary exercise to the immobilized lower limbs. To further assess the injured ankle, computed tomography (CT) and magnetic resonance imaging (MRI) scans of the injured ankle, and X-rays of the healthy ankle on AP and lateral views, were performed. Axial CT images showed that the intact distal fibula was displaced from the normal tibial notch and fixed behind the posterolateral tibial tubercle. Unexpectedly, multiple free osteochondral fragments were found between the distal tibial plafond and the talar dome, which were also observed in the subsequent MRI images (). In addition, MRI of the coronal plane revealed the rupture of the deltoid ligament ().
At 19 days after injury, the infection and swelling of the ankle joint had been obviously reduced. Ankle arthroscopy–assisted surgery was conducted to minimize the risk of intraoperative trauma and postoperative complications. The operative procedure is described below.
First, ankle arthroscopy (2.7 mm, 30 arthroscopes) under thigh tourniquet was performed using standard anteromedial and anterolateral portals without traction. The hematoma and several osteochondral loose fragments (size ~0.5 to 1 cm2) located in the middle and medial side of the posterior tibiotalar space were smoothly removed after the ankle plantar flexion (). The other bone fragments attached to the posterior capsule are located behind the posterior malleolus and do not need to be removed because they do not affect ankle movement. According to preoperative CT and intraoperative exploration, we confirmed that the free bone fragments were avulsed from the posterior distal tibia surface. Because of the small size of cartilage defect, no microfracture treatment was performed. Second, the surgeon attempts to clamp the distal fibula with cloth forceps, apply outward and forward force, and pull the distal fibula with posterior dislocation out of the posterior distal tibia and then reposition the distal fibula to the lower tibiofibular notch with internal rotation force. Then, two 3.5-mm quadricortical lag screws transversely fixed the syndesmosis with the ankle held in dorsiflexion of 90°. All the procedures were monitored with C-arm X-ray. Although X-ray and arthroscopic examination showed an anatomical and stable reduction of the syndesmosis, however, a slightly widened medial joint space was observed compared to the normal left mortise. We assumed it might be related to the rupture of the deltoid ligament. Then, a medial approach was performed to observe the partial whole layer of deltoid ligament avulsed from the medial malleolus, which was consistent with the preoperative MRI scan findings. Finally, two anchor sutures were inserted into the tip of the medial malleolus to repair the torn deltoid ligament (). The final intraoperative radiographic AP and lateral views showed closely anatomical ankle joint space and a satisfactory syndesmosis position. Postoperative images of X-ray and CT also showed acceptable position of the injured ankle ().
Postoperatively, a plaster cast was applied for 4 weeks and non-weight bearing for 2 months was advised after surgery. The progressive postoperative rehabilitation protocol was well complied by the patient. Three months after surgery, the syndesmosis screw was removed, and the subsequent images of X-ray and MRI showed a satisfactory position of the ankle joint and the continuous deltoid ligament (). At the last follow-up of 6 months, the patient recovered well and obtained a pain-free range of motion of the ankle with passive 10° dorsiflexion and 40° plantar flexion (), and luckily resumed her normal gait and daily activities. The American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale score was 92 points at the final follow-up.
During the follow-up period, complications such as skin necrosis, infections, stiffness, and hardware failure were not observed.


A 58-year-old woman was admitted to our hospital due to irregular vaginal bleeding that had persisted for more than 1 month. Physical examination showed normal superficial lymph nodes, flat abdomen, no evidence of tumor in the vulva, cervical hypertrophy, a 3-cm cervical nodule, vaginal fornix involvement, and hysterauxesis with no neoplastic ovarian cyst. A cervical biopsy revealed a moderate to poorly differentiated adenocarcinoma. The patient was diagnosed with moderately differentiated cervical adenocarcinoma and underwent radical hysterectomy under general anesthesia, including bilateral adnexectomy, pelvic lymph node dissection, para-aortic lymphadenectomy, greater omentectomy, multi-point intestinal membrane biopsy, and intestinal adhesion lysis.
Postoperative pathology suggested endometrial adenocarcinoma (grade I, 6 × 3 ×1.5 cm), localized foci (grade II) accompanied by squamous cell differentiation, and high-grade serous carcinoma differentiation. The depth of myometrial invasion was more than one-half, and the depth of infiltration from the cervical mucous to the shallow layer interstitium was less than one-third. The cancer also transferred to or infiltrated the right common iliac (0/2, no metastases in 2 lymph nodes removed), right external iliac (0/1), right groin deep (0/4), right internal iliac and obturator (1/2), left common iliac (0/1), left external iliac (0/2), left groin deep (0/2), left internal iliac and obturator (0/2), as well as para-aortic (4/8) lymph nodes (). A high-grade primary serous carcinoma of the right fallopian tube (5 × 3 × 1 cm) infiltrated into muscular layer was diagnosed. The left fallopian tube and bilateral ovarian tissues showed suppurative inflammatory changes without abscess formation or cancer cells. Fibers and adipose tissues (omentum, left paracolic sulcus, right paracolic sulcus, retrograde peritoneum of bladder, uterine and rectal fossae) were also found (). As shown in , hematoxylin and eosin staining and immunohistochemistry of monoclonal antibody and cancer gene markers showed the following: estrogen receptor (uterus ++50%, fallopian tube ++60%), progesterone receptor (uterus ++60%, fallopian tube ++30%), p53 (uterus + 10%, uterus ++50%, fallopian tube + 70%), p16 (uterus + 50%, fallopian tube +), cancer antigen 125 (CA125; uterus +, fallopian tube +), Wilms’ tumor protein (WT-1; part uterus +, part fallopian tube +), paired-box gene 8 (PAX-8; part uterus +, part fallopian tube +), and Ki-67 (uterus + 10%, fallopian tube + 70%), where + indicates staining intensity.
Macroscopic assessment showed that the endometrial adenocarcinoma and primary serous fallopian tube carcinoma were continuous and in close proximity (). The patient was diagnosed with a collision tumor comprising endometrial adenocarcinoma and primary serous fallopian tube carcinoma. She received paclitaxel (200 mg, d1) and carboplatin (area under the curve = 5; d1, q3w), as well as intensity-modulated radiation therapy (tumor-absorbed dose [DT]: CTV 45Gy/25F) in 10v-x (10 megabytes of radiation energy) pelvic lymph node drainage area. One month after pelvic radiotherapy, the patient developed brain metastases and died.


A 22-year-old lactating Indian woman presented with sudden painless onset diminution of vision in her left eye for 8 days. General examination revealed purpuric rashes over the wrist [] and non-pitting pedal edema with a venous ulcer on the right foot []. She had a history of multiple episodes of painful oral ulcers in the last 6 months. Her menstrual history was unremarkable, with no history of abortions.
Visual acuity was 20/20 in the right eye (RE) and 20/600 in the left eye (LE) with a relative afferent pupillary defect. Rest of the anterior segment was unremarkable in both eyes. Fundus was normal in the right eye []. The left eye had optic disc edema along with diffuse phlebitis, multiple dot hemorrhages in all quadrants, and diffuse thickening of the retina at the macula []. The general background of the fundus was pale when compared with the right eye. Fundus fluorescein angiography (FFA) of the left eye confirmed the presence of diffuse occlusive phlebitis with a filling defect in the supero-temporal vein, persisting till late phase [Fig. and ]. Optical coherence tomography (OCT) of the left eye confirmed the presence of macular edema [] with a neuro-sensory detachment. FFA and OCT of the right eye were within normal limits [].
Her vitals were normal, total leucocyte count was 15,500 per microliter and hemoglobin was 8.5 gm/dl. Keeping in mind a predominant venous involvement, HLA typing was performed and HLA B-52 turned out to be positive. Other causes of vasculitis were ruled out as anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (cANCA), and anti-phospholipid antibody (APLA) were negative.
A diagnosis of BD was made based on ocular and systemic manifestations and she was started on intravenous dexamethasone 200 mg for 3 days followed by oral prednisolone 45 mg once daily which was tapered slowly by 5 mg per week. The response to steroids was good with complete disappearance of skin lesions on the upper limb [] and a significant reduction in pedal edema within 10 days of initiation of treatment []. Visual acuity improved to 20/200, macular edema had resolved completely. [] The phlebitis healed, with FFA showing a significant reduction in retinal vascular leakage [Fig. and ]. Visual acuity in the right eye was maintained at 20/20 until 1 month following the initial presentation when it dropped to 20/32. OCT at this visit showed focal photoreceptor outer segment loss, which was healthy in the previous visits [Fig. and ]. At this point, the vasculitis in the left eye had healed completely and steroids were tapered slowly.
Two months later she presented with ascites and was referred to a physician for the same, where she was diagnosed to have BCS with an obstruction in the supra-hepatic Inferior Vena Cava (IVC) []. She had been advised surgery for relieving the IVC obstruction.


A 45-year-old woman was presented to our emergency department with complaints of severe sharp epigastric pain radiating to back for two days, with associated nausea and vomiting. She did not have any history of cough, dyspnea, or fever. The patient denied any history of alcoholism, smoking, and similar complaints in the past. On physical examination, she was afebrile and had tachycardia (102 bpm) with an oxygen saturation of 97% on room air. Her abdominal examination showed severe epigastric tenderness with a soft, non-distended abdomen. Her laboratory investigations showed elevated serum amylase (364 U/L) and lipase (293 U/L) levels, WBC of 12.5×103/μL, a hemoglobin level of 12.6 g/dl, and platelets 184×103/μL. The liver enzymes including alkaline phosphatase, γ-glutamyl transferase, alanine transaminase, aspartate aminotransferase, and total bilirubin were within normal ranges. CT scan of the abdomen showed a diffusely increased volume of the pancreas, with the acute peripancreatic fluid collection and peripancreatic inflammatory changes suggestive of acute interstitial edematous pancreatitis. CT severity index score was 4 (). She was admitted and treated symptomatically with fluid replacement, optimization of electrolyte balance and empiric antibiotics. In the first week, she developed acute hypoxic respiratory failure, with an SpO2 of 85 percent requiring oxygen supplementation. Her HRCT revealed multifocal ground- glass opacities in both lungs, more in the lower lobes with peripheral distribution. These findings were highly suspicious for COVID 19 pneumonia with a CORADS score of 5 (). Later, nasal swab for COVID reverse transcriptase polymerase chain reaction (RT-PCR) tested positive. The patient was isolated and conservatively managed. She had an uneventful recovery with gradual resolution of her abdominal and pulmonary symptoms.


An 81-year-old Caucasian man presented to the Rheumatology Outpatient Clinic complaining about painful and indurated skin lesions in the upper and lower extremities during the last 3 months, initially affecting his thighs bilaterally. He had been diagnosed with non-small-cell lung cancer (NSCLC) 1½ years ago and since then had been treated with the programmed death cell protein 1 (PD-1) inhibitor pembrolizumab. He had already undergone a full-thickness skin biopsy of the lesion on his right leg revealing scleroderma-like features: thickening and hyalinization of the connective tissue of the deep dermis, subcutaneous fat and muscular fascia, perivascular and focal interstitial lymphocytic and plasma cell infiltrates in the subcutaneous fat and localized atrophy of the adnexal structures. No eosinophilic infiltrates were found. He had been receiving 16 mg of methylprednisolone and 2 g of mycophenolate mofetil daily for the last 10 days since he had been initially diagnosed with scleroderma.
On his first visit, the patient denied Raynaud’s syndrome, dyspnea, gastroesophageal reflux, joint pain, diarrhea or other clinical manifestations compatible with systemic scleroderma or other connective tissue disorders.
His clinical examination revealed sclerotic skin lesions on his legs and forearms, sparing the fingers, trunk and face, and a linear depression of the skin along the course of the veins especially on the forearms, a positive “groove sign” (Fig. ). Ulcers, telangiectasia, joint sensitivity and inflammation were not present according to the thorough clinical examination.
The patient had a positive anti-nuclear antibody (ANA) test with a titer of 1/160, normal eosinophil counts (while receiving corticosteroids) and no other remarkable laboratory findings. Erythrocyte sedimentation rate (ESR) and C-reactive protein levels were not available on his first visit.
Due to the lack of systemic manifestations, the diagnosis of systemic sclerosis was not substantiated. However, based on the localized cutaneous induration, positive groove sign and absence of Raynaud’s syndrome, the diagnosis of eosinophilic fasciitis (EF) was made. The histopathologic findings confirmed the diagnosis of a scleroderma-like disorder affecting the fascia.
The high incidence of immune-related adverse events (irAEs) due to the treatment with checkpoint inhibitors (CPIs) and the correlation of the onset of patient’s symptoms to the initiation of pembrolizumab made the latter a potential cause of these EF-like manifestations. Therefore, pembrolizumab was temporarily discontinued. The patient remained on 16 mg methylprednisolone per day for the next 3 weeks, and the mycophenolate mofetil was withdrawn.
During follow-up, skin sclerosis was improved but not eliminated, and eosinophil counts remained within the normal range. The corticosteroids were slowly tapered to a dose of 4 mg daily, and pembrolizumab was re-administered after having been withheld for 2.5 months. Until his last evaluation, he had shown a complete response to pembrolizumab.
Written informed consent was obtained from the patient for publication of this case report and accompanying images.


A 69-year-old woman complained about experiencing asthenia and dyspnea with dizziness and diaphoresis.
A 69-year-old woman arrived at the emergency department with a 15-d history of progressive asthenia, dyspnea on moderate exertion and progressive worsening shortness of breath associated with dizziness and diaphoresis.
The patient was diagnosed in 2005 with alcoholic cirrhosis, without any decompensation since 2011. She followed an adequate follow-up in the hepatology department of the hospital and she had been abstinent since the last decompensation. Her last abdominal Doppler-ultrasonography from May 2019 showed liver cirrhosis with signs of portal hypertension, mild ascites and cholelithiasis. Furthermore her last upper gastrointestinal endoscopy from June 2019 showed esophageal varices and portal gastropathy. She also received treatment with beta-blockers and diuretics with good tolerance and adherence. Thereafter, she had a biological aortic valve replacement for severe aortic stenosis in December 2018, and since then, she remained asymptomatic.
The vital signs were within range and the physical examination was fairly normal. She had no chest discomfort or palpitations, orthopnea or an increase in the perimeter of lower limbs. She also denied having fever, chills, cough or expectoration, abdominal distention or any weight loss. In addition, she had a regular cardiac rhythm without cardiac murmur or rub noted, and the jugular venous pressure was not elevated. Her lungs were clear on auscultation and the oxygen saturation was correct without oxygen therapy. Her abdomen was also soft, non-tender and had no hepatosplenomegaly or clear signs of ascites. Moreover, she had no leg swelling, bruising or petechiae. There was no clubbing or cyanosis of her feet or hands. Signs of liver cirrhosis were found on examination, such as spider angioma and mild palmar erythema.
The blood test at admission revealed an impaired renal function with a creatinine of 1.82 mg/dL and a glomerular filtration rate of 28 mL/min/1.73 m2, mild hyponatremia with sodium of 132.3 mmol/L, elevated pro-brain natriuretic peptide (923 pg/mL) and high D-dimer (917 ng/mL).
Her chest X-ray showed pathological signs. Due to the high suspicion of pulmonary embolism (PE) in a patient allergic to iodine, a ventilation/perfusion lung scan was performed, which did not exhibit any signs of PE. Contrasted echocardiography was requested to rule out portopulmonary hypertension or hepatopulmonary syndrome as the cause of the dyspnea of the patient. The test did not reveal signs of pulmonary hypertension nor shunts and showed a preserved systolic function (left ventricular ejection fraction [LVEF]: 58%) and a normally functioning prosthetic aortic valve. Unexpectedly, a mass at the posterior wall of the RA of 32 by 20 mm suggestive of an intracavitary thrombus was detected.
Magnetic resonance imaging was performed to confirm this finding due to its higher sensitivity and specificity. The mass inside the RA coming from the liver through the IVC was noted. This image was suggestive of an infiltrating HCC tumor thrombus (TT) (Figure ). With the previous premedication, an abdominal multiphase CT was finally performed, thereby confirming the presence of a lesion in segment VIII with extension to segments V and I, suggestive of hepatocarcinoma (Figure ). Left suprahepatic vein thrombosis with extension to the IVC until the RA and thrombosis in the left portal vein was noted, suggestive of tumor infiltration (Figure ). On further work-up, her alpha-fetoprotein level was 6856.1 ng/mL.


A 17-year-old female with a history of Sickle cell disease (Hb SS disease) received a hematopoietic stem cell transplant (HSCT) from an unrelated donor due to her transfusion-related iron overload, and abnormal transcranial Doppler (TCD) findings. The post-transplant course was complicated with graft versus host disease (GVHD) in skin and lungs, human herpesvirus 6 (HHV6) reactivation, and oral/labial herpes simplex (HSV) infection.
Approximately seven months after the HSCT, she was found to have 16% of immature mononuclear cells on a complete blood count (CBC) differential report. A follow-up peripheral blood flow cytometry study showed a B cell population with a dim expression of CD5, which comprised 66% of lymphocytes (A and B). Other T cell markers (CD3, CD4, CD8, CD2, and CD7) were negative (C, D, and E). Negative CD23 expression with positive FMC helped to rule out chronic lymphocytic leukemia (CLL) (F). No evidence of a monoclonal B-cell population was identified by kappa and lambda analysis (kappa/lambda ratio of 2.3:1 (G)). These cells also lacked plasma cell markers (bright CD38, CD138 (H)), and immature markers (CD34 and CD117) were also negative (I). These cells also did not express CD10, CD15, and CD56. These findings were interpreted as a reactive process; therefore, no further treatment or workup was performed. A repeat peripheral blood flow cytometry performed 22-months post-transplant demonstrated a persistent population of B1a cells, comprising 18% of lymphocytes. Chimerism studies performed at that time were noted to be 99-100% donor.


A 36-year-old previously healthy male presented to our hospital with sudden onset bilateral, painless loss of vision of 12 hours duration along with left-sided continuous headache of moderate to severe intensity and one episode of vomiting. 10 hours prior to the vision loss, he also had one episode of exertional pre-syncope after running a 5-km circuit. There were no other relevant past or family history.
On initial examination, the patient was well oriented, had stable vitals with a regular pulse of 60/min, blood pressure of 128/86 mmHg, and respiratory rate 14/min with SpO2 of 98%. His neurological examination was essentially normal. However, his visual acuity was < 6/60 though bilateral pupils were equally reactive to light with a normal fundus on examination. Cardiovascular examination was normal. ECG revealed ST depression in inferior leads with bradycardia.
Non-contrasted computed tomography (NCCT) of the brain revealed an acute ischemic infarct in left Middle Cerebral Artery (MCA) -Posterior cerebral artery (PCA) watershed areas and distal MCA region along with multiple old lacunar infarcts (A). His biochemical parameters remained normal except for a rise in ESR (Erythrocyte Sedimentation Rate, Normal Value ≤ 15 mm/hr) to 30 mm/hr within 3 days. The patient was managed as a case of Stroke in Young. As multiple infarcts on NCCT indicated a thromboembolic phenomenon, a TEE was done to rule out any cardiac cause. On TEE, a left atrial (LA) mass measuring 2.93 cm2, mobile, attached to the interatrial septum (IAS) near the Inferior Vena Cava (IVC) junction was noted with suspicion of atrial myxoma (B).
The ejection fraction was 65%. However, a cardiac MRI done subsequently favored a diagnosis of LA thrombus over myxoma as no stalk was demonstrated. After that, the patient was started on IV Heparin and was taken up for surgery 10 days later. Intraoperatively, a 3cm x 2cm pedunculated LA mass with rough villous surface and a calcified stalk arising from IAS, was noted. He underwent excision of the left atrial mass with autologous pericardial patch closure of the septal defect through the bi-atrial approach. The diagnosis of atrial myxoma was confirmed on histopathologic examination with characteristic features of stellate shaped myxoma cells embedded in a myxoid background (). The post-operative period was uneventful.