A 32-year-old man from north of Iran who worked at a supermarket was presented with a history of painless, livid, verrucous nodular swelling and exudative erythematous lesions and pustules of the 5th finger of right hand. The first skin lesion had appeared on the extensor side of the finger 1.5 months ago. This case was treated with Cephalexin 500 mg/Q6H without any improvement. There were no systemic complaints and vital signs were stable. The patient mentioned an injury at the site of the first lesion. He did not have contact with domestic animals and never been in the tropics, but his family had owned an aquarium with tropical fish for the past 2 years and he cleaned it regularly. There were no risk factors for HIV infection. Family history of skin diseases was negative. Clinically, a long, painless, solid, livid, verrucous infiltrate 15 × 10 mm in diameter was localized on the extensor side of the right hand and Sporotrichoid pattern of distribution was obviously present. Histopathology examination of the lesions showed nonspecific inflammation to granuloma formation. Results of gram stain and routine culture from biopsy of skin lesions in both blood agar and McConckey agar were negative. In laboratory tests complete blood count and ESR were in normal range but PPD was 21 mm. A smear from the walls of the necrotic center when stained for acid-fast bacilli revealed organisms consistent with mycobacteria. The skin lesion was cultured for mycobacteria on Lowenstein-Jensen at 30 and 37˚C. Growth occurred after 12 days at 30˚C and did not grow at the incubation temperature of 37˚C. The results of the biochemical tests were indicative of M. marinum. On the basis of antibiogram, Treatment started with Ethambotul 800 mg/daily, Rifampicin 600 mg/daily and clarerithromycin. After 2.5 months all signs and symptoms disappeared and treatment were discontinued after 4 months.


The patient was a single 28 year old man from Amol city in Iran .he was shopkeeper and since four weeks ago developed a single purple papule on bake side of his left hand. Lesion was painful but he did not have any complaint about itching or burning after some days the lesion changed to erythematous nodule and crusted ulcer. He did not have contact with domestic animals and never been in the tropical area and in his familial and medical history there were no significant problem. He reported irregular but multiple cleaning of aquarium during last year. Due to resistance to medication biopsy was done and acid fast bacilli was seen in culture and smear. The skin lesion was cultured for mycobacteria on Lowenstein-Jensen at 30˚C and 37˚C. Growth occurred after 12 days at 30˚C and did not grow at the incubation temperature of 37˚C. The results of the biochemical tests were indicative of M. marinum.
Histopathology examination of the lesions showed nonspecific inflammation to granuloma formation. Results of gram stain and routine culture from biopsy of skin lesions in both blood agar and McConckey agar were negative. In laboratory tests complete blood count and ESR were in normal range but PPD was 25 mm. On the basis of antibiogram, treatment started with clarerithromycin 500 mg/bid and after 3 months patient cured completely and treatment discontinued after 4 months ().


A 68-year-old man underwent a first cadaveric orthotopic liver transplantation for hepatitis B virus and alcohol-induced cirrhosis that was complicated by hepatocellular carcinoma. After an induction therapy using antithymocyte globulins (ATG), his initial immunosuppressive therapy was based on tacrolimus, mycophenolate mofetil, and steroids. At day 11, because Aspergillus fumigatus was found in a systematic tracheal aspiration, a 21-day course of voriconazole was given. By day 60, he experienced a steroid-resistant acute rejection, which required ATG antirejection therapy. By day 78, he presented with isolated fever. C-reactive protein was 100 mg/L. Total lymphocyte count was 375/mm3. CD4-positive cell count was 60/mm3. Liver function tests were within the normal ranges. Blood-culture and urine-culture were negative for bacteria and fungi. Aspergillus antigenemia was negative. Cytomegalovirus DNAemia was negative. The bronchoalveolar lavage did not reveal the presence of any bacteria, virus, or fungi. In the absence of any identified cause of infection, he underwent a chest and abdominal CT scan, which showed an isolated rounded cardiac collection. Thus, a cardiac MRI was performed as soon as possible to enable diagnosis and close monitoring of the evolution of the cardiac lesion.
The CMRI pointed out a 3 cm diameter collection within the epicardium and myocardium, on the apex posterior wall, without any mass effect. On T1-weighted MRI, the lesion showed a thick rim and a hypointense core. The core was hyperintense on T2-weighted and T2-black blood SPIR MRI, suggesting a cystic core. Only the thick rim was enhanced on postgadolinium MRI. No ischemic lesion or heart-motion abnormality was found. Thus, we hypothesized an infectious cardiac abscess. Because the abscess was very close to the anterior interventricular artery, the radiologists and cardiac surgeons could not perform any abscess puncture for microbial diagnosis. Despite a negative Aspergillus antigenemia and because of the patient's recent history of aspergillosis, we initiated a dual antifungal therapy of caspofungin and liposomal Fungizone.
A second CMRI, performed one week later, showed the abscess had grown. Because of a history of tuberculosis in childhood, this prompted us to initiate an antituberculosis therapy (isoniazid, rifampicin, ethambutol, and pyrazinamide) though mainly pericardial abscess has been described []. A CMRI performed 3 months after diagnosis showed stability of the abscess, with the patient still receiving antituberculosis and double antifungal therapies. At that time, liposomal Fungizone was replaced by voriconazole. Because of increased liver-enzyme levels, voriconazole was stopped 1 month later, and the patient was continued on caspofungin alone. Antituberculosis therapy was also continued. By 6 months after diagnosis, a CMRI showed several new growing epi- and myocardial abscesses on both left and right atria and ventricles (). Multiple small and confluent soft-contoured nodules were observed on CT examination and could definitively be attributed to Aspergillus fumigatus infection as, at that time point, the latter was found for the first time in serum, blood, urine, and lung. For the first time, Aspergillus antigens were also positive. Urgent heart surgery was discussed but was rejected due to the patient's altered physiological status and to the extent of the lesions. A few days later, the patient died from a septic shock and multiple organ failure caused by disseminated aspergillosis. Postmortem examination confirmed that multiple aspergillosis abscesses were located in the epicardium, myocardium, and endocardium and were associated with lung, liver, kidney, and skin aspergillosis abscesses.


Patient 1 was 12-month-old female who required intubation for 2 days after she presented with acute liver failure. Upon extubation, she developed stridor and increased work of breathing. Airway examination documented Grade III, soft subglottic stenosis and balloon dilation was performed. Repeat balloon dilations were performed at 2 weeks and 4 weeks after the initial balloon dilation (). The airway was stable 3 months after the first balloon dilation. The child has been followed for 14 months with no stridor or increased work of breathing.


Patient 2 was a 14-week-old male who required intubation for 8 days after he presented to emergency department with respiratory failure. He failed extubation twice. Airway examination documented Grade II, soft subglottic stenosis and balloon dilation was performed (). Repeat balloon dilations were performed at 13 days and 10 weeks after the initial balloon dilation. The airway was stable 5 months after the first balloon dilation. The child has been followed for 21 months with no stridor and increased work of breathing.


Patient 3 was a 6-month-old male who was born at 28 weeks of gestational age. He required endotracheal intubation for 3 weeks. He was discharged home after an 8-week stay in the intensive care unit. He developed bronchiolitis and croup after discharge. He presented to emergency department with a 1-month history of progressively worsening stridor and increased work of breathing. Assessment of the airway documented Grade II, soft subglottic stenosis, and balloon dilation was performed. Repeat balloon dilations were performed at 3 weeks, 7 weeks, and 10 weeks after the initial balloon dilation. The airway was stable 4 months after the initial balloon dilation. The child has been followed for 20 months with no further stridor or increased work of breathing.


A 55-year-old Saudi woman was admitted to the Emergency Department with a chief complaint of episodes of paroxysmal abdominal pain. The pain started two weeks previously that was aggravated for the last two days with nausea, vomiting, and constipation. Past medical and surgical history revealed that she was diabetic since last 12 years and was on oral metformin 500 mg three times a day and she underwent total abdominal hysterectomy (TAH) and bilateral salpingooophorectomy (BSO) sixteen months back for uterine leiomyosarcoma outside of our hospital without any adjuvant treatment.
During physical examination, moderate tenderness over the right epigastric and hypochondrial areas and active bowel sounds were observed. Plain abdominal X-ray showed dilatation of small bowel without any gas-fluid levels; . Baseline hematology showed leukocytosis (12.4 × 109/L), high absolute neutrophil count (10.4 × 109/L), and normal hemoglobin and platelets counts. Serum chemistry showed lactate dehydrogenase (LDH) was 237 U/L ↑ (normal: 135–214), sodium 132 mmoL/L ↓ (normal: 135–145), serum creatinine was 226 μmoL/L ↑ (normal: 44–80), urea 15.1 mmoL/L ↑ (normal: 2.5–6.4), anion gap was 31.2 mmoL/L (normal: 12–20), and lactate was 2.3 mmoL/L (normal: 1.1–2.2). Computed tomography (CT) abdomen without contrast showed distended stomach, proximal small bowel loops extending down to midabdominal level where there was abrupt change in caliber of the bowel, and collapse of distal small bowel loops. At this transition point appeared a soft tissue density containing vessels, which raised the possibility of intussusception with a lesion; . Patient underwent exploratory laparotomy on the same day. During exploration, a jejunal mass of size 6 cm was found which was resected and anastomosis was performed. Histopathology of jejunal mass was leiomyosarcoma arising from mucosa. Further immunohistochemistry (IHC) favored jejunal mass as metastatic leiomyosarcoma rather than primary leiomyosarcoma (positivity for SMA and negativity for S100, DC117, CD34, and CK AE1/AE3); . Further histopathological review of primary surgery specimen showed 7 cm uterine leiomyosarcoma involving out half of myometrium without any lymphovascular invasion (LVSI) which confirmed the diagnosis; .
After her successful postoperative recovery, staging workup was done. Bone scintigraphy was found normal. CT chest showed multiple pulmonary metastatic nodules; largest one was of size 10 × 6 cm in right middle and lower lobes invading adjacent mediastinum, mediastinal pleura, pericardium, and right pulmonary vein and bronchus; . CT brain revealed multiple intra- and extracranial enhancing lesions at left occipital, left parietal subdura (5.6 × 3.5 cm) with midline shift and vasogenic edema, and right cerebellum. Also there was superior sagittal sinus tumoral thrombosis.
After discussing her case in multidisciplinary board meeting, she was given palliative cranial radiotherapy 20 Gy in 5 fractions over a week and then she was started on systemic chemotherapy based on single agent doxorubicin (60 mg/m2).
At time of publication patient was found alive and was receiving chemotherapy.


In July 2005, a 33 year old Zimbabwean female, resident in the UK for 8 years, was admitted with a week history of fever, headache, and neck stiffness. She had no past medical history of note. Systemic examination showed fever and meningism but no focal neurological deficits. Blood tests revealed mild anaemia, lymphopenia, and raised C-reactive protein. An HIV test was positive with CD4 count of 51 cells/μL (4%). CT head without contrast showed marked meningeal inflammation but no focal lesions. A lumbar puncture (LP) revealed raised opening pressure (OP) of 27 cms H20, lymphocyte count (30/cu mm), protein (1.33 g/L), and CSF: serum glucose ratio of 50%. Cerebral spinal fluid (CSF) microscopy showed multiple yeast with high cryptococcal antigen (CRAG) titre of >1 : 25,600. CSF Acid-alcohol fast bacilli (AAFB), toxoplasmosis, and viral screens were negative. The patient was started on standard amphotericin with flucytosine and prophylactic cotrimoxazole.
On day five of therapy, she began to complain of increasing headache and neck stiffness. A right-sided sixth nerve palsy was noted as a new neurological sign. An MRI brain showed changes in keeping with chronic meningitis and occipitoparietal changes (). Repeat LP revealed OP of 40 cms H20 with persistently high protein and lymphocyte count. Over the next two weeks, the patient required a lumbar drain to alleviate excruciating pressure-related headaches.
CSF cultures revealed Cryptococcus neoformans sensitive to amphotericin B (Minimum Inhibitory Concentration “MIC” 0.125 mg/L) and itraconazole (MIC 0.03 mg/L) and intermediate to fluconazole (MIC 4.0 mg/L) and flucytosine (MIC 8.0 mgL). Amphotericin and flucytosine were continued for four weeks and then switched to oral fluconazole 800 mg once daily. This prolonged initial phase was based on symptom severity, high fungal burden, and relatively high MIC to fluconazole. A repeat MRI head showed regression of the previous changes.
Four weeks into cryptococcal treatment, combined antiretroviral therapy (cART) was initiated with Kivexa (abacavir and lamivudine) and efavirenz. The patient then developed a new, persistent headache and subsequent LPs showed raised OPs, lymphocytes, and protein. Yeast cells persisted in CSF for 3 months after starting amphotericin and flucytosine and CSF cultures remained positive until September 2005 (2 months after treatment start).
By October 2005, CSF cultures were negative for Cryptococcus and the patient had improved clinically. VL was undetectable and CD4 counts had risen minimally from 51 (4%) to 67 cells/μL (6%). She was discharged home on fluconazole (800 mg OD), cotrimoxazole, and cART.
The patient then went on to have a difficult clinical course with recurrent admissions over the subsequent 14 months ().


A 64-year-old white male with an unremarkable past medical history presented with acute-onset diplopia. His symptoms began 2 months prior to his initial neurosurgical evaluation. There was no obvious history of trauma. The patient reported that his double vision was exacerbated by looking down and was improved when tilting his head to the left. He also was experiencing significant right frontal headaches that worsened throughout the day. On physical examination, he was found to have diplopia on downward gaze to the right, which suggested a right-sided trochlear nerve palsy with no other focal neurological deficits. The remainder of his neurological exam was unremarkable.
Magnetic resonance imaging (MRI) of the brain with and without contrast revealed a well-circumscribed, heterogeneously enhancing space-occupying lesion in the right ambient cistern. The mass measured 9 mm × 7 mm × 11 mm and compressed the adjacent anterior aspect of the upper pons. It appeared to have a broad base with a thin enhancing tail extending inferolaterally along the meninges (Figures and ) [–].
The patient was transferred to the operative table and placed in the lateral decubitus position. A lumbar drain was placed at this time. His head was placed in a Mayfield 3-point fixation system, which was aligned to maximally expose the right temporal region. The operative site was prepped and draped in the usual sterile fashion. A curvilinear incision was made overlying the right temporal region that began approximately 1.5 cm anterior to the external auditory canal and was carried superiorly to the superior temporal line. It was then carried posteriorly approximately 5 cm. The skin flap was rotated inferiorly and posteriorly and affixed into place with hooks. The temporalis muscle was mobilized anteriorly. This exposed the right temporal region. An electric drill was taken, and a right temporal craniotomy was elevated and the microscope was moved into the field.
Approximately 20 mL of CSF was removed from the lumbar drain at this time to promote brain relaxation. An extradural subtemporal dissection ensued. Dissection continued medially and the greater superficial petrosal nerve was identified. Dissection continued medially until Meckel's cave was identified extradurally. Anteriorly, the middle meningeal artery was seen coursing through the foramen spinosum and posteriorly was the superior petrosal sinus.
A middle fossa retractor was inserted and extradural elevation of the right temporal lobe was performed. Careful attention was paid to avoid excessive retraction of the temporal lobe. An anterior petrosectomy was performed as originally described by Kawase et al. [, ]. The superior petrosal sinus was cauterized laterally. An incision was made beginning along the temporal dura and carried through the superior petrosal sinus and into the posterior fossa. This allowed identification of the 5th nerve at the nerve root entry zone. The tentorium was cut medially, and the dura overlying Meckel's cave was removed resulting in excellent visualization of the tentorial incisura region. A large mass was clearly identified at this time; the trochlear nerve appeared to enter directly into the lesion (). The capsule was cauterized and incised. Multiple specimens were sent for pathological analysis, and the pathology of the specimens was consistent with a schwannoma. The trochlear nerve was now cut proximally to allow further mobilization of the mass. Following intratumoral debulking, progressive mobilization of the capsule resulted in a gross total resection. The retractor was removed, the wound was closed in a multilayer fashion, and a dressing was applied.
The patient had an uneventful postoperative course and was discharged to home on postoperative day 3. As expected, the patient continued to experience diplopia with downward gaze. At 1-month followup, the patient had recovered well from the surgery with no complaints. The right trochlear nerve palsy persisted as anticipated. Followup MRI of the brain performed 6 months postoperatively revealed no evidence of residual disease (Figures and ).


A-52-year-old male presented to Lincoln Medical and Mental Health Center in March 2012 with fever, chills, dyspnea, and productive cough for 3 days. The physical exam was significant for tachycardia, tachypnea, fever of 102°F, and fine crackles heard in the right side of the chest. The patient's CBC showed neutropenia with ANC 900, mild anemia with hemoglobin 12.2 g/dL, and thrombocytopenia with platelets 79 × 103. Initial blood smear demonstrated a limited number of white blood cells. A chest X-ray revealed right lower lobe consolidation. Computerized tomography (CT) scan of chest and abdomen revealed enlargement of the mediastinal lymph nodes and a mildly enlarged spleen. Within 24 hours of admission, the patient went into respiratory failure requiring ventilator support. He was subsequently placed on antibiotics for community acquired pneumonia with improvement in symptoms. On the 3rd day of hospitalization, physical exam was notable for development of a generalized erythematous papular rash on the abdomen and vesicles and bullae on the extremities. A punch skin biopsy was performed and the patient was started on systemic steroids with improvement of the rash.
One week later, despite clinical improvement, patient had persistent pancytopenia. A diagnostic bone marrow biopsy was performed. No aspirate was able to be obtained despite multiple attempts. Bone marrow core biopsy show large lymphocytes with small cytoplasmic projections (). The neoplastic cells stained positive for CD45, CD19, CD20, CD11c, CD22, CD25, and CD103, consistent with hairy cell leukemia. Concurrently, the skin biopsy showed neutrophilic dermatosis, consistent with Sweet syndrome ().
Given resolution of his pneumonia, the patient received cladribine 0.1 mg/kg intravenous continuous infusion daily for 7 days as inpatient. The use of neupogen was deferred in the setting of neutrophilic dermatosis with concerns of possibly exacerbating the rash. The rash resolved after administration of chemotherapy. The patient was placed on prophylactic antibiotics, antivirals, and antifungals during the duration of myelosuppression. Within three months, his ANCED recovered and prophylactic medications were stopped. In six months, his CBC normalized with Hg of 13 g/dL and platelet 263 × 103. Followup bone marrow biopsy showed persistent involvement by hairy cell leukemia. Since the patient remained asymptomatic, undomiciled, and unwilling, treatment for residual disease was deferred.


We describe a case of a 78-year-old male who 24 hours after an anterior rectum surgical resection with a terminoterminal anastomosis for a rectal neoplasm,showed sudden pain among the soft tissues of right flank and fever (39°C).
The patient did not have any primary or acquired immunodeficiency; he was under treatment for diabetes and had no other risk factors for necrotizing fasciitis such as immunological disorders or previous administration of chemotherapy.
Clinical examination showed a swollen and hot skin and “crackling snow crepitus” among the right flank. No bullae or other skin signs predicting necrosis were appreciable.
The surgeon, after the clinical examination, requested from our Emergency Department a contrast enhanced CT (CECT) of thorax and abdomen.
We performed a precontrast phase, arterial phase, and an early venous phase.
CT scans showed the outcomes of the surgery and two drainage pipes were present, one in the right pelvis and one in the left flank.
Close to the right drainage access a suspected infection characterized by huge air-densities collections and edema extending along the soft tissues as right subcutaneous fat were observed; parietal abdominal muscles and subcutaneous tissues were also involved ().
Scout of subcutaneous emphysema which extends up to the supraclavicular region was seen (). Solution of continuity, 1,3 cm × 1,5 cm in size, of the rectus abdominis muscles was observed ().
After the contrast medium administration the fascia did not appear enhanced in the arterial phase; in the early portal phase the fascia appeared weakly enhanced; areas of low attenuation within the muscles and the fat tissues structures of the right flank were observed ().
As collateral findings the mesenteric fat tissue appeared hyperdense and small amount of pleural and pericardial effusion was seen; in Sagittal Multiplanar Reconstruction it was clearly appreciable that the infection started from the right drainage pipe ().
CT findings, such as the presence of fluid collections, the presence of subcutaneous gas, the invasion of the fascia, and the presence of areas of low attenuation within the muscles, were suggestive, in accordance with the clinical history of the patient, of a wide necrotizing infectious fasciitis (NIF) starting from the right drainage pipe with an involvement of the rectum abdominis muscles.
Signs of systemic infection, such as pleural and pericardial effusion and the hyperdensity of the mesenteric fat tissue, were also present.
Patient, due to the widespread of the disease, underwent immediately surgical debridement of the involved tissue; suture of the rectum abdominis muscles was made; intraoperative findings and the histological examination of the removed muscles confirmed the presence of necrosis among the fascia and diagnosis of NIF was made.
Antibiotics were administrated and the patient survived after the surgery.
After the surgery clinical conditions of the patient suddenly improved; antibiotics were administrated for two weeks and no other radiological exams were performed.


The case of a nine-year-old female child, who was born with congenital lymphedema of the left leg, is reported. She was referred for treatment when she was one year old. Diagnosis of lymphedema was clinical with perimetric measurements (every 3 cm) along the foot and leg (). Cervical stimulation using the Godoy & Godoy technique was performed until the age of six. It was initially carried out by the medical team but, after teaching the mother, she performed the cervical stimulation with clinical control being carried out by the medical team initially every week, then every fortnight, and eventually once per month. Cervical stimulation is the only lymph drainage technique that has been evaluated in isolation and proven to be efficacious in the reduction of edema. The hypothesis of the mechanism of action is that cervical stimulation causes the contraction of the lymphangions thereby increasing drainage []. Cervical stimulation as monotherapy reduced the perimetry of the limb to within the clinically normal size range without signs of edema in the early morning when the child got up within around three months. At the age of six, a diagnosis of growth hormone deficiency was reached and hormone therapy was initiated. The child began to grow quickly with aggravation of the lymphedema with an increase of 3 cm in the perimetry of the dorsum of the foot. A hand-made low-stretch compression stocking of a cotton-polyester fabric (grosgrain) was added to the treatment regimen. This fabric has low stretch across the material and elasticity in the other direction thus allowing good flexibility of the limb but providing compression. The association of compression to the treatment reduced and controlled the edema. The patient, now nine years old, has been receiving hormones for three years with her leg remaining within the normal size range compared to the contralateral limb. Normalization of the edema using an association of a grosgrain compression stocking and cervical stimulation occurred in about three months ().
When the child wanted to do ballet classes, the mother was advised not to allow her due to repetitive movements involved and the exertion of the foot. As the child insisted, she was permitted and encouraged to use a cotton-polyester compression stocking; changes in the size of the leg were monitored every week, clinically and by perimetry. There were no variations in the size of the leg and the child took ballet classes for more than one year.
This study was approved by the Research Ethics Committee of FAMERP (number 3822010).


An 85-year-old Caucasian, postmenopausal female presented to the outpatient clinic with a palpable mass in her left breast. Initial diagnostic mammography identified spiculation and architectural distortion inferior to the 2.1 cm mass at the 12 o'clock position of the left breast. Targeted left breast ultrasound demonstrated two distinct hypoechoic lesions in the 12:00 axis of her left breast, which was classified as BIRADS-5. Ultrasound-guided biopsy revealed invasive ductal carcinoma (ER positive, PR positive, and Her2-Neu negative) in three different areas within her left breast. Left modified radical mastectomy with sentinel lymph node biopsy and axillary lymph node dissection was performed. Three of six sentinel lymph nodes were found to be positive on frozen section (one with macrometastasis and two with micrometastasis), and a full axillary lymph node dissection was performed.
The patient was convalescing satisfactorily until the afternoon of postoperative day one, when the output of her surgical drains became sanguineous and voluminous. A pressure dressing was applied to the chest wall. On postoperative day two, her hemoglobin had dropped to 8.8 g/dL from 13 g/dL preoperatively, and her platelet count decreased from 132,000/mm3 to 8,000/mm3. A fluid collection was noted along the length of her incision, primarily in the left axilla. She had extensive bruising along the incision and axilla, tracking downward on the abdomen. Despite these findings, the patient remained asymptomatic and hemodynamically stable. A peripheral blood smear demonstrated no cellular fragmentation. A review of the patient's current medications revealed no potential cause for a drug-induced thrombocytopenia, and a review of her past medical history revealed no other possible etiologies for thrombocytopenia. Given this, the patient was diagnosed with presumptive idiopathic thrombocytopenic purpura (ITP).
Beginning on postoperative day two, the patient began receiving 40 mg prednisone daily, and she received platelet transfusion. Following these measures, her platelet count increased to 87,000/mm3 and continued to improve thereafter. She was discharged from the hospital on postoperative day four in stable condition with a platelet count of 186,000/mm3. Her systemic steroids were then tapered over the course of four weeks.


A 25-year-old male with no significant past medical or surgical history presented with 2 weeks of moderate to severe right upper quadrant and epigastric abdominal pain. His pain was occasionally associated with heavy exercise and meals. Physical exam and clinical laboratory findings were unremarkable.
Initial radiographic evaluation demonstrated abnormal frontal and lateral chest images (Figures and ). Following the descending aortic shadow inferiorly, a subtle opacity with a rounded contour was identified superior to the gastroesophageal (GE) junction. This was not well appreciated on the lateral view, possibly due to the overlapping shadow of the posterior mediastinum. These radiographic findings were suspicious for a retrocardiac posterior mediastinal mass.
Given the vague right upper quadrant and epigastric symptoms, a right upper quadrant ultrasound (US) was performed. However, the exam was noncontributory. Continued suspicion for a mass prompted further evaluation with computed tomography (CT) (Figures , , , and ). A 4.4 × 3.7 × 3.2 cm paraesophageal mass was demonstrated just superior to the gastroesophageal (GE) junction. The mass consisted of a peripheral rim of heterogeneous tissue (1 cm in thickness) with moderate enhancement and a central ovoid region of lower density (average 19 Hounsfield units). No local or distant lymphadenopathy was present. No discrete fistulous esophageal connection was identified; however, the mass demonstrated broad abutment along the distal esophagus with evidence of mild contouring and adjacent luminal irregularity and narrowing. The imaging characteristics (size, attenuation, contours, and enhancement) were most consistent with a subepithelial mass, though the tissue of origin remained uncertain. Given the patient demographics, tumor size, and CT appearance, a gastrointestinal stromal tumor was initially favored. Due to the distal esophageal location, heterotopic pancreas was not initially considered in the differential diagnosis. Subsequently, esophagogastroduodenoscopy (EGD) visualized multiple small holes in the esophageal wall overlying the mass, thought to represent fistulous tracts (Figures and ). Biopsies in this region were performed; however, they were ultimately deemed nondiagnostic. Endoscopic ultrasound (EUS) revealed a well-circumscribed heterogeneous hypoechoic subepithelial mass abutting the aorta (). Though the EGD and EUS findings were nonspecific, the apparent fistulous tracts raised the suspicion of abnormal connection with an airway or possibly with another subjacent anatomic structure.
An upper gastrointestinal (UGI) double contrast fluoroscopic exam was performed to further characterize the subepithelial mass and to investigate the apparent fistulas. Upright frontal and left anterior oblique low-dose fluoroscopic images demonstrated classic UGI findings of a subepithelial mass: a smooth-surfaced, hemispheric lesion forming obtuse angles with the adjacent luminal contour [] (Figures and ). Interestingly, the UGI series also demonstrated trace slivers of extraluminal contrast, presumably representing extension into the tumor proper. Notably, there was no evidence of contrast extravasation within the airways, subpleural space, or lung parenchyma.
Despite extensive imaging and numerous biopsy attempts, the differential diagnosis remained broad and included both benign and malignant processes. Considering the possibility of malignancy, a positron emission tomography (PET) scan was performed utilizing fluorine-18 fluorodeoxyglucose (F-18 FDG). The mass demonstrated increased FDG avidity, with a standardized uptake value average of 6.0 and maximally of 10.0 (Figures , , , and ). The remainder of the study demonstrated physiologic uptake. The associated FDG uptake immediately raised concern for a neoplasm. However, FDG is not a cancer-specific agent and uptake can be seen with inflammatory, infectious, and neoplastic processes. Moreover, normal uptake of FDG commonly occurs in various sites throughout the body. The gastroesophageal junction region is known to occasionally show normal uptake [].
In the absence of a tissue diagnosis or diagnostic imaging, optimal management remained unclear. In order to obtain definitive tissue diagnosis, left-sided video-assisted thoracic surgery was performed which revealed a soft, mobile, cyst-like structure upon direct visualization. Pathologic analysis demonstrated presence of pancreatic heterotopia with overlying unremarkable squamoglandular mucosa (Figures and ). The pathologic findings excluded the possibility of metaplasia, dysplasia, or malignancy.


A 12-year-old boy presented with a 1-year history of a slow-growing, painless mass in the radial aspect of the proximal phalanx of the left index finger. The patient's past medical history was unremarkable. Physical examination revealed a 2 cm, firm, immobile, nontender, subcutaneous mass (). There was no limitation of motion in neighboring joints. Neurovascular examinations were normal. Laboratory data were within normal limits.
Plain radiographs revealed a discernible soft tissue lesion with saucerization and sclerosis of the underlying cortex (). Computed tomography (CT) scans confirmed the presence of a periosteal-based lesion without calcification (). Magnetic resonance imaging (MRI) exhibited a well-circumscribed juxtacortical mass measuring 1.8 × 1.2 × 0.8 cm. The mass showed intermediate signal intensity on T1-weighted images () and high signal intensity on T2-weighted images (). Contrast-enhanced fat-suppressed T1-weighted images demonstrated peripheral and septal enhancement (). Based on these findings, periosteal chondroma was considered.
The operative procedure was carried out under general anesthesia with tourniquet control. A zigzag incision was made on the volar aspect of the left index finger. The mass was adherent to the periosteum of the proximal phalanx and extended into the bone cortex. It was completely excised together with the overlying peritoneum, and the underlying bone cortex was curetted. There was no sign of invasion into the medullar cavity. Bone graft was not done. Histologically, the tumor was well demarcated and surrounded by a periosteum-like fibrous capsule. The tumor consisted of hyaline cartilage with clusters of bland chondrocytes (). Binucleated cells were occasionally observed, but mitotic activity was absent. The histological findings were compatible with periosteal chondroma.
The postoperative course was uneventful, and the patient is doing well without evidence of local recurrence eight months after surgery.


A 25-year-old gravida 3, para1 was admitted at 19 weeks of pregnancy with a history of vaginal bleeding for 1 week and pain in abdomen. She was told that she had a low lying placenta during her second trimester scan. A lower segment caesarean section for cephalopelvic disproportion was done 2 years back and the baby was alive and well. This was followed by a missed abortion at 8 weeks for which a curettage was done. At admission, her vitals were stable. Uterus was irritable. Hb was 7 gm/dL. Ultrasound done after admission showed a live fetus of 20 weeks and anterior placenta with a thin, bulging, and deficient lower uterine segment. The decidual interface between the placenta and myometrium was partially absent and there were large dilated vessels in the same area. These sonographic features were suggestive of a placenta accreta. Patient continued to bleed; 4 units of blood were crossmatched and injection of methotrexate 50 mg was given intramuscularly on the day of admission. Prophylactic uterine artery embolisation was done on day 2 but the bleeding continued. The next day she was taken up for hysterotomy under general anaesthesia. Entry into peritoneal cavity was difficult because of dense adhesions. There was no hemoperitoneum. Bladder was adherent to the lower uterine segment which was severely deficient. Placenta was encroaching on the left broad ligament and was covered by a thin layer of peritoneum. Bladder was dissected from the lower uterine segment and incision was given at the previous scar. Fetus was extracted out first and placenta was then clearly seen to be firmly adherent to myometrium at several sites. Most of it could be removed piecemeal. Hemorrhage was controlled by uterotonics and hemostatic sutures at the placental bed. The estimated blood loss was approximately 1 litre. Two units of blood were transfused intraoperatively. Her postoperative Hb was 8 gm/dL. Catheter was removed on day 5. Recovery was uneventful. She was discharged 1 week later on iron tablets and contraceptive advice.


A 64-year-old Caucasian man presented to our institution with a 6-month history of progressive leukocytosis. Per the patient’s outside medical records, a bone marrow biopsy at initial presentation had shown a 100% cellular marrow with marked myeloid hyperplasia. Conventional cytogenetics demonstrated a diploid male karyotype. Fluorescence in situ hybridization studies (FISH) were negative for myelodysplasia-associated abnormalities. Molecular studies were negative for BCR-ABL rearrangement, and JAK2 and MPL mutations. Based on these features, he was diagnosed with myelodysplastic/myeloproliferative neoplasm, unclassifiable, and was started on hydroxyurea, 1.5 grams daily. At presentation to our institution, his white blood cell (WBC) count was 44.6 ×109/L with 76% neutrophils, 6% metamyelocytes, 10% monocytes, 6% lymphocytes, 1% eosinophils and 1% blasts, with absolute monocytosis (4.46 × 109/L) and eosinophilia (0.45 × 109/L). He was anemic (hemoglobin 9.0 g/dL) and mildly thrombocytopenic (platelet count 119 × 109/L). He did not have splenomegaly on physical examination. Bone marrow evaluation performed at presentation to our institution revealed a 100% cellular bone marrow with myeloid hyperplasia. Megakaryocytes were decreased in number and included rare dysplastic forms. Wright-Giemsa stained smears prepared from the bone marrow aspirate were remarkable for increased myeloid cells and trilineage dysplasia; a 500-cell differential count showed mildly increased monocytes (6%) and myeloid blasts (7%). The constellation of findings was diagnostic of chronic myelomonocytic leukemia (CMML-1). Conventional cytogenetics showed trisomy 8 in two of twenty analyzed metaphases; this was confirmed by fluorescence in situ hybridization (FISH) using an alpha-satellite (D8Z2) CEP8 probe (positive in 4% of the cells studied). Reverse transcriptase polymerase chain reaction (RT-PCR) performed on the bone marrow aspirate was negative for BCR-ABL fusion. Targeted next-generation sequencing mutation analysis was negative for 53 “hotspot” mutations analyzed as described previously [].
The patient was enrolled on the SGI-110 clinical trial, a phase 1–2 dose escalation, multicenter study of SGI-110, a DNA hypomethylating agent, in subjects with intermediate or high-risk myelodysplastic syndromes (MDS) or AML. He received two courses of SGI-110, after which he experienced rapidly progressive leukocytosis with a peak WBC count of 126 × 109/L and new onset of peripheral eosinophilia (11%). Bone marrow evaluation performed at this time demonstrated nearly 100% cellularity with myeloid hyperplasia; in contrast to the previous biopsy, prominent eosinophilia and moderate myelofibrosis were noted in this sample (Figure a-b). Wright-Giemsa stained smears showed increased granulocytes with left-shifted maturation and prominent eosinophilia (16%) in a background of trilineage dysplasia. There was no significant increase in bone marrow monocytes (5%). Myeloid blasts comprised 12% of total nucleated cells. The unexpected and abrupt presence of prominent eosinophilia in the peripheral blood and bone marrow at this point in time prompted us to evaluate for PDGFRA rearrangement. FISH analysis performed using a LSI-4q12 tricolor rearrangement probe that hybridizes to the chromosome 4q12 region containing the FIP1L1, CHIC2 and PDGFRA genes revealed deletion of the CHIC2 gene in 86.5% of the cells analyzed indicating the presence of the FIP1L1-PDGFRA rearrangement. The FIP1L1-PDGFRA fusion transcript was further confirmed by RT-PCR. Low-level trisomy 8 was also detected by FISH in this sample. Based on these findings a diagnosis of myelodysplastic/myeloproliferative neoplasm with eosinophilia and PDGFRA rearrangement was rendered. A follow-up bone marrow biopsy after one month showed acute myeloid leukemia with 26% blasts. In addition to persistent low-level trisomy 8, conventional cytogenetics and FISH demonstrated a new clone with TP53 gene deletion. FISH was positive for deletion of the CHIC2 gene, TP53 deletion and trisomy 8 in 90%, 10% and 9% of the analyzed cells, respectively.
The patient was then started on imatinib mesylate 400 mg daily along with a short course of idarubucin and subcutaneous cytarabine for cytoreduction. He achieved complete hematologic and morphologic remission and went on to receive a matched unrelated allogeneic stem cell transplant (SCT). To date, the patient remains in complete hematologic, morphologic and molecular remission with successful engraftment as demonstrated by chimerism studies. The sequence of events is provided in Table .


A 69-year-old Asian woman was admitted to our hospital because of diminished appetite. She had no previous medical history and was not complaining of fever and, therefore, she was not taking oral non-steroid anti-inflammatory drugs. Computed tomography revealed a gastric tumor measuring 56 × 55mm, accompanied by calcification (Figure ). Angiography via her left gastric artery showed staining of the tumor (Figure ), and endoscopic ultrasonography demonstrated a heterogeneous lesion 60mm in diameter, arising in the posterior wall of the stomach (Figure ). Laboratory examinations revealed hypoproteinemia (4.8g/dL; normal range, 6.5 to 8.0), hypoalbuminemia (2.2g/dL; normal range, 3.8 to 5.3), and severe proteinuria (8.47g/dL; normal range, 0 to 0.15), and her protein creatinine ratio was 14.3g/g and amount of urine for 24 hours was 1200mL, clinically suggesting nephrotic syndrome. Therefore, to avoid an invasive inspection, a kidney biopsy was not carried out. There were no neurologic symptoms or skin disease.
Despite albumin administration, her hypoalbuminemia did not improve preoperatively. She was given a diagnosis of GIST of the stomach accompanied by nephrotic syndrome, and partial gastrectomy was performed. Macroscopically, a well-demarcated, hard, whitish submucosal tumor arose from the gastric wall (Figure a); histological and immunohistochemical examinations revealed a spindle-cell tumor positive for CD34 and c-kit (Figure b, c), and a GIST was diagnosed.
Her postoperative course was uneventful. One week after her operation, her serum albumin (3.3g/dL) and urinary protein (1.71g/dL) levels remarkably improved after removal of the tumor. She remains well with no recurrence of the tumor or nephrotic syndrome (her recent urinary protein level: 1.19mg/mL) 2 years after surgery.


A 29 year old Latina female with a history of papillary thyroid carcinoma was initially treated with a total thyroidectomy, central and bilateral neck lymph node removal and subsequently with radioiodine therapy. Following this, evaluation indicated locoregional progressive disease and micrometastatic involvement in both lungs. Therapy was then initiated with 200 mg of oral sorafenib every 12 hours. However, after 4 days the patient presented with cutaneous lesions in the sole of the foot and in the first finger of the left hand which was associated with a burning pain in soles and palms and an intolerance to contact with hot surfaces. She also had significant ambulatory limitations and patchy lesions were evident in several areas of the foot and yellow blisters on the lateral aspect of the foot, metatarsal region and on the proximal phalanx of the first finger of the left hand (Figure ). Given these clinical findings the dermatological reaction was classified as Grade 3 and the Sorafenib treatment was discontinued. We then initiated treatment with a topical steroid, oral antihistamines and local management with ice packs around the lesions and observed the beginning of recovery seven days after the patient discontinued the drug therapy (Figure ).


The patient was a 66-year-old man with a history of cholelithiasis and inflammatory pseudo-tumors of the abdomen and chest wall. The patient was followed up every 6 months with MRCP and CT for the pancreatic branch type of intraductal papillary mucinous neoplasm. In 2015, computed tomography (CT) demonstrated a ~ 10 mm tumor in liver segment 4 with enhancement seen in the arterial phase (Fig. A, B). Based on the radiological findings, the tumor was highly suggestive of a hemangioma. As for additional testing, hepatitis B and C markers were negative, Child–Pugh grade was A, and liver damage was grade A. In addition, levels of tumor markers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 19–9, and α-fetoprotein were within their respective normal ranges. The tumor gradually increased in size during the 5-year follow-up period (Fig. ). CT revealed that the tumor size had progressed to 20 mm by 2020. The tumor showed enhancement during the arterial phase and iso-density during the late phase, which was located close to the left first branch of the Glisson (Fig. E, F). There was no lymph node metastasis seen around the hepatoduodenal ligament nor any distant metastases. On ethoxybenzyl magnetic resonance imaging (MRI), the tumor showed low signal intensity upon T1 weighted imaging, but high signal intensity upon T2 weighted and diffusion-weighted imaging (Fig. A, B). The tumor showed high intensity during the early phase and loss of primovist® uptake during the hepatocyte phase (Fig. C). No infiltration into surrounding vessels was observed. Positron emission tomography–CT identified an accumulation of fluorodeoxyglucose (standardized uptake value max 5.3) at the tumor site (Fig. ). Based on these findings, the pre-operative diagnoses were HCC, ICC, and CoCC. Thereafter, left hepatectomy was performed. Intraoperatively, the liver was normal, and peritoneal seeding or ascites were not observed in the abdomen. The operative time was 424 min, and the intraoperative blood loss was 500 mL. On macroscopic examination, the tumor was well-defined, grayish-white, and solid. The tumor was 15 mm × 15 mm in diameter (Fig. ). Microscopically, the atypical cuboidal epithelium became multi-nodular, forming small tubular glands and cord-like structures. Nuclear atypia was mild, and no mucus production was observed. Atypical, poorly formed cuboidal epithelium at the margins formed large and small dilated tubular glands, showing a cholangioma-like morphology (Fig. A, B). Immunohistochemical staining revealed that the cells tested positive for cytokeratin (CK)-7, CK-19, and CEA. Epithelial membrane antigen (EMA) was strongly stained in the membrane of the cancer duct, exhibiting a membranous pattern. The cytoplasm of tumor cells was positive for neural cell adhesion molecule 1 (NCAM1) (Fig. A, B). Based on these findings, the final pathology report revealed that the tumor was CoCC (T1N0M0, stage IA), according to the Japanese General Rules for the Clinical and Pathological Study of Primary Liver Cancer 6th edition. On the 18th post-operative day, the patient was discharged without any complications. The post-operative course of the patient was uneventful, without any recurrence happening 1 year after the surgery.


A 56-year-old woman participating in the Beijing Eye Study 2001, 2006 and 2011, showed a LC, a vertically oval shaped optic disc, and parapapillary gamma zone on the fundus photograph taken in 2001 (Fig. a). Due to cortical-nuclear cataract, her best corrected visual acuity (BCVA) was 0.4 (20/50 Snellen) with a refractive error of − 19.0 diopters (spherical equivalent), and the intraocular pressure (IOP) was 10 mm Hg. When re-examined in 2006, the fundus photograph revealed an enlarged gamma zone, while the LC was no longer detectable (Fig. b). BCVA had remained unchanged, refractive error (spherical equivalent) was − 20.0 diopters, and IOP measured 17 mmHg. At the last examination performed in 2011, nuclear cataract had markedly progressed, BCVA had deteriorated to 0.2 (20/100 Snellen), and IOP was 11 mmHg. Refractive error was − 20.0 diopters and axial length measured 30.69 mm. As in 2006, the LC was not visible, while gamma zone had further enlarged (Fig. c). On optical coherence tomographic (OCT) images taken in 2011, a defect of the BM or RPE in the region of the former LC was not visible (Fig. ). BM was corrugated suggesting a decreased BM strain []. The gamma zone enlargement occurred in a direction perpendicular to the direction of the former LC (Fig. a-c). In addition, the distance between the optic disc and choroidal vessels (as marked on Fig. ) increased during the study period suggesting a change in the position of the large choroidal vessel in relationship to the large retinal vessels and the optic disc.


A 66-year-old female, with no prior pertinent personal or family medical history, presented to a local hospital in Venezuela following episodes of constipation and abdominal pain. She had no pertinent medical history prior to this presentation. The patient was found to have an obstructing lesion at the sigmoid colon, multiple hepatic lesions, and a pancreatic tail lesion. She underwent emergency laparoscopic left hemicolectomy with creation of an end-colostomy. Surgical pathology indicated the sigmoid lesion to be moderately-differentiated adenocarcinoma (4 × 2 × 2 cm in size). Margins were negative. The hepatic metastases were biopsied and were found to be consistent with adenocarcinoma of pancreatic origin. In Venezuela, she received two cycles of attenuated FOLFIRINOX, which were reportedly well tolerated.
Soon thereafter she transferred her care to the United States and was seen in outpatient clinic. The pathology slides were reviewed, and the diagnosis was confirmed to be moderately to poorly differentiated adenocarcinoma consistent with a pancreatobiliary primary. Original imaging studies were not available. A CT Chest Abdomen with contrast indicated a prominent pancreatic tail mass invading the splenic hilum, stomach, and splenic flexure, encasing the splenic vessels (). Multiple omental lesions were seen, notably one adjacent to her stoma site (). Multiple hepatic lesions visualized (). A liquid biopsy (Guardant360) was sent out, and she was found to have the following targetable mutations: FGFR amplification, BRCA D1923N, and a KRAS G12R variant. Her case was discussed in tumor board. She was given one cycle of FOLFIRINOX at full dose, however, this was poorly tolerated. Clinical status continued to decline, and subsequently the patient elected not to have any further chemotherapy. Thereafter, the family's decision was to enroll the patient into hospice care.


A 35-year-old male presented with chief complaints of severe back pain and dehydration. Hours earlier, his family found him floating in a hot tub outside his parent’s suburban home, exposed to the midday summer heat of central Texas. His past medical history was pertinent for bipolar type schizoaffective disorder and substance use disorder (methamphetamines, marijuana, and cocaine). In the past, he had been admitted for his schizoaffective disorder and recently had been released from a correctional facility where he had been incarcerated for drug-related offenses. Collateral history from the patient’s family revealed the patient was recently released from a correctional facility and missed an appointment to receive a long-acting injectable antipsychotic (risperidone), but he was otherwise unmedicated and had no psychiatry follow-up. He was brought to the emergency department under a police order of emergency detention (POED) with chief complaints of extreme back pain and the sense that his house was “full of snakes.” The patient requested the medical team to perform a “full-body transplant” to alleviate his back pain and so he would be able to move on to “a new life.” The patient disclosed that he had been in the hot tub for several hours because it would, “protect [him] from the mind-controlling electric machine which creates these snakes that attack [him].” The patient denied any recent recreational or illicit substance use. The remainder of the history was deferred due to the patient’s psychosis. Initially, the patient was infused with two liters of Ringer's lactate solution in the emergency room and given a sitter to prevent him from leaving the patient care room.
Physical examination
On general inspection, the patient had a first-degree burn covering his bilateral upper torso, arms, and calves. He smelled of salt and appeared very dehydrated with dry mucus membranes of the mouth. Capillary refill was delayed to roughly four seconds and his forehead was covered in a fine coat of salt. Vital signs were pertinent for sinus tachycardia to the 120s and systolic blood pressure in the 110s/60s (mmHg). However, the patient was hemodynamically stable and did not require intensive stabilization or surgical intervention.
Laboratory results
A complete blood count (CBC), complete metabolic panel (CMP), urinalysis, toxicology screen, and HIV test were obtained. The patient’s urine sample was a dark brown color, like that of a dark tea, which led the team to order a creatine kinase (CK) level. The patient’s CK serum level was elevated at approximately 90,000 mg/dL (22 to 198 mg/dL). The patient’s urinary toxicology screen was positive for both benzodiazepines and methamphetamines. The CMP revealed a creatinine of approximately 5 mg/dL, significantly elevated blood urea nitrogen (BUN), and mild transaminitis, while other laboratory values were within normal limits (Table ). While awaiting laboratory findings, the primary care team ordered an abdominal ultrasound (US), which demonstrated no acute changes or morphologic alterations to the kidney parenchyma, ureters, or other urinary structures. Furthermore, the abdominal US did not demonstrate findings on the liver, gall bladder, or other gastrointestinal structures. These laboratory values and the imaging study led the primary medicine team to consult the nephrology team for potential hemodialysis for acute renal failure (ARF) secondary to rhabdomyolysis.
Consultant team’s recommendations for management
Based on the patient’s clinical condition, the nephrology team recommended aggressive IV fluid resuscitation at 200 mL/hr to facilitate the renal clearance of myoglobin. The nephrology team acknowledged that if the patient’s creatinine kinase levels continued to increase, they may need to begin hemodialysis. However, they were hopeful that conservative management would permit physiological recovery. As the patient faced a life-threatening condition and clearly lacked the capacity to refuse treatment, the psychiatry team acknowledged that they would likely need to file for an order of protective custody (OPC) to ensure that he would not be able to leave in his altered state, they also stated that they would start 1 mg of oral risperidone given once daily to treat his psychosis and baseline schizoaffective disorder and adjust the medications as needed from there.
Psychiatric complications
Shortly after starting treatment for the ARF, the patient complained that he had no issues with his kidneys and that he wanted a transfer to another location to obtain a new body, exclaiming that “if you don’t even have a muscle regeneration machine, how can you call this a hospital?”. He stated that he did not want the IV catheter placed, the fluids given, or an X-ray taken as he “doesn’t want his plasma taken out.” After his mother arrived, the patient successfully removed his IV catheter and attempted to leave against medical advice (AMA), which he was unable to do secondary to his POED. The patient became increasingly agitated and required 5 mg of haloperidol, 2 mg of lorazepam, and 50 mg of diphenhydramine by intramuscular injection. Despite this, he continued to be agitated and aggressive, which necessitated another intramuscular injection of 5 mg of haloperidol and 2 mg of lorazepam. Reestablishing IV access proved to be very difficult leading to a six-hour delay in resuming fluid infusion.
Over the following days, the patient was amenable to taking oral risperidone. However, he also called the police a total of four times stating that he was being held against his will and that the hospital was working to harm him. These accusations necessitated the medical team to collaborate with the police. With the support of the head of security, the team summoned a police officer from another floor to “answer the call” from the patient. The officer kindly explained that they had received his call, but that he had a legal order to remain in the hospital, and that it was important to listen to the doctors and take his medications. The patient agreed to take an oral dose of risperidone and expressed his willingness to restart the IV fluids. This helped resolve some of the patient’s guardedness, allowing for continued IV restoration of fluid status without the patient removing his catheter. Over the next several days, the patient’s urine output normalized, and laboratory tests returned reassuring serum creatinine levels. The primary care team transitioned the patient from IV fluid replacement to aggressive oral fluid replacement and the IV catheter was removed, which surprisingly alleviated nearly all of the patient’s paranoid ideations and distrust toward the medical team. After a total of 11 days of hospitalization, during which pharmacy, physical therapy, occupational therapy, and case management all worked to ensure his proper physical and social care, the nephrology team and internal medicine team cleared him for discharge to inpatient psychiatry for treatment of his schizoaffective disorder. He was discharged on a 0.1 mg clonidine extended-release patch to be replaced weekly, 1 mg of risperidone taken orally twice daily, and 800 mg of sevelamer to be taken three times a day with meals. He and his parents were given education regarding his adherence to his medications, major signs and symptoms associated with medication use, and finally his rehabilitation plan for after the psychiatric hospitalization was discussed with the patient and his case manager.


An 81-year-old woman presented for evaluation of an enlarging lesion on her left forearm of two-years duration. She had applied garlic to the lesion; however, there was no improvement. Complete cutaneous exam revealed a tan 11 x 10 x 2 millimeter keratotic nodule with a peripheral collarette and central horn on the left forearm (Figure ). The entire lesion was removed using the shave biopsy technique.
Microscopic examination, at low magnification, showed an epithelial tumor with a cup-shaped pattern suggestive of verruca vulgaris. There was massive hyperkeratosis, prominent acanthosis, and slight papillomatosis. At the lateral edge of the lesion, there was an inward pointing of the epidermis. A central horn-like mass of parakeratotic keratin, overlying the epidermal lesion, was indicative of a cutaneous horn. Higher magnification showed koilocytes in the upper layers of the epidermis, elongated epidermal rete ridges, and dilated blood vessels in the dermal papillae (Figure ).
Correlation of the pathologic findings and clinical presentation established the diagnosis of cup-shaped verruca vulgaris associated with an overlying cutaneous horn. Follow-up evaluation three weeks later showed no sign of recurrence. No further treatment was required.


In March 2014, an 80-year-old male presented with resistant diffuse large B-cell lymphoma (DLBCL; activated B-cell type). The patient was treated with rituximab-mini CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). In May 2019, the patient relapsed and was treated with R-bendamustine and lenalidomide. In March 2020, the patient relapsed again and was treated with ibrutinib. Initially, no significant toxicity developed, although the patient suffered muscle pains. However, after three months of ibrutinib treatment, the disease progressed. After progression, venetoclax was started at 20 mg/day with a ramp-up schedule while ibrutinib was continuing. However, one week later, Babinski positivity, tachycardia, arrhythmia, respiratory distress, and disorientation developed. Non-contrast cerebral computed tomography (CT) showed a hypodense nodular lesion with edema in the right frontal region (Figure ). First, cerebral lymphoma involvement was suspected; however, magnetic resonance imaging (MRI) with conventional and perfusion imaging showed bilateral nodular lesions with edema around the lesion, peripherally restricted diffusion, and peripheral enhancement. These lesions were hypoperfused in perfusion-weighted images (Figure ). All these radiologic findings were compatible with opportunistic infections. Bilateral patchy ground-glass opacities, consolidation, and left pleural effusion were observed on thorax CT (Figure ). These radiological images were compatible with opportunistic lung infection. A serum Aspergillus antigen (galactomannan) test was positive. When the diagnosis of aspergillosis was microbiologically proven, neutropenia was not detected. Then, amphotericin B and meropenem were started. However, three days later, multisystem organ failure developed. Hemodiafiltration for acute renal failure and intravenous immunoglobin for hypogammaglobulinemia was administered; despite these interventions, the patient died on the eighth day.


A 30-year-old male who is normally fit and well with no significant past medical history of note was diagnosed with CML in a different institution in 2015 and failed imatinib. Dasatinib was started after, but the patient was not compliant with the medication due to generalized bone pain and fatigability; however, due to the unavailability of detailed medical notes during this period we could not certify the clinical course of his disease at that time. He presented to our center in February 2020 with fever, productive cough, and chest pain. BCR/ABL P210 mRNA transcript was detected and estimated to represent 61% on international scale and complete blood count showed a hemoglobin of 90 g/L (135-180 g/L), platelets of 64×109/L (150-400x109/L), mean corpuscular volume of 97.5 fL (76.0-96.0 fL), and leukocytes of 54.50×109/L (4.0-11.0×109/L), with neutrophils 22.89×109/L, lymphocytes 11.44×109/L, blasts 27%, monocytes 1.09×109/L, metamyelocytes 2%, myelocytes 3%, and bands 1.09×109/L. This result indicates transformation to a blast crisis. The patient required intensive care unit (ICU) admission for pneumonia. HU 2000 mg was started as a cytoreductive agent followed by induction with idarubicin/cytarabine (7+3) protocol. Following remission status, which was confirmed by bone marrow examination, the patient was discharged on dasatinib with a plan to work him up for HSCT. However, two weeks later he presented with shortness of breath and chest pain. Chest X-ray revealed a worsening of bilateral pleural effusion and dasatinib was discontinued. TKI treatment was switched to ponatinib 15 mg then 30 mg plus aspirin, and the patient was discharged to be reviewed in the outpatient clinic. After 12 days from starting ponatinib the patient presented with abdominal pain and vomiting. Labs showed a neutrophil count of at least of 1.5x109/L at presentation and for the previous four weeks and lactic acid of 5.8 mmol/L (0.50-2.20 mmol/L) which was normal until two days before presentation. CT abdomen showed scattered air foci indicating perforated viscus (Figure ), and a diagnostic laparoscopy confirmed jejunal perforation around 20 cm from the duodenojejunal junction which was treated with small bowel resection. The histopathology revealed an active inflammation with submucosal edema and serositis, and neither thrombosis nor malignancy was identified. Since our patient had no other risk factors for bowel perforation, ponatinib had to be discontinued due to this complication and TKI treatment switched to nilotinib but again this had to be stopped due to prolonged Q-T interval. The patient’s general condition did not improve, and he needed a prolonged post-operative care in the ICU. Meanwhile his acute leukemia worsened with circulating blasts reaching 50% associated with multi-organ failure. Therefore, the patient was deemed not fit for further intensive therapy and his care was mainly palliative and he passed away in June 2020.


A 31-year-old gravida 3, para 2002 presented to the emergency department with abdominal pain at 9 weeks 2 days’ gestation dated by last menstrual period (LMP), consistent with ultrasound. She conceived after taking a 5-day course of over-the-counter 50 mg clomiphene citrate, obtained abroad, on alternating days following her LMP. She reported that she used ovulation predictor kits to help time intercourse and correlated results with moliminal symptoms such as pelvic pain. ß-hCG was 169,989 mIU/mL, and transvaginal ultrasound revealed an intrauterine dichorionic diamniotic twin gestation, with fetus A measuring 9 weeks 5 days’ gestation and fetus B measuring 9 weeks 3 days’ gestation. The left ovary was not seen and had free fluid around it, suggesting hemorrhagic cyst rupture. A corpus luteum cyst was in the right ovary. The patient's hemoglobin was 8.9 g/dL, a substantial decrease from her prepregnancy baseline of 13 g/dL. Her abdominal examination was benign, the patient was hemodynamically stable, and she responded appropriately to pain medication. Because of her stable presentation with a nonspecific adnexal mass and visualized intrauterine pregnancy, the presumptive diagnosis of ruptured hemorrhagic cyst was made. The patient was discharged home in stable condition.
She returned 4 days later with severe abdominal pain and vaginal bleeding. Ultrasound showed a gestational sac and fetal pole with cardiac activity at 225/min in the left adnexa, consistent with an ectopic pregnancy. Crown rump length measured 2.3 cm, consistent with 9 weeks 0 days’ gestation. Complex free fluid was noted superior to the left adnexa in the Morison pouch. The twin intrauterine pregnancy was redemonstrated on this study and showed appropriate interval growth, measuring 10 weeks 1 day of gestation ().
Because of concern for ruptured ectopic pregnancy, the patient was taken to the operating room for laparoscopic salpingectomy. When the laparoscope was inserted, a ruptured left fallopian tube and approximately 1 L of hemoperitoneum were noted. Ectopic pregnancy was confirmed on tissue diagnosis.
Recovery from surgery was uneventful, and the patient was sent home postoperatively. Her pregnancy was otherwise uncomplicated, and she continued routine prenatal care until 28 weeks 4 days’ gestation when she was admitted overnight for threatened preterm labor and found to be 4 cm dilated. She was given tocolysis and betamethasone and discharged in stable condition. She presented again at 36 weeks 5 days’ gestation in preterm labor and was 9 cm dilated with malpresentation of both fetuses. She underwent primary cesarean delivery and was discharged home with healthy twins on postoperative day 2.


A 32-year-old Filipino woman, with no significant medical and family history, presented to our emergency department complaining of two months of frank hematuria, suprapubic pain, intermittent low-grade fever, loss of appetite and unintentional weight loss of 10 kilograms in the last three months. Symptoms like night sweats, cough, hemoptysis, breathing difficulty, flank pain, joint pain or skin rash were denied. Her physical examination was within normal limits except for mild suprapubic tenderness on abdominal examination. Her temperature was 37 °C, respiratory rate was 19 breaths/min, blood pressure 100/55 mmHg, and pulse rate was regular at 82 beats/min. Prominent lab findings included a total leukocyte count of 6,200/mm3, elevated erythrocyte sedimentation rate of 49 mm/hr. and C-reactive protein of 1.4 mg/dL. Urea (10.7 mmol/L) and creatinine (122 µmol/L) were mildly elevated, and creatinine normalized after proper hydration. Liver function tests were normal and autoimmune workup (RF, C4, C3, ANA, ANCA) was negative. Serology examinations revealed negative results for HIV, HBsAg and anti-HCV. Urinalysis demonstrated urinary pH 6.0, WBC > 100, RBC > 100, bacteria 2+ , protein 2+; no nitrite, leukocytes, glucose or ketones. Blood and urine cultures had no growth of pyogenic agents. Renal ultrasonography and renal colic computed tomography were done to rule out bladder or ureteric stones and showed inflammatory changes in the right kidney. A provisional diagnosis of disseminated TB was established taking into account the clinical presentation, laboratory investigations and imaging findings; therefore, the patient was admitted to our internal medicine department for workup completion. A purified protein derivative (PPD) skin test was obtained and revealed negative. Renal biopsy was taken while waiting for TB workup results. TB work-up included; lower respiratory bronchoalveolar lavage and biopsies from lung and kidneys revealed negative TB-PCR. Mycobacterium TB was positive in acid-fast bacillus polymerase chain reaction (AFB-PCR) of the urine sample, which was delayed due to unavailability of test and COVID-19 restrictions, and the diagnosis of GU-TB was confirmed. Ultrasonography of the lower abdomen showed moderate hydronephrosis and bilateral mildly increased echogenicity of renal parenchyma. Contrast-enhanced computed tomography of chest, abdomen and pelvic was performed looking for other organ involvement to guide diagnostic approach. Contrast-enhanced computed tomography of the chest revealed bilateral diffuse tree-in-bud pattern without consolidation, cavitation, pleural effusion, mediastinal adenopathy or miliary nodularity (Figures , ). Contrast-enhanced computed tomography of the abdomen and pelvis subsequently revealed right dilated kidney calyces and renal pelvis, mild proximal dilatation of the right ureter, thickening of the renal pelvis and ureteric wall, and mild diffuse thickening of the urinary bladder wall. Additionally, it demonstrated multiple mildly enlarged para-aortic and retrocaval lymph nodes and multiple enlarged mesenteric lymph nodes calcifications (Figures , ).
Pathological reporting of transbronchial lung biopsy showed necrotizing granuloma with negative AFB stain for TB and non-reactive PAS stain for fungi. A renal biopsy under light microscopy demonstrated focal segmental glomerulosclerosis with mild interstitial fibrosis and tubular atrophy, 2/8 glomeruli reveal global sclerosis, one of the glomeruli shows adhesion of capillary loops at the tubular outlet of the glomerulus and one artery shows focal mild intimal fibrosis. Immunofluorescence staining for IgG, IgA, IgM, C3, C1q, kappa, lambda, albumin, and fibrinogen was negative. Electron microscopic findings demonstrated mesangial electron-dense deposits and diffuse effacement of the podocytes foot process.
Treatment of TB with rifampicin, isoniazid, pyrazinamide, and ethambutol was started after establishing a diagnosis and is to be continued for six months. Upon the patient’s clinical improvement, she was discharged from the hospital after arranging for follow-up visits and educating the patient and her family.


A 40-year-old Caucasian man with a past medical history of uncontrolled type 2 diabetes mellitus with peripheral neuropathy, alcohol abuse, and chronic pancreatitis presented to the emergency department for a three-day history of profuse watery diarrhea, shortness of breath, and ataxia.
Diarrhea reportedly began soon after the patient had attended a group barbecue. Initially, the patient experienced two to three loose stools per day, which gradually occurred more and more frequently, up to one to two times per hour at the time of initial presentation. In addition to profuse diarrhea, the patient also became progressively short of breath and confused. The patient denied knowledge of any other guests experiencing similar symptoms, including his partner. He also denied any other sick contacts or consumption of undercooked food. He denied any melena or hematochezia. The patient’s vital signs were remarkable for tachypnea and tachycardia. On physical examination, he was in mild acute distress, covered in feces, with very dry mucous membranes and obvious tachypnea. He was initially alert and oriented to person, place, time, and situation.
In the ED, initial labs were notable for sodium of 114, creatinine of 1.44 (likely secondary to severe diarrhea and resultant dehydration), glucose of 379, elevated anion gap at 32, and arterial blood gas (ABG) showing pH of 7.006, PCO2 of 9, HCO3 of 2, and urinalysis positive for ketones, consistent with acute diabetic ketoacidosis (DKA).
A Clostridium difficile antigen test was performed and returned negative. Stool studies including stool Shiga toxin, Campylobacter antigen, and stool culture, as well as blood cultures were obtained. Due to the patient’s reported sexual exposures, a rapid HIV test was also done to assess the patient’s immune status, which returned negative. The patient was then admitted to the intensive care unit (ICU) for further management of acute DKA and hypovolemic hyponatremia secondary to severe diarrhea with unclear etiology.
Over the next 24 hours, the patient’s anion gap closed and DKA resolved, however, he became febrile, hypotensive (systolic blood pressures in the low 80’s and diastolic blood pressure in the low 50’s), and his mental status became increasingly altered (alert and oriented only to person) raising concern for septic shock. CT abdomen and pelvis with contrast was obtained to evaluate for a source of infection and was notable for diffuse colonic wall thickening which was concerning for infectious colitis (Figures , ).
The patient was started on broad-spectrum antibiotic therapy with vancomycin and Zosyn, without any decrease in stool output (max output within a 24-hour period was approximately 5200mL), resolution of fever, or improvement in mental status. Stool and blood culture results returned positive for Shigella flexneri on hospital day three and showed resistance to ampicillin, ampicillin/sulbactam, and trimethoprim/sulfamethoxazole. At this point, infectious disease was consulted for treatment recommendations, and the patient was started on ceftriaxone 2g IV every 24 hours to be continued for two weeks once negative blood cultures were obtained. Due to the unclear route of transmission (food-borne vs anal-oral), it was also recommended that a repeat HIV RNA test be performed three weeks after the initial test was completed to confirm HIV status. After ceftriaxone therapy was initiated, the patient’s vitals improved and stabilized, daily stool output steadily trended downward, and his mental status gradually returned to baseline.
The patient had a peripherally inserted central catheter (PICC)-line placed to allow him to be discharged home to complete the course of IV ceftriaxone. Prior to discharge he was advised to avoid sexual intercourse for at least one week after the cessation of diarrhea and was counseled on following safe sexual practices for several weeks after, as Shigella can remain in the stool for an extended period of time.


A 20-year-old male was admitted to hospital with vomiting and headache; he was a cannabis user and cigarette smoker (40 cigarettes a day). He referred paresthesia in the upper limbs, psychomotor agitation and aggressive behavior. The neurological examination pointed out a palpebral ptosis and a right eye ophthalmoplegia including paralysis of the left facial nerve. A CT scan of the brain was performed and showed a hyperdense nodule in the right parietal lobe and along the Sylvian fissure, the leptomeningeal spaces were described as affected by an inflammatory process (). Fifteen minutes after the CT scan, he died. The study of the medical record and the sudden onset of symptoms defined death as “sudden”. The accuracy of the autopsy examination, the histological investigation (H&E and immunohistochemistry), attributed his death to a rare form of primary cerebral melanoma.
No ethical committee was required. Written informed consent was obtained from his relatives.


A 74-year-old male was admitted to the Department of Cardiology, Daejeon St. Mary’s Hospital (Daejeon, Korea), for the evaluation of exertional dyspnea (New York Heart Association (NYHA) functional class III), palpitations, and bilateral leg pitting edema for several months. His electrocardiography and Holter monitoring showed atrial fibrillation and rare premature ventricular complexes. He underwent transthoracic echocardiography (TTE), which showed RCM with biatrial enlargement and small pericardial effusion (A–D). His coronary artery angiogram was normal and other secondary causes of RCM were not found. Cardiac magnetic resonance (CMR) images revealed normal left ventricle (LV) chamber size, borderline diffuse left ventricular hypertrophy and very large atria. Contrast enhanced CMR images demonstrated extensive transmural late gadolinium enhancement (LGE) in the apical wall and mid myocardial patchy LGE in the ventricular septum (E–H).
We recommended clinical evaluation and genetic counseling for his family members because he presented a family history of heart disease, with two affected daughters. The proband’s second daughter had mild exertional chest discomfort. Her TTE showed asymmetric septal hypertrophy of the LV and a mildly dilated left atrium (LA) (A–D). Her diastolic dysfunction was grade I according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging criteria []. The proband’s fourth daughter also had asymmetric septal hypertrophy of the LV, with mild enlargement of the LA (E–H). CMR images of the two daughters showed asymmetric septal hypertrophy of the LV, consistent with a diagnosis of HCM. LGE was not found in either daughter.
To resolve the potential genetic cause of cardiomyopathy in a Korean family (I-1, II-2, and II-4 in A), the proband’s genomic DNA was analyzed by whole exome sequencing (WES). The exomic DNA of the proband was enriched using Agilent’s SureSelect XT Human All Exon v5 (Agilent Technologies, Santa Clara, CA, USA), and paired-end sequencing was conducted on an Illumina HiSeq2500 (Illumina, San Diego, CA, USA) for the detection of variants, given the suspicion of familial disease. Base calling, alignment, variant calling, annotation, and quality control reporting were performed using a GATK Best Practices workflow for germline short variant discovery and were manually reviewed by medical laboratory geneticists. In particular, the annotation of the identified variants with respect to the results of their mutation in the reported genes was estimated using the dbNSFP [] and Ensembl Variant Effect Predictor []. By estimating sequence quality along all sequences, 5973 million reads were generated from the proband. A percentage of bases above the average of 30× was achieved for 92.3% of the target region, and the mean read depth (×) was 110. WES of the proband identified five heterozygous variants within the coding region of each gene as candidate causes of autosomal dominant inherited heart diseases with a population allele frequency within the Genome Aggregation Database < 0.001. To determine which variant was the cause of cardiomyopathy in the affected family members, Sanger sequencing was performed additionally. As a result, Sanger sequencing confirmed the presence of a heterozygous frameshift mutation (NM_000256.3:c.3313_3314insGG; p.Ala1105Glyfs*85) in MYBPC3 in the proband (I-1) and his affected daughters (second (II-2) and fourth (II-4)), but not in his unaffected granddaughter (III-3) (B). The variant is not listed in public genome databases from gnomAD (; accessed on 8 November 2020) and the Korean Reference Genome Database (; accessed on 8 November 2020). Although the four remaining variants (KALRN: NM_007064.5: c.1702C>T, p.Pro568Ser; KCNH2: NM_000238.4:c.442C>T, p.Arg148Trp; SKI: NM_003036.4: c.30T>G, p.Cys10Trp; TTN: NM_133378.4: c.54293T>C, p.Ile18098Thr) were the likely candidates, there was no exact correlation between the genotype of these variants and the clinical phenotype in the proband and his family members as determined by Sanger sequencing. Therefore, the MYBPC3 frameshift mutation seemed to be the pathogenic variant.


Patient information
Our patient was a 16-year-old male with no significant past medical history who presented initially with a skin rash on the lower extremities, lower extremity joint pain, and left knee swelling. He was prescribed oral steroids at his pediatrician’s office, but the symptoms did not improve. Also, he started having abdominal pain a few days later, which was diffuse, constant, and limited his oral intake. He also had nausea, vomiting, blood-streaked stools, and dark brown urine. Two weeks after the onset of symptoms, he presented to our tertiary hospital, and he was admitted. There was no history of the use of non-steroid anti-inflammatory drugs (NSAIDs) before the presentation.
Clinical findings
He was afebrile at admission with a BP of 136/60 mmHg, and his bodyweight at admission was 71 kg. He had lost 7 kg of weight in two weeks since the onset of illness. He had diffuse, erythematous, non-blanching, purpuric skin rash involving the extensor surface of lower extremities on physical exam (Figure ).
He also had tenderness and mild swelling on the left knee. The initial lab results were significant for a white blood cell (WBC) count of 19 × 103/μl and hemoglobin of 10.7 g/dL; the platelet count was normal at 336 × 10³/μl. There was significant renal dysfunction at presentation with a blood urea nitrogen (BUN) level of 74 mg/dL (reference range: 7-20 mg/dL) and serum creatinine of 2.4 mg/dL (reference range: 0.3-1.2 mg/dL). The serum albumin was low at 2.4 g/dL (reference range: 3.5-5 g/dL). The C-reactive protein (CRP) was 17.1 mg/dL (reference range: <1 g/dL). The urinalysis showed large amounts of blood, 300 mg/dL of protein, several red blood cell casts/high power field on urine microscopy, and the urine protein and creatinine ratios were high at 6.4 (reference range: <0.2). The stool occult blood-guaiac was positive. The abdominal ultrasound (US) was negative for intussusception. The renal US showed bilateral echogenic kidneys with kidney sizes of 11.9 cm on the right kidney and 12.3 cm on the left kidney.
Diagnostic assessment
Infectious studies, including stool culture and blood culture, were obtained at presentation and were negative. The tick-borne disease antibody panel was also negative. Glomerulonephritis was diagnosed based on the urinary findings, elevated BP, and high BUN and serum creatinine. The differentials of glomerulonephritis, such as post-infectious glomerulonephritis, lupus, and vasculitis, were considered. The immunological workup showed normal ranges of complement C3 and C4. The anti-nuclear antibody (ANA) screen was negative. The anti-nuclear cytoplasmic antibody (ANCA) screen revealed negative myeloperoxidase immunoglobulin G (IgG) and negative proteinase-3 IgG.
We diagnosed the presence of HSP based on the clinical presentation of skin rash, diffuse abdominal pain, joint symptoms, and significant renal involvement. Given the high BUN and serum creatinine, we were also concerned about the presence of rapidly proliferative and crescentic glomerulonephritis. The patient underwent a renal biopsy one day after the admission, which showed IgA nephropathy with no cellular crescents, but the glomeruli were hypercellular.
Therapeutic assessment
We started intravenous (IV) pulse steroid therapy (methylprednisolone) at admission to treat HSP-associated inflammation and kidney disease, beta-blockers (labetalol) to treat blood pressure, and IV proton-pump inhibitors for gastroprotection. The rationale for starting IV steroid therapy was related to a severe degree of glomerulonephritis seen at presentation. The serum creatinine levels improved to 1.5 mg/dL after three days, and we initiated oral steroid (prednisone) treatment at a dose of 30 mg twice a day. There was an improvement in joint symptoms; however, the patient continued to have abdominal pain and diarrhea for one week after treatment initiation. He was discharged home with instructions for close follow-up in a pediatric nephrology clinic. The hemoglobin level was 10.1 g/dL at the time of discharge.
Follow-up and outcomes
Four weeks after the treatment initiation with steroids, the patient presented to the ER with bright red stool and syncope. The stool guaiac was positive. The hemoglobin was very low at 3.5 g/dL, and he was suspected of having symptomatic anemia secondary to GI bleed. The BUN level was 78 mg/dL, and serum creatinine was 1.4 mg/dL at presentation. The elevation in BUN may also have been contributed by GI bleed. The patient required blood transfusions. Esophagogastroduodenoscopy (EGD) and colonoscopy with biopsy were performed. Surprisingly, the EGD did not show active bleed. However, the colonoscopy showed dark fluid in the colon's lumen, raising the possibility of a more proximal or ileal source of bleeding (Figure ).
The biopsy showed mild ileitis. Pill-cam capsule endoscopy was subsequently performed, which showed the bleeding from the terminal ileum, and the presence of Meckel's diverticulum adjacent to it was detected. However, the GI bleeding had significantly improved by the time the capsule endoscopy was done, and the hemoglobin remained stable without further blood transfusions. Surgery service was consulted, but given the risk of surgical complications with HSP vasculitis involving the GI tract and the rapid improvement in GI bleeding, surgery was not performed. The patient was closely monitored, and there was no major recurrence of lower GI bleeding.
Six weeks after the initial treatment with steroids, the patient presented with dizziness, lightheadedness, and palpitations. In the ER, the EKG was suggestive of atrial fibrillation with accelerated ventricular rhythm. While he was on telemetry, the patient had another arrhythmia episode, now showing non-sustained ventricular tachycardia (Figure ).
The troponins were elevated at 0.101 ng/mL (reference range: 0-0.034 ng/mL). The echocardiogram showed good biventricular function. Even though previous reports of arrhythmia secondary to HSP were rare, a diagnosis of HSP-induced arrhythmia was made based on elevated troponins and arrhythmia patterns. He was started on amiodarone and metoprolol, and there were no further recurrences of arrhythmia.
Seven weeks after initial treatment with steroids, there was an elevation in serum creatinine, and new-onset neurological findings were observed. These neurological findings included the presence of tremor, gait disturbance, proximal muscle weakness, bilateral ankle and knee clonus, upper extremity clonus with positive Hoffman sign, and generalized hyperreflexia. The tremor was present in the tongue as well as both extremities. These findings were suspected to be secondary to the central nervous system (CNS) vasculitis, steroids, or amiodarone. The MRI of the brain showed diffuse sulcal prominence (Figure ).
The cerebrospinal fluid (CSF) exam was negative for infection. The autoimmune encephalitis antibody panel was also negative. The patient was treated with clonazepam.
Simultaneously, the serum creatinine was found to be elevated at 2 mg/dL, and the patient continued to have significant proteinuria with a random urine protein creatinine ratio of 9. A second renal biopsy was performed, and it showed 75% of glomeruli with cellular crescents (Figure ).
The patient was treated with IV cyclophosphamide, and he was started on mycophenolate while the steroids were weaned off due to neurological side effects. The neurological findings improved after weaning off of steroids.
After cyclophosphamide therapy, there was no recurrence of cardiac, GI, or neurological complications from HSP. The patient was closely followed up in the nephrology clinic. Lisinopril was added to his treatment regimen as the serum creatinine improved. Nine months after presentation, the serum creatinine was found to be 1 mg/dL; the proteinuria had improved with urine protein and creatinine ratio of 0.5, and serum albumin was normal at 3.9 g/dL. The patient was maintained on lisinopril and mycophenolate.


A 43-years-old non-smoking man, being obese with a BMI of 31.9 kg/m2, was diagnosed with a stage IIIC (pT3bpN1a(sn)M0) BRAF-wild type melanoma disease. He received a 3 mg/kg nivolumab adjuvant therapy every two weeks for 12 months (26 cycles). Three months after the beginning of the infusions, he developed painful nodules and abscesses of the axillary folds and groins. Most lesions cleared or drained spontaneously but there were new flares every week, requiring sometimes surgical drainage. The patient had a history of severe acne during puberty. He had no personal/family history of HS and no other medical condition associated with metabolic syndrome. On examination, there were inflammatory nodules and plaques, abscesses, but no fistula nor scars (A,B). Bacterial culture on pus swab from a fistulated abscess and folliculitis were positives for a Streptococcus Agalactiae group B and a Staphylococcus Epidermidis.
A diagnosis of nivolumab-HS, stage Hurley 1 was made. Following an unsuccessful three month-period lymecycline 300 mg q.d. therapy, he received a combination of doxycycline 100 mg b.i.d. and zinc gluconate 60 mg q.d. The doxycycline was discontinued after one week because of the occurrence of gastro-intestinal symptoms. The patient was finally maintained under zinc gluconate alone with an excellent outcome (C). Eighteen months after nivolumab cessation, he is finally cleared of HS lesions and remains in remission for melanoma disease.


We report the case of a 9-year-old Caucasian female affected by suprasellar non-germinomatous germ cell tumor (NGGCT) associated with multiple pituitary deficit, who tested positive for SARS-CoV-2 an April 1, 2020.
Her problem began 2 years earlier, with polyuria, polydipsia (she drank almost 8 liters of water/day) and growth delay. In October 2019, she came to Verona’s Paediatric Emergency Department in a state of confusion. Brain magnetic resonance imaging revealed a suprasellar mass, compatible with germinoma (). This hypothesis was confirmed by high levels of alfa-fetoprotein and human chorionic gonadotropin (hCG) in plasma and cerebrospinal fluid (CFS). Based on alfa-fetoprotein and hCG levels the tumor was classified as a non germinomatous germ cell tumor (NGGCT). Ophthalmologic evaluation and a study of visual fields were normal. At the time of diagnosis, blood exams tests confirmed a multiple pituitary deficit with diabetes insipidus, central hypothyroidism, hypocortisolism, growth hormone deficiency and mild hyperprolactinemia. The patient’s laboratory test results at time of diagnosis are shown in . The girl started therapy with levothyroxine (initially at dosage 25 mcg/day) and desmopressin (initially intranasal, then sublingual). She was given dexamethasone after the MRI to reduce tumoral edema. Over the next few days the patient was found to have “cerebral salt wasting” with hyponatremia, high urinary sodium excretion (129 mmol/L) and persistent polyuria, so we started fludrocortisone. It was stopped after four days when laboratory tests normalized. She continued therapy with desmopressin, levothyroxine and hydrocortisone and the patient had periodical laboratory tests and therapeutic adjustments.
In October 2019 chemotherapy according to SIOP CNS GCT II standard risk protocol for non-germinomatous germ cell tumor (NGGCT) was started. The first cycle was complicated by hydrocephalus that required ventricular-peritoneal derivation. At the end of the third cycle, the MRI showed a partial response to chemotherapy. Therefore, in January 2020, the patient underwent neurosurgery. The histopathological examination was conclusive for immature teratoma. Follow-up MRI one month after surgery showed a suspected small residual lesion. Chemotherapy with high-dose etoposide was started.
From the 8 March, the “lockdown” for all Italy was adopted together with the use of surgical mask, hand hygiene, and social distancing, to prevent the massive spread of SARS-CoV-2; moreover, a screening program by nasopharyngeal swab (NPS) for any patient and caregiver parent accessing the Pediatric Hematology Oncology Unit was started (). On March 12, the patient (and her mother) underwent the NPS and both resulted negative for SARS-CoV-2. She was taking desmopressin (sublingual tablets 60 mcg, 2 + 1+2, 300 mcg/day), levothyroxine at 75 mcg/day and hydrocortisone at 8,92 mg/m2.day divided into 2 doses. Therapy with recombinant GH was not yet started. Since her neurosurgical operation, she suffered from hypothalamic obesity (incontrollable hyperphagia, decreased satiety and decreased physical activity) with massive weight gain.
On March 5 she was admitted to the Pediatric Oncology Unit for mobilization chemotherapy with high-dose etoposide and granulocyte colony-stimulating factor (G-CSF) followed by peripheral stem cell collection for autologous stem-cell transplantation (ASCT). On April 1 she was admitted to the Pediatric Oncology Unit for ASCT. Her weight was 40,9 kg (93,21 percentiles based on Cacciari’s charts) and her height was 120,2 cm (6,08 percentiles based on Cacciari’s charts), with a BMI of 28,31 kg/m2 (99,06° centiles based on Cacciari’s charts).
When she came for screening, a second NPS for SARS-CoV-2 was performed on the patient and parent caregiver (the father) and both resulted positive. The pre-transplant conditioning regimen (HD PEI cycle - cisplatin, etoposide and ifosfamide- according to SIOP CNS GCT II protocol) was already started on April 2 in the morning, and was therefore withdrawn as soon as the result of NPS was communicated in the evening of the same day (administration of day 1 of conditioning regimen). Both patient and father were quarantined in a pediatric COVID19 section of the department to monitor the patient’s symptoms or signs of SARS-CoV-2 infection. During observation, blood count, urine tests. inflammatory markers, chest X-ray were unremarkable. In particular, her blood exams showed leukocytes 6,87x10^9/L, neutrophils 5,77x10^9/L and lymphocytes 0,40x10^9/L. No respiratory, cutaneous signs, or fever appeared during recovery and the patient continued her previous therapies. The most significant laboratory tests before, during and after Sars-Cov2 infection are summarized in . Her diuresis remained in the range of 2-2,9 ml/kg/h. The patient was discharged 3 days later, in good general conditions. Her weight at discharge was stable. Another two nasal and pharyngeal swabs were both negative after 28 days (). The ASCT was performed on April 30 after a conditioning regimen with high dose ifosfamide, etoposide and cisplatin. She received 4.38 x 106/kg CD34+. The patient engrafted on day + 9 for neutrophil and on day + 12 for platelets and was discharge home in good clinical conditions. In accordance with Verona University and University of Verona Institutional review Board (IRB) policies, case reports are not considered to be research subject to IRB review and are thus except from formal IRB approval for publication. Written informed consent was obtained from the patient’s legal guardians for the publication of any potentially identifiable images or data included in this article.