A 73-year-old man with a history of hypertension and congestive cardiac failure was admitted at our hospital for progressive jaundice of unknown etiology. During prior hospitalizations multiple hepatic nodular lesions of uncertain nature had been reported at various imaging exams; furthermore, two ultrasound-guided liver biopsies had already been formerly performed, leading to a diagnosis of nodular regenerative hyperplasia of uncertain interpretation.
After admission to our hospital, laboratory tests revealed increased direct bilirubin levels (9.59 mg/dl), while liver enzymes were within the recognized normal ranges. Moreover, search for autoantibodies and serologic tests for hepatotropic viruses were negative and no anomaly was noted for blood iron parameters.
Abdominal contrast-enhanced US revealed multiple hyperechoic, anaechoic, and isoechoic hepatic nodules (Fig. ). Abdominal contrast-enhancement computerized tomography (CT) and magnetic resonance imaging (MRI) revealed increased liver volume, with left lobe hypertrophy and heterogeneous appearance of the parenchyma: multiple confluent lesions with numerous blanks were detected, respectively showing low-density attenuation at CT and heterogeneous low intensity on T2-weighted imaging (WI) and heterogeneous high intensity on T1-weighted imaging (WI) at MRI. After contrast administration, a well-developed vascularization of the blanks was noted with both the methods, namely, with inhomogeneous and incomplete enhancement on T2-weighted imaging (WI) on MRI (Fig. ). These atypical radiological findings were utterly unspecific for any particular disease: not only for their diffuse and bilobar massive spreading throughout the liver but also for the involvement of both central and peripheral areas of the hepatic parenchyma. The blank characteristics suggested the presence of vascular spaces, somehow recalling those observed in benign lesions such as hepatic peliosis.
After multidisciplinary team discussion, a laparoscopic liver biopsy was performed. The histological findings were suspicious for a vascular lesion but, before a definitive diagnosis could be made, 3 days after the procedure the patient’s conditions rapidly worsened, evolving in acute respiratory distress syndrome (ARDS) and severe liver failure. Ultimately, the patient developed hepato-renal syndrome and died.
In order to find the cause of the sudden deterioration of the liver function, an autopsy was requested. Grossly, the liver had an irregular surface and revealed blood filled cavities and gray-brownish spongy areas surrounded by recognizable residual normal hepatic parenchyma at cut examination (Fig. ). No other lesions were found in any other organ.
Twenty-four tissue samples were taken from the liver and then fixed in 10% formalin solution and embedded in paraffin blocks. Four-micrometer-thick sections were obtained and stained with hematoxylin and eosin for histopathological examination. Immunohistochemical staining for CD 31 (clone JC/70A, DAKO, dilution 1:50), CD34 (clone QBEND/10, Novacastra, dilution 1:200), and ERG (clone EPR3864, Abcam, dilution 1:200) was performed.
Microscopically, multiple cavernous spaces covered by highly atypical endothelial cells were observed (Fig. ), along with nodular areas made up of spindle cells surrounded by dilated sinusoids filled with neoplastic cells were seen (Fig. ). The atypical cells showed diffuse and strong positivity for endothelial markers, such as CD-31 (Fig. ), CD-34 (Fig. ), and ERG.
A chronic occupational vinyl chloride exposure was retrospectively discovered. Based on these clinical data and the morphologic features, the diagnosis of multifocal HAS was established.


In March 2009, a 55-year-old woman presented to a physician with multiple cervical nodules. The patient reported that the nodules had been present for several weeks. The patient's medical history also included hyperlipidemia and hypertension. She was a housewife and had no discrete occupational exposure to chemicals, etc Family history included no known instance of cancer. During the physical examination, multiple bilateral lymphadenopathies of the anterior cervical chain and supraclavicular were detected on palpation, which was not tender and was neither erythematous nor warm to the touch. Findings of the remainder of the physical examination were normal. The patient's medical history revealed no fever, weight loss, and night sweats. A cervical excisional biopsy was done, and the pathologist reported "Follicular Lymphoma grade ШB."
Further evaluations, including chest/abdomen CT and cervical sonography and bone marrow aspiration/biopsy, detected no more findings (stage I follicular lymphoma). The patient received standard treatment, including four R-CHOP regimen courses (cyclophosphamide, doxorubicin, vincristine, and prednisone plus the monoclonal antibody rituximab) followed by involved filed radiation therapy (IFRT). Cervical lymph nodes were completely resolved in neck CT after completion of chemotherapy and radiotherapy. Routine, annual visits, and physical examination were recommended and continued up to April 2016.
In April 2016, an approximately 4 centimeter mass of the right inguinal region was detected in the physical examination, which was not tender and was neither erythematous nor warm on palpation. Abdominopelvic CT showed multiple lymphadenopathies of para-aorta and iliac chains with a maximum SAD of 14 millimeters in favor of metastasis. Chest CT had no abnormal findings. Excisional biopsy of inguinal/lower abdomen mass was done, and pathology/IHC study made the diagnosis of "Mesothelioma" (positive for Pan-CK, CK7, calretinin, and WT-1 and negative for CD20, P63, TTF1, and CEA), which was confirmed by two pathologists (Figure ).
The patient received a cisplatin+pemetrexed chemotherapy regimen. Abdominopelvic CT after completion of chemotherapy showed that inguinal mass and lymphadenopathies are completely resolved. Routine, periodic visits, and physical examination were recommended and continued up to May 2019.
In May 2019, an incidental finding of pelvic CT reported a mass-like lesion of rectum and fat stranding of around. A colonoscopic study revealed a large ulcerative tumor of the rectum. Complementary studies confirmed "Adenocarcinoma of Lower Rectum T3 N2 M0." The patient received the standard treatment of rectal adenocarcinoma (neoadjuvant chemoradiation followed by surgery).
Our patient is a 66-year-old woman and is alive 11 years after the diagnosis of follicular lymphoma, 4 years after diagnosis of mesothelioma, and 1 year after diagnosis of rectal adenocarcinoma.


We report the case of a 70-year-old man with no medical history. After experiencing a motor sensory deficit in his left lower limb for 24 hours, he went to the emergency room (ER). He also reported he had been suffering from bilateral upper arm neuralgia for over a year. A contrast-enhanced medullary MRI showed a bleeding intra medullary tumor next to C7-T1 (Fig. ). A left cerebellar tonsil lesion was also viewed.
The initial work-up was completed by a chest, abdomen and pelvis (computerized tomography) scan as well as and a PET-TDM (Positron Emission Tomography): no sign of metastatic spread was evidenced. The C7-D2 intramedullary lesion from hypermetabolic (SUV 5.2). A skin melanoma was ruled out after a dermatology consultation as no cancer lesion was seen during skin and mucosal examination.
First, the tumor was removed on 7/12/2016 but surgery did not solve the motor deficit problem. The patient left the hospital and had home physical therapy sessions. The pathology report leaned towards a melanocytic tumor without mitotic figures and with low Ki67proliferation index (Fig. ). The molecular study showed p.Q2019L mutation of GNAQ, an elective mutation in uveal and meningeal melanocytic tumors.Secondly, the patient received 30 Gy in ten sessions of radiotherapy, from 8/19/2016 to 9/1/2016. He also had 6 cycles of nivolumab (3 mg/kg), from 9/7/16 to 11/23/16, representing a total dose of 1260 mg. A disease stability of 13 months was observed following immunotherapy. The patient developed a postimmunotherapy hypothyroidism that was treated with levothyroxine.
During follow-up, MRIs revealed a persistent growing residual tumor. One year after the last nivolumab injection, the patient experienced a very painful brachial neuralgia which led him to the ER again. The MRI performed there showed the tumor had progressed. Thus, the patient was hospitalized and underwent a second surgery on 12/27/17. The postop MRI showed no residual tumor and no rachis hematoma. Pathological examination revealed a meningeal melanocytoma similar to the first 1, with Ki <5%.Then, the patient spent a few months in a rehabilitation center.
Three months later, the MRI evidenced a tumor recurrence. In the following months, the tumor kept growing. In December 2018, a national multidisciplinary team meeting dedicated to spinal cord tumors decided on 3 cycles of chemotherapy by temozolomide. Treatment was started in April 2019 as the MRI showed the tumor had stopped growing. Three additional cycles of temozolomide were prescribed. The patient received a total dose of 7720 mg of temolozomide. Chemotherapy first cycles were initiated at a dose between 150 and 200 mg/m2. This dosage was reduced to 100 mg/m2 the last 2 cycle due to toxicity associated with an alteration of patient general condition. Despite local symptomatic treatment, the patient suffered from bedsores in the sacrum area so he went to the ER in a local hospital. After a few days, the bedsores became infected so the patient was admitted in the dermatology unit in a teaching hospital. There, he was given piperacillin and amikacin. The sixth cycle of temozolomide was then interrupted on 9/12/2019.
The patient's condition got worse: his need of oxygen increased and a lower limbs oedema occurred. A thoracic computerized tomography angiography showed a right proximal pulmonary embolism for which he spent a short time in the Intensive Care Unit (ICU) and had surgical debridement. The patient died a few days after returning in the dermatology unit.


A 68-year-old male presented to the ED at the local Veterans Administration Medical Center for severe lower extremity weakness and paresthesia. Three months prior, he first sought medical attention for progressive, ascending numbness and paresthesia of his lower extremities and hands. At that time, he met diagnostic criteria for acute inflammatory demyelinating polyneuropathy including characteristic electrodiagnostic and cerebrospinal fluid (CSF) analysis findings. He demonstrated moderate improvement with five doses of intravenous immunoglobulin (IVIg) at 0.4 mg/kg IV per day. One month later, he presented to the ED with worsening sensory neuropathy and weakness and new-onset dysarthria. Repeat electromyography/nerve conduction studies (EMG/NCS) showed progressive demyelination consistent with chronic inflammatory demyelinating polyneuropathy (CIDP) (Figure ).
He was treated with an additional five doses of IVIg and oral steroids, this time with minimal improvement. In the subsequent weeks, he reported worsening lower extremity weakness, becoming too weak to stand, and the onset of several other neurologic complaints including dysarthria, mild dysphagia to thicker liquids and saliva, intermittent dizziness, and nocturnal leg twitching. He also exhibited constitutional symptoms including marked fatigue, unintentional weight loss of 25 pounds, and asthenia, associated with lower extremity muscle wasting. He had not experienced other classical B-symptoms, headaches, visual changes, abnormal bleeding or bruising, new skin rashes, myalgias, or neuropathic pain symptoms. He denied exposure to sick contacts, recent travel history, or tick bites.
Past medical history was significant for hypothyroidism, mild sensorineural hearing loss, and plaque psoriasis. He was up to date with age-appropriate cancer screening including colonoscopy and prostate-specific antigen (PSA) testing, which had both been normal. His only medication prior to the onset of his symptoms was levothyroxine 25 mcg daily per os. His past surgical history was only significant for bilateral cataract surgery. Prior to the onset of his neurologic symptoms, he was healthy and active, and was working as a scuba diving instructor. Over the course of three months, he had become progressively reliant on his wife for assistance with his activities of daily living. He denied any smoking history or illicit drug use including intravenous drugs and reported occasional social consumption of 1-2 glasses of wine on weekend nights but denied binge drinking. His family history included testicular mesothelioma in his father, but there was no other known history of cancer, bleeding disorders, thrombotic disorders, or neurologic disorders. By physical examination, the patient was cachectic with obvious signs of proximal muscle wasting. His vital signs were within normal limits. Examination of his cervical, axillary, and inguinal lymph nodes was unremarkable, and no rashes or bruising was noted. His abdomen was soft, without palpable masses or appreciable hepatosplenomegaly. Several abnormalities were noted in his neurologic exam, including left-eye horizontal nystagmus on left lateral gaze. His strength was grossly diminished, particularly in the lower extremities. Hyporeflexia was present, including 1+ patellar reflexes and absent upper extremity and ankle jerk reflexes. Sensory exam revealed hypersensitivity to pinprick and diminished sensation to soft touch and vibration in all four extremities. Finger-to-nose testing revealed dysmetria. Romberg’s test was positive. His gait was limited by his bilateral leg weakness but was consistent with ataxia with a spastic component.
Laboratory and imaging investigations performed during previous admissions included tests for associated infections (Lyme, HIV, hepatitis B and C, Epstein-Barr virus, cytomegalovirus, syphilis and bacterial cultures of the blood, urine, and CSF), vitamin and mineral deficiencies (vitamin B1, B6, or B12, folic acid, or copper), paraproteinemia (serum protein electrophoresis), inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), and compressive neuropathy (MRI of the brain and spinal cord) and were all normal (Figure ).
CSF analysis revealed a high CSF protein of 800 mg/L with a normal CSF white blood cell count of 5/mm3 and oligoclonal bands. EMG/NCS showed evidence of demyelination.
During the current admission, complete blood count was normal except for mild thrombocytopenia and anemia without iron deficiency. Serum electrolytes, coagulation studies, and hepatic and renal function tests were also largely within normal limits. An autoimmune paraneoplastic panel was negative for many common autoantibodies: ANNA-1 (Hu), ANNA-2 (Ri), PCCA-1 (Yo), amphiphysin, and CV2.1. CSF analysis was repeated with similar findings. CSF flow cytometry was negative for abnormal cells.
Serum protein electrophoresis was performed with immunofixation, which revealed an elevated M-protein of 1.2 g/L with IgM kappa restriction. Positron emission tomography (PET) and CT imaging studies revealed splenomegaly with borderline hepatomegaly, and increased prevalence of mediastinal, axillary, and mesenteric lymph nodes without enlargement or increased fluorodeoxyglucose (FDG) avidity (Figure ).
Moderate hypermetabolism throughout the bone marrow of the axial and appendicular skeleton was present. Repeat MRI of the brain showed FLAIR signal abnormality and slight contrast enhancement of the superior cerebellar peduncles bilaterally, more so on the right, suggestive of demyelination (Figure ).
Bone marrow biopsy revealed hypercellularity with DLBCL accounting for 15-30% of cells, and double-hit status was negative. Lactate dehydrogenase was 210 U/L and uric acid was 0.24 mmol/L. The patient’s international prognostic index (IPI) was calculated to be 3 (age >60, performance status >1, and stage IV disease), the intermediate risk for central nervous system (CNS) disease.
Treatment with multiagent chemotherapy including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was planned with the consideration of high-dose methotrexate to improve CNS penetration [] due to the patient’s intermediate risk for CNS disease. Given the patient’s poor performance status, he was hospitalized for two cycles of plasmapheresis prior to initiation of chemotherapy. Following two cycles of plasmapheresis, the patient’s neurologic symptoms began to improve, and he had substantial improvement in performance status. Following cycle one of R-CHOP, the decision was made to not give high-dose methotrexate as the neurologic syndrome was felt to be paraneoplastic. Prolonged pancytopenia with severe neutropenia delayed treatment in the third, fifth, and sixth cycles, despite supportive care including scheduled granulocyte colony-stimulating factor. There were also multiple hospitalizations for febrile neutropenia during his treatment course. No dose reductions were made during treatment. Though eight cycles were offered, therapy was stopped after six cycles due to the patient's preference.
The patient has been seen at intervals of three, six, and 12 months since completion of therapy. Prior pancytopenia and hypogammaglobulinemia have fully resolved, and no new laboratory abnormalities were detected. PET/CT imaging at those intervals showed no evidence of active disease or splenomegaly (Figure ).
MRI brain was also repeated once at 12 months and did not demonstrate lymphoma or persistence of the possible cerebellar demyelination (Figure ).
Due to the disease being primarily detected in the bone marrow, a biopsy was repeated at three and 12 months with low-normocellular marrow, and without evidence of lymphoma, dyspoiesis, or other clonal expansion.
He has not been hospitalized since completing chemotherapy. He has worked hard to regain strength, initially with physical therapy, followed by a daily weight-lifting and bicycling regimen at home. While he believes he has not fully regained his level of physical fitness from prior to therapy, he is highly active, and his only residual symptom is low-grade peripheral neuropathy of his bilateral feet. He recently resumed scuba diving instruction and deep-sea diving per his preference. We plan to follow the patient with repeat PET/CT imaging and bone marrow biopsy at two years, after which point he will be followed by labs and exams in conjunction with his primary care physician.


A previously healthy 58-year-old right-handed woman presented to an outside institution for difficulty reading and writing. MRI revealed a 23 cm () (4.0 cm max. diameter) contrast-enhancing lesion in the left posterior temporal lobe. She underwent near complete resection without complication, and histopathology confirmed the diagnosis of GBM with positive O ()-methylguanine-DNA methyltransferase (MGMT) methylation, negative mutant IDH1 (R132H), and 60% EGFRvIII positivity. She completed three months of standard-of-care chemoradiation therapy (Stupp Protocol) and was then referred to the University of Pennsylvania with Karnofsky Performance Status (KPS) of 90, no focal neurologic deficits, and no steroid requirement. Surveillance MRI with dynamic susceptibility contrast (DSC) perfusion imaging revealed elevated rCBV suggesting tumor recurrence 6 months after initial resection (). She was enrolled in our EGFRvIII-directed CAR T for recurrent GBM trial (NCT02209376).
Twenty-six days after leukapheresis, she underwent intravenous infusion of 9.2 x 107 autologous EGFRvIII-directed CAR T cells. Two weeks prior to infusion, she had reported worsening pressure headaches, an increase in word-finding difficulty, and a “whooshing” sound in her left ear. These symptoms improved with a one-week steroid taper. On post-infusion day 7, she reported mild flu-like symptoms, including arthralgia, myalgia, and headache. She was managed conservatively with acetaminophen, which relieved her symptoms. Three months after CAR T cell infusion, the patient experienced increasingly severe headaches, requiring the re-initiation of dexamethasone. MRI demonstrated increased size of the enhancing lesion with increasing FLAIR abnormality, concerning for tumor progression vs. treatment response, the latter supported by decreased tumor relative cerebral blood volume (rCBV) (). To address her clinical complaints, and to potentially guide further therapy with tissue diagnosis, the patient underwent a second craniotomy on post-CAR T day 104. The pathology was consistent with recurrent GBM. She was discharged home with KPS 80 on post-operative day 2. At her post-operative visit, she reported difficulty with reading, consistent with a partial (quadrant) visual field deficit.
The patient enjoyed good functional status and received no additional chemotherapy for 18 months following her second operation (). After 15 months, serial MRIs revealed gradual tumor progression (arrows, ). At 32 months from CAR T infusion, she developed a methicillin sensitive S. aureus osteomyelitis in her right lower extremity and required operative debridement. After surgery she had a rapid, unexpected decline, never fully regaining her mental status, and in accordance with her and her family’s wishes she was transferred to hospice care. Her overall survival was 36 months from the date of initial tumor recurrence, and 34 months from CAR T infusion.


A 27-year-old female with a pertinent medical history of tobacco use and intrauterine device implantation presented to the emergency department (ED) with a chief complaint of progressively worsening shortness of breath for two days. Associated symptoms included a non-productive cough, tactile fevers, diaphoresis, muscle aches, and chest pain when coughing. Symptoms were present for two weeks and were felt to be improving until four days prior. The patient was also evaluated in the ED the previous day and was prescribed prednisone and doxycycline for a diagnosis of atypical pneumonia. Additional review of symptoms was negative for hemoptysis, extremity pain or swelling, history of venous thromboembolic disease, or any travel.
Physical examination was significant for an anxious and diaphoretic female in moderate respiratory distress. She appeared uncomfortable and was in a tripod position. Auscultation revealed bilaterally diminished breath sounds with mild expiratory wheezing. The rest of the examination was unremarkable except for tachycardia. Initial vital signs were a temperature of 98.1° degrees Fahrenheit (36.7° Celsius), pulse of 107 beats per minute, blood pressure of 134/75 millimeters of mercury, respiratory rate of 24 breaths per minute, and pulse oximetry of 91% on two liters oxygen via nasal cannula.
In view of the patient’s respiratory distress, she was given nebulized ipratropium bromide and albuterol, in addition to an intravenous (IV) anxiolytic. This resulted in an improvement in her respiratory effort and work of breathing. The hypoxia improved through the implementation of 100% oxygen via a non-rebreather mask, which was subsequently converted to a high-flow nasal cannula. Oxygen saturations stabilized and remained greater than 95% after she received the above treatments. The patient was empirically treated with IV ceftriaxone and doxycycline and two liters of IV normal saline. Both plain chest radiograph and computed tomography angiography of the chest were negative for acute findings.
Laboratory findings were significant for leukocytosis of 15.4 x 103 microliters (μL) (reference range 3.6–11 × 103//μL); lactic acid of 2.3 millimoles per liter (mmol/L) (reference range 0.4 – 2.0 mmol/L); C-reactive protein of 5.12 milligrams per deciliter (mg/dL) (ref range 0.00–0.30 mg/dL); creatine kinase of 7,646 units/L (ref range 26–192 U/L); and creatine kinase MB (CK-MB) of 42.0 nanograms per milliliter (ng/mL) (ref range 0.0–5.6 ng/mL). Rapid influenza diagnostic testing was negative. M. pneumoniae antibody testing and viral panel studies were also collected but did not result until later in the admission. Patient denied illicit drug use, including methamphetamine abuse, which was confirmed by a negative urine drug screen. She was admitted to the intensive care unit and treated with aggressive IV hydration therapy, supplemental oxygen, and antibiotics.
During her hospitalization, both the serum creatine kinase and CK-MB levels were monitored serially and continued to rise with peaks on day two of 29,427 U/L and 87.3 ng/mL, respectively. These levels gradually trended down to a normal reference range by day seven and day four, respectively ( and ). Renal function was unaffected and remained normal with an initial creatinine of 0.76 mg/dL and a peak of 0.79 (reference range 0.43 to 1.13 mg/dL). Relevant admission findings included reactive immunoglobulin M antibodies to M. pneumoniae. She also remained persistently hypoxic for several days but ultimately was successfully weaned off all supplemental oxygen and discharged home after a seven-day hospitalization.


A 72-year-old man presented one month ago with a sudden pulsating continuous headache with anumeric rating scalescore of 8. Brain magnetic resonance imaging and brain magnetic resonance angiography were performed to identify structural lesions. A cerebral aneurysm of 6.2 mm in maximal diameter was detected in the anterior communicating artery (ACoA), and the patient was transferred to the neurosurgery for coil embolization. Cerebral angiography performed before the procedure found no stenosis or sign of vasospasmof the carotid and intracranial arteries. Coil embolization was successfully completed (). However, the day after the procedure, the patient complained that a small fixed dark gray square was visible on the inferior central area and felt that hisvision was out of focus. The confrontation test did not show prominent visual field defects. On anterior segment examination, no abnormality was observed in both eyes. Intraocular pressure (IOP) measured using non-contact tonometry was 15/16, the corrected visual acuity was 20/20 in the right eye and 20/63 in the left eye, and pupillary light reflexes were intact. The retina showed partial whitening (0.5 DD) in the perimacular area at the 12 o’clock position, indicating the possibility of cilioretinal artery occlusion (CLRAO). Moreover, there was a branch retinal artery occlusion 1 DD (disc diameter) away from the optic disc to the inferior temporal area, accompanied by inner retinal edema, and macular pigment epithelial detachment (PED) was detected.
The diagnosis was cilioretinal artery occlusion with branch retinal artery occlusion (BRAO). Two weeks later, the IOP measured in both eyes was 14/13, visual acuity was 20/20 in the right eye, 20/63 in the left eye, with slight difference tobefore. Optical coherence tomography (OCT) showed that the edema remained, but the size of PED slightly decreased.
At a one month follow-up, there was no change in the IOP, but the patient’s vision improved to 20/32 in the left eye, compared with the previous examinations. Fundus examination showed reduced ischemic lesions in the perimacular area, and the overall artery flexus defect showed a slight improvement in OCT angiography, but some ischemic lesions remained. Tests performed using the Humphrey visual field analyzer (30-2 program) showed preserved function in the perimacular area. Two months later, visual acuity was still 20/32 in the left eye, but ischemic lesions in the retina recovered almost completely. The capillary perfusion also improved in OCT angiography, and the patient is currently under outpatient follow-up care ( and ).


A 10-month-old female with regular neurological development and no previous medical history was admitted to our hospital for an acute onset of vomiting, followed by a progressive deterioration of her neurological status, requiring tracheal intubation. The computed tomography scan showed a large right intraventricular mass with recent bleeding associated with moderate midline shift. Magnetic resonance imaging (MRI) with contrast media and time-of-flight magnetic resonance angiography (ToF MRA) confirmed the presence of a large, hemorrhagic, intensely enhancing intraventricular mass, centered in the atrium of the right lateral ventricle, without invasion of the adjacent brain parenchyma, fed by a moderately enlarged anterior choroidal artery (). Whole spine MRI excluded signs of cerebrospinal fluid seeding. The patient was scheduled for the following day to perform endovascular embolization and surgical excision.
A preoperative three vessel angiography (bilateral internal carotid artery and dominant vertebral artery) confirmed the presence of a slightly enlarged right anterior choroidal artery feeding the tumoral blush. No feeders were observed from the posterior circulation; embolization was obtained with n-butyl cyanoacrylate (NBCA) superselective injection (0.4 mL) via a microcatheter (Magic 1.2F-Balt, Montmorency, France; aided by a microguidewire Hybrid 0.008-Balt, Montmorency, France) navigated near the tumor pedicle, distally, to the plexal point of the anterior choroidal artery (). The positioning of the microcatheter distally, in the anterior choroidal artery, determined, as expected, a rectification of the artery, and a panoramic injection (guiding catheter Envoy 5F-Codman Neuro, Raynham, MA-positioned in the internal carotid artery) revealed an absence of flow within the anterior choroidal artery. The total time that elapsed between micro-catheterization, glue injection and retrieval of the microcatheter was 6 min. The subsequent control angiography revealed the exclusion of the tumor blush and a re-opening of the anterior choroidal artery. Total contrast media of 30 mL (300 mgI/mL), fluoroscopy time was 11 min, total series of 9, and cumulative DAP 20 710 mGycm2.
Immediately after the endovascular procedure, the patient underwent a surgical excision of the tumor. Opening of the right parietal craniotomy and dura revealed a herniation of the superior parietal lobule. The cortex was incised, leading to the spontaneous drainage of an intralesional haemorrhage and the identification of the neoplastic tissue, which was soft and scarcely bleeding. A gross total resection was easily achieved and an external drainage was left for 4 days postoperatively and then removed. Total blood loss was estimated to be approximately 200 cc, mainly during soft tissue opening. Histopathological analysis of the specimen was consistent with WHO grade III choroid plexus carcinoma (Immunophenotype S100: +; CAM 5-2: +; MNF116: +, MIB1 > 20%). The patient was discharged at 8 days with no neurological sequelae, and was planned for adjuvant chemotherapy according to CPT-SIOP 2009 recommendation (6 cycles alternating Cyclophosphamide and Carboplatin). Follow-up at 3 months revealed regular development of the child and absence of recurrent disease at MRI ().


A 62-year-old, hypertensive woman, with type 2 diabetes, obesity, and dyslipidemia, was undergoing ambulatory investigation for postprandial fullness with a gastroenterologist. She had no family or personal history of rheumatic diseases, episodes of digestive hemorrhage, postprandial pain, abdominal traumas, alcoholic beverage consumption, pancreatitis, or recent weight loss. Angiotomography showed a large IPDAA, with dimensions of 54 x 60 mm, connecting the SMA to the gastroduodenal artery. The SMA did not have ostial plaque, while the CT had ostial plaque causing stenosis estimated at approximately 20% (). A transthoracic echocardiogram found no evidence of pathological changes.
The management option chosen was arteriography followed by superselective navigation with microcatheters and embolization with microcoils. The procedure was performed in the angiography suite, under local anesthesia and conscious sedation, with femoral access and a 5 Fr introducer (Terumo Medical, Somerset, United States). After arteriographic study with sequential and selective catheterization of the CT and SMA, the decision was taken to catheterize the SMA and perform superselective navigation with a microcatheter via the inferior pancreaticoduodenal artery to the large aneurysm. Embolization was performed using a Rebar-18® microcatheter (ev3; Plymouth, United States) and a SilverSpeed-16® microguidewire (ev3; Plymouth, Minnesota, United States), followed by embolization with 6 18 mm x 40 cm Axium® Prime 3D detachable microcoils (ev3; Plymouth, United States). After complete embolization of the aneurysm, a second selective arteriographic study via the CT and SMA showed complete exclusion of the IPDAA and improved perfusion of the intestinal loops ().
Postoperative monitoring took place in the intensive care unit, with good progress and hospital discharge on the second day after the procedure. Control angiotomography at 1 month showed the SMA and CT were patent, with complete exclusion of the IPDAA. At 1-year outpatients follow-up, the patient reported resolution of the postprandial complaints described previously ().


A previously healthy 2-year-old girl presented with a 4-week history of a cutaneous pruritic eruption that initially appeared on her legs and subsequently progressed to affect her soles, arms and face sparing the trunk and palms. The child had already been treated three-times with topical administration of benzyl-benzoate lotion as a trial treatment for scabies without any improvement. History revealed that 2 weeks prior to the eruption, the child had received hepatitis B vaccination. On physical examination, she was afebrile with erythematous papules and vesicles on the cheeks, arms, hands and legs (A & B) with bullous transformation on the soles (C & D). There was no lymphadenopathy or hepatosplenomegaly. The patient experienced intense pruritus causing sleep disturbances. In the view of parents’ demand and atypical clinical presentation, a skin biopsy was performed and histopathologic examination of a specimen from the left buttock revealed the presence of parakeratosis and mild acanthosis in the epidermis. Focally, mild interface dermatitis is noted without apoptosis. Moderately intense perivascular and periadnexial lympho-histiocytic infiltrate is also noted in the superficial and mid-dermis with focal exocytosis of lymphoid cells (). The child was diagnosed with atypical GCS following hepatitis B vaccination. Because symptoms were unresponsive to topical betamethasone 0.05% and oral antihistaminic drug, she received oral administration of dexamethasone 0.5 mg/5 ml for 4 days and the eruption resolved partially.
Three months later, the child presented with a similar papulovesicular monomorphic pruritic eruption localized on the face, arms and legs, sparing the trunk as well (A–C). The MMR vaccine (measles, mumps and rubella) was administered 7 days prior to the eruption. A history of intercurrent viral illness was noted by the parents at the time of vaccination. The patient was treated only with topical corticosteroids and an oral antihistaminic drug.


A 43-year-old Lithuanian male was admitted to a hospital because of fatigue, malaise, fever up to 39 °C, and swelling and pain of the right groin. These symptoms lasted for three days. One week prior, the patient removed a tick from the medial side of the right knee. The patient was previously healthy and had no chronic diseases. He reported keeping a dog and a cat. Although he owned a sheep farm, he did not have direct contact with these animals.
Upon admission, his vital signs were: temperature 36.8 °C, blood pressure 100/60 mmHg, and pulse rate 84 beats/minute. An ulcer 1 cm in diameter on the medial side of the right knee was observed, where the tick had been attached. There was a palpable and painful 3 cm × 6 cm lymph node conglomerate in the right groin area, with erythema of the overlying skin. A laboratory analysis revealed a normal white blood cell count (6860 cells/μL) and increased concentration of C-reactive protein (CRP) (118.8 mg/L). The urine analysis showed no essential changes. The chest X-ray was normal, and negligible hepatosplenomegaly was detected during an abdominal ultrasound. Two blood cultures and culture from the ulcer yielded negative results. Empirical parenteral amoxicillin/clavulanic acid (1.2 g four times a day) was initiated. Suspecting tularemia, parenteral gentamycin (80 mg three times a day) was added, although the initial serological test, Western blot (WB) to IgG antibodies of Francisella tularensis, was negative.
After three days of treatment, the pain and size of the lymph node conglomerate diminished, erythema of the overlying skin disappeared, and the concentration of CRP decreased to 65.3 mg/L, but the febrile fever persisted. The patient started to complain of myalgia, heart palpitations, and breathing difficulties on the fourth day of hospitalization. It was difficult for the patient to walk and even to open his mouth due to myalgia. Repeated laboratory analysis revealed leukocytosis in serum (15,110 cells/μL), elevated concentrations of CRP—184 mg/L, alanine aminotransferase (ALT)—609 IU/L, aspartate aminotransferase (AST)—1662 IU/L, creatine kinase (CK)—42,670 IU/L, lactate dehydrogenase (LDH)—1446 IU/L, troponin I—2201 ng/L, myoglobin—>12,000 μg/L, and potassium—6.3 mmol/L. The concentration of creatinine remained normal. The urine sample was dark brown, and proteinuria of 1.0 g/L and 8–9 erythrocytes per visual field were observed. Rhabdomyolysis was suspected, and the patient was transferred to the intensive care unit. A large amount of intravenous fluid therapy was initiated to prevent kidney damage, continuing intravenous antibiotic therapy. After two days, the patient’s muscle pain decreased, and there were no signs of acute kidney damage or fever. He was transferred to the Department of Internal Diseases, continuing the intravenous antibiotic therapy and rehydration.
The patient responded well to treatment: the patient’s general condition improved, his body temperature decreased to a normal level, the muscle pain disappeared, the lymph nodes in the right groin area decreased in size, and the wound on the medial side of the right knee healed. CRP, ALT, AST, CK, troponin I, myoglobin, LDH, and potassium concentration decreased to normal levels. On the seventeenth day of hospitalization, the patient was discharged from the hospital in a satisfactory condition.
Analyses for various infectious agents were performed. Serological tests for tick-borne encephalitis virus, Borrelia burgdorferi, Cytomegalovirus, viral hepatitis B and C, Epstein–Barr, HIV infection, and syphilis, as well as molecular tests for influenza A and B and respiratory syncytial virus infection, were negative. During hospitalization, three WB tests for detecting Francisella tularensis IgG antibodies were conducted: the first one was negative (on the first day of hospitalization), the second one was faintly positive (threshold) (on the eighth day of hospitalization), and only the third one was positive (on the sixteenth day of hospitalization). Based on this presentation, the patient was diagnosed with ulceroglandular tularemia complicated by rhabdomyolysis.


A 44-year-old male with a diagnosis of psoriasis since adolescence and chronic mild nephropathy since 2016 came to our attention seeking medical treatment. The patient was previously treated with topical and systemic steroids, cyclosporin A, adalimumab, and phototherapy. None of these therapies led to a constant improvement of cutaneous manifestations. During the dermatological evaluation, psoriasis with an inverse and a palmoplantar component was evidenced (). A Psoriasis Area Severity Index (PASI) of 15 was calculated. The patient underwent nephrological consultation for a stage-three renal failure, with a glomerular filtration rate (GFR) of 50 mL/min. Before starting any systemic treatment, a complete panel of blood exams (blood count, ALT, AST, HBSAB, anti-HCV, creatinine, total cholesterol, glycemia, gamma gt, serum protein electrophoresis, ana, ena screen, Interferon Gamma Release Assay, etc.) was performed. The results of this panel were unremarkable except for creatininemia, which was 1.8 mg/dL.
A treatment with anti-interleukin 17 Ixekizumab (160 mg at week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks) to treat psoriasis was started.
During the first follow-up visit, three months after the beginning of treatment, cutaneous lesions were dramatically improved (PASI 5). After six months, another complete blood panel was performed. Creatinine dropped to 1,0 mg/dL, and therefore a GFR exam was performed; results showed a filtration rate of 95 mL/min, corresponding to a stage-one renal failure. After one year of anti-interleukin 17 therapy, at the third follow-up visit, the patient’s skin clearance was almost complete (PASI 1), and creatininemia was still 1.0mg/dL ().


A six-year-old intact female mixed breed dog was presented with acute pruritus of ears, muzzle, and abdomen. The dog has been previously vaccinated and treated for both internal and external parasites. The physical examination revealed a decreased diameter of the auditory canal of the left ear with inflammation and brown granular content with a strong rancid odor, compatible with the overgrowth of Malassezia spp. that was further confirmed by cytology. Erythema and papular skin lesions were present on the abdomen. An additional nodular lesion was detected in the subepidermal area of the third nipple of the left mammary chain. The owner was aware of this lesion for at least 1 year before the dog was presented to the hospital, without causing any pain or discomfort to the animal. The dog was treated with corticosteroids (prednisolone administered orally at 0.5 mg/kg BID for 3 days, followed by the same dosage SID for 3 days, and then QID for other 3 days) along with cleansing and topical application of Canaural® ear drops for the treatment of otitis externa. Excision of the mammary mass was advised and performed ~2 months later, after complete recovery of the dermatological signs.
The lesion was surgically removed, fixed in 10% neutral buffered formalin and submitted for histological examination.
For histology, the samples were cut and processed routinely, and sections were stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS). Immunohistochemistry was performed using the Novolink™ Max-Polymer detection system (Novocastra, Newcastle, UK), employing the following monoclonal antisera: pan-cytokeratin (clone AE1/AE3, Zymed) diluted 1:50; vimentin (clone V9, Dako) diluted 1:100; uncoupling protein-1 (UCP1) (clone ab23841, Abcam) diluted 1:20 and p53 (clone BP53.12, Zymed) diluted 1:400. Positive controls consisted of sections of mouse perirenal adipose tissue () and canine sebaceous gland adenocarcinoma () known to express UCP1 and p53, respectively. A section of subcutaneous adipose tissue of a dog was used as negative control for UCP1 ().
Grossly, the tissue fragment was represented by a nipple, with an exophytic nodular and dense mass, measuring 12 mm × 6 mm × 4 mm. In cross-section, the lesion was well-delimited, partially encapsulated, with a homogenous appearance and white-yellow color.
Histological examination revealed a well-defined, partially encapsulated, multinodular and highly cellular neoplastic mass, effacing and expanding the subepidermal area of the nipple (). The tumor was composed of round to polygonal cells arranged in nests and delimited by thin fibrovascular stroma. The neoplastic cells presented variably distinct cellular borders, clear or pale eosinophilic cytoplasm, containing one or multiple optically empty vacuoles, mainly resembling lipocytes (). The vacuolar content was PAS-negative and was consistent with, although not proven to be, lipid. The nuclear:cytoplasm (N:C) ratio was low, and the nuclei were round to oval, central or occasionally eccentrically positioned, with fine granular chromatin and 1–2 small, basophilic nucleoli. Anisocytosis and anisokaryosis were mild, and the number of mitotic figures varied from 0 to 2 per high power field (0.237 mm2) (). Scattered mononuclear inflammatory cells, represented by small lymphocytes, plasma cells, and some macrophages were observed within the lesion. There were no evidence for vascular invasion of neoplastic cells.
The neoplastic cell population did not exhibit any immunoreactivity for cytokeratin AE1/AE3 () and p53 () but showed strong positive immunostaining for vimentin () and UCP1 ().
Based on morphological, histochemical, and immunohistochemical findings, a diagnosis of a subepidermal nipple hibernoma was made.


An 18-year-old Caucasian male patient, with ulcerative colitis, came to our attention, about 2 weeks after a drug-induced car accident. The patient was hospitalized for 7 days at the Plastic Surgery Department of the University Polyclinic in Bari, Italy. The patient presented with a nasal septum fracture, a bruise wound at the level of the upper lip, and several scrapes and bruises at the level of the mid-third of the face at the pre-maxillary level.
The study received the approval of the Ethical Committee (n.4743) and signed informed consent was obtained from the patient. All procedures were undertaken in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
The PRICE 2020 checklist for case reports was used in this study.
Extra-oral and intra-oral photographic documentation was obtained using a digital camera (Nikon D7100, 105 mm Macro lens, R1C1 Macro flash) with standardized camera settings (shutter speed 1/80 and aperture settings f32 for intra-oral documentation; and shutter speed 1/100 and aperture settings f10 for extra-oral documentation).
The images of the face of the patient immediately after the trauma are represented in .
A decision tree summarizing the steps of the first stage of the TBM is shown in .
An intraoral camera Soprocare (Acteon) was used to detect caries, plaque, calculus and gingival inflammation, one month after trauma ( and ).
The D-BIOTECH CLINICAL APPROACH is a topographic technique in dentistry used for biofilm detection.
Patient motivation occurs through presentation of intra-oral images showing bacterial biofilm residue to improve at-home oral hygiene, with particular care applied to the most plaque retentive sites, and to avoid inflammation and/or demineralization in these areas. This approach is aided by the selection of the most appropriate technologies, tools and clinical approaches for de-plaquing and debridement.
The plaque detector (GC TRI PLAQUE ID GEL) was applied with a brush on the buccal and vestibular surfaces of the teeth. The oral biofilm was detected in three different colors ():
red/pink—indicated a recently formed bacterial biofilm;
blue/purple—indicated the presence of mature bacterial biofilm (over 48 h);
light blue/blue—accurately detected the high-risk areas where the bacteria were most active, highlighting their acidic ph.
The images were discussed with the patient and the hygienist motivated the patient regarding the importance of restoring the balance in the excessively acidic environment of the oral cavity. The D-BIOTECH clinical approach allows for minimally invasive work and acts as a guide for the operator to use these tools, which allow selective polishing and/or scaling by following the topography of the bacterial biofilm.
Intraoral photographic images were collected to document the dental situation () and the color matching (). Color-matching procedures are usually carried out using a Spectroshade Spectrophotometer, but in this case the Vita 3DMaster scale was preferred in order to avoid contact of the spectrophotometer with the teeth surface.
In the presented case, the innovation was the introduction of Polarized Polychromatic Incoherent Low Energy Radiation (PILER) using a Bioptron® Device (Zepter; Wollerau, Switzerland) [].
The Bioptron Device provides polarized visible polychromatic noncoherent light with 90 W; light wavelength = 480–3400 nm; degree of polarization = 95%; specific power density = 40 mW/cm2; energy density = 2.4 J/cm.
The patient started the phototherapy with the Bioptron® Device (Zepter; Wollerau, Switzerland) the second day after the trauma. The applications were performed daily with a duration of 15 min at a distance of 5 cm, for 5 consecutive days, after brushing.
The subjective change of pain was measured on a visual analogue scale the day after each application, and the level of pain diminished from value 10 to value 3 after the first week of treatment, according to the following assessments:
VAS scores: day 1—10, day 2—8, day 3—7, day 4—6, day 5—5, day 6—4, day 7—3.
Then, Bioptron applications were performed during the following three months, twice per week, for a total of 24 times, 15 min duration, 5 cm distance (); the healing of the soft tissues at three months follow-up is shown in .
specifically shows the healing of the outer scar of the upper lip without any pathological changes after 24 phototherapy cycles. The lip philtrum appears to be conserved and retains its natural aesthetics and morphofunctional projection. The skin covering the scar, initially red and overgrown, has improved significantly during the first cycles with the Bioptron. The overall effect is smoothening of the tissues covering the scar and full chromatic regeneration of the skin.
On the 10th day after trauma, the plastic surgeon removed the stitches placed on the face. At this stage, it was possible to start the dental treatment.
The Tailored Brushing Method (TBM) is a novel protocol for at-home oral hygiene. This method is based on the concordance between patients and professionals to choose together the best strategies (tools and their use) for home oral hygiene procedures, regardless of the technique used [].
The Tailored Brushing Method is based on a two-stage decision process.
FIRST STAGE
At the baseline, the following clinical characteristics of the patients are assessed:gingival biotype; dental morphology (natural tooth, crown on natural tooth, crown on implant) and presence of diastema; patient’s manual skills; patient’s personality profile.
Use of the plaque test helps to communicate with the patient and to exactly show the points and areas within the oral cavity and mineralized tissue where the oral hygiene needs to be improved. Communication with the patient is achieved using new technologies, such as intra-oral cameras, that allow the collection of intra-oral images of biofilm, plaque and calculus, and the assessment of enamel hypomineralization both on vestibular and occlusal teeth surfaces.
Based on these evaluations, the clinical analysis is shared with the patient, to obtain a mutual concordance on the protocol of at-home oral hygiene to adopt. The concept of “compliance”, in which the patient passively incorporates and learns some stereotyped movements, is here innovated with the concept of “concordance”, which assumes an active interaction between the patient and the healthcare provider.
SECOND STAGE
The second stage is sub-divided into two clinical steps: Concordance1 (C1) and Concordance2 (C2).
C1 is related to the techniques of oral hygiene to be used during domiciliary oral care.
C2 is related to the choice of toothbrush and interdental brush.
TBM requires that dental hygienists and patients choose the most suitable tools to reach every dental surface, including interproximal spaces or areas commonly inaccessible with traditional techniques.
TBM recommends that toothbrushes are always intended to be used in association with interproximal brushes. Toothbrushes with an arrangement bristle in tufts disposed on multiple levels, with angled orientation, and a narrower conformation of the working part, and a handle and neck with flexibility, should be preferred. Interdental brushes made of flexible rubber are very useful, due to the ease of use and the lower risk of papillary trauma. The choice of tools is patient-tailored, based on manual skills and personality profile.
The tailored brushing protocol was used to determine and establish with the patient the personalized protocols for at-home oral hygiene procedures, immediately post-trauma and before full tooth rehabilitation.
Toothbrushing instructions were given to the patient, involving use of a soft toothbrush (GUM® Technique® PRO toothbrush, medium bristles, Sunstar Europe, Etoy, Switzerland) and use of an electric brush. Moreover, the patient was instructed on the usage of interdental brushes. To avoid irritating the interdental papilla, interdental rubber flexible brushes (GUM Soft-Picks Advanced, Sunstar Europe, Etoy, Switzerland) were used ().
A professional oral hygiene treatment was performed, including airpolishing (Combi touch-all in one, Mectron, Mectron Spa, Carasco (GE), Italy) with: (i) bicarbonate powder with <120 μm to remove extrinsic stains and partially to remove calculus; (ii) glycine powder <63 μm (Mectron Glicyne powder).
Then, supragingival ultrasonic scaling with a universal tip (Mectron S1) using the “soft mode” setting of the scaler (Mectron Multipiezo pro) was performed. The allows proper cleaning to be achieved for sensitive patients (same frequency, lower amplitude). ( and )
Application of the remineralizing mousse (CURASEPT BIOSMALTO CARIES, ABRASION & EROSION-IMPACT ACTION MOUSSE PROFESSIONAL USE with F-ACP COMPLEX) was performed. F-ACP COMPLEX is a complex of amorphous calcium phosphate (ACP) functionalized with fluorine, carbonate and citrate. Amorphous calcium phosphate (ACP) is a highly reactive non-crystalline material that rapidly converts to hydroxyapatite. F-ACP COMPLEX is a patented technology designed to deliver, activate and bioavail this hydroxyapatite precursor [,]. The application of Curasept Biosmalto Professional mousse was repeated three times, at baseline, after 15 days and at two months. In addition, from the baseline and for the following 90 days, the patient applied the CURASEPT BIOSMALTO CARIES, ABRASION & EROSION-IMPACT ACTION MOUSSE HOME TREATMENT twice a day after brushing for the whole period and without interruptions.
The patient reported teeth hypersensitivity when in contact with foods, liquids and air. A desensitizing treatment with application of a fluoride-based varnish (FLUOR PROTECTOR S, Ivoclar Vivadent) was performed. The varnish contains synthetic resins with insulating and protecting effects against thermal and chemical stimuli []. Moreover, calcium and sodium fluoride protect the enamel surface by direct remineralizing effect. ().
Prior to prosthetic rehabilitation, one in-office session with 35% hydrogen peroxide bleaching was performed six months after the trauma on the upper six and lower four teeth with esthetic relevance (ENA white power, Micerium) ().
A direct resin restoration was performed at the first visit and then rehabilitation with a ceramic veneer was achieved ().
During the COVID-19 pandemic it was not possible to achieve the full rehabilitation of 1.1. and show the recall procedures based on TBM, one year after trauma.


Patient 1 is a 5-year-old girl, who was observed to have severe hypotonia in her infancy and developmental delay. She was incapable of lifting her head when she was 7-month-old as well as was incapable of sitting by herself and had trouble imitating speech or actions when she was 1-year-old. By the age of 14 months, she was found to lack the ability to maintain eye contact and displayed head-shaking, hand-clapping and hand-wringing as well as bruxism. While she exhibited purposeful hand use, she presented recurrent, febrile or non-febrile, generalized tonic-clonic seizures at the age of 18 months. After receiving treatment with Levetiracetam (LEV) at 20 months, she achieved seizure-free status at the age of 2 years. At the age of 18 months and 2 years, the findings of her EEG tests revealed spike-and-slow waves with bilateral temporal involvement. Her MRI findings at the age of 14 months indicated a widened subarachnoid space ().


Patient 2 is a female who is currently 5 years 9 months old. She exhibited a delay in achieving some developmental milestones, such as head lifting at 4 months, independent sitting at 1 year and independent walking at 2 years. She could say “baba,” or “mama” at the age of 1 year but exhibited regression in development with subsequent instances of only unconscious articulation. Nevertheless, she possessed non-verbal communication skills. Hand clapping was observed at 8 months. She displayed good eye contact as well as a purposeful hand use. She presented recurrent, febrile or non-febrile, generalized tonic-clonic seizures at 10 months; after being treated with LEV at the age of 15 months, she achieved a seizure-free status. Her seizure, which was characterized as a generalized tonic seizure without fever, relapsed at the age of 3 years and was treated with valproate (VPA) and LEV. She achieved a seizure-free status when she was 3.5 years old. EEG (15 months) findings revealed spike-and-slow waves with bilateral temporal and occipital involvement. MRI findings at the age of 10 months were normal ().


Patient 3 is a female who is currently 4 years 4 months old. She showed some signs of developmental delay, such as lifting her head at the age of 5 months, sitting independently at the age of 9 months, and walking at the age of 2 years; she also did not exhibit any non-verbal communication skills and could not imitate actions or babble. Poor eye contact was observed at the age of 8 months. Hand clapping and hand wringing were observed when she was 1 year 6 months old. She demonstrated purposeful hand use, and at the age of 8 months, she experienced recurrent, febrile or non-febrile, generalized tonic-clonic seizures. She presented with status epilepticus, which later became absence status epilepticus at the age of 3 years 2 months. At this time, she was started on LEV medication but showed no response to it; subsequently, VPA was added to the treatment strategy at the age of 3 years 6 months, and the patient finally achieved a seizure-free status at the age of 4 years. Her EEG tests at the age of 15 months demonstrated sharp-slow synthetical waves at the left central and left parietal-frontal regions. EEG showed generalized sharp-slow waves and MRI findings indicated delayed myelination in the periventricular area at the age of 3 years 2 months ().


Patient 4 is a female who is currently 2 years 10 months old. Developmental delay was observed with regard to lifting of her head only at the age of 7 months and the ability to sit independently only at the age of 1 year; she also did not have the ability to walk independently and did not display any non-verbal communication skills. Although she could say the words “baba” or “mama” at the age of 2 years, she displayed a regression in development and only showed signs of unconscious articulation subsequently. Poor eye contact, head shaking, hand clapping, hand wringing, and bruxism were observed at the age of 1 year 3 months. Purposeful hand use was presented and retained. She experienced recurrent, febrile or non-febrile, generalized tonic-clonic seizures at the age of 11 months. Dystonic seizure occurred at 14 months. LEV was administered at the age of 16 months and the patient achieved seizure-free status at the age of 2.5 years. Her EEG (15 months and 2.5 years) and MRI (3 year) findings revealed normal findings ().


Patient 6 is a male who is currently 2 years 7 months old. He was observed to have severe hypotonia in his infancy and developmental delay. He was incapable of lifting his head at the age of 5 months but could sit independently at 9 months; however, he exhibited a regression in development and was unable to walk independently. He also did not show any non-verbal communication skills and was unable to imitate or babble. Poor eye contact, head shaking, hand clapping and hand wringing were observed at the age of 1 year and 6 months. The patient displayed purposeful hand usage. He also presented recurrent, febrile or non-febrile, generalized tonic-clonic seizures at the age of 9 months. Topiramate, VPA and LEV were used but none of them showed a positive effect; this treatment was withdrawn at the age of 2 years. At present, the patient's daily seizures have been characterized as myoclonic. EEG findings obtained at the age of 10 months revealed spike-slow waves with bilateral-central-frontal involvement. MRI scans taken at the age of 15 months showed developmental malformation of the corpus callosum ().


Patient 7 is a female who is currently 2 years 5 months old. She experienced severe hypotonia at infancy and was observed to have developmental delay. She was incapable of both lifting her head at the age of 7 months and sitting independently at the age of 2 years; she was also unable to walk independently, demonstrated no non-verbal communication skills, and was unable to imitate or babble. Poor eye contact as well as head-shaking and hand-clapping behavior were observed at the age of 1 year. She did not display purposeful hand usage. She did not experience seizure. EEG test conducted at the age of 2 years revealed 2–3 Hz sharp-slow waves at the left parietal-occipital region. MRI scans taken at the age of 14 months showed malformation of the corpus callosum, delayed myelination and leukomalacia in the periventricular region ().


A 51-year-old man with end-stage renal disease was referred to a dermatologist for full-body skin evaluation as part of a kidney transplant preoperative workup. The patient noted brown-colored nevi all over the body but none of them had acutely changed, itched, or bled. During the initial visit, three shave biopsies were taken from suspicious, discolored lesions on the left upper back and right shoulder. The biopsy from the left upper back was positive for a 2.9-mm thick melanoma with a mitotic rate >1/mm2 and no ulceration. The lesion involved the deep and peripheral margins. The remaining two biopsies were positive for basal cell carcinoma. The patient was referred to the plastic surgery service for further management of melanoma.
Preoperatively, a positron emission topography (PET) scan showed no evidence of metastatic disease. The patient was given a preoperative injection of Tc-99 on the morning of surgery (Figure ). Under general anesthesia, 0.1 mL of ICG was injected intradermally into the melanoma (Figure ). A wide local excision of the melanoma was performed with cold knife in a rhomboid fashion. Our attention then turned to the left axilla. A gamma probe confirmed the presence of two SLNs as revealed by lymphoscintigram. An NIR light subsequently identified two hotspots on the skin, which corresponded to the two SLNs. We were able to identify the tract from the intra-lesion injection of ICG toward the left axilla and into two SLNs (Figures -). These intraoperative findings were consistent with the gamma probe and preoperative lymphoscintigram findings. The SLNs were excised and sent to the pathologist (Figures , ).
The patient was discharged home later that day. His postoperative course was uneventful. Final pathology results revealed residual invasive malignant melanoma (Breslow thickness 1.5 mm) with negative deep (1.3 cm) and peripheral (2.5 cm) margins. Both SLNs were benign.


A 35-year-old female graphic designer presented with sharp pain in the neck, upper back, and sternum area of 4 weeks duration. The pain radiated to substernal, interscapular, and subscapular areas as a gripping and squeezing sensation without numbness. The symptoms were worse in the evening, and lying on her back while sleeping aggravated the pain. Her medical history indicated a chronic history of neck pain, heart burn, acid reflux, and period pain. After the lock-down during the pandemic, she remained inside her apartment and reported sitting on the bed at her computer while working. Her neck pain gradually became severe and was rated at 8/10 on a numeric pain scale. Her laboratory, barium swallow study and orthopedic tests were negative and ruled out major visceral pathology. The patient reported supragastric belching and regurgitation for at least six months and sometimes experienced a burning sensation in the chest. Changing position from sitting to standing could partially relieve acid reflux. She denies dysphagia, vomiting or blood in her stool. Upper gastrointestinal endoscopy performed two months prior revealed mild inflammation in the distal esophagus and at the gastroesophageal junction, compatible with gastroesophageal reflux disease (GERD). She was prescribed antacids, histamine 2 receptor blockers, and dietary restriction which provided temporary relief only for the heartburn. The patient then sought chiropractic care for her neck pain.
Upon initial evaluation, the patient presented with a forward head and slouching posture. Joint mobility was assessed and indicated restriction at C5–7 and T10-L2 levels. Muscular hypertonicity was evaluated and indicated present in bilateral upper trapezius, levator scapulae, sternocleidomastoid, and subscapularis. Her cervical range of motion was limited and painful at 10° extension (normal > 60°) and 45° of right rotation (normal > 80°). The orthopedic and neurological examinations were within normal limits. Full spine EOS® radiographs showed a picture of degenerative spondylosis of the lower cervical spine with osteophytes at posterior C5 and C6, C7/T1 disc-space narrowing, straightened cervical lordosis, thoracic hyperkyphosis, induced lumbar kyphosis, and cystic change of the right humeral head (). Patients presented with a global thoracic curve of 64° and lumbar curve of 42°. In general, the average angle of thoracic kyphosis and lumbar lordosis is 43.55 ± 6.44 and 32.42 ± 6.29, respectively. Based on the symptoms of heartburn relating with neck pain and the exclusion of systemic disorders, the patient was given a diagnosis of upper cross syndrome with GERD.
The patient was treated with cervical adjustment and soft tissue massage (STRIG Massage Device, Seoul, Korea) three times per week with emphasis on restoring mobility to stiff joints and relieving muscle tightness [,,]. At the end of first month, the patient reported that her neck and upper back pain was fully recovered. She also stopped all medications as her symptoms of heartburn had concurrently eliminated. A rehabilitation program including tuck chin exercises and lifestyle modification was added to the second phase of treatment plan to strengthen the muscles [,,,]. The patient continued to receive chiropractic adjustment twice per month for correcting spinal alignment. Restoration of the posture was demonstrable on the full spine radiographs at 9 months follow-up (). At 12 months after initiating treatment, the patient remained healthy, free of pain and GERD, in the pandemic home-office.


A 69-year-old man presented to our clinic with a four-month history of edematous erythema of the left upper eyelid. He had a history of hypertension and polymyalgia rheumatica. His antinuclear antibody titer was 1:40, with a homogeneous pattern. His serum angiotensin-converting enzyme (7.2 U/L), immunoglobulin (Ig) G (1290 mg/dL), IgG4 (65 mg/dL), creatine phosphokinase (114 U/L) levels, and C-reactive protein (CRP) (0.03 mg/dL) were within normal limits. Additionally, his white blood cell (WBC), including absolute neutrophil and lymphocyte counts was within normal (WBC: 3430/μL, neutrophil: 1400/μL, lymphocyte: 1640/μL). Physical examination revealed edematous erythema with left upper eyelid infiltration (a). Skin biopsy of the edematous, erythematous eyelid lesion showed a normal epidermis with dense lymphocytic infiltration in the reticular dermis (a). Immunohistochemistry showed a predominance of CD4+ T cells compared to CD8+ T cells and few CD20+ B cells (b–e). Mucin deposition was not detected on Alcian blue staining (f). He was treated with 16 mg of oral methylprednisolone daily. Since we observed a good response (b), we tapered the methylprednisolone dose by 4 mg every four weeks until the dose was 6 mg/day. This dose was further tapered over eight months, and the total duration of treatment was 11 months (c). Throughout the clinical course, all laboratory data was within the normal range.


A 21-year-old woman presented to our clinic with a three-month history of edematous induration of the left upper eyelid. She had no history of any other major disease. Her serum IgG4 (16.2 mg/dL), C1-inhibitor (81%), and C4 levels (20 mg/dL) were within normal limits. CRP was mildly elevated (0.78 mg/dL). Additionally, her WBC, including absolute neutrophil and lymphocyte counts was also within normal (WBC: 3800/μL, neutrophil: 1748/μL, lymphocyte: 1089/μL). On physical examination, we observed erythematous swelling of the left upper eyelid (a). Skin biopsy of the left eyelid showed lymphocytic infiltration of the dermis (h). Immunohistochemistry showed a predominance of T cells, a majority of which were CD4+ cells. A few CD20+ B cells were also observed (j–l). There was no mucin deposition in the dermis (n). We treated her with 16 mg of oral methylprednisolone daily. Since we observed a good response (b), we tapered the methylprednisolone dose by 4 mg every eight weeks until the dose was 8 mg/day, following which we further reduced it by 2 mg every four weeks. The total duration of treatment was 11 months (c). Throughout the clinical course, all laboratory data was within the normal range.


A 68-year-old man presented with a four-year history of erythematous plaques on the right eyelid. He experienced multiple episodes of symptom remission and recurrence over a period of four years. We observed edematous erythema on his right cheek (a). He had no fever, local warmth, or cheek pain. He had a history of rheumatoid arthritis. His serum IgG (983 mg/dL), IgG4 (32 mg/dL), CRP (0.03 mg/dL), and WBC, including absolute neutrophil and lymphocyte counts, were within normal limits (WBC: 4460/μL, neutrophil: 1953/μL, lymphocyte: 1971/μL). He tested negative for the rheumatoid factor. The differential diagnoses were sarcoidosis and granuloma faciale. Skin biopsy revealed a normal epidermis with dense lymphocytic infiltration of the reticular dermis (o). There was no mucin deposition in the dermis. Immunohistochemical staining revealed aggregates of CD3+ and CD8+ T cells, but not of CD4+ T cells, in the dermis (p–r). A few CD20+ B cells were observed (s). The diagnosis of LIE was made, and we started treatment with 8 mg/day of oral methylprednisolone. Due to the good response (b), we tapered the methylprednisolone dose by 2 mg every two months. The duration of treatment was eight months (c). Throughout the clinical course, all laboratory data was within the normal range.


A 54-year-old female with HIV virally suppressed on TDF, emtricitabine and efavirenz (Atripla) for the preceding 10 years, presented with progressive, intractable bilateral hip and lower extremity pain along with weakness in the lower extremities, progressive gait disturbance, and recurrent falls over 18 months. Her other medications included vitamin D 400 IU daily, calcium carbonate 600 mg daily, and nonsteroidal anti-inflammatory drugs (NSAIDs) which the patient reported were used sparingly for pain with incomplete relief. A serum creatinine done nine months prior was 1.2 mg/dl [estimated glomerular filtration rate (eGFR) 47 mL/min]. Mild qualitative proteinuria was present for two years prior to this presentation.
On exam, the patient was afebrile and had normal vital signs. Bilateral lower extremity strength was decreased and noted to be 4/5. A detailed musculoskeletal exam was limited by excruciating pain upon lower extremity range of movement. Upper extremity strength and mobility were intact. Laboratory studies revealed a normal blood count, and abnormal metabolic panel with hyperchloremia, acidosis, elevated serum creatinine and alkaline phosphatase. The serum phosphate level was decreased, the calcium level normal, and the Parathyroid hormone (PTH) level was elevated. Notably, Vitamin D levels were within reference ranges. Detailed laboratory values are listed in .
A spot urine test showed new onset glycosuria and phosphaturia, with a calculated fractional PO4 excretion of 62.3% (reference range <5%).
Endocrinology was consulted for “unexplained hypophosphatemia” in the setting of bone pain. The patient’s laboratory studies were consistent with a hyperchloremic non-anion gap metabolic acidosis, consistent with proximal renal tubular acidosis (RTA) attributed to Fanconi syndrome. Skeletal X-ray studies revealed the presence of bilateral subtrochanteric Looser’s Zones with non-displaced proximal diaphyseal fractures of the first and third metatarsals of her right foot (). A bone scan demonstrated increased uptake bilaterally in the lesser trochanter region of the proximal femur, distal right femur, right ankle, and the right first and third metatarsals ().
Based on these findings, a diagnosis of TDF-related Fanconi syndrome with associated hypophosphatemia and osteomalacia was established. TDF was replaced by abacavir after human leukocyte antigen (HLA) testing was negative for the B5701 allele. Repletion with oral PO4 250 mg three times daily, and calcitriol 0.25mcg daily was commenced. The patient experienced complete clinical, biochemical () and radiographic resolution within 14 weeks of follow up, allowing for discontinuation of oral phosphate and calcitriol and initiation of maintenance cholecalciferol at 2000 IU/day. A DEXA scan performed following resolution of her symptoms demonstrated T scores at the forearm of −2.4, at the femoral neck of −0.9, and total hip of −0.3. There was no evidence of axial osteopenia (L1-L4 T score +2.1).
A written informed consent was obtained from the patient for publication of this case.


An 11-month-old Indian girl, the first child of a non-consanguineous couple, presented to the pediatric neurology clinic with complaints of seizures and global developmental delay. Pregnancy was uneventful. The child was born by cesarean section at term with a birth weight of 3 kg. At birth, the child was admitted to the neonatal intensive care unit with high total serum bilirubin (24.5 mg/dL) and treated with exchange transfusion and phototherapy. At that time, no other systemic complications were noticed. The child had a global developmental delay. At present, partial neck holding, no hand opening, no mother regard, and only making cooing sounds. The child had seizures three days before the visit to the clinic with an upper respiratory infection. In the last three days, the child had multiple episodes of generalized clonic seizures that last for the one-to-three minute duration.
On examination, head circumference was 44 cm (25th centile), weight was 7 kg (<3rd centile) and height was 72 cm (25th centile). Physical examination showed dysmorphic features include frontal bossing, high forehead, depressed nasal bridge, low set ears, high arched palate, and long philtrum (Figure ). Neurological examination revealed irritability, no visual fixation, nystagmus, central hypotonia, normal deep tendon reflexes, and choreoathetoid movements. The other systemic examination was normal. No skeletal anomalies were noticed.
Extensive investigations including complete blood picture, blood sugar, renal function tests, thyroid profile, lactate, creatine phosphokinase, alkaline phosphatase (ALP), vitamin B12, and vitamin D3 were normal. Both blood and urine amino acids and organic acids were unremarkable. Fundoscopy was normal. Cerebrospinal fluid analysis showed normal levels of glucose, proteins, lactate, and pyruvate. Abdominal ultrasonography and cardiac imaging were normal. Electroencephalography (EEG) revealed high amplitude diffuse slow waves background activity without any epileptiform discharges. MRI of the brain showed generalized atrophy without any focal lesions (Figure ).
DNA sequencing with a next-generation sequencing platform revealed a homozygous missense variation in exon 10 of the PIGT gene (chr20: g.45424323C>T) that results in the amino acid substitution of tryptophan for arginine at codon 448 (p. Arg448Trp) was detected. This variant is classified as likely pathogenic in the ClinVar database.
Seizures were controlled with levetiracetam (20 mg/kg/day) and clobazam (0.7 mg/kg/day). Physiotherapy was initiated. Again child had seizures at 15 months of life with fever and controlled with an increased dose of levetiracetam (30 mg/kg/day). On follow-up, there were no further seizures. Now child's age was three years and completely bedridden, had feeding difficulties, and failure to thrive without recurrence of seizures.


A 78-year-old male with history of myelodysplastic syndrome (MDS), dementia and a previous episode of endocarditis 10 years prior which required bioprosthetic aortic valve replacement, presented with a three-day history of progressive left eye vision loss accompanied with floaters. He denied chest pain, shortness of breath or fever. At presentation, vital signs were a heart rate of 90 bpm, blood pressure 129/56 mmHg, temperature of 98.2°F and respiratory rate of 17 rpm. Pertinent physical exam findings consisted of a grade II/VI systolic ejection murmur at the left sternal border. There were no peripheral signs suggestive of endocarditis such as Osler’s nodes, Janeway lesions, or splinter hemorrhages. Ophthalmic examination of the left eye revealed a visual acuity of 20/30 and intraocular pressure by tonopen of 8 mmHg with pupils equal and reactive to light. There was evidence of conjunctival injection with dilated episcleral vessels and scattered retinal hemorrhages with cells obscuring the posterior chamber. The results of external, slit-lamp, and fundus examinations of the right eye were normal. Laboratory data was significant for a leukocytosis of 20,300 with left shift and a thrombocytopenia of 27,000.
Following ophthalmologic evaluation, given the high concern for EE, he underwent emergent left eye vitrectomy with vitreous sample and culture. He received prophylactic intravitreal antibiotics with vancomycin, ceftazidime and amphotericin B as well as systemic intravenous vancomycin and voriconazole. Both blood and vitreous cultures grew Streptococcus viridans. He was diagnosed with left eye endogenous endophthalmitis and started on ceftriaxone according to bacterial sensitivities for a planned 42-day intravenous antibiotic course. He underwent further evaluation with transthoracic echocardiogram to assess for the primary source of infection which demonstrated an ejection fraction of 60%, grade 1 diastolic dysfunction and findings suggestive of aortic valve regurgitation without evidence of vegetation. Five days after initiation of antibiotics, a transesophageal echocardiogram revealed severe aortic regurgitation with severe bioprosthetic aortic valve abscess with dehiscence along the aorto-mitral curtain (Videos -). The patient’s hospital stay was complicated with worsening thrombocytopenia from 27,000 to 12,000 not responsive to multiple platelet transfusions raising concern for superimposed drug-induced thrombocytopenia. The patient’s antibiotic regimen was changed from ceftriaxone to vancomycin with no improvement in platelet count. A bone marrow biopsy was performed which revealed worsening MDS. On his fourth day of hospitalization, he developed acute hypoxic respiratory failure secondary to new onset acute diastolic congestive heart failure requiring transfer to the intensive care unit. A pro-BNP was obtained and elevated at 30,000 pg/dL. He was evaluated by cardiothoracic surgery for aortic valve replacement and deemed a poor surgical candidate secondary to critically ill condition, thrombocytopenia and advanced dementia. The patient and his wife ultimately elected to pursue hospice care.


History and physical exam
A 28-year-old male presented to the general emergency department with a fever (maximum temperature of 38.8 °C) that had started two months ago. The fever was episodic, with each episode usually lasting four days and recurring every three weeks. These episodes were always accompanied by odynophagia that subsided when the fever disappeared, and occasionally by painful oral aphthous ulcers that tended to last longer than the febrile episode. He had been seen by different physicians during each of the episodes, and these consultations had invariably led to a diagnosis and treatment of upper respiratory airway infection. The patient had a previous history of multiple episodes of pharyngitis (usually treated with antibiotics) during his childhood, adolescence, and early adult life, which had ceased at the age of 24 after he had undergone elective tonsillectomy. He denied any history of recent travels, contact with animals, or unprotected sex. The physical findings upon admission were as follows: low-grade fever (38.5 °C), tachycardia (130 beats per minute), hyperemia of the oropharynx, and unilateral enlarged cervical lymph nodes.
The patient was initially diagnosed with a respiratory infection, started on empirical treatment with intravenous ceftriaxone, and was admitted to the Internal Medicine ward for investigation of a comorbid condition predisposing to recurrent upper airway infections or an alternate diagnosis. The patient completed a seven-day course of ceftriaxone and the fever was only present during the first four days. He was discharged and referred for outpatient follow-up.
Three weeks after the discharge, the patient had another episode of fever, odynophagia, and oral ulcers that remitted spontaneously after four days.
Investigations
Laboratory work at the time of admission showed elevation of inflammatory markers [leukocytosis of 17 x 109 cells/L with 81.2% of neutrophils and C-reactive protein (CRP) of 9.28 mg/dL (reference range: <0.5 mg/dL)]; the chest radiograph was normal.
Infection studies were all negative throughout the hospital stay, namely blood and sputum cultures, acid-fast bacillus testing, rapid plasma reagin (RPR), and serology for Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus (HIV), hepatitis B and C virus, Coxiella burnetti, Rickettsia connori, and antigens for Legionella, Streptococcus pneumoniae (S.
pneumoniae), and influenza A and B.
The peripheral blood smear showed a moderate anisocytosis and left skewing of granulocyte; the serum protein electrophoresis revealed a slightly reduced albumin concentration (3.0 g/dL) consistent with an inflammatory state, and we observed an elevation of immunoglobulin A and D [574 mg/dL (reference range: 70-400 mg/dL) and 284 kUI/L (reference range: <100 kUI/L), respectively]. Complement proteins were normal. Antinuclear antibodies were positive (titer 1:320; fine granular pattern; negative mitotic cells and nucleoli), but anti-double-stranded DNA (anti-dsDNA), anti-SSA, and anti-SSB were all negative.
Imaging studies of the thorax (Figure ) and abdomen (Figure ) were normal, and a cervical ultrasound showed multiple bilateral lymph node conglomerates, with the larger one measuring 30 x 10 mm (Figure ). Although initially considered reactive to the inflammatory process, a second ultrasound was performed after discharge when the patient was asymptomatic and, since the largest conglomerate was still present, it was aspirated using a fine needle. The cytology did not show any signs of a lymphoid neoplasm.
The inflammatory markers subsided before discharge and were completely negative during the asymptomatic period.
Differential diagnosis
In a patient presenting with recurrent fever, the differential diagnosis must encompass a vast number of etiologies, including infection, autoimmunity/autoinflammation, and neoplasia.
The presence of fever and pharyngitis and the disappearance of symptoms after the initiation of antibiotics raised the suspicion of recurrent infection of the pharynx as the etiology for this clinical picture. The elevation of inflammatory markers only during the episodes was also suggestive of an infection. However, the fixed frequency of the episodes (every three weeks), the long duration of these recurrent episodes (since childhood), and the absence of other signs of immunodeficiency (no recurrent infections in other locations, absence of complications like abscesses, normal spleen on abdominal imaging, negative serology for HIV, and no reduction in immunoglobulins levels) reduced the likelihood of an infection causing this presentation. It seems far more likely that the clinical improvement with antibiotics resulted from a self-limiting process, as was observed when the subsequent episode was not treated with medications.
Hematologic malignancies, particularly the ones derived from the lymphoid lineage, should always be considered in a patient presenting with recurrent fever and lymph node enlargement. In our patient, there were accompanying symptoms (odynophagia and aphthous ulcers) besides the cervical adenopathy, which suggested a different etiology. Also, the fact that these episodes were of several years' duration and the absence of constitutional symptoms like weight loss, night sweats, or worsening fatigue made this diagnosis less likely. Nonetheless, the patient was submitted to a fine needle aspiration of the adenopathy, which showed no signs of malignancy.
The long history of febrile episodes, associated with a periodic recurrence every three weeks, strongly suggested an autoinflammatory syndrome, especially because recurrent fever is the hallmark of autoinflammation. Although frequently diagnosed during childhood, some patients only start to show symptoms later in life or when they reach adulthood with no diagnosis despite being symptomatic. Febrile episodes in familial Mediterranean fever and tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are usually accompanied by abdominal pain, arthralgia, conjunctivitis, myalgia, or rash, and cryopyrin-associated periodic syndromes (CAPS) episodes that are usually present since birth (generally associated with rashes and sometimes triggered by cold exposure). Our patient did not present with any of these characteristics and so we ruled these diagnoses out. The presence of cervical adenopathy and elevation in immunoglobulin A and D was compatible with hyperimmunoglobulin D syndrome but, similar to the previously described syndromes, hyperimmunoglobulin D syndrome is frequently associated with pain episodes, diarrhea, vomiting, lymphadenopathy outside the cervical area, and arthralgia, which the patient did not have. Additionally, none of these autoinflammatory syndromes are truly periodic, with inter-attack periods varying in the same patient. Our patient presented with a complaint of true periodic fever (three weeks' intervals between episodes), which is only suggestive of PFAPA and cyclic neutropenia (which is not an autoinflammatory syndrome and is characterized by neutropenia during febrile episodes, a feature not present in our patient). The presence of periodic fever accompanied by aphthous stomatitis, pharyngitis, and adenitis was strongly suggestive of PFAPA syndrome. The resolution of symptoms following tonsillectomy was also characteristic of this entity and, although infrequent, there are several case reports of recurrence after remission with tonsillectomy. To confirm the diagnosis of PFAPA, we administered 60 mg of prednisolone orally at the onset of the episodes, which resulted in complete resolution of symptoms in hours with no recurrence of fever for another three weeks. This finding is highly specific to PFAPA among patients presenting with features of an autoinflammatory syndrome and hence the diagnosis was confirmed.
Treatment and outcome
Treatment options were discussed with our patient and we agreed upon episodic treatment with prednisolone 60 mg.
One year after the diagnosis, the patient continues to have episodic attacks at three-week intervals, which he has been controlling with single-dose prednisolone. No other clinically significant symptoms were noted throughout the follow-up period.


A 70-year-old male was diagnosed with rectal carcinoma by biopsy whereas a solitary and solid peripheral pulmonary nodule with well-defined edges measuring 13 × 13 × 15 mm in the right lower robe was incidentally observed on abdominal CT scan (Fig. A, arrowhead). No clinical symptoms (e.g., coughing, sputum, hemoptysis and fever) were revealed. Due to the suspicious of metastasis, contrast-enhanced CT scan was performed after radical resection of rectal cancer, which showed mild centripetal enhancement of the nodular (Fig. B-C, arrowheads). However, the diagnosis of metastatic tumor could not be completely ruled out. 18F-FDG PET/CT was performed for further evaluation. The maximum intensity projection PET image revealed no abnormalities in the whole body (Fig. D). Transverse chest CT, corresponding PET and fusion PET/CT (Fig. E-G, red arrowheads) images showed a solitary pulmonary nodular (SPN) without accumulation of 18F-FDG (maximum standard uptake value, SUVmax 0.6) in the right low lobe, probably a benign tumor. However, a thoracoscopic wedge resection of the right lower lobe was performed 2 months after radical resection of rectal cancer owing to the suspicion of lung metastasis, albeit the possibility was very low.
Pathological examination (Fig. A) revealed a well-circumscribed nodular with adjacent uninvolved pulmonary parenchyma. Spindle-shaped cells with poorly defined cell borders arranged in whorls (Fig. B). The tumor cells were immunohistochemically positive for EMA and vimentin, and negative for TTF1 (Fig. C-E). Ki-67 index was less than 5% (Fig. F). These findings are supporting the diagnosis of pulmonary meningioma (World Health Organization grade I). The final diagnosis of PPM was based on PET/CT images that showed no involvement of central nervous system.


The patient reported in this case is a 69-year-old Saudi man, status post excision of right renal cell carcinoma 20 years ago, presented to King Fahd University Hospital on March 17, 2016, complaining of urinary incontinence for one month. On examination, the patient was conscious, alert with no systemic or neurological deficits. Brain magnetic resonance imaging (MRI) and computed tomography (CT) scan with and without contrast showed solitary pineal region mass lesion measuring 1.6x1.3x1.6 cm, occupying the posterior part of the third ventricle and causing obstructive hydrocephalus. The mass was hyperdense on plain CT scan (Figure ) and hyperintense with contrast on MRI (Figure ). Tumor markers for primary pineal tumors were negative. CT scan of chest and abdomen were normal.
The patient was treated with endoscopic third ventriculostomy (ETV) and biopsy of the pineal mass. Hydrocephalus resolved; however, the histological diagnosis of the biopsy was inconclusive and consisted of fibrous tissue. The patient was then discharged in a stable condition and was scheduled for a follow-up appointment in the neurosurgical outpatient clinic. Readmission was planned for further management and repeated biopsy of the mass lesion. The patient did not show up in the outpatient clinic.
One and a half years later on July 25, 2017, he presented to the ER complaining of confusion, forgetfulness, postural imbalance, difficulty in walking, and decreased vision for two weeks. On examination, he was lethargic and confused with papilledema. Brain MRI with contrast (Figure ) showed the tumor was markedly enlarged in the pineal region, causing obstructive hydrocephalus, heterogeneous in appearance, and foci of hemorrhage. The pineal mass was extending down with mid-brain compression and bilateral thalamic compression.
The patient was re-operated with an ETV and tumor biopsy. External ventricular drain (EVD) was left in the ventricle. The histological studies with hematoxylin and eosin (H&E) stain showed sheets of cells with pleomorphism that were consistent with a tumor (Figure ).
Immunoassay studies with the vimentin, CD10, and PAX-8 stain were also done because of the patient’s past history of renal tumor excision. The findings were positive and compatible with metastasis from renal cell carcinoma (Figure ).
Post-operatively, the patient remained confused with the Glasgow coma scale of 13. The patient developed Pseudomonas in the cerebrospinal fluid (CSF), for which he received the appropriate antibiotics and it resolved within a few weeks. He had several trials of weaning from EVD but failed, so a ventriculoperitoneal (VP) shunt was inserted. The patient did not improve and on October 20, 2017, he suffered cardiorespiratory arrest and passed away.


A 57-year-old Caucasian man with a history of coronary artery disease (CAD) with multi-vessel PCI to the ostial and distal left main coronary artery (LMCA) bifurcation three months ago, chronic obstructive pulmonary disease (COPD), hyperlipidemia, severe PAD with right above the knee amputation, and stage IIIa lung cancer status - post-pneumonectomy and chemotherapy was referred to our institution from a nearby hospital for coronary revascularization. Initially, he presented to their facility with loss of consciousness and respiratory distress. Initial vitals were significant for BP 76/42 mm Hg, HR of 96 bpm, and significant hypoxia requiring mechanical ventilation. Electrocardiogram (EKG) revealed normal sinus rhythm with anterior septal q-waves and diffuse ST-T abnormalities (Figure ). Their investigations revealed non-ST segment elevation myocardial infarction (NSTEMI) with a troponin of 12.4 ng/ml. He was initiated on norepinephrine 20 mcg/min and dobutamine 7.5 mcg/kg/min to maintain a mean arterial pressure of 65 mm Hg. Coronary angiography revealed a calcified 95% stenosis of the distal LMCA that extended into the left anterior descending (LAD) and left circumflex (LCx) coronary arteries. The right coronary artery (RCA) showed 50% non-obstructive disease (images of the angiogram from the outlying facility were not provided to us). Transthoracic echocardiogram (TTE) revealed a left ventricular ejection fraction (LVEF) of 38%, with hypokinesis of the apex, distal anterior, and anterolateral walls. An intra-aortic balloon pump (IABP; Maquet, Fairfield, NJ) was inserted and the patient was transferred to our institution for coronary revascularization. Three months prior to presenting to the outside facility, he was hospitalized for chest pain and shortness of breath. He underwent PCI with the placement of one drug-eluting stent (DES) in the ostial LMCA and two DES in the distal LMCA with coverage of the ostial and proximal LAD (details of the intervention from the outlying facility were not provided to us).
Upon arrival to our institution with an IABP (left femoral access) in place, he was also on mechanical ventilation. Vitals were significant for a blood pressure of 84/60 mmHg while on norepinephrine 30 mcg/min and dobutamine 7.5 mcg/kg/min with a heart rate of 90/min. Pertinent physical examination findings included bibasilar crackles, feeble bilateral femoral pulses, and a right above-the-knee amputation. The patient was sedated, yet his cognitive and neurological conditions were deemed to be intact as evaluated by the medical ICU team. A heart team approach was undertaken, and the cardiothoracic surgical team deemed that he was not a candidate for coronary artery bypass graft surgery, given his significant comorbidities, precarious hemodynamic status, and multiple prohibitive risk factors. Laboratory results revealed potassium of 3.3 mEq/L, WBC of 13.2/mm3, Hb 9.7 of g/dl, troponin of 1.34 ng/ml, and BNP of 900 pg/ml. Chest X-ray demonstrated prominent right lung interstitial markings. EKG remained unchanged from the initial EKG.
The decision was made to proceed with LV Impella-assisted high-risk PCI (Abiomed, Danvers, MA). The indications, benefits, risks, and rationale were discussed with the patient's family, and they agreed to proceed with this high-risk procedure. The patient was then taken to the cardiac catheterization lab. Two perclose sutures (Abbott Cardiovascular, Santa Clara, CA) were deployed for left femoral pre-closure in preparation for the insertion of the Impella CP 4.0 device. The IABP was then exchanged for the Impella, which was successfully placed in the LV via left femoral arterial access and set to P7.
The right radial artery was accessed, and a 7-French EBU 3.5 guide catheter was used to engage the LMCA. A coronary angiogram revealed a 95% stenosis of the distal LMCA, extending into the LAD and LCx (Videos and 2). Two separate interventional wires were introduced in the LAD and the LCx. Kissing percutaneous transluminal coronary angioplasty (PTCA) of the distal LMCA bifurcation towards the LAD and LCx was performed using 3.0 × 12 mm2 and 2.5 × 12 mm2 NC balloons, respectively. A 4.0 × 15 mm2 NC balloon was used to perform balloon angioplasty of the LAD lesion. High-risk coronary atherectomy was avoided given the history of recent PCI with stenting three months ago.
Current results with PTCA were suboptimal (Video ), as there was persistent stent recoil and suspected stent under-expansion. S-IVL was therefore considered as an off-label option to optimize stent expansion and luminal gain. Informed consent had been obtained for S-IVL from the patients’ family. A 3.5 × 40 mm2 shockwave balloon was advanced into the distal LMCA and the LAD and a total of 80 pulses were administered with the balloon inflated to between 3 and 6 atmospheres (Video ) with lesion modification with yielding of the extraluminal calcification. Following S-IVL angiogram was performed (Video ), and then we proceeded with PTCA of the distal LMCA to ostial LCx which was also performed with a 3.0 × 15 mm2 angiosculpt balloon (Koninklijke Phillips, Nevada).
Intravascular ultrasound (IVUS) initially revealed an under-expanded stent in the distal LMCA (Figure ). An IVUS guided 4.0 × 23 mm2 DES was deployed in the LMCA into the LAD, overlapping with the prior stents. Subsequently, it was post-dilated initially with a 4.5 × 20 mm2 NC balloon followed by a 5.0 × 20 mm2 NC balloon. Finally, there was TIMI-III flow in the LAD as well as LCx with less than 40% residual stenosis in the ostial LAD and the ostial LCx (Videos and 7). The impella CP device was then removed, and both perclose sutures were deployed and tightened, with excellent vascular hemostasis. The patient tolerated the procedure well without complications or major adverse cardiovascular events (MACE). Activated clotting time levels were maintained therapeutically with the utilization of intravenous heparin. He was extubated on the following day. His Hb level was stable and his Cr level returned to baseline at 1.4 mg/dL. He was weaned off pressors successfully and he was started on guideline-directed medical therapy with aspirin and prasugrel (10 mg/day) being the dual antiplatelet agents. He remained stable from a neurological standpoint. He was discharged to an outpatient rehabilitation facility after a total of five days of hospitalization. At a two-week follow-up, the patient was doing well and had returned to baseline independence. A TTE performed at three-month follow-up demonstrated an improved LVEF of 55%. He continues to do well on follow-up in our outpatient clinic. He was advised to remain on long-term dual antiplatelet therapy (DAPT) and high-dose high-intensity statin therapy.