A 27-year-old female with chronic neck pain and cervicogenic headache since 2007 presented to our clinic with chief complaint of worsening neck pain. Initial onset of symptoms was noted eight years ago with status after a motor vehicle collision in which she sustained a whiplash neck injury. She reported experiencing excruciating periorbital and neck pain with unilateral right arm weakness at the time. Her symptoms deteriorated to the point where she underwent a C4–C6 laminectomy in 2009. She regained strength in her right upper extremity postoperatively. However, she continued to report neck stiffness. In 2013, she sustained a concussion after a second motor vehicle collision, further exacerbating her neck pain and headaches. She subsequently underwent several procedures including third occipital nerve blocks, cervical epidural steroid injections, and multilevel cervical facet joint injections (C2–C5), but with little to no pain relief. On presentation to our Spine Pain Center, her pain was 9/10 by visual analog scale and described as cramping, burning, and aching in quality. Pain was localized suboccipitally with radiation to her jaw and posterior aspect of her neck, worse on the right than left, and aggravated by postural changes and neck rotation.
Neck cavitation, sleep, and NSAIDs provided mild pain relief; otherwise, the pain was unrelenting. Associated symptoms included clicking of her temporomandibular joint, neck stiffness, teeth clenching, bilateral headaches with periorbital pain, numbness and tingling, anxiety, and fatigue. Pertinent negatives included no chest pain, fever, odynophagia, photophobia, syncope, dysphagia, diplopia, and blurry vision, weakness, or weight loss. She worked on a desk computer as a home sales agent. Four weeks prior to clinic visit, she noted severe functional limitations in driving, talking, eating, and work-related tasks. She was on a regimen of anxiolytics, tricyclic antidepressants, topical analgesics, and opioids but with suboptimal pain control. Conservative treatments including physical therapy, relaxation, and biofeedback failed to provide pain relief.
On physical examination, she was noted to have tenderness to palpation of the proximal aspect of the right sternocleidomastoid muscle and suboccipital region and mild scapular winging (left > right) and pain with active neck rotation. Cervical flexion rotation test was positive and maximal side bending of the ipsilateral cervical spine with contralateral rotation in a chin-tuck position reproduced the pain at the AA joint. Neurological testing for cranial nerves, deep tendon, and Hoffman's reflexes was normal. Modified Sharp Purser test was negative for atlantoaxial instability. Spurling's and lateral shear testing were also normal except for bilateral paresthesias in her fingers.
Her baseline Neck Disability Index Total Score was 25/50 suggesting moderate to severe disability. Magnetic Resonance Imaging of the cervical spine was positive for degenerative changes in the cervical spine, multilevel disc desiccation at C2–C5 without disc height loss, C2-C3 and C3-C4 disc bulge with uncovertebral joint hypertrophy and bilateral neural foraminal narrowing, and spinal canal stenosis (). Differential diagnosis considered at this time included cervical facetogenic pain, cervical radiculopathy, and degenerative zygapophyseal joint arthropathy. Recent diagnostic blocks up the cervical spine at C2-3 and C3–5 2 did not yield any pain relief. Combined with physical exam and clinical history, her pain was localized to the C1-2 joint.
She subsequently underwent bilateral C1-C2 intra-articular joint diagnostic “blocks” with 1% lidocaine and noted 75–80% relief in pain score. A second follow-up confirmatory block was performed at a different time, again with 75% pain relief from baseline. She was then scheduled for bilateral thermal radiofrequency ablation of the C1-C2 joint since intra-articular anesthetic blockade of the joint was both diagnostic and therapeutic. The rationale for the RFA was to obtain longer-lasting pain relief with intra-articular joint lesioning. After informed consent, the procedure was performed in aseptic fashion under fluoroscopic guidance, with patient in prone position. The beam of the C-arm was oriented to expose the atlantooccipital and axial joints. Asking the patient to open her mouth allowed an open-mouth view for clear visualization of the joints.
A 22-G RFN needle with 5 mm active tip was inserted in the neck targeting the posterior aspect of the lateral third of the inferior articular process of the atlas. This allowed for access to the joint and avoids contact with the C2 spinal nerve and ganglion. Contacting bone allowed safe depth of needle insertion to be established. Lateral and anterior views were obtained to confirm placement. The needle was then slightly withdrawn and reinserted carefully into the joint (). To confirm intra-articular placement, a joint arthrogram using a small amount of contrast medium (0.5 cc) was obtained. There was no spread into the epidural space, laterally or posteriorly. Aspiration did not reveal blood or CSF fluid. After sensory and motor testing at 0.6 volts and confirming absence of motor fasciculations or radicular symptoms with stimulation, lesioning was performed at temperature of 90°C with total lesion time of 150 s (25 s ramp time and 125 s burn time).
After lesioning, a 1 mL mixture of 0.5% bupivacaine and 8 mg/mL of triamcinolone was injected in the lesioned area with the goal to decrease postprocedure pain. Immediately after the procedure, the patient reported headaches but denied blurry vision, dysgeusia, or other associated symptoms. Her symptoms improved with fluid hydration. She was monitored for an hour after procedure and discharged without any signs of pain on lateral neck rotation. Follow-up occurred at 2, 4, 8, and 12 weeks to compare baseline and postprocedure scores in the following functional measures: Neck Disability Index (NDI), Visual Analog Scale for pain (VAS), and the RAND 36-Item Short Form Health Survey (SF-36) for health related quality of life. The minimal clinically detectable change for NDI is reported as 5 points or 10% points []. Since there are no established clinically meaningful changes in SF-36, an arbitrary cut-off of 50% improvement from baseline scores was used as indicator of treatment success. The patient was also referred to physical therapy and neuropsychology for exercise and behavioral pain management interventions.
Using the visual analog score, the patient reported a pain score of 9 at baseline. The pain score peaked 4 weeks after the procedure. By 8 and 12 weeks after the procedure, she rated her pain score lower than at baseline and with the most optimal score observed at week 12 () with score of 7.
Baseline neck disability index was reported to be 25 at baseline. Similarly, neck disability index measures peaked at 4 weeks. However, NDI continued to decrease, with a clinically meaningful difference detected at week 12 ().
The patient noted improvement in all areas except for role limitation due to physical health and emotional problems ().


A 15-year-old male with history of chronic, progressive and bilateral visual loss accompanied by nyctalopia, first noticed at age 6 presented for ophthalmologic evaluation. He had been previously diagnosed with retinal dystrophy. Upon examination, his best corrected visual acuity (BCVA) was counting fingers at 1 m in both eyes. Intraocular pressure was 11 mmHg in the right eye (OD) and 13 mmHg in the left eye (OS). Ocular motility was normal. Anterior segment examination was unremarkable and the lens was transparent. Fundus examination revealed fine pigmented dust in the vitreous gel, hyper and hypopigmented retinal pigment epithelium (RPE) changes forming ‘bone spicules’ scattered in the posterior pole up to the equator and pigment clumping in both macular zones. Arteries and veins were slightly narrow or attenuated (Fig. ).
Electroretinogram (ERG) showed diminished b-wave amplitudes in both photopic and scotopic phases with a marked reduction in the amplitude of all waves, implicit time delay of the flicker response and flattening of oscillatory potentials (Fig. ). The electrooculogram showed an abnormal RPE response. Automated visual fields registered a generalised decrease in sensitivity and profound central scotomas. Fluorescein angiography evidenced central hypofluorescence due to contrast blockage in the areas with pigment accumulation and patchy hyperfluorescence due to window defects in RPE atrophy areas (Fig. ).
The patient denied using any medication and had no relevant medical history for infectious or systemic diseases. Fundus changes and abnormal scotopic and photopic ERG responses made the diagnosis particularly difficult. The absence of nystagmus, strabismus or photophobia along with an older age of presentation and slower rate of progression made a diagnosis of Leber’s congenital amaurosis less likely, progressive CRD can have a very similar clinical presentation with ERG photopic responses initially more affected than scotopic traces, a difference that becomes more subtle as the disease progresses until it becomes negligible.
Severe affection of both rods and cones in ERG made a diagnostic distinction difficult. The presence of nyctalopia, no history of photophobia and characteristic appearance of bone spicules oriented the diagnosis towards a case of inverse RP, although CRD with macular hyperpigmentation could not be discarded completely.
The patient started follow up in the retina clinic and was instructed on the use of visual aids and genetic counseling was provided. Regular consultations were scheduled every 6 months without worsening of symptoms or BCVA; all examinations were reported as stable.
On a follow-up visit, 3 years after initial consultation, examination of the OD revealed a white asymptomatic eye with fine translucent ‘stellate’ keratic precipitates scattered over the entire endothelium and mild cellular reaction in the anterior chamber with no synechiae, iris nodules or heterochromia but subtle stromal atrophy of the iris crypts in comparison with the OS (Fig. ). BCVA was unchanged and IOP was 16 mmHg OD and 12 mmHg OS. Dilated fundus exam did not show any sign of vasculitis, retinitis or choroiditis. The OS showed no signs of inflammation thus matching the criteria for unilateral Fuchs’ heterochromic iridocyclitis (FHI) Visual Fields were severely affected (Fig. ) .


A 67-year-old Hispanic woman with a past medical history of hypothyroidism, hypertension, and recently diagnosed stage II pulmonary sarcoidosis (confirmed through transbronchial biopsy 2 months prior) presented with a 1-month history of progressive impairment of consciousness that was associated with decreased strength and progressed to prostration and loss of sphincter control. At initial evaluation in the emergency department, she was found to be haemodynamically stable, febrile (39°C), somnolent, with non-comprehensible speech, and with no signs of neurological focalization. The rest of her physical examination was unremarkable. Cerebrospinal fluid (CSF) showed protein levels of 0.66 g/L (normal value < 0.5 g/L), 70 cells (mostly mononuclear), glucose levels of 45 mg/dL (normal value > 60 mg/dL), and adenosine deaminase (ADA) levels of 3.3 U/L (normal value < 7 U/L). Gram stain was negative for bacteria and the bacterial and fungus cultures were negative. Computed tomography (CT) of the brain revealed hydrocephalus without structural lesions. The study was complemented with magnetic resonance imaging (MRI) that revealed non-specific periventricular changes and diffuse meningeal enhancement, quadriventricular hydrocephalus, and diffuse leucoencephalopathy. The image was compatible with NPH (Figs. , ).
Complementary studies, including HIV and venereal disease research laboratory (VDRL) tests, were negative. Electroencephalogram (EEG) showed non-specific changes suggesting diffuse encephalopathy due to metabolic abnormalities, and the patient had normal thyroid panel, complement and B12 levels, with negative connective tissue serologies. Chest X-ray showed grade II pulmonary sarcoidosis (Fig. ).
After a multidisciplinary evaluation, a ventriculoperitoneal (VP) shunt was installed without complications, and the patient was started on steroid therapy with prednisone of 0.5 mg per kg, with rapid improvement in her symptoms. After 2 years of follow-up, patient recovery was successful, without fever or evidence of infection. Current medication includes prednisone of 5 mg per day and azathioprine of 100 mg per day.


An 86-year-old Caucasian gentleman with a past medical history of dilated cardiomyopathy, aortic insufficiency, and left knee osteoarthritis status after total knee arthroplasty complicated by prosthetic joint infection treated with parenteral vancomycin as well as placement of a vancomycin impregnated joint spacer presented with a chief complaint of diffuse nonpruritic bullous rash involving skin and oral mucosa. The rash appeared nine days after vancomycin spacer placement and five days after starting intravenous vancomycin, first appearing as yellow peri-incisional, but then progressing to the more classical diffuse polymorphic, erythematous vesiculobullous rash two days later. The patient denied any other systemic symptoms. Vitals signs were stable on presentation. On examination, the patient was found to have multiple eruptions including 1–4 cm tense bulla (blisters) filled with serous and hemorrhagic fluid, superficial erythematous erosions, 0.2–2 cm targetoid macules and papules with perilesional vesicles, and some coalescing in a herpetiform distribution. In addition he had a 2 cm oral mucosal ulcer. Lesions were located along the extensor surfaces of his arms and legs, as well as his back and palms of hands (Figures , , , and ). He had periorbital erythema as well as conjunctival injection of the left eye. Laboratory results revealed a white blood cell count of 12,000/microliter, creatinine of 1.5 mg/dL (near baseline), and a vancomycin trough level within normal limits.
Other results were unremarkable and included negative anti-nuclear antibodies and anti-double-stranded DNA antibodies. Dermatology was consulted and biopsy of a lesion over the chest showed focal subepidermal blistering with numerous neutrophils and some eosinophils as well as neutrophil collections within the dermal papillae ().
The differential diagnosis included linear IgA bullous dermatosis, bullous systemic lupus erythematosus, or dermatitis herpetiformis. Direct immunofluorescence microscopic examination of perilesional tissue showed linear deposits of IgA at the basement membrane zone (). Based on the history and correlation of events to the initiation of vancomycin, physical examination, and light and immunofluorescence microscopic examination, the diagnosis of linear IgA bullous dermatosis secondary to vancomycin was made. Prior to admission, Infectious disease was consulted and empirically switched his vancomycin to daptomycin based on organism susceptibilities and a timeline suggesting a drug reaction. Orthopedic Surgery was consulted and recommended keeping the antibiotic spacer to optimize future joint mobility. Ophthalmology was asked to weigh in on the patient's ocular findings and recommended conservative compress therapy given lack of concerning eye involvement. Colchicine therapy was utilized instead of dapsone as the patient was anemic.
The patient was discharged on colchicine 0.6 mg twice daily for fourteen days to a subacute rehabilitation facility. Two weeks following discharge, the patient was seen in the Dermatology clinic. He had complete resolution of his linear IgA bullous dermatosis at that time.


A 16-year old girl from a remote village in Sri Lanka is described.
She was referred from the Paediatric Cardiology Unit to the University Unit of Lady Ridgeway Hospital for Children (LRH) for further evaluation of jaundice. She was the only child born to non consanguineous healthy parents and was well till 14 years of age, when she sought medical advice from the local hospital for exertional dyspnoea. At presentation to the local hospital she was detected to have central cyanosis and clubbing but otherwise clinically normal. Her haemoglobin was 18 g/dl and the packed cell volume was 54%. Her platelet count was 73 × 109/l and SpO2 82%. The echocardiogramme revealed a pulmonary arteriovenous malformation (AVM). The ultra sound scan (USS) of the abdomen showed a normal liver and no splenomegaly.
She was referred to the cardiology unit of LRH for further evaluation. At LRH contrast echocardiogramme was performed which showed evidence of pulmonary arteriovenous fistula. The finding at cardiac catheterization was compatible with bilateral diffuse pulmonary AVMs. Due to the diffuse nature of the pulmonary AVM she was managed conservatively.
Two years later, at the age of 16 years she developed spontaneous recurrent epistaxis. She was also noted to have jaundice. Examination revealed deep jaundice, plethora, central cyanosis and clubbing. There were no other peripheral stigmata of chronic liver disease. She had coarse facial appearance. There was no cutaneous telangiectasia. Abdominal examination revealed a firm hepatomegaly of two cm, but no splenomegaly or ascites. Rest of the abdominal examination was normal. Cardiovascular system examination revealed a systolic murmur best heard over the pulmonary area. Blood pressure was normal. Rest of the examination including respiratory system and central nervous systems were clinically normal. Ultra sound scan examination of abdomen at sixteen years revealed heterogeneous linear (Liver) echo texture, increased peri portal echogenicity with splenomegaly and varices compatible with chronic liver disease and early portal hypertension. A focal lesion was seen in segment Vl of the liver. Magnetic resonance imaging (MRI) revealed a dilated splenic vein draining separately through the diaphragmatic hiatus between the inferior vena cava and the aorta possibly into the superior vena cava through the azygous vein. She continued to be managed conservatively.
At nineteen years of age she remained jaundiced. There were telangiectases over the oral mucosa and conjunctiva. Eye referral revealed telangiectatic vessels in the right optic disc. Hepatomegaly was unchanged.
She had attained menarche at 16 year of age but had amenorrhea for several years, and now has her menstrual periods infrequently. Although she has a masculine habitus her secondary sexual characteristics were feminine. There was no clitoromegaly. Endocrinological evaluation was done to investigate for her masculine built and irregular menstruation. There was no family history suggestive of polycystic ovarian syndrome. At 19 years of age, she had an elevated serum testosterone level of 15.97 nmol/L (normal adult female range 0.52–2.43), but serum DHEAS (dehydroepiandrosterone sulfate) level were low (1.0 μmol/L, normal range 1.7–13.4). Serum 17 OHP, FSH, LH and serum estradiol levels were normal. She also had marginally low free T4, with normal TSH. USS abdomen repeated at 19 years of age was compatible with chronic liver disease with early portal hypertension. She had normal uterus and normal ovaries with no evidence of poly cystic ovaries.
MRI abdomen (Fig. ) showed changes of chronic parenchymal liver disease with multiple nodules in both lobes of the liver. The nodules were hyperplastic with low T2 signal intensity. A 47 × 45 mm size nodule was seen in the right lobe of the liver. A liver biopsy was not done due to the risk of bleeding in the presence of multiple AVMs. MRI brain done to identify any cerebral vascular malformation was normal.
A diagnosis of hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu syndrome) was made based on the presence of three out of four Curacao criteria []. The three criteria she fulfilled were recurrent spontaneous epistaxis, visceral (pulmonary) arterio venous malformation and telangiectasia in the oral mucosa []. The patient along with the family was counselled regarding the diagnosis and the prognosis.


A 65-year-old woman was referred to the Fajr Health Center. The chief complaint was a lip lesion that began 2 months prior as a slowly enlarging nodule. Patient reported that the lesion began as a small soft mass, which ulcerated later. Clinical examination showed a necrotic ulcer of the left lower lip vermillion. The lip was erythematous and edematous from midline to the left commissure mediolaterally (Fig. ). With suspicion of basal cell carcinoma and squamous cell carcinoma, skin scraping, culture, and PCR were accomplished. Touch impression smears and culture were positive and the parasite was characterized by PCR as L. tropica.


A 75-year-old woman came to the Dermatology Clinic of Saadi Hospital complaining about a lesion on his right lower lip. She reported that the lesion appeared about 3 months before. The clinical examination revealed a round nodular lesion in the right lower lip which was slightly shiny and red colored. Palpation of the lesion revealed a firm consistency (Fig. ). The differential diagnosis of a nodular lesion of the lip included: neoplasia (basal cell carcinoma), and tumors from mesenchymal origin (fibroma, lipoma, and neuroma). Giemsa stain and culture were negative. PCR depicted the parasite as L. tropica.


A 40-year-old, generally healthy woman complained of persistent lip enlargement and sore that appeared after several days of fever and had been present for 2 months. At clinical examination, the left side of the upper lip appeared erythematous and distended, with overlying yellow crusting lesion extending to the wet line. No lymphadenopathy was associated (Fig. ). Giemsa-stained smears and culture were positive (Fig. ). PCR identified the parasite as L. major.


A 28-year-old man expressed displeasure about a swelling localized to the left side of the upper lip. The patient also stated that the swelling had appeared about 2 months before and that it rapidly enlarged up to the current morphology and size. Clinical examination showed the presence of a swelling which involved the left side of the upper lip. The surface of the swelling was slightly erythematous and irregular, because of the presence of lesion and scaling (Fig. ). Consistency was parenchymatous-hard. With suspicion of mycotic infection, laboratory tests were carried out. Slit dermal smears and culture were positive. PCR characterized the parasite as L. tropica.


A 10-year-old girl was referred to the Dermatology Clinic of Saadi Hospital. The patient had become infected with CL on the left side of her mentum 3 months before. Three weeks prior to referral, the lesion had spread to the mucosal part of the lower lip. The patient improved diffuse severe swelling of the lower lip. On physical examination, erythema, ulceration, and scaling of the left side of the mentum were detected. There was a diffuse swelling cheilitis of the lower lip extra to ulceration and bleeding of the labial mucosa (Fig. ). Giemsa-stained smears and culture were positive. PCR identified the parasite as L. major.


An 8-year-old girl presented to the Leishmaniasis research laboratory of the Fajr Health Center with complaint of wound on her upper lip. The lesion started 3 months prior as a small nodule in the center of the upper lip which slowly enlarged over a few weeks and then ulcerated. Clinical examination showed an indurated, crusted, and scaled necrotic ulcer with swelling on the midline of the upper lip, extending to the vermilion. There was purulent discharge from the lesion (Fig. f). With suspicion of cheilitis granulomatosa, slit dermal scraping, culture and PCR were performed. Giemsa-stained smear and culture were positive. PCR portrayed the parasite as L. major.


A 4-year-old girl presented with a 2 month history of increasing swelling and painful ulcer on the right upper lip. On clinical examination, an erythematous infiltrated, crusted, scaled and fissured plaque of the upper lip leading to macrocheilitis was observed. Cervical lymph nodes were noticed to be enlarged (Fig. ). With suspicion of granulomatous macrocheilitis; slit impression smear, culture and PCR were achieved. Just PCR was positive and characterized the parasite as L. infantum.
The studied patients were examined in the Dermatology Clinic of Saadi Hospital and Fajr Health Center from January 2014 to the end of December 2015. All patients were came from endemic regions of Fars province. A structured questionnaire was used to collect clinical and therapeutic data from all patients.
The margin dermal scrapings were prepared with a no. 15 disposable sterile surgical blade (Unicut, Chicago, USA) to make a slit in the border of the lesion. Dermal tissues were stained with Giemsa (Merck, Darmstadt, Germany), and exhibited amastigotes by light microscope. Employing Giemsa, amastigotes are seen within the cytoplasm of macrophages as pale blue oval bodies with a dark blue nucleus and a small rod-shaped kinetoplast with a specified mitochondrial frame that contains extra-nuclear DNA.
In addition, an aspirate from the active indurated margins of the same lesions was transferred to two tubes of the modified NNN culture medium. Modified NNN medium consists of two phases, horse blood agar base and an overlay Locke’s solution. The specimens were inoculated into the liquid phase of the biphasic medium and incubated. Positive cultures were run in RPMI-1640 medium (Gibco, Frankfurt, Germany) supplemented with 10% heat inactivated FCS (Gibco, Frankfurt, Germany), 100 U/mL penicillin, and 100 μg/mL streptomycin (Gibco, Frankfurt, Germany) for mass cultivation. Promastigotes were harvested and kept at -20 °C until used.
Total genomic DNA was extracted from each clinical sample using the AccuPrep® Genomic DNA Extraction Kit (Bioneer, Daejeon, Korea), according to manufacturer’s instructions. The quantification and quality control of the DNA extraction procedures were performed using a nano spectrophotometer (NanoDrop 1000, Thermo Fisher Scientific, Waltham, Massachusetts, USA). The DNA was stored at −20 °C until being used.
The conserved area of the minicircle kDNA from the Leishmania species was amplified by Semi-Nested PCR. The primers LINR4 (forward) (5’-GGG GTT GGT GTA AAA TAG GG-3’), LIN17 (reverse) (5’-TTT GAA CGG GAT TTC TG-3’), and LIN19 (reverse) (5’-CAG AAC GCC CCT ACC CG-3’) were used for amplification []. Standard PCR was carried out with 40 cycles, each consisting of 30 s at 94 °C, 30 s at 52 °C (for LINR4 and LIN17) or 58 °C (for LINR4 and LIN19), 1 min at 72 °C, and a final extension at 72 °C for 10 min in an Eppendorf thermal cycler (Hamburg, Germany). PCR products were visualized by UV after electrophoresis on 1.5% agarose gel using TAE buffer and staining with GelRed (Biotium Inc., Hayward, CA). All primers were synthesized by Macrogen Genomics Laboratories (Macrogen, Seoul, Korea). A 650-bp fragment was amplified for L. major, whereas a 760-bp and 720-bp fragments were amplified for L. tropica and L. infantum, respectively (Fig. ).
The PCR products were purified by using QIAquick Gel Extraction Kit (QIAGEN, Hilden, Germany) and sequenced through the sequencing service of Macrogen Genomics Laboratories (Seoul, Korea). The resulting sequences were aligned and compared with those of existing sequences related to Leishmania in GenBank. A Maximum Likelihood (ML) tree was constructed using the MEGA-7 program [], and genetic distances were calculated with the Maximum Composite Likelihood method. The sequences of three patients of L. tropica showed 100% identity to the published isolate IranJWtrop (AB678350). Also, these three isolates showed 99% identity to the published isolates from UK, Egypt, and Iran (AF308689, X84845, and KM491168) (Fig. ). The sequences of three patients of L. major showed 100% identity to the published isolate IranJWmaj (AB678349), In addition, the three L. major showed 99%, 99% and 98% identity to the published isolates from UK and Iran (AF308685, KM555292, and KM555295) respectively (Fig. ). The sequence of L. infantum showed 99% identity to the published isolate IranJWinf (AB678348). Plus, this isolate showed 98% identity to the published isolate from Spain (EU437407) (Fig. ).
The patients received intramuscular injections of Meglumine antimoniate (Glucantime®; Sanofi-Aventis, Paris, France), 20 mg/kg/day over a 3-week period with good results [, ]. All lesions resolved after 3 weeks of therapy. After 1 year of follow up, the patients were completely normal and no relapses were observed.


A 27-year-old Caucasian male with a past medical history of hypertension presented to the emergency room (ER) for evaluation of a cardiac arrest. He had a one-month history of unexplained progressive fatigue and decreased oral intake. He experienced a witnessed collapse at home from a seated position, and emergency medical services (EMS) were called. No bystander cardiopulmonary resuscitation (CPR) was given prior to EMS arrival, and ECG in the field found the patient to be in acute ventricular fibrillation. He was defibrillated emergently which resulted in immediate asystole. CPR was performed, and return of spontaneous circulation (ROSC) was achieved. The rhythm strip at this time revealed significant ST segment elevations in V1–V2, AVL, and AVR; Q waves in V1–V2; as well as diffuse ST depressions in II, III, AVF, and V3–V6 (Fig. ). These findings were relayed to the coordinating ER, and a STEMI protocol to allow for urgent cardiac catherization was initiated.
On route to the hospital, the patient again developed acute asystole. CPR was initiated and was in process at arrival to the ER. On exam, the patient was pale, cold, markedly cachectic, and severely volume depleted. Central venous access could not be achieved, and peripheral venous access allowed for the infusion of medications and resuscitation fluids but not for withdrawal of blood for laboratory testing due to marked venous collapse.
Advanced cardiovascular life support (ACLS) was continued for approximately 40 min. During this time, it was noted that asystole consistently converted spontaneously to ventricular tachycardia/fibrillation, and defibrillation would consistently result in asystole. The patient received epinephrine, vasopressin, bicarbonate, and normal saline during this period. ROSC was achieved, and all vasopressin, dopamine, and norepinephrine were required to maintain a perfusing blood pressure. At this time, an initial in-hospital ECG was acquired (Fig. ).
Given the findings and presentation, the patient was then taken emergently to the cardiac catheterization lab for coronary angiography. Blood samples for laboratory testing were then drawn from femoral access catheters, and coronary angiography was performed. The coronary arteries were found to be fully patent. Echocardiography revealed normal cardiac systolic function without wall motion abnormalities or pericardial effusion.
A right femoral angiogram revealed an extremely small right common femoral artery, which was nearly completely occluded by the utilized 6-french catheter. Distal pulses were absent, and the patient’s foot was cold to touch. The catheter was removed promptly, and the patient was transferred to the coronary care unit (CCU) for initiation of therapeutic hypothermia and further care.
Upon arrival to the CCU, laboratory testing began to reveal several marked laboratory abnormalities (Table ) including profound hyperkalemia with a serum potassium of 9.8 mEq/L and disseminated intravascular coagulation (INR of >5, D-dimer >20 μg/mL, and fibrinogen <60 mg/dL). Emergent hemodialysis to correct his metabolic abnormalities was performed, and fresh frozen plasma was administered to correct his coagulopathy. After hemodialysis, his ECG normalized (Fig. ).
The remainder of his hospitalization was complicated by aspiration pneumonia, shock liver, acute kidney injury, and mild anoxic brain injury all due to prolonged resuscitation. However, he slowly recovered with supportive care. The etiology of his severe volume depletion and profound renal failure was never identified. He was transferred from the hospital to a rehabilitation facility with a need for intermittent scheduled hemodialysis and eventually discharged home.


An 83-year-old woman presented with a slow-growing, palpable, painless mass in her left shoulder. She was known for auricular fibrillation, a type of hypothyroidism. The patient had no symptom; she just noticed the apparition of this mass two years earlier. At examination, no limitation in shoulder range motion was found and a mass of about 6 cm diameter was palpable.
Conventional X-rays were normal. CT scan and magnetic resonance imaging (MRI) were performed and showed an important prescapular necrotic cystic-like mass measuring 9.5 × 6.0 cm (Figures –) with scapular encroachment (bony erosion) (). Finally, a guided biopsy under ultrasonographic control was performed. Four samples were taken in the periphery of the lesion. They showed a cystic lesion with necrotic debris in its center. At histological examination, a myxoid aspect with few cells was noticed. Some fusiform cells of little size, regular, elongated aspect nuclei were found, without hyperchromasia or mitotic activity. The myxoid matrix was abundant and loose. The lesion was not vascularized (Figures –). The diagnosis of a benign tumor of myxoma type was retained. Simple follow-up was decided due to the lack of symptoms and the age of the patient. One year later, she was still asymptomatic.


A 61-year-old man with prostate cancer, presented with worsening mental status, without evidence of trauma. On examination, the patient was oriented to only person and place, without pronator drift, and was found to have subdural collections (Fig. ). He was taken to the operating room for an evacuation where he was found to have a solid mass instead of fluid (Fig. ). Postoperatively, on the contrary, MRI revealed the subdural mass with subsequent mass effect and shift (Fig. ). Hence, the patient has expired.


A 7-year-old boy with a history of a biopsy-proven sporadic desmoid tumor within the right anterolateral thigh was referred for MRgFUS therapy. The patient’s tumor was previously resected with intra-operative radiation therapy at the time of surgery (12 Gy). Initial recurrence was identified on imaging 10 months following the surgery. After the initial recurrence, the patient completed courses of vinblastine/methotrexate (25 doses), with continued tumor growth, followed by sorafenib, which was discontinued after a short trial of therapy as the patient tolerated the medication poorly and developed a severe widespread dermatitis requiring hospitalization. The patient’s tumor continued to grow, measuring up to 21.4 × 8.3 × 7.1 cm, approximately 770 cm3, prior to treatment.
MRgFUS of the tumor within the thigh was performed under general anesthesia. The patient was positioned in the right lateral decubitus position on a 3.0T system (Discovery MR750w, GE Medical Systems, Milwaukee, WI). MRgFUS was performed with the ExAblate 2000 MRgFUS system with an in-table 1-MHz transducer (InSightec, Tirat-Carmel, Israel). The procedure was performed with 96 treatment sonications. Total energy per sonication ranged between 1423 and 2846 J with an average of 2168 J. Each individual sonication was 20 s long. Temperature varied between 60 and 85 °C with each sonication. Postcontrast imaging immediately following the treatment demonstrated 75% non-enhancing volume (Fig. ).
However, the patient’s first treatment was complicated by a third-degree far-field skin burn. This burn occurred in the region where sound energy was leaving the patient, as opposed to the near-field skin entry site which was submerged in a small water bath. On average, the center of the typical sonication spot was approximately 3–4 cm away from the region of the burn. The overall region of the burn measured up to 17 × 10 cm. The parents deferred skin grafting, and the burn was treated with silvadene cream. The area healed within four months following the initial treatment.
Because of the significant non-perfused volume following the first treatment and the potential side effects of alternative therapies, the parents and referring clinicians referred the patient for additional MRgFUS therapy. Three enhanced safety measures were developed to reduce the likelihood of a burn.
First, MR-compatible fiberoptic probes (Lumasense Inc, Santa Clara, CA) were used to directly monitor skin temperature where the far-field beam exited the patient. A small amount of ultrasound gel was placed between the skin and the probe. Temperatures that measured pretreatment were typically around 30–31 °C. A temperature rise of 2–3 °C was noted at the peak of each sonication, with a temperature return to approximately 0.2 to 0.5 °C above the baseline temperature by the end of the cooling period. Theoretically, there is a small risk of heating between the probe and the skin; however, we did not see clinical evidence of significant heating in this region.
In addition to the fiberoptic probes, cold plastic water bags were placed along the far-field skin in order to both directly cool the skin and serve as a conduit for acoustic energy to propagate beyond the far-field air-skin interface. The plastic water bags were refrigerated to approximately 1.6 °C the night before the procedure. No active cooling mechanism was used to maintain their temperature during the procedure. Of note, the use of water bags resulted in a large signal void centrally within the MR image by confounding the scanner’s autoprescan function, resulting in overflipping of the spins. This artifact was corrected by decreasing the transmitter gain by about 20% in manual prescan.
Finally, in addition to the probes and water bags, treatment team members developed a system of regular skin checks every 15–20 sonications in order to directly monitor any changes in the skin.
The patient went on to have four subsequent treatments in the 14 months since the first treatment (Table ). While tumor regrowth occurred between treatments, each successive treatment resulted in progressively increased non-perfused volume of the tumor, which measured up to 90% following the patient’s most recent treatment. Single small subcentimeter blisters were observed in the far-field following two of these subsequent treatments, which may represent a small area where air was trapped since the water bags did not perfectly conform to the contour of the patient’s skin. Otherwise, no complication was observed, and these blisters resolved within the first week following the treatment.


A 21-year-old woman with a history of a biopsy-proven sporadic desmoid tumor within the posterior left thigh was referred for MRgFUS therapy. The patient had previously been treated with sulindac and celexocib therapy; however, she palpated interval enlargement and increased firmness of the mass while taking these medications. A repeat MRI was performed demonstrating interval growth of the mass which measured up to 13.5 cm in maximum dimension, increased from 11.5 cm 1 year prior. Referral was made to radiation oncology. However, there was concern for significant left ovarian radiation exposure and risk of infertility. Referral was also made to orthopedic oncology. However, the patient was advised that resection would be associated with a significant risk of recurrence and damage to the adjacent neurovascular structures within the posterior thigh, including the sciatic nerve.
At this time, the patient was referred for MRgFUS therapy. The tumor measured up to 24 × 8.6 × 8.5 cm in maximum dimension with pretreatment volume of approximately 730 cm3 and was associated with medial displacement of the sciatic nerve. Her symptoms at this time included limiting tolerance for sitting and difficulty with strenuous activities that relied on use of the left hamstring group.
MRgFUS of the tumor within the thigh was performed under general anesthesia. The patient was positioned in the left lateral decubitus position in order to minimize the risk to the sciatic nerve. MRgFUS was performed with the same MRgFUS system. Because despite the rapid growth of her tumor, the patient was relatively high-functioning; only the central portion of the tumor was targeted. The procedure was performed with 38 treatment sonications. Enhanced safety measures were used as described in case 1. Total energy per sonication ranged between 1062 and 1911 J with an average of 1539 J. Each individual sonication was 20 s long. Temperature varied between 52 and 77 °C with each sonication. Thermal dose volume was 25.7 cm3. Postcontrast imaging immediately following the treatment demonstrated a relatively low non-perfused volume of the central half of the mass, which measured approximately 30% of the target or 15% of the entire mass (Table ). Review of the sonication data revealed that 20/39 treatment sonications did not definitely reach 60 °C, including 10/39 which did not clearly reach 57 °C based on the MR thermometry sequences. Overall, the average temperature was 60.8 °C following each sonication. Review of the imaging data demonstrated a subtle fascial band in the soft tissues which potentially contributed to poor heating during the treatment. Several sonications did demonstrate heating accumulating along this interface.
The patient returned after 6 months for a repeat treatment. The upper half of the tumor was targeted. A slight obliquity of the left lateral decubitus position was used in order to shift the location of the previously noted fascial band. The procedure was performed with the same treatment setup, and 117 treatment sonications were performed. Because the procedure tolerated the first procedure well without any evidence of a skin injury, significantly increased energy was also used compared to the prior treatment with the energy per sonication ranging between 1474 and 6026 J with an average of 3861 J. Thermal dose volume measured 74.3 cm3. There was approximately 70% non-enhancing volume within the targeted superior 1/2 of the mass (where there had been the most interval growth following the prior treatment) (Fig. ). Interestingly, despite the increased non-perfused volume, average temperature was slightly lower in this treatment with an average of 59.0 following each sonication. The patient experienced no complications following either treatment.


The third patient was a 13-year-old girl with a biopsy-proven sporadic desmoid tumor within the posterior aspect of the left thigh. The lesion was initially discovered by palpation by the patient’s parents, with a rapid increase in size over the subsequent 2 months. Pretreatment tumor volume was approximately 440 cm3 with dimensions of 12.9 × 8.7 × 5.9 cm. The anterior portion of the tumor circumferentially encased the sciatic nerve over 9 cm of the length of the nerve. The left lateral decubitus position and enhanced safety measures were again used as described previously. Sixty-five treatment sonications were used which ranged in energy between 1790 and 2268 J with an average of 1952 J. Because of the close relationship with the sciatic nerve, relatively low energies were used during the first treatment. Thermal dose volume measured 23.9 cm3. There was a relatively low non-perfused volume of approximately 30% (Table ). The patient returned after 7 months for repeat treatment. The procedure was performed with the same treatment setup, and 140 treatment sonications were performed. Because the procedure tolerated the first procedure well without any evidence of a skin injury, significantly increased energy was also used compared to the prior treatment with the energy per sonication ranging between 1502 and 6094 with an average of 3362 J. These increased energies resulted in an increased non-perfused volume of approximately 70% (Fig. ). The patient experienced no complications following either treatment.


A 24-year-old male presented for evaluation of palpitations. There was no history suggestive of rheumatic fever. On examination, blood pressure was 104/60 mm Hg in right upper limb in supine position and pulse rate was of 86/min. Jugular venous pressure was normal in height with C-V waveform. The apex was in the sixth left ICS, 2 cm outside the mid-clavicular line and hyperkinetic in character. On auscultation, S1-soft, S2-wide variable split with loud P2 and LVS3 were present. A grade 4/6 pan-systolic murmur radiating towards the axilla was heard. There was also a pan-systolic murmur in the left third parasternal region which increased during inspiration. ECG showed normal sinus rhythm. Chest X-ray revealed cardiomegaly with evidence of pulmonary venous congestion. On transthoracic echocardiography in apical four-chamber view, it showed SMA () in the postero-lateral wall of the left ventricle. Color Doppler showed severe mitral regurgitation with an eccentric jet towards left atrium and severe tricuspid regurgitation (). Color Doppler in apical five-chamber view showed mild aortic regurgitation (). Transesophageal echo in four-chamber view with transducer positioned in esophagus displayed severe mitral regurgitation with an eccentric jet (). So, SMA was diagnosed and referred to cardiothoracic department for further management.


The authors describe the case of a 17-year-old female admitted with complaints of exertional dyspnea, worsening fatigue and pedal edema. On physical examination, she was hemodynamically stable (blood pressure 136/75 mm Hg, heart rate in atrial fibrillation (AF) with ventricular rate 68 bpm (average), eupneic at rest, with raised JVP with prominent wave and variably split first heart sound and S2 with normal inspiratory split). Laboratory tests, including thrombophilia screen, were normal. Lower limb venous Doppler did not reveal any evidence of deep vein thrombosis. She was not on any central venous lines or any indwelling catheter. The electrocardiogram showed AF (average heart rate 81 bpm). The chest X-ray documented cardiomegaly (CT ratio 70%) due to enlargement of the right atrium (RA).
The transthoracic echocardiogram was s/o EA (Carpentier classification type C), showing massively dilated RA, atrialized RV and small and dysfunctional RV (FRV) (, , Supplementary Videos 1, 2, www.cardiologyres.org), abnormal TV with 2.3 cm apical displacement of septal leaflet of tricuspid valve (STL) and STL was small, dysplastic and tethered to interventricular septum. Anterior leaflet of tricuspid valve (ATL) was long sail like with decreased movement (, Supplementary Video 3, www.cardiologyres.org), there was stagnation of blood flow in RA due to hypofunctional RV with low velocity flow (1 cm/s) across TV with no evidence of tricuspid regurgitation (), and the massively dilated RA was filled with dense spontaneous echo contrast and a large free floating clot in RA (). Left ventricular systolic function was preserved. Administration of intravenous contrast (agitated saline) revealed no evidence of any PFO with intact interatrial septum (). Transesophageal echocardiography subsequently confirmed the findings with no evidence of a PFO and clearly showed patent normal pulmonary valve and pulmonary artery which was not clearly visualized on transthoracic echo (, Supplementary Video 4, www.cardiologyres.org).
In view of AF and dense spontaneous contrast and large clot in RA, it was decided to start anticoagulation therapy. Patient was advised surgical correction (TV repair, right ventricular plasty and surgical removal of RA clot), but patient defered surgery due to personal reasons.


A 54-year-old Asian man with IgA nephropathy underwent living-donor kidney transplantation 14 years previously. His medical condition had been almost stable for 14 years. He developed multifocal salmon-pink skin discoloration, and swelling and spontaneous pain in the left knee and leg. The symptoms had gradually expanded across the right forearm and outside of the right thigh. He was admitted to our hospital for the evaluation of fever (39 °C) and multifocal cellulitis (Fig. ). Two months before admission, he had developed chronic diarrhea. His serum creatinine level was stabilized at 1.7 mg/dL with maintenance immunosuppressive therapy comprising tacrolimus (3 mg/day), mycophenolate mofetil (1500 mg/day), and prednisone (4 mg every other day). The tacrolimus trough concentration was 6.3 ng/mL. The patient had been a dog breeder for 12 years. On admission, his white blood cell count was 12,400/μL and his C-reactive protein level was 3.9 mg/dL. The patient was initially treated with ampicillin/sulbactam (9 g/day intravenously). Two days after the initiation of this therapy, he was afebrile. Four days later, an automated blood culture (Bactec FX®; Becton–Dickinson and Company, Sparks, MD, USA) showed positivity for gram-negative spiral bacilli. A colony obtained from the patient’s blood culture was analyzed by MALDI-TOF MS (Biotyper ver. 3.0®; Bruker Corporation, Germany). The identification score was 2.064 (>2.0), indicating accurate identification of H. cinaedi (Fig. ). Additional evaluation of the patient’s blood specifically for H. cinaedi by means of gyrase subunit B (gyrB)-targeted PCR assays (using the forward primer AGGGATTCCACAAAGTGAGC and the reverse primer TCTTGTCCTGTGCGTTCATC to amplify the region of the gyrB gene) yielded positive results. We performed gyrB-targeted PCR using a single colony isolated from a blood culture. We used distilled water (DNA- and DNase-free water) as a negative control to prevent contamination of gyrB-targeted PCR (Fig. ). In addition, we performed 16S rRNA gene sequencing of this strain, and the results were > 99% consistent with the existing sequence (Fig. ). Given these results, we diagnosed the patient with H. cinaedi bacteremia with cellulitis. We examined the genomic heat shock protein (HSP) 60 sequence of the blood culture isolate, which resulted in identification of cluster B H. cinaedi. A blood culture obtained at 11 days was positive for H. cinaedi, but a culture obtained at 15 days was negative. The patient’s cellulitis gradually resolved. The patient continued antibiotic treatment for a total of 6 weeks (ampicillin-sulbactam in a drip for 2 weeks and oral levofloxacin for 4 weeks), and he had no recurrence 6 months after this therapy. His stool culture was negative, although it was taken after treatment. We did not apply enteric bacteria elimination in this case.


A 57-year-old male with a history of hypertension and benign prostatic hypertrophy presented with complaints of decreased appetite, leg cramps with associated discomfort in his right groin and swelling in the right leg. The patient also reported fatigue with a 10-pound weight loss over the preceding month. He denied fever, chills or night sweats. On physical examination, the spleen was palpable one finger breadth below the costal margin with mild adenopathy in the right and left inguinal regions. Pitting edema in the left lower extremity was present. A computed tomography (CT) scan of the abdomen and pelvis revealed a large conglomeration of lymph nodes involving the right periaortic region extending to the right pelvic side wall with areas of central necrosis. Also seen was a right inguinal lymph node measuring about 2.8 x 2.1 cm and splenomegaly. A CT scan of the chest showed extensive mediastinal adenopathy measuring up to 1.3 x 1.4 cm and bilateral axillary lymphadenopathy with the largest lymph node measuring 1.5 x 1.1 cm.
Initial blood work showed a lactate dehydrogenase (LDH) level of 634 U/L, white cell count of 7.36 million cells/mcL with a normal differential, hemoglobin of 11.9 g/dL and a platelet count of 276,000/microliter. Coagulation studies and a comprehensive metabolic panel were within normal limits.
An excisional biopsy of the right inguinal lymph node was performed, and pathologic exam revealed a biphasic lymphoid population consisting of a large cell population strongly positive for B-cell antigens, CD20 and PAX5, and germinal center cell antigens, CD10 and BCL6. Ki-67 was expressed in 80-90% of the cells. The cell regulatory protein p53 was expressed in the majority of the larger cells, supporting the diagnosis of germinal center-like large B-cell lymphoma. Unexpectedly, the small cell component was also positive for the B-cell antigens, CD20 and PAX 5, with aberrant co-expression of the T-cell antigen CD43 (dim). Distinct nuclear positivity for cyclin D1 (BCL1) was present. BCL2 was also positive, consistent with a diagnosis of mantle cell lymphoma. Epstein-Barr encoding region (EBER) in situ hybridization was negative (Figure ).
To confirm the presence of two clonally unrelated neoplasms rather than large cell transformation of MCL, PCR analysis of IGH chain and IGK light chain gene rearrangements were performed on the two components after macrodissection. Fluorescent in situ hybridization (FISH) analysis was positive for rearrangement of CCND1/IGH in 13% of the cells and multiple gains of chromosomes resulting from the t(11;14) (q13;q32) translocation, which is most commonly associated with MCL. Hence, we reached the final diagnosis of B-cell lymphoma CD10 positive (80-90% large cell lymphoma) and MCL (10-20%).
Subsequently, the patient underwent a positron emission tomography-computed tomography (PET-CT) scan which revealed extensive fluorodeoxyglucose-avid (FDG-avid) lymphadenopathy above and below the diaphragm with a maximum standard uptake value (SUV) of 39.8 measured at the 15 x 7.5 cm conglomerate of lymph nodes within the right pelvic sidewall. Multiple FDG-avid lesions were also seen within the liver and spleen along with a right rib lesion.
Bone marrow biopsy and aspirate findings were consistent with mild hypercellularity (50-60%) with increased interstitial lymphocytes, predominantly small to medium in size with irregular nuclei and distinct nuclear positivity for cyclin D1 (BCL1). Immunohistochemistry and FISH studies were consistent with mantle cell lymphoma with no evidence of large cell lymphoma. Further studies included cerebrospinal fluid (CSF) analysis, which was negative for malignant cells. Multigated acquisition (MUGA) scan showed an ejection fraction of 68%. The patient was treated with six cycles of a chemotherapy drug combination of rituximab, cyclophosphamide, hydroxydaunomycin, Oncovin® and prednisone (R-CHOP), along with four doses of intrathecal methotrexate given with the first four cycles of chemotherapy. A central nervous system (CNS) prophylaxis was administered because of the presence of visceral and rib disease. A repeat PET-CT scan after the completion of chemotherapy showed resolution of the previously FDG-avid lesions, and bone marrow biopsy was negative for the presence of any lymphoproliferative disorder. The patient is currently on consolidation chemotherapy and has received two cycles of cytarabine to be followed by high-dose methotrexate. He is planned to undergo an autologous stem cell transplantation following consolidation.


A 51-year-old white man with past medical history of depression and multidrug abuse presented to our emergency department with altered mental status and complaining of chest pain. Limited history suggested the patient was binge drinking and discharged a nail gun into his chest in a suicide attempt. However, the resulting chest pain became unbearable causing him to call a friend for transport to the emergency department. Past medical history included major depressive disorder, alcohol, tobacco and cocaine abuse, and chronic obstructive pulmonary disease (COPD). Investigations into his social history suggested his wife had died six months ago and he had been abusing alcohol, tobacco, cocaine, and marijuana heavily since. Vital signs did not suggest hemodynamic compromise: pulse was 93 bpm, blood pressure was 100/60 mmHg, and respirations were at 14 breaths/minute. The examination revealed that he was an overweight white man, weighing 75 kg and measuring 178 cm in stature. The patient was alert, although confused. A head exam showed temporal wasting and poor dental health. The pulses in the extremities were diminished but palpable, and carotid upstrokes were felt bilaterally. One puncture wound at the right sternal border between the fourth and fifth ribs was present. Additionally, the patient had decreased capillary refill and increased AP diameter. The rest of the physical exam including the cardiac and pulmonary exam were normal.
Laboratory investigations showed an elevated WBC count at 13,000/mcL and ethanol serum level at 156 mg/dL. Otherwise, his complete blood count, metabolic panel, and liver function tests were normal. Chest X-ray (Figures -) and computed tomography (CT) of the chest (Figures -) revealed a three-inch tapered foreign body consistent with a nail, with the tip adjacent to the abdominal aorta. The tail end of the nail was located within the right ventricular wall. Remarkably, he was not hemodynamically compromised and consented to immediate surgery for removal of the nail.
An intraoperative transesophageal echocardiogram confirmed the location of the nail and normal physiologic cardiac function. A median sternotomy was performed. The patient was found to have extensive pericarditis, and dissection down to the heart was required. The nail had punctured entirely through the anterior right ventricular wall, left atrium, the diaphragm, and into the abdomen, with the tail end remaining in the posterior right ventricular wall. Removal of the nail and closure of the two heart wounds and diaphragm with Prolene® Suture (Ethicon, NJ, USA) was uncomplicated. The chest was closed following the placement of two pacing wires and thoracostomy tube. Postoperative echocardiogram showed no physiologic changes from prior to removal of the foreign body. The patient did well and was extubated immediately following surgery. The patient was held for psychiatric evaluation, but was eventually discharged on postoperative day 8.


A 72-year-old male underwent right nephrectomy in 2006 and 2 years later total bladder cystectomy due to disseminated ureteral transcellular carcinoma. In November 2010, patients’ renal function deteriorated, and after diagnosis of complicated pyelonephritis, he underwent left-side nephrectomy. Since then he was on chronic HD. He also has a history of arterial hypertension and smoking.
In June 2014, he was hospitalized due to swollen and painful wrists, proximal interphalangeal and metacarpophalangeal joints, and subfebrile temperature. Physical examination revealed lowered right basilar respiratory ton and systolic precordial murmur. Laboratory findings at admission revealed high CRP level and low hemoglobin level, despite erythropoietin therapy and iron supplementation (Table ). Arterial blood gases pointed out acute partial respiratory insufficiency (pO2 7.3 kPa, pCO2 3.4 kPa, O2 saturation 90%). Chest radiography and computed tomography (CT) have shown bilateral pleural effusion (more pronounced in the right side) with subsequent compressive atelectasis and possible consolidation in lower right lung. Diagnostic pleural puncture confirmed exudation (protein level 33 g/L). Klebsiella–Enterobacter was isolated from the sputum culture, and patient is understood to have respiratory infection. Echocardiography revealed mild aortic stenosis and pericardial effusion (10 mm), without endocardial vegetations. Abdominal ultrasound was insignificant, apart form the missing kidneys. Other tests were performed in order to explain clinical status and high CRP level including bacteriology (hemocultures, coprocultures, nasal and pharyngeal swabs), tumor markers (prostate-specific antigen, carcinoembryonic antigen, CA 19-9, AFP), and markers of viral hepatitis (hepatitis B surface antigen, anti-HCV, anti-HIV), and they all were negative. Esophagogastroduodenoscopy and total colonoscopy were done, and results indicated mild erosive gastritis and diverticulosis sigmae.
Antibiotic therapy according to sputum antibiogram (Meropenem) was started together with non-steroid and anti-inflammatory drug. After 14 days of antibiotic therapy, joints were still swollen and painful, CRP level was still high (139.3 mg/L), and chest radiography revealed infiltrations in middle and upper zones of the right lung and middle zone of the left lung (Figure ). We performed respiratory function assessment which pointed out restrictive pattern of respiratory disorder [spirometry: forced expiratory volume in 1 s (FEV1) 55%, FVC 56%, FEV1/FVC 101%], and lung diffusion capacity (DLCO) was 59% of anticipated and pulmonary CT angiography ruled out pulmonary thromboembolism. Results of serology analysis confirmed high levels of anti-MPO antibodies and perinuclear antineutrophil cytoplasmic antibody (p-ANCA) positivity (Table ).
Since we could not perform kidney biopsy but have strongly positive MPO-ANCA, musculoskeletal and lung symptoms, as well as ruling out other reasons for ANCA positivity, diagnosis of MPA was established (Table ). Specific induction therapy with intravenous cyclophosphamide (six monthly doses of 800 mg) and intravenous methylprednisolone (six monthly pulses with 3 days of 1 g) was prescribed, followed by oral prednisone (0.5 mg/kg). After 1 month, there were no joint symptoms, CRP level was almost normal (9.8 mg/L), and arterial blood gases were recovered, and after 3 months, chest radiography was normal (Figure ). After 6 months, control MPO-ANCA was 0.62 RU/mL and p-ANCA 1:80.
Patient is still in stable remission after 27 months of induction therapy followed by maintenance therapy (oral azathioprine 100 mg/day).


The patient is a 17-year-old Caucasian boy that presented with intention tremor, palpitations, and marked anxiety at age 15. He was medicated with propranolol and hydroxyzine with partial improvement of symptoms and was referred to a hospital pediatric appointment.
The adolescent and his father had genetically confirmed CS [heterozygous frameshift mutation in exon 5 of PTEN gene: c.405_406insA (C136Mfs∗44) NM_000314]. The patient's father was submitted to a total thyroidectomy for multinodular goiter at age 23 and died at 60 years old of brain tumor (anaplastic oligodendroglioma). His paternal grandfather had thyroid cancer.
Other notable features in our patient's previous medical history were macrocephaly, the presence of a hemangioma in his left lower limb, learning disabilities, and a cognitive evaluation that concluded that a global delay in cognitive development with an intelligence quotient (IQ) at the lower limit of the normal range was present. On physical examination, he had a coarse facies, slight prognathism, facial trichilemmomas, abdominal keratoses, and an irregular, elastic, and diffusely enlarged thyroid gland (Figures and ). Exophthalmia was not apparent.
Thyroid function tests were consistent with a hyperfunctioning thyroid state: thyrotropin (TSH) < 0,005 IU/mL (normal range 0,358–3,740 IU/mL), free thyroxine (fT4) 4,97 ng/dL (normal range 0,76–1,46 ng/dL), free triiodothyronine (fT3) 27,58 pg/mL (normal range 2,18–3,98 pg/mL), with positive anti-thyroid autoantibodies: thyroid peroxidase antibodies (anti-TPO) > 3340 IU/mL (normal range 0–100 IU/mL), thyroglobulin antibodies (anti-Tg) > 24400 IU/mL (normal range 0–344 IU/mL), and thyrotropin receptor antibodies (TRAbs) 14,3 IU/mL (normal range < 1,2 IU/mL). Thyroid ultrasonography at diagnosis showed a heterogeneous, hypoechoic, and high volume goiter (43 × 94 × 38 mm left lobe and 49 × 100 × 44 mm right lobe), with no visible nodules.
He was started on methimazole, maximum dose 20 mg/day, and propranolol treatment, lasting for a 2-year period, without achieving an euthyroid state.
Thyroid ultrasonography, 2 years after GD diagnosis, revealed dominant isoechoic solid nodules of 10 mm and 12 mm in the left and right lobes, respectively. Fine needle aspiration (FNA) cytology result was benign, consistent with hyperplastic/adenomatoid nodule (designed according to The Bethesda System for Reporting Thyroid Cytopathology) ().
A multidisciplinary team, including Pediatric Endocrinologist, Adult Endocrinologist, and Pediatric Surgeon, met in order to discuss the therapeutic options. Attending to the voluminous goiter and risks inherent to CS, a total thyroidectomy was the definite treatment consensus. That was also the patient's choice. Potassium iodide-iodine solution (Lugol) was used in preoperative preparation and surgery went uneventful. On gross examination, the surgical specimen weighed 218 g, with a larger left (95 mm) than right lobe (90 mm). The microscopic examination revealed lymphocytic thyroiditis (Figures –). He was started on replacement therapy with oral levothyroxine 125 ug/day and he is currently compensated.


Our patient is a 33-year-old previous healthy female with no documented past medical history and insignificant family history who presented with severe abdominal pain, nausea, and emesis in July 2012 at an outside institution. A computed tomography (CT) scan of the abdomen revealed thickening of her cecum. She was taken to emergent surgery for what was thought to be a perforated appendix. Intraoperatively, the procedure was switched to a right hemicolectomy due to the presence of a right-sided colon mass.
Gross pathologic examination of the 14.8 cm in length right hemicolectomy specimen revealed a 7.3 cm cecal mass extending to the ileocecal valve and terminal ileum with no macroscopic perforation. Histopathology revealed a moderately differentiated colonic adenocarcinoma with invasion through the muscularis propria into the subserosal adipose tissue and areas of CD-like lymphoid aggregates adjacent to and deep to the tumor with mild to moderate intratumoral lymphocytes (Figures and ). While highlights a focal area of poorly differentiated adenocarcinoma, the tumor has between 50% and 95% glandular architecture designating it as grade 2 moderately differentiated. shows an in situ component of the adenocarcinoma arising from the luminal surface. The tumor did not extend to the serosal surface and the margins of resection were negative. Lymphovascular invasion was present, with metastatic disease found in eight out of the 18 lymph nodes sampled. shows an example of one lymph node with metastatic involvement. No tumor buds or satellite nodules were identified grossly or microscopically.
Mismatch repair protein (microsatellite instability [MSI]) immunohistochemical stains were performed at the originating outside regional hospital and revealed no loss of MLH1, MSH2, MSH6, and PMS2 protein expression within the invasive tumor cells (Figures –). This is consistent with microsatellite stable colonic adenocarcinoma. Given the patient's young age, right-sided location of carcinoma, and microsatellite stability (by immunohistochemical stains with intact protein expression), HNPCC/Lynch Syndrome (MLH1/MSH2/MSH6/PMS2) Gene Sequencing and Deletion/Duplication testing was performed at ARUP Laboratories (Salt Lake City, UT). This additional full gene sequencing revealed no pathogenic mutations detected in the MLH1, MSH2, MSH6, and PMS2 genes.
The patient then underwent eleven cycles of adjuvant FOLFOX chemotherapy, which was completed in January 2013. A follow-up CT scan of her abdomen in February 2013 showed diffuse colonic thickening, which was concerning for inflammatory bowel disease versus irritable bowel syndrome. Of note, the CT scan revealed no evidence of PSC. In June 2013, a colonoscopy demonstrated patchy erythema, change in vascular pattern, mild friability with no spontaneous bleeding, numerous superficial ulcerations, and granularity in the colon in a patchy distribution. Biopsies revealed cryptitis in the terminal ileum and chronic crypt destructive colitis in the right colon, transverse colon, left colon, and rectum. In July 2013, a positron emission tomography (PET) scan revealed a 1.3 cm paraduodenal lymph node anterior to the inferior vena cava and multiple mesenteric lymph nodes with diffuse uptake. Endoscopic ultrasound-guided biopsy revealed metastatic carcinoma. She was placed on FOLFIRI chemotherapy.
Upon further questioning, the patient reported chronic diarrhea with loose, frequent bloody stools since she was 14 years old. She was referred to the gastroenterology service of our university health system for consultation to confirm her diagnosis of inflammatory bowel disease and plan treatment. The initial right hemicolectomy case was sent to us to evaluate for presence of inflammatory bowel disease, to confirm whether the colitis and chronic diarrhea were a result of inflammatory bowel disease or the chemotherapy regimens.
Upon our pathologic review of the right hemicolectomy case, the background nonneoplastic colonic mucosa located a few centimeters away from the tumor was noted to show focal chronic-active colitis characterized by marked crypt distortion, crypt abscesses, and reactive epithelial atypia (see Figures –, which demonstrate focal transmural neutrophilic inflammation forming a deep fissuring ulcer as well as large hyperplastic lymphoid aggregates). There were no evidence of epithelioid granulomas and no documented upper gastrointestinal tract or perianal disease or fistulizing tracts. The gross description in the outside institution's pathology report did not mention strictures, fat wrapping, serosal adhesions, or cobblestoning of the mucosa. Eight of 18 lymph nodes were positive for adenocarcinoma, but no granulomas or multinucleated giant cells were identified in the nodes. Given the histopathologic findings and the clinical history of unexplained chronic diarrhea for approximately 19 years, the clinicians concluded that the patient most likely had an undiagnosed CD. Calprotectin level and ANCA laboratory tests were not performed, but the patient had elevated C-reactive protein and erythrocyte sedimentation rate levels. As of this report, the patient has no documented evidence of extraintestinal symptoms, such as arthropathy, pyoderma gangrenosum, erythema nodosum, oral aphthous ulcers, episcleritis, or uveitis. She has since completed six cycles of FOLFIRI in March 2014 and is being treated for CD. She has intermittently been seen in clinic for her CD symptoms, which include hematochezia and bowel incontinence. She has had a few colonoscopies demonstrating moderately active ileitis and colitis attributed to her Crohn's disease.


A 31-year-old Japanese man was referred to our hospital with renal dysfunction in April 2014. He had a history of hypertension, hyperuricemia, and pituitary dwarfism, but had not taken any medications. He was 159.4 cm in height and 42.6 kg in weight (body surface area 1.398 m2). Initial blood tests showed anemia and renal dysfunction: blood urea nitrogen (BUN) 64.6 mg/dl, creatinine (Cr) 5.66 mg/dl. A chest X-ray performed to evaluate cardiomegaly revealed a mediastinal tumor in his right thorax; a computed tomography (CT) scan confirmed the mass to be a well-defined, homogeneous solid tumor (53×35 mm) in his anterior mediastinum (Fig. ). An additional blood examination showed a high level, 322.6 ng/ml, of alpha-fetoprotein (AFP, normal <9 ng/ml), but his beta-human chorionic gonadotropin (β-hCG) level was within normal range. A CT-guided biopsy of the mediastinal tumor showed the presence of tumor cells with mixed sinusoidal-like, cystic, and papillary structures (Fig. ) and Schiller–Duval body (Fig. ), which was positive by immunohistochemistry (IHC) for cytokeratin (CK) AE1/AE3 and AFP, and negative for placental alkaline phosphatase (PLAP), β-hCG, and CD30 (Fig. ), resulting in a diagnosis of primary mediastinal yolk sac tumor. Because of the complication of end-stage renal insufficiency, surgery was selected as the first treatment; following surgery, his AFP level decreased to the normal range. Subsequently, chemotherapy with cisplatin (10 mg/m2) and etoposide (60 mg/m2) was conducted daily from day 1 through to day 5. HD was started 1 hour after infusions of these agents. Appendicitis with grade 4 neutropenia occurred, so an appendectomy was performed after the first cycle. In addition, grade 3 anemia and grade 4 neutropenia appeared under prophylactic treatment with granulocyte-colony stimulating factor (G-CSF). Because severe hematological toxicities occurred, we conducted chemotherapy without dose escalation on the second cycle. In contrast to the first cycle, toxicities were admissible with 10 mg/m2 cisplatin and 60 mg/m2 etoposide in the second cycle. To elevate the dose intensity, the doses were escalated from the third to the fifth cycles: cisplatin to 15 mg/m2 and etoposide to 75 mg/m2. Grade 4 neutropenia and thrombocytopenia as well as grade 3 anemia were sustained over 7 days in spite of prophylactic treatment with G-CSF. After five cycles of chemotherapy, his AFP level remained in the normal range and there has been no recurrence for 1 year.
During the third and fourth cycles, free cisplatin blood concentrations were measured as part of a multicenter study. Venous blood samples were collected five times each day: (1) before cisplatin infusion, (2) immediately after infusion, (3) before HD, (4) after HD, and (5) 4 hours after HD on days 1 to 5. In addition, blood was collected before HD on day 8 once in each course (Fig. ). The time-concentration curve in the third cycle is shown in Fig. . Our patient was administered 15 mg/m2 cisplatin, and maximum concentration (Cmax) of free cisplatin was 0.8 to 0.9 μg/mL. Just before treatment with cisplatin, the concentration had not recovered to the level observed after the previous HD. The concentration before infusion of cisplatin gradually increased each day during the 5 days of treatment, and this phenomenon was observed until 8 days after the start of chemotherapy. During the fourth cycle, chemotherapy was administered using the same doses used in the third cycle, and PK was similar to that of the third cycle.


A 65-year-old Caucasian gentleman with a history of acquired immunodeficiency syndrome (AIDS) on HAART and chronic obstructive pulmonary disease (COPD) was admitted to the intensive care unit (ICU) after having cardiopulmonary arrest secondary to hyperkalemia with a value of 7.5 meq/L (reference range: 3.4–5.2 meq/L). Following the placement of the orogastric tube (OG) and endotracheal tube (ETT), significant amounts of blood were noticed in the ETT. His hemoglobin dropped from 9.6 mg/dL to 6.7 mg/dL over the following five days and his stool was positive for occult blood. He underwent upper GI endoscopy and colonoscopy. Upper endoscopy revealed multiple large hypervascularized violaceous submucosal nodular lesions with stigmata of recent bleeding on the soft palate and pharynx and within the cricopharyngeal area close to the vocal cords. No active bleeding was noted. The examination of the distal esophagus revealed severe ulceration with a small hiatal hernia (see Figures –)
A biopsy from the soft palate lesions showed proliferation of neoplastic spindle shaped cells arranged in bundles with slit-like capillary spaces containing erythrocytes consistent with Kaposi's sarcoma. Biopsy was also positive for HHV-8.
Colonoscopy was unremarkable for similar lesions, polyps, or diverticulosis. There were no cutaneous manifestations of the disease. The patient was started on proton pump inhibitors. The bleeding stopped spontaneously without intervention and his hemoglobin stabilized prior to discharge. After his discharge from the hospital, he was scheduled for capsule endoscopy as outpatient to evaluate the small bowel, but unfortunately he expired prior to the exam.


A 35-year-old African American woman with a past medical history of an episode of pericarditis presented to the Emergency Department complaining of chest pain and fatigue of a weeks' duration. She reported a sudden onset of pleuritic chest pain associated with cold-like symptoms but no complaints of any fever or chills. In addition, she had reported difficulty lying supine, which caused some dyspnea along with some discomfort under the left breast. She had gone to the Emergency Department of another hospital, two days ago, and was discharged with the diagnosis of a viral syndrome. Upon further investigation, she reported a possible diagnosis of pericarditis when she went to another hospital in 2010. She then went on to give a history of hair loss and arthralgia in her hands. There was no other past medical history and family history was significant for SLE in a half-sister. She had 3 children and a 1st trimester miscarriage. She denied alcohol and drug use.
On admission, physical examination revealed a young woman with mild distress with tachycardia of 102. Other vital signs were within the normal limit. Only other significant findings on physical examination were a pericardial friction rub and nonscarring alopecia. Electrocardiogram (ECG) showed concave ST elevations in the inferior and lateral leads (). Chest X-ray (CXR) showed no abnormalities (). Labs including complete blood count and comprehensive metabolic panel were within normal limits. The first two sets of cardiac troponins were within normal limits. She was initially diagnosed as having pericarditis and was started on Indomethacin with Pantoprazole, but she could not tolerate NSAIDs. Hence, she was started on Colchicine with Prednisone. Additional labs, including antinuclear antibody (ANA), antidouble stranded DNA (Anti-ds DNA), and complement C3 and C4 were sent for further evaluation.
Later during the day, she complained of increasing shortness of breath with chest pain and found to be desaturating down to 87% on room air. She was noted to have crackles and trace pedal edema on physical examination. Arterial blood gas revealed hypoxemia. Her oxygen saturation improved after placing her on a nasal cannula with 2 liters of oxygen. A repeat chest X-ray showed an interval development of small bilateral pleural effusions (). Repeat labs including Beta natriuretic peptide (BNP) and troponin were sent. A transthoracic echocardiogram (TTE) revealed moderately reduced left ventricular systolic function with an Ejection Fraction of 35–40% and a moderate pericardial effusion without any signs of tamponade ().
The patient was transferred to the intensive care unit (ICU) for closer monitoring and started on lasix, metoprolol, and lisinopril. Troponin trend was 0.60 ng/ml > 0.49 ng/ml > 0.74 ng/ml, which was expected for myocarditis, and no heparin drip was indicated. She was very weak with marked dyspnea on exertion and could not get out of bed. Creatinine phosphokinase (CPK) was 435 U/L and BNP was elevated at 488 pg/ml. ANA returned positive at 1 : 160 with low C3 of 74 mg/dl and C4 of 25 mg/dl. SM/RNP, dsDNA, RPR, HIV, and HBsAg were negative. She was subsequently diagnosed with SLE, according to the new criteria, with pericarditis, myocarditis, and small pleural effusion but also ANA, low C3, and hair loss with alopecia. Prednisone was held and methylprednisolone was started. Colchicine was also held, as the patient developed diarrhea. Vitals remained stable with improvement in overall clinical status while the patient was in ICU but continued to feel weak. She was then transferred to a tertiary care center and had a cardiac magnetic resonance (CMR) imaging 3 days later, which showed normal biventricular size and systolic function, edema, and subepicardial enhancement in the lateral wall and confirmed the presence of myocarditis.


A 72-year-old Caucasian woman with a past medical history significant for diabetes mellitus, hyperlipidemia, hypothyroidism, and osteoarthritis was admitted for an elective left total knee arthroplasty. Her medications included aspirin 81 mg daily, simvastatin 40 mg daily, glipizide 2.5 mg daily, iron sulfate 325 mg daily, vitamin D3 2000 units daily, and ezetimibe 10 mg daily. She was allergic to formaldehyde. Perioperatively, she received spinal anesthesia with bupivacaine and intravenous propofol, phenylephrine, midazolam, epinephrine, cefazolin, and vancomycin. Notably, no heparin was given, no blood reinfusion or salvage devices were used, and no central venous or arterial catheters were used intraoperatively.
Postoperatively, her hospital medications included ondansetron, metoclopramide, diphenhydramine, acetaminophen, and morphine. On postoperative day (POD) 1, laboratory results revealed white blood cell count (WBC) of 12.9 K/mL (range: 3.7–10.1 K/mL), hemoglobin (Hgb) 10.8 g/dL (range: 11.5–15.4 g/dL), platelets 179 K/mL (range: 156–352 K/mL) sodium 143 mmol/L (range: 136–145 mmol/L), potassium 4.0 mmol/L (range: 3.5–5.1 mmol/L), chloride 107 mmol/L (range: 97–107 mmol/L), bicarbonate 26 mmol/L (range: 21–32 mmol/L), blood urea nitrogen (BUN) 8 mg/dL (range: 7–18 mg/dL), and creatinine 0.7 mg/dL (range: 0.6–1.3 mg/dL). She was continued on her home medications with the addition of gabapentin, celecoxib, oxycodone, and pantoprazole. Her home aspirin was stopped and she was started on aspirin 325 mg twice daily for deep vein thrombosis (DVT) prophylaxis. She was discharged on POD3 to a rehabilitation center for physical therapy. Her laboratory results on discharge were WBC 11 K/mL, Hgb 9.9 g/dL, and platelets 183 K/mL.
On POD12, while ambulating with a walker at the rehabilitation center, she developed acute shortness of breath and subsequently lost consciousness. The patient was found to be hypotensive at 105/37 mmHg, tachycardiac at 117, having respiratory rate of 33, and oxygen saturation of 80% on pulse oximeter. She was transported to the nearest hospital.
On arrival to the hospital, she was unresponsive and cyanotic with a blood pressure of 80/57 mmHg, pulse of 123, respiratory rate of 38, and oxygen saturation of 86%. She was intubated and placed on vasopressors. Initial work-up was significant for WBC 22.1 K/mL, Hgb 10.4 g/dL, platelets 85 K/mL, sodium 136 mmol/L, potassium 4.0 mmol/L, chloride 102 mmol/L, bicarbonate 18 mmol/L, BUN 12 mg/dL, creatinine 1.1 mg/dL, and calcium 8.6 mg/dL. Computed tomography (CT) angiography of the chest revealed bilateral pulmonary emboli. A transthoracic echocardiogram (TTE) showed an ejection fraction of 72% with a dilated hypocontractile right ventricle, mild right atrial enlargement, and right ventricular systolic pressure (RVSP) of 45–50 mmHg. She had no prior history of heart failure or pulmonary hypertension. She was initiated on unfractionated heparin infusion for treatment of pulmonary embolism. Repeat laboratory testing 14 hours later showed a subsequent decrease in platelet count to 48 K/mL. She was then transferred to our institution (a tertiary care facility) for further management of her hypoxic respiratory failure secondary to pulmonary embolism, cardiogenic shock, and thrombocytopenia.
On arrival at our institution, laboratory testing revealed WBC 19.6 K/mL, Hgb 7.2 g/dL, platelets 25 K/mL, d-dimer >20 μg/mL (range: <0.43 μg/mL), fibrinogen 315 mg/dL (range: 231–486 mg/dL), haptoglobin 154 mg/dL (range: 14–258 mg/dL), lactate dehydrogenase (LDH) 427 u/L (range: 100–240 u/L), prothrombin time (PT) 17.2 s (range: 12–15.1 s), and activated partial thromboplastin time (aPTT) 135.7 s (range: 23.3–35.7 s). Due to concern for heparin-induced thrombocytopenia (HIT), unfractionated heparin was discontinued. She received 1 unit of packed red blood cells (pRBC) for anemia and was started on intravenous argatroban with a goal aPTT of 50–80 s. Pulmonary angiogram demonstrated extensive clot in the right middle and lower arteries and left lower artery. Given hemodynamic instability, she underwent catheter-directed thrombolysis with alteplase at 1 mg/hour. Bilateral upper and lower extremity duplex ultrasounds revealed thrombosis in the superficial left cephalic, left common femoral, left popliteal, and right posterior tibial vein.
A hypercoagulable work-up, which included lupus anticoagulant, dilute russell viper venom time, anticardiolipin IgG and IgM, and beta-2-glycoprotein IgG and IgM antibodies, was negative. Testing for platelet factor 4 (H/PF4) antibodies using IgG-specific enzyme immunoassay (EIA) (Immucor) was strongly positive at 2.971 optical density (OD) units (normal range: <0.399 OD units). Subsequent serotonin release assay testing (BloodCenter of Wisconsin, Inc.) showed 100% release with low-dose heparin (0.1 U/mL) and 1% release at high dose heparin (100 U/mL), which was strongly consistent with the diagnosis of HIT.
The patient was continued on intravenous argatroban infusion and alteplase for approximately 36 hours. Alteplase was stopped on POD 14 due to platelet count and fibrinogen nadir of 14 K/mL and 152 mg/dL, respectively. The patient was also hemodynamically stable without vasopressors at this point. Repeat TTE postcatheter-directed thrombolysis demonstrated a modest improvement in RVSP and right ventricular systolic function and dilation. Unfortunately, on POD 16 the patient developed worsening neurologic exam with decreased alertness and right upper extremity weakness. CT of the head without contrast demonstrated left thalamic and parietal hematoma, scattered subarachnoid hemorrhage in the posterior left cerebral hemisphere, vasogenic edema, and mass effect with a 2 mm left-to-right midline shift without herniation. Due to the patient's intracerebral hemorrhage, argatroban was stopped, and a retrievable Denali inferior vena cava filter was placed via the right femoral vein. Argatroban had been within therapeutic range except for one supratherapeutic level (101 s) 24 hours prior to the onset of neurologic symptoms and alteplase had been stopped for 36 hours. Neurosurgical intervention was not felt to be beneficial in this situation. Instead, the platelet transfusion threshold was increased to 50 K/mL. She remained off anticoagulation therapy over the following 7 days. Her Hgb stabilized to 9.0 g/dL and her platelet count continued to improve to 148 K/mL on POD 22.
The neurosurgery service felt comfortable restarting anticoagulation therapy at a prophylactic dose 1-week postintracranial hemorrhage, on POD 23. As there was no suitable alternative low-dose or prophylactic anticoagulants approved for HIT, a discussion with the patient and family was initiated regarding the risk of intracranial hemorrhage with resumption of therapeutic anticoagulation therapy versus the risk of recurrent thrombosis off anticoagulation therapy.
With the patient and family's consent, intravenous argatroban infusion was restarted with a lower aPTT goal of 45–60 s. Over the following two weeks, she remained neurologically stable, with no further evidence of bleeding on repeat radiological imaging. Her platelet count continued to improve to 198 K/mL on POD 28. At this time, she was bridged to warfarin in preparation for outpatient anticoagulation management. There were concerns about compliance with warfarin monitoring and significant difficulties titrating her warfarin dosing over the next 2 days due to the effect of argatroban on International Nationalized Ratio (INR) levels. Given this, she was switched to apixaban 5 mg twice daily on POD 30 with platelet count of 188 K/mL and discharged to complete 3 months of therapy with recommendations to follow up with her local primary care physician. Unfortunately, the patient was lost to follow-up and long-term outcomes regarding further thrombosis or hemorrhage were unable to be monitored.


A 58-year-old woman with no oral complaints visited our dental surgery for a routine check-up.
Chronic periodontitis was detected, associated with mobility of the left permanent mandibular first premolar. The orthopantomogram only showed a small radiolucent area adjacent to the dental element (). The patient's history only included hypertension with the use of an ACE inhibitor and a diuretic drug. The tooth was extracted and the patient was seen again three months later to evaluate the bone healing process, with a view to fitting a dental implant after a full dental-hygiene program. The CT scan revealed the presence of a radiolucent cyst-like lesion in the mandible with thin expanded buccal cortical plate and localized erosion and a polylobate appearance on the lingual aspect of the cortical plate (Figures –). The left permanent mandibular second incisor and canine gave a negative result during pulp testing. The teeth were extracted and the bony lesion underwent thorough curettage.
The histological description of the sample reported the presence of an aggressive lesion with widely distributed giant cells (Figures –). Moreover, several giant cells displayed scattered cannibalistic processes, in the absence of bizarre figures like those reported in complex cannibalism of OSCC (Figures and ).
The pathologist provided the diagnosis of central giant-cell granuloma (CGCG).
Nevertheless, another X-ray carried out six months later revealed multiple bilateral radiolucencies throughout the jaw, in both the molar and the premolar regions. In addition, widespread cortical plate erosion was observed and the left permanent mandibular first molar showed signs of root resorption, while the right permanent mandibular second molar showed periodontal ligament enlargement. There was no sign of neurological involvement, although the nerves appeared to be dislocated (Figures –).
Given the latest clinical and radiographic presentation of the lesion, several pathological entities were considered for differential diagnosis.
KCOT is associated with frequent multiple relapses of the lesion after unsuccessful complete curettage, but the histological predominance of giant cells within the pathologic tissue excluded this hypothesis [].
The same consideration was made as regards an aggressive variant of ameloblastoma, since its histological appearance is completely different, even if its radiographic behavior can be similar [].
Aneurysmal bone cysts may contain many giant cells but show far more cellular pleomorphism, hyperchromatism, and a variety of other cells often of indeterminate appearance [].
Fibrous dysplasia may present some giant-cell foci, but its radiographic appearance, histological features, and behavior are distinctive [].
Giant-cell lesions can be present in Paget's disease, but in this case there was no sign of pagetoid bone [].
Osteosarcoma contains numerous giant cells but displays far more cellular pleomorphism, hyperchromatism, and a variety of other cells often of indeterminate appearance [].
Metastasis from a misdiagnosed primary malignancy could arise in the jaw, but this is rare and should produce neurological complications in the early stages, with more aggressive destructive behavior in the jaws and alveolar ridges. Histological analysis could be used to determine the primary tissue from which the malignancy originated [].
The multiple lesions described in Figures – required maxillofacial evaluation for surgery, but a decision was made to verify whether the pathology was limited to the mandible or whether other body areas were involved. As the patient had had X-rays of other areas of the body during the same period, they were collected together and compared.
MRI and CT scans of the patient's left knee revealed the presence of a cyst-like, polylobate lesion in the kneecap, with regular borders, cortical thinning, and localized erosion (Figures and ). The radiologist affirmed that the lesion was very similar to those discovered in the mandible. Furthermore, chondrocalcinosis was noted in the right shoulder. The patient reported asthaenia, muscular tension, and mild depression. It was advisable to complete the head examination by prescribing an X-ray of the cranial vault, which showed multiple osteolytic areas with a salt-and-pepper appearance ().
A full blood chemistry analysis, including a full range of bone metabolism parameters, was prescribed. The alkaline phosphatase levels were found to be raised (374 U/L) and mild anaemia was present (RBC 3.51 106/μL; Hb 10.1 g/dL; HCT 31.6%). However, the most important alterations involved the parathormone (PTH 1014 pg/mL) and calcium (13.1 mg/dL) levels ().
With this data, the final diagnosis was brown tumors, with suspected primary hyperparathyroidism. Due to hypercalcemia, the patient was admitted immediately and underwent perfusion with saline water to prevent the risk of complications to the neurological and cardiovascular districts. Once hypercalcemia was treated, a neck ultrasound revealed the presence of a nonhomogeneous tumefaction involving the left inferior parathyroid gland, while the other glands were normal in size and trophism. This finding ruled out the presence of primary parathyroid hyperplasia. Primary hyperparathyroidism is often associated with adenoma, but also a functional carcinoma could not be ruled out until histopathological evaluation.
General surgeons proceeded to remove the parathyroid lesion, which received a histopathological diagnosis of atypical parathyroid adenoma (Figures –).
Another two orthopantomograms carried out 4 months and 2 years later, respectively, showed advanced and complete healing of the bony lesions in the mandible (). The patient was able to avoid maxillofacial surgery with resection, which would not have resolved the problem, since the origin of the condition was primary hyperparathyroidism.


A 41-year-old active woman with no particular history presented with left breast carcinoma tumor in 1987. Biological and radiological clinical assessments had revealed no distant extension.
The patient underwent a surgical treatment of Patey technique in the left breast with axillary dissection. The anatomopathological study revealed that it was an invasive galactophoric adenocarcinoma and five to 23 positive nodes were detected. Four cycles of adjuvant chemotherapy with cyclophosphamide, doxorubicin, and 5-fluouracil were administered.
Seven years following the chemotherapy, a nodule appeared on the intervention scar. The biopsy confirmed a local recurrence of breast cancer. After a staging that was featureless, radiotherapy targeting the chest wall, the collarbone, and armpit with a dose of 45 Gy for five weeks was performed. Hormone therapy with tamoxifen 20 mg per day was administered.
Two years after the treatment, the patient developed a significant lymphedema of the left arm, starting from the wrist and reaching the left shoulder, which required regular sessions of lymphatic drainage. 20 years after the appearance of the left mammary neoplasia and the occurrence of chronic lymphedema of the left arm, a burn of second degree appeared on the affected limb. A local treatment was administrated.
In September 2007 (one month after healing), the patient began to complain about a small hard erythematous-violet nodule at the rear and upper side of the left arm and reaching the posterior brachial region. They increased and became more painful and had a hard-bloody consistency on contact causing total functional left upper limb impotence (Figures and ).
The patient was hospitalized for additional tests following a radiography of the left arm showing significant swelling of the soft tissues. An exam of the biological tumor markers (CA 19-9) indicated that those were in range. An ultrasound of the soft tissue showed a significant subcutaneous edema. A computed tomography scan revealed a member with a fluid collection under fascial muscular near the lower third of the humerus and diffused a thick septa anterosuperior arm (), while an upper limb MRI showed the presence of a nodular formation in fatty tissue of the lower third of the arm ().
A biopsy of the soft parts of the upper limb and brachial region was performed and the histological analyses confirmed the diagnosis of cutaneous angiosarcoma of chronic lymphedema. Immunohistochemistry indicated the vascular nature of the tumor thus eliminating the diagnosis of cutaneous metastases. Following this diagnosis, a complete staging was performed. The abdominal ultrasound and thoracoabdominal and bone scans revealed no remote extension. A radical decision was made including a dislocation of the left shoulder followed by two cycles of chemotherapy. The evaluation marked alteration of the general condition and dyspnea related to tumor spread in the lungs (pleurisy abundance). The histological tests revealed metastatic character of angiosarcoma. In April 2008, approximately eight months after the start of symptoms, the patient developed multiorgan failure that resulted in her death.


We report a 31-year-old female patient, from São Mateus (ES) that presented to
the emergency room of University Hospital Cassiano Antonio Moraes (HUCAM) in
Vitória (ES) with extensive severe ulcerative-necrotic lesions involving the
abdomen, upper and lower limbs. Lesions first appeared on the legs one year before
with vasculitis diagnosed at another hospital. Treatment consisted of prednisone
80mg/day, progressing to remission. The daily use of the medication continued for
four more months, and after she dropped out the treatment.
The patient reported a 2-month history of worsening of skin lesions, glycemic
decompensation and signs of secondary infection. She was referred to the emergency
room of HUCAM for investigation. On admission, the patient was in a bad general
state, pale, and febrile (38.2° C). Dermatological examination revealed extensive
aspect of shallow polygonal ulcers with fibrinonecrotic base and irregular
erythematous edges, mostly present on the limbs and less frequently on the abdomen
and face. Bilateral necrosis on the ear, elbows, buttocks and toes was identified.
The left ankle revealed tendon exposure ( and ).
Laboratory tests showed anemia (hemoglobin: 8.6 g/dL; hematocrit: 27.2%; MCV:
71.4fL); normal white blood cell count (9760/mm³; bands: 5%); high levels of
C-reactive protein (206mg/L); negative serology for viruses B, C and HIV; VDRL 1:4;
negative FAN, anti-ENA and anti-DNA; Normal C3 and C4; positive results for IgM
anticardiolipin (234,8GPL-U/ml); and negative IgG.
After considering the hypothesis of LP, we performed a biopsy of the edge of an ulcer
on the right thigh. Histopathology revealed superficial and deep inflammatory
perivascular lymphohistiocytic infiltrate, with Virchow’s cells and vascular
thrombosis, bacilli on the lumen, on the vessel wall and invading endothelial cells,
BAAR 6/6+, globi 3/3+, confirming the diagnosis of LL with LP ( and ).
The patient received clinical care, was treated with antibiotics (meropenem and
vancomycin), underwent chemical and surgical debridement of the lesions, and was
submitted to multibacillary multidrug therapy (MDT-MB) associated with
pentoxifylline. We observed significant improvement of skin lesions 45 days after
the start of treatment ().


We report a 29-year-old female patient who presented with asymptomatic hypopigmented
macules on her upper limbs since she was four. She reported that the macules become
more visible when the arms hang down and disappear when the arms are raised ( and ). Complementary exams revealed iron deficiency anemia, positive
ANA-Hep2 (1/160) with a fine speckled pattern, and low levels of protein C (57.1)
(reference value: 70-140). Beta 2 microglobulin, anti-ENA, anti-native DNA, syphilis
serology, cryoglobulins, anticardiolipin, PCR, and metabolic panel were all
normal.