A 52-year-old Chinese man presented with a history of diarrhea lasting 10 months (5–6 episodes per day, with liquid yellow stools). He gradually lost his appetite, felt sick when eating fatty foods, and had substantially reduced his food intake.
About 50 days after the onset of diarrhea, skin hyperpigmentation and atrophy of the fingernails and toenails began to appear. All the symptoms continuously increased. The findings of upper gastrointestinal endoscopy performed in the hospital suggested hypertrophic gastritis with extensive erosion. The patient demonstrated substantial weight loss (about 23 kg) since disease onset.
The patient was previously healthy, and he had no family history of gastrointestinal polyposis. In the past half year, a cauliflower-like neoplasm was observed around the anus, of approximately 1.0 cm in size initially, which grew rapidly to more than 2 cm in the past 2 months.
The patient appeared emaciated. Physical examination findings included a sunken abdomen, systemic cutaneous hyperpigmentation (mainly on the hands, feet, and forehead), and apparent atrophy of the fingernails and toenails. A cauliflower-like bulge (2.5 × 2.0 cm) with a soft texture and congested surface was seen outside the anus (Fig. )
Laboratory tests revealed that the patient's white blood cell count was 8.50 × 109/L, hemoglobin was 160 g/L, and the platelet count was 343 × 109/L. The fecal occult blood test was positive (++). Serum albumin was 27.8 g/L, and the globulin was 21.8 g/L. Antinuclear antibodies were all negative. The erythrocyte sedimentation rate, C-reactive protein, immunoglobulin, complement system, and other immunological indicators were all normal.
Abdominal computed tomography indicated uneven gastric wall thickening. Upper gastrointestinal endoscopy revealed that the esophageal mucosa was smooth without any polyps, but there were diffusely distributed 0.3-1.5-cm polyps in the gastric cavity. These were mainly flat polyps, mixed with some semi-pedunculated polyps, with significant hyperemia on the surface. The polyps in the antrum and gastric body showed a carpet-like distribution, and normal gastric mucosa was rarely seen (Fig. ). Colonoscopy revealed hundreds of polyps (0.2–2.0 cm in diameter) scattered throughout the terminal ileum, colon, and rectum. Marked vascular congestion was found on the surface of these polyps. The polyps in the ileocecal junction and the proximal part of the ascending colon were distributed in clusters. The ileocecal valve was not normal-shaped and was covered by hundreds of polyps of different sizes (Fig. ). Single balloon enteroscopy via the transoral and transanal approaches showed scattered polyps (0.3–1.2 cm in diameter), which were more densely distributed in the duodenum, proximal jejunum, and terminal ileum. Capsule endoscopy magnification revealed that the intestinal villi were hyperplastic, prolonged, and presenting a seaweed-like appearance (Figs. and ).
The histopathological findings of the stomach, colon, and small intestinal polyps were consistent, showing irregular, distorted, cystically dilated glands, lamina propria edema, multiple chronic inflammatory cell infiltration, chronic inflammatory cell infiltration, and eosinophilic granulocyte infiltration. After perianal tumor resection, pathology suggested that this was a perianal condylomatous lesion with malignant transformation, as well as well-differentiated squamous cell carcinoma. No tumor involvement was observed on the incisal margins (Fig. ).
The patient presented with diffuse gastrointestinal polyposis, accompanied by alopecia, hyperpigmentation, and onychatrophia. All these symptoms were consistent with the diagnosis of CCS.
Treatments included glucocorticoids (methylprednisolone 40 mg IV qd, which was gradually reduced to 30 mg PO), glutamine to protect the intestinal lining (3% alanyl glutamine 50 ml IV qd), and fat emulsion, amino acids, and glucose injection solution for nutritional support.
After about 3 weeks of treatment, the diarrhea and anorexia improved significantly, and the patient's body weight increased by 2.5 kg. At present, the patient has been followed up for 4 years. The patient was glucocorticoid-dependent: when the dose of methylprednisolone decreased to less than 20 mg/d, anorexia, diarrhea, and other clinical symptoms recurred. Thus, azathioprine (1.5 mg/kg/day) was added as a combination treatment and was effective in controlling the symptoms. At present, the hormone has been discontinued and azathioprine (1.0 mg/kg/day) continues as maintenance therapy. His body weight had increased by 13 kg (compared to the weight at hospitalization), and there has been no recurrence of the perianal lesions after resection.


A 47-year-old Caucasian female, gravida 4 para 4 (two normal deliveries and two cesarean sections), came to the Emergency Department for severe vaginal bleeding in the past 48 hours associated with syncope and hemodynamical instability. She had been complaining of intermittent menometrorrhagia over the past year that was attributed to a polyfibromatous uterus visualized on abdominal ultrasound, but the patient had declined all medical and surgical treatments. Two years prior to this event, she had a non-complicated hysteroscopic myomectomy for a 4 cm intracavitary myoma with no malignancy at the pathology.
Upon admission, the patient appeared pale but responsive with a pulse of 105 bpm, blood pressure (BP) 130/80 mmHg, and a hemoglobin value of 5.6 g/dL. Clinical examination revealed an enlarged uterus with a 6-7 cm firm non-sensitive mass protruding from the cervix. Transfusion was initiated upon the patient's initial refusal of a surgical treatment along with anti-fibrinolytic treatment to stop the bleeding. A pelvic MRI enhanced with gadolinium was interpreted with caution as it showed a 12.8 x 10 x 9.5 cm uterus presenting an unusual bell shape with a highly vascularized 11 x 7.9 x 6.6 cm intracavitary lesion (most probably a leiomyoma) that was protruding through the cervix (Figure ). Despite adequate medical treatment and receiving six packs of red blood cells, the bleeding couldn’t be stopped and her hemoglobin level remained at 7.3 g/dL. The patient finally consented to a total abdominal hysterectomy after discussing other possible conservative surgical management. The surgery uncovered an enlarged polyfibromatous uterus with a fundus collapsed in the middle creating a gap and grasping the right adnexa. The vagina, on the other hand, was elevated around the uterus creating a turtle neck (Figure , ). Surgery was difficult as the anatomical landmarks were markedly distorted; ureteral dissection was carried out by an experienced urologist to avoid any accidental lesion. Upon completion of the hysterectomy, the uterus unfolded spontaneously revealing the uterine inversion that had distorted its aspect on MRI. The pathology examination, along with a reconstitution of the uterine inversion, revealed that two side-by-side submucosal fundal leiomyomas measuring 5.5 and 2 cm each had collapsed the fundus and protruded partly from the cervix, therefore leading to a chronic, non-puerperal uterine inversion. These leiomyomas had hemorrhagic modifications due to ischemic necrosis; no evidence of malignancy was found.
During her hospitalization, the patient received a total of 10 packed red blood cells (PRBC) and two fresh frozen plasma (FFP). She made a full uneventful recovery and was discharged home on day four.
This case was submitted to our institution's ethics committee for approval and was registered as CEHDF-1137.


A 66-year-old Macedonian male presented with symptoms of constipation and blood in the stool (hematochezia) for 3–4 months before seeing a gastroenterologist. Review of his medical records revealed no family history of note. The outer anal examination revealed old thrombosed hemorrhoids, and endoscopy revealed an obstructive neoplastic mass located 5–7 cm from the anus. The tumor tissue showed diffuse ulcerations and bled when touched. Eight biopsy specimens were taken for pathohistological examination. The diagnosis of mucinous AC with signet ring cells was made. Radiographic examination showed no pathological findings in the liver, pancreas, spleen and lungs, but revealed a tumor mass in the left lower kidney pole with infiltrating border that caused compression to the collector system. Preoperative computed tomography confirmed synchronous tumors in the kidney and rectum (Fig. ). The patient was admitted to the University Clinic of Abdominal Surgery in Skopje for surgical treatment. Laboratory tests showed elevated values for the enzymes lactate dehydrogenase (612 U/L), alkaline phosphatase (387 U/L) and C-reactive protein (up to 45.7 mg/L). A medial laparotomy was performed, with surgical resection of the anterior rectal area, simultaneously with left nephrectomy. Carcinosis in the small pelvis was observed.
Tissue samples were analyzed at the Institute of pathology, Faculty of Medicine in Skopje. Gross rectal examination of tissue specimens showed a rectal tumor measuring 5.5 cm infiltrating into the perirectal fat. The kidney contained a yellowish round tumor measuring 5 cm, with necrosis and hemorrhage. The adrenal gland was slightly enlarged into perirenal fat. The tissue specimens were fixed in formalin, embedded in Paraffin and routinely stained with hematoxylin & eosin stain. Microscopic analysis revealed PSRCCR with nodal metastasis, lymphatic and vascular tumor emboli and uncommon metastasis to synchronous RCC and to the adrenal gland (Fig. ). The tumor was classified as Stage IV according to the pTNM/UICC staging system. All specimens were analyzed immunohistochemicaly with CK20, CDX2, vimentin, RCC, E-cadherin and the mismatch repair (MMR) proteins MLH1, MSH2, MSH6 and PMS2. Signet ring cells were positive for CDX2 and CK20 (Table ). The absence of expression of E-cadherin in the metastasized cells indicated that they were the same as those in the primary carcinoma (Fig. ).
There was nuclear expression only of MMR protein MSH6, whereas the MMR proteins MLH1, MSH2 and PMS2 showed loss of the nuclear signal (Fig. ). Therefore, the tumor was further analyzed molecularly using the ABI 310 DNA analyzer (Applied Biosystems, Foster City, CA, USA), which revealed a microsatellite stable (MSS) tumor. Molecular analysis showed mutations in TP53 and ERBB2, as determined by next-generation sequencing of AKT1, BRAF, EGFR, ERBB2, FOXL2, GNA11, GNAQ, KIT, KRAS, MET, NRAS, PDGFRA, PIK3CA, RET and TP53. The patient died a few months after surgical treatment.


A 56-year-old man with a history of a WHO grade II astrocytoma for which a right posterior temporal lobe resection (without 5-ALA as it had not yet been approved in the United States) had been performed 15 years previously at another institution presented with an episode of left arm stiffening, aphasia, and altered mental status that was concerning for a new-onset seizure. Magnetic resonance imaging (MRI) studies demonstrated an enlarging mass with enhancing foci adjacent to the previous resection cavity, likely representing tumor recurrence and malignant transformation (Figure ). He was referred to our institution for further management, and surgical resection was recommended.
The patient underwent a repeat right temporoparietal craniotomy. In accordance with the hospital protocol, he was given oral 5-ALA (GleolanTM NX Development Corporation, Lexington, KY, USA) at the standard dose of 20 mg/kg three hours preoperatively, which successfully yielded tumor fluorescence when viewed with the specialized blue filter on the operative microscope (Zeiss Pentero microscope, Carl Zeiss Meditec, Inc., Dublin, CA, USA) (Figure ). The tumor was resected until the surgeon felt that maximal resection had been achieved. To confirm this extent of resection, intraoperative MRI (iMRI) studies were obtained using a 1.5 Tesla movable iMRI device (IMRIS, Inc., Minnetonka, MN, USA). These images demonstrated resection of all enhancements with minimal residual T2/fluid-attenuated inversion recovery abnormality in the posterior aspect of the resection cavity, which was subsequently resected prior to closure. The patient tolerated surgery well with no new neurological deficits and was discharged on postoperative day two. Surgical pathology confirmed a WHO grade III anaplastic astrocytoma with an isocitrate dehydrogenase 1 R132H point mutation, and the patient was referred for chemotherapy and radiation therapy.
During his hospitalization, in the early postoperative period, the patient developed mild diffuse erythema of his skin, including on his extremities and torso. The intensity of the erythema was most severe on the right side of his head and neck where there was associated blistering and peeling of the skin in a distribution defined by the region of the surgical field (Figure ). Notably, the right side of his head and neck were the only areas of his body that had been exposed to the intense surgical lights (Berchtold Chromophare halogen lights, Stryker, Kalamazoo, MI, USA) in the operating room. Similar erythema and blistering was not observed on any other part of his body, including the left side of his head and neck, which had remained covered during surgery. He had not been exposed to any sources of natural light during his hospitalization and had been kept in a dark room postoperatively. No reddening of skin had been observed before surgery. He had no renal disease that may have compromised excretion of 5-ALA. The blistering on his head and neck persisted until his one-week postsurgical follow-up visit. He never experienced fever, rashes, or other symptoms during this time period. He treated the blisters with over-the-counter lotion and they resolved uneventfully over a few weeks. Consultation with dermatology was recommended to the patient, but he did not pursue it as the skin changes were resolving spontaneously.


A 16-year-old girl was admitted to the hospital with a 6-month history of left cervical lymphadenopathy. At the beginning of the disease, the lymph nodes were painless with 0.5 cm size, but over time, they became mobile, rubbery, painful, and larger (About 2.5 cm) (Figure ). Three months after initial of symptoms, she had frequent fevers, night sweats, myalgia, and weight loss. One month later, the patient complained of hair loss and erythematous plaques on the face, limbs, and hands (Figure ). The patient did not have any history of autoimmune or infectious disease before symptom onset.
Complete blood count showed elevated erythrocyte sedimentation rate (ESR, 98 mm/h), lactate dehydrogenase (LDH, 865 IU/L), and C-reactive protein (CRP, 25 mg/dL). On the other hand, white blood count (WBC, 3600/mcL), red blood count (RBC, 3.3 million/mcL), hemoglobin (HB, 9 g/dL), and hematocrit were decreased. Immunoassay for autoimmune disease was 50 IU/mL for antidouble stranded DNA (anti-dsDNA) and 1/1000 titer for antinuclear antibody (ANA). Serology test was negative for rheumatoid factor (RF), human immunodeficiency virus (HIV), and hepatitis B and C. Blood culture to detect bacteria, fungi, or other common germs was also negative.
A core needle biopsy was performed from a 0.7 × 0.7 × 0.1 cm cervical lymph node under ultrasound guided. Immunohistochemistry assessment revealed cores of lymphoid tissue with well-defined paracortical necrotic lesions with nuclear debris. In addition, there was no infiltration of polymorphonuclear (PMN) leukocytes or plasma cells in microscopic examination (Figure ). The diagnosis of Kikuchi-Fujimoto disease (KFD) was made for the patient.
The patient was initially supposed to be given prednisolone, but due to fever and cough, prednisolone was refused. The patient was re-admitted, and after PCR test, she was diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The patient underwent supportive treatment, and interestingly after 7 days, the cervical lymphadenopathy and skin rashes significantly improved (Figure ).


We present the case of a 70-year-old male patient, with proximal weakness of the upper limbs for several years, who came to the Neurology Department of our hospital for gradual worsening of the weakness. Two months prior to the presentation, he experienced weakness of the lower limbs with important gait disturbance and frequent falls. The patient had no significant medical history or long-term treatment.
On the clinical examination (Figure ), we observed bilateral muscle atrophy of the shoulder girdle, a kyphoscoliotic spine, and varicose veins in the lower extremities. The oxygen saturation level was 98%, blood pressure was 120/85 mm Hg, and the heart rate was 63 beats per minute.
According to the Medical Research Council Scale (MRC), the neurological clinical examination revealed the following values of muscle strength as presented in Table .
Deep tendon reflexes were generally absent in the upper limbs, but present in the lower limbs.
Abdominal reflexes were depressed on the left side, and the Babinski sign was present bilaterally. There was also a tactile exteroceptive hypoesthesia in the upper left limb with occasional paresthesias, and also urinary incontinence. Moreover, the patient described muscle fasciculations of the upper limbs in the recent history. Cranial nerves were normal, and no family history of neurodegenerative disorders was described.
To rule out a peripheral nervous system pathology, we performed nerve conduction studies (NCS) in the upper and lower limbs, with normal parameters (latency, amplitude, motor and sensory nerve conduction velocity) for all the nerves (Table ).
A needle EMG (electromyography) was also performed in bilateral biceps brahii, left deltoideus, brachioradialis, first bilateral dorsal interossei, vastus lateralis, and anterior left tibial muscles suggesting a chronic, slow evolutive neurogenic pattern.
Considering the patient's clinical signs, phenotype, age and because cervical myelopathy is widely spread among elderly, being one of the most important ALS mimics, we performed a cervical spine MRI. The nonenhanced MRI (Figure ) demonstrated the following: C2-C3 circumferential disk protrusion, without obvious dural or root conflict, C3-C4 posterior disk hernia, approximately 8 mm, with significant compressive spinal cord suffering and bilateral root conflict and stenosis of the spinal canal of about 70%, C4-C5 left posterolateral intraforaminal and extraforaminal disk herniation, of about 5 mm, with dural contact, left root conflict and spinal canal stenosis of about 40%, C5-C6 circumferential disk protrusion, with dural contact, bilateral root conflict, spinal canal stenosis of about 50%, and microinjuries associated with diffuse spinal edema in the C2-C5 segment.
A head CT was also performed for the exclusion of brain lesions describing cerebral atrophy, with no other pathological findings.
The laboratory studies showed hypoproteinemia (6.31 mg/dL) and hypoalbuminemia (3.49 g/dL) with no other significant findings. A urine culture was also performed to exclude a urinary tract infection, with a negative result.
Based on the electrodiagnostic (EDX) studies and MRI, a positive diagnosis of severe polydiscopathic compressive cervical myelopathy was confirmed.


A 65-year-old man presented with a 6.5 × 4.5-mm, symmetrical, well-circumscribed, non-pigmented, deep-red papule surrounded by an indented moat with collarette scales, on the right thigh (Figure ). The patient had experienced trace bleeding and painful eruption 3 days prior.
Dermoscopic examination revealed milky-red globules and chalice-like vessels surrounded by a well-circumscribed hyperkeratotic rim showing a white double–ring configuration due to thick scales. In the collarette, a whitish-pink ovoid nest and translucent-brown globules representing poorly visualized chalice-like vessels were observed (Figure ). Chalice-like vessels were classified as branched vessels with rounded, looped, or coiled terminal endings and characteristic rounded silhouettes.
Histological examination revealed sharply circumscribed, small cuboidal epithelial cells with monomorphous ovoid nuclei and compact eosinophilic cytoplasm. Cytoplasmic vacuoles were observed. The lesion was a poroid neoplasm mainly on the dermis, although it slightly extended to the epidermis as well. The surrounding stroma was edematous with dilated vessels of various sizes. The area of the tumor showed parakeratotic hyperkeratosis with crusting, and the granular layers had thinned or disappeared (Figure ). At the lesion boundary, epithelial invagination was noted. Orthokeratotic hyperkeratosis, hypergranulosis, and irregular epidermal hyperplasia were observed in the skin tissues surrounding the tumor. At the boundary where epithelial invagination was noted, fissures and tearing of the thickened stratum corneum were visible. Invasion and anastomotic images of the tumor nest were identified outside the epidermal invagination, and the surrounding stroma was mildly edematous with poorly visualized vessels (Figure , A-D). A tumor tissue specimen was cut vertically, and four collarette parts at both ends were examined as histopathological images.
A clinical diagnosis of EP was made, and surgical resection of the affected tissue with a 2-mm margin of normal tissue was performed. Written informed consent was obtained from the patient for the use of the tissue samples in this study.
The final diagnosis based on histopathological findings was EP, which was completely curatively resected. The postoperative course was encouraging, showing no evidence of a local recurrence. At present, 1 y after the operation, no findings suggesting a recurrence have been recognized and careful postoperative follow-up is planned.


Our patient is a 33-year-old Honduran female with poorly-controlled diabetes (hemoglobin A1c of 9.5% to 11%), diagnosed at the age of 8, requiring multiple hospitalizations secondary to diabetic ketoacidosis (DKA) with findings of elevated aminotransferases []. Her medical history is notable for severe gastroparesis, requiring endoscopic botox injections, recurrent pancreatitis of unknown etiology, and hypothyroidism. Her surgical history was significant for cholecystectomy done in her mid-20s. In terms of her social history, she had denied any alcohol use, smoking, or usage of any recreational drugs. There was no known family history of any gastrointestinal pathology.
At the age of 25, the patient had initially presented with dyspepsia, early satiety, and diarrhea that required her to obtain an endoscopy demonstrating gastritis but with no other abnormal findings otherwise. During that time, she required a five-day hospital stay due to noted abnormal liver tests that were attributed to gastroenteritis at that time, as the patient had no history of alcohol abuse, no evidence of cholelithiasis, and a negative hepatitis panel. During her mid-20s, the patient was found to have numerous hospital admission secondary to DKA, at which time the patient was found to have erratic blood sugars (40s-500s) with an endocrinologist closely following her case. Her diabetes was being treated with both Tresiba (insulin degludec) and inhaled insulin, Afrezza. It was at this time that she was also found to have significant elevations in her liver tests, which consisted (at their highest) of an aspartate aminotransferase (AST) of 7,184 U/L (reference: 8-48 U/L), alanine aminotransferase (ALT) of 650 U/L (reference: 7-55 U/L), and alkaline phosphatase (ALP) of 443 U/L (reference: 40-129 U/L). Physical exam demonstrated hepatomegaly, which was confirmed on CT. She continued to present to the hospital numerous times with these flares, found to have fluctuations in both her blood glucose levels and aminotransferases. Other imaging, such as an abdominal ultrasound during these times had demonstrated fatty liver with an atrophic pancreas. She also had had multiple endoscopic ultrasounds and magnetic resonance cholangiopancreatography (MRCP) that demonstrated normal common bile duct (CBD). Due to this, the patient was tested for numerous other etiologies for the cause of these findings, including autoimmune hepatitis, infectious, ischemic, and drug-induced hepatitis, all being ruled out at this time. Some of these tests included a hepatitis panel, acetaminophen levels, ceruloplasmin level, alpha-1-anitrypsin level, anti-tissue transglutaminase antibody just to name a few.
Finally, after exhausting some of these diagnostic tests, our patient was sent for a liver biopsy for further evaluation and to definitively rule out an autoimmune cause for her condition. The liver biopsy, however, demonstrated glycogenotic hepatocytes with the patient subsequently being diagnosed with GH. Subsequent hospitalizations were due to abdominal pain, nausea, and vomiting secondary to gastroparesis and chronic pancreatitis. She continued to frequently obtain endoscopic Botox injections for her gastroparesis, as well as celiac plexus block for the alleviation of her pain due to pancreatitis. Her blood glucose levels remained better controlled during these later hospitalizations, with less frequent hypoglycemic episodes, which was reflected on her liver tests that appeared mildly elevated to almost normal. This improvement was additionally portrayed on repeat imaging done during one of the patient's later hospitalizations (Figures -).


A 18-year-old woman presented to our department with a 5-day history of diplopia and headaches. She had developed 15 days earlier a high-grade fever, and had been diagnosed as having typhoid fever and treated with fluoroquinolone. On examination, the patient’s best-corrected visual acuity was 20/20 in both eyes. Ocular motility examination revealed a left lateral gaze restriction (Fig. a and b). Lancaster test confirmed the presence of left abducens palsy (Fig. c). There was no relative afferent pupillary defect. The anterior chamber and the vitreous were quiet in both eyes. Intraocular pressure was normal bilaterally. Fundus examination showed optic disc swelling in both eyes (Fig. a and b). There also were a superotemporal retinal hemorrhage and a small retinal infiltrate with retinal hemorrhage in the nasal periphery in the left eye (Fig. b). Late-phase fundus fluorescein angiograms showed diffuse optic disc leakage in both eyes (Fig. c and d). Macular SD-OCT was unremarkable in both eyes. SD-OCT scan across the retinal infiltrate in the LE showed a focal area of inner retinal thickening and increased reflectivity with posterior shadowing (Fig. e).
Results of physical examination, including neurologic evaluation, were unremarkable. Laboratory work-up showed raised C-reactive protein (CRP), mild thrombocytopenia, and mildly elevated liver enzymes. Magnetic resonance imaging (MRI) of the brain and orbits showed no abnormalities. Rickettsial disease was suspected, and the serologic test for Richettsia Typhi was positive. The patient was treated with doxycycline (100 mg every 12 h) for 15 days. Symptoms rapidly improved, with complete resolution of diplopia and headaches. Two weeks after initiation of doxycycline therapy, ocular motility examination revealed recovery of the left lateral rectus motility (Fig. a and b). Fundus examination showed the complete resolution of optic disc swelling, retinal hemorrhages, and retinal infiltrate (Fig. c and d). Late-phase fundus fluorescein angiography showed the resolution of optic disc leakage in both eyes (Fig. e and f).


A 57-year-old woman with a medical history significant for coronary artery disease (a history of stent placement), hypertension, smoking, and hyperlipidemia had presented with a 1-day history of worsening abdominal pain. She also reported diarrhea, fever, and a chronic cough that exacerbated her abdominal pain. The initial laboratory test results showed a white blood cell count of 9.4 109/L, C-reactive protein of 4 mg/L, and creatinine of 0.8 mg/dL. An abdominal computed tomography (CT) scan revealed inflammatory changes surrounding an aortic abdominal aneurysm (AAA) measuring 3.8 cm × 4.3 cm (). She had no knowledge or history of the aneurysm before her presentation. She was also tested for COVID-19, with a positive test result. Given the presenting symptoms and the acute, inflammatory findings on the CT scan, the differential diagnosis was highly suspicious for an inflammatory or mycotic aneurysm. Blood cultures were obtained, and empiric antibiotics were started. She was admitted for management of her COVID-19 infection, with a vascular surgery consultation for evaluation and management of the AAA. On physical examination, she was moderately tachypneic and diaphoretic, with tenderness to palpation of the left abdomen and flank near the aneurysm region. Her pulses were 2+ palpable in the bilateral upper and lower extremities. During the next 3 days after admission, her abdominal pain progressed. Therefore, a follow-up CT angiogram was obtained. The repeated scan revealed a stable size aneurysm, with, however, increased surrounding inflammatory changes. There were also notably increased infiltrative findings of the right upper lung lobe, consistent with COVID-19 pulmonary manifestations. Given her worsening clinical physical examination, evidence of increasing inflammatory findings, and concern for the risk of rupture in the setting of hemodynamic stability, we decided to proceed with endovascular aneurysm repair (EVAR). Her COVID-19 illness was treated with hydroxychloroquine for 5 days, which was completed 4 days before she underwent EVAR.
On the day of surgery, the laboratory test results showed a white blood cell count of 10.9 109/L, C-reactive protein of 14.1 mg/L, and creatinine of 1.1 mg/dL. The hospital COVID-19 precautions included the surgical team and staff wearing N-95 masks and full personal protective equipment attire. The procedure was performed in a negative pressure outfitted room with one team inside and one team outside the room boundary to gather additional equipment. Intraoperatively, EVAR was performed in the standard fashion. The initial angiogram (, A) revealed the targeted region and appropriate size acquired. A 26 mm × 12 mm × 16 cm right-sided endovascular graft was deployed in the infrarenal aorta and right common iliac artery (, B). After placement of the left common iliac 14-cm excluder, a completion angiogram was performed, which showed satisfactory results (, C). Postoperatively, she had no hemodynamic instability and experienced immediate resolution of abdominal pain and tenderness. Blood cultures performed on hospital days 1 and 2 continued to show no growth, and the empiric antibiotics were stopped on postoperative day 5. She remained hospitalized for continued management of her COVID-19 pulmonary symptoms and was discharged on postoperative day 5 (hospital day 12).
A follow-up CT angiogram, performed at 6 weeks after surgery, revealed a successfully excluded aneurysm. The aortic stent was noted to be positioned appropriately, without evidence of an endoleak (). The previously noted inflammatory findings had resolved. On examination, she had completely recovered from her COVID-19 pulmonary symptoms and had no abdominal or flank pain.


This 44-year-old female presented with daily productive cough and expectoration for 4 years and experienced recurrence for more than half a year. The respiratory symptoms were predominantly nocturnal and more severe in the winter. She was diagnosed with chronic cough and was treated with cough medications for cough symptoms, which did not prevent the disease from worsening. Seven months prior, the chest film and spirometry test were almost normal; however, 4 months prior, the cough returned and the patient suffered from cough-related syncope for 3 h. She denied chest pain, chest distress, shortness of breath, heartburn, or acid regurgitation. She had no known allergies and denied smoking. The patient presented no abnormality on physical examination. White blood cell count, eosinophil count, and serum immunoglobulin E (39.1 IU/mL, normal value <100 IU/mL) were normal. Chest high-resolution CT (HRCT) (), pulmonary ventilation and single-breath diffusing capacity of the lung for carbon monoxide were normal. The methacholine challenge test for bronchial hyperreactivity was negative (). In pulmonary function testing, the forced vital capacity (FVC) was 2.99 L (100.9% of predicted value), the forced expiratory volume in 1 s (FEV1) was 2.45 L (96.5% of predicted value), and the FEV1/FVC ratio was 81.99% (). The patient's electrocardiogram (ECG) showed normal sinus rhythm with frequent premature ventricular beats (PVCs) (). The 24 h-Holter ECG monitor showed normal sinus rhythm with 27553 PVCs (). The frequent occurrence of PVCs was associated with repetitive coughing. Two-dimensional color echocardiography was normal except for trivial regurgitant flow (). Subsequent treatment with oral antiarrhythmic drugs was ineffective. Therefore, radiofrequency ablation of the arrhythmogenic focus was proposed. Surprisingly, cough disappeared after radiofrequency ablation, and no recurrence of arrhythmia or cough was observed ().


A 77-year-old man with severe aortic stenosis and persistent AFL was admitted for elective aortic valve replacement and concomitant surgical AFL ablation. Written informed consent for cardiac mapping (MEC-2015-274) was obtained prior to surgery.
Before induced cardiac arrest, a mapping array of 128 electrodes (interelectrode distance: 2 mm) was used to cover the epicardial atrial surface of Bachmann's bundle (BB), the right atrium (RA), anterior LA including the left atrial appendage (LAA), and pulmonary vein area. In addition, recordings of the endocardial right atrial septum were obtained.
U-EGMs, sampled at a frequency of 1000 Hz, were automatically analyzed offline and manually checked using customized software. Local activation times were defined as the steepest negative deflection of U-EGM potentials and used to reconstruct wavemaps during 10 seconds of AFL.
Subsequently, distribution of AFL cycle length (AFL-CL) and AFL-CL variability were assessed at all locations. Variability of AFL-CL is defined as standard deviation of the AFL-CL histogram.
In line with prior mapping studies, the proportion of lines of CB was calculated as the number of lines of CB (interelectrode conduction time > 11 ms) relative to the total number of interelectrode connections. A cut-off value of >11 ms was derived from prior mapping studies in which this degree of delay was associated with reversal of wavefront direction at the other side of the line of CB. Beat-to-beat consistency in patterns of activation was evaluated by comparing entry sites of the AFL wave and main direction of propagation in consecutive wavemaps for each location. Frequency of fractionated potentials, defined as electrogram potentials consisting of 2 or more negative deflections, were quantified as the number of fractionated potentials relative to the total number of potentials. As we previously demonstrated that fractionated unipolar potentials are caused by remote, asynchronous activation of the atrial wall,, , all deflections of fractionated potentials were annotated in a separate analysis to identify electrical asynchrony in deeper tissue layers.
Median AFL-CL ranged from 270 ms to 273 ms. The shortest (223 ms) and longest AFL-CL (321 ms) were both found at the superior part of the RA. AFL-CL variability per region ranged from 2 to 5 ms.
Lead II of the surface electrocardiograms depicted in the upper panel of shows the typical saw-tooth flutter waves that were present before and during cardiac surgery.
The arrows in the schematic presentation of both the RA and LA including BB in the middle panel of demonstrate direction of activation at all mapping locations. The main pattern of activation matches that of typical AFL, consisting of counter-clockwise activation of the RA and passive activation of BB and LA. This pattern of activation was consistent throughout the entire mapping procedure. Remarkably, both at the BB and the superior RA, the main pathway of the AFL wavefront is considerably curved.
Local activation time maps of these 2 sites are plotted in the lower panel. These maps show that the curvatures in wave trajectories were caused by long lines of CB, indicated by thick black lines. The proportion of CB lines is 20% at the BB and 15% at the high mid RA free wall. This is considerably higher compared to other atrial sites (5.1% at the posterior LA, 3.5% at the LAA, 0.2% at the LA apex, and 0.8%–4.5% at the remaining RA sites).
shows the frequency of single potentials at each electrode within every mapping location. Fractionated potentials predominantly occurred at the BB, the high RA, and the LAA. In contrast, from the inferior LA and lower RA mainly single deflections were recorded.
Patterns of activations of the BB and the high RA constructed by this mapping approach are shown in and , respectively. At the BB (), the first wavefront enters from the lower right border (the RA side) and propagates towards the upper border of the array, following a slightly curved trajectory. After 32 ms, a second wavefront appears in the lower left corner, then zigzags towards the upper border. The outline of this second wavefront can be also recognized as the line of CB in and as a transition zone from predominantly single to fractionated potentials in . Fractionation in this region was thus caused by a distinct, second wavefront propagating at deeper layers.
The pattern of activation at the high RA is even more complex, as multiple wavefronts propagate in opposite directions (). The right and left border of the mapping array are oriented towards the high and low RA, respectively. The first 2 wavefronts pass from the right to the left border, respectively, while the wavefront originating from the right border activates the majority of the mapping area. It propagates towards the left lower corner to activate the lower region for the second time. In the meantime, another wave enters from the upper left border and crosses towards the right border again, reactivating the upper part of the array. Annotation of fractionated potentials at this location thus also reveals the presence of different wavefronts activating tissue layers asynchronously; the very short delays (7–16 ms) between these consecutive wavefronts can, owing to atrial refractoriness, not represent reactivation of the same tissue. It is likely that electrical barriers between different strands of cardiomyocytes prevent transmurally asynchronous activation and give rise to different conduction corridors within the atrial wall.


The 11-month-old male patient was born at full term to non-consanguineous parents with no complications. His birth weight and height were both normal. He presented with poor motor development and muscle weakness that gradually progressed after birth. He began to raise his head in prone position when he was at 43 days old, and was able to kick frequently at 3 months old, but he was still unable to grasp his feet at 6 months old. Subsequently, he had decreased muscle strength in lower limbs with diminished tendon reflexes at 7 months old. He presented at our hospital with muscle weakness and delayed development. Before coming to our hospital, he had received rehabilitation exercise treatment at the local agency.
At the initial visit when he was 6 months old, we first performed neurological and physical examinations of the patient and found decreased muscle strength, especially in the lower limbs, which could not induce the tendon reflex. The remainder of his examination was normal. Next, clinicians evaluated his developmental level based on clinical manifestations. The patient did not reach the milestone for motor development of rolling over and could not sit straight or pronate alone. However, his cognitive development was normal, and he had no significant medical history.
We reviewed the patient's family history and found that he belonged to a Chinese family with four members of two generations, including two males and two females. None of the other three family members exhibited any clinical anomalies.
Furthermore, the patient's electromyogram (EMG) showed a large number of positive sharp waves and fibrillation. High-amplitude coupled with long-duration motor unit potentials (MUPs) were also found in examined muscles, including the tibialis anterior, peroneus, rectus abdominis, and deltoid. No sensory deficits were found in nerve conduction studies. All the above findings indicated motor neuron damage.
Muscle weakness is a chronic and progressive symptom often caused by neuromuscular transmission disorders. It occurs at an early stage with specific clinical manifestations, which has a special relationship with genetic factors. The various causes of muscle weakness can be divided into neurogenic diseases and muscular diseases; therefore, genetic testing, electromyography, and laboratory inspection are necessary for diagnosis. In this case, muscle weakness, poor motor development, and spinal cord anterior horn cell injury suggested the possibility of SMA, a genetic disorder of congenital muscle weakness that was common in infancy.


A 27-year old man presented to the emergency department with acute chest pain for 2 h. Blood pressure was 115/78 mmHg and heart rate 113/min. Heart and lung sounds were clear and radial and pedal pulses symmetrically palpable. Electrocardiogram (ECG) showed ST-elevation in leads II, III, avF, V4-V6 (Fig. ). The patient admitted consumption of alcohol, cannabis and N2O in the hours before symptom onset. His medical history was notable for Hodgkin-Lymphoma treated with curative radio-chemotherapy 3 years previously. Differential diagnosis of ST-elevations and chest pain in a young male include myocardial infarction due to a non-atherosclerotic origin (i.e. coronary embolism, cocaine induced vasospasm), spontaneous coronary artery dissection, peri-myocarditis, early repolarization, or pneumothorax. The patient was referred for urgent coronary angiogram, which revealed a thrombotic lesion in the proximal left anterior descending artery (LAD) (Fig. , panel A, white arrow; Additional File : Fig. S1; Additional File : Video S1). Intracoronary OCT yielded no plaque rupture, but adhesive non-occlusive predominantly white thrombi superimposed on a fibrous plaque, suggestive of plaque erosion [] (Fig. , panel B; Additional File : Video S2). Distal embolization of the thrombus material was suspected to be the correlate for the concomitant inferior ST-elevations observed on initial ECG. Left ventricular function was 55% with apical akinesia. Laboratory analysis yielded normal hemoglobin and thrombocyte count, normal INR, an alcohol plasma level of 1.7 per mill and newly diagnosed dyslipidemia (total cholesterol 5.3 mmol/l, low-density lipoprotein cholesterol (LDL-C) 3.9 mmol/l). High-sensitivity troponin T on admission was 180 ng/l and peak level 896 ng/l. Screening for anti-phospholipid syndrome was negative and urine toxicology confirmed the consumption of tetrahydrocannabinol, but was negative for other illicit drugs including cocaine. Transthoracic echocardiogram showed normal biventricular function, normal dimensions of all cardiac cavities, no thrombi, and normal valve function.
The lesion in the LAD was successfully treated with direct implantation of a XIENCE Sierra™ 4.0/18 mm drug-eluting stent and postdilatation with a 4.0/15 mm non-compliant balloon with good result on angiography (Fig. , panel C; Additional File : Video S1). Dual-antiplatelet therapy with aspirin long-term and the potent P2Y12 inhibitor prasugrel for 1 year, as well as high-intensity lipid lowering therapy, betablocker (IIaB recommendation []) and ACE-inhibitor (IIaA recommendation []) were initiated, in accordance with current recommendations []. The patient underwent lifestyle change counseling with emphasis on smoking cessation and information on the adverse effects of cannabis and N2O consumption. The course of hospitalization was uneventful and the patient was discharged to home after 48 h rhythm monitoring.
At 6-months follow-up, the patient reported good recovery after STEMI with no complaints of chest pain or dyspnoe. He had been actively engaged in an outpatient cardiac rehabilitation program 3 times per week and been able to abstain from drug consumption and reduce smoking (Table ).


A 48-year-old man without a significant past medical history was found to have an incidental upper abdominal tumor by abdominal ultrasonography at an annual health check. All laboratory examinations, including hemoglobin, albumin, pancreas enzyme, were within normal ranges. The carcinoembryonic antigen (CEA) concentration was slightly elevated as 4.6 ng/mL (< 2.5) without any smoking history. The carbohydrate antigen (CA19-9) concentration was within the normal range as 18 U/mL (< 37), as was DUPAN-2 (< 150 U/mL).
Ultrasonography showed two heterogeneous echogenic round contiguous masses, 5 cm in size each, at the region of the pancreatic head (Fig ). Abdominal computerized tomography (CT) confirmed these findings (Fig a), which were in-homogeneously enhanced, and invading into the superior mesenteric vein (SMV) (Fig b). Colonoscopy demonstrated a red, raised wheal with a minute ulcer in the transverse colon, indicating submucosal invasion of an extramural tumor (Fig ). Endoscopic biopsies revealed inflammation with no malignancy. Angiograms showed a hyper-vascular tumor fed by the right branch of the middle colic artery (Fig ). The SMV was poorly visualized and narrowed. The tumor was not fed from any pancreatic or duodenal arteries. Upper gastrointestinal endoscopy showed no abnormality, including the papilla of Vater. Magnetic resonance cholangiopancreaticogram (MRCP) showed no abnormality in the pancreaticobiliary duct.
The mass was diagnosed as a malignant submucosal tumor originating from mesenchymal cells in the mesentery of the transverse colon, which directly invaded the duodenum or pancreatic head based on CT and colonoscopy findings although endoscopic biopsies could not get the malignancy. The patient underwent exploration towards curative-intent surgery and found to have a tumor mainly located in the mesentery of the transverse colon, which invaded both the uncinate process of the pancreas and the transverse colon. To achieve en bloc R0 resection, a combined PD, right hemicolectomy, and segmental cylindrical resection of the superior mesenteric vein (SMV) with lymph node dissection were performed and reconstruction was done with Billroth-I (Imanaga) reconstructive technique involving the gastric remnant, pancreatic duct, and biliary tree in that order.
The resected tumor measured 9 × 7 × 6 cm. The cut section of the specimen showed a yellowish-white color with central necrosis. The tumor was mainly located in the wall of the transverse colon and colonic mesentery. Histological examination revealed that a large part of the tumor was poorly differentiated adenocarcinoma, and pleomorphic sarcomatous tumor cells were seen in the part of hemorrhagic necrosis, where the transition of carcinomatous to sarcomatous tumor cells was observed (Fig. a). The carcinoma component was exposed in the ulcer base of the colon (Fig. b). Immunohistochemically, the carcinomatous component was positive for CK7 (Fig. a), CK20, EMA, CDX2, AFP, and partly positive for vimentin. On the other hand, the spindle-shaped pleomorphic sarcomatous component was strongly positive for vimentin (Fig. b) and negative for CK7, CK20, EMA, CDX2, AFP, KIT, CD34, desmin, and S-100 protein. Based on, the histologic findings, and the immunohistochemistry results, the tumor was diagnosed as carcinosarcoma of the colon. Invasion of carcinosarcoma to the pancreas, duodenum, and SMV was not identified and just fibrous adhesion. Furthermore, there was no lymph node metastasis.
The postoperative course was uneventful. The patient received adjuvant chemotherapy with six cycles of 5-fluorouracil/leucovorin therapy based on the chemotherapy regimen for colon cancer. The patient has survived 18 years to the date after surgery with no recurrence.


A two-year-old boy of Palestinian-Lebanese descent was initially seen in our clinic at five months of age. His perinatal history was unremarkable except for high IRT levels (156) in newborn screening. His parents are distant relatives, and his siblings were normal. Sweat chloride was 124 mmol/L, and he had very low stool pancreatic elastase.
Based on this, CFTR mutation for 139 mutations was initially done in Germany, and it did not identify any disease-causing mutations. Clinical examination was unremarkable except for failure to thrive (less than the third percentile at initial presentation). He was started on an airway clearance regimen, pancreatic enzyme supplements, and fat-soluble vitamin supplementation. A routine cough swab at five months of age grew pseudomonas aeruginosa, which was treated with oral ciprofloxacin, and he was nebulized with tobramycin. Repeat cultures after eradication treatment were negative. Routine CF investigations were unremarkable except for mildly elevated aspartate aminotransferase (AST) (99 units/L). Chest X-ray did not show any abnormality, and ultrasound abdomen revealed a mild increase in liver size and prominent periportal tracts (Figure ).
Based on the clinical presentation and screening test results, a full CFTR gene (NM_000492.3) sequencing was done, which identified a novel frameshift variant, c.3623del, in apparent homozygosity. This variant was previously identified in the homozygous state in only one male patient with cystic fibrosis but was absent from large population studies such as the genome aggregation database (gnomAD) and the Greater Middle East (GME) Variome database. The child was subsequently followed up in our department at frequent intervals. He did not have any recurrent pulmonary exacerbations or pseudomonas regrowth. Pancreatic elastase was persistently low even after adjusting the pancreatic enzyme doses. At present, he is gaining weight (weight at 25th centile), has no recent pulmonary exacerbations, and is on a regular airway clearance regimen.


A 28-year-old male presented to the emergency department with left forearm pain following a riot-related ballistic injury 12 hours prior. The patient sustained the injury while engaged in an urban protest in light of the recent controversial death of Minneapolis resident George Floyd. As a part of non-lethal measures of riot control, the patient was hit in the arm with a wooden projectile fired from a police officer cannon (Figure ).
Standard clinical and radiographic workup determined that the patient had an isolated closed fracture of the ulnar diaphysis, more commonly known by its eponym, a “nightstick fracture” (Figures -). After ruling out any excessive compartmental pressure with clinical examination, the patient was determined to be in absence of any distal radioulnar joint or radial head instability that could have resulted secondary to this high energy injury. Fracture displacement and angulation were well within the acceptable tolerances, and the patient was placed in a short arm cast in neutral pronation/supination for a six-week immobilization period. Informed consent for participation in clinical research endeavors was obtained prior to the initiation of this publication.


A 45-year-old man, farmer by occupation, presented clinically with a slow growing, slightly tender, firm mass on the plantar aspect of left foot for 3 years, measuring 5×4×3 cm. There were multiple discharging sinuses covered with blood mixed purulent exudates. Radiograph showed features of osteomyelitis and soft tissue shadow. A tentative clinical diagnosis of tuberculous osteomyelitis was proposed. Imprint smears were made from the discharge and fine needle aspiration cytology (FNAC) was done using a 23-gauge needle, attached to a 10-ml syringe. Aspirate consisted of sero-sanguinous, pus like material. Alcohol fixed smears were stained with Papanicolaou (Pap stain), while air-dried smears were stained with May-Grünwald-Giemsa (MGG) stain. Simultaneously, Periodic acid Schiff (PAS), Gram’s stain and acid fast bacilli (AFB) stains were performed. Additionally, fungal and bacterial cultures were carried out.
Both FNAC smears and imprint smears comprised plenty of pus cells, some lymphocytes, histiocytes and foreign body giant cells in a necrotic background. Several brown to black colonies were seen. On higher magnification, these consisted of septate, branching fungal hyphae embedded in a cement-like matrix [Figures and ]. PAS stain highlighted the branching hyphae []. AFB and Gram’s stains were negative. The cytological diagnosis of eumycotic mycetoma was rendered with suggestion of Madura foot. The excised surgical specimen confirmed the diagnosis of eumycetoma. The fungal species was identified as Madurella mycetomatis on subsequent fungal culture.


A 46-year-old female smoker was admitted to the emergency department of our hospital due to cough with blood-tinged sputum for the last four days before admission. She did not complaint of any other symptom. Her past medical history was unremarkable. She denied any exposure to toxic substances and gave no history of handling dogs or having ever reared sheep. The physical examination revealed no specific findings and there was no sign of respiratory or cardiovascular dysfunction. Lung auscultation revealed a mild decrease in the intensity of breath sounds, whereas heart examination was completely normal, without extra sounds or murmurs. The electrocardiogram (ECG) was lacking remarkable findings. The patient had negative reaction of the Mantoux tuberculin skin test. Moreover, all routine laboratory test results, including liver and kidney function tests, serum proteins and urinanalysis were normal. The erythrocyte sedimentation rate was normal (ESR 12 mm/hr). Sputum specimens for mycobacteria and other pathogens were smear and culture negative. Serological tests for cancer or virus were negative but serology for echinococcosis showed an indirect immunohemagglutination test positive. Other autoimmune markers were negative. Chest x-ray depicted multiple calcified cystic formations (Figure ). A Multi-Detector Computed Tomography (MDCT) of the chest [] and abdomen identified localized bronchiectatic lesions of the right upper lobe, calcified spots at both the lung fields, probably from previous disease (chickenpox, tuberculosis or occupational disease), a low density solitary lesion with peripheral calcification located at the myocardium of LV (compatible with calcified echinococcus cyst) (Figure ) and other three similar but smaller findings were located at the liver. The CT scan of the brain showed no disease. No lung disease was diagnosed with the bronchoscopy. Transthoracic contrast echocardiography revealed a cyst-like echoluscent structure 5 × 2 cm, occupying the Posterior Wall of Left Ventricle (PWLV). It gave the impression of endomyocardial localization due to the decreased thickness of the PWLV (Figure ). The rest of examination was normal with an estimated ejection fraction of 60%, without regional wall motion abnormalities. Coronary angiography revealed normal coronary arteries.
Excision of the cardiac cyst was planned by using cardiopulmonary bypass and the patient received perioperative chemotherapy with albendazol 10 mg/kg. After a median sternotomy the patient was connected to the cardiopulmonary bypass by cannulating the ascending aorta and right atrium. The pericardial cavity was free of adhesions. Under condition of normothermic cardiopulmonary bypass the aorta was crossclamped and the heart was arrested with a dose of antegrade cold blood-based cardioplegia. The heart was lifted and the free surface of the cyst was seen as a white tense mass in the lateral wall of left ventricle (Figure ). By palpation, it was partially calcified. The lateral wall of the left ventricle was localized by gauzes irrigated by 10% NaCl solution. A small incision was made into the cyst corresponding its free wall, and a viscous sub-yellow fluid was aspirated. The sub-epicardial wall of the cyst was then excised and its contents were completely aspirated (Figure ). The cyst was then injected, first with 10 ml of 10% NaCl solution and then with 5 ml of povidone iodine solution, which was left inside for 3 min and then aspirated. The resultant cavity was then obliterated by a continuous 4-0 prolene suture (Figure ). To complete this obliteration, we avoided to use any prosthetic material such as pledgets, to prevent possible postoperative infection. After de-clamping of the aorta and de-airing of the heart, the patient was easily weaned off bypass with no inotropic support. Cytology of the aspirated cyst fluid and histology of the cyst wall was consistent with the diagnosis of hydatid cyst (Figure ). The patient had an uneventful recovery and at the fifth postoperative day she discharged from the hospital with a normal echocardiographic examination which confirmed preserved function of the mitral valve apparatus, with only minimal regurgitation.
Follow up at 6 and 12 months, with echocardiography (Figure ) and CT scan, which confirmed the excellent post-surgery result without complications or recurrence of the disease. The findings of the liver were stable and brain CT was clear.


A three-year-old boy was presented to the hospital because of abdominal distention, hair on the scrotal area, and enlarged penile size, noticed 2 months prior to the presentation. Ultrasonography demonstrated a liver mass, and the patient was referred to the Department of Pediatric Oncology. Protuberant abdomen, hepatomegaly (palpable 14 cm below the costal margin), scrotal hair, enlarged testes (volume 6 ml/6 ml), and enlarged penile size (8 cm) were noted on physical examination ( and ). Laboratory investigation revealed a leukocyte count of 14 100/mm3, a platelet count of 83 500/mm3, normal transaminase levels, increased testosterone (4.02 ng/ml; normal <0.1 ng/ml), alpha-fetoprotein (AFP) (>30 000 ng/ml; normal 3-14 ng/ml) and hCG (33.1 IU/L; normal 0-5 IU/L) levels. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were in the prepubertal ranges. Ultrasonographic examination showed a heterogenic liver tissue and abdominal free fluid. The diagnosis of hepatoblastoma was made by liver biopsy. Chemotherapy (the PLADO protocol) was administered, and the patient was referred to surgery. Ten months later, testis volumes were below 4 ml bilaterally, and penile length was 5.5 cm. Serum testosterone, AFP, and hCG levels decreased (0.14 ng/mL, 1.2 ng/mL, 5.41 IU/L, respectively) to normal ranges.


A 13-year-old female patient, a known case of acute lymphoblastic leukemia (ALL), received chemotherapy and was in remission for more than 1 year. She presented with fever, tachycardia, and sweating. She was admitted for investigation for possible relapse. Among the imaging procedures ordered was gallium-67 citrate whole body scan. Total body gallium scan was normal except for the prominent increased uptake in the enlarged thyroid gland [], suggesting an inflammatory process (e.g. thyroiditis). Thyroid scan was performed using technetium 99m and showed no tracer uptake by the thyroid gland [], raising the probability of thyroiditis suspected on gallium scan. Thyroid function test showed raised FT4 and suppressed thyroid stimulating hormone (TSH). All these findings explained the signs and symptoms of the patient, which were related to thyrotoxicosis and not to relapse of her original disease.


An 11-year-old boy was admitted following a head-on collision with a stationary vehicle, after riding downhill on a bicycle without any headgear, approaching at a speed of around 25 miles/hr at moment of impact.
On arrival, his airway was patent and his cervical spine was immobilised in a collar. His pulse rate was 160/min, blood pressure 105/60 mmHg, respiratory rate 28/min, and oxygen saturation 99% on 15 L/min of oxygen. Glasgow Coma Scale at the scene was 4/15, improving to 8/15. Clinically evident injuries included a large degloving injury of the scalp, multiple facial and lip lacerations, comminuted fracture of the right humerus, and fracture of the left femur. He also had decreased air entry on the left side of the chest with some mild bruising on the left chest wall.
He was resuscitated with intravenous fluids and a urinary catheter was inserted, and this did not reveal any haematuria. Following elective intubation and ventilation, he underwent trauma series X-rays and contrast-enhanced computed tomography (CT) scans.
CT thorax revealed a substantial left-sided pneumothorax, which was relieved by a left chest drain. X-rays of his cervical spine and pelvis were normal. X-rays of his right humerus and femur revealed comminuted fractures of both long bones. CT head revealed normal appearances of the ventricles and basal cisterns with no intracranial haemorrhage; there was a small linear fracture of the left maxillary antrum.
Abdominal CT revealed a small amount of free fluid/blood seen around liver with multiple lacerations seen in the left kidney with a left perinephric and retroperitoneal haematoma. The left renal vein and artery appeared intact. There was no evidence of free intraperitoneal air or bowel wall thickening to suggest bowel trauma. The liver, spleen, pancreas, gall-bladder, and right kidney appeared normal; however, there was some image degradation artefact secondary to the arms being by the side of the abdomen (Figures and ).
During CT scanning he became haemodynamically unstable and required further resuscitation with boluses of colloid and two units of blood. At this stage an emergent laparotomy was considered but not performed as he stabilised and was transferred to intensive care unit (ICU) for observation. His haemoglobin was 11.1 g/dL and platelet count 176. Urea and electrolytes were within the normal range.
Within the next 4 hours, following review by orthopaedic surgeons and neurosurgeons, he was taken to theatre for necessary operative interventions. These included suturing of lacerations, stabilisation of fractures, and insertion of an intracranial pressure (ICP) monitoring bolt.
Over the subsequent 24 hours he remained haemodynamically unstable on the ICU with his haemoglobin dropping to 5.9 g/dL and a platelet count of 21. He received a further two units of blood plus cryoprecipitate. Examination revealed a soft abdomen with no evidence of bruising. Further 24 hours later he was hypotensive, urine output decreased, and he developed abdominal distension. Following a further blood transfusion, he underwent a repeat contrast-enhanced CT scan of his abdomen.
The CT scan revealed intraperitoneal blood, which had increased since the previous scan, mainly in the right and left paracolic gutter, lower abdomen, and pelvis. There was decreased enhancement of the spleen, suggesting a splenic injury (Figures and ). He underwent an emergency laparotomy, and the spleen was found to be completely avulsed and in two pieces (). The spleen was removed and the pedicle transfixed. He made an uneventful recovery and was discharged home on postoperative day 12.


A three-year-old boy was sitting on the handlebars of a motorcycle that was involved in a head-on collision with another motorcycle and suffered blunt trauma to his abdomen. He was admitted to the local hospitals A&E Department. Upon admission his pulse rate was 144/min, blood pressure 105/52 mmHg, and GCS 5/15. He was intubated ventilated, and subsequently trauma series X-rays and CT scans were performed.
Clinical findings of note were an abrasion to his lower anterior abdominal wall and bluish discoloration of his abdomen. The only positive radiological finding of note was the presence of free fluid in his abdomen on the abdominal CT scan.
He underwent an emergency laparotomy because of persistent hypotension despite resuscitation. At laparotomy, his spleen was in three pieces and completely avulsed off its pedicle. There was a 30 cm long tear in the small bowel mesentery with the related gut showing signs of ischaemia. The rest of his bowel and solid organs were normal. He underwent splenectomy and resection of small bowel and end-to-end anastomosis. He made an uneventful recovery except for an incisional hernia that has been repaired successfully. Subsequent review of his CT scans revealed subtle features of nonenhancement of the spleen compared to the liver in the portal venous phase suggestive of splenic pedicle injury. There was active extravasation of contrast around the splenic hilum suggestive of ongoing active bleeding (Figures and ).


A fully conscious 47-year-old man was transferred to the hospital after collapse and severe head injury. Twelve years prior to this incident, the patient underwent heart transplantation for treatment of dilatative cardiomyopathy. At admission, computer tomography (CT) revealed traumatic brain injury with an occipital skull fracture, left frontal contusion bleedings, and a traumatic subarchnoid hemorrhage. On the second day of hospitalization, he suddenly suffered from general seizures associated with severe arterial hypotension. After intubation and resuscitation, the patient was treated with anticonvulsants and sedative drugs. A new CT scan excluded any new cerebral injuries or bleedings.
The patient was then transferred to the ICU. In the presence of fever and clinical and laboratory signs of systemic inflammation, calculated antimicrobial treatment with clindamycin and ciprofloxacin was initiated. Routine clinical, radiological, and microbiological examinations, however, did not reveal any sources of infection. An attempt to reduce sedation to better assess neurological status resulted in severe bronchospasm and impaired lung function as indicated by wheezing and a markedly prolonged expiratory phase. Dynamic hyperinflation occurred and finally led to hypoxia and to cardiac arrest. Cardiopulmonary resuscitation was performed, and lung function was compromised with a paO2/FiO2 ratio of 225 at high airway pressures. Consequently, increasing doses of sedatives became necessary and a combination of midazolam (60 mg · h−1), ketamin (200 mg · h−1), clondine (120 μg · h−1), and sufentanil (75 μg · h−1) was needed to protect the patient from any stimuli during positioning and to prevent additional severe events of bronchospasm. We administered the bronchodilators salbutamol (1.5 mg) and ipratropium bromide (500 μg) as aerosole three times per day, magnesium sulfate (20 mmol) intravenously and theophylline (400 mg loading dose over 20 min, then 40 mg · h−1) intravenously. Theophylline dose was then adjusted to maintain therapeutic blood levels between 10 and 20 mg · L−1 []. Both chest X-ray and spiral chest CT scan showed small pleural effusion but again no sign of pneumonia. Repeated microbiological examinations and cultures of tracheal aspirates, urine, or catheter tips did not document any pathogens. A diagnostic bronchoscopy for bronchoalveolar lavage (BAL) was halted due to life-threatening episodes of bronchial obstruction and bronchospasm.
On day 12 after admission, recurrent episodes of bronchospasm led to an increase of arterial pCO2 to 63 mmHg. At this point, still unable to provide adequate sedation, we decided to start inhalative isoflurane therapy with the Anaesthetic Conserving Device Conserving Device (AnaConDa, Sedana Medical, Sundbyberg, Sweden). Inspiratory gas concentration was set to 0.6% which led to Ramsay-score of 5 to 6 points. This allowed appropriate ventilation and adjustment of pCO2 to a concentration of 38 mmHg. IV sedation could then be reduced stepwise. Bronchoscopy was repeated successfully and revealed rigid mucus and a highly sensitive bronchial tree that reacted to mild stimuli with bronchoconstruction. Despite this impediment, we performed a bronchoalveolar lavage in the right band, left lower lobes (Segments 7 or 8, resp.). Microbiological cultures of the lavage did not reveal bacterial or fungal growth and polymerase chain reaction (PCR) for cytomegalovirus DNA was also negative. However, PCR for Herpes simplex Typ 1 (HSV-1) virus DNA revealed a high load of 9,300,000 genomic equivalents (ge) mL−1. In the throat lavage 19,000,000 ge mL−1, HSV-1 was found.
Following this discovery, antiviral treatment with acyclovir was initiated. Dosage was adjusted to 2 × 800 mg i.v. according to renal function. Over the next few days, both intensity and frequency of bronchospasm decreased. Six days after the beginning of the antiviral treatment, isoflurane was safely reduced in a stepwise manner and was stopped after a 12-day treatment period. Over the next few weeks, HSV-1 DNA concentrations consistently decreased in throat lavage to 6,200,000 ge mL−1 on day 8 and to 250,000 ge mL−1 on day 17 of acyclovir treatment. The patient had had a history of impaired renal function and suffered from acute renal failure on day 5 after admission, which made renal replacement therapy necessary from hospital day 5 to 10. However, when isoflurane was initiated, renal function had already recovered (), and the patient did not require renal replacement therapy any longer.
Neurologically, the patient recovered quickly after the termination of sedation. At discharge, he was fully awake and had no focal neurological deficiency.
Tracheostomy was performed on hospital day 19 to facilitate weaning from the ventilator. On day 39, the patient was eased off mechanical ventilation. He was transferred to a rehabilitation centre 40 days after hospital admission. At discharge, he was fully awake and had no focal neurological deficiency.
Seven months after the event, the patient was discharged from rehabilitation with no neurological deficiencies. Long-term outcome (as assessed by phone call) was excellent.


A 26-year-old female with NYHA class III dyspnea on exertion and easy fatigability was referred for surgery with the diagnosis of congenitally corrected transposition of great arteries (CCTGA), restrictive subaortic ventricular septal defect (VSD) and severe subpulmonic left ventricular outflow tract (LVOT) obstruction. She was on Propranolol. Clinical examination showed an acyanotic patient with low volume pulses and a grade 3/6 ejection systolic murmur over the left sternal border. Chest X-ray revealed normal heart size, left ventricular (LV) type of apex, right aortic arch, and convex left upper border, suggestive of dilated ascending aorta and normal lung vascularity.
Transthoracic echocardiography (TTE) showed situs solitus, levocardia, AV concordance, side by side orientation of the ventricles, and an anterior leftward aorta. The aorta appeared to override the interventricular septum but no definite VSD could be seen probably because of poor echo window. The pulmonary artery was seen to arise from the right ventricle with no evidence of pulmonary stenosis. A high velocity jet was seen in the subaortic region with a gradient of 100 mmHg. Double outlet right ventricle (DORV) with severely restrictive VSD, L-malposed aorta and unrestricted pulmonary blood flow was suspected on echo.
Electrocardiogram (ECG) revealed sinus rhythm, right axis deviation and LV dominance. The right axis deviation in the ECG was probably due to the side by side orientation of the ventricles. Catheterization showed situs solitus, atrioventricular (AV) and ventriculoarterial (VA) concordance with L-malposed aorta, LV pressure of 215 mmHg and RV pressure of 25 mmHg. There was a gradient of 140 mmHg during pullback from LV to aorta, suggesting severe subaortic LVOT obstruction. LV angiogram [] showed severe hypertrophy of LV, long tunnel-like fixed subaortic stenosis and mid-ventricular systolic narrowing. A diagnosis of ACMGA with severe tunnel-like obstruction of the LVOT was made after catheterization. She underwent LVOT resection and LVOT enlargement with modified Konno technique (ventricular septum opened below the subaortic area with resection of hypertrophied septum, followed by closure of iatrogenic VSD with bovine pericardial patch). The abnormal segmental relationship [] necessitated a combined transaortic and transatrial approach. She had an uneventful postoperative period. Postoperative echocardiogram revealed good relief of LVOT obstruction with residual gradient of 45 mmHg, mainly at mid cavity region []. On 6 months follow up, she was asymptomatic with mild to moderate AR and LVOT turbulence with a gradient of 20 mmHg.


An 8-year-old boy presented with NYHA class II breathlessness since 5 years. He was evaluated at the other institute and all intra cardiac anomalies were ruled out. Patient had central cyanosis and grade III clubbing. There were no telangectasia of skin or mucous membrane. Physical examination was unremarkable with normal heart sounds and no murmurs. His oxygen saturation, as recorded on the pulse oxymeter, was 87% while breathing room air. Hemogram revealed hemoglobin of 19.3 mg/dl and packed cell volume (PCV) of 68%. His electrocardiogram was normal. Contrast echocardiogram showed appearance of contrast in the in the left atrium after three to four cycles following the opacification of the right-sided chambers, suggesting the presence of pulmonary arteriovenous fistula (PAVF). Computed tomographic pulmonary angiogram revealed multiple PAVF in the right lung [].
The right femoral artery and vein were cannulated using 6F and 7F sheaths, respectively. Pulmonary angiogram, done using a 7F balloon tipped angiographic catheter, revealed a large PAVF in right lower lobe and another three smaller sized PAVF in upper lobe of right lung []. Using 6F internal mammary artery catheter, right lower lobe pulmonary artery was negotiated and a guide wire (0.035 × 260 cm, Terumo, Japan) was passed across the fistula. Then, 90-cm long 7F coil delivery system was positioned on the same wire. Check angiogram revealed the largest diameter of fistula to be 12 mm. A 15 mm × 8 cm coil (0.052", Cook Inc., Bloomington, IN, USA), which was 3 mm larger than the fistula diameter, was selected. With the help of introducer and delivery system, the coil was deployed into the fistula in a stable position. Since this did not occlude pulmonary AV fistula completely, another 8 mm × 8 cm coil was deployed close to the initial coil
[]. The check angiogram revealed tiny residual flow.
The other fistulae, one in the right lower lobe and three in the right upper lobe, were subsequently occluded in a similar manner using 8 mm × 8 cm, 5 mm × 5 cm, 5 mm × 6 cm, 8 mm × 5 cm (Cook Inc.) coils, respectively. The check angiogram revealed near complete occlusion of all the fistulae. The patient remained stable post procedure with an oxygen saturation of 97% while breathing room air, and was discharged. At 6-month follow up, a repeat pulmonary angiogram was done. It showed partial recanalization of the upper lobe fistula while the lower lobe fistulae continued to show complete occlusion. Room air oxygen saturation was 87%, but the patient continued to remain symptom free [].


In 2000, a 42-year-old Kenyan man, who had sex with other men, was diagnosed with HIV infection and neurosyphilis while he was being evaluated for chronic sinusitis and headache. His initial CD4+ count was 595 cells/μl, and his HIV viral load was 5,490 copies/ml. Neurosyphilis was successfully treated, but the patient opted to defer HAART. In 2003, he had unilateral and painless right thigh enlargement and underwent surgical excision of a low-grade leiomyosarcoma. No adjuvant treatment was recommended, and he remained in good health for an additional two years, during which time his CD4+ count and his HIV viral load remained >550 cells/μl and <5,500 copies/ml, respectively.
In 2006, the patient had a precipitous and persistent fall in CD4+ count to <120 cells/μl and his HIV viral load increased to 35,000 copies/ml. However, he declined to begin HAART for fear of untoward medication-associated side effects. Over the next two years he lost 15 pounds, had waxing and waning adenopathy, and was hospitalized on one occasion with bacterial pneumonia. By June, 2008 he had greater than 15 discrete KS lesions on his legs, his CD4+ count was 30 cells/μl and his HIV viral load was 34,000 copies/ml ().
In 2009, he was hospitalized for treatment of methacillin-susceptible staphylococcus aureus pneumonia and bacteremia. He subsequently agreed to begin HAART, but was poorly adherent with treatment, stopping and restarting his HIV medications on a number of occasions.
In April 2010, he was hospitalized with intermittent fevers, night sweats, mild pancytopenia, hypoalbuminemia, and anasarca. A computerized tomogram (CT) of chest, abdomen, and pelvis revealed diffuse but modest adenopathy. He was ultimately discharged to home when assorted cultures and special studies returned negative for an acute infection. He was strongly encouraged to take HAART, now consisting of darunavir, etravirine, raltegravir, and ritonavir.
One month later he was readmitted with recrudescent fevers, palpable axillary and groin adenopathy, worsening anasarca, and more numerous KS lesions on his neck, trunk, and legs. Laboratory studies were notable for the following, WBC 2400/mm3; hematocrit 24%, platelet count 48,000 cells/mm3, alkaline phosphatase 409 units/L (normal <150 U/L), lactate dehydrogenase 636 units/L (normal <243 U/L), and serum albumin 2.9 g/dL, and a serum protein electrophoresis revealed elevated globulins but no monoclonal gammopathy. His CD4+ count was 24 cells/μl, HIV viral load 1,792 copies/ml, and HHV-8 viral load was 10,000,000 copies/ml. A repeat CT scan showed moderate progression of adenopathy which was most prominent in the axilla and retroperitoneum (). An axillary lymph node was biopsied and showed changes in keeping with MCD. In addition, numerous B cell follicles contained broad mantle zones with numerous larger plasmablastic cells that formed microscopic clusters and sheets within the germinal centers and in the interfollicular areas. These plasmablastic cells expressed HHV-8 and lambda light chain consistent with so-called microlymphoma, which was supported by additional studies. A focus of HHV-8 positive KS spindle cells was also identified (Figures –).
The patient, now age 52, began treatment consisting of liposomal doxorubicin (20 mg/m2 every 14 days) in conjunction with Rituximab (375 mg/m2 weekly times four) and concurrent HAART consisting of the same regimen listed above. More aggressive treatment with multiagent chemotherapy was not given since the patient had only premalignant plasmablastic microlymphoma, and not frank HHV8+ plasmablastic lymphoma, and MCD and KS have been shown to respond to this more conservative treatment.
At eight-months followup, anasarca had resolved and he had regained lost weight. Cutaneous KS was less prominent, and a CT scan showed diminished adenopathy. Laboratory studies are now notable for a gradual improvement in complete blood count, hepatic transaminases, and alkaline phosphatase. His serum albumin has returned to normal, his HIV viral load is nondetectable; although, his CD4+ count remains <50 cells/μL, and his HHV-8 viral load has decreased by greater than two orders of magnitude.


A 53-year-old Caucasian British woman originally presented to her local hospital in 2002 with shortness of breath secondary to atrial fibrillation. During the admission, chest radiography revealed widespread pulmonary nodular infiltrates, and a subsequent computed tomography (CT) scan confirmed the presence of widespread pulmonary metastases, most marked in the lower lung fields (Figure ). The CT scan also demonstrated extensive retroperitoneal and para-aortic lymphadenopathy and hepatic abnormalities consistent with metastases, but no obvious primary site for the disease (Figure ).
Before admission, our patient had no symptoms of liver dysfunction and her medical history was otherwise unremarkable. She had no family history of malignancy. Routine haematology, clotting, serum biochemistry and liver function tests, hepatitis screen and tumour markers were all within normal limits. After the standard medical management for atrial fibrillation was completed, a CT-guided biopsy of the predominant hepatic lesion was performed.
Histological examination of the biopsy confirmed the presence of an infiltrating tumour with pleomorphic elongated cells that stained positively with the vascular markers Factor VIII, CD31, and CD34. These morphological and immunohistochemical features were consistent with the diagnosis of HEH. In the presence of disseminated disease, surgical management was not indicated, and our patient was referred to the oncology team for ongoing management.
In response to radiological evidence of disease progression, first-line therapy with interferon was commenced in accordance with the dosing recommendations published in an earlier case report []. A CT scan performed after three months therapy demonstrated stable disease; however, as our patient was experiencing significant interferon-related side effects, the treatment was discontinued. After a six-month break from therapy, there was evidence of disease progression within the spleen seen on an updated CT scan, and the decision was taken to explore treatment with thalidomide.
Starting initially at 100 mg per day, the dose of the drug was increased at weekly intervals up to 400 mg. Treatment was well tolerated and currently remains at 400 mg daily, more than seven years later. During this period, our patient has had regular restaging by CT scans; the disease has remained stable in the lungs and liver by Recist criteria, but with the development of calcification within the predominant liver lesion (Figure Figure ). At present, our patient continues to have no symptoms of the disease, and throughout the course of treatment has not had any treatment-related toxicity that has required either hospitalization or dose reduction.


A 25-year-old male who suffered a work-related accident in a plastic manufacturing industry was brought to our emergency department after hot molten plastic splashed into his right eye. He was brought 6 h after the incident. The patient complained of immediate vision loss associated with severe pain and a burning sensation. According to the patient, he was not using any protective glasses and the temperature of the molten polymer was 240 degrees Fahrenheit. No first-aid was administered to him during this period.
On examination, he had no light perception in his right eye. The left eye vision was 20/20; J1. The right eye showed severe periocular edema with a black hardened plastic foreign body protruding from the lower lid and medial canthal area []. Superficial burns involving the right cheek were evident. Extraocular movements were restricted in all gazes Examination of the anterior segment of the right eye showed conjunctival congestion and chemosis with diffuse corneal edema. The pupil was fixed and mid-dilated with normal anterior chamber depth. Intraocular pressure (IOP) with tonopen was 86 mmHg. An examination of the fundus showed hyperemic optic disc with blurred margins, diffuse retinal edema with scattered pre- and sub-retinal hemorrhages.
The patient was started on actazolamide 500 mg tablets and timolol maleate 0.5% eye drops. Lateral canthotomy with cantholysis of both crura of lateral canthal tendon was performed as well. A computed tomography (CT) scan was ordered, which showed a hyper dense IOrFB in the inferomedial quadrant of the right orbit, displacing the globe upwards. Hypodense areas inside the mass were evident, suggestive of air entrapment []. There was no extension to the sinuses or the nasal cavity, and the globe was intact. The optic nerve was not clearly visualized.
The patient was operated under general anesthesia. The hardened plastic material was lying embedded at the right medial canthal area and the lower lid. The entry wound was enlarged and the foreign body was removed in toto. It measured 2.5 × 3.5 × 5.0 cm []. The globe was found to be intact. However, the wound depth extended down to the periosteum of the inferior orbital rim with extensive edema of the surrounding skin. The lower lid wound was sutured in one layer using interrupted 6-0 nylon sutures.
Postoperatively, the patient was administered intravenous injections of cefotaxime (1 gm) and dexamethasone (4 mg) twice daily in the ward. On the second postoperative day, the wound was healthy. The cornea was clear and IOP was 18 mmHg. The pupil remained dilated and fixed. B-scan ultrasonography (USG) showed widening of Tenon’s space, suspicious of blood clot around the optic nerve. Three daily doses of intravenous methyl prednisolone (1 gm/day) were administered, but the patient reported no improvement in his vision. The patient was discharged on Ciprofloxacin tablets 1 gm/day and prednisolone tablets (1 gm/kg body weight) in a weekly tapering dose.
At the 3-week follow-up consultation, the skin of the medial three-fourth of the lower lid surrounding the entry wound had sloughed out. The necrosis of the tissues extended up to the orbital rim, medial portion of the upper lid and the medial canthal area []. Wound debridement was required and broad-spectrum systemic antibiotics (capsule ampicillin + dicloxacillin 500 mg twice/day) was restarted. Fundus examination showed resolution of retinal hemorrhages and optic atrophy. A staged reconstruction of the right medial canthal area, including the upper and lower eyelids, was performed using a combination of forehead and tarso-conjunctival flaps techniques [Figs. and ]. Although acceptable cosmesis was achieved [], the patient did not recover his vision. Protective polycarbonate glasses for constant wear was prescribed to the patient.


In December 2006, a 60-year-old female patient, non-smoker, with a medical history of diabetes mellitus, osteoporosis, peripheral vascular disease, and hypertension presented to an outside facility with complaints of right knee pain. An MRI of her knee showed abnormal bone marrow signaling. At presentation, complete blood cell counts were also made, showing white blood cell count of 44.11 × 109/L, with a differential of 79% neutrophils, 4% lymphocytes, and no basophils. Her hemoglobin concentration was 14 g/dL and platelet count was 158 × 109/L. At initial presentation, she had no other complaints; however, on review of systems, she did recall a 3- to 4-month history of subjective night sweats, along with constipation alternating with diarrhea. Leukocyte alkaline phosphatase score was elevated at 319 (normal 25–130). In addition, she had a mildly elevated γ-globulin level of 3.9 g/dL, as well as an elevated level of β-microglobulin at 3.1 mg/L. In January 2007, the patient’s peripheral blood underwent cytogenetic and FISH analyses for BCR and ABL; both tests were negative. PCR was also negative for BCR and ABL. Bone marrow biopsy for persistent neutrophilia showed overall hypercellularity, with plasma cell percentage 7% and normal cytogenetics. Computed tomography imaging of the chest, abdomen, and pelvis showed no significant abnormalities, including a normal spleen size at 11.3 cm. She remained asymptomatic with neutrophilia for several months. In July 2007, the patient was referred to our institution for a second opinion, given her persistently elevated neutrophil count (white blood cell count of 48.74 × 109/L, with a differential of 92% neutrophils).
Repeat FISH and RT-PCR on the peripheral blood were both negative for BCR/ABL; JAK2-V617F mutation was also negative. Bone survey and spinal MRI were negative for findings consistent with multiple myeloma. However, results of a repeat β2-microglobulin analysis showed that levels were still elevated at 2.1 mg/L. Serum protein immunoelectrophoresis with immune-fixation revealed an IgA-κ monoclonal gammopathy concentration of 1305 mg/dL (normal 80–350 mg/dL) and relatively normal concentrations of IgG of 840 mg/dL (620–1400 mg/dL) and IgM of 36 mg/dL (45–250 mg/dL). Urine protein electrophoresis showed an M spike of IgA heavy chain with mild proteinuria. Extensive work-up for infectious process and a full screening evaluation for underlying occult neoplasm were both negative.
To determine the clonal origin of the hematopoietic cells in our patient, we employed a transcriptional clonality assay based on exonic polymorphism (C146T) of the X-chromosome-linked gene iduronate-2-sulfatase (IDS). Allele-specific PCR was used to detect the IDS gene polymorphism, by extracting and amplifying the DNA from the peripheral blood. Mononuclear and polymorphonuclear leukocytes were obtained by differential centrifugation with Lympholyte®–poly; platelets were obtained by high speed centrifugation of fresh plasma. Per methods developed by Gregg et al., we amplified 3 ng of DNA using 250 pmol forward primer IDS1 and reverse primer IDS2R in 50 μL of PCR product with 1.25 Units iTaq polymerase (Bio-Rad, Hercules, CA) and reactant concentrations suggested for the enzyme. Five microliters of this first PCR product were used for the allele-specific reaction using the common reverse primer IDS2R and the specific forward primers, either IDS3C or IDS4T, in 50 μL of PCR product. The products were analyzed in 1.5% agarose gel with 0.4 μg/mL ethidium bromide to determine whether the sample was heterozygous for the polymorphism and informative for clonality. Because our patient was informative for this polymorphism (), we tested expression of the IDS allele in distinct hematopoietic lineages in peripheral blood. Using this PCR analysis, a polyclonal expression pattern was found in all analyzed cell types (granulocytes, mononuclear cells, and platelets) ().
Based on the polyclonality, we concluded that our patient’s neutrophilia was most probably secondary to the underlying monoclonal gammopathy. The patient remained asymptomatic; therefore, we opted to monitor her closely rather than initiate treatment.


A 35-year-old Caucasian man presented to his local general hospital emergency department with a history of acute urinary retention. He had a background history of grade 1 astrocytoma in the posterior fossa at the age of six that was resected in 1979, and required re-excision in 1982 followed by radiotherapy resulting in residual hydrocephalus, epilepsy and mild learning difficulties. There was no history of testicular maldescent, orchidopexy or other inguino-scrotal surgery. On examination he was found to have no new neurological deficits, but right testicular enlargement was noted. An ultrasound study confirmed a 9×8 cm heterogeneous mass replacing the body of the right testis. His serum β-human chorionic gonadotrophin level was 5047 U/L (normal range 0 to 5 U/L), serum α-fetoprotein level was 7413 kU/L (normal range 3 to 8 kU/L) and lactate dehydrogenase level was 1452 IU/L (normal range 230 to 460 IU/L). His liver and renal biochemistry was normal.
A urethral catheter was placed, and drained normal urine. He underwent a radical left inguinal orchidectomy five days later. Histology indicated a non-seminomatous germ cell tumor, with predominantly yolk sac tumor and small amounts of undifferentiated teratoma. The overall histological diagnosis was malignant teratoma intermediate (British Testicular Tumour Panel (BTTP) classification) or embryonal carcinoma (World Health Organization (WHO) classification). Lymphovascular involvement was noted, with widespread blood vessel involvement seen (Figure ). The spermatic cord was not involved (pT2 classification).
A staging computed tomography (CT) scan revealed extensive disease within the thorax with multiple bilateral pulmonary metastases measuring up to 3 cm in both lungs (Figure ). In addition there was bulky mediastinal adenopathy with nodes measuring up to 3.8 cm in the prevascular space and also abnormal adenopathy was noted in both pulmonary hilum, measuring 2.6 cm versus 2.1 cm on the right and left, respectively. Two prominent interaortocaval nodes measuring up to 7 mm, bilateral 8 mm external iliac and 7.5 mm right inguinal nodes were seen. There were no significant anatomical abnormalities of the renal tract or major vessels. Postoperatively, upon catheter removal retention of urine continued. A flexible cystoscopy examination demonstrated a penile urethral tumor, and an incision biopsy was performed. A suprapubic catheter was placed. An MRI scan of the penile lesion demonstrated bilateral inguinal nodes measuring up to 9 mm along with bilateral external iliac nodes measuring up to 8 mm and bilateral internal iliac nodes smaller than 1 cm. An 8 mm pelvic lymph node adjacent to the anterolateral aspect of the bladder was noted. There were two areas of abnormality noted in the ischium, which gave a low signal on T1 and a high signal on the short T1 inversion recovery (STIR) MRI sequences consistent with bony metastasis. Within the penile shaft, 3 cm proximal to the glans penis, a soft tissue mass was confirmed measuring 2 cm in long axis, involving both the penile corpora (Figure ). A technetium bone scan showed a low-grade tracer uptake in the left ischium corresponding to the site of morphological abnormality on the MRI scan.
Histology of the urethral mass confirmed a metastatic malignant undifferentiated teratoma (Figure ). Immunochemistry was positive for placental alkaline phosphatase and CD30 (Figure ). The diagnosis was of an International Germ Cell Cancer Collaborative Group (IGCCCG) poor prognosis metastatic nonseminomatous germ cell tumor. Four cycles of bleomycin, etoposide and cisplatin chemotherapy were administered without complication. Then, 12 weeks after starting chemotherapy, his suprapubic catheter was clamped and he was able to micturate per urethera. His catheter was then removed. A reassessment CT scan of the chest and abdomen (Figure ) four weeks after completion of chemotherapy indicated excellent response to treatment. At the site of pulmonary metastasis, there was complete resolution of the pulmonary masses with only residual ill-defined areas of nodularity and lacunae seen. There was also a reduction in the size of all retroperitoneal and pelvic lymph nodes to less than 5 mm. His serum α-fetoprotein level fell to normal by week one post-chemotherapy with a plasma half life of six days, his serum β-human chorionic gonadotrophin level normalized prior to starting chemotherapy and his lactate dehydrogenase level fell to normal by week five post-chemotherapy. A repeat MRI of the pelvis six weeks after completion of chemotherapy indicated partial resolution of the penile (Figure ) and bony lesions. A further repeat MRI scan of the penis performed 14 weeks later confirmed further resolution of the penile metastasis, which is now a fibrotic scar-like 9 mm lesion (Figure ). Our patient remains in clinical, marker and radiological remission 10 months after diagnosis. His post-treatment follow-up continues.


A 21-year-old healthy man suffered from sudden loss of vision in the left eye for aduration of 3 weeks. He denied any history of trauma. Best corrected visual acuity in the right eye was 20/20 and in the left eye was 1/200. Fundus examination of the right eye was normal; however, his left eye showed a significant vitreous hemorrhage obscuring the view with a massive sub retinal yellowish old blood in the posterior pole with epiretinal fresh blood on the fovea (). Intra-venous Fluorescein angiography (IVFA) revealed fluorescence blockage by blood and dye leakage at a late frame that resembled the appearance of occult sub-retinal neovascularizations (). Indocyanine green (ICG) test revealed a branching of choroidal vascular network and collection of small polypoidal dilation of the vessels (). Based on these findings, the diagnosis of IPCV was made and the patient received photodynamic therapy (PDT after 3 weeks from date of presentatrion and then was repeated after 11 weeks from the first injection because the disease was still active. After a follow-up period of 9 months from first presentation the hemorrhage and sub macular fluid subsided leaving a macular fibroid scar (). Final VA in the left eye was 20/200.


In 1998 a 45 year old female patient presented with complete left sided hemiparesis after a cerebral embolism. While focusing on the reason for this clinical presentation a large mass lesion was found in the atrium via echocardiography whereby suspicion of atrial myxoma was raised. The patient was referred to our department and operative resection of the large myxoma was performed which was predominant prolapsed into the left ventricle at the distal roof of the left atrium above the mitral valve. Both intraoperative and inpatient course progressed without complications and the patient was rapidly discharge for early neurological rehabilitation.
Three years later, a left atrial tumor was seen in a routine cardiological echocardiography follow up and the suspicion of a relapse of the atrial myxoma was raised. A resection of the two-hazelnut-sized myxoma at the posterior wall of the left atrium was performed again. The operation and inpatient course again proceeded without complications and the patient was rapidly discharged again.
After a period of four years an echopenic structure with freely moving component parts was found at the left side during a transesophageal echocardiography and the suspicion of a second relapse was raised. Making additionally there were found sutures of the previous operations at the septum. But making a clear differentiation between a thrombus at the previous suture line and a myxoma relapse was not possible; therefore a three months oral anticoagulation with phenprocoumon was started.
With a positive family history for myxomas (the patients's brother and grandfather) and multiple lentigines an evaluation of the presence of Carney complex, an autosomal dominant disorder, was conducted. After genetic analysis the diagnosis of Carney complex type I with a deletion mutation in the PRKAR1A gene was detected. Carney complex type I is characterized by recurrent atrial myxomas, skin, conjunctiva and lips lentigines, subclinical hypercortisolism and nodular thyroid changes.
After three months of effective oral anticoagulation the structure at the atrial septum was not increased in size. A conservative approach was agreed while maintaining oral anticoagulation and regular echocardiographic follow up. Three years later an echocardiographic study revealed a new tumor, however this time the location was the right atrium. The left sided structure was unchanged. An operative resection was carried out again via re-sternotomy with an oscillating saw after preoperative evaluation (computed tomography (CT) scan of the thorax, transthoracic doppler echocardiogram, doppler examination of the femoral vessels, and lower limb arteries). The cardiopulmonary bypass with systemic 32°C mild hypothermia was established via ascending aortic and bicaval cannulation. The right atrial tumor (approximately 3 cm in diameter) was located at the confluence of inferior vena cava and the lateral atrial wall. An atrial myxoma was confirmed histologically with a tumour-free resection margin. The postoperative course was again without complication. During the last echocardiographic follow up a progressive left atrial structure was seen and the decision was made to resect the fourth atrial myxoma (Figure ). Again the postoperative course went without complications.