A 74 year-old male with history of prior tubular adenoma of the ascending colon removed via snare polypectomy, hyperlipidemia, coronary artery disease status post angioplasty with stent placement, prior traumatic left frontotemporal subdural hematoma status post evacuation, urethral stricture status post multiple dilatations with recurrent urinary tract infections, and an anucleate right eye secondary to childhood trauma presented for a surveillance colonoscopy. At colonoscopy, a 7 mm rectal polyp was discovered which was removed by cold snare ().
On pathologic gross examination, the polyp was a 1.0 x 0.4 x 0.4 cm fragment of tan-red mucosal tissue that was bisected and submitted for histologic examination. Microscopically, H&E stained sections of the polyp showed fragments of denuded colonic mucosa with an edematous and congested lamina propria, overlying fibrinopurulent debris, and adjacent granulation tissue (). Within the intact colonic mucosa, the crypts were elongated and branching with dilatation and abundant mucin production. No dysplasia was identified. The granulation tissue consisted of a fibrous stroma with abundant prominent small blood vessels and a marked mixed acute and chronic inflammatory infiltrate. At the junction of the intact colonic crypts and the adjacent granulation tissue, there was a small focus of woven bone formation. No bone marrow was present within the bone fragment.


A 51-year-old gentleman was admitted with a 2-day history of right-sided abdominal pain. There was associated nausea, but no vomiting, diarrhoea, or fever. He had a background of hypertension, hyperlipidaemia, ischaemic heart disease, a previous stroke, and a previous gastric perforation which was managed nonoperatively. He was a chronic smoker with a 20-pack-year history and was an ex-alcoholic, drinking 5 bottles of beer a day, stopping 9 months prior. He had two previous pancreatitis-related admissions, with the most recent admission 7 months prior. Ultrasound of the abdomen did not reveal gallstones. Lipid panel and calcium panel were unremarkable; hence, alcohol was adjudged to be the aetiological factor for his recurrent acute pancreatitis.
At the previous admission for acute-on-chronic pancreatitis, a computed tomography (CT) scan of the abdomen revealed a 4.1 cm pancreatic pseudocyst in the distal pancreatic body (). Ca19-9 was 14 units/mL and serum amylase levels were 160 units/L. He made an uneventful recovery and was discharged after 2 days. A month later, he had an outpatient endoscopic ultrasound (EUS) which revealed a 27 mm pseudocyst in the distal pancreas.
At this current admission, a chest radiograph on admission revealed consolidation in the right lower zone associated with an ipsilateral pleural effusion (). He did not have any shortness of breath and had good oxygen saturations; hence, no intervention was required at this time. However, the next day he was unable to maintain oxygen saturations and required increasing amounts of supplemental oxygen. The patient was noted to be in Type 1 respiratory failure on arterial blood gas and chest radiograph showed worsening of the right pleural effusion (). Ultrasound-guided percutaneous drainage of the pleural effusion drained 1000 mL of haemoserous fluid. Biochemical analysis of the pleural fluid revealed it to be exudative with a fluid amylase level of >2000 units/L. Fluid cultures grew Klebsiella pneumoniae and a culture-directed course of antibiotics was prescribed. In view of the high pleural fluid amylase levels, a diagnosis of a PPF was made and he was given octreotide 100 mcg 8-hourly subcutaneously for 5 days. The pleural drain was left in situ for 7 days and it drained 2.5 litres of haemoserous fluid in total prior to removal.
The patient subsequently underwent magnetic resonance cholangiopancreatography (MRCP) to delineate PPF anatomy. A retroperitoneal collection communicating with the distal main pancreatic duct was evident. Dilated extrahepatic and intrahepatic bile ducts with a focal stricture in the distal common bile duct (CBD) were also noted. The liver function test was normal. In view of these findings, the case was discussed at the Hepatopancreatobiliary Multidisciplinary Conference. The conference recommended EUS with fine needle aspiration (FNA) to rule out malignancy as the cause of the biliary stricture. EUS revealed a large periampullary diverticulum to be the cause of the CBD dilatation. No strictures or filling defects were noted in the CBD and there was no head of pancreas lesion. Gallbladder adenomyomatosis was also noted.
He completed 2 weeks of intravenous antibiotics and oral antibiotics were continued until the day of surgery. Surgery was planned after 4 weeks. Due to ongoing antibiotic treatment, a decision was made to administer splenectomy vaccinations postoperatively. Elective open distal pancreatectomy with splenectomy and cholecystectomy was performed. Total operative time was 3.5 hours. The patient made an uneventful recovery and was discharged home on postoperative day 5 with postsplenectomy vaccinations administered at 1-month follow-up. Histology revealed chronic cholecystitis, chronic pancreatitis, and a pancreatic pseudocyst with haemorrhage. No malignancy was seen. He remains well at 12 months' follow-up.


The 12-year-old, melanodermic female patient searched for treatment accompanied by her mother in the Mato Grosso Cancer Hospital's Department of Dentistry, complaining of difficulty to swallow for about 15 days.
An extraoral physical examination of the patient showed satisfactory mouth opening and free and palpable condyles, without changes.
The intraoral physical examination showed asymptomatic nodular lesion at the base of the tongue, which was difficult to see ().
The CT scan showed a round, well defined hyperdense lesion of approximately 25.8 mm at its largest diameter, with infiltrative growth in the posterior region of the base of the tongue ().
The proposed treatment was complete resection of the nodular lesion at the base of the tongue (excisional biopsy).
The surgical procedure was performed using intraoral access under general anesthesia. After incision and detachment of the lingual mucosa, it was possible to visualize a red-colored round-shaped nodular lesion at the base of the tongue and to excise it (Figures
–).
The patient remained hospitalized for twenty-four hours and then was discharged. The medications prescribed were cefalotin 1 g, dipyrone 1 g, ketoprofen 100 mg, hydrocortisone 500 mg, ranitidine 50 mg, and ondansetron 4 mg.
She reported improvement in swallowing after surgery, even though she was complaining of moderate pain in early postoperative period.
The histopathological diagnosis was lingual thyroid ().
After the diagnosis of lingual thyroid was established, the patient was referred to an endocrinologist for exams and medical follow-up. The patient is currently under medical supervision, but there is no need for hormone replacement therapy.
The informed consent of the patient's legal guardian was obtained before submission of the manuscript.


An 80-year-old female patient underwent total hip replacement for primary osteoarthritis of left hip through minimally invasive Watson jones approach (). During the surgery uncemented press fit acetabular cup and uncemented femoral stem were used. We did not use any screw for acetabular cup fixation. Immediate postoperative period was uneventful and patient was discharged from the hospital 6 days after surgery. As per our hospital protocol we use low molecular weight heparin for 6 weeks for thromboprophylaxis in total hip replacement patients.
After 3 months of surgery, patient came back with the complaint of pain in the left inguinal region and development of ecchymosis over the left inguinal region. Patient was readmitted to the hospital for observation and further investigation. Next morning patient started complaining of weakness of left lower limb and numbness over medial aspect of thigh and knee. On physical examination, the patient was found to have grade 3/5 motor function of the quadriceps muscle, as well as decreased light touch and pinprick sensation over the femoral nerve distribution area. Patient did not have any spine tenderness.
Blood investigations showed mild anemia with haemoglobin level of 9.0 g/dL. There were no abnormal findings of bleeding tendency or disorders of hemostasis and she had not been treated with any anticoagulant drugs. The anteroposterior and lateral radiographs of the pelvis and left hip showed no abnormality except previously performed total hip replacement, with no displacement or dislocation of the prosthesis noted (). A radiograph of lower spine was normal. MRI of lower spine was normal. Computerized tomography (CT) examination of pelvis showed 8 × 10 cm mass around the left lesser trochanter extending in thigh in vastus intermedius muscle (Figures and ). So the case was diagnosed as femoral nerve palsy due to delayed hematoma development in iliopsoas region. We have tried to aspirate the hematoma under sterile precautions but only 6 mL of occult blood comes out. CT guided aspiration of hematoma was refused by radiologist as hematoma was organized. Surgical decompression was planned after opinion of vascular surgeon.
Incision was given through direct anterior approach. A hematoma was found in the lesser trochanter region and in front of joint. The femoral nerve was found stretched by the hematoma. Femoral nerve and artery were identified and secured with mersilene tape. The organized hematoma around 150 gms was removed. Fresh bleeding starts once the hematoma was removed, because the ruptured pseudoaneurysm was occluded only by tamponade effect of the hematoma. Bleeding vessel was identified as branch of profunda femoris artery and sutured. A drain was kept in situ and closure was done. Postoperative culture reports of hematoma were sterile. The inguinal pain was relieved completely after the surgery. Patient was started walking with knee brace. The power of the quadriceps femoris recovered gradually.


A 36-year-old female with no previous illness presented with an acute onset pain over the right hypochondrium for 3 days associated with intermittent fever and anorexia. Physical examination revealed a tender and guarded right upper abdomen. Hematological and biochemical tests were normal. Abdominal radiographs were unremarkable. Abdominal sonography revealed a double walled solid mass in the right upper abdomen very close to the liver and bilateral ovarian cysts. In view of patient's general condition and lack of facilities, CT scan and Colonoscopy could not be done. With differential diagnoses of ruptured hydatid cyst, duodenal ulcer perforation, acute acalculous cholecystitis, and an ulcerated GIST (Gastrointestinal Stromal Tumour) an emergency diagnostic laparoscopy followed by midline laparotomy was performed. At diagnostic laparoscopy purulent and fibrinous reaction in the subhepatic region was noted based on which decision to proceed further was made. At laparotomy, a mass measuring 8 × 7 × 5 cm arising from the hepatic flexure of colon was noted as shown in . Right hemicolectomy with ileotransverse anastomosis was performed.
Histopathologically, gross examination confirmed the operative findings and the cut section revealed an obvious bulge in the serosa caused by the mass that seemed to involve the full thickness of bowel wall, besides its glary myxoid appearance as shown in .
Microscopically, there was an intact mucosal lining and the mass was located in the submucosa spreading up to the serosa. There was low cellularity with proliferation of spindle-to-stellate shaped cells in a myxoid-to-pink hyalinized background. The stellate cells had plump nuclei and conspicuous nucleoli. The intervening vascularity was prominent with associated moderate mixed inflammatory infiltrates with large number of eosinophils. The serosal aspect showed necrosis with collections of acute inflammatory exudates. There was no evidence of cellular atypia, pleomorphism, or increased mitotic activity as shown in . The features were in favor of IFP with a differential diagnosis of GIST.
Immunohistochemical staining was found negative for CD34, CK PAN, and CD117 as shown in Figures and and hence the diagnosis of IFP was confirmed.
The patient had an uneventful recovery and was discharged on the 10th postoperative day. At one-year follow-up, she remained symptom-free.


A twelve-year-old female patient with OI was referred to our clinic for routine eye examination from the genetic department. Bilateral best corrected visual acuity of the patient was obtained – 5/10 (corrected with +3.50 for right eye, +5.00 for left eye) – with a standard Snellen scale at a distance of 6 m. She had growth retardation and typical facial appearance compatible with OI, such as triangular shaped face, large skull, a prominent nose, elongated columella of the nose, smaller maxilla, slightly larger mandible (Fig. ). Anterior chamber, iris and lens examination of both her eyes were unremarkable. Neither of her eyes had blue sclera. Both glob measurements measured by Hertel’s exophthalmometer were 21 mm. Bilateral corneal diameters were 10 mm at vertical axis and 9.5 mm at horizontal axis. Bilateral intraocular pressures were 12 mmHg with Applanation tonometry. Examinations of motolities of both her eyes were normal. Central corneal thicknesses of her right and left eyes with ultrasound corneal pachymetry were 500 and 510 microns, respectively. In her fundus examination, bilateral stage 2 papilledema according to Frisen Scale and wrinkles in papillomacular bundle were noticed (Fig. ). Bilateral colour vision examinations by Ishihara plates were normal. Initially, optical coherence tomography (OCT) images revealed the macular pucker and thickening in the retinal nerve fibre layer (RNFL) of both her eyes (Fig. ) but after 5 months when the papilledema subsided, the distinct thinning in both RNFL was obvious (Fig. ). Computed tomography (CT) images revealed that there were hyperostosis in the skull base, maxillofacial and frontal bone structures. In addition to extreme hypoplazic appearance in the sphenoid sinus, the other periorbital sinuses were not monitored in CT images due to their abnormal ossification (Fig. ). In her visual field examination using the Humphrey field analyser, we noted remarkable enlarged blind spot and bitemporal partial hemianopia (Fig. ). As the papilledema regressed spontaneously and neurological examination of the patient was normal, we decided to follow up our patient with OCT and visual field tests without treatment. In her last control examination, bilateral best corrected visual acuity was 6/10. Anterior segment examinations were normal. Bilateral colour vision examinations using Ishihara plates were normal. Bilateral optic discs were pallor (Fig. ). RNFL analyses of both her eyes still revealed distinct thinning (Fig. ). In her visual field examination, despite the improvement in the enlarged blind spot, bitemporal partial hemianopia was still remarkable (Fig. ).


A 63 year-old female with longstanding type-1 diabetes mellitus and hypertension developed chronic renal failure in 2002 and underwent a pre-emptive renal allograft transplant from her donor husband in 2004 without requiring prior dialysis. Both the donor and recipient were cytomegalovirus-negative. She received basiliximab 20 mg prior to her transplant surgery and another 20 mg on day 4 post-transplant. Following transplantation she was immunosuppressed with mycophenolate mofetil, prednisone and tacrolimus. She had longstanding stable kidney function following transplantation with a baseline GFR of 84 mL/min and a creatinine of 80 micromol/L. Her past medical history was remarkable for iatrogenic hypothyroidism following parathyroidectomy for primary hyperparathyroidism, and she had no prior history of malignancy.
In April 2015, after ten years of immunosupression, she developed an irregular hyperpigmented and evolving lesion on her left upper back which was resected in May 2015. The biopsy of the left scapular site revealed a superficial spreading invasive melanoma with a maximum Breslow thickness of 2.59 mm, Clark level of IV, with, mitoses of 5/mm2. No ulceration was identified, but tumor infiltrating lymphocytes and tumor regression were present. Peripheral margins were uninvolved, but deep margin was involved by a satellite nodule and microsatellitosis was also present. Wide-local excision and bilateral axillary lymph node biopsies were performed July 2015, as lymphoscintigraphy had identified drainage of each of the lesion to the contralateral axilla when injected with technetium 99 sulfur colloid. Three right axillary lymph nodes were removed and were negative for malignancy, but 1 left axillary lymph node was removed and pathology revealed an 8.5 mm × 7.5 mm melanoma deposit with extranodal extension. As a result, the patient required a wide local excision with a 2 cm margin and pathology demonstrated residual disease and microsatellites, with negative margins. A second lesion was excised at the time of surgery in the right scapula, again consistent with superficial spreading invasive melanoma, Breslow thickness 1 mm, Clark level II, without ulceration, no mitoses and clear margins (pT1a). Completion lymph-node dissection August 2015 retrieved 22 lymph nodes, all of which were negative for melanoma, with final American Joint Committee on Cancer (AJCC) pathological staging of pT3aN2c.
Staging CT in July 2015 showed a non-specific 6.5 mm non-calcified right lower lobe (RLL) lung nodule, not previously present. BRAF mutation test of the with real-time PCR assay using the Qiagen BRAF RGQ kit was BRAF wild-type. The patient was not offered adjuvant radiotherapy and declined high-dose adjuvant interferon.
Follow-up CT imaging in October 2015 demonstrated increase in size of the RLL lung nodule and the appearance of at least eight new subcentimeter bilateral pulmonary nodules, along with increased mediastinal and left hilar lymphadenopathy (12 mm). The patient was asymptomatic. A follow-up 2-deoxy-2[F-18] fluoro-D-glucose (FDG) PET-CT scan in December 2015 demonstrated an intensely hypermetabolic (SUV max 9.9) left hilar lymph node enlarging to 16 mm, along with non-FDG avid pulmonary nodules. An endobronchial ultrasound-guided biopsy of the hilar lymph node (station 11 L) demonstrated atypical cells reactive for S100/melanA, confirming metastatic melanoma. Her case was discussed at the multidisciplinary tumor board and renal transplantation team, and a recommendation for anti-PD-1 treatment was made, based on available safety data and high risk of cancer-related mortality. Full discussion with patient and her husband regarding the risks and benefits of treatment were had and the patient wished to proceed with treatment including unknown risks of allograft rejection. Immunosuppressive medications were titrated off and she was left on 10 mg of prednisone daily, with no deterioration in renal function prior to nivolumab administration.
The patient received her first treatment of nivolumab (anti-PD-1 treatment for metastatic melanoma, single intravenous dose of 324 mg) on January 7th, 2016. She reported no subjective toxicities within the first week of treatment, but on day 8 the patient developed lethargy, abdominal pain, nausea, vomiting and loose stools (4 times per day), malaise, anorexia and fatigue. Physical examination demonstrated signs of uremia and concurrent tenderness in the lower abdomen at the site of allograft implantation without peritoneal signs. Laboratory investigations showed a creatinine rise to 577 micromol/L without any change in electrolytes. The ultrasound Doppler of her kidney showed markedly abnormal appearance of the transplant kidney with findings suggestive of acute medical renal disease, poor perfusion and elevated resistive indices concerning for transplant dysfunction. She received a pulse of corticosteroids (methylprednisolone 500 mg IV × 1), and developed diabetic ketoacidosis requiring insulin infusion and initiation of hemodialysis. She had a second pulse of steroids with close endocrinologic monitoring and insulin sliding scale, after which prednisone was tapered down. Renal allograft function did not return and she was discharged home on hemodialysis. Nivolumab was withheld and the patient was observed.
Restaging CT thorax on February 2016 demonstrated a partial resolution of bilateral pulmonary nodules, hilar lymph nodes and mediastinal lymph nodes but right lower pleural thickening was noted. However, the patient had subsequent clinical deterioration 6 weeks later in March 2016 with dyspnea, cough and hypoxia with CT thorax showing significant progression of lung parenchymal disease and multiple new lung nodules. Infection was ruled out by bronchoscopic examination, and empiric treatment with piperacillin/tazobactam. After careful consideration and multidisciplinary review, the patient was re-administered nivolumab starting April 2016, with both ongoing clinical and radiographic response. Restaging 12-week CT thorax June 2016 on nivolumab shows almost total resolution of previously noted multiple bilateral pulmonary nodules and consolidations (Fig. ), but some slight increase in size of mediastinal and hilar lymph nodes not meeting criteria for progression by immune-related response criteria (irRC) in solid tumors []. At the time of publication the patient has an ongoing (8-month) response in lung metastases and stable mediastinal/hilar lymph nodes, but slight growth of a single axillary lymph node.


A 65-year-old woman with a history of hyperlipidemia had experienced headache and vomiting for 10 days before admission to another hospital. Magnetic resonance imaging (MRI) showed enlargement of both lateral ventricles and a mass at the foramen of Monro. The patient was then referred to our hospital.
Neurological examination on admission to our hospital showed memory disturbance (Mini-Mental State Examination 20/30) and a wide-based gait disturbance. Computed tomography (CT) showed a 16 mm mildly hyperdense mass with no calcification at the foramen of Monro, and the mass was causing obstructive hydrocephalus. MRI revealed a well-delineated mass at the foramen of Monro with heterogeneous signal intensity on both T1- and T2-weighted images; the mixed-signal core appeared as a popcorn-like lesion typical of cavernous angioma (Fig. ). Gadolinium-enhanced T1-weighted imaging revealed mild enhancement of the mass (Fig. ). There were no vascular abnormalities on CT angiography or CT venography. We considered a colloid cyst, central neurocytoma, subependymoma, ependymoma, low grade astrocytoma, and arteriovenous malformation as differential diagnosis; however, despite the unusual location of the mass, a diagnosis of intraventricular cavernous angioma was made because of its typical appearance on MRI.
We performed endoscope-assisted transcortical removal of the mass (Fig. ). The entry point was made using the StealthStation S7 navigation system (Medtronic Inc., Louisville, CO), and a flexible videoscope (VEF-V, Olympus Corporation, Tokyo, Japan) was inserted. Intraoperative neuroendoscopic imaging revealed a reddish lobular mass with a hematoma and obstruction of the foramen of Monro. We observed the cavum septum pellucidum because of the high intracranial pressure associated with hydrocephalus. After right frontal mini-craniotomy, the Viewsite Brain Access System (Vycor Medical Inc., Boca Raton, FL) was inserted (Raza et al. ); we used the 17 mm wide retractor in the 7 cm length. Endoscope-assisted surgery with the Viewsite was performed with technique similar to microsurgery. A 2.7 mm rigid endoscope (Karl Storz, Tuttlingen, Germany) fixed by UniArm (Mitaka Kohki, Tokyo, Japan) was inserted. The working ambience was air because of its advantages over fluid ambience especially when dealing with a relatively vascularized pathology. Other microsurgical instruments were used parallel to the endoscope. The endoscope served only as an optic apparatus. We used the Viewsite as an access port to enable dual instrumentation (endoscope and microsurgical instrumentation). The tumor was bluntly dissected from the ventricle wall, and total en bloc resection of the lesion was performed by one surgeon using the two-handed technique. Bleeding was well controlled with irrigation and bipolar coagulation.
The resected tumor was reddish and consisted mainly of clotted blood vessels and xanthochromic tissue. Histological examination revealed a cavernous angioma with evidence of large vascular spaces filled with an organized thrombus (Fig. ).
Postoperative MRI confirmed complete removal of the tumor, and a return to normal ventricular size (Fig. ). The patient’s symptoms resolved immediately, and there were no postoperative complications. She was discharged without any neurological deficit. No complications or neurological impairment were observed at the 1-year follow-up.


A 40-year-old male patient presented to our department with complaints of right sided neck swelling that had gradually progressed in size over the past 5 yrs. He does not give any history of hoarseness of voice, recent cough, or light headedness. He complains of difficulty swallowing and also in neck movements. On examination of the patient, a firm, immobile, nontender swelling of size 10 × 10 cm was found, which involved the right side of neck. It was seen extending from behind the right sternocleidomastoid muscle to just across the midline of neck. Vertically, it extended from the hyoid bone to the sternal end of right clavicle. It was nonpulsatile and no murmur was audible. Carotid artery was displaced clinically by the mass. Examination revealed all cranial nerves to be within normal limits. No other swellings were palpable in the neck ().
Cervical spine and thoracic X-rays were taken to see for tracheal obstruction and mediastinal shadow as well as pre-op planning. Cervical X-ray did not show any tracheal narrowing while there was a slight suspicion of mediastinal widening ().
For further characterisation of the swelling, a contrast enhanced computed tomography was done which showed presence of fairly well-defined hypodense mass lesions in the right side of neck extending to upper mediastinum. The largest lesion was approximately 4.2 × 5.4 cm in anteroposterior and transverse dimensions. The craniocaudal extent of the lesions was approx. 17.8 cm. There was poor contrast enhancement of the lesions with few mildly enhancing internal components. The upper part of the mass was abutting the pterygoid muscles and the C2 vertebrae. The lower level of the lesion was at the level of the carina. The masses in the neck were mainly involving the right carotid space displacing and separating the carotid arteries and the internal jugular vein suggestive of a neurogenic tumor. The lesions were also displacing the right SCM muscle and right submandibular gland. The thyroid and cricoid cartilages, hypopharynx, larynx, and trachea were displaced to the left without obvious evidence of erosion or infiltration. In the mediastinum, the lesion was seen to displace the azygous vein, right brachiocephalic vein, and superior vena cava and abutting the aortic arch and right main bronchus. The thyroid gland appeared normal. There was no obvious cervical lymph node enlargement, no intracranial extension, nor any obvious bone or cartilage erosion in the area of study. The present CECT was suggestive of a neurogenic tumor probably from the right vagus nerve ().
A Tc99m thyroid scintigraphy was done from another institution before presentation which showed presence of normal thyroid gland with normal uptake, but for the presence of a cold nodule in the right lobe. Under USG guidance, an FNA was done from the cold nodule in the right lobe of thyroid. FNAC result revealed a benign colloid nodule. As malignancy was ruled out, no further action was taken on the thyroid gland. The swelling in question was not evident on the scintigraphy ().
An FNA was taken from the swelling in question, which was inconclusive.
Further routine workup was done which included basic blood and renal and thyroid workup which were within normal limits, and patient was prepared for surgery.
Under general anesthesia, a collar-line transverse incision was made 1 cm below the cricoid cartilage and extending along the anterior border of the right sternocleidomastoid. After raising subplatysmal flaps, the strap muscles were separated, and the lesion was visualised. A yellowish mass lesion was visualised extending beyond the midline which appeared well-defined and well-encapsulated. It was dissected from the adjacent tissue and found to have posterior attachment to the ipsilateral vagus nerve. The vagus nerve was splayed over its surface and carefully dissected off the swelling, thereby preserving the whole of the nerve. There was an episode of bradycardia during this manoeuvre, but it was transient and the rest of the procedure was uneventful ().
After successful removal of the lesion, there were multiple other similar swellings seen discontinuous from the first, along the vagus nerve, proximal and distal to the first swelling. They were also dissected away from the vagus nerve and removed in toto. Lesions involving the submandibular area were also resected. The mediastinal lesion seen on imaging was removed along with the first specimen via the same incision itself. Hemostasis was ensured and the wound was closed in layers after placing a suction drain. The patient had an uneventful postoperative period and was discharged on the 5th post-op day. There was no obvious evidence of vagus nerve injury, no hoarseness, or cough ().
In total, there were 5 specimens, of which one was a lymph node from level 2 that was also excised ().
Final histopathology report showed the presence of schwannoma with degeneration, composed of focal hypercellular (Anthony A) areas and hypocellular areas (Anthony B). Immunohistochemical examination of tumor cells showed strong S-100 positivity. Therefore, a final diagnosis of vagal nerve schwannomatosis was obtained. The lymph node was histologically unremarkable.


The first patient is an 83-year-old man who presented with vague upper abdominal discomfort, weight loss, and general weakness. Blood work was normal and upper and lower gastroscopy revealed no specific lesion or malignancy.
A solitary lesion in the left lobe of liver was found on computed tomography (CT) scan. Tumor markers were noncontributory and hepatitis serology was negative.
He has a medical history of hypertension controlled with antihypertensive medications. Liver biopsy showed hepatocellular carcinoma. Surgical resection of segments 2 and 3 including the mass was performed.


The second patient is a 56-year-old female who presented to the emergency department with abdominal pain. Medication used included oral contraceptive and hormonal supplements. CT scan showed 11 cm heterogeneous liver mass in the right lobe with evidence of intralesional hemorrhage and associated contrast extravasation requiring urgent surgical intervention. The lesion was resected. Hepatitis serology result was negative.
Macroscopic examination of the first lesion showed a partial hepatectomy with 4 cm lobulated green/yellowish mass with surrounding nodular and fibrotic liver parenchyma. The second lesion consisted of an ill-defined tumor, 13 cm size, with a yellow/brown cut-surface and a small peripheral rim of grossly normal liver parenchyma ().
Microscopically, both cases showed HCC with admixed trabecular and pseudoacinar patterns. The malignant hepatocytes were enlarged and contained prominent, densely eosinophilic intracytoplasmic globules, many of which had surrounding clear halos admixed with Mallory hyaline bodies (arrow) (Figures and ).
The globular structures were negative for Masson's trichrome, amyloid, and Periodic Acid Schiff/Periodic Acid Schiff Diastase (PAS/PASD) special stains.
By immunohistochemistry (Dako, Carpinteria, CA, USA) the intracytoplasmic globules showed expression of p62 and focal positivity for ubiquitin (Figures and ).
CAM5.2 showed very focal, weak expression. Fibrinogen, alpha-fetoprotein, AAT, alpha 1-antichymotrypsin, and fibrinogen immunohistochemistry were all negative. The morphology and predominant CAM5.2 negativity in the majority of the inclusions suggest they are mainly HBs while the focal, weak CAM5.2 staining indicates a focal MDB component.


A 68-year-old female patient with a past medical history of diffuse large B-cell (double hit) lymphoma, status post chemotherapy, as well as peripheral stem cell transplantation (PSCT) complicated by disseminated M. abscessus infection of the skin was referred to the gastroenterology clinic for evaluation of postprandial abdominal pain, diarrhea, weight loss, and melena. She had been recently started on clofazimine and tigecycline due to previous adverse effects from azithromycin. Two months before PSCT (November 2012), the patient developed a catheter-related blood stream infection with M. abscessus that was treated with catheter removal and initial therapy with oral azithromycin, levofloxacin, and amikacin. Two days later, levofloxacin was changed to amikacin after the organism was identified as M. abscessus and preliminary susceptibilities determined resistance to fluoroquinolones. The patient completed a 4-week course of antimicrobial therapy with azithromycin, imipenem, and amikacin complicated by amikacin-induced ototoxicity and nephrotoxicity. The patient rapidly cleared the bacteremia within 48 hours after central venous catheter removal and had no other manifestations of infection. In January 2013, she underwent autologous PSCT and within 2 months she developed multiple skin nodules. Nodule biopsies led to the diagnosis of relapsed disseminated M. abscessus infection. The patient had previously documented ototoxicity secondary to amikacin and was therefore started on treatment with azithromycin, tigecycline, and imipenem. In addition, the patient was found to have new lung nodules on a thoracic computed tomography scan. After 3 months of therapy (June 2013), she developed hepatotoxicity with severe transaminitis and diarrhea. An extensive hepatology evaluation attributed the hepatotoxicity to azithromycin. Because of the patient's history of ototoxicity and renal injury due to amikacin and the possible hepatotoxicity from azithromycin, clofazimine treatment was initiated. In vitro susceptibility testing of the M. abscessus demonstrated susceptibility to tigecycline and clofazimine with resistance to augmentin, bactrim, and linezolid. After obtaining compassionate use and Investigational New Drug (IND) approval through the Florida Department of Health, the patient's regimen was changed to high-dose clofazimine (200 mg by mouth daily) and tigecycline (50 mg IV twice daily). High-dose clofazimine was chosen based on history of disseminated and recurrent mycobacterial infection in a highly immunocompromised patient. Four months later (October 2013), the patient's skin lesions had resolved and repeat chest imaging revealed resolution of the previously noted lung nodules (Figure ).
One month after initiating clofazimine, the patient developed severe diarrhea with up to 20 watery bowel movements a day. Her diarrhea persisted despite discontinuation of her azithromycin. The evaluation for weight loss demonstrated severe malabsorption including anemia (hemoglobin of 10 g per dL), with macrocytosis (mean corpuscular volume 109.1 fl, red cell distribution width 19.3% [reference range, 11.5%–15.0%]), decreased levels of prealbumin of 8 mg per dL (reference range, 20–40 mg per dL), and decreased albumin (2.1 g per dL [reference range, 3.2–5 .0 g per dL]). Laboratory evaluation also revealed a fat-soluble vitamin deficiency as well as other vitamin deficiencies including folate, vitamin D, 25-OH, and total serum carotene.
After 7 months on high-dose clofazimine, she presented with hematochezia, failure to thrive with a 17-pound weight loss (127 lb to 110 lb), persistent diarrhea, and right lower quadrant abdominal pain. Physical examination revealed tenderness of the right lower quadrant on deep palpation, 2+ pitting edema in the lower extremities bilaterally, and maroon stools on rectal exam. She had no evidence of recurrent mycobacterium infection nor of relapsing lymphoma.
Endoscopic evaluation revealed black pigmentation of the duodenum. Colonoscopy demonstrated severely congested mucosa with petechiae in the terminal ileum (Figure 2A). Small bowel and terminal ileum biopsies revealed intestinal mucosa with focal villous blunting and widening due to numerous crystal-laden macrophages infiltrating the superficial lamina propria, consistent with crystal-storing histiocytosis, which is indicative of clofazimine enteropathy (Figure 2B). Clofazimine and all M. abscessus treatment was subsequently discontinued, and the patient had no further gastrointestinal bleeding. She experienced complete resolution of her diarrhea 3 months later, with a 15-pound weight gain noted within 4 months of the discontinuation of the clofazimine. She was initially treated with parenteral nutrition but is now maintained on an oral diet with no recurrence of her gastrointestinal symptoms or of her mycobacterial infection 2 years after the diagnosis of clofazimine enteropathy. This adverse drug effect was reported to the US Food and Drug Administration (FDA).


A 57-year-old female patient who had no underlying disease was admitted to our hospital for arthroscopic meniscus resection for a right meniscus tear. Preoperative electrocardiogram (ECG) showed a sinus bradycardia of 54 beats/min and left anterior fascicular block (Fig. ). Cardiologists in our hospital assessed the risk of surgery and concluded that the patient was at low risk. The other preoperative findings were normal.
On the day of surgery, in the operating room, her measured vital signs were normal, with blood pressure of 146/86 mm Hg, heart rate of 66 beats/min, and SpO2 of 97%. In the right lateral decubitus position, the skin over the lumbar spine was sterilized with potadine, and 1% lidocaine 3 mL was injected at the level of L3–4, for subcutaneous anesthesia. After dural puncture using a 23-gauge Quincke needle via a median approach, the flow of clear cerebrospinal fluid was confirmed. After 11 mg of 0.5% heavy bupivacaine was injected through the spinal needle, she felt a sense of warmth in her lower extremities; her position was then changed to a supine position. A pinprick test was performed and the upper level of sensory loss was confirmed at T6. Dexmedetomidine infusion was planned at a loading dose of 1.0 mcg/kg/min over 10 minutes, followed by 0.7 mcg/kg/minutes intravenously, as a sedative. Thus, 20 minutes after heavy bupivacaine injection, injection of the loading dose of dexmedetomidine was commenced at a rate of 1 mcg kg−1 min−1 to sedate the patient. Two minutes after dexmedetomidine injection, the patient's heart rate had decreased to 31 beats/min and progressed to asystole within 10 seconds. Dexmedetomidine administration was stopped immediately. Mask ventilation and chest compressions were performed, along with intravenous injection of atropine (0.5 mg) and epinephrine (1 mg). Shortly after initiation of cardiopulmonary resuscitation (CPR), the cardiac rhythm returned to sinus rhythm and the femoral pulse became palpable. At that time, her heart rate was 130 beats/min (Fig. ).
After radial artery catheterization, surgery was successfully performed under general anesthesia. Mild pulmonary edema was observed on the postoperative chest X-ray, but the patient recovered spontaneous respiration and left the operating room without mask ventilation. Four days later, pulmonary edema was improved (Fig. ). During hospitalization, further evaluation of her cardiovascular function showed T-wave abnormalities on ECG and local wall motion abnormalities on echocardiography. No stenosis of the coronary arteries was seen in coronary angiography. Thus, these changes were considered to be typical of stress-induced cardiomyopathy, which often occurs after CPR. At 4 days after discharge, during which she experienced no abnormalities, the patient complained of intermittent dizziness. A 24-hour Holter ECG was then performed, but her average heart rate was 63 beats/min, with less than 3 premature ventricular contractions and premature atrial contractions. When she visited the cardiology outpatient clinic at 1 month and at 3 months after surgery, her symptoms had improved and she had no complaints.


An 86-year-old man presented to the emergency department with chronic respiratory failure and severe pneumonia. Comorbidities included diabetes, uncontrolled hypertension, ischemic heart disease, Parkinson’s disease, and bronchial asthma. As his condition continued to deteriorate further, he was admitted to the intensive care unit (ICU). The patient was unable to maintain adequate arterial oxygen saturation via a face mask and nasal prongs. The attending physician ordered non-invasive ventilation (NIV) and a continuous positive airway pressure (CPAP) mask was applied. On day three of his ICU stay, one of the authors noticed a Grade II pressure ulcer on the bridge of his nose (Figure ).
Examination of the patient showed a tight-fitting full facial mask. On inquiry, the caregivers revealed that the CPAP mask had been kept in place for almost 24 hours without any formal monitoring or inspection of pressure areas. The patient’s family refused to consent to the physician's request for invasive ventilation. Unfortunately, the patient progressively deteriorated due to worsening of his septicemia and respiratory failure and died five days following his admission to ICU. Verbal informed consent to present the case report was obtained from the immediate family members.


A one-month-old female infant was evaluated because of limb shortening, hypercalcemia, and epilepsy. She was born at the 39th week of gestation by Caesarean section with a birthweight of 2070 g as the first child of consanguineous parents. Her prenatal ultrasound and family medical history were normal. The APGAR score was 7 at 1 minute and 10 at 5 minutes after birth. Metabolic acidosis and seizures were observed in the first day of life. Intubation was attempted because of respiratory failure. She was referred to our hospital because of myoclonic seizures that were not controlled after phenobarbital and phenytoin therapy. On her physical examination at one month old, her weight was 2470 g (<3th centile), her height was 50.5 cm (3th-10th centile), and her head circumference was 35.5 cm (10th-50th centile). A flattened facial appearance, broad forehead, flattened nasal bridge, bilateral low-set ears, short neck, narrow thorax, shortening of left arm and dimples on knees, hepatomegaly palpable 2 cm below the right costal margin, and 2/6 systolic murmur were detected ().
Her skull and long bones radiographies showed distorted trabeculation, reduced mineralization, metaphyseal irregularities, cupping, diaphyseal shortening, shortness of the right humerus, ulna, and radius (). Craniosynostosis was not observed. Her echocardiography detected ostium secundum atrial septal defect. Renal ultrasonography revealed medullary hyperechogenicity suggesting medullary nephrocalcinosis. Her ophthalmologic examination, cranial magnetic resonance imaging, and electroencephalography were normal.
The results of blood serum tests were as follows: calcium 14.5 mg/dL (N: 8.8-10.2), phosphorus 7.1 mg/dL (N: 4.5-5.5), ALP 1 IU/L (N<70), magnesium 1.8 mg/dL (N: 1.7-2.55), parathyroid hormone (PTH) 5.5 pg/mL (N: 15-65), and 25-hydroxy vitamin D3 49.5 ng/mL (the cut-off for vitamin D3 deficiency is <20). Urinary calcium excretion was high with a calcium/creatinine ratio of 0.64. Her complete blood count and routine biochemistry tests for renal, liver, thyroid functions, immunoglobulins, tandem mass spectrometry, urinary and plasma amino acid analysis, urinary organic acid analysis were all found to be within normal limits.
Her seizures, refractory to previous antiepileptic therapy, were under control after pyridoxine (vitamin B6) administration (100 mg/day initial, 50 mg/day maintenance dose, PO). Intravenous hydration with saline plus furosemide was started at the time of admission to treat hypercalcemia, and dietary calcium intake was restricted. This therapy had minimal effect on calcium levels, and serum calcium was 13.8 mg/dL on the 3rd hospital day. The hypercalcemia was resistant to other treatment options including prednisolone (2 mg/kg/d). Normocalcemia was achieved with a single dose of calcitonin (4 U/kg/d).
Chromosome analysis of peripheral leukocytes using high-resolution binding technique showed a normal 46,XX karyotype. A homozygous p.267_268delHF (c.799_804delCACTTC) mutation was detected in ALPL gene. The parents were also heterozygous for the new mutation. Genomic DNA of both parents and the index patient was screened for mutations in ALPL gene, and Sanger-sequencing revealed a novel homozygous mutation, p.267_268delHF (c.799_804delCACTTC), in the index patient (, , ). This alteration was not annotated in National Center for Biotechnology Information or the human gene mutation database, and both parents were heterozygous carriers for this novel mutation in ALPL gene.


A 54-year-old postmenopausal woman was evaluated for a left-sided breast mass. A 14x11 mm mass located in the upper-middle part of the left breast with a breast imaging-reporting and data system (BI-RADS) 5 score was determined at breast ultrasound and mammography. The patient’s cancer was staged as IA (T1N0M0). Preoperative lymphoscintigraphic images were obtained using a large field of view gamma camera (ECAM, Siemens, Illinois, USA) on anterior and oblique positions at 5, 30 and 60 min. following the periareolar-subdermal injection of 99mTc-labeled nano-colloid in a dose of 74 MBq/0.2 mL to the left breast. In the scintigraphic image, the two focal uptakes in nodal basin () were considered as sentinel lymph nodes (SLNs). These foci were marked on skin in the left axillary region (). The patient underwent 3D F-SPECT guided breast surgery with a two-day protocol. 24h after tracer injection, we scanned the breast and the axilla for a 2-4 min period in different directions (1 min each in the medial, dorsal and medial-dorsal directions) according to the procedure described by Wendler et al. (8). A sufficient count rate was determined by using a color code in green. The number and position of the sentinel nodes were observed on a computer screen and the completion of the surgical procedure was confirmed by repeat screenshots. 3D F-SPECT revealed two main radiotracer uptakes on the injection site (83%) and in the left level I axillary lymph nodes (17%) (). The lymphatic hot spot (mean count rate: 165 cps/s) was reached through a skin incision under the guidance of realtime 3D navigation definitions (). After histological frozen section examination of the excised SLNs was reported as tumor negative, the procedure was completed with breast-conserving surgery with safe surgical margins (). Final histopathology of the tumor revealed infiltrative ductal carcinoma.


A 40-year-old premenopausal woman had a 21x15 mm mass in the upper-outer quadrant of her right breast compatible with BI-RADS 4c score on breast ultrasound and mammography. The patient was classified as Stage IIA (T2N0M0) breast cancer according to the imaging studies. A tru-cut biopsy was reported as infiltrative ductal carcinoma. Preoperative lymphoscintigraphy and F-SPECT guided surgery was performed using same radiotracer, injection and imaging techniques with the one-day protocol. Scintigraphic examination showed high nodal uptake in the right axillary region and this area was marked on the skin. 4 hours after radiotracer injection, breast surgery was started with the guidance of 3D F-SPECT imaging. The real-time image from 3D F-SPECT detected meaningful radiotracer uptakes in two hot spots on the injection site and the right axilla. The hot spot which was located within the right level II axillary lymph nodes was accessed (mean count rate: 322 cps/s) and removed surgically. Frozen section evaluation revealed reactive lymph nodes that were tumor negative. The surgeon completed the operation with breast-conserving surgery with safe surgical margins.


A 1-year-old female baby visited our department for the evaluation and treatment of an accessory opening above the left nostril which had been existed since her birth. The patient and her parents’ medical history was non-specific except that the patient had an accessory nostril. Also, the age of her mother was 32 years old and there was nothing wrong at parturition.
Physical examination showed a left accessory nostril that connected to the normal left nostril. The internal diameter of the accessory opening was measured about 0.2 cm (Fig. ). Normal ipsilateral nostril was a little smaller than the other side, but the size of the alar base was similar to the right nostril. There was no columellar deviation. The nasal cavity structure was normal. Also, there was no any other deformity on her body. The patient was diagnosed to have a supernumerary nostril.
Surgery was operated under general anesthesia. First, we drew the abnormal structure around the left nostril by gentian violet solution (Fig. ). The incision was performed around the accessory nostril, and then, dissection of the tract was done by using Metzenbaum scissors (Fig. ). After opening the nostril, the soft tissue across the normal and false nostril was removed. De-epithelialized part of false and normal nostril was attached to each other (Fig. ). A wedge-shaped tissue of the alar side wall was removed. Layered suture of the alar rim was applied (Fig. ). Minimal surgical procedure was applied. To consider her growth, rhinoplasty will be left as an option for treatment.
After 1-year follow up, the accessory nostril on the left side was totally obstructed but the irregular-shaped soft tissue was remained (Fig. ). The operated left nostril was larger than the contralateral side. To correct the nostril asymmetry, rhinoplasty was performed (Fig. ). The patient got cured without special problem. At 1-year postoperative examination, the result and cosmetic appearance was satisfied (Fig. ).
The nose develops from a frontonasal process in the early fourth week of gestation. The frontonasal process is formed from the forebrain by enlarging and pushing the ectoderm anteriorly and laterally. Nasal placode appears on both sides of the frontonasal process. The nasal placode is the surface ectoderm becoming thicker in two to three cell layers on frontonasal process. In the beginning of the fifth week, the center of the nasal placode sinks to form a nasal groove. As a result, a horseshoe-shaped lateral and medial nasal process appear. As the lateral nasal process and the medial nasal process develop, the nasal groove gets deeper and forms a nasal pit. In the end of the fifth week, the nasal pit gets deeper and becomes nasal sacs. The nasal sacs move into the middle, as maxillary process develops medially. And then, the nasal sacs forms nasal cavity and nostrils [].
Although the exact pathogenesis of supernumerary nostril has not been revealed, it might cause problem of division of lateral nasal process.
In 1906, Lindsay was first to report the bilateral supernumerary nostril []. An accessory nostril was above the normal nostril and connected to the ipsilateral nasal cavity. In 1920, Tawse reported the case of unilateral supernumerary nostril above the right normal nostril []. An accessory nostril was connected to the right nasal cavity. In 1962, Erich reported a patient who has two noses []. He described that if the position of the accessory olfactory pit is too lateral, the fusion of the laminae is not interfered, which causes the supernumerary nostril. In 1987, Nakamura and Onizuka reported a patient who has divided right alar to medially and laterally []. An accessory nostril was located medially. Nakamura and Onizuka hypothesized that supernumerary nostrils resulted from fissuring of the lateral nasal process accidentally. They proposed that the lateral nasal process is divided into two segments and each segment develops into each nostril on the one side of the nose. Also in 1987, Reddy and Rao reported a patient with triple nostrils []. An accessory nostril is located below the left normal nostril and connecting into the nasal cavity posteriorly. They assumed that if an accessory olfactory pit appears either above or below the normal location of the placode, consequently, a supernumerary nostril will be formed. In 2009, Kashyap and Khan reported a case of supernumerary nostril on the left side with an accessory alar cartilage []. An accessory cavity was smaller than the normal cavity and was not connected with the ipsilateral nasal cavity. Kashyap and Khan proposed that the presence of alar cartilage from the accessory nostril describes the embryological fissuring of the lateral nasal process. In most of the cases, the supernumerary nostril was located on the left side and above the normal nostril. It was either isolated or associated with other congenital anomalies such as cleft lip and palate, naso-ocular cleft, esophageal atresia, and patent ductus arteriosus []. Franco et al. reported that 45 % of the patients were related to other congenital anomaly [].
In the treatment of supernumerary nostril, it is important to remove the accessory nasal tract entirely and preserve the normal nostril. In most cases of supernumerary nostril, fistulectomy and reconstruction with local flaps was performed as a surgical technique. Surgery should be performed as early as possible, because in early age, it is easier to access the deep portion of the nasal cavity, avoid serious affect to nasal cartilage, and avoid deformity around the ala nasi due to fistula. In this case, the accessory opening was obstructed by using simple incision and primary closure without forming local flap. Although the patient had two surgeries to remove the accessory nostril, small and recognizable residual defect on nostril rim of affected side is observed. For the patient’s psychosocial growth, rhinoplasty will be performed after re-evaluating face.


A 41-year-old female with no significant past medical history presented to her primary care physician with mucinous and bloody vaginal discharge. A pelvic ultrasound revealed thickened endometrium. An endometrial biopsy was performed and demonstrated mucinous epithelium of gastrointestinal origin. The patient underwent a colonoscopy and an esophagogastroduodenoscopy, which revealed no evidence of a primary tumor. She then underwent a diagnostic laparoscopy which showed diffuse peritoneal carcinomatosis of the diaphragm, anterior surface of the liver, omentum, pelvic peritoneum, and a mucinous mass lesion in the distal appendix. Initially, an appendectomy was performed. Slides from the appendectomy specimen were reviewed and demonstrated fibrous obliteration of the majority of the appendiceal lumen with a low-grade appendiceal mucinous neoplasm present at the tip of the appendix. No destructive desmoplastic invasion was identified. There was an area of possible microscopic perforation with rare strips of extra-appendiceal neoplastic epithelium and the final pathologic diagnosis was LAMN with a high risk of recurrence.
She was referred to our institution for further surgical therapy where she underwent complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. This included omentectomy, excision of mucin from the lesser sac and bowel surfaces, peritonectomy of the bilateral diaphragms and pelvis, hysterectomy, and bilateral salpingo-oophorectomy. Pathology demonstrated low-grade mucinous neoplasm diffusely involving the endometrial surface, ovaries, and other resected specimens. The neoplastic endometrial surface epithelium was histomorphologically identical in appearance to the peritoneal disease (Figures and ). There was no invasion of endometrial stroma. Immunohistochemical stains demonstrated that the neoplastic epithelium was positive for CK7, CK20, villin, and CDX-2 and negative for vimentin and PAX-8, indicating intestinal differentiation (Figures –). All immunohistochemical studies had appropriately positive external and internal tissue control staining. The patient continues to do well and is without evidence of recurrence 2 years after surgery.


A 76-year-old woman with no previous medical history, including that of head trauma, presented to us with a minor transient headache and was examined. The results of the patient’s general and neurological examinations were normal. No abnormal appearances were found on her scalp.
Radiography showed the presence of a linear bone deficit in the left parietal diploe (Fig. ). The lesion measured 1 cm × 8 cm in size, and was located almost parallel to the coronal suture. Computed tomography (CT) imaging identified hyperosteosis in the skull around the bone deficit, but the lesion did not yet eroded the outer layer of the skull (Fig. b). After comparing this CT image with a previous one that had been obtained 5 years before at another hospital (Fig. a), we determined that the lesion had expanded. Magnetic resonance imaging (MRI) of the brain was performed to examine the contents of the lesion. The lesion had an outer membrane that was iso-intensity on both T1- (Fig. b) and T2-weighted (Fig. d) images and was slightly enhanced with gadolinium contrast media (Fig. c). The main part of the inside appeared at iso- and low intensities on T1- (Fig. b) and T2-weighted (Fig. d) images, respectively, and it was clearly enhanced with gadolinium contrast media to the same extent as vessel lumens (Fig. a, c). As the results of these studies suggested the presence of a vascular abnormality, CT angiography was performed. In the 3D reconstructed images, a club-shaped lesion was visible in the venous phase (Fig. a, b). At the medial end, the lesion passed through the inner table of the skull and drained into the superior sagittal sinus. However, the lateral side did not appear to communicate with any vessels, and it did not cross the coronal suture.
The patient opted for surgical treatment. During surgery, a portion of the skull that was assumed to be on the lesion was exposed via a linear skin incision. Neither substantial changes nor deficits were found on the skull surface, but a part of the surface that was located around the lateral end of the lesion contained a reddish-blue tinge, suggesting the thinning of the outer table of the skull. The bluish part of the outer table of the skull was removed to expose a membrane of a sac-like structure which was filled with liquid. The membrane was not pulsating. The sac had several communications with the diploic veins that we assumed to be feeding vessels. By interrupting these inflows, the sac deflated. A section at the end of the sac was cut out and sent for histological examination. There was copious bleeding from multiple interdiploic venous channels, and it was controlled by the bone wax. On the other hand, bleeding from the edge of the sac was not so heavy, suggesting that main feedings no longer remained. The edge was then ligated and the scalp was closed in layers.
Histopathological study of the lesion showed a membranous wall that consisted mainly of fibrous tissues with scattered spindle cells (Fig. a). No oncocytes were present. The membranous wall was considered to be a dilated venous wall as it contained a single layer of luminal endothelial cells (Fig. b) that was positive for CD31 staining (Fig. c), but lacked elastic laminae after silver staining (Fig. d).
The post-operative course of the patient was uneventful. MRI showed that there was an intensity change in the inside of the sac on T2-weighted images. The main part of the inside of the sac showed low intensity prior to surgery (Fig. d) but changed to high intensity after surgery (Fig. e), suggesting that it had been filled with thrombi. In addition, magnetic resonance venography showed that there was no longer any blood inflow into the sac (Fig. c, d). At a follow-up time-point of 15 months, there was no recurrence of abnormal venous flow.


The posteroanterior (PA) radiograph of a 51-year-old female patient showed an intraosseous lytic lesion of the right capitate bone () that was associated with a marked radionuclide uptake in all carpal bones using bone-granulocyte scintigraphy () and magnetic resonance imaging (MRI) demonstrated low to intermediate signal intensity of the lesion without soft-tissue extension (). Due to these findings, an osteomyelitis of the capitate bone was suggested by the radiologist. At first, free intraosseous sample was taken that revealed a benign GCT in histological examination. The chest radiograph did not show pulmonal pathology. Second, intralesional curettage and packing of the cavity with cancellous iliac crest bone grafts combined with a fusion of the third carpometacarpal (CMC III) joint using a 2,0 mm titanium plate (Medartis, Basel, Switzerland) were performed.
One year after, the PA and lateral radiographs showed union of the CMC III joint fusion without hardware failure, but there was pronounced destruction at the proximal pole of the reconstructed capitate bone and at the distal facet of lunate bone, and a positive ring sign associated with distinctive volar tilt of scaphoid bone in the absence of an injury after the second procedure (). Third, the CMC III joint fusion plate was removed and the midcarpal joint completely excised. The histological examination did not show recurrence of GCT but revealed pronounced midcarpal osteoarthritis (OA). Intraoperatively, a nonunion at the waist of scaphoid bone was seen. Postoperatively, computed tomography (CT) scans showed complete union of CMC III joint fusion associated with sufficient osseointegration of cancellous bone grafts at the capitate bone and additionally the humpback deformity due to a nonunion at the waist of scaphoid bone (). Fourth, an open 4CF with excision of the entire scaphoid bone using a corticocancellous iliac crest bone graft and two cannulated headless titanium compression screws (Medartis, Basel, Switzerland) was performed. One 2,2 mm screw was transversely inserted into triquetrum bone, and the second 3.0 mm screw was longitudinally inserted into the reconstructed capitate bone in an antegrade manner breaching the articular surface of lunate bone. Intraoperatively, there was a safe subchondral placement of the longitudinally inserted compression screw at the lunate bone ().
One year after 4CF, a migration of the longitudinally inserted compression screw into radiocarpal joint with erosion of the articular surface at the distal radius was present (). The patient declined a total wrist fusion (TWF), and a TWA using the relatively new angle-stable Maestro™ Wrist Reconstructive System (WRS, Biomet, Warsaw, Indiana/USA) with the use of a scaphoid augment distally was performed (). After that, the course was uncomplicated.
At the 3-year follow-up (including 1-year follow-up after TWA), the radiographs did not show recurrence of GCT, the TWA was not loosened, and there were no signs of impingement nor instability with terminal ranges of motion (Figures -). Pain improved from 8 to 2 in visual analog score (0–10 points). Patient-rated wrist evaluation (0–100 points) improved from 88 to 37. Wrist extension and wrist ulnar deviation improved from 20° to 45° and from 20° to 30°. Wrist flexion and wrist radial deviation were equal to preoperative. The forearm motion arc with 90° supination and 90° pronation was 100% to the opposite forearm (). The patient reported that she would have the motion-preserving TWA again.


A 65-year-old female patient was referred to our hospital with complaints of swelling and nodular skin lesions on both legs. She had a history of rheumatoid arthritis and treatment with corticosteroid medication for five years. On physical examination, dark blue-purplish macular and nodular skin lesions were observed on the legs along with pretibial edema (). The lesions that had appeared within a few months were not painful. She was diagnosed with KS with biopsy of the skin lesions (). Laboratory tests were within normal limits except an elevated erythrocyte sedimentation rate. Anti-HIV antibody was negative. She was referred to our department for initial staging with 18F-FDG PET/CT imaging. A whole body 18F-FDG PET/CT imaging was performed 60 minutes after 370 megabequerel 18F-FDG injection using an integrated PET/CT scanner (Siemens, Biograph mCT, Germany). 18F-FDG PET/CT imaging showed multiple nodular skin lesions with increased FDG uptake on both legs (SUVmax: 6.1). In addition, there were hypermetabolic bilateral inguinal and popliteal lymph nodes (SUVmax: 3.6-5.6) ().


A 32-year-old man working as a carpenter in Lomé, Togo, was admitted in August 2015 to the University Hospital Campus of Lomé for a 3 day history of severe headaches, vomiting, fever, and intense agitation (Table ). He had no particular medical history and no risk factors for immunodeficiency. At admission, the body temperature was of 36.4 °C, and the general state was acceptable, with a correct conservation of consciousness. The neurological examination did not show any sign of motor or sensitive defect, of cranial nerve dysfunction or cerebellar symptoms. There was no hearing or skin abnormalities, no obvious neck stiffness, and the rest of the clinical examination was normal. Acute meningeal hemorrhage was evocated as the initial diagnosis. Cranial computed tomography could not be performed and a symptomatic treatment associating antalgic, antipyretic, and anticonvulsant medication was initiated. At the second day of admission, the patient was febrile, agitated, and still suffered from severe headaches and vomiting. The neck had become stiff, and Kernig and Brudzinski signs were positive. The meningeal signs led to the realization of a lumbar puncture, which yielded a turbid cerebrospinal fluid (CSF) concluding to the diagnosis of bacterial meningitis. An empiric intravenous antibiotic treatment associating ceftriaxone (2 g, 2×/d for 24 h then 1 g, 2×/d), ofloxacin (200 mg, 3×/d), and metronidazole (500 mg, 2×/d) was started.
CSF analysis showed 2,800 leukocytes/mm3 (65 % lymphocytes and 35 % neutrophils), a protein concentration of 1.8 g/L, and a glucose concentration of 0.47 g/L (2.6 mmol/L) with a plasma glucose concentration of 1.41 g/L (7.8 mmol/L; ratio = 0.33). Gram staining did not reveal any microorganism. Blood and CSF cultures, after 48 h and 24 h of incubation, respectively, grew small beta-hemolytic colonies on horse blood agar plates. The bacteria were catalase negative, gram-positive cocci, in chains or in pairs. They were identified as S. suis (score 2.56) by MALDI-TOF (Matrix Assisted Laser Desorption Ionisation Time Of Flight) spectrometry (BrukerTM) and as S. suis serotype 1 (97 % probability) by VITEK 2 Gram-positive card system (bioMérieux, Marcy l’Etoile, France). Slide agglutination with type-specific hyperimmune serum and specific multiplex PCR identified the isolate as S. suis serotype 2, indicating a serotype misidentification by the automated card system, and concluding, together with Multi-Locus Sequence Typing [–], to an infection due to S. suis serotype 2, Sequence-Type (ST) 1, one of the most virulent and frequently isolated clone all over the world [, ]. Antimicrobial drug-susceptibility testing performed according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations characterized the strain as susceptible to penicillin (Minimum inhibitory concentration (MIC) < =0.25 mg/L), erythromycin, clindamycin, levofloxacin, and linezolid and resistant to tetracycline.
After S. suis was identified, the patient reported working as a pork butcher every week-end. The patient did not have any sign or symptoms of endocarditis, and the antibiotic treatment was replaced by ampicillin (2 g, 3×/d) and gentamicin (80 mg, 2×/d) for 7 days. While the patient was receiving treatment for 1 day, vertigo and tinnitus developed, for which he received adjunctive corticoid therapy and the treatment was completed with no particular adverse events. Hearing disorders, especially hearing loss, are the most common sequelae of S. suis infections and affect more than 50 % of patients who survive meningitis []. In that case, hearing disorders evolved into severe hearing loss in the left and right ears (80 dB), and the patient was still suffering from tinnitus 9 months after the diagnosis. One year later, tinnitus had disappeared and the patient’s auditory function had improved from severe to moderate hearing loss.


A one-year-old, 9.5-kg male was admitted to our hospital (Guangzhou Women and Children Medical Centre, China) with tachypnoea. He had a history of recurrent pneumonia, sweating and growth retardation.
On admission, a physical examination revealed grade II/VI systolic murmur at the left sternal border. Moreover, cardiac dextroposition and a radiopaque right hemithorax were confirmed on a chest X-ray examination . Echocardiography showed an enlarged right cardiac chamber, partially anomalous pulmonary venous drainage, an 8-mm secundum atrial septal defect (ASD). The systolic pulmonary arterial pressure was 63 mmHg, calculated from tricuspid regurgitation velocity.
The computerised tomography angiography (CTA) revealed partially anomalous pulmonary venous drainage to the IVC, APC originating from the abdominal aorta, and hypoplasia of the right lung , which confirmed the diagnosis of scimitar syndrome. The patient’s parents refused conventional surgical intervention, considering the high risk of postoperative events.
As an alternative, stepwise transcatheter intervention and coil embolisation of the APC and closure of the ASD were selected to decrease the left-to-right shunt and reduce pulmonary arterial hypertension. The patient proceeded to have cardiac catheterisation under general anaesthesia. A 4-F Cobra cathether (Cook, Bloomington, IN) was delivered to the APC via the femoral artery and then two 8 × 50-mm MReye embolisation coils (Cook, Bloomington, IN), five 5 × 30-mm MReye embolisation coils and two 5 × 30-mm Cook coils (Cook, Bloomington, IN) were deployed for occlusion .
After percutaneous entry of the femoral vein, a sizing balloon 8-F MPA2 catheter was introduced over an extra-stiff guide wire positioned in the left upper pulmonary artery to measure the pulmonary arterial pressure (pathway: IVC->RA: right atrium->RV: right ventricule->MPA: main pulmonary artery). Using an exchange 260-cm Cordis guidewire, an occlusion balloon catheter was introduced into the left atrium to determine the stretched diameter of the ASD (pathway: MPA->RV->RA->ASD->LA). A 10-mm Amplatzer septal occluder (AGA Medical, MN) was implanted after balloon sizing the defect (diameter: 8 mm) . The procedure was successful.
The total surgical time was 150 min; fluoroscopy time was 45 min. Pulmonary-to-systemic flow ratio (Qp/Qs) dropped from 2 to 1.2 and pulmonary arterial pressure decreased from 70/41 (50) mmHg to 45/14 (24) mmHg.
After intervention, the patient improved clinically and was treated with asprin and frusemide. Three months later he was asymptomatic, and he was clinically well at the 12-month follow-up assessment. The indicators of right cardiac chamber and pulmonary arterial pressure estimated by echocardiography were normal.


A 22-year-old woman with no significant past medical history presented to the ED with hip pain after hitting an old wooden table while walking by. The patient reported she felt something “go in” but was unable to retrieve the foreign body herself. She described the pain as dull, 3/10 in severity, non-radiating, and worse with ambulation. The patient’s vital signs on arrival were as follows: temperature 37.4°C; blood pressure 118/68 mmHg; heart rate 68 beats per minute; respiratory rate 14 breaths per minute; oxygen saturation 99% on room air. Physical exam of the hip revealed a 3mm puncture wound in the anterior-lateral thigh, approximately 10cm distal to the anterior-superior iliac spine. There was noted to be 1cm diameter of surrounding erythema; however, there was no fluctuance or induration that was appreciated. No foreign body was palpated on exam. No pain was elicited on passive extension of the hip or knee.
A plain film radiograph showed no evidence of retained foreign body. However, given clinical suspicion for a radiolucent retained foreign body, bedside US was done, which confirmed the presence of a foreign body in the anterior thigh (). The US probe was placed in an orientation that allowed for direct visualization of the longitudinal axis of the foreign body. Using sterile technique at the bedside, a new tract was created using a scalpel and the foreign body was removed using forceps with traction applied along the longitudinal axis.


A previously healthy 16-year-old male with blunt abdominal injury sustained in a road traffic accident was referred to our department. On arrival, he was in severe hemorrhagic shock, and his vital signs were as follows: heart rate 160 bpm, blood pressure unmeasurable, respiratory rate 27/min, and Glasgow Coma Scale E3V4M6. His chest X-ray revealed no apparent hemothorax and pneumothorax, and pelvic X-ray revealed no unstable fracture of the pelvic ring. Focused assessment with sonography for trauma was positive; thus, we suspected intra-abdominal hemorrhage. The arterial blood gas assessment showed metabolic acidosis, and the laboratory test on admission revealed coagulopathy (Table ). The fluid resuscitation (crystalloid 1000 ml bolus infusion) improved his blood pressure to 71/37 mmHg. REBOA was placed with a 12-Fr sheath on the right femoral artery by the Seldinger method without sonography 10 min after admission, and the balloon placement at zone 1 was confirmed by chest X-ray. The patient was prepared for an emergency laparotomy 25 min after admission. During the surgery, we found splenic rupture, stomach perforation, hepatic injury, rectal and omental injury, and splenectomy; temporary repair of the injury, gauze packing, and vacuum packing closure were performed as damage control measures (operation time 65 min, intraoperative blood loss 2470 g). REBOA was performed for 25 min with total occlusion and deflated after the control of major bleeding. Postoperative enhanced computed tomography (CT) revealed extravasation from the left kidney and posterior segment of the liver. Thus, we performed angiography for embolization. After admission to the intensive care unit, coagulopathy and hypothermia were corrected with massive blood transfusion; however, his vital signs continued to remain unstable. A chest drainage tube was inserted for left hemothorax removal. Due to increased amount of blood discharge from the chest, we performed exploratory thoracotomy and re-laparotomy. During the second surgery, the blood leakage was found to originate from the hepatic injury and passed through the diaphragmatic injury into the thoracic cavity; we then arrested the bleeding. Fourteen hours after admission, the patient became stable. However, we retained the sheath for a potential repeat of REBOA in the event of re-bleeding. Twenty-eight hours after admission, swelling and paleness were observed in his right lower leg (Fig. ). Suspecting lower extremity ischemia and compartment syndrome, we removed the sheath with a manual maneuver and performed fasciotomy for the lower leg (Fig. ). The color of the right lower limb was thus partially resolved, and we guessed the ischemic change was improved. However, amputation was necessary because of ischemic necrosis on day 32. On day 81, he was transferred to a community hospital for rehabilitation.
We describe the severe ischemic complication of the lower extremities associated with sheath placement for REBOA. Potential ischemic complications of REBOA include acute kidney injury, vascular injury, bowel ischemia, spinal cord ischemia, and lower extremity ischemia []. However, incidence of these complications is very rare [].
We believe that the use of large-sized sheaths for REBOA is a critical risk factor for lower extremity ischemia. In a prospective REBOA case registry, 74 % (34/46) of all REBOA interventions were performed using a 12- or 14-Fr sheath []. Although 7-Fr sheaths for REBOA are currently available and frequently used in Japan, this was not the case at the time of treatment of this patient. Therefore, we had to use a 12-Fr sheath. As blood flow is inversely proportional to the vessel cross-sectional area [], it is acceptable that large-sized sheaths may decrease blood flow to the extremities. For example, the cross-sectional area of the blood flow was shown to reduce by 50 % in a model wherein a 12-Fr sheath (diameter 4 mm) is inserted in an artery with 5.6-mm diameter (the size of the femoral artery in our case) (Fig. ). In a patient who underwent an attempted transfemoral transcatheter aortic valve replacement, a high sheath femoral artery diameter ratio and sheath femoral artery area ratio estimated on CT angiogram were reported as significant predictors of vascular complications []. Our patient was physically small (156 cm), and the diameter of his femoral artery on the contralateral site of sheath placement was also small (5.6 mm), according to the CT imaging after the primary surgery (Figs. and ). Therefore, disproportion of the sheath and femoral artery sizes may have caused the ischemic complication. We propose that the use of large-sized sheaths in small arteries increases the risk for lower extremity ischemia. Additionally, hypotension and occlusion of the aorta with REBOA may further aggravate the risk of ischemic complications due to decrease in lower extremity arterial flow. A retrospective study showed that 7-Fr sheaths for REBOA can be safely used []; however, even 7-Fr sheaths should be used with caution especially in small-built patients such as women or adolescents.
We believe that decreasing the duration of sheath placement and aorta occlusion may also help avert lower extremity ischemia. The reported median duration of sheath placement in a study was 28 (18–45) h, which is equal to the duration in our case (28 h) []. In an animal experiment, 60 min of REBOA was well tolerated and recoverable [], and the median time of total balloon occlusion was reported as 26 (10–35) min, which is similar to that in our case []. Although the duration of sheath replacement and aorta occlusion in our case were believed to be tolerable, had we decreased the duration of sheath placement and aortal occlusion to as short as possible, the complication may have been averted.
Monitoring of lower extremity perfusion is essential to detect ischemia. We relied on visual examination and Doppler study for this purpose; however, we could not avoid the ischemic complication as both these methods lack objectivity and are prone to inter-observer variability. This probably contributed to the delay in the detection of ischemia. Near-infrared spectroscopy (NIRS) is reported as a good monitoring tool to detect lower extremity ischemia and compartment syndrome [, ]. Use of NIRS for this purpose should be considered.


A 20-year-old healthy male presented to the emergency department after falling from a skateboard. He sustained blunt trauma to his right chest wall, resulting in pleuritic pain and mild dyspnea. Diagnostic workup included chest radiography (CXR), which showed no acute findings (). Further evaluation with chest computed tomography (CT) scan demonstrated fractures of the right 4th through 6th ribs. Herniation of the middle lobe of the right lung was also identified on CT scan ().
The patient was admitted for observation and pain management. His pain and dyspnea improved and he was managed conservatively. A repeat CXR on hospital day two was stable, and the patient was discharged home. Ten days after discharge a follow-up chest CT scan was completed and demonstrated a decrease in herniated lung ().


A 44-year-old man without systemic underlying disease suffered from painless gross hematuria combined with urine retention for days. He had LUTS for years and became worse recently. Stony-hard prostate with markedly enlarged size was found during digital rectal examination, but the PSA level was detected within the normal range (total PSA: 0.42 ng/mL). Transrectal ultrasonography (TRUS) revealed multiple nodules in the prostate. The largest nodule is 6.3 cm and the whole prostate measures about 300 grams. Architecture derangement of prostate, possible central necrosis with hemorrhage, and enlarged right internal iliac lymphadenopathy were found on prostate magnetic resonance imaging (MRI) (). No bony metastasis was detected on the bone scan. We performed TRUS-guided prostate biopsy but massive gross hematuria attacked days after the procedure. Thus, cystoscopy for checking bleeding was done and the specimen resected from prostate was reported as malignant peripheral nerve sheath tumor (). For further staging, we arranged chest computed tomography (CT), which revealed a solitary 0.9 cm nodule in the right upper lobe.
Considering the difficulty of radical surgery due to huge size of prostate, we prescribed neoadjuvant chemotherapy (5-Fluorouracil + Cisplatin + Ifosfamide) for 5 cycles. Regression of previous lung nodule was found on follow-up chest CT. Pelvic MRI revealed residual tumor lesion within the visible prostate gland, whose size regressed to 83 grams. The radical cystoprostatectomy was performed, and tumor invasion to bladder was found during operation. Bilateral pelvic lymph node dissection was also done and no metastasis was found. The pathologic diagnosis reported was consistent with MPNST.
After the operation, we prescribed adjuvant concomitant chemoradiation therapy (Cisplatin + 5-Fluorouracil + Ifosfamide with external beam radiation therapy 6600 cGy, 33 fractions). Follow-up abdominal CT done in postoperative 3 months showed multiple ill-defined poorly enhanced nodules in the liver and a 3.5 cm gallbladder mass. The target therapy, Pazopanib 400 mg per day, was given for palliative treatment due to suspect disease progression. However, his clinical condition went downhill and he expired three months later.


A 58-year-old female after allogeneic stem cell transplant (SCT) for acute myelogenous leukemia (AML) presented with cough productive of brown sputum and right shoulder pain. Her symptoms progressed over the course of 2 weeks. She did not have fever, chills, or shortness of breath. She denied chest pain, vomiting, or diarrhea and she did not report headache, loss of consciousness, or seizures.
She was diagnosed with AML 2 years ago for which she underwent allogeneic SCT. Thereafter she developed chronic graft versus host disease (cGVHD), which was treated with steroids and mycophenolate mofetil. Her home medications included prednisone, mycophenolate mofetil, and dapsone.
On examination, she was afebrile with a heart rate of 57, blood pressure of 150/74, and oxygen saturation of 93% on room air. Lung examination revealed reduced air entry and rhonchi over the right upper lung zone. Heart exam revealed regular heart sounds without murmurs and her abdomen was soft without tenderness or organomegaly.
Laboratory tests showed white blood cell count of 7.6 × 109 cells/L (88% neutrophils), hemoglobin of 94 g/L, platelets of 34 × 109 cells/L, and creatinine of 70 μmol/L. Chest computed tomography (CT) scan was done and is shown in . Bronchoalveolar (BAL) stains and cultures were negative for bacteria, mycobacteria, and fungi. Serum as well as BAL galactomannan and serum cryptococcal antigen were negative. Her prednisone dose was reduced and she was discharged home on ertapenem and voriconazole that were given on empirical basis.
The patient's symptoms persisted, so a follow-up chest CT scan was done 2 weeks into treatment (). She was readmitted to the hospital and started on broad-spectrum antibiotics: linezolid, imipenem, amikacin, and liposomal amphotericin B. Her vital signs on admission were stable with an oxygen saturation of 93% on room air. Labs were within her baseline. A repeated BAL was performed.
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A 16 days old newborn female from Saudi Arabia was presented to the clinic with a skin defect localized on the scalp since birth. The baby did not suffer from any ailments, and her medical history was unremarkable. Her mother, 32 years old, denied any history of illnesses during her pregnancy, infection or drug intake taking including Non-Steroidal Anti-Inflammatory Drugs (NSAID) or methimazole. She completed 38 weeks of gestation, and delivered her baby via a normal vaginal delivery.
The newborn did not sustain any birth injury and did not suffer from any other abnormalities or feeding difficulties. She did not require any intensive care, and went home from hospital with her mother. Upon local examination, the defect was solitary, localized with an irregular shape and approximately 6×6 cm in size (). The lesion involved the epidermis and the upper dermis only. Neurosurgical team was involved in the care of this patient. A CT Scan of the head was performed, and no deep tissue involvement was noted.
Reconstruction solutions were offered to the parents but they insisted on non-surgical intervention. Therefore, the patient was treated with non-invasive debridement of the lesion and local therapy, including gentle water cleansing and the application of topical antibiotic ointment. 6 months later, the patient has returned for a follow up. Scar tissue has formed over the defect (). Family history revealed that none of her parents had the same condition; however, two of her sisters did, and were diagnosed with cutis aplasia. The elder one is currently 4 years of age, with right unilateral terminal reduction of the first and second toes (). The other sister was born prematurely and died shortly after birth due to cardiac anomalies.


A 69-year-old male patient, without any comorbidities, presented with fullness in the left axilla. The initial examination showed lymphocytosis and lymphadenopathies in the bilateral axillary and inguinal region. There was neither hepatosplenomegaly nor pathological lymph nodes in the abdominal and thoracic cavity. Lymphocytosis and basket cells were seen in the blood smear. Excisional biopsy from the left axilla showed infiltration by CD5-positive cells. Immunohistochemistry was consistent with a diagnosis of chronic lymphocytic leukemia (CLL) infiltration. The bone marrow biopsies supported the diagnosis with hypercellularity and diffuse interstitial infiltration of small atypical lymphoid cells. The patient had been followed with a diagnosis of CLL for 2 years. Due to initial stage 1 disease, the patient had been periodically followed without medical therapy.
In a routine outpatient visit, the clinically asymptomatic patient was evaluated with lymph node excisional biopsy due to progression of the pathological lymph nodes in order to exclude Richter’s transformation. In addition, bone marrow sampling was performed. Pathology revealed small atypical lymphoid cells consistent with an ongoing lymphoproliferative disease and infiltration of an adenocarcinoma as a second primary malignancy. Further immunohistochemical staining was inconclusive for the origin of the tumor. The age of the patient, osteoblastic metastatic lesions detected in a bone scan, and prostate-specific antigen (PSA) level of 1712 ng/mL led us to order a work-up for prostate cancer. Transrectal prostate biopsy showed prostate adenocarcinoma with a Gleason score of 10. The patient was treated with goserelin (10.8 mg SC, every 12 weeks) and bicalutamide (50 mg daily). The analysis of bone scans before hormonal therapy showed metastatic lesions in the bilateral scapula, thoracic vertebral column, pelvis, bilateral humerus, and femur. For skeletal metastatic disease, zoledronic acid (4 mg intravenous, every 4 weeks) was started and palliative radiotherapy was planned for painful metastatic lesions in the thoracic vertebrae. Radiotherapy to T3-6 and the right scapula with a total of 30 Gy divided into 10 fractions was planned. Pathological lymph nodes associated with CLL, ranging between 1 and 3 cm in diameter in the bilateral inguinal areas, axilla, neck, and hilum, were noted for follow-up. On day 7 of radiotherapy the patient complained about mild nausea, progressive malaise, and perioral numbness. Physical examination was normal except for pathological lymph nodes with minimal regression and paleness. The largest lymph node in the right axilla had regressed from 3 to 2 cm and the other pathological nodes were stable. The hilar fullness in chest X-ray was stable. The only medications used were drugs for prostate cancer (bicalutamide and goserelin), lansoprazole for dyspepsia, and dexamethasone (8 mg), which was planned with the radiotherapy. The laboratory evaluation revealed acute renal failure complicated with TLS (). The PSA value was stable. The patient was hospitalized and aggressively hydrated with 0.9% NaCl at 500 mL/h in the first 6 h of follow-up with monitorization of hourly urine output. In the initial evaluation, due to hypocalcemia (5.2 mg/dL) with neuromuscular symptoms and prolonged QT interval of 0.50 s, the patient was treated with calcium gluconate replacement under cardiac monitorization. Laboratory results were checked at 4-h intervals. Until we could use rasburicase, allopurinol was the initial specific therapy for TLS. The dosage was titrated according to glomerular filtration rate and a 0.2 mg/kg single dose of rasburicase could be added to therapy on day 3 of hospitalization. The patient’s symptoms and renal dysfunction progressively improved (). The patient was free of any findings of infection or septicemia. The leukocytosis was linked to the dexamethasone therapy, which was planned during radiotherapy for anti-edema prophylaxis. After stopping the drug, leukocytosis improved. Analysis of the dose-volume histogram showed that during palliative radiotherapy to the thoracal vertebrae, mediastinal, axillary, and supraclavicular lymph nodes were also affected with maximums of 24.8 Gy (mean: 19.8), 34.2 Gy (mean: 20), and 28.1 Gy (mean: 19.1), respectively. A digitally reconstructed radiograph of the scapula field included axillary lymph nodes, supraclavicular lymph nodes, and the upper mediastinal lymph node area (). After improvement of TLS, reanalysis of the patient for progression of CLL showed minimal regression of the pathological mediastinal and axillary lymph nodes. There was no progression in other lymph nodes or new organomegaly. With stable clinical findings of CLL and history of lymph node resection three months ago without any aggressive form of lymphoproliferative disease or Richter transformation, rebiopsy was not planned. After six months of follow-up the patient was stable for CLL and the PSA level progressively decreased.


An 11 year old boy from a rural area in Sri Lanka presented to us with polyuria, polydipsia of one year duration and intermittent headache of one month duration.
He was the first born child to second degree consanguineous parents from a poor socio-economic background. The antenatal and the perinatal periods were uneventful. He was born at term with a birth weight of 2.5 kg(-2SD) and length of 46 cm (-2SD). His developmental milestones were delayed, and he achieved his pincer grasp at 2 years, was able to walk at 3 years and spoke his first meaningful word at 4 years.
At the age of 7 years the child had developed darkening of the skin involving the neck and axillae, which had gradually increased in severity. The parents had also noticed that this boy had excessive hair growth all over his body. Two months prior to the current presentation he had become thin and was very lethargic thus prompting parents to seek medical attention. Except for few upper respiratory tract infections he did not have any significant past medical problems. There were no hospital admissions with hypoglycemia or hyperglycemia before. There is no family history of any significant medical problems. His two younger siblings are healthy and did not have any dysmorphic features.
On examination he weighed 17.5 kg (-3SD), his height was 111 cm (-6SD), head circumference 47 cm (-3SD), weight for height was -1SD to –2SD indicating significant growth failure. Facial dysmorphism characterized by small head, large ears, broad nose, prognathism, malocclusion of teeth were noted along with prominent nipples. There was extensive acanthosis nigricans, hypertrichosis, thick finger nails and coarse hands (Figs. and ).
Examination of the cardiovascular system, respiratory system and neurological system were apparently normal, abdominal examination did not reveal any organomegaly and his external genitalia appeared to be normal. The blood pressure was 100/60and was within the normal limits for his age. Developmental assessment showed that his motor skills and vision were age appropriate, but his speech was delayed and he could make only two word sentences. Formal assessment showed that this boy also has moderate learning difficulties.
Investigations revealed significantly raised Random blood sugar (RBS), Fasting blood sugar (FBS)and Glycated Hemoglobin (HbA1c) (Table ). There was no associated ketonuria or ketonemia. Serum electrolytes and renal functions were within the normal range. Ultrasonography of the renal tract revealed that both his kidneys were significantly enlarged for the age. Measuring the insulin levels and C-peptide levels would have been very useful at this point, but due to the unavailability of these tests in state hospitals and the cost we could not perform the tests.
Based on the clinical findings, our patient underwent genetic studies to detect possible mutations in the INSR gene. Genomic DNA was isolated from the patient’s blood sample and enriched for the coding exons of targeted genes using hybrid capture technology. Prepared DNA libraries were then sequenced using a next generation sequencing technology at Fulgent Diagnostics, California, USA. Variants were interpreted manually using locus specific databases, literature searches, and other molecular biological principles. A homozygous variant in the INSR gene, NM_000208.2:c.1042A > T (p. Ile348Phe), was identified in our patients’ sample. This particular missense mutation has not been reported previously in patients with RMS. Polyphen2 online tool was used to assess the effect of this novel missense mutation and it was stated as possibly damaging.
After the initial assessment the boy was started on a combination of Soluble and Isophane insulin 0.5U/kg/day and then increased to 1U/kg/day. As the blood sugars were still high, Metformin was added to counter the insulin resistance. Subsequently the dose of Insulin was further increased to achieve normal glycemic control. With a Metformin dose of 500 mg three times a day and Insulin dose of 2U/kg/day the blood sugar levels were maintained below 15 mmol/L. After starting the treatment in order to titrate the Insulin doses this boy underwent blood sugar series test which showed that the pre-prandial sugar levels were in the in the range of 10-12 mmol/L and post prandial blood sugar levels were 12-14 mmol/L. Due to the financial constraints on the family, expensive newer diabetes drugs were not considered.
Referrals to the Dermatologist, Orthodontist and Endocrinologist were done for management of other associated problems. Parents were counselled about the course of the disease, management options, long term prognosis and recurrence in the family. The counselling was very useful to alleviate the psychological stress of the parents and to face the challenges in dealing with a child with RMS. None of the immediate family members of the index patient had any physical features or biochemical abnormalities suggestive of Rabson Mendenhall syndrome. Unfortunately, due to the high cost of the test, parents and the siblings did not undergo the genetic analysis.
In our patient the diagnosis of RMS was made based on the clinical presentation with significant acanthosis nigricans, hirsuitism, dysmorphic characteristics, growth retardation, insulin dependent diabetes requiring large amounts of insulin and this was confirmed by genetic analysis.