We report a case of a 21-year-old man, admitted to our hospital, for a sudden onset of a severe holocranial pain and diplopia. The headache was continuous, and changing position, particularly orthostatism, caused worsening of symptoms which conversely were relieved by lying flat. The patient did not complain about phonophobia, vertigo or tinnitus and vomiting, but reported photophobia and nausea.
Neurological examination was normal other than for cranial nerves evaluation that showed diplopia due to mild restricted adduction of the left eye toward right and ipsilateral partial ptosis. Pupils were equal and reactive to light (both directly and consensually) and accommodation. Diplopia disappeared within 2 h. Saccadic eye movements and ocular examination were normal with visual fields full to confrontation.
The patient did not experience head or neck trauma and fever or rashes were not present. To exclude a possible subarachnoid hemorrhage (SAH), the patient underwent a brain CT scan which was negative for hemorrhage. To rule out a diffuse inflammatory disease or neoplastic processes, routine blood, rheumatic and autoimmune tests, paraneoplastic markers, serum levels of angiotensin-converting enzyme, thoracic radiography and abdominal ultrasound, were performed and resulted normal.
Brain and spine magnetic resonance imaging (MRI) without contrast revealed a mild descent of the brainstem with mild cerebellar tonsillar herniation and flattening of pontine surface, dilated sagittal sinus and enlargement of the pituitary gland (Fig. a), associated with a subdural hematoma, surrounding bilaterally the fronto-parietal and temporo-polar regions. The latter findings were consistent with hygroma. Another subdural fluid collection was present in the anterior section of the spinal cord (at C5–D1 level) with a consequent posterior dislocation. In addition, symmetrically dilated vascular structures, with abnormal epidural venous engorgement, were again seen anterior to the cervical cord without cord compression, from C4 level up to atlanto-occipital junction (Fig. b). After gadolinium, MRI showed diffuse pachymeningeal enhancement in supratentorial and infratentorial regions (Fig. c). Dural enhancement was also notable in the spinal cord at C1–D1 level.
MR myelography showed no signs of spreading cerebrospinal fluid (CSF) at the level of the cervical and dorsal root pockets (Fig. d).
According to the International Headache Society (IHS) ICHD-II criteria, the MRI findings and the clinical history were consistent with a diagnosis of headache attributed to low CSF pressure. Although ICHD-II comments suggest that “dural puncture should be avoided in patients with positive MRI signs, such as meningeal enhancement with contrast” we performed CSF analysis to corroborate our diagnostic hypothesis. CSF opening pressure was of 5 cmH2O and a lymphocytic pleocytosis (20 cells/ml) was detected.
Initially, the case was managed by bed rest, hydration and steroidal therapy, but after 3 weeks of conservative treatment with limited benefit on the orthostatic headache, the SIH syndrome was successfully managed with the application of lumbar epidural blood patch (EBP) using approximately 28 mL of autologous blood, resulting in immediate relief of clinical symptoms. After 6 months, clinical follow-up revealed complete resolution of symptoms. In contrast, MRI findings were substantially unmodified, showing only a mild reduction of brain sagging, with persistent subdural fluid collection in the same regions, epidural venous engorgement and diffuse meningeal enhancement in supratentorial and infratentorial regions (images not shown).


The 37-year-old woman presented with a three-month history of continuous pain in the right shoulder and chest. She was taken to our department of cardiothoracic surgery. Physical examination was remarkable for palpable lymph nodes in the bilateral supraclavicular fossae. Chest computed tomography (CT) revealed an oval mass located in the anterior mediastinum. Circumambient lung tissue was involved. Haematological findings were: WBC 15.40 × 109/L, platelets 364 × 109/L, prothrombin time 10.3 sec. Her erythrocyte sedimentation rate (ESR), blood biochemistry, electrolytes, blood urea nitrogen and serum creatinine, urine analysis and the endocrine profile were within normal range except hemoglobin (106 g/L) and tumor specific growth factor (67 U/ML). The abdominal ultrasonography did not reveal any other abnormality.
The surgery was performed with the patient under general anesthesia and left lateral decubitus position. The procedure revealed an oval tumor, volume of which was 7 cm × 4.5 cm × 2.5 cm, in the anterior mediastinum and circumambient lung tissue was involved. Pathologic findings during surgery showed that the tumor was off-white with obscure boundaries and hard in consistence (Figure ). The result of pathology hinted that the tumor maybe malignant lymphoma. The tumor and circumambient lung tissue which was involved were excised.
Histology showed the tumor was nodular and different nodules were separated by collagen fibers (Figure ). There were two morphologically and immunophenotypically distinct components. The great mass of nodules showed a pleomorphic cellular infiltrate containing lymphocyte, eosinophile granulocyte, neutrophile granulocyte and numerous large Hodgkin/Reed-Sternberg cells. The Reed-Sternberg cells were positive for CD30, CD15 and MUM1 but negative for CD20, CD79a, CD3, Pax-5, CD68, bcl-6, CD10, CD45, Igκ, Igλ and epithelial membrane antigen (Figure , Figure ). Other nodules displayed sheets of relatively uniform large lymphoid cells with typical morphologic features of large cell lymphoma which showed uniform expression of CD20, CD79a, MUM1, CD45, Igλ, Pax-5 and absence of CD30, CD15, CD3, CD10, bcl-6, Igκ, CD68 and epithelial membrane antigen (Figure , Figure ). All the primary antibodies are listed in Table . Neither cell population showed makers of EBV infection by EBER in situ hybridization (PanPath Company, Amsterdam, Netherlands). On the basis of histomorphology at light microscopy, the presence of immunohistochemical staining and in situ hybridization, a diagnosis of CL, combination of NSHL and DLBCL, in the anterior mediastinum was made. The patient received six courses of CHOP chemotherapy (a course of treatment every two weeks) and twenty three times radiotherapy (Gross Tumor Volume, GTV = 40Gy/20f; Planning Target Volume, PTV = 36 Gy/20f). After treatment, lymph nodes in the bilateral supraclavicular fossa disappeared. The total follow-up period was thirty three months after surgery. The repeated CT scans, abdominal ultrasonography and tumor specific growth factor every three months revealed no recurring or residual lesion.


A 28-year-old man was admitted to our hospital because of reduced livido and increased fatigability. He had been in good health until 1 year earlier, when he noticed reduced livido. Four months before admission, he noticed frequent headaches, thirst, polydipsia, and polyuria. Because he was voiding urine every hour, he visited his family doctor. Magnetic resonance imaging (MRI) revealed a suprasellar mass, and he was thus referred to our hospital for further evaluation and treatment. Although polydipsia and polyuria had been gradually relieved by the time of admission, he became aware of increased fatigability.
At the time of admission, he was 176 cm tall and weighed 72 kg. His temperature was 37.6°C, pulse rate was 60/min, and blood pressure was 110/60 mmHg. No goiter or enlargement of lymph nodes was noted. Axillar and pubic hair were lost and there was palpable erythematous rush on his forehead (). The remainder of the physical examination was unremarkable.
Laboratory results revealed the following results: blood urea nitrogen 9.6 mg/dL, creatinine 0.79 mg/dL, serum sodium 141 mEq/l, potassium 4.0 mEq/l, chloride 100 mEq/l, calcium 9.4 mg/dL, phosphate 3.7 mg/dL, fasting plasma glucose 80 mg/dL, and C-reactive protein 0.07 mg/dL. Endocrinologic data revealed a mild decrease in free T4 level (0.6 ng/dL) with normal thyroid-stimulating hormone (TSH) level (0.9106 μU/mL) and decreased cortisol (4.7 μg/mL), adrenocorticotropic hormone (ACTH; 6 pg/mL), luteinizing hormone (LH; 0.2 mIU/mL), follicle stimulating hormone (FSH; 1.3 mIU/mL), and testosterone (0.05 ng/mL) levels. Urinary cortisol was undetectable. Plasma osmolality was 288 mOsm/kgH2O, with a urinary osmolality of 239 mOsm/kgH2O, and arginine vasopressin (AVP) was undetectable (<0.15 pg/mL). Urinary output was from 1.5 to 2.2 L/day.
His clinical course and laboratory findings led us to suspect CDI with anterior pituitary dysfunction. We thus performed hormonal provocative tests. The patient was given an infusion of 5% saline at a rate of 0.05 mL/kg for 120 min. Although plasma AVP was undetectable before and after administration of hypertonic saline, urine osmolality (391 mOsm/kgH2O) increased above the plasma levels (296 mOsm/kgH2O) (). Hormonal provocative tests revealed that growth hormone (GH) response to GH-releasing hormone was normal, TSH response to TSH-releasing hormone was low and blunted, and FSH and LH response to LH-releasing hormone were low and blunted (). Although ACTH response to corticotrophin-releasing hormone (CRH) was normal, cortisol response to CRH was low (maximum 13.0 μg/mL). Cortisol response to rapid ACTH stimulation test was low (maximum 15.9 μg/mL). Results of these hormonal tests were compatible with the diagnosis of CDI with partial GC deficiency.
MRI revealed enhancing lesion centrally in the pituitary stalk, which spread continuously to the bottom of the third ventricle, and the high intensity of the posterior lobe was lost, compatible with the diagnosis of CDI (). Considering the patient's age, we first suspected of neurohypophysial germinoma. However, this was unlikely because cerebrospinal fluid was negative for malignant cells, and β-human chorionic gonadotropin (HCG) levels were normal. Next, we suspected sarcoidosis because chest X-ray revealed hilar enlargement. A biopsy from the skin of the forehead was performed, which revealed noncaseating granuloma composed of epithelioid cells (). Multinucleated giant cells were also present. Thus, the diagnosis of sarcoidosis was made.
While waiting for histologic confirmation of biopsy results, hydrocortisone replacement was begun with a dose of 20 mg daily. Soon after the replacement therapy was begun, moderate polyuria (3.5–4.0 liters daily) occurred (). After the diagnosis of sarcoidosis was confirmed, he was treated with 40 mg of prednisolone and his general condition improved. The hypertonic saline test was repeated while he was taking 40 mg of prednisolone. Plasma AVP was undetectable during the hypertonic saline test and urine osmolality was consistently below plasma levels, which was compatible with a diagnosis of CDI (). He was treated with 1-desamino-8-D-arginine vasopressin (dDAVP).
MRI following prednisolone therapy revealed a reduction in the size of the affected lesion. However, his pituitary function remained unchanged, and he is currently being treated with prednisolone, levothyroxine natrium, HCG, and dDAVP.


In this report, we describe the case of an 80-year-old woman of Greek Caucasian origin, gravida 2 para 2, with an undetermined obstetric and gynecologic history. After her second delivery, no data referring to the clinical history of the patient was available because the patient deferred any preventive or diagnostic medical examination until she presented to our hospital. Her last menstrual period had occurred 28 years ago. Her medical history included hypertension and angina pectoris.
The patient was examined in the gynecological oncology outpatient department and was found to have chronic pruritus vulvae and a recent onset palpable inflammatory lesion on the left labium majus. The lesion bled occasionally. During her gynecological examination, a 4 cm × 5 cm warty lesion with ulcerous and hemorrhagic areas (Figure ) was found in the middle of the left labium majus.
Initially, multiple biopsies from the center of the lesion and from the lateral margins were obtained, the histological examination of which revealed the presence of squamous cell carcinoma. At the periphery of the lesion, the squamous stratified epithelium exhibited abnormalities consistent with vulvar intra-epithelial neoplasia (vulvar intra-epithelial neoplasia (VIN) grade I/II). Numerous lesional cells showed koilocytic atypia, which is representative of HPV-related infection. However, initial hybrid capture 2 testing for HPV was negative in all the samples tested, which were obtained from either the center or the periphery of the lesion. A pre-operative computed tomographic scan of the abdomen and inguinal areas showed bilaterally enlarged inguinal lymph nodes with central fusion.
The patient underwent radical vulvectomy extending centrally to the level of the perineal membrane, as well as bilateral inguinal lymphadenectomy. Post-operatively, the woman had no major complications and was discharged 14 days after the procedure.
A histopathological examination of the excised specimen verified the presence of squamous cell carcinoma grade II/III with superficial ulcerations (Figures and ). Carcinoma cells invaded the stroma and the underlying adipose tissue with irregular invasive margins. The full thickness of the lesion from the surface to the deepest point was 1.2 cm. As noted regarding the pre-operative biopsies, the adjacent squamous stratified epithelium exhibited VIN grades I and II lesions (Figure ). Furthermore, metastases of the squamous cell carcinoma involving two of 11 right inguinal lymph nodes and two of five left inguinal lymph nodes were found. The vulvar lesion was excised within normal tissues.
In the tissue specimen obtained pre-operatively for the performance of liquid-based Cytology (The Thin prep - pap test, Cytyc Corp., Marborough, Massachusetts, USA), we used a polymerase chain reaction (PCR) assay with CLINICAL ARRAYS Human Papillomavirus Kit (Genomica, Madrid, Spain) and a Hybrid Capture 2 HPV DNA test (Digene, Madrid, Spain). The latter test is an accurate qualitative and quantitative method used to detect five low-risk types of HPV (6, 11, 42, 43 and 44) and 13 high-risk types of HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68). It can also determine the viral load. This technology is based on hybrid analysis to identify indentifying a signal enhancement in a microplate using chemiluminescence. Samples containing the target DNA are hybridized with a specific detector HPV RNA. Hybrid-produced RNA-DNA binds to the surface of a microplate coated with specific antibodies for RNA-DNA hybrids. The immobilized hybrids react with alkaline phosphatase (ALK)-conjugated antibodies and are detected with a chemiluminescence substrate. While the binding ALK cleaves the substrate, it attracts light, which is measured by chemiluminescence in relative light units [].
For the purpose of this study, we also used the CLINICAL ARRAYS Human Papillomavirus Kit (Genomica, Madrid, Spain), which is a commercially available HPV genotyping microarray test (Figure ). The kit was used according to the manufacturer's protocol. We used 10 μL of purified DNA for each specimen. The kit employs biotinylated primers to define a sequence of 451 nucleotides within the polymorphic L1 region of the HPV genome. A pool of HPV primers is used to amplify HPV DNA from 35 mucosal genotypes, including 15 high-risk genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82), three potentially high-risk genotypes (26, 53 and 66), 11 low-risk genotypes (6, 11, 40, 42, 43, 44, 54, 61, 70, 72 and 81) and six genotypes of unknown risk (62, 71, 83, 84, 85 and 89). In addition to the microarray analysis, PCR was performed with the HPV consensus primers MY09 and MY11 (18). PCR was performed consecutively as follows: 95°C for 15 minutes and 40 cycles of 94°C for 15 seconds, 52°C for 30 seconds and 72°C for 45 seconds [].
In our case, none of the above-mentioned HPV types was detected with the use of hybrid capture 2 testing. The DNA of HPV-66 was the only one detected using the CLINICAL ARRAYS Human Papillomavirus Kit.
On the basis of these results, a standard PCR assay was also performed. Four histological specimens from four different levels of the lesion, as well as from a lymph node with metastasis, were examined. Extraction of total DNA from formalin fixed, paraffin-embedded sections was performed using the QIAamp DNA Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. The quality and integrity of extracted DNA were assessed by PCR amplification of an amplicon of the interferon (IFN)-γ gene and by agarose gel (0.6%) electrophoresis, respectively. A nested, multiplex, highly sensitive PCR method (approximately 1 fg/103 viral copies) was used for HPV detection and genotyping. In this assay, consensus primers for first-run amplification of a broad spectrum of mucosal HPV genotypes, including all high-risk HPV genotypes, were combined with nested PCR amplifications of type-specific primers. Despite robust detection of the IFN-γ gene product amplification, no positive signal for HPV presence was found in any of the examined samples, even after substantially increasing the PCR cell cycles. Considering that there were clear indications of HPV infection in the microscopic examination of the specimens, the PCR assay was unable to detect the DNA of the virus, most probably because of low viral load in the specimens examined, which could have been caused and amplified by inadequate superficial lesional tissue. Furthermore, tissue fixation techniques could have a negative impact on the preservation of the viral genome.


Case 1 is a 14-year-old male patient in early-stage disease with a 15-day history of low visual acuity in his left eye. Visual acuity was 20/20 in the right eye and counting fingers in the left eye. Biomicroscopy revealed mild vitritis. Fundus examination revealed multifocal, evanescent, white-yellowish lesions near the superior temporal arcade and the presence of a subretinal worm adjacent to the lesions. The worm was destroyed using photocoagulation and visual acuity improved to 20/60. illustrates SD-OCT findings for this patient. (a) shows abnormal foveal architecture with a thinning in central macular thickness (201 μ compared to 246 μ in the fellow eye). (b) shows increased intraretinal hyperreflectivity in the area in which the subretinal worm was located. shows the RNFL map with a diffuse thinning. Average thickness is 87 μ compared to 105 μ in the normal fellow eye.


Case 7 is a 23-year-old male patient in late-stage DUSN who presented with a 6-month history of low visual acuity. Initial visual acuity was 20/20 in the right eye and counting finger in the left. Fundus examination revealed optic nerve pallor, narrowing of vessels, and diffuse pigmentary changes. The subretinal worm was identified in the nasal retina, and prompt laser photocoagulation was performed. Despite treatment, visual acuity remained counting fingers 90 days after treatment. SD-OCT features for this patient are presented in . shows the B-scan in the foveal area, with reduced macular thickness and loss of normal foveal contour. Figures and illustrates the RNFL map in the normal eye and a diffuse and pronounced RNFL thinning in the affected eye.


A four-year old female was found to have thyroid enlargement by her primary care provider. At four years of age, she was referred to a pediatric endocrinologist with a large goiter causing compressive symptoms, including sleep apnea and occasional inspiratory stridor. The child had profound hyperkenesis and difficulty with concentration. There was no family history of RTH.
At 4 years of age, the child was at the 40th percentiles for height and weight. The blood pressure was 112/61, and the resting heart rate was 120 beats per minute. A large goiter was present. Ultrasonography revealed a diffusely enlarged gland without extension into the thoracic cavity. The estimated gland volume based on ultrasonography was 150 ml.
The total T3 was > 2,000 ng/dL (normal range 80-180 ng/dL); the total T4 was 15.1 ug/dL (normal range 4-12 ug/dL); the free T4 was 1.8 ng/dL (normal 0.7-1.9 ng/dL); the TSH was 60 mU/L (normal range 0.5-6 mU/L). The skeletal age was 3 years at a chronological age of 3 years, 11 months. A magnetic resonance imaging (MRI) study of the brain did not reveal any brain abnormalities nor pituitary enlargement.
Genetic analysis revealed a novel mutation of the thyroid receptor-β gene, E445X. This mutation introduces a stop-codon in exon 10.
The patient was treated with 25 mg atenolol twice a day, which controlled the tachycardia and reduced the hyperkinetic activity. A trial of triiodothyronine (LT3; 25-75 mcg per day) was not successful, as the child developed abdominal pain, nausea, and worsening of her behavioral symptoms. Thus, surgery was performed to alleviate upper airway compression.
In preparation for surgery the patient was treated orally with methimazole (10 mg per day) and supersaturated potassium iodine solution for two weeks (3 drops, t.i.d). Surgery was performed under general endotracheal anesthesia. The thyroid gland was diffusely enlarged and total thyroidectomy was performed preserving the parathyroid glands, recurrent laryngeal nerves and external branches of the superior laryngeal nerves.
Pathological evaluation of the thyroid gland revealed a 125 gm specimen (Figure ; normal for age 2 gm) []. The right lobe measured 8.5 × 5 × 3 cm, the left lobe measured 9.5 × 5 × 3 cm, with an isthmus of 2.5 × 2 × 1.6 cm. Histological examination demonstrated diffuse papillary hyperplasia (Figure ). Postoperatively, the compressive upper airway symptoms resolved immediately.
Postoperative treatment with LT3 was considered. Due to parental concerns about the previous unfavorable trial of LT3, treatment with levo-thyroxine (LT4) was begun. On large doses of LT4 (175 mcg/day) the T4 was 19.6 ug/dl (252 nmol/L), the free T4 was 210 ng/dl (270 nmol/L); the total T3 was 210 ng/dl (3.2 nmol/L), and the TSH measured 922 uIU/ml.
On the basis of observations in other patients with severe RTH [,], LT3 therapy was introduced every other day, with gradual dose escalations every few months. After two years, TSH levels declined from levels ranging between 900 to 1,000 uIU/ml, to about 300 uIU/ml when the every-other day dose reached 200 ug. At this time, the heart rate was about 90 beats per minute. Two year after surgery, a CT scan obtained when the patient suffered mild-head trauma, indicated that pituitary size was normal.


A 40-year-old Caucasian man presented to the emergency department with a painless mass in the left anterolateral abdomen. During a physical examination, the mass was firm, nontender and fixed to the abdominal wall. The patient stated that the mass was gradually increasing in size. He had no relevant family history and did not smoke, drink alcohol or take any medications. Analyzed blood parameters were within the normal range, and tumor marker results were negative. The patient had a history of previous urgent abdominal surgery for traumatic rupture of the left colonic flexure and part of the small bowel after a shotgun injury two years earlier.
An ultrasound examination was performed and demonstrated a large mass of heterogeneous echogenicity with smooth, sharply defined margins in the left anterolateral abdominal wall (Figure ). Preoperative CT scan images revealed a well-circumscribed, large mass (9 × 8 × 6 cm) of attenuation equal to that of muscle. The mass originated from the left rectus abdominis muscle and after intravenous administration of contrast medium demonstrated mild enhancement even in the delayed images. No pathologic adenopathy was present (Figure ).
Radical resection of the affected abdominal wall musculature down to the peritoneum was performed to include a peripheral margin of 3 cm of healthy tissue. The defect was reconstructed with polypropylene mesh. Macroscopically, the lesion had a firm, gritty texture. On the cut surface, it was glistening white and coarsely trabeculated, resembling scar tissue (Figure ). The histologic diagnosis was of desmoid tumor (Figure ).
The postoperative course was uneventful, and the patient was discharged on the sixth postoperative day. The patient remained well at three years of follow-up with no evidence of tumor recurrence or development of incisional hernia.


A 9-year-old girl presented with history of abdominal pain, prolonged diarrhea, and rectal bleeding. She presented cutaneous leishmaniasis at 3-year-old, diffuse verruca vulgaris, recurrent skin, and respiratory infections.
She was hospitalised two years ago for pneumonia. Physical examination found hepatosplenomegaly and cervical adenopathy. The only abnormal laboratory test was an increase of γ-globulin count at 26,9 g/L. Inflammatory and infectious biological tests were normal. The humoral and cellular immunity was normal.
Ultrasonography and computed tomographic scan of the chest and abdomen showed numerous mesenteropelvic and inguinal gonglions and homogenous hepatosplenomegaly. The liver and the spleen had a size of 19 cm and 12 cm respectively.
Biopsy of an adenopathy showed a non specific mixed follicular and paracortical hyperplasia, with by place eosinophil's infiltration. The liver biopsy was normal.
The patient was lost to followup, and she was rehospitalized after two years. The physical examination revealed a pale, cachectic girl whose spleen was palpable 2 cm below the left costal margin and the liver had a size of 12 cm. She had a numerous superficial lymph nodes measuring 1 cm. The rectal examination ached and revealed some blood.
The laboratory workup showed a normal leukocyte count at 9700/mm3 with hypereosinophilia at 1700/mm3. The haemoglobin and the platelet counts were normal. The erythrocyte sedimentation rate was 26 mm/hour, and the γ-globulin was increased to 26,5 g/L. The biologic hepatic and renal functions were normal.
We completed during this hospitalization the exploration with endoscopic examinations. The gastroscopy revealed a normal stomach, multiple polypoid lesions measuring 0.2 cm, and friable mucosa in duodenum. Multiple biopsy specimens were taken. Microscopic examination showed lymphoid hyperplasia.
The colonoscopy and rectoscopy revealed an extended colitis with superficial ulcerations, friable mucosa, and bleeding rectal polyps measuring 2 cm ( and 1(b)).
The histopathological study showed a diffuse infiltration of the colonic mucosa by numerous histiocytes with cytoplasmic inclusions (), which stain positively with periodic acid-Schiff, Von Kossa, and Prussian blue stains (). Histiocytes had characteristic Michaelis-Gutmann bodies. The final diagnosis was malacoplakia with primary involvement of the gastrointestinal system.
The patient was treated with oral fluoroquinolone (Ciprofloxacin) 10 mg/Kg × 2/day. The patient's course was uneventful, and she was followed well (5 months after starting treatment). Diarrhea and rectal bleeding had stopped and hepatosplenomegaly decreased. The colonoscopy was controlled after two years of antibiotic treatment; we found that infiltration and ulceration of intestinal mucosa had decreased with a normal rectum (). The histologic examination showed a non specific inflammation without Michaelis-Gutmann bodies.
Actually, the patient has a normal growth. The hepatosplenomegaly was present with normal biologic tests. The follow up is of a three-year period.


The asymptomatic patient, a 60-year-old man, was referred to a radiology clinic to undergo examination for the purpose of implant planning. The panoramic radiograph revealed no important alterations in the mandible (). The patient underwent multidetector computed tomography (MDCT) (Synergy Helicoidal, General Electric Company, Milwaukee, WI), with slices and intervals of 0.625 mm, field of view 15.8 cm, matrix 512 × 512, standard filter, 120 kV and 200 mA.
The tomographic images clearly showed multiple cavitary defects, two in the anterior region (anterior variant) and one in the posterior region (posterior variant) (Figures , , and ). Intracavitary tomographic density (Hounsfield units) suggested glandular tissue in the anterior defects and fat in the posterior defect.


A 12-year-old boy was referred to the Department of Pediatric Dentistry, Dicle University, Diyarbakır, Turkey for examination, evaluation and treatment of gross attrition and considerable sensitivity of his teeth. A detailed medical, dental, and social history was obtained. He was both self-conscious and unhappy as regard the appearance of his teeth. Clinical examination revealed that tissue loss affected all teeth. The enamel layer was very thin and Brown (pigmented), the cuspal structure was completely absent in the occlusal portion of the molars which were most severely affected, and enamel pit defects (pigmented stains deep) were present in the anterior teeth (Figures , , and ). However, the clinical appearance of cervical and approximal enamel seemed to be normal. It was thought that the patient likely suffered from a hypomature type of AI. The patient's occlusal vertical dimension and rest vertical dimension were assessed. The interocclusal rest space had increased because of attrition of the molars. The exposed dentin was hypersensitive. Clinical and radiographic examination of the patient revealed deep carious lesions in the maxillary four teeth, and the mandibular left first molar had been extracted because of severe attrition and caries approximately 10 months earlier.
A treatment plan was developed with the following aims: to reduce the reported sensitivity of the teeth, to modify the occlusion, to restore mild crowding and masticatory function, and to improve the aesthetics. The patient was informed of the diagnosis and all treatment plans were discussed with him and his parents. He could not afford prosthetic treatment, including porcelain or ceramic restorations. Therefore, the treatment plan included placement of direct composite resin restorations in maxillary and mandibular anterior and posterior teeth. These materials were chosen because it cost less than ceramic and porcelain restorations and with the hope that it would ensure aesthetic and functional rehabilitation until the patient could cover the cost of porcelain restorations.
Firstly, according to the manufacturer's directions maxillary and mandibular posterior teeth of patient were restored using posterior composite resin (3 M ESPE-Filtek P60, St. Paul, MN, US), after deep caries in maxillary premolar and molar teeth were removed. Later, on the maxillary and mandibular anterior teeth, a 0.5 mm facial reduction was prepared for direct composite resin laminate veneers. In addition, the finish line at the proximal and cervical aspects of the teeth preparations was extended, and a rounded finish line throughout was prepared for the restoration. All teeth preparations were completed without sharp line angles. Maxillary and mandibular anterior teeth of the patient were restored using composite resin (3 M ESPE-Filtek Supreme XT Universal, St. Paul, MN, US) (Figures , , and ).
The patient was recalled at 2-month intervals. The 24-month recall clinical and radiographic examination revealed no pathology associated with the rehabilitation, and the patient's aesthetic and functional expectations were satisfied ().


A 26-year-old Caucasian man with history of diabetes mellitus presented to our emergency department complaining of diffuse headache that had developed two months prior to presentation. He also reported nausea and vomiting that became progressively worse. He denied fever, chills, photophobia or any other symptoms. He was born in Mexico and moved to California when he was 18 years old. A physical examination revealed a temperature of 37°C and mild neck stiffness but an examination including funduscopy and ophthalmologic examination was otherwise normal. Initial laboratory findings indicated a white blood cell count of 6500/mm3 with 75% polymorphonuclear leukocytes, 15% lymphocytes and 8% monocytes. His serum glucose was 90 mg/dL. The remainder of the laboratory data was normal. An initial computed tomography (CT) scan of his head showed hydrocephalus (Figure ). A lumbar puncture was performed and cerebrospinal fluid (CSF) analysis revealed an opening pressure of 400 mmHg, with 330 white blood cells/mm3 with 14% neutrophils, 45% lymphocytes, 38% monocytes, 3% eosinophils, 3 red blood cells/mm3, a protein level of 84 mg/100 mL and a glucose level of 43 mg/100 mL. A Gram stain and India ink stain of CSF were negative and final bacterial, viral, fungal and mycobacterial cultures were negative. Our patient was initially started on antimycobacterial therapy for empiric treatment of possible tuberculous meningitis. Magnetic resonance imaging (MRI) of his brain revealed an absence of meningeal enhancement, dilated lateral and third ventricles, with aqueduct stenosis and a possible small cystic area in or adjacent to the inferior aqueduct (Figures , , ). An enzyme-linked immunosorbent assay of the CSF was positive for immunoglobulin G (IgG) cysticercosis antibody, with 1.31 optical density units (OD) (positive result > 0.50 OD). His serum IgG cysticercosis antibody was positive with 4.42 OD. The serological diagnosis was confirmed by enzyme-linked immunoelectrotransfer blot assay performed for both serum and CSF. On further history, our patient mentioned that he used to eat undercooked meat when he was in Mexico. A diagnosis of extraparenchymal NCC was made. Our patient underwent endoscopic removal of the cyst and three weeks of therapy with albendazole (15 mg/kg/day) and corticosteroids was initiated. Postoperatively, our patient had a full range of extraocular movements, no periaqueductal injury and complete resolution of his presenting symptoms. Pathology findings confirmed the diagnosis of NCC (Figure ).


A 15-year-old East African boy was referred to our hospital with a diagnosis of recurrent TB. Upon review, the patient was found to have a history of productive cough and intermittent low-grade evening fevers for one year and shortness of breath for one week prior to presentation. One year and five months prior to his presentation to our hospital, he had presented to a peripheral hospital with similar symptoms and had been diagnosed with sputum acid-fast bacilli (AFB) and smear-positive TB. He had been treated with anti-TB medications, which brought him only mild relief. Two months after completing anti-TB therapy, his cough and fevers worsened, for which a re-treatment regimen of anti-TB medications, including two months of intramuscular streptomycin, were started on the basis of clinical findings. The sputum examination for AFB had not been repeated. Four months into the course of his second course of anti-TB therapy, the patient stopped taking his medications because he reportedly experienced only mild relief of his symptoms. Repeat Ziehl-Neelsen staining performed two months prior to his admission to our institution was negative for AFB, and no more drugs were given. One week prior to his admission to our hospital, the patient developed progressively worsening shortness of breath, which was even worse while he was lying flat and was associated with dull left-sided chest pain.
His social history was significant for crushing stones (rock cutting) for two years, but he had no history of smoking or working in the mining industry. He had no history of TB or other lung disease in his family.
His physical examination revealed that he was fully conscious, afebrile, slightly wasted, and dyspneic. His oxygen saturation level was 96% on room air, and his other vital signs were normal. His respiratory examination revealed a respiratory rate of 25 cycles/minute and chest bulging on his left side, but his trachea was centrally located. Other findings on the left side included decreased chest expansion, increased tactile vocal fremitus, dull percussion note, and bronchial breath sounds. The rest of the respiratory examination was unremarkable.
The patient was admitted to the medical ward with a diagnosis of recurrent TB with massive left-sided consolidation. A complete blood count revealed a white blood cell count of 8.7 cells/mm3 with a differential of 69% neutrophils, 23% lymphocytes, 6% monocytes, and 1% eosinophils. His hemoglobin level was 10.6 g/dL, and his platelet count was 504 cells/mm3. His erythrocyte sedimentation rate was 20 mm/hour. His renal and liver function tests were within normal ranges. A rapid test for HIV was performed and was negative. Sputum tests for Gram staining and Ziehl-Neelsen staining were both negative. A chest radiograph revealed features of huge left-sided consolidation with complete opacification of the left hemithorax (Figure ). His chest ultrasound revealed that the left lung was completely consolidated. There was no pleural or pericardial effusion, and his right lung was completely normal. Following these examinations, the patient was empirically re-started on the retreatment regimen for recurrent TB, and the cardiothoracic surgery team was consulted about performing a lung biopsy. The cardiothoracic surgery team felt that the patient was too unstable for surgery and requested that medical management be continued until the patient's condition improved.
On hospital day 3, the patient's condition started deteriorating, with worsening shortness of breath, wheezing, and hypoxia (oxygen saturation 82% to 90% on room air). He was admitted to the intensive care unit, where his anti-TB medications were continued, together with oxygen therapy. On hospital day 7, the patient died before any further intervention could be performed.
A post-mortem examination was performed by the hospital's pathologists. As shown in Figures and , the histopathologic examination revealed a huge mass in the left lung with necrosis and suppurative caseation. Microscopic examination of caseous material was negative for AFB. PAS staining was positive and cytological examination revealed yeast cells and capsules of non-viable fungi, suggestive of H. capsulatum. Because of resource limitations at our hospital, no further tests could be performed. The pathologist's impression was that the patient had had pulmonary histoplasmosis.


A 57-year-old G7P7 postmenopausal woman presented with a 3-year history of a foul smell and bleeding lesions in the genital region. A gynecologic examination revealed multiple large papillomatous, pedunculated, and lobulated lesions that were cherry-red and infective in appearance. There was a 2-cm lesion at the upper intersection of the labia majora, a 2-cm lesion on the right labium majus, and a 4-cm lesion on the clitoris (). There was no vaginal or cervical pathology. An ultrasound examination revealed a normal uterus and adnexa. The patient complained of itching, and the lesions were asymptomatic, except for occasional bleeding. There was no history of any trauma other than that caused by itching for 2-3 years. The tissue smear and Gram smear from the lesions did not reveal any organisms. Serology for herpes, syphilis, and human immune deficiency viruses were negative. There was no palpable inguinal or pelvic lenfadenopathy.
All lesions were excised and sent for histopathological examination (), which revealed an ulcerated polypoidal structure with extensive proliferation of vascular channels lined by a single layer of endothelium (). The intervening stroma, consisting of collagen, was infiltrated by lymphomononuclear cells. The histopathological features were consistent with PG. There was no noticeable recurrence until six months after the excision.


The second patient was a 30-year-old male, a Saudi security officer, who presented a history of progressive jaundice for 2 years. He had unremarkable past history, denying drug or alcohol abuse, and medications, including herbal medicines. There was no family history of liver disease or history of contact with jaundiced patients. His physical examination showed normal vital signs. He had deep jaundice, but the rest of the general examination was normal. The chest, the cardiovascular, and the abdominal examinations were normal. His baseline workup showed CBC (WBC 8.4 k/μl, Hg11.5 g/l, Plat 373), LFT (AST 531 U/L, ALT 250 U/L, ALP 682 U/L, GGT 205 U/L, TBil 344, Direct Bil 278, albumin 17, total protein 80), PT 13.3, and the renal functions were normal. The ultrasound examination of the abdomen showed hepatomegaly, but there were no evidence of biliary obstruction.
The ANA, SMA, AMA, LKM-1, HBV serology, HCV serology and the HIV testing were all negative. The serum IgG level was 25. Testing for Wilson's disease, by serum copper, ceruloplasmin and 24 hours urine copper, revealed normal results. Similarly, the serum iron and the total iron binding capacity (TIBC) and the transferrin saturation were normal. He had MRCP that showed a normal biliary system cholangiography. A liver biopsy was performed and it detected marked sinusoidal dilatation, infiltration of the biliary tracts with chronic inflammatory cells (mostly lymphocytes and some plasma cells), associated with bile duct damage. There was also chronic inflammatory cell infiltration of the hepatic lobules. The hepatocytes showed cholestasis. In some areas some of the hepatocytes were replaced by macrophages. There was also a mild portal and sinusoidal fibrosis.
He was given a trail of prednisolone (40 mg, daily) and UDCA (250 mg, three times a day), but excessive acne and skin rash appeared. Prednisolone was reduced to 30 mg and azathioprine (50 mg, daily) was started then gradually increased (to100 mg, daily). The treatment was maintained for more than 8 months; however, he had only transient improvement in the liver enzymes and bilirubin levels in the first few weeks of the treatment; nonetheless, latter on he lost that response while still on prednisolone and azathioprine. The serum ALT and AST were maintained at the 3-4 times above the normal, but the ALP and bilirubun progressively increased (Figure ); so prednisolone and azathioprine were discontinued. Because of severe symptomatic cholestasis, he was selected for liver transplantation.


The third patient was a 36-year-old Indian male who had progressive jaundice and itching for 10 month. He also noticed darkening of the urine and he also complained of intermittent melena, alternating with fresh rectal bleeding, over the past few months. Six month later, he had right upper quadrant abdominal pain of moderate severity. Two month prior to his clinical appointment, he start having progressive abdominal distention, and lower limb edema, for which he was given diuretics in a polyclinic; the ascites had improved. He did not have history of fever or hepatic encephalopathy during that period. There was no history of medication or herbs intake, drug or alcohol abuse, contact with jaundiced patients and family history of liver disease. His general examination was remarkable for jaundice, palmar erythema, spider nevi, itching marks and mild lower limb edema. The chest examination revealed right-sided pleural effusion. The cardiovascular examination depicted a short systolic murmur. On the abdominal examination, he had a moderate amount of ascites and splenomegaly. The lab data showed: CBC (WBC 3.82 k/μl, Hg12.7 g/dl, Plat 106 k/μl), PT 17.9 seconds, LFT(AST 223 U/L, ALT 74 U/L, ALP 174 U/L, GGT 215 U/L, TBil 144 μmol/L, DBil 12 μmol/L, albumin 22 g/L, TP 66 g/L), the renal functions were normal. The immunological profile was negative for ANA, LKM-1, AMA, ANCA, HBV, HCV and HIV. The SMA was weakly positive. The serum IgG was elevated 26.6 g/L and the serum IgM was normal. Tests for Wilson's disease, by serum and urine copper studies, and by ceruloplasmin testing, were normal. Similarly, the serum iron, transferrin, TIBC and transferrin saturation were also normal. The level of alpha-1 antitrypsin was also normal. The ultrasound examination of the abdomen showed hepatosplenomegaly and moderate amount of ascites. The echocardiogram was normal. Upper gastrointestinal endoscopy showed grad III esophageal varices. Endoscopic examination of the colon revealed internal piles, but the colonic mucosa was normal. Because of the clinical and laboratory evidence of advanced cirrhosis, the liver biopsy was deferred. He was thought to have late stage of AIH and was given a trial of prednisolone (30 mg, daily). Over the following 3 month of treatment, he had neither clinical nor biochemical improvements. His liver function tests at the end of the 3 month of the treatment with prednisolone showed ALT 247 U/L, AST 181 U/L, ALP 174 U/L GGT 167 U/L and total Bil 98 μmol/L. He was advised to undergo liver transplantation; therefore, he traveled back to India to have it done there.


The patient, a 16-hour-old Nigerian baby boy was brought to our children's out-patient clinic on account of fusion of the two legs from birth. The baby was delivered at term by spontaneous vaginal delivery after an unsupervised pregnancy and was the second of a set of triplets. The first triplet, a boy, was alive and well, but the third triplet (also a boy) died soon after birth. The mother was 20 years old and the father 26 years old. Both parents were from Hausa ethnic group, and had no formal education and were unrelated. The mother had no medical illness and did not take fertility drugs. This was her first pregnancy. There was no family history of congenital abnormality.
The baby had a birth weight of 1 kg. There was fusion of the entire lower limbs from the hip to the ankle with bones present in the thighs (femur) and the legs (tibia and fibula). There was no anal opening and no discernable external genital organs (Figures and ). There was a spinal defect at the level of L2-L3. The umbilical stump revealed only one artery and one vein. The heart sounds were normal. The parents refused any investigation or intervention when the prognosis was explained to them and took the baby away.


The first case was of a 46-year-old Caucasian man who presented with a four-year history of axial low back pain and radiculopathy that was described as 7 out of 10 on average and as 10 out of 10 at its worst on an 11-point Likert scale, of mechanical type (exacerbated by standing or walking for extended periods of time and improved by lying down), and refractory to extensive conservative treatment. During a physical examination, our patient showed no sensory-motor deficits. Lumbar MRI showed a grade 2 spondylolisthesis at L5-S1 with endplate Modic changes and severe bilateral foraminal stenosis. The operative time was 197 minutes, and blood loss was minimal (50 mL). Treatment with the AxiaLIF System reduced the spondylolisthesis to grade 1. Our patient was ambulatory after surgery and reported relief from back pain (maximal pain severity of 10 at pretreatment to 3 at post-treatment), resolution of radicular symptoms (10 to 1), improvements in back function (68% to 15% on the Oswestry Disability Index), and no complications. Our patient was discharged from the hospital two days after the procedure. To confirm the adequate placement of the instrumentation and to accurately evaluate the final constructs, a computed tomography scan was obtained after the operation (Figure ). Wide indirect neuroforaminal decompression and solid fixation constructs were achieved. Successful fusion, defined as no motion at the treated segment on flexion/extension radiographs and evidence of bone growth between the adjacent vertebral bodies on reconstructed computed tomography images, was demonstrated at one-year follow-up (Figure ).


The second case was a 51-year-old Caucasian female who presented with a 10-year history of axial low back pain and a one-year history of radiculopathy. The pain was described as 9 out of 10 on average and 10 out of 10 at its worst, of mechanical type, and refractory to conservative treatment. During a physical examination, our patient showed no sensory-motor deficits. Lumbar MRI showed a grade 2 spondylolisthesis at L5-S1 with severe bilateral foraminal stenosis. The operative time was 173 minutes, and blood loss was minimal (50 mL). Treatment with the AxiaLIF System reduced the spondylolisthesis to grade 0. Our patient was ambulatory after surgery and reported relief from back pain (10 to 2), resolution of radicular symptoms (10 to 1), improvements in back function (65% to 10%), and no complications. Our patient was discharged from the hospital two days after the procedure. Wide indirect neuroforaminal decompression and solid fixation constructs were achieved with successful fusion at one-year follow-up.
In the third case, a 50-year-old Caucasian man presented with an 18-year history of axial low back pain and a one-year history of radiculopathy. The pain was described as 8 out of 10 on average and 10 out of 10 at its worst, of mechanical type, and refractory to conservative treatment. During a physical examination, our patient showed no sensory-motor deficits. Lumbar MRI showed a grade 2 spondylolisthesis at L5-S1 with severe bilateral foraminal stenosis and a grade 1 spondylolisthesis at L4-5. The operative time was 323 minutes, and blood loss was minimal (50 mL). Treatment with the AxiaLIF System reduced the spondylolisthesis to grade 0 at L5-S1 and at L4-5. Our patient was ambulatory following surgery and reported relief from back pain (10 to 3), resolution of radicular symptoms (10 to 2), improvements in back function (69% to 14%), and no complications. Our patient was discharged from the hospital three days after the procedure. Wide indirect neuroforaminal decompression and solid fixation constructs were achieved with successful fusion at one-year follow-up.


A 66-year-old Japanese woman with swelling of the right buccal mucosa was referred to our hospital. She was generally healthy and her medical, dental, and family histories were normal. Routine laboratory examinations did not reveal any abnormalities.
The lesion was excised and was pathologically diagnosed as a MALT lymphoma tumor with a t(11;18)(q21;q21) chromosome translocation []. Swelling of the right buccal mucosa recurred 2 years later. Clinical examination at that time revealed a sessile, hard, elastic, and movable mass in the right buccal mucosa; similar to previous clinical findings, this mass was covered with normal mucosa.
The recurrent tumor was excised under general anesthesia, and general safety margins were maintained. The recurrent tumor was similar to the primary tumor; a sessile, white, elastic, and circumscribed mass. The recurrent tumor was well demarcated and was covered with normal mucosa. The length of the recurrent tumor was 3.3 cm.
To determine whether the lymphoma had spread to other sites, computed tomography (CT) scans and magnetic resonance imaging (MRI) of the whole body were performed and endoscopic examination of the stomach was added. All test results were negative for the presence of lymphoma in the other sites. Clinically, the patient remained in good general health, and evidence of tumor reactivation 6 months after the treatment was lacking.
Paraffin sections of the primary tumor revealed (under a low-power field) some colonized lymphoid follicles with a mantle zone and diffuse proliferation of tumor cells in the marginal zone (Figure ). On the other hand, paraffin sections of the recurrent tumor revealed that the tumor cells showed follicular colonization in the germinal centers throughout the tumor (Figure ).
Under high-power fields, small- or medium-sized centrocyte-like cells with indented nuclei and moderate cytoplasm volume were found in the primary and recurrent tumor (Figure and ). Monocytoid B-cells with round nuclei and abundant, pale cytoplasm and neoplastic cells with Dutcher bodies were more abundant in the primary tumor than in the recurrent tumor (Figure and ).
In addition, plasmacytoid differentiation was more prevalent in the recurrent tumor than in the primary tumor (Figure and ).
For immunohistochemical analyses, paraffin sections were incubated with primary antibodies, including CD10 (M0727, DAKO, Copenhagen, Denmark), CD20 (M0755, DAKO), CD43 (MT1 clone, Leica Microsystems, UK), CD79a (JCB117 clone, Dakocytomation, Denmark), Bcl-2 (M0887, DAKO), Bcl-6 (M7211, Dakocytomation), IgG (A0423, DAKO), IgG4 (05-3800, Nichirei-Zymed, Tokyo, Japan), IgM (A0425, Dakocytomation), Lambda (A0193, DAKO), Kappa (A0191, DAKO), cyclin D1 (SP4 clone, DBIOSYS, Washington D.C, U.S.A), CK (AE1/3) (M0835, DAKO), and Helicobacter pylori (B0471, Dakocytomation).
The sites for antigen-antibody reactions were visualized using a standard avidin-biotinylated-peroxidase complex method. The primary tumor cells were positive for bcl-2, CD20, CD43, CD79a, Lambda, Kappa and was negative for CD10, IgG, IgG4, IgM, cyclin D1, bcl-6, CK (AE1/3), and Helicobacter pylori (data not shown) []. The overall staining results of the recurrent tumor were similar to those of the initial tumor. The recurrent tumor showed negativity for CD10, IgG, IgG4, IgM, cyclin D1, Bcl-6, CK (AE1/3), and Helicobacter pylori (data not shown) except that the recurrent tumor showed negativity for lambda and weak positivity for kappa.
A previous study revealed that MALT lymphomas that express CD5 tend to recur and disseminate []. To ascertain whether the primary tumor expressed CD5, the tumor specimen was incubated with a CD5 antibody. Moreover, expressions of lambda and kappa in the primary tumor specimen were compared with those in the recurrent tumor specimen.
Immunohistochemical examination of CD5, lambda, and kappa expressions revealed that the primary tumor was positive for CD5 (Figure ), kappa (Figure ), and lambda (Figure ), but the recurrent tumor was weakly positive for CD5 (Figure ) and kappa (Figure ).
With respect to lambda positivity, the recurrent tumor showed negativity (Figure ).


A 32-year-old Caucasian man from Switzerland was referred for further evaluation of an elevated serum ferritin, the test for which was ordered because of tiredness. His serum ferritin concentration at presentation was markedly elevated at 1314 μg/L (normal range 30-400 μg/L), but the serum transferrin saturation of 23.3% was within our laboratory reference interval (normal range 15-50%).
Our patient had no history of alcohol abuse or other metabolic diseases and no family history of hereditary hemochromatosis (HH). Clinical examination revealed no abnormalities. Further laboratory evaluation showed normal liver enzymes and normal hematological parameters.
Genetic tests for HH showed a heterozygous H63D substitution in the HFE gene but wild-type sequence at the HFE C282Y locus. The histology of a liver biopsy specimen was normal, and did not show iron accumulation or steatosis. Together, these findings exclude a diagnosis of HH.
Upon further evaluation, our patient revealed a history of bilateral cataracts at four years of age. His mother, his maternal aunt and maternal grandfather had all had nuclear cataracts at an early age (Figure ). Slit-lamp examination, direct illumination and retro-illumination of his lenses showed scattered, radially oriented flecks and crystalline deposits in both lenses (Figure ). Sequencing of the FTL gene using a previously described method [] showed a heterozygous c.33 C > A transversion in the IRE within the FTL 5'UTR. This mutation has been previously associated with the HHCS phenotype [].


A 49-year-old Caucasian man was referred to our department for further examination of a markedly elevated serum ferritin concentration, of 2012 μg/L (normal range 30-400 μg/L). This had been identified as an incidental finding during the investigation of an allergy. His serum transferrin saturation of 29% was within the normal range. His liver enzymes and hematological evaluation were normal. The HFE gene showed wild-type sequence and an abdominal ultrasound showed normal liver echotexture. Our patient reported bilateral lens replacements 20 years ago due to bilateral juvenile cataracts. His family history was not available because he was an orphan. Deoxyribonucleic acid (DNA) sequencing of the FTL 5'UTR revealed a heterozygous c.32G > C transversion. This mutation is also known to be associated with the clinical phenotype of HHCS [].


An 80-year-old Caucasian woman was admitted to our hospital with a 12-year history of an endocrine inactive steady sellar mass lesion (13 mm in diameter; Figure ). Our patient had been previously asymptomatic with no pituitary hormone deficiency or visual impairments. Moreover, our patient had a medical history of good health with only minor health issues that included hypertension and osteoporosis. However, prior to hospital admission, she had recently experienced two severe headache attacks; the last episode was accompanied by nausea, vomiting and blurred vision. Hyponatremia (120 mEq/L) with low serum osmolality (247 mOsm/L) and highly elevated urine osmolality (695 mOsm/L) were detected. An endocrinological investigation revealed hypocortisolism with no other hormone disturbances. Fundoscopy showed no pathological findings. However, further ophthalmologic examination with Goldman perimetry confirmed a bitemporal hemianopsia accentuated on her right side. Her neurological examination results were otherwise normal. After substitution therapy with hydrocortisone, our patient rapidly improved and her headaches subsided.
Findings from a magnetic resonance imaging (MRI) scan were suggestive of an acute hemorrhage of the sellar process, consistent with pituitary apoplexy (Figure ). Except for an age-consistent vascular leukoencephalopathy, the diagnostic imaging showed no further pathological findings. Our tentative diagnosis at this point was a pituitary adenoma with pituitary apoplexy.
Due to these clinical and radiological findings, the decision was made to surgically remove the tumor. A gross total extirpation using a transnasal, transsphenoidal approach to the pituitary mass was successfully performed. Intraoperatively, the tumor appeared yellowish-brown, was relatively firm and was located within a sellar hematoma cavity, which was evacuated.
Postoperatively, our patient's visual field deficits improved markedly on clinical examination and Goldman perimetry confirmed a partial recovery of her bitemporal visual field deficits. Endocrinological studies showed panhypopituitarism with partial and transient diabetes insipidus. Our patient received substitution therapy with hydrocortisone, levothyroxine and transient therapy with desmopressin. Overall, our patient remained in good health with a satisfactory level of performance. A repeat MRI scan taken 16 months after surgery showed good chiasmatic decompression with no residual tumor mass (Figure ).
The resected tumor was examined with light microscopy, which revealed a small, well circumscribed, non-adenomatous tumor surrounded by slightly compressed remnants of adenohypophyseal parenchyma (Figure ). The tumor was richly vascularized with an observable reticular mesh of thin-walled capillaries interspersed with large epithelioid-looking cells (Figure ). Pale eosinophilic cytoplasm showed xanthomatous or vacuolar change (Figure ). Immunohistochemistry confirmed the expression of the endothelial-associated markers CD31 and CD34 in the intratumoral capillaries, although not in the stromal cells themselves. Conversely, the stromal cells were diffusely immunoreactive for vimentin, with a minority of cells also coexpressing S100 protein and epithelial membrane antigen (Figure ). No inflammatory infiltrate was detected except for the occasional mast cell (Figure ). Staining for cytokeratins tested negative, as did the Langerhans-cell-associated marker CD1a. Less than 1% of lesional cell nuclei were labeled with the cell proliferation-associated antigen Ki-67.
Given the above findings, we identified the tumor as an intrapituitary example of capillary hemangioblastoma (World Health Organization grade I). Since our patient displayed no clinical stigmata of VHL disease, genetic testing was not performed.


A 66 year-old male presented to the emergency department (ED) with a one-week history of progressive pruritic erythematous rash, dry cough and two days of episodic high fevers. He had suffered a fall 12 weeks prior that had resulted in a pelvic fracture requiring an open-reduction internal fixation, which subsequently became infected with methicillin-resistant Staphylococcus aureus (MRSA) and treatment with intravenous vancomycin was initiated. After four weeks of vancomycin therapy he developed a rash. This was initially thought to be due to a red-man syndrome variant. Infusion rates were slowed, and premedication with diphenhydramine was initiated, but the rash worsened, with the subsequent development of episodic daily fevers, documented to be as high as 40°C.
His past medical history was significant for heterozygous hemochromatosis, a remote splenectomy secondary to traumatic rupture, and non-anaphylactic adverse reactions to penicillin and sulfa antibiotics. He had no history of reactive airway disease and had no travel history, living in an Ontario city.
In the ED he was hemodynamically stable with a normal mental status. He had a severe erythematous macular rash involving his face and trunk (see Figure ), and some facial edema. He had no mucous membrane involvement. He had palpable bilateral cervical and left axillary lymphadenopathy. Cardiorespiratory examination was normal, and his abdominal exam revealed central obesity and a scar from his remote splenectomy. Initial laboratory investigations are shown in Table . A computed tomography (CT) scan of his pelvis showed no abscess formation. A skin biopsy of the initial rash showed a mild perivascular lymphocytic infiltrate, consistent with a drug reaction.
Our initial working diagnosis was Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) secondary to vancomycin, which was immediately discontinued. Initially, his liver enzymes and eosinophilia appeared to improve spontaneously, thus management was mainly supportive with topical hydrocortisone and oral H1 and H2 receptor antagonists (cetirizine 20 mg PO BID and ranitidine 150 mg PO BID). On the third day of admission, however, his white blood cell (WBC) and eosinophil counts increased and continued to rise (see Figure ) leading to the initiation of systemic corticosteroids. He was initially given hydrocortisone 40 mg IV every 8 hours for 2 days followed by prednisone 60 mg PO daily. Despite this treatment, his eosinophil count continued to rise and peaked on Day 10 (see Figure ). He became dyspneic with diffuse wheezing on exam, requiring repeated bronchodilator treatments. The chest x-ray was repeated and a CT chest performed. Chest imaging revealed a diffuse interstitial pattern that was suggestive of eosinophilic pneumonitis (Figure ). There was no evidence clinically or on echocardiography of heart failure. While initially his renal function was close to normal, starting on Day 8 it began to worsen (see Figure ), peaking on Day 18 at 432 micromol/L despite aggressive fluid administration and good urine output. A renal ultrasound was normal, but microscopic urinalysis revealed persistent WBC casts consistent with worsening interstitial nephritis as an explanation for the acute renal failure. During this time, he became delirious, with no causative abnormalities found on neurological examination, laboratory investigations or CT head, indicating the likely cause to be his underlying DRESS. High dose methylprednisolone 125 mg IV q8 hourly was initiated, and his renal function slowly improved, negating the need for a renal biopsy in the opinion of the consultant nephrologist. His wheezing and mental status also improved with the subsequent reduction in his WBC and eosinophil counts. Peripheral blood flow cytometry did reveal an atypical plasmacytoid population, but serum and urinary protein electrophoresis were negative for a monoclonal protein.
Our initially broad differential diagnosis was narrowed as our patient's clinical presentation developed. Red man syndrome, an infusion and dose-related mast cell degranulation in reaction to impurities found in vancomycin, was excluded early upon hospital presentation []. The fact that his rash persisted despite vancomycin discontinuation, the multisystem nature of his presentation and the moderate eosinophilia was suspicious for a more serious process. Churg-Strauss Syndrome (CSS) was also considered, but our patient had no history of asthma or any bronchodilator or corticosteroid use in the past, and therefore it was lower on our differential. Nonetheless, anti-neutrophil cytoplasmic antibodies (ANCAs), a test with only about 40% sensitivity for CSS, was sent and found to be negative []. This was sent 8 days after initiation of corticosteroids, which may have decreased the test's sensitivity. However the predictive value of a negative ANCA in the face of our low clinical probability was sufficient to exclude this diagnosis. CSS, often described as having three phases, the asthmatic, the hypereosinophilic and the vasculitic phases, is almost always preceded by a usually escalating asthmatic phase that can last up to years and is rarely subtle []. Seldom, asthma can be a late feature. However, we have followed our patient over time, and complete tapering of corticosteroid left him with no residual respiratory symptoms, making CSS highly unlikely.
Microscopic stool examination for ova and parasites was negative as was Stongyloides stercoralis serology. No further parasitic work-up was completed as the patient had no risk factors or gastrointestinal symptoms. Severe systemic bacterial infections, with the exception of scarlet fever, cause eosinopenia [], and at the time of admission our patient had in fact been recovering from an MRSA bacteremia. Genetic testing for hypereosinophilic syndromes (HESs) with FIP1L1 and PDGFRA were negative, and although these are positive in only about 30% of patients with HESs [], a secondary cause of hypereosinophilia was apparent and thus helped exclude this diagnosis with more certainty.
On day 39 from initial presentation, our patient returned to hospital with a methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia and severe left shoulder pain. He was admitted under orthopedic surgery for exploration and debridement of both the shoulder and pelvis as well as removal of the pelvic hardware. Evidence of osteomyelitis in the pelvic bone was found during the surgery. He remains on cefazolin and is being followed by the infectious diseases service. Meanwhile, a taper of his prednisone was attempted around day 50 over a two week period. Unfortunately, his rash and eosinophilia returned shortly after its discontinuation, requiring re-initiation and a slower tapering attempt. This was finally successful more than four months after initial presentation. He is currently managed with an oral H1 receptor antagonist alone, and his peripheral eosinophil count has remained suppressed.


A 33 year old male sought hospital care after anorexia, and fever for 10 days followed by a vague right hypochondrial discomfort, vomiting and jaundice for 3 days with dark urine and some reduction in urine output. There was an associated diarrohoea with yellow stools. He did not complain of pruritus. He did not give a contact history with muddy water and denied blood transfusions, promiscuity or intravenous drug abuse.
He had been employed as a driver and had no significant past medical history or travel history to a malarial endemic area. He consumed alcoholic beverages only at social functions and denied any recent binges. He was not using any medication prior to this admission including antibiotics.
Examination revealed an ill looking patient with deep icterus with mild dehydration but without any scratch marks. He had no stigmata of chronic liver disease or evidence of encephalopathy. Fever was documented and no lymphadenopathy was detected. There was tender firm hepatomegaly with moderately enlarged soft spleen. The gall bladder was not palpable. Cardiovascular, respiratory and neurological examination was normal.
The urine full report showed bile in the urine with normal levels of urobilinogen. Full blood count showed a borderline leucopaenia - 4.8 × 103/μl with 51% neutrophils and 44% lymphocytes. The platelet count was 175 × 103/μl and never dropped significantly throughout his hospital stay. The initial ESR was 35 mm/h and the CRP was elevated 96 mg/l. The blood picture showed only mild rouleaux formation.
The liver biochemistry showed normal albumin levels with elevation of AST and ALT which were 120 units/l and 240 units/l respectively The alkaline phosphatase was 1500 units/l, Indirect Bilirubin was 1 mg/dl and the Direct Bilirubin was 10 mg/dl (Table ). The serum electrolytes and renal function were within normal limits.
The ultrasound scan of the abdomen showed an enlarged liver at 17.5 cm with a coarse echo pattern and a markedly dilated gall bladder with normal wall thickness. The intra and extra-hepatic bile ducts were not dilated nor were any calculi visualized. There was splenomegaly at 15.5 cm.
Blood culture, urine culture, serology studies for viral hepatitis, leptospirosis and dengue ere dispatched and, he was empirically treated with IV crystalline penicillin as leptospirosis was endemic in the region despite the negative contact history.
His fever continued for four days post-hospital admission and the icterus progressively worsened despite treatment for suspected leptospirosis. On serial monitoring the liver biochemistry showed further derangement with marked increase of direct bilirubin to a maximum of 16 mg/dl and alkaline phosphatase to a maximum of 1600 Units/L and mild increase of transaminases, with a maximum AST of 125 Units/L and ALT of 255 units/L (Table ).
The Leptospira microscopic agglutination test was equivocal and hepatitis serology was negative for Hepatitis A, B and C. The Dengue IgG was positive in low titres however with a negative IgM.
The patient refused to give consent for a percutaneous liver biopsy.
His blood culture yielded a growth of Salmonella typhi after 5 days incubation, with antibiotic sensitivity to Ciprofloxacin (MIC < 0.5 mg/L) and Cefotaxime (< 0.25 mg/L). The strain was resistant to Ampicillin (MIC > 1 mg/L) and Chloramphenicol (MIC > 2 mg/L)
He was started on IV Cefotaxime 2 g three times a day for 3 days. Oral Azithromycin 1 g daily for 7 days was also added. This combination of antibiotics is the usual recommendation by the department of microbiology of our hospital.
He demonstrated marked clinical improvement with defervescence in 48 hours and gradual resolution of jaundice and constitutional symptoms over the next 7 days. The liver biochemistry subsequently showed decline of cholestasis with improvement of transaminases (Table ) by day 30. The persistence of mild enzyme derangement at this stage could be due to residual hepatic damage. Further monitoring of liver enzymes was planned to detect chronic liver disease.
He was discharged after seven days of hospital treatment with oral Cefixime and Azithromycin. He returned one week later and was clinically well with just a tinge of jaundice with absence of hepatomegaly and splenomegaly. The liver biochemistry was gradually improving and by day 30 of the illness was just about baseline.


A 69-year-old Japanese woman with no previous medical history presented with postmenopausal bleeding. Her first period started at the age of 16, and stopped at the age of 50. She was gravida 2, para 2 (both of them were vaginal deliveries). Cytology and biopsy of the endometrium were obtained, which revealed endometrioid adenocarcinoma. Laboratory data showed no abnormal findings except for the elevation of CA125 (138.2 U/mL, normal < 35.0 U/mL). Total abdominal hysterectomy, bilateral salpingo-oophorectomy, lymph nodes dissection as well as the biopsy of the greater omentum were performed. Atypical cells were noted in the intraoperative cytology of the peritoneal washing (Figure ). In addition, peritoneal nodules suspicious for dissemination were found. However, it turned out to be granulation tissue with proliferating mesothelial cells in the intraoperative frozen section as well as its permanent section.
Grossly, the uterine corpus showed a papillary mass measuring 8 cm in greatest diameter. Bilateral ovaries, fallopian tubes and broad ligaments showed small grayish nodules measuring about 2 mm in diameter.
Histologically, the tumor of the uterine corpus showed diffusely proliferating atypical endometrial glands. Squamous differentiation was also noted (Figure ). There was no solid growth, and a diagnosis of endometrioid adenocarcinoma (Grade 1) was made. The tumor invaded beyond a half of the myometrium and extended to the uterine cervix (FIGO IIb). Lymph node metastasis was not found.
Granulomas were observed on the serosal surface of the bilateral ovaries, fallopian tubes and broad ligaments, and contained eosinophilic laminated keratin deposits with ghost squamous cells. They were surrounded by epithelioid cells, foreign body type giant cells, neutrophils, lymphocytes and plasma cells (Figure ). Reactive mesothelial cells with papillary and gland-like structures were also noted (Figure ). Immunohistochemical stains were performed on the representative section of peritoneal keratin granulomas. The following primary antibodies were used: AE1/AE3 (dilution, 1:50; Dako, Glostrup, Denmark), calretinin (dilution, 1:100; Novocastra, Newcastle, UK), Ber-EP4 (dilution, 1:50; Dako), CAM 5.2 (dilution, prediluted; Becton Dickinson, San Jose, CA), CEA (dilution, 1:50; Dako) and D2-40 (dilution, 1:50; Dako). The ghost squamous cells were positive for only AE1/AE3 (Figure ). Reactive mesothelial cells were stained with AE1/AE3 (Figure ), calretinin (Figure ), CAM 5.2 and D2-40. These reactive mesothelial cells showed higher MIB-1 (dilution, 1:50; Dako) labeling index (10-20%) than surrounding normal mesothelial cells. Ber-EP4 and CEA positive cells were not found within the granulomas. Ziehl-Neelsen and Grocott's methenamine silver stains did not reveal any acid-fast bacilli and fungi.
Postoperative chemotherapy was administered, and she has been alive with no evidence of recurrence for 6 months postoperatively.


A 43-year-old Asian man was incidentally detected to have a loose, well-defined, homogenously enhancing soft tissue density lesion in the right adrenal gland. This lesion was found while the patient was undergoing investigations for hypertension of six years' duration being controlled with α- and β-blockers and a diuretic. The patient had a history of myocardial infarction nine earlier for which he underwent coronary angioplasty and he was taking an antiplatelet agent.
During this admission, he had undergone ultrasonography of the abdomen, which revealed an adrenal mass. No other significant history or findings were noted.
On examination, the patient's blood pressure was 150/90 mm Hg. A chest radiograph revealed prominent vascular markings in bilateral lung fields with cardiomegaly. MRI suggested adrenal myolipoma with a large, well-defined, altered signal intensity lesion in the right suprarenal region measuring 119 × 105 mm in size. Other organs were unremarkable. No lymph node enlargement was noted. CT scan revealed a large, well-defined, soft tissue density lesion with intrinsic fat density areas in the right adrenal region measuring 116 × 100 mm in size (Figure ). On laboratory investigations, the patient's random blood sugar was 82.6 mg/dL and his renal and liver functions and electrolytes were within normal range. The patient's hemoglobin was 10.6 g/dL, and counts were within normal range and were nonreactive to HIV, hepatitis B surface antigen and hepatitis C virus on enzyme-linked immunosorbent assay. Urine analysis and microscopic findings were unremarkable. His 24-hour urinary vanillylmandelic acid level was 4.7 mg (reference range, 2-8 mg/24 h). The patient was subjected to transperitoneal laparoscopic adrenalectomy. On gross examination, a well-encapsulated tumor mass weighing 810 g measured 15 × 11.5 × 6.5 cm in size (Figure ). The external surface was smooth and grey-yellow colored, and the adjacent adrenal gland measuring 6 × 1.5 × 0.5 cm in size was unremarkable. The cut surface was homogenous, yellow and fatty with myxomatous areas or a jelly-like appearance and soft to firm in consistency. Microscopy revealed a well-encapsulated tumor composed of mature adipose tissue with myxoid degenerative changes and normal adrenal parenchyma (Figure ).
The patient had an uneventful postoperative course and is stable with the same medications continued for one month. The patient is now taking a beta-blocker and antiplatelet agents, and he has stopped taking the alpha-blocker and diuretic that he needed previously for blood pressure control.


A 67-year-old Japanese women, gravida 2, para 2, visited our hospital for regular (once 2 years) gynecologic screening. She had no family history for ovarian/breast carcinoma. There were no remarkable findings on physical examination/trans-vaginal ultrasonography. Endometrial cytology demonstrated abundant nests of adenocarcinomatous cells with peripherally located nuclei among sheets of non-atypical endometrial cells (Fig. ). Endometrial biopsy resulted in insufficient materials with only a few atypical cells. Abdominopelvic CT/MRI did not show enlargement of bilateral adnexa, endometrial thickenings lymphadenopathy, or ascites. Blood tests including tumor markers, CA125, CA19-9, and CEA were all within normal limits.
Because of the cytology/biopsy findings, hysterectomy and bilateral salphingo-oophorectomy with sampling of intra - pelvic lymph nodes were performed. During surgery, there were no visible lesions in the abdominopelvic space with only a small amount of yellowish to slightly muddy ascites. However, intraoperative cytology of the ascites demonstrated many adenocarcinoma nests (Fig. ).
The surgical specimen showed bilateral, normal - appearing ovary and uterus with smooth/thin endometrium and a few myoma (Fig. ). There was no sign of disseminated tumor. Interestingly, compared to the right fimbrial ende, the left one was composed of shorter/dense fimbria when observed from the back-side (Fig. ).
Since there was no evident adenocarcinomatous lesion was on gross inspection, the whole surgical specimen was cut into histological section, in order to find the origin of the tumor. Bilateral adnexae except fimbria were cut into section at 5 mm intervals and each fimbriated end was cut sagitally into two.
Pathologically, intraepithelial, non-invasive adenocarcinoma was found solely in the left fimbria (Fig. ). There was no tumor in the uterine cavity, right adnexa, lymph nodes, or left adnexa other than the fimbriated end. Immunohistochemically, adenocarcinoma was positive for p53 (Fig. ) and negative for calretinin/mesothelin. At the periphery of the left fimbrial ende, more than 12 normal - appearing nonciliated epithelial cells were positive for p53 in a consecutive fashion, so-called "p53 signatures" [] (Fig. ).


On March 9, 1898, a 6-year-old boy presented with congenital talipes equina varus. Cushing brought him to the operating room on March 15 for an operation entitled “tendon transplantation for relief of paralytic club foot.”
“Tenotomy of tendon Achilles does not allow foot to be well corrected and to remain so. Evidently the muscles to the inner side of the foot are under greater tension than those to the outer side. This seems to be chiefly due to the proprius pollicis extensor which holds the toe extended in marked hammer toe. Transplantation of tendon deemed advisable.
Oblique incision made from cuboid bone across ankle joint to position of long extensor tendon ().
The tendon sheath of long extensor of great toe was opened and tendon drawn up. A small incision was made over the tendon in the foot, proximal to the junction with the small extensor. Tendon was divided there and drawn up into the ankle wound.
A grooved dissector was then passed from the empty tendon sheath under the ant. annular ligament and [therefore] under the artery and nerve which were uninjured. A large probe with large eye was then passed through, the tendon threaded in this eye, and passed under the ligament.
The end of the tendon was then sutured by 3 mattress sutures to the cuboid periosteum and extensor of the peroneus brevis muscle. The attachments held the foot in natural position without support. Wounds closed with silver wire. Foot put up in plaster.”
The patient was discharged on postoperative day 6. A letter from the patient's father, dated 18 August, 1898, said that the child “is doing well and in my opinion is acquiring better use of his feet. He plays baseball and uses it with much more naturalness than formerly.”


On May 2, 1898, a 29-year-old male presented with “talipes equine varus.” The admission note documented:
“both legs are very much atrophied and thigh slightly so [...] the right foot shows a scar on outer side just below and anterior to malleolus [...] the scar is the result of a blow from an axe when patient was nine years old and to which he attributes all his trouble although for a year after the accident he was able to move easily and naturally.”
He was brought to the operating room on May 11 for a tendon anastomosis.
“I. tenotomy of tendon Achilles. II incision across foot from cuboid to site of extensor proprius tendon above ant. annular ligament. This tendon exposed. III. Incision over site of this tendon just proximal to site of attachment of ext. brevis pollicis. Tendon divided at this point and drawn out of wound above annular ligament.
Tendon then passed under ant. annular ligament emerging just at prominence of cuboid where it was sutured to the periosteum of the cuboid and to the exposed tendon of the peroneus brevis muscle.
Foot stayed in excellent position after the transplantation. The tendon of transplanted muscle ran smoothly in its new bed.
Wounds closed with silver wire.
Plaster holding foot in over corrected position.”
Cushing documented the patient's postoperative course. On May 23:
“The plaster removed and foot found in good position. The wounds healed per primam. Sutures removed.
Foot can be flexed without the inward motion, and can be held by patient in flexed position.
Put back in plaster, and discharged to be treated by his local physician.”
No further follow-up information was available.


On October 31, 1898, a 14-year-old boy presented with “acquired club foot. Talipes Equina.”
He was brought to the operating room on November 16 for bilateral operations ():
“Right Foot.
Subcutaneous tenotomy of tendo Achilles which allowed the foot to be held almost at a right angle. Longitudinal incision (12 cm) along middle of dorsum of foot and lower half of ant portion of leg. Lower part of belly of tibialis anterior muscle exposed and found to be pale (dry leaf appearance) characteristic of paralysis. Tendon and part of muscle of ext long hallucis exposed muscle deep red (normal).
(Ex. Long hallucis) muscle was divided about quarter of way toward origin and the corresponding tendon split longitudinally down to near ant. annular ligament when it was cut off. The splice was brought into edge of ext tendon of tibialis anterior tendon, the appearing surfaces […] united by interrupted silk sutures. The foot being held in dorsal flexion. This produced a flaccid condition of the intact section of the ext. long hallucis – which is expected.”
Left Foot
Subcutaneous division of plantar fascia – Long longitudinal incision about 20cm over tendo-achilles from insertion up gastrocnemous (lower part) exposed and found to be pale brown (paralyzed). The perronei muscles brevis and longus were exposed. Dark red (active) and split longitudinally with their tendons as far as ext. malleolus where the split portion was divided. The half tendons of each muscle were brought over and threaded through incisions made in the tendo-achilles.
The muscle and tendon of tibialis posterior were likewise longitudinally spit on the inner side and its tendon splice brought through in a third hole in the tendon Achilles.
The foot was then held in corrected position and the tendons sutured in their holes by interrupted through and through silk suture.”
The patient was discharged on January 17, 1899, following a 79-day admission. A follow-up letter dated March 14, 1899 described the patient's condition:
“Left foot. When I left the Hospital there was a scab on it, the scab came off and it discharged some matter, another scab formed and yesterday it discharged a little matter but none today, and looks as if it is going to heal up.
There is not any soreness to the touch.
I can stand on my tip toes, with the help of the right foot and can move my foot inward […] with ease. The circumference five inches below the knee cap is eleven and seven-eighth inches. I still wear a bandage.
Right foot: Wounds are allright [sic]. I can move my foot upward and outward and downward but cannot move it but a very little bit inward. The circumference five inches below the kneecap is eleven and one half inches.
Both feet are a great deal stronger now than they were when I left the Hospital and are still improving. I think I have improved in my walking and feel a great deal stronger on my feet.”
No further follow-up information was available.


A 58-year-old woman from India residing in the U.S. presented to the emergency department with a 10-day history of progressively worsening post-prandial lower abdominal pain and nausea accompanied by non-bilious and non-bloody vomiting. She was in her usual state of health prior to this illness. She had a past medical history of well-controlled non-insulin dependent diabetes mellitus and hypertension. A recent colonoscopy was unremarkable and she denied any history of melena or bright red blood per rectum. Physical exam was notable only for abdominal tenderness in the lower quadrants. Laboratory studies revealed a normochromic normocytic anemia with hemoglobin of 7.7 g/dL, hematocrit of 22.6%, MCV 87 fL and normal iron studies (Table ). A CT scan of the abdomen and pelvis showed no specific abnormalities. The patient was discharged to home with anti-emetics and instructions to follow up with her primary care physician.
Five days later, the patient returned to the emergency department with worsening abdominal pain, nausea and bilious vomiting. Physical exam was remarkable for diffuse abdominal tenderness and pale conjunctivae. Laboratory evaluation was notable for anemia with hemoglobin of 8.8 g/dL, hematocrit of 23.5%, MCV of 87 fL and corrected reticulocyte count of 7%. The patient was admitted and subsequently underwent extensive evaluation for gastrointestinal abnormalities including esophagogastroduodenoscopy and colonoscopy, both of which were unremarkable. Review of the peripheral blood smear demonstrated normochromic, normocytic anemia with extensive coarse basophilic stippling of the erythrocytes (Figure ). This triggered a screening for heavy metals, which revealed an elevated blood lead level (BLL) of 102 μ g/dL (normal < 10 μ g/dL). Zinc protoporphyrin (ZPP) was subsequently found to be elevated at 912 μ g/dL (normal < 35 μ g/dL). The clinical picture was consistent with lead poisoning. Upon further questioning, the patient disclosed that she had been taking an Indian Ayurvedic medicine called Jambrulin. The patient had obtained the medication from Unjha pharmacy through a family member in India. She had been taking 2 pills daily over a period of 5 to 6 weeks in an effort to enhance control of her diabetes. She stopped taking the medication approximately 2 weeks prior to admission because of the abdominal pain.
The patient was instructed not to take Jambrulin and was started on dimercaptosuccinic acid (DMSA), an oral lead chelator at a dose of 10 mg/kg three times a day for five days followed by 10 mg/kg twice a day for two weeks. At the end of chelation therapy, her BLL decreased to 46 μg/dL, with improvement of her anemia and resolution of her abdominal pain (Figure and Table ). Of note, the patient's sister and brother had also been taking the same medication prior to our patient's diagnosis. They were subsequently found to have BLLs of 100 and 51 μg/dL, respectively and were advised to discontinue the supplement.
Examination of the remaining medication from the patient revealed 1.25 × 1.0 cm ovoid black pills (Figure ). In addition, a radiographic study of the Jambrulin pills showed them to be diffusely opaque, containing flakes of high attenuating material, consistent with the presence of lead or other heavy metals (Figure ). One of the Jambrulin pills was crushed and solubilized in nitric acid and lead content was measured after serial 10-fold dilutions using a LeadCare II Blood Lead Test System as well as graphite furnace atomic absorption spectrophotometry. The pill tested was found to contain approximately 21.5 mg of lead. The pills were also sent to the Connecticut Department of Public Health Adult Blood Lead Epidemiology and Surveillance Program and Public Health Laboratory and were found to contain approximately 3.5% lead by weight or 35,000 μg/g.


A 32-year-old woman without previous medical history was referred to the emergency department with dizziness for one day. On admission, the vital signs were unstable, with a blood pressure of 70/40 mmHg, heart rate of 91 beats/min, and body temperature of 35.4°C. White blood cell count was 16,470 109/L and troponin I was 2.563 ng/mL. Arterial blood gas analysis showed metabolic acidosis. EKG demonstrated sinus tachycardia. Hemodynamic status showed rapid deterioration during the subsequent hours. Systolic blood pressure was below 90 mmHg, with a heart rate faster than 100 beats/min. Urine output decreased, too. Hypoxemia did not resolve with supplementary oxygen. Echocardiogram showed a left ventricular ejection fraction of 21% with global hypokinesia. She was admitted to the intensive care unit (ICU) with a diagnosis of probable viral myocarditis. Ventilator therapy was initiated. She developed atrial fibrillation with rapid ventricular response. Hemodynamic status showed further worsening. Urine output further decreased and she developed hypoxemia with pulmonary edema, lactic acidosis. On the second day of admission, we decided to place the patient on a T-PLS. A 17 French femoral venous and a 14 French arterial cannula were inserted percutaneously. The pump was started with a flow of 2.13 L/min/m2, a pump rate of 47/min, and 100% oxygen at 4 L/min. The membrane oxygenator was replaced as required when oxygenation is not adequate (PaO2 < 100 with FiO2 of 1.0) due to plasma leakage. Serial chest X-rays showed improving pulmonary edema after T-PLS insertion (Figure ). On day 10, T-PLS was weaned down slowly and removed. Changes of inotropic agent and pump flow rate are shown in Table . Blood serology showed elevated titers of Coxsackievirus B4(1:64), Coxsackievirus B2(1:16), Coxsackievirus B3.5(1:8), and Adenovirus IgM. Six days after removal of T-PLS, echocardiography showed improved cardiac function (LVEF of 68%) with minimal pericardial effusion. The patient was discharged on the 25th hospital day. Six months later, echocardiography was normal, with LVEF of 64%.


We describe the case of a 23-year-old girl with unknown HCM, that has syncope after a basketball game. In the medical evaluation Cardiac auscultation in left lateral decubitus and orthostatic position revealed no systolic murmur, and she did an echocardiogram that reveals HCM. She has septal hypertrophy ( and see VIDEO 1 in Supplementary Material available online at doi10.5402/2011/346797), and she does not have systolic anterior movement of mitral valve (SAM) or intraventricular gradient (VIDEO 1 and VIDEO 2).
Treadmill exercise echocardiogram was performed, using the standard Bruce protocol, and the patient did not develop LVOT gradient at peak exercise ().
After finishing the exercise we maintained the patient in orthostatic position and SAM of mitral valve and LVOT gradient greater than 100 mmHg ( and VIDEO 3) developed. With evidence of falling systolic arterial pressure from 130 to 110 mmHg in that moment we put the girl in supine position. Previously considered a nonobstructive HCM, after the exercise echocardiography, the patient was considered to have an obstructive pattern with probable influence in clinical symptoms. Therefore, she was medicated with bisoprolol 5 mg a day.


A 77-year-old man with known prostate cancer presented with a four-month history of left retro-orbital pain followed by left eye ptosis. At presentation, he had complete left third nerve palsy. His visual acuity was intact in both eyes, with full visual fields to confrontation. Brain magnetic resonance (MR) imaging () showed a heterogeneously enhancing mass lesion that measured 29 × 17 × 29 mm involving the sella, with invasion of the left cavernous sinus and the upper clivus. The lesion extended to the inferior orbital fissure and was centered in the sella turcica and the cavernous sinus. A biopsy was obtained via a transnasal transsphenoidal approach. A diagnosis of metastatic prostate carcinoma was made. He subsequently underwent chemotherapy and focused radiation to the sellar region and was noted to have stable neurological examination findings two months after surgery, with no change in his ophthalmoplegia.


An 82-year-old woman with known history of breast cancer presented with several weeks' complaint of progressive left-sided hearing loss as well as facial pain and numbness in the first and the second divisions of the trigeminal nerve, respectively. On neurological examination, left-sided hearing loss and facial numbness along the V1 and V2 distributions were confirmed. MR imaging showed evidence of a heterogeneously enhancing mass in the left petrous apex that extended to involve Meckel's cave, the lateral cavernous sinus, and the internal auditory canal (). A left frontotemporal craniotomy was performed for biopsy. The histopathological evaluation was consistent with a metastatic adenocarcinoma of the breast. She was discharged home on postoperative day three in stable condition for followup with oncology.


A 79-year-old man with known history of prostate cancer presented with several weeks' history of progressively worsening double vision and eventual right eye ptosis. Neurological examination revealed complete third and sixth nerve palsies on the right side. The visual fields were full to confrontation in both eyes with intact visual acuity. MR imaging disclosed an enhancing soft tissue mass involving the clivus, pituitary fossa, cavernous sinus, and posterior nasal cavity () that surrounded both internal carotid arteries in the cavernous sinuses. An endonasal transsphenoidal approach to the sphenoid sinus was carried out to obtain a biopsy of the lesion. A histopathological diagnosis of metastatic melanoma was made, and evaluation was undertaken by the oncology team. (This patient was included in the cases described by McCutcheon et al. [].)


A 21-year-old man with a remote history of osteosarcoma and newly diagnosed metastatic renal cell carcinoma had complaints of worsening vision and facial pain. Because there was a discrepancy in the pupillary size between his eyes, he underwent a computed tomography (CT) scan of the head, followed by craniofacial MR imaging, which revealed an enhancing mass in the right sphenoid sinus with adjacent extension. On neurological examination, he was noted to have complete hemifacial numbness and Horner's syndrome on the right side. MR imaging of the face demonstrated a homogeneously contrast-enhancing lesion centered within the right sphenoid sinus measuring 33 × 20 × 27 mm (). The lesion extended into the carotid canal, pterygopalatine fossa, and optic nerve canal with destruction of the vidian canal and foramen rotundum on the right. No optic nerve involvement was recorded in the images. The patient was referred to the oncology service for radiation and possible chemotherapy.


A 42-year-old woman with several weeks of frontal headaches initially presumed to be secondary to a sinus infection underwent MR imaging after antibiotic medications failed to alleviate her symptoms. Her neurological examination was nonrevealing except for mild gait instability. Brain MR imaging demonstrated a lobulated, 25 × 20-mm sellar and suprasellar lesion with extension into the right cavernous sinus and encasement of the right internal carotid artery. This lesion was isointense on T1- and T2-weighted images and heterogeneously enhancing with gadolinium administration. A CT scan was consistent with a lytic lesion involving the central skull base extending laterally and posteriorly to involve the bilateral medial sphenoid wings and the clivus, respectively. A transnasal approach was undertaken to obtain a biopsy of the lesion. Histopathologic evaluation was consistent with a diagnosis of diffuse large B-cell lymphoma ().


A 53-year-old woman presented with a known diagnosis of breast cancer and a one-year history of worsening left eye vision with a more precipitous decline in the last month. MR imaging of the brain demonstrated a skull base lesion involving the left sphenoid bone, the anterior clinoidal process, and the cavernous sinus. On neurological assessment, the patient was noted to have an acutely diminished visual acuity in her left eye to a level of finger counting with left temporal visual field cut. MR imaging (not shown) showed a homogenously contrast-enhancing lesion of the skull base involving the greater sphenoid wing and the anterior clinoidal process with encasement of the optic nerve on the left. A left frontotemporal craniotomy was performed for biopsy of the lesion and to decompress the optic nerve and the cavernous sinus with a subtotal resection. Histopathological analysis confirmed the diagnosis of metastatic breast carcinoma. The patient did not experience improvement in her vision postoperatively. She underwent fractionated radiotherapy to the involved area. One year after surgery, her neurological findings were unchanged, and her systemic disease was under control.