A 63 year old male with history of ischemic cardiomyopathy and single chamber ICD with a dual coil active fixation lead implanted twelve months prior to presentation, underwent routine echocardiography identifying the lead localized in the aortic root and crossing the aortic valve. The proximal coil was adjacent to the right coronary cusp. The patient had recurrent gastrointestinal bleeding prohibiting long term anticoagulation therapy. Considering the thromboembolic risk of arterial lead placement and concern for adhesion near the ostium of the right coronary artery, we opted to proceed with transarterial lead extraction. Under general anesthesia and in the hybrid operating room, the subpectoral pocket was exposed. Thoracic aortic arch and carotid angiography was performed, and distal embolic filter wires were deployed in the right and left internal carotid arteries following anticoagulation with unfractionated heparin. Intravascular ultrasound of the left subclavian artery was performed to localize the lead entry point at the left subclavian artery and determine appropriate reference vessel sizing for stent graft placement. As the lead was withdrawn, a covered stent was deployed at the entry site as described previously. There were no neurological or vascular complications following the procedure. Reimplantation of a cardiac resynchronization device was performed electively via the left subclavian vein without any complications.


This patient is a 65 years old Caucasian male who was diagnosed with multiple myeloma in December 2010 based on an IgG kappa paraprotein (3 g/dl), 25% kappa light chain restricted- plasma cells in bone marrow biopsy, and the presence of anemia (hemoglobin 9 g/dl). His past medical history was significant for type II diabetes mellitus well controlled with Metformin and Sitagliptin. On December 30, 2010, he was started on therapy with single agent bortezomib given at 1.3 mg/m2 intravenously weekly. Dexamethasone was not given due to concern for hyperglycemia with his underlying diabetes. On January 20, 2011, lenalidomide was added at 10 mg a day two weeks on and one week off schedule. On February 15, 2011, during approximately the third cycle of bortezomib treatment, the patient started having severe pain in both legs extending from his thighs to his calves that he described as “toothache-like” pain as well as some mild paresthesias and muscle spasms. His chemotherapy was stopped on March 8, 2011. He also developed progressively worsening bilateral lower extremity weakness. Within one week, the patient was unable to walk. He could not move his legs and required the assistance of a wheelchair for mobility.
On physical examination: the cranial nerves were normal and extraocular muscles were intact. Manual motor test was performed and showed: Deltoid, biceps, triceps, and wrist extensor 5/5, finger extensor 4/5 bilaterally, first dorsal interosseous 3+/5 bilaterally, abductor digiti minimi 3/5 bilaterally, abductor pollicis brevis 4/5 bilaterally. Iliopsoas 4/5 right and 4-/5 left, quadriceps femoris 5/5 bilaterally, hamstrings 4/5 bilaterally, tibialis anterior 4-/5 in the right and 1/5 left. Sensory Examination: Decreased pin prick in distal gradient distribution to above ankles. Temperature sensation was intact. Vibratory sensation at toes was 1 bilaterally, at knees 4 bilaterally, and at right finger 5. Deep tendon reflexes were zero throughout. Magnetic resonance imaging of cervical, thoracic, and lumbosacral spine was normal. Cerebrospinal fluid showed normal cell count at 2 × 106/L, but high protein level at 133 mg/dl. Nerve conduction study (NCS) and electromyogram (EMG) showed electrophysiological evidence of widespread severe sensory motor peripheral neuropathy with the predominantly axonal demyelination features. Serum anti-GM1, anti-NS6S, anti-MAG, anti-GQ1b, anti-Ho and anti-Yu antibodies were negative.
The patient underwent plasma exchange five times. After the second exchange, he was able to ambulate with a walker. However, his condition subsequently worsened. On May 31, 2011 prednisone 40 mg PO daily was initiated. Within one to two days after prednisone, his motor strength started to improve. Two months later, prednisone was gradually tapered and was completely off on September 9, 2011. At the time of discontinuation of prednisone, he was able to ambulate with a cane and currently his performance status is back to his status prior to bortezomib treatment. He is currently in complete remission from multiple myeloma.


A 74-year-old Caucasian man, who was a regular drinker and heavy cigarette smoker, presented to a rheumatologist for pain at motion of his left thumb. The physician diagnosed a tendonitis, and the patient was prescribed anti-inflammatory drugs, which allowed for a moderate improvement in the pain.
The patient presented one month later to our clinic complaining of persistent pain in his left hand, even at rest. A physical examination revealed a severe tenderness of the first metacarpophalangeal joint and, though less severe, of the lateral carpal region. Pain increased with the mobilization of the wrist and the thumb.
The patient was prescribed plain radiographs of his left hand which showed diffuse osteoporosis and signs of osteoarthritis of the trapeziometacarpal joint (Figure ). A diagnosis of thumb carpometacarpal osteoarthritis was made. A hand surgeon prescribed a specific brace.
We had no contact with the patient after his follow-up, which was held two months after his presentation to our clinic, until he was admitted to the internal medicine department of our hospital three months later for severe asthenia and a weight loss of 10kg over the previous five months. The patient declared to have been eating normally until the last month when his appetite was reduced. The patient was examined by one of the authors of this report for an enormous mass that involved his whole left hand (Figure ). Severe pain discouraged the patient from using his left hand in daily activities. Pain was even present on raising the hand from a table. Physical examination showed a large mass of his left hand, deep tenderness, an increase in local temperature and edema. Simply touching the hand caused excruciating pain. No palpable lymph nodes were present. The results of laboratory tests showed: an alkaline phosphatase of 408mg/dL, erythrocyte sedimentation rate, leukocytes, C-reactive protein, antistreptolysin O, rheumatoid factor, immunoglobulin G (IgG), IgA, IgM, C3, C4, circulating immune complexes, antinuclear antibodies, antimitochondrial antibodies, carcinoembryonic antigens, α-fetoprotein and prostate-specific antigen were normal. Calcemia was also in the limits of normality. An ecography of the hand revealed ‘synovial hypertrophy, with rich vascularisation’. The patient received a new plain X-ray of his hand, which revealed a diffuse osteoporosis of the whole hand, with resorption of almost the whole trapezium, about 50% of the trapezoid, and erosion of the distal part of the scaphoid. The metacarpal and phalangeal bones were severely osteoporotic (Figure ). A chest X-ray induced the suspicion of a malignant lesion in the superior lobe of the patient’s left lung. A subsequent computed tomography (CT) scan of the chest showed a large mass in that area (Figure ).
At this point, the patient received a total-body bone scan with Tc99, which revealed the presence of a unique hot area corresponding to the left hand (Figure ). A total-body CT scan was negative for other locations.
The patient underwent an open biopsy. Histology revealed an undifferentiated large-cell carcinoma (Figure ). Immunohistochemistry was thyroid transcription factor-1 positive, which was a confirmation of the lung origin (Figures and ). The diagnosis was metastasis of undifferentiated large-cell lung carcinoma. Magnetic resonance imaging (MRI) was attempted twice without success because the patient could not tolerate to keep his left hand steady.
We performed an amputation at the distal third of the forearm.
At six-month follow-up, the amputated forearm was in perfect condition. The patient was submitted to chemotherapy but, at present, his general condition is worsening because of respiratory problems.


A 35-year-old Bengali man presented with complaints of intermittent pain in his epigastric region with occasional vomiting for two years. Over the last year, our patient had several episodes of heartburn followed by vomiting. The episodes lasted for a couple of days and occurred at an interval of two to three months. He denied any other symptoms. He was previously prescribed anti-ulcerant medication, which relieved him of his symptoms for a brief period of time. A physical examination was unremarkable.
In view of his history and clinical presentation, our patient was referred for an upper gastrointestinal endoscopy with the clinical diagnosis of peptic ulcer disease. Upper gastrointestinal endoscopy revealed duodenal ulcer disease in remission and a deformed bulb of the duodenum. An endoscopy 14 months before admission had shown erosions and a submucosal swelling at the antrum and an ulcer at the bulb of the duodenum, and an endoscopy made eight months before admission had shown a healed duodenal ulcer and partial narrowing of the channel. In view of his repeated intermittent abdominal pain, a barium meal follow-through of the stomach and duodenum was carried out. This showed the bulb of the duodenum to be deformed, with a smooth filling defect with eccentric linear passage of contrast in part of the duodenum (Figure ) suggesting a diagnosis of a mass lesion, probably a GIST. On ultrasonography, a sharp-margined complex mass with both solid and cystic component was seen in his epigastric region superimposing on the first part of his duodenum. A contrast-enhanced CT scan confirmed the ultrasonography finding, showing a well-defined, oval, mixed density, soft tissue mass measuring 9.1×5×5.1cm in his upper abdomen, compressing his duodenum (Figures and ). The mass was separated from his pancreas, right kidney, gall bladder and liver. Ultrasonography-guided fine needle aspiration cytology showed blood products and a small number of mononuclear cells without anaplastic cells.
A diagnosis of GIST in the first part of duodenum was made.
A xifo-umbilical median laparotomy was made; intraoperative findings confirmed the radiographic findings. In light of these findings, a subtotal gastric resection was performed, removing more than half of the stomach, followed by gastrojejunal anastomosis. Macroscopic examination revealed a lesion in the antrum extending 8cm along its longitudinal axis (Figure ). The cut surface was grayish white and lobulated. On histology, the lesion showed features of a hamartomatous polyp with necrosis and ulceration of the mucosal surface. The lesion was composed of two proliferations, one composed of dilated pancreatic-type ducts surrounded by smooth muscle bands, interspersed with mucous secreting glands and the other containing Brunner’s glands (some of which were pseudoadenomatous) (Figure ). This composition resembled a myoepithelial hamartoma.
The postoperative period was unremarkable and our patient’s general conditions were optimal at discharge two weeks after surgery. Our patient was followed-up at two months and six months after discharge with a complete physical examination and ultrasonography of his whole abdomen, and had no recurrence of symptoms.


A 51-year-old Japanese man who had advanced castration-resistant PC was admitted to our hospital because of extensive purpura and severe anemia. Although his platelet count was within the reference range and plasma clotting time was slightly prolonged, the fibrinogen level was low. Plasma levels of thrombin-antithrombin complex (TAT), fibrin and/or fibrinogen degradation products (FDPs), D-dimers and plasmin-antiplasmin complex (PAP) were high. Plasma α2-antiplasmin (α2-AP) level was low and a fibrin monomer test was positive (Table
). These data indicated that he had DIC. Plasma TAT, FDPs, and D-dimers decreased (Figure
) and platelet count increased after administration of low-molecular-weight heparin (LMWH). However, fibrinogen and α2-AP did not increase and PAP did not decrease (Figure
). Bleeding diathesis continued whereas DIC parameters were improved by the treatment. To inhibit activation of fibrinolysis, administration of tranexamic acid was started together with LMWH. Then, PAP level decreased and levels of α2-AP and fibrinogen increased. Bleeding tendency disappeared. High-dose anti-androgen therapy (fosfestrol) for PC was also performed on day 20 for PC. Prostate-specific antigen level decreased to 482.4ng/mL.
To investigate a correlation of coagulation and fibrinolysis markers, we analyzed the values of 31 plasma samples obtained during the 90-day hospitalization. As shown in Figure
, the patient’s fibrinogen level correlated with levels of α2-AP (r2=0.7811, P<0.0001) and PAP (r2=0.5394, P<0.0001), and D-dimer/FDP ratio (r2=0.6473, P<0.0001). There was no correlation between levels of fibrinogen and TAT. The level of α2-AP (r2=0.7060, P<0.0001) correlated positively with D-dimer/FDP ratio and negatively with PAP level (r2=0.5549, P<0.0001). The prostate tissue biopsied for the initial diagnosis was immunostained using monoclonal antibodies specific for human TF
[] or uPA (Fuji chemical, Toyama, Japan). This analysis revealed that the cancer cells were positive for both TF and uPA (Figure
).


A 22-year-old male presented to our clinic with recurrent episodes of hemoptysis over a 4-week period with 3 distinct events. He stated that this started with an incidence of heavy coughing. He then would cough up to 2–4 tablespoons of blood. After presentation to the emergency room, it was initially thought this was related to epistaxis, and he was sent home with treatment for allergic rhinitis. He had no other symptoms, denying fever, weight loss or gain, chest pain, easy bruising, dyspnea, or rash. He did complain of chronic postnasal drip, nasal congestion, and occasional pruritis, which he attributed to allergies. He had a past medical history of eosinophilic colitis, obsessive-compulsive disorder, history of an aneurismal bone cyst status post-removal, and allergic rhinitis. He had also been recently diagnosed with hypogonadism over the last 5 months, and was on injectable testosterone supplementation. He denied smoking, alcohol, and illicit drug use and had no known inhalant exposures and trauma to the airway that he could recall. His family history included a brother with eosinophilic colitis and his mother had vascular ectasias of her spinal cord. He did note that these episodes seemed to occur 5 days after his dose of intramuscular testosterone. Physical exam was otherwise unremarkable and laboratory values were unrevealing. Computed tomography did not reveal any notable lesion of the upper airway or lung parenchyma.
Upon flexible bronchoscopic evaluation, the following lesion was seen in the distal trachea (). The purple, vascular lesion was approximately 1–1.5 cm in size located 3 cm from the carina at the 5 o'clock position along the posterior wall attached by a short pedicle. A biopsy was taken at that time which only showed fibrin products and inflammatory cells. Hemostasis was difficult to obtain without use of cold saline, several injections of topical epinephrine and Argon Plasma Coagulation. Due to unavailability of pathology and the location of the lesion, the patient was taken to the operating suite where a therapeutic flexible bronchoscope was used with utilized. The lesion was obtained by electrocautery loop snare and endoscopic basket. The pathology revealed the diagnosis of lobular capillary hemangioma (Figures and ). The superficial portions of the lesion had undergone secondary, nonspecific changes including stromal edema, capillary dilation, inflammation, and a granulation tissue reaction. It demonstrated diagnostic, lobular arrangements of capillaries at its base, which consisted of discrete clusters of endothelial cells. The cellular architecture was made up of an inflammatory infiltrate of neutrophils and monocytes.
Upon followup, the patient had no hemoptysis episodes and has subsequently stopped his testosterone therapy.


A 52-year-old North African Tunisian Caucasian woman was admitted with a six-week history of headache to hospital. She had been diagnosed with seropositive destructive RA nine years before, without any extra-articular manifestations. She received methotrexate 7.5mg per week, low doses of prednisone 7.5mg per day and anti-inflammatory drugs. She presented with a six-week history of bilateral temporal headaches. There was no fever or vomiting. Her body temperature was normal and her blood pressure was 120/60mmHg. Physical examination revealed typical joint deformities of RA, but with no subcutaneous nodules or skin lesions. Synovitis was noted at both wrists as well as at the second and third metacarpophalangeal joints of both hands. Her neurological examination was normal including her deep tendon and plantar reflexes. There was no evidence of meningitis or focal neurological signs. Her temporal pulses were brisk and symmetric. Laboratory tests revealed the following results: erythrocyte sedimentation rate of 27mm/hour, C-reactive protein of 14mg/l (normal: <6) and hemoglobin of 14.9mg/DL. The white blood cell count was normal (8180/mm3) as were her platelets (380,000/mm3). Liver and kidney function tests were normal, as well as blood glucose levels. No obvious infection, disseminated intravascular coagulation, atlanto-axial dislocation or other collagen diseases were recognized by physical and blood examinations. Electrophysiological studies showed no evidence of peripheral nerve lesion or denervation. Tests were positive for rheumatoid factor (512UI/ml) and for antinuclear antibodies (1/640). Her serum complement, circulating immune complexes, and antineutrophil cytoplasm antibodies were normal. The fundus examination and the fluorescein angiography did not reveal any signs of vasculitis. Magnetic resonance imaging (MRI) of her brain with the T2 sequence showed high-intensity signal images at the frontal and parietal-cortico-subcortical junction suggesting hemispheric vasculitis (Figure
,
). Our patient had not had any severe neurological manifestation or any systemic non-neurological manifestation. She suffered only from persistent headache. Intensification of the methotrexate therapy (15mg per week) was enough to give a good outcome. Her headache disappeared in two weeks and there were no symptoms of meningitis or focal neurological signs after four months.


A twenty three-year old male patient sustained BAT due to fall from a 3-meter height. Initial vital signs were: blood pressure136/80 mmHg, heart rate 64 BPM, respiratory rate 20 per minute, oxygen saturation of 100% on room air, and temperature of 36.9°C. Patient was fully conscious with neither external bleeding nor neurological deficits. Abdominal examination showed mild generalized tenderness and voluntary guarding at epigastric and suprapubic regions. Pelvic, genitourinary & rectal examinations revealed no abnormality.
Initial chest and pelvic X-rays () and focused abdominal ultrasonography for trauma (FAST) were unremarkable. Routine laboratory investigations were unremarkable. CT abdomen and pelvis showed no bony injuries and no intraperitoneal free fluid or air (Figures and ). A Foley's catheter was inserted and revealed frank hematuria that was clearing up. Patient was reassessed 6 hours later; pain was remarkably reduced and he tolerated soft diet with no vomiting, passed motion and had no fever. Abdominal examination revealed mild suprapubic tenderness and normal bowel sound.
On the following day, Foley's catheter was removed for a short duration. Consequently he developed urine retention and hence a Foley catheter was inserted with immediate drainage of 850 mL of clear urine. Repeated CT scan of abdomen reported no free fluid or air within the abdomen. However, the Foley's catheter was found crossing the UB wall. A formal cystogram was done and revealed free intraperitoneal extravasation of contrast denoting intraperitoneal UB perforation (Figures and ). Laparoscopic exploration showed a linear tear of 3 cm at the dome of the UB with the Foley's catheter balloon floating freely in the peritoneum through the tear (Figures and ). Laparoscopic repair was done using 2/0 Vicryl suture in a continuous interlocking water tight fashion and no drains were left. Foley was removed on the tenth post-operative day, a following a normal cystogram (Figures and ). Postoperative follow up was unremarkable.


A 30-year-old female patient was admitted to an internal medicine clinic with the complaint of difficulty on swallowing for a month and endoscopy revealed external compression on the middle part of the esophagus. She was referred and admitted since the chest MRI revealed a subcarinal mass in the middle mediastinum. The past medical history revealed a surgery for hydatic liver cyst.
The physical examination revealed a blood pressure of 110/70 mmHg, pulse of 88/ min and a respiratory rate of 18/min. All system findings were normal. Laboratory findings revealed minimal hypochromic microcytic anemia in complete blood count. Biochemical tests were normal. The erythrocyte sedimentation rate was 32/h. Arterial blood analysis revealed slight hypoxemia. Lung function tests revealed medium obstruction and restriction (FEV1: 63%, FVC: 68%, FEV1/FVC: 81%).
The chest X-ray was normal. Lung CT and MRI examinations showed a subcarinally located 5.5×4.8×3.1 cm mass in the middle mediastinum, which had a multilocular cystic/necrotic appearance with multiple septa (). No endobronchial lesion was detected on bronchoscopic examination. A mucopurulent fluid was obtained with transbronchial needle aspiration performed with a Wang 122 needle through the subcarinal region. As cytological and bacteriological examination of the fluid did not yield an exact diagnosis, diagnostic thoracotomy was performed. Histopathological examination of the material obtained by thoracotomy revealed tuberculous lymphadenitis (). Lesions improved completely with a full dose combined treatment with four anti-tuberculosis medications.


A 75-year-old man was referred to the department of otolaryngology of Imam Hospital of Jundi Shapur Ahvaz University of Medical Sciences complaining of headache. On clinical examination, the left globe had severe pro-ptosis causing visual loss and lid retraction (). This problem had a 10-year duration. The patient had no history of previous facial trauma. Computed tomography (CT) of the orbit revealed a 5 × 3 cm well-defined markedly radiodense lesion arising from the left frontoethmoid sinus (). The mass had destroyed the lamina papyracea, the left rectus muscles, the left optic nerve and the left nasal wall (). A working diagnosis of osteoma was made based on the clinical and radiographic findings. The lesion was removed surgically under generalized anesthesia. Microscopic examination showed mature bone containing lacunae and marrow spaces (). A diagnosis of compact osteoma was made. The patient was examined in order to detect any osteomas in the other bones and also the polyps of the small and large intestine. The answer was negative.


A 26-year-old woman came to the department of oral and maxillofacial surgery of Imam Khomeini Hospital of Jundi Shapur Ahvaz University of Medical Sciences for evaluation of a one-year-duration swelling in the left mandible which had grown slowly. She complained of dull pain in the left mandible in the last two weeks. A mild facial asymmetry was observed. Clinical examination revealed a painful firm well-circumscribed palpable mass in the buccal and lingual vestibule of the left mandible. The lesion was covered by normal mucosa. The patient had no paresthesia. The patient was in good health with a history of previous first molar extraction a few months ago.
On panoramic radiography, a moderately well-defined radiopaque lesion was seen adjacent to the inferior border of the left mandible extending from the first premolar to the third molar, not associated with the teeth and with some degree of extension to the ramus (). CT revealed a 3.9 × 4.2 cm well-defined, radiodense lesion arising from the left lingual aspect of the mandible displacing the lingual and buccal cortex (). Under local anesthesia, the incisional biopsy was performed.
Microscopic examination revealed mature bone with prominent compact components (). The histological features indicated the diagnosis of compact osteoma. Gardner’s or polyposis syndrome was ruled out. There was no osteoma in the other bones.


A European 6-year-old male was admitted in our hospital for nonspecific constant middle back pain radiated to the limbs. Complaints include discomfort, progressive weakness of legs with abnormal sensations leading to unusual walk and limping. Symptoms increase with bending back and forward. He also suffered from chills, fever, anorecia and weight loss for 6 weeks without any infectious or traumatic context anorexia. On examination he was pale, irritable, in poor condition and painful. No tingling was described; no bladder or bowel loss of control was present. Cutaneous sensitivity and motor reflexes seemed normal. Abdominal palpation was normal. Blood investigations showed isolated anemia, major systemic inflammatory response (ESR = 109), and elevation of LDH (2328 U/L) and neuron-specific enolase (NSE = 69.5 ng/mL). Alkaline phosphatase and BUN were normal. Total spine X-ray and CT scan were normal and excluded any osseous vertebral abnormality; bone 99 Tc-scintigraphy was also normal. Sagittal spine MRI showed heterogeneity of gadolinium captation in some vertebrae, suggesting bone marrow infiltration (). Ultrasonography and MRI showed two paravertebral tumours: an extrapleural left homogenous paravertebral mass located along dorsal vertebrae T7–T9, measuring 52 × 22 mm and another paravertebral mass located in dorso- lombar (T 12–L2) measuring 40 × 10 mm. Those two tumours extended through the neural foraminae into the epidural space (Figures , , ). The cerebrospinal fluid (CSF) analysis revealed the absence of tumoral cells and both proteinorachy and CSF NSE were normal. Extension assessment showed nodular bilateral nephromegaly (Figures and ) without renal dysfunction.
The association of paravertebral masses, serum NSE elevation and probable bone marrow infiltration suggested at first a neuroblastoma diagnosis.
A transparietal tumoral biopsy was performed and pathological examinations revealed homogenous basophilic cells of intermediate size with hyperchromatic nuclei containing nucleoli (). The tumor cells had a high mitotic activity and apoptotic debris were noted. Immunophenotypic features demonstrated mature B cells positive for CD45, CD20, CD10 and negative for TdT and CD99. Lymphoma cells were monotypically positive IgM + D + Lambda, BCL2 negative, and BCL6 positive. Translocation 8;14 was identified, confirming the definitive diagnosis. The EBV RNA was not found in the specimen.
The patient was immediately treated by chemotherapy alone. Neurological symptoms rapidly resolved and the patient is now well and in first complete remission at 5 years.


A 61-year-old man first noticed a small subcutaneous nodule in the left axillary area in 2005. The nodule gradually increased in size and he was referred to our hospital in November 2007. Clinical examination revealed an irregular immobile hard mass, measuring roughly 85 mm × 51 mm in the left axilla (). Computed tomography (CT) showed an exposed and lobulated 77 mm soft tissue density mass with faint calcification in wide contact with skin (). Also, CT showed suspicious direct involvement of the left subclavian vein, enlarged lymph nodes in the left axilla, and small round lymph nodes less than 10 mm in the mediastinum. Magnetic resonance imaging (MRI) and ultrasonography (US) revealed no primary lesion in the ipsilateral breast tail and bilateral mammary gland. Additionally, positron emission tomography (PET)/CT demonstrated no evidence of any malignant or occult primary lesions, but the axillary tumor.
An incisional biopsy histologically revealed proliferation of atypical cells of variable size in the subcutis. The cells had enlarged and irregular nuclei and formed a luminal structure unconnected with the epidermis, indicating an adenocarcinoma compatible with breast carcinoma (). Immunohistochemically, both of the estrogen receptor (ER) and progesterone receptor (PgR) were positive, and human epidermal growth factor receptor type 2 (HER2) was negative. And, the immunoexpression of proliferation factor Ki67 was high (about 24%). These findings were strongly suggestive of mammary carcinoma originating in an accessory mammary gland in the axilla. We regarded the axillary tumor as locally advanced accessory breast cancer that was difficult to resect completely and, therefore, planned neoadjuvant chemotherapy.
The patient was subjected to 4 courses of FEC chemotherapy (5-Fu at 500 mg/m2, epirubicine at 100 mg/m2, and cyclophosphamide at 500 mg/m2) every 3 weeks, but sequential docetaxel chemotherapy at 75 mg/m2 was discontinued due to a severe allergic reaction, and he, therefore, received additional 2 courses of FEC chemotherapy. The tumor was finally reduced to 55 mm in diameter, and the partial response to the neoadjuvant chemotherapy was also confirmed by CT (). Wide radical excision was then performed with preservation of the axillary vein and brachial plexus, despite suspicious involvement of the tumor. Radical axillary lymph node dissection was also performed, as well as subsequent reconstructive surgery to fill the resulting skin defect with a local flap of the latissimus dorsi muscle to preserve shoulder joint movement.
The final pathological examination of the surgical specimen showed moderately differentiated adenocarcinoma compatible with invasive ductal breast carcinoma, which was the same as the result obtained with the earlier excisional biopsy. And, the decrease of immunoexpression of Ki67 due to the effect of neoadjuvant chemotherapy was confirmed. There was no evidence of intraductal components or lymph node structures in the specimen. The surgical margin was negative. Accordingly, a course of hormone therapy (tamoxifen at 20 mg/day) was started after surgery. The patient has not presented with any metastatic lesions in the four years since the operation and has been receiving hormone therapy.


A seventy-year-old patient underwent a prostatectomy due to the presence of a prostate cancer (cT3) in 2005, at the urology unit of our hospital and was discharged in good clinical condition. He underwent varians cycles of radiotherapy (RT).
Given that, during the periodical followup, an increase in the values of PSA was detected, it was decided to submit the patient to a pelvic CT scan, in which a node was found, near the anastomosis. For this reason, the patient was once more checked in to the urology unit of the same hospital, in order to undergo HIFU treatment with Ablatherm (EDAP-TMS) in a single, one-hour session.
During the first post-HIFU checkups, the patient complained of burning upon urination and mictional urgency with a reduced flow of urine, as well as outflow of urine from the anus. For this reason, he was once more checkedin to the hospital, to undergo radiological exams, under the suspicion that he had a urethrorectal fistula (RUF). A catheter was placed in his bladder.
Since the cystography is one of the most sensitive diagnostic exams for confirming the suspicion of a fistula, and the patient had already been catheterized, it was decided to carry out, as the initial radiological exam, a retrograde cystourethrography (), which allowed us to observe an “expansion of the media contrast at the neck of the bladder.” Before emptying the bladder of the contrast media, it also was decided to supplement this exam with a CT scan of the pelvis. This exam was done in order to be sure that the bladder was not involved in the problem and that only the urethra was affected by the fistula. This was necessary in order to carry out a conservative treatment.
After having obtained an antro-posterior (AP) radiogram in basal condition, we proceeded to gradually fill the bladder with 150 cc of organoiodate contrast media (Omnipaque 350 mg I/mL, GE healthcare) and 150 cc of physiological solution. When the bladder was completely full, we effected AP and oblique radiograms ().
the CT scan of the pelvis was done using a 64-slice MDCT scanner (LightSpeed VCT, General Electric Medical System, Milwaukee, WI, USA) without administering i.v. and oral contrast media. All the images were acquired with the patient in a supine position and holding his breath. The parameters of acquiring the scan are as follows: slice thickness 1,25 mm, 120 kV, and 280 mA. The images were reconstructed on a dedicate CT work station (Advantage WorkStation 4.4, General Electric Medical System, Milwaukee, WI, USA with multi-planar-reconstruction (MPR), multiintensity projection (MIP), and volume rendering (VR) reconstruction (). The images were evaluated by two radiological experts.
Since the CT scan confirmed that the fistula involved solely the urethra and not the bladder, it was possible to employ a conservative treatment by positioning a Foley catheter of monthly duration, in order to allow the urethra to rest. This treatment is also advisable for treating patients who cannot be operated on due to the presence of a cardiac comorbidity. During a followup 70 days later, the direct cystography with contrast media showed the closure of the fistulous tract (). Still today, after 6 months, the patient is in good clinical condition and has not shown signs of a recurrence of the fistula.


A 34-year-old man was referred to our surgical unit from a cottage hospital on the day he was involved in a road traffic accident as a pedestrian. He was going to work when he was hit by an overlapping van along the road. He fell down and the van ran over his left thigh and left inguinal area. He lost consciousness and found himself at a private hospital where initial resuscitation was performed and he was transferred to Kenyatta National Hospital. On examination he was found to be dehydrated, had peritonitis, degloving injury over the left inguinal area, and bruised perineum. Radiological investigations revealed pelvic fracture (). He was optimized and laparotomy was performed a day after admission. Intraoperatively, the sigmoid colon was found to be bruised and perforated, 10 cm of which were resected and Hartman's colostomy performed. Debridement of the injured left inguinal abdominal wall left a 5 cm by 10 cm defect (). An attempt was made to stitch it to the skin over the thigh. On the third postoperative day the attempted stitching gave way due to infection. The patient also started to bleed on an off from the pelvic fracture through the defect. The bleeding was managed by tranexamic and packing and later stopped by the tenth postoperative day. The wound was managed by daily dressing until it was well granulated by the fifth month after the injury. Decision was made to reverse the colostomy and close the abdominal wall defect at the same time to save time and money. Colostomy reversal and pedicled tensor fascia lata flap were used to close the defect in the anterior abdominal wall defect. Split thickness skin graft was used from the same thigh to close the other defect. On the fifth postoperative day he developed burst abdomen. This was repaired a day later after optimization and healed well. The flap and the graft took well (). He has been discharged and is on follow up in the surgical outpatient clinic with no complications.


The 51-year-old male patient exhibited a 10-day history of low back pain, limited waist motion and right lower limb numbness. The patient reported no pain at other sites, exhibited no fever or night sweats and was unable to recall any recent injury. The patient’s past medical history was unremarkable for trauma or other bone diseases. A physical examination demonstrated localized tenderness and percussion pain over the L4 spinous process, restricted waist motion and numbness of the right leg. Laboratory tests, including full blood cell count, serum electrolytes, renal and liver function tests, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), did not reveal any abnormalities. An X-ray revealed that the lesion was limited to the left lateral mass of the atlas, causing a potential instability (). Computed tomography (CT) revealed an osteolytic lesion in the right lateral mass of the L4 and accessories, accompanied by a paravertebral and intraspinal soft tissue extension (). Magnetic resonance imaging (MRI) revealed osteolytic destruction of the vertebral body associated with a mild compression fracture that exhibited hypointensity on T1-weighted (T1-W) images and hyperintensity on T2-weighted (T2-W) images (). On the basis of the radiological features of the lesion, there was a high possibility that the patient had a neoplastic lesion. However, the radiological features of the lesion were not sufficient to establish the diagnosis of LCH with certainty. A C-arm X-ray machine-guided needle biopsy of the vertebral body was performed and the histopathological diagnosis was LCH. Immunohistochemical staining was positive for CD1a and S-100 (). Further diagnostic evaluation included a bone scan, CT of the lungs, pituitary hormonal evaluation and brain CT and abdominal ultrasound evaluation. No other LCH infiltration was identified in the patient and the patient was treated as suffering from a single-system and single-site disease.
The patient underwent PVP (Stryker, Inc., Meyzieu, France) under local anesthesia in the prone position with the belly suspended in midair, under C-arm imaging guidance (). The amount of bone cement used to fill in the L4 was 3.6 ml. The blood loss during surgery was 5 ml. The spread of the cement was ideal with the exception of a small amount of paravertebral leakage of cement () which did not cause any symptoms. No complications were observed during the surgery or follow-up. After lying in bed for 6 h, the patient was able to sit freely and 24 h postoperatively, the patient was allowed to walk freely. Following the procedure, the low back pain was resolved completely and the patient’s neurological symptoms were rapidly alleviated and then gradually continued to be alleviated. The patient required the use of a weak opioid prior to the PVP but did not receive an analgesic afterwards. Notably, CT revealed a significant decrease in the paravertebral and intraspinal soft tissue extension 5 days after the PVP ().
The patient received chemotherapy following PVP. The chemotherapy regime was 100 mg etoposide (days 1–3) and 60, 40 and 20 mg prednisone (days 1–7, 8–14 and 15–21, respectively) for 3 cycles. There were no serious side-effects of the chemotherapy. CT revealed that the paravertebral and intraspinal soft tissue extension disappeared after 3 cycles (). The height of the vertebral body remained stable without further collapse and lumbar kyphosis did not occur. There was no recurrence and no other complaints over a 6-month follow-up period ().


A 10-year-old girl presented with failure to thrive despite good appetite for 3 years. She also had a history of polyuria and polydipsia for one year. She was incidentally found to have a blood pressure of 170/110 mmHg. Her body weight was 21 kg (50th percentile for 7 years old), height was 128 cm (10th percentile), and her bone age was about 7 year. Her pulse was 120/min and rest of physical and systemic examinations were unremarkable. A 24-hour urine analysis revealed urine vanillylmandelic acid (VMA) of 25.4 mg/24hours (normal range, 0.4-0.6), metanephrine over 960 mcg/24hours (normal range, 0-350), and normetanephrine over 3840 mcg/24hours (normal range, 0-600). Her serum aldosterone and cortisol levels were normal. Other laboratory tests were within normal limits. Abdominal ultrasonography revealed solid heterogeneous mass with micro cysts, measuring 68 x 58 mm at the left adrenal region. CT scan of the abdomen showed a solid hetero-density mass lesion, measuring approximately 60 mm in diameter, near the upper pole of the left kidney (Fig. 1). Echocardiogram and ECG were unremarkable.
She was given phenoxybenzamine (alpha blocker) for 14 days preoperatively; starting with 2.5 mg 12 hourly to 10 mg three times a day for resistant hypertension. Patient was also given propranolol (beta blocker) 5 mg four times daily starting from 11th day of preoperative preparation for 4 days. Intravenous hydration was given 24 hours prior to the surgery. After stabilizing her blood pressure and other vital signs she underwent laparoscopic left adrenalectomy (Fig. 2).
The child was placed in dorsal decubitus slightly turned to her right side at a 45° angle. Insufflation was performed through a 10 mm port that was inserted under direct vision at mid clavicular line about 1.5 cm bellow costal margin. A 30° telescope was inserted and, under visual control, three other ports were inserted including one 10 mm (1.5 cm bellow costal margin) and two 5 mm ports (one of them in xiphoid region and one in posterior axillary line 1.5 cm bellow costal margin). The Gerota’s fascia was incised by a 5 mm ligasure. The adrenal gland was released from the spleen, pancreatic tail, and left kidney. Left adrenal vein was exposed and secured with clips and the excised lesion removed in an endoscopic retrieval bag through the 10-mm trocar. A drain was positioned bellow the spleen. All trocars were removed and the wounds closed. The operation time was about 90 minutes. The excised mass was a 30gram encapsulated creamy-gray soft mass measuring 6x5x3.5 cm. Pathological examination of the tumor showed features of pheochromocytoma.
The postoperative period was uneventful. Her blood pressure became normal (120/90 mm Hg) without any medication. 24-hour urine studies were repeated which showed normal level of VMA, metanephrine and normetanephrine. The patient was discharged on postoperative day 4 tolerating a regular diet. At twenty months postoperative follow up, she remained in excellent condition with no clinical or imaging signs of recurrence and her growth index increased significantly.


A 50-year-old man with autosomal dominant polycystic kidney disease (ADPKD) evolved to end-stage renal failure and hemodialysis was started in 1992. Because of voluminous kidneys, a right nephrectomy was performed in 1992, followed by the left one in 1994. In April 1998, a deceased donor kidney transplantation was performed in the right iliac fossa. Induction therapy consisted in seven days of polyclonal anti-T-cell globulin (thymoglobulin), because of delayed graft function. Maintenance immunosuppression consisted of cyclosporine (CsA) and prednisone. Steroids were withdrawn in December 1998. No acute rejection was observed. At one month, the serum creatinine was 130 μmol/L and the glomerular filtration rate was estimated at 61 mL/min/1.73 m2 by MDRD. The serum creatinine remained stable during the followup and was of 113 μmol/L in March 2011.
During the followup in our outpatient clinic, the patient suffered from recurrent episodes of hepatic cyst infections, treated by antibiotics. In April 2007, bloating and abdominal discomfort developed. An abdominal MRI was performed showing a marked hepatomegaly with incomplete chronic Budd-Chiari syndrome, due to extrinsic venous compression by voluminous liver cysts. Because of worsening symptoms and many hepatic cyst infections, a new MRI was performed in June 2008, showing an increasing liver volume without progression of the Budd-Chiari syndrome. The liver volume was 3517 mL at this time. Because of preliminary data suggesting a potential benefit of mammalian target of rapamycin (mTOR) inhibitors therapy on hepatic cyst growth, CsA was stopped and sirolimus started at 0.5 mg/d to achieve serum levels between 4 and 6 ug/L (). MRIs were performed during the mTOR therapy because of worsening symptoms, and a followup was made with volumetric hepatic MRI. Only total hepatic volume was measured. Six months later, a new MRI showed a continuing increase in liver volume, which was estimated at 3883 mL. In November 2009, the liver volume was 4240 mL and in June 2010, 4400 mL (). The chronic partial Budd-Chiari syndrome did not change.
Under sirolimus therapy, our patient did not report adverse events like cutaneous rash, diarrhea, and aphthous stomatitis, but he developed important legs edema. Hyperlipidemia was controlled with pravastatin and there was no significant proteinuria. Because of the continuing increase in liver volume (i.e., no significant effect of sirolimus) and the important discomfort due to bilateral legs edema, sirolimus was stopped and CsA restarted in June 2010. The differential diagnosis of leg edema was venous compression due to hepatomegaly. After restarting CsA therapy, the leg edema resolved, which was consistent with a sirolimus side effect. Fifteen months after sirolimus was stopped, a new MRI was done. The liver volume was at 4700 mL (). The average hepatic growth over the two years of sirolimus therapy was of 37.5 mL per month versus 20 mL per month with cyclosporine.


A six-year-old boy was reported with chief complaint of large tooth in the lower jaw. His medical and family history was noncontributory. Intraoral examination revealed unusual presence of large fused triple teeth at incisor region on right side and erupted permanent central and lateral incisors on left side of mandible (Figures and ). There was deep vertical groove at the union without caries or any other dental abnormalities. Intraoral periapical radiograph shows fusion of two primary incisors with supernumerary tooth (triple teeth), with separate pulp chamber and root canals, erupting succedaneous lateral incisor and canine but absence of central incisor on right side as its position and mesiodistal dimension resemble erupted lateral incisor on left side (). It was diagnosed as an unusual case of triple teeth in deciduous anterior region which is of incomplete fusion. Since the fused teeth were asymptomatic, recall examination was planned until exfoliation of triple teeth.


A 12-year-old girl was admitted to our orthopaedic department for intoeing and shoulder instability. She had a previous history of tuberculous meningitis and was treated with antituberculous therapy for nine months when she was 17 months old. At that time, she was hospitalized for two months. When she was six years old, she began to feel snapping, locking, and pain in her right shoulder, which was apparent at external rotation and abduction, and her symptoms were aggravated at the last one year.
She complained especially of pain in her right shoulder for overhead activities. In the physical examination of her shoulder, painful anterior inferior instability was observed with 90 degrees of abduction and 70 degrees of external rotation. Her shoulder also dislocated with 60 degrees of external rotation in a neutral position and after 120 degrees of forward flexion. Apprehension and fulcrum tests and sulcus sign were all positive. Neurovascular examination, deep tendon reflexes, and electromyography findings were normal. Shoulder radiographs and CT scan showed no bony pathology or any glenoid deficiency. A capsulolabral tear could be seen with MRI (Figures and ).
Detailed information on surgical interventions was provided to the patient and her family. An informed consent form concerning the operative techniques to be performed was signed by her parent. She and her family were enlightened about the rehabilitation program to be instituted. We performed shoulder arthroscopy to identify the Bankart lesion and to detect the presence of associated possible lesions through standard posterior, anteroinferior, and anterosuperior portals in the lateral decubitus position (). No signs of joint tuberculosis nor synovial problems were detected. We performed inferior capsulolabral repair with a 3 mm knot tying suture bioanchor (Bio-corkscrew, Arthrex, Naples, FL, USA). Rotator interval closure was done in order to obtain absolute stability (). We also made a dynamic shoulder stability examination with arthroscopy at the end of the surgery. On the second postoperative day, the patient was directed to the physical therapy department with a shoulder sling. Isometric shoulder-strengthening exercises were provided for six weeks. The sling was removed at week six after surgery, and passive range of motion was started. Active-assisted and active exercises were started at week eight postoperatively. The intensity and frequency of the scapulothoracic strengthening exercises were gradually increased; rotator cuff strengthening exercises were done in a side-lying position, and active, resistive strengthening and stretching exercises were begun 10 to 12 weeks postoperatively. At her one-year followup, there was no history of instability nor a dislocation recurrence. Provocative tests became negative, and forward flexion was 170°, abduction was 150°, and external and internal rotations were 70° (). Outcomes of the surgery were evaluated with the Rowe Shoulder Instability Score []. The Rowe score increased from 25 points (poor) at preoperative to 90 points (excellent) at postoperative sixth month. Anterior inferior capsulolabral complex was detected to be completely intact and restored on a postoperative MRI control (Figures and ).


This 58-year-old female presented with recurrent, multiple, flaccid bullae, and erosions with oozing and crusting at places and severe painful oral ulcerations of 1-year duration. Various treatments including repeated courses of systemic corticosteroids at a peripheral center would provide temporary relief but recurrences and exacerbations were causing marked discomfort and disability. The cutaneous lesions were widespread and predominantly distributed over trunk and limbs. She had severe erosions/ulceration of the vermilion lips, palate and tongue (), and conjunctival congestion (conjunctivitis). Oral lesions had preceded the skin lesion by 2 months. She also had episodes of moderate to high fever, productive cough and breathlessness, easy fatigability, bouts of abdominal pain, and watery diarrhea. She was sick, experienced pain while swallowing, dehydrated and had multiple crusted and denuded skin and few flaccid bullae over face, abdomen, back and limbs involving about 30% body surface area. The painful erosive lesions over right forehead were suggestive of herpes zoster ophthalmicus. Tzanck smear from a skin erosion and right forehead lesion showed acantholytic cells () and multinucleated giant cells (for herpes zoster), respectively. The deposition of IgG and complement in the basement membrane zone and intercellularly in the epidermis were seen on direct immunofluorescence (DIF) of perilesional skin. Histologic features of suprabasal acantholysis, dyskeratotic keratinocytes, and/or basal vacuolization and interface dermatitis (dyskeratotic keratinocytes, basal vacuolization, epidermal exocytosis) and absence of eosinophilic spongiosis and inflammatory infiltrate of eosinophils and neutrophils within the superficial dermis were suggestive of PNP (cf. pemphigus vulgaris). (). Lab workup showed low hemoglobin (7.5 gm%), leukocytosis with predominant lymphocytosis (total leucocyte count 38900/cmm, L89%, N11%), elevated erythrocyte sedimentation rate (ESR 60 mm in 1st hr, Westergren method), and normal platelet counts (2,63000/cmm). Peripheral blood film showed dimorphic anemia and chronic lymphocytic leukemia (CLL) picture (). Serum urea and creatinine were 59 mg% and 1.4 mg%, respectively. Hepatic functions, blood glucose, serum electrolytes, and urinalysis were essentially normal. Fine needle aspiration cytology from a small axillary lymph node showed features of small cell lymphocytic lymphoma/CLL (). Radio-imaging studies (Figures and ) showed bilateral hilar lymphadenopathy and segmental atelectasis in chest X-rays and retroperitoneal lymph node enlargement involving those from epigastrium to aortic bifurcation and external iliac group, concentric thickening of sigmoido-rectal wall and fractured/collapsed vertebrae in ultrasonography (USG) and computed tomography (CT scan) of abdomen. The pathology of thickened sigmoido-rectal wall could not be ascertained as she did not consent for the colonoscopic biopsy due to ill health.
With the diagnosis of CLL-associatedparaneoplastic pemphigus, bronchilitis obliterans, and iatrogenic (steroid induced) vertebral fractures, she was put on treatment with dexamethasone-cyclophosphamide-pulse (DCP) therapy (dexamethasone 100 mg in 500 mL of 5% dextrose given by a slow IV infusion over 2-3 hours on three consecutive days along with 500 mg of cyclophosphamide IV on the second day and repeat DCP doses at 3-week interval). Prednisone 40 mg/d and cyclophosphamide 50 mg/d PO during intervening days between two DCPs were added. She also received aciclovir 800 mg five times/d and amoxiclav 1 gm twice/d for 1 week, probiotics, nutritional supplements, and other supportive measures. For CLL, cyclophosphamide was considered adequate. During next 2 months of hospitalization most of her mucocutaneous lesions showed epithelization/healing, oral intake of food/fluids and general wellbeing improved, and she had no recurrence of diarrhea. After 3 DCPs she was put on COP regimen (single intravenous dose of cyclophosphamide 1 gm and oncovin/vincristine 1 mg, and prednisolone 20 mg, t.i.d × 7 d, PO). All her skin lesions had healed and new lesions stopped coming but she developed leucopenia (TLC 2400/cmm) after 7 COP doses. She received 8th COP dose after blood counts improved (TLC 7000/cmm) following transfusion of 2 units of whole blood and 3 doses of human granulocyte colony stimulating factor (G-CSF 300 μm/d) administrated subcutaneously. Subsequently, she is being treated with chlorambucil (5 mg/d × 5 days) and prednisolone 20 mg t.i.d. × 7 days in a month, PO. Her skin lesions are in remission, the sigmoido-rectal thickening has reduced and all involved lymph nodes are reduced in size and number as seen in repeat CT scan abdomen.


A 48-year-old woman presented to the emergency department with a sharp, severe left lower quadrant pain. Ultrasound imaging of the abdomen and pelvis demonstrated an enlarged uterus with multiple masses (highly suggestive of leiomyoma), an 8.7 cm left adnexal complex mass, and minimal fluid in the pelvis. Subsequent computed tomography (CT) scan of the abdomen and pelvis confirmed the above findings.
Pelvic examination revealed a posterior cervix with an enlarged, boggy uterus, but no tenderness. The cervix could not be visualized on speculum exam due to a distorted uterus. No palpable inguinal lymph nodes were identified. The remainder of the physical exam was unremarkable. Laboratory workup was notable for an elevated CA-125 level (125.9 U/mL).
The patient's past medical history was significant for breast cancer status after lumpectomy, radiation therapy, and Tamoxifen therapy. Her past gynecologic history was remarkable for laparoscopic myomectomy (12 years prior to this encounter). She resumed having regular cycles every 30 days and denied any recent abnormal bleeding, weight loss, and gastrointestinal or genitourinary symptoms.
The patient was advised that the best approach would be to remove the uterus and ovaries and send them for intraoperative consultation during the surgery. Subsequently, the patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO).
Exploration of the pelvis at the time of surgery revealed a large multilobated uterus that was about 16 weeks in size, as well as hemorrhagic cysts on both ovaries. The left ovary was no longer 8 to 9 cm, but was instead around 4 to 5 cm. Additionally, there was also some blood in the pelvis. Pelvic washings were obtained, and a representative section from the left ovary was submitted for frozen section examination. The diagnosis was reported as a benign hemorrhagic cyst. The surgery and the postoperative course proceeded without complication and the patient was discharged home on postoperative day 4.


We evaluated a 45-year-old female who presented with a 2-week history of easy bruising 4–6 weeks after taking only tamoxifen (20 mg/day). She was stage II (T1N1M0) left breast adenocarcinoma patient treated with partial mastectomy and axillary lymph node dissection followed by chemotherapy with adriamycin, cytoxan, and paclitaxel followed by irradiation. The patient's bruisability was associated with 45 min of bleeding after tooth extraction. She had no previous bleeding history that includes surgeries for a decompressive laminectomy and fusion, an iliac crest bone graft, bilateral breast reduction, ankle surgery, and the mastectomy. The patient denied oral ingestion of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or selective serotonin reuptake inhibitors (SSRIs), which are known to affect platelet function. Physical examination showed one large bluish-purple ecchymosis on the left leg and few smaller resolving bruises on both lower limbs. In the laboratory she had a normal complete blood count, renal and hepatic function, PT, APTT, fibrinogen, factor XIII, von Willebrand antigen and multimers, ristocetin cofactor assay, ristocetin-induced platelet aggregation, and no platelet-associated immunoglobulin. Platelet function studies revealed normal ADP-, epinephrine-, arachidonic acid-, and collagen-induced platelet aggregation and ATP release (). However, the patient had reduced mepacrine uptake but with normal release, suggesting an acquired storage pool disorder [, ]. It is recognized that patients with acquired storage pool disorders can have normal platelet aggregation and secretion studies [, ]. After tamoxifen was stopped, the patient's bruising ameliorated. Repeat platelet function studies performed 3 months later revealed normal platelet function studies and full correction of the mepacrine uptake defect ().


We report the case of a 56-years-old Caucasian male a histoty of clear cell renal carcinoma status post right nephrectomy 2 years prior, and who subsequently developed lung metastasis. The patient had progression of disease after several lines of treatment including to sutent, pazopanib and temsirolimus, and he was ultimately started on axitinib 5 mg by mouth twice a day with good initial clinical and radiological response after 1 one month of treatment.He presented to the emergency department of our institution complaining of 3-day-progressive dyspnea on minimal exertion, associated to dry cough and difficulty to speak. Vital signs on admission revealed a blood pressure of 93/59 mmHg, tachycardia, tachypnea, and hypoxemia with oxygen saturation of 90% on room air. Chest examination showed absent breath sounds in the left side of his chest. Chest X-ray (CXR) revealed a left-sided tension pneumothorax, which required thoracostomy by cardiothoracic surgery in an emergent fashion; a new CXR showed complete resolution of left pneumothorax, and for that reason after 3 days the chest tube was removed and the patient was discharged home. Unfortunately the next day he returned to the emergency department with a new onset of shortness of breath and left-sided chest pain; a new CXR showed left recurrent pneumothorax; thus chest tube was inserted again. High resolution CT scan showed biapical bullae and blebs, a small left pneumothorax, subcutaneous emphysema, and a 4.3 × 2.6 cm pneumatocele within the anterior segment of the left upper lobe.
Cardiothoracic surgery decided to perform a left video assisted thoracoscopy with apical blebs resection as a definitive treatment. In the operation room, and after performing a left upper lobe wedge resection of the blebs, reexpansion of the left lung was achieved and it revealed a large left upper lobe air leaking caused by 4 × 3 cm cavitated necrotic tumor at the level of the main pulmonary artery, so the decision was made to proceed with a left thoracotomy. During the procedure it was found that the necrotic mass was not resectable, and for that reason the lesion was covered and repaired via pericardial fat flap placement. Multiple biopsies were taken from this mass, with a final pathology report of a lesion consistent with mRCC with extensive associated necrosis (Figures and ). Postoperative course was also complicated with a left side empyema and new onset atrial fibrillation that were successfully treated and the patient eventually was discharged home. A comparative review of interval imaging studies before- and afteraxitinib use showed an initial 4 × 3 cm mass seen in the same location of this large cavitated necrotic tumor (Figures and ). Apparently this mass transformed into a cavitated tumor after one month of axitinib treatment and caused the recurrent pneumothorax.


A 64-year-old male presented to the emergency department as a “stroke alert” with new left-sided facial droop and aphasia one hour prior to arrival. The patient had a past medical history of hypertension, coronary artery disease, and ischemic cardiomyopathy with heart failure. Emergency Medical Services (EMS) stated that on their arrival to the scene, the patient had aphasia, left-sided facial droop and was somnolent. EMS reported that the patient had a Glascow Coma Score of 14, and the patient was easy to arouse to verbal stimuli. Pertinent positives in the review of systems included neck stiffness, nausea, vomiting, speech change, headache, and loss of balance. The patient's vital signs on arrival included blood pressure of 179/102 mm Hg, pulse rate of 79 beats per minute, temperature 36.9 degrees Celsius (oral), respiratory rate of 20 breaths per minute, and a pulse oximeter reading of 97%. Pertinent physical exam findings included an expressive aphasia, left-sided facial droop, nonfatiguable horizontal and vertical nystagmus bilaterally, full range-of-motion of the neck, no pronator drift bilaterally with normal strength in the upper and lower extremities bilaterally, past-pointing of the left upper extremity on finger-to-nose examination, and two plus pitting edema of the lower extremities bilaterally.
The patient underwent a CT with angiography of the head and neck per the department's stroke protocol (see Figures , , and ) which revealed a 25 mm basilar aneurysm with partial thrombosis and no evidence of rupture with a secondary saccular aneurysm of the left posterior cerebral artery. The neurosurgery and neurology services were both consulted with no direct intervention recommended. The patient was started on anticoagulation with heparin due to thrombus within the aneurysm and MRI performed (). A radial arterial line was placed and the patient was kept normotensive prior to being admitted to the neurology intensive care unit without further decompensation prior to transport.
On hospital day three, the patient became difficult to arouse and his heparin infusion was discontinued. An emergent noncontrast CT of the head () revealed diffuse blood products in the subarachnoid spaces and early ventricular dilation. The patient was reevaluated after returning from CT and found to have fixed, midposition pupils, absent corneal reflexes, and no response to painful stimuli. The patient was made Do Not Resuscitate (DNR) due to his terminal condition and he subsequently expired.


After resection of an acrolentiginous melanoma a 59-year old patient developed metastases of the subcutaneous tissue of her right forearm, for which she was treated with surgery and radiotherapy. Additionally, lung and adrenal gland metastases appeared. Radiotherapy (20×2.5 Gray; total 50 Gray) was started three weeks before ipilimumab initiation while ipilimumab (3 mg/kg body weight) was started five days before the final radiation. Five days later the patient developed blisters within the radiated area (). These symptoms completely resolved under conservative local treatment with urea lotion and sulfadiazine silver and restaging showed stable disease. Importantly, an adverse reaction to the radiotherapy itself cannot be completely ruled out. However, the timely association with the initiation of ipilimumab therapy and the fact that no blister-formation was induced by radiotherapy alone, is highly suggestive for an ipilimumab-induced skin toxicity in the radiated area.


A 47-year old female patient received ipilimumab in an adjuvant setting (10 mg/kg body weight). Two weeks after the first infusion, erythematous maculae developed in sun-exposed regions a few hours after two short outdoor stays despite extensive sun protection (sun protection factor 50+; ultraviolet (UV)-B/UV-A). The erythema disappeared during the next five days. Further treatment was complicated by diarrhea (up to 10 times/day; treated with i.v. and subsequently oral steroids) 37 weeks after treatment initiation. In addition, circumscribed depigmented, non itchy areas below both knees, a pronounced itchy rash, erythematous macules and infiltrated plaques affecting the lumbar and inguinal region, the flexural areas, scalp, both palms and the lower right leg, were reported. Laboratory blood tests showed no signs of inflammation. Histological evaluation demonstrated a spongiotic epidermis with parakeratosis and acanthosis, a discrete edema in the dermal papillae and a perivascular infiltrate of lympho-histiocytes with some eosinophils. Based on these findings, a pruritic exanthema and/or a drug eruption was postulated, which completely subsided under treatment with topical steroids.


A 55-year old man with lung, bone and lymph node melanoma metastases and a history of diverticular disease developed diarrhea (9–10 times/day) and cramp-like abdominal pain two weeks after the third ipilimumab infusion (3 mg/kg body weight). Intravenous steroids were given and symptoms improved. Since the abdomen was soft without signs of rebound tenderness, steroids were continued orally (2 mg/kg body weight). However, after switching to oral steroids, acute abdominal pain with signs of peritonitis developed. Computed tomography (CT) imaging demonstrated pneumoperitoneum highly suspicious for a perforation. The perforated sigmoid was resected and a colostomy was performed. Histological findings demonstrated an exacerbated purulent diverticulitis (positive for Prevotella intermedia, streptococci and Escherichia coli) and perforation. Steroids were continued after surgery and subsequently tapered.
In this case the colitis initially seemed completely controlled by intravenous (i.v.) steroid treatment, yet rapidly deteriorated under steroid reduction. This implicates incomplete suppression of ipilimumab-triggered autoimmune effects or masking of symptoms under steroid treatment. Importantly, a known inflammatory condition like diverticular disease might represent a relative contraindication for ipilimumab. This may require special caution with prior ultrasound examination and/or prophylactic steroid treatment.


A 44-year old woman with stage IV melanoma developed diarrhea (up to 30 times/day) and a subsequent acute abdomen sixteen weeks after initiation of ipilimumab treatment. X-ray showed ballooned bowels. A perforation was feared and a colostomy was performed to relief pressure. Interestingly, the colostomy showed no signs of healing and a revision was performed two weeks later. Histological findings showed ulcers and a granulocytic infiltrate in the mucosa. No bacterial or viral pathogens were found and the patient fully recovered from this AE.


Ipilimumab treatment (3 mg/kg body weight) was initiated in a 67-year old male with multiple melanoma metastases. Since the patient developed abdominal pain a colonoscopy was conducted but showed no signs of ulceration or colitis. However, the small intestine could not be investigated. Twelve weeks after the first ipilimumab treatment, the patient was admitted with acute abdomen and an emergency small bowel resection was performed. At this time, he also suffered from purulent peritonitis, thus no steroids were given. Staging showed a PR with regression of all metastases except bone lesions.
Detailed treatment algorithms for the management of ipilimumab-induced diarrhea/colitis exist . Whereas in previous reports three out of four patients with colonic perforation were refractory to initial treatment with high-dose steroids , perforations in our study occurred after initial symptom improvement and steroid reduction. Steroids should be slowly tapered (30–60 days) and in cases of symptom recurrence, steroids should immediately be administered i.v. and if symptoms do not improve within 24 hours of therapy, additional immunosuppressive therapy (e.g. infliximab) should be initiated.


A 72-year old female received ipilimumab (3 mg/kg body weight) due to progressive metastatic melanoma affecting lymph nodes, subcutaneous tissue and the gastrointestinal tract (cecum and jejunum without signs for passage disorders). Shortly after the first infusion, the patient underwent a complete surgical resection of all metastases with histological confirmation of the excised lesions. After the third infusion, the patient developed generalized pruritus including eyes and genital mucosa, which responded to antihistamines. Staging after the fourth treatment showed no metastases but a new strong diffuse fluordesoxyglucose (FDG)-enhancement in the gastric wall (most intense in the gastric corpus). Since the patient was asymptomatic with normal S100 values, radiologic follow-up without further action was advised. The next positron emission tomography (PET)-CT scan demonstrated no enhancement in the stomach mucosa. However, three months later, a strong FDG-enhancement in the corpus of the stomach was detected again, suggesting the presence of gastritis without further evidence of metastases. Radiological findings and an ongoing anemia eventually causing dyspnea, prompted a gastroscopy. Biopsy showed an ischemic gastritis compatible with the endoscopic findings (). No helicobacter pylori (HP) or metaplasia were detected. Symptoms spontaneously resolved and the last PET-CT scan detected no enhancement of the gastric wall.


A 71-year old man with stable stage IV B-cell non-Hodgkin lymphoma suffered from metastatic melanoma. After the second ipilimumab treatment, the patient presented in a reduced general condition and with massive increase of liver transaminases and creatinine. Systemic steroids induced a slight improvement in liver transaminases within 24 hours. However, creatinine levels further increased and the patient required dialysis. In addition, his neurologic condition rapidly deteriorated with reduced responses to his environment and reduced respiration (spontaneous oxygenation below 60%). An inflammatory-induced capillary leak syndrome completely abolished renal function. Despite full symptomatic supportive treatment in the intensive care unit the patient died three days after admittance. Autopsy showed necrotic metastases and septal infiltration of the liver with CD3+ lymphocytes. This finding supports an ipilimumab-induced reaction and is less likely induced by lymphoma progression.
Unfortunately, this hepatotoxicity described above was steroid-refractory and resulted in fatal outcome. Importantly, successful treatment of a fulminant hepatitis refractory to treatment with steroids and mycophenolate mofetil with antithymocyte globulin (1.5 mg/kg for four times) has been reported .


A 74-year old male with no history of brain metastases received ipilimumab (3 mg/kg bodyweight) due to progressive metastatic disease affecting both adrenal glands. Shortly after the second treatment, he showed progressive ataxia and aphasia. MRI ruled out newly developed brain metastases and hypophysitis was suspected. Except for a slightly decreased testosterone, no hormonal changes were observed. Oral steroids (dexamethasone) were started and tapered. After two weeks, a decrease in thyroid hormones and testosterone was noted. Due to steroid therapy, the likewise decreased cortisol levels could not be used for interpretation. A second MRI demonstrated improvement of the morphological changes. Thyroid-hormone substitution was initiated and steroids tapered. After discontinuing steroid treatment, progressive ataxia and aphasia developed again. At this time, laboratory findings revealed hyponatraemia (serum sodium 125 mmol/l, normal range 135–145 mmol/l), and reduced levels of cortisol (2.6 µg/dl, normal range 5–25 µg/dl), testosterone (0.5 ng/ml, normal range 2.8–8.5 ng/ml) and dehydroepiandosterone (DHEAS) (<150 ng/ml, normal range 800–5000 ng/ml). Adrenocorticotropic hormone (ACTH), LH, prolactin, free triiodothyronine (fT3) and fT4 (under treatment with thyroid hormones) were normal. A third MRI showed similar results to the second MRI scan, but pituitary impairment persisted. Under i.v. steroids (dexamethasone 4×4 mg) ataxia and aphasia subsided and serum sodium levels normalized. In conclusion, the observed hyponatraemia appeared due to an acute Addison crisis after steroid withdrawal because of persisting corticotropin deficiency. Although the clinical course was further complicated by a steroid-induced psychosis and a bacterial infection of unknown origin, the patient is now free of symptoms under hormonal substitution with thyroid hormones, hydrocortisone and testosterone.


A 67-year old man with multiple melanoma metastases received stereotactic irradiation for a single parietooccipital brain metastasis (4 mm diameter) and developed a new cerebellar metastasis. Four consecutive treatments with ipilimumab (3 mg/kg body weight) were well tolerated apart from a slight decrease in thyroid-stimulating hormone (TSH) (0.3 mU/l; normal range: 0.4–4.9 mU/l) with normal fT4 before the third treatment. After the third treatment the cerebellar metastasis was stereotactically irradiated. Fourteen weeks after initiation of ipilimumab, the patient presented with acute onset of nausea, dizziness and ataxia. On examination, a blurred speech was noticed, prolactin was elevated with 30.7 ng/ml (normal range 3.5–19.5 ng/ml), cortisol and TSH were decreased with <1.0 µg/dl (normal range 4.3–22.4 µg/dl) and 0.27 mU/l (normal range 0.4–4.9 mU/l), respectively. CT scan showed the previously described irradiated metastases with adjacent edema as well as an increase in volume of the pituitary gland with signs of brain edema. Under i.v. steroid treatment (dexamethasone 16 mg/day) symptoms ameliorated.
In agreement with previous reports, 4 out of 12 hypophysitis patients require ongoing hydrocortisone replacement and in some cases additionally thyroid hormones and testosterone/estrogen , .


A 50-year old man with stage IIIA melanoma experienced transient chills without fever eight weeks after initiation of ipilimumab. In addition, two weeks later right-sided facial paresthesia and muscle weakness in both legs were observed. Paresthesia in his face deteriorated and extended to the whole face. Additionally, singultus and nausea appeared and persisted. Twelve weeks after start of ipilimumab, his neurological condition suddenly worsened resulting in sensoric ataxia and a disabling progressive paraparesis affecting both legs. All examinations for bacterial, fungal and viral causes were negative. No melanoma cells could be detected by lumbar puncture, and a marked lymphocytic pleocytosis was seen. Blood CD4/CD8 ratio was markedly increased at 4.3 (normal range 1.1–3.0) with an increase of absolute CD4-lymphocytes (1.8/nl; normal range 0.5–1.2/nl). The MRI showed an enhancement in both trigeminal nerves and, additionally, three parenchymal lesions with no indication for meningiosis carcinomatosa or pituitary enlargement. Because of suspected ipilimumab-induced granulomatous disease high dose steroids were initiated and quickly improved symptoms. Brain lesions disappeared in a subsequent MRI and symptoms completely resolved.


A 65-year old male patient with primary skin melanoma without brain metastases or thyroid disease received ipilimumab (3 mg/kg body weight) due to progressive metastatic melanoma. Eighteen weeks after the first dose of ipilimumab, the patient presented with acute onset of strong pain above his right eye that radiated to the paranasal sinus, epiphora and double vision. In addition, dizziness and nausea was reported. The ophthalmologist recorded a mydriasis of the right pupil and a ptosis with paresis of the oculomotorius nerve leading to limited mobility and inability to completely open the right eye, compatible with a Tolosa-Hunt-Syndrome. Brain MRI revealed a markedly prominent neural sheath of the right optic nerve, no alteration in the cavernous sinus and no metastases. Except for a stable anemia and an increased CRP (54 mg/l, normal range <5 mg/l), laboratory values were within normal range with normal TSH and negative thyroid autoantibodies. Interestingly, an unclear FDG-enhancement in the left thyroidal lobe had been previously detected by FDG-PET/CT. High-dose steroids (initially i.v. methylprednisolone and subsequently oral dexamethasone) and local radiotherapy (10×3 Gray) was simultaneously started. This treatment combination markedly and promptly reduced the ocular pain and paresis but showed only little impact on the vision disturbances. Staging showed progressive disease with new liver metastases.


A 52-year old female with melanoma metastases affecting lymph nodes, soft tissue, liver, and bones (sacral vertebra, 2 ribs and temporal bone) presented with nausea, vomiting, chills and rash, three weeks after the first ipilimumab infusion. Therapy included rehydration, antiemetics, novaminsulfon and topical steroids. One week later, she presented with agitation, disorientation, aggressive behaviour and the inability to make contact with other people. Since she was screaming and physically attacking the physicians, a blood draw required four people holding the patient in addition to sedation with esketamin (50 mg) and midazolam (15 mg). Body temperatures had risen to 39°C but no signs of meningism were observed. Treatment with i.v. ceftriaxon, ampicillin as well as acyclovir and dexamethasone was initiated. Liquor analyses revealed mostly lymphomonocytic cells (mainly CD3-positive lymphocytes) and excluded a meningiosis neoplastica or herpes simplex infection. Brain MRI showed four new brain metastases (<1 cm in diameter each) and an accentuation of the temporal bone metastasis. After electroencephalography (EEG), transcranial ultrasound, and repeated liquor examinations, an aseptic ipilimumab-induced meningitis was suspected. Ipilimumab treatment was permanently discontinued and symptoms resolved completely. Unfortunately, the patient demonstrated disease progression despite subsequent gamma knife and fotemustine treatment.
Physicians should be aware that neurologic symptoms can exacerbate unexpectedly at any time. The patient described above would have died of meningitis if no relatives would have been around. Importantly, it has been reported that prior therapy with neurotoxic agents may increase the risk of neurological-related adverse reactions , however, these findings are not confirmed in our study population.


A 66-year old male patient presented with progressive left-sided iliac lymph node metastases and bulky tumor growth on the left-sided abdomen, the groin and left thigh despite lymph node dissection, hyperthermal limb perfusion, dacarbazine monochemotherapy, polychemotherapy with temozolomide, vindesine and cisplatin and fotemustine. In addition, arterial and venous compression, infiltration and thrombosis led to a massive increase of the pre-existing lymph edema of the left leg. An attempt of brachytherapy failed. Upon the second treatment with ipilimumab, the patient reported a considerable reduction of the tumor mass and lymph edema. At this time, the tumor bulk on the left-sided abdomen showed two ulcerations with minimal foetid secretion (). Four weeks later, tumor infiltration and lymph edema of the left leg were nearly resolved. Both ulcerations were still present and sore. Abdominal examination revealed a ballottement and a highly inflammatory induration of the entire lower abdominal wall. No hyperphosphatemia, hyperkalemia, hyperuricemia or hypocalcemia were observed. An ultrasound-guided tumor incision on the right side of the abdomen released approximately 400 ml of a liquefied, partially necrotic and putrefied tumor bulk. Further CT-controlled drainage of the abdominal mass did not result in any improvement and the patient unfortunately died shortly after the third treatment despite antiseptic treatment including broad spectrum antibiotics, presumably as a consequence of septicaemia.
This case illustrates ipilimumab’s potential to induce strong antitumor immune responses with rapid and sustained tumor destruction (). Tumor destruction releases antigens, including non-self antigens as well as endogenous danger signals, which trigger inflammation, cytokine release and the infiltration of immune cells in the tumor-affected organs. Extended inflammation, tumor destruction and necrosis may induce multi-organ failure similar to a tumor lysis syndrome.


A 68-year-old white male with a history of hypertension, gastroesophageal reflux disease, and congestive heart failure was found by his son lying on the floor of his home. The son activated the EMS system, and the paramedics found the patient with altered mentation, responsive to pain and mumbling. The patient was incontinent of feces and urine. The son last spoke to the patient two days earlier and reports that he was in his normal health. The patient's history included depression, benzodiazepine dependence, and anxiety disorder. The patient's daily medications included furosemide 40 mg, isosorbide dinitrate 30 mg, lisinopril 20 mg, and atorvastatin 10 mg. The patient was known to ingest large amounts of over-the-counter antacids and baking soda mixed with water for indigestion. His social history was significant for tobacco and alcohol.
Upon arrival to the emergency department (ED) the patient's blood pressure was 218/111, the cardiac monitoring showed sinus tachycardia at 127/minute, a rectal temperature 98.6°F was measured, the room air SPO2 was 94%, and respirations were 16/minute. The patient was able to follow simple commands. He opened his eyes to voice and moved his extremities, including pulling his EKG wires. The patient had pale skin, lateral nystagmus, and signs of poor hygiene. The remainder of the physical exam was unremarkable except for abdominal pain, nausea, vomiting, or generalized pain. The patient was given labetalol 10 mg for hypertension and aggressive intravenous fluid hydration and IV folic acid, magnesium sulfate, multivitamin, and thiamine.
Significant laboratory results included calcium of 18.7 mg/dL, bicarbonate 45 mmol/L, BUN 55 mg/dL, creatinine 4.5 mg/dL, chloride 83 mmol/L, and WBC 22.46 K/cumm. Arterial blood gas revealed a pH of 7.54, pCO2 of 58 mmHg, and pO2 of 60 mmHg. Parathyroid hormone was undetectable (normal range is 14–72). Liver function tests, coagulation studies, and lipase were normal. EKG showed sinus tachycardia and head CT showed no acute changes.
The patient was admitted to the intensive care unit with a BP of 184/116, pulse 88/min, and respirations of 16/min. A chest X-ray showed infiltrates, concerning for pneumonia. The patient was placed on a nitroglycerin drip to control his blood pressure, antibiotics for presumed infection, IV fluids and a bisphosphonate for hypercalcemia, and risperidol for signs of delirium.
The patient was admitted for a total of 16 days. Upon discharge the patient's mental status had returned to nearly normal, the patient was found to have an underlying dementia not previously diagnosed. The discharge blood values showed calcium 8.5 mg/dL, bicarbonate 21 mmol/L, BUN 19.0 mg/dL, creatinine 1.4 mg/dL, and WBC 10 K/cumm. demonstrates the progressive resolution of the patient's metabolic alkalosis, hypercalcemia, and renal failure throughout this hospital course. The patient was placed on Protonix for reflux, given instruction to avoid antacid use and to follow up with the internal medicine clinic.


Patient FC, African descent, 26 years old, male, HIV+, exposure category man who have sex with men (MSM), last CD4 cell counts 67 cells/mm3, virological status 5000 copies/mm3, came to the Center for Study and Care of Special Patients(CEAPE), School of Dentistry, Paulista University(UNIP), SP, Brazil, with minor RAU in the upper () and lower right side lip, measuring about 5 mm, and major RAU in tongue and the tonsillar pillar () measuring 2 cm. Reported pain at the site of ulcers and difficulty in eating (swallowing). The patient is HIV positive since 2008 and makes use of antiretroviral therapy (HAART): tenofovir, Kaletra, and 3TC. He reported symptoms of night sweats, diarrhea, fever, arthralgia, myalgia, and weight loss. Due to the medication already used by the patient and the condition of lesions, was advocated as the treatment of RAU the use of a diodo laser Gallium Aluminum Arsenide (GaAlAs) with a wavelength of 660 nm and with a spot size of 0.07 cm² (), the laser therapy was released with a power of 0.03 W, a fluence rate of 0.428 W/cm², in continuous mode and irradiation of 4 Joules each point for 2 minutes and 13 seconds and energy Fuency of 57.14 J/cm², being two points per lesion according to their size []. The objective was to help reverse the damage and decrease the symptoms. After one week there was remission of the lesions and the patient reported decrease in the pain (Figures , , and ). In the 12-month followup the patient was reported as not having the ulcer that he presented in this case.
The case report was approved by the Ethics Committee of Paulista University (643/09), and the patient has signed the informed consent.


A 7-year-old boy was referred to our hospital with complaints of abdominal discomfort and high fever. Four days before admission, the patient complained of uneasiness and sneezing and was afebrile. On the following day, the patient complained of increasing abdominal pain and appetite loss. One day before admission, the symptoms worsened and the patient’s temperature rose to 39.1°C. There was no history of recurrent diarrhoea, malnutrition or failure to thrive. On admission, the white blood cell count remained within normal limits, but C-reactive protein was elevated to a concentration of 3.6 mg/dL. An abdominal ultrasound revealed a mildly swollen appendix. In addition, a few mildly swollen lymph nodes, up to 10 mm in diameter, were seen in the mesentery. A diagnosis of acute appendicitis was made and appendectomy was performed on the second day of hospitalisation.


Our patient was a 70-year-old white Anatolian Turkish woman with primary school education who had been living alone for the past five years. She presented to our Psychiatry Department complaining of ‘feeling large worms moving in her body’. The complaint had been present for the past six months and started after she presented to an internist with complaints of weight loss, bilateral fine tremor of the upper extremities, shaking, sweating, palpitations and intolerance to heat. After the evaluation, she was hospitalized for a diagnostic work-up in our Endocrinology Department with a preliminary diagnosis of hyperthyroidism. Restlessness, increased speech and the feeling of ‘large worms migrating through her body’ were observed on the second day of hospitalization.
After psychiatric consultation, our patient was diagnosed with a psychotic disorder due to a general medical condition (hyperthyroidism). She was started on 2mg/day of haloperidol. This treatment was chosen because of the preliminary nature of the diagnosis and because our patient may have had delirium. Thyroid ultrasonography revealed five nodules measuring 2mm to 5mm in the left lobe and a heterogeneous nodule measuring 5mm to 10mm in the right lobe. None of the nodules displayed microcalcification, solidity or a reduced echogenicity pattern. The solitary nodule in the right lobe displayed an irregular contour. Lymphadenopathy and invasion of the neighboring structures were not noted. Scintigraphy revealed that all of the nodules were hyperfunctioning. She had no history of exposure to ionizing or environmental toxins, and no personal or family history of multiple endocrine neoplasia. A fine needle aspiration biopsy ruled out malignancy. The level of antibody to thyroid stimulating hormone receptor was found to be 2.5IU/L, thereby confirming Graves' disease.
As a result of the surgical consultation, medical follow-up was advised. On the third day, propylthiouracil 150mg/day and propranolol 30mg/day were started and the doses were maintained at 100mg/day and 40mg/day, respectively, after the first week. Restlessness, increased speech and DP remitted on the 10th day of treatment and haloperidol was stopped. She was discharged on the 20th day with a prescription of levothyroxine sodium 100μg/day (weight, 59kg; dose, 1.7μg/kg/day). A fortnight after discharge, she started to feel the worms. After presenting to the Departments of Dermatology, Microbiology and Infectious Diseases, Endocrinology, and Neurology, she was referred to the Department of Psychiatry and hospitalized. Her past medical and psychiatric histories were negative for pathology and her family history did not reveal evidence of psychopathology. She was teetotal and she was receiving no drugs or supplements at the time of evaluation other than levothyroxine sodium. She had no history of drug use or abuse and an inpatient follow-up lasting a month did not reveal any signs or symptoms of withdrawal.
At the baseline examination, she was noted to be cooperative and have reduced self-grooming. Her speech was fluent although restricted to the topic of tapeworms. Her mood and affect were anxious. She was orientated to people, space and time. Her attention, concentration and memory were within normal limits. She reported tactile hallucinations. Her judgment, reality testing and abstract thinking were impaired and her thought process was perseverative and circumferential. Her thought content was positive for somatic delusions. Motor retardation was observed while sleep and appetite were normal. Assessment with the Positive and Negative Syndrome Scale and Mini Mental State Examination revealed scores of 82 (positive: 19; negative: 18; general psychopathology: 45) and 28, respectively.
Laboratory examinations including levels of vitamin B12, folate and ferritin, the Venereal Disease Research Laboratory test, and a toxicology screen were within normal limits other than elevated thyroid function tests (our patient was noncompliant with her levothyroxine treatment, Table
). After an endocrinology consultation, it was advised that she be followed without medication for a month; thereafter, levothyroxine sodium 100μg/day was restarted. Consultations from the departments of Internal Medicine, Neurology, Hematology and Oncology ruled out the presence of an organic disorder. Electroencephalography and cranial magnetic resonance imaging were normal. Therefore our patient was diagnosed as having DP, presumably secondary to the hyperthyroidism. A baseline electrocardiogram (ECG) demonstrated a corrected QT interval (QTc) duration of 450ms. Previous ECGs revealed that her QTc duration varied between 440ms and 490ms. Therefore, psychiatric treatment was initiated with pimozide 2mg/day and later the dose was titrated to 4mg/day. At the eighth week of treatment her thyroid function tests returned to normal limits along with a remission of the delusions. The QTc duration at this time was measured as 470ms. Our patient was discharged from the hospital and followed-up at the outpatient department. Her thyroid levels remained normal for a year and she was free of psychiatric symptoms. Therefore, pimozide was titrated down to 2mg/day. After 15 months her thyroid hormone levels increased again due to an irregular use of medication. Consequently, she began to feel the tapeworms again.
Her complaints disappeared when her anti-thyroid medication was reinstituted. After 20 months of follow-up the pimozide was stopped and she was followed without antipsychotic treatment for an additional nine months. At her last examination she was euthyroid, not receiving antipsychotics and having no delusions.


A 55 year old male former bus driver with a history of deafness was referred to Neurology with a 4-year history of falls, speech disturbance and weight loss. His only medication was Gliclazide for diabetes mellitus that had been diagnosed two years previously. He had bilateral sensorineural deafness for 15 years prior to his neurological presentation for which no explanation had been given, but hearing aids were of benefit. He neither smoked nor drank alcohol. He was unaware of any family history of a similar disorder.
Examination revealed macroglossia (A) with associated dysarthria, bilateral hearing aids and bilateral pes cavus. He had a prominent dorsocervical fat pad (B) and a lipoma on his posterior right thigh with an otherwise thin habitus. Muscle bulk was reduced but without focal wasting or fasciculation. Tone was normal but there was a global mild reduction in power, most marked proximally. Reflexes were suppressed in both upper and lower limbs and plantar responses were flexor. Sensory testing revealed reduced dorsal column sensation at the toes and ankles. He had dysmetria of upper and lower limbs with a broad based gait. He was unable to perform a tandem gait. Romberg's testing was normal.
Routine blood tests were unremarkable. Cranial MR imaging showed generalised brain atrophy and fatty infiltration of the tongue (C). CSF was acellular with normal protein and glucose but a raised CSF lactate of 3.7 mmol/L (normal range, 1.1–2.4 mmol/L). Very long chain fatty acids, plasma (including CK) and white cell enzymes were all normal.
Neurophysiology revealed active denervation in all muscles in the lower limbs and the right bicep. Those muscles not showing active denervation demonstrated significantly reduced recruitment. There were no changes to support a myopathic or a large fibre neuropathic process. A tongue biopsy failed to show any evidence of amyloidosis but confirmed fatty infiltration consistent with a lipoma. A clinical diagnosis of mitochondrial disease was made on the basis of a multisystem disorder involving diabetes, deafness, myopathy, ataxia, mid-line lipomata and raised CSF lactate. A right tibialis muscle biopsy was performed under local anaesthetic.


A 56-years-old woman was admitted at our neuroscience department complaining a recent slight diplopia and persistent headache which had arisen about five-six months before, initially NSAID responsive, that was progressively increasingly. A first medical examination showed peripheral right facial nerve and right abducent nerve paralysis. At the examination, vital signs and blood parameters were normal. No other neurological signs were detected.
A CT brain scan was performed with reconstruction in 2D MPR and VR that showed a presence of a giant expansive lesion on the right side of posterior cranial fossa ().
The lesion developed from the posterior cranial fossa toward foramen magnum () till middle fossa, causing a compression of right temporal lobe, that was displaced upwards and laterally, and a more serious compression of brainstem that was displaced on the left side.
A cerebellar vermis on the IV ventricle was displaced too () causing hydrocephalous.
Volume rendering and MPR images showed massive erosion of the right petrous apex and great wing of sphenoid, followed the diameter increasing of right inferior orbital foramen.
The densitometric difference evidenced during the examination showed an a cranial area iso-hypodense (−10/−5 HU) and a hypodense caudal area (−50/−60 HU) that seemed like a fat component.
CT scan showed, moreover, a different marked hypodense lesions (−150/−180 HU) spreading over supratentorial cisternal and cortical spaces (Figures and ).
To reach a more comprehensive view about the lesion and its relationship with the intracranial circulation, an MR scan was performed.
The FSE T2-weighted, FLAIR, EPI, 3D T1-fat suppression, and 3D T1-enhancement sequences were performed on the three orthogonal planes.
Moreover evaluation of intracranial circulation was assessed trough the acquisition of 3D-TOF, used for post-processing images like 3D-MIP and 2D-MPR.
The lesion caudal area appeared homogeneously hyperintense (Figures and ) and heterogeneously hyper/hypointense signal in the cranial area both in SE T1-w, FSE T2-w and in FLAIR sequences.
The dark signal in the lesion was suggestive for hemosiderin presence linked by previous bleeding (Figures and ). After intravenous administration of 12 mL of Gadolinium-DTPA, lesion didnot show contrast enhancement.
The other multiple hyperintense areas in T2-w and T1-w images (linkable with fatty droplets) appeared spreading to the supratentorial cisternal and cortical spaces (from cerebral base to convexity); after contrast administration no enhancement was showed. (Figures , , , and ).
In 3D-TOF sequences, we have found abnormal course of the basilar artery dislocated and stretched toward the left side, the right posterior cerebral artery that was raised and lengthened and the right posterior communicant artery that appeared extremely stretched.
The careful analysis of the acquired data provides the clue of the primary disorder: a giant dermoid cyst.
The patient underwent partial resection of the lesion with transtemporal approach whose aim was to reduce mass effect on the brainstem and right temporal bone.
During the surgery, many hair and some bone fragments escaped confirmed its origin.
By the way material was collected to perform the histological investigation which, at the last, confirmed the dysembryogenic nature of the lesion. ().