A 21-year-old female patient was submitted to programmed palatine tonsillectomy with diagnosis of relapsing peritonsillar abscess. Preoperative workup including chest radiography and electrocardiography was normal. She went on surgery under general anesthesia with orotracheal intubation. Standard surgical technique was used, and dissection of palatine tonsil was performed on the subcapsular plane to avoid excessive trauma. Hemostasis was performed by means of bipolar electrocoagulation. The surgical procedure progressed uneventfully, with minimal bleeding, but the dissection was difficult because of the adhesion of the tonsils to the tonsillar bed. The patient recovered from anesthesia well, using oxygen mask for a while.
During the first postoperative hours, the patient presented cough and had an episode of emesis. Later, in the afternoon of the same day, the patient complained of pain in the right submandibular area. A physical examination revealed right mild, painless swelling of the right submandibular area. Inspection of the oral cavity did not evidence any bleeding from the tonsillar beds or the presence of any mucosal tear. No signs of airway or ventilator distress were evident. The patient was administered analgesics and food intake was forbidden. However, during a few hours further swelling was noticed, extending upwards to the right facial area and downwards to the lateral right cervical area. On palpitation the swelling was soft and painless, but characteristic crepitus was evident.
A neck and chest X-ray revealed subcutaneous cervical emphysema () and a computed tomography scan of the neck () confirmed the diagnosis. A chest computed tomography performed simultaneously showed the presence of pneumomediastinum (Figures and ). Since the patient did not present with respiratory distress and hemodynamically was stable, conservative management was decided. A combination of broad-spectrum antibiotics was administered and the patient was restricted to bed rest and instructed to refrain from coughing. Further course was uneventful, the subcutaneous emphysema decreased substantially, and a new chest plain radiography showed absence of air. The patient was discharged a week after surgery and follow-up examinations did not reveal any abnormal findings.


A 76-year-old male with a past history of traumatic epilepsy presented to Shiga University of Medical Science Hospital (Otsu, Japan) with fever and fatigue. Physical examination revealed jaundice in the patient’s bulbar conjunctiva and no superficial lymph nodes were palpable. The patient did not describe symptoms of acrocyanosis. Laboratory tests demonstrated marked anemia and elevation of total bilirubin and lactate dehydrogenase (hemoglobin, 7.4 g/dl; mean cell volume, 90 fl; white blood cell count, 5.3×109/l; lymphocytes, 2.3×109/l; lactate dehydrogenase, 558 IU/l; bilirubin, 131.7 μmol/l; and soluble interleukin-2 receptor, 1,220 U/ml). Systemic surveillance by imaging studies failed to detect any tumorous lesions, lymphadenopathy or hepatosplenomegaly.
The direct antiglobulin test was positive, with anti-C3d specificity. Anti-IgG was negative and indirect antiglobulin test was also positive. Cold agglutinins were present with a titer of 8,192 at 4°C and <1 at 37°C. Bone marrow aspiration and biopsy were performed.
Subsequently, R-THP-COP (rituximab, 375 mg/m2; pirarubicin, 40 mg/m2; vincristine, 0.8 mg/m2; cyclophosphamide, 650 mg/m2; and prednisolone, 40 mg/m2) therapy was performed. Following six cycles of R-THP-COP therapy, the cold agglutinin titer was markedly decreased (by <4), and bilirubin (15.6 μmol/l) and lactate dehydrogenase (186 IU/l) levels were also reduced. Bone marrow aspiration revealed no neoplastic lymphocytes. Following 19 months of the initial chemotherapy, malignant lymphoma relapsed. Cold agglutinins were present again with a titer of 4,096 at 4°C. The patient ultimately succumbed to the disease.
The formalin-fixed, paraffin-embedded tissue blocks were sectioned (3-μm-thick), deparaffinized and rehydrated. Each section was stained with hematoxylin and eosin and used for immunostaining. Immunohistochemical analyses were performed using an autostainer (Benchmark XT system; Ventana Medical Systems, Inc., Tucson, AZ, USA) according to the manufacturer’s instructions. The following primary antibodies were used: Mouse monoclonal antibodies against bcl-2 (bcl-2/100/D5), bcl-6 (P1F6), CD3 (PS1), CD5 (4C7), CD10 (56C6), CD20 (L26) (all Novocastra Laboratories, Ltd., Newcastle upon Tyne, UK), CD138 (B-A38; Cell Marque Corp., Rocklin, CA, USA) and MUM-1 (MUM1p; DakoCytomation, Glostrup, Denmark), as well as rabbit monoclonal antibody against cyclin D1 (SP4; Nichirei Biosciences Inc., Tokyo, Japan).
Bone marrow aspiration and biopsy revealed hypercellularity with proliferation of large-sized lymphoid cells containing irregular-shaped large nuclei with conspicuous nucleoli (). No bone trabeculae destruction was noted and no lymphoma cells were detected in the peripheral blood.
Lymphoid cells in the bone marrow were positive for CD20, bcl-2, bcl-6 and MUM1 (), but negative for CD3, CD5, CD10, CD138 and cyclin D1. According to these results, an ultimate diagnosis of primary bone marrow DLBCL accompanying CAD was concluded.


A 58-year-old woman, with a prior thyroid cancer history about 13 years ago, detected a firm nodular lesion in the periareolar region of her right breast self-examination.
Subsequently mammography and echographic studies were performed.
Mammographic imaging (Figures and ) showed a thickening with microcalcifications in the periareolar region of the right breast, while echographic study () highlighted, in the same area, some nodular lesions.
A fine needle aspiration cytology was performed but it was unsatisfactory for diagnosis because of inadequate material.
The patient underwent a surgical biopsy with wide excision of the lesion: the specimen () was a 5 × 5 × 2 cm mammary tissue with a 3 × 1 cm overlying skin ellipse. On cut section an irregular whitish nodule of about 3 cm of diameter was found with a 8 mm small pseudocyst area.
On microscopic examination the tumour showed a solid arrangement composed of cells with microglandular and microacinar features (Figures and ).
The cyst-like area was composed of highly pleomorphic cells with high mitotic count and apoptotic bodies, arranged in solid nests with a central comedo-type necrosis (); in the microacinar areas glandular structures with central lumina () interspersed within fat or fibrous septa could be seen. The central lumina contained an eosinophilic, colloid-like, PAS positive, and diastase-resistant secretory material ().
The cells appeared to have abundant eosinophilic cytoplasm and round nuclei with prominent nucleoli. At high power examination, the tumour cells focally showed a cytoplasm engulfed by eosinophilic granules (), appearing PAS positive and thus reminiscent of Paneth cells.
Microcalcifications were also observed within the tumour.
Glandular structures were devoid of myoepithelial basal layer such as evidenced by negative immunostaining for CD10, actin, and CK5/6.
Neoplastic cells showed immunoreaction for EMA (), CK7, E-cadherin, S100 (), α-1-antitrypsin (), lysozyme (), and amylase (). NSE, chromogranin, synaptophysin, androgen receptor, estrogen receptor, Her-2, TTF-1, and thyroglobulin were negative. GCDFP-15 resulted to be focally positive in the microacinar areas as well as progesterone receptor (). CD56 stained only the solid areas.
At the periphery of the tumor typical and atypical MGA was observed, it gradually merged into the ACC ().
Based on the morphological and immunohistochemical findings a diagnosis of salivary gland-like tumour of the breast with features of ACC arising in MGA was made.
An ultrastructural study was performed on formalin fixed paraffin embedded tissue: it showed variable sized electron dense cytoplasmatic granules ().
Since the tumour involved the surgical margins, surgeons performed a re-excision that showed some further focal areas of MGA. A sentinel node biopsy was also performed and the lymph node was negative for neoplastic deposits.
Moreover, the slides of the previous thyroid cancer were reviewed confirming a diagnosis of anaplastic thyroid cancer though were observed some areas with a differentiated follicular pattern containing a colloid-like eosinophilic secretion.


The proband is an Italian 9-years-old boy, offspring to first cousins, with an older and healthy sister. We followed this patient since the age of 2 years. He was born at 40 weeks after an uneventful pregnancy and delivery. During the first months of life, the child presented hypertonus and eye rolling movements. Afterwards, a severe delay of psychomotor development became apparent, characterized by legs hypertonia, axial hypotonia, dyskinetic movements and myoclonic jerks of the arms and the head, no eye contact, and uncoordinated eye movements. The first epileptic seizure occurred at 5 months without fever, characterized by salivation, loss of contact and clonic jerks on the left side of the body. The first seizure lasted 20 minutes and the interictal EEG showed slow waves on the left occipital regions. Over time, several seizure types occurred, characterized by: a) left eye and head deviation with clonic jerks on the left side of the body; b) generalized hypertonia, loss of contact, uncoordinated movements of eye and limbs, cyanosis, and facial and arms twitching; or c) loss of contact, generalized hypotonia and clonic jerks, and tachycardia or bradychardia. Occasionally, at the end of the ictal event, dyskinetic (particularly choreiform) movements of the limbs appeared, without recovery of consciousness. The seizures, with or without fever, could be prolonged (20–30 minutes) and were frequently followed by sleep. Between seizures, the child always showed head tonic extension, erratic limb movements and tremor. The interictal EEG showed multifocal spikes over the right centro-temporal and the left parieto-occipital regions.
At three years of age, absences with eye up deviation and eyelid myoclonus appeared (). The other seizure types persisted, although reduced in frequency. Seizures were resistant to many drugs (phenobarbital, benzodiazepine, valproic acid, levetiracetam, lamotrigine); absences frequency was improved by ethosuximide. The EEG recordings showed slowing background activity, multifocal, diffuse paroxysmal abnormalities, and a transitory photosensitivity.
Clinical examination showed dysmorphisms(bilateral epicanthus, arched palate, pronounced Cupid’s bow, narrow naris, clinodactyly of the IV and V fingers) and head circumferences between 3 and 10 percentiles. Neurologic examination showed oculo-motor apraxia, strabismus, nystagmus, axial and leg hypertonia, head tonic extension, erratic limb movements, tremor and brisk symmetric reflexes. At the most recent follow-up, it was substantially unchanged, and the child had two types of seizures: very brief absences during wakefulness and tonic-clonic seizures during sleep, which were prevalent on the left side. Laboratory investigations showed hyperglycaemia, and glicosuria. Genetic (high resolution karyotype, analysis for Angelman and Dravet syndromes) and metabolic investigations (urine organic acids, amino acids, isoelectric focusing of transferrins), including those for mitochondrial pathology, were all negative. The ECG and cardiac examination were normal. Brain MRI was remarkable for cerebellar atrophy ().


The patient is a 36-year-old woman who was admitted to the hospital complaining of a dull ache in the right inguinal area. On physical examination a firm mass was palpated in that area. Imaging with ultrasound (U/S) scan examination revealed a solid mass measuring 3 × 2 cm (). Fine needle aspiration of the mass was inconclusive and complete surgical excision was decided. During surgery it was noted that the tumor was attached to the wall of the greater saphenous vein, and it was removed en bloc with a small part of the vein. The resected specimen was submitted for pathologic evaluation. Grossly the specimen consisted of a firm, well-circumscribed, oval shaped mass measuring 4 × 2 × 1.5 cm. Its cut surface was white in colour and had a whorling pattern reminiscent of leiomyoma. Microscopic examination confirmed the gross impression and proved it to be a smooth muscle tumor (). The diagnosis was also confirmed with immunohistochemical stains (desmin +, SMA +, and S-100 protein −) (). The tumor also had no areas of necrosis. Its cellularity was moderate and there was no significant nuclear atypia. The mitotic activity was low (up to 1 mitotic figure/40 HPF) and the proliferation index Ki-67 was also low (approximately 1%). Morphologically this tumor was a leiomyoma. The patient was discharged on the first postoperative day.


A 51-year-old woman presented with acute onset of chest pain, coughing, and dyspnea. Blood pressure was elevated. She reported many years of cigarette smoking as a cardiovascular risk factor. White blood cell count was elevated with 13.22 G/l (normal: 4.4–11.3 G/l); Fibrinogen (724 mg/dL, normal: 210–400 mg/dL) and CRP were increased (237.6 mg/dL, normal: <8.0 mg/dL). Nonenhanced computed tomography (CT) () depicted a semicircular, hyperdense vessel wall thickening, extending from right after the left subclavian artery's origin to the iliac arteries. CT-angiography (CTA) showed a small intramural contrast medium deposit in the proximal descending aorta () as in a penetrating atherosclerotic ulcer of the aorta (PAU).
A primarily conservative therapy, that is, analgesic, antihypertensive, anti-inflammatory, and antibacterial medication, did not improve the patient's symptoms: chest pain persisted while the general condition of the patient deteriorated rapidly. On day four an interdisciplinary committee decided to perform an endovascular therapy, during which a Valiant aortic stent graft (type TF 30-30-C-150, Medtronic, Fridley/MN, USA) was implanted proximal to the left subclavian artery, close to the left common carotid artery (). Adequate cerebral perfusion was granted via the right vertebral artery which had previously been verified in MR angiography. After endovascular therapy, the patient fully recovered and was discharged 11 days after intervention with well-controlled blood pressure.
Three weeks after endovascular therapy, the patient presented with back pain and increased blood pressure. CTA depicted a newly developed circumscribed dissection of the thoracoabdominal aorta which extended almost to the celiac trunk () with broad communication between true and false lumina (). Stent graft patency and location were optimal, and intramural hematoma was resorbed almost completely (). Despite the blood pressure had been normalized due to adapted antihypertensive medication, the whole aortic lumen diameter at the dissection site proximal to the celiac trunk increased by 1 cm (from 3.5 cm to 4.5 cm). Therefore, two months after primary intervention two overlapping Jotec E vita stent grafts (33 × 150 mm) were implanted coaxially in order to extend the primary stent graft into the abdomen. The membrane of the distal stent graft ended immediately proximal to the origin of the celiac trunk, completely covering the dissection site (Figures –). The bare end overlapped the celiac trunk to improve fixation in the healthy vessel wall. Spinal CSF pressure was normal during and after the procedure. After coaxial distal extension of the stent graft the patient recovered rapidly. No thoracic/abdominal pain, neurological symptoms or arm claudication were reported. The patient presented free of symptoms, after 3 years and 7 months. CTA showed an excellent outcome without any signs of recurrence ().


A 52-year-old Caucasian male presented with tinnitus and fullness in left ear for one day. He complained of dizziness but denied any hearing loss or earache. He reported a 10 pound weight loss over the last three months. He also complained of occasional night sweats and progressively worsening lethargy for six months prior to hospitalization.
Physical examination revealed an average sized male with no acute distress. Vital signs were within normal limits. There was no lymph node enlargement in neck, supraclavicular fossa, axillary, inguinal, and femoral regions. Both liver and spleen were enlarged on percussion, measuring 14.8 cm and 8.0 cm, respectively. Cranial nerves 2–12 were intact and motor strength was equal in all four extremities. Bilateral external auditory canal and tympanic membrane were assessed to be normal. No nystagmus was detected.
Workup revealed a hemoglobin count of 9.1 g/dL, white blood cell count of 685 × 103/μL, and a platelet count of 164 × 103/μL. Peripheral smear showed a marked increase in the granulocyte series and myeloid precursors with some blast cells, promyelocytes, myelocytes, and metamyelocytes ().
Further workup revealed an elevated lactate dehydrogenase level of 1025 U/L (suggestive of excessive myeloid proliferation), uric acid level of 9.8 mg/dL, and leukocyte alkaline phosphatase level of zero.
The initial impression was chronic myelogenous leukemia (CML) with hyperleukocytosis. A bone marrow aspiration and biopsy were performed. Although the patient tolerated biopsy well, he continued to bleed excessively from the biopsy site. He was started on hydration, hydroxyurea (1 gm thrice a day), and allopurinol (300 mg twice a day). His urine was alkalinized with intravenous bicarbonate. On day two of hospitalization, the patient's white blood cell count dropped to 646 × 103/μL, and his uric acid was down to 5.8 mg/dL.
Next day, patient developed sudden slurred speech along with shaking movements involving all extremities. Cranial magnetic resonance imaging revealed multiple hemorrhages throughout the brain, with most prominent hemorrhage in left peri-insular region (). Cranial magnetic resonance angiogram showed no significant stenosis or aneurysm. Since the white blood cell count was still very elevated (525 × 103/μL), we decided to increase the dose of hydroxyurea (2 gm four times a day). Repeat blood work showed an international normalized ratio of 1.60 (prothrombin time (PT): 19.5 sec and activated PTT 34.2 sec).
Bone marrow biopsy results revealed a hyper cellular marrow (>95% cellularity), increased myeloid cells in all maturation stages, M : E ratio of >10 : 1, and blasts of 9% (). The fluorescence in situ hybridization (FISH) technique was positive for BCR-ABL fusion gene. This confirmed the diagnosis of CML (chronic phase), and we decided to start the patient on nilotinib. Hydroxyurea was continued until insurance coverage for nilotinib was approved.
On day nine of hospitalization, patient developed sudden bilateral hearing loss. Physical examination was compatible with sensorineural deafness. Patient's white blood cell count had dropped to 62.9 × 103/μL and platelet count was 133 × 103/μL. Repeat magnetic resonance imaging revealed multiple new hemorrhages throughout the brain (). Computer tomography of the temporal bones showed marked inflammatory changes in right mastoid cells and mild inflammatory changes in left mastoid cells. However, bilateral auditory canal, semicircular canals, middle ear cavity, and cochlea appeared to be normal (). Repeat international normalized ratio was 1.39 (PT: 21 sec and activated PTT: 32.4 sec). Patient also developed a rash on his face and arms which was thought to be secondary to allopurinol. Since patient's white blood cell count had dropped to 62.9 × 103/μL, we decided to stop the allopurinol.
Patient's white blood cell count continued to decrease. Hepatosplenomegaly was resolving but there was no improvement in hearing. Nilotinib was started on day eleven of hospitalization. On the following day, patient's white blood cell count dropped to 4170/μL, so we decided to hold the hydroxyurea. On day fourteen of hospitalization patent's white blood cell count further dropped to 890/μL. Nilotinib was held and patient was started on filgrastim.
Although, the blood counts started improving, there was no improvement in hearing (). Patient was discharged from the hospital and was asked to follow up, in order to restart nilotinib once his counts stabilized. Four months later, the patient continued to have bilateral sensorineural deafness and was treated with bilateral transmastoid cochlear implants. Six months later, a repeat bone marrow biopsy showed no evidence of residual CML


A 38-year-old woman was referred for evaluation to the outpatient otorhinolaryngology clinic by the neurology department. The patient complained of intermittent episodes of moderate, nonthrobbing, and severe pressure-like headache since early adulthood. The headache was typically located at the anterior part of the cranium, mainly over the frontal, the anterior parietal, and temporal area. The symptoms usually lasted for hours and were sufficiently relieved by common analgesics such as paracetamol and nonsteroid anti-inflammatory drugs. The pain was not accompanied by facial swelling and was not related to head position (bending forward, lying down, or sitting up). Palpation of the face and anterior cranium did not reproduce the symptoms and no palpable or visually evident anatomic deformity was noted.
Neurologic and ophthalmologic examinations were unremarkable. Routine laboratory parameters were within normal range. Nasal endoscopic examination did not reveal pathologic findings. The nasal septum was slightly deviated while the maxillary and sphenoid ostia appeared patent. Although the frontal sinus ostium could not be visualized endoscopically on either side, no mucosal abnormalities were apparent at the area of the frontal sinus outflow tract.
A high resolution CT scan revealed that all the paranasal sinuses and especially the frontal sinuses were excessively enlarged. Similarly, the mastoid air cells showed bilaterally excessive pneumatization. No signs of bony erosion or thinning were evident in the CT scan. The frontal sinus extended posteriorly and laterally, encroaching the ophthalmic bulb. The frontal lobe appeared to be smaller in size, due to the posterior enlargement of the frontal sinus. No other abnormalities were found, apart from a retention cyst in the right maxillary sinus (Figures –).
Measurements of the linear dimensions of the frontal sinuses were performed according to the procedure described by Tatlisumak et al. []. The width, height, and anteroposterior length of each frontal sinus and the total width of both sinuses were calculated (Figures and ).
Volumes of the frontal, sphenoid and maxillary sinuses, and mastoid air cells were calculated according to the method used by Karakas and Kavakli [] and Pondé et al. []. The area of each sinus was measured in every axial CT image () and multiplied by the slice thickness. The sum of all measurements was equal to the volume of the sinus.
The type of extensive maxillary sinus pneumatization (EMSP) was determined according to the classification of Kalavagunta and Reddy [] comparing the height and width of the maxillary sinus with the diameter of the ipsilateral ophthalmic bulb ().


A 57-year-old man was referred to the ophthalmology department with binocular horizontal diplopia that was present for 2 weeks. The diplopia occurred in only left direction of gaze and had progressed over the past days. There was no associated pain, erythema, or discharge. And past medical history of the patient was negative for any orbital trauma or infection.
During ophthalmological examination, corrected visual acuity was 20/20 OD and 20/20 OS. The external examination revealed no inflammation, mass, or proptosis. There was no difference between the right and left eye in the exophthalmometry evaluation and extraocular movements were full in both eyes. At eyelid eversion examination of the right eye, small cystic mass was identified on the anterior aspect of the palpebral lobe of the lacrimal gland. The cyst appeared smooth and translucent and was attached to the underlying conjunctiva.
Magnetic resonance (MR) imaging revealed a 11 × 6.5 mm well-circumscribed cystic lesion adjacent to the lateral rectus and contiguous with the inferior palpebral lobe of the lacrimal gland (). The globe and the remaining lacrimal gland tissue were normal and there was no associated periorbital or soft-tissue inflammation.
A lateral orbitotomy was performed. During excision, the cyst was ruptured and thin, watery, clear fluid gushed out. Postoperatively, the patient's diplopia was resolved.
Histopathological examination of the surgical specimen revealed a cystic space lined by columnar epithelial cells consistent with ductal origin and this finding was compatible with the diagnosis of dacryops.


A 74-year-old man with distal bile duct cancer and gastric cancer underwent extended pancreaticoduodenectomy. Thereafter, leakage of pancreatic juice occurred, for which drainage treatment was performed. At 12 days after surgery, a bleeding from the drainage tube and low blood pressure were observed, so an emergency angiography was performed. A bleeding from the celiac artery was observed on angiography (), and a 5 Fr balloon catheter was inflated in the celiac artery for temporary hemostasis, because we needed some time to discuss with surgeons and to prepare a stent graft. Then, a stent graft (Niti-S; Century Medical, Tokyo, Japan) with a diameter of 10 mm and a length of 5 cm was placed at the celiac artery to the common hepatic artery successfully (). Resection of the residual stomach, residual pancreas, and spleen was immediately performed following the stent grafting. After that, wound infection and insufficient anastomosis of the esophagus and jejunum were observed; leukocyte count was 5,400/μL and C-reactive protein level was 5.4 mg/mL. So, drainage treatment was performed. At 40 days after this stent grafting and surgery, melena and reduction of blood pressure were observed. Therefore, emergency angiography was performed, which revealed a bleeding from the celiac artery (). It seemed to be from a distal site apart from the site of the first bleeding, and it was considered not a leakage but a new bleeding. Under fluoroscopy, it was confirmed that the stent graft was not broken. Temporary balloon hemostasis was performed again. Then, we discussed with our surgeon and decided to perform the stent grafting, because it seemed really difficult to reach the celiac artery under laparotomy due to strong adhesion caused by the previous operation. Thereafter, the stent graft (Niti-S) with a diameter of 10 mm and a length of 6 cm was placed at the inside of the initial stent graft to the distal site successfully (). There was no recurrence of bleeding during a 3-month followup period. No antithrombotic therapy was given during follow-up.


A 32-year-old man (case number 2 in ) suffered a soft tissue lesion of his left dorsal foot and weight-bearing sole with exposure of the transverse tarsal joint after a motor vehicle accident. He was admitted to our unit 10 days after the injury. Dislocation of the transverse tarsal joint had been treated elsewhere by open reduction and internal fixation with Kirschner wires. The size of the defect was 19×15 cm. It was successfully repaired with a 20×16 cm extended ALT septocutaneous perforator flap 6 days after admission. In this case, the microvascular anastomosis was performed end to end onto the tibialis anterior vessels and saphenous vein. The donor site was closed with a split-thickness skin grafting. The flap and donor sites healed without complication. Because the thick flap did not undergo a thinning procedure, the patient received a debulking procedure 3 months later. The whole flap was degloved to full thickness skin and then grafted in situ. Contour adaptation was good and the patient did not require custom shoes. No ulceration occurred during a 36 month follow-up (–).


A 27-year-old man (case number 8 in ) had a 17×15 cm soft tissue defect of his right dorsal foot with exposure of the tendon and bone after a motor vehicle accident. This was repaired and covered with a 18×16 cm thinned extended ALT musculocutaneous perforator flap 10 days after the trauma. Split-thickness skin grafting was used for the donor site. Since only one perforator was located within the flap territory, a cuff of deep fascia was retained around the perforator. The vessel anastomosis was performed end to end onto the tibialis anterior vessels and saphenous vein. The flap survived completely and the result was satisfactory (–).


A 42-year-old man (case number 13 in ) involved in a road traffic accident sustained a degloving injury to the right foot resulting in 24×15 cm defect with loss of all of the digits. This was repaired and covered with a 25×16 cm thinned extended ALT musculocutaneous perforator flap 9 days after the trauma. Three perforators were identified and dissected back to the descending lateral circumflex femoral vessel. A small cuff of deep fascia was kept around the cutaneous perforators to protect them. The vascular anastomosis was performed end to end onto the tibialis anterior vessels and saphenous vein, and split-thickness skin grafting was used for the donor site. The flap survived completely without any complications (–).


A 31-year-old man (case number 20 in ) presented with a crush injury to the left foot, sustaining a soft tissue defect (23×15 cm) over the posterior foot and medial ankle. This was repaired and covered with a 24×16 cm extended ALT musculocutaneous perforator flap. Because of its analogous structure, the fascia of the flap was used as a substitute for a partial defect of the Achilles tendon 8 days after the trauma. The arterial anastomosis was performed end to end onto the tibialis posterior vessels and saphenous vein. Split-thickness skin grafting was used for the donor site. The flap and the donor site healed unevenly. The patient complained of fatigue while ascending and descending stairs. A visual gait analysis showed only minor abnormalities and the patient was not hindered from running (–).


A 29-year-old young male law graduate, morbidly obese since adolescence, has been symptomatic since the last 7 years with fatigue, generalized weakness, and fluctuating jaundice. He was 160 kg at the time of presentation with a BMI of 55.36 kg/m2. He was diagnosed to have cirrhosis with persistently high bilirubin which fluctuated between 2 and 5 mg/dL. His Child's score at presentation was B9 with a MELD score of 14. Extensive evaluation for the etiology of liver disease including viral markers and autoimmune markers and iron and copper studies were all negative. There was no history of alcohol intake; hence, in view of morbid obesity and dyslipidemia, the diagnosis of nonalcoholic steatohepatitis for cirrhosis was considered. His gastroduodenoscopy showed small varices with portal hypertensive gastropathy, and a triple-phase CT scan of the abdomen showed a shrunken liver with splenomegaly, multiple portosystemic collaterals, and no ascites. He was listed for deceased donor liver transplantation and advised weight reduction with dietary and behavioral measures. However, he did not show any significant improvement over the next three months. Since he was morbidly obese and had failed medical therapy for weight reduction, he was planned for bariatric surgery after counseling for worsening of liver disease in the postoperative period and a possible requirement for immediate liver transplantation in that eventuality. A prospective living donor was identified in the family and completely worked up in case the patient showed signs of worsening liver disease following bariatric surgery. He underwent laparoscopic sleeve gastrectomy and had a smooth postoperative course. Following bariatric surgery, he had a significant reduction of weight from 160 kg to 102 kg in six-month period. However he developed worsening of his liver disease in the form of progressive jaundice, ascites, and recurrent episodes of hepatic encephalopathy. His Child's score worsened from B9 to C12, and MELD score increased to 24 over the next six months. In the absence of availability of cadaveric donor, living donor liver transplantation was considered as his weight had now decreased substantially. He underwent a modified right-lobe LDLT from his sister-in-law as the donor with a graft weight of 837 grams and an acceptable GRBWR of 0.81. The postoperative period was smooth except for basal atelectasis, which required intense physiotherapy and intermittent BIPAP for a few days.


A 51-year-old, Caucasian, male patient, diagnosed with schizophrenia was admitted following an exacerbation of OCS. He had contamination obsessions and cleaning compulsions for 10 years. He had persecution delusions. He was thinking that he was followed by police. He was hoarding garbage. He was brought to the emergency room by his family. Both the patient and his family reported that he had benefitted most from clozapine treatment. He was on clozapine 100 mg/day for 4 years. However, when the dose of clozapine was increased to a dose of 150 mg/day, an increase in OCS was observed. His family reported that a year ago after he had 10 sessions of electroconvulsive therapy (ECT), his psychotic and OCS decreased; but for the last 5–6 months, there was an exacerbation in psychotic and obsessive symptoms. Patient was hospitalized. During admission, his Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Yale–Brown Obsessive Compulsive Scale (Y-BOCS) scores were 151, 74, and 40, respectively.
A 30-mg/day dose of aripiprazole was added on to his ongoing 100-mg/day dose of clozapine treatment. After 2 weeks of combination treatment with 100 mg/day clozapine and 10 mg/day aripiprazole, plasma levels of both drugs were measured to be low. Clozapine dose increased to 250 mg/day and aripiprazole doze increased to 30 mg/day gradually. At the end of the sixth week, during discharge, his PANSS, BPRS, and Y-BOCS scores were 50, 20, and 20, respectively.


A 28-year-old, Caucasian, male patient, with a diagnosis of residual schizophrenia, treated for 2 years with clozapine 100 mg/day was admitted because of the worsening of his psychotic symptoms. His OCS first was seen at age of 13. He had control and symmetry obsessions and compulsions. After 5 years of OCS, he had psychotic symptoms. He reported that he could not leave the house for the last 2 years, due to his persecution delusions, skepticism, and resentment. He was on a treatment of clozapine 100 mg/day for 2 years.
He was hospitalized with a dose of 10 mg/day aripiprazole added on to his ongoing 100-mg/day clozapine treatment. The plasma level of clozapine and norclozapine were lower than therapeutic level at the admission. At the end of the second week, clozapine dose increased to 200 mg/day and aripiprazole to 30 mg/day gradually. The clozapine, norclozapine, aripiprazole doses and the clinical rating scale scores are given at Table
. During discharge, his scores of PANSS was 49 (78 at admission), BPRS was 27 (39 at admission), and Y-BOCS was 15 (40 at admission).


A 34-year-old, Caucasian, male patient with a diagnosis of paranoid schizophrenia for 14 years was admitted for psychiatric examination with complaints of repeating some words and washing hands frequently. He was on clozapine 100 mg/day treatment for 2 years. He was hospitalized due to exacerbation of psychotic and OCS.
A 10-mg/day dose of aripiprazole was added on to his ongoing 100-mg/day clozapine treatment. At the end of the first week, clozapine dose increased to 150 mg/day and aripiprazole dose to 30 mg/day gradually. The plasma clozapine and norclozapine levels were over therapeutic level as 746.1 and 519.1 ng/mL at the end of the third week, so clozapine dose decreased to 100 mg/day. The clozapine andaripiprazole doses, plasma drug levels, and the clinical rating scale scores are given at Table
. During discharge, his scores of PANSS was 50 (141 at admission), BPRS was 20 (74 at admission), and YBOCS was 20 (40 at admission).


A 27-year-old, Caucasian, male patient, diagnosed with substance-induced psychotic disorder, was hospitalized due to exacerbation of psychotic symptoms despite clozapine dose of 150 mg/day for two years. His family reported exacerbation of obsessive-compulsive symptoms, such as contamination obsessions and frequent handwashing, for 3 months. Clozapine and norclozapine plasma levels were lower than therapuetic level on admission. a 15-mg/day aripiprazole was added on and clozapine dose increased to 200 mg/day. At the end of the first week, aripiprazole dose was increased to 30 mg/day. Plasma clozapine and norclozapine levels were found to be higher than therapeutic level with a clozapine dose of 200 mg/day, and clozapine dose decreased to 100 mg/day. The clozapine and aripiprazole doses, plasma drug levels, and the clinical rating scale scores are given in Table
. At the end of the fourth week, during discharge, his scores of PANSS was 46 (159 at admission), and YBOCS was 10 (30 at admission).


A 82-year-old man presented to the emergency room prostrated, with recent onset of fatigue and malaise. A few days earlier, he started feeling urinary urgency and had started treatment with oral fluoroquinolones for an alleged prostatitis.
Physical examination was unremarkable, there were no abdominal masses, and Giordano's sign was negative. Laboratory revealed mild anemia (Ht: 33%; Hb: 11.3 mg/dL), leukocytosis (29.570 WBCs/mm3; 1% myelocytes, 6% band neutrophils), and altered renal function tests (serum creatinine: 2.65 mg/dL; urea: 80 mg/dL). Urinalysis showed leukocyturia (10 leukocytes/field) and hematuria (10 blood cells/field). Urine culture was negative.
A chest X-ray was normal. An abdominal ultrasound showed a 9.6 cm right kidney with poorly defined limits and an internal image suggestive of a choraliform stone. Left kidney was normal, as well as the remainder of the abdominal organs.
The patient was started on IV antibiotics (cefepime) and hydration. After the initial treatment, the patient evolved with worsening of his clinical and laboratory findings. A noncontrasting abdominal and pelvic computerized tomography (CT) revealed a large heterogeneous mass in the right kidney, in contiguity with the lumbar musculature, the liver, and the vena cava, also dislodging the pancreatic head and the duodenum. In the collecting system of the right kidney, a large choraliform stone was found.
In spite of the placement of a percutaneous drain in the perirenal space, the patient worsened, with progressive tachycardia, fever, and leukocytosis. Renal function, however, improved (serum Creatinine 1.4 mg/dL). An abdominal CT with intravenous (IV) contrast was then ordered and confirmed a large perirenal abscess (), and surgery was indicated. An open radical nephrectomy was performed in the right kidney, which was sent to pathologic examination.
Pathology revealed an 8.0 cm moderately differentiated (Grade 2) squamous carcinoma of the renal pelvis (). Necrosis was present in roughly 30% of the tumor, which extended to the renal parenchyma and the perirenal fat. There was a positive surgical margin in the perihilar region.
The patient survived the perioperative period; however, his clinical condition has not evolved as expected. Roughly one month after the surgical procedure, the patient became septic and died of septic shock of an unknown source. Sepsis was presumed to be urinary, since chest X-rays were normal, and all cultures were negative at the time of death.


A 42 year-old Italian man diagnosed with HIV-1 infection since 1993, was admitted at our hospital in April 2011 complaining about an acute pain at the right zygoma. At medical examination he had a vegetated lesion of the gingiva, arising from the superior maxilla, and an enlargement of right supraclavear lymph nodes. Examination of the other organs was normal. CD4+ cell count was 243/mm3 and HIV-1 RNA in plasma was 68 copies/mL.
At clinical history, cutaneous and pulmonary KS had been diagnosed in 1993 and at that time successfully treated with interferon alfa and chemotherapy. CD4+ cell count nadir was 52/mm3 and hepatitis C virus coinfection was documented. In recent years, only occasional bacterial pneumonia had occurred. cART was started in 1997 and changed to various regimens up to 2008, since when the current cART based on co-formulated tenofovir-emtricitabine, raltegravir, and darunavir/ritonavir had been prescribed. This salvage therapy was chosen after HIV genotypic resistance test that documented mutation associated with multidrug resistance. CD4+ cell count had stably risen above 200/mm3 since December 2008 and HIV-1 RNA level was constantly below 500 copies/mL since October 2009.
During hospitalization a total body computerized tomography (CT) showed multiple nodular lesions in both lungs, minimal right pneumothorax, pathological soft tissue in the right maxillar sinus, and enlargement of supraclavear lymph nodes. CT scan of the brain was normal. Biopsy specimen from gingival lesion revealed squamous cell carcinoma, while tissue taken from supraclavear lymph node showed histological features of KS. HHV8-DNA by polymerase chain reaction (PCR) was negative on blood. Four cycles of chemotherapy using liposomial doxorubicin (20 mg/m2) were performed, and after only two cycles an improvement of CT findings was documented. Then, ten sessions of radiotherapy on maxillofacial site for carcinoma were performed (total dose 30 Gy).
In October 2011, the patient showed bilateral spontaneous pneumothorax and was treated with chest drainage. After 25 days, he presented generalized seizures. A magnetic resonance imaging (MRI) of the brain showed three focal brain lesions, two that involved the right frontal lobe (20 and 14 mm) and one the right cerebellum hemisphere (16 mm). On FLAIR T2-weighted images the lesions of the right frontal lobe were hyperintense, with hypointense halo and surrounding edema. Diffusion-weighted imaging (DWI) showed restricted diffusion and low apparent diffusion coefficients (ADCs) in the lesions (range avg 0,458-0,566x10(-3)mm(2)/s). A new total body CT displayed a worsening of the previously described pulmonary lesions and the development of new intestinal lesions. A multi-disciplinary consultation excluded the possibility to carry out a cerebral biopsy, because of the lesion high risk of bleeding. CD4+ cell count was 142/mm3 and HIV-1 RNA in plasma was 225 copies/mL. HHV8-DNA by PCR on blood was repeatedly negative and IgG anti-Toxoplasma gondii antibodies were absent. Nevertheless, empiric anti-Toxoplasma treatment with pyrimetamine plus sulfadiazine, combined with steroids and phenobarbital, was prescribed. Brain MRI after 26 days of treatment showed worsening of the CNS disorder, with the appearance of a new lesion in the left frontal lobe displaying the same radiological characteristics. There was no change in signal intensity or size of the lesions already described in the previous examination. The lesions appeared as inhomogeneous masses, hyperintense on T1- and on T2-weighted images (Figure
A, B, C), with halo hypointense sign and surrounding edema, minimal mass effect and faintly ring enhancement. DWI of the lesions showed restricted diffusion (Figure
D) and lower ADC (avg 0,285×10(-3)mm(2)/s). Thallium-201 single-photon emission computed tomography (201Tl SPECT) of the brain did not show an increased uptake in the brain. 18 F-2-Fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) of the neck, thorax and abdomen showed hyperperfused tissue in the right cervical lymph nodes, skeleton, right adrenal gland, lungs, right maxillar sinus, duodenum. On the 1st of December a cycle of paclitaxel (100 mg/m2) was administered, and then ten sessions of whole brain radiotherapy were performed (total dose 30 Gy). At the end of December a massive right spontaneous pneumothorax occurred and pleural drainage was necessary again. The patient died on January 6th, 2012.
A full autopsy, including neuropathological examination, was performed. Tissue samples were taken from all organs. KS was found in the lungs, the ampulla of Vater, the pancreas, the duodenum, the adrenal gland and the cerebrum. Macroscopic examination revealed hemorrhagic nodules, variegated in appearance, with cystic degeneration in the organs involved. Multiple bilateral areas of consolidation with cavitation and necrotizing nodular lesions were present in the lungs. Cavities were extended to the pleura. Coronal section of the brain showed multiple hemorrhagic nodules with swelling of the cerebrum without displacement of midline structures. Lesions were localized in the frontal lobes at the gray/white matter interface, near the falx and in the cerebellum. Microscopic appearance of the tumor nodules was composed of monomorphic spindle cells arranged in ill defined fascicles (Figure
A) and separated by slit like vessels containing erythrocytes. Brain parenchyma of both cerebellar and cerebral hemispheres was invaded by the tumor cells directly or through the perivascular space (Figure
B). Neoplastic nodules showed hemorrhagic necrosis with pigmented macrophages (Figure
C). Immunohistochemical staining of the tumour cells revealed strong expression of CD34 (Figure
D). Real time PCR assays
[] revealed HHV8 DNA sequences in the tissue samples from the duodenum, the lungs and the brain. Quantitative evaluation of HHV8 DNA in the lungs, the Vater’s papilla and the brain showed: 15872 copies/106 cells, 7789 copies/106 cells and 2316 copies/106 cells respectively.


A 41-year-old man with a history of IVDU with injection of heroin initially presented to our clinic with a 3-month history of lower back pain radiating to the lower limbs bilaterally. Findings on neurological examination were normal, and he was treated with oral non-steroidal anti-inflammatory drugs. Three months later, he developed myelopathic symptoms with weakness of both lower limbs and severe back pain and presented to the neurosurgery clinic of our institute. Magnetic resonance imaging (MRI) of the lumbar spine showed diffuse bone marrow infiltration plus endplate erosion level at L3 and L4 characterized by low signal intensity on a T1-weighted image and high signal intensity on a T2-weighted image, with enhancement in affected bodies and cystic enhanced lesions in the epidural and paraspinal regions after administration of gadolinium (Figure ). Radiologically, pyogenic discitis, vertebral osteomyelitis, and epidural and paraspinal abscesses had to be considered. The patient was treated with oral non-steroidal anti-inflammatory drugs at the clinic. On examination, there was generalized weakness of grade 4 in related muscle groups and positive myelopathic signs in the lower extremities. The initial laboratory findings revealed an elevated erythrocyte sedimentation rate (ESR) (98 mm/hr; normal range, <10 mm/hr) and anemia (12.3 g/dL; normal range, 14–17 g/dL). However, the results of other laboratory tests were within normal limits, including the white blood cell count (12,500 cells/mm3).
Radiography of the lumbar spine revealed spondylosis of the lumbar spine with osteophyte formation and decrease disc height at L3–4. The patient underwent surgery for symptomatic relief; left laminotomy over L3, discectomy over L3–4 under a microscope, and debridement of the disc and endplate were performed and showed necrotic debris and fluid accumulation in the L4–5 disc and endplates as well as a disc bulging over the L3–4 level. The patient was treated empirically with intravenous cefuroxime and gentamycin until candidal infection was confirmed 3 days later. The clinical diagnosis was CaLS, and the patient was subsequently treated with intravenous fluconazole 400 mg/day for 6 weeks and then oral fluconazole 300 mg/day for another 3 months. Nine months later, the patient’s ESR was 8 mm/hr; he had recovered from his neurological deficit with complete return of motor function in the lower limbs and was walking normally, and the motor weakness and pain in his legs had resolved completely. Serial follow-up radiographs after surgery and MRI showed significant shrinkage of the vertebral osteomyelitis, discitis, and paraspinal abscesses (Figure ), although there were still abnormal signal and enhanced lesions in the disc adjacent to the affected vertebral bodies. The patient recovered very well during the 9-month follow-up period and does not have human immunodeficiency virus infection.
This is the first report of CaLS in a patient with IVDU. Although Candida species are low-virulence organisms that inhabit the skin and mucous membrane of humans, the incidence of disseminated and deep-seated Candida infections in patients with IVDU is increasing [-]. A new pattern of spondylodiscitis in IVDU is emerging, characterized by more frequent unusual pathogen involvement, a severe clinical course, and a need for surgery. Our patient was treated with surgical debridement and antifungal medications.
Because fungal infection has been rarely suggested as a cause of vertebral osteomyelitis [], we conducted an evidence-based literature review (Table ) with the keywords “vertebral osteomyelitis”, “fungus”, “spondylodiscitis”, “spine infection”, “fungal spondylitis”, and “fungal spinal osteomyelitis”. Sixty-one patients with fungal vertebral osteomyelitis were reported worldwide (Table ) [-]. Men were more likely to have fungal vertebral osteomyelitis than women, usually around middle age. The most common clinical presentations include local pain, leg weakness, and paraesthesias of the lower extremities. The involved sites of the spine included the cervical spine in two cases, the thoracic spine in seven cases, and the lumbar spine in 52 cases. The pathogens included Candida albicans (21), Candida tropicalis (6), Aspergillus fumigatus (6), Blastoschizomyces capitatus (6), Candida parapsilosis (5), Pseudallescheria boydii (2), Nattrassia mangiferae (2), Rhizopus rhizopodiformis (2), Scedosporium apiospermum (2), Candida glabrata (2), Coccidioides immitis (1), Trichosporon asahii (1), Scedosporium prolificans (1), and Blastoschizomyces dermatitidis (1). Combined surgical intervention and antifungal therapy has been used since the 1980s; overall, of the 61 patients, five died, two experienced a relapse, and 54 patients recovered well.
There are no non-invasive diagnostic tests or typical radiological findings in CaLS. Reports by Waldvogel and Gathe showed that the delay in diagnosis between the onset of symptoms and the diagnosis of CaLS ranges from 1 month to several years, with an average of 3.3 months []. Symptoms such as low-grade fever, malaise, and weight loss are non-specific. Similarly, anemia, neutrophilia, and elevated ESR are also non-specific, representing a chronic inflammatory process, although a markedly elevated ESR is suspicious of infection.
Candida spondylodiscitis usually involves the intervertebral disc space with narrowing of the disc cartilage, causing destruction and lysis of the vertebral endplates and underlying vertebral bone []. The findings on MRI include an absence of disc hyperintensity and preservation of the internuclear cleft on T2-weighted images in addition to increased signal intensity on gadolinium-enhanced T1-weighted images and early disc destruction and paraspinal abscesses []. The delay of antifungal medical or surgical treatment in our case allowed us to evaluate the natural course of the disease. Candida affects the spinal segments probably through hematogenous dissemination, and once a focus develops in the vertebral body, it continues an indolent course []. In our case, vertebral collapse, psoas abscess formation, and neurological deficits became apparent within 3 months of the onset of symptoms. The reasons for delayed suspicion and diagnosis in our case included a delay in presentation and a delay of investigation. A high index of suspicion and immediate MRI would have confirmed the pathologic lesions before vertebral collapse and neurological compromise developed. As soon as lumbar spondylodiscitis is suspected, MRI and percutaneous biopsy should be performed, followed by medical therapy. This may halt the progression of bony destruction and prevent the need for surgical treatment []. Surgery is primarily indicated for failure of or relapse after conservative treatment, significant spinal collapse, and neurological deficits [].
The management of patients with CaLS includes conservative treatment with biopsy, medical therapy, and bed rest; posterior surgical stabilization and transpedicular biopsy with or without fusion; or anterior debridement of the abscesses, tissue diagnosis, and fusion combined with posterior stabilization. Some investigators have recommended primary reconstruction for all pyogenic infections of the spine to maximize eradication of the infection [], and others have recommended surgery to aid in diagnosis as well as decompression and stabilization of the spine at the same time []. Combined debridement and treatment with an antifungal agent was performed in this case because there is controversy regarding the use of instrumentation in the presence of infection, and in this case the infection was successfully eradicated and the neurological deficits were resolved.


The R. monacensis positive patient was an eight-year-old girl living in an urban environment. Six days prior to the hospital visit the patients mother had noticed a red annular rash on her daughter’s face. The rash expanded throughout the following day and during the hospital visit three EM lesions were noticed: around the left eye (7×14 cm), at the anterior side of the right thigh (9×12 cm) and on the right gluteus (11×17 cm). The skin biopsy was taken from the gluteal EM. The patient complained about itching but no other symptoms were reported or noted during the visit. Neither the patient nor her mother recollected any tick bites. After the diagnosis of Lyme borreliosis presenting as multiple EMs following dissemination of the infection, treatment with azithromycin (10 mg/kg) was initiated. The antibiotic was administered twice on the first treatment day and once daily until day five. The EMs started to fade during the second treatment day and had disappeared by day four. Serology later confirmed the diagnosis of Lyme borreliosis but did not show a seroconversion towards spotted fever group Rickettsia (data not shown). Throughout the disease course, no symptoms indicating a rickettsial co-infection were noticed. At check-ups two weeks and two months after the initial visit, the skin was clear and the patient was fully recovered.


A 44-year-old Arab woman presented with a four-month history of rapidly increasing painless mass in her right breast. On clinical examination, the mass was lobulated and ulcerative taking almost all of the mammary gland and involving breast skin and the nipple areola (). No axillary lymph nodes were palpable. An ultrasonography of the breast identified a hypoechoic and heterogeneous mass with an axillary lymphadenopathy measuring 9.2 cm × 7.6 cm × 6 cm and 1.3 cm, respectively. Core needle biopsy of the mass was performed. Pathology revealed tumor comprised of hyperchromatic spindle cells arranged in fascicles, with marked pleomorphism, atypical nuclei, and a moderate mitotic activity (6/10 high power field) (). Immunohistochemistry showed that the tumor cells were positive for desmin and H-caldesmon while they were negative for cytokeratin ().
The extent of disease was evaluated by systemic physical examination and chest and abdominopelvic computed tomography which revealed diffuse pulmonary metastasis.
Palliative chemotherapy based on doxorubicin (60 mg/m²) and ifosfamide (9 g/m²) every 3 weeks was indicated. After three cycles of this regimen, we noted a clear local and distant progression including the increase in the size of the mammary tumor and the occurrence of a well-circumscribed and ulcerative cutaneous nodule in the abdominal wall (). Second line docetaxel (75 mg/m² day 8)—gemcitabine (900 mg/m² days 1 and 8) regimen was proposed, but the patient died of disease one month later.


A 40-year old male was diagnosed with a silent ACTH-secreting pituitary adenoma in 1997 when an MRI of his sinuses demonstrated a 3 cm enhancing area of soft tissue within the inferior aspect of the sella consistent with a pituitary adenoma with no evidence of expansion. MR spectroscopy showed metabolically inert tissue. Since he was asymptomatic, he underwent active surveillance with annual MRI scans. His ACTH levels ranged between 100 and 120 pg/mL, but there was no clinical evidence of Cushing's syndrome and urine free cortisol was normal. Lab values were normal for prolactin, testosterone, LH, FSH, free T4, TSH, and alpha subunit. There was no family history of pituitary adenomas or other endocrine disorders.
In 2004, seven years after initial discovery, his cortisol levels started to increase and he developed clinical features consistent with Cushing's syndrome including weight gain, facial rounding, hypertension, and edema. His ACTH levels increased to >300 pg/mL, which was accompanied by an increase in his late night salivary cortisol (). An MRI showed a 2.5 × 3.3 cm enhancing mass arising in the pituitary fossa. The mass displaced the optic chiasm, invaded the sphenoid sinus, and exerted mass effect on the cavernous sinus bilaterally (). He underwent transsphenoidal surgery (TSS) debulking of this invasive tumor. Pathology showed pituitary adenoma of corticotroph-type staining positive for ACTH and negative for TSH, prolactin, LH, GH, and FSH. Postoperative MRI showed substantial debulking with a near-complete tumor removal (). This initially resulted in reduction of plasma ACTH to 105 pg/mL and improvement in symptoms. However, over the next year his cortisol levels continued to increase and symptoms worsened. He received adjuvant radiation therapy using a 5-field noncoplanar arrangement. A total dose of 50.4 Gy was delivered in 28 fractions over 38 days. Despite radiation therapy, his cortisol levels remained elevated. He developed radiation-induced optic neuritis manifesting with blurry vision and decreased visual acuity of the left visual field. He was treated with prednisone, pentoxifylline, and hyperbaric oxygen with improvement in his symptoms. Despite the elevated cortisol levels, his MRI over the next 2.5 years demonstrated stable disease and he developed no new symptoms.
In late 2008, an MRI showed significant enlargement in mass size and he underwent another TSS tumor debulking in January 2009. Residual tumor remained predominantly in the left cavernous sinus and lateral sphenoid area. Postoperatively, late night salivary cortisol remained elevated and the patient had continued progressive signs and symptoms of hypercortisolism. He was enrolled into a clinical study with mifepristone in February 2010 (SEISMIC study). However, he experienced no clinical improvement with mifepristone which was discontinued ten weeks after initiation due to tumor enlargement. An MRI in July 2010 showed predominately left-sided extensive tumor regrowth in the sella, sphenoid sinus, and bilateral cavernous sinuses. Consequently he underwent an endonasal endoscopic tumor resection in July 2010 with substantial debulking, but significant residual tumor remained in the cavernous sinuses (Figures and ). Pathology confirmed an ACTH-staining adenoma with a Ki-67 of 5–7% and P53 negative (). Postoperative late night salivary cortisol and urine cortisol remained elevated. In October 2010 he was started on TMZ 200 mg/M2 administered orally on the first 5 days of a 28-day cycle with initial improvement in cortisol levels ().
He was monitored and in January 2011, his ACTH levels began to increase again. Repeat MRI showed dramatic progression with tumor regrowth in the sellar and sphenoid sinus region as well as marked tumor growth in the left cavernous sinus and left middle fossa causing mass effect and edema on the left temporal lobe. TMZ was stopped and he was started on carbergoline. There was no reduction in ACTH with this treatment and it was subsequently stopped. Clinically, he had significant visual impairment and headache. Additional radiation therapy was not an option due to prior radiation exposure. In May 2011 he consequently underwent two-staged tumor debulking including a left temporal craniotomy followed 3 days later by redoendonasal endoscopic tumor debulking (Figures and ). Pathology revealed marked tumor progression with nuclear anaplasia, numerous mitoses and dramatic increase in Ki-67 ranging from 80 to 90%; P53 remained negative; ACTH immunocytochemistry was positive (Figures –). His postoperative brain and sellar MRI confirmed significant tumor debulking, but a restaging chest and abdominal CT showed a 16.3 mm solitary metastasis in segment five of the right hepatic lobe. This was biopsied and pathology confirmed poorly differentiated ACTH-pituitary carcinoma identical to the primary site tumor (Figures and ).
Given the high proliferation index and the presence of metastatic disease, he was started on cisplatin 80 mg/M2 and etoposide 100 mg/M2 administered every 3 weeks in July 2011. Pituitary MRI after 1 cycle demonstrated interval decrease in tumor extension along the planum sphenoidale, left orbital roof, and left cranial fossa. He displayed a dramatic clinical improvement in right eye vision and headache resolution. After 3 cycles, pituitary MRI continued to show significant parasellar tumor shrinkage (). An abdominal CT demonstrated decreased size of the liver lesion to 6 mm.
In early September 2011, he developed abrupt onset of relative hypotension, marked fatigue, and weakness. These features were consistent with acute adrenal insufficiency. Laboratory studies showed a plasma ACTH of 14 pg/mL. His basal cortisol was 0.5 ug/dL and increased to 2.6 ug/dL after the administration of cosyntropin. He had immediate clinical improvement with glucocorticoid administration. Transient adrenal insufficiency did not previously occur with any of the transsphenoidal surgeries.
After 3 cycles, the chemotherapy regimen was changed to carboplatin AUC 5 and etoposide 100 mg/M2 due to renal insufficiency. A total of 6 cycles was administered every 3 weeks. He had stable disease based on serial pituitary MRIs. In January 2012, he was admitted with seizures. MRI spine revealed leptomeningeal enhancement and CSF cytology was positive for malignant cells. Chemotherapy was stopped and the patient died soon thereafter. A post mortem examination was not performed.


Our patient is a 63-year-old female with osteoarthritis in the lumbar spine and bilateral knees. Knee X-rays showed bilateral mild osteoarthritic changes. MRI of left knee showed grade II-III patellar chondromalacia and mild osteoarthritic changes. Her left knee pain was uncontrolled with conservative measures including NSAIDs and narcotics. Steroid injections were provided once with no pain relief. Subsequently, over a period of five years, she received multiple courses of sodium hyaluronate injections to the left knee without complications, waiting at least six months between each series of five injections. The skin was thoroughly examined prior to each injection and was noted to be in a good condition, with no breaks, rashes, or bruises evident. She had great pain relief from the Hyalgan injections and repeatedly requested them. Clean technique was employed prior to each of these injections, including use of betadine, alcohol, and gloves.
Pertinent past medical history included treatment for invasive ductal left breast cancer with lumpectomy and radiation five years prior to this hospital presentation. She had been in remission until four months prior to hospitalization, when she was diagnosed with recurrent left breast ductal carcinoma. She then underwent mastectomy with axillary lymph node dissection and received one round of chemotherapy treatment, with Taxotere, Carboplatin, and Herceptin, 11 days prior to hospital admission. The surgery and chemotherapy proceeded without complications.
Five days after the last sodium hyaluronate injection to the left knee, she presented to the hospital with complaint of left leg pain that woke her from sleep. She initially noticed a small area of erythema in the left popliteal fossa. Over the next few hours, she developed rapidly progressive swelling, expansion of the erythema, and formation of multiple large bullae extending from the thigh to proximal leg. By the time she arrived at the hospital, the bullae and erythema had expanded to the gluteal fold and inguinal region. CT of left lower extremity showed free gas through the adductor musculature and posterior and superior to ischial tuberosity. Given the aggressive symptoms, the patient was emergently taken to operating room for extensive debridement and amputation at the lesser trochanter. She was then admitted to intensive care unit on broad spectrum antibiotics for septic shock secondary to necrotizing fasciitis of the left lower extremity, involving both posterior and anterior compartments. She deteriorated and required vasopressors, intubation and multiple debridements. Over the next 3 days, she suffered multiorgan failure and required hemodialysis. Given her wishes and poor prognosis, life support was withdrawn. She died 20 days after last chemo, 13 days after the most recent Hyalgan injection, and 7 days after the onset of necrotizing fasciitis.


A 77-year-old woman visited our hospital with an incidentally identified right renal tumor by a screening abdominal ultrasonography procedure for hepatitis C infection. All laboratory test results were within normal limits. An abdominal computed tomography revealed a hypovascular tumor with focal calcification, measuring 2.5 × 2.3 cm, in the upper pole of the right kidney (Figures and ). The tumor was clinically diagnosed as a right RCC with calcification and was classified as cT1aN0M0, according to the tumor-node-metastasis system []. The patients underwent the implantation of a pacemaker due to sick sinus syndrome and had poor ejection fraction. Laparoscopic right radical nephrectomy was performed. The cut surface of the tumor was beige in color and indicated that the tumor was an extensively ossified mass (Figure ).
Histological analysis revealed three distinct morphologic components of the tumor, which consisted of compact epithelial cells arranged in a nested pattern (Figure ). The cells contained eosinophilic cytoplasm with accentuated cell borders, and the centrally located nuclei had wrinkled peripheral borders and varying degrees of hyperchromatism. Admixed with the CRCC were extensive areas of sarcomatoid spindle cells with marked nuclear pleomorphism and brisk mitotic activity (Figure ). The spindle cells were arranged in ill-defined fascicles with a focal storiform pattern, exhibiting an aggressive growth pattern with extracapsular invasion into the adipose tissue. Another feature of this tumor was the presence of multiple foci of metaplastic ossification (Figure ). There were also hyaline degenerative change and fibrosis in all areas.
The patient is alive and free from disease 12 months after surgery.
To the best of our knowledge, this is the first reported case of CRCC with concomitant osseous metaplasia and sarcomatoid transformation.
A number of recent studies concerning the prognosis of patients with CRCC have reported relatively good survival rates for this disease [,], and cancer-related death occurred in 22%, 16%, and 8.6% of clear, papillary, and CRCC cases, respectively []. The good survival outcomes in these cases were probably because more than 70% of patients had organ-confined disease and more than 60% of tumors were low grade [].
The incidence of sarcomatoid transformation is approximately 5% in RCC [], increasing to 8% in the CRCC subtype [,]. Heterologous sarcomatoid components, such as chondrosarcomatous, osteosarcomatous or rhabdomyosarcomatous component have also been reported []. Akhtar et al. suggested that sarcomatoid development in CRCC might be associated with its peculiar genetic profile, which makes cells prone to hyperploidization []. Bruneli et al. demonstrated that both the epithelial and sarcomatoid elements in a CRCC have different genetic abnormalities and that the latter show multiple gains of chromosomes 1, 2, 6, 10, and 17 []. The coexistence of both CRCC and sarcomatoid carcinoma may be due to either the dedifferentiation of the more highly differentiated chromophobe cell tumor or the coincidental development of two synchronous tumors []. The former model is more widely accepted as it is based on the evolution of renal carcinoma into a spindle cell population. This sarcomatoid change may be the result of extensive chromosomal rearrangement, leading to identical spindle morphology [].
Sarcomatoid CRCC is a more aggressive neoplasm and has a very poor prognosis compared with classic chromophobe carcinoma []. The presence of a sarcomatoid component has been reported to be associated with an increased risk of metastasis and an unfavorable prognosis [,,]. Previously reported cases of CRCC with sarcomatoid differentiation have shown distant organ metastases to sites including the bone, liver, lung, and lymph nodes [].
RCCs exhibit a number of changes such as hemorrhage, necrosis, fibrosis, and hyalinization. However, although calcification is a well-recognized feature of renal tumors, they are rarely ossified. Daniel reported that 10.3% of RCCs had calcified foci, based on a review of 2,709 renal masses at the Mayo Clinic []. Moreover, reports of histopathologically confirmed osseous metaplasia or bone formation within RCC are rare []. The presence of ossification in CRCC, however, was noted in four previously reported cases [].
The mechanism of ossification is unclear, although it might involve a metaplastic or reparative response either in the tumor or in the surrounding tissue, the production of bone by tumor cells, or the ossification of a preexisting mucin or calcium deposit []. Osseous metaplasia may occur secondary to ischemia, necrosis, or inflammation in the tumor or surrounding tissues [].
The prognostic significance of ossification in CRCC remains unclear because of the limited number of cases reported to date. However, several studies demonstrated that ossification is a significant prognostic marker for patients with RCC [,] and is usually representative of an early stage without invasion or metastasis []. Therefore, RCC with osseous metaplasia implies a more favorable prognosis, although this is contradicted by some reports, suggesting that ossification is actually associated with high-grade tumors and a poor prognosis [].


A 61-year-old smoker woman was admitted to the emergency department with retrosternal localized typical acute chest pain that started three days prior to presentation. Pain occurred at rest and was associated with shortness of breath. Upon arrival to the emergency room patient was still in pain, but vital signs were stable. The heart and lung examinations were remarkable for the presence of regular heart sounds with S3 gallop as well as bilateral fine basal crackles. Neither cutaneous nor mucosal petechia nor purpura was noted. The rest of the physical exam was normal. Her past medical history was significant for two uneventful pregnancies and chronic immune thrombocytopenic purpura (ITP) currently in remission. Ten years ago ITP was refractory with relapse during steroid tapering. Subsequently splenectomy was performed, establishing remission. Laboratory blood tests revealed hemoglobin of 15 mg/dL, platelet count of 322 × 109/L, normal PT and PTT, troponin of 0.5 ng/mL, and CKMB 7.7 ng/mL. Inferior ST elevation was present on initial ECG with poor R wave progression anteriorly. She received in the emergency room nitroglycerin and morphine as well as 300 mg of clopidogrel and 325 mg of aspirin along with 5000 units of heparin bolus. Primary percutaneous coronary intervention was performed. The right common femoral artery was accessed with a 6 French sheath. Diagnostic angiography revealed acute 99% thrombotic occlusion of proximal LAD with an ejection fraction estimated at 25% on the left ventriculogram. The left circumflex and right coronary arteries were patent with right system dominance. A 6 French XBLAD 3.5 guiding catheter was used to intubate the left coronary system. Prior to stent placement, 4000 units of heparin and 0.25 mg/kg loading dose of abciximab were administered followed by a 0.125 mg/kg infusion of abciximab. An activated clotting time of 260 seconds was achieved. A 3.5∗20 mm tacrolimus eluted stent was deployed in the proximal segment of LAD with optimal angiographic result and TIMI flow 3 in the left anterior descending artery. The sheath introducer was removed after 6 hours with manual compression of the puncture site. Subsequently a small localized ecchymosis developed with spontaneous resolution in the following two days. The patient was discharged on aspirin 325 mg and clopidogrel 75 mg. Her platelet level upon discharge was 262 × 109/L. Four years later she presented with a relapse of thrombocytopenia without active bleeding. All antiplatelets were held and intravenous steroids as well as intravenous immunoglobulins were administered. On the 3rd day platelets were 97 × 109/L and clopidogrel was restarted with indication to restart aspirin after 2 weeks if platelet count remained stable.
Patient was readmitted within one month with mucosal hemorrhagic blisters and platelet count of 7 × 109/L. A regimen of steroid and intravenous immunoglobulin pulse therapy was instituted with rise in platelet count to 90 × 109/L on discharge. Clopidogrel was restarted. Rituximab was to be started at a later stage.


A 55-year-old male smoker presented with typical anginal chest pain for three days. Upon arrival to the emergency room, pain was slightly improved and found to have NSTEMI with normal electrocardiogram and elevated troponins. The physical examination was unremarkable. The past medical history was significant for hypertension, dyslipidemia, and chronic ITP which responded to steroids and immunoglobulins in the past. Laboratory blood tests revealed a hemoglobin level of 15 mg/dL, platelet count of 42 × 109/L, and normal PTT and PT. He was admitted to the coronary care unit and was started on simvastatin and nitroglycerin and clopidogrel was held. The patient was given one dose of IVIG and was started on prednisone. On the 7th day of hospitalization, the platelet count was 208 × 109/L and the patient underwent cardiac catheterization through the right femoral artery. A drug eluted stent was placed in the obtuse marginal and a therapeutic ACT was reached after heparin administration. On the 8th day of hospitalization, the patient was discharged on aspirin 325 mg, clopidogrel 75 mg, and prednisone. Patient tolerated these medications well and remained in remission.
After six years, he presented again to the hospital with NSTEMI. The episode occurred one day after receiving dexamethasone and rituximab for ITP relapse. The physical exam was unremarkable and the platelet count was 23 × 109/L. He received in the emergency room nitroglycerin and morphine as well as aspirin 81 mg and the patient was started on IV dexamethasone and IVIG. On the fifth day, the platelet count was 180 × 109/L and the patient underwent cardiac catheterization through the femoral artery. Ostial triple vessel disease was treated with off pump bypass surgery with heparin to maintain an ACT > 300 through the procedure. The platelet count was 149 × 109/L after receiving two days of dexamethasone and the patient was discharged on aspirin 325 mg orally daily. Both patients were followed up for two years without further complications.


A 62-year-old Asian man consulted a doctor because of asthmatoid wheeze, anarthria, purpura and gait disturbance. He has no history of hypertension. He pointed out proteinuria for the first time two months ago before the consultation. He was diagnosed with a cerebral hemorrhage following a computerized tomography scan (Figure ). His laboratory findings revealed that his serum creatinine concentration was 0.66 mg/dl, his serum IgE concentration was 18230 IU/ml (normal: <170 IU/ml), and his eosinophil count was 18900/μl. His urinary analysis revealed 1.61 g/gCr of proteinuria. Coagulation tests revealed a prolonged activated partial thromboplastin time at 61.2 seconds and a prothrombin time of 25.5 seconds. In addition, FV activity alone severely decreased to 4.4% of normal, and an FV inhibitor was present at a titer of 2.5 BU/ml, suggesting the presence of antibody-mediated circulating inhibitors specific for FV (Table ). The patient was diagnosed with a cerebral hemorrhage, eosinophilia, hyper IgE syndrome and acquired FV inhibitors. Steroid therapy with prednisolone (1 mg/kg) for the treatment of purpura and acquired FV inhibitors was administered. Treatment with steroid led to the improvement of his clinical symptoms including purpura, normalization of the coagulation tests, and disappearance of eosinophilia. To confirm the diagnosis of proteinuria, we performed a renal biopsy. Fine granular depositions were observed at the subepithelial layer in the glomerulus upon IgG fluorescent staining (Figure ). Spike formations were partially observed at the subepithelial layer upon Periodic acid-methenamine-silver (PAM) staining (Figure ). An impaired lamina rara layer and endothelial cell swelling and detachment were observed with high-density deposits at the lamina rara externa upon electron microscopic analysis (Figure , Additional file : Figure S1 and Additional file : Figure S2). We determined that the patient had developed MN with glomerular endothelial cell damage. After the administration of steroid therapy, the proteinuria improved gradually.


A 35 year old male patient with non-contributory medical history reported in the post-graduate clinics of our college and hospital, having pain in the left maxillary posterior region. The clinical examination showed large carious lesions in tooth #25 and 26 with pulp exposure. The patient was sensitive to percussion and palpation on both teeth. Vitality tests (hot, electric pulp test [EPT]) on the involved tooth showed abnormal responses indicating that irreversible pulpitis had occurred. Preoperative radiograph was taken which revealed deep carious lesions in tooth #25 and 26 approaching the pulp (Fig. ). The radiograph also revealed a complex root canal anatomy in tooth #25. Three distinct roots were observed in second premolar resembling the maxillary first molar. The pulp chamber in tooth #25 was located more apically and also the mesiodistal width of crown was approximately equal to its mesiodistal width at the mid-root region. Nonsurgical endodontic treatment was planned in both #25 and 26 over two visits with the use of calcium hydroxide as inter-appointment, intra-canal medicament. After the administration of the local anesthetic, 2% Lignocaine with 1:100,000 epinephrine (Xicaine, ICPA Health Products Ltd, Gujarat, India), access cavity was prepared in tooth #25 under the rubber dam isolation. Access opening was given a ‘T’ shaped outline to locate all the three root canal orifices. On entry into the pulp chamber, three canal orifices were observed i.e., mesiobuccal, distobuccal and palatal, positioned as in maxillary first molars (Fig. ). All the three root canal orifices were located using #10 K-file (Dentsply Maillefer, Ballaigues, Switzerland). Working length was established with radiograph by #15 K-files (Fig. ) and confirmed using an Apex locator (Root ZX, J. Morita Inc). The canals were cleaned and shaped with hand K-files and nickel titanium rotary files (Protapers, Dentsply Maillefer, Switzerland) frequently irrigating with 5% sodium hypochlorite and 17% EDTA. Calcium hydroxide was used as an intracanal medicament and the access cavity was sealed with Cavit (ESPE, Seefeld, Germany). Cleaning and shaping was also performed in tooth 26 using K-files and nickel titanium rotary files (Protapers, Dentsply Maillefer, Switzerland) followed by placement of calcium hydroxide intracanal medicament. The access cavity in first molar was sealed with Cavit (ESPE, Seefeld, Germany). In the next appointment, one week later, the patient was asymptomatic. Intracanal calcium hydroxide dressing was removed from tooth #25 and the canals were irrigated with 5% sodium hypochlorite. Canals were dried with sterile paper points and obturated with gutta-percha and AH Plus sealer (Dentsply DeTrey GmbH, Germany) by cold lateral condensation technique. Access cavity was restored with composite resin. Tooth #26 was subsequently obturated with gutta-percha and AH Plus sealer (Dentsply DeTrey GmbH, Germany) using cold lateral condensation technique and restored with composite resin. Radiograph was taken to confirm the quality of the obturation (Fig. ). Periapical radiograph was also taken in relation to right maxillary premolars in the same patient which revealed the presence three separate roots in tooth #15 (Fig. ).


A 66-year-old gentleman, non-smoker, with no known allergies or significant respiratory medical history, presented to the Allergy Medicine service with a chief complaint of cough. He describes that he suffered a respiratory infection approximately three months prior to the visit. After it was treated, the majority of symptoms resolved, but the cough and coughing spells persisted with post-nasal drainage and clearing of the throat. The CT scan revealed an asymmetrically smaller and completely opacified left maxillary sinus with left-sided periosteal thickening as well as lateral bowing/bone remodeling of the uncinate process. The opacified left maxillary sinus had hyperdensities which could represent chronic dense secretions (Figure ). The left ostiomeatal complex was occluded (Figure ). The initial diagnosis was chronic sinusitis. He was prescribed antibiotics for 10 days, was advised to have a new sinus CT scan, and was referred to otorhinolaryngology.
Two months later when the patient presented to otorhinolaryngology for follow-up, there had been no clinical changes. The physical exam showed some asymmetry of both eyes with mild hypoglobus of the left eye. His nose had a moderate anterior septal deformity to the left with mucoid drainage. He was unaware of vision changes, but testing demonstrated double vision when looking to the extreme right. The rest of the exam was normal.
The new sinus CT scan showed no significant change. The interpretation was a persistent opacified hypoplastic left maxillary sinus with obstructed left ostiomeatal unit with lateralization of the uncinate process. The pattern was consistent with type 2 maxillary sinus hypoplasia. A sinonasal endoscopy confirmed the previous imaging findings.
The patient underwent a turbinoplasty and endoscopic sinus surgery (antrostomy) to address the total opacification of his left maxillary sinus. The nasal sinus symptoms and cough resolved after the procedure. Correction of the enopthalmos was not necessary.


A 26-year-old man presented black stools and anemia. He had not taken any medication and had no specific family or past medical history. His height and weight were 172.3 cm and 93.4 kg (the body mass index was 31.5 kg/m2). His body temperature was 36.7°C, blood pressure was 137/77 mmHg and radial pulse rate was 80 beats/min and regular. Complete blood count showed the red blood cell count of 326 × 104/μl, hemoglobin concentration of 8.6 g/dl (reference range: 13.5 to 17.6 g/dl), and mean corpuscular volume of 87 fl. Serum chemistry showed that hemoglobin A1c was 4.2% (National Glycohemoglobin Standardization Program number). Endoscopic examination of the upper digestive tract revealed a large pedunculated polyp arising from gastroduodenal junction, close to pyloric ring on the side between minor curvature and anterior wall (Figure
A). The head of the polyp was incarcerated toward duodenal lumen. The lower side of the polyp showed hemorrhage in part. The stalk was too thick to be removed by endoscopic mucosal resection. Instead, distal gastrectomy with lymph node dissection was performed. No metastasis was found in the dissected lymph nodes.
The postoperative period was uneventful that the hemoglobin concentration gradually increased and became 11.6 g/dl on day 12. He was subsequently discharged without any complications and was in good health with 1 year follow-up.
The surgically resected specimen showed a lobulated polyp sized 6.4 × 3 cm (Figure
B) and the cut surface was solid and white (Figure
C). Histologically, the stalk of the polyp projected from duodenal mucosa, not pyloric mucosa. In the lesion, marked proliferation of Brunner’s glands was noted showing lobular structures separated by fibromuscular septa (Figure
A). Acini and ducts were well preserved (Figure
C) and cystically dilated ducts were scattered (Figure
B). Lymphocytic infiltrate was observed in the entire lesion and lymphoid follicle formation was intermingled in and between the lobules of hyperplastic Brunner’s glands (Figure
B). The upper two thirds of the polyp was covered by a surface epithelium histologically similar to gastric foveolar epithelium (Figure
A), randomly with surface erosions (Figure
E). No evidence of malignancy was found within the specimen (Figure
C). These findings suggested that the lesion was composed of normal tissue elements of duodenal mucosa and submucosa, but formed a disorganized aberrant mass. Thus, we diagnosed this lesion as Brunner’s gland hamartoma. Helicobacter pylori infection was not detected in Giemsa stain.
Then, we sought to clarify the possible pathogenesis of this lesion by immunohistochemical analyses for mucin phenotypes, CDX2 expression and MIB-1 labeling. The surface epithelium resembling gastric foveolar epithelium was positive for MUC5AC (Figure
B), indicating gastric foveolar metaplasia, while the epithelium in deeper portion and Brunner’s glands were positive for MUC6 (Figure
C). The epithelial cells at the transition zone between MUC5AC- and MUC6-positive areas showed concomitant expression of MUC5AC and MUC6 (Figure
B and C). These results confirmed that the surface epithelium differentiated towards gastric foveolar epithelium but preserved intestinal epithelial nature in the deeper portion. Interestingly, the MUC5AC-positive epithelium and adjacent MUC6-positive epithelium were diffusely positive for MIB-1 (Figure
D), and the Brunner’s glands beneath them showed high MIB-1 labeling index (7.9%; Figures
D and
A).
The similar staining pattern was observed in the area with surface erosion (Figure
E-H), where most of surface epithelium was lost, but the deeper portion of the epithelium was minimally left (Figure
E), showing MUC5AC/MUC6 double positivity (Figure
F and
G) with significantly high MIB-1 labeling (Figure
H). Moderately high MIB-1 labeling of Brunner’s glands (9%) was accompanied (Figures
H and
B).
On the other hand, surface epithelium in the lower part of the polyp showed a villous structure containing goblet cells without apparent gastric foveolar metaplasia (Figure
I). Immunohistochemically, positivity of MUC5AC staining decreased in the lower one third of the polyp, particularly on the distal side. In the same area, CDX2-positive nuclei (Figure
J) and MUC2-positive goblet cells (Figure
K) were observed at the surface epithelium showing intestinal nature. Below the surface epithelium preserving intestinal nature, Brunner’s glands had less proliferative activity with low MIB-1 labeling index (0.77%) (Figures
L and
C). These results suggest that gastric foveolar differentiation is possibly related with the observed proliferative activity of Brunner’s glands.


A 34 years-old gravida 4 para 1 woman was
admitted with abdominal distension, 6 days after
embryo transfer. She had undergone controlled
ovarian stimulation and in vitro fertilization (IVF);
antagonist protocol with 150 IU recombinant FSH
for 9 days, Cetrorelix for 5 days, and recombinant
hCG were used for ovulation trigger. About
13 oocytes were retrieved and two embryos were
transferred. She had a history of Caesarean section
after a successful IVF cycle due to unexplained infertility
3 years ago without a history of OHSS.
Transvaginal ultrasound showed ascites, enlarged
ovaries (right ovary: 70×75 mm, left ovary: 80×85
mm) and endometrium appearing 10 mm in thickness.
White blood cell count (WBC) and hemoglobin and hematocrit levels were 40900/L, 15.76
g/dl, and, 47.3%, respectively. Blood urea nitrogen
(BUN), creatinine, total protein and albumin
concentrations were 16 mg/dl, 1.0 mg/dl, 6.4 g/dl
and, 3.3 g/dl, respectively. Urinalysis revealed no
proteinuria. Body mass index (BMI) was 22 kg/m2.
The patient was hospitalized with the diagnosis of
severe OHSS, while intravenous fluid replacement,
low molecular weight heparin, and vaginal progesterone
were begun. Β-hCG was 6076 mIU/ml at
hospitalization and decreased onwards. Chest tubes
were inserted bilaterally due to severe dyspnea and
bilateral pleural effusion, while paracentesis was
performed several times due to abdominal distension.
The biochemical values normalized during
hospitalization in 2 months; however, ascites persisted
and new-onset hypertension developed. The
24 hour urine protein analysis was 18.9 gr, while
renal biopsy revealed global and segmental sclerosis
in glomeruli and mesangial arteritis, as well
as proliferations in visceral epithelial cells (IgA
nephropathy, Figes, ). Corticosteroid and immunosuppressive
treatment was begun, but symptoms
of nephrotic syndrome persisted.


A 45 year old healthy woman presented with a thigh mass for one and a half year. The mass insidiously increased in size with no associated pain; however it was associated with difficulty in walking and maintaining upright posture during sitting. There were no associated co-morbids. The clinical suspicion was that of a malignant soft tissue neoplasm. Preoperative findings revealed that the mass was well circumscribed peripherally and not adherent to adjacent muscles, however it was firmly adherent to the underlying bone. Trucut biopsy of the mass was done and the diagnosis was suggestive of a lipomatous tumor.
X-ray revealed a well defined radiolucent lesion in the soft tissues of lower one-third of the thigh along antero-medial aspect of the femur. It shows areas of ossification with fine trabeculations (Figure ).
MRI revealed a well defined lesion with signal intensity suggestive of fat along the distal shaft of the femur, predominantly along its antero-medial aspect. It measures approximately 8 cm × 6.5 cm × 14 cm (APx TSx CC) displacing and wrapping the adjacent muscles. It shows lobulated and trabeculated areas which appear low on pulse sequences, most likely representing areas of ossification with no evidence of erosion of underlying bone (Figure ).
Hematoxylin and eosin sections of the tumor revealed mature adipocytes having eccentric nuclei devoid of atypia and large clear cytoplasmic vacuoles intermixed with adipocytes, possessing mature bony trabeculae with prominent osteoblastic rimming. Zonation pattern was absent. Intervening fibrous septa were appreciated with absence of lipoblast, atypical cells in soft tissue component of the tumor and fibroblastic type stroma (Figure ).


A 15 year old male reported to the Department of Dentistry, University College of Medical Sciences, with the chief complaint of having lost most of his teeth and inability to chew with the remaining ‘loose’ teeth.
Medical history revealed that the patient had been suffering from recurrent skin infections since an early age with thickening and subsequent peeling of the skin of his hands and feet, for which he had been undergoing intermittent treatment. His grandfather had similar dermatological lesions.
Past dental history revealed that the patient had lost all his deciduous teeth by about 3 years of age. A number of his permanent teeth also became mobile soon after eruption and were subsequently extracted.
On clinical examination, the patient presented with a reduced facial height and a senile appearance. There was bilateral palmoplanter keratoderma with symmetric, well-demarcated, yellowish, keratotic plaques on the skin of his palms and soles extending onto the dorsal surfaces (Fig. ).
Intraoral examination revealed that most of his teeth were missing and those present were Grade III mobile. The Panoramic radiograph demonstrated advanced bone loss giving the teeth a characteristic “Floating in air” appearance (Fig. ).
Routine clinical investigations such as complete blood hemogram, liver profile, renal profile and ultrasound of the abdomen and pelvis were all normal. Histopathological examination of gingival tissue as well as punch biopsy of skin of palms and soles revealed mild acanthosis and dense chronic mononuclear infiltrate in the connective tissue.
An assessment of the patient’s intellect using Bhatia’s Battery of Intelligence test revealed that he had an IQ of 97, which falls in the category of Average Intelligence.
Co-relating the characteristic medical and dental history, intraoral findings and laboratory and histopathological investigations, the condition was diagnosed as Papillon-Lefèvre Syndrome. Since all the patient’s remaining teeth had very poor prognosis due to extensive bone loss, they were planned for extraction. Following due informed consent, the extractions were carried out in a phased manner followed by a healing period of 8 weeks, which was uneventful.
Treatment options for prosthodontic rehabilitation were discussed and considering the patient’s age and poor socioeconomic status, a set of complete dentures was planned for now, not ruling out the use of dental implants in future. Complete maxillary and mandibular dentures were delivered (Fig. ) and the patient was recalled for follow up and necessary adjustments.
The patient was referred to the Department of Dermatology for management of cutaneous lesions where treatment with emollients and Acretenin was initiated.


The patient, a 61-year-old woman, presented to the Oral Surgery and Implantology Center for implant placement in the jaw. The patient’s medical history was positive for osteoporosis and she had been taking oral alendronate (70 mg/weekly) for 6 years and 6 months. After consultation with her orthopaedic surgeon, the medication was removed 6 months before making the serum CTX test. The result was 340 pg/mL, a value that corresponds with “no risk of ONJ” according to Marx et al. () criteria. Dental implants at 4.5 (series 4 of 13mm) and at 4.7 (series 3 of 13mm) (Defcon® Avantblast, Impladent, Senmenat, Barcelona, Spain) were placed, following the guidelines of the AAOMS of 2007. Surgery was minimally invasive, proceeding without incident, in a single phase, and placing crestal healing abutments (Fig. ). Postoperative prescriptions consisted of amoxicillin 500 mg and 125 mg of clavulanic acid, 1/8h, for 7 days. Two weeks later, the patients presented an asymptomatic bone exposure of 1mm x 3mm, in the lingual area of implant 4.5 (Fig. D). A periapical radiography revealed a radiolucency distal of 4.5 (Fig. A). After 6 weeks with no tissue healing (criterion established by the AAOMS in 2007) and no remission of the bone necrosis, and after dismissing other possible causes of the lesion, the patient was classified as stage 1 of ONJ (exposed and necrotic bone in asymptomatic patients without evidence of infection). The treatment indicated by the AAOMS in these patients was established: rinses (0.12%, 3 times/day) and gel (0.2% 3 times/day) of chlorhexidine. The importance of maintaining good oral hygiene was emphasized to the patient.
Healing improved with this treatment, decreasing the area of exposed bone (Fig. E), with neither infection nor pain at any time. Treatment was maintained resulting in complete uneventful healing of the surgical site at 7 months. Clinical (Fig. F) and radiographic examination showed bone resorption distal of 4.5 (Fig. B), disap-pearance of the radiolucent image suggestive of necrotic bone, and being bone resorption higher in this region (distal of the implant in 4.5) than in unaffected regions (mesial of the implant in 4.5; mesial and distal of the implant in 4.7). At 1 year, no clinical or radiographic changes were observed (Fig. C); peri-implant bone level was stable. The prosthesis over implants was placed 3 months after healing (Fig. ).


A 65-year-old Hispanic male was brought to the emergency department due to severe shortness of breath at home. The shortness of breath started approximately one week prior to presentation and had progressively worsened over time. Upon arrival to the emergency department the patient was hypoxemic and in severe respiratory distress, with minimal bilateral breath sounds on auscultation and an oxygen saturation of 88%.
He had a past medical history of severe chronic obstructive pulmonary disease (COPD), treated with home oxygen over the last year, history of AIDS for 17 years, receiving antiretroviral medications, (last documented HIV RNA load of 14,070 copies/mm3 and a CD4 count of 285/mm3). He had history of intravenous heroin use which he quit 6 years earlier, active heavy marijuana smoking for the last 20 years on a daily-basis, and no history of tobacco use.
On physical examination the patient was intubated on mechanical ventilation, with reduced bilateral breath sounds and minimal chest wall expansion. Arterial blood gas analysis showed respiratory acidosis with no other laboratory abnormalities. serum antineutrophil antibodies (ANA) were negative; serum angiotensin converting enzyme (ACE) and alpha 1 antitrypsine were at normal levels. Chest X-ray showed hyperinflation with increased lucency in bilateral upper lobes (). Chest CT revealed multiple large subpleural bullae occupying more than one-third of the hemithorax, characteristic of VLS (Figures and ).
During the course of hospitalization, while on mechanical ventilation, the patient developed a tension pneumothorax secondary to ruptured bullae, requiring a chest tube placement. He was later referred for surgical bullectomy.