Comparison of the effects of surgical dissection devices on the rabbit liver.

PURPOSE: Multiple energy-based surgical dissection and coagulation modalities are available to facilitate surgical dissection and hemostasis, but there is limited information regarding the acute tissue effects of these devices. Our objective was to compare the functional characteristics and tissue effects of four energy-based surgical dissection and coagulation modalities on the rabbit liver. METHODS: Linear incisions were created in the rabbit liver using monopolar electrocautery, a harmonic scalpel, a PlasmaBlade and a new ferromagnetic induction loop device. Subjective cutting and coagulation characteristics for each device were recorded, and the histological tissue effects were evaluated. RESULTS: Each of the modalities successfully incised the liver tissue. The PlasmaBlade and the ferromagnetic induction loop exhibited significantly less perceived tissue drag during the incision, significantly less collateral tissue damage and significantly better margin uniformity than the monopolar electrocautery device. Each device showed comparable subjective hemostasis. The harmonic scalpel did not demonstrate a significant difference compared with any of the other devices in any of the parameters examined. The histological analysis revealed that the least lateral thermal damage resulted when the PlasmaBlade, harmonic scalpel and ferromagnetic induction loop were used, and the most damage occurred with the use of monopolar electrocautery. CONCLUSIONS: Each of the newer energy-based surgical tools showed improvement over monopolar electrocautery with regard to lateral thermal injury, and the ferromagnetic induction device and the PlasmaBlade demonstrated superior surgical tissue handling characteristics to the monopolar electrocautery device.

Giant necrotic pituitary apoplexy.

Apoplexy of the pituitary gland is a rare complication of pituitary adenomas, involving hemorrhage with or without necrosis within the tumor. This condition may be either asymptomatic or may present with severe headache, visual impairment, ophthalmoplegia, and pituitary failure. Transsphenoidal surgery is the treatment of choice, and early intervention is usually required to ensure reversal of visual impairment. Reports of pituitary apoplectic lesions exceeding 60.0mm in diameter are very rare. A 39-year-old man with long-standing history of nasal congestion, decreased libido and infertility presented with a sudden onset of severe headache and diplopia. MRI of the head demonstrated a massive skull base lesion of 70.0 × 60.0 × 25.0mm, compatible with a giant pituitary macroadenoma. The lesion failed to enhance after administration of a contrast agent, suggesting complete necrotic apoplexy. Urgent surgical decompression was performed, and the lesion was resected via a transnasal transsphenoidal approach. Pathological analysis revealed evidence of necrotic pituitary apoplexy. At the 2 month follow-up, the patient had near-complete to complete resolution of his visual impairment. To the authors' knowledge, this report is unique as the patient demonstrated complete necrotic apoplexy and it underlines the diagnostic dilemma in such a case.

Functional genomics identifies drivers of medulloblastoma dissemination.

Medulloblastomas are malignant brain tumors that arise in the cerebellum in children and disseminate via the cerebrospinal fluid to the leptomeningeal spaces of the brain and spinal cord. Challenged by the poor prognosis for patients with metastatic dissemination, pediatric oncologists have developed aggressive treatment protocols, combining surgery, craniospinal radiation, and high-dose chemotherapy, that often cause disabling neurotoxic effects in long-term survivors. Insights into the genetic control of medulloblastoma dissemination have come from transposon insertion mutagenesis studies. Mobilizing the Sleeping Beauty transposon in cerebellar neural progenitor cells caused widespread dissemination of typically nonmetastatic medulloblastomas in Patched(+/-) mice, in which Shh signaling is hyperactive. Candidate metastasis genes were identified by sequencing the insertion sites and then mapping these sequences back to the mouse genome. To determine whether genes located at transposon insertion sites directly caused medulloblastomas to disseminate, we overexpressed candidate genes in Nestin(+) neural progenitors in the cerebella of mice by retroviral transfer in combination with Shh. We show here that ectopic expression of Eras, Lhx1, Ccrk, and Akt shifted the in vivo growth characteristics of Shh-induced medulloblastomas from a localized pattern to a disseminated pattern in which tumor cells seeded the leptomeningeal spaces of the brain and spinal cord.

Reducing bodies and myofibrillar myopathy features in FHL1 muscular dystrophy.

OBJECTIVE: Some pathologic features of the FHL1 myopathies and the myofibrillar myopathies (MFMs) overlap; we therefore searched for mutations in FHL1 in our cohort of 50 patients with genetically undiagnosed MFM. METHODS: Mutations in FHL1 were identified by direct sequencing. Polymorphisms were excluded by using allele-specific PCR in 200 control subjects. Structural changes in muscle were analyzed by histochemistry, immunocytochemistry, and electron microscopy. RESULTS: We detected 2 novel and 1 previously identified missense mutation in 5 patients. Patients 1-4 presented before age 30, display menadione-nitro blue tetrazolium-positive reducing bodies, and harbor mutations in the FHL1 LIM2 domain. Patient 5 presented at age 75 and has no reducing bodies, and his mutation is not in a LIM domain. The clinical features include progressive muscle weakness, hypertrophied muscles, rigid spine, and joint contractures, and 1 patient also has peripheral neuropathy. High-resolution electron microscopy reveals the reducing bodies composed of 13-nm tubulofilaments initially emanating from Z-disks. At a more advanced stage, abundant reducing bodies appear in the cytoplasm and nuclei with concomitant myofibrillar disintegration, accumulation of cytoplasmic degradation products, and aggregation of endoplasmic reticulum and sarcotubular profiles. CONCLUSIONS: FHL1 dystrophies can be associated with MFM pathology. Mutations in the LIM2 domain are associated with reducing bodies composed of distinct tubulofilaments. A mutation extraneous to LIM domains resulted in a mild late-onset phenotype with MFM pathology but no reducing bodies.

Malignant peripheral nerve sheath tumour of the trigeminal nerve: case report and literature review.

Although all trigeminal nerve schwannomas are uncommon, malignant schwannomas are extraordinarily rare. We describe a patient who presented with clinical and radiological features of a trigeminal schwannoma; however, pathological analysis showed a malignant peripheral nerve sheath tumour (WHO Grade IV). We discuss these extremely rare tumours and their management.

Isolated intradural lumbosacral tailgut cyst with carcinoid features.

Tailgut cysts are developmental cysts that arise from remnants of the embryonic postanal gut and are typically located within the presacral, retrorectal space. Isolated cases of aberrant locations, including prerectal, perirenal, perianal, retrovesical, and subcutaneous locations, have been reported. Malignant transformations with the presence of adenocarcinomas or carcinoids have been recognized within these entities. It is well recognized that anterior sacrococcygeal abnormalities are present and are frequently caused by the slow-growing nature of the tailgut cysts and related mass effect; however, the authors are aware of no reports in the literature of isolated tailgut cysts within the thecal sac in direct contact with neural elements, without extension into the peritoneal cavity. In this case, a 28-year-old woman presented with progressive back pain, frequent urinary tract infections, and bowel dysfunction. She was found to have a purely intradural tailgut cyst with malignant transformation consistent with carcinoid. No peritoneal extension of her disease was found. The authors hypothesize that this is a rare developmental aberration that has not been commonly recognized and potentially has implications for embryological development.

Coexisting rathke cleft cyst and pituitary adenoma presenting with pituitary apoplexy: report of two cases.

The authors report two cases of coexisting Rathke cleft cyst (RCC) and pituitary macroadenoma. Both patients presented at the university hospital with pituitary apoplexy symptoms of sudden-onset headache while undergoing treatment with Coumadin (warfarin). Magnetic resonance imaging was consistent with a pituitary adenoma in one case and RCC in the other. Intraoperative findings and pathological work-up identified RCC along with adenomatous tissue displaying hemorrhagic pituitary adenoma in one and hemorrhagic RCC in the other. Clinical symptoms of pituitary apoplexy were present in both cases, making pituitary and RCC apoplexy clinically indistinguishable. RCC and concomitant pituitary adenoma are a rare intraoperative finding that must be considered as a differential diagnosis in patients with symptoms of pituitary adenoma apoplexy.

Cystic granular cell tumor mimicking Rathke cleft cyst.

Symptomatic granular cell tumors of the neurohypophysis are a rarely reported entity. To the authors' knowledge, they report the first fully described case of a symptomatic granular cell tumor with a large cystic component. A 31-year-old woman presented with headaches and visual complaints with imaging findings confirming a cystic sellar and suprasellar mass. The lesion was resected, and histological examination confirmed the diagnosis. The literature has shown that granular cell tumors are rarely reported as being symptomatic but may actually be a fairly common finding in autopsy studies. The authors review the literature with a specific focus on radiographic findings in patients with symptomatic granular cell tumors.

Capillary telangiectasias: clinical, radiographic, and histopathological features. Clinical article.

OBJECT: Brain capillary telangiectasias (BCTs) are small, clinically benign, angiographically occult lesions that are usually incidental findings. Large capillary telangiectasias have not been reported previously as most BCTs are very small. Symptomatic BCTs are also rare, with few reports in the literature. The authors review the clinical manifestations, imaging, and histopathological characteristics of BCTs to further elucidate the diagnostic and clinical features of these vascular malformations. METHODS: The authors completed a retrospective radiological review of all cases of BCTs in the neuroradiology database at the University of Utah involving patients treated between January 1993 and December 2007. The MR imaging scans were reviewed, and the BCT was measured in 2 dimensions. They arbitrarily chose > 1 cm to define a large BCT as a majority of these lesions were smaller than that. The medical chart and the electronic database were used to gather each patient's clinical information. RESULTS: One hundred thirty patients were identified in the archived neuroradiology database of capillary telangiectasias. Cases involving 105 patients with definite capillary telangiectasias were reviewed, and from these, 7 patients were identified to have a large capillary telangiectasia measuring > 1 cm. Upon further review, 2 of these patients were identified as having symptoms likely related to their capillary telangiectasia. These 2 cases are reported in the article. No patients with smaller BCTs were found to have symptoms related to their lesion. CONCLUSIONS: Brain capillary telangiectasias are small vascular malformations that rarely cause symptoms. They are often overlooked on imaging because of their clinically benign nature; however, they have been misdiagnosed as glial tumors in the past. Specific MR imaging sequences (T1-weighted postcontrast and gradient refocused echo) are valuable in aiding diagnosis, as histopathological diagnosis is often not possible. These cases highlight that BCTs can cause symptoms, a finding that may actually be related to the size of the lesion (28.6% of large BCTs in this series were symptomatic, whereas none of the small ones were).

Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1.

We recently identified the X-chromosomal four and a half LIM domain gene FHL1 as the causative gene for reducing body myopathy, a disorder characterized by progressive weakness and intracytoplasmic aggregates in muscle that exert reducing activity on menadione nitro-blue-tetrazolium (NBT). The mutations detected in FHL1 affected highly conserved zinc coordinating residues within the second LIM domain and lead to the formation of aggregates when transfected into cells. Our aim was to define the clinical and morphological phenotype of this myopathy and to assess the mutational spectrum of FHL1 mutations in reducing body myopathy in a larger cohort of patients. Patients were ascertained via the detection of reducing bodies in muscle biopsy sections stained with menadione-NBT followed by clinical, histological, ultrastructural and molecular genetic analysis. A total of 11 patients from nine families were included in this study, including seven sporadic patients with early childhood onset disease and four familial cases with later onset. Weakness in all patients was progressive, sometimes rapidly so. Respiratory failure was common and scoliosis and spinal rigidity were significant in some of the patients. Analysis of muscle biopsies confirmed the presence of aggregates of FHL1 positive material in all biopsies. In two patients in whom sequential biopsies were available the aggregate load in muscle sections appeared to increase over time. Ultrastructural analysis revealed that cytoplasmic bodies were regularly seen in conjunction with the reducing bodies. The mutations detected were exclusive to the second LIM domain of FHL1 and were found in both sporadic as well as familial cases of reducing body myopathy. Six of the nine mutations affected the crucial zinc coordinating residue histidine 123. All mutations in this residue were de novo and were associated with a severe clinical course, in particular in one male patient (H123Q). Mutations in the zinc coordinating residue cysteine 153 were associated with a milder phenotype and were seen in the familial cases in which the boys were still more severely affected compared to their mothers. We expect the mild end of the spectrum to significantly expand in the future. On the severe end of the spectrum we define reducing body myopathy as a progressive disease with early, but not necessarily congenital onset, distinguishing this condition from the classic essentially non-progressive congenital myopathies.

Recurrent cerebellar hemangioblastoma with enhancing tumor in the cyst wall: case report.

OBJECTIVE: Hemangioblastomas are the most common primary intra-axial tumors of the adult posterior fossa and the tumors most often associated with von Hippel-Lindau disease. Resection of cerebellar hemangioblastomas involves tumor excision and drainage of associated cysts. The cyst wall is considered devoid of tumor cells and is not excised. We present an unusual variant of a hemangioblastoma that showed pathological evidence of a tumor within the cyst wall that correlated with radiographic cyst wall enhancement in a patient with a recurrent hemangioblastoma. CLINICAL PRESENTATION: A 38-year-old woman with von Hippel-Lindau disease presented with a recurrent cerebellar hemangioblastoma despite two previous operations during which the mural nodule was removed but the cyst wall was not. Magnetic resonance imaging showed a cystic lesion with an enhancing mural nodule with atypical nodular enhancement throughout the cyst wall. INTERVENTION: Because the patient had a history of multiple recurrences, gross total resection of the mural nodule and cyst wall was performed. At surgery, neovascularization and neoplasia within the cyst wall were visualized. Histopathological examination showed a capillary hemangioblastoma with tumor tissue inside the cyst wall. No clinical or radiographic evidence of recurrence was observed during 2 years of follow-up monitoring. CONCLUSION: This unusual case of a hemangioblastoma with cyst wall enhancement demonstrates a correlation between enhancement on magnetic resonance imaging and presence of neoplasia within the cyst wall, as well as the importance of considering complete resection of these areas, including the cyst wall, for the prevention of recurrence.

Sporadic fatal insomnia masquerading as a paraneoplastic cerebellar syndrome.

BACKGROUND: Sporadic fatal insomnia is a rare prion disease that has recently been recognized. OBJECTIVE: To report a unique case of sporadic fatal insomnia in a woman with progressive cerebellar deterioration who was originally thought to have a paraneoplastic cerebellar syndrome. DESIGN: Case report describing a patient with autopsy-proven sporadic fatal insomnia. PATIENT: A 56-year-old woman with progressive cerebellar ataxia who was found to have a retroperitoneal non-Hodgkin lymphoma. RESULTS: Autopsy demonstrated marked degenerative changes in the thalamus, cerebellum, and inferior olivary nucleus. A mild spongiform change was present in the thalamus and cortical gray matter. Western blot analysis confirmed the presence of abnormal, protease-resistant prion protein (PrP(Sc)), characteristic of sporadic fatal insomnia. CONCLUSIONS: Clinicians should be aware of this rare prion disease and should strongly consider the importance of autopsy toward the investigation of unusual neurological diseases.

Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy.

Reducing body myopathy (RBM) is a rare disorder causing progressive muscular weakness characterized by aggresome-like inclusions in the myofibrils. Identification of genes responsible for RBM by traditional genetic approaches has been impossible due to the frequently sporadic occurrence in affected patients and small family sizes. As an alternative approach to gene identification, we used laser microdissection of intracytoplasmic inclusions identified in patient muscle biopsies, followed by nanoflow liquid chromatography-tandem mass spectrometry and proteomic analysis. The most prominent component of the inclusions was the Xq26.3-encoded four and a half LIM domain 1 (FHL1) protein, expressed predominantly in skeletal but also in cardiac muscle. Mutational analysis identified 4 FHL1 mutations in 2 sporadic unrelated females and in 2 families with severely affected boys and less-affected mothers. Transfection of kidney COS-7 and skeletal muscle C2C12 cells with mutant FHL1 induced the formation of aggresome-like inclusions that incorporated both mutant and wild-type FHL1 and trapped other proteins in a dominant-negative manner. Thus, a novel laser microdissection/proteomics approach has helped identify both inherited and de novo mutations in FHL1, thereby defining a new X-linked protein aggregation disorder of muscle.

Hypericin-mediated photodynamic therapy of pituitary tumors: preclinical study in a GH4C1 rat tumor model.

OBJECTIVE: Hypericin-mediated photodynamic therapy (PDT) is receiving greater interest as a potential treatment for a variety of tumors and nonmalignant disorders. PDT involves systemic administration of a photosensitizer that selectively accumulates within tumor tissue followed by focal light activation. In the presence of molecular oxygen, a photochemical reaction generates a reactive oxygen species that induces apoptosis in target cells. The purpose of this preclinical study was to evaluate the efficacy of hypericin-mediated PDT for treatment of pituitary adenoma in a rodent model. METHODS: Wistar-Furth rats were implanted with a pituitary adenoma rat cell line, GH4C1. Tumor masses were allowed to develop over 28 days; rats with tumors of comparable sizes were then assigned to three treatment groups: control (neither hypericin nor light); light only; and hypericin and light. Hypericin was administered in four doses (1 mg/kg) at 28-h intervals prior to light exposure, wherein those rats treated with light were exposed to a light source four hours after the last hypericin dose. Tumor size was measured up to 12 days after treatment. RESULTS: Over the short interval examined, hypericin-mediated PDT was not effective against large tumors greater than 1 cm(3), but this treatment significantly slowed tumor growth for tumors less than 1 cm(3). Histological evaluation and TUNEL assay of the treated tumor identified apoptotic clusters on the periphery of the PDT-treated specimens. CONCLUSIONS: Hypericin-mediated PDT shows promise in its effectiveness in the treatment of residual small tumor rests.

Extranodal NK/T-cell lymphoma presenting as a pituitary mass. Case report and review of the literature.

Primary pituitary lymphomas (PPLs) are rare tumors of the central nervous system, and most are of B-cell origin. Extranodal NK/T-cell lymphomas are uncommon neoplasms that are highly aggressive and show a strong association with Epstein-Barr virus. They most commonly affect the nasal cavity and paranasal sinuses; manifestation as a primary pituitary tumor has never been described. The authors report a case of NK/T-cell lymphoma of the pituitary gland and review 17 cases of PPL from the literature. All patients had been evaluated at presentation for clinical, neuroimaging, and histopathological findings. Patients who had systemic lymphoma with secondary involvement of the pituitary gland were excluded. The mean patient age was 55.5 years (range 26-86 years); the male/female ratio was 13:5. The most common presentation was pituitary insufficiency (72%), followed by headache (56%), diplopia (39%), visual loss (28%), and fever (22%). Thirteen patients (72%) exhibited anterior hypopituitarism and seven (39%) had diabetes insipidus at presentation. Magnetic resonance imaging demonstrated enhancing parasellar masses with diffuse enlargement of the pituitary gland (94%), suprasellar extension (44%), cavernous sinus extension (39%), and stalk thickening (22%). Thirteen patients (72%) had B-cell lymphoma, four (22%) had T-cell lymphoma, and one (6%) had NK/T-cell lymphoma. Primary pituitary lymphomas are rare entities with a range of clinical presentations and neuroimaging findings that are unique from those of patients who present with pituitary adenomas. The pathological entity of NK/T-cell lymphoma is distinct, and its course is very aggressive with a poor prognosis.

Neuroradiologic characteristics of astroblastoma.

INTRODUCTION: Astroblastoma is a rare glial tumor of uncertain origin. Only a few scattered case reports and one small case series have described the radiologic appearance of this uncommon tumor. Many features previously identified are similar to those of other primary malignant brain tumors. We report the largest imaging series to date and further delineate the CT and MRI features of astroblastoma. We identify those features that may be useful in distinguishing astroblastoma from other neoplasms. METHODS: The radiologic images, pathology reports, and clinical information of 12 patients with pathology-confirmed astroblastoma were retrospectively reviewed. CT and MRI findings including location, morphology, signal intensity, and presence and patterns of enhancement were tabulated. RESULTS: Patients ranged in age from 0 (newborn) to 50 years with a mean of 20 years at the time of initial diagnosis. A striking female preponderance (11:1) was found. All tumors were supratentorial. There were multiple intratumoral cysts in 7 (58%) of the 12 patients. Nine (75%) showed strong rim enhancement and 3 (25%) showed no rim enhancement. CONCLUSION: The imaging features of astroblastoma are identified in 12 previously unreported cases. Distinguishing features that can be used to narrow the differential diagnosis with more common primary brain neoplasms reflect a combination of age, anatomic location, and specific imaging findings such as demarcation, heterogeneous tumor enhancement, rim enhancement, and a multicystic "bubbly" appearance. Intraventricular location, intratumoral hemorrhage with a fluid-fluid level, and dural "tails" are less common but important additions to the imaging spectrum.