Biomedical subjects

Bernd W Scheithauer

Publications and source records attributed to Bernd W Scheithauer.

At least 19 recordsLinked to original sources

PubMed2007

Microglia in gemistocytic astrocytomas.

OBJECTIVE: Although gemistocytic astrocytomas are graded as World Health Organization II astrocytomas, they behave more aggressively than other astrocytomas. Their proliferative potential is low, and it remains an intriguing question why these tumors are so biologically "successful." They show a high mutation rate of the P53 gene, cytological abnormalities, and frequent perivascular mononuclear infiltrates. Microglial cells, a feature of this astrocytoma variant, are of increasing interest in the context of glioma growth. METHODS: We selected 23 tumor biopsies from 201 samples obtained from patients with gemistocytic astrocytomas operated at Mayo Clinic between 1985 and 1998. These tumors were formerly analyzed for P53 mutations, p53 protein, and proliferative activity (). Immunolabeling for three microglial markers, including CR3/43, Ki-M1P, and iba1, was performed on adjacent tissue sections. In addition, in situ hybridization for the alpha-chain of the major histocompatibility complex (MHC) Class II molecule recognized by the CR3/43 monoclonal antibody was performed. RESULTS: A high number of microglia was detected in gemistocytic astrocytomas. More microglia were present if the fraction of gemistocytic tumor cells was high (correlation coefficient = 0.699; P < 0.0002). Interestingly, a number of gemistocytes were immunoreactive for MHC Class II molecules, an observation confirmed by in situ hybridization. Importantly, the higher the number of Class II immunoreactive gemistocytes, the fewer Class II positive microglial cells could be detected (correlation coefficient = -0.5649; P < 0.005). CONCLUSION: Our results support the view that gemistocytic astrocytomas contain unusually high numbers of microglial cells. We propose that the finding of aberrant MHC Class II expression by gemistocytic tumor cells correlates with a loss of immune-competent MHC Class II-expressing microglia. This may be related to the especially poor prognosis of gemistocytic astrocytomas for which induction of T cell anergy could provide one explanation.

Adult↗

PubMed2007

Genetic aberrations in gliomatosis cerebri.

OBJECTIVE: Identifying the genetic alterations in gliomatosis cerebri (GC) may yield clinically useful prognostic markers and provide clues as to whether GC represents a distinct pathological entity or is an extreme form of diffusely infiltrative glioma. METHODS: Clinical histories, treatment histories, magnetic resonance imaging, and pathological analysis of patients with GC treated at either the University of California San Francisco or the Mayo Clinic were reviewed. Degenerate oligonucleotide-primed polymerase chain reaction was performed on biopsy samples of GC. Comparative genomic hybridization was used to determine relative deoxyribonucleic acid copy number. We evaluated relationships of clinical and radiological treatment and comparative genomic hybridization data to survival after diagnosis with Cox regression analysis. RESULTS: Radiographic analysis and biopsy specimens were available for study in 29 patients (17 men, 12 women). Comparative genomic hybridization was successfully performed in 22 patients. Contrast enhancement was the most significant predictor of poor survival (P = 0.0026). Loss of chromosomes 13q and 10q and gains of 7q were also independent significant predictors of poor survival (P = 0.0032, 0.0335, and 0.0487, respectively). Patients treated with temozolomide or with radiation therapy had improved survival, but this effect did not reach statistical significance (P = 0.180 and 0.124, respectively). CONCLUSION: Chromosomal aberrations associated with aggressive astrocytomas are predictors of poor outcome in patients with GC. This suggests that GC may be an architectural variant of diffuse astrocytomas. The presence of these aberrations and the presence of any contrast enhancement on magnetic resonance imaging scans are possible stratifiers for patients with GC. Stratification of GC into higher- and lower-grade forms may be useful in tailoring treatments to patients with this disease.

Adult↗

PubMed2006

Central neurocytoma: management recommendations based on a 35-year experience.

PURPOSE: To examine the outcomes of patients with histologically confirmed central neurocytomas. METHODS AND MATERIALS: The data from 45 patients with central neurocytomas diagnosed between 1971 and 2003 were retrospectively evaluated. Various combinations of surgery, radiotherapy (RT), and chemotherapy had been used for treatment. RESULTS: The median follow-up was 10.0 years. The 10-year overall survival and local control rate was 83% and 60%, respectively. Patients whose tumor had a mitotic index of <3 (per 10 high-power fields) experienced a 10-year survival and local control rate of 89% and 74%, respectively, compared with 57% (p = 0.040) and 46% (p = 0.14) for patients with a tumor mitotic index of > or =3. The 10-year survival and local control rate was 90% and 74% for patients with typical tumors compared with 63% (p = 0.055) and 46% (p = 0.41) for those with atypical tumors. A comparison of gross total resection with subtotal resection showed no significant difference in survival or local control. Postoperative RT improved local control at 10 years (75% with RT vs. 51% without RT, p = 0.045); however, this did not translate into a survival benefit. No 1p19q deletions were found in the 19 tumors tested. CONCLUSION: Although the overall prognosis is quite favorable, one-third of patients experienced tumor recurrence or progression at 10 years, regardless of the extent of the initial resection. Postoperative RT significantly improved local control but not survival, most likely because of the effectiveness of salvage RT. For incompletely resected atypical tumors and/or those with a high mitotic index, consideration should be given to adjuvant RT because of the more aggressive nature.

Adolescent↗

PubMed2006

Significance of necrosis in grading of oligodendroglial neoplasms: a clinicopathologic and genetic study of newly diagnosed high-grade gliomas.

PURPOSE: High-grade gliomas (HGGs; WHO grades 3-4) are highly diverse, with survival times ranging from months to years. WHO 2000 grading criteria for high-grade oligodendroglial neoplasms [anaplastic oligoastrocytoma (AOA) and anaplastic oligodendroglioma (AO)] remain subjective, and the existence of grade 4 variants is controversial. PATIENTS AND METHODS: Overall survival (OS) of 1,093 adult patients with a cerebral HGG newly diagnosed between 1990 and 2005 was analyzed by univariate and multivariate models for significance of the following factors: patient age, surgery type, year of diagnosis, endothelial proliferation, necrosis, oligodendroglial histology, treatment center, and chromosome 1p, 19q, 7p (EGFR), and 10q (PTEN) abnormalities by fluorescence in situ hybridization (FISH). RESULTS: Necrosis was a statistically significant predictor of poor OS on univariate and multivariate analyses in AOA but not in AO. Median OS for patients with necrotic AOA (22.8 months) was significantly worse than for patients with non-necrotic AOA (86.9 months; P < .0001) but was better than conventional glioblastomas (9.8 months; P < .0001). In addition to patient age, the following were significant independent prognostic factors (P .001): grade and surgery type for the entire HGG cohort; modified grade for AOA (3 v 4); and modified grade, 1p/19q codeletion status, and oligodendroglial histology for the 586 HGGs analyzed by FISH. CONCLUSION: Stratification of AOA, but not of pure AO, into grades 3 and 4 on the basis of necrosis is prognostically justified and is more powerful than the current approach. Both routine histology and genetic testing provide independent, prognostically useful information.

Adult↗

PubMed2006

Low grade malignant peripheral nerve sheath tumor with smooth muscle differentiation.

Malignant peripheral nerve sheath tumors are usually Schwann cell derived. Differentiation along mesenchymal lines is uncommon. Herein we present an example with smooth muscle differentiation occurring in the left distal forearm of a 62-year-old male with neurofibromatosis type I. Incisional biopsy of the slowly growing mass demonstrated a low-grade malignant peripheral nerve sheath tumor with strong S-100 protein immunoexpression as well as focal smooth muscle actin staining in atypical neoplastic cells. Immunostains for epithelial membrane antigen, neurofilament protein, glial fibrillary acidic protein, CD57, desmin, and myogenin were negative. The MIB-1 labeling index was 5.4%. Electron microscopy revealed arrays of microfilaments (actin myofilaments) variably associated with fusiform dense bodies, plasmalemmal micropinocytotic vesicles, and foci of external lamina (basement membrane) consistent with smooth muscle differentiation. Smooth muscle should be added to the spectrum of differentiation exhibited by malignant peripheral nerve sheath tumors. Its recognition requires exclusion of the alternative diagnosis of leiomyosarcoma.

Biopsy↗

PubMed2006

Ependymomas with neuronal differentiation: a morphologic and immunohistochemical spectrum.

The category of mixed glioneuronal tumors of the CNS is rapidly losing its definition as encompassing tumors composed of histologically distinct neuron variants and glia. We encountered five ependymomas with neuronal differentiation seen in two by histology, in two by immunohistochemistry alone, and in one by electron microscopy. Antibodies against GFAP, S-100 protein, neurofilament protein, chromogranin, synaptophysin, Neu-N, and EMA were applied. Ultrastructural studies were also performed. In addition, 33 randomly selected ependymomas of various histologic types were screened for these same antigens. Cases 1 and 2 were anaplastic and showed clearly defined neuropil islands or pale islands as in nodular desmoplastic medulloblastoma, respectively. The tumors affected a 16-year-old male and a 5-year-old female and involved the right frontoparietal lobe and fourth ventricle, respectively. The islands were positive for synaptophysin and Neu-N (cases 1 and 2), and chromogranin (case 1). Cases 3-5, as well as 7 of the 33 screened ependymomas, showed a suggestion of neuronal differentiation by immunohistochemistry alone, including immunoreactivity for Neu-N (n = 8), synaptophysin (n = 4), neurofilament protein (n = 4), and chromogranin (n = 2). Five tumors each were WHO grade II and III. Electron microscopy performed on the two cases with neuronal islands demonstrated microtubule bundles and dense core granules (case 1) and poorly differentiated cells with high nuclear/cytoplasmic ratios, with intermediate filament accumulation and rare cilia (case 2). Cases identified by immunohistochemistry or electron microscopy demonstrated dense core granules (n = 5) and aligned microtubules (n = 3). Neuronal differentiation occurs in ependymomas but is less frequently definitive (histologic, ultrastructural) than merely a limited immunohistochemical finding. The clinical significance of these observations is unknown but deserves further exploration.

Adult↗

PubMed2006

Unusual malignant glioneuronal tumors of the cerebrum of adults: a clinicopathologic study of three cases.

Malignant glioneuronal tumors of the brain are rare and poorly characterized. Herein, we report the clinicopathologic features of three examples with unusual morphologies including both glial and neuronal differentiation. Hematoxylin and eosin-stained slides were reviewed in all cases. Immunohistochemical stains were performed on formalin-fixed, paraffin-embedded sections. Transmission electron microscopy (EM) was performed on both formalin-fixed (n=1) and paraffin embedded tissue (n=2). The immunogold technique for localization of GFAP was also performed. Two patients were male and one was female, age 66, 84, and 34 years, respectively. Radiologic studies demonstrated hyperdensity on CT (n=3), multicentricity (n=2), and a cortical based solid component with a cystic extension into underlying white matter (n=2). At surgery, all three tumors were superficial and relatively circumscribed. Histologically, they were composed of large epithelioid cells (n=3), spindle cells (n=1), and poorly differentiated smaller cells with high nuclear/cytoplasmic ratios (n=1). Brisk mitotic activity and coagulative non-palisading necrosis were present in all cases. The tumors were immunopositive for GFAP (n=3), S-100 (n=3), synaptophysin (n=3), chromogranin (n=3), Neu-N (n=2), and neurofilament protein (n=2). Stains for EMA were negative. EM demonstrated convincing neurosecretory granules in one case, some in filament-containing cells immunogold labeled for GFAP. Two patients expired 3-5 weeks after surgery. True malignant neoplasms with glial and neuronal differentiation do occur in the central nervous system of adults and may pursue a highly aggressive course. The use of minimal diagnostic criteria, e.g., immunoreactivity for a single antigen like neurofilament protein, may not be sufficient and should be discouraged.

Adult↗

PubMed2006

Phase III trial of carmustine and cisplatin compared with carmustine alone and standard radiation therapy or accelerated radiation therapy in patients with glioblastoma multiforme: North Central Cancer Treatment Group 93-72-52 and Southwest Oncology Group 9503 Trials.

PURPOSE: In patients with newly diagnosed glioblastoma multiforme, to determine whether cisplatin plus carmustine (BCNU) administered before and concurrently with radiation therapy (RT) improves survival compared with BCNU and RT and whether survival using accelerated RT (ART) is equivalent to survival using standard RT (SRT). PATIENTS AND METHODS: After surgery, patients were stratified by age, performance score, extent of surgical resection, and histology (glioblastoma v gliosarcoma) and then randomly assigned to arm A (BCNU plus SRT), arm B (BCNU plus ART), arm C (cisplatin plus BCNU plus SRT), or arm D (cisplatin plus BCNU plus ART). RESULTS: Four hundred fifty-one patients were randomly assigned, and 401 were eligible. Frequent toxicities included myelosuppression, vomiting, sensory neuropathy, and ototoxicity and were worse with cisplatin. There was no difference in toxicity between SRT and ART. Median survival times and 2-year survival rates for patients who received BCNU plus RT (arms A and B) compared with cisplatin, BCNU, and RT (arms C and D) were 10.1 v 11.5 months, respectively, and 11.5% v 13.7%, respectively (P = .19). Median survival times and 2-year survival rates for patients who received SRT (arms A and C) compared with ART (arms B and D) were 11.2 v 10.5 months, respectively, and 13.8% v 11.4%, respectively (P = .33). CONCLUSION: Cisplatin administered concurrently with BCNU and RT resulted in more toxicity but provided no significant improvement in survival. SRT and ART produced similar toxicity and survival.

Adult↗

PubMed2006

Anaplastic medulloblastoma with granular cell change.

Granular cell change secondary to lysosomal accumulation has been described in a variety of tumors of the nervous system of presumed glial or schwannian derivation. Herein we report the case of a 15-year-old female with an anaplastic medulloblastoma which histologically demonstrated areas with granular cell change. These granular cells co-expressed neuronal immunohistochemical markers, including synaptophysin, chromogranin, and Neu-N, and demonstrated accumulation of lysosomes and dense core granules in the same cells at the ultrastructural level. This unusual finding suggests that the spectrum of granular cell change should be expanded to include tumors with primarily neuronal differentiation.

Adolescent↗

PubMed2006

Coexisting secondary intraneural and vascular adventitial ganglion cysts of joint origin: a causal rather than a coincidental relationship supporting an articular theory.

OBJECTIVE: To introduce the clinical entity of an intraneural ganglion cyst coexisting with a vascular adventitial cyst arising from the same joint. DESIGN: Retrospective review. PATIENTS: Two patients presented with predominantly deep peroneal neuropathy due to complex superior tibiofibular joint-related cysts. In addition to having peroneal intraneural ganglion cysts, these patients had vascular adventitial cysts: one involving a capsular arterial branch, the other a capsular vein [as well as a large, recurrent, intramuscular (extraneural) ganglion]. We then reviewed MRIs of 12 other consecutive cases of intraneural ganglia (10 peroneal and 2 tibial) arising from the superior tibiofibular joint that we treated, as well as other reported cases in the literature to determine if there were other (unrecognized) examples supporting the combination of clinical findings and radiographic patterns. RESULTS: Retrospective analysis of MRIs in the two surgically proven cases of peroneal intraneural ganglia with vascular adventitial cyst extension showed a common imaging pattern that we have termed "the wishbone sign," consisting of the connection of the ascending limb of the peroneal intraneural ganglion and the longitudinal limb of the vascular adventitial cyst in the axial plane. Our review suggests that vascular adventitial cyst extension occurs in a large proportion of cases of peroneal intraneural ganglia. A similar growth pattern was noted in a case of a tibial intraneural ganglion. CONCLUSIONS: The combination of intraneural and vascular adventitial cysts is understandable given our knowledge of normal and pathologic anatomy of para-articular cysts. The combination of intraneural ganglia and vascular adventitial cysts broadens the spectrum of clinical presentations of these cysts and suggests that cysts and their content can dissect from a joint along neurovascular bundles. These cases provide important evidence to support the articular theory for the pathogenesis of not only neural but vascular adventitial cysts as well.

Diagnosis, Differential↗

PubMed2006

Immunohistochemical expression of nestin in the non-tumorous hypophysis and in pituitary neoplasms.

The aim of the present work was to investigate whether nestin, a member of the intermediate filament family, is immunohistochemically expressed in the non-tumoral human hypophysis and pituitary neoplasms. Twenty-three normal pituitaries and 125 pituitary neoplasms were included. The tissues were formalin-fixed and paraffin embedded. The neoplasms were identified on hematoxylin-eosin stained sections and were classified by immunohistochemistry as well as electron microscopy. For immunohistochemistry, the streptavidin-biotin-peroxidase complex method was applied using appropriate controls. Several corticotrophs in the autopsy obtained pituitaries showed cytoplasmic nestin immunopositivity. No nestin immunoreactivity was found in other cell types in non-tumorous adenohypophyses and in the cells of various pituitary adenomas. Nestin was, however, expressed in a small proportion of endothelial cells in both anterior and posterior lobes. Staining was also noted in several pituicytes, neurohypophysial nerve fibers, and Herring bodies. In contrast to CD-34 and Factor-8 immunostaining which demonstrated immunopositivity in practically all endothelial cells of every capillary, nestin expression was only focally seen suggesting that the functional status of the immunoreactive and non-staining endothelial cells was not the same. No statistically significant correlation was apparent between nestin immunoreactivity and patient age, gender, tumor size, mitotic index, Ki-67, labeling nuclear index, hormonal immunoprofile, and tumor type. In conclusion, nestin expression in adenomas cannot be viewed as a biologically relevant marker of cell proliferation and as a prognostic indicator. The patchy expression of nestin in endothelial cells remains unexplained and its significance requires further studies.

Adenoma↗

PubMed2006

Modulation of VEGF/Flk-1 receptor expression in the rat pituitary GH3 cell line by growth factors.

Both vascular endothelial growth factor (VEGF) and its receptor Flk-1 are expressed in normal pituitary cells and in the prolactin- and growth hormone-producing GH3 cell line of the rat, thus suggesting autocrine/paracrine function. Regulation of the Flk-1 receptor system in pituitary cells is poorly understood, but evidence suggests that up-regulated growth factors play a role in its expression and activation. To study the role of growth factors in this process, we examined changes in VEGF and Flk-1 expression in GH3 cells following varied exposure to betaFGF, EGF, and TGFbeta1. Immunofluorescence labelling and laser scanning cytometry were used to measure changes in VEGF and Flk-1 expression. Results showed that betaFGF, EGF and TGFbeta up-regulated the VEGF/FLK-1 receptor system. Distinct patterns of activation were detected. At 2 hours, EGF and TGFbeta caused no significant changes in VEGF and Flk-1 expression; however, betaFGF up-regulated VEGF expression in 99% of cells but only induced modest changes in Flk-1 overexpression. A similar percentage of cells overexpressed VEGF after 24-hour incubation with betaFGF, but more prominent Flk-1 overexpression was detected. At 24 hours, EGF and TGFbeta1 induced a significant increase in both VEGF and Flk-1 expression. In summary, our findings show that VEGF/Flk-1 expression in pituitary cells may be altered by different growth factors. This may affect angiogenesis and the progression of pituitary tumors.

Animals↗

PubMed2006

Angiomyxofibromatous tumor of the falx cerebri.

We report a distinctive angiomyxofibromatous lesion arising from the falx cerebri of a 48-year-old woman. The tumor was composed of bland-appearing, spindle, and stellate cells in a myxoid matrix with prominent vascularity. The tumor cells were immunopositive diffusely for vimentin and focally for S-100 protein, but were immunonegative for epithelial membrane antigen, CD34, MIC2, Bcl-2, glial fibrillary acidic protein, cytokeratin CAM 5.2, desmin, and smooth muscle actin. This lesion could not be categorized according to the current World Health Organization classification of tumors of the nervous system, thus underscoring a need to enhance our understanding of myxoid mesenchymal neoplasms and reassess their nosology.

Angiofibroma↗

PubMed2006

Vascularization of rat pituitary autografts.

Pituitary autotransplantation eliminates direct vascular contact between the hypothalamus and the adenohypophysis, and enables us to study the role of the hypothalamus in regulating adenohypophysial endocrine activity. The aim of this study was to investigate vascularization of the pituitary autografts. Three-month-old male Wistar rats were hypophysectomized, and their adenohypophyses were autotransplanted under the renal capsule. The animals were killed 3 weeks after autotransplantation. The grafts were removed and studied by using histology, immunohistochemistry and transmission electron microscopy. In the central portion of the grafts, organizing necrosis was apparent. The peripheral portion of the graft contained all adenohypophysial cell types, with a predominance of lactotrophs. Vascular endothelial growth factor and hypoxia-inducible factor were expressed in the graft mainly in the perinecrotic areas. Several capillaries inside the grafts were lined by continuous unfenestrated epithelium, while others were lined by fenestrated endothelium, suggesting that neovascularization is the result of two processes: ingrowths of capillaries from the renal capsule to the graft, and neoformation of capillaries from pre-existing adenohypophysial vessels. In conclusion, hypoxia seems to be an important factor in the vascularization of pituitary autografts. Mediated via hypoxia-inducible factor, hypoxia stimulates vascular endothelial growth factor secretion, which plays a crucial role in angiogenesis.

Animals↗

PubMed2006

Primary melanocytic tumor of the cerebellopontine angle mimicking a vestibular schwannoma: case report.

OBJECTIVE: The majority of tumors of the cerebellopontine angle (CPA) are benign. We report the case of a primary malignant melanoma of the CPA that mimicked a vestibular schwannoma (acoustic neuroma). We discuss the differential diagnosis and prognosis of melanotic lesions at this location. CLINICAL PRESENTATION: A 49-year-old man presented with a 7-year history of unilateral deafness and a several month history of imbalance, intractable nausea and vomiting, as well as weight loss. A neurological work-up revealed a large tumor in the left CPA radiographically diagnosed as a vestibular schwannoma. INTERVENTION: A translabyrinthine approach revealed a pigmented, vascular neoplasm encasing vessels and cranial nerves of the left CPA. The tumor was subtotally resected, and a histopathological diagnosis of melanoma was made. The patient had no history of cutaneous melanoma and no other site of disease was ever discovered. CONCLUSION: This case most likely represents primary melanoma of the central nervous system that mimicked a vestibular schwannoma. The differential diagnosis of melanotic lesions of the CPA is discussed as are the prognostic implications of each diagnosis.

Cerebellar Neoplasms↗

PubMed2006

Pathobiology of pituitary adenomas and carcinomas.

OBJECTIVE: To examine relationships between pituitary tumors and lesion size, invasiveness, resectability, deoxyribonucleic acid ploidy, cell cycle profile, mitotic activity, and immunoreactivity for MIB-1, proliferating cell nuclear antigen (PCNA), p27Kip1, and p53. PATIENTS AND METHODS: One hundred fifty-three adenomas of most pathological subtypes, including 20 medically treated and prolactin and growth hormone-containing tumors, as well as 10 premetastatic tumors and 13 pituitary carcinomas, were studied. RESULTS: Significant (P < 0.05) differences were noted between functional versus nonfunctional adenomas (percent aneuploidy, percent S phase, p27Kip1 labeling indices [LI], male sex, tumor size, and frequency of visual disturbance); Cushing's versus silent adrenocorticotropin adenomas (percent hypertetraploidy, p53 LI, tumor size, visual disturbance, and resectability); untreated versus medically treated prolactin cell adenomas (MIB-1 LI, p53 LI, and resectability); untreated versus medically treated growth hormone-containing adenomas (percent diploidy, percent S phase, MIB-1 LI, p53 LI, and p27 LI); untreated prolactin cell adenomas versus premetastatic tumors (percent hypertetraploidy, PCNA LI, p53 LI, invasiveness, and resectability); untreated growth hormone-containing adenomas versus premetastatic tumors (percent diploidy, percent S phase, PCNA LI, p53 LI, invasiveness, and resectability); Cushing's adenomas versus premetastatic tumors (percent diploidy, percent hypertetraploidy, percent S phase, MIB-1 LI, p53 LI, tumor size, invasiveness, visual disturbance, and resectability); Nelson's adenomas versus premetastatic tumors (p53 LI, tumor size, invasiveness, and resectability); silent adenomas as a whole versus nonfunctional adenomas (percent nondiploid, percent S phase, invasiveness, and respectability); silent adrenocorticotropin adenomas I and II versus silent adenoma Subtype III (invasiveness); silent adrenocorticotropin adenoma Subtypes I and II versus premetastatic tumors (MIB-1 LI and invasiveness); silent adenoma Subtype III versus premetastatic tumors (PCNA and p53 LI); and premetastatic tumors versus metastatic pituitary carcinomas (MIB-1 LI). CONCLUSION: Only trends toward differences were noted between Cushing's versus Nelson's adenomas and between prolactinomas of reproductive female patients versus those of menopausal female patients and male patients. Too few "atypical adenomas" were encountered to permit their comparison with premetastatic tumors, but our results suggest that most pituitary carcinomas arise by malignant transformation from adenomas.

Adolescent↗

PubMed2006

Patterns of gene expression in pituitary carcinomas and adenomas analyzed by high-density oligonucleotide arrays, reverse transcriptase-quantitative PCR, and protein expression.

Very few of the genes that are important in pituitary tumor initiation, progression, and metastasis have been identified to date. To identify potential genes that may be important in pituitary tumor progression and carcinoma development, we used Affymetrix GeneChip HGU-133A-oligonucleotide arrays, which contain more than 15,000 characterized genes from the human genome to study gene expression in an ACTH pituitary carcinoma metastatic to the liver and four pituitary adenomas. Reverse-transcriptase real-time quantitative- PCR (RT-qPCR) was then used to analyze 4 nonneoplastic pituitaries, 19 adenomas, and the ACTH carcinoma. A larger series of pituitary adenomas and carcinomas were also analyzed for protein expression using tissue microarrays (TMA) (n = 233) and by Western blotting (n = 18). There were 4298 genes that were differentially expressed among the adenomas compared to the carcinoma, with 2057 genes overexpressed and 2241 genes underexpressed in the adenomas. The beta-galactoside binding protein galactin-3 was underexpressed in some adenomas compared to the carcinomas. Prolactin (PRL) and ACTH tumors had the highest levels of expression of galectin-3. The human achaetescute homolog-1 ASCL1 (hASH-1) gene was also underexpressed in some adenomas compared to the carcinoma. Prolactin and ACTH tumors had the highest levels of expression of hASH-1. ID2, which has an important role in cell development and tumorigenesis, was underexpressed in some adenomas compared to the carcinomas. Transducin-like enhancer of split four/ Groucho (TLE-4) was over-expressed in adenomas compared to the ACTH carcinoma. The differential expression of these genes was validated by RT-qPCR, by immunohistochemistry using TMA and by Western blotting. These results indicate that the LGALS3, hASH1, ID2, and TLE-4 genes may have important roles in the development of pituitary carcinomas.

ACTH-Secreting Pituitary Adenoma↗

PubMed2006

Contiguous conventional and plexiform schwannomas. Report of two cases.

The authors present clinical, imaging, and histological features of two adult patients found to harbor a conventional schwannoma contiguous with a deep plexiform schwannoma. One patient had neurofibromatosis (NF) Type 2 (NF2), and both intracranial (bilateral oculomotor, trigeminal, acoustic, and hypoglossal schwannomas as well as meningiomas) and intraspinal (schwannomas and meningiomas) lesions. The proximal forearm lesions consisted of a conventional schwannoma and an underlying plexiform component. The second patient, who did not have NF2, presented with a similar enlarging mass in the distal arm; two contiguous lesions were resected. Both patients exhibited distinct, readily identifiable, magnetic resonance imaging features. Plexiform schwannomas are rare lesions that occur sporadically or, on occasion, in association with NF2 or meningiomas with or without multiple schwannomas. The authors believe that a more careful examination of patients with NF2 may show that these people have a higher incidence of plexiform schwannoma than previously thought. Pathological confirmation is crucial in distinguishing plexiform schwannomas from plexiform neurofibromas, because the latter are directly associated with NF1 and have a significant tendency to undergo malignant transformation. To the best of the authors' knowledge, this is the first report of a conventional schwannoma contiguous with a deep plexiform schwannoma.

Adult↗