B K Kleinschmidt-DeMasters

University of Colorado, Denver, Colorado, United States

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Publications (194)909.12 Total impact

  • David Ryan Ormond · B. K. Kleinschmidt-DeMasters
    No preview · Article · Mar 2016 · Journal of Neuro-Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: SOX10 is important in nonneoplastic oligodendroglial development, but mRNA transcripts and protein expression are identified in a wider variety of CNS glial neoplasms than oligodendrogliomas. We previously demonstrated high levels of SOX10 mRNA and protein in pilocytic astrocytomas (PAs) but not ependymomas (EPNs). We now extend these studies to investigate subsets of these 2 tumors that affect infants, pilomyxoid astrocytomas (PMAs) and infant (<1 year) ependymomas (iEPNs). By gene expression microarray analysis, we found that iEPNs and all EPNs in older children showed very low SOX10 expression levels, on average 7.1-fold below normal control tissues. EPN groups showed no significant difference in SOX10 expression between iEPN and EPN. PAs/PMAs had 24.1/29.4-fold higher transcript levels, respectively, than those in normal tissues. Using immunohistochemical analysis of adult, pediatric, and infantile EPNs and of PAs/PMAs, we found that EPNs from multiple anatomical locations and both age groups (n = 228) never showed 3+ diffuse nuclear immunostaining for SOX10; the majority were scored at 0 or 1+. Conversely, almost all pediatric and adult PAs and PMAs (n = 47) were scored as 3+. These results suggest that in select settings, SOX10 immunohistochemistry can supplement the diagnosis of PMA and PA and aid in distinguishing them from EPNs.
    No preview · Article · Mar 2016
  • E. Kelly S. Mrachek · David Davis · B. K. Kleinschmidt-DeMasters
    [Show abstract] [Hide abstract] ABSTRACT: Objectives: Meningiomas usually can be readily diagnosed on H&E alone, although occasionally immunohistochemistry (IHC) confirmation is desirable. Studies exploring the diagnostic utility of either podoplanin (D2-40) or E-cadherin IHC in meningiomas have conflicted, and no studies exist in which the two IHCs have been used in combination for diagnosis. Methods: E-cadherin and D2-40 IHC was performed on 77 meningiomas (31 ordinary; eight microcystic; four rare myxoid; six metaplastic; six invasive of orbit, muscle, and/or soft tissue; two metastatic; six brain-invasive World Health Organization [WHO] grade II, nine non-brain-invasive WHO grade II; and five anaplastic WHO grade III), with semi-quantitative scoring on a three-tier scale (0, focal [1+], strong/diffuse [2+]). Results: All meningiomas were either E-cadherin or D2-40 IHC+, with 69 of 77 showing dual immunostaining, most at the 2+ level. No downregulation of E-cadherin IHC was found in invasive or high-grade meningiomas. Conclusions: Dual E-cadherin/D2-40 IHC can supplement diagnosis of meningioma.
    No preview · Article · Dec 2015 · American Journal of Clinical Pathology
  • Jared Shows · Carrie Marshall · Arie Perry · B.K. Kleinschmidt-DeMasters
    No preview · Article · Oct 2015 · Brain Pathology
  • Jeffrey Schowinsky · Michelle Leppert · Douglas Ney · B.K. Kleinschmidt-DeMasters
    [Show abstract] [Hide abstract] ABSTRACT: Brain parenchymal involvement of mycosis fungoides (MF) is very rare. This study reports a patient with known cutaneous MF (under treatment) who presented with a CNS syndrome and multiple brain lesions. Brain biopsy demonstrated massive eosinophilic infiltrates but no MF cells. Despite treatment, new lesions developed and the patient died. At autopsy, there was massive involvement MF cells, suggesting that the eosinophilic infiltrates presaged the severe involvement of the CNS by MF.
    No preview · Article · Sep 2015
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: The aim of this study was to examine whether differential expression of somatostatin receptors (SSTR) 1-5 and downstream effectors are different in densely (DG) and sparsely (SG) granulated histological growth hormone (GH) pituitary tumor subtypes. Methods: The study included 33 acromegalic patients with 23 DG and 10 SG tumors. SSTR1-5 were measured by qPCR and immunoblotting. Signaling candidates downstream of SSTR2 were also assessed. Results: SSTR2 mRNA and protein levels were significantly higher in DG compared to SG tumors. Downstream of SSTR2, p27(kip1) was decreased (2.6-fold) in SG compared to DG tumors, suggesting a potential mechanism of SSA resistance in SG tumors with intact SSTR2 expression. Re-expression of E-cadherin in GH pituitary cell increased p27(kip1) levels. Conclusions: Histological subtyping correlated with SSTR2, E cadherin and p27 (kip) protein levels and these may serve as useful biomarkers in GH tumors to predict behavior and response to therapy with SSA.
    No preview · Article · Sep 2015 · Molecular and Cellular Endocrinology
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    [Show abstract] [Hide abstract] ABSTRACT: Introduction Pediatric adamantinomatous craniopharyngioma (ACP) is a histologically benign but clinically aggressive brain tumor that arises from the sellar/suprasellar region. Despite a high survival rate with current surgical and radiation therapy (75–95 % at 10 years), ACP is associated with debilitating visual, endocrine, neurocognitive and psychological morbidity, resulting in excheptionally poor quality of life for survivors. Identification of an effective pharmacological therapy could drastically decrease morbidity and improve long term outcomes for children with ACP. Results Using mRNA microarray gene expression analysis of 15 ACP patient samples, we have found several pharmaceutical targets that are significantly and consistently overexpressed in our panel of ACP relative to other pediatric brain tumors, pituitary tumors, normal pituitary and normal brain tissue. Among the most highly expressed are several targets of the kinase inhibitor dasatinib – LCK, EPHA2 and SRC; EGFR pathway targets – AREG, EGFR and ERBB3; and other potentially actionable cancer targets – SHH, MMP9 and MMP12. We confirm by western blot that a subset of these targets is highly expressed in ACP primary tumor samples. Conclusions We report here the first published transcriptome for ACP and the identification of targets for rational therapy. Experimental drugs targeting each of these gene products are currently being tested clinically and pre-clinically for the treatment of other tumor types. This study provides a rationale for further pre-clinical and clinical studies of novel pharmacological treatments for ACP. Development of mouse and cell culture models for ACP will further enable the translation of these targets from the lab to the clinic, potentially ushering in a new era in the treatment of ACP.
    Full-text · Article · May 2015
  • B K Kleinschmidt-DeMasters · M B S Lopes · Richard A Prayson
    [Show abstract] [Hide abstract] ABSTRACT: Context .- Most sellar region masses (85%-90%) are pituitary adenomas; however, other neoplasms or even inflammatory or cystic nonneoplastic lesions may occasionally be encountered in this location. A practical, non-electron-microscopically based approach is essential for the daily practice of diagnosing and subclassifying adenomatous and nonadenomatous sellar region lesions. Objective .- To provide an algorithmic approach to sellar region masses for the pathologist and to formulate a cost-effective, limited panel of stains and immunostains that can be used in daily practice at most small to medium-sized centers. Design .- Pool collective experience of 3 neuropathologists practicing at academic medical centers with expertise in diagnosis and treatment of sellar region masses to craft a single-page algorithmic diagram and to liberally illustrate the range of lesions present in the sellar region. Results .- After formulating a differential diagnosis, the general pathologist can generate a confident final diagnosis of adenoma using 1 histochemical (reticulin) and 1 immunohistochemical (synaptophysin) stain, supplemented by 5 immunohistochemical stains (CAM5.2, follicle-stimulating hormone, growth hormone, prolactin, and adrenocorticotropic hormone), which provide subtyping of the adenoma in the overwhelming majority of examples. CAM5.2 and clinical information further help identify clinically aggressive variants such as sparsely granulated growth hormone adenomas and silent adrenocorticotropic hormone adenomas, respectively. MIB-1, thyroid transcription factor 1, and S-100 protein can be of further assistance in select cases where increased mitotic activity or possible nonadenomatous spindle cell lesions are suspected. Conclusions .- Adenomas, normal anterior or posterior gland, and nonadenomatous masses can be easily diagnosed in a nontertiary pathology laboratory setting.
    No preview · Article · Mar 2015 · Archives of pathology & laboratory medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Bevacizumab blocks the effects of VEGF and may allow for more aggressive radiotherapy schedules. We evaluated the efficacy and toxicity of hypofractionated intensity-modulated radiation therapy with concurrent and adjuvant temozolomide and bevacizumab in patients with newly diagnosed glioblastoma. Patients with newly diagnosed glioblastoma were treated with hypofractionated intensity modulated radiation therapy to the surgical cavity and residual tumor with a 1 cm margin (PTV1) to 60 Gy and to the T2 abnormality with a 1 cm margin (PTV2) to 30 Gy in 10 daily fractions over 2 weeks. Concurrent temozolomide (75 mg/m(2) daily) and bevacizumab (10 mg/kg) was administered followed by adjuvant temozolomide (200 mg/m(2)) on a standard 5/28 day cycle and bevacizumab (10 mg/kg) every 2 weeks for 6 months. Thirty newly diagnosed patients were treated on study. Median PTV1 volume was 131.1 cm(3) and the median PTV2 volume was 342.6 cm(3). Six-month progression-free survival (PFS) was 90 %, with median follow-up of 15.9 months. The median PFS was 14.3 months, with a median overall survival (OS) of 16.3 months. Grade 4 hematologic toxicity included neutropenia (10 %) and thrombocytopenia (17 %). Grades 3/4 non-hematologic toxicity included fatigue (13 %), wound dehiscence (7 %) and stroke, pulmonary embolism and nausea each in 1 patient. Presumed radiation necrosis with clinical decline was seen in 50 % of patients, two with autopsy documentation. The study was closed early to accrual due to this finding. This study demonstrated 90 % 6-month PFS and OS comparable to historic data in patients receiving standard treatment. Bevacizumab did not prevent radiation necrosis associated with this hypofractionated radiation regimen and large PTV volumes may have contributed to high rates of presumed radiation necrosis.
    No preview · Article · Dec 2014 · Journal of Neuro-Oncology
  • Jeffrey T Schowinsky · D Ryan Ormond · B K Kleinschmidt-DeMasters
    No preview · Article · Dec 2014 · Journal of Neuropathology and Experimental Neurology
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    D. Ney · B. K. Kleinschmidt-DeMasters · J. Carlson · D. Damek · L. Gaspar · B. Kavanagh · A. Waziri · K. Lillehei · K. Reddy · C. Chen
    [Show abstract] [Hide abstract] ABSTRACT: BACKGROUND: Hypofractionated RT schemes may result in increased occurrence of clinically-significant radionecrosis (CSRN), but this potentially might be mitigated by bevacizumab (BEV). METHODS: 30 patients received hypo-IMRT to the surgical cavity and residual tumor with a 1cm margin (PTV1) to a total dose of 60 Gy in 10 daily fractions and to the T2 abnormality with a 1cm margin (PTV2) to 30 Gy. Concurrent TMZ (75mg/m2 daily) and BEV (10mg/kg every 2 weeks) was administered followed by adjuvant TMZ and BEV for 6 months. CSRN was defined as progressive MRI changes not attributable to tumor progression resulting in neurological deficits. Differentiation from tumor progression was based on perfusion weighted imaging showing hypoperfusion in areas of MRI change. RESULTS: 16/30 developed CSRN at a median of 12.5 months. The median PTV1 volume in these patients was 131.0 cm3(range: 37.9-241.7), and the median PTV2 volume was 337.3 cm3 (range: 130.6-519.2.0). PTV1 and PTV2 volumes were not statistically different between those patients who developed CSRN and those who did not (p = .88, p = .40). Median OS of patients with CSRN was 18.4 months versus 16.9 months in those without (p = 0.05). Development of CSRN was not associated with MGMT methylation status (p = 0.66). Four patients underwent re-operation (showing 60-100% necrosis), 13 patients died, and 2/13 underwent autopsy. One patient (survival 10.1 months), showed predominantly RN with scant residual tumor cells, whereas the second (survival 17.5 months) manifested focal RN with extensive, residual, bulky leptomeningeal tumor at surrounding base of brain, brainstem, and spinal cord. CONCLUSIONS: CSRN was extensive in this cohort and not mitigated by BEV. Development of RN not only failed to prolong survival, but in at least one patient allowed development of known late complications of GBM, ie., distant spread beyond original tumor bed.
    Preview · Article · Nov 2014 · Neuro-Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: Growth hormone (GH) pituitary tumors are associated with significant morbidity and mortality. Current treatments, including surgery and medical therapy with somatostatin analogs (SSA), dopamine agonists and/or a GH receptor antagonist, result in disease remission in approximately half of patients. Predictors of GH tumor response to different therapies have been incompletely defined based on histologic subtype, particularly densely (DG) versus sparsely (SG) granulated adenomas. The aim of this study was to examine our own institutional experience with GH adenomas and correlate how subtype related to clinical parameters as well as response to surgery and medical therapies. A retrospective chart review of 101 acromegalic patients operated by a single neurosurgeon was performed. Clinical data were correlated with histologic subtype and disease control, as defined by IGF-1 levels, and random growth hormone levels in response to surgery and/or medical therapies. SG tumors, compared to DG, occurred in younger patients (p = 0.0010), were 3-fold larger (p = 0.0030) but showed no differences in tumor-invasion characteristics (p = 0.12). DG tumors had a higher rate of remission in response to surgery compared to SG, 65.7 vs. 14.3 % (p < 0.0001), as well as to medical therapy with SSAs (68.8 % for DG vs. 28.6 % for SG tumors; p = 0.028). SG tumors not controlled with SSAs consistently responded to a switch to, or addition of, a GH receptor antagonist. Histological GH tumor subtyping implicates a different clinical phenotype and biologic behavior, and provides prognostic significance for surgical success and response to medical therapies.
    No preview · Article · Aug 2014 · Endocrine
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    [Show abstract] [Hide abstract] ABSTRACT: Objectives: Metastatic leptomeningeal spread from spinal cord gangliogliomas (GGs) is exceedingly rare. Methods: Two adult women, aged 27 and 51 years, died of massive disseminations of cervicothoracic GGs 4 and 6 years, respectively, after initial diagnoses; full autopsies were performed. BRAF status was assessed by VE1 immunohistochemistry (IHC), Sanger sequencing, and a single-nucleotide base extension assay (SNaPshot, Applied Biosystems, Princeton, NJ). Results: The 27-year-old underwent two biopsies, chemotherapy, radiation, and ventriculoperitoneal shunt placement; she developed craniospinal and peritoneal dissemination. Autopsy confirmed shunt-mediated peritoneal metastases, microscopic bone marrow involvement, and profuse spinal and supratentorial leptomeningeal and parenchymal spread. The 51-year-old underwent two resections, radiation, and chemotherapy and developed pancytopenia with biopsy-proven bony metastases 15 months before death. Autopsy demonstrated leptomeningeal, subpial, and subependymal metastases. The tumors in both primary and metastatic sites were BRAF negative by VE1 IHC and two different mutational analyses. This compared with negative BRAF results for an additional four nonmetastatic adult nonsupratentorial GGs and in our study. Conclusions: We document two rare cases of massively metastatic spinal cord GGs in adult patients who were negative for BRAF V600E mutations via multiple methods.
    Preview · Article · Aug 2014 · American Journal of Clinical Pathology
  • Bette Kleinschmidt-DeMasters · T. Cummings · M. Lopes
    No preview · Conference Paper · Jun 2014
  • Bette Kleinschmidt-DeMasters · Andrew Donson · Nicholas Foreman
    No preview · Conference Paper · Jun 2014
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    [Show abstract] [Hide abstract] ABSTRACT: BACKGROUND: LMD in children with recurrent medulloblastoma and other PNETs carries a poor prognosis and novel therapies are urgently needed to improve disease control. Somatostatin receptor-2 (SSR-2)is overexpressed in medulloblastoma and other central PNETs and can serve as a target for radionuclide tagged somatostatin analogues like 177Lu-DOTA-TATE that has shown considerable efficacy in adults with SSR-2 positive neuro-endocrine tumors. As a preliminary step prior to testing this agent in children with LMD, we performed an efficacy study of i.t. 177Lu-DOTA-TATE in athymic rats bearing LMD from MBL. METHODS: The subarachnoid space was accessed through the animal's cervical spine and a catheter was threaded along the dorsal aspect of spinal cord to the lumbar region and injected with 1 x 107 D341 human MBL cells and treatment initiated 3 days later. Groups of 10 animals received a single i.t. dose of 2, 3, or 5 mCi of 177Lu- DOTA-TATE or saline control. Animals were followed 300 days for survival. RESULTS: Treatment with 2 mCi resulted in an increase in median survival of 58.3% compared with saline control (p < 0.001). Treatment with 5.0 mCi of 177Lu-DOTA-TATE increased median survival by 75.0% compared with the saline control group while a single dose of 3.0 mCi 177Lu-DOTA-TATE increased median survival compared with saline controls by 519.4%. Long-term survivors were seen in 0 of 10 animals treated with saline, 4 of 11 treated with 3 mCi, and 3 of 12 treated with 5.0 mCi. CONCLUSION: Intrathecal 177Lu- DOTA TATE is efficacious in controlling LMD from medulloblastoma in athymic rats. A phase I trial of this agent is being planned in children with LMD from recurrent MBL and other CNS PNETs.
    Full-text · Article · Jun 2014 · Neuro-Oncology
  • No preview · Conference Paper · Jun 2014
  • Bette Kleinschmidt-DeMasters · Seth Lummus
    No preview · Conference Paper · Jun 2014
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    [Show abstract] [Hide abstract] ABSTRACT: The clinical features, pathologic changes, and immune repertoire in a remarkable case of chronic varicella-zoster virus (VZV) ganglioneuritis without rash are described.
    Full-text · Article · Nov 2013 · Neurology
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    Janice C Wong · Brent O'Neill · Cynthia E Hawkins · B K Kleinschmidt-Demasters · Lili-Naz Hazrati
    [Show abstract] [Hide abstract] ABSTRACT: Astrocytic dysfunction is implicated in epilepsy through many proposed molecular mechanisms, but there is also a clinicopathologic entity of epilepsy featuring astrocytic inclusions.(1) At least 17 cases of early-onset epilepsy with eosinophilic, hyaline astrocytic inclusions have been reported since the early 1990s.(2-8) Most of these cases also involve developmental delay.(2-8) The diagnosis is made by neuropathologic analysis that demonstrates brightly eosinophilic, hyaline, refractile astrocytic inclusions seen under light microscopy with hematoxylin & eosin stain.(2-8) We review the clinicopathologic entity of pediatric epilepsy with hyaline astrocytic inclusions and report an illustrative case.
    Full-text · Article · Jul 2013 · Neurology

Publication Stats

6k Citations
909.12 Total Impact Points


  • 1990-2014
    • University of Colorado
      • • Department of Neurosurgery
      • • Department of Neurology
      • • Department of Pathology
      Denver, Colorado, United States
  • 1988
    • United States Department of Veterans Affairs
      Бедфорд, Massachusetts, United States