Mark A Edgar

Emory University | EU · Department of Pathology and Laboratory Medicine

Although most cases of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) can be diagnosed solely on the basis of histologic features, those lacking diagnostic histologic features require ancillary studies for accurate classification. Fluorescent in situ hybridization (FISH) for amplification of MDM2 has been considered the gold st...

Background: This study describes the cytologic features of 26 angiosarcomas diagnosed on fine-needle aspiration. Methods: Twenty-six angiosarcomas from 20 patients were confirmed by cytomorphology and immunocytochemical (immunohistochemistry) positivity for at least 2 of 3 vascular markers. Specimens were examined for spindled/epithelioid/plasma...

The histologic features and outcome of 58 cases of epithelioid schwannoma were studied to determine the significance of atypical histologic features. Cases were retrieved from personal consultation files from 1999 to 2013. Patients (31 male and 26 female patients) ranged in age from 14 to 80 years (median, 38 y). Two patients had schwannomatosis 1....

Typical myofibromas are biphasic tumors composed of a central zone of immature spindled to rounded cells arranged in a pericytic pattern and a peripheral zone of myoid nodules. Central necrosis is occasionally seen. A small but undefined subset of myofibromas displays atypical features that may lead to a misdiagnosis of sarcoma. To more completely...

Vascular tumors of bone represent a variety of neoplasms, ranging from benign hemangiomas and epithelioid hemangiomas, to intermediate grade hemangioendotheliomas, to frankly malignant angiosarcomas. Over the years, there has been considerable debate concerning the aggressivity, nomenclature and mere existence of various nosologic entities, due to...

Low Grade Fibromyxoid Sarcoma (LGFMS), first reported by Evans in 1987, is a rare deceptively bland-looking fibroblastic sarcoma that typically arises either in the deep soft tissues of the proximal extremities or of the trunk of young adults(1) . It has a protracted clinical course characterized by local recurrences and late distant metastases nec...

Reasons for failure in prior human glioma convection-enhanced delivery (CED) clinical trials remain unclear. Concentration-dependent volume of distribution (Vd) measurement of CED-infused agents in the human brain is challenging and highlights a potential technical shortcoming. Activity of iodine isotope 124 ((124)I ) in tissue can be directly meas...

Epithelioid sarcoma-like (pseudomyogenic) hemangioendothelioma (ESHE) represents a rare soft tissue and bone tumor that typically presents as nodule(s) in the distal extremities of young adults. The nodules traverse several tissue planes simultaneously and can involve the dermis, subcutis, skeletal muscle and bone. ESHE shares clinical and microsco...

Small cell carcinoma of the anus is a rare tumor that has been infrequently described in the literature. In contrast to squamous cell carcinoma, which is known to be associated with high-risk subtypes of human papillomavirus (HPV), the etiology of small cell carcinoma of the anal canal is not established. We present a case of a patient with small c...

Soft tissue chordomas (STCs) have never been systematically studied because of their rarity and the difficulty in separating them from similar-appearing lesions. Using brachyury to confirm the diagnosis, we have analyzed our experience with 11 cases. Cases coded as "chordoma" or "parachordoma" were retrieved from institutional and consultation file...

Several soft tissue tumors are characterized by fibrous stroma with a conspicuous vascular component including cellular angiofibroma, nasopharyngeal angiofibroma, and solitary fibrous tumor. Recently, a distinctive fibroblastic tumor composed of bland spindle cells and a complex vascular network has been characterized morphologically and shown to h...

Prostate-specific membrane antigen (PSMA) is expressed in endothelium of vessels in malignant solid tumors but not in normal vessels. To examine whether neovasculature of glioblastoma multiforme (GBM) expresses PSMA. Design.-After institutional review board approval at Memorial Sloan-Kettering Cancer Center, formalin-fixed paraffin-embedded tissue...

Tumors of peripheral nerve are largely neuroectodermal in nature and derived from 2 elements of nerve, Schwann or perineurial cells. In contrast, mesenchymal tumors affecting peripheral nerve are rare and are derived mainly from epineurial connective tissue. The spectrum of the latter is broad and includes lipoma, vascular neoplasms, hematopoietic...

Monoclonal antibodies have the potential to target therapy for high-grade gliomas. Monoclonal antibody 8H9 is specific for membrane protein B7H3 and is reactive with most human high-grade gliomas. We tested the 8H9scFv-PE38 recombinant Pseudomonas immunotoxin in a preclinical model of high-grade glioma. The half maximal inhibitory concentration (IC...

Purpose To determine the prognostic significance of histologic type in radiation-associated soft tissue sarcomas (RASs) and determine whether RASs are associated with an inferior prognosis compared with sporadic soft tissue sarcomas (STSs). Patients and Methods One hundred thirty primary RASs were identified from 7,649 STS patients from 1982 to 20...

Purpose Since activity of sorafenib was observed in sarcoma patients in a phase I study, we performed a multicenter phase II study of daily oral sorafenib in patients with recurrent or metastatic sarcoma. Patients and Methods We employed a multiarm study design, each representing a sarcoma subtype with its own Simon optimal two-stage design. In ea...

A critical need exists for the development of novel forms of treatment for high-grade glioma. Molecular characterization of high-grade glioma has shown overexpression of the epidermal growth factor receptor, antagonists to which, including erlotinib, may prevent tumor growth. Interstitial infusion is a mode of local delivery which bypasses the bloo...

Extra-axial ependymomas are very rare but have been reported in the ovary, broad ligament, sacrococcygeal region, lung, and mediastinum. The histogenesis is obscure, and a thorough immunohistochemical analysis is lacking. We reviewed the morphologic and immunohistochemical features of 5 extra-axial ependymomas occurring in adults, 1 arising in an i...

The importance of adult stem cells in the development of neoplastic diseases is becoming increasingly well appreciated. We hypothesized that sarcomas of soft tissue could be categorized by their developmental/differentiation status from stem cell to mature tissue, similar to the hematological malignancies. We conducted gene expression analyses duri...

Primitive neuroectodermal tumors (PNETs) are a family of primary malignant brain tumors that include medulloblastomas. Although genetic models of a subset of medulloblastomas are documented over the past decade, the molecular basis of other subclasses of PNET remains unclear. As elevated c-Myc expression, activation of Wnt/beta-catenin signaling an...

As we write, novel antibodies that may well alter the routine practice of surgical neuropathology are in development, characterization, and the early stages of clinical use. These will be used for purposes of tumor subclassification, as prognostic markers, as identifiers of potential therapeutic targets, and as predictors of treatment response. To...

Context.—As we write, novel antibodies that may well alter the routine practice of surgical neuropathology are in development, characterization, and the early stages of clinical use. These will be used for purposes of tumor subclassification, as prognostic markers, as identifiers of potential therapeutic targets, and as predictors of treatment resp...

Malignant fibrous histiocytoma (MFH), now termed high-grade undifferentiated pleomorphic sarcoma, is a commonly diagnosed mesenchymal tumor, yet both the underlying molecular mechanisms of tumorigenesis and cell of origin remain unidentified. We present evidence demonstrating that human mesenchymal stem cells (hMSCs) are the progenitors of MFH. DKK...

Background context: Paragangliomas are neuroendocrine tumors that most frequently arise in the adrenal medulla, carotid body, and glomus jugulare. However, they have been reported in many other sites throughout the body. Within the central nervous system, the overwhelming majority of paragangliomas arise intradurally in the area of the cauda equin...

Glioneuronal tumor with neuropil-like islands (GTNI) is a rare neoplasm harboring circumscribed loci of neuronal differentiation and diffusely infiltrating astroglial and oligodendrocytelike components. We report 8 previously unpublished examples of GTNI, specifically studied for chromosome 1p and 19q allelic losses. All tumors showed characteristi...

A case of metastatic renal cell carcinoma (RCC) to a capillary hemangioblastoma (HAB) of the central nervous system in a 52-year-old woman with von Hippel-Lindau (vHL) syndrome is described. We review the literature on metastatic RCC to HAB, summarize the histologic and immunohistochemical features that can distinguish between the 2 tumors, and com...

A case of metastatic renal cell carcinoma (RCC) to a capillary hemangioblastoma (HAB) of the central nervous system in a 52-year-old woman with von Hippel-Lindau (vHL) syndrome is described. We review the literature on metastatic RCC to HAB, summarize the histologic and immunohistochemical features that can distinguish between the 2 tumors, and com...

Several distinctive mixed glioneuronal tumors that warrant recognition as clinicopathologic entities have been recently described by neuropathologists. To summarize important clinical, radiologic, and pathologic findings for 3 novel glioneuronal tumors (papillary glioneuronal tumor, rosetted glioneuronal tumor, and rosette-forming glioneuronal tumo...

Context.—Several distinctive mixed glioneuronal tumors that warrant recognition as clinicopathologic entities have been recently described by neuropathologists. Objective.—To summarize important clinical, radiologic, and pathologic findings for 3 novel glioneuronal tumors (papillary glioneuronal tumor, rosetted glioneuronal tumor, and rosette-formi...

Neuropsychiatric systemic lupus erythematosus, which often entails cognitive disturbances and memory loss, has become a major complication for lupus patients. Previously, we developed a murine model of neuropsychiatric lupus based on Abs that cross-react with dsDNA and the NMDA receptor (NMDAR). We showed that these murine Abs impair cognition when...

Biomarkers can facilitate diagnosis, monitor treatment response, and assess prognosis in some patients with cancer. YKL-40 and matrix metalloproteinase-9 (MMP-9) are two proteins highly differentially expressed by malignant gliomas. We obtained prospective longitudinal serum samples from patients with gliomas to determine whether YKL-40 or MMP-9 co...

We retrospectively analyzed the results of eight patients who underwent endoscopic biopsy of a newly diagnosed primary intracranial germ cell tumor (GCT), and correlated tumor pathology with serum and cerebrospinal fluid (CSF) tumor markers and treatment outcome in order to determine the reliability of GCT sampling by this method. A biopsy diagnosi...

Glioneuronal neoplasms are rare tumors that typically affect patients in the first three decades of life. Since the publication of the World Health Organization (WHO) 2000 classification of tumors, further variants of these tumors have been reported. We present an 83-year-old gentleman who presented with a history of ataxia and weight loss. MRI and...

Hypomelanosis of Ito has been associated with precocious puberty in two cases. This study reports a third case involving a female with hypomelanosis of Ito including severe mental retardation and seizure disorder with autonomic symptoms (gastroesophageal reflux and asthma). At age 5 she developed vaginal discharge, thelarche, and adrenarche. Soon a...

We describe a patient with diffuse leukoencephalopathy, a rare central nervous system complication of systemic lupus erythematosus, who died of brain herniation despite aggressive management. Brain magnetic resonance imaging revealed diffuse white matter hyperintensities consistent with vasogenic edema. Autopsy revealed only widespread cerebral ede...

Interstitial infusion of IL13-PE38QQR, a tumor specific, chimeric cytotoxin, into the rat brain stem was performed in an effort to assess safety. Six rats underwent stereotaxic cannula placement into the pontine segment of the brain stem followed by a 24-h infusion of IL13-PE38QQR (volume of infusion (Vi) 200 microl) at a concentration of 10 microg...

Interstitial infusion of carmustine (BCNU) into the rat brain stem in conjunction with systemic administration of O6-benzylguanine (O6-BG) was performed in an effort to assess clinical tolerance. A total of 12 rats underwent stereotactic cannula placement into the pontine segment of the brain stem. Six of the rats underwent a 24-h infusion of BCNU...

The advent of sentinel lymph node (SLN) biopsy for breast cancer has had a considerable impact on clinical oncology. The SLN procedure has been widely adopted, but major clinical issues remain unresolved pending the outcome of randomized trials. Pathologic handling of SLNs is less controversial; however, significant pitfalls in their handling have...

Spinal vascular malformations show close histopathologic similarity to their intracranial counterparts with the classification of both partially depending on the presence and character of the intervening neural parenchyma. A fundamental distinction is made between racemose lesions (in which the abnormal vessels are clustered together with interveni...

Prolonged convection-enhanced delivery was used in an attempt to achieve large volumes of distribution (V(d)) in the rat brainstem. Clinical assessment and histological analysis were performed to establish the safety of this approach. For evaluation of V(d,), 10 rats underwent stereotactic cannula placement into the brainstem. Five rats underwent a...

Primary tumors of the heart are exceedingly rare with a prevalence rate of around 0.01% in autopsy studies. A majority of primary cardiac tumors are benign. Rhabdomyomas are the most common of benign pediatric cardiac tumors. A newborn female infant presented with perioral cyanosis and respiratory distress. She deteriorated progressively. The infan...

A central question in Alzheimer's disease concerns the mechanism by which beta-amyloid contributes to neuropathology, and in particular whether intracellular versus extracellular beta-amyloid plays a critical role. Alzheimer transgenic mouse studies demonstrate brain dysfunction, as beta-amyloid levels rise, months before the appearance of beta-amy...

Convection-enhanced delivery (CED) can safely achieve high local infusate concentrations within the rat brain stem with predictable distribution volumes. The authors investigated the effects of co-infusion or systemic administration of hyperosmolar mannitol on distribution parameters for infusions into the rat brain stem. Fifteen rats underwent ste...

Convection-enhanced delivery (CED) can be used safely to achieve high local infusate concentrations within the brain and spinal cord. The use of CED in the brainstem has not been previously reported and may offer an alternative method for treating diffuse pontine gliomas. In the present study the authors tested CED within the rat brainstem to asses...

Four studies have examined the cross-sectional area of the anterior commissure (AC) for variation with sex, with conflicting results. One also reported the AC to be larger in homosexual as opposed to heterosexual men. We examined the cross-sectional area of the AC in postmortem material from 120 individuals, and found no variation in the size of th...

Alzheimer's disease (AD) neuropathology is characterized by accumulation of "senile" plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are principally composed of aggregates of up to 42/43 amino acid beta-amyloid (A beta) peptides. The discovery of familial AD (FAD) mutations in the genes for the amyloid precursor pr...

Four studies have examined the cross-sectional area of the anterior commissure (AC) for variation with sex, with conflicting results. One also reported the AC to be larger in homosexual as opposed to heterosexual men. We examined the cross-sectional area of the AC in postmortem material from 120 individuals, and found no variation in the size of th...

Unilateral Adie pupil is usually a benign finding. The authors report the case of a 73-year-old man in whom pupillary abnormality was accompanied by areflexia, generalized sensorimotor neuropathy, and autonomic dysfunction. Anti-Hu antibody associated with small cell lung cancer was found in the serum and cerebrospinal fluid. Unilateral Adie pupil...

The interstitial nuclei of the human anterior hypothalamus (INAH1-4) have been considered candidates for homology with the sexually dimorphic nucleus of the preoptic area of the rat. Volumetric sexual dimorphism has been described for three of these nuclei (INAH1-3), and INAH3 has been reported to be smaller in homosexual than heterosexual men. The...

A variety of lesions may present as intraventricular masses in children. We report quantitative proton magnetic resonance spectroscopy (MRS) of two intraventricular tumors of the choroid plexus: choroid plexus carcinoma (CPC) and choroid plexus papilloma (CPP). Both lesions were characterized by high levels of choline-containing compounds and a com...

For adult meningiomas, the staining index (SI) for the anti-Ki-67 monoclonal antibody MIB-1 is well correlated with histological atypia and tumor recurrence. MIB-1 SIs for meningiomas in the pediatric population have not been previously reported. Meningiomas tend to be more histologically aggressive and to recur more frequently in children, compare...

OBJECTIVE: For adult meningiomas, the staining index (SI) for the anti-Ki-67 monoclonal antibody MIB-1 is well correlated with histological atypia and tumor recurrence. MIB-1 Sis for meningiomas in the pediatric population have not been previously reported. Meningiomas tend to be more histologically aggressive and to recur more frequently in childr...

Malignant and atypical meningiomas are prone to recurrence and aggressive growth, which affects treatment planning and prognostication. Investigators have used diffusion-weighted imaging and apparent diffusion coefficient (ADC) maps to compare tumor grade and cellularity with the histopathologic findings of intraaxial primary brain neoplasms. The p...

The authors describe a patient with Carney's complex who presented with sciatica due to a lumbar nerve root sheath tumor. A far-lateral approach was used to resect a nonpsammomatous melanotic schwannoma. Neurosurgeons surgically treating peripheral nerve sheath tumors should be aware of the features of Carney complex because the extent of the preop...

The four interstitial nuclei of the anterior hypothalamus (INAH) have been considered as candidate human nuclei for homology with the much studied sexually dimorphic nucleus of the preoptic area of the rat. Assessment of the INAH for sexual dimorphism has produced discrepant results. This study reports the first systematic examination of all four I...

Alzheimer's disease (AD) is characterized by the deposition of senile plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are composed of aggregated beta-amyloid (Abeta) 40/42(43) peptides. Evidence implicates a central role for Abeta in the pathophysiology of AD. Mutations in betaAPP and presenilin 1 (PS1) lead to ele...

Post-mortem studies of the brain of an Alzheimer patient indicate fewer senile plaques in the crests of cortical gyri underneath an omental transposition than in neighboring cortical areas.