Background

The nervous system has traditionally been divided into the central nervous system which includes the brain and spinal cord, and the peripheral nervous system which consists of all other nerves besides the twelve cranial nerves. This distinction is somewhat artificial since one is connected with the other. The peripheral nervous system interfaces with skeletal muscle at the neuromuscular junction. Brain biopsies have become increasingly common with the AIDS epidemic with many rare infections and tumors of the brain becoming more common.  The study of the entire brain, however, is still reserved for autopsies.  A thorough study of the brain requires several weeks as the brain requires extensive fixation in formalin.   Pathologists specializing in disorders of the neuromuscular system are called neuropathologists. They must have an accurate knowledge base of clinical neurology and neurosurgery as well as mastery of pathology. Tumors of the brain and spinal cord are covered in a separate section.

Adult Polyglucosan Body Disease
Alzheimer's Disease
Amytrophic Lateral Sclerosis (ALS, Lou Gehrig's Disease)
Anencephaly
CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
Canavan Disease
Demyelinating Pseudotumor
Diabetes Insipidus
Huntington Disease (Huntington's Chorea)
Guillain-Barre Syndrome
Moyamoya Disease
Multiple Sclerosis
Myasthenia Gravis
Parkinson Disease
Primary Hypophysitis
Progressive Multifocal Leukoencephalopathy (PML)
Sinus Pericranii
Stroke
Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
Tuberous Sclerosis

OUTLINE

Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Commonly Used Terms
Internet Links

RADIOLOGY/ LABORATORY	CHARACTERIZATION
RADIOLOGY
WHITE MATTER LESIONS
Cerebral white matter lesions, retinopathy, and incident clinical stroke. Wong TY, Klein R, Sharrett AR, Couper DJ, Klein BE, Liao DP, Hubbard LD, Mosley TH. Department of Ophthalmology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260.	JAMA 2002 Jul 3;288(1):67-74 Abstract quote CONTEXT: White matter lesions (WMLs) detected on cerebral imaging scans have been hypothesized to have a microvascular etiology and to precede the development of clinical stroke. However, few clinical data are available to support these hypotheses. OBJECTIVE: To examine the relationship of WMLs, retinal microvascular abnormalities, and incident clinical stroke in healthy, middle-aged men and women. DESIGN AND SETTING: The Atherosclerosis Risk in Communities Study (ARIC), a prospective, population-based cohort study conducted in 4 US communities and initiated in 1987-1989. PARTICIPANTS: A total of 1684 persons aged 51 to 72 years who had cerebral magnetic resonance imaging (MRI) and retinal photography at the third examination (1993-1995). MAIN OUTCOME MEASURES: Odds of WMLs, defined by standardized methods from MRI, by presence or absence of specific retinal microvascular abnormality (eg, microaneurysm, retinal hemorrhage) on retinal photograph; incident clinical stroke, ascertained after a median follow-up of 4.7 years, according to presence or absence of WMLs and retinopathy. RESULTS: Persons with retinopathy were more likely to have WMLs than those without retinopathy (22.9% vs 9.9%; odds ratio, 2.5; 95% confidence interval [CI], 1.5-4.0, adjusted for age, sex, race, and vascular risk factors). The 5-year cumulative incidence of clinical stroke was higher in persons with vs without WMLs (6.8% vs 1.4%; adjusted relative risk [RR], 3.4; 95% CI, 1.5-7.7) and in persons with vs without retinopathy (8.0% vs 1.4%; adjusted RR, 4.9; 95% CI, 2.0-11.9). Persons with both WMLs and retinopathy had a significantly higher 5-year cumulative incidence of stroke than those without either WMLs or retinopathy (20.0% vs 1.4%; adjusted RR, 18.1; 95% CI, 5.9-55.4). CONCLUSIONS: In this cohort, middle-aged persons with cerebral WMLs detected on MRI were more likely to have retinal microvascular abnormalities and to have an increased risk of clinical stroke than people without WMLs. The risk of stroke was higher when retinopathy was simultaneously present in persons with WMLs.

 

GROSS APPEARANCE/ CLINICAL VARIANTS

CHARACTERIZATION

 

HISTOPATHOLOGICAL VARIANTS	CHARACTERIZATION
EPILEPSY
Clinicopathologic findings in patients with infantile hemiparesis and epilepsy. Prayson RA, Hannahoe BM.	Hum Pathol. 2004 Jun;35(6):734-8. Abstract quote Infantile hemiparesis may be associated with significant morbidity and may have a profound impact on a child's physical and social development. There are little published data evaluating the clinicopathologic features of patients with infantile hemiparesis. The present study retrospectively examines these clinicopathologic features in a surgical series of 21 patients with infantile hemiparesis. The study group was comprised of 21 patients, 13 females and 8 males, ranging in age from 5 to 41 years (mean, 20 years) at the time of surgery. Hemiparesis involved the right side in 16 patients and the left side in 5 patients. Imaging studies identified porencephaly in 8 patients (38%), encephalomalacia in 5 patients (24%), focal cerebral atrophy in 9 patients (43%), ventricular dilatation in 6 patients (29%), and white matter hyperintensities in 4 patients (19%). Concomitant neurologic diseases included medically intractable epilepsy in all 21 patients and visual field defects in 11 patients (52%). Significant perinatal history included prematurity in 7 patients (33%) and cesarean section, forceps delivery, placental abruption, fetal distress, and prolonged rupture of membranes each in 1 patient (5%). The remainder of the patients had an uncomplicated perinatal course (43%). Twelve patients underwent functional hemispherectomy (57%), 8 patients underwent lobectomy (38%) and 1 patient underwent "cyst" resection (5%). Histological evaluation demonstrated lesional (corresponding to radiographic findings) tissue in 15 of the 21 cases (71%). Infarction, malformations due to abnormalities of cortical development (cortical dysplasia) and gliosis with microcalcifications were each found in 6 patients (29%). Infarction and a geographically distinct area of cortical dysplasia were found to coexist in 1 case. Histopathologic findings in the 6 cases in which excised tissue was considered nonlesional included gliosis in all 6 of the cases, hippocampal sclerosis in 2 cases (10%), and neuronal heterotopia in 2 cases (10%). An osteoma was identified in 1 patient. The most common pathological findings observed in our series were infarction and cortical dysplasia, although radiographically, infarct-related changes were the most evident. Hippocampal sclerosis was encountered in 2 patients, suggesting that a subset of cortical dysplasias and hippocampal sclerosis may be caused by an in utero ischemic event.
METHOTREXATE-RELATED NONNECROTIZING MULTIFOCAL AXONOPATHY
Methotrexate-Related Nonnecrotizing Multifocal Axonopathy Detected by -Amyloid Precursor Protein Immunohistochemistry Brian E. Moore, MD, Nathan P. Somers, AB, and Thomas W. Smith, MD From the Department of Pathology, University of Massachusetts Medical School, Worcester, Mass.	Arch Pathol Lab Med 2002;Vol. 126, No. 1, pp. 79–81. Abstract quote We describe a 64-year-old woman with biphenotypic leukemia involving the meninges who received 2 doses of intrathecal methotrexate. Soon after treatment, the patient developed postural rigidity and a marked decline in mental status. The patient died of respiratory failure 1 month after methotrexate treatment was initiated. At autopsy, the brain was grossly normal. Routine microscopy showed no evidence of leukemic infiltrates or necrotizing lesions. However, when stained with -amyloid precursor protein, multifocal axonal injury was evident in the brain, spinal cord, and nerve roots. Our findings show that immunohistochemical staining for -amyloid precursor protein can effectively demonstrate axonal injury associated with methotrexate neurotoxicity, even when conventional staining procedures are negative. This technique may therefore reveal a possible pathologic substrate for some of the neurological complications seen in patients with methotrexate neurotoxicity.
TEXTILOMA
Textiloma (gossypiboma) mimicking recurrent intracranial tumor. Ribalta T, McCutcheon IE, Neto AG, Gupta D, Kumar AJ, Biddle DA, Langford LA, Bruner JM, Leeds NE, Fuller GN. Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Suner (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.	Arch Pathol Lab Med. 2004 Jul;128(7):749-58. Abstract quote   CONTEXT: Resorbable substances used to achieve hemostasis during neurosurgical procedures comprise 3 principal classes based on chemical composition: (1) gelatin sponge, (2) oxidized cellulose, and (3) microfibrillar collagen. Nonresorbable hemostatic aides include various forms of cotton and rayon-based hemostats (cottonoids and kites). Resorbable and nonresorbable hemostatic agents have been reported to cause symptomatic mass lesions, most commonly following intra-abdominal surgery. Histologic examination typically shows a core of degenerating hemostatic agent surrounded by an inflammatory reaction. Each agent exhibits distinctive morphologic features that often permit specific identification. Hemostat-associated mass lesions have been variously referred to as textilomas, gossypibomas, gauzomas, or muslinomas. OBJECTIVES: The aims of this study were to (1) identify cases of histologically proven cases of textiloma in neurosurgical operations, (2) characterize the specific hemostatic agent associated with textiloma formation, and (3) characterize the preoperative magnetic resonance imaging appearance of textiloma. DESIGN: Cases in which a textiloma constituted the sole finding on repeat surgery for recurrent brain tumor, or was a clinically significant component of a radiologically identified mass lesion together with residual tumor, constituted the study set. RESULTS: Five textilomas were identified and evaluated. The primary neoplasm was different in each case and included pituitary adenoma, tanycytic ependymoma, anaplastic astrocytoma, gliosarcoma, and oligodendroglioma. In all cases, preoperative magnetic resonance imaging suggested recurrent tumor. Textilomas included all categories of resorbable hemostatic agent. Other foreign bodies were present in some cases; the origin of these foreign bodies was traced to fibers shed from nonresorbable hemostatic material placed temporarily during surgery and removed before closure (cottonoids and kites). Inflammatory reactions included giant cells, granulomas, and fibroblastic proliferation. Microfibrillar collagen (Avitene) textilomas were associated with a striking eosinophil infiltration that was not seen with any other hemostatic agent. CONCLUSIONS: Hemostatic agents may produce clinically symptomatic, radiologically apparent mass lesions. When considering a mass lesion arising after intracranial surgery, the differential diagnosis should include textiloma along with recurrent tumor and radiation necrosis.

 

SPECIAL STAINS/ IMMUNO-HISTOCHEMISTRY

CHARACTERIZATION

 

DIFFERENTIAL DIAGNOSIS

KEY DIFFERENTIATING FEATURES

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Alzheimer type II astrocyte-These special astrocytes are found in the gray matter. They are characterized by nuclei which are 2-3 times the size of a normal astrocyte. Unlike the name it shares, it is not a characteristic change of Alzheimer's disease. Instead, it is often found in conditions of metabolic disturbance, such as liver failure.

Astrocytes-This is found in both white and gray matter and are primarily responsible for repair and scar formation or gliosis.

Corpora amylacea-These are round lamellated structures found with increasing age. They represent degenerative changes within astrocytes.

Ependyma-These are the lining cells of the brain's ventricular system.

Glial cells-These are supporting cells of the nervous system. They support the neurons, play important roles in cellular metabolism, and initiate repair. They are composed of astrocytes, oligodendrocytes, ependyma, and microglia.

Gliosis-This is scarring in the brain, formed by proliferation of astrocytes.

Gray and white matter-The brain is broadly divided into these two types of tissues. Gray matter contains the neurons while the white matter contains the myelinated nerves.

Oligodendrocytes-These are mainly found in white matter. They produce the myelin that surrounds nerve fibers insulating them and allowing for rapid neural transmission.

Microglial cells-These are the scavenger cells of the CNS, functioning as macrophages.

Rosenthal fibers-These are thick, elongated, brightly eosinophilic structures. They are found in conditions of long standing gliosis, occasional tumors, and rare metabolic degenerative disorders.

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
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Last Updated June 9, 2005

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