Diseases of the Pituitary Gland

A wide variety of distinct pathological conditions may affect the pituitary, causing hormonal dysfunction and/or compression of surrounding structures. This chapter describes and illustrates the main pituitary lesions. Pituitary adenomas represent 10% to 20% of intracranial neoplasms in neurosurgical series. Their classifications are based on multiple factors, including histology and immunohistochemistry, ultrastructure and endocrine activity. Pituitary carcinomas are extremely rare. Pituitary hyperplasia is a rare cause of pituitary hyperfunction. Inflammatory (lymphocytic hypophysitis, granulomatous hypophysitis) and vascular (pituitary infarction, pituitary apoplexy, Sheehan syndrome) lesions can cause hypopituitarism. Craniopharyngiomas are the second most common neoplasm of the sellar region, following pituitary adenomas, and the most common suprasellar neoplasm in children.

Pathology of Peripheral Nerve

This chapter gives a current classification of diseases of peripheral nerve and then describes and illustrates the pathology of peripheral nerve, particularly from the perspective of the nerve biopsy. After a description of the clinical indications for the biopsy, an introduction to the general laboratory techniques, and a brief review of the normal morphology of peripheral nerve, the general reactions of peripheral nerve to injury (primary axonal degeneration and primary segmental demyelination) are described. Neuropathies can be separated into acquired and hereditary neuropathies. Inflammatory neuropathies include immunopathological disorders of unknown cause (e.g. inflammatory demyelinating polyradiculoneuropathy), neuropathies due to infectious agents (e.g. leprosy), or those associated with systemic vasculitis. Neuropathy also occurs secondarily, in association with hematological diseases and neoplasms. Metabolic (diabetic) and toxic neuropathies are subsequently discussed. The chapter also gives an account of the importance of incorporating recent advances in molecular genetics in the evaluation of hereditary neuropathies (i.e. hereditary motor and sensory neuropathies, hereditary sensory and autonomic neuropathies, and familial amyloid polyneuropathies).

Hereditary Metabolic Diseases

This chapter describes and illustrates the morphologic CNS changes in hereditary metabolic disorders. In some disorders, the metabolic derangements are most prominent in the cytosol and are linked to the dysfunction of a single cellular organelle. In these disorders there may be intracellular accumulation of an intermediate metabolite, resulting in a “storage disease” or accumulation of the abnormal substance within the cell. The organelles most commonly involved in these disorders are lysosomes, peroxisomes, mitochondria, and the cytoplasmic compartment. The other disorders are not linked to a specific cellular organelle. They are defined by an enzyme deficiency, the biochemical pathways involved (metabolic disorders of sugars, copper, amino acids, or structural protein), or only by morphologic/clinical features.

Infections of the Central Nervous System

This chapter describes and illustrates the different lesions observed in CNS infections. A wide variety of pathogenic infectious organisms may affect the CNS. They can be classified as “pathogenic” (causing disease in every individual) or “opportunistic” (affecting only patients with immunodeficiency). Bacteria may cause pyogenic infections or so-called “specific infections,” in which the morphology of the lesions is suggestive of a specific agent. Mycoses and parasitic infections used to be uncommon, restricted to certain countries; however, due to increasing incidence of immunodeficiency conditions and intercontinental travel, they are now more frequently encountered. Viral infections of the CNS cause nonspecific lesions due to immune-mediated reactions or more specific encephalitides. In AIDS, infection by the human immunodeficiency virus causes a unique encephalitis and immunodeficiency with a wide range of secondary opportunistic infections.

Tumors of the Central Nervous System

This chapter presents the most up-to-date classification of tumors of the nervous system, based on the histological appearance of the neoplasm and also on information derived from cytogenetics and molecular biology, now recognized worldwide as increasingly important for more precise diagnosis, prognosis, and therapeutic guidance. The chapter provides a detailed morphologic description of each major tumor type, with numerous illustrations of macroscopic and microscopic lesions. First we consider primary tumors of the nervous system, including those derived from neuroepithelial tissue (astrocytic, oligodendroglial, ependymal, neuronal, and glioneuronal), pineal tissue, peripheral nerve sheath, and meninges. Next lymphomas, hematopoietic neoplasms, and secondary (metastatic) neoplasms are described.

Human Prion Diseases

This chapter describes and illustrates the neuropathology of prion diseases, also known as transmissible spongiform encephalopathies. These diseases are characterized pathologically by varying combinations of spongiform change, neuronal loss, reactive gliosis, and prion protein (PrP) deposition. The morphologic pattern depends on the etiology of the disease and the genotype of the patient. Different clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (CJD) have been described depending on the PRNP codon 129 genotype and the PrP isotype. A novel form known as variably protease-sensitive prionopathy has been recently identified. Familial prion diseases include familial CJD, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. Over 40 different PRNP mutations have been identified. Acquired prion diseases include Kuru; iatrogenic CJD, particularly in recipients of contaminated human pituitary hormone, and variant CJD, which seems closely related to bovine spongiform encephalopathy.

Neuropathology of Vascular Disease

The classification of vascular diseases of the central nervous system followed here first considers two large groups of entities: relatively large intraparenchymal hemorrhage due to rupture of blood vessels and infarction from occlusion of major vessels affecting large areas of the brain. The underlying pathology of the vessels is discussed, as are the reactions of nervous tissue to irreversible injury over time. Intracranial hemorrhages can also be seen in the context of rupture of vessels with outpouring of blood into the subarachnoid spaces, in cases of ruptured aneurysm or vascular malformations. Next we consider small vessel disease, in which the lesions affect the microcirculation and may also cause dementia, encephalopathies, or multifocal neurological deficits, the result of multiple micro-hemorrhages, small infarcts, or both. Vascular diseases affecting the small blood vessels include hypertensive cerebrovascular disease and cerebral amyloid angiopathy. Less common entities include hereditary disorders (i.e., CADASIL) and vasculitides.

Pathology of Skeletal Muscle

This chapter offers a contemporary approach to the classification of diseases of skeletal muscle and describes and illustrates the pathology of muscle disease, particularly from the perspective of the muscle biopsy. After an introductory exposition of the relevant laboratory techniques and a synopsis of the normal appearance of skeletal muscle, the basic reactions to injury are described. The ranges of diseases of skeletal muscle are then systematically considered and their specific morphologic, biochemical, and molecular genetic abnormalities are discussed in detail. The approach is to subdivide muscle disease into two broad categories: conditions that result in denervation of muscle (i.e., neurogenic atrophy) and diseases where the primary abnormality is in the muscle cell itself (i.e. myopathies). Genetically determined diseases of skeletal muscle discussed include muscular dystrophies, congenital myopathies, myofibrillar myopathies, and metabolic myopathies. Next described are the inflammatory myopathies, which are divided into two groups according to whether the causative agent is a known microorganisms or whether the inflammatory process is believed to be an autoimmune phenomenon.

Central Nervous System Trauma

This chapter describes and illustrates the various pathological processes that result from head injury. Clinical, neuroradiological, and pathological data allow the separation of focal or diffuse damage. Focal lesions include scalp and skull lesions, contusions and lacerations of the brain, and intracranial hemorrhages. Diffuse lesions in traumatic brain injury include diffuse ischemia, diffuse traumatic axonal injury, and diffuse brain swelling. The consequences of penetrating injuries, blast injuries, and chronic traumatic encephalopathy resulting from repetitive head injury are also described. Separate sections are devoted to spinal cord injury and the consequences of brain injury in infants and children.

Congenital Malformations and Perinatal Diseases

This chapter describes and illustrates the changes of the CNS in congenital malformations and perinatal diseases; it also provides insights into the genetic abnormalities associated with these conditions. Congenital malformations include neurulation failure resulting in neural tube closure defects, disorders of development of the prosencephalon, malformations of the cortical plate (neuronal heterotopia, polymicrogyria, lissencephaly, and focal cortical dysplasia, a frequent cause of epilepsy in children), and disorders of hindbrain development, particularly malformations of the cerebellum. Destructive lesions of developing brain are described in association with a variety of situations generally resulting in “hypoxia-ischemia.” They may affect the neocortex, causing porencephaly or hydranencephaly, the basal ganglia (status marmoratus), or the white matter (perinatal telencephalic leukoencephalopathy and periventricular leukomalacia).