Craniopharyngioma

Overview

Definition

Craniopharyngiomas are rare squamous epithelial tumors with a solid and/or cystic Cystic Fibrocystic Change structure, which arise from the remnants of Rathke’s pouch along the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types stalk, in line from the nasopharynx Nasopharynx The top portion of the pharynx situated posterior to the nose and superior to the soft palate. The nasopharynx is the posterior extension of the nasal cavities and has a respiratory function. Pharynx: Anatomy to the diencephalon Diencephalon The paired caudal parts of the prosencephalon from which the thalamus; hypothalamus; epithalamus; and subthalamus are derived. Development of the Nervous System and Face (in the suprasellar region).

Craniopharyngiomas have benign Benign Fibroadenoma histology but malignant behavior, meaning that they tend to invade the surrounding structures and can shorten life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids. Therefore, despite their benign Benign Fibroadenoma appearance on histology, they are considered low-grade malignancies.

Classification of nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification tumors

Epidemiology

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: rare
  • Approximately 2 cases per 1,000,000 person years
  • Constitute 1%–3% of all primary brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumors
• Race/ethnicity: more common in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship of Japanese and African descent
• Gender Gender Gender Dysphoria: equally common in men and women 
• Age and subtype: A bimodal age distribution is observed.
  • Children:
    • Peak diagnosis at 5–14 years of age
    • More commonly adamantinomatous subtype
  • Adults:
    • Peak diagnosis at 50–75 years of age
    • More commonly the papillary subtype
• High recurrence rate (50%)
• High morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status rate
  • Headaches
  • Visual symptoms
  • Hormonal disturbances
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Mental health disturbances

Classification

There are 2 primary types of craniopharyngiomas:

• Adamantinomatous type:
  • Arise from the embryonic cells of the craniopharyngeal duct
  • Solid or cystic Cystic Fibrocystic Change structures filled with a dark-brown or black fluid
  • Tumor Tumor Inflammation calcification is common.
• Papillary type:
  • Arise from the cells of the anterior portion of the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types gland
  • Well circumscribed, solid or cystic Cystic Fibrocystic Change, and filled with a viscous yellow fluid
  • Tumor Tumor Inflammation calcification is rare.

Etiology and Pathophysiology

Craniopharyngiomas are squamous epithelial tumors that arise along the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types stalk in the suprasellar region, adjacent to the optic chiasm Optic Chiasm The x-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. The Visual Pathway and Related Disorders.

Etiology

Two main hypotheses have been proposed to explain the etiology of craniopharyngiomas:

• Embryonic theory:
  • Postulates that embryonic cells from the Rathke’s cleft and the remnants of the craniopharyngeal duct are the site of origin
  • The more likely etiology in the adamantinomatous type, which is more common in children
• Metaplastic theory:
  • Postulates that residual, mature squamous cells of the anterior hypophysis Hypophysis The pituitary gland, also known as the hypophysis, is considered the “master endocrine gland” because it releases hormones that regulate the activity of multiple major endocrine organs in the body. The gland sits on the sella turcica, just below the hypothalamus, which is the primary regulator of the pituitary gland. Pituitary Gland: Anatomy undergo metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation
  • The more likely etiology in the papillary type, which is more common in adults

Genetic mutations Genetic Mutations Carcinogenesis

• Adamantinomatous type: CTNNB1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations → mutations in β-catenin protein
  • A transcription factor Transcription factor Generic term for proteins necessary for transcription Regulation of Transcription in the Wnt signaling pathway 
  • Involved in patterning decisions during embryonic development, cell proliferation, and cell adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies
• Papillary type: activating mutations in the BRAF V600E oncogene → inhibition of apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage/enhanced cell survival

Tumor Tumor Inflammation growth and extension Extension Examination of the Upper Limbs

• Arise in the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types stalk in the suprasellar region
• Project into the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus
• May extend horizontally along the path of least resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing, which may be anteriorly, posteriorly, and/or laterally:
  • Anterior extension Extension Examination of the Upper Limbs:
    • Prechiasmatic cistern
    • Subfrontal spaces
  • Posterior extension Extension Examination of the Upper Limbs:
    • Prepontine cistern
    • Interpeduncular cistern
    • Cerebellopontine angle Cerebellopontine angle Junction between the cerebellum and the pons. Acoustic Neuroma
    • 3rd ventricle
    • Posterior fossa
    • Foramen magnum
  • Lateral extension Extension Examination of the Upper Limbs: toward the subtemporal spaces
• Clinical presentation will depend on the affected areas of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification. Commonly affected areas include:
  • Anterior pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types (and its hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types)
  • Optic chiasm Optic Chiasm The x-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. The Visual Pathway and Related Disorders and/or optic nerves
  • 3rd ventricle (leading to obstructive hydrocephalus Obstructive Hydrocephalus Hydrocephalus in Children)

Clinical Presentation

Craniopharyngiomas are slow-growing tumors; therefore, there is an insidious development of symptoms usually after the tumor Tumor Inflammation attains a diameter > 3 cm. The onset of symptoms is usually 1‒2 years after the tumor Tumor Inflammation develops.

General symptoms

• Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess:
  • Most common presentation, seen in 50%‒80% of cases
  • Presentation is progressive, dull, continuous, and positional.
• Lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia 
• Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and/or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia

Visual disturbances

Visual disturbances are seen in about 40%‒65% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship and include: 

• Bitemporal hemianopia Hemianopia Transient Ischemic Attack (TIA)
• Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis
• Decrease in visual acuity Visual Acuity Clarity or sharpness of ocular vision or the ability of the eye to see fine details. Visual acuity depends on the functions of retina, neuronal transmission, and the interpretative ability of the brain. Normal visual acuity is expressed as 20/20 indicating that one can see at 20 feet what should normally be seen at that distance. Visual acuity can also be influenced by brightness, color, and contrast. Ophthalmic Exam 
• Constriction of visual field Visual Field The Visual Pathway and Related Disorders

Endocrine dysfunction

Some type of endocrine dysfunction is common in craniopharyngiomas, and is seen in about 65%‒90% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Deficiencies in growth hormone (GH), gonadotropins, thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH), and adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones (ACTH) can all be seen.

• GH deficiencies:
  • In young patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: growth failure Growth failure Chronic Granulomatous Disease and delayed puberty Delayed Puberty Delayed puberty (DP) is defined as the lack of testicular growth in boys past the age of 14 and the lack of thelarche in girls past the age of 13. Delayed puberty affects up to 5% of healthy boys and girls, and half of all cases are due to constitutional growth delay. Delayed Puberty 
  • In adults: obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
• Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism (↓ TSH, approximately 40% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
  • Weight gain/ obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Cold intolerance
  • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation 
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia 
  • Amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System in women
  • Impotence in men
• Adrenal dysfunction (↓ ACTH, approximately 25% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
  • Orthostatic hypotension Orthostatic hypotension A significant drop in blood pressure after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm hg decrease in systolic pressure or a 10-mm hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include dizziness, blurred vision, and syncope. Hypotension
  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia 
  • Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia 
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Cardiac arrhythmias 
• Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus insipidus (↓ antidiuretic hormone Antidiuretic hormone Antidiuretic hormones released by the neurohypophysis of all vertebrates (structure varies with species) to regulate water balance and osmolarity. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a cystine. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the kidney collecting ducts to increase water reabsorption, increase blood volume and blood pressure. Hypernatremia, approximately 20% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
  • Polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus
  • Polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation
• Panhypopituitarism: leads to a combination of the above detailed clinical manifestations

Cognitive dysfunction and behavioral issues

Cognitive dysfunction and behavioral issues may be due to impact on the thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus: Anatomy, hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus, and frontal Frontal The bone that forms the frontal aspect of the skull. Its flat part forms the forehead, articulating inferiorly with the nasal bone and the cheek bone on each side of the face. Skull: Anatomy lobes.

• Hyperphagia 
• Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
• Psychomotor retardation
• Emotional immaturity
• Apathy Apathy Lack of emotion or emotional expression; a disorder of motivation that persists over time. Wernicke Encephalopathy and Korsakoff Syndrome 
• Short-term memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment deficits
• Incontinence 

Signs of increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension ( ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP))

Increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension may occur due to obstructive hydrocephalus Obstructive Hydrocephalus Hydrocephalus in Children, and the signs/symptoms may include:

• Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension
• Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis
• Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess

Diagnosis

Diagnosis of craniopharyngiomas should be a multidisciplinary process, including the involvement of specialists in endocrinology, neurology, neuro-ophthalmology, and neurosurgery Neurosurgery Neurosurgery is a specialized field focused on the surgical management of pathologies of the brain, spine, spinal cord, and peripheral nerves. General neurosurgery includes cases of trauma and emergencies. There are a number of specialized neurosurgical practices, including oncologic neurosurgery, spinal neurosurgery, and pediatric neurosurgery. Neurosurgery.

Imaging

The main approach to the diagnosis of craniopharyngiomas is by using radiological imaging, specifically MRI and CT, which reveal a sellar/suprasellar calcified cyst (note: calcification is rare with papillary type). The tumors may have both solid and cystic Cystic Fibrocystic Change components.

• MRI with and without contrast:
  • Considered the gold standard
  • Provides better information on the tumor Tumor Inflammation location and its association with the surrounding structures
  • Tumors enhance with contrast.
  • Extension Extension Examination of the Upper Limbs:
    • Cystic Cystic Fibrocystic Change components typically extend anteriorly and/or laterally, and may wrap around solid components.
    • Solid components typically extend posteriorly and/or laterally.
  • T1-weighted images T1-Weighted Images Imaging of the Head and Brain:
    • Cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change can have a variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables appearance depending on the protein, blood, and/or cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism content.
    • Solid components appear isointense.
  • T2-weighted images T2-Weighted Images Imaging of the Head and Brain:
    • Cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change are hyperintense Hyperintense Magnetic Resonance Imaging (MRI).
    • Solid portions are heterogenous and isointense to hypointense Hypointense Magnetic Resonance Imaging (MRI).
• CT:
  • The best test to detect calcifications, as they are seen vividly on CT
  • Tumors enhance with contrast.
  • Cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change present as hypodense lesions (resemble the fluid density of CSF).
  • Solid portions are isodense.

Histology

• Adamantinomatous type:
  • Reticular epithelial masses are observed.
  • Compactly arranged squamous cells
  • Palisading basal layer of small cells
  • A stellate reticular zone enclosed by the basal layer of cells
  • “Wet keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis”: nodules of keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis that appear plump (aggregated wet keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis is what calcifies)
• Papillary type:
  • Islands of squamous metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation and fibrovascular tissue seen in connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology stroma
  • No keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis nodules

Additional workup

The following should be completed if not done at initial presentation:

• Full neuro exam
• Ophthalmology assessment
• Endocrine workup:
  • TSH levels
  • GH levels
  • Gonadotropin levels:
    • Follicle stimulating hormone ( FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle)
    • Luteinizing hormone ( LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle)
  • Prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy
  • Morning and evening cortisol Cortisol Glucocorticoids levels
  • Serum electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
  • Serum and urine osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation

Management and Prognosis

Primary management options

Surgery is indicated in almost all cases, but there are 2 primary management options:

• Aggressive approach: total surgical resection
  • Total resection is the preferred treatment approach.
  • Total surgical resection is dependent on the location and size of the tumor Tumor Inflammation.
  • Considered with caution in children due to a high association with hypothalamic injury and deficits with gross total resection
• Conservative approach: subtotal resection + radiotherapy 
  • Considered more often to ensure a good quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life postoperatively
  • Indications:
    • Residual tumor Tumor Inflammation after surgery
    • Recurrence of the tumor Tumor Inflammation
  • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy options:
    • Stereotactic radiosurgery
    • Intensity-modulated radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy
    • Proton beam radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy

Cyst management

While surgical management is typically required, there are additional options available to reduce cyst size/ mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast effect, including:

• Percutaneous aspiration Percutaneous Aspiration Pyogenic Liver Abscess (especially if the cyst is impinging on the optic anatomy)
• Intracavitary irradiation
• Intracavitary chemotherapy Chemotherapy Osteosarcoma (can leak from a cyst and cause severe neurotoxicity)

Complications

• Craniopharyngiomas can cause several complications:
  • Endocrine
  • Neurologic
  • Visual
  • Vascular
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be managed by multidisciplinary teams to address issues specific to each patient.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• The prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas of craniopharyngiomas depends on the recurrence of the tumor Tumor Inflammation. 
• Frequent recurrence is usually associated with a poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
• Survival rates:
  • Approximately 90% survival rate at 2 years
  • Approximately 85% survival rate at 5 years 
• 5-year survival based on age:
  • 93% in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 1‒14 years of age
  • 88% in adolescents and young adults
  • 78% in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship > 40 years of age

Differential Diagnosis

The conditions listed below should be considered in the differential diagnosis for craniopharyngiomas. Most cases will present similarly and can be differentiated based on differences in imaging and histology.

• Pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types adenomas: benign Benign Fibroadenoma tumors within the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types gland, many of which are hormonally active. The most common type is a prolactinoma Prolactinoma A pituitary adenoma which secretes prolactin, leading to hyperprolactinemia. Clinical manifestations include amenorrhea; galactorrhea; impotence; headache; visual disturbances; and cerebrospinal fluid rhinorrhea. Hyperprolactinemia, although they may secrete any of the hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types produced by the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types gland. The clinical presentation may include headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, bitemporal hemianopia Hemianopia Transient Ischemic Attack (TIA) and/or diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis, and findings associated with elevated hormone levels. Like craniopharyngioma, pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types adenomas are located within the sella, but only rarely contain cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change or calcifications.
• Glioblastoma multiforme Glioblastoma multiforme Glioblastoma multiforme is a high-grade astrocytoma, an aggressive brain tumor arising from astrocytes, with an unknown cause and a poorly understood link to risk factors. There are two main types: primary, a more aggressive form seen more commonly in older patients, and secondary, developing from lower-grade astrocytomas and seen more commonly in younger patients. Glioblastoma Multiforme: a rapidly progressive WHO grade IV astrocytoma Grade IV Astrocytoma Astrocytoma that arises from astrocytes Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system – the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from ‘star’ cells) are irregularly shaped with many long processes, including those with ‘end feet’ which form the glial (limiting) membrane and directly and indirectly contribute to the blood-brain barrier. They regulate the extracellular ionic and chemical environment, and ‘reactive astrocytes’ (along with microglia) respond to injury. Nervous System: Histology ( glial cells Glial Cells The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain barrier and blood-retinal barrier, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. Nervous System: Histology in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification) and clinically presents as headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, drowsiness, blurred vision Blurred Vision Retinal Detachment, personality changes, and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures. Imaging, clinical presentation, and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma are the mainstays for diagnosis. Management includes radiotherapy, chemotherapy Chemotherapy Osteosarcoma, and surgical excision. Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is poor even with treatment. Unlike hemangioblastoma Hemangioblastoma Hemangioblastomas are vascular neoplasms of the CNS. Hemangioblastomas are rare and are often associated with von Hippel-Lindau disease (VHL). The most common presentation is a headache and, depending on the size and location of the tumor, patients may present with sensory deficits and motor weakness. Hemangioblastoma, glioblastoma multiforme Glioblastoma multiforme Glioblastoma multiforme is a high-grade astrocytoma, an aggressive brain tumor arising from astrocytes, with an unknown cause and a poorly understood link to risk factors. There are two main types: primary, a more aggressive form seen more commonly in older patients, and secondary, developing from lower-grade astrocytomas and seen more commonly in younger patients. Glioblastoma Multiforme is not associated with von Hippel-Lindau (VHL) disease.
• Hemangioblastoma Hemangioblastoma Hemangioblastomas are vascular neoplasms of the CNS. Hemangioblastomas are rare and are often associated with von Hippel-Lindau disease (VHL). The most common presentation is a headache and, depending on the size and location of the tumor, patients may present with sensory deficits and motor weakness. Hemangioblastoma: a rare vascular tumor Tumor Inflammation of the CNS, often associated with VHL disease VHL disease Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic condition resulting from a deletion or mutation in the VHL gene. Individuals diagnosed with VHL disease have tumors and cysts in various parts of their bodies and may present with hemangioblastomas, renal cell carcinoma (RCC), pheochromocytoma, endolymphatic sac tumors of the middle ear, pancreatic tumors, and papillary cystadenomas of the epididymis or the broad ligament. Von Hippel-Lindau Disease, which usually affects the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification but can also involve the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy or retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy. Presenting symptoms include headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess and neurological deficits based on the location of the tumor Tumor Inflammation. While hemangioblastomas Hemangioblastomas A benign tumor of the nervous system that may occur sporadically or in association with von Hippel-Lindau disease. It accounts for approximately 2% of intracranial tumors, arising most frequently in the cerebellar hemispheres and vermis. Histologically, the tumors are composed of multiple capillary and sinusoidal channels lined with endothelial cells and clusters of lipid-laden pseudoxanthoma cells. Usually solitary, these tumors can be multiple and may also occur in the brain stem, spinal cord, retina, and supratentorial compartment. Cerebellar hemangioblastomas usually present in the third decade with intracranial hypertension, and ataxia. Von Hippel-Lindau Disease may have both solid and cystic Cystic Fibrocystic Change components, they tend to be located in the cerebellum Cerebellum The cerebellum, Latin for “little brain,” is located in the posterior cranial fossa, dorsal to the pons and midbrain, and its principal role is in the coordination of movements. The cerebellum consists of 3 lobes on either side of its 2 hemispheres and is connected in the middle by the vermis. Cerebellum: Anatomy or spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy and do not generally calcify.
• Meningioma Meningioma Meningiomas are slow-growing tumors that arise from the meninges of the brain and spinal cord. The vast majority are benign. These tumors commonly occur in individuals with a history of high doses of skull radiation, head trauma, and neurofibromatosis 2. Meningioma: a tumor Tumor Inflammation arising from the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy. Meningiomas are commonly asymptomatic, but can present with headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, and visual disturbances. Meningiomas are diagnosed using MRI and a biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Asymptomatic cases are typically observed while symptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are treated surgically or with radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma. Unlike craniopharyngiomas, meningiomas are always near the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy and often have imaging findings of dural attachment (e.g., dural tail sign Dural tail sign Marginal dural thickening that tapers peripherally Meningioma).