Achieve Mastery of Medical Concepts

Study for medical school and boards with Lecturio

Von Hippel-Lindau 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. The diagnosis is by genetic testing, laboratory evaluation of BUN, laboratory evaluation for the presence of catecholamines in the blood or urine, fundoscopic exam of the eye to detect hemangioblastoma of the retina, and CT/MRI to detect any other tumors. Management of the disease includes surgical removal of tumors. 

Last updated: Oct 17, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Von Hippel-Lindau (VHL) disease is an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder characterized by hemangioblastomas of the 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 and CNS; 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 involving the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy, pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy, and epididymis Epididymis The convoluted cordlike structure attached to the posterior of the testis. Epididymis consists of the head (caput), the body (corpus), and the tail (cauda). A network of ducts leaving the testis joins into a common epididymal tubule proper which provides the transport, storage, and maturation of spermatozoa. Testicles: Anatomy; renal cell carcinoma Renal cell carcinoma Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma ( RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma); pheochromocytomas; and pancreatic islet cell Islet cell Pancreatic Neuroendocrine Tumors (PanNETs) tumors.

Etiology

  • Mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the VHL tumor-suppressor 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 located on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 3 causes VHL disease.
  • The mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations may be de novo or can occur through autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance inheritance.
  • 80% of cases are genetically inherited.
  • 20% of cases are new mutations.

Epidemiology

  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency is estimated to be 1 in 30,000 to 1 in 50,000 live births.
  • Men and women are equally affected.
  • The average age of diagnosis is 26 years; however, individuals are diagnosed at any time from birth to death.
  • VHL disease is the most frequent cause of hereditary renal cancer.
  • The 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 of pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma is up to 60% in individuals with VHL disease.

Classification

  • Type 1 Type 1 Spinal Muscular Atrophy, without pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma
  • Type 2 Type 2 Spinal Muscular Atrophy, with pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma:
    • Type 2A: Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma is present along with a low 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 of RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma.
    • Type 2B: Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma is present along with a high 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 of RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma.
    • Type 2C: Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma is present without 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 or RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma.

Pathophysiology

  • Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations of the VHL tumor-suppressor 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 on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 3 leads to the formation of abnormal VHL protein (pVHL).
  • Abnormal or absent pVHL results in the uninhibited upregulation of hypoxia-inducible factor (HIF).
  • Upregulated growth factors (e.g., vascular endothelial growth factor Vascular endothelial growth factor A family of angiogenic proteins that are closely-related to vascular endothelial growth factor a. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. Wound Healing, erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology)
  • The above factors lead to the formation of 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 and hypervascular tumors that are characteristic of VHL disease.

Clinical Presentation

The presentation varies depending on the size and location of the tumor Tumor Inflammation. Family history Family History Adult Health Maintenance is a key piece of information, as the majority of cases are inherited. Physical examination is usually nonrevealing, with the exception of affected individuals who present with neurologic abnormalities in the setting of hemangioblastomas.

  • Hemangioblastomas:
    • Well-circumscribed, capillary vessel-rich neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors
    • Benign Benign Fibroadenoma, do not invade locally or metastasize
    • Occur in 60%–84% of individuals with VHL disease
    • Common in the 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, 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, 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
    • May cause visual deficits if present on the 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
    • May cause focal neurologic deficits Neurologic Deficits High-Risk Headaches if present 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 
  • RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma:
    • Occurs in ⅔ of affected individuals
    • Clear cell tumors are the most common variant of RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma seen in individuals with VHL disease.
    • Most often multicentric and bilateral
    • Can arise either in conjunction with 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 de novo from noncystic renal parenchyma
    • Affected individuals present with flank pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, and renal dysfunction.
  • Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma:
    • Present in up to 16% of individuals with VHL disease
    • Usually presents in the 2nd decade of life
    • May cause episodic hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension with palpitations Palpitations Ebstein’s Anomaly, panic attacks, diaphoresis, and mood changes
  • Endolymphatic sac tumors of the middle ear Middle ear The space and structures directly internal to the tympanic membrane and external to the inner ear (labyrinth). Its major components include the auditory ossicles and the eustachian tube that connects the cavity of middle ear (tympanic cavity) to the upper part of the throat. Acute Otitis Media:
    • Highly vascular lesions arising within the posterior portion of the temporal bone Temporal bone Either of a pair of compound bones forming the lateral (left and right) surfaces and base of the skull which contains the organs of hearing. It is a large bone formed by the fusion of parts: the squamous (the flattened anterior-superior part), the tympanic (the curved anterior-inferior part), the mastoid (the irregular posterior portion), and the petrous (the part at the base of the skull). Jaw and Temporomandibular Joint: Anatomy
    • Clinical manifestations include hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss, tinnitus Tinnitus A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. Cranial Nerve Palsies, vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo, and facial muscle weakness.
    • Often bilateral
    • Most commonly seen in the younger age group
  • Pancreatic tumors:
    • Usually asymptomatic
    • Can present with epigastric pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and abdominal discomfort
  • Papillary cystadenoma of the epididymis Epididymis The convoluted cordlike structure attached to the posterior of the testis. Epididymis consists of the head (caput), the body (corpus), and the tail (cauda). A network of ducts leaving the testis joins into a common epididymal tubule proper which provides the transport, storage, and maturation of spermatozoa. Testicles: Anatomy or broad ligament Broad Ligament A broad fold of peritoneum that extends from the side of the uterus to the wall of the pelvis. Uterus, Cervix, and Fallopian Tubes: Anatomy:
    • Bilateral papillary cystadenomas are almost pathognomonic of VHL disease.
    • Benign Benign Fibroadenoma and generally asymptomatic; thus, no treatment is required

Mnemonic

HIPPEL:

  • Hemangioblastoma
  • Increased risk of RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma
  • Pheochromocytoma
  • Pancreatic lesions ( 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, cystadenomas, and neuroendocrine tumors Neuroendocrine tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via apud cells), the presence of tumor-associated antigens, and isozyme composition. Gastrinoma)
  • Eye Lesions (retinal angiomas or 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)

Diagnosis

  • Clinical criteria used to diagnose VHL disease:
    • > 1 CNS 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
    • Visceral manifestation of VHL disease
    • VHL manifestation in addition to a family history Family History Adult Health Maintenance significant for VHL disease
  • Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies:
    • Heterozygous pathogenic variant of the VHL 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 confirms the diagnosis of inherited VHL disease.
    • Pathogenic variants may arise from de novo mutations.
    • Rare cases exhibit clinical features of VHL disease but there are no detectable mutations.
  • Fundoscopic/ophthalmologic eye exam:
    • To detect 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 of the eye
    • To detect retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment
    • To check for cataracts
  • Audiometric testing: may show hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss secondary to an endolymphatic sac tumor Tumor Inflammation
  • Laboratory tests:
    • BUN and creatinine levels to determine renal involvement
    • Presence of catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones and/or their metabolites in blood and/or urine to detect pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma
  • CT/MRI imaging studies to detect:
    • RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma
    • Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma
    • 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
    • Endolymphatic sac tumors of the middle ear Middle ear The space and structures directly internal to the tympanic membrane and external to the inner ear (labyrinth). Its major components include the auditory ossicles and the eustachian tube that connects the cavity of middle ear (tympanic cavity) to the upper part of the throat. Acute Otitis Media

Management

Treatment of VHL disease is tailored depending on the location and size of the lesions, symptoms of the individual, and the extent of the disease.

  • CNS hemangiomas are surgically removed:
    • Recurrence is possible after surgical removal.
    • Gamma knife radiosurgery is an alternative treatment.
  • Retinal capillary hemangiomas are usually treated with diathermy, xenon, laser photocoagulation, and external beam radiotherapy:
    • Small hemangiomas that do not interfere with vision Vision Ophthalmic Exam can be observed.
    • Laser photocoagulation is the preferred treatment for small lesions.
    • Cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma is the preferred treatment when fluid is present underneath the 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.
  • Nephrectomy Nephrectomy Excision of kidney. Renal Cell Carcinoma:
    • The preferred approach in cases of RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma associated with VHL disease
    • Cryoablation Cryoablation Fibroadenoma and radiofrequency ablation Radiofrequency ablation Removal of tissue using heat generated from electrodes delivering an alternating electrical current in the frequency of radio waves. Hepatocellular Carcinoma (HCC) and Liver Metastases are preferred for small tumors.
  • The preferred treatment for symptomatic pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma is the surgical removal after appropriate supportive therapy:
    • Preoperative alpha-adrenoceptor and beta-adrenoceptor blockers are prescribed to avoid excess catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones.
    • Laparoscopic adrenalectomy Adrenalectomy Excision of one or both adrenal glands. Cushing Syndrome is the preferred surgical approach except in cases where the tumor Tumor Inflammation is invasive or > 6.0 cm.
  • Treatment of endolymphatic sac tumors of the middle ear Middle ear The space and structures directly internal to the tympanic membrane and external to the inner ear (labyrinth). Its major components include the auditory ossicles and the eustachian tube that connects the cavity of middle ear (tympanic cavity) to the upper part of the throat. Acute Otitis Media is primarily by surgical removal to prevent hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss.
  • Surgical resection is preferred for pancreatic neuroendocrine tumors Pancreatic Neuroendocrine Tumors Pancreatic neuroendocrine tumors (PanNETs) arise from the endocrine pancreas (islet cells) and represent 2%-5% of primary pancreatic neoplasms; the other 95%-98% of pancreatic neoplasms are from the exocrine pancreas. The majority of PanNETs are nonfunctional (50%-75%), while others that are functional may be benign or malignant. Pancreatic Neuroendocrine Tumors (PanNETs):
    • Indicated for tumors > 3 cm
    • Indicated if the tumor-doubling rate is < 500 days
Surgically removed pheochromocytoma

Surgically removed pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma

Image: “Adrenal paraganglioma Paraganglioma A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion, such as the carotid body, or medulla of the adrenal gland (usually called a chromaffinoma or pheochromocytoma). It is more common in women than in men. Hearing Loss clinical Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma” by Michael Feldman. License: CC BY 2.0

Differential Diagnosis

  • MEN2: an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance inherited condition characterized by a hormone-producing tumor Tumor Inflammation. The MEN2A variant is associated with primary hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism, whereas MEN2B is associated with neuromas and Marfanoid habitus Marfanoid Habitus Multiple Endocrine Neoplasia. Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast, lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node enlargement, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, 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 pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma are the presenting symptoms. Diagnosis is based on lab studies, CT, and RET mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations analysis. Surgical removal of the tumor Tumor Inflammation is the primary treatment modality.
  • Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma: a catecholamine-secreting tumor Tumor Inflammation derived from chromaffin cells Chromaffin cells Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia of the sympathetic nervous system. Adrenal Hormones. Symptoms result from excessive catecholamine production and include hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, 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 sweating. Diagnosis is made on the basis of clinical examination, laboratory studies, and CT. Approximately 90% of pheochromocytomas are benign Benign Fibroadenoma, and surgical resection is the only curative treatment. Pheochromocytomas are associated with VHL disease but some cases present in isolation without other findings of VHL disease.
  • Neurofibromatosis type 1 Neurofibromatosis type 1 Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas. Neurofibromatosis Type 1 ( NF1 NF1 Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas. Neurofibromatosis Type 1): an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance inherited condition characterized by an abnormality in the tumor-suppressor 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, giving rise to nerve tumors. Affected individuals present with café au lait spots, neurofibroma Neurofibroma A moderately firm, benign, encapsulated tumor resulting from proliferation of schwann cells and fibroblasts that includes portions of nerve fibers. The tumors usually develop along peripheral or cranial nerves and are a central feature of neurofibromatosis 1, where they may occur intracranially or involve spinal roots. Pathologic features include fusiform enlargement of the involved nerve. Microscopic examination reveals a disorganized and loose cellular pattern with elongated nuclei intermixed with fibrous strands. Neurofibromatosis Type 1, skinfold freckling Freckling Neurofibromatosis Type 1, optical pathway gliomas, and Lisch nodules Lisch Nodules Neurofibromatosis Type 1. The diagnosis is based on the NIH clinical criteria and imaging studies. Selumetinib and surgery are the treatment modalities.
  • RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma: the most common cancer of the kidney. Renal cell carcinomas are often asymptomatic and can present with hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, flank pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and an abdominal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast. Diagnosis is based on imaging studies and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Treatment is by removing the kidney in part or entirety. In addition to being associated with VHL disease, RCC RCC Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma is also encountered in several paraneoplastic syndromes Paraneoplastic syndromes Paraneoplastic syndromes are a heterogeneous group of disorders caused by an abnormal immune response to a neoplasm. The substances produced are not due to the direct effect of the tumor, such as metastasis, mass effect, or invasion. Antibodies, hormones, cytokines, and other substances are generated and affect multiple organ systems. Paraneoplastic Syndromes that cause hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia, anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, and amyloidosis Amyloidosis Amyloidosis is a disease caused by abnormal extracellular tissue deposition of fibrils composed of various misfolded low-molecular-weight protein subunits. These proteins are frequently byproducts of other pathological processes (e.g., multiple myeloma). Amyloidosis.

References

  1. Plon, E.S., Jonasch, E. (2020). Clinical features, diagnosis, and management of von Hippel-Lindau disease. UpToDate. Retrieved August 21, 2021, from https://www.uptodate.com/contents/clinical-features-diagnosis-and-management-of-von-hippel-lindau-disease
  2. Plon, E.S., Jonasch, E. (2020). Molecular biology and pathogenesis of von Hippel-Lindau disease. UpToDate. Retrieved August 21, 2021, from https://www.uptodate.com/contents/molecular-biology-and-pathogenesis-of-von-hippel-lindau-disease
  3. Mikhail, M.I., Singh, A.K. (2021). Von Hippel Lindau Syndrome. NCBI. Retrieved August 21, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK459242/
  4. Leeuwaarde, R.S., Ahmad, S., Links, T.P., Giles, R.H. (2018). Von Hippel-Lindau Syndrome. NCBI. Retrieved August 21, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK1463/
  5. Chittiboina, P., Lonser, R.R. (2016). Von Hippel–Lindau disease. NCBI. Retrieved August 21, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121930/
  6. Gulani, A.C., Defendi, G.L. (2019). von Hippel-Lindau Disease. MedScape. Retrieved August 21, 2021, from https://emedicine.medscape.com/article/1219430

USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.

Create your free account or log in to continue reading!

Sign up now and get free access to Lecturio with concept pages, medical videos, and questions for your medical education.

User Reviews

¡Hola!

Esta página está disponible en Español.

Details