Post contrast T1 weighted MRI demonstrates intense enhancement of both the eye and the endolymphatic sac tumor

An endolymphatic sac tumor (ELST) is a very uncommon papillary epithelial neoplasm arising within the

endolymphatic sac From the posterior wall of the saccule a canal, the endolymphatic duct, is given off; this duct is joined by the utriculosaccular duct, and then passes along the vestibular aqueduct and ends in a blind pouch, the endolymphatic sac, on the poste ...

endolymphatic duct From the posterior wall of the saccule a canal, the endolymphatic duct, is given off; this duct is joined by the ductus utriculosaccularis, and then passes along the aquaeductus vestibuli and ends in a blind pouch (endolymphatic sac) on the pos ...

. This tumor shows a very high association with Von Hippel–Lindau syndrome (VHL).

Classification

The ELST has been referred to as adenocarcinoma of endolymphatic sac, Heffner tumor, papillary adenomatous tumor, aggressive papillary adenoma, invasive papillary cystadenoma, and papillary tumor of temporal bone. However, these names are not encouraged as they do not accurately classify the current understanding of the tumor.

Signs and symptoms

Patients with ELST may present clinically with progressive or fluctuating, one sided sensorineural

hearing loss Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spoken la ...

which may mimick

Ménière's disease Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initi ...

due to the development of tumor associated endolymphatic hydrops. Patients may also experience

tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...

vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties ...

, and loss of vestibular function (

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of t ...

). Alternatively, symptom onset may be sudden, due to intralabyrinthine hemorrhage. Patients may also present with other symptoms related to von Hippel–Lindau syndrome in other anatomic sites, which will result in imaging evaluation of the head.

Imaging findings

Imaging studies help to identify the tumor and the specific anatomic site of involvement. Magnetic resonance images show a hyperintensity (

hypervascularity Hypervascularity is an increased number or concentration of blood vessels. In Graves disease, the thyroid gland is hypervascular, which can help in differentiating the condition from thyroiditis. 90% of thyroid papillary carcinoma cases are ...

) of a heterogeneous mass by T1 weighted images.

Computed tomography A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...

shows a multilocular, lytic destructive temporal bone mass, centered on the vestibular aqueduct (between

internal auditory canal The internal auditory meatus (also meatus acusticus internus, internal acoustic meatus, internal auditory canal, or internal acoustic canal) is a canal within the petrous part of the temporal bone of the skull between the posterior cranial fossa ...

and

sigmoid sinus The sigmoid sinuses (sigma- or s-shaped hollow curve), also known as the , are venous sinuses within the skull that receive blood from posterior dural venous sinus veins. Structure The sigmoid sinus is a dural venous sinus situated within the du ...

Pathogenesis

The von Hippel–Lindau tumor suppressor gene generally has a

germline mutation A germline mutation, or germinal mutation, is any detectable variation within germ cells (cells that, when fully developed, become sperm and ova). Mutations in these cells are the only mutations that can be passed on to offspring, when either a ...

. This

suppressor gene Epistasis is a phenomenon in genetics in which the effect of a gene mutation is dependent on the presence or absence of mutations in one or more other genes, respectively termed modifier genes. In other words, the effect of the mutation is dep ...

is also called elongin binding protein and G7 protein. The VHL protein is involved in up-regulation of hypoxic response via the hypoxia inducible factor [HIF1 alpha">IF.html" ;"title="hypoxia inducible factor [HIF">hypoxia inducible factor [HIF1 alpha. Mutations generally prevent the production of any functional VHL protein or result in a change of structure of VHL protein. This genetic disorder shows an autosomal dominant inheritance pattern, with about 20% of patients possessing a new mutation. There are usually several other tumors which are part of the syndrome, including tumors of the central nervous system, kidneys,

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an en ...

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex w ...

epididymis The epididymis (; plural: epididymides or ) is a tube that connects a testicle to a vas deferens in the male reproductive system. It is a single, narrow, tightly-coiled tube in adult humans, in length. It serves as an interconnection between t ...

broad ligament The broad ligament of the uterus is the wide fold of peritoneum that connects the sides of the uterus to the walls and floor of the pelvis. Structure Subdivisions Contents The contents of the broad ligament include the following: * Reproduc ...

, along with the endolymphatic sac. The vast majority of patients with an endolymphatic sac tumor have von Hippel-Lindau syndrome.

Pathology findings

Tumors range from several millimeters up to 10 cm, with larger tumors more frequently seen in older patients. If the tumor is bilateral, it is almost always seen in a VHL patient. The tumor destroys the mastoid air spaces and extends into the

middle ear The middle ear is the portion of the ear medial to the eardrum, and distal to the oval window of the cochlea (of the inner ear). The mammalian middle ear contains three ossicles, which transfer the vibrations of the eardrum into waves in ...

and/or

posterior cranial fossa The posterior cranial fossa is part of the cranial cavity, located between the foramen magnum and tentorium cerebelli. It contains the brainstem and cerebellum. This is the most inferior of the fossae. It houses the cerebellum, medulla and pons ...

. The microscopic appearance shows an unencapsulated, destructive growth, remodeling and invading bone. The tumor is arranged as simple, broad, non-complex papillary projections without large cystic spaces. The spaces are often fluid filled, have extravasated erythrocytes and/or inspissated material. The cells are cuboidal, usually single layered along the papillary structures, showing indistinct cell borders. The nuclei are round and hyperchromatic.

Immunohistochemistry

The neoplastic cells are reactive with

keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ...

, CK7, and Epithelial membrane antigen, but negative with TTF-1 and

CK20 Keratin 20, often abbreviated CK20, is a protein that in humans is encoded by the ''KRT20'' gene. Keratin 20 is a type I cytokeratin. It is a major cellular protein of mature enterocytes and goblet cells and is specifically found in the gast ...

Cytogenetics

The germline mutations of VHL tumor suppressor gene will be found on 3p25-26 (short arm of

chromosome 3 Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans almost 200 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA i ...

), usually between base pair 10,158,318 to 10,168,761.

Differential diagnosis

The clinical and pathology differential are different. From a pathology perspective, an endolymphatic sac tumor needs to be separated from

metastatic Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, res ...

, metastatic thyroid papillary carcinoma, middle ear adenoma,

paraganglioma A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). When the same type of tumor is found in the adrenal gland, they are referred to as a pheochromocytoma. They a ...

choroid plexus papilloma Choroid plexus papilloma, also known as papilloma of the choroid plexus, is a rare benign neuroepithelial intraventricular WHO grade I lesion found in the choroid plexus. It leads to increased cerebrospinal fluid production, thus causing increa ...

, middle ear adenocarcinoma, and

ceruminous adenoma A ceruminous adenoma is a benign glandular neoplasm which arises from the ceruminous glands located within the external auditory canal. These glands are found within the outer one third to one half of the external auditory canal, more common alo ...

Management

Wide excision is the treatment of choice, although attempting to preserve hearing. Based on the anatomic site, it is difficult to completely remove, and so while there is a good prognosis, recurrences or persistence may be seen. There is no metastatic potential. Patients who succumb to the disease, usually do so because of other tumors within the von Hippel-Lindau complex rather than from this tumor. Surgery is the primary treatment modality, but in some rare instances adjuvant radiation therapy may be used.

Epidemiology

This is a very rare tumor, since only about 1 in 35,000 to 40,000 people have VHL, of whom about 10% have endolymphatic sac tumors. Patients usually present in the 4th to 5th decades without an gender predilection. The tumor involves the endolymphatic sac, a portion of the intraosseous inner ear of the posterior petrous bone.