Hyperlipoproteinemia type I

Abstract

Xanthoma of the temporal bone is extremely rare; we describe only the fourteenth reported case. Our case is further remarkable because it is the first report of such an occurrence in a patient with familial type III hyperlipoproteinemia. Moreover, while otalgia, infection, hearing loss, and tinnitus were the most common initial symptoms in the previous 13 cases, our patient reported only diplopia, vertigo, and unstable gait. The patient underwent a simple mastoidectomy and debulking, and his diplopia, vertigo, and unstable gait resolved.

Introduction

Xanthomas are soft tissue tumors composed of lipid-laden tissue histiocytes. They are nonneoplastic, reactive proliferations that often occur in patients who have pathologic levels of serum lipids. Although they occasionally occur in normolipidemic patients, experimental and clinical evidence supports their increased incidence in hyperlipidemic populations. [1,2]

Elevated plasma lipoprotein levels are caused by hypothyroidism, diet, insulin deficiency, alcoholism, oral contraceptive use, nephrotic syndrome, and obstructive biliary disease. In some patients, hyperlipoproteinemia is the result of a primary hereditary defect in the synthesis or degradation of lipoprotein particles. The hereditary types of hyperlipoproteinemia are familial lipoprotein lipase deficiency and/or apoprotein C-II deficiency (type I or V), familial hypercholesterolemia (type IIa or IIb), familial dysbetalipoproteinemia type III), familial hypertriglyceridemia (type IV), and combined hypercholesterolemia (type IIa, IIb, and/or IV) (table). [3] Xanthoma formation is associated with all types of hyperlipidemia, and its severity is often determined by the severity and duration of the elevated lipid levels. [4]

The pathogenesis of xanthomas involves the accumulation of blood lipids in connective tissue. Serum lipoproteins escape from the vascular compartment and enter connective tissue at sites of increased vascular permeability. Tissue macrophages in the localized areas ingest the escaped particles, degrade them to lipids, and release the lipids into extracellular spaces. Undigested cholesterol builds up in crystalline form in the connective tissue and induces the inflammatory and fibrotic changes that are characteristic of the xanthomatous process. [1,2] Histologically, xanthomas appear as sheets of foamy histiocytes interspersed with inflammatory cells and extracellular cholesterol clefts.

The nidus of xanthoma formation is often a site of local trauma. Trauma can cause the release of vasoactive histamine and bradykinin, which results in increased vascular permeability. Thus, the most common sites of xanthomas are areas that typically experience repeated trauma (e.g., the knees, elbows, and buttocks), skin that is subjected to constant creasing and folding (e.g., the eyelids), tendons that are subjected to friction from neighboring joints, and in rare cases bone. [1]

The occurrence of a xanthoma in the temporal bone, which is extremely rare, is associated with the presence of hyperlipoproteinemia IIa, IIb, and V. [5,6] In this article, we describe only the fourteenth reported case of a temporal bone xanthoma. What makes our case unique is that it occurred in a patient who had type III hyperlipoproteinemia.

Case report

A 28-year-old man came to our institution for an evaluation of recent-onset diplopia, vertigo, and unstable gait. The patient denied headache, hearing loss, and tinnitus. The physical examination revealed that the cranial nerves were intact. There was no nystagmus, and his extraocular movements were normal. The tympanic membranes were clear bilaterally, and cerebellar function was intact. Xanthomas were noted over the extensor surfaces of the hands, knees, and buttocks.

The medical history included recurrent pancreatitis of 6 years' duration, type III hyperlipoproteinemia, and hyperuricemia. Several years earlier, he had had a lumboperitoneal shunt placed for presumed pseudotumor cerebri and diminished vision in the left eye associated with optic nerve atrophy. The patient's social history was significant for smoking one pack of cigarettes per day for 10 years and drinking two or three beers per day. His family history was significant only for the familial type III hyperlipoproteinemia (his father). He had no known drug allergies. His regular medications included meclizine and aspirin; he also reported taking gemfibrozil and pravastatin, but not on a consistent basis.

Laboratory results at the time of admission were significant for a cholesterol level of 406 mg/dl (normal: 118 to 239), a triglyceride level of 2,622 mg/dl (normal: 25 to 100), and lipidemic blood. His audiogram was normal. Computed tomography revealed a soft tissue density of the right mastoid and temporal bone, which was associated with significant bone destruction. Magnetic resonance imaging revealed compression of the right cerebellar hemisphere, decreased flow through the sigmoid sinus, and tumor extending into the middle cranial fossa toward the temporal lobe (figure 1).

The patient underwent a simple mastoidectomy and debulking. Biopsy revealed that the lesion was a xanthoma (figure 2). The patient did well postoperatively and reported that his diplopia, vertigo, and unstable gait had resolved. He was discharged from the hospital on gemfibrozil, pravastatin, meclizine, and aspirin.

Discussion

Familial type III hyperlipoproteinemia is a genetic disorder in which the plasma concentrations of both cholesterol and triglycerides are elevated as a result of the accumulation of chylomicron remnants and intermediate-density lipoproteins (IDL). The normal uptake of chylomicrons and IDL by the liver cannot occur because of a defect in apoprotein E, which normally facilitates the binding of chylomicrons and IDL to their respective receptors. Affected individuals usually do not manifest hyperlipidemia or any clinical features of the disease until the third decade of life.

When the disease does manifest, patients typically develop palmar xanthomas, which appear as a yellowish discoloration of the hand and finger creases, and tuberous xanthomas, which are bulbous cutaneous growths located on the elbows and knees. In addition, atherosclerosis involving the coronary arteries, carotid arteries, and the abdominal aorta is common. Sequelae include early myocardial infarction, stroke, and claudication of the lower extremities. [3] To date, xanthoma of the bone has not been found in any patient with familial type III hyperlipoproteinemia.

Cutaneous xanthomas usually present few diagnostic difficulties. On the other hand, deep xanthomas, which occur most often in tendons or synovium but rarely in bone, pose more of a diagnostic problem. [7,8] The complexity and inaccessibility of the skull base structure make the diagnosis and treatment of lesions in this area an even greater challenge. Pathologic processes in this region can develop silently, not manifesting until they have reached an advanced stage. The later stages are characterized by involvement of adjacent structures, and they can prompt a variety of complaints, including cranial nerve palsies and cerebellar signs.

There is a wide spectrum of pathology capable of producing bony erosion of the temporal bone. Among the possible causes are (1) congenital lesions, such as osteogenesis imperfecta and cholesteatomas; (2) inflammatory lesions and diseases, such as cholesterol granulomas, osteomyelitis, and mastoiditis; (3) fibro-osseous disease, such as fibrous dysplasia and Paget's disease; (4) benign and malignant neoplasms, such as chordomas and nasopharyngeal carcinomas; and (5) infiltrative lesions, such as eosinophilic granulomas and xanthomas. [9] Although radiologic studies are invaluable in determining the extent of disease, surgical modalities are usually necessary to provide histologic confirmation and ultimate treatment. [10,11]

In an extensive literature search, we found only 13 previously reported cases of temporal bone xanthoma. [5,12] Otalgia, infection, hearing loss, and tinnitus were the most common initial symptoms in these 13 patients. In contrast, the patient we describe reported diplopia, vertigo, and disequilibrium. Although hyperlipidemia was documented in approximately one-half of the previously reported cases of temporal bone xanthoma, this is the first report of an accompanying familial type III hyperlipoproteinemia.

Because xanthomas are not true neoplasms, a conservative therapeutic approach is recommended. Treatment should be individualized. A vigorous search for the underlying cause of the hyperlipidemia is required, and if such a search is successful, initial treatment should aim to correct it. Regression of extratemporal xanthomas has been reported with medical control of hyperlipidemia. [13] A low-fat diet, control of obesity, and treatment with cholesterol-lowering medications are the mainstays of xanthoma management. Surgical intervention is indicated for biopsy, debulking of the mass for symptom relief, and management of infectious complications. However, because surgically treated xanthomas tend to recur, medical therapy for hyperlipidemia should continue after any surgical procedure. [6] There is little evidence to support the benefits of radiation therapy for xanthomas of the temporal bone. [14]

References

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(4.) Enzinger FM, Weiss SW. Soft Tissue Tumors. St. Louis: Mosby-Year Book, 1995:310-3.

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(8.) Siegelman SS, Schlossberg I, Becker NH, Sachs BA. Hyperlipoproteinemia with skeletal lesions, Clin. Orthop 1972;87:228-32.

(9.) Friedman I. Pathology of the Ear. New York: Churchill Livingstone, 1993:299-305.

(10.) Lloyd GA, Phelps PD. The investigation of petro-mastoid tumours by high resolution CT. Br J Radiol 1982;55:483-91.

(11.) Flood LM, Kemink JL. Surgery in lesions of the petrous apex. Otolaryngol Clin North Am 1984;17:565-75.

(12.) Algoed L, Caemaert J, Achten E, et al. A large intracranial xanthoma in familial hypercholesterolemia. Clin Neurol Neurosurg 1994;96:79-82.

(13.) Palmer AJ, Blacket R. Regression of xanthomata of the eyelids with modified fat diet. Lancet 1972;1:67-8.

(14.) Koch HL, Lewis JS. Hyperlipidemia xanthomatosis with associated osseous granuloma. N Engl J Med 1956;255:287-9.

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