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Xanthomas Workup

  • Author: Kara Melissa T Torres, MD, DPDS; Chief Editor: Dirk M Elston, MD  more...
Updated: Mar 25, 2015

Laboratory Studies

Primary hyperlipidemia is primarily a diagnosis of exclusion. Appropriate blood, urine, and radiographic workups are required to rule out a secondary cause of hyperlipidemia. Lipoprotein profiles are primarily used to assess cardiac risk and to aid in the diagnosis of lipid metabolism disorders.

Plasma levels of triglyceride, cholesterol, and HDL-cholesterol are measured following a 12-hour fast before venipuncture. Cholesterol and triglyceride levels are usually measured by enzymatic methods. HDL-cholesterol levels can be measured after the apoprotein B–containing lipoproteins (chylomicrons, VLDL, IDL, LDL, Lp[a]) are removed by polyanion-divalent cation precipitation. LDL and VLDL can then be calculated as follows:

  • LDL = Total Cholesterol Level – (Triglyceride Levels/5 + HDL Level)
  • VLDL = Triglyceride Levels/5*

*If triglycerides are greater than 700, the denominator is 10.

Chylomicrons, because of their high lipid-protein ratio, are less dense and form a creamy layer when plasma is left standing for several hours. Ultracentrifugation fractions can be electrophoretically examined for the presence of beta-VLDL and Lp(a). Quantification of apolipoproteins, particularly B and A-I, can be achieved by immunologic methods.

Lipoprotein patterns can be determined as follows:

  • I - Elevated triglyceride levels with increased chylomicron levels
  • IIa - Elevated cholesterol level because of increased LDL level
  • IIb - Elevated cholesterol and triglyceride levels because of increased LDL and VLDL levels
  • III - Elevated cholesterol and triglyceride levels, with the presence of beta-VLDL
  • IV - Elevated triglyceride levels because of increased VLDL level
  • V - Elevated triglyceride levels because of increased VLDL level and the presence of chylomicrons

The risk for cardiovascular disease can be determined on the basis of the total cholesterol, LDL-cholesterol, and HDL-cholesterol values in adults and children.


Imaging Studies

Ultrasonography and magnetic resonance imaging (MRI) may enhance the diagnosis of Achilles tendon xanthomas.[71]

Positron-emission tomography/computed tomography may be used to detect disease extent and assess treatment response in cases of xanthoma disseminatum.[72]


Histologic Findings

Changes in the skin and the tendons are characterized by the presence of vacuolated macrophages (foamy macrophages). These macrophages are filled with lipid droplets, which are dissolved and removed from the tissue during histologic processing. Lipid stains are of no use in routinely processed tissue. In contrast, frozen sections can be stained with lipid stains. Foamy histiocytes usually have 1 nucleus, but multinucleated histiocytes (Touton giant cells) are often identified.

See the image below.

Microscopic image of a xanthelasma. The lesion is Microscopic image of a xanthelasma. The lesion is composed of lipid-laden macrophages located in the superficial dermis. Courtesy of Duke University Medical Center.

Eruptive xanthomas may contain infiltrates of lymphocytes and typically contain extracellular lipid. Rarely, eruptive neutrophilic xanthomas with prominent leukocytoclasis may occur.[73] Xanthelasma shows superficially located foamy cells and the characteristic appearance of eyelid skin. Tendinous and tuberous xanthomas may contain prominent fibrosis and occasional cholesterol clefts. Verruciform xanthoma is histologically characterized by hyperkeratosis or parakeratosis with acanthosis, lipid-laden histiocytes within the dermal papillae, and often with a polymorphonuclear infiltrate. Red wedge-shaped areas of epidermal necrosis are characteristically present.[74] Epidermolytic acanthoma is rare but may occur.[75]

Contributor Information and Disclosures

Kara Melissa T Torres, MD, DPDS Visiting Research Fellow, Ackerman Academy of Dermatopathology

Kara Melissa T Torres, MD, DPDS is a member of the following medical societies: Philippine Dermatological Society

Disclosure: Nothing to disclose.


Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Edward F Chan, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine

Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Ponciano D Cruz, Jr, MD Professor and Vice-Chair, Paul R Bergstresser Chair, Department of Dermatology, University of Texas Southwestern Medical Center

Ponciano D Cruz, Jr, MD is a member of the following medical societies: Texas Medical Association

Disclosure: Received consulting fee from RCTS for independent contractor; Received honoraria from Mary Kay Cosmetics for consulting; Received grant/research funds from Galderma for principal investigator.


Kevaghn P Fair, DO Consultant Pathologist and Founder, Dominion Pathology Laboratories

Kevaghn P Fair, DO is a member of the following medical societies: American Society for Clinical Pathology, American Society of Dermatopathology, and College of American Pathologists

Disclosure: Nothing to disclose.

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Xanthelasma. Courtesy of Duke University Medical Center.
Eruptive xanthomas. Courtesy of Duke University Medical Center.
Tuberous xanthomas. Courtesy of Duke University Medical Center.
Microscopic image of a xanthelasma. The lesion is composed of lipid-laden macrophages located in the superficial dermis. Courtesy of Duke University Medical Center.
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