Medscape is available in 5 Language Editions – Choose your Edition here.


Verruciform Xanthoma Workup

  • Author: W Clark Lambert, MD, PhD; Chief Editor: William D James, MD  more...
Updated: Oct 31, 2014

Laboratory Studies

The results of all blood studies, including cholesterol triglyceride level, phospholipid levels, free fatty acid levels, glucose determinations, and lipoprotein serum fraction are within the reference range in most verruciform xanthoma patients in whom these studies were carried out, with the following exceptions: one patient with diabetes mellitus, one patient with increased serum cholesterol levels, and one patient with a lipid storage disease.


Histologic Findings

Similar to their range of clinical presentations, verruciform xanthomas may appear verrucous, papillary, or cauliflowerlike, or they may show a lichenoid pattern histologically. A mixture of the above patterns may also be observed. A variable degree of parakeratosis is observed that is usually more marked in verrucous and papillary lesions, with parakeratosis present in the crypts between papillae. No epithelial atypia is present. The lesion is exophytic, with the rete ridges in the lesion not extending into the underlying dermis. The connective tissue papillae are of variable length and thickness; they often extend close to the surface. The papillae may be extremely long and thin. Rarely, the entire process may occur in a cystlike structure.

The most striking and characteristic histologic feature of the verruciform xanthoma is the presence of large foam cells in the connective tissue papillae. These cells characteristically fill the entire papilla but only rarely extend beyond the base of the papilla. Most or all of the papillae are involved with these cells, which occasionally may also be seen in the epithelium (ie, epidermis, mucosa).

Ultrastructurally, most studies have concluded that the foam cells in verruciform xanthoma are fat-laden macrophages, although other cell types, including Langerhans cells and even fibroblasts have been proposed. Immunohistochemical analysis revealed these cells to be positive for LCA and CD68 and negative for S100, a marker pattern also characteristic of macrophages. A few S100 negative dendritic or granular cells have been reported in these lesions as well and may represent Langerhans cells. The contents of the cells stain with lipid stains, and the vacuoles that contain this material are decorated by anti–human lysosome antibody. They are also periodic-acid-Schiff (PAS) positive and diastase resistant, indicating that the PAS-positive material is not glycogen.

At electron microscopy, this material also demonstrates the appearance of lipid. Chemical studies by gas chromatography of extracted material show a preponderance of cholesterol esters. In addition to the lipid material, Zagarelli et al also noted the presence of what they interpreted as degenerating epithelial cells in the foam cells.[54, 55] Cobb et al described myelin figures, reduplication of the overlying basal lamina and fibroblasts, in addition to macrophagelike cells, which contained lipid inclusions.[56]

A slight inflammatory infiltrate may be present beneath the verruciform xanthoma lesion. Occasional verruciform xanthomas have been associated with a massive or lichenoid infiltrate. No granulomatous change has been described other than the presence of the foamy macrophages. Microorganisms are not characteristically present. Although bacteria and fungal hyphae are occasionally described, they appear to play no role in the etiopathogenesis. The results of extensive probing for viruses have been negative.

Contributor Information and Disclosures

W Clark Lambert, MD, PhD Professor and Head, Dermatopathology, Departments of Pathology and Dermatology, Rutgers New Jersey Medical School

W Clark Lambert, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Dermatopathology, International Academy of Pathology, Medical Society of New Jersey, Sigma Xi, Society for Investigative Dermatology

Disclosure: Nothing to disclose.


Hong Li, MD Pathologist and Dermatopathologist

Hong Li, MD is a member of the following medical societies: American Society for Clinical Pathology, College of American Pathologists

Disclosure: Nothing to disclose.

Peter C Lambert, MS St George's University School of Medicine, Grenada

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.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: XOMA; Biogen/IDEC; Novartis; Janssen Biotech, Abbvie, CSL pharma<br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor and intermittent author; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

  1. Snider RL. Verruciform xanthomas and lymphedema. J Am Acad Dermatol. 1992 Dec. 27(6 Pt 1):1021-3. [Medline].

  2. Grosshans E, Laplanche G. Verruciform xanthoma or xanthomatous transformation of inflammatory epidermal nevus?. J Cutan Pathol. 1981 Oct. 8(5):382-4. [Medline].

  3. Haustein UF. [Xanthomatous cells in inflammatory linear verrucous epidermal nevus or nevoid verruciform xanthoma?]. Dermatol Monatsschr. 1984. 170(7):475-8. [Medline].

  4. Buchner A, Hansen LS, Merrell PW. Verruciform xanthoma of the oral mucosa. Report of five cases and review of the literature. Arch Dermatol. 1981 Sep. 117(9):563-5. [Medline].

  5. Hu JA, Li YN, Li SY, Ying H. [Study of the clinicopathology on verruciform xanthoma of the oral cavity]. Shanghai Kou Qiang Yi Xue. 2005 Aug. 14(4):370-3. [Medline].

  6. Mostafa KA, Takata T, Ogawa I, Ijuhin N, Nikai H. Verruciform xanthoma of the oral mucosa: a clinicopathological study with immunohistochemical findings relating to pathogenesis. Virchows Arch A Pathol Anat Histopathol. 1993. 423(4):243-8. [Medline].

  7. Oliveira PT, Jaeger RG, Cabral LA, Carvalho YR, Costa AL, Jaeger MM. Verruciform xanthoma of the oral mucosa. Report of four cases and a review of the literature. Oral Oncol. 2001 Apr. 37(3):326-31. [Medline].

  8. Platkajs MA, Scofield HH. Verruciform xanthoma of the oral mucosa. Report of seven cases and review of the literature. J Can Dent Assoc. 1981 May. 47(5):309-12. [Medline].

  9. Rowden D, Lovas G, Shafer W, Sheikh K. Langerhans cells in verruciform xanthomas: an immunoperoxidase study of 10 oral cases. J Oral Pathol. 1986 Jan. 15(1):48-53. [Medline].

  10. Shin HI, Choi KS, Nagatsuka H, Murata M, Nagai N. Verruciform xanthoma of the oral mucosa: an immunohistochemical and ultrastructural study of two cases. Oral Oncol. 1997 Jul. 33(4):279-83. [Medline].

  11. Sklavounou A, Laskaris G, Angelopoulos A. Verruciform xanthoma of the oral mucosa. Dermatologica. 1982 Jan. 164(1):41-6. [Medline].

  12. Yu CH, Tsai TC, Wang JT, et al. Oral verruciform xanthoma: a clinicopathologic study of 15 cases. J Formos Med Assoc. 2007 Feb. 106(2):141-7. [Medline].

  13. Blanco C, Miranda C, Fernandez F, Val-Bernal JF, Garijo F, Saiz-Bustillo R. Verruciform xanthoma of the lip: two lesions in a woman. Am J Dermatopathol. 1988 Apr. 10(2):176-8. [Medline].

  14. Colonna TM, Fair KP, Patterson JW. A persistent lower lip lesion. Verruciform xanthoma. Arch Dermatol. 2000 May. 136(5):665-6, 669. [Medline].

  15. Toida M, Koizumi H. Verruciform xanthoma involving the lip: a case report. J Oral Maxillofac Surg. 1993 Apr. 51(4):432-4. [Medline].

  16. Amantea A, Gaudio E, Catricala C, Donati P, Balus L. [Verruciform xanthoma of the penis]. G Ital Dermatol Venereol. 1989 Jan-Feb. 124(1-2):37-40. [Medline].

  17. George WM, Azadeh B. Verruciform xanthoma of the penis. Cutis. 1989 Aug. 44(2):167-70. [Medline].

  18. Kraemer BB, Schmidt WA, Foucar E, Rosen T. Verruciform xanthoma of the penis. Arch Dermatol. 1981 Aug. 117(8):516-8. [Medline].

  19. Laguna Urraca G, Concha Lopez A, Tudela Paton MP. [Verruciform xanthoma of the penis]. Actas Urol Esp. 1990 May-Jun. 14(3):210-3. [Medline].

  20. Lonsdale RN. Verruciform xanthoma of the penis. Br J Urol. 1992 Nov. 70(5):574-5. [Medline].

  21. Pellice C Jr, Sole M, Pellice C, Carretero P. [Verruciform xanthoma of penis]. J Urol (Paris). 1987. 93(1):41-2. [Medline].

  22. Torrecilla Ortiz C, Marco Perez LM, Dinares Prat J, Autonell J. [Verruciform xanthoma of the penis]. Actas Urol Esp. 1997 Sep. 21(8):797-9. [Medline].

  23. Leong FJ, Meredith DJ. Verruciform xanthoma of the vulva. A case report. Pathol Res Pract. 1998. 194(9):661-5; discussion 666-7. [Medline].

  24. Santa Cruz DJ, Martin SA. Verruciform xanthoma of the vulva. Report of two cases. Am J Clin Pathol. 1979 Feb. 71(2):224-8. [Medline].

  25. de Rosa G, Barra E, Gentile R, Boscaino A, Di Prisco B, Ayala F. Verruciform xanthoma of the vulva: case report. Genitourin Med. 1989 Aug. 65(4):252-4. [Medline].

  26. Griffel B, Cordoba M. Verruciform xanthoma in the anal region. Am J Proctol Gastroenterol Colon Rectal Surg. 1980 Apr. 31(4):24-5. [Medline].

  27. Duray PH, Johnston YE. Verruciform xanthoma of the nose in an elderly male. Am J Dermatopathol. 1986 Jun. 8(3):237-40. [Medline].

  28. Than T, Birch PJ, Dawes PJ. Verruciform xanthoma of the nose. J Laryngol Otol. 1999 Jan. 113(1):79-81. [Medline].

  29. Jensen JL, Liao SY, Jeffes EW 3rd. Verruciform xanthoma of the ear with coexisting epidermal dysplasia. Am J Dermatopathol. 1992 Oct. 14(5):426-30. [Medline].

  30. Chyu J, Medenica M, Whitney DH. Verruciform xanthoma of the lower extremity--report of a case and review of literature. J Am Acad Dermatol. 1987 Oct. 17(4):695-8. [Medline].

  31. Kimura S. Verruciform xanthoma of the scrotum. Arch Dermatol. 1984 Oct. 120(10):1378-9. [Medline].

  32. Nakamura S, Kanamori S, Nakayama K, Aoki M. Verruciform xanthoma on the scrotum. J Dermatol. 1989 Oct. 16(5):397-401. [Medline].

  33. Shindo Y, Mikoshiba H, Okamoto K, Morohashi M. Verruciform xanthoma of the scrotum. J Dermatol. 1985 Oct. 12(5):443-8. [Medline].

  34. Travis WD, Davis GE, Tsokos M, et al. Multifocal verruciform xanthoma of the upper aerodigestive tract in a child with a systemic lipid storage disease. Am J Surg Pathol. 1989 Apr. 13(4):309-16. [Medline].

  35. Graff SG, Burk JL Jr, McKean TW. Verruciform xanthoma. First case reported in a black person. Oral Surg Oral Med Oral Pathol. 1978 May. 45(5):762-7. [Medline].

  36. Frankel MA, Rhodes HE, Euscher ED. Verruciform xanthoma in an adolescent: a case report. J Low Genit Tract Dis. 2012 Jan. 16(1):70-4. [Medline].

  37. Cumberland L, Dana A, Resh B, Fitzpatrick J, Goldenberg G. Verruciform xanthoma in the setting of cutaneous trauma and chronic inflammation: report of a patient and a brief review of the literature. J Cutan Pathol. 2010 Aug. 37(8):895-900. [Medline].

  38. Hashimoto K, Prada S, Lopez AP, Hoyos JG, Escobar M. CHILD syndrome with linear eruptions, hypopigmented bands, and verruciform xanthoma. Pediatr Dermatol. 1998 Sep-Oct. 15(5):360-6. [Medline].

  39. Zamora-Martinez E, Martin-Moreno L, Barat-Cascante A, Castro-Torres A. Another CHILD syndrome with xanthomatous pattern. Dermatologica. 1990. 180(4):263-6. [Medline].

  40. Gantner S, Rütten A, Requena L, Gassenmaier G, Landthaler M, Hafner C. CHILD syndrome with mild skin lesions: histopathologic clues for the diagnosis. J Cutan Pathol. 2014 Oct. 41(10):787-90. [Medline].

  41. Cooper TW, Santa Cruz DJ, Bauer EA. Verruciform xanthoma. Occurrence in eroded skin in a patient with recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 1983 Apr. 8(4):463-7. [Medline].

  42. Meyers DC, Woosley JT, Reddick RL. Verruciform xanthoma in association with discoid lupus erythematosus. J Cutan Pathol. 1992 Apr. 19(2):156-8. [Medline].

  43. Miyamoto Y, Nagayama M, Hayashi Y. Verruciform xanthoma occurring within oral lichen planus. J Oral Pathol Med. 1996 Apr. 25(4):188-91. [Medline].

  44. Fite C, Plantier F, Dupin N, Avril MF, Moyal-Barracco M. Vulvar verruciform xanthoma: ten cases associated with lichen sclerosus, lichen planus, or other conditions. Arch Dermatol. 2011 Sep. 147(9):1087-92. [Medline].

  45. Gehrig RD, Baughman RA, Collins JF. Verruciform xanthoma in a young male patient with a past history of pemphigus vulgaris. Oral Surg Oral Med Oral Pathol. 1983 Jan. 55(1):58-61. [Medline].

  46. Drummond JF, White DK, Damm DD, Cramer JR. Verruciform xanthoma within carcinoma in situ. J Oral Maxillofac Surg. 1989 Apr. 47(4):398-400. [Medline].

  47. Mannes KD, Dekle CL, Requena L, Sangueza OP. Verruciform xanthoma associated with squamous cell carcinoma. Am J Dermatopathol. 1999 Feb. 21(1):66-9. [Medline].

  48. Takiwaki H, Yokota M, Ahsan K, Yokota K, Kurokawa Y, Ogawa I. Squamous cell carcinoma associated with verruciform xanthoma of the penis. Am J Dermatopathol. 1996 Oct. 18(5):551-4. [Medline].

  49. Allen CM, Kapoor N. Verruciform xanthoma in a bone marrow transplant recipient. Oral Surg Oral Med Oral Pathol. 1993 May. 75(5):591-4. [Medline].

  50. Rawal SY, Kalmar JR, Tatakis DN. Verruciform xanthoma: immunohistochemical characterization of xanthoma cell phenotypes. J Periodontol. 2007 Mar. 78(3):504-9. [Medline].

  51. Khaskhely NM, Uezato H, Kamiyama T, et al. Association of human papillomavirus type 6 with a verruciform xanthoma. Am J Dermatopathol. 2000 Oct. 22(5):447-52. [Medline].

  52. Hegde U, Doddawad VG, Sreeshyla H, Patil R. Verruciform xanthoma: A view on the concepts of its etiopathogenesis. J Oral Maxillofac Pathol. 2013 Sep. 17(3):392-6. [Medline]. [Full Text].

  53. Ide F, Obara K, Yamada H, Mishima K, Saito I, Kusama K. Cellular basis of verruciform xanthoma: immunohistochemical and ultrastructural characterization. Oral Dis. 2008 Mar. 14(2):150-7. [Medline].

  54. Zegarelli DJ, Aegarelli-Schmidt EC, Zegarelli EV. Verruciform xanthoma. A clinical, light microscopic, and electron microscopic study of two cases. Oral Surg Oral Med Oral Pathol. 1974 Nov. 38(5):725-34. [Medline].

  55. Zegarelli DJ, Zegarelli-Schmidt EC, Zegarelli EV. Verruciform xanthoma. Further light and electron microscopic studies, with the addition of a third case. Oral Surg Oral Med Oral Pathol. 1975 Aug. 40(2):246-56. [Medline].

  56. Cobb CM, Holt R, Denys FR. Ultrastructural features of the verruciform xanthoma. J Oral Pathol. 1976 Jan. 5(1):42-51. [Medline].

  57. Cuozzo DW, Vachher P, Sau P, Frishberg DP, James WD. Verruciform xanthoma: a benign penile growth. J Urol. 1995 May. 153(5):1625-7. [Medline].

  58. Rawal SY, Kalmar JR, Tatakis DN. Verruciform xanthoma: immunohistochemical characterization of xanthoma cell phenotypes. J Periodontol. 2007 Mar. 78(3):504-9. [Medline].

Xanthelasma. Courtesy of Duke University Medical Center.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.