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Anais Brasileiros de Dermatologia

Print version ISSN 0365-0596On-line version ISSN 1806-4841

An. Bras. Dermatol. vol.84 no.3 Rio de Janeiro July 2009 



Eruptive xanthoma with unexpected granuloma annulare-like microscopic appearance - Case report



Patrícia P. S. FagundesI; Analice Souza Teixeira PintoII; Paulo Augusto Teixeira PintoIII; Antônio José TebcheraniIV; Neusa Yuriko Sakai ValenteV

ISpecialist medical doctor by the Brazilian Society of Dermatology – São Paulo (SP), Brazil
IISpecialist medical doctor by the Brazilian Society of Dermatology – São Paulo (SP), Brazil
IIIAssistant Physician of the Department of Dermatology of Complexo Hospitalar Padre Bento – Guarulhos (SP), Brazil
IVMaster of Medicine, Pathologist of the Department of Dermatology of Complexo Hospitalar Padre Bento – Guarulhos (SP), Brazil
VPhD in Medicine by the Department of the Dermatology of Faculdade de Medicina da University de São Paulo (USP) - São Paulo (SP), Brazil

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Eruptive xanthoma with unexpected granuloma annulare-like microscopic appearance - Case report Abstract: Eruptive xanthoma and granuloma annulare are dermatological diseases with different clinical findings that, sometimes, exhibit histopathological similarities with potential for misinterpretation. We report a case of an eruption of yellow-orange papules with erythematous borders in a 34-year-old male with high levels of serum triglycerides and cholesterol. The skin biopsy specimen has diagnosed granuloma annulare. Review of the histologic material revealed eruptive xanthoma. Remission of the eruption after treatment of dyslipidemia confirmed the diagnosis of the eruptive xanthoma and motivated research about the histological similarities and differences between these diseases.

Keywords: Biopsy; Granuloma annulare; Xanthomatosis




Eruptive xanthoma (EX) is a type of dermatosis due to lipid deposits on the skin, which manifests itself though the abrupt appearance of yellow-orange to red-brownish papulas with an erythematous halo, located preferentially on the surface of extremities, especially on the knees, elbows, buttocks, chest, and abdomen1. It is associated to hypertriglyceridemia and high levels of kilomicrons or very-low-density lipoproteins. It can also be seen in diabetic patients that do not respond to insulin therapy. Its spontaneous resolution has been reported.1 On the other hand, granuloma annulare (GA) is a benign dermatosis of known cause usually characterized by single or multiple papula(s), normochromic or pinkish, sometimes with a rounded shape, preferably located on the dorsum of the fingers, hands and feet.2

The microscopic findings used most often for diagnosis are: in EX, a cluster of macrophages filled with lipids without significant lyphocyte infiltrate1; and in GA, multifocal skin granulomatous reaction with epitheliod histiocytes and multinucleated giant cells, around and between disarranged thickened collagen fibers interspersed with mucin.2



Thirty-four-year-old man with asymptomatic yellowish lesions on the body for about 25 days, which increased in number. He had type II diabetes mellitus and was on glimepiride and metformin. He denied family history of dyslipidemias and/or diabetes mellitus. Dermatological examination showed papulas and isolated yellowish nodules surrounded by erythematous halos on the abdomen, dorsum, buttocks, and thighs (Figures 1A and 1B). Laboratory tests showed normal CBC, fasting glycemia of 210mg/dl, 2400mg/dl triglycerides, 772 mg/dl total cholesterol and lipemic serum. Triglyceride values above 400mg/dl prevented calculating fractions. Excision biopsy was obtained from a yellowish papula, with the initial pathologic-anatomical diagnosis of granuloma annulare. A revision of the result was requested because of a clinical picture strongly suggestive of EX. After careful analysis, the diagnosis was eruptive xanthoma, and HE staining of the upper dermis showed the presence of nodular infiltrate with histiocytes, some of which with foamy cytoplasm (Figure 2 and 3). Smaller collections of these histiocytes were arranged around vessels. Staining with Alcian-blue/ PAS showed mucin among histiocytes and disorderly collagen fibers (Figura 4). Weigert staining showed rarefaction of elastic fibers on the areas occupied by the histiocyte infiltrate (Figure 5).











The patient was referred for treatment of cand 15 days after the introduction of diet and bezafibrate, he presented complete resolution of the lesions (Figure 6). This clinical-dermatological response would be highly unlikely if the patient had disseminated granuloma annulare, which, in spite of descriptions of spontaneous involution, is more often persistent for long periods, sometimes even for decades.3 The treatment for disseminated GA can be tried with antimalarial agents, steroids, cytotoxic drugs, niacinamide, PUVA, etretinate, isotretinoin, vitamin E, 5-lipoxygenase inhibitors, tacrolimus, pimecrolimus or infliximab, all with variable responses.4-10 Until the completion of this paper, there was no report in the medical literature of disseminated granuloma annulare that had improved with the use of bezafibrate.




Eruptive xanthoma and granuloma annulare are clinically different dermatoses, which, however, may share some histological features. This fact has been scarcely reported in the literature.11

Cooper et. al compared the presence of the following microscopic aspects in EX and GA:11 1- one or multiple lesions on the superficial dermis; 2- interstitial and perivascular infiltrate; 3- disorderly reticular dermis; 4- interstitial histiocytes; 5- perivascular histiocytes; 6- perivascular lymphocytes; 7- interstitial lymphocytes; 8- xantomized histiocytes; 9- epitheliod histiocytes; 10- multinucleated cells; 11- lipid deposits; 12- necrobiosis; 13- cellular necrosis; 14- deposit of hyaluronic acid; 15- alteration of elastic fibers.

The first four items in the list above have been observed in both conditions indistinctively. The other aspects showed differences between the two diseases: perivascular histiocytes and xantomized histiocytes are abundant in EX and few or absent in GA; lipid deposits are present in EX and absent in GA; perivascular and interstitial lymphocytes, epitheliod histiocytes and multinucleated cells are few or absent in EX and abundant in GA; necrobiosis and evidence of cellular necrosis are absent in EX and present in GA; deposits of hyaluronic acid can be seen in both diseases, however, in EX they are on the edges and in GA, in the center of lesions; elastic fibers are not clearly affected in EX and they are few or absent when there is well established necrobiosis in GA. However, it has to be mentioned that staining of elastic fibers may fail to show changes if the lesion is recent.

Using the criteria listed above in the revision of this case’s microscopic specimen, the histopathological features found, and which permitted diagnosing EX, were: presence of xanthomatose histiocytes, absence de multinucleated giant cells and associated lymphocyte infiltrate.,/

Limiting observation only to the presence of mucin and rarefaction of elastic fibers seen in Figures 5 and 6, respectively, in fact, cold have suggested the diagnosis of GA. This may be what happened in the first microscopic examination.

It is important to highlight that we did not perform fat research because it was impossible to repeat the biopsy due to the patient’s rapid response to treatment.

According to Ackerman,12 the crucial difference between EX and GA is the intracellular lipid deposit in the center of the palisade of histiocytes in EX, in contrast with the mucin deposit in GA.

As seen in the case herein reported, it is possible to reach a hasty and wrong microscopic diagnosis if only a few features are analyzed. In addition to Cooper et. al, this fact had already been described by Ackerman and Pistone.12-13

The objective of this case report is to highlight the existence of microscopic similarities between these two diseases that are very different clinically, and, as a result, stress the importance of valuing their clinical presentation.

The possible microscopic similarity between EX and GA, which many pathologists are unaware of, results from the scarcity of reports about this fact in the literature, and may account for the initially wrong microscopic diagnosis of the case reported.



1. Seymour CA. Xantoma and abnormalities of lipid metabolism and storage. In: Burns T, Breathnach S, Cox N, Griffiths C. Rook’s Textbook of Dermatology. 7th ed. Oxford: Blackwell Science; 2004. p. 57.65-8         [ Links ]

2. Burns DA. Granuloma annulare. In: Burns T, Breathnach S, Cox N, Griffiths C. Rook’s Textbook of Dermatology. 7th ed. Oxford: Blackwell Science; 2004. p. 57109-119         [ Links ]

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4. Sahin MT, Ermertcan AT, Ozturkcan S, Turkdogan P. Generalized granuloma annulare in a patient with type II diabetes mellitus: successful treatment with isotretinoin. J Eur Acad Dermatol Venereol.. 2006;20:111-3         [ Links ]

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6. Smith KJ, Norwood C, Skelton H. Treatment of disseminated granuloma annulare with a 5-lipoxygenase inhibitor and vitamin E. Br J Dematol. 2002;146:667-70         [ Links ]

7. Setterfield J, Huilgol SC, Black MM. Generalised granuloma annulare successfully treated with PUVA. Clin Exp Dermatol. 1999;24:458-60         [ Links ]

8. Harth W, Linse R. Topical tacrolimus in granuloma annulare and necrobiosis lipoidica. Br J Dermatol. 2004;150:792-4.         [ Links ]

9. Rigopoulos D, Prantsidis A, Christofidou E, Ioannides D, Gregoriou S, Katsambas A. Pimecrolimus 1% cream in the treatment of disseminated granuloma annulare. Br J Dermatol. 2005;152:1364-5         [ Links ]

10. Hertl MS, Haendle I, Schuler G, Hertl M. Rapid improvement of recalcitrant disseminated granuloma annulare upon treatment with the tumour necrosis factor-alpha inhibitor, infliximab. Br J Dermatol. 2005;152:552-5         [ Links ]

11. Cooper PH. Eruptive xanthoma: a microscopic simulant of granuloma annulare. J Cutan Pathol. 1986;13:207-15         [ Links ]

12. Pistone GA. Pathology quiz case 1: eruptive xanthoma (associated with type 5 hyperlipoproteinemia). Arch Dermatol. 1984;120:1366-8         [ Links ]

13. Ackerman AB. Histologic diagnosis of inflammatory skin diseases. Philadelphia: Lea & Febiger; 1978        [ Links ]



Mailing Address:
Patrícia P. S. Fagundes
Rua Jacques Félix, 96 110R V. N. Conceição
04509-000 São Paulo SP
Tel./fax: (11)38426208



Conflict of interest: None
Financial funding: None
How to cite this article: Fagundes PPS, Pinto AST, Pinto PAT, Valente NYS, Tebcherani AJ. Xantoma eruptivo com aspecto histopatológico inusitado simulando granuloma anular – Relato de caso. An Bras Dermatol. 2009;84(3):289-92.

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