British journal of Dermatology {1992) \27, 177-181.
Multiple xanthogranulomas in an adult: case report and literature review S. ELIZABETH WHITMORE Deparlwent of Dermatolofiij. The Johns Hopkins Medical Institutions. 6(10 North Woife Street, Balliniore, Ml) 21205, U.S.A. Accepted for publication 19 February 1992
Summary
An otherwise healthy 30-year-old male developed multiple xanthogranulomas over a 1-year period. A review of the literature on adult xanthogranulomas and a tahulated outline of the differential diagnosis is presented.
luvenile xanthogranuloma is a benign, self-healing disorder characterized by one. or commonly many, yellow, reddish-yellow, tan, or brown papules or nodules which favour the upper body. Lesions usually develop within the first few months of life, but not uncommonly may be present at birth or develop during childhood.' - Xanthogranulomas in adults are thought to be relatively uncommon,- and when they do occur, they are most often solitary." ' A report is presented on an adult who developed multiple xanthogranuiomas, and a tabulated summary is given of a literature review highlighting key features of similar entities.
appeared on the back, but subsequently developed on the abdomen and arms. The lesions were asymptomatic. His past medical history included childhood-onset allergic asthma, nasal polyps, chronic sinusitis, and recently detected mild hypercholesterolaemla. For the latter condition, he had attempted to reduce his dietary
Case report A 30-year-old Caucasian male presented for evaluation of 'a dozen new moles'. He stated that initially the 'moles'
f >\
Figure 1. One of 10 Xiiiithogranuiomas scattered over the trunk iiiid
arm.
if .^ •.
Figure 2. Photomicrograph showing a nodular dermal aggregate of histiocytic cells and scattered Touton giant ceils i haematoxylin imd eosin x 125),
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cholesterol intake. He denied polydypsia and polyuria. rhere was a family history of mild hypcrcholesterolaemiu. Examination revealed 10 3-5-mm-dlameter yellowish-brown, dome-shaped papules scattered over the back, abdomen, and flexor aspect ofthe left arm (Fig. 1). The eyes and oral mucosa were normal. An excision biopsy of one of the lesions was performed. Histology revealed a circumscribed mixed dermal infiltrate of Touton giant cells, foam cells, and histiocytic and lymphoid cells (Fig. 2). S-l()() protein stain shovved staining of epidermal melanocytes and scattered dermal interdigitating reticulum cells, but no staining of the cells of the infiltrate, indicating that the lesional histiocytic cells were not Langerhans cells. Laboratory studies, including a full blood count, biochemistry, and Iipid profile (cholesterol. HDL, LDL. and triglyceridesl, were all within normal limits. Ophthalmological examination was normal.
Discussion Naevoxanthoendothelioma was initially fully described in 1912 by McUonagh.'ln 1954. Helwig and Hackney' renamed the condition juvenile xanthogranuloma. pointing out that it occurred in infants and children, was composed of lipid-containing histiocytes. and was not a naevus. Nine years later. Cartmann and Tritsch^ first reported xanthogranuloma in an adult. In 1976, Rodriguez and Ackcrman' reported nine cases of xanthogranulomas in adults seen at their institution over a I 5month period. Six patients had solitary lesions, while three each bad two. three, and 2b lesions, respectively. (Jianotti and Zina'' were the first to recognize and classify juvenile xanthogranuiomas clinically into micronodular and macronodular forms. In the micronodular type, several to hundreds of 2-S mm, red to yellow, iirm, dome-shaped papules are scattered predominantly over the upper body. The macronodular type is similar, except lesions are less numerous and are 1-2 cm in size.-" " With all cutaneous juvenile xanthogranulomas, volar and mucous membrane lesions are uncommon.^ Visceral involvement with juvenile xanthogranuloma most often affects various parts ofthe eye and may cause significant morbidity. Most serious are uveal lesions which may lead to glaucoma, recurrent hyphaema (anterior chamber haemorrhage), miosis, photophobia, or iris discoloration.**** In the macronodular type, other visceral lesions may occur in the colon, testes, ovaries, lungs, pericardium, aud bones. These lesions are usually inct)nsequential. but involvement ofthe three latter sites
has led to dyspnoea.'" cardiovascular compromise and respiratory distress (due to haemopericardium).'' and pathological fracture.- To date, there are no reports of adults with cutaneous xanthogranulomas having visceral lesions, although adults (and children) may have isolated ocular xanthogranulomas.' '^'The histopathological features of xanthogranulomas are dependent on their stage of evolution. Early lesions consist of a monomorphous histiocytic infiltrate in the upper dermis. Mature lesions show lipid-laden histiocytes ('foam cells'), infiltration by eosinophils. plasma cells, and neutrophils. and foreign-body and Touton giant-cell formation. More advanced lesions may show fibrosis. Stains for fat are positive, while S-l()() staining to identify Langerhans ceUs is negative.' ^'' ^ The differential diagnosis of multiple xanthogranulomas in an adult includes xanthoma disseminatum, papular xanthoma. generalized eruptive histiocytomata. histiocytosis X with xanthoma-like lesions, and eruptive xanthomas. Key features of these entities are outlined in Table 1,
Acknowledgment The author would like to thank Dr Thomas Horn tor providing the histopathology slides.
References 1 HelwigEB, Hackney VC. ]uvenile xanthogranuloma (Nevoxanthofn(Ji>thelJoma). Am I I'athol 1954: iO: f>2S ft. 2 Cuinncpain MT. Puissant A. Juvenile xanthogranuloma. G Hal Vencreol Dermatol 1 9 8 0 ; 1 1 5 ; l O l - S .
} Rodriguez J, Ackerman AB. Xanthogranuloma in adulu. Arch Dermatol 197(-.; 112:45-4. 4 McDonagh |KR. A contribution lo our knowledge of nevoxanthocndotheiioma. lir / Dermatol 1912; 24( i): H4-9S. 5 llartmann H, 'lYitsch H. Kcin und grobknotiges naevoxanthoendotheliom. Arch Klin Exp Derm 196 5; 215: 409-21. h C^ianoiti F. Zina G. Xaiithofjrtinuhmaloses juveniles. XIII c C o n g r e s de ['Association des Uermatologistes el Syphiligraphcs dc Langue Francaise. Turin. 1969. Paris: Masson, 1971:105-58. 7 t'lianotti F. Caputo R, HistiocytiL- syndromes: a review. / Am Acad Dermatol 198S; \i: J8i-4()4. 8 Blank H. liglick PC, Beerman H, Nevoxantho-endothelioma with ocular involvement. Pedialrirs 1949; 4: J49-54, 9 Sanders TE. Intraocular juvenile xantho-granuloma Inevoxanthoendothelioma). Am j Ophtlialmol 1962: 54: 455-62. 10 Lamb ]H, Lain RS. Ncvo-xantho-endothelioma: its relation to juvenile xanthoma. South Med I I 9 i 7 : J0(6): 58S-94. 11 Webster SB, Reister HC, Harman LE. Juvenile xanthogranuloma with extracutaneous lesions. A case report and review of the literature. Arch Dermatol 1966: 9J: 71-6. 12 Winkelmann RK, Adult histiocytic skin disease. G Ital DermatoJ Venereo! 1980: 115:67-76.
MULTIPLE XANTHOGRANULOMAS IN AN ADULT
1 J l£ver W¥. Schaumburg-Ix:ver (i. Ilistopatholofin oj tlir Skin, 6th end. New York: IB Lippincntt, 1985: 396-9. 14 Kalz V. Hoffman MM, i.afrancc A. Xanthoma disscminaluiii. Dermatologica 1970; 140; 129-41. 15 Altman ]. Winkelmann RK. Xanthoma disseminalum. Arch Dermiitol 1962; 86: 582-96. I h KriohlcrRM, Neumann RA.CJebharl WclH/.Xaiiihttma disseminalum with progressive involvement of the central nervous and hepatohiliary systems. / Am Acmi Dermntol I 490; 2 i; 541 - 6 . 1 7 lioodenberger M!;. VValdenstrom's maiToglobulinemia tied to xanthoma disseminntum. Dernnnohfiji News. Nov-I)ec, 1989: 8. 18 Maize ]C, Ahmed AR. ProvosI T!'. Xanthoma disseminatum and multiple myeloma, Anh Dermatol 1974: 110: 758-61. 19 (lallant C'|, From I,. |uvenile xanthogranulomas and xantiiorna disseminatum —variations on a single theme. \ Am .\cnd Dermntol I9S6; IS; HIH 9.
181
10 Winkelmann RK, CuUtneous syndromes of non-.\ hisliocytosis. Arrh Dermiitol 1981; 117: 6f>7-72. 21 Caputo R, Gianni E. Imondi D et ai Papular xanthoma in children. I Am Acad Dermiitol 1990:22: l(IS2-6. 11 Winkelmann RK. Muller SA. Generalized eruplive histiocyloma. Arch Dermiitol I9h}: 8S: SS6-9fi. 2 5 Allman |, Winkiemann RK. Xanthomatous cutaneous lesions of histiocytosis X . Arrh Dermtito! 196J: 87: 164-70. 24 Hu I'H. Winkelmann RK. Unusual normolipidemic cutaneous xanthomatosis; A comparison of two cases illustrating the differential diagnosis. Acta Derm VenereoKStockh) 1977: S7: 421-9. 25 Caputo R, Gelmetti C, lirmacora V, et al, Xanthomatous cutaneous lesions in patients affected by histiocytosis X. Ped Dermiitol (/(J;WH) 1988; 7: 14 21, 26 Parker I', Xanthomas and hyperlipidemias, / Am Acud Dermutnl 1985; 11: l-il).
Multiple xanthogranulomas in an adult: case report and literature review S. ELIZABETH WHITMORE Deparlwent of Dermatolofiij. The Johns Hopkins Medical Institutions. 6(10 North Woife Street, Balliniore, Ml) 21205, U.S.A. Accepted for publication 19 February 1992
Summary
An otherwise healthy 30-year-old male developed multiple xanthogranulomas over a 1-year period. A review of the literature on adult xanthogranulomas and a tahulated outline of the differential diagnosis is presented.
luvenile xanthogranuloma is a benign, self-healing disorder characterized by one. or commonly many, yellow, reddish-yellow, tan, or brown papules or nodules which favour the upper body. Lesions usually develop within the first few months of life, but not uncommonly may be present at birth or develop during childhood.' - Xanthogranulomas in adults are thought to be relatively uncommon,- and when they do occur, they are most often solitary." ' A report is presented on an adult who developed multiple xanthogranuiomas, and a tabulated summary is given of a literature review highlighting key features of similar entities.
appeared on the back, but subsequently developed on the abdomen and arms. The lesions were asymptomatic. His past medical history included childhood-onset allergic asthma, nasal polyps, chronic sinusitis, and recently detected mild hypercholesterolaemla. For the latter condition, he had attempted to reduce his dietary
Case report A 30-year-old Caucasian male presented for evaluation of 'a dozen new moles'. He stated that initially the 'moles'
f >\
Figure 1. One of 10 Xiiiithogranuiomas scattered over the trunk iiiid
arm.
if .^ •.
Figure 2. Photomicrograph showing a nodular dermal aggregate of histiocytic cells and scattered Touton giant ceils i haematoxylin imd eosin x 125),
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cholesterol intake. He denied polydypsia and polyuria. rhere was a family history of mild hypcrcholesterolaemiu. Examination revealed 10 3-5-mm-dlameter yellowish-brown, dome-shaped papules scattered over the back, abdomen, and flexor aspect ofthe left arm (Fig. 1). The eyes and oral mucosa were normal. An excision biopsy of one of the lesions was performed. Histology revealed a circumscribed mixed dermal infiltrate of Touton giant cells, foam cells, and histiocytic and lymphoid cells (Fig. 2). S-l()() protein stain shovved staining of epidermal melanocytes and scattered dermal interdigitating reticulum cells, but no staining of the cells of the infiltrate, indicating that the lesional histiocytic cells were not Langerhans cells. Laboratory studies, including a full blood count, biochemistry, and Iipid profile (cholesterol. HDL, LDL. and triglyceridesl, were all within normal limits. Ophthalmological examination was normal.
Discussion Naevoxanthoendothelioma was initially fully described in 1912 by McUonagh.'ln 1954. Helwig and Hackney' renamed the condition juvenile xanthogranuloma. pointing out that it occurred in infants and children, was composed of lipid-containing histiocytes. and was not a naevus. Nine years later. Cartmann and Tritsch^ first reported xanthogranuloma in an adult. In 1976, Rodriguez and Ackcrman' reported nine cases of xanthogranulomas in adults seen at their institution over a I 5month period. Six patients had solitary lesions, while three each bad two. three, and 2b lesions, respectively. (Jianotti and Zina'' were the first to recognize and classify juvenile xanthogranuiomas clinically into micronodular and macronodular forms. In the micronodular type, several to hundreds of 2-S mm, red to yellow, iirm, dome-shaped papules are scattered predominantly over the upper body. The macronodular type is similar, except lesions are less numerous and are 1-2 cm in size.-" " With all cutaneous juvenile xanthogranulomas, volar and mucous membrane lesions are uncommon.^ Visceral involvement with juvenile xanthogranuloma most often affects various parts ofthe eye and may cause significant morbidity. Most serious are uveal lesions which may lead to glaucoma, recurrent hyphaema (anterior chamber haemorrhage), miosis, photophobia, or iris discoloration.**** In the macronodular type, other visceral lesions may occur in the colon, testes, ovaries, lungs, pericardium, aud bones. These lesions are usually inct)nsequential. but involvement ofthe three latter sites
has led to dyspnoea.'" cardiovascular compromise and respiratory distress (due to haemopericardium).'' and pathological fracture.- To date, there are no reports of adults with cutaneous xanthogranulomas having visceral lesions, although adults (and children) may have isolated ocular xanthogranulomas.' '^'The histopathological features of xanthogranulomas are dependent on their stage of evolution. Early lesions consist of a monomorphous histiocytic infiltrate in the upper dermis. Mature lesions show lipid-laden histiocytes ('foam cells'), infiltration by eosinophils. plasma cells, and neutrophils. and foreign-body and Touton giant-cell formation. More advanced lesions may show fibrosis. Stains for fat are positive, while S-l()() staining to identify Langerhans ceUs is negative.' ^'' ^ The differential diagnosis of multiple xanthogranulomas in an adult includes xanthoma disseminatum, papular xanthoma. generalized eruptive histiocytomata. histiocytosis X with xanthoma-like lesions, and eruptive xanthomas. Key features of these entities are outlined in Table 1,
Acknowledgment The author would like to thank Dr Thomas Horn tor providing the histopathology slides.
References 1 HelwigEB, Hackney VC. ]uvenile xanthogranuloma (Nevoxanthofn(Ji>thelJoma). Am I I'athol 1954: iO: f>2S ft. 2 Cuinncpain MT. Puissant A. Juvenile xanthogranuloma. G Hal Vencreol Dermatol 1 9 8 0 ; 1 1 5 ; l O l - S .
} Rodriguez J, Ackerman AB. Xanthogranuloma in adulu. Arch Dermatol 197(-.; 112:45-4. 4 McDonagh |KR. A contribution lo our knowledge of nevoxanthocndotheiioma. lir / Dermatol 1912; 24( i): H4-9S. 5 llartmann H, 'lYitsch H. Kcin und grobknotiges naevoxanthoendotheliom. Arch Klin Exp Derm 196 5; 215: 409-21. h C^ianoiti F. Zina G. Xaiithofjrtinuhmaloses juveniles. XIII c C o n g r e s de ['Association des Uermatologistes el Syphiligraphcs dc Langue Francaise. Turin. 1969. Paris: Masson, 1971:105-58. 7 t'lianotti F. Caputo R, HistiocytiL- syndromes: a review. / Am Acad Dermatol 198S; \i: J8i-4()4. 8 Blank H. liglick PC, Beerman H, Nevoxantho-endothelioma with ocular involvement. Pedialrirs 1949; 4: J49-54, 9 Sanders TE. Intraocular juvenile xantho-granuloma Inevoxanthoendothelioma). Am j Ophtlialmol 1962: 54: 455-62. 10 Lamb ]H, Lain RS. Ncvo-xantho-endothelioma: its relation to juvenile xanthoma. South Med I I 9 i 7 : J0(6): 58S-94. 11 Webster SB, Reister HC, Harman LE. Juvenile xanthogranuloma with extracutaneous lesions. A case report and review of the literature. Arch Dermatol 1966: 9J: 71-6. 12 Winkelmann RK, Adult histiocytic skin disease. G Ital DermatoJ Venereo! 1980: 115:67-76.
MULTIPLE XANTHOGRANULOMAS IN AN ADULT
1 J l£ver W¥. Schaumburg-Ix:ver (i. Ilistopatholofin oj tlir Skin, 6th end. New York: IB Lippincntt, 1985: 396-9. 14 Kalz V. Hoffman MM, i.afrancc A. Xanthoma disscminaluiii. Dermatologica 1970; 140; 129-41. 15 Altman ]. Winkelmann RK. Xanthoma disseminalum. Arch Dermiitol 1962; 86: 582-96. I h KriohlcrRM, Neumann RA.CJebharl WclH/.Xaiiihttma disseminalum with progressive involvement of the central nervous and hepatohiliary systems. / Am Acmi Dermntol I 490; 2 i; 541 - 6 . 1 7 lioodenberger M!;. VValdenstrom's maiToglobulinemia tied to xanthoma disseminntum. Dernnnohfiji News. Nov-I)ec, 1989: 8. 18 Maize ]C, Ahmed AR. ProvosI T!'. Xanthoma disseminatum and multiple myeloma, Anh Dermatol 1974: 110: 758-61. 19 (lallant C'|, From I,. |uvenile xanthogranulomas and xantiiorna disseminatum —variations on a single theme. \ Am .\cnd Dermntol I9S6; IS; HIH 9.
181
10 Winkelmann RK, CuUtneous syndromes of non-.\ hisliocytosis. Arrh Dermiitol 1981; 117: 6f>7-72. 21 Caputo R, Gianni E. Imondi D et ai Papular xanthoma in children. I Am Acad Dermiitol 1990:22: l(IS2-6. 11 Winkelmann RK. Muller SA. Generalized eruplive histiocyloma. Arch Dermiitol I9h}: 8S: SS6-9fi. 2 5 Allman |, Winkiemann RK. Xanthomatous cutaneous lesions of histiocytosis X . Arrh Dermtito! 196J: 87: 164-70. 24 Hu I'H. Winkelmann RK. Unusual normolipidemic cutaneous xanthomatosis; A comparison of two cases illustrating the differential diagnosis. Acta Derm VenereoKStockh) 1977: S7: 421-9. 25 Caputo R, Gelmetti C, lirmacora V, et al, Xanthomatous cutaneous lesions in patients affected by histiocytosis X. Ped Dermiitol (/(J;WH) 1988; 7: 14 21, 26 Parker I', Xanthomas and hyperlipidemias, / Am Acud Dermutnl 1985; 11: l-il).
