Xanthoma Disseminatum Dept. of Endocrinology and Metabolism Sang Youl Rhee, MD

Contents Histiocyte and related cell Xanthoma Disseminatum Discussions about this patient

Histiocyte Differentiated from monocyte Function of monocyte family - phagocytosis - antigen presenting to lymphocyte - secrete cytokines  interferon, plasminogen activator, prostaglandin, colony stimulating factor

Histiocyte Histiocyte  macrophage in the tissue Dendritic cell antigen presenting Diameter : 15-20 um Phagocyte foreign body  lipophage, neutrophage, erythrophage, siderophage

Histiocyte

Classification of the histiocytosis Odell et al., JCEM 76(3), 1993

Immunohistochemistry findings Favara et al., Med Pediatr Oncol 29(157), 1997

Favara et al., Med Pediatr Oncol 29(157), 1997

Contents Xanthoma Disseminatum (XD) Histiocyte and related cell Discussions about this patient

Xanthoma Disseminatum (XD) A rare nonmalignant histiocytic disorder Describe by Montgomery for the first time Considered as definite disease entity by Altman et al. Montgomery et al., Arch Dermatol Syphilol 37, 1938 Altman et al., Arch Dermatol 86, 1962

Xanthoma Disseminatum Epidemiology - about 100 cases reported until 1985 - male : female = 2.4 : 1 - onset of disease  64% of pt, < age 25 yrs Blobstein et al. Arch Dermatol 121, 1985 Altman et al., Arch Dermatol 86, 1962

Xanthoma Disseminatum Normolipidemic  XD caused by lipid phagocytosis of histiocyte Most commonly have skin xanthomata, xanthomata involving the upper respiratory tract DI, sometimes transient  about 40% of total patient Parker et al., J am Acad Dermatol 13, 1985 Ford et al., Proc R Soc Med. 78 (suppl), 1985

Skin manifestation of XD Hundreds of papules  red-brown colored at first  become yellowish  quickly to merge  form verrucous papules site  trunk, face, eyelid, prox. extremity, flexures and folds Odell et al., JCEM 76(3), 1993

Skin manifestations of XD Scully et al., NEJM 338(16), 1998

Skin manifestations of XD Pfeiffer et al., Eur Neurol 44, 2000

Skin manifestations of XD Hisanaga et al., Dermatology 208, 2004

Upper airway and mucosal invasion of XD Mucous membrane involve - 50% of total pt - site :  mouth, pharynx, larynx, conjunctiva Woollons et al., Clinic and Exper Dermatol 23, 1998

Pathologic findings of XD Diffuse lipid laiden histiocytosis  foam cell Touton type giant cell Immunohistochemistry Favara et al., Med Pediatr Oncol 29(157), 1997

Pathologic findings of XD Skin Hisanaga et al., Dermatology 208, 2004

Pathologic findings of XD Larynx Scully et al., NEJM 338(16), 1998

Differential diagnosis Juvenile Xanthogranuloma (JXG) - JXG and XD  clinical variants - same immunohistochemistry pattern - diagnose by clinical presentation • JXG : usu. head, neck, upper trunk, childhood  can arise during adolescence or adult • XD : affects more older pts, disseminated pattern Freyer et al., J Pediatr 129, 1996 Knobler et al. J Am Acad Dermatol 23, 1990 Hammond et al. Clin Neuropathol 14, 1995

Prognosis Usually self-limited, benign Classified as 3 clinical form  review 7cases - Self-healing form - Persistent form - progressive form Weiss et al., Clin Invest 71, 1993 Caputo et al., Clin Investig 190, 1995

Prognosis Few fatal cases also reported  CNS involve  airway obx. d/t laryngeal involve  pulmonary involvement Knobler et al., J Am Acad Dermatol 23, 1990 Scully et al., NEJM 338(16), 1998 Hisanaga et al., Dermatology 208, 2004

Management Usually not helpful Systemic glucocorticoid and antimitotic agents Vasopressin for DI associated condition Clofibrate Electrocautery Odell et al., JCEM 76(3), 1993 Pandhi et al., Arch Dermatol 126, 1990 Kumakiri et al., J Am Acad Dermatol 4, 1981

Contents Further Discussions about this patient Histiocyte and related cell Xanthoma Disseminatum Further Discussions about this patient

GI mucosal invasion of XD Hisanaga et al., Dermatology 208, 2004

Possibility of GI mucosal involvement We should consider possibility about gastric and colon mucosal involvement in this patient EGD finding of patient performed in 6th Mar, 2003

CNS invasion of XD Pfeiffer et al., Eur Neurol 44, 2000

Evidence of CNS involve ? Does the Cb and Cbll infarction of patient correlate with XD ? MRI finding of patient performed in 19th Jun, 2005

Evidence of Pituitary & Stalk disease ? We should also consider possibility about pituitary & stalk disease and CNS involvement MRI finding of patient performed in 19th Jun, 2005

Bony invasion of XD Only 2 cases report until 1995  osteolytic bony lesion  do not evaluate skeletal examination other than XR or bone scan Odell et al., JCEM 76(3), 1993

Evidence of Osteolytic lesion? We could also find osteolytic & osteoporotic bony lesion in Knee XR of this patient Knee XR of patient performed in 19th Mar, 2003

Current cases reporting in Korea Total 4 cases reporting in Korea

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