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

2. Contents Histiocyte and related cell Xanthoma Disseminatum
Discussions about this patient

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

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

5. Histiocyte

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

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

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

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

10. 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

11. 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

12. 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

13. 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

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

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

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

17. 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

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

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

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

21. 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

22. 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

23. 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

24. 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

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

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

27. 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

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

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

30. 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

31. 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

32. 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

33. Current cases reporting in Korea
Total 4 cases reporting in Korea

34. Thank you for your attention