ࡱ>  Bbjbj hh9H H 8k$.Z   `.b.b.b.b.b.b.$03. "   ..!!! `.! `.!!:&,<'>1& L..0.&Re4e4<'<'e4,x  !     ..   .    e4         H Q: A 55 Year-Old Man with Swollen Eyes, Asthma and Elevated Free Kappa Light Chains California Tumor Tissue Registrys Case of the Month CTTR COTM Vol 11:10 HYPERLINK "http://www.cttr.org"www.cttr.org July, 2009 A 55-year-old man with a ten year history of swollen eyes presented with asthmatic symptoms. He was found to have enlarged upper and lower eyelids with ocular secretions that prevented him from seeing properly. The clinical differential included inflammatory pseudotumor of the orbits, proptosis from Grave's disease and multiple myeloma. The workup showed an elevation of free kappa light chains. A periocular biopsy was performed. The examined tissue consisted of a diffuse infiltration of lymphocytes admixed with lipid-laden histiocytes (xanthoma cells). They had small rounded nuclei and abundant clear or vacuolated cytoplasm (Fig. 1). There were also scattered multi-nucleated giant cells of the Touton type (Fig. 2). Within the lymphoid component were prominent follicles with parafollicular fibrosis (Fig.3). Immunohistochemically, the foamy histiocytes were strongly positive for CD68 and negative for S100. The lymphoid infiltration had a reactive profile with the germinal cells being CD20 positive and negative for Bcl-2. The parafollicular T cells were CD3 positive (Fig. 4). Diagnosis: Adult-Onset Asthma and Periocular Xanthogranuoloma Jin Guo MD, Jun Wang MD and Donald R. Chase MD Department of Pathology, Loma Linda University and Medical Center, Loma Linda, California California Tumor Tissue Registry, Loma Linda, California Adult-onset asthma with periocular xanthogranuoloma (AAPOX) was first described by  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Jakobiec%20FA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Jakobiec et al in 1993 when they reported 6 patients with periocular xanthogranulomatous disease associated with adult onset asthma, but lacking necrobiosis. The entity has now been placed into a heterogeneous group of syndromes called adult xanthogranulomatous disease (AXGD) that are rare and poorly understood. AXGD has variable clinical features which have resulted in subclassification into: Adult onset xanthogranuloma Necrobiotic xanthogranuloma Erdheim-Chester disease, and AAPOX Histopathologically, each of these four entities is characterized by infiltration of hallmark cells specifically foamy histiocytes and Touton-type giant cells, both of which are negative for S100 and CD1. The infiltration along with accompanying lymphocytes can replace the normal lacrimal gland architecture, causing mass effects and loss of tear production. Adult onset xanthogranuloma is an isolated xanthogranulomatous lesion without significant systemic involvement. Necrobiotic xanthogranuloma is characterized by subcutaneous skin lesions that tend to ulcerate and become fibrotic. Associated systemic findings frequently include paraproteinaemia and multiple myeloma. Erdheim-Chester Disease is an idiopathic condition of lymphohistiocytic infiltration of the heart, lungs, retroperitoneum, bones, and other tissues. The elements are xanthogranulomatous with Touton giant cells and are accompanied by regional fibrosis.. The condition is often fatal, with death due to cardiomyopathy, severe lung disease, or chronic renal failure. AAPOX often presents with bilateral yellow-orange, elevated, indurated and non-ulcerated xanthomatous eyelids and/or orbital masses. It typically extends into the anterior orbital fat, and sometimes involves the extraocular muscles and/or the lacrimal gland(s). Most patients experience adult-onset asthma within a few months to a few years of onset. Even when asthmatic symptoms are severe enough to require systemic corticosteroids and/or inhalation therapy, a chest X-ray may be negative. AAPOX is rare with only 21 previous reported cases. Like other AXGDs, it usually has sheets of mononucleated foamy histiocytes, with lymphocytes, plasma cells and Touton giant cells. The cells characteristically infiltrate the orbicularis muscles and the anteriorbital tissues. Their Touton cells have a ring of nuclei about a central eosinophilic zone which is surrounded by a zone of pallor extending to the periphery of the cell. Lymphoid follicles are commonly scattered throughout. Unlike Erdheim-Chester Disease, fibrosis is usually minimal to moderate and unlike necrobiotic xanthogranuloma there is no necrobiosis of collagen. Because the eyelids remain intact and the process does not reach the deep orbital and perioptic connective tissues, visual acuity may not be affected and ocular motility is generally well preserved unless the extraocular muscles are involved. Only rarely are the corneas exposed to the infiltrate, but in rare cases where lacrimal gland involvement causes punctuate corneal epitheliopathy the patient may suffer from a dry eye condition. CT scanning may reveal preseptal and anterior orbital involvement with occasional posterior tracking along or within the orbital muscles and fat, usually sparing the perioptic nerve connective tissues. Facial bones are usually not involved. Systemic evaluations are usually normal except for rare reports of elevated alpha high-density cholesterol and/or M-protein (IgG) on serum immunoelectrophoresis. The latter suggests that the inflammatory infiltrates have stimulated B cell populations. The main differential diagnoses of AAPOX include other AXGDs including the aforementioned adult onset xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester Disease. These conditions all share similar lymphogranulomatous infiltrates but have subtle differences in the amount of lymphoid follicles, number of Touton giant cells, degree of fibrosis and presence of necrosis. Curiously, these features may vary within the same specimen and change with time and treatment. Based upon morphology alone, therefore, the AXGDs are difficult to sub-classify on histomorphologic grounds alone and usually require correlation with patterns of systemic involvement. Necrobiosis with palisading epithelioid histiocytes is most often seen in necrobiotic xanthogranuloma whereas large lymphoid aggregates with germinal centers are often found in cases of AAPOX. Whereas orbit/adnexal xanthogranulomas tend to be anterior in adult-onset xanthogranuloma, AAPOX, and in necrobiotic xanthogranuloma, in Erdheim-Chester disease the disease is often diffuse (and posterior) leading to visual loss. Bone involvement is common and death may occur despite aggressive therapies. While the majority of cases can be classified as one of the four syndromes, there are cases that fall in between. These patients have varying combinations of periocular xanthogranuloma and other blood dyscrasias including thrombocytopenia, paraproteinaemia and/or monoclonal gammopathy of undetermined significance (MGUS). In addition to AXGDs, AAPOX should also be differentiated from other non-Langerhans disorders of histiocytes, including juvenile xanthogranuloma (JXG). This tumor is usually manifested as a self-limited, corticosteroid-sensitive skin tumor that rarely has systemic manifestations. Infants and small children are mainly affected with head and neck lesions. Many extracutaneous sites, however, have been reported, particularly the eye where JXG may cause spontaneous hyphema and result in secondary glaucoma and eventual blindness. Approximately one half of patients with ocular involvement also have skin lesions. Other entities involving ocular adnexal or orbital tissue that may require distinction from adult xanthogranulomatous disease include: Langerhans histiocytosis Rosai-Dorfman syndrome Inflammatory MFH Inflammatory myofibroblastic tumor (inflammatory pseudotumor) Graves disease Multiple myeloma, and Lymphoma. Despite surgical debulking, AAPOX often recurs within 6-12 months. Although systemic prednisone treatment may cause temporal shrinkage, it alone is usually not successful in causing a lasting resolution. Combined prednisone and systemic chemotherapy for paraproteinaemia may result in more complete resolution of the xanthogranulomatous eyelid deposits. Radiotherapy has also been successfully employed, but the results are more anecdotal than statistical. The eyelid lesions in necrobiotic xanthogranuloma can be successfully be treated with radiotherapy or systemic prednisalone and chlorambucil unless extensive destruction has occurred. Patients without detectable systemic disease at the time ocular adnexal lesions appear should be spared surgical debulking because of possible scarring. In this setting high doses of systemic corticosteroids and low doses of periobital radiotherapy may be given with hope of protection of the globe. If this approach fails, systemic corticosteroids and light chemotherapy may be tried. In patients with MGUS, follow-up should include serial serum protein immunoelectrophoresis and bone biopsy as needed. A recent study evaluated the efficacy of methotrexate in the treatment of the periorbital changes in adult-onset xanthogranuloma with or without asthma. With follow-up of over 3 years, 10-20 mg/weeks of methotrexate with folate supplementation and a course of corticosteroids showed promising results in significantly reducing inflammation and ptosis. In summary, AAPOX as well as other entities in the adult xanthogranulomatous disease are rare and pose challenges in daily clinical practice. Recognizing their clinical and histopathological features will facilitate early diagnosis and appropriate therapeutic management. Suggested reading:  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Sivak-Callcott%20JA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Sivak-Callcott JA,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Rootman%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Rootman J,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Rasmussen%20SL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Rasmussen SL,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Nugent%20RA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Nugent RA,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22White%20VA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" White VA,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Paridaens%20D%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Paridaens D,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Currie%20Z%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Currie Z,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Rose%20G%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Rose G,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Clark%20B%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Clark B,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22McNab%20AA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" McNab AA,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Buffam%20FV%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Buffam FV,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Neigel%20JM%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Neigel JM,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Kazim%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Kazim M. Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review. Br J Ophthalmol 90(5):602-8, 2006. Jakobiec FA, Mills MD, Hidayat AA, Dallow RL, Townsend DJ, Brinker EA, Charles NC. Periocular xanthogranulomas associated with severe adult-onset asthma. Trans Am Ophthalmol Soc 91:99-125, 1993. Hammond MD, Niemi EW, Ward TP, Eiseman AS. Adult orbital xanthogranuloma with associated adult-onset asthma. Ophthal Plast Reconstr Surg 20(4):329-32, 2004. Hayden A, Wilson DJ, Rosenbaum JT. Management of orbital xanthogranuloma with methotrexate. Br J Ophthalmol 91(4):434-6, 2007.  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Vick%20VL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Vick VL,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Wilson%20MW%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Wilson MW,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Fleming%20JC%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Fleming JC,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Haik%20BG%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Haik BG. Orbital and eyelid manifestations of xanthogranulomatous diseases. Orbit 25(3):221-5, 2006. Rayner SA, Duncombe AS, Keefe M, Theaker J, Manners RM. Necrobiotic xanthogranuloma occurring in an eyelid scar Orbit 27(3):191-4, 2008. Chaudhry IA, Al-Jishi Z, Shamsi FA, Riley F. Juvenile xanthogranuloma of the corneoscleral limbus: case report and review of the literature. Surv Ophthalmol 49(6):608-14. Review, 2004 Elner VM, Mintz R, Demirci H, Hassan AS. Local corticosteroid treatment of eyelid and orbital xanthogranuloma. Trans Am Ophthalmol Soc 103:69-73, 2005     CTTRs COTM July, 2009 Page  PAGE \* MERGEFORMAT 1 TU # ) L M n r z }pleaeaeZaZSOaShv h "h h "h6h h "h_hhOp5CJOJQJaJ#h'Sh0J5CJOJQJaJ(jh'Sh5CJOJQJUaJh<=5CJOJQJaJh'Sh5CJOJQJaJh'Sh5CJOJQJaJhhl56CJaJhh56CJaJ#jhhFX#6UmHnHuTUx ' ( h i 23$CI & Fgd & Fgd0Qgd6^gd6gd "$a$gd$a$gd / A B h i j n y   $ & ] ` a s    * ǻzrhZYB*ph333hL;HB*ph333hkB*ph333hvB*ph333h "h_B*ph333hmhL;Hhkhv h "h_ h "h6hfHq h "hfHq &h "hB*fHphq h "hB*ph h "hh,* a b w {    % ( 4 : ; K h 23FJZ[de»m'h "h[n0J>*B*CJ\aJphjh "h[nB*Uphho67G$BFfgh! 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~L$v-{7~Q{r{z~~yb~qiqjSqVIsZndY]nXdLmy1mr}hdhXU~}uqsm3yum[~zzuny^wj{nIn7v9vuj{|~~~zmr]vQ4equyZ~}XU~Z~Ua9jz~yzn~]_~pQqee~~~zY~rwz~==^m~vX~=hlkhMu 4\;` ^w}Sar<xz]]zuyPaXi}TmXnTLnV~J`KP]~9~UyivSylkPmLajS]TUisuiynPMHEq|riaw( :Zf~~yeE~k_>=x~queuHueuiTmqy~rir~y~ui>vuY~9~6mw~uq1au3mie~zvf~~~~uz\z<7vzvv}dL8oE~yqU~l.irymm~w~v|~LPm<5rm(^~T~Dg~q^~~~uiump\y`Rehdp\DjP\~ytp`dh`Rm~\uUYnuhLa~M`Lu~~dk~aa^dUa7jxqo~-43ImLYUTm4eumqm~=meumtY<{{~uUuaY~}UlY\~~r~:z\_9rWz{~vzA~z=Yz@,]~~|2aRe}Rmisax~}y]yMDYuP!!4Ewzf{zs~wyzy~z~uzmPnqq,K,AraLoyDZny~|~2uhynv $m$)@]8zX~~dhT]uuq~izY~i_7~o\3Mq``Smq\]~<m~~Yzvz~z{z|~mivTeLey\0QyXXuuj<mmu3at}HY~uX<9wu=Q^k}^uuXE{~\LYfNqLEyy`TP}q0mh`m}pReRyY7b][~w}X4aiaToX 8DXaiqxaWiKHxR6~D@]2i4MMPY8zV]]im}SiM*K,I l u~~Yzia`eyz4i]zuXr~i}TY}OqL]7nXzz~z9zViPAaHiasaP0em~ryamii}+D0U9~zY~qKL0e1qT-I}7jY>{Zz{ma{{mP]Sar)a =lF@K@Z(Llnset Asthma and 8'+!H'!9R2288T? =lF@K@? (LPeriocular Xanthogranuoloma <-,2,82,H28!822,28822R23TT =lF@K@(LP s6 % % % TT?lF@K@LP - T` #lF@K@ .LJin Guo MD, Jun Wang MD and Donald R. Chase MD(2H22YH(22_,21YH,22H22,2CC2,(,YITT  #lF@K@ LP K T%lF@K@ALDepartment of Pathology, Loma Linda University and Medical CenterH,2,!N,22!8,22331;2N,<23,H22,!'0,22Y,2,,C,2-!TX%IlF@K@LP, TdJ%3lF@K@JLTLoma<3N,TT3%_lF@K@3LP - Tp lF@K@LX TT lF@K@LP Ty lF@K@LpLinda, CaliforniaZ;22,C,!3!2-TTz lF@K@zLP - TT \|lF@K@eLPCBCT] a |lF@K@]eLalifornia Tumor Tissue Registry,!2!2,=2N2!=''2,C,1'#0TXb  |lF@K@b eLP, T G |lF@K@ eLxLoma Linda, California<2N,<22,D,!2!2-TTH t |lF@K@H eLP - TT~lF@K@LP c- % % % TlblF@K@KLXAdult޽H22TTblF@K@KLP-!TblF@K@K Lhonset asthma 22',,'2N,TdblF@K@KLTwithH2TTblF@K@KLP RTblF@K@K;Lperiocular xanthogranuoloma (AAPOX) was first described by 2,!2,2,!3,2231!,2222N,!HH8HH!H,'!!'2,',!2,240 Rp@Times New Roman_ _ _ _ Wc_ _ l_ _ Uc_ _ we_ _ $xeXG*Ax Times ew Roman0_ j:el_ l_ ye_ $dv% % % TlFlF@K@ L`Jakobiec ֭$)-..))% % % TGd@lF@K@GLtet al in 1993 when c,,22222H1,2TdA&" WMFC xx|dlF@K@ALTthey2.0TTdlF@K@LP !Td<lF@K@3Lreported 6 patients with periocular xanthogranuloma{!,23!,222,,2'H22,!2,2,!3,2222!,222N,Tl<dlF@K@<LXtous 22' Tx HlF@K@1L\disease2',,',TT&HlF@K@1LP 9TX'yHlF@K@'1LPas,'T`z HlF@K@z1.Lsociated with adult onset asthma, but lacking '2,,,2H2-2222',,'2N,22,,221T _ HlF@K@ 1 Ldnecrobiosis2-,!222''TT` x HlF@K@` 1LP.ƽTTy  HlF@K@y 1LP {TT  HlF@K@ 1LP {1T` EHlF@K@ 1LTThe=2,TTF^HlF@K@F1LP T_HlF@K@_1 Ldentity has ,3/3,'TdHlF@K@1LTnow 22H TJ|lF@K@Llbeen placed into2,,22,-,222TT}JlF@K@}LP TJlF@K@DLa heterogeneous group of syndromes called adult xanthogranulomatous ,2,-!31,3,22'1!2222!)023!3N,',,,2,223,2222!,222N,22' Tx .lF@K@L\disease2',,',TT&.lF@K@LP ƽTX'.lF@K@'LP(A!ITT.lF@K@LPX1HT`.lF@K@LTGD)HH!TT.lF@K@LP TlR.lF@K@LXthat 2,T`S.lF@K@SLTare,!,TT.lF@K@LP TO .lF@K@Lrare and poorly understood. !,!,,22222!0222-!'222TTP h .lF@K@P LP ΥTTi  .lF@K@i LPAsHTT  .lF@K@ LPXHTX  .lF@K@ LPGDHHTT  .lF@K@ LP {RT` & .lF@K@ LThas))2,'TT' ? .lF@K@' LP ޽T@ .lF@K@@ Lpvariable clinical 3,!,2,,2,, T|0)lF@K@L\features!,,2",'TT*0BlF@K@*LP TC0lF@K@CLxwhich have resulted inH2,22,3,!,'2,22TT0lF@K@LP )T01 lF@K@Lxsubclassification into'22,,''!,,2222TT2 0M lF@K@2 LP:TTN 0z lF@K@N LP s-Rp @Times New RomanUe5{v_ leH, e we_ _ \ xe2d G , Ax Times ew Roman(_ j:ed_ d_ ye_ \ dv% % Rp @Times New Roman_ _ $_ _ Wc$_ _ _ _ Uc$_ _ we_ $_ \+xeXG*Ax Times ew Roman+uP_ j:e_ _ ye_ \+dv% % %  Rp @Symbol_ _  _ _ Wc _ _ _ _ Uc _ _ we_ _ 'xeX5Symbolv?_ +eL_ j:e_ _ ye_ 'dv% % % TTlF@K@LP.Rp @"Arial_ _ _ _ Wc _ _ _ _ Uc _ _ we_ _ <)xeX3.*Cx ArialT_ ԓcL_ j:e_ _ ye_ <)dv% % % TTlF@K@LP Zh% % % TTalF@K@LPAνHTblF@K@b L`dult onset2222',% % % TTlF@K@LP Z% % % T`lF@K@LTxan3,2TlF@K@ Ldthogranuloma221!,222N,TTlF@K@LP -R&WMFC xx| % % % TTlF@K@LP!.% % % TT%lF@K@LP h% % % TT%alF@K@LPN޽HTb%lF@K@bLecrobiotic xanthogranuloma s,,!222,3,2222!,232N,TT% lF@K@LP -% % % % %  % % % TTlF@K@LP.% % % TTlF@K@LP Jh% % % TxqlF@K@L\ErdheimR=!22,NTTrlF@K@rLP-!TxlF@K@L\ChesterC2,',!% % % TTlF@K@LP 9% % % TlF@K@Lhdisease, and 2',,(,,22TT lF@K@LP - % % % TTlF@K@tLPJ.% % % TTlF@K@tLP ch% % % TlrlF@K@tLXAAPOXZZHH8HITTslF@K@stLP - TTlF@K@LP ƭ- T VplF@K@Y#LHistopathologically, each of these H'22,2221,,0-,,32!2,',TlW plF@K@WYLXfour !22!T\ plF@K@ Y-Lentities is characterized by infiltration of Ɯ,2,'',2,!,,,!-,2402!!,222! 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New Roman---2 U cA 55 Year  2 U(c-2 U,cOld Ma   2 UXcn 2 U`c 22 Uccwith Swollen Eyes, Asthma     C2 e%cand Elevated Free Kappa Light Chains     2 ec @Times New Roman--- 2 usc @Times New Roman--->2 "cCalifornia Tumor Tissue Registrys    2 c %2 DcCase of the Month   2 c  2 sc %2 cCTTR COTM Vol 11:     2 c10 2 c --- 2  cwww.cttr.org - @ !D-  2 c 2 YcJuly2 pc, 2 vc2009 2 c --- 2 Zc 2 ZcA 55 2 qc-2 vcyear 2 c-2 cold 2 cman  2 c 2 cwith 2 c "2 ca ten year hist2 cory of 2 0c 52 3cswollen eyes presented with   2 casthma 2 ctic :2 Zcsymptoms. He was found to have    2 c =2 !cenlarged upper and lower eyelids  2 cwith  2 c 2 cocular s2 Z csecretions 2 cthat r12 cprevented him from seeingo   2 "c 2 % cproperly. 2 Qc  2 Tc @2 W#cThe clinical differential included  - @ !S- 2 Z cinflammatory  12 cpseudotumor of the orbitso 2 c, proptoD2 >&csis from Grave's disease and multiple     - @ !Z- 2 Z cmyeloma. o   2 c %2 cThe workup showed  2 c D2 &can elevation of free kappa light chain 2 cs 2 c.2 c 2 cA 2  cperiocular ,2 Zcbiopsy was performed.   2 c  2 (Zc (2 6ZcThe examined tissued  2 6c 2 6 cconsisted of 2 6ca 2 6cdiffuse G2 6((cinfiltration of lymphocytes admixed with   2 6c 2 DZclipids 2 Dpc-+2 Dtcladen histiocytes (xa2 D cnthoma cells) 2 Dc. The 2 D3cy 2 D8c "2 D;chad small round 2 Dced 2 Dc )2 Dcnuclei and abundant >2 RZ"cclear or vacuolated cytoplasm (Fig 2 Rc. 1T 2 R c)&2 Rc. There were also 2 Rec "2 Rhcscattered multi  2 Rc-#2 Rcnucleated giant 82 `Zccells of the Touton type (Fig. 2 `c  2 `c2 2 `c)C2 `%c. Within the lymphoid component werei     2 `c  3332 ` cprominent    3332 mZcfollicle2 m|cs with e  2 mcparafollicular 2 mc  2 mcfibrosis (Fig. 2 mc3 2 m#c). Immunohisto 2 mm cchemically 2 m c, the foamy    333L2 {Z+chistiocytes were strongly positive for CD68   2 {+c +2 {.cand negative for S1002 {c. T2 { che lymphoid    3332 Z cinfiltration 2 chad ah 2 c 2  creactive #2 cprofile with the  2 c 2 " cgerminal  2 P ccells being 2 c 2  cCD20 positive  2 c 2 cand   3332 Z cnegative for 2 c 2 cBcl  2 c- 2 c22 c. The e2 cparafo2  cllicular 2  cT cells were  2 P cCD3 positive  2 c 2 c(Fig. 4) 2 c. 2 c   333 2 Zc  @Times New Roman--- 3332 Z cDiagnosis:  2 cAdult  2 c- 2 cO #2 cnset Asthma and   52 cPeriocular Xanthogranuoloma   2 c --- 2 Zc P2 ~.cJin Guo MD, Jun Wang MD and Donald R. Chase MD     2 c m2 ~AcDepartment of Pathology, Loma Linda University and Medical Center     2 c, 2 cLoma  2 c 2 ~c  2 c %2 cLinda, California 2 c  2 ~cC:2 california Tumor Tissue Registry 2  c, ,2 &cLoma Linda, California  2 c  2 Zc ---2 ZcAdult  2 uc-2 y conset asthma  2 cwith  2 c d2 ;cperiocular xanthogranuoloma (AAPOX) was first described by     @Times New Roman---2 !Z cJakobiec ---(2 !cet al in 1993 when n2 !cthey 2 !c X2 !3creported 6 patients with periocular xanthogranuloma  2 !ctous 2 /Zcdisease) 2 /|c 2 /casP2 /.csociated with adult onset asthma, but lacking   2 /c cnecrobiosis 2 /c. 2 /c  2 /c 2 /cThee 2 /c 2 / centity has 2 /cnow #2 <Zcbeen placed into 2 <c q2 <Dca heterogeneous group of syndromes called adult xanthogranulomatous   2 JZcdisease) 2 J|c 2 Jc(A 2 JcX 2 JcGD)e  2 Jc 2 Jcthat s2 Jcaret 2 Jc 52 Jcrare and poorly understood.  2 J[c  2 J^cA 2 JfcX 2 JocGD  2 Jc 2 Jchast 2 Jc &2 Jcvariable clinical 2 XZcfeatures 2 Xc ,2 Xcwhich have resulted in 2 Xc ,2 Xcsubclassification into 2 XWc: 2 XZc   @Times New Roman- - @Times New Roman- - - @Symbol- - - 2 glc@"Arial- - - 2 gqc --- 2 g~cA2 g cdult onset- - - 2 ac ---2 gcxant2 g cthogranuloma  2 g c - - - 2 ulc- - - 2 uqc --- 2 u~cN42 ucecrobiotic xanthogranuloma   2 uc - - - - - - - - 2 lc- - - 2 qc ---2 ~cErdheims 2 c-2 cChesters- - - 2 ~c --- 2 cdisease, and  2 c - - - 2 lc- - - 2 qc ---2 ~cAAPOXe  2 c  2 Zc @2 Z#cHistopathologically, each of these 2 cfour eO2 -centities is characterized by infiltration of  2 Zc 2 _challmark cells 2 c 2  cspecifically 2 c 52 cfoamy histiocytes and Touton  2 tc-.2 xctype giant cells, both 2 cof 2 c 2 cwhich 2 Zcarec 2 hc 2 k cnegative for  2 cS100 and CD1.  2 c 2 cThec 2  c 2   cinfiltration A2 C$calong with accompanying lymphocytes   --ccbbbbbbbbbbbbbbbbaaaaaaaaaaaaaaaa````՜.+,D՜.+,x4 hp  LLUMChy9 IA 55 Year-Old Male with Swollen Eyes and Elevated Free Kappa Light Chain Title 8@ _PID_HLINKSArmT6http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Haik%20BG%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA\s3http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Fleming%20JC%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA%0http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Wilson%20MW%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusArH-http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Vick%20VL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA=*http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Kazim%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA8'http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Neigel%20JM%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA$$http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Buffam%20FV%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA;!http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22McNab%20AA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA'http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Clark%20B%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA5http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Rose%20G%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusAd@http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Currie%20Z%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA8http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Paridaens%20D%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA6http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22White%20VA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA *http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Nugent%20RA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlusA! 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