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Corneal and conjunctival crystals in paraproteinemia
CORNEA1 AND CONJUNCTIVAL
CRYSTALS IN PARAPROTEINEMIA
avoiding paraffin. lin-eosin placed on
aqttt~us f’ixatives. ‘[‘he tissue NJS etnbcdded in Sections Ivere made and stained M.ith hrtnatoxvand periodic acid-Schif‘f. Some sections were l,ol~-I)-l~sine-oated slides and stained with antihunlan K md A light chains and Ig.4. I,qM. IgD, and I@; hea\,y c-hains along with known I\mphom.t controls. ‘[‘he ~Itrtaraltlehvtle-fised tissue was processed 101 electron mc’roscop!‘, and epon pl;istir-embedded thick sections were stained with toluidine blue. Exatnitiation of‘r he niicroscx~pic- sec~tions showed an at)sence of refractile ct-vstalline deposits; however, ir showed the presence of iritracvtoplasIliic crvstallinr iticlttsions in c.onjuncti\al tnacrophages. fibrocytes’. ;tnd ettdothrlial cells (Fig 1). [‘he inclusions were best seen in 1he plastic,embedded tolrtidine blue-stained thick set ticms. It~~t~~unohistochemical stains using the perosidase anti-peroxidase rechtiiqtte showed positive staining 01‘ the inclusions fi)r K light chain and IgA heavy chain deterntinants in macrophages. fibrocvtes. and vascular endothelittm (Fig I). The controls were appropriarelv positive ;~nd negative where expet-ted. Examinarion of’ tile transmission &c.lrott microSrapha showed longitudinal and cross-sec.(ional profiles ot ttltt.;tcvlopl;tst~~i~ c-rvstalline inclusions in vascular rndothedial ceils, fibrocvtes. and macrophages (Fig 2). .l‘he findings were consistent with paraprotein c.ristal\.
I-he clinical appearance of. the c omhinartoti of corneal at~d conjuncti\ al c:rvsTals has been reported to occur in cvstinosi~,’ Bietti’s crvstalline dystroph\,,” gout,’ multiple t;iveloma, oxalosis.’ ancl I)araproteitiemia.” .-2 c-linical point o1~clit’f’erentiation is that Bietti’s crvstalline Sdvstrophy and osalosis ma\ cause retinal crvstalline deposition.‘~’ (:otijttnctival bio;,sy can aid in the &agnosis of these conditions. It is recommended that the biops! specimen he placed in absolute eth\ I alcohol or f&en sections obtained in ordet to avoid q&r or uric acid crystal dissolution in aqueous fixatives.‘,’ ‘[‘he conjunctival crystals in cvstinosis appear as ref’ractile bodies scattered throughout I he conjunctival subexamination shows the Wntia propria. ‘.’ Ultrastructural ct-vstals to appear as menlbrane-bound electt-on-lucent rectangular strttctttres present in the c) toplaztn of‘ ITlaCrOphages and fihroblasts.’ In ultrastrucrural srudies. the cryscalline structures in Bietti’s crystalline dystrophy have been shown to appear as clef‘t-like spaces itt conjunctival fibroblasts and extracellular matrix.” These inclttsions x-e not clcarlv niembrane-bountl. Gout has clinically been associated with inflammatorv manittstations including keratitis. in scleritis. and irid~,cvc:litis.” The ut-ate crvstals present gout dissolve in aqu’eous fixatives; thereltire, hiopsv specimt~s should he placed in absolute alcohol. The cqptallinv deposition in osalosis occ.urs in ;I perixascula~ distrtbution and appeat-s as hretringerlt crystals.’ Ilht-astrucrural findings disclose laminated, electron-dense tnaterial that mav he f’ragtnentecl, causing a spiculated appearance.’ This material is htncl in vascular lumens and walls. Thr histopathologic,. itr~tnunohistoc~hemical, and ultrastructural ftatures of the c~onjuncrival crysAline inclusions it1 multiple mveloma
1181
HUMAN PATHOLOGY
Volume 21, No. 11 (November 1990)
FIGURE 1. Fop) The conjunctival biopsy specimen displays intracytoplasmic crystals in a fibrocyte [fib), macrophage [arrowhead), and endothelium (asterisk]. floluidine blue stain, magnification x 250.) (Bottom) lmmunohistochemical stains demonstrate positive intracytoplasmic staining in a macrophage (arrowhead] for I@ light chain determinants (arrowhead). [Peroxidase antiperoxidase stain; magnification x 250.)
1182
CASE STUDIES
FIGURE 2. A macrophage [mat) adjacent to a lymphocyte (lvm) contains crystalline tntracytoplasmic immunoglobulin, some of which has a hexagonal configuration (asterisk). (Uranyl acetate and lead citrate stain; magnification x 7,992.) (Inset] A macrophage (mat) and fibrocyte [fib) contain tntracytoplasmic crystalline structures. (loluidine blue stain: magnification x 400.)
:III~ I’“r”p”)teitlelliia line structures .lre
appear to be identical. due to immunoglobulin
as the crystal-
deposition in both processes.!’ InlmLlnoglobulin histologicall~~ appears as inrracellular crvdline inclusions (Fig Z).“’ Immunohistothe light and heaw chain chemical stains (an clemonstrate determinanls 01’ rhese inclusions (Fig 1).I” Cltrastrkturai studies show the inclusions to correspond with dectrondense material that appears hexagonal on cross section (Fig 2). I” Systemic rvaluation, including hone marrow biopsy, will determine rhe presence 01 multiple mveloma I ersus a benign p~r;ll”oteinemia.” REFEREN(:I:S
1183
CRYSTALS IN PARAPROTEINEMIA
avoiding paraffin. lin-eosin placed on
aqttt~us f’ixatives. ‘[‘he tissue NJS etnbcdded in Sections Ivere made and stained M.ith hrtnatoxvand periodic acid-Schif‘f. Some sections were l,ol~-I)-l~sine-oated slides and stained with antihunlan K md A light chains and Ig.4. I,qM. IgD, and I@; hea\,y c-hains along with known I\mphom.t controls. ‘[‘he ~Itrtaraltlehvtle-fised tissue was processed 101 electron mc’roscop!‘, and epon pl;istir-embedded thick sections were stained with toluidine blue. Exatnitiation of‘r he niicroscx~pic- sec~tions showed an at)sence of refractile ct-vstalline deposits; however, ir showed the presence of iritracvtoplasIliic crvstallinr iticlttsions in c.onjuncti\al tnacrophages. fibrocytes’. ;tnd ettdothrlial cells (Fig 1). [‘he inclusions were best seen in 1he plastic,embedded tolrtidine blue-stained thick set ticms. It~~t~~unohistochemical stains using the perosidase anti-peroxidase rechtiiqtte showed positive staining 01‘ the inclusions fi)r K light chain and IgA heavy chain deterntinants in macrophages. fibrocvtes. and vascular endothelittm (Fig I). The controls were appropriarelv positive ;~nd negative where expet-ted. Examinarion of’ tile transmission &c.lrott microSrapha showed longitudinal and cross-sec.(ional profiles ot ttltt.;tcvlopl;tst~~i~ c-rvstalline inclusions in vascular rndothedial ceils, fibrocvtes. and macrophages (Fig 2). .l‘he findings were consistent with paraprotein c.ristal\.
I-he clinical appearance of. the c omhinartoti of corneal at~d conjuncti\ al c:rvsTals has been reported to occur in cvstinosi~,’ Bietti’s crvstalline dystroph\,,” gout,’ multiple t;iveloma, oxalosis.’ ancl I)araproteitiemia.” .-2 c-linical point o1~clit’f’erentiation is that Bietti’s crvstalline Sdvstrophy and osalosis ma\ cause retinal crvstalline deposition.‘~’ (:otijttnctival bio;,sy can aid in the &agnosis of these conditions. It is recommended that the biops! specimen he placed in absolute eth\ I alcohol or f&en sections obtained in ordet to avoid q&r or uric acid crystal dissolution in aqueous fixatives.‘,’ ‘[‘he conjunctival crystals in cvstinosis appear as ref’ractile bodies scattered throughout I he conjunctival subexamination shows the Wntia propria. ‘.’ Ultrastructural ct-vstals to appear as menlbrane-bound electt-on-lucent rectangular strttctttres present in the c) toplaztn of‘ ITlaCrOphages and fihroblasts.’ In ultrastrucrural srudies. the cryscalline structures in Bietti’s crystalline dystrophy have been shown to appear as clef‘t-like spaces itt conjunctival fibroblasts and extracellular matrix.” These inclttsions x-e not clcarlv niembrane-bountl. Gout has clinically been associated with inflammatorv manittstations including keratitis. in scleritis. and irid~,cvc:litis.” The ut-ate crvstals present gout dissolve in aqu’eous fixatives; thereltire, hiopsv specimt~s should he placed in absolute alcohol. The cqptallinv deposition in osalosis occ.urs in ;I perixascula~ distrtbution and appeat-s as hretringerlt crystals.’ Ilht-astrucrural findings disclose laminated, electron-dense tnaterial that mav he f’ragtnentecl, causing a spiculated appearance.’ This material is htncl in vascular lumens and walls. Thr histopathologic,. itr~tnunohistoc~hemical, and ultrastructural ftatures of the c~onjuncrival crysAline inclusions it1 multiple mveloma
1181
HUMAN PATHOLOGY
Volume 21, No. 11 (November 1990)
FIGURE 1. Fop) The conjunctival biopsy specimen displays intracytoplasmic crystals in a fibrocyte [fib), macrophage [arrowhead), and endothelium (asterisk]. floluidine blue stain, magnification x 250.) (Bottom) lmmunohistochemical stains demonstrate positive intracytoplasmic staining in a macrophage (arrowhead] for I@ light chain determinants (arrowhead). [Peroxidase antiperoxidase stain; magnification x 250.)
1182
CASE STUDIES
FIGURE 2. A macrophage [mat) adjacent to a lymphocyte (lvm) contains crystalline tntracytoplasmic immunoglobulin, some of which has a hexagonal configuration (asterisk). (Uranyl acetate and lead citrate stain; magnification x 7,992.) (Inset] A macrophage (mat) and fibrocyte [fib) contain tntracytoplasmic crystalline structures. (loluidine blue stain: magnification x 400.)
:III~ I’“r”p”)teitlelliia line structures .lre
appear to be identical. due to immunoglobulin
as the crystal-
deposition in both processes.!’ InlmLlnoglobulin histologicall~~ appears as inrracellular crvdline inclusions (Fig Z).“’ Immunohistothe light and heaw chain chemical stains (an clemonstrate determinanls 01’ rhese inclusions (Fig 1).I” Cltrastrkturai studies show the inclusions to correspond with dectrondense material that appears hexagonal on cross section (Fig 2). I” Systemic rvaluation, including hone marrow biopsy, will determine rhe presence 01 multiple mveloma I ersus a benign p~r;ll”oteinemia.” REFEREN(:I:S
1183