Acta Clinica Belgica International Journal of Clinical and Laboratory Medicine
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: https://www.tandfonline.com/loi/yacb20
Angio-Immunoblastic Lymphadenopathy D.W.A. Surmont, G. Verdonk, H. Roels & J.R. Quatacker To cite this article: D.W.A. Surmont, G. Verdonk, H. Roels & J.R. Quatacker (1979) Angio-Immunoblastic Lymphadenopathy, Acta Clinica Belgica, 34:2, 70-80, DOI: 10.1080/22953337.1979.11718670 To link to this article: https://doi.org/10.1080/22953337.1979.11718670
Published online: 17 May 2016.
Submit your article to this journal
Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=yacb20
70
ANGIO-IMMUNOBLASTIC LYMPHADENOPATHY D.W.A. Surmont*, G. Verdonk*, H . Roets••, J.R. Quatacker••
SUMMARY
A case of angio-immunoblastic lymphadenopathy is reported. The patient is a 56-year old 1'cmalc. Sh -: exhibited a generalized lymphadenopathy of acute onset, hepatosp lenomcgaly, edema, rash and general symptoms. Polyclonal Ig\1 dysproteinaem ia was present. Deterioration of the patient's condition was accompanied by a rarely described aregenerative anaemia. Pathological findings before and during steroid treatment are described in de tai l. Treatment seem to have caused hyalinisation of the vessels and differentiation of th e cell population Lo small lymphocyte with disappearance of younger immunobla Ls and plasmocytes. Acta Clin. Belg., 34, 2, 70.
INTRODUCTION Angio-imm unoblas tic lymphadenopathy ( AIL) i a rather recently de cribed disea e. De pite more than hundred a e reports since the fir t description by Frizzera in 1974 (7), the etiology and pathogene i of thi condition are till unknown. We report a new ca e of angio-immunobla tic lymphadenopathy and de cribe the influence of therapy on the li ght mi• Dien t voor algemene inwcndige ziekten, nutritionele ziekten en geriatric. •• Laboratorium voor pathologi he ontleedkunde. Akademisch Ziekenhui , Rijk univ r iteit Gent De Pintelaan 135 B-9000 Gent - Belgium
Acta
ll11ica Be/gica, 34, 2 (1979 )
croscopical and ultrastructural a pe t ot the lymph node. CASE REPORT Three weeks prior to admis ion, a 56year old female patient who had n ver been ill, developed quite suddenly edema in both leg and arm . Her leg xhibited a reddi h-purple non itchy rash with variable inten ity. Edema di appeared pontaneou ly, but a few days la ter the patient tarted complainin g of gen ral symptom uch a weating, thir t, nau ea and occa iona l fever. She on ul · ted a phy ician only when he tarted vomiting and felt enlarged lymph node . She wa immediately admitted in the department of internal medicine of the univer ity ho pita!. She had n t re eived any prior treatment. On admi ion her general ondilion wa well pre erved. She had no fever, but anorexia and nau ea were pronoun ed. Enlarged lymph node were found in the cer ical, uboccipita l, retro-auricu lar, upra- and infraclavicular, axi ll ar and inguinal ar a . They w re rath r oft, mobile and lightly tend r. The Jarg t one with a diameter of 3 m were found in the groin . An enlarged liver wa palpable one cm below th e ost I margin. There \: a n plen megaly. B th leg howed a diamond haped purple ra h and the right
J1NGIO-IMMUNOBLASTIC LYMPHADENOPATHY
leg wa" still slightly edematous. Despite an atypical symptomatology, heparin treatment for thrombophlebitis was initiated. Two days later the aspect of the legs had returned to normal. The next week, temperature rose lo 38,7°C and th e patient's genera l condition deteriorated. Parenteral feeding became nece sa ry. There was pronounced ni ghtsweating and generalized itching without any obvious skin lesion. Large spectrum antibiotic failed to improve these symptoms. Two week after admis ion the patient had Jost 13 kg of body weight. Neverthele s the lymph nodes had decreased in size; the axil lar ones had even di appeared. The patient received blood tran fusion to correct her anaemia (see laboratory data). Three weeks after admission, the diagno i of AIL being confirmed, a treatment with tero id (Predni olone 1 mg/ kg) was tarted . Improvem nt wa remarkable. Bod tempera ture returned to normal within 24 hr( ). Two week lat r the only remainin g mptom \ a minimal night- weating. Onl one inguinal lymph node wa till palpable. Polychemotherapy (Nitrogen mu s tard , Vin cri stine, Procarbazine) wa added. After the first MOPP ure, an attempt to interrupt corticoid admini tration failed : th patient developed a ra h, fever, i liting, sweating and lo t app tile. Predn i olone treatment wa r in lated \ ith an immediate fa ourable re ult. A pronoun d sensorimotori pol neuriti prev nt d a sixth Vincri tin e admini tration. Twent two month after th b ginning of her illne the pati nt i till on 15 mg Pr dni olone dail and appear to b in rerni s ion.
71 nia (white ce ll count 3.600/mm3) and an increased number of monocytoids ( 18 % ) ; there was no anaemia (red cell count 4.140.000/mm3); total LDH was increased ( 1,5 IU/ml; normal 0,4 to 0,7 IU) with elevated isoenzym es LDH 2 (35,9 % ) and LDHJ ( 28,9 % ) ; elec trophoresis hawed a polyclonal IgM increase and heterogeneous l g though total protein and albumin re mained within normal limit ( IgC 690 m g % , I gM 348 mg % , IgA 238 mg %). When the patient's condition deteriorated (see clini al da ta ), pancytopenia with triking anaem ia and no reticulocytes was noted (red cell count 2.990.000/mm3; white cell· count 2.600/ mm3; trombocyte count 107.000/mm3); peripheral blood mears showed up to 30 % monoc toid cell (no e tera e activity); no immunobla t were een. On bone marrow mears, red ce ll precur or were irtuall absent; megakaryocyte and m eloid were normally r pr en ted the myeloid/ r throid ratio bein g 12/ l ; neither immunobla t nor other pathological ell w re ob erved .
INVESTIGATIO
Other laborator data remained normal. They in clu ded a number of serolo i al te t ( toxopl a ma, Jue , rub Ila, mononu leo i inf ctio a, a id range of iru e ), rh uma t t , oomb te t , A F, LE- ell , r globulin , mooth mu cle antibodi , urin and fa ce anal e . Ther wer no ign of ha mol i . X ra and KG were normal. Bon marrow, peripheral blood cell ount and LDH normali zed hortl after initiation of L roid Lr atment. The light d · prol ina mia manife t during linical deteriorati n \ or n d during tr atment (maximal I gM lev l : 720 mg %) but di appear d t th time of the fifth MOPP our e.
On admi ion, laborator amin tion howed a li ght! a eel rnt d E R ( 40 in the e ond hour), moderat' leukop ·-
ra ale e ho-graph di clo ed mod rate h pato plenom ga ly and enlarg d 1 mph node in the para-aortic re11 ta
li11ica B lgi a, 34, 2 (1979)
72
ANGIO-I MMUNOBLAS T!C LYMPHADEN OPATHY
gion . Enlarged nod es in inguin a l, ili aca l and para-aortic regions were demonstrated by lymphograp hy. The diagnosis AIL was m ade on pathologica l exam in ation of an inguinal lymph node. MATERIAL : Tis ues for li ght microscopy were fixed in buffered formalin. Sections from paraffin.em bedded material were s ta in ed by H.E., th e PAS-reaction, the Giemsa s ta in and rcticulin (Gordon a nd Sweet method). Tissues for enzyme-hist ochemical tudi es were quenched in isopen tan e, coo led by liquid ni trogen. Kryostat sec tion s were tained for a specific cs terase, a lkalin e pho phata e, acid phosphata e, 5 nucleotidase and ATP-ase. Diped preparation s of the lymph node were stai ned by the MayGri.inwald Giemsa stain and the PASreaction. Tis ue for e lectron microscopy was imm edia te ly fixed in buffered formaldehyde olution at 4°C during 24
Fi g. 1 : sec tion of th e first biopsy, slwiving th e num erou ve nule , lin ed by ivollen endothelial cells and urrounded by ly mpltocyt es, immunoblasts and plasmocy tes. Giemsa ff;(} x Acta
linica Belgica, 34, 2 ( 1979)
hr( s), rin ed overnight in a 0.1 M phosphate buffer with 6 % ucrose. !' ... : fixation was done with a l % osm ium tetroxide solution . The materia l was embedded in Epon 812 and cutted on a LKB microtome III, using glass knives . The stain ing so lutions were alcoholic uranyl acetate an lea d citrate (Reynolds 1963 ).
OBSERVAT IONS: a) Light microscopic al findings :
Th e original follicular tructure of the lymp h node had di sappeared. The le ion was c haracterized by an exuberant proliferation of branching venules, li ned by a wollen endothelium . Betwee n the ve se l , a dense population was observed, composed mainly of plasmocy tes, lymphocyte , severa l immunoblas ts, histiocytic reticulum cells and ma t ce ll (fig. 1 and fig. 2). The PAS-reac tion revealed the pre-
73
ANG/0-/MMUNOBLASTIC LYMPHADENOPATHY
Fig. 2 : high power view, demonstrating a few venules with lympliocyte , som e plasnzocytes, everal immunobla ts and 1 mitotic figure in an immunoblast. H. E. 640 x
ence of PAS-po itive granular material in the cytopla m of the hi tiocytic reticulum cells and th immunobla t . In the diped preparation of the lymph nod , thi PAS-po itive m aterial wa al o observed in the topla m of the e cell typ but wa homogeneou 1 di tributed. No inter titial PAS-po itive material was noted. Th histological picture of th econd lymph node biop wa disturbed by the previou lymphograph . Large opticaily em pty spac \. ere een. Between them, the I mph nod paren h ma wa visible and did not how an follicular structur . The e el were prominent than in the fir t biop , a a result of a mark d thi kening of th wall of the v nule , partl due to h alini ation.
The cell population between the ves els had changed : the predominant cell was a mall, well d.iffer ntiat d lymphocyte, and only very rare immunobla t and few plasmocytes were ob erved. The mast cell s were till pr sent in the same proportion a in the fir t biop y (fig. 3 and fig. 4 ). The PAS-reaction revealed PASpo itive material in th cytoplasm of many mall I mphoe te . b) Electron micro co pie examination :
In the first biop y the endothelial cell or th e v nule w re marked) ' alien. The lum n f the e venules wa narrow, ed. Th ell had a pal , oval nucleu and a ytop lasm, with e ral rounded or oval mitochondria, ome r ugh endoActa
linica Be/gica, 34, 2 (1979)
74
Acta Cf'i111ca . Bel g1.ca, 34, Z (1979)
ANG!O./MMUNOB L ASTIC LYMPH ADENOPATHY
ANGIO-! MMUNOBLASTJC LYMPHADENOPATHY
Fig. 4 : l1igl1 po1Ver vielV of th e
75
eco11d biopsy. Giem a 640 x
Acta
li11ica Belgica, 34, 2 (1979)
76
ANG /Q ./ MMUNOBLASTIC LYMPHADENOPATHY
plasmi c reticulum and sa me polysomes. The lume n of th e vesse l was fill ed with an electro n dense proteinaceous material, which was also found b e twee n th e cells. Some elec tron dense material wa al o observed around th e base ment m embran e of the vesse l . In thi s area a few co ll agen fibres were id entifi ed a well as a fine fibrillar material , with a periodicity of a 1300 A. Around the ve els we found the same cell a tho e de cribed in the li ght mi cro co pi ca l exa mination . Numerou immunobla ts, whose nucleu s had often multipl e nucl eo li w ere identifi ed . Their cytoplasm showed a few sign of rough endopl as mic r e ticulum and many polysomes. The pla ma cells had an ordinary structure, with a nucl eu with dense chromat in blocs whi le th Golgi zone wa clearly visib le and th e rou gh endopla mic reticulum wa well developed. Th e re ti-
culum cell were mainly interdi gitating reticulum cells. Some hi stiocytic re ticulum ce ll contained degraded material (fig. 5 ). The second biopsy showed a differe nt pic ture. The number of mature lymphocy tes wa increa ed. Their cy toplasm wa electro n den e and co nta ined only very few mitochondria. Their nucleu had very often a very irregular hape. The endo thelial cell s had no longer the wol len a pect of the first Th e chromatin of their nubiop de n er. The hape of the nuwa cleu cleu was very irregular with deep cytopla mic indentations. Large area around th e blood ve els and be tw en the cell were occupied by fine fibri ll ar material, with a 1300 A peric.dicity as well a by large bundle of collagen fibres. The hi tiocy tic reticulum cell s were very active and contained inge ted material (fig. 6 ).
a periodicit y of 130 polyso111 e and a f ew mic r e1ic11/11111 ca11 be of 1/1e i111mu11oblast
Acta
linica Bel gica, 34, 2 (1979)
11111 (arrow h ead) . Ma11 y strands of rough endoplas· obse rved i11 t/Ji cytopla 111 7.500 x ( I ).
ANGIO-IMMUNOBLASTJC LYMPHADENOPATHY
77
Fig. 6: e/eclron micro copy of th e second biopsy aft er trea tm en t with co r ticoids. Th e endothelial ce lls ( E) show a higllly indent ed nucl eus and are le s swollen . Th e /11m e11 is fr ee of elec-
tron dense mat erial. Th e large interstitial space is filled wilh collagen fib ril (arrow) and ot11er fibrou 111a1erial showin g a 130 nm periodicity (arrow l1 ea d) . 8.400 x
DISCUSSION
lymph nodes are rather oft, mobile and s lightl y tend e r, with an average diameter of about 2 to 3 cm. The de criptions of skin les ion in the literature r emain rather vague (ra h, erythema) (11, 15, 19). In our ca e, kin I ... ion were restricted to the legs and may have b een a livedo rcticulari . Some authors u p ect that medi ation is a provoking factor (8. 12, 16, 26). Although our pati e nt wa taking psy hopharmaca, we cou ld not find drug supposed to play a ro le in th e initi ation of th di ease u h a Pen icillin, Sulfonamid s, A pirin, Halothan e, Dilantin or Gri eofulvin . An a ut on e t of Hine in an otherwi health p r on i a l o a ommon findin g. 70 o/o of all pa ti nt are
Since AIL wa recognized a a di tinct pathological en tit (7 , 12, 24 ), about hundred case hav been report d in the litera tur . Although ome clinical and biological featur characterize this illne , the diagno i i till ba ed on th e hi topathologi al examination of a I mph nod e (5, 7, 8, 13, 16 ). The clini ca l pre ntation of our patient typ ical. In decrea ing fr qu nc the symptom ar : ge nera li zed lymphadenopathy, hepa tom ega l , gen ral mptom (fever, hill , wea ting, weight lo , anorexia, pruritu ), pl enom ega l , kin ruption and edema (5, , 12, 16, 24, 34) . Th
Acta
lini
aB
l gica, 34, 2 (1979)
78
SEANCE ANATOMO-CLINIQUE DE L'HOPITAL BRUGMANN
over fifty years old and 57 years is the medium age in Lukes' series (8, 12) .
nounced (9, 12, 14, 30, 32). Cryoglobulins are m e ntioned by some authors ( 18, 29).
Our laborato ry findings however are less common. In fact, a n aregenerative anaemia is rarely seen (5, 23 ). Though modera te anaemia (PCV > 30 % ) is usua l, the more pronounced anaemia which is commonl y seen at th e moment of rapid c linica l de te rioration is usually due to (merely Coombs positive) ha emolysis (5, 8 34). Pa ncytopenia has bee n seen in some cases shortly before dea th (12) . The ra pid response of bone marrow and p eripheral blood ce ll counts to cort icoid treatm ent suggests that immun e phe no · mena mi ght have played a m ajor role in our case. Bone marrow invasion by immunobl as ts is r are ly de tec ted during life (8, 23, 27, 32), but eem to be a rul e in pos tmortem findings (8) . Recentl ey, Pangali s found hi s tological c ha nges similar to those seen in lymph performed systematically on nodes bone marrow biop ies (23 ). Lymph node biopsy is s till recommended to es tablish diagnosis (3, 6, 7, 8, 12, 13, 25). morphologica l changes in skin, liver, spl een , lung, pleura a th ey were seen in vivo, b eing less typical (8, 10, 11, 15, 17, 31, 35). The original follicu lar s tructu re of the lymph node has disappeared. The lesion is characterized by a proliferat ion of mall vessels and polymorphous cellul ar infiltrate consist ing m a inly of immunoblasts. Acidophylic tron gly PAS-positive interstitial m aterial is frequently noted. We observed the evolution of lymph node structure durin g corticoid treatment. Th e treatment ha s apparently r esulted in a hya lini a tion of the vessels and in a differe n tia tion of th e cell population to small lymphocytes with a di sappearance of the younger immunoblasts and of the plasmocytes. Only Frizzera described an ana logou fact in the li vin g patient ( 8, 14, 20, 22). We found polyclonal I gM dysproteinaem ia, but hypergammoglobulin aem ia a nd hypoa lbumin aemi a were Jes pro-
The causing agent of AIL is still unknown (2, 4, 5, 9, 14, 26, 28, 33), and the treatment remains a moot point ( 1, 2, 4, 5, 7, 8, 13, 27) .
Acta CUnica Belgica. 34, 2 (1979)
SAMENVATTING We bespre ken de ziektegcschiedeni s van een 56-jarige patiente bij wie de ctiagnose a ngio-immunoblastische lymfadcnopathi e ges teld werd . Hct klinisch beeld bes tond uit veralgemeende oehepatosplenomegalie, lymfadenopathieen, dee m, huiduitslag en veralgemeende sy mptomen zoals koorts en nach tzwcten. De ziekte Lrad vrij snel in en ee n zware achteruitgang van de algemene toestand ging me t sterke ane mie ge. paard. In tegenstellin g tot de mees te auteurs, steldcn wij op dit m omen t geen hemolyse, doch we! een nag zeldzaam beschreven onderdrukking van de rode reeks rns t. Tcvens was e r TgM dysproteinemie. De typische vera nd crin ge n van de lymfekliers tru ctuur, alsook de patholooganato mische wijziging : n tijdens prcdnisolonebchandeling warden toegelic ht. De bchandeling blijkt a l gevolg te hebbcn cen hya linisati e van de blocdvaten, ee n wijzing van de celpopu la ti e in klei ne lymfocy ten en ee n verdwijnen van de jonge immunoblas te n. RESUME L'aspect clinique, biologiquc ct hi stologique d'un cas de lym phadt'nopa thi e angio-immunoblastique est presente. L'affection survint brutalement chez un e femme agee de 56 a ns, ous forme d'adenopathics generali sces, hepa tosplenom ega lie, redemes, manifestations cutanees et symplomes generaux. Une dysprotc' ncmic polyclonale IgM fut notcc. L'aggravation rapide de la maladie s'accompagna d'an cmi grave due a une diminution de la regeneration des erythro"ides; ii n'y eut pa d'hemoly e. La Prednisone et la polychimicthcrapie ont eu un effe t favorab le dans ce cas. Nous decrivon s l'a pec t anatomopa th ologiq ue d'un ga nglion Jymphatique avant e t pendant un c corticothera pie. La Pr dnisone semble provoquer un e hya linisation de vaisseaux, la di sp::i rition de immunobl astes e t de plasmocytcs, ct le developpement d'un e p:>pul::ition cci'ulair compo ce surtout de petit lymphocytes. ACKNOWLE DGEMENTS : we a re indebted to Dr. W. Va n Hove a nd Dr. J . Ha mer for the interpre tation of bone marrow a nd pcriph cr::i l blood s mea rs.
79
ANGIO-IMMUNOBLASTIC LYMPHADENOPATHY
REFERENCES I. ABU-ZAHRA, H.T., McDO ALO, D.B. and HORNE, W.1 . ( 1975), Anglo-immunobla ti
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: https://www.tandfonline.com/loi/yacb20
Angio-Immunoblastic Lymphadenopathy D.W.A. Surmont, G. Verdonk, H. Roels & J.R. Quatacker To cite this article: D.W.A. Surmont, G. Verdonk, H. Roels & J.R. Quatacker (1979) Angio-Immunoblastic Lymphadenopathy, Acta Clinica Belgica, 34:2, 70-80, DOI: 10.1080/22953337.1979.11718670 To link to this article: https://doi.org/10.1080/22953337.1979.11718670
Published online: 17 May 2016.
Submit your article to this journal
Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=yacb20
70
ANGIO-IMMUNOBLASTIC LYMPHADENOPATHY D.W.A. Surmont*, G. Verdonk*, H . Roets••, J.R. Quatacker••
SUMMARY
A case of angio-immunoblastic lymphadenopathy is reported. The patient is a 56-year old 1'cmalc. Sh -: exhibited a generalized lymphadenopathy of acute onset, hepatosp lenomcgaly, edema, rash and general symptoms. Polyclonal Ig\1 dysproteinaem ia was present. Deterioration of the patient's condition was accompanied by a rarely described aregenerative anaemia. Pathological findings before and during steroid treatment are described in de tai l. Treatment seem to have caused hyalinisation of the vessels and differentiation of th e cell population Lo small lymphocyte with disappearance of younger immunobla Ls and plasmocytes. Acta Clin. Belg., 34, 2, 70.
INTRODUCTION Angio-imm unoblas tic lymphadenopathy ( AIL) i a rather recently de cribed disea e. De pite more than hundred a e reports since the fir t description by Frizzera in 1974 (7), the etiology and pathogene i of thi condition are till unknown. We report a new ca e of angio-immunobla tic lymphadenopathy and de cribe the influence of therapy on the li ght mi• Dien t voor algemene inwcndige ziekten, nutritionele ziekten en geriatric. •• Laboratorium voor pathologi he ontleedkunde. Akademisch Ziekenhui , Rijk univ r iteit Gent De Pintelaan 135 B-9000 Gent - Belgium
Acta
ll11ica Be/gica, 34, 2 (1979 )
croscopical and ultrastructural a pe t ot the lymph node. CASE REPORT Three weeks prior to admis ion, a 56year old female patient who had n ver been ill, developed quite suddenly edema in both leg and arm . Her leg xhibited a reddi h-purple non itchy rash with variable inten ity. Edema di appeared pontaneou ly, but a few days la ter the patient tarted complainin g of gen ral symptom uch a weating, thir t, nau ea and occa iona l fever. She on ul · ted a phy ician only when he tarted vomiting and felt enlarged lymph node . She wa immediately admitted in the department of internal medicine of the univer ity ho pita!. She had n t re eived any prior treatment. On admi ion her general ondilion wa well pre erved. She had no fever, but anorexia and nau ea were pronoun ed. Enlarged lymph node were found in the cer ical, uboccipita l, retro-auricu lar, upra- and infraclavicular, axi ll ar and inguinal ar a . They w re rath r oft, mobile and lightly tend r. The Jarg t one with a diameter of 3 m were found in the groin . An enlarged liver wa palpable one cm below th e ost I margin. There \: a n plen megaly. B th leg howed a diamond haped purple ra h and the right
J1NGIO-IMMUNOBLASTIC LYMPHADENOPATHY
leg wa" still slightly edematous. Despite an atypical symptomatology, heparin treatment for thrombophlebitis was initiated. Two days later the aspect of the legs had returned to normal. The next week, temperature rose lo 38,7°C and th e patient's genera l condition deteriorated. Parenteral feeding became nece sa ry. There was pronounced ni ghtsweating and generalized itching without any obvious skin lesion. Large spectrum antibiotic failed to improve these symptoms. Two week after admis ion the patient had Jost 13 kg of body weight. Neverthele s the lymph nodes had decreased in size; the axil lar ones had even di appeared. The patient received blood tran fusion to correct her anaemia (see laboratory data). Three weeks after admission, the diagno i of AIL being confirmed, a treatment with tero id (Predni olone 1 mg/ kg) was tarted . Improvem nt wa remarkable. Bod tempera ture returned to normal within 24 hr( ). Two week lat r the only remainin g mptom \ a minimal night- weating. Onl one inguinal lymph node wa till palpable. Polychemotherapy (Nitrogen mu s tard , Vin cri stine, Procarbazine) wa added. After the first MOPP ure, an attempt to interrupt corticoid admini tration failed : th patient developed a ra h, fever, i liting, sweating and lo t app tile. Predn i olone treatment wa r in lated \ ith an immediate fa ourable re ult. A pronoun d sensorimotori pol neuriti prev nt d a sixth Vincri tin e admini tration. Twent two month after th b ginning of her illne the pati nt i till on 15 mg Pr dni olone dail and appear to b in rerni s ion.
71 nia (white ce ll count 3.600/mm3) and an increased number of monocytoids ( 18 % ) ; there was no anaemia (red cell count 4.140.000/mm3); total LDH was increased ( 1,5 IU/ml; normal 0,4 to 0,7 IU) with elevated isoenzym es LDH 2 (35,9 % ) and LDHJ ( 28,9 % ) ; elec trophoresis hawed a polyclonal IgM increase and heterogeneous l g though total protein and albumin re mained within normal limit ( IgC 690 m g % , I gM 348 mg % , IgA 238 mg %). When the patient's condition deteriorated (see clini al da ta ), pancytopenia with triking anaem ia and no reticulocytes was noted (red cell count 2.990.000/mm3; white cell· count 2.600/ mm3; trombocyte count 107.000/mm3); peripheral blood mears showed up to 30 % monoc toid cell (no e tera e activity); no immunobla t were een. On bone marrow mears, red ce ll precur or were irtuall absent; megakaryocyte and m eloid were normally r pr en ted the myeloid/ r throid ratio bein g 12/ l ; neither immunobla t nor other pathological ell w re ob erved .
INVESTIGATIO
Other laborator data remained normal. They in clu ded a number of serolo i al te t ( toxopl a ma, Jue , rub Ila, mononu leo i inf ctio a, a id range of iru e ), rh uma t t , oomb te t , A F, LE- ell , r globulin , mooth mu cle antibodi , urin and fa ce anal e . Ther wer no ign of ha mol i . X ra and KG were normal. Bon marrow, peripheral blood cell ount and LDH normali zed hortl after initiation of L roid Lr atment. The light d · prol ina mia manife t during linical deteriorati n \ or n d during tr atment (maximal I gM lev l : 720 mg %) but di appear d t th time of the fifth MOPP our e.
On admi ion, laborator amin tion howed a li ght! a eel rnt d E R ( 40 in the e ond hour), moderat' leukop ·-
ra ale e ho-graph di clo ed mod rate h pato plenom ga ly and enlarg d 1 mph node in the para-aortic re11 ta
li11ica B lgi a, 34, 2 (1979)
72
ANGIO-I MMUNOBLAS T!C LYMPHADEN OPATHY
gion . Enlarged nod es in inguin a l, ili aca l and para-aortic regions were demonstrated by lymphograp hy. The diagnosis AIL was m ade on pathologica l exam in ation of an inguinal lymph node. MATERIAL : Tis ues for li ght microscopy were fixed in buffered formalin. Sections from paraffin.em bedded material were s ta in ed by H.E., th e PAS-reaction, the Giemsa s ta in and rcticulin (Gordon a nd Sweet method). Tissues for enzyme-hist ochemical tudi es were quenched in isopen tan e, coo led by liquid ni trogen. Kryostat sec tion s were tained for a specific cs terase, a lkalin e pho phata e, acid phosphata e, 5 nucleotidase and ATP-ase. Diped preparation s of the lymph node were stai ned by the MayGri.inwald Giemsa stain and the PASreaction. Tis ue for e lectron microscopy was imm edia te ly fixed in buffered formaldehyde olution at 4°C during 24
Fi g. 1 : sec tion of th e first biopsy, slwiving th e num erou ve nule , lin ed by ivollen endothelial cells and urrounded by ly mpltocyt es, immunoblasts and plasmocy tes. Giemsa ff;(} x Acta
linica Belgica, 34, 2 ( 1979)
hr( s), rin ed overnight in a 0.1 M phosphate buffer with 6 % ucrose. !' ... : fixation was done with a l % osm ium tetroxide solution . The materia l was embedded in Epon 812 and cutted on a LKB microtome III, using glass knives . The stain ing so lutions were alcoholic uranyl acetate an lea d citrate (Reynolds 1963 ).
OBSERVAT IONS: a) Light microscopic al findings :
Th e original follicular tructure of the lymp h node had di sappeared. The le ion was c haracterized by an exuberant proliferation of branching venules, li ned by a wollen endothelium . Betwee n the ve se l , a dense population was observed, composed mainly of plasmocy tes, lymphocyte , severa l immunoblas ts, histiocytic reticulum cells and ma t ce ll (fig. 1 and fig. 2). The PAS-reac tion revealed the pre-
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Fig. 2 : high power view, demonstrating a few venules with lympliocyte , som e plasnzocytes, everal immunobla ts and 1 mitotic figure in an immunoblast. H. E. 640 x
ence of PAS-po itive granular material in the cytopla m of the hi tiocytic reticulum cells and th immunobla t . In the diped preparation of the lymph nod , thi PAS-po itive m aterial wa al o observed in the topla m of the e cell typ but wa homogeneou 1 di tributed. No inter titial PAS-po itive material was noted. Th histological picture of th econd lymph node biop wa disturbed by the previou lymphograph . Large opticaily em pty spac \. ere een. Between them, the I mph nod paren h ma wa visible and did not how an follicular structur . The e el were prominent than in the fir t biop , a a result of a mark d thi kening of th wall of the v nule , partl due to h alini ation.
The cell population between the ves els had changed : the predominant cell was a mall, well d.iffer ntiat d lymphocyte, and only very rare immunobla t and few plasmocytes were ob erved. The mast cell s were till pr sent in the same proportion a in the fir t biop y (fig. 3 and fig. 4 ). The PAS-reaction revealed PASpo itive material in th cytoplasm of many mall I mphoe te . b) Electron micro co pie examination :
In the first biop y the endothelial cell or th e v nule w re marked) ' alien. The lum n f the e venules wa narrow, ed. Th ell had a pal , oval nucleu and a ytop lasm, with e ral rounded or oval mitochondria, ome r ugh endoActa
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ANGIO-! MMUNOBLASTJC LYMPHADENOPATHY
Fig. 4 : l1igl1 po1Ver vielV of th e
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eco11d biopsy. Giem a 640 x
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ANG /Q ./ MMUNOBLASTIC LYMPHADENOPATHY
plasmi c reticulum and sa me polysomes. The lume n of th e vesse l was fill ed with an electro n dense proteinaceous material, which was also found b e twee n th e cells. Some elec tron dense material wa al o observed around th e base ment m embran e of the vesse l . In thi s area a few co ll agen fibres were id entifi ed a well as a fine fibrillar material , with a periodicity of a 1300 A. Around the ve els we found the same cell a tho e de cribed in the li ght mi cro co pi ca l exa mination . Numerou immunobla ts, whose nucleu s had often multipl e nucl eo li w ere identifi ed . Their cytoplasm showed a few sign of rough endopl as mic r e ticulum and many polysomes. The pla ma cells had an ordinary structure, with a nucl eu with dense chromat in blocs whi le th Golgi zone wa clearly visib le and th e rou gh endopla mic reticulum wa well developed. Th e re ti-
culum cell were mainly interdi gitating reticulum cells. Some hi stiocytic re ticulum ce ll contained degraded material (fig. 5 ). The second biopsy showed a differe nt pic ture. The number of mature lymphocy tes wa increa ed. Their cy toplasm wa electro n den e and co nta ined only very few mitochondria. Their nucleu had very often a very irregular hape. The endo thelial cell s had no longer the wol len a pect of the first Th e chromatin of their nubiop de n er. The hape of the nuwa cleu cleu was very irregular with deep cytopla mic indentations. Large area around th e blood ve els and be tw en the cell were occupied by fine fibri ll ar material, with a 1300 A peric.dicity as well a by large bundle of collagen fibres. The hi tiocy tic reticulum cell s were very active and contained inge ted material (fig. 6 ).
a periodicit y of 130 polyso111 e and a f ew mic r e1ic11/11111 ca11 be of 1/1e i111mu11oblast
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11111 (arrow h ead) . Ma11 y strands of rough endoplas· obse rved i11 t/Ji cytopla 111 7.500 x ( I ).
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Fig. 6: e/eclron micro copy of th e second biopsy aft er trea tm en t with co r ticoids. Th e endothelial ce lls ( E) show a higllly indent ed nucl eus and are le s swollen . Th e /11m e11 is fr ee of elec-
tron dense mat erial. Th e large interstitial space is filled wilh collagen fib ril (arrow) and ot11er fibrou 111a1erial showin g a 130 nm periodicity (arrow l1 ea d) . 8.400 x
DISCUSSION
lymph nodes are rather oft, mobile and s lightl y tend e r, with an average diameter of about 2 to 3 cm. The de criptions of skin les ion in the literature r emain rather vague (ra h, erythema) (11, 15, 19). In our ca e, kin I ... ion were restricted to the legs and may have b een a livedo rcticulari . Some authors u p ect that medi ation is a provoking factor (8. 12, 16, 26). Although our pati e nt wa taking psy hopharmaca, we cou ld not find drug supposed to play a ro le in th e initi ation of th di ease u h a Pen icillin, Sulfonamid s, A pirin, Halothan e, Dilantin or Gri eofulvin . An a ut on e t of Hine in an otherwi health p r on i a l o a ommon findin g. 70 o/o of all pa ti nt are
Since AIL wa recognized a a di tinct pathological en tit (7 , 12, 24 ), about hundred case hav been report d in the litera tur . Although ome clinical and biological featur characterize this illne , the diagno i i till ba ed on th e hi topathologi al examination of a I mph nod e (5, 7, 8, 13, 16 ). The clini ca l pre ntation of our patient typ ical. In decrea ing fr qu nc the symptom ar : ge nera li zed lymphadenopathy, hepa tom ega l , gen ral mptom (fever, hill , wea ting, weight lo , anorexia, pruritu ), pl enom ega l , kin ruption and edema (5, , 12, 16, 24, 34) . Th
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over fifty years old and 57 years is the medium age in Lukes' series (8, 12) .
nounced (9, 12, 14, 30, 32). Cryoglobulins are m e ntioned by some authors ( 18, 29).
Our laborato ry findings however are less common. In fact, a n aregenerative anaemia is rarely seen (5, 23 ). Though modera te anaemia (PCV > 30 % ) is usua l, the more pronounced anaemia which is commonl y seen at th e moment of rapid c linica l de te rioration is usually due to (merely Coombs positive) ha emolysis (5, 8 34). Pa ncytopenia has bee n seen in some cases shortly before dea th (12) . The ra pid response of bone marrow and p eripheral blood ce ll counts to cort icoid treatm ent suggests that immun e phe no · mena mi ght have played a m ajor role in our case. Bone marrow invasion by immunobl as ts is r are ly de tec ted during life (8, 23, 27, 32), but eem to be a rul e in pos tmortem findings (8) . Recentl ey, Pangali s found hi s tological c ha nges similar to those seen in lymph performed systematically on nodes bone marrow biop ies (23 ). Lymph node biopsy is s till recommended to es tablish diagnosis (3, 6, 7, 8, 12, 13, 25). morphologica l changes in skin, liver, spl een , lung, pleura a th ey were seen in vivo, b eing less typical (8, 10, 11, 15, 17, 31, 35). The original follicu lar s tructu re of the lymph node has disappeared. The lesion is characterized by a proliferat ion of mall vessels and polymorphous cellul ar infiltrate consist ing m a inly of immunoblasts. Acidophylic tron gly PAS-positive interstitial m aterial is frequently noted. We observed the evolution of lymph node structure durin g corticoid treatment. Th e treatment ha s apparently r esulted in a hya lini a tion of the vessels and in a differe n tia tion of th e cell population to small lymphocytes with a di sappearance of the younger immunoblasts and of the plasmocytes. Only Frizzera described an ana logou fact in the li vin g patient ( 8, 14, 20, 22). We found polyclonal I gM dysproteinaem ia, but hypergammoglobulin aem ia a nd hypoa lbumin aemi a were Jes pro-
The causing agent of AIL is still unknown (2, 4, 5, 9, 14, 26, 28, 33), and the treatment remains a moot point ( 1, 2, 4, 5, 7, 8, 13, 27) .
Acta CUnica Belgica. 34, 2 (1979)
SAMENVATTING We bespre ken de ziektegcschiedeni s van een 56-jarige patiente bij wie de ctiagnose a ngio-immunoblastische lymfadcnopathi e ges teld werd . Hct klinisch beeld bes tond uit veralgemeende oehepatosplenomegalie, lymfadenopathieen, dee m, huiduitslag en veralgemeende sy mptomen zoals koorts en nach tzwcten. De ziekte Lrad vrij snel in en ee n zware achteruitgang van de algemene toestand ging me t sterke ane mie ge. paard. In tegenstellin g tot de mees te auteurs, steldcn wij op dit m omen t geen hemolyse, doch we! een nag zeldzaam beschreven onderdrukking van de rode reeks rns t. Tcvens was e r TgM dysproteinemie. De typische vera nd crin ge n van de lymfekliers tru ctuur, alsook de patholooganato mische wijziging : n tijdens prcdnisolonebchandeling warden toegelic ht. De bchandeling blijkt a l gevolg te hebbcn cen hya linisati e van de blocdvaten, ee n wijzing van de celpopu la ti e in klei ne lymfocy ten en ee n verdwijnen van de jonge immunoblas te n. RESUME L'aspect clinique, biologiquc ct hi stologique d'un cas de lym phadt'nopa thi e angio-immunoblastique est presente. L'affection survint brutalement chez un e femme agee de 56 a ns, ous forme d'adenopathics generali sces, hepa tosplenom ega lie, redemes, manifestations cutanees et symplomes generaux. Une dysprotc' ncmic polyclonale IgM fut notcc. L'aggravation rapide de la maladie s'accompagna d'an cmi grave due a une diminution de la regeneration des erythro"ides; ii n'y eut pa d'hemoly e. La Prednisone et la polychimicthcrapie ont eu un effe t favorab le dans ce cas. Nous decrivon s l'a pec t anatomopa th ologiq ue d'un ga nglion Jymphatique avant e t pendant un c corticothera pie. La Pr dnisone semble provoquer un e hya linisation de vaisseaux, la di sp::i rition de immunobl astes e t de plasmocytcs, ct le developpement d'un e p:>pul::ition cci'ulair compo ce surtout de petit lymphocytes. ACKNOWLE DGEMENTS : we a re indebted to Dr. W. Va n Hove a nd Dr. J . Ha mer for the interpre tation of bone marrow a nd pcriph cr::i l blood s mea rs.
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REFERENCES I. ABU-ZAHRA, H.T., McDO ALO, D.B. and HORNE, W.1 . ( 1975), Anglo-immunobla ti
