Angiotropic malignant melanoma Report of two cases Twe) cases of malignanf nu-lane)ma are- de-se-ribed that slu)vved fbcal i)erineural in\'asie)n a n d e-xhibited striking tre)])ism for small a n d nu-ehtim-sized ve-sse-ls, primarily \'eins. The- inelane)ma cells j)i'olilerateel withm the ve-ssel walls, e-x|)anding and re]:)lae-ing the m u s c l e h u e r but s p a r i n g (he endothelia. Intraxasetilar i i u a s i o n w a s not se-eii. lmmiine)liiste)ehe-mie'al sttidie's ee)nlirnu-el the |:iattern eil gre)wtli within vessel walls and the inte-grity ejf their end o t h e l i a . In e)ne of (he eases, similar vasenlar trc)|:)ism was ence)tmtcre-d iii a eajrisiilar vein from a regieinal Kinph ne)de. We |:)re)pe)se the term "angiejtro|:)ie m a l i g n a n t nu-lanoma" for this |:)henomenon and stiggest (hat angiotro|)ism may be a rare me'clianism feir ine-lane)nia s|)re-ad and ])re)gressie)n. Me)reiic) A, Tls|)aiie)l I, Re)mage)sa V. Angie)tre)|:)ie m a l i g n a n t m e l a n o m a . 'Twe) e'ases. J . CUitaii Fatlu)! 1992: 19: 32:'i-329.
C u t a n e o u s maligtianf m e l a n o m a is a neoplasm c h a r a c t e r i z e d by \'arious pa((erns e)f gre)w(h, some e)f w h i e h are assoeiated with speeifie biologieal significance. The' raelial gi'e)wtli ]3hase represents a perie^d e)r cellular |:)re)liferation with ei^idercnal a n d papillary de'i'inal gi'e)wtli (1). MelaiU)mas in radial gre)W'lh are' pre)bably tillable to metastasize because ibcy lack the ability tc3 generate a mass (2). T h e vertical growth phase is eharaeterized by (time)r cells that proliferate to form a mass (nstially ne)dnle, occasionally |)lac|tie), with sc-eondary inliltration ol ihe- ele-rmis and de-e-p (isstie-s (2). M e l a n o m a s in vertical g r o w t h are ca|:)able ol vasetilar in\'asie)n and m e t a s t a s e s . 'The progne)sis of stage I m a l i g n a n t nu-la n o n i a ol the- skin d e p e n d s heavily on the vertieal g r o w t h phase (3,4), particularly on its thickness (3,,")). Netirofcopic n i e l a n o m a (6) is eharaeteri/.c-d by tume)r i^reilife-ration along peripheral nerves with tuniejr extension far form the p r i m a r y Iheus. This type
Abelardo Moreno, Isabel Espafiol, Vicens Romagosa Deparlmenf of Pathology. Hospifal Princeps d'Espanya. Barcelona, Spain.
Abelardo Moreno, Deparfment of Pafhology. Hospifal Princeps d'Espanya, Feixa Llarga s/n, 08907 L'Hospifalet, Barcelona. Spain. Accepted for publication ??
e)f t u m o r iiu'asion can be fe)lle)we-el by ee-iifral nerxoiis system in\'e)l\'eme-nt. In this |)aper, we repeirt two eases of m a l i g n a n t m e l a n o m a with a peculiar p a t t e r n of growth. 1( was eharaeferize-d by ftime)r eell in\'asie)n t)f fhe walls of small and iiu-ditim-sized xeiiis, widi s e c o n d a r y spread aleing the \'ein walls sexeral millimetres away lre)m the base of the t u m o r . T h e walls of the in\'eil\'e-d \'esse-ls appe-ared (hie-kc-iu-d and re|)lae'eel l)y m a l i g n a n l nu'lancima e'e'Us, whe-reas ciule)llu-lia re-mainc-d intaet.
Material and methods Case reports ('a.se I. \u !-)(l-year-e)ld m a n w a s referred te) t h e H o s p i t a l for t r e a t m e n t e)fa p i g m e n t e ' d t u m o r e)n his Ibrelu-ad. A presimi]:iti\'e elinieal eliagne)sis e)f l e n t i g o m a l i g n a ine-lane)ma w a s m a d e , a n d the- pafient tm-
Table I. Anfibodies and dilutions employed Anfibody
Type
Source
Dilution
Epifhelial membrane anfigen
Mouse monoclonal
Dako
1/50
Low weight keratin Cam 5.2
Mouse monoclonal
Becton-Dickinson
Predilufed
HMB-45
Mouse monoclonal
Enzo
1/1,400
S-fOO profein
Polyclonal
Dako
1/fOO
Vimenfin
Mouse monoclonal
Biogenax
Predilufed
Muscle actin
Mouse monoclonal
Enzo
1/100
Utex europaeus
Lecfin
Dako
1/100
325
Moreno et al.
I'ii;. I. Radial growth phase elemotistralitig atypical melanocytic proliferation along the dertno-epidcrmal juuetion anel dermal nielanophages (Case I).
de-rwent wide surgical excision of his lesion. Eive mejnths later, the patient was doing well, without evidenee of residual disease or metastases. Case 2. A 71-year-e)lcl woman with a pigmented maeule on her left heel that had been present for years required medical atten(ie)ii Ix-eause e)f bleeding fre)m her lesie)n. Physieal examination revealed an irregular, pigmented plaque, 1.8 X \ .5 em in size, surrounded by small satellite lesions. After a diagnostie biopsy, (he le'sie)n was siirgieally excised as were the left inguinal ne)des. Two years later, the patient presented with regional cutaneous metastases. When last seen, she had multiple eutaneous "in transit" papular and nodular metastases limited te) the- involved leg.
root sheatli of hair fbllieles. The de-rmis showed a sparse perivaseular lymplioeytic infiltrate with melanophages (Eig. 1). The eentral nodule was superfieally uleerated and eovered by a erust. 'The vertieal growth phase was eomposed of epithelie)icl and spindled melane)eytes with moderate nuelear atypia and 1 to 3 mitotic figures per high power field. Melanin was easily demonstrated within lumor eells and stromal melanophages. The maximal thickness was ,5.98 mm. At the base e)f the tumeur, the melanoma eells we-re spindle shaped and showed foei of perineural invasie)n (Eig. 2). Tlu- sugieal sample from ease 2 measured 5 X 4 em. The cutaneous surface showed a slightly raised, brown to blaek plaque, 1.8 X 1.5 em in size, that was surrounded by 0.1 te) 0.3-em satellite lesions. Mieroseopie examinatie^n sheiwed a malignant melanoma wifhe)ut radial gi'e)wth |:)hase. Small size "nevoeytie" me-lanoma eells invaded the deep retieular dermis. The maximal thiekness was 3.43 mm. Perineural invasie)n was fe)eally denu)nstrated. The satellites showed similar melanoma eells limited to the papillary dermis and laeking e-|)iderme)tro]:)isni. One of the reseete'd lymph nodes showed miere:)metastases.
Tumor samples
'Ehe surgieal speeimens were fixed in 10% buffered formalin, routinely proeessed, and e-mbedded in paraffin. Seetions were stained with H&E, Masson's triehrome, and stains lor elastic fibres. Immunohistoehemieal studies were perfbrmed e)n paraffin-embedded tissue. The antibodies and dilutions are listed in Table I. The avidin-biotin-peroxidase complex (ABC) procedure (7) was used. Results
The gross speeimen from ease 1 was a eutaneous ellipse, 2.5 X 2 em in maximal dimensiejn. The epidermal surfaee showed a pigmented maeule that oecupied an area measuring \ .5 X 1 cm. There was a central pigmented nc:)dtjle, 1.2 em in size. Mieroseopie examination revealed a radial growth phase melanoma with the distinetive features of lentigo maligna. The epidermis was atrophie. Atypieal s])indled melanoma eells proliferated in a lentiginous pattern along the basal eell layer of the dermoepidermal junetion and the e)uter 326
Fii;. 2. Pcritu-ural (Case 1).
invasion
by malignant
tiic-latioma
cells
Angiotropic melanoma
/•'/i;. 'i. A s t i i a l l s n h c i t t a t i e o n s x c ' i t i e x l n h t t i t i g p e r i v a s c e t l a r i t i \ a . s i o n h \ t n m o r cc-lls ( C a . s c 1 ) .
/'/if. 4. I ^ c - t a t l o l a t i i c d i u n i - s i / . c - c f \ ' e i n clc-j)ic t e d u i h L ^ u r e t i . 1 l u ' r e IS l ) u l k \ hut
replacc-nic'iit ol t h e s u i o o t h m u s c l e h y u i c l a i i o n i a
uiaiutaitianee of t h e endotiieliai .mcl acl\cutitial
cells
iiitc'i;rit\
(Case I).
Small and nu-ditim-sized ve-ins at the base- of both lesions showed invasion e)f their walls by (tinieir cells (Eig. 3). The eells showe-d nuide-rate \'ariatie)n in size and sha]:)e, and melanin pignu-ii( eeiiild e)eeasie)nally be de'nu)ns(rated. \'ase-iilar in\'t)l\'e-meiit was obvious and exte-nsive in Clase I but e)nly Ibeally pre-sent in Case 2. The inve)lve'cl \'essels had a distinetive appearance. Their walls were e)ccttpied by tume)r eells while the integrity of their endothelia was maintained (l'i,g 4). In small vesse-ls, ttmior inliltration was usually asse)eiate-d with partial oeelusiein e)f lumina, although immmiostaining with Ule.\ eti~ ropat'ti.s lectin c:onsistcn(ly demonstrated a spaced endothelial layer (Tig. 5). In nu-dium-sized xessels, there was partial or eomplefe desfruetion of fhe muscle eells and elastie fibres and replaeement by melanoma eells. Ttiinor eells did not penetrate fhe adventitia. The melaiu)nia cells ai)]:)eared to spread along vessel walls and eould be elemonsfrated several millimetres away fre)in the- base and lateral aspects ol fhe tume)r (T'ig. fi). In e)ne of the lymph nodes from Patient 2, a similar pattern of in\'asie)n was observed in a eapsular vein (Eig 7). Serial seetions denie)nstrated fbcal ne)clal inveilvement.
The- immunohisteieheinieal findings conlirmcd tluligln mieroscopic e)bse-r\'a(ions. .As noted a b e n e , tluintegrity of the endothclial layer was ce)nlirmcd by LUex europaeu.s lectin itiiinune)stainiiig. Anti-nuisdeactin antibexly was helpful in the demeinsfratie)n e)f musele eell effacement (Eig. 8). The nu-lanoma cc-lls were diffusely positixe- fbr S-100 ])i'e)(e-in, \'ime-nliii, a n d H M B - 4 5 a n d ne-g,i(i\'e for low molc-eiilar we-igh( k e r a d n s a n d e|)illie-lial membrane- antige-ii.
Discussion The- two cases re-pe)rted herein exliif)i(ed elistine'(i\'evasetilar involvement by m a l i g n a n t m e l a n o m a thai was e h a r a c t e r i z e d by t n m o r infil(ratie)n, proliferation, a n d s p r e a d within the walls of small a n d m e d i u m - s i z e d veins in the a b s e n c e e)f endothelial injury. Jain a n d Allen, in their p a p e r e)n desnioplastie m e l a n o m a (8), illnstratc-d circumferential invasion e)f ai'tei'ies, but llie iiu'olved vessels were' situated within the' tunuir. In e'e)ntrast, the- x a s e u l a r involvenu'nf in o u r eases extended for some distatu e from tlu- m a m e-e)ne'e'ntratie)n e)f ne-e)]:)lasm. The" te'rin
327
Moreno et al.
'\
1
J Fig. 5. P a r t i a l l u m i u a l cieclttsiott citie t o t i i e l a n o m a eell infilt r a t i o n . tHex n m l x m i . ' , sin'in h i g h l i g h t s t h e s p a r e d e n d c j t e l i a l cells (Case 1).
/'\^'. 6. Involved hlood vessels located in (he suhcutancous tis.sue.s, separated Irom the vertical nfowlli phase hy uiiiuvolved fat (Case 1).
Fig. 7. Involved vein in the vicinity of the capsule of a re-frional lytnph node (Case 2).
328
Angiotropic melanoma /•'/.!;. H. I'cical sparing of muscle lihres as shown hy imniunostainitig for inuscle actit) (Ciasc 2).
"angiod'opie" seems appro]:)ria(e- Ibr (he Ie-siems we describe. Neui-o(re)|)ic melaiie)ma has a ])c-culiar (ro|Dism for perij:)heral cu(aneous nerves (6,9) and may proliferate along them. Inve)lvenu-nt of the central nervous syste-in may be- re-la(e-el (o inlraneural e)r pe-rine-ural extension (6). Tlowever, the patlicjgenesis of these two forms of troj^ism, neural and vascular, is probably ejtiite dilfe-re-ii(. In ncurotreipic mclaneima, thc melane)ma cells a|)pear to aeejuire pre)perties of Schwann cells (10). Spread ale)ng nerves and the tendeney te) Ibrm iu-rve--like structures may lluis reflect partial transformation of the melaneima cells, themselves. On the othe-r hand, the angiotro|:)ic melanomas described here- were- "common" melane)nias, with the- exee]:)tiejii of the-ir unique pattern of vasctilar wall invasie)n. We were- unable to demonstrate e-vidence of e-iulothelial e)r museular dilTerentia(ie)n, either with light microscopy e)r immtmohis(c)chemis(ry. Me)re-o\'e-r, (he results of our immuneistaining were- consistent with the)se of malignant melaiuinia (11). It could be speetilated that the vaseular wall repre-se-nts a locu.s miiiori.s
ic.si.slentiae
along whieh
limite-d
progressiein of t u m o r cells is lave)red. It is alse) ])ossible- (ha( |)e'i'ine-ural inxasion (focaify preseiu in o u r (wo cases) could have inllueneed the growth of tume:)r ce-lls via the- vasa n e r v o r u m . l'\irtlu-r study e)f similar cases will be required to better u n d e r s t a n d the |:)athe)genesis a n d biologic significance- of (his distinctive p a t t e r n of vascular invasioti.
References 1. Clark W l l . folhcrg R. .Xiuswcit th . \ M . I'mnor pi'cigi cssioti iu primal') human cnlaiu-ous m.ihgiiant melanoma In: Clark W H . Coldman I.I. Mastratigelo MJ c-ds. Human malignaut uu-lanoma. Nc-xv \ork: (iiuiic- & .Siiatlon, 1979. 2. l'',lde-r Df',, Cucrrv I). I'.pstciti MN. et al. Iinasivc malignatit melanomas lacking eompc-lence for metastasis. Am | Derniatc)i)atlic)l 1984: ()(Snppl I): :').'). 3. fjalch C M . .Soong S-J, .Shaw HM. Milton (iW. Ati analysis ol prognostic factors in 4000 patients with c utaiieous melanoma. In: Baich C M . Miltoti (;\V. c-ds. Malignant niclanon)a. C:iiiiieal manage iiic-ut and ticMtuic-nt rc-sults worldwide-. Philadc-lphia: j . B. Iappinccill, 198.'). I. McKic RM. \'c>uiig 1). Human malignanl melanoma, lnt ) Dermatol 1984: 23: 433. 5. Wc-isstnatm A. Roses DF, Harris MN. Duhin .N. Prcdiclion ol Kinpli node metastasc-s from the liislologic features of prtmary hnman malignatit melanomas. .Am j Dermatopalhol 1984: (i(Snppl I): •^5. (). Reed RJ, l.c-onard DI). Neurcitropic tiielanoma: a xarianl of desmoplaslie tiu-latuima. Am j Surg Pathol 1979: 3: 301. 7. Hstt SN. Raitie I,. Kanger 11. 'flu- use of avidin-hiotitiperoxidase complc-x (.ABC) and uulabellc-d aiitihod\ (P.AP). J Histochem Cytochctii 1981: 29: 511. 8. Jain S, .Alleu WP. nesmoplastic malignant nielanoma and ils variatits. A slndy of 4.") case-s. Atn j Stirg Pathol 1989: 13: 9. Kossatel S. Dolu-rtv 1',. Mvtrray 1',. Nettrotropic tnelanotrta. A variatit ol desmoplastie tiielanotna. .Arch fVrmatol 1987: 12:!: 9(17. 10. Wartict 'fl'CS. Hafez (JR. Fiticli Rf']. Btandcnhcrg J H . Seliwanu eell leatutes in iieurc)trci|)ie nu-lanoma. ) C:ulan Palhol 1981: 8: 177. 11. Wiek MR, Swanson VV.. Rocamora .A. Reccigniiion of nialittgtiatit tnclanotiia hy me)tie)cl()iial antil)e)dy HMB-4.''). An immunoliistoeliemical stnd\ of 200 iiarallhi-emhc-ddc-d entalu-ous tumors. I Cuiaii Pathol 1988: I.''): 201.
329
C u t a n e o u s maligtianf m e l a n o m a is a neoplasm c h a r a c t e r i z e d by \'arious pa((erns e)f gre)w(h, some e)f w h i e h are assoeiated with speeifie biologieal significance. The' raelial gi'e)wtli ]3hase represents a perie^d e)r cellular |:)re)liferation with ei^idercnal a n d papillary de'i'inal gi'e)wtli (1). MelaiU)mas in radial gre)W'lh are' pre)bably tillable to metastasize because ibcy lack the ability tc3 generate a mass (2). T h e vertical growth phase is eharaeterized by (time)r cells that proliferate to form a mass (nstially ne)dnle, occasionally |)lac|tie), with sc-eondary inliltration ol ihe- ele-rmis and de-e-p (isstie-s (2). M e l a n o m a s in vertical g r o w t h are ca|:)able ol vasetilar in\'asie)n and m e t a s t a s e s . 'The progne)sis of stage I m a l i g n a n t nu-la n o n i a ol the- skin d e p e n d s heavily on the vertieal g r o w t h phase (3,4), particularly on its thickness (3,,")). Netirofcopic n i e l a n o m a (6) is eharaeteri/.c-d by tume)r i^reilife-ration along peripheral nerves with tuniejr extension far form the p r i m a r y Iheus. This type
Abelardo Moreno, Isabel Espafiol, Vicens Romagosa Deparlmenf of Pathology. Hospifal Princeps d'Espanya. Barcelona, Spain.
Abelardo Moreno, Deparfment of Pafhology. Hospifal Princeps d'Espanya, Feixa Llarga s/n, 08907 L'Hospifalet, Barcelona. Spain. Accepted for publication ??
e)f t u m o r iiu'asion can be fe)lle)we-el by ee-iifral nerxoiis system in\'e)l\'eme-nt. In this |)aper, we repeirt two eases of m a l i g n a n t m e l a n o m a with a peculiar p a t t e r n of growth. 1( was eharaeferize-d by ftime)r eell in\'asie)n t)f fhe walls of small and iiu-ditim-sized xeiiis, widi s e c o n d a r y spread aleing the \'ein walls sexeral millimetres away lre)m the base of the t u m o r . T h e walls of the in\'eil\'e-d \'esse-ls appe-ared (hie-kc-iu-d and re|)lae'eel l)y m a l i g n a n l nu'lancima e'e'Us, whe-reas ciule)llu-lia re-mainc-d intaet.
Material and methods Case reports ('a.se I. \u !-)(l-year-e)ld m a n w a s referred te) t h e H o s p i t a l for t r e a t m e n t e)fa p i g m e n t e ' d t u m o r e)n his Ibrelu-ad. A presimi]:iti\'e elinieal eliagne)sis e)f l e n t i g o m a l i g n a ine-lane)ma w a s m a d e , a n d the- pafient tm-
Table I. Anfibodies and dilutions employed Anfibody
Type
Source
Dilution
Epifhelial membrane anfigen
Mouse monoclonal
Dako
1/50
Low weight keratin Cam 5.2
Mouse monoclonal
Becton-Dickinson
Predilufed
HMB-45
Mouse monoclonal
Enzo
1/1,400
S-fOO profein
Polyclonal
Dako
1/fOO
Vimenfin
Mouse monoclonal
Biogenax
Predilufed
Muscle actin
Mouse monoclonal
Enzo
1/100
Utex europaeus
Lecfin
Dako
1/100
325
Moreno et al.
I'ii;. I. Radial growth phase elemotistralitig atypical melanocytic proliferation along the dertno-epidcrmal juuetion anel dermal nielanophages (Case I).
de-rwent wide surgical excision of his lesion. Eive mejnths later, the patient was doing well, without evidenee of residual disease or metastases. Case 2. A 71-year-e)lcl woman with a pigmented maeule on her left heel that had been present for years required medical atten(ie)ii Ix-eause e)f bleeding fre)m her lesie)n. Physieal examination revealed an irregular, pigmented plaque, 1.8 X \ .5 em in size, surrounded by small satellite lesions. After a diagnostie biopsy, (he le'sie)n was siirgieally excised as were the left inguinal ne)des. Two years later, the patient presented with regional cutaneous metastases. When last seen, she had multiple eutaneous "in transit" papular and nodular metastases limited te) the- involved leg.
root sheatli of hair fbllieles. The de-rmis showed a sparse perivaseular lymplioeytic infiltrate with melanophages (Eig. 1). The eentral nodule was superfieally uleerated and eovered by a erust. 'The vertieal growth phase was eomposed of epithelie)icl and spindled melane)eytes with moderate nuelear atypia and 1 to 3 mitotic figures per high power field. Melanin was easily demonstrated within lumor eells and stromal melanophages. The maximal thickness was ,5.98 mm. At the base e)f the tumeur, the melanoma eells we-re spindle shaped and showed foei of perineural invasie)n (Eig. 2). Tlu- sugieal sample from ease 2 measured 5 X 4 em. The cutaneous surface showed a slightly raised, brown to blaek plaque, 1.8 X 1.5 em in size, that was surrounded by 0.1 te) 0.3-em satellite lesions. Mieroseopie examinatie^n sheiwed a malignant melanoma wifhe)ut radial gi'e)wth |:)hase. Small size "nevoeytie" me-lanoma eells invaded the deep retieular dermis. The maximal thiekness was 3.43 mm. Perineural invasie)n was fe)eally denu)nstrated. The satellites showed similar melanoma eells limited to the papillary dermis and laeking e-|)iderme)tro]:)isni. One of the reseete'd lymph nodes showed miere:)metastases.
Tumor samples
'Ehe surgieal speeimens were fixed in 10% buffered formalin, routinely proeessed, and e-mbedded in paraffin. Seetions were stained with H&E, Masson's triehrome, and stains lor elastic fibres. Immunohistoehemieal studies were perfbrmed e)n paraffin-embedded tissue. The antibodies and dilutions are listed in Table I. The avidin-biotin-peroxidase complex (ABC) procedure (7) was used. Results
The gross speeimen from ease 1 was a eutaneous ellipse, 2.5 X 2 em in maximal dimensiejn. The epidermal surfaee showed a pigmented maeule that oecupied an area measuring \ .5 X 1 cm. There was a central pigmented nc:)dtjle, 1.2 em in size. Mieroseopie examination revealed a radial growth phase melanoma with the distinetive features of lentigo maligna. The epidermis was atrophie. Atypieal s])indled melanoma eells proliferated in a lentiginous pattern along the basal eell layer of the dermoepidermal junetion and the e)uter 326
Fii;. 2. Pcritu-ural (Case 1).
invasion
by malignant
tiic-latioma
cells
Angiotropic melanoma
/•'/i;. 'i. A s t i i a l l s n h c i t t a t i e o n s x c ' i t i e x l n h t t i t i g p e r i v a s c e t l a r i t i \ a . s i o n h \ t n m o r cc-lls ( C a . s c 1 ) .
/'/if. 4. I ^ c - t a t l o l a t i i c d i u n i - s i / . c - c f \ ' e i n clc-j)ic t e d u i h L ^ u r e t i . 1 l u ' r e IS l ) u l k \ hut
replacc-nic'iit ol t h e s u i o o t h m u s c l e h y u i c l a i i o n i a
uiaiutaitianee of t h e endotiieliai .mcl acl\cutitial
cells
iiitc'i;rit\
(Case I).
Small and nu-ditim-sized ve-ins at the base- of both lesions showed invasion e)f their walls by (tinieir cells (Eig. 3). The eells showe-d nuide-rate \'ariatie)n in size and sha]:)e, and melanin pignu-ii( eeiiild e)eeasie)nally be de'nu)ns(rated. \'ase-iilar in\'t)l\'e-meiit was obvious and exte-nsive in Clase I but e)nly Ibeally pre-sent in Case 2. The inve)lve'cl \'essels had a distinetive appearance. Their walls were e)ccttpied by tume)r eells while the integrity of their endothelia was maintained (l'i,g 4). In small vesse-ls, ttmior inliltration was usually asse)eiate-d with partial oeelusiein e)f lumina, although immmiostaining with Ule.\ eti~ ropat'ti.s lectin c:onsistcn(ly demonstrated a spaced endothelial layer (Tig. 5). In nu-dium-sized xessels, there was partial or eomplefe desfruetion of fhe muscle eells and elastie fibres and replaeement by melanoma eells. Ttiinor eells did not penetrate fhe adventitia. The melaiu)nia cells ai)]:)eared to spread along vessel walls and eould be elemonsfrated several millimetres away fre)in the- base and lateral aspects ol fhe tume)r (T'ig. fi). In e)ne of the lymph nodes from Patient 2, a similar pattern of in\'asie)n was observed in a eapsular vein (Eig 7). Serial seetions denie)nstrated fbcal ne)clal inveilvement.
The- immunohisteieheinieal findings conlirmcd tluligln mieroscopic e)bse-r\'a(ions. .As noted a b e n e , tluintegrity of the endothclial layer was ce)nlirmcd by LUex europaeu.s lectin itiiinune)stainiiig. Anti-nuisdeactin antibexly was helpful in the demeinsfratie)n e)f musele eell effacement (Eig. 8). The nu-lanoma cc-lls were diffusely positixe- fbr S-100 ])i'e)(e-in, \'ime-nliii, a n d H M B - 4 5 a n d ne-g,i(i\'e for low molc-eiilar we-igh( k e r a d n s a n d e|)illie-lial membrane- antige-ii.
Discussion The- two cases re-pe)rted herein exliif)i(ed elistine'(i\'evasetilar involvement by m a l i g n a n t m e l a n o m a thai was e h a r a c t e r i z e d by t n m o r infil(ratie)n, proliferation, a n d s p r e a d within the walls of small a n d m e d i u m - s i z e d veins in the a b s e n c e e)f endothelial injury. Jain a n d Allen, in their p a p e r e)n desnioplastie m e l a n o m a (8), illnstratc-d circumferential invasion e)f ai'tei'ies, but llie iiu'olved vessels were' situated within the' tunuir. In e'e)ntrast, the- x a s e u l a r involvenu'nf in o u r eases extended for some distatu e from tlu- m a m e-e)ne'e'ntratie)n e)f ne-e)]:)lasm. The" te'rin
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'\
1
J Fig. 5. P a r t i a l l u m i u a l cieclttsiott citie t o t i i e l a n o m a eell infilt r a t i o n . tHex n m l x m i . ' , sin'in h i g h l i g h t s t h e s p a r e d e n d c j t e l i a l cells (Case 1).
/'\^'. 6. Involved hlood vessels located in (he suhcutancous tis.sue.s, separated Irom the vertical nfowlli phase hy uiiiuvolved fat (Case 1).
Fig. 7. Involved vein in the vicinity of the capsule of a re-frional lytnph node (Case 2).
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Angiotropic melanoma /•'/.!;. H. I'cical sparing of muscle lihres as shown hy imniunostainitig for inuscle actit) (Ciasc 2).
"angiod'opie" seems appro]:)ria(e- Ibr (he Ie-siems we describe. Neui-o(re)|)ic melaiie)ma has a ])c-culiar (ro|Dism for perij:)heral cu(aneous nerves (6,9) and may proliferate along them. Inve)lvenu-nt of the central nervous syste-in may be- re-la(e-el (o inlraneural e)r pe-rine-ural extension (6). Tlowever, the patlicjgenesis of these two forms of troj^ism, neural and vascular, is probably ejtiite dilfe-re-ii(. In ncurotreipic mclaneima, thc melane)ma cells a|)pear to aeejuire pre)perties of Schwann cells (10). Spread ale)ng nerves and the tendeney te) Ibrm iu-rve--like structures may lluis reflect partial transformation of the melaneima cells, themselves. On the othe-r hand, the angiotro|:)ic melanomas described here- were- "common" melane)nias, with the- exee]:)tiejii of the-ir unique pattern of vasctilar wall invasie)n. We were- unable to demonstrate e-vidence of e-iulothelial e)r museular dilTerentia(ie)n, either with light microscopy e)r immtmohis(c)chemis(ry. Me)re-o\'e-r, (he results of our immuneistaining were- consistent with the)se of malignant melaiuinia (11). It could be speetilated that the vaseular wall repre-se-nts a locu.s miiiori.s
ic.si.slentiae
along whieh
limite-d
progressiein of t u m o r cells is lave)red. It is alse) ])ossible- (ha( |)e'i'ine-ural inxasion (focaify preseiu in o u r (wo cases) could have inllueneed the growth of tume:)r ce-lls via the- vasa n e r v o r u m . l'\irtlu-r study e)f similar cases will be required to better u n d e r s t a n d the |:)athe)genesis a n d biologic significance- of (his distinctive p a t t e r n of vascular invasioti.
References 1. Clark W l l . folhcrg R. .Xiuswcit th . \ M . I'mnor pi'cigi cssioti iu primal') human cnlaiu-ous m.ihgiiant melanoma In: Clark W H . Coldman I.I. Mastratigelo MJ c-ds. Human malignaut uu-lanoma. Nc-xv \ork: (iiuiic- & .Siiatlon, 1979. 2. l'',lde-r Df',, Cucrrv I). I'.pstciti MN. et al. Iinasivc malignatit melanomas lacking eompc-lence for metastasis. Am | Derniatc)i)atlic)l 1984: ()(Snppl I): :').'). 3. fjalch C M . .Soong S-J, .Shaw HM. Milton (iW. Ati analysis ol prognostic factors in 4000 patients with c utaiieous melanoma. In: Baich C M . Miltoti (;\V. c-ds. Malignant niclanon)a. C:iiiiieal manage iiic-ut and ticMtuic-nt rc-sults worldwide-. Philadc-lphia: j . B. Iappinccill, 198.'). I. McKic RM. \'c>uiig 1). Human malignanl melanoma, lnt ) Dermatol 1984: 23: 433. 5. Wc-isstnatm A. Roses DF, Harris MN. Duhin .N. Prcdiclion ol Kinpli node metastasc-s from the liislologic features of prtmary hnman malignatit melanomas. .Am j Dermatopalhol 1984: (i(Snppl I): •^5. (). Reed RJ, l.c-onard DI). Neurcitropic tiielanoma: a xarianl of desmoplaslie tiu-latuima. Am j Surg Pathol 1979: 3: 301. 7. Hstt SN. Raitie I,. Kanger 11. 'flu- use of avidin-hiotitiperoxidase complc-x (.ABC) and uulabellc-d aiitihod\ (P.AP). J Histochem Cytochctii 1981: 29: 511. 8. Jain S, .Alleu WP. nesmoplastic malignant nielanoma and ils variatits. A slndy of 4.") case-s. Atn j Stirg Pathol 1989: 13: 9. Kossatel S. Dolu-rtv 1',. Mvtrray 1',. Nettrotropic tnelanotrta. A variatit ol desmoplastie tiielanotna. .Arch fVrmatol 1987: 12:!: 9(17. 10. Wartict 'fl'CS. Hafez (JR. Fiticli Rf']. Btandcnhcrg J H . Seliwanu eell leatutes in iieurc)trci|)ie nu-lanoma. ) C:ulan Palhol 1981: 8: 177. 11. Wiek MR, Swanson VV.. Rocamora .A. Reccigniiion of nialittgtiatit tnclanotiia hy me)tie)cl()iial antil)e)dy HMB-4.''). An immunoliistoeliemical stnd\ of 200 iiarallhi-emhc-ddc-d entalu-ous tumors. I Cuiaii Pathol 1988: I.''): 201.
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