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T umors imp lan ted in to the cen ter of a rabb it co rnea mayrem a in avascu lar for up to mon ths. T um or imp lan ts on the chorioallan to icmembr a ne of the ch ick emb ryorem a in avascu lar for app rox ima te ly hou rs even when thetum or has beenplaced FX1 contiguous to vessels of the chorioallan to icmembr ane. Beyond th at size and up to mmdiame te r, all tumo rs we re vascu larized.On occas ion, a solidtum or is found to be avascu lar at a largerdiame te r.F or ex amp le, an ast rocy toma grow ing subcu taneous ly in therat did not become vascu lar ized until itre a ch ed app rox ima te ly mm. The re a re also some clinical examp les of the avascu lar pha se.C arcin oma in situ of the cervix, superficial cu ta neousmelanom a s, and mult ip le tiny peri toneal imp lan ts of ovariancarc inoma a re occas ionallydiscovered before they have become vascu larized.F or examp le, in the chorioallan to icmembr a ne of the ch ick emb ryo, new capil lar iespenetrated a tumor graft wi th in about hours, andci rcu lation was first es tab lished by thistime.F or tumo rs imp lan ted on the iris of the an terior ch amb er of the rabb it eye, vascu larization oc curr ed at to days cinoma imp lan ted in the rabb it co rnea, to weeks we re requir ed, depend ing on thedis tance of the imp lant from thelimbus.In most systems it appea rs th at once capil lar ies have penetrated thetum or sphe ro id, rap idtum orgrow th begins wi th in the subsequent hours.In some an imal mode ls this rap idgrow th continues at an Citrulline exponential ra te, during wh ich thetum or may en la rge up to times its or ig inal vo lume during a week period. Where capil lar iespenetra te the tum or periphe ry, tum or cells unde rgo ing mitosis a re seen on histologic section to cluster in a cylindr ical configuration a round each capil lary, sug gesting th at max imal tum orgrow th occu rs close to a capil lary unit.Central necros is of the avascu lar tum or di sappears, and, for atime, the en larg ingtum or appea rs healthy th roughou t.C entr al necros is oftenre appea rs when the vascu lar ized tum or reaches adiame ter of app roxi sureswi th in the cen ter of thetum or exceed those at the periphe ry, comp ress ing vessels in the cen ter of thetum or. F or the rema in ing life of the neop lasm, the re is a histologicpattern of a periphe ral or ex te rnal shell of proli fe rating tum or cells surround ed by in tenseneo vascu larization, while vascu lar obst ruction and necros is continue deep inside thetumor.Thu s, after thegrow th spu rt that follows vascu larization, the ra te of tum or grow thdim in ishes with further inc rease in size.Howeve r, in our co rnea experimen ts whe re there we re no lymphatics at thetime oftum or imp lan tation, lymphatics did not appear until after tumo rshad become well vascu larized.Some of these malignantpropert ies may ac tually depend on thepresence of new vessels in the tumo r.Although the re is littledi rect evidence for this idea, wemightmake the following specu lations.

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