General Microscopic Changes
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1 Generl Microscopic Chnges 2 This chpter covers collection of microscopic chnges tht lck dignostic specificity ut occur in different specific diseses, s will ecome pprent in susequent chpters. Almost ll of these chnges re responses to injury, generlly involving the squmous epithelium nd the lmin propri. Fig. 2.1 Ppillomtosis, sl cell hyperplsi, nd spongiosis. ( ) In contrst to norml squmous mucos in which the ppille of lmin propri re limited to the sl fifth, in this squmous epithelium the ppille extend close to the surfce. Ech of these ppille is surrounded y severl lyers of sl cells; in other words, there is n expnsion of the prolifertive zone, lso known s sl cell hyperplsi, which is common rection to injury in ll squmous surfces including oth skin nd mucous memrnes. Since the most common injury to the squmous esophgus is gstroesophgel reflux, chnces re tht reflux is the culprit whenever this is found in distl esophgel iopsy. Infections nd direct toxic injury produce the sme response, however, so it lcks specificity. ( ) This is more dvnced exmple with much longer ppille tht extend nerly three qurters or more of the wy to the surfce. The lyers of sl cells round the ppille re thicker. In ddition, the sl cells nd squmous cells re seprted so intercellulr ridges re esily seen. This is the result of intrepithelil edem or spongiosis. In the esophgus, it is lso referred to s dilted intercellulr spces S.R. Owens, H.D. Appelmn, Atls of Esophgus nd Stomch Pthology, Atls of Antomic Pthology, DOI / _2, Springer Science+Business Medi New York
2 12 2 Generl Microscopic Chnges Fig. 2.2 Acute ppillry hemorrhge. All the firovsculr ppille tht extend into the squmous epithelium from the lmin propri re filled with extrvsted lood ( ie, cute hemorrhge). This my e due to trum from the iopsy procedure ut in some cses it my e due to in vivo injuries, reflux eing one. In fct, in the pst, it ws touted s one of the chrcteristic reflux-ssocited chnges Fig. 2.3 Blloon cell chnge. Within the squmous epithelium, severl cells hve no nuclei ut insted hve lrge smooth proteinceous inclusions filling the cytoplsm referred to s lloon cell chnge. This is response to surfce injury in squmous mucose in different sites, nd, in the esophgus, the most common injury inducing this chnge is reflux. The inclusions re plsm proteins nd fluid tht presumly hve leked into dmged squmous cells Fig. 2.5 Generic ulcer ed. There is no epithelium on the surfce. Insted, the mucos consists entirely of lmin propri, which contins smll vessels with hypertrophied endothelil cells, proly cpillries nd venules. The lmin propri lso contins spindle cells, presumly myofirolsts, nd scttered inflmmtory cells including polymorphonucler leukocytes (PMNs). On the surfce re few strnds of firin mixed with some of these spindle cells, evidence of orgniztion. This is the ed of n cute superficil ulcer. It lcks chronicity chnges, such s plsm cells. The chnges hve no specificity in terms of defining the injury tht cused the ulcer. Most of these re in the distl esophgus where reflux is y fr the most common cuse Fig. 2.4 Generic cute inflmmtion with microscesses. ( ) In this field, there is row of tiny scesses, lso known s microscesses, in the superficil squmous epithelium. Below this row, the squmous cells pper reltively norml. ( ) This is more intense vrint with lrger intrepithelil scesses. This pttern of cute injury usully leds to serch of the slide for n infectious cuse, the most common eing Cndid. However, ll too often, no cuse is found. In fct, in mny cses, cuse my never e identified. We hve seen couple of cses of pillinduced injury with similr cute inflmmtion. We hve virtully no follow-up iopsies to give us clue s to the nturl history of these chnges
3 2 Generl Microscopic Chnges 13 c d Fig. 2.6 Hypertrophied myofirolsts in the ed of n ulcer (ulcerocytes). ( ) This is the se of n ulcer with prongs of regenerting squmous cells t the surfce. There re numerous lrge plump spindle cells with lrge, hyperchromtic, nd pleomorphic nuclei in the ulcer ed. ( ) At high power, the nucler chnges re striking nd the resemlnce of these cells to some kind of spindle cell mlignncy is ovious. ( c ) With the kertin stin, the cells re negtive wheres the prongs of primitive squmous cells t the ulcer edge re strongly positive. ( d ) In contrst, in the Vimentin stin, the spindle cells re strongly nd diffusely positive. These cells hve the ultrstructurl fetures of myofirolsts nd firolsts. We refer to them s ulcerocytes. For some odd reson, they re more common in the se of esophgel ulcers thn nywhere else in the gut. Becuse the pleomorphism mkes them look like type of spindle cell mlignncy, they re rel dignostic pitfll. We emphsize tht these cells should never e clled mlignnt
4 14 2 Generl Microscopic Chnges Fig. 2.7 Heling ulcer in squmous mucos. Extending from the thin squmous mucos with lrge hyperchromtic nuclei nd little cytoplsm on the left, thinner lyer of squmous cells grows eneth some exudte on the right. Becuse this is typicl of chnges in squmous mucos right t the edges of ulcers of ll cuses, this hs no specificity other thn to identify the iopsy site s n ulcer edge. The next step in ulcer heling is the extension of the long squmous prongs from this regenerting lyer of squmous cells into the strom. Such prongs re in Fig. 2.8 Fig. 2.8 Ulcer edge chnges in squmous mucos. ( ) This mucos hs thin lyer of superficil squmous cells from the se of which project prongs of drk squmous cells which project into the hypervsculr lmin propri lmost to the inner fiers of the musculris mucose. We refer to this loclly s long-prong disese. ( ) In the higher-power imge, the cells in these prongs hve high N:C rtio nd frequent mitoses. There is little cytoplsmic differentition, ut there is some spongiosis towrd the top. This pttern of regenertion is typicl of wht hppens t the edges nd eventully t the ses of ulcers in squmous mucose. With time, these prongs ecome thicker nd more differentited nd the superficil lyer lso ecomes thicker, thus reconstituting the norml squmous epithelium
5 2 Generl Microscopic Chnges 15 Fig. 2.9 Florid ulcer edge chnges, mimicking squmous cell crcinom. ( ), In this exmple, the prongs of regenerting squmous epithelium re very long nd thin, nd they hve extensive interconnections. ( ), At higher mgnifiction, the poor differentition of the cells in these prongs is evident. There is considerle nucler pleomorphism nd mny nuclei hve prominent nuclei. Mitoses re lso present. Becuse of the complex rchitecture nd the primitive ppernce to the cells, it my e tempting to dignose this s squmous cell crcinom. It is siclly form of pseudoepitheliomtous hyperplsi Fig Mturing ulcer edge chnges. In comprison with Figs. 2.8 nd 2.9, the superficil lyers of squmous cells nd sl prongs re thicker nd the squmous cells re more mture. This squmous epithelium is much closer to norml
6 16 2 Generl Microscopic Chnges Fig Long prong nd ulcerocytes in single iopsy, gret tempttion for mlignnt dignosis. ( ), From the thinned surfce, the typicl long prongs of regenerting primitive squmous epithelium extend into the lmin propri, which contins mny typicl stroml cells with typicl nuclei chrcteristic of the weird myofirolsts in ulcer eds descried in Fig ( ) This cn e seen in etter detil in higher mgnifiction. Bsed on these chnges, one must resist the tempttion to cll this spindle cell squmous crcinom when it is nothing more thn the edge of n ulcer in the squmous esophgus Fig Kertinizing surfce epithelil metplsi, lso referred to s hyperkertosis. The norml esophgus hs no grnulr lyer or surfce kertin; ecuse oth re present in these imges, the epithelium resemles hyperkertotic epidermis. The cuse is not well defined ut presumly is response to surfce injury. Surprisingly, there is very little pulished informtion out this chnge, either in the literture or in the textooks. Yet, in usy iopsy service, this ppers periodiclly. Sometimes the endoscopist will recognize it s white re or plque Fig Atypicl regenertive chnges in squmous epithelium with multinucletion nd nucler pleomorphism. This is hyperplstic squmous epithelium t the edge of n ulcer. Mny of the nuclei in the deeper cells re enlrged nd hyperchromtic. Towrd the right, there is collection of such cells with more pleomorphic nuclei, nd some of these cells re even multinucleted. This is well-recognized pttern of squmous repir or regenertion tht cn e seen in numer of situtions including following rdition or fter the use of severl drugs tht re toxic for esophgel squmous epithelium. The key in seprting this pttern from squmous dysplsi is tht this epithelium mtures normlly. Further, the cells with the typicl nuclei hve undnt cytoplsm, so lthough it looks frighteningly izrre there is little chnge in the N:C rtio
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