Oral granular-cell tumors

Oral granular-cell tumors

Oral granular-cell tumors Report of twenty-five electron microscopy cases with Arthur S. Miller, D.D.S., X.S.D.,* Crrlci~ Leifer, D.D.S., Sow-I’eh ...

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Oral granular-cell tumors Report of twenty-five electron microscopy



Arthur S. Miller, D.D.S., X.S.D.,* Crrlci~ Leifer, D.D.S., Sow-I’eh C’he)l, H.U.D., Ph.D.,“** and Robert D. Harwick, Philadelphia, Pa. TEhIl’LF,






Ph.D.,**” X.D.,“““*


Twenty-five eases of granular-cell tumor of the oral cavity are reported. The clinical findings are similar to previously published data. Of five cases studied by electron microscopy, three were processed directly from fresh surgical specimens and two cases were processrd following initial formnlin fixation. The granules for the most part are morphologically compatible with lysosomes except for :I single variety con tnining viruslike particles. Thtare is increasing eridrncc in support of a neural origin, but the indications are that more than one cell type may bt, the progenitor of granular cells of the granular cell tumor.


he granular-cell tumor (granular-cell myoblastoma) is a benign lesion, the histogencsis of which is still poorly understood and somewhat controversial. \Yhethcr the lesion is rcactire or nroplastic remains to he tletcrmincd. The lesions occur in varied parts of the body, hut the oral cavity, particularlythe tongue, appars to hc the most common location. Although it has been reportctl that thcrc is no tliffcrcncc in the incidence of owurrcnw twtween males and females,*. ? thwr is increasing evitlcncc of a female pretliloction. 3* a It is also of interest that lesions identical to the granular-cell myol)lastoma have hccn rcprted in the horse and dog.5~ Ii Thta purpose of this article is to report twenty-fire cases of oral granular-cell tumors accessioned from 1969 to 1976 and to describe the ultrastruvtural frat.urcs of this lesion. This study was supported Institute, National Institutes *Professor of Pathology, ‘.*Associatr Professor of ***Assistant Professor of ****Clinical Professor of

in part 1)y Grant T1208144-08 of Health, Bethesda, Mtl. School of Dentistry. Pathology, School of Dentistry. Pathology, School of Dentistry. Surgery, Sr~hool of Medicine.





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Right anteroventral surface of tongue Right dorsolateral surface of tongue Right lateral border of tongue Dorsurn of tongue Left lateral border of tongue Right floor of mouth Left tonsillar pillar Lo\rer lip ,\nterior tongue Lipper lip Right lateral border ol tongue Junction of hard/soft palate Left lateral border of tongue Left lateral border of tongue Right lateral border of tongue Ventral burpace of tongue Left lateral border of tongue Kight floor of mouth 1Left lateral border of tongue Ventral surface of tongue Right commissure Left lateral border of tongue Right lateral border of tongue Right anteroventral surface of tongue Right buccal mucosa

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I. Case 9. Granular-call lesion on anterior tongue (trrrowsj. 8. Cnsr 15. X:lisd, nonulcer:ttfd lesion on right latclral horde .I. Cast 21. Raised, nonu1cer:~tw.l lesion on right commisswe

of tongw. of lip (arrow).

hufYcr ant1 dehydrated througll an ethyl alcohol srries. The dchylrated tissues were infiltrated with a 1 :1 mixture of Epon-Araltlitc and propylene oxide and ~~hc~ltlcd in Epon-Aralditc (Slollenhauer) .; Two biops!- spccimcns which had hrcn rcwived in 10 per cent phosphate-hu~eretl formalin were washed overnight with 0.08 AI sodium cacoclylate buffer ilt pH 7.2, mincrcl into dws of 1 mm.:‘, ancl post-fixed for 1 hour in 1 per writ osmium tctroxiclc huffcretl with 0.05 JI sodium cacotlylate at pH 7: 1. Specimens wew tlehytlratctl through graded ethanol aIltl cmheddetl in 15poii 812. Thin sections were preparccl on c’ol)pc’r grids, st,ained with uranyl acetate and leatl eitrat,e, and cxaminetl with u Philips EN300 electron miwwscope. Thick KIwii-;1raltlite swtions w’crc stainctl with 1 pc’r’ writ mrtliylciic hlue for liglitmkroscwpie examination. RESULTS Clinical


8ixtcen of twenty-five patients (61 per cent) were female (Table I). Seventeen of’ twcntp-fin: Icsions (68 per cent) were located on the tongue. Other loca-



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w\.rrittg cpitheliunt, granular wlls wcrc itttimatcly atljaccttt to cpithelial ~11s with no separation by collagen fibers. (‘ptoplastnic proccsscs of basal cells of the c~pitheliutn protruded into thr granular-w11 region without an apparent c’ontt(w tivo tissue condensation. Electron


(iroups of granular cells were surrounded by basal lamina which frequentl;l showvcti twluplicatioti resultin g in multilaycritig. The cells were generally- ovoid or polyhedral (Fig. 1). The nuclei wcrc owi(l, although frequently- indented, apparently caused by compression of e,vtoplasmic granules. The c~ltromatin was tlispCtwc1, iJlltl a moderately large nucleolus was frequently observed. The cytoplasm rontained varying numbers of mitochottdria, free ribosomcs, twugli cndoplasntic~ reticulum, and c~ytoplastttic~ filaments. A (iolgi complex was sometimes observed. Tltv caltara&ristic* cytoplastttic~ granules wcw trtoderatcl~ large, and many WPW larger than tnitochondria (Fig. 5). In some instances, the, granules comprtwcd other cyvtoplasmic structurw. Although the concentration of granules varied from cell to cell, several distinctive types of granules were consistently itlcntifietl in thv five cases studied : (1 ) lysosomc-like sttwturcs compatible with













1~ul~lishcv.lfindings.:‘. 4 The fcmalc I)rcdilection in our series was similar to that of Tha\vl(~~~ant1 Ogura.’ Thr tlistrilmtion OFlesions within the oral ravity was also similar to tlic tlistril)ution rcportctl 1~ others ; the tonguc~ was tlic most common lwatioil. Slany i~ttcnll)ts ha\-c been tllatlc to clcterminc~the histogcwcsis of the granular culls. Rtywrtctl possihilitics inclntl(~ striwtcxtl and smooth muscle origin, peripheral

Fig. 9. Granular tures (A’s) containing yranulnr cell.

cells and axonlike structures. cytoplnsmic~ filaments and

(Magnification, microtubules


~14,400.) partiallp

Axonlike enclorrtl

strucby a

Favowd a degenerated perineural fibroblastic origin. Pour and associateslR reportr>cl granular cells in two cases of plexiform neuroma and interpreted them as tlcgctlcrativc alterations of Schwann cells. Our investigations showed that cytoplnsmic processes, similar to neuritcs, wre somctimcs observed to be surrounded by ;I. single granular ccl1 (Fig. 9). 111other areas, segmentation of cytoplasm by tlcq) in\-aginations of plasma membrane resembled the infolding of the plasma m~~ml~ranc of Schwann cells ( F’ig. 5). The desmosomal junctions bctwcen granular wlls (Fig. 5) is indicative of cctodcrmal origin of these cells. Thr ultrastrncturc of tliv q?oplasmic granules has been inwstigatctl bcforl,,‘.“, 1:;. 1;1.,‘(-2” \\‘ith the exception of the viruslike particles the tlcscriptions of of’ Iysosomc~s \-arious stages. 1110 prallulcs iire cwnsistcnt with tlic aplwaranw Scvc>txl authors, invludinp Sobel ant1 (Jhurg,” Clarstcns,!’ Sobel ant1 associates,” an(l (‘aput and associatcs,ll have noted three clistinct types of granule. In the J”‘cStWt study, four t>-pes of grallule wcrc consistently itientificd. Three wwc illtwpwt (‘(1 as lysosomal structures in different phases. d fourth was an aggreKate of viruslike particlw. ()ur results intlicate that the granules are, for the most part. l~sosomcs. Th(~ autophagic ~~uolcs, myclin figures, and oval dense botlic3 \\-ith cwcntricall~located vacuoles are characteristic stages of lysosomal I,umsdcn lo have noted, the granules represent dif(Icgradation. As Aparacio illld I’t~rcwt c>\-olntionary stages of the same entity (lysosomcs). The presence of acid ilt


4. 5. Ii. 7. 8. 9. 10. Il. 12. 1::. 14. 1.3. 16. Ii. IS. 10. 20. PI.

of Oral Pnthology, l,ll. 3, Shafrr, IV. Cr., Hint,, M. K., aud Lwy, B. M. : A Trxtl~ook Pt’hil:cdelphia, lRi4, \V. H. Saunders Company, pp. 182-183. J. R. : Multiple Granular Ccl1 Myohlastonms Pnl)ngc’orgiou, H., Litt, J. Z., and Pomcranz, in (‘hildren, Arch. Dt~rmatol. 96: 168-l il, 1967. (:oll~crg, J. E. : Granular Cell Myol)lastoma, Hurg. Obstet. Gynwol. 115: 205213, 1062. ‘I’h:~wley, 8. E., and Ogura, J. H. : Granular Cell Mpohlastoma of the Head and N(vk, South hltvl. .J. 67: 1020- 1024, 1974. Misdorp, IV., and Nauta-van Gc~ltlvr, 11. I,.: Granular-Cc,11 Myol)lastonw in the Horsr~. R(armri of Four Casw. Patliol. \‘vt. 5: 3X5-394. 1968. i;ilw, R. C‘., Montjiomrry, C. A., and Izvn, i.: Caninrl Lingual Granular Cc,11 Myol~lnstoma: A\ (“ant’ R(>port, ,11n. 1. V’clt. Kw. 35: 135i-1359, 1974. Kvsill Emlwdtling Mt~thods, .J. Hiophys. Biochcm. I,uft, J. 11.: lmprowments in Epoxy Cytol. 9: 404.419, 1961. Solwl, H. J., ant1 Churg, ,I.: Granular Cells an(l Granular (‘(>I1 Lcsiorrs, lYrch. Pattlol. 77: 1X-141, 1964. (‘arstcns, P. H. H.: LVrastruc’tnrv 01’ Granular Cell Myot~lastorna, Acta Pathol. Microlliol. Bcand. 78-A: 6X5-694, 1970. Sol,el, H. J., Marcluet, E., Avrirr, E., and Svhwarz, R. : Granular Cell Jlyolbtomn: An Elwtron Micvroscopic and Cytochc~mical Study 1 llustratinp thcl Gvnwis of Granules ant1 Aging of M~oblastomn Cells, ;hn. .J. Pnthol. 65: 59-78, 1971. Caputo, R., Bcllonr, 11. G., and Tagliavine, R.: Ultrastructure of the Granular Cell JIyom l~lwtomn : So-called Abrikossoff’s Tumor. Arch. Dermatol. Forsch. 242: 127-136. 1972. ITaiskcn, W., and Langw, E. : I)iv sulxnikroskopischr Strurtur des sogenannten ifyohlastwnryorns, Frankfurter Z. Pathol. 71: 600-616, 1962. 8olwi, H.’ J’., Mnrquet, E., and Hchwarz, H.‘: Ts Schn-annoma Related‘ to Granular Cell M~ol~lastoma? ilrch. Pathol. 95: 396-401, 1973. I’wrw, d. G. : Histogenrsis of Granular Cell Myot)lastoma, 1. Pathol. Hacteriol. 62: 351. -36“i. 1950. I (‘oo&r, P. II., and Goodman, M. I).: Multilayering of the Capillary Basal Lamina in the Granular Cell Tumor: d Marker of Cellular Injury. Hum. Pathol. 5: 327-338. 19i4. (“hCI1. S.-Y. : Adenoid Cvstic Carcinoma of h&n&: Salirarv Gland: Histoehemical ant1 El(,c.t’ron-hlic.ro~~~,l~i(, Stu&s of Cystlike Spaces, ORAL fiVRG: 42: 606-621, 1976. 1~‘rithiof. I~.: Ultrastrwtuw of the Basemolt Mrmbranc, in Normal and Hvuerulnxtic Human Oral E;r)ithrliuni Cornmired Wit11 That in Prrinrnsivc and Invasive Carcinoma. Acta I’atllol. MivrLl,iol. Rupp. 260: 3-25, 1969. Pour, I’.. ~Ylthoff. J., and Cardew, .I.: Granular Cells in Tumors ant1 in Eon-tumorous Tissue, lirvll. Patiio1.‘95: I:%-138, 19i3. .1paracio, R. R., and Lumsdcn, (1. E. : Lightand Electron-Microscopic Studies on the Granular Cvll Myol~lastomn of tlw Tongue, J. Pathol. 97: 3339-355, 1969. Moscovic~, 1:. A., and Azar, II. d.: Multiple Granular Cell Tumors (“Myohlastomas”) : A Cnw Kcport \Vith Electron Mivroscol,i~ Olw%rvations and Rrvicw of the Literature, Cancer 20. .- “03‘‘-904i kI 1967. Fiwher, E. Hi, and \Vechsler, IT. : Granular Cell Myol~lastoma--h Misnomer Electron Mir~rowopic Evidrnw Conwrning Its Rchwann Cell 1)erivntion and Natuw (Granular Ccl1 Schrwnnoma), Caner 15: 936954, 1962. \Vhittvn. J. Ii.. Jr.: The Finch Structure of an Intraoral Granular-WI Mvohlastoma, ORAL Sr-RC:. 26: “0%‘~ a<,I ? 1968 . Sotwl, II. J., Arrin. E.. Marauc,t. E., aud Sclrwars. R.: Rclac’tiw (iranular Cells in Sitw of ‘I’rxurn:~, Am. .J. Cli;,. f;:rthol.~61: 223.234, 1974. ‘l’horcw, L. : On Nature and Pathogenesis of Ho-call(vl r\l)rikossoft’ Tumor, Ups. Lak. Forh. 55:



hlin, H. TX., Miller, A. S., Leifcr, C., ant1 l’utoug, l’.: Basal Gland, i\wh. Otolaryngol. 99: 88-93, 1974. \\vcnisc,r, G. and [email protected], &%.: Elcktrolirll-optia~tl~ Untersuchung iiircw N~wrorns. Vircahows 1\wh. [Pathol. hnat.] 358: I!lR-204, Ecprint



Dr. .2rthur S. Miller ‘Temple l_‘nirersitp Hcl~ool 33223 North Broad St. Phil:rdell~l~in, Pa. 19140

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0x11 Atlcnorna cur Histogenrsr 1973.

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