Vet. Pathol./ 5: 725-73\ (1978)

Granular Cell Variants in a Rat Schwannoma

Evidence of Neurogenic Origin of Granular Cell Tumor (M yoblastoma)

J . J . BERMAI', J . M. RICE and J . STRANDB ERG

Experimenta l Pathology Branch, National Ca ncer Institu te, Bethesda, Md .: and Department of Pathology and Division of Co m pa rative Medicine, Johns Hopkins University, Baltimore , Md .

Abstra ct. A large , intraabd om ina l rat schwa nno ma had numerou s gra nule-co nta ining cell s cytologically identical to cell s of granular cell tumor (myo blasto ma) . The sma ll eosin ophilic granules sta ined positively by the peri odi c ac id-Schiff (P AS) reaction , with intensity not reduced by diastase pretreatment. G ra nu les stained positi vely with the Tibor Pap silver impregnation for reticulin and by electron microscop y were ident ical to myoblastoma cell granules. The nuclei of granular cells were morphologically identical to those of the neoplastic Schwann cells . T he granu lar cells were in numerous foci within the tumor, freq uently were seen in mitosis, and possessed an extremely variable volume of cytoplasm . They seemed to evolve from neoplastic Schwarm cell s. Cells with onl y a nar row perinuclear rim of granu lar cytoplasm were of the sa me size and general co nfigur a tio n as adj ac ent neoplastic Schwarm cells, while ce lls with increasing volumes of gra nula r cyto plas m were increasingly swollen and round . One a rea of the tumor was composed almos t en tirely of suc h lar ge cell s a nd was histologically identical to cla ssic granular cell tum or.

The cytogenesis of granular cell tumor ("myoblastoma") has been a subject of controversy since the description of this neoplasm in 1926 [I ]. Abrikossoffs original descriptions were of tumors of the tongue, the cells of which in some growths seemed to show transitions to muscle fibers. The lack of resemblance of the granular cells to true myoblasts, however , and the occurrence of similar tumors at extralingual sites devoid of muscle, caused the myogen ou s origin of granular cell tumor to be challenged as early as 1937 [5]. A neuroectodermal or igin for gr anular tumors in man currently is favored by several line s of evidence [3, 6,14-1 6]. A case of human schwannoma has been reported in which granule-containing cells rese mbling th ose seen in myoblastoma were visible by electro n microscopy [15]. In that ca se, no granular cells could be distinguished by light microscopy, and hence, no granular cell variants typical of those seen by light microscopy in myoblastoma were identified. Small granular cell tumors may originate in , or adjacent to , the perineurium of nerves, particularly in the intestinal serosa, or from a myenteric plexus of the colon 725 Downloaded from vet.sagepub.com at GEORGIAN COURT UNIV on May 3, 2015

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[6]. O ne such tumo r has been reported to have a histologic patt ern suggestive of tra nsition to neurofibroma [6]. T he lite rature, however, conta ins no description of a typica l granu lar cell tumor arisi ng in and appa rently derived from anoth er tum or of unequivocal neuroectoderm al origin. We presen t a schwa nno ma ind uced in an F344 rat by the poten t ca rcinogen met hy l(ace toxymethy l)nitrosamine (DMN -OAc), whic h conta ined Anto ni type A and type B tissue ty pica l of schwanno ma as well as numero us gra n ular cells identical cytologically an d histochemically by light an d electron microscop y to " myoblastorna" cells. Materials and Met hods T he tu mor specime n was o bta ine d fro m o ne of a group o f 30 fema le F344 rat s trea ted wit h 0.095 m illim oles DMN-OAc/kg bod y weigh t in p H 5.5 ph osph ate bu ffer, adm in istere d as a single intraperito nea l injec tion when the rat was 5 week s o ld . The rat was cage d o n co rnco b bedd ing, ha d unlimited access to Pur ina La bo rato ry C how® a nd tap wat e r. an d received no fu rt her treatm en t. Eleve n mont hs after treatment it was kill ed wh en sig ns of an intraa bdom inal mass were noted. The rat was necro psied an d a ll tissues fixed in 4% aq ueous forma lde hy de . Parts of tissue s were embedded in paraffin for ligh t m icroscopy a nd sect ion s stained wit h hem atoxylin and eosin ( HE ), by the pe riodic acid-Sc hiff (PAS) procedure with and wit hout diastase pretreatment, and by a modified Tibor Pa p silver imp regnatio n [101 for reticulin. Tissues (5 m rn") fixed in formali n were was hed overnight in Sorenson 's phosp ha te buffe r (0.2 mo l/ I, pH 7.2). Tissues we re cu t into cu bes ( I mm "), fixed in 2% gl utara lde hy de , was hed in ph osphat e buffer wit h 0.2 mol/l sucrose, a nd then fixed in M illonig's ph osphat e buffered OsO .. with glucose (pl-l, 7.3). T he frag me nts we re th en deh yd rat ed in gra de d a lco ho ls and em be dded in Spurr low viscosity em bed d ing medium [171 . Bloc ks were sectioned o n an ult rami cro tom e with a d ia mo nd knife. Section s wer e stai ned with Reyno lds lead citra te [11] a nd 2% aqueous ur an yl ace ta te an d viewed on a n e lectro n mtcroscope.

Results

At necropsy, the ra t was fou nd to have a large mass 2 centime ters d ia meter attached to and apparently arising fro m the uterine serosa a nd filling the lower a bdo minal cavi ty. By light microscop y th is tum o r contai ned areas of typ ical Antoni type A and type B tissue characteristic of schwannom a, as well as a peric ellul ar retic ulin netw ork typical of well-d ifferentiated schwa nnom a. T he type B tissue contained many cysts lined by tumor cells, (fig. I) which are typi cal of che mica lly ind uced schwa nno mas (ne ur ino mas) in the rat [19, 21]. Most of thi s tum or was identical by ligh t microscop y to schwa nno mas ind uced in rat s by alkylnitrosoureas [19, 21]. Treatment of rats with 0.095 millimo les/ kg DM N-O Ac int rap er iton eall y is known to pro d uce schwannomas arising from the serosa l nerves of intraa bdo mina l organs [8], Ma ny nests of cells filled with fine eosi no philic cytopl asmi c gra nules identica l to the cells of myobl astom a were identified (fig. I, 2). T hese nests were seen throu ghout the tumor but predominated in typ e B tissue , a nd occ ur red in no discern ible relati on to bloo d vesse ls, cysts or othe r struc tur es. Certa in a reas of the tum or were ent irely of gra n ula r cell type (fig. 3). Cell varia nts could be seen that were intermediate between

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Ne uroectode rma l Origin of Myob lastoma

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the typ ical Schwa nn cell, with its stellate or spindle shape and scant cytoplasm, and the larger gra nular cell with its round shape and abundant cytoplasm. Gran ular cells possessed varia ble qu antities of cytoplasm packed with eosinophilic granules that were PAS pos itive and were not affected by treatment with diastase. T his is characteristic of th e cells of gran ula r cell tu mors (6). The PAS-positive granules also were impreg nated by the Ti bor Pap retic ulin stain (fig. 4). A similar silver im pregnation has been rep orted to stain the gran ules of human granular cell tumors (1 3). Typical Schwa rm cells, gra nular cells and their transition forms all had identical nuclei as judged by light and electron microscopy (fig. 1-6). Occasional mitotic figures could be seen in gra nular cells, in abo ut the same frequency as in the typ ical schwannoma cells (fig. 2). By electron microscop y th e no n-granular cells had typical Schwarm cell morphology (fig. 5). Basemen t membrane occasionally could be seen on the external surface of Schwann cells (fig. 5). In some Schwann cells there were small fibri ls around the centr iole and some collagen produ ction. Gran ula ted cells with myo blas toma cell morphology contained gra nules of various

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Fig,3: Low magnificati on of part of tumor composed entirely of granular cells . H E. Fig. 4: Silver impregnation for reticulin . Abunda nt fine fiber s ch aracteristic of schw ann om a surro und most cells. Intracytopl asmic gra nules of gra nular cells also intensely sta ined . Ti bor Pap.

sizes, some sma ll and some large a nd complex. The la rge, complex granules contained small round structures, or structures of angular outline, features typ ical of myoblastoma cells [3, 14-16]. Also contained were vesicular forms , amorphou s structures and laminated membrane structures. A granular cell is illustrated in figure 6. Junctional complexes were seen between granular cells.

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Neuroec toderma l Or igin of Myob lastoma

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Granular cell variants in a rat schwannoma. Evidence of neurogenic origin of granular cell tumor (myoblastoma).

Vet. Pathol./ 5: 725-73\ (1978) Granular Cell Variants in a Rat Schwannoma Evidence of Neurogenic Origin of Granular Cell Tumor (M yoblastoma) J ...
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