studies of guinea pig tumors i. report of fourteen...

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Studies of Guinea Pig Tumors I. Report of Fourteen Spontaneous Guinea Pig Tumors, with a Review of the Literature* JAMESB. ROGERSANDHERMANT. BLUMENTHAL (Department of Anatomy, University of Louisville, School of Medicine, Louisville, Ky., and the Institute of Experimental Pathology, The Jewish Hospital, St. JMUÕS, Mo.) SUMMARY Fourteen spontaneous tumors of an inbred strain of guinea pigs have been described. No tumors were found in guinea pigs under 3 years of age, thus supporting the ob servation of Papanicolaou and Olcott (43) that spontaneous tumors occur rarely in guinea pigs which do not survive to senility. While this constitutes an incidence of only 2.4 per cent of the total population of this colony, it represents an incidence of 14.4 per cent of the animals surviving 3 years or longer. These fourteen tumors bring the total number of reported spontaneous neoplasms in guinea pigs to 138. The latter have been tabulated as to site of origin and micro scopic characteristics, and they are reported for the convenience of investigators encountering additional instances of spontaneous tumors or as a frame of reference for those studying the induction of tumors in guinea pigs. Despite the prevalent use of the guinea pig as an experimental animal, surprisingly few spontaneous tumors have been reported in this species. Re views dealing with this subject have been pub lished by Heim and Schwartz (21), Maury (36), Leader (28), Warren and Gates (53), and most re cently by Tamaschke (51). The reviews preceding that of Warren and Gates in 1941 were incomplete in that they did not include a number of reports dealing with spontaneous tumors of the respiratory tract (Sternberg [49], Spronck [48], Goldberg [16], and seven other spontaneous tumors observed by Woglom [54]). The most recent review by Ta maschke (51) is incomplete in that it includes only seventeen spontaneous tumors, a number far smaller than that reported by Warren and Gates 14 years earlier, although it mentions a spon taneous tumor reported by Gouyon, not men tioned in previous reviews. Since the review by Warren and Gates (53), a number of additional cases have been reported, and we have been able to * This work was supported by Research Grant #C-1590 (Cl-6) from the National Cancer Institute of the National In stitutes of Health, Department of Health, Education, and Welfare. assemble a total number prior to the present report of only 124 spontaneous tumors. This figure in cludes ten cases described in detail by Papanicolaou and Olcott (41-43) but does not include approxi mately 90 which these investigators collected but have not reported.1 It also does not include 23 cases of an ovarian "tumor" described by Loeb (32) and several additional ones by others (8, 11, 30) cited by Loeb. This "tumor" consists of em bryonal structures, apparently of parthenogenetic origin, which should not be considered as a true neoplasm, since, as Loeb has pointed out (32), they have limited duration of life, being destroyed at an early date and replaced by connective tissue. The rarity of spontaneous tumors in guinea pigs can be appreciated also by other reports. Thus, in three inbred families of guinea pigs at the Belts- ville Agricultural Station of the U.S. Department of Agriculture, studied by Wright and Eaton (56), no neoplasms were found in 15,000 animals. Simi larly, Haagensen and Krehbiel (19) have stated that in their colony of several thousand guinea pigs only two spontaneous tumors were found. Other reports indicate a somewhat higher incidence. Thus, Spronck (48) was able to collect 56 spon- Received for publication July 10, 1959. ; Personal communication from G. N. Papanicolaou. 191 Research. on February 11, 2019. © 1960 American Association for Cancer cancerres.aacrjournals.org Downloaded from

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Studies of Guinea Pig Tumors

I. Report of Fourteen Spontaneous Guinea Pig Tumors,with a Review of the Literature*

JAMESB. ROGERSANDHERMANT. BLUMENTHAL

(Department of Anatomy, University of Louisville, School of Medicine, Louisville, Ky., and the Instituteof Experimental Pathology, The Jewish Hospital, St. JMUÕS,Mo.)

SUMMARY

Fourteen spontaneous tumors of an inbred strain of guinea pigs have been described.No tumors were found in guinea pigs under 3 years of age, thus supporting the observation of Papanicolaou and Olcott (43) that spontaneous tumors occur rarely inguinea pigs which do not survive to senility. While this constitutes an incidence ofonly 2.4 per cent of the total population of this colony, it represents an incidence of14.4 per cent of the animals surviving 3 years or longer.

These fourteen tumors bring the total number of reported spontaneous neoplasmsin guinea pigs to 138. The latter have been tabulated as to site of origin and microscopic characteristics, and they are reported for the convenience of investigatorsencountering additional instances of spontaneous tumors or as a frame of referencefor those studying the induction of tumors in guinea pigs.

Despite the prevalent use of the guinea pig as anexperimental animal, surprisingly few spontaneoustumors have been reported in this species. Reviews dealing with this subject have been published by Heim and Schwartz (21), Maury (36),Leader (28), Warren and Gates (53), and most recently by Tamaschke (51). The reviews precedingthat of Warren and Gates in 1941 were incompletein that they did not include a number of reportsdealing with spontaneous tumors of the respiratorytract (Sternberg [49], Spronck [48], Goldberg [16],and seven other spontaneous tumors observed byWoglom [54]). The most recent review by Tamaschke (51) is incomplete in that it includes onlyseventeen spontaneous tumors, a number farsmaller than that reported by Warren and Gates14 years earlier, although it mentions a spontaneous tumor reported by Gouyon, not mentioned in previous reviews. Since the review byWarren and Gates (53), a number of additionalcases have been reported, and we have been able to

* This work was supported by Research Grant #C-1590(Cl-6) from the National Cancer Institute of the National Institutes of Health, Department of Health, Education, andWelfare.

assemble a total number prior to the present reportof only 124 spontaneous tumors. This figure includes ten cases described in detail by Papanicolaouand Olcott (41-43) but does not include approximately 90 which these investigators collected buthave not reported.1 It also does not include 23cases of an ovarian "tumor" described by Loeb

(32) and several additional ones by others (8, 11,30) cited by Loeb. This "tumor" consists of em

bryonal structures, apparently of parthenogeneticorigin, which should not be considered as a trueneoplasm, since, as Loeb has pointed out (32), theyhave limited duration of life, being destroyed at anearly date and replaced by connective tissue.

The rarity of spontaneous tumors in guinea pigscan be appreciated also by other reports. Thus, inthree inbred families of guinea pigs at the Belts-ville Agricultural Station of the U.S. Departmentof Agriculture, studied by Wright and Eaton (56),no neoplasms were found in 15,000 animals. Similarly, Haagensen and Krehbiel (19) have statedthat in their colony of several thousand guinea pigsonly two spontaneous tumors were found. Otherreports indicate a somewhat higher incidence.Thus, Spronck (48) was able to collect 56 spon-

Received for publication July 10, 1959. ; Personal communication from G. N. Papanicolaou.

191

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192 Cancer Research Vol. 20, February 1960

taneous papillary adenomas of the bronchus, andPapanicolaou and Olcott (41-43) have found

about 100 tumors in a group of 7,000 guinea pigs(1.4 per cent). Congdon and Lorenz (10) have reported an incidence of leukemia of 5 per cent in aninbred strain, and Loeb (32) has reported an incidence of parthenogenetic "tumors" of at least 5

per cent in female guinea pigs. This latter lesionprobably occurs with even greater frequency, sincetheir limited duration of life with replacement byscar tissue undoubtedly results in a failure to detect many of them. Papanicolaou and Olcott (43)have attributed their relatively high incidence tothe fact that many of the autopsied animals weresenile, since the tumors rarely occurred in guineapigs less than 4-5 years old.

Between the years 1941 and 1951 one of us(JBR) maintained two separate inbred strains ofguinea pigs. During that period no animals were

TABLE 1THE FREQUENCYOFSPONTANEOUSTUMORS

Total no. livebirths:Total

no. survivingover 3 years:Males

FemalesNo.

with tumors:MalesFemalesSusceptible

strain4,00097

(2. 4 per cent)257214

(14.4 percent)*8(12.0 " )*

11(15.3 " )*Nonausceptible

strain2,00017

(0 .9 per cent)4

130

* Per cent of total number of animals surviving over 3 years.

withdrawn from these colonies for experimentalpurposes, and they were permitted to live out theirlife span. In one of these strains spontaneous tumors first appeared in 1948, and in the period1948-1951 fourteen spontaneous tumors were detected. This has been designated the tumor-susceptible strain. No tumors developed in the secondstrain during this period of observation, nor haveany developed since 1951, although animals havebeen withdrawn for experimental purposes. Thepresent report deals primarily with the characteristics of these fourteen spontaneous tumors, and acomparison is drawn as to frequency and typewith guinea pig tumors heretofore reported. Furthermore, all the tumors reported to date havebeen classified as regards histologie type and organof origin for purposes of subsequent comparisonwith induced tumors in the guinea pig.

MATERIALS AND METHODSThere were 4,000 live births in the tumor-sus

ceptible colony during the period 1941-1951 and

2,000 in the nonsusceptible strain. Each animal ofthe two strains, on death, was perfused with 20 percent formaldehyde and subsequently autopsied.When tumors were encountered, they were described, measured, and blocks were taken formicroscopic study. The latter were embedded inparaffin, sectioned at 6 m/j. and stained withhematoxylin and eosin.

RESULTSIncidence of spontaneous tumors.—Spontaneous

tumors were detected in fourteen of the 4,000 animals (0.4 per cent) in the susceptible strain (Table1). However, since no tumors were found in animals under 3 years of age, data reflecting this factare perhaps more pertinent. Slightly less than 2.5per cent of guinea pigs of the susceptible strainsurvived over 3 years, and of this group the findingof fourteen tumors represents an incidence of 14.4per cent. The frequency in males surviving over 3years was 12 per cent and in females, 15.3 per cent.

The proportion of the nonsusceptible strain surviving over 3 years was only about one-third thatof the susceptible strain. The females of the non-susceptible colony are known to be susceptible to atoxemia of pregnancy, and this would account, tosome extent at least, for the smaller number of livebirths and for the smaller proportion of femalessurviving over 3 years; however, it would not account for the smaller proportion of males. For reasons not yet known, the life span of the non-susceptible strain is shorter than that of the susceptible strain.

Distribution and characteristics of the tumors.—

Seven primary anatomic sites were representedamong the fourteen spontaneous tumors. The organ most frequently involved in this strain was theuterus, where seven tumors were found. Two of thelatter were benign leiomyomas, and one was abenign adenomyoma. Sarcomatous degenerationwas found in the remaining four, one of which wasa leiomyosarcoma, one a fibrosarcoma, one amyxosarcoma, and one a mesenchymal mixed tumor. Two tumors were found in the liver, a hepatic-cell adenoma in one case, and a cavernous he-mangioma in another. There was one case each ofan embryonal carcinoma of the testis, a papillomaof the gall bladder, papillary pulmonary adeno-matosis, a subcutaneous fibrolipoma, and a case oflymphoblastic leukemia. In none of the tumorsconsidered histologically malignant was evidenceof metastasis found.

The leiomyomas of the uterus were discrete, encapsulated tumors showing the typical pattern ofintermingling bundles of elongated smooth musclecells. Differing from the latter only in that the tumor contained endometrial glands was the single

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ROGERSANDBLUMENTHAL—SpontaneousTumors in Guinea Pigs 193

case of adenomyoma (Fig. 1). The one tumor considered to be a leiomyosarcoma was also encapsulated grossly, and microscopically it retained alamellated structure (Fig. 2), with the bundlescompactly arranged and with little or no interstitial structure. The cells were also closely packed,and mitotic figures were fairly numerous. The tumor diagnosed as a fibrosarcoma was confinedwithin the serosa (Fig. 3). In the latter tumor thecells were somewhat more loosely arranged andwere spindle-shaped rather than straplike, as inthe tumors of smooth muscle origin (Fig. 4). Thiswas taken to be an indication that this tumor arosefrom the interstitial connective tissue of the uterus

TABLE2REPORTEDSPONTANEOUSTUMORSOF

THE REPRODUCTIVETRACT

TumorOvary:Embryoma

orteratomaU

titíu

uuUterus:I^iomyoma

(grossonly)uFibromyomaAdenomyomar.eiomyosarcomaFibrosarcomaMyxosarcomaMesenchymal

mixed tumorTestis:Embryonal

carcinomaTotalNo.

cases11112111111113AuthorandyearMontroni,

1930,citedbyLeader(28)Giordano,

1931(15)Haranghyet al.,1954(20)Papanicolaou

andOl-cott,1942(42)PresentreportLipschutz,

1941(31)Presentreportuuu

uU

tíu

uu

u

rather than from smooth muscle. The same interpretation was placed on the case of myxosarcoma,in which the tumor cells exhibited an even looserarrangement (Fig. 5). The latter tumor was grosslymore diffuse and less well demarcated than in theforegoing cases, but had also not extended throughthe serosa. The tumor designated as a mesenchy-inal mixed tumor of the uterus differed from themyxosarcoma only in the fact that cystic endo-metrial glands were incorporated in the neoplasticmass (Fig. 6).

The two tumors of the liver were both considered benign. One was a typical, grossly purple,cavernous hemangioma, and microscopicallyshowed numerous dilated vascular channels consisting of a single layer of endothelium and filledwith blood. The second grossly consisted of a smallwhite nodule measuring a few millimeters in di

ameter; microscopically, it showed a thin, intactfibrous capsule enclosing liver cells, with evidenceof sinusoids and the usual cordlike pattern, butdevoid of bile duct structures (Fig. 7). Between thecapsule and the mass of liver cells there was a thinlayer of large vacuolated phagocytes containingbrown pigment. This was considered to be a smallhepatic-cell adenoma. The gall bladder papillomapresented as a small cauliflower-like growth on

TABLE 3

REPORTEDSPONTANEOUSTUMORSOFTHERETICULOENDOTHELIALSYSTEM

Tumor

Spleen:Splenoma (lymphosarco-

ma?)

Lymph glands:Cervical, lymphosarcoma

Leukemia

Total

No. cases

1

13

Author and date

Guérinand Guérin,1925 (18)

Dickson, 1915 (14)Miguenz, 1918 (37)

Snijders, 1926 (47)Heston and Deringer,

1952 (22)Congdon and Lorenz,

1954 (10)Lorenz et al., 1954 (33)Present report

TABLE 4

REPORTEDSPONTANEOUSTUMORSOFTHE RESPIRATORYTRACT

TumorBronchus:Papillary

Adenomaattu

tt""tí

Utí

UAdenocarcinomaTotalNo.

cases2561131165Author andyearSternberg,

1903(49)Spronck,1907(48)Norris,

1947(40)Hestonand Deringer,1952(22)Lorenz

el al., 1954(33)PresentReportGoldberg,

1920 (16)

gross inspection, and microscopically showedfronds and glands lined by tall hyperchromaticepithelial cells (Fig. 8). There was no evidence ofinvasion into muscle.

The single case of papillary adenomatosis of thelung presented grossly as two tiny white nodules inthe left upper lobe. Microscopically these growthsconsisted of numerous papillary structures, with acore of loose connective tissue covered by a singlelayer of somewhat hyperchromatic cuboidal epithelium (Fig. 9).

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194 Cancer Research Vol. 20, February 1960

The embryonal carcinoma of the left testis wasdetected at autopsy as a yellow-gray, irregularnodule occupying about two-thirds of that structure. Microscopically it consisted of areas of compactly arranged small cells with scanty vacuolatedcytoplasm, other areas with pseudogland formations, and in a few foci papillary-like structures(Figs. 10 and 11).

Finally, the single case of leukemia was discovered at routine autopsy. Suspicion was firstaroused by an enlarged liver and spleen and thediagnosis confirmed by sections. Infiltration withleukemic cells was particularly marked in theliver, spleen, kidneys, and bone marrow. The leukemic cells were characterized by large vesicularnuclei and scant basophilic, agranular cytoplasm(Fig. 12).

DISCUSSIONThe frequency of 14.4 per cent found in the tu

mor-susceptible strain represents a minimum figure, since these were all grossly visible tumors;

when examination of all the autopsied guinea pigsin this group has been completed it is possible thatother microscopic tumors may be encountered. Itis evident from the data in Table 1 and the characteristics of the tumors that females are more susceptible than males, and that the most strikingfeature in females is the susceptibility of the muscular and fibrous elements of the uterine wall tothe development of neoplasms. The three tumorsfound in males were the papillary adenomatosis ofthe lung, the testicular tumor, and the hepatic-celladenoma of the liver.

Since no grossly visible tumors were found inguinea pigs under 3 years of age, the present reportsupports the observation of Papanicolaou andOlcott (41-43) that in this species tumors rarelyoccur in animals which do not survive to senility.Although in the present study no tumors werefound in the nonsusceptible inbred strain, the survival rate beyond 3 years in the latter colony wasso low that the absence of tumors may have been aa reflection of a shorter life span.

TABLE5REPORTEDMESENCHYMALTUMORSNOTINSPECIFICORGANS

TumorFibrosarcoma,

subcutaneousuauituau

aFibrolipomaSarcoma

(fibro?)Glioma(schwannoma)LipomyxofibromaXeurogenic

fibrosarcomaXeurilemmoma(multiple)Fibrosarcoma

coexistentwithliposarcomaTotalSiteNeckForelegBackChestpAbdomen?Abdominal

wallPsoasmuscleJawMesenteryChest

wallNo.

casesiiiiii13Author andyearDickson,

1915(14)Wood,1916(55)Lubarsch,

1919(34)Lubarsch,1919(34)Haagensenand Krehbiel, 1936(19)Present

reportRoffo,1025(44)Babletand Block, 1934(4)Kröning

and Wepler, 1938(27)Warrenand Gates, 1941(53)Papanicolaou

and Olcott, 1942(42)Papanicolaou

and Olcott, 1942 (42)

TABLE 6

REPORTEDSPONTANEOUSMAMMARYTCMOHSIN GUINEAPIGS

TumorAdenocarcinoma""""•LipofibrosarcomaAdenomaPapillary

cystadeno-maTotalNo.

cases2111ä

(inmales)1(inmale)11212Author

andyearKatase,

1912(24)Sternberg,1913(50)Jones,

1916(23)BlumensaatandCham-py,

1948(7)Migunow,1931(38)Twort

and Twort,1932(52)Murray,

1916(39)AndersonandLumbro-sa,

1933(1)Apolant,

1908 (2)

In Table 2 are listed the reported spontaneoustumors of the reproductive tract, including thoseof the present study, but exclusive of the ovarianparthenogenetic "tumors" of Loeb (32). While we

have added no tumors of the ovary, the group ofseven uterine tumors constitutes a sizable additionto those previously reported, since only two tumors of the uterus have been reported prior to thepresent study. The testicular tumor found in thepresent study appears to be the only reported instance of a spontaneous tumor of the male reproductive system in the guinea pig.

In Table 3 are listed the tumors of the reticulo-endothelial system, to which we have added only asingle case of leukemia. The number of cases ofspontaneous leukemia may actually be greaterthan that shown, since in the study of Congdon

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ROGERSANDBLUMENTHAL—SpontaneousTumors in Guinea Pigs 195

and Lorenz (10), dealing in part with the inductionof this disease by irradiation, there was evidencesuggesting that the latter agent may not have beenresponsible for the leukemia cases which appearedin the experimental group.

In Table 4 are tabulated the tumors of the respiratory tract, to which we have again added onlya single case of papillary adenomatosis of thebronchus. It is noteworthy that Grumbach (17)claims to have induced such lesions in the lungs ofguinea pigs by inoculating a diphtheroid bacillus

greater number of spontaneous tumors of this organ. The cavernous hemangioma and the hepatic-cell adenoma of the liver also appear to be the firstreported instances of a spontaneous origin of thesetumors in this organ.

In Table 5 are shown the various tumors ofmesenchymal origin, not located in specific organs,which have been reported. Here we have addedonly a single benign fibrolipoma to the group ofsubcutaneous tumors.

It is evident from Tables 2 to 7 that a large

TABLE7MISCELLANEOUSREPORTEDSPONTANEOUSTUMORS

OrganSkinEyeBrainHeartaGastrointestinal

tractutíu

uKidneyuEndocrine

systemfitiU

UBoneuNot

statedLiveruGall

bladder

TotalTumorEpithelioma

adenoidescysticumDermoid

ofcorneaTeratoma

ofponsRound

cell sarcoma (lymphosarcoma ?)FibrosarcomaFibromyoma

of stomachLipoma of stomachLiposarcoma ofintestineOsteosarcoma

Round cell sarcoma (lymphosarcoma?)Carcinoma

of adrenal cortexAdenoma of thyroid (gross only)Adenoma of adrenalcortexOsteosarcoma

ChondrosarcomaCarcinomaHepatic

cell adenomaCavernoushemangiomaPapillomaNo.

cases1111

14

111

11

1111111122Author

andyearHaranghy

et al., 1953(20)Brunschwig,

1928(9)Lutz,

1910(35)Bender,

1925 (6)Athias, 1937(3)Papanicolaou

and Olcott, 1940 (41), 1942 (42)" « « 1942(42)

«1942(42)Twort

and Twort, 1932 (52)Ball and Pagnon, 1935(5)Roskin,

1930 (45)Papanicolaou and Olcott, 1942 (42)

" 1940(41)Leader,

1937 (28)Papanicolaou and Olcott, 1943(43)Gouyon,

1876, cited by Tamaschke(51)Present

reportPresentreportPresent

report

isolated from the lymph nodes of patients withHodgkin's disease; he is particularly impressed by

their similarity to jagziekte of sheep, an opinionshared by Cowdry and Marsh (12). The infre-quency of this tumor in our colony, however, failsto support transmission by an infectious agent.

The single instance of a papilloma of the gallbladder is also worthy of comment. This appearsto be the first reported instance of a spontaneoustumor of this organ, despite the fact that thebiliary tract of the guinea pig appears to be unusually susceptible to the development of inducedmalignancy (Kazama [25, 26], Leitch [29], Delbetand Godard [13], Schmid [46]). Perhaps more careful examination of the gall bladder would yield a

variety of spontaneous tumors have been observedin the guinea pig. Of the 138 such tumors reported(including the fourteen in the present study), 88(62.4 per cent) were epithelial in origin. An additional fifteen (10.9 per cent), including the leuke-mias, were reticulo-endothelial in origin, and inthis figure we have also included the two instancesof round-cell sarcoma of the heart and of the kidney, which were, in all likelihood, lymphosar-comas. The remaining 34 (24.8 per cent) were tumors of mesenchymal origin, and this includes thecavernous hemangioma of the liver. While thiscompilation thus shows a predominance of tumorsof epithelial origin, Papanicolaou found a largepercentage of fibrous tumors in his colony.1

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196 Cancer Research Vol. 20, February 1960

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31. LIPSCHUTZ,A. Spontaneous Fibromyoma in a FemaleGuinea Pig. Arch. Path., 31:702-5, 1941.

32. LOEB,L. The Parthenogenetic Development of Eggs in theOvary of the Guinea Pig. Anat. Ree., 61:373-408, 1932.

33. LORENZ,E.; JACOBSON,L. O.; HESTON,W. E.; SHIMKIN,M.; ESCHENBRENNER,A. B.; DERINGER,M. K.; DONIGER,J.; and SCIIWEISTAL,R. In: R. E. Zirkle (ed.). BiologicalEffects of External X and Gamma Irradiation, pp. 24-148.New York: McGraw-Hill Book Co., 1954.

34. LUBARSCH,0. Ueber spontane Impfsarkome bei Meerschweinchen. Ztschr. f. Krebsforsch., 16:315-17, 1919.

35. LUTZ,B. Ein Teratom am KleinhirnbrückenwinkelbeimMeerschweinchen. Arb. a.d. neurol. Inst. a.d. Wien. Univ.,18:111-17, 1910.

36. MAURY,A. I/es tumeurs chez le cobaye. Revue critique.Versailles: J. Aubert et Cie, 1931.

37. MIGUENZ,C. Sarcoma espontáneo transplantable en elcobaye. Rev. d. Inst. bact., 1:147-54, 1918.

FIG. 1.—Adenomyoma of the uterus. Hematoxylin-eosinstain, Mag. approx. X100. The top represents the serosal surface of the uterus. In the center there is a dense, demarcatednodule of interweaving bundles of muscle containing a fewcystic endometrial glands and groups of smaller glandularstructures.

FIG. 2.—Leiomyosarcoma of the uterus. Hematoxylin-eosin stain, Mag. approx. X100. There are bundles of smoothmuscle coursing in several directions. Muscle fibers are compactly arranged, and there is a marked paucity of stromal connective tissue.

FIG. 3.—Grossspecimen of fibrosarcoma of the uterus. Thenodule has been bisected and arranged so that one-half showsthe intact serosal surface (A) and the other half the cut surfaceof yellow-gray tumor with small, dark foci of hemorrhage (B).

FIG. 4.—Fibrosarcoma of the uterus. Hematoxylin-eosinstain, Mag. approx. X250. This is a microscopic section ofgross tumor (Fig. 3) and shows compactly arranged spindlecells. Arrows indicate mitotic figures.

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FIR. 5.—Myxosarconiü of the uterus. Hematoxylin-eosin

stain, Mag. iipprox. X100. The tumor is composed of looselyarranged stellate cells which can be seen causing a separationof muscle bundles.

FIG. 6.—Mesenchymal mixed tumor of the uterus, llcina-toxylin-eosin stain, Mag. ¡ipprox.X100. The connective tissueelement of this tumor is similar to that seen in Figure .). Atthe upper left margin there is a cystic endornetrial gland.

Flo. 7.—Hepatic cell adenoma of the liver. Ilematoxylin-eosin stain, Mag. approx. X100. At top and bottom edges canbe seen the capsule of the nodule. Hepatic cells are arranged incords, but there is a total absence of bile duct structures.

FIG. 8.—Papilloma of the gall bladder. Heinatoxylin-eosinstain, .Mag. approx. XlOt). The upper part of the photomicrograph shows a papillary-glandular arrangement of epithelialstructures. Serosa is at the lower edge.

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FIG. 9.—Papillary adenoma of the bronchus. Hematoxylin-eosin stain, Mag. »p]>ro\.XK'II. In the «niterthere are numerous papillary fronds covered by cuboidal epithelium. Alongthe right edge are pulmonary alveoli.

FIG. 10.—Kinbryonalcarcinoma of the testis. Ilcmaloxylin-eosiu stain. Mag. approx. X100. The photomicrograph showsglands and compactly arranged small cells with scanty cytoplasm.

FIG. 11.—Same tumor as Figure 10. Ilcmatoxylin-eosinstain, Mag. approx. X100. Papillary structures are seen covered by hyperchromatic cuboidal epithelium.

FlCi. H.—Liver with lenkcinic infiltration. Ileinatoxylin-eosin stain, Mag. approx. Xl"0. Hepatic cords are evident,with marked vaeuolization of hepatic cells. There are severalnodular leiikeinic infiltrations, as well as thin chains of leiike-mic cells.

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ROGERSANDBLUMENTHAL—SpontaneousTumors in Guinea Pigs 197

88. MIGUNOW,B. I. Primäre spontane Neubildungen beiVersuchstieren. Centralbl. f. allg. Patii, u. path. Anat.,61:417-20, 1931.

39. MtFRRAY,J. A. A Transplantable Sarcoma of the GuineaPig. J. Path. & Bact., 20:260-68, 1916.

40. NoRRis, R. F. Pulmonary Adenomatosis ResemblingJagziekte in the Guinea Pig. Arch. Path., 43:553-58, 1947.

41. PAPANICOLAOU,G. N., and OLCOTT,C. T. Studies of Spontaneous Tumors in Guinea Pigs. I. A Fibromyoma of theStomach with Adenoma (Focal Hyperplasia) of the RightAdrenal. Am. J. Cancer, 40:310-20, 1940.

42. . Studies of Spontaneous Tumors in Guinea Pigs.II. Tumors of the Stomach and Intestine. Arch. Path.,34:218-28, 1942.

-. Studies of Spontaneous Tumors in Guinea Pigs.43.HI. A Chondrosarcoma of Iliac Bone with Metastasis toMammary Region. Cancer Research, 3:321-25, 1948.

44. ROFFO, A. H. Sobre un sarcoma transplantable en uncobaye. Biol. Inst. de med. exp. para el estud. y. trat. d.cancer, 1:546-61, 1925.

45. ROSKIN, G. Eine bösartige Geschwulst beim Meerschweinchen zur vergleichenden Histologie und Cytologie dernormalen und pathologischen Nebenniere. Virch. Arch. f.path. Anat., 277:466-88, 1930.

46. SCHMID,H. O. Die Wirkung bestrahlten Ergosterine und

verwandter Stoffe auf Epithelgewebe. Ztsclir. f. Krebsforsch., 34:335-46, 1937.

47. SNIDJEHS,E. P. Over een overentbare leukaemie bijcavia's. Nederl. tijdschr. v. geneesk., 70:1256-62, 1926.

48. SPRONCK,C. H. H. Over adenoma destruens bij cavia cobaya; eei bijdrage tot de erfelijkheid van kanker. Nederl.tijdschr. v. geneesk., 1:1033-40, 1907.

49. STERNBERG, C. Adenomähnliche Bildungen in derMeerschweinchenlunge. Verhandl. d. deutsch, path. Ge-sellsch., 6:134-36, 1903.

50. . Ein Adenokarzinom der Mamma bei einemMeerschweinchen. Ibid., 16:362-65, 1913.

51. TAMASCHKE,C. Die Spontantumoren der kleinen Laboratoriumssäugerin ihre Bedeutung fürdie experimentelleOnkologie. Strahlentherapie, 96:150-68, 1955.

52. TWORT,C. C., and TWORT,J. M. Sarcoma and Carcinomain a Guinea Pig. J. Path. & Bact., 35:976, 1932.

53. WARREN,S., and GATES, O. Spontaneous and InducedTumors of the Guinea Pig. Cancer Research, 1:65-68,1941.

54. WoGLOM,W. H. Review of Thesis by Maury. Am. J. Cancer, 23:844, 1935.

55. WOOD,F. C. A. A Sarcoma in a Guinea Pig. Proc. N.Y.Path. Soc., 16:1-6, 1916.

56. WRIGHT,S., and BATON,O. N. Persistence of Differentiation among Inbred Families of Guinea Pigs. TechnicalBull., Vol. 103: U.S. Dept. of Agriculture, 1929.

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1960;20:191-197. Cancer Res   James B. Rogers and Herman T. Blumenthal  LiteratureSpontaneous Guinea Pig Tumors, with a Review of the Studies of Guinea Pig Tumors: I. Report of Fourteen

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