Germinoma of the Pineal Its Identity with Gcrminoma ( Scminoma") of the Testis

Major Nathan B. Friedman, MC, AUS (From the Army Institute ot Pathology, \X/ashillgto~L D. C.) (Received for publication December 10, 1946) In 1944 Dorothy Russell (15) published the re- gcrminonmtous elements. Only 2 tulnors in this suits of a study of pineal tumors. She presented a group of 8 appeared to bc of neural origin; one, rational explanation for the well known similarity which had the pattern of a classic pinealoma, was in histologic appearance of "pinealomas" and "semi- TABLE l: DATA IN T\VENTY-THREt CASES OF PlNEAL nomas." She suggested that in'any "pincalomas" NEOPI.ASM ucre in truth teratoid tumors. The present report Case Age, Type of proposes to confirln h er.~obscrvations and to extend No. Sex years npoplasm s features her interpretations in accord with the teratologic CRovP 1 concepts gained through study of nearly 1,000 tu- 1 M 29 Neural mors of the testis at the Army Institute of Patho- 2 XI 22 Germinoma Extrapineal. Pitui- logy (6). tary involved. Dia- The files of the Institute contain pathologic ma- betes insipidus. Hypogonadism. terial from 23 patients with tumors of the pineal or ectopic "pinealomas." Fifteen tumors were submit- 3 1~i 17 Neural ted by military installations ~ (Group 1), and 8 were 4 1~I 18 Germinoma Pituitary involved. obtained from civilian sources e (Group 2). The Diabetes insipidus. _~I 21 essential data in all 23 cases arc listed in Table I. Puhnonary metas- tases. Radiosensi- Seven of the 15 tumors in group 1 were identical tMty. with the tcsticular tumor termed "spheroidal cell 6 hi 23 '" Pituitary im'olved. carcinoma," or "atypical teratoma," by Russell (1 ~) Diabetes insipidus. 7 ~1 18 " Pituitary involved. and called "~scminoma" by many pathologists; this 8 M 28 " neoplasm is identical with the disgerminolna of the 9 M 24 Neural ovary. Because this type of new growth is probably 10 M 30 " made up of germ cells, possibly even of primordial l 1 M 26 Genninoma germ cells, the designation "germinonla," which has 12 M 28 Neural 13 Xl -- " been suggested (6) for the tumor which occurs in 14 M 34 Teratocarcin- Pulmonary metas- the gonads, is equally appropriate for that which ap- oma tases. pears in the pineal. Two neoplasms in group 1 wcrc 1 ~ lXI 26 Teratoma teratomatous tumors; 1 was an adult teratoma, and c~muv 2 the other was a teratocarcinoma which also had ger- 16 F 22 Germinoma Extmpineal. Pitui- minomatous areas. Although there were 6 neural tary involved. Dia- tumors in the group, only 2 prcscnted the biphasic betes insipidus. cellular mosaic of the classic pinealoma. Polyglandular in- Of the 8 neoplaslnas in group 2, 3 were germi- sufficiency. nomas and 3 wcrc tcratocarcinomas. One of the 17 M ] 8 " Spinal metastasis. lattcr also contained both chorioepitheliomatous and 18 M 10 Teratocarcin- Pubcrtas praecox oma 1 Cases 5 and 14 are being reported in detail by Tomp- 19 M 13 Genninoma kins, Campbell and Itaymaker. 20 ...... Teratocarcin- 2 Material supplied from the laboratories of Dr. Shields oma Warren, Dr. Lawrence \V. Smith, Dr. Norman Elton, Dr. 21 -- -- Percival Bailey, Dr. Joseph H. Globus, and Dr. Abner 22 F 7 Neural Wolf. 23 M 10 " Pubertas praecox 363

Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 1947 American Association for Cancer Research. Friedman--Germinoma of the Pineal 365 diagnosed by Bailey (3), at the seminar of the size, structure and arrangement of the true pinealo- American Society of Clinical Pathologists in 1943, ma and the pineal germinoma which Russell (15) as a pinealoblastoma. The tumor presented at that emphasized. same meeting as a pinealoma falls into the germino- The s~tructural patterns observed in the teratoma- ma category. tous tumors of the pineal are comparable with those Of the entire group of 23 tumors, 10 were germi- seen in testicular tumors. For example, chorionepi- nomas and 5 were teratomas or teratocarcinomas. If thelioma and combinations of teratoma and germi- this group can be considered representative, approxi- nolna (Fig. 9) or embryonal carcinoma and germi- mately 2 of every 3 neoplasms of the pineal are not noma as well as typical teratocarcinoma were en- neural tumors. countered. The germinomatous tissue observed in In Figs. 1, 2, 3 and 4 the histologic appearance pineal teratomas in the past has usually been incor- of representative "pinealomas" (pineal germinomas) rectly considered a focus of "pinealoma." Even some is compared...... " with~" ,that of testicular neoplasms of the new growths of the pineal which appear frankly tera- germinoma type~ It is remarkable that all the pat- tomatous in photomicrographs (Horrax and Bailcy terns encountered in germinomas of the testis can [12], case 1, Figs. 3 and 5; Baggenstoss and Love be matched in tiie pineal tumors of this type. For [2], case 4), have been classified as neurogenic tu- example, the pineal germinoma in case 17 showed nlors. a granulomatous reaction (Fig. 5) such as is com- There is no universally acceptable explanation for monly seen in both testicular and ovarian germino- the development of both the gonadal and the extra- mas; similar granulomatous stroma and giant cells genital teratomatous tumors. One may postulate are evident in the "pinealomas" in Figs. 21, 27 and that neoplastic development of the germ cells nor- 29 of the report by Globus and Silbert (8). Some mally present in the testis and ovary gives rise to the germinomas of the gonads and the pineal lack "lym- teratomas of those organs. It is more difficult to phoid stroma" altogether; others form pseudotubu- explain the origin of the extragenital growths. Such lar structures. Finally, the cytoplasm of the princi- neoplasms may develop from displaced germ cells or pal cells may be either clear or darkly stained. arise from somatic cells which have retained some On the basis of the published illustrations, one embryonic potencies, a hypothesis which Schlum- may conclude that the tumors in cases 1, 2, 3 and 4 berger (16) recently employed in attributing medi- of Globus' 1941 report (7), those in cases 4 and 7 astinal teratomas to dislocations of tissue during em- of the 1925 study by Horrax and Bailey (11) and bryogenesis. the neoplasm in case 2 of Baggenstoss and Love (2) The theory that the primordial germ cells are se- are germinomas. gregated from the somatic cells early in embryonic In view of the nmrphologic identity of the two life and migrate through certain tissues before arriv- types of neoplasms, it is interesting that they some- ing in the gonadal region affords a logical explana- times exhibit a similar sensitivity to irradiation. The tion for the origin of the extragenital teratomas and testicular germinoma ("seminoma") is a notoriously germinomas. The possible importance of such wan- radiosensitive neoplasm; in one case in group 1 strik- dering germ cells is emphasized by the fact that ing regression of a pineal gcrminoma took place af- ectopic "pinealomas," usually of the germinoma ter irradiation, a course of events which has been type, have been found in the third ventricle and noted in other instances of "pinealoma" (1, 10). other structures near the pineal (case 2, group 1; The fact that two different biphasic tumors, the case 16, group 2; Russell [15]; Ford and Muncie pinealoma and the germinoma, occur in the same [5]). However, no explanation for the localization of tiny organ has led to much confusion. However, Figs. germ cells in the pineal region has been advanced. 6, 7 and 8show the striking differences in cellular Swift (17) described primordial germ cells in the

DESCRIPTION OF FIGURES 1 TO 4 FIG. 1.--Germinoma of pineal; compare with germin- FIe. 3.--Gcrminoma of testicle; compare with neo- oma of testicle in Fig. 2. This pattern, in which sheets plasm of pineal in Fig. 4. Intimately intermingled lymphoid of uniform neoplastic elements are traversed by trabeculae elements and neoplastic cells make up one pattern encoun- of connective tissue containing lymphoid cells, is common tered in both pineal and testicular germinomas. Mag. )< (case 19). Mag. X 160. 250. Fro. 2.--Germinoma of testicle; compare with tumor Fro. 4.--Germinoma of pineal; compare with photo- of pineal, shown at same magnification, in Fig. 1. Mag. micrograph, taken at same magnification, of testicular >( 160. tumor in Fig. 3 (case 7). Max. X 250.

Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 1947 American Association for Cancer Research. Friedman--Germinoma of the Pineal 367 head region of a chick embryo of 2 5 somites, and his SUMMARY paper includes a picturc showing a group of such Study of 23 neoplasms of the pineal collected at cells in a vessel immediately adjacent to the developing forcbrain. However, such primordial germ cells the Army Institute of Pathology confirms the view, expressed by other workers, that many so-called pi- move caudad and reach the genital ridge via the mescntcry, and it appears reasonable to assume that ncalomas are identical with certain tumors of the tumors originating from such elements would deve- testicle. It is suggested that such new growths may lop in the caudal periaortic mesenchyme (9, 13) arise from primordial germ cells and should be called rather than in the pineal. Because of the route taken germinomas. This hypothesis would account for the by the primordial germ cells their inclusion in relative frequency of teratomas in the pineal. Only Rathkc's pouch, which might afford a means of en- 1 of 3 tumors of the pineal originates from neural trance to the central nervous system, also appears clcments. unlikely. The alternative possibility, that somatic cells with REFERENCES undeveloped potencies arc included in the developing pineal gland and later give rise to tcratomatous 1. ALAJOUANINEand GILBERT. Pineal Tumor Treated growths, has already been advanced. Krabbe (14) by the Roentgen Ray. Abstr., Trans. Soc. d. Neurol. d. Paris, January 6, 1927. Arch. Neurol. & Psy- stated that the fact that the "germ of the gland" chiat., 18:301. 1927. came near the surface of the developing embryo faci- 2. BACCENSTOSS,A. It., and Love, J. c. Pinealomas. litated the penetration of elements of foreign tissue. Arch. Ncurol. & Psychiat., 41:1187-1206. 1939. Charlton (4), in discussing a teratoid tmnor of the 3. BAILEX', P. Proceedings of 1943 Tumor Seminar of pineal in a mackerel, expressed the opinion that the the American Society of Clinical Pathologists on neoplasm arose from "mesectodemF' and pointed Intracranial Tumors. Am. I. Clin. Path., 13:538- 541. 1943. out that the pineal develops near the anterior neu- 4. CnARI:rON, II. It. A Tumor of the Pineal Cartilage ropore, where ectoderm and neurectodcrm meet. Al- Fommtion in the Mackerel, Scomber Scombrus. though the pineal actually develops farther caudad Anat. Ree., 43:271-276. 1929. than Charlton implied, it may be significant that 5. FORD, F. R., and M~JNCIE, \V. Malignant Tmnor the sacrocococygcal teratomas occur in ,~.he region Within the Third Ventricle. Three Cases of Un- of the posterior neuroporc and ncurenteric canal. usual Type with Invasion of the Ventricular Walls. Arch. Neurol. & Psychiat., 39:82-95. t938. Until cmbryologic investigation supplies a saris- 6. FRIEDMAN. N. B., and MOORE, R. A. Tumors of factor3, explanation of the genesis of pineal germi- the Testis: A Report on 922 Cases. Military Sur- nomas and tcratomas, the point of view of the path- geon, 99:573-593. 1946. ologist must remain that stated in 1932 by Harris 7. GLOBUS, J. II. Pincaloma. Arch. Path.. 31:533- and Cairns (10): "... we are not able to exclude 568. 1941. the possibility that this pineal tmnour is a tumour 8. GLO~3US,J. H., and SILBEr~T, S. Pinealomas. Arch. of toti-potcnt cells. It may be more than coincidence Neurol. & Psychiat., 25:937-985. 1931. that both the pineal gland and the testis . . . which 9. t-IA?,~LETT, G. \V. D. Primordial Cells in a 4.5-ram. are known to give rise to teratomas, also give rise to Human Embryo. Anat. Rec., 61:273-279. 1935. 10. HARRIS, \V., and CAnoNS. H. Diagnosis and Treat- spheroidal celled ~umours that bear a strong resem- ment of Pineal Tumours. With Report of a Case. blance to one another." Lancet, 1:3-9. 1932.

DESCRIPTION OF FIGURES 5 TO 9

Fro. 5.--Gemainoma of pineal. Epithelioid cells in tion, in Fig. 6. Small lymphoid cells in germinonaas are lower portion of photomicrograph form a granuloma simi- separate, distinct components and show no transitions to lar to those encountered in germinomas of testis and large neoplastic elements (case 17). Mag. X 160. ovary. (case 17). Mag. )< 250. Fro. 8.--Pinealoma showing transitions between 2 cellu- FIG. 6.--Pinealoma with classic biphasic cellular mo- lar components of mosaic; the 2 cell types do not merge saic comparable to pattern seen during normal morpho- in germinoma. Photomicrograph was taken at same magni- genesis of pineal. Compare size and structure of cells fication as Figs. 6 and 7 (case 22) Mag. )< 160. with those of pineal germinoma, shown at same magnifica- Fro. 9.--Teratocarcinoma of pineal. In upper right tion in Fig. 7 (case 1). Mag. X 160. portion of photomicrograph is germinonaatous area such FIG. 7.--Germinoma of pineal; compare size of cells as is occasionally encountered in teratocareinoma of testicle with those of true pinealoma, shown at same magnifica- (case 21). Mag. X 60.

11. HORRAx, G., and BAILEY, P. Tunmrs of the Pineal in Sexual Development. Endocrinology, 7:379- Bodv. Arch. NeuroI. & Psychiat., 13:432-467. 414. 1923. 192~. 15. RUSSELL, DOROTHY S. The Pinealoma: Its Relation- 12. HORRAX, G., and BAInF.y, P. Pineal Pathology. ship to Teratoma. J. Path. & Bact.. 56:145-150. Further Studies. Arch. Neurol. & Psychiat., 19: 1944. 394-414. 1928. 16. SCHT.UMUE~G~R, It. G. Teratoma of the Anterior 13. JORDAN, H. E. Embryonic History of the Germ- Mediastinum in the Group of Military Age; a Cells of the Loggerhead Turtle. Papers from the Study of Sixteen Cases, and a Review of Theories Department of Marine Biology, Carnegie Institu- of Genesis. Arch. Path., 41:398-444. 1946. tion of Washington, 11:313-344. 1917. 17. SWIFT, C. H. Origin and Early History of the 14. KRABBE,K.H. The Pineal Gland, Especially in Re- Primordial Germ-Cells in the Chick. Am. J. Anat., lation to the Problem on Its Supposed Significance 15:483-516. 1914.

Books and World Recovery The desperate and continued need for American publi- The generous support which has been given to the Book cations to serve as tools of physical and intellectual recon- Center has made it possible to ship more than 700,000 struction abroad has been made vividly apparent by ap- volumes abroad in the past year. It is hoped that this peals from scholars in many lands. The American Book amount will be doubled before the Book Center closes. Center for War Devastated Libraries has been urged to The books and periodicals which your personal or in- continue meeting this need at least through 1947. The stitutional library can spare arc urgently needed and will Book Center is therefore making a renewed appeal for help in the reconstruction which must preface world un- American books and periodicals--for technical and scholar- derstanding and peace. ly hooks and periodicals in all fields and particularly for Ship your contributions to the Anrerican Book Center. publications of the past ten years. We shall especially care of The Library of Congress, Washington 25, D. C., wdcome complete or incomplete files of Cancer Research freight prepaid, or write to the Center for further in- and the American Journal of Cancer. formation.

Nathan B. Friedman

Cancer Res 1947;7:363-368.

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