Seminoma appearing as a retroperitoneal mass Seminoma associated with a testicular scar

EDWARD M. COHEN, D.O. Detroit, Michigan

lesions. The purpose of this paper is to report a case in Seminoma usually presents as a primary which a widespread retroperitoneal seminoma was tumor of a testis. Germ cell tumors, present without a clinically evident primary gonadal including seminoma, have also been tumor, but associated with a testicular scar. A discus- reported as having origin from pineal sion of the possible embryogenesis and pathogenesis gland, anterior mediastinum, and will attempt to shed some light on the controversy retroperitoneal areas. Retroperitoneal regarding this type of lesion. seminomas also have been reported in association with "burned out" testicular Report of case lesions. A case of retroperitoneal A 26-year-old white man was admitted to the hospi- seminoma associated with a testicular tal with a chief complaint of colicky pain in the right scar is presented. An elevated urinary flank, with radiation to the right lower quadrant of chorionic gonadotropin level (16,000 the . This had been present for approxi- units/L.) developed during the course of mately 8 weeks. The patients previous health had the disease. The patient died and autopsy been good, and he had had no complaints referable showed massive tumor involvement of to the genitourinary or gastrointestinal system, ex- the retroperitoneum, liver, and pelvis as cept constipation. A tender mass was palpable in the well as invasion of the stomach and midabdominal region. Palpation of the mesentery of the small intestine. The showed them to be in the scrotal sacs and apparently portal vein showed thrombosis secondary of normal size and contour. Laboratory studies gave to tumor. Possible modes of pathogenesis results within normal limits except for increases in include displaced germ cells during the alkaline phosphatase (AP), lactic dehydrogenase embryogenesis as well as primary (LDH), and glutamic oxaloacetic transaminase testicular seminoma with retroperitoneal (GOT) levels of the serum. X-ray study of the chest metastasis and regression of the primary showed no abnormality. An intravenous pyelogram tumor in the testis. showed a soft tissue mass displacing the right laterally to the right. An aortogram and superior mesenteric angiogram showed displacement of ves- sels about the lesion. A cavagram demonstrated ob- struction of the right iliac vein at its junction with the In 1927 Prym l reported observing at autopsy of a vena cava inferior. The latter vein was not vis- 51-year-old man a widespread chorioepithelioma ualized, and drainage of the lower extremities by associated with atrophy of the right , which way of the collateral circulation via the ascending supported a 1 cm. fibrous scar. Since that report lumbar veins was noted. A lymphangiogram showed there have been other reports of germ cell tumors, displacement of the paravertebral lymphatic vessels involving the retroperitoneum particularly, without to the left side. At surgery, a large retroperitoneal evidence of associated gonadal tumors. In several of mass was noted adjacent to the medial border of the these cases burned-out primary lesions within the right . The tumor compressed and distorted testes have been described, 2- 4 but in other cases 5-10 the vena cava inferior and extended to the iliac ves- no clinically evident lesion was seen in the gonads. sels, to which it was fixed. The tumor was considered These observations lead to certain questions regard- unresectable, and therefore only an incisional ing the embryogenesis and pathogenesis of such biopsy specimen of the mass was removed. Examina-

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Fig. 1. Biopsy specimen of reiropersioneal seminoma (hematoxylin and eosin slain, x 100). Fig. 2. Biopsy specimen magnified x400. tion of the frozen section gave an impression of right orchiectomy was performed. probable lymphoma. A metastatic testicular tumor Pathologic examination showed a sharply cir- was considered less probable because there was no cumscribed, greyish white mass measuring 2.5 cm. testicular mass. Permanent sections (Figs. 1 and 2) in length by approximately 1 cm. in diameter at the showed the tumor to consist of large round or superior pole of the testicle. Its surface was semifirm polyhedral cells with distinct cell borders, clear or and greyish white, with a few tan areas. The border slightly granular cytoplasm, and large, centrally of the lesion with the normal part of the testis was placed, hyperchromatic round nuclei with promi- distinct in some areas; however, in other areas there nent nucleoli. The cells were closely packed and was an irregular margin. Microscopic examination partitioned into lobules by an inconspicuous stroma. (Fig. 3) of the firm, greyish white area showed it to Small, hyperchromatic cells resembling mature consist of densely hyalinized connective tissue sup- lymphocytes were distributed about the tumor cells porting lymphocytes and histiocytes containing and within the stroma. Because of the unusual pre- iron-positive hemosiderin. Staining for acid-fast sentation in this case and because of the rarity of pigment gave negative results. Near the margins, primary retroperitoneal germ cell tumors, outside ghostlike remnants of seminiferous tubules were consultations were requested. The final diagnosis seen. In some areas microcalcification was noted. after consultation was seminoma, either primary in Tumor was not seen within the testicle, epididymis, the retroperitoneum or metastatic from the testes, or associated spermatic cord. with a silent primary lesion." 2 The patient did well and was discharged approx- A postoperative determination of urinary imately 4 weeks after admission. chorionic gonadotropin (UCG) gave negative re- Subsequently, he received radiotherapy in a basic sults. The testicles were reexamined closely, and it tumor dose of 2,600 rads to the pelvis, re- was thought that a small nodule may have been troperitoneum, epigastrium, mediastinum, and present in the right testicle. Subsequently, a radical bilateral supraclavicular areas. This dose to the re-

821/90 showed the presence of seminoma. Twelve days postoperatively chemotherapy was begun. A slide test for UCG at this time was positive. A 24-hour urine specimen showed 16,000 units of UCG per liter. Subsequently severe pancytopenia, gastrectasis, and tachycardia developed. The patient died 29 days after this admission. Autopsy showed hemorrhagic and necrotic tumor involving the entire retroperitoneal space from the diaphragm down to the pelvis. Tumor was seen also within the mesentery of the small intestine. The liver had been almost totally replaced by tumor (Figs. 4 and 5). The portal vein (Fig. 6) also had been in- volved by tumor, and thrombosis had occurred. The tumor involved other abdominal structures as well. Fig. 3. Section of scar on right testicle shooing calcium deposits (hema- The posterior wall of the stomach had been invaded toxylin and eosin stain, x100). by tumor, and extreme gastrectasis was evident. There were multiple adhesions between loops of troperitoneal mass was supplemented with 2,400 small bowel. Examination of the remaining testicle rads, for a total dose of 5,000 rads to the area. (Fig. 7) showed it to be somewhat atrophic. Leydig Eleven and one-half months later, the patient was cells appeared to be hyperplastic. The lungs were readmitted to the hospital with a chief complaint of congested and showed intra-alveolar edema. Col- abdominal fullness and pain. Also he was weak and onies of bacteria were noted in the lungs and in the had anorexia. There was distention of the abdomen, gastric mucosa. Microscopic examination of multi- with pain on deep palpation in the suprapubic area. ple sections of the tumor (Figs. 8 and 9) showed it to Palpation revealed the liver to be enlarged. Laborat- retain its initial pattern. Foci of choriocarcinoma ory tests showed moderate pancytopenia with eleva- were searched for but were not seen in the sections tions of AP, LDH, and GOT in the serum. Uric acid made. The tumor appeared to be slightly more ana- also was markedly elevated. The albumin-globulin plastic than it was at the initial observation. Sections ratio was reversed, but the total protein content was of bone marrow showed marked hypoplasia with normal. Angiography indicated obstruction of the fatty replacement. inferior mesenteric artery and celiac arteries. Further angiography and radioactive scanning dem- Comment onstrated metastatic disease involving the liver. An Testicular tumors represent approximately 2 per- intravenous urogram showed partial obstruction of cent of all malignant visceral neoplasms in men. the left ureter. Between 35 and 40 percent of testicular tumors are An exploratory laparotomy revealed the presence seminomas. Seminoma usually manifests itself as a of approximately 1,200 ml. of serosanguineous fluid scrotal mass. The mean age of patients is 38 years. in the peritoneal cavity. The retroperitoneal areas The usual spread of seminoma is by way of lympha- were extensively involved with tumor, which ex- tic channels to the , and from tended to the omentum and mesentery as well as the this region tumor may spread superiorly to the enlarged liver. Biopsy of the liver and omentum mediastinum, or backward to the pelvic and iliac

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Fig. 4. Gross appearance of cut section of seminoma secondary to liver. Fig. 5. S ection seminoma, secondaty to liver (hematoxylin and eosin stain, x100).

Fig. 6. Gross appearance o fseminorna in portal vein. Fig. 7. Section from left testicle showing Leylig cell hyperplasia (hematoxylin and eosin stain, x100).

Fig. 8. Section of retroperitoneal seminoma obtained at autopsy (hematoxylin and eosin stain, x 100). Fig. 9. Section of retroperitoneal seminoma magnified x400.

823/92 nodes. The gross and microscopic characteristics of widespread teratoid tumor with an associated tes- seminoma have been adequately described ticular lesion consisting of a fibrous scar in which previously." Primary germ cell neoplasms have viable neoplastic tissue was either absent or less than been described also in the pineal gland," in the 5 mm. in diameter. A characteristic finding was 15 anterior mediastinum, and in the retroperitoneal amorphous and granular hematoxylin -staining de- area s Seminomas usually are radiosensitive, and posits apparently located within dilated seminifer- tests for UCG usually are negative. ous tubules. Histochemical studies suggested that Dixon and Moore" stated that the undifferen- the hematoxylin-staining substance represented tiated gonads arise on the ventral surface of the necrotic neoplastic tissue. In two of the 17 cases mesonephros during the fifth and sixth embryonic there were hematoxylin-staining bodies within the week. The origin of the primordial germ cells, which testicular scar tissue, which was otherwise devoid of are conspicuous in the gonad at this stage, is dis- tumor or atypical cells. This type of lesion had not puted. It has been variously described as occurring been reported previously in scars secondary to in the entoderm of the yolk sac and in the mesothel- trauma or orchitis. ial covering of the gonad. Origin in the yolk sac Subsequently, Azzopardi and Hoffbrand 2 re- would require migration to the gonad at some time ported a case of retrogression of a testicular during embryogenesis. If the origin of germ cells seminoma with viable metastases and discussed six were in the mesothelial covering of the gonads, no similar cases. They noted a pattern that was similar migratory step would be needed. Since it is widely in all cases and formulated the steps in regression of held that seminomas, as well as teratoid tumors, the testicular seminoma. They postulated that nec- originate from germ cells, these considerations with rosis of tumor results in accumulations of ghosts of regard to the embryonic development of the gonads neoplastic cells in which cytologic detail is lost. The are important. Another possibility would be that necrotic area is surrounded by palisaded histiocytes. extragenital germ cell tumors represent aberrations Cholesterol and its esters may appear in this zone, in somatic development, although Friedmans" and foam cells may be present at the periphery. study suggested that this is improbable. Lipofuscin, of ceroid type, may be seen. Hematoxy- If extragonadal germ cell tumors, particularly in lin deposits may be scattered throughout the necro- the retroperitoneum, occurred with clinically and tic areas, which are surrounded by a dense, fibrous microscopically normal testes, then the occurrence scar. The authors theorized further that eventually of primary retroperitoneal germ cell tumors would only a fibrous scar may remain. Evidence of calcifi- not be in dispute. The problem arises because an cation may be present. occult tumor or a resolving lesion in a stage of fibr- The foregoing evidence seems to indicate that in ous organization may be seen in the testis. 2-4.17 The several cases of what initially was thought to be a testicular lesions associated with retroperitoneal primary retroperitoneal germ cell tumor, a regres- germ cell tumors have been closely studied, and sing primary lesion subsequently was found in the some authors have expressed the opinion that these testicle. In other cases in which a retroperitoneal testicular lesions are highly characteristic." Furth- lesion was the presenting condition, an occult prim- ermore, a differentiation based on histologic fea- ary testicular tumor was noted. tures has been made between those lesions found However, there have been other reports 3.7-1 ° of with teratoid tumors and those occurring with retroperitoneal seminoma without a clinically rec- seminomas. ognizable testicular lesion. In some cases no lesion Azzopardi and associates 3 presented 17 cases of was palpated at physical examination of the testes,

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and none developed subsequently. In other cases, Med Bull 12:12-25, Feb 54 the homolateral testicle was examined pathologi- 5. Abell, M.R., Fayos, J.V., and 1.ampe, I.: Retroperitoneal germinomas (seminomas) without evidence of testicular involvement. cally and found to be free of lesions. The evidence in 18:273-90, Mar 65 these cases is difficult to refute, because often the 6. Howat, J.M., and Massarella, G.R.: Unusual presentation of seminoma. Br J Urol 41:89-99, Feb 69 homolateral testicle is the one involved with a re- 7. Bliss, W.R., and Barnett, W.H.: Retroperitoneal seminoma (ger- gressive lesion. The reports of pineal and anterior minoma) without evidence of testicular involvement. Am J Surg 120:363-5, mediastinal germ cell tumors lends further support Sep 70 8. Abbassian, A.: Seminoma metastatic to retroperitoneal to the theory that primary extragonadal germ cell without testicular lesion. Case report. Harper Hosp Bull 20:208-13. Sep- tumors occur. Abell and associates attempted to set Oct 62 down anatomic criteria for primary retroperitoneal 9. Phalakornkule, S., and Woodruff, M.W.: Extra gonadal retroperitoneal seminoma. J Urol 91:579-81, May 64 seminomas. 10. Kahle, P. J.: Retroperitoneal seminoma (germinoma). Report of a case, Kay and Coleman" reported duplication of an histogenic and diagnostic considerations. Am Surg 20:538-48, May 54 undescended left testicle; they said that polyor- 11. Enzinger, F.M.: Personal communication 12. Naylor, B.: Personal communication chidism can be explained by splitting of the inner 13. Dixon, FJ., and Moore, R.A.: Tumors of the male sex organs. In Atlas epithelial mass during development within the geni- of tumor pathology, Sec. 8, fascicles 31 band 32. Armed Forces Institute of tal ridge. This probably is a rare occurrence, and Pathology, Washington, D.C., 1952. 14. Friedman, N.B.: Germinoma of the pineal. Its identity with ger- development of a germ cell tumor within a dupli- minoma ("seminoma") of the testis. Cancer Res 7:363-8, Jun 47 cated undescended testicle would be rare, since dup- 15. Woolner, L.B., Jamplis, R.W., and Kirklin„J.W.: Seminoma (ger- lication of testes is much less common than primary minoma) apparently primary in the anterior mediastinum. N Engll Med 252:653-7, 21 Apr 55 retroperitoneal germ cell tumor. 16. Friedman, N.B.: The comparative morphogenesis of extragenital and An interesting point in our case was the positive gonadal teratoid tumors. Cancer 4:265-76, Mar 51 reaction for UCG, which was detected after the sec- 17. Slater, GS., Schultz, H.A., and Kreutzmann, W.B.: Occult testicular tumor. J AMA 157:911-2, 12 Mar 55 ond operation. This possibly can be explained in two 18. Kay, S., and Coleman, F.P.: Duplication of left undescended testicle. ways. The first would attribute it to the nonspecific- Report of a case. J Urol 75:815-8, May 56 ity of the UCG test, since positive results may occur 19. Hobson, B.M.: The excretion of chorionic gonadotrophin by men with testicular tumours. Acta Endocrinol (Kbh) 49:337-48, Jul 65 as a result of elevation of pituitary gonadotropin with testicular seminomas. 19 The finding at autopsy of Leydig cell hyperplasia in the left testis would Submitted for publication in February 1975. Updating, as neces- seem to support this possibility. The other possibility sary, has been done by the author. would be that small foci of chorioepithelioma were This paper was presented to the American Osteopathic College of Pathologists at their annual meeting held in Bal Harbour, present in the seminoma but not in the tissue ex- Florida, October 27-31, 1974. amined. Dr. Cohen is an associate pathologist at Detroit Osteopathic Hospital Corporation, 1. Prym, P.P.: Spontanheilung eines bosartigen, wahrscheinlich Detroit. At the time this paper was written, chorionepitheliomattisen Gewichses im Hoden. Virchows Arch (Pathol he was a resident in the Department of Anat) 265:239-58, Aug 27 Pathology under Allan R. Fox, D.O., and 2. Azzopardi, J.G., and Hoffbrand, A.V.: Retrogression in testicular Sidney J. Katz, D.O., FAOCPA. seminoma with viable metastases. J Clin Pathol 18:135-41, Mar 65 Dr. Cohen, Detroit Osteopathic Hospital, 3. Azzopardi, J.G., Mostofi, F.K., and Theiss, E.A.: Lesions of testes ob- served in certain patients with widespread choriocarcinoma and related 12523 Third Avenue, Detroit, Michigan tumors. The significance and genesis of hematoxylin-staining bodies in the 48203. human testis. Am. J Pathol 38:207-25, Feb 61 4. Rather, L.J., Gardiner, W.R., and Frerichs, J.B.: Regression and mat- uration of primary testicular tumors with progressive growth of metas- tases. A report of six new cases and a review of the literature. Stanford

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