Adenocarcinoma of the Rete Testis

THE JOURNAL OF UROLOGY

Vol. 82, No. 3, September 1959 Printed in U.S.A.

ADENOCARCINOMA OF THE RETE TESTIS SHELDON S. SCHOEN*

AND

BENJAMIN F. RUSH, JR.

From the Departments of Surgery of the Baltimore City Hospitals and the Johns Hopkins University School of Medicine, Baltimore 5, Md.

Carcinoma of tbe rete testis is one of the rarest tumors of the genital tract. Mostofi, chief of the urological section of the Armed Forces Institute of Pathology, has suggested that this may be due to the fact that their anatomical location makes detection unlikely before they have grown to a size and extent that precludes localization of their origin. Feek and Hunter, in their report of a case of papillary carcinoma of the rete testis, attempt to establish rough criteria to differentiate tumors of the rete from embryonal adenocarcinomas and teratomas of the testis. These same criteria help to separate rete tumors from those of the tunics and also from secondary tumors. They demand, in addition to appropriate histological character a) a maximum involvement of the mediastinum testis with but minimum involvement of the corpus; b) evidence of "outward" rather than "inward" growth from the mediastinum as manifested by no more than moderate compression of normal tubules; and c) growth outside the testis into the sac of the tunica vaginalis, but not outside the parietal layer of tbe tunica. Tbcse criteria outline "ideal conditions," but several of the cases reported in the literature (Dundon, Laird, Shillitoe, Willis) appear to be quite valid, even though growth bad progressed to marked invasion of tbe corpus. Whether such tumors are rarely found, or merely rarely recognized, a search of the literature has revealed only 12 cases of carcinoma of the rete testis and the validity of some of these is open to question (table 1). The small number that have accumulated since Curling reported the first case in 1853 serves to emphasize tbe rarity of the neoplasm. The following case is the thirteenth in the literature, and the oldest patient as yet reported. CASE REPORT

H. C. (B.C.H. No. 223319), an SO-year-old white man, was admitted to the Baltimore City Accepted for publication December 15, 1958. * Present address: The Department of Urology, Barnes Hospital, St. Louis, Mo. Supported in part by a grant from the American Cancer Society, Maryland Division. 356

Hospitals on January 11, 1957, for domiciliary care. His past history revealed a 5-year history of pulmonary tuberculosis, with arrest on drug therapy, and a large left "inguino-scrotal hernia" present for at least five years. Physical examination revealed occasional ralcs in the left lung, moderate cardiomegaly, and a large irreducible left scrotal mass which was somewhat cystic and felt as though it contained bowel. The right testis was normal; the left could not be palpated. An x-ray of the cbest shmved the pleural scarring of old tuberculosis. A barium enema revealed a redundant colon without abnormality. An upper gastrointestinal series revealed only a small hiatus hernia. Except for a nonprotein nitrogen determination of 43 mg. per cent, and a corrected erythrocyte sedimentation rate of 30 mm., the laboratory studies were within normal limits. The patient was asymptomatic until July 29, 1957, when he passed a large amount of bright red blood from the rectum. Digital rectal examination vrns negative and routine physical examination revealed no new findings. However, the following morning, as the patient was being prepared for sigmoidoscopy, it was noted that the left scrotal mass had increased acutely in size and was 14 by 15 by 22 cm. in diameter, tensely cystic, and moderately tender. The mass could be transilluminated, but there appeared to be two compartments. It was irreducible. On July 30, 1957, the patient was operated upon through a left inguinal incision. There was a moderate degree of weakness of the transversalis fascia, but there was no indirect hernia sac, and there was no bowel in tbe scrotum. The scrotal sac was entered from above and the hydrocele sac was aspirated of clear amber fluid, at which time it was appreciated that there definitely were two sacs. The lower sac was then aspirated, tbis fluid being cloudy and bloody. The testis and tunics were delivered and when the tunics were opened a large number of friable, grey-white papillary excrescences up to 0.5 cm. in diameter were noted on the external surface of the testis and the internal surface of the tunica vaginalis.

TABLE !I

Au th0 r

I Curling I

Cw,es found on revie'll· of

i

Aue o 0-.f Patient

s;t e OL..

11853

37

Not. stated

Orchim,tomy

HJ40

3,)"

Hight

Orchioctomy and x-ray to scrotum, abdomen and kidneys

I

Year

I

p,;;:~;d

i

Tumor

Treatment.

I Appearance of iVIetastases

I

Course and Length of Follow-Up

Comment

J\l one when last known alive

Well 6 mos. after operation and 13 mos. after appearance of tumor

None when last knowll alive

7 yrs. without recurrence

Described as a Lcnign tumor with multiple cysts. The site of cystic change is established as rote testis. Case in doubt because of obscure description. Not accepted as rete testis tumor l\lalignant transformation of lining cells in tubules at junction of rete and serniniferous tubules noted. However, case in doubt because Aschheirn-Zondek test was weakly positive 6 a11d 12 mos. after operation. Not accepted as rete testis tumor. Tumor in space between tunics and between seminiferous tubules at rete. Rete tubules filled with tumor and rete cpi theli urn seen 1n transition to tu-mor. Accepted as rete testis tumor. 1Tumor acini in mediastinurn i testis between rete tubules. Accepted as rete testis tumor.

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I 2

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Gilbert

I

I

I 3

:Feek and HuntPr

1%5

59

Left

Or chi ectomy and hydrocelectomy

None when last kno\vn alive

7 wks. after admission with cerebrovascular accident

I I 4

SraiHy and

Parham

1948

48

Right

Bilateral orchiectomy and x-ray

Pulmonary metas- Right middle lobe atelectasis was initial 1 tasis was initial finding. finding 18 wks. ' Testes were normal. before testis Bronchoscopy showed symptoms and extrinsic compression. findings Destructive lesion of 9th rib noted 7 w ks. lat.er, Testis enlarged 11 wks. after that. 1Yietastases were resistant to x-rny l)ied 10 mos. after first, .,ymptoms

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TABLE 1.-Continued Case No.

Author

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6

7

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Year

Reported

Age of Patient

Site of Tumor

Treatment

Appearance of Metastases

c.n "' 00 Course and Length of Follow-Up

Badenoch 11951 and Dukes

30

Right

Orchiectomy and x-ray

None when last known alive

Well 4 mos. after operation

Dundon

20

Not stated

Orchiectomy and x-ray

1 positive regional lymph node

Well 5 mos. after operation

I Shillitoe

I 1952 I

I 1952 I

44

31

8

I

Willis

I 1953 I

9

I

Willis

I 1953 I Not

stated

I Left

I Right

Orchiectomy; xray therapy given later after appearance of metastases.

1 supraclavicular lymph node 1 mo. after operation. Pulmonary metastasis 27:2 mos. after operation

Dysphagia and hemoptysis 2,l,1 mos. after operation. Pulmonary metastases seen on x-ray. Symptoms relieved by xray therapy. Asymptomatic 8 mos. after operation

Anti-luetic chemotherapy

Pulmonary metastases 6 mos. after operation. Widely disseminated at autopsy Not stated

Diagnosed and treated as luetic orchitis. Wassermann converted but testis continued to enlarge. Died 7 mos. after initial symptoms Invasion of cord and scrotal skin. Time and followup not stated.

Not I Orchiectomy stated

Comment

Papillary intracystic adeGrossly, nocarcinoma. tumor Ill mediastinum and spreading out toward corpus. Accepted as rete testis tumor. Testis had been undescended and was brought down to scrotum 10 years previously. Tumor described as infiltrated amidst seminiferous tubules and in continuity with rete tubules. Accepted as rete testis tumor. Papillary adenocarcinoma with transition of normal rete epithelium into tumor. Tumor infiltrated most of corpus and invaded epididymis. Isolated tumor seen in spermatic cord. Accepted as rete testis tumor. Almost entire corpus invalved in tumor. Sections do not show tumor in rete but histology is quite typical. Accepted as rete testis carcinoma. Some evidence of squamous metaplasia. Accepted as rete testis carcinoma.

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Laird

Fraser

Schoen and Rush

1953

1954

1957

1958

59

21

,n

80

Bilateral

Right

Right

Left

Bila tern! orchi .. ectomy (for alleged carci · noma of prostate)

Orchicctomy and x-ray

Orchiectomy

Orchiectomy; methotrexate (mnethopterin) given later after appear11nce of metastases.

Not stated

Not stated

1 tumor found in rnodiastirmm of one testis. 3 tumors found in other testis, only one in medi1 astinum, the others being quite far away. Histology resembles tubular adcnoma. Accepted as I rcte testis carcinoma. I No followup No fol!owup Testis was ectopic in groin. Entire tumor was within corpus. Sections do not show tumor in rete. Case in doubt because the finding of glands in epididymis lined by goblet cell epithelium suggests teratoma. Not accepted as rete testis carcinoma. None to date Papillary anaplastic epiGood health 3~~ yrs. thelial tumor intimately after operation associated with rete Case in doubt because frog test positive 3;,,z yrs. after operation. Not accepted as rete testis carcinoma. J1i ac node inDied 9 mos. after operaTumor seen in area between volvement and tion with cachexia from seminiferous tubules and wound seeding 8 metastases and toxic rete with transition to mos. after operreaction to chemotherrete epit.helium. ation apy 1

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360

S. S. SCHOEN AND B. F. RUSH, JR.

Fm. 1. Specimen removed at operation. Over external surface of tunica albuginea there were round 0.2 to 0.5 cm. solitary and confluent nodules, whitish-red in color, slightly firm in consistency, and with an irregular surface. Tunica vaginalis over its entire surface bore irregularly distributed nodules similar in character to those described on surface of tunica albuginea. The corpus testis appeared to be normal in size and consistency as was the epididymis. Frozen section examination of one of the papillary masses was reported as "malignant tumor of unknown origin." Therefore an orchiectomy with removal of the cord up to the internal inguinal ring was performed. Grossly, the specimen consisted of a left testicle with its tunics and 17 cm. of the sperma tic cord (fig. 1). The testicle measured 4.5 by 3 by 2.5 cm. Over the external surface of the tunica albuginea there were round 0.2 to 0.5 cm. solitary and confluent nodules whitish-red in color, slightly firm in consistency, and with an irregular surface. On cut section the internal surface of each of these nodules was smooth and white in color. The testis on cut section appeared light brown and soft in consistency, while the mediastinum testis was white in color and slightly firm in consistency. The septula and lobuli testis were delicate. The epididymis on cut section was irregular and brownish in color. The testis was surrounded by 3.5 by 8 cm. of tunica vaginalis. The tunica vaginalis propria over its entire surface bore irregularly distributed solitary and confluent 0.3 to

0.5 cm. nodules with characteristics similar to those of the nodules described on the surface of the tunica albuginea. The vas deferens was slightly dilated. The vessels of the cord were patent. Microscopically, an invasive tumor was found that was noteworthy for its lack of invasion of the corpus testis. Many broad-based and sessile papillary growths were seen spread over the surface of the tunica albuginea. There were many islands of tumor within the substance of the tunica albuginea, but no evidence of growth through that layer into the corpus. The tumor cells in these islands and elsewhere showed a definite tendency toward formation of ductile structures (fig. 2). Many of the ducts were irregularly branched, suggestive of rete testis morphology. Papillary formations were frequent in the lumina of these alveoli. The cells forming the ductal pattern were of moderate size with round to oval nuclei with a dark, well-defined staining characteristic, and a deeply staining cytoplasm with sharply marked cell borders. In other areas of tumor, particularly in the loose tissue of the tunica vaginalis, less well differen-

ADENOCARCINOMA OF '!.'HE RETE TESTIS

Fm. 2. X 165. Photomicrograph demonstrates section from tunica albuginea. Tumor cells show definite tendency toward formation of ductile structures. Many ducts were irregularly branched, sug gestive of rete testis morphology. Papillary formations were frequent in lurnina of these aveoli.

Fm. 3. X 165. Photomicrograph of section ta1rnn from area where rete testis and corpus testis a.re adjacent. Serniniferous tubules with suppression of spermatogenesis compatible with pat,ient's age of 80 years are seen on right side. Just to right and below midpoint of photomicrograph is re1e tubule which appears to be lined along its lower half by normal flat epithelium. In its upper lrnlf epi llrnlimn blends into an area of malignant change.

tiated growth was found with scattered irregular masses of tumor cells. The cells here had palestaining cytoplasm with irregular outlines and somewhat larger, paler nudei, some of whieh were surrounded by clear halos. Most suggestive of the site of origin of this neoplasm were areas of tumor growth in the junctional zone between the seminiferous tubules and the retc tubules. These areas were very well differentiated papillary structures with markedly irregular branching fronds. The stalks, as well as the surface epithelium, were occasionally continuous with the .adjacent normal rete structures (fig. 3). The cells

in this area of the tumor were small, with darkly staining oval and spindle-shaped nuclei. In areas the tumor epithelium bknded into the flat epithelium lining the rete tubules (fig. a). The seminiferous tubules showed depression of spermatogenesis compatible with the patient's age, Search of many sections failed to reveal any c;vi dence of teratomatous or seminonmtous growth. Final pathologic diagnosis was: Adenoeareinoma, probably of rete testis origin, involving the epididymis and the testicular tunics, but not the testis proper. In view of the patient's advanced age it was

362

S. S. SCHOEN AND B. F. RUSH, JR.

believed that no additional therapy was indicated at the time, and the patient was subsequently observed at intervals of eight to ten weeks. On March 9, 1958, he was readmitted because of marked increase in generalized ,Yeakness and the development of two skin nodules in the medial end of the old incision. Physical examination at that time revealed two masses, each 1.5 cm. in diameter, red, but with intact surface epithelium, firm, but freely movable, in the medial end of the old healed incision. A hard, fixed, lobular mass, about 8 by 10 cm. in size, was palpable deep in the left lower abdominal quadrant. The iliac and femoral arteries were palpable over the anterior surface of this mass. The liver was palpable 2 cm. below the right costal margin. The hematocrit was 27.7 per cent. An x-ray of the chest shmved no evidence of metastatic disease. Intravenous urography revealed marked lateral displacement of the left ureter at the brim of the true pelvis without obstruction, and study by barium enema showed extrinsic compression. Biopsy of the skin nodule was reported as metastatic anaplastic carcinoma, and it was felt that the left lower abdominal mass was a cluster of deep iliac lymph nodes involved in tumor and manifestly 11011-resectable. The patient's general physical condition quite rapidly deteriorated, so that on April 2, 1958, an attempt at palliation with the antimetabolite methotrexate (amethopterin) was decided upon. The drug was given by the cancer chemotherapy team at the Baltimore City Hospitals in a dose of 5 mg. per kilogram of body weight. Almost immediately the patient manifested a severe toxic reaction to the drug. His urinary output dropped off sharply and his platelet count dropped to 48,200. Within two days he began to manifest slow bleeding from the pharynx, gastrointestinal tract, and lung. This was followed by signs of acute liver failure. The platelet count remained depressed, the scrum urea nitrogen and serum bilirubin levels rose, and the patient expired on April 10, 1958. Permission for postmortem examination was refused. DISCUSSION

It was Ewing's contention that all tumors of the testis are teratomas. He stated that the area where the spermatic tubules enter the rete testis was the site of the sex cells whose normal development into spermatogonia has been sup-

pressed, but whose potencies remain intact and ready to express themselves in the various forms of teratomas. He thus felt that this area of the rete was the usual area of origin of teratoma testis and stated that tumors which apparently had one cell type were almost invariably teratomas in ,vhich the one layer had overgrown the others. We believe that the origin of the tumor reported here was in the rete because of a) the microscopic evidence of points of transition of normal rete epithelium to neoplastic cells (fig. 3), b) the lack of invasion of the corpus testis; and c) the failure to find any evidence of teratomatous elements on specific search. Clinically, this tumor must be differentiated from a secondary tumor metastatic from a primary site elsewhere in the body. While the absence of postmortem examination makes exclusion of another source impossible, we feel that the morphology and manner of growth of the tumor, coupled with the negative x-rays and other special studies, make a primary tumor almost certain. Pathologically, this tumor resembles in some respects the so-called mesothelioma. However, the fact that the tumor here described was highly malignant, that there was a strong tendency to acinar formation, particularly of the peculiar irregular spaces typical of the retc, reinforces the evidence of transition mentioned above, and points to an epithelial origin in the rete. Table 1 summarizes the previously reported cases. The youngest patient in the series was 21 years old, and the oldest, our patient, was 80. Of the cases for v,hich information is available, there were six tumors occurring in the right testis, three in the left, and one case of bilateral tumors. It is of interest that in this group of 13 cases there were two tumors in maldescended testes, one of which had been placed in the scrotum by orchiopexy 10 years previously. Five patients were treated by orchiectomy alone, while six received x-ray therapy in addition to orchiectomy. Antimetabolic cancer chemotherapy was prescribed for one patient after orchiectomy, and one patient was treated with antibiotics. The degree of malignancy of these tumors is indicated by the fact that five of the 10 cases in which some followup information is given showed metastases in less than one year. Most of the followup periods are too short for productive evaluation. Hm,:ever, 4 patients were dead in less

ADENOCARCINOMA OF THE RETE TESTIS

than one year, and the diagnoses in the 2 cases with long survival (3½ and 7 years) are in doubt because of the development of significant levels of urinary gonadotrophin following operation. SUMMARY AND CONCLUSIONS

A case of adenocarcinoma of the rete testis in an 80-year-old man, the thirteenth and oldest in the literature, is reported. The criteria applied to identify this tumor were the microscopic evidence of points of transition of normal rete epithelium to neoplastic cells, the lack of invasion of the corpus testis, and the failure to find any evidence of teratomatous elements on specific search. Review of the thirteen reported cases found in the literature suggests that this neoplasm is of a high degree of malignancy with half of the patients who were followed being dead within one year of establishment of the diagnosis. The authors would like to express their thanks for the help and counsel of Dr. Donald Mark of the Department of Pathology.

363

REFERENCES BADENOCH, A. W. AND DUKES, C.: A case of adenocarcinoma of the rete testis. Brit. J. Urol., 23: 230--232, 1951. CURLING, T. B.: Observations on cystic disease of the testicle. Medico-Chir. Trans., 36: 449, 1853. DUNDON, C.: Carcinoma of the rete testis occurring ten years after orchidopexy. Brit. J. Urol., 24: 58-63, 1952. EWING, J.: Teratoma testis and its derivatives. Surg., Gynec. & Obst., 12: 230--261, 1911. FEEK, J. D. AND HUNTER, W. C.: Papillary carcinoma arising from rete testis. Arch. Path., 40: 399-402, 1945. FRASER, W. E.: Personal communication, 1957. GILBERT, J. B.: Studies on malignant tumors of the testis. J. Urol., 43: 722-733, 1940. LAIRD, R. l\lI.: Adenocarcinoma of the excretory ducts of the testicle. J. Urol., 72: 904-907, 1954. MosTOFI, F. K.: Personal communication, 1958. ScuLLY, R. E. AND PARHAM, A. R.: Testicular neoplasms, II. Interstitial cell and miscellaneous neoplasms. Arch. Path., 46: 229-242, 1948. SHILLITOE, A. J.: Carcinoma of the rete testis. J. Path. & Bact., 64: 650--651, 1952. WILLIS, R. A.: Pathology of Tumours, 2nd ed. London: Butterworth and Company Ltd., 1953, pp. 577-578.