INTRATESTICULAR PAPILLARY MUCINOUS CYSTADENOCARCINOMA* AHMAD ELBADAWI, M .D. MARIANA M . BATCHVAROV, M .D . CHARLES A . LINKE, M .D . From the Department of Pathology and Division of Urology, University of Rochester Medical Center, Rochester, New York
ABSTRACT - The first case of intratesticular papillary mutinous cystadenocarcinoma is described . The tumor was histopathologically different from other types of papillary carcinoma related to the testicle and is believed to have originated from an intratesticular mullerian duct remnant .
Papillary cystadenocarcinomas of nongerminal origin have never been reported as intratesticular neoplasms . Those of rete testis origin primarily involve the mediastinum testis and grow outward into the tunica vaginalis sac with minimal involvement of the corpus testis .' The exceedingly rare papillary adenocarcinoma of the appendix testis projects from the upper pole of the testicle into the cavity of the tunica vaginalis, metastasizes to the tunica vaginalis without involvement of either epididymis or testicular parenchyma, and has an oviduct-type epithelium ."' Teiluma depicts a unique paratesticular papillary cystadenocarcinoma with psammoma bodies similar to the ordinary ovarian papillary serous cystadenocarcinoma . Herein we report the first case of intratesticular papillary mucinous cystadenocarcinoma, and discuss its histogenesis in relation to the normal as well as the vestigial epithelial components of the testicle . Case Report A sixty-year-old white man presented with enlargment of the left testicle which had been discovered recently by the family physician on *Supported Fund.
the Henry C, Buswell
routine physical examination . There was no past history of trauma, disease, or operation in the scrotal region, and the past medical history was negative . On physical examination there were a blood pressure of 110/80 mm . Hg, normal vital signs, normal head and neck, chest, and abdomen, and no abnormal rectal findings . The left testicle was enlarged, firm, and nontender, with no transillumination . The scrotal skin, right scrotal contents, and left epididymis, spermatic cord, and inguinal region were normal . Chest x-ray film, urinalysis, blood analysis, and SMA 12 values were normal . Based on the clinical diagnosis of a testicular tumor, the left scrotal contents were exposed through an inguinal incision . The inguinal spermatic cord was clamped with a rubbery shod clamp, and the intrascrotal structures were examined . The left testicle was enlarged by a mass occupying roughly its central two-thirds . A left orchiectomy, including the spermatic cord to the level of the internal inguinal ring, was performed . A direct inguinal hernia was repaired, and the incision was closed . The postoperative course was uneventful except for a subcutaneous wound infection that was rapidly controlled by drainage and antibiotics . Based on the histopathologic diagnosis of an intratesticular malignant epithelial neoplasm, the patient was subjected to further evaluative
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FIGURE L Cystic neoplasm (N; outlined by arrows) occupies central two thirds of testicle, has pearly white wall ; and contains mucoid material . E : caput epididynddes ; T: residual testicular parenchyma at each pals ; M : mediastinum testis; SC : spermatic cord, loner end ; V: reflected tunica vaginalis .
studies postoperatively . An intravenous pyelogram, cystourethroscopy, lymphangiogram, gastrointestinal tract study, and metastatic survey (brain, liver, spleen, and bone scans) were n ;gative . Without the benefit of previously reported experience with a similar tumor, retroperitoneal lymphadenectomy was performed six weeks after orchiectomy . All twenty-eight lymph nodes dissected from the specime-a were free of tumor . The postoperative course was uneventful . At his last follow-up examination, two years later, the patient continued to maintain good health without any abnormal findings in the scrotum, abdomen, or chest . Pathalot .1 The orchiectomy specimen consisted of a 5 by 3 .5 by 2.5-cm . testicle, with its tunical covering, epididymis, and a 13-cm . long segment of spermat c cord attached . The tunica vaginalis was incised and reflected around the epididymis and lo'; er cord . The tunica albuginea was grayish white and smooth with normal vascular marking s . The parietal tunica vaginalis, epididymis . and spermatic cord had normal gross appearance and consistency . A moderately firm mass . with borders ill defined to palpation, and opaque to transillumination, replaced the
equatorial two thirds of the testicle . On coronal bisection of the gonad along its anti-epididymal border, this mass was found to be a 3 by 2 by 2-cm . multilocular cyst filled with viscid greenish yellow mucoid material containing innumerable silvery white flakes (Fig- 1) . Vertically, the mass extended internal to the mediastinum testis from just beneath the- level of the caput epididymides to a short distance from the inferior pole of the testicle, Residual testicular parenchyma, with large whitish areas of lost architecture and poor stringing effect, was identified as a narrow crescentic ca ;> over the mass at each testicular pole (Fig_ I . In a transverse direction, the mass eshr'nded obliquely across the equator testis, from the mediastinum to the free border, where it was covered by an intact tunica albuginca v ithout discernible intervening testicular pin vii( hyena . The cystic mass was multilocular with freely communicating compartments, and had a pearly white, 1 to 1 .5-mm . thick rigid wail, with a wrinkled and multifocally papillary lining . The tumor did not encroach on either epididymis or spermatic cord, both of which had n-Mmalappearing cut surfaces at several levels . With the belief that we were dealing v'ith an exceedingly unusual testicular tumor, the entire testicle and epididymis were sectionedi after formalin fixation at intervals of 5 rune_, and a total of 32 blocks were submitted for histologic examination . Serial hematoxvlu-eosin sections, and sections stained with per odtc acidSchiff (PAS), diastase-PAS, Kreyberg, F1badawi hexaehrome,s and modified Riley re'iculin stains, were obtained from several blocks of tumor . Microscopic examination co,nfirmrd the truly intratesticular location of the tumor, its multilocular cystic structure, and its grossly observed spatial relationships to Manors anatomical testicular landmarks . The mass had a well-defined fibrous wall except at its epididymal border . where it was walled off by compressed structures of' the mediaartinum testis . At the free border of the tcstic e, the mass was covered by an intact tunica adbuginea, with a tenuous intervening zone of in aiinized testicular parenchyma . The residual I'ipolar testicular parenchyma was largely li} ahnized . with some scattered islands of pre erved spermatogenic tubular structure . Both epididymis and spermatic cord were histok-gically normal . The tumor mass had an irregular distr!bution of four different types of lining, with transition
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Section of neoFIGURE 2 . plasm at level of caput epic didymides (E), neoplasm (N) is cystic and multilocular, has well-defined fibrous capsule (C) except in vicinity of mediastinum testis (M), is independent of tunics albuginea (A), rete testis tubules (R), and ductuli efferentes (D) ; its epithelial lining has multifocal papillary projections; parts of cystic tumor wall contain abundant cholesterol clefts beneath epithelial lining (arrow) . Adjacent testicular parenchyma (T) is considerably hyalinized .
from one to the other (Fig . 2). The predominant type was an anaplastic pseudostratified columnar epithelium, which was slightly corrugated or papillary (Fig . 3A) . The component cells were tall columnar with moderately defined borders, eosinophilic partially vacuolated cytoplasm, and moderately pleomorphic, 12-20 µm. spherical, ovoid, or elongated nuclei . Many cells contained acidic mucin secretary material (Fig . 3B) . The mitotic index averaged 1 per cent, with occasional atypical forms . In some areas the lining was identical to that of ovarian mucinous cystadenoma with benign tall columnar mucin-secreting epithelium . The cells were uniform, had basal nuclei and mucin-containing apical cytoplasm, and focally displayed abrupt transition to the anaplastic pseudostratified epithelium already described (Fig . 3C) . In other areas no epithelium was discernible, the cyst being lined by loose fibrous tissue, riddled with cholesterol clefts, open-ended vascular channels, mononuclear inflammatory cells, erythrocytic extravasates, hemosiderin deposits, and multinucleate giant cells (Fig . 3D) . Similar tissue extended beneath some epithelialized areas of the tumor cyst wall (Fig . 2) . In a few foci, there was a benign pseudostratified columnar ciliated epithelium with frequent apical secretory cupolas, similar to that of the oviduct (Fig . 3E) . There was no stromal (capsular) invasion by malignant epithelial elements, no epithelial or mesenchymal teratomatous component, no communication between the tumor lining and testicular tunics, appendix testis, rete testis tubules, ductuli efferentes, or epididymal tubules, and no invagination of either tunica
albuginea or tunica vaginalis . In view of these negative findings, and in the absence of evidence of a mucinous carcinoma of any kind elsewhere in the patient's body, the tumor was diagnosed as a low-grade papillary mucinous cystadenocarcinoma of the testicle . Comment Despite the lack of stromal invasion, an important criterion in the diagnosis of ovarian cystadenocarcinoma,e the tumor epithelium in our case displayed sufficient cytomorphologic atypia to be considered malignant. As such the tumor represents the malignant counterpart of the unique intratesticular papillary cystadenoma described by Herschman and Ross 7 in a fiftysix-year-old man . A histologically similar epididymal carcinoma was described by Abell and Holtz 9 in a sixty-six-year-old man . Histologic examination of the tumor in our case provided no definitive clues as to the histogenesis of the tumor. However, several possibilities may be considered . Germinal origin as a one-sided differentiation of a malignant teratoma cannot unequivocally be ruled out, but is unlikely in view of the patient's age, the lack of any epithelial component other than the mucinous carcinomatous epithelium, and the absence of ectoderm- or mesoderm-derived elements in the tumor . Origin from the visceral tunica vaginalis, in a manner analogous to the development of ovarian cystadenoma and cystadenocarcinoma from germinal epithelium of the ovarian serosa, 9 may be suggested by the histopathologic characteristics of the tumor . However, this is
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FIGURE 3 . (A) Ana plastic pseudostratified columnar epithelial lining with papillae and pseudo gland formation ; nui^ay cells have vacuolated or clear cytoplasm and some are in mitosis (arrows) . Hemnto .eyiin-eosin (HE); scc ..le = 50 µm . (B) Anaplastic pseudostratified columnar epithelial lining with arborescent and fusing papillae: many cells contain acidic mucin secretion (bright blue) . Kreyberg stain ; scale = 100 ic'n ; (. ) Focus of abrupt transition from benign mucin-secreting columnar epithelium (right) to anaplastic pseudrrstratified columnar epithelium (left) . HE ; scale = 50 µm . (D) Focus in cyst wall lined by fibrous tissue containing eholesteral clefts, mononuclear inflammatory cells, erythrocytic extravasate, and multinucleate giant cells (arrows, , HE ; scale = 50 µm . (E) Focus of benign oviduct-type epithelium ; columnar cells have foamy cytoplasm with apical cilia or secretory cupolas . HE ; scale = 50 µm .
improbable in the absence of a demonstrable connect%on between the tumor and tunica vaginalis, and of a tumor-related invagination or dimpling of this tunic . Origin from the rete testis is equally improbable since the tumor does not fulfill any of the criteria indicative of such derivation, namely, (1) demonstrable direct transition between the
tumor and normal rote tubular epithelium ; (2) predominant growth within the medastinum testis with no or minimal involvement of the corpus testis ; and (3) "`outward" growth into the cavity of the tunica vaginalis . 1 .10- 'L Origin from the ductuli efferentes iaay be suggested by the focal presence 4 P5enign columnar ciliated epithelium - similar to that
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normally lining these ducts - in direct transition to malignant epithelium . However, tumors originating in the ductuli efferentes, classically exemplified by papillary cystadenoma of the epididymis, 1346 are known to : (1) grow primarily within or adjacent to the globus major epididymides without involvement - but may be compression - of the corpus testis ; (2) be associated with ectatic or microcystic ductuli efferentes with transition within the ductuli from normal to neoplastic epithelium ; and (3) have a clear cell component with occasional eosinophilic nonmucinous thyrocolloid-like material within the cytoplasm. The remaining possibility, namely, origin from a mullerian vestige thus appears to be the most plausible . Such a derivation would explain the intratesticular location of the tumor along the mediastinum testis and caudal to the testiculoepididymal junction, its independence of the rete testis, ductuli efferentes, and testicular tunics, its close histologic resemblance to primary ovarian mutinous cystadenocarcinoma, and its residual benign ciliated epithelium similar to that of the oviduct (Fallopian tube) . The appearance of abundant cholesterol clefts in some portions of the tumor wall is similar to that observed in the wall of some appendix testis cysts . 17 Although the appendix testis is the most frequently encountered mullerian remnant, obviously it is not the origin of the tumor we are reporting . Though complete obliteration of the more caudal part of the mullerian duct is the rule, exceptional specimens contain patent (tubular) duct segments . These are independent of gonadal tunics, spermatogenic tubules, and ductuli efferentes, and follow a line extending along the testiculoepididymal groove from the base of the appendix testis to a level as high as the ductuli efferentes and as low as the distal part of the corpus epididymides .'s Sundarasivarao mentioned that a persistent duct may become distended with mucoid material,' 8 an expression of the inherent mucosecretory capability of mullerian epithelium . It seems most likely, therefore, that the tumor herein described originated from a nonobliterated (tubular) mullerian duct vestige . As such it represents a hitherto unrecognized type of testicle-related papillary cystadenocarcinoma, distinguishable by its unique intratesticular spatial relationships from the equally rare but well-documented tumors of similar growth pattern arising from the rete testis, appendix testis, or epididymal parenchyma .
Confinement of the tumor by a well-defined fibrous capsule around most of its circumference, and its low grade of malignancy, would suggest a less ominous prognosis than that known of adenocarcinoma of the rete testis . 1z•'a Our patient is alive and tumor-free two years after orchiectomy. The analogous epididymal carcinoma reported by Abell and Holtzs neither recurred nor metastasized after orchiectomy, and the patient died of gastric carcinoma ten years later . The treatment plan of intratesticular mucinous cystadenocarcinoma, particularly the role of retroperitoneal lymphadenectomy, irradiation and/or chemotherapy, must remain a matter of individual decision, until a sufficient number of cases have been accumulated . Department of Pathology State University of New York Upstate Medical Center Syracuse, New York 13210 (DR. ELBADAWI) References 1 . Feek JD, and Hunter WC : Papillary carcinoma arising from rete testis, Arch . Pathol. 40: 399 (1945). 2 . Bailer CN, Willis BA, and Wilson IV: A case of adenocarcinoma of the appendix testis, J . Pathol . Bacteriol . 69; 326 (1955) . 3 . Olesen H: Quoted by Teilum C, in : Special Tumors of Ovary and Testis, Philadelphia, J . B . Lippincott Co ., 1976, p. 466 . 4 . Teilum G ; Special Tumors of Ovary and Testis, Philadelphia, J . B. Lippincott Co., 1976, p. 469 . 5. Elbadawi A : Hexachrome modification of Movat's stain, Stain Techn . 51 : 249 (1976) . 6 . Hart WR, and Norris HJ ; Borderline and malignant mutinous tumors of the ovary, Cancer 31 : 1031 (1973) . 7. Herschman BR, and Ross MM : Papillary cystadenoma within the testis, Am . J . Clin, Pathol. 61: 724 (1974) . S . Abell MR, and Holtz F ; Testicular and paratesticular weplume in patients 60 years of age or older, Cancer 21 : 852 (1968) . 9 . Woodruff JD, and Novak ER : Papillary serous tumors of the ovary, Am. J . Obstet . Gynecol . 67: 1112 (1954) . 10 . Schoen SS, and Rush BF, Jr : Adenocarcinoma of the rote testis, J . Urol. 82: 356 (1959). 11 . Whitehead ED, Valensi QJ, and Brown JS : Adenocaminoma of the rete testis, ibid. 107: 992 (1972) . 12 . Turner RW, and Williamson J : Adenocarcinoma of the rete testis: report of a case, ibid . 109: 850 (1973) . 13 . Hill RB, Jr : Bilateral papillary, hyperplastic nodules of epididymis, ibid. 87: 155 (1962). 14. Chan Y-H, Schinella RA, and Draper JW : Papillary clear cell cystadenoma of the epididymis, ibid. 100: 661 (1968). 15 . Price EB : Papillary cystadenoma of the epididymis . A clinicopathologic analysis of 20 cases, Arch . Pathol . 91 : 456 (1971) . 16. Tsuda H, et al : Familial bilateral papillary cystadenoma of the epididymis, Cancer 37 : 1831 (1976) . 17 . Herbut P : Urological Pathology, London, Henry Kempton, 1952, vol. 2, pp. 1058-1059, 18 . Sundarasivarao D : The miillerian vestiges and benign epithelial tumors of the epididymis, J . Pathol . Bacterial. 66 : 417 (1953) . 19. Schapira HE, and Engel M : Adenocarcinoma of rete testis, N .Y . State J . Med . 72 : 1283 (1972).
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