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ADENOCARCINOMA ORIGINATING FROM A MATURE OF THE TESTIS

Resit Dogan Koseoglu,1 Bekir Suha Parlaktas,2 Nurper Onuk Filiz,1 Fikret Erdemir,2 Nihat Uluocak,2 and Ozden Tulunay3 Departments of 1Pathology and 2Urology, School of Medicine, Gaziosmanpasa University, Tokat, and 3Department of , School of Medicine, Ankara University, Ankara, Turkey.

Malignant transformation in testicular has been reported very rarely in the literature. Al- though testicular teratomas in childhood are regarded as benign , these tumors, if left un- treated until advanced ages, may present the risk of . We report a case of differentiated originating from colonic in primary testicular teratoma.

Key Words: adenocarcinoma, malignant transformation, mature teratoma, testis (Kaohsiung J Med Sci 2007;23:265–8)

Malignant transformation of testicular teratomas has on palpation were determined in the right hemiscro- been reported very rarely in the literature. Although tum in physical examination. The right testis had a testicular teratomas in childhood are regarded as be- consistency of alternating hard and soft areas. Scrotal nign neoplasms, these tumors, if left untreated until ultrasonography (US) revealed an increase in the size advanced ages, may present the risk of malignant of the right testis and there was a diffuse hypoechoic transformation [1]. Teratomas, localized especially in pattern with extensive punctuated calcifications in the the retroperitoneum and , can undergo parenchyma of the right testis. Dimensions of the testis malignant transformation via induction of chemother- were 47 × 47 × 37 mm. Lobulated hypoechogenic areas apy and radiation [2,3]. But malignant transformation were also observed in the upper and lower poles of the in testicular teratoma cases that had not faced any right testis on US. Scrotal US findings were concor- radiation or received any are extremely dant with a testicular tumor. His past medical history rare [2]. was unremarkable. There was no history of trauma or We report a case of differentiated adenocarcinoma any other disease. Serum α-fetoprotein and β-human that originated from colonic glands in the primary chorionic gonadotropin (β-HCG) levels were within testicular teratoma. normal limits. Clinical and radiologic search for any primary malignant disease was unrevealing. With the diagnosis of a primary testicular tumor, right high CASE PRESENTATION inguinal orchiectomy was performed. The orchiectomy specimen included a testis that A 38-year-old male patient was admitted to the measured 5.5 × 3.5 × 3 cm. An irregular mass of size Department of Urology with a swelling in his right 2.5 × 2 × 1.5 cm protruding from the tunica albuginea scrotum for 2 days in March 2004. Pain and sensitivity was noted. Sections of the testis demonstrated an intra- testicular tumor, 3 × 2 × 1.3 cm in size, connected with this extratesticular tumoral protrusion (Figure 1A). The Received: August 1, 2006 Accepted: September 11, 2006 tumor consisted of lobulated solid white and cystic Address correspondence and reprint requests to: Dr Resit areas. The noncystic tumor demonstrated a Dogan Koseoglu, Department of Pathology, School of Medicine, Gaziosmanpasa University, Tokat, Turkey. few calcified foci, and were filled with extensive E-mail: [email protected] yellowish-tan necrotic material (Figure 1B).

Kaohsiung J Med Sci May 2007 • Vol 23 • No 5 265 © 2007 Elsevier. All rights reserved. R.D. Koseoglu, B.S. Parlaktas, N.O. Filiz, et al

A B

Figure 1. (A) The tumoral mass projecting outside the tunica albuginea in the right orchiectomy. (B) Intratesticular component of the tumoral lesion consisting of lobulated, solid, white-brownish (arrows) and cystic areas in the cut section of the testis. Note the extensive yellowish-tan necrotic material in the cysts (arrowheads).

A B

C D

Figure 2. (A) Low power appearance of the tumor shows extensive necrotic areas (hematoxylin & eosin [H&E], 8×). (B) Cystic com- ponent of the tumor neighboring the parenchyma of the testis (H&E, 16×). (C) Cryptic and glandular structures with dysplastic char- acter, resembling colonic crypts in solid areas of the tumor (H&E, 80×). (D) Cytologic and architectural atypia concordant with adenocarcinoma in most areas of the tumor (H&E, 160×).

Microscopic features the tumor (Figure 2D). Mucicarmine and periodic The cysts of the tumor were filled with necrotic debris acid-Schiff-positive intracytoplasmic material was (Figure 2A). The lining of the cysts, forming papillae- present. like projections and rarely nestings, was intestinal Immunohistochemical (IHC) studies using the type columnar (Figure 2B). Beneath this streptavidin–biotin peroxidase method along with ap- columnar epithelium, normal or dysplastic intestinal propriate positive and negative controls revealed crypts and glandular structures with goblet cells that the tumor cells stained for carcinoembryonic were found (Figure 2C). In solid tumoral areas, antigen (CEA) (Monoclonal, Clone 85A12, Novocastra, atypical glandular organization was noted. Stromal 1/150), antigen 19-9 (CA 19-9) (Monoclonal, infiltration of atypical glands in a few foci was Clone C241:5:1:4, Novocastra, 1/200) and cytokeratin observed. Cytologic and architectural atypia, which 20 (CK20) (Monoclonal, Clone CK205, Novocastra, was more evident focally, was present in most of 1/50) (Figure 3). However, tumor cells were negative

266 Kaohsiung J Med Sci May 2007 • Vol 23 • No 5 Adenocarcinoma originating from testicular teratoma

A B C

Figure 3. (A) Focal cytokeratin 20 positivity in the columnar epithelium of the tumor (3-amino-9-ethylcarbazole, AEC, 40×). (B) Extensive and strong reactivity for cancer antigen 19-9 in the tumor (AEC, 160×). (C) Weak, widespread for in the columnar epithelium covering papillary configurations and lumen of cystic structures in the tumor (AEC, 200×). for cytokeratin 7 (CK7) (Monoclonal, Clone LP5K, cystic teratomas that have undergone malignant trans- Novocastra, 1/10). formation was reported as 6.8% in the literature [5]. On the basis of histopathologic and IHC findings, Despite the frequent demonstration of gastrointestinal the case was accepted as adenocarcinoma of gastroin- epithelium in ovarian mature cystic teratomas, adeno- testinal type, resembling colon cancer. The stromal infil- originating from the gastrointestinal epi- tration of atypical glandular structures in a few foci and thelial component is extremely rare [4]. Ueada et al [7] protrusion of the tumor from the tunica albuginea were reported a case of mucinous adenocarcinoma that de- the evidence of on histopathologic basis. veloped from ovarian mature cystic teratoma in 1993. As there was no sign and finding of another malignant We also found one more case of mucinous adeno- neoplastic disease, the tumor was accepted as primary carcinoma arising from the gastrointestinal epithelial testicular . Due to the observation of intestinal component of benign cystic teratoma of the in crypts and glandular structures in atypical appearance the literature, which was reported by Fishman et al [4]. and the existence of cystic growing pattern in the Malignant transformations arising from mature tumor, we suggest that the tumor in the right testis of teratomas in extraovarian sites are rare [3]. Chemo- our patient is an adenocarcinoma that originated from therapy or radiation (radiotherapy or other sources) primary testicular mature teratoma. The patient was is blamed to the malignant transformation observed closely followed up for 29 months and no recurrence in mature teratomas. Mature teratomas in mediastinum and metastatic disease was reported during that period. and retroperitoneum are especially sensitive to the transforming effect of chemotherapy or radiation [2,3]. Teratomas in these locations most commonly over- DISCUSSION grow into sarcomatous elements via induction of chemotherapy or radiation [3]. In addition, mature Teratomas and other tumors can occasionally teratomas in metastases of treated testicular germ cell undergo transformation into somatic type malignant tumors also have a predisposition of transformation tumors [2]. The term “teratoma with malignant trans- to sarcomatous tumors. TMT seen at metastatic sites formation (TMT)” is used to describe these nongerm of a testicular is also thought to be cell tumors arising within the teratomas [3]. TMT is a induced by chemotherapy or radiation [4]. However, well-known of mature cystic teratoma of adenocarcinomatous transformation in mediastinal, the ovary. Malignant changes have been reported in retroperitoneal, intracranial, sacrococcygeal teratomas 1.8–1.9% of ovarian mature cystic teratomas [4,5]. The and metastatic testicular teratoma is very rare [3]. The malignant change that occurs most frequently in ma- occurrence of adenocarcinomatous transformation in ture teratomas of the ovary is primary mature teratoma of the testis is exceedingly [2]. This is followed by tumor and adenocar- rare. To our knowledge, only two cases of adenocar- cinoma, respectively [6]. Adenocarcinoma originating cinoma arising from primary mature teratoma of the from ovarian mature cystic teratoma is very rare [2,4]. testis have been reported in the literature. The year of The frequency of adenocarcinoma in ovarian mature publication of both case reports was 2003. The cases

Kaohsiung J Med Sci May 2007 • Vol 23 • No 5 267 R.D. Koseoglu, B.S. Parlaktas, N.O. Filiz, et al reported by Kasai et al [2] and Asano et al [1] were adenocarcinoma determined in their case was sug- 52- and 55-year-old men, respectively. Their scrotal gested on the basis of routine histologic features. masses had been present since childhood. These cases TMTs are chemoresistant and prognosis depends had not received any previous treatment for their on the nature of the malignant elements. Surgical resec- scrotal masses. Adenocarcinomatous transformation tion is the main therapy [2]. Adenocarcinoma usually determined in testicular teratomas of both cases was behaves aggressively. The authors note that chemo- accepted as “de novo TMT” by the authors [1,2]. therapy- or radiation-induced TMT is generally aggres- TMT appears in two different clinical and patho- sive, whereas de novo TMT occurs in older patients logic conditions. Clinical conditions are: (1) chemother- with teratomas of long-standing duration and follows apy- or radiation-induced TMT and (2) de novo TMT. a more benign course [3]. Pathologic mechanisms that are responsible for the According to the literature, our patient was the third development of TMT are: (1) malignant differentiation case of TMT to show adenocarcinomatous trans- of the totipotential germ cell to neoplasia of the somatic formation in primary testicular teratoma. A unique type and (2) malignant transformation of the preexist- feature of this case was the younger age at presenta- ing mature teratoma elements [2]. De novo TMT occurs tion compared to the other two previously reported in older patients with a long-standing mature teratoma cases. Histopathologically and immunohistochemi- [2,3]. Kasai et al [2] and Asano et al [1] suggested that cally, we determined that the adenocarcinoma in the the adenocarcinoma in their cases occurred via malig- testicular teratoma of our case originated from colonic nant transformation of the gastrointestinal epithelial glandular epithelium. Like the other authors, we also component of preexisting testicular mature teratoma. suggest that the malignant transformation occurred The definition of the adenocarcinoma origin is de novo in the mature gastrointestinal epithelial com- meaningful therapeutically and prognostically. But it is ponent of the primary testicular teratoma as our pa- mostly difficult to determine the origin of adenocarci- tient had not received any chemotherapy or radiation in TMT on the basis of routine histologic fea- therapy previously. tures. The immunohistochemistry, particularly CK immunostaining, may be helpful in revealing the ori- gin of adenocarcinoma. arising from REFERENCES the epithelium of are generally negative for CK7. In contrast, adenocarcinomas of the 1. Asano T, Kawakami S, Okuno T, et al. Malignant trans- lung, , breast, and female genital tract are pos- formation in a mature testicular teratoma left untreated for more than 50 years since childhood. Scand J Urol itive for CK7. Immunostaining that is positive for CK20 Nephrol 2003;37:177–8. and negative for CK7 suggests a gastrointestinal origin. 2. Kasai T, Moriyama K, Tsuji M, et al. Adenocarcinoma Positivity for both CK20 and CK7 indicates ovarian arising from a mature cystic teratoma of the testis. Int J adenocarcinoma. Immunostaining for CK20 and CK7 Urol 2003;10:505–9. is considered to be helpful in separating the origin of 3. Murphy DP, Bancila E, Ciocca RG, et al. Adeno- carcinoma arising within a testicular . Urology adenocarcinoma [2]. However, other IHC markers may 1998;51:632–4. also be used for determination of the adenocarcinoma 4. Fishman A, Edelstein E, Altaras M, et al. Adeno- origin and combined IHC analysis may give an oppor- carcinoma arising from the gastrointestinal epithelium tunity for a better definition of the adenocarcinoma ori- in benign cystic teratoma of the ovary. Gynecol Oncol gin. The combined positive immunostaining of CEA, 1998;70:418–20. 5. Sumi T, Ishiko O, Maeda K, et al. Adenocarcinoma aris- CA 19-9 and CK20 strongly suggests the diagnosis of ing from respiratory ciliated epithelium in mature ovar- colonic adenocarcinoma [4]. Adenocarcinoma cells ian cystic teratoma. Arch Gynecol Obstet 2002;267:107–9. arising from primary testicular mature teratoma in the 6. Chapter 19–Female Reproductive System: Ovary- case reported by Kasai et al [2] showed positivity of Tumors-Germ cell tumors-Somatic type tumors devel- epithelial membrane antigen, CEA and CK20, while oping in mature cystic teratoma. In: Rosai J. Rosai and th the cells were negative for CK7 [2]. IHC analysis was Ackerman’s Surgical Pathology, Volume 2, 9 edition. New York: Mosby, 2004:1689. not performed in the case of adenocarcinoma originat- 7. Ueada Y, Fijita M, Ogawa H, et al. Adenocarcinoma in a ing from primary testicular mature teratoma reported benign cystic teratoma of the ovary: report of a case with by Asano et al [1]. The gastrointestinal origin of a long survival period. Gynecol Oncol 1993;48:259–63.

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