Tumors of the Testis

and Pilar González-Peramato²

(1)

Department of Anatomy, Histology and Neuroscience, Universidad Autónoma de Madrid, Madrid, Spain

(2)

Department of Pathology, University Hospital La Paz, Universidad Autónoma de Madrid, Madrid, Spain

5.1 Ovarian Epithelial-Type Tumor

5.2 Juvenile Xanthogranuloma

5.3 Vascular Tumors

5.4 Other Tumors

Keywords

Testicular neoplasmsTesticular ovarian epithelial-type tumorTesticular juvenile xanthogranulomaTesticular hemangiomaTesticular adrenal rest tumorIntratesticular inflammatory myofibroblastic tumorLow-grade myxofibrosarcoma of the testisMyxoid neurofibroma of the tunica albugineaIntratesticular mesothelial cyst

Under this umbrella term, there are very diverse entities that only share their absolutely no relationship with germ cell tumors nor with those of the gonadal stroma. Even within the diversity of the entities, it is possible to clearly differentiate four groups of tumors: ovarian epithelial-type tumors, juvenile xanthogranuloma, vascular tumors, and other tumors. Examples of tumors reminiscent of the tumors of the epithelial-like ovarian surface include an example of each of the following entities: serous cystadenoma, serous borderline tumor, serous cystadenocarcinoma, and endometrioid adenocarcinoma. In the subgroup of juvenile xanthogranuloma, an example of this tumor is included in the pediatric age and another one in the adult with its peculiar differential diagnoses. The subgroup of vascular tumors is represented by three cases: the first one a capillary hemangioma, the second one a hemangioma in the pubertal age with macroorchidism, and the third one a curious case of diffuse hemangiomatosis of the testicle. The fourth subgroup consists of examples of each of the following entities: testicular adrenal rest tumor, intratesticular inflammatory myofibroblastic tumor, low-grade myxofibrosarcoma of the testis, myxoid neurofibroma of the tunica albuginea, and intratesticular mesothelial cyst.

5.1 Ovarian Epithelial-Type Tumor

Case 79. Nonpapillary Serous Cystadenoma of the Epididymis

Clinical case. A 51-year-old patient with a slowly increased left testicle. The testicular tumor markers were negative. The ultrasonography revealed a paratesticular unilocular cystic lesion, 4 cm in diameter, and multiple small cystic formations in the head of the epididymis.

Pathological findings. The wall of the cystic formation is lined by a columnar epithelium with some ciliated cells of elongated and hyperchromatic nuclei and apical snouts. The cytoplasm frequently possesses subnuclear vacuoles. Groups of cells of pale cytoplasm and spherical nucleus are observed focally, located in depressions of the epithelium. The epithelium rests on a thick fibrous wall. Peripherally, in some sections, ducts of the epididymis are recognized. No sperm is observed in the cyst fluid. The epithelial cells express CK7, vimentin, EMA as well as receptors for estrogen and progesterone. They are negative for CD10, CK20, and calretinin. A cystic transformation of the rete testis is observed at the level of the head of the epididymis and upper pole of the testicle.

../images/471462_1_En_5_Chapter/471462_1_En_5_Figa_HTML.jpg — Fig. 1

Longitudinal section of the testicle. At an epididymis level, there is a cystic formation larger than the testicle. The extratesticular rete testis shows a marked cystic transformation

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The wall of the cyst has a fibrous capsule in whose thickness sections of several ducts are observed

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The epithelium shows scalloped surface. There are sections of efferent ducts on the wall

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Although the epithelial surface is very irregular, infiltration of the fibrous wall is not observed

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The collapse of the cyst wall, where the capsule is thinner, allows the appearance of folds, which give a false image of papillary structures

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Columnar epithelium with some ciliated cells. Isolated ovoid or spherical cells of clear cytoplasm are observed between these cells

../images/471462_1_En_5_Chapter/471462_1_En_5_Figg_HTML.jpg — Fig. 7

Cells with alternating spherical and euchromatic nuclei are observed in the pseudostratified epithelium. Other cells, also columnar, have elongated and hyperchromatic nuclei. Note the absence of atypia

../images/471462_1_En_5_Chapter/471462_1_En_5_Figh_HTML.jpg — Fig. 8

Focally, in the thickness of the cylindrical epithelium, there are nests of cubic cells with spherical nucleus and pale cytoplasm. These cell groups are located deeply and most of the time they do not reach the lumen

Comment. The cystic formation meets the morphological and immunohistochemical characteristics of a serous cystadenoma of the epididymis. It is a benign neoplasm of Müllerian origin. It is a very uncommon neoplasm: half a dozen cases have been reported. The age of presentation varies from 12 to 64 years. In one case, it has been described associated to bilateral Sertoli cell adenomas in a patient with CAIS. The mucinous cystadenoma of the testicle and paratesticular structures is even less frequent. It is important to keep this tumor in mind when diagnosing testicular and paratesticular cystic lesions, as a simple excision is curative. The differential diagnosis must be considered with borderline variants and other cystic formations such as spermatoceles and mesothelial cysts.

References

1.

Fernandez-Aceñero MJ, Renedo G, Fortes J, Manzarbeitia F. Non-papillary serous cystadenoma of the epididymis: cases of a rare entity.Urology. 2010;75:563–5.
2.

AbdullGaffar B, Al-Hasani S, El-Fayomy A. Multiple bilateral nonpapillary serous cystadenoma of the epididymis. Urology. 2013;82:e24–5.
3.

Fernandez-Vega I, Santos-Juanes J, García-Pravia C. Bilateral Sertoli cell adenoma in gonads, associated with serous cystadenoma. Pol J Pathol. 2014;65:154–6.
4.

Kim G, Kwon D, Na HY, Kim S, Moon KC. Mucinous cystadenoma of the testis: a case report with immunohistochemical findings. J Pathol Transl Med. 2017;51:180–4.
5.

Draeger DL, Kraeft SK, Protzel C, Hakenberg OW. A paratesticular multicystic tumor of the tunica vaginalis testis as rare paratesticular cystadenoma. Urol Int. 2018;101:245–8.

Case 80. Serous Borderline Cystadenoma of the Testis

Clinical case. Adult patient with tumor in the left testicle. The rest of the clinical data are unknown.

Pathological findings. Most of the testicular parenchyma is taken by a large cystic formation. The largest diameter reached 3.5 cm. In the inside, it contains many papillary projections that branch roughly. All of them have a thick connective axis and an epithelial lining. The height of the epithelium varies from cubic to pseudostratified cylindrical. The nuclei range from spherical and pale to elongate and hyperchromatic with slight atypia. The tumor is externally delimited from the testicular parenchyma by a thick capsule. In the albuginea, there is a cyst without papillae covered by an epithelium similar to that of the tumor. Epithelial cells express AE1/AE3, PAX8, and have estrogen and progesterone receptors.

../images/471462_1_En_5_Chapter/471462_1_En_5_Figi_HTML.jpg — Fig. 1

Cross-section of the testicle. The tumor takes most of the section. It is cystic and shows many papillae inside. Periferically, it has a capsule of connective tissue that comes to rest on the albuginea. There is a cystic formation in the thickness of the albuginea

../images/471462_1_En_5_Chapter/471462_1_En_5_Figj_HTML.jpg — Fig. 2

The epithelium of the cyst is of irregular height from cylindrical to pseudostratified. It rests on a thick capsule. On the outside, in the testicular parenchyma, some tubules with spermatogenesis are still preserved

../images/471462_1_En_5_Chapter/471462_1_En_5_Figk_HTML.jpg — Fig. 3

Thick papillae branching arborescently protrude from the wall

../images/471462_1_En_5_Chapter/471462_1_En_5_Figl_HTML.jpg — Fig. 4

The epithelium of the cyst wall and that of the papillae is similar, its height being very variable

../images/471462_1_En_5_Chapter/471462_1_En_5_Figm_HTML.jpg — Fig. 5

Cross-section of four papillae. They have a broad central axis with vessels, spindle cells, and marked edema. The epithelium shows a crenellated appearance

../images/471462_1_En_5_Chapter/471462_1_En_5_Fign_HTML.jpg — Fig. 6

The lining of the papillae shows moderate atypia

../images/471462_1_En_5_Chapter/471462_1_En_5_Figo_HTML.jpg — Fig. 7

The epithelium, cubic in the central part and cylindrical in the periphery of the cyst wall, rests on a thick fibrous layer

../images/471462_1_En_5_Chapter/471462_1_En_5_Figp_HTML.jpg — Fig. 8

Cyst of the albuginea. The epithelium has the same characteristics as the rest of the tumor

Comments. The architectural and cytological features are typical in this case of a borderline serous tumor. The differential diagnosis of this intratesticular neoplasia could be posed with adenocarcinoma of the rete testis and malignant mesothelioma. The adenocarcinoma of the rete testis is a tumor centered in the mediastinum, it does not have a capsule and it infiltrates the testicular parenchyma. Malignant mesothelioma is usually an extratesticular tumor and its immunohistochemical profile (positive for D240, thrombomedulin, and calretinin) is different from the immunohistochemical markers of cystadenoma [expression for CK7, EMA, CD15 (Leu-1), CA125 (cancer antigen 125) PAX8, Ber-EP4, and mutation of BRAAF V600E in some cases]. Epithelial tumors of the testis and paratesticular structures of the ovarian type are very rare, with six subtypes: serous, mucinous, endometrioid, clear cell, transitional (Brenner), and squamous. Serous tumors are more frequent than mucinous ones, similarly to what occurs in the ovary. Serous and mucinous tumors may be benign (cystadenomas), borderline, and malignant (carcinomas). It is suggested that their origin would be a Müllerian metaplasia of the epithelium (mesothelial intratesticular inclusions during the development).

References

1.

Kosmehl H, Langbein L, Kiss F. Papillary serous cystadenoma of the testis. Int Urol Nephrol. 1989;21:169–74.
2.

Meister P, Keiditsch E, Stampfl B. Intratesticular papillary cystadenoma. A rare analogue of serous papillary cystadenoma of the ovary. Pathologe. 1990;11:183–7.
3.

Albino G, Nenna R, Inchingolo CD, Marucco EC. Hydrocele with surprise. Case report and review of literature. Arch Ital Urol Androl. 2010;82:287–90.
4.

Olla L, Di Naro N, Puliga G, Tolu GA. Intraparenchymal serous papillary cystadenoma of the testis: a case report. Pathologica. 2013;105:15–7.
5.

Bürger T, Schildhaus HU, Inniger R, Hansen J, Mayer P, Schweyer S, Radzun HJ, Ströbel P, Bremmer F. Ovarian-type epithelial tumours of the testis: immunohistochemical and molecular analysis of two serous borderline tumours of the testis. Diagn Pathol. 2015;10:118.
6.

Hsieh A, Miller M, He W, Shin D. Serous borderline tumor of the testis and associated magnetic resonance imaging findings. Urol Case Rep. 2017;14:30–2.
7.

Aravind S, Nayanar SK, Varadharajaperumal R, Satheeshbabu TV, Balasubramanian S. High grade serous cystadenocarcinoma of testis-case report of a rare ovarian epithelial type tumour. J Clin Diagn Res. 2017;11:ED13–5.
8.

Scholz B, Beckert M, Mordstein V, Hohmann N, Walther R, Papadopoulos T. Seromucinous borderline tumor of the testis-A case report. Hum Pathol. 2017;60:188–91.
9.

Lin M, Awalt H, Ayala AG, Ro JY. Clear cell carcinoma of testis: A review. Ann Diagn Pathol. 2019;40:26–9.

Case 81. Mucinous Cystoadenocarcinoma of the Testis

Clinical case. A 56-year-old patient who presented with a 3-month-long thickening of the right testicle. The ultrasound showed a hypoechoic 3.5-cm nodule with anechoic areas. The left testicle and both epididymis were normal. Testicular tumor markers stayed within normal limits. The patient presented with an enlargement of the left testicle 4 months later. The ultrasonography disclosed a 2.5 cm in diameter tumor in the epididymis. Both tumors were removed. The digestive tract exploration was normal.

Pathological findings. Neoformation of gelatinous surface that contacts the albuginea and penetrates into the epididymis. The tumor is made up of multiple cavities of different shapes and sizes. The cavities are incompletely lined by a cylindrical or pseudostratified epithelium, with two cell types, hyperchromatic nucleus cells, and basophilic cytoplasm with many apical microvillis and goblet cells. The cysts contain a positive PAS material and desquamated epithelial cells. No vascular infiltration is observed. The cells show immunoexpression for CEA, CK20, and CDX2 and negative staining for CK7.

../images/471462_1_En_5_Chapter/471462_1_En_5_Figq_HTML.jpg — Fig. 1

Longitudinal section of the testicle. There is a spherical grayish mass and a bright mucosal surface at the upper part

../images/471462_1_En_5_Chapter/471462_1_En_5_Figr_HTML.jpg — Fig. 2

Histological section showing the good delimitation of the tumor with the testicular parenchyma, the infiltration of the epididymis, and the many cystic formations that constitute the tumor

../images/471462_1_En_5_Chapter/471462_1_En_5_Figs_HTML.jpg — Fig. 3

A thin capsule can be seen between the tumor and the parenchyma. The tumor shows thin septa that define cavities of different sizes

../images/471462_1_En_5_Chapter/471462_1_En_5_Figt_HTML.jpg — Fig. 4

The conjunctival septa are partially lined by a mucosecretor epithelium. In the interior of the glandular formations, tumor cells are also observed

../images/471462_1_En_5_Chapter/471462_1_En_5_Figu_HTML.jpg — Fig. 5

The epithelium varies from cylindrical to pseudostratified. The tumor cells show marked atypia. Some cells present in supranuclear vacuoles

../images/471462_1_En_5_Chapter/471462_1_En_5_Figv_HTML.jpg — Fig. 6

Epithelial cells show strong immunostaining for embryonic carcinogen antigen

../images/471462_1_En_5_Chapter/471462_1_En_5_Figw_HTML.jpg — Fig. 7

All the epithelial cells, both those forming the epithelium lining the cavities and those located in the mucus, contain immunostaining for CK20

../images/471462_1_En_5_Chapter/471462_1_En_5_Figx_HTML.jpg — Fig. 8

Epithelial cells express CDX2

Comments. The present tumor is morphologically similar to tumors of the intestinal-type ovarian surface epithelium. The differential diagnosis focuses on ruling out the metastasis of a tumor of the digestive tract, lung, prostate, and infiltration of the primary rete testis, epididymis, and testicular appendix, so these organs must be thoroughly explored, not only from the clinical point of view, but with the use of different immunohistochemical protocols. Half a dozen cases of cystadenocarcinomas or primary mucinous testicular adenocarcinomas have been reported, of which more than half developed distant metastases.

References

1.

Elbadawi A, Batchvarov MM, Linke CA. Intratesticular papillary mucinous cystadenocarcinoma. Urology. 1979;14:280–4.
2.

Nistal M, Revestido R, Paniagua R. Bilateral mucinous cystadenocarcinoma of the testis and epididymis. Arch Pathol Lab Med. 1992;116:1360–3.
3.

Ulbright TM, Young RH. Primary mucinous tumors of the testis and paratestis: a report of nine cases. Am J Surg Pathol. 2003; 27:1221–8.
4.

Elliott JE, Klein JR, Drachenberg DE. Primary testicular mucinous neoplasms: case report and literature review. Can Urol Assoc J. 2010;4:E112–5.
5.

Iuga AC, Mull J, Batra R, Miller W. Mucinous cystadenocarcinoma of the testis: a case report. Hum Pathol. 2011; 42:1343–7.
6.

Azuma T, Matayoshi Y, Nagase Y. Primary mucinous adenocarcinoma of the testis. Case Rep Med. 2012;2012:685946.
7.

Celdrán JO, Rodríguez CS, Valverde FM, Compiano LO. Primary mucinous cystadenocarcinoma of the testis: An extremely rare ovarian-type surface epithelial carcinoma. J Cancer Res Ther. 2015;11:647.

Case 82. Endometrioid Adenocarcinoma of the Testis

Clinical case. A 56-year-old patient who presented with a tumor in the right testicle. He states having received neither a hormonal treatment (estrogen) nor chemotherapy. Serum levels of testicular tumor markers were negative.

Pathological findings. A 2-cm in diameter tumor well delimited from the testicular parenchyma by a thick capsule. It is constituted by glands, often cystically dilated or with small papillae inside. The epithelium that covers them is cylindrical and their cells show vacuoles, sometimes subnuclear, sometimes supranuclear and often coinciding both in the same gland. The mitotic index is very low. The cells are negative for AFP and glypican-3 and positive for EMA and CK7. No other tumor component is observed. GCNIS is not observed in the peritumoral parenchyma. Focally, an area of endometriosis was found on the periphery of the tumor.

../images/471462_1_En_5_Chapter/471462_1_En_5_Figy_HTML.jpg — Fig. 1

The tumor reaches the vicinity of the rete testis, from which it is separated by a dense connective tissue. It is formed by glandular and papillary structures

../images/471462_1_En_5_Chapter/471462_1_En_5_Figz_HTML.jpg — Fig. 2

Peripherally, a thick capsule separates it from the testicular parenchyma that shows tubules with spermatogenesis next to other tubules that are atrophic due to tumor compression. The tumor presents a great variety regarding the shape and size of the glands

../images/471462_1_En_5_Chapter/471462_1_En_5_Figaa_HTML.jpg — Fig. 3

Glands formed by a cylindrical epithelium with oval, hyperchromatic, and basal nuclei. The glandular lumens contain an eosinophilic granular material

../images/471462_1_En_5_Chapter/471462_1_En_5_Figab_HTML.jpg — Fig. 4

Group of glands located back to back, formed by a columnar epithelium showing both basal and apical vacuoles in their cytoplasm

../images/471462_1_En_5_Chapter/471462_1_En_5_Figac_HTML.jpg — Fig. 5

Intense positivity for CK7 in the glands with cells without vacuoles; such positivity is weaker in the glands with vacuolated epithelium

../images/471462_1_En_5_Chapter/471462_1_En_5_Figad_HTML.jpg — Fig. 6

Part of a gland of the focus of endometriosis with an eosinophilic material in its interior next to a tumor glandular formation. The epithelium has a marked dysplasia

../images/471462_1_En_5_Chapter/471462_1_En_5_Figae_HTML.jpg — Fig. 7

Gland of the area of endometriosis with cubic epithelium in a stroma with strong immunoexpression for CD10

Comments. The tumor shows a pure glandular pattern. When in the presence of a glandular pattern, it is necessary to consider three situations: metastasis of an adenocarcinoma, somatic-type adenocarcinoma in a teratoma, and glandular pattern of yolk sac tumor. Once metastasis has been discarded after clinical investigation and an adequate immunohistochemical staining, the differential diagnosis continues between somatic-type adenocarcinoma and glandular (endometrioid) pattern of the yolk sac tumor. Both tumors are usually observed to also form part, to a greater or lesser extent, of a mixed germ cell tumor. Histologically, the glands of both tumors show differential features: while in the somatic-type adenocarcinoma the vacuoles that the cells may show are usually supranuclear, in the endometrioid pattern of the yolk sac tumor they are both subnuclear and supranuclear. Immunohistochemically, while in the first the cells show positivity for CK7 and EMA, in the second one they express glypican-3 and AFP. In the event that the tumor, as in the present case, has an endometrioid pattern, it is not associated with another germ cell tumor, it is present in an older adult and there is no previous history of chemotherapy due to germ cell tumor, an endometrioid adenocarcinoma must be considered. In these cases, the cells are positive for CK7 and EMA and, which is pathognomonic, they are associated with endometriosis foci.

References

1.

Numakura K, Tsuchiya N, Tsuruta H, Obara T, Saito M, Inoue T, Narita S, Horikawa Y, Satoh S, Nanjyo H, Habuchi T. A case of intratesticular endometrioid papillary cystadenocarcinoma. Jpn J Clin Oncol. 2011;41:674–6.
2.

Magers MJ, Kao CS, Cole CD, Rice KR, Foster RS, Einhorn LH, Ulbright TM. Somatic-type malignancies arising from testicular germ cell tumors: a clinicopathologic study of 124 cases with emphasis on glandular tumors supporting frequent yolk sac tumor origin. Am J Surg Pathol. 2014;38:1396–409.
3.

Obliers A, Hinz R, Erbersdobler A. Endometrioid borderline tumor of the testis. A rare cause of cystic neoplasia. Pathologe. 2014;35:504–7.
4.

Hazarika P. Endometrioid like yolk sac tumor of the testis with small teratomatous foci: a case report and review of the literature. Indian J Pathol Microbiol. 2015;58:557–9.
5.

Chander A, Otis CN, Cole LL. Pure glandular endometrioid-like yolk sac tumor of the testis. Int J Surg Pathol. 2015;23:30–1.

5.2 Juvenile Xanthogranuloma

Case 83. Juvenile Xanthogranuloma

Clinical case. A 1-year-old patient with left testicle enlargement. The ultrasound showed a 0.7-cm in diameter perfectly delimited lesion. Testicular tumor markers were negative. Enucleation was performed.

Pathological findings. The tumor is well defined, not encapsulated, and focally contacts with the surgical resection border. It is constituted by a proliferation of mononuclear cells similar to histiocytes that separate and dissociate the seminiferous tubules. Scattered among these cells there are some lymphocytes and a few eosinophils. There is an isolated mitosis. No cellular atypia is observed. Giant cells are not recognized. The immunohistochemical study showed positive expression for vimentin, CD68, Factor XIIIa, CD4 and CD45, and negativity for S100.