Cell Tumors Derived from Germ Cell Neoplasia In Situ

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

 




Keywords

Testicular neoplasmsGerm cell neoplasia in situSeminomaEmbryonal carcinomaYolk sac tumorPostpubertal-typeChoriocarcinomaTeratomaPostpubertal-typeMixed germ cell tumorsNon-seminomatous germ cell tumorRegressed germ cell tumor (burn-out GCT)


1.1 Introduction


Germinal cell neoplasia in situ (GCNIS) is characterized by the presence of cells morphologically and immunohistochemically similar to gonocytes located inside the seminiferous tubules between the basement membrane and the Sertoli cells. They have spherical nuclei with irregularities in the kariotheca, one or two nucleoli and chromatin granulations. The cytoplasm is broad and clear. Immunohistochemically, these cells express PLAP, OCT3/4, and D2-40, among other markers. In the beginning, they develop in the testicle in a patchy way, and later on they can affect most of the parenchyma. They are a very frequent finding in the peripheral parenchyma of seminomas and their presence is constant in that of non-seminomatous tumors and in 3–5% of the testes contralateral to the tumor. Many of the testicles show other findings of the entity known as testicular dysgenesis. GCNIS is disseminated intratubularly with a pagetoid growth, displacing germ cells, Sertoli cells, and even the epithelial cells of the rete testis into the lumen. In their growth inside the tubules, they can completely take them up while preserving the same cytological and immunohistochemical characteristics (intratubular seminoma), or adopting new ones with cells with higher pleomorphism that do not express PLAP and acquire new markers such as CD30, cytokeratins, AFP, glypican 3, beta-HCG depending on the differentiation.


1.1.1 GCNIS


Two cases has been selected to highlight the morphological and immunihistochemical characterisits of GCNIS: one case of peritumoral GCNIS, one case of GCNIS and infertility.



Case 1. Peritumoral GCNIS


Clinical case. A 31-year-old patient presented with a right testicular mass evolving for the last 3 months. After orchiectomy, it was diagnosed as seminoma. The figures correspond to the peritumoral parenchyma.


Pathological findings. Peritumoral parenchyma shows an intratubular germinal neoplasm, mixed atrophy (seminiferous tubes with spermatogenesis next to others with Sertoli cell-only), Sertoli cell nodules, and infiltration of the rete testis. The tubules with GCNIS are characterized by their smaller diameter, absence or marked decrease of their lumina, thickening of the wall, and presence, most of the time, of only two types of cells, the tumor cells similar to gonocytes and Sertoli cells. The GCNIS cells are large cells located over the basement membrane. The Sertoli cells show small-sized spherical nuclei and appear displaced towards the lumen. Sertoli cell nodules are formed by conglomerates of seminiferous tubules that usually contain only Sertoli cells but in this case they are infiltrated by GCNIS cells. The rete testis also shows a pagetoid infiltration by GCNIS cells. Among the most common immunohistochemical techniques to confirm, the presence of GCNIS are: placental alkaline phosphatase (PLAP), OCT3/4, and D2-40.


Comments. Identification of GCNIS cells in the adult is easy due to the nuclear characteristics of the cells and their disposition over the basement membrane. In case of doubt, most of the times due to poor fixation of the surgical specimen, immunohistochemical techniques are very useful. The tumor cells express the same markers as embryonic germ cells and seminoma cells. GCNIS is the neoplasm from which seminomas, embryonal carcinoma, teratomas postpubertal-type, yolk sac tumor postpubertal-type, and choriocarcinoma originate. It is present in the adjacent non-tumoral parenchyma of 90% of seminomas and in almost all non-seminomatous tumors. The findings observed in the peritumoral parenchyma in this patient (GCNIS, Sertoli cell nodules, mixed atrophy) suggest, as is common in many testes with germ cell tumors, that the testicle carries a primary anomaly, triggered during fetal life, which has altered the estrogen/androgen ratio, a situation known as testicular dysgenesis.




References



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Fig. 1

Seminiferous tubules longitudinally sectioned, one with GCNIS cells, the other one normal. The tubule with GCNIS has only two layers of cells. Larger cells with pale cytoplasm are tumor cells


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Fig. 2

Cross sections of tubules with GCNIS and tubules with normal spermatogenesis. Of note in the GCNIS tubules are their small diameter, the absence of lumen and an epithelium formed by a peripheral ring of cells with clear cytoplasm and another inner one with the nuclei of Sertoli cells


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Fig. 3

Cross section of a tubule with GCNIS. Tumor cells have a large nucleus with irregularities in the kariotheca, one to three nucleoli and clear cytoplasm


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Fig. 4

GCNIS cell. The largest cell resting on the basement membrane has an irregular kariotheca, three nucleoli, accumulated organelles next to the nucleus, and several empty cytoplasmic areas resulting from extraction of glycogen in the sample processing


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Fig. 5

GCNIS cells show immunostaining in the peripheral cytoplasm and as a perinuclear dot for PLAP


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Fig, 6

Intense immunostaining for OCT 3/4 of GCNIS cells


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Fig. 7

Hypoplastic tubules of a Sertoli cell nodule (pseudostratified arrangement of Sertoli cells retaining prepubertal morphology and presence of microliths) infiltrated by GCNIS. GCNIS cells also appear next to seminiferous tubule


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Fig. 8

Tubule of a Sertoli cell nodule. In the central part, a GCNIS cell cluster with PLAP immunostaining can be seen


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Fig. 9

Rete testis epithelium with pagetoid spreading of GCNIS. The tumor cells are arranged on the basement membrane, displacing the epithelium towards the lumen


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Fig. 10

PLAP immunostaining highlights infiltration of the rete testis epithelium by tumor cells in a pagetoid manner



Case 2. GCNIS and Infertility


Clinical case. A 36-year-old patient with oligozoospermia. His testicles were of normal size. Serum determinations of FSH, LH, and testosterone were normal. There was no history of cryptorchidism. The testicular ultrasound examination showed a slight decrease of the testicular size and normal echogenicity. A bilateral testicular biopsy was performed.


Pathological findings. The right testicle showed mixed atrophy. The images correspond to the left testicle. The sample included part of four lobules. The tubules of one lobule show slight ectasis and complete spermatogenesis. Another lobule is formed by smaller tubules showing GCNIS cells which are easily identifiable by their cytological characteristics. This finding is also supported immunohistochemically by nuclear immunostaining for OCT3/4 and plasma membrane reactivity for PLAP. The remaining two lobules have complete spermatogenesis, but in the same tubule there is a large number of GCNIS cells in the basal compartment next to spermatogonia. These cells are also observed in the seminiferous tubules filled with sperm. Some tubules contain megalospermatocytes.


Comments. Four important lessons are drawn from this case: First, the testicular biopsy can offer us a surprise. Do not forget that in 0.6–0.8% of biopsies performed due to infertility there is a GCNIS. Second, if the fixation is not correct, the cytological characteristics of the tumor cells are distorted and the diagnosis is difficult, even more if tubules with tumor cells and spermatogenesis that may have a normal size predominate. Third, GCNIS is initially focal, adopts a lobular distribution, but later on it adopts a pagetoid growth pattern and can be extended to 100% of the seminiferous tubules. Finally, fourth, do not confuse GCNIS cells either with hypertrophic spermatogonia or with megalospermatocytes.




References



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    Nistal M, Codesal J, Paniagua R. Carcinoma in situ of the testis in infertile men. A histological, immunocytochemical and cytophotometric study of DNA content. J Pathol. 1989;159:205–10.


     

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    Giwercman A, Thomsen JK, Hertz J, Berthelsen JG, Jensen V, Meinecke B, Thormann L, Storm HH, Skakkebaek NE. Prevalence of carcinoma in situ of the testis in 207 oligozoospermic men from infertile couples: prospective study of testicular biopsies. BMJ. 1997;315:989–91.


     

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    Lifschitz-Mercer B, Elliott DJ, Schreiber-Bramante L, Leider-Trejo L, Eisenthal A, Bar-Shira Maymon B. Intratubular germ cell neoplasia: associated infertility and review of the diagnostic modalities. Int J Surg Pathol. 2001;9:93–8.


     

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    Soltanghoraee H, Pourkeramati F, Khoddami M, Amirjannati N, Akhondi MM, Soltani A. Prevalence of carcinoma in situ in testicular biopsies of infertile Iranian men. Andrologia. 2014;46:726–30.


     

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Fig. 1

Part of two lobules separated by an interlobular septum. The tubules of a lobule have complete spermatogenesis while those of the contiguous lobule show GCNIS


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Fig. 2

Part of a seminiferous tubule with complete spermatogenesis next to other tubules with GCNIS is shown. Tumor cells are recognized by their basal location, large nuclei, and pale cytoplasm. Note an infrequent fact: the tubules with GCNIS cells present a dilated lumen


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Fig. 3

Lobular distribution of the tubules with GCNIS revealed with immunostaining for PLAP


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Fig. 4

Seminiferous tubules with complete spermatogenesis. Most have been colonized by GCNIS cells (immunostaining for PLAP)


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Fig. 5

Seminiferous tubule with spermatogenesis and GCNIS. Some GCNIS cells leave the basement membrane and are located between the spermatocytes


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Fig. 6

Partial section of two seminiferous tubules. One presents complete spermatogenesis and GCNIS, the other one complete spermatogenesis and megalospermatocytes


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Fig. 7

If the fixation has not been optimal, the GCNIS cells are easy to identify with PLAP


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Fig. 8

Section of a seminiferous tubule filled with sperm, absence of spermatogenesis, and presence of GCNIS cells


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Fig. 9

The inward displacement of Sertoli cells is revealed in the figure with the intense reactivity of their cytoplasms for inhibin


1.2 Germ Cell Tumors of a Single Histological Type


When GCNIS infiltrates the wall of the seminiferous tubule, it gives rise to the following tumors: seminoma, embryonic carcinoma, postpubertal-type yolk sac tumor, choriocarcinoma and postpubertal-type teratoma in both its pure and mixed forms. The following cases are presented in this chapter: six pure seminomas, one seminoma with syncytiotrophoblast cells, three embryonal carcinoma, two yolk sac tumors postpubertal-type, two choriocarcinomas, seven teratomas postpubertal-type.


1.2.1 Seminoma


Seminomas represent 50% of the germ cell tumors of the testicle and their gonocyte-like cells (spherical nucleus, prominent nucleolus, broad and clear cytoplasms, and crisp cytoplasmic membranes) grow diffusely interrupted by septa with abundant lymphoid cells. In most cases, the diagnosis of a seminoma poses no problems. But there are situations in which either the type of growth is different or the morphology of the cells does not resemble gonocytes. Thus, the growth can be tubular, intertubular, or microcystic and the morphology of the cells can range from plasmocytoid to signet-ring. These variants are included in the following seven cases, and their corresponding differential diagnoses are commented.



Case 3. Seminoma


Clinical case. A 41-year-old patient who consulted for a non-painful enlargement of the left testicle for more than 6 months. Tumor markers were negative. The tumor extension study was also negative.


Pathological findings. Surgical specimen that corresponds to a radical orchiectomy. The testicle measures 6.9 × 5.6 × 4 cm. The section shows a tumor that occupies 4/5 of the testicle. It is lobed, bulging from the surrounding parenchyma, grayish with areas of necrosis. Histologically, it is constituted by a proliferation of cells in sheets interrupted by thin septa with lymphocytes. The tumor cells are characterized for having a broad, clear, or slightly eosinophilic cytoplasm, and crisp plasma membranes. The nucleus is central and shows one or two nucleoli. Mitoses are very abundant. In the septa, the presence of groups of macrophages and sarcoid granulomas is frequent. GCNIS and tubules with preserved spermatogenesis are observed in the peritumoral parenchyma. The epididymis and the spermatic cord show no alterations.


Comments. The macroscopic aspect of a lobed mass that protrudes from the parenchyma at the sectioned surface is suggestive of seminoma. Conventional histology, both in regard to tumor cells and to the presence of fine septa with lymphocytes and granulomas, is characteristic. The ultrastructure shows that the cell population is not homogeneous. The differences are not in the nuclei that resemble those of GCNIS (irregular nuclear membrane, several large nucleoli) but in the cytoplasm that varies from full of glycogen to complete absence of it. In the cytoplasm, the presence of annular lamellae stands out, a fact that can occur in other tumors, but that in seminoma is a constant. In the past, the high number of mitoses was considered typical of the so-called “anaplastic seminoma,” an obsolete term without prognostic interest. Seminomas represent 50% of all germ cell tumors of the testicle, and the age of presentation is 10 years older than that of the rest of germ cell tumors.




References



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    Akhtar M, Ali MA, Huq M, Bakry M. Fine-needle aspiration biopsy of seminoma and dysgerminoma: cytologic, histologic, and electron microscopic correlations. Diagn Cytopathol. 1990;6:99–105.


     

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    Creta M, Mirone V, Di Meo S, Buonopane R, Longo N, Fusco F, Forte NR, Imperatore V. A case of highly aggressive anaplastic seminoma of the testis presenting as fungating scrotal lesion. Arch Ital Urol Androl. 2017;89:158–9.


     

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    Dieckmann KP, Anheuser P, Simonsen H, Höflmayer D. Pure testicular seminoma with non-pathologic elevation of alpha fetoprotein: a case series. Urol Int. 2017;99:353–7.


     

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    Aparicio J. Prognostic factors for relapse in stage I testicular seminoma: tumor size and rete testis invasion revisited. Clin Transl Oncol. 2018;20:1358–9.


     

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    Hu B, Daneshmand S. Retroperitoneal lymph node dissection as primary treatment for metastatic seminoma. Ther Adv Urol. 2018;2018:7978958.


     

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    Chovanec M, Cheng L. Molecular characterization of testicular germ cell tumors: chasing the underlying pathways. Future Oncol. 2019;15:227–9.


     

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Fig. 1

Testicle sectioned longitudinally. The tumor that protrudes on the surface of the section is lobed, grayish and with areas of necrosis in the largest lobes


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Fig. 2

Tumor cells have a solid growth crossed by thin connective septa with lymphocytes


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Fig. 3

The tumor cells show marked uniformity and a clear cytoplasm with crisp plasma membranes. A lymphocyte corona surrounds tumor proliferation


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Fig. 4

In this field, the seminoma has greater cellular atypia, there is a greater irregularity in the shape and size of the nuclei, the cytoplasms are slightly eosinophilic and the mitosis abundant


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Fig. 5

The tumor cells show spherical nuclei with many irregularities in the kariotheca and one or two nucleoli. The electrolucent appearance of the cytoplasm is due to the presence of glycogen


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Fig. 6

A small Golgi complex, several mitochondria with scant crests and a group of annular lamellae parallel to one another are recognized


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Fig. 7

Tumor cell with absence of glycogen, abundant ribosomes, and grouping of organelles


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Fig. 8

Lymphocytes appear interspersed between tumor cells. There are sarcoid granulomas at either end of the figure



Case 4. Seminoma with Intense Lymphoid Infiltrates and Granulomatous Reaction


Clinical case. A 40-year-old patient with a several-month-old non-painful enlargement of his right testicle. Tumor markers were negative.


Pathological findings. The surgical specimen comprises testicle, epididymis, and 9 cm of spermatic cord. The testicle measures 8 × 6.5 × 5 cm. The sectioned surface shows a tumor that comprises most of the parenchyma. It is a lobed grayish tumor with areas of necrosis and hemorrhage. Histologically, it is constituted by a proliferation of cells with clear cytoplasm that are arranged in sheets or cords. The interstitium shows a dense lymphoid infiltrate that forms lymphoid follicles. In other fields, the infiltrate is disposed between the cords of tumor cells until erasing all tumor structures. Several tumor nodules show a granulomatous infiltrate with plenty uni- or multinucleated histiocytes and areas of intense fibrosis with microliths. The epididymis and the spermatic cord show no alterations. The peritumoral parenchyma also shows marked tubular atrophy with abundant lymphoid infiltrates.


Comments. The intensity of the lymphoid infiltrates is very variable from one seminoma to another, and even in different areas within the same seminoma. The most abundant lymphoid cells are the T lymphocytes but it is not uncommon to observe other cells such as plasma cells and eosinophils. The largest accumulations are observed around the vessels. The presence of important infiltrates with lymphoid follicles as in this case is rare. Another peculiarity of this case is the intense granulomatous reaction composed by histiocytes that are arranged in clusters with or without giant cells, which can make observation of the tumor cells difficult. The marked fibrosis with hyalinization that separates the cords of the tumor cells is also noteworthy. In tumors in which this pattern predominates, immunohistochemistry may be necessary to rule out a granulomatous orchitis. The presence of microliths, both in the tumor and in the peritumoral atrophic testicular parenchyma, can also be the expression of an underlying testicular dysgenesis.




References



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    Morozumi K, Ozawa M, Kuromoto A, Sato M, Hoshi S, Numahata K. High orchidectomy and histopathology to differentiate granulomatous orchitis from testicular malignancy: case report and literature review. Hinyokika Kiyo. 2018;64:75–8.


     

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Fig. 1

Longitudinal section of the testicle. There is no respected parenchyma. The surface is grayish and nodular with areas of necrosis and hemorrhage. In the central part of the tumor, the surface is encephaloid


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Fig. 2

Proliferation in sheet of cells with pale cytoplasm. Presence of a lymphoid follicle with a prominent clear center and lymphocytic infiltrates in the septa


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Fig. 3

Lymphocyte infiltrates between the cords of tumor cells


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Fig. 4

Dense infiltrate of lymphocytes between which isolated tumor cells with spherical nucleus, large nucleolus, and clear cytoplasm are observed


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Fig. 5

Tumor cells are not easy to recognize among the lymphoid infiltrate


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Fig. 6

Three details stand out that facilitate recognizing the tumor cells: their size is several times larger than that of lymphocytes, the clear cytoplasm, and the crisp cytoplasmic membrane


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Fig. 7

Dense granulomatous infiltrate with lymphocytes and histiocytes between tumor cells and surrounding a microlith


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Fig. 8

Cords of tumor cells separated by a highly collagenized hypocellular stroma



Case 5. Seminoma with a Tubular Pattern


Clinical case. A 36-year-old man who sought consultation for an increase in the size of his right testicle. Testicular tumor markers were negative. Radical orchiectomy was performed.


Pathological findings. The surgical specimen weighs 42 g. The testicle measures 4.5 × 3.5 × 2.5 cm. A well-defined tumor takes two-thirds of the testicular parenchyma, with a uniform and bright surface, without areas of necrosis or hemorrhage. The tumor presents a tubular pattern consistent in lace with focal pseudoglandular changes. In the periphery, a cord-like growth predominates. The cells, with a spherical nucleus, a voluminous nucleolus, and clear cytoplasm, were supported by very thin septa. The tumor lacks lymphocytic infiltrates or a granulomatous reaction. There are both pagetoid growth and eosinophilic cytoplasmic inclusions in the epithelial cells at the level of the rete testis.


Comments. Tubular pattern is a rare growth pattern in seminomas. It can raise a differential diagnosis with Sertoli cell tumors, and in some cases with other tumors such as carcinoid tumor and yolk sac tumor. It is noteworthy that in Sertoli cell tumors the septa separating the cellular cords are highly hyalinized, that tubular formations usually show lumina of rigid contours, and that they show no pagetoid infiltration of the rete testis or GCNIS in the neighboring parenchyma. In case of doubt, immunohistochemistry confirms the diagnosis (immunoreaction for PLAP, 0CT3/4 support the diagnosis of seminoma; immunoexpression for cytokeratins, inhibin and calretinin that of Sertoli cell tumor; neuroendocrine markers such as synaptophysin, chromogranin, and CD56 support the diagnosis of carcinoid tumor; and finally, AFP and glypican-3 are positive in yolk sac tumor).




References



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    Young RH, Finlayson N, Scully RE. Tubular seminoma. Report of a case. Arch Pathol Lab Med. 1989;113:414–6.


     

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    Takeshima Y, Sanda N, Yoneda K, Inai K. Tubular seminoma of the testis. Pathol Int. 1999;49:676–9.


     

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Fig. 1

Well-delimited, non-encapsulated tumor with a bright surface without areas of necrosis or hemorrhage


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Fig. 2

The tumor is arranged in irregularly anastomosing trabeculae, separated from each other by thin walls devoid of lymphocytes


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Fig. 3

Tumor cells tend to be arranged in the peripheral part of the tubular formations. They show a low grade of pleomorphism


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Fig. 4

The tubules are lined by cubic cells of clear cytoplasm. The cells are supported by a thin basement membrane


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Fig. 5

In transverse or oblique sections of the tubular formations, it can be seen how they get to surround those tubular formations resting on the septa. Many cells show a vacuolated appearance of the subnuclear cytoplasm


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Fig. 6

Cord growth at the periphery of the tumor. Part of a semi-solid tubule is observed


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Fig. 7

Note nuclear immunoexpression of tumor cells for OCT3/4


../images/471462_1_En_1_Chapter/471462_1_En_1_Figaq_HTML.jpg

Fig. 8

Rete testis in which pagetoid infiltration by GCNIS is transforming into solid tumor nodules



Case 6. Seminoma with an Intertubular Growth Pattern


Clinical case. A 34-year-old patient who presented with infertility (severe oligozoospermia). His left testicle was slightly enlarged. The ultrasonography showed a 1-cm hypoechoic tumor in the lower pole. Tumor markers only showed a slightly elevated beta-HCG.


Pathological findings. The tumor, located in the lower pole of the testicle, is well delimited and corresponds to a seminoma with syncytiotrophoblast cells. GCNIS is observed in the tubules of several testicular lobules. In the parenchyma distant from the tumor, which presents a mixed atrophy and diffuse hyperplasia of Leydig cells, an infiltration in rows or cords of tumor cells stands out. These cells are introduced among peritubular myoid cells both in the tubules with spermatogenesis and in Sertoli cell-only tubules and also infiltrate the rete testis.


Comments. Seminomas usually destroy the seminiferous tubules and only in a third of the cases in the periphery of a tumor nodule a localized intertubular growth is observed. Ulbright in 1999 reported 12 cases of seminoma that showed this type of growth in the absence of a discernable clinical mass.


The intertubular seminoma has been defined (Browne 2005) as the presence of intertubular growth not contiguous to the main tumor and presents at least three high-power fields away from the tumor mass. The tumor frequently infiltrates the rete testis and its behavior is more aggressive. It can raise a differential diagnosis with the intertubular growth of some metastases of prostate adenocarcinoma.




References



  1. 1.

    Ulbright TM, Amin MB, Young RH. Tumors of the testis, adnexa, spermatic cord and scrotum. Washington, DC: US Armed Forces Institute of Pathology; 1999.


     

  2. 2.

    Henley JD, Young RH, Wade CL, Ulbright TM. Seminomas with exclusive intertubular growth: a report of 12 clinically and grossly inconspicuous tumors. Am J Surg Pathol. 2004;28:1163–8.


     

  3. 3.

    Browne TJ, Richie JP, Gilligan TD, Rubin MA. Intertubular growth in pure seminomas: associations with poor prognostic parameters. Hum Pathol. 2005;36:640–5.


     

  4. 4.

    Ulbright TM, Young RH. Metastatic carcinoma to the testis: a clinicopathologic analysis of 26 nonincidental cases with emphasis on deceptive features. Am J Surg Pathol. 2008;32:1683–9.


     

  5. 5.

    Menon S, Gujral S, Bakshi G, Tongaonkar HB. Bilateral testicular metastasis from prostatic adenocarcinoma mimicking an intertubular pattern of seminoma and expressing Rhamm. J Cancer Res Ther. 2010;6:97–9.


     

../images/471462_1_En_1_Chapter/471462_1_En_1_Figar_HTML.jpg

Fig. 1

Longitudinal section of the testicle. A gray-whitish tumor located in the lower pole of the testicle without areas of hemorrhage or necrosis


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Fig. 2

The tumor contacts the albuginea and is well delimited from the testicular parenchyma


../images/471462_1_En_1_Chapter/471462_1_En_1_Figat_HTML.jpg

Fig. 3

Proliferation in sheets of cells showing a spherical nucleus, a large nucleolus, and a clear cytoplasm. Absence of lymphoid infiltrates


../images/471462_1_En_1_Chapter/471462_1_En_1_Figau_HTML.jpg

Fig. 4

Tubule with complete spermatogenesis next to tubules with intratubular seminoma


../images/471462_1_En_1_Chapter/471462_1_En_1_Figav_HTML.jpg

Fig. 5

The testicular parenchyma has tubules with complete spermatogenesis, diffuse hyperplasia of Leydig cells, and peritubular rings of tumor cells


../images/471462_1_En_1_Chapter/471462_1_En_1_Figaw_HTML.jpg

Fig. 6

Partial section of four seminiferous tubules with spermatogenesis. Attached to the tubular wall are rows of tumor cells. None of the seminiferous tubes has GCNIS


../images/471462_1_En_1_Chapter/471462_1_En_1_Figax_HTML.jpg

Fig. 7

Tumor cells revealed with PLAP immunostain between two seminiferous tubules


../images/471462_1_En_1_Chapter/471462_1_En_1_Figay_HTML.jpg

Fig. 8

Tubules with Sertoli cell-only surrounded by tumor cells. These cells are preferably arranged in the wall of the tubules between the myoid cells and the peritubular fibroblasts. The interstitium shows diffuse hyperplasia of Leydig cells and isolated tumor cells between them


../images/471462_1_En_1_Chapter/471462_1_En_1_Figaz_HTML.png

Fig. 9

Pagetoid infiltration of the rete testis (PLAP immnunostaining) by tumor cells



Case 7. Plasmacytoid Seminoma with Syncytiotrophoblastic Cells


Clinical case. A 36-year-old patient presented with a painless left testicle enlargement for the last 6 months. The tumor markers were: AFP negative, beta-hCG 129 mUI/L.


Pathological findings. The testis measures 8.2 × 7.1 × 6.8 cm. It shows a tumor that only respected half of the testicular parenchyma at the lower pole. When sectioned, the tumor shows a grayish encephaloid surface with small hemorrhagic areas and necrosis. A mild hydrocele is also present. Histologically, a sheet growth pattern is observed of cells with plasmocytoid appearance (broad eosinophilic cytoplasm, eccentric nucleus). There are small clusters of perivascular lymphocytes. In the vicinity of the vessels, there are isolated syncytial cells. The tumor does not infiltrate testicular mediastinum, epididymis, or spermatic cord. Plasmocytoid-like cells are PLAP positive while syncytial cells show immunoexpression for beta-hCG.


Comments. The plasmacytoid aspect of some seminomas has been related to the proximity of their cells to necrotic areas. But there are tumors in which the cells are clearly separated so we should consider that this is one of the most varied patterns a seminoma can show. The differential diagnosis is basically posed with primary or secondary testicular plasmacytomas, metastasis of plasmacytoid carcinomas, and plasmacytoid melanoma. Immunohistochemistry may be essential. Of note in this case is the presence of syncytial cells distributed regularly within the tumor. This finding is reported in 10–20% of seminomas. The prognosis of plasmacytoid seminoma is similar to that of the other seminoma variants.




References



  1. 1.

    Young RH. Testicular tumors—some new and a few perennial problems. Arch Pathol Lab Med. 2008;132:548–64.


     

  2. 2.

    Raspollini MR. Histologic variants of seminoma mimicking lymphatic malignancies of the testis: a literature review with a report of case series focusing on problems in differential diagnosis. Appl Immunohistochem Mol Morphol. 2014;22:348–57.


     

../images/471462_1_En_1_Chapter/471462_1_En_1_Figba_HTML.jpg

Fig. 1

Longitudinal section of the testicle. The tumor is formed by a conglomerate of nodules with geographic contours that protrude over the parenchyma


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbb_HTML.png

Fig. 2

Proliferation in sheets of cells with spherical or angulated nucleus and eosinophilic cytoplasm. Absence of lymphoid infiltrates


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbc_HTML.png

Fig. 3

The tumor cells are arranged in coarse cords. The nuclei are eccentric and show a central nucleolus. The cytoplasm is broad and eosinophilic


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbd_HTML.jpg

Fig. 4

The nuclei of tumor cells are aligned at the periphery of the cords in such a way as to confer a seudoacinar glandular appearance to the tumor. The cytoplasms converge towards the central part. Several mitoses and isolated lymphocytes are observed in the vicinity of a venule


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbe_HTML.jpg

Fig. 5

In the upper part of the figure, there is a conglomerate of nuclei corresponding to a syncytiotrophoblast cell


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbf_HTML.jpg

Fig. 6

Intense immunostaining for PLAP of all cells except for those at the central part of the figure


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbg_HTML.png

Fig. 7

Syncytiotrophoblast cells have been disclosed through immunostaining for beta-HCG



Case 8. Seminoma with a Microcystic Pattern, Signet-Ring Cells, and Early Embryonal Carcinoma


Clínical case. A 42-year-old infertile male with a clinical history of right cryptorchidism descended at 10 years of age and later removal of testicular remnants was referred to the Urology department. He also had a medical history of gonorrhea, condylomata acuminata, and molluscum contagiosum. He sought consultation for slow and progressive increase of his left hemiscrotum since 2–3 months ago. No other symptoms were observed. Testicular serum markers were negative.


Pathological findings. The radical orchioepididectomy specimen weighed 61 g. The testicle measured 7 × 5 × 5 cm. A tumor was observed upon sectioning that was taking the greater part of the testicle; it had a whitish nodular surface with central hemorrhagic areas. The epididymis, the testicular covers, and the spermatic cord were free of infiltration. Histologically, the tumor comprises two types of cells. The first cell type form most of the neoplasm. It consists of a proliferation in sheets of medium-sized cells separated by thin septa of connective tissue with few lymphocytes. The nuclei of these tumor cells vary from spherical to triangular; a large nucleolus stands out in the spherical ones, and a marked hyperchromatism is noticeable in the triangular cells. The cytoplasm, in general, is eosinophilic. Focally, groups of tumor cells show signet-ring morphology. The tumor adopts a microcystic pattern, mainly in these areas. The second cell type is arranged around the vessels. These cells have higher pleomorphism, irregular karyotheca with bizarre nucleoli and heterochromatin granules. The immunohistochemical study shows in the first cell type positive expression for PLAP and in the second cell type positivity for cytokeratins and CD30.


Comments. Most of the tumor is a plasmacytoid seminoma with signet-ring cells. Immunostaining for PLAP and absence of cytokeratins staining confirm this diagnosis. The second component is constituted by perivascular islets of cells that express cytokeratins and CD30, which is identified as a differentiation from embryonal carcinoma. It is a very uncommon case. On the one hand, it is a seminoma in which microcystic, plasmocytoid, and ring-ring cell patterns are combined. On the other hand, an embryonal carcinoma is developing in the form of perivascular nests. The role of immunohistochemistry is essential for the correct identification of these cases.




References



  1. 1.

    Ulbright TM, Young RH. Seminoma with conspicuous signet ring cells: a rare, previously uncharacterized morphologic variant. Am J Surg Pathol. 2008;32:1175–81.


     

  2. 2.

    Miyai K, Yamamoto S, Iwaya K, Asano T, Tamai S, Tsuda H, Matsubara O. Allelotyping analysis suggesting a consecutive progression from intratubular germ cell neoplasia to seminoma and then to embryonal carcinoma of the adult testis. Hum Pathol. 2013;44:2312–22.


     

  3. 3.

    Nettersheim D, Heimsoeth A, Jostes S, Schneider S, Fellermeyer M, Hofmann A, Schorle H. SOX2 is essential for in vivo reprogramming of seminoma-like TCam-2 cells to an embryonal carcinoma-like fate. Oncotarget. 2016;7:47095–110.


     

../images/471462_1_En_1_Chapter/471462_1_En_1_Figbh_HTML.jpg

Fig. 1

Longitudinal section of the testicle. A whitish nodular tumor with central hemorrhagic areas that takes most of the testicle


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbi_HTML.jpg

Fig. 2

Tumor cells show low cohesiveness giving rise to cystic spaces. Some cells appear in their inside


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbj_HTML.jpg

Fig. 3

Several details are added to the microcystic aspect: the angled profile of the nuclei, the eosinophilic cytoplasm in some cells, the presence of a large vacuole in others, and the absence of a crisp plasma membrane in most of them


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbk_HTML.jpg

Fig. 4

Signet-ring tumor cells next to cells with eosinophilic cytoplasm. Isolated lymphocytes between tumor cells


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbl_HTML.jpg

Fig. 5

Proliferation in sheets of plasmacytoid cells. Isolated cells in the central part with vesicular nuclei and scarce cytoplasm


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbm_HTML.jpg

Fig. 6

Surrounding a small vessel there are a dozen cells that have very different morphological characteristics from the plasmacytoid cells of the tumor: larger nucleus, clear with heterochromatin granulation, large nucleolus, and a weakly eosinophilic cytoplasm


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbn_HTML.jpg

Fig. 7

Cellular nest in the central part of the figure next to well-delimited congestive vessels of the tumor with plasmocytoid pattern


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbo_HTML.jpg

Fig. 8

Intense immunostaining for PLAP of the plasmocytoid cells and absence of immunostaining in the cells of the central area


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbp_HTML.jpg

Fig. 9

The tumor cells of the perivascular central nodule show immunostaining for AE1/AE3 cytokeratins


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbq_HTML.jpg

Fig. 10

Strong immunostaining of central cells for CD30


1.2.2 Seminoma with Syncytiotrophoblastic Cells



Case 9. Seminoma with Syncytiotrophoblastic Cells


Clinical case. A 35-year-old patient complaining of a progressive increase of his right testicle over the last 4 months. The testicular markers were: AFP normal, beta-hCG 210 mUI/mL. Radical orchiectomy was performed.


Pathological findings. The testicle averages 6.3 × 5.9 × 5 cm. The epididymis was highly thickened with a maximum thickness of 3 cm at the level of the body and tail. The spermatic cord showed no alterations. When sectioned, the testicle shows a whitish tumor that takes its central part in continuity with the epididymal tumor. Histologically, the pattern of tumor growth is in sheets. Tumor cells have spherical nuclei, central nucleoli, and pale cytoplasm with crisp cytoplasmic membranes. There are multinucleated cells of eosinophilic cytoplasm among them. There are lymphocytes and sarcoid granulomas in the septa that score the tumor. Surrounding the tumor there are several groups of seminiferous tubules filled with tumor cells. Most of these tumor cells, both with growth in sheets or with intratubular growth, are positive for PLAP immunostaining. Multinucleated giant cells observed among the tumor cells are beta-HCG positive.


Comments. The presence of syncytiotrophoblast cells is relatively frequent in all tumors derived from GCNIS. Its frequency is estimated in seminomas at about 10 and 20%. What is very variable is the number of cells and their distribution within the tumor. In this tumor, they are very abundant in some fields. Syncytiotrophoblast cells are easily differentiated from other multinucleated giant cells that are often present in these tumors. They are located between the cells of the seminoma, the nuclei are frequently arranged in mulberry-like clusters, and vacuoles can be observed in their cytoplasm. Frequently, the syncytiotrophoblast cells are associated with small hemorrhages. The second type of giant cells that can be seen in the seminoma are Langhans-type cells. These cells are usually located in the septa and are accompanied by other inflammatory cells forming granulomas. Syncytiotrophoblast cells are responsible for the presence of high beta-HCG levels in these patients so their serum determination can be useful for monitoring them.




References



  1. 1.

    Schwartz BF, Auman R, Peretsman SJ, Moul JW, Deshon GE, Hernandez J, Rozanski RA, Thrasher JB. Prognostic value of BHCG and local tumor invasion in stage I seminoma of the testis. J Surg Oncol. 1996;61:131–3.


     

  2. 2.

    Bjurlin MA, August CZ, Weldon-Linne M, Totonchi E. Histologically pure stage I seminoma with an elevated beta-hCG of 4497 IU/l. Urology. 2007;70:1007.e13–5.


     

  3. 3.

    Vesprini D, Chung P, Tolan S, Gospodarowicz M, Jewett M, O’Malley M, Sweet J, Moore M, Panzarella T, Sturgeon J, Sugar L, Anson-Cartwright L, Warde P. Utility of serum tumor markers during surveillance for stage I seminoma. Cancer. 2012;118:5245–50.


     

  4. 4.

    Ruf CG, Khalili-Harbi N, Sachs S, Isbarn H, Wagner W, Matthies C, Meineke V, Fisch M, Chun FK, Abend M. The search for biomarkers of metastatic seminoma. J Urol. 2013;190:1046–51.


     

  5. 5.

    Hes O, Pivovarcikova K, Stehlik J, Martinek P, Vanecek T, Bauleth K, Dolejsova O, Petersson F, Hora M, Perez Montiel D, Peckova K, Branzovsky J, Slouka D, Vodicka J, Kokoskova B, Matej R, Michal M. Choriogonadotropin positive seminoma—a clinicopathological and molecular genetic study of 15 cases. Ann Diagn Pathol. 2014;18:89–94.


     

  6. 6.

    Lempiäinen A, Sankila A, Hotakainen K, Haglund C, Blomqvist C, Stenman UH. Expression of human chorionic gonadotropin in testicular germ cell tumors. Urol Oncol. 2014;32:727–34.


     

  7. 7.

    Rajpert-De Meyts E, Nielsen JE, Skakkebaek NE, Almstrup K. Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs. Folia Histochem Cytobiol. 2015;53:177–88.


     

../images/471462_1_En_1_Chapter/471462_1_En_1_Figbr_HTML.jpg

Fig. 1

Cross section of testicle and epididymis. The intratesticular neoformation is nodular and partially cystic, with several tumor nodules around it. It infiltrates the mediastinum and extends to the epididymis showing a central area of necrosis at this level


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbs_HTML.jpg

Fig. 2

Growth in sheet of tumor cells crossed by fine septa with perivascular lymphoid infiltrates


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbt_HTML.jpg

Fig. 3

Tumor cells have spherical nuclei, large nucleoli, chromatin clusters, and pale cytoplasms. Among them, in the thin septa, isolated lymphocytes can be observed. Tumor cells show slight anisocytosis and scarce mitosis


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbu_HTML.png

Fig. 4

Syncytiotrophoblast cell with the characteristic accumulation of the nuclei in the central part is observed among tumor cells


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbv_HTML.jpg

Fig. 5

Syncytiotrophoblast cells with large cytoplasmic vacuoles


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbw_HTML.jpg

Fig. 6

Several syncytiotrophoblast cells surround a hemorrhagic area


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbx_HTML.png

Fig. 7

Intense positivity expression for beta-HCG in syncytiotrophoblast cells


../images/471462_1_En_1_Chapter/471462_1_En_1_Figby_HTML.jpg

Fig. 8

Sarcoid granuloma with Langhans cells surrounded by epithelioid cells and lymphocytes next to a vessel in a tumor septum


../images/471462_1_En_1_Chapter/471462_1_En_1_Figbz_HTML.jpg

Fig. 9

Peritumoral nodule formed by the intratubular growth of the seminoma. Among seminiferous tubules there is a diffuse hyperplasia of Leydig cells


../images/471462_1_En_1_Chapter/471462_1_En_1_Figca_HTML.jpg

Fig. 10

Intense immunostaining for PLAP in the cells of three seminiferous tubules. In the seminiferous tubule with spermatogenesis, all cells are negative


1.2.3 Embryonal Carcinoma


Pure embryonal carcinoma is rare (3% of germ tumors). Its most frequent growth patterns are solid, glandular or tubular and papillary. In some tumors, the presence of a dense lymphoid infiltrate raises the differential diagnosis with seminomas; in others, the cytoplasm is not eosinophilic but pale and it is necessary to rule out not only a seminoma but a yolk sac tumor, and so it will be necessary to resort to immunohistochemistry. Finally, there are embryonal carcinomas with a growth pattern that is neither solid, nor glandular or papillary, but rather it is constituted cysts inside which there are formations similar to blastocysts. In the three cases of embryonal carcinoma that follow, the differential facts are illustrated and commented on.



Case 10. Embryonal Carcinoma with Syncytiotrophoblastic Cells


Clinical case. A 27-year-old patient with a rapidly growing painless tumor in the left testicle. Tumor markers: only beta-hCG was slightly elevated, the rest were normal. Retroperitoneal metastases were observed in the extension study.


Pathological findings. The surgical specimen of radical orchiectomy consisted of a testicle measuring 5.8 × 4.5 × 4.2 cm. The section showed a well-defined reddish central mass with hemorrhagic areas. The epididymis and the spermatic cord were normal. Histologically, the tumor is separated from the parenchyma by connective tissue with a dense lymphoid infiltrate. Tumor cells adopt solid growth in some areas, and papillary and microcystic patterns in others. Tumor cells show significant anisocytosis and anisocariosis, and frequent mitosis. They infiltrate the testicular mediastinum and permeate the lymphatic vessels. Among these cells, multinucleated giant cells with large cytoplasmic vacuoles are occasionally observed. The tumor cells are positive for CD30 and OCT3/4 and negative for glypican-3 and AFP. In the peritumoral parenchyma, there is GCNIS and mixed atrophy.


Comments. This case can be considered the prototype of an embryonal carcinoma with solid growth in some areas, papillary growth in other areas and microcystic or glandular growth still in other areas. The presence of syncytiotrophoblast cells is also frequent (60% of cases). The presence of intratubular necrosis and the extensive infiltration of the lymphatic vessels that justifies, as in this case, the great tendency to metastasize, are also characteristic. The tumor in this patient does not pose the usual differential diagnoses of embryonal carcinoma such as seminoma and yolk sac tumor. The ultrastructure and immunohistochemistry support the diagnosis. Pure embryonal carcinoma is a rare tumor (less than 3% of all germ cell tumors). Embryonal carcinomas do not show AFP rise. If this were found, the identification of a yolk sac tumor should put us in the alert. In these cases, it would be a mixed tumor.




References



  1. 1.

    Jones TD, Ulbright TM, Eble JN, Baldridge LA, Cheng L. OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma. Am J Surg Pathol. 2004;28:935–40.


     

  2. 2.

    Ulbright TM. Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol. 2005;18(Suppl 2):S61–79.


     

  3. 3.

    Kao CS, Ulbright TM, Young RH, Idrees MT. Testicular embryonal carcinoma: a morphologic study of 180 cases highlighting unusual and unemphasized aspects. Am J Surg Pathol. 2014;38:689–97.


     

  4. 4.

    Gerber D, Wright HC, Sussman RD, Stamatakis L. Embryonal carcinoma presenting as a calcified solitary testicular mass on ultrasound. BMJ Case Rep. 2017;2017. pii: bcr-2017-220081.


     

../images/471462_1_En_1_Chapter/471462_1_En_1_Figcb_HTML.jpg

Fig. 1

The tumor is located in the central part of the testicle, extending from the albuginea to the testicular mediastinum. It has a reddish color with hemorrhagic areas


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcc_HTML.png

Fig. 2

A connective tissue with abundant lymphoid infiltrates separates the tumor from the testicular parenchyma


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcd_HTML.png

Fig. 3

Tumor cells adopt a solid growth. They have marked pleomorphism. There are no lymphoid cells in the septum


../images/471462_1_En_1_Chapter/471462_1_En_1_Figce_HTML.png

Fig. 4

Branched papillae formed by a central axis with fine vessels and a lining of cylindrical cells of vesicular nucleus, prominent nucleolus and eosinophilic cytoplasm


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcf_HTML.png

Fig. 5

There are several cystic formations within the solid growth. Some are just a cluster of necrotic cells


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcg_HTML.jpg

Fig. 6

In this solid growth pattern, embryonal carcinoma cells have large nuclei with folds in the karyotheca and large nucleoli. The cytoplasm is wide with many polyribosomes, small Golgi complex, and some cisternae of rough endoplasmic reticulum. The cells are joined by long tight junctions (EM)


../images/471462_1_En_1_Chapter/471462_1_En_1_Figch_HTML.jpg

Fig. 7

Syncytiotrophoblast cell with several cytoplasmic vacuoles in the periphery of the solid pattern of an embryonal carcinoma nodule


../images/471462_1_En_1_Chapter/471462_1_En_1_Figci_HTML.png

Fig. 8

Group of necrotic tumor cells surrounded by a dense lymphoid infiltrate. In the periphery, seminiferous tubules with spermatogenesis


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcj_HTML.png

Fig. 9

Infiltration of the testicular mediastinum and the rete testis cavities by tumor cells


../images/471462_1_En_1_Chapter/471462_1_En_1_Figck_HTML.png

Fig. 10

Tumor infiltration of the periarterial lymphatic vessels in the tunica vasculosa


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcl_HTML.png

Fig. 11

Sections of five seminiferous tubules with necrosis of intratubular embryonal carcinoma


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcm_HTML.png

Fig. 12

Immunoexpression of OCT3/4 in tumor cells. In the seminiferous tubule with necrosis, some unaffected cells are still observed



Case 11. Embryonal Carcinoma with Lymphoid Stroma


Clinical case. A 18-year-old patient who presented with progressive painless increase of the left testicle in the last 3 months. Ultrasonography showed that the left testicle was taken by a 5 × 3 × 3 cm mass with hypoechoic areas alternating with hyperechoic areas that focally encompasses the epididymis. The tumor has left the lower pole free. Testicular tumor markers were negative.


Pathological findings. The testicle size is 5 × 4 × 4 cm. It shows a 3.2-cm tumor located in the upper pole and extending to the epididymis. The tumor is whitish-gray with hemorrhagic areas. Histologically, the cells are arranged in nests separated by thick septa that show dense lymphoid infiltrates. The tumor nests are made up of cells with great nuclear pleomorphism, spherical nuclei next to other triangular or folded with different sizes. The cytoplasm is generally eosinophilic but there are areas where it is clear or vacuolated. The lymphoid infiltrate shows no sarcoid granulomas and in some fields it is so dense that the tumor cells are barely distinguishable. The cells are keratin positive and express CD30. Placental alkaline phosphatase is positive in isolated cells. GCNIS is observed in most of the tubules in the rest of the parenchyma, as well as tubular hyalinization in the remaining tubules.


Comments. Histologically, the first diagnostic impression was that of a seminoma because of its frequency and because of the abundant lymphoid stroma, and the focal presence of clear cytoplasm cells. The study at higher magnification makes it possible to specify, both in the cells of the eosinophilic cytoplasm, and in those of the clear cytoplasm, the enormous pleomorphism of the nuclei with the presence of important notches and some large cells compared to the relative good sphericity of the nuclei of seminoma cells. The immunoexpression for CD30 and cytokeratins AE1/AE3 facilitates the diagnosis. Pure embryonal carcinoma only accounts for 2–3% of germ cell tumors and only 7% of embryonal carcinomas show a dense lymphoid infiltrate. In view of these data, it is not surprising that the diagnosis was fast.




References



  1. 1.

    Kao CS, Ulbright TM, Young RH, Idrees MT. Testicular embryonal carcinoma: a morphologic study of 180 cases highlighting unusual and unemphasized aspects. Am J Surg Pathol. 2014;38:689–97.


     

../images/471462_1_En_1_Chapter/471462_1_En_1_Figcn_HTML.jpg

Fig. 1

Longitudinal section of the testicle. Whitish-gray tumor of ill-defined contours extending to the epididymis with areas of hemorrhage


../images/471462_1_En_1_Chapter/471462_1_En_1_Figco_HTML.jpg

Fig. 2

Solid cell proliferation furrowed by thick septum with abundant lymphoid cells


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcp_HTML.jpg

Fig. 3

The lymphoid infiltrate is so intense that it is difficult to recognize the tumor cells. The panoramic view suggests large lymphoid follicles


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcq_HTML.jpg

Fig. 4

Several tumor nests with geographic contours in a dense lymphoid infiltrate


../images/471462_1_En_1_Chapter/471462_1_En_1_Figcr_HTML.jpg

Fig. 5

Nest of embryonal carcinoma cells surrounded by lymphocytes. The morphological characteristics of both the nucleus (large, irregular karyotheca, large nucleolus) and the cytoplasm (markedly eosinophilic) are well appreciated


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Fig. 6

Embryonal carcinoma cells isolated in the lymphoid infiltrate


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Fig. 7

Tumor cells retaining nuclear pleomorphism have acquired a clear cytoplasm


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Fig. 8

A thin septum with some lymphocytes separates two parts of the tumor growth. The tumor cells have a clear cytoplasm reminiscent of the seminoma but the nuclear pleomorphism is characteristic of embryonal carcinoma


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Fig. 9

Strong immunostaining of tumor cells for CD30


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Fig. 10

Tumor cells express cytokeratins (AE1/AE3)


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Fig. 11

Focal immunostaining for PLAP in isolated tumor cells


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Fig. 12

Most of the lymphoid cells that accompany the tumor are CD3-positive lymphocytes



Case 12. Embryonal Carcinoma with Blastocyst-Like Pattern


Clinical case. A 36-year-old patient with painless enlargement of the left testicle since the last 7 months. Tumor markers (AFP and beta-hCG) were negative.


Pathological findings. The testicle size is 9 × 8 × 8 cm. The sectioned surface was mottled with whitish nodular areas, hemorrhagic areas, and necrotic areas. A small peripheral crescent of testicular parenchyma was recognized. Histologically, it was a mixed germ cell tumor with teratoma of the postpubertal-type, seminoma and embryonal carcinoma in similar proportions. The images have been selected from the embryonal carcinoma component only. The embryonal carcinoma showed solid, papillary and cystic areas, the latter predominating. Inside the cysts, originating in the epithelium that covers them, there are multiple vesicular formations. The lining of the vesicles is flat with vacuolated cytoplasm cells except at a pole where the cells are cubic or cylindrical. Different vesicles resembling blastocysts are anastomosed through this area. All cells are positive for CD30 and cytokeratins. The cells express D2-40 on the outer surface of the vesicles.


Comments. Less than 1% of embryonal carcinomas, whether presented as pure forms or as part of a combined tumor, show this peculiar type of pattern. The knowledge of the existence of this pattern within embryonal carcinomas is important. In particular, it must be distinguished from a cystic pattern of yolk sac tumor. The absence of yolk sac markers such as AFP and glypican-3 support the diagnosis.




References



  1. 1.

    Kao CS, Ulbright TM, Young RH, Idrees MT. Testicular embryonal carcinoma: a morphologic study of 180 cases highlighting unusual and unemphasized aspects. Am J Surg Pathol. 2014;38:689–97.


     

  2. 2.

    Gerber D, Wright HC, Sussman RD, Stamatakis L. Embryonal carcinoma presenting as a calcified solitary testicular mass on ultrasound. BMJ Case Rep. 2017;2017. pii: bcr-2017-220081.


     

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Fig. 1

Surgical specimen with a 6.3 × 6.2 × 5.8 cm tumor of mottled surface with whitish, microcystic, and hemorrhagic areas affecting the entire testicle


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Fig. 2

Many cystic formations are surrounded by myxoid stroma and present epithelial projections towards their interior


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Fig. 3

The epithelium that lines the wall has one to three layers of cells of variable size, large nucleoli, and eosinophilic cytoplasm. It develops vesicular formations that go into the interior


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Fig. 4

Group of vesicles inside a cystic formation. The vesicles are formed by a wall of one or two cellular layers and an irregular cavity


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Fig. 5

A vesicle sectioned by the central part, and the tangential part of others are observed. In the vesicles, a cellular nest with columnar cells stands out, the rest being covered by flattened cells


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Fig. 6

Intense positive expression for cytokeratins 8, 18, and 19 of all cells in both vesicles


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Oct 1, 2020 | Posted by in UROLOGY | Comments Off on Cell Tumors Derived from Germ Cell Neoplasia In Situ
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