Cell Tumors Unrelated to 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 neoplasmsSpermatocytic tumorYolk sac tumor, prepubertal-typeTeratoma, prepubertal-type


Following 2016 WHO classification, tumors that meet these three characteristics are included in this group: they are not associated with GCNIS, they do not present 12p chromosome amplification, usually in the form of 12p isocromosome, and they do not settle on testes with testicular dysgenesis. Three entities are included: spermatocytic tumor (type III germ cell tumor), teratoma, prepubertal-type (type I germ cell tumor of the testis), and yolk sac tumor, prepubertal-type (type I germ cell tumor of the testis). The spermatocytic tumor probably originates in premeiotic germ cells (cells in transition between spermatogonias and spermatocytes). Cytogenetically, it is characterized by gains of chromosome 9. It is an exclusive tumor of the testicle and appears in ages older than the tumors derived from GCNIS (mean of age is 52–59 years). In most cases, their behavior is benign. Two cases are included: the first one we could consider characteristic with some peculiarities, and the second one, although it is not admitted as a variant of the spermatocytic tumor, has some interesting and unusual data.


The other two germ cell tumors not related to GCNIS are teratoma, prepubertal-type and the yolk sac tumor, prepubertal-type. They are typical of the first few years of life. Teratoma, prepubertal-type is characterized by being constituted by derivatives of one or more blastodermic leaves. It can be seen in both the child and the adult. All the teratomas, prepubertal-type described in childhood, as some teratomas prepubertal-type reported in adults do not metastasize and their behavior is benign, enucleation being adequate as their treatment. Due to the great diversity of tissues that may be present, a total 8 cases distributed in the following manner have been selected: two cases that can be considered conventional, four cases that include a dermoid cyst, a teratoma that simulates a burned-out tumor, a broken epidermoid cyst that also simulates a burned-out tumor, a hybrid cyst (epidermoid and trichilemmal) and two teratomas, prepubertal-type in adults. Yolk sac tumor prepubertal-type is the second most common germ cell tumor in childhood behind teratomas, prepubertal-type. Most times it appears in the first 2 years of life. It is a tumor that differentiates extraembryonic structures such as yolk sac, allantois, and extraembryonic mesenchyme. This confers it a diversity of histological patterns, so it is usual that several patterns can be identified in the same tumor. The prognosis is much better than in its adult’s counterpart. Three cases with different combinations of structural patterns have been chosen.


Yolk sac tumors, prepubertal-type require aggressive chemotherapy and orchiectomy. Three cases of yolk sac tumor, prepubertal-type have been chosen to show the different tumor patterns.


2.1 Spermatocytic Tumor



Case 39. Spermatocytic Tumor


Clinical case. A 59-year-old patient who presented with a 1-year-long painless progressive growth of the right testicle. He disclosed negative tumor markers (AFP, hCG, and LDH).


Pathological findings. In the orchiectomy specimen, the testicle measures 8 × 7 × 6.5 cm. The section was taken by a gray-white, lobular-shaped tumor with no hemorrhagic or necrotic areas, limited to the testicle. The surface was bright. In the peripheral areas, testicular parenchyma was recognized. Histologically, the arrangement of the cells is very varied, with prevalence of the sheet, pseudoglandular, cystic and follicular patterns, all of them with a common denominator, intense edema. No lymphoid infiltrates are observed. Three cell types are identified, lymphocyte-like cells by their hyperchromatic nucleus, medium-sized cells, and giant cells. In these last two cell types, chromatin has a filamentous appearance reminiscent of first-order spermatocytes. Many tubules with intratubular growth are observed. The number of mitoses is high. There is no infiltration of vessels or paratesticular structures.

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Fig. 1

Longitudinal section of the testicle. It is completely taken by a lobed, whitish-gray-colored tumor without areas of necrosis or hemorrhage


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Fig. 2

Solid cell proliferation divided by fine septa, without lymphocytes. Marked cellular pleomorphism is observed


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Fig. 3

Inside a solid proliferation, large cysts are observed, probably secondary to the accumulation of edema


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Fig. 4

The tumor has many small follicles separated from each other by intense edema


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Fig. 5

Pseudoglandular appearance of the tumor. Absence of lymphoid infiltrates


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Fig. 6

Proliferation in sheets of tumor cells with marked pleomorphism. Cells of medium size predominate against small cells (lymphocyte-like) and giant cells


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Fig. 7

Around a cystic formation, there are giant cells with one or several nuclei and abundant small-size cells


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Fig. 8

Tubules with spermatogenesis and tubules with intratubular tumor are shown. In the background, a solid tumor proliferation


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Fig. 9

The seminiferous tubule with complete spermatogenesis shows a greater cellular pleomorphism than the tubule filled with tumor cells


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Fig. 10

Tumor cells with abundant organelles in the vicinity of the nuclei and many ribosomes in the peripheral cytoplasm. Desmosome-like intercellular junctions


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Fig. 11

Tumor cells other than incomplete desmosomes are joined by bridges in which a plasma membrane boost is observed


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Fig. 12

Small cell with poor polyhedral cytoplasm poor in organelles


Comments. The presence of three cell types in the same tumor associated with the characteristics of the chromatin of medium and large cells that resembles germ cell spiremas at the beginning of the first meiotic division, makes the diagnosis of the spermatocytic tumor very easy. Interesting facts in this case are the intense edema that determines the appearance of a macrocystic pattern and the formation of structures similar to thyroid follicles. Spermatocytic tumor is a tumor only seen in the testicle. Its incidence is 0.4 cases per million, 0.61% of all germ cell tumors. The age of presentation (53.5 years) is higher than that of the seminoma and has no greater incidence in cryptorchidic patients. About 6% of cases present sarcomatous transformation with rhabdomyosarcoma being the most frequent component. In these cases, the behavior is aggressive. Exceptionally, spermatocytic tumors, without a sarcomatous transformation, can metastasize. The immunohistochemical markers common in the studies of germ cell tumors (PLAP, AFP, podoplanin, CD30, OCT3/4) are negative. Markers such as GAGE7 and NY-ESO-1 may be more useful. The electron microscopy shows a distribution of chromatin that recalls the spiremas of the first-order spermatocytes.




References



  1. 1.

    Narang V, Gupta K, Gupta A, Kumar S. Rhabdomyosarcomatous differentiation in a spermatocytic seminoma with review of literature. Indian J Urol. 2012; 28:430–3.


     

  2. 2.

    Xu N, Li F, Tian R, Shao M, Liu L, Guo K. A rare case of bilateral sequential spermatocytic seminoma.World J Surg Oncol. 2013;11:175.


     

  3. 3.

    Kao CS, Badve SS, Ulbright TM. The utility of immunostaining for NUT, GAGE7 and NY-ESO-1 in the diagnosis of spermatocytic seminoma. Histopathology. 2014. doi: 10.1111/his.12365.


     

  4. 4.

    Stein ME, Charas T, Drumea K, Sabo E, Ben-Yosef R. Spermatocytic variant of classic seminoma: a report of five cases and a brief review of the literature. Rambam Maimonides Med J. 2014;25(5):e0021.


     

  5. 5.

    Narins H, Chevli K, Gilbert R, Duff M, Toenniessen A, Hu Y. Bilateral spermatocytic seminoma: a case report. Res Rep Urol. 2014;6:63–5.


     

  6. 6.

    Hu R, Ulbright TM, Young RH. Spermatocytic seminoma: a report of 85 cases emphasizing its morphologic spectrum including some aspects not widely known. Am J Surg Pathol. 2019;43:1–11.


     

  7. 7.

    Jha RK, Mathur S, Saidha NK. A case of spermatocytic seminoma in young individual. Med J Armed Forces India. 2018;74:276–9.


     

  8. 8.

    Pandey V, Khatib Y, Khade AL, Pandey R, Khare MS. Spermatocytic seminoma with rhabdomyoblastic differentiation: case report and review of literature. Indian J Pathol Microbiol. 2018;61:437–9.


     

  9. 9.

    Wagner T, Grantham M, Berney D. Metastatic spermatocytic tumour with hybrid genetics: breaking the rules in germ cell tumours. Pathology. 2018;50:562–5.


     


Case 40. Anaplastic Variant of Spermatocytic Tumor


Clinical case. A 32-year-old patient who over 1 month had had progressive enlargement of the left testicle with discomfort but without fever. The ultrasound examination showed a very heterogeneous left testicle with multiple hyperechoic areas. The 3-cm in diameter epididymis head was also hyperechoic. Hydrocele was also observed but tumor markers were negative.


Pathological findings. A tumor consisting of several poorly defined whitish nodules with a tendency to be located in the upper pole of the testicle and the testicular mediastinum. The tumor infiltrates the albuginea and extends widely to the epididymis. The tumor cells are arranged in sheets. They constitute a relatively uniform population of medium-sized cells with a round nucleus having finely granular to filamentous chromatin. The nucleolus is larger in the larger cells that appear irregularly distributed among the others. The cytoplasm varies from clear to basophilic. The number of mitosis is high. No lymphoid infiltrates or epithelioid granulomas are observed. Areas of necrosis are frequent. The tumor cells are negative for PLAP, OCT3/4, CD30, and cytokeratins and positive for C-kit. In the vicinity of the tumor nodules, there are many tubules filled with tumor cells.

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Fig. 1

Longitudinal section of the testicle, epididymis, and initial portion of the spermatic cord. The testicle shows multiple whitish nodules arranged in the vicinity of the testicular mediastinum. The epididymis and the spermatic cord show the same color


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Fig. 2

Proliferation in sheet of medium-sized cells with slight anisocytosis and basophilic cytoplasm. There are no connective septa or lymphoid infiltrates


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Fig. 3

Tumor cells have spherical nuclei and clear or basophilic cytoplasm. Plasma membranes are not evident


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Fig. 4

Scarce anisokayosis. Presence of small nucleoli. Distribution of the chromatin simulating the spirema at the beginning of the first meiotic division


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Fig. 5

Necrosis in the central part of a testicular nodule


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Fig. 6

Infiltration of the epididymis. Tumor cells surround a section of the main duct of the epididymis


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Fig. 7

Intratubular growth of the spermatocytic tumor. Sertoli cells are respected for a certain time (immunostaining for inhibin)


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Fig. 8

Section of two seminiferous tubules filled with tumor cells. The persistence of non-tumor cells on the basement membrane is striking. Tumor cells are positive for c-kit


Comments. The tumor meets the characteristics of the so-called anaplastic variant of the spermatocytic tumor by some. It is characterized by the proliferation in sheets of medium-sized monomorphic cells. The other two cell types of these tumors are very rare or absent. This case adds another peculiarity, its aggressive behavior infiltrating paratesticular structures. A differential diagnosis could be considered with seminoma (does not express PLAP or OCT3/4), with embryonal carcinoma (does not express CD30 or cytokeratins) and with a lymphoma (absence of specific markers). It is a tumor, which, as in this case, appears at a younger age than the usual spermatocytic tumor. Less than a dozen cases have been published, one of them bilateral. Whether or not it is a variant with more aggressive behavior is a matter for discussion.




References



  1. 1.

    Dundr P, Pesl M, Povýsil C, Prokopová P, Pavlík I, Soukup V, Dvorácek J. Anaplastic variant of spermatocytic seminoma. Pathol Res Pract. 2007;203:621–4.


     

  2. 2.

    Lombardi M, Valli M, Brisigotti M, Rosai J. Spermatocytic seminoma: review of the literature and description of a new case of the anaplastic variant. Int J Surg Pathol. 2011;19:5–10.


     

  3. 3.

    Gentile G, Giunchi F, Schiavina R, Franceschelli A, Borghesi M, Zukerman Z, Cevenini M, Vagnoni V, Romagnoli D, Colombo F, Martorana G, Brunocilla E. First case of bilateral, synchronous anaplastic variant of spermatocytic seminoma treated with radical orchifunicolectomy as single approach: case report and review of the literature. Arch Ital Urol Androl. 2014;86:41–2.


     

  4. 4.

    Mikuz G, Böhm GW, Behrend M, Schäfer G, Colecchia M, Verdorfer I. Therapy-resistant metastasizing anaplastic spermatocytic seminoma: a cytogenetic hybrid: a case report. Anal Quant Cytopathol Histpathol. 2014;36:177–82.


     

2.2 Teratoma, Prepubertal-Type



Case 41. Teratoma, Prepubertal-Type (Ectodermic and Endodermic Preferential Differentiation)


Clinical case. A 10-month-old boy with progressively growing right testicle over the last 3 months. The ultrasonography revealed intraparenchymatous cystic lesions with hyperechoic areas inside. The tumor markers were negative.


Pathological findings. The testicle size is 2.8 × 2.5 × 2.4 cm. The sectioned surface shows a cystic structure. Some of those cysts are larger than 1 cm. Some contain a serous material and others a sebaceous one. Histologically, the wall of the cysts is very varied: skin structures (epidermis and dermis with their annexes), digestive tube (mucosecretor epithelium and smooth muscle wall), respiratory (mucosa surrounded by cartilaginous nests), and even nerve tissue with choroidal plexuses. GCNIS is not observed in the peritumoral parenchyma.

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Fig. 1

Most of the tumor is constituted by a large cavity, partially collapsed, surrounded by smaller ones. As part of the wall of these smaller cavities, there are several nests of cartilage


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Fig. 2

Cyst partially covered by skin. In its depth, it rests on bone tissue


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Fig. 3

Skin with an obliquely sectioned hair follicle and abundant sebaceous glands that are arranged superficially in the vicinity of the epidermis


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Fig. 4

Keratinized squamous epithelium in continuity with a non-keratinized squamous epithelium inside the abundant keratin cyst


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Fig. 5

Section of a structure reminiscent of an intrapulmonary bronchus. In the central part, the mucosa is surrounded by a ring of muscle cells, and externally there are several cartilaginous nodules


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Fig. 6

The mucosal arrangement with a mucosecretor epithelium and the different layers of smooth muscle cells suggest differentiation to the large intestine


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Fig. 7

Nervous tissue covered by ependyma and a small cyst with squamous lining next to it


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Fig. 8

Choroidal plexuses in the wall of the cyst of the previous figure


Comments. This teratoma shows the most typical characteristics of teratoma, prepubertal-type: it derives from several blastodermal leaves, absence of immature tissues, an arrangement of tissues in an easily identifiable organoid pattern, and what is definitive, absence of GCNIS. However, it should not be forgotten that in older children and in pubertal patients, teratomas may be associated with GCNIS and, despite their age, postpubertal-type teratoma should be considered.




References



  1. 1.

    Tanaka N, Yoneda A, Fukuzawa M. Mature teratoma arising from an intraabdominal testis in a 2-month-old boy: case report and review of intraabdominal testicular tumors in children. J Pediatr Surg. 2009;44:E15–8.


     

  2. 2.

    Fan R, Zhang J, Cheng L, Lin J. Testicular and paratesticular pathology in the pediatric population: a 20 year experience at Riley hospital for children. Pathol Res Pract. 2013;209:404–8.


     

  3. 3.

    Hoag NA, Afshar K, Youssef D, Masterson JS, Murphy J, Macneily AE. Cystic intratesticular lesions in pediatric patients. J Pediatr Surg. 2013;48:1773–7.


     

  4. 4.

    Epifanio M, Baldissera M, Esteban FG, Baldisserotto M. Mature testicular teratoma in children: multifaceted tumors on ultrasound. Urology. 2014;83:195–7.


     

  5. 5.

    Cornejo KM, Cheng L, Church A, Wang M, Jiang Z. Chromosome 12p abnormalities and IMP3 expression in prepubertal pure testicular teratomas. Hum Pathol. 2016;49:54–60.


     


Case 42. Enterogenous Cyst of the Testis in a Child


Clinical case. A 6-year-old boy with a history of testicular trauma 3 years ago, in follow-up consultation due to increased size of the right testicle. The ultrasonography revealed that the testicle measured 30 × 15 mm and presented a nodular lesion that took two third of the testis, with hypoechoic areas. The head of the epididymis was heterogeneous with calcifications. Tumor markers (AFP, b-HCG, and lactate dehydrogenase) were within normal limits. Lumpectomy was performed.


Pathological findings. The orchiectomy specimen weighed 18 g. The external surface was irregular. The sectioned surface shows cystic formations with yellowish-green mucous material that replaces most of the testicular parenchyma. Histologically, the greater cavity is partially lined by an epithelium similar to that of the large intestine, both in the surface epithelium and in the glands, which even have Paneth cells. Beneath it, there is a poorly organized layer of smooth muscle cells. Other cystic formations lack lining epithelium, and both mucosa and other lymphoid cells are prominent in the interior and wall. The peritumoral parenchyma is compressed, presents spermatogonia, and lacks GCNIS.

../images/471462_1_En_2_Chapter/471462_1_En_2_Figac_HTML.jpg

Fig. 1

Complete section of the tumor. Two cavities are observed, one is completely covered by mucosecretor epithelium with glands, the other one lacks lining epithelium and contains abundant mucus


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Fig. 2

The mucosecretor epithelium is surrounded by several layers of smooth muscle cells


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Fig. 3

The wall of the cystic formation is composed by a mucosa, which hardly has glands, a submucosa and a layer of smooth muscle cells


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Fig. 4

Abundant glands similar to those of the large intestine in the wall of the larger cyst


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Fig. 5

Complete differentiation of Paneth cells in the bottom of the crypts of the intestinal mucosa


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Fig. 6

The epithelial lining is missing in large areas. At this level, there are small mucous cysts and a dense lymphoid infiltrate


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Fig. 7

Abundant histiocytes (muciphages) and lymphocyte clusters coinciding with the areas in which the cyst lacks coating epithelium


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Fig. 8

The seminiferous tubules lack GCNIS. In its vicinity there are some macrophages with ample cytoplasm with ceroid pigment


Comments. The most prominent features of this tumor are its cystic aspect, the mucous content, the organoid pattern that forms a wall similar to that of the large intestine and the lack of atypia in all its components. At a first view, the organoid pattern, the patient’s age, and the absence of GCNIS would suggest a prepubertal-type teratoma. But there are some histological data that suggest that this is not a good diagnosis: the perfect organization of the larger cyst wall, the intestinal-type epithelium with glands surrounded by a layer with abundant smooth muscle cells. And, which is more important, there is absence of any derivative of another blastodermic leaf. These two facts rule out the diagnosis of teratoma and, on the other hand, suggest the diagnosis of an enterogenous cyst.


The reported enterogenous cysts are preferably located in the mediastinum, the peritoneal cavity, the spinal canal subarachnoid space, and the cerebral ventricle. So far, only one case has been reported in a child. The most accepted histogenesis that could explain the enterogenic cysts of other locations, the “Split notochord syndrome,” is difficult to apply to testicular enterogenic cysts. A good alternative is based on the embryology of the testicle. Primordial germ cells originate in the extraembryonic mesoderm in intimate relation with the wall of the yolk sac, and until they colonize the genital crests that develop in the 4th and 5th weeks they travel a long way through the dorsal mesentery. It could occur that at any moment of the development they dragged cells of the primitive intestine that would end up developing the enterogenic cyst.

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