Germ Cell Origin of Testicular Carcinoid Tumors

Abbosh, Phillip H.; Zhang, Shaobo; MacLennan, Gregory T.; Montironi, Rodolfo; López-Beltrán, Antonio; Rank, Joseph; Baldridge, Lee Ann; Liu, Cheng

doi:10.1158/1078-0432.ccr-07-4146

Cited by 47 publications

(33 citation statements)

References 31 publications

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“…We analyzed the spatial distribution of the green and red signals to detect the specific patterns of signal aggregation consistent with i(12p), as previously reported. [10][11][12][13][14][15][16][17] The quantitative criteria to determine 12p overrepresentation were described previously. [10][11][12][13][14][15][16][17] Classical seminoma specimens with known positive i(12p) and 12p overrepresentation was used as a positive control for FISH analyses.…”

Section: -17mentioning

confidence: 99%

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Molecular genetic evidence supporting the neoplastic nature of fibrous stroma in testicular teratoma

et al. 2012

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Testicular teratoma typically consists of heterogeneous mixtures of diverse epithelial and stromal components. The biological nature and genetic characteristics of the fibrous stroma of testicular teratomas have not been thoroughly investigated. Chromosome 12p abnormalities are the hallmark genetic alterations of germ cell tumors. We studied chromosome 12p abnormalities in the fibrous stroma and other components of pure testicular teratomas from 32 patients using interphase fluorescence in situ hybridization. Overall, 72% (23/32) of pure testicular teratomas had chromosome 12p abnormalities. Isochromosome 12p or 12p overrepresentation independent of isochromosome 12p was detected in the fibrous stroma in 53% (17/32) and 41% (13/32) of cases, respectively. Among the 17 cases positive for isochromosome 12p, 8 (47%) also had 12p overrepresentation. In 31% (10/32) cases, the fibrous stroma showed neither 12p overrepresentation nor isochromosome 12p. Isochromosome 12p and 12p overrepresentation were identified, respectively, in the gastrointestinal-type epithelium of 14/23 (61%) and 15/23 (65%) cases; in the respiratory-type epithelium of 41% (7/17) and 41% (7/17) cases; in the squamous epithelium of 62% (8/13) and 54% (7/13) cases; and in the cartilage of 63% (5/8) and 38% (3/8) cases. Concordant chromosomal 12p abnormalities were observed between the fibrous stroma and epithelial elements of testicular teratomas. Our results indicate that the fibrous stroma of testicular teratomas frequently has genetic abnormalities similar to those of the epithelial components. Concordant chromosome 12p alterations between the fibrous stroma and epithelial elements provide further evidence that both epithelial and fibrous components of teratoma are derived from a common progenitor.

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Section: -17mentioning

confidence: 99%

“…5,[9][10][11][12][13][14][15][16] Thus, chromosome 12p alterations are clinically relevant markers for tumors of germ cell origin. Multiple molecular and genetic studies show that testicular teratomas share the same chromosome 12p abnormalities that are observed in all histological subtypes of the vast majority of testicular germ cell tumors.…”

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confidence: 99%

Molecular genetic evidence supporting the neoplastic nature of fibrous stroma in testicular teratoma

et al. 2012

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“…Abbosh et al observed Isochromosome 12 p on the carcinoid tumour tissue in all four cases of testicular carcinoid tumour arising in mature teratoma. This study shows that testicular carcinoid tumours associated with teratoma, a germ cell neoplasm that shares the same clonal origin as yolk sac, embryonal carcinoma and choriocarcinoma, are of germ cell origin (4).…”

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confidence: 68%

A Small Cell Carcinoma in the Testis Associated with Testicular Teratoma

Türkmen¹,

Erdoğan²,

Kodaz³

et al. 2014

Balkan Med J

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Dear Editor, Neuroendocrine neoplasms of the testis are extremely rare, accounting for 0.2% of all testicular neoplasms. Although the origin of the primary testicular neuroendocrine tumour is controversial, components of mature teratoma, leydig cells and intratubular germ cell neoplasia have been reported as precursor lesions (1, 2). Although a case of small cell carcinoma (SmCC) originating from an ovarian teratoma has been reported (3), to our knowledge there are no reports in English including SmCC of the testis originating from a testicular teratoma. In this paper, we present a metastatic SmCC of the testicle associated with testicular teratoma, along with its pathological properties, clinical course and treatment results.A 44-year-old male patient with a painless testicular mass underwent left radical orchiectomy in another hospital in 2010. The histopathological diagnosis was a 12 cm mixed germ cell tumour (GCT) composed of mature teratoma and embryonic cell carcinoma. Beta-human-chorionic-gonadotropin, alpha-fetoprotein levels and lactate-dehydrogenase levels were normal. Multiple pulmonary nodules (the largest 6 cm) and paraaortic lymphadenopathy (the largest 1.5 cm) were detected by computed tomography (CT).The patient was relatively old for non-teratoma non-seminoma GCT and tumour markers were normal; thus the orchiectomy material was reexamined in our centre to exclude other neoplasms besides GCT. Immunohistochemical and morphological findings were consistent with SmCC originating from mature teratoma (chromogranin, synaptophysin, neuron-specific enolase positive, CD56, MIC-2, GFAP negative).Although the patient had a diagnosis of SmCC, we treated him according to the principles of GCT treatment. Based on the knowledge that extrapulmonary SmCCs may behave in a different way than pulmonary SmCCs in terms of the organ of origin, we opted for germ cell carcinoma treatment rather than classical SmCC. As the chemotherapy protocol (cisplatin/ etoposide/bleomycin) that is effective against GCT involves similar agents and doses as the cisplatin/etoposide protocol used against SmCC, we applied four cycles of cisplatin/etoposide/bleomycin. After partial response had been achieved, two additional cycles of cisplatin/etoposide were applied (to protect against bleomycin toxicity). After six courses of chemotherapy, the paraaortic lympadenopathy in the abdominal CT disappeared and a large number of lesions disappeared on the thorax CT, but three lesions (the largest 2 cm) remained. Three months after the completion of chemotherapy, pathological FDG involvement was not observed in residual pulmonary lesions on PET/CT.In accordance with the GCT treatment approach, metastasectomy oriented to teratoma and microscopic residual disease was planned. However, the patient declined surgery. The patient has since been followed without recurrence and metastasis for 15 months. Although it was not possible to apply surgical treatment oriented to lung metastasis in our case, the efficiency of our treatment led us to believe that ...

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“…Primary testicular carcinoids were once thought to arise from Argentaffin cells within the gonad, but this notion has been discarded due to the absence of these cells in the testis [10]. Some workers have proposed the origin of primary testicular carcinoids from Leydig cells, however Abbosh et al showed identical genetic aberrations within primary testicular carcinoids and coexisting mature teratoma [11,12]. Primary testicular carcinoid tumors are now thought to be of germ cell origin, arising either as a monodermal germ cell tumor or existing as the remaining component of a burnt out teratoma [2].…”

Section: Discussionmentioning

confidence: 99%

“…Though carcinoids are presumed to be of germ cell origin, they do not show significant numerical abnormalities of the X chromosome as in other testicular germ cell tumors [27]. Cytogenetic abnormalities reported in testicular carcinoids include aneuploidy, tetraploidy, isochromosome 12 and 12p over-expression [12,28].…”

Section: Testicularmentioning

confidence: 97%

Well Differentiated Neuroendocrine Carcinoma of the Testis in a Nigerian Male

Nz¹,

Fc²,

Dawodu³

et al. 2015

JCR

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Abstract:Testicular carcinoids are very rare tumors that account for less than 1% of all testicular neoplasms. We present the first case of a testicular carcinoid tumor in a Nigerian male who had radical orchiectomy on account of a painful left testicular mass. Histology showed a thinly encapsulated lesion composed of sheets of closely packed spindle cells having a uniform 'salt-and-pepper' chromatin pattern, and moderate pale cytoplasm within a scant dense fibrocollagenous stroma. Mitoses were scanty and necrosis absent. There was no evidence of an intratubular germ cell tumor. The lesional cells stained positive, on immunohistochemistry, for CD 56, NSE and S100, though they were negative for chromogranin A and synaptophysin. They also showed positivity for AE 1/3 in a para-nuclear dot-like fashion. There was complete negativity for CD 99, CD 117, PLAP and EMA. The cells were weakly positivity for inhibin, while CD 45 marked only a small population of lymphocytes. A diagnosis of a spindle cell type carcinoid tumour/well differentiated neuroendocrine carcinoma was made. The presence of a fibrous capsule suggested a primary testicular lesion and subsequent abdomino-pelvic CT scan showed no intra-abdominal primaries. However, investigations to rule out a focus from the lungs are yet to be done.

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Germ Cell Origin of Testicular Carcinoid Tumors

Cited by 47 publications

References 31 publications

Molecular genetic evidence supporting the neoplastic nature of fibrous stroma in testicular teratoma

Molecular genetic evidence supporting the neoplastic nature of fibrous stroma in testicular teratoma

A Small Cell Carcinoma in the Testis Associated with Testicular Teratoma

Well Differentiated Neuroendocrine Carcinoma of the Testis in a Nigerian Male

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