In 1907, a German pathologist named Oberndorfer explored the term carcinoid (karzinoide) to distinguish a group of tumors found in the small intestine 1
. The first case of a primary TCT was reported by Simon et al. 3
in 1954. The histogenesis of neuroendocrine neoplasms of the testis remains unclear, although several hypotheses have been proposed. Abbosh et al. 4
suggested that TCTs typically occur in the background of a teratoma. They found that isochromosome 12p and 12p over-representations were present in both the carcinoid tumor cells and in the cells of the co-existing mature teratoma. Mai et al. 5
proposed that TCTs arise from Leydig cells, which may be new members of the diffuse neuroendocrine system. In addition, using immunohistochemical methods, Davidoff et al. 6
found neuronal and neuroendocrine cell substances in the cytoplasm of the interstitial Leydig cells of human testes. These findings support the hypothesis that both carcinoid tumor cells and Leydig cells may have the same cell origin in the primary TCT.
Tumor grade is used as the basis for prognostic classification systems, including those proposed by the European Neuroendocrine Tumor Society (ENETS) and the World Health Organization (WHO) 7,8. In 2010, the revised WHO classification of neuroendocrine neoplasm defined three tumor grades based on either the mitotic rate (mitoses per 10 HPFs) or the Ki67 index (%):
Grade 1 (NET G1): 2 mitoses/10 HPFs or Ki67 index <2%
Grade 2 (NET G2): 2-20 mitoses/10 HPFs or Ki67 index 320%
Grade 3 (NET G3): >20 mitoses/10 HPFs or Ki67 index >20%.
The term carcinoid tumor is used for NET G1.
In 2016, testis carcinoid tumors were identified as well-differentiated NETs, as part of the WHO classification for tumors of the urinary system and male genitalia. The cases may be pure primary neoplasm as well as with teratomas or epidermoid/dermoid cysts. Most primary TCTs have a benign clinical behavior, regardless of association with teratomas or epidermoid/dermoid cysts. However, lesions with the morphology of an atypical carcinoid can occasionally display metastatic spread. Atypical carcinoid tumors have either coagulative necrosis or increased mitotic activity, with 2-10 mitoses per 10 HPFs. In a series of 29 cases, 1 of the 3 atypical carcinoid tumors had agressive behavior, with a lymph node metastasis and a lung metastasis 9.
In this case study, the patients tumor showed a mitotic rate of 1 mitosis per 10 HPFs by using phospho-histone H3 (pHH3) immunohistochemical stain and a ki67 proliferation index of 1%. There was no necrosis. So that pathological diagnosis was NET G1.
The most common presentation of a TCT is a painless testicular enlargement, followed by testicular pain and the presence of a hydrocele. Carcinoid syndrome occurs in 10-20% of all carcinoid tumors. No carcinoid syndrome was observed in this case.
Grossly, the tumors appear to be yellow/tan-colored and solid, with a firm, cut surface due to desmoplasia. The average tumor size is 4.6 cm (ranging from 1.0 cm to 9.5 cm). On histopathologic examination, there are insular, trabecular patterns of monotonous neoplastic cells, with abundant eosinophilic cytoplasm, round-to-oval nuclei, and a distinct nuclear membrane displaying a salt and pepper chromatin pattern. The tumor shows positive immunostaining for chromogranin, synaptophysin, and CD56, and negative immunostaining for placental alkaline phosphatase, CD30, β-HCG, AFP, and epithelial membrane antigen. The Ki67 proliferation index is <1% in tumor cells.
Morphologically, primary TCTs cannot be distinguished from well-differentiated neuroendocrine carcinoma. The diagnosis of a primary TCT was made after ruling out extratesticular NET, using both clinical and radiology data. The treatment course decided was radical orchiectomy. While carcinoid tumors usually have an excellent prognosis, factors such as large tumor size, the presence of carcinoid syndrome, and distant metastases can worsen the prognosis 10.
The primary carcinoid tumor of the testis is a rare tumor, and this case will contribute to the literature. It should be exclude the metastasis of TCT, because the primary tumor is indistinguishable from the metastatic ones with the morphological and histological characteristics.