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Pathological risk factors for metastatic disease in patients with testicular non-seminomatous germ cell tumors are debated. The tumor-node-metastasis (TNM) classification eighth edition for testicular cancers includes divergent versions, by the International Union Against Cancer (UICC) and by the American Joint Committee for cancer (AJCC). We investigated pathological predictors of metastatic disease at presentation in 219 non-seminomatous germ cell tumors with reference to both classifications. Age, tumor size, percentage of embryonal carcinoma, lymphovascular invasion, invasion of stromal rete testis, hilar soft tissue, epididymis, spermatic cord, and tunica vaginalis, as well as tumor at spermatic cord margin, were assessed and correlated with clinical stage at presentation. Of the 219 NSGCT cases, 151 (69%) were clinical stage I, 68 (31%) were clinical stage II/III. On univariate analysis, tumor size (P = 0.028), percentage of embryonal carcinoma (P = 0.004), lymphovascular invasion (P = 0.001), stromal rete testis invasion (P = 0.001), hilar soft tissue invasion (P = 0.010), epididymis invasion (P = 0.010), direct spermatic cord invasion (P = 0.001), and tumor at spermatic cord margin ((P = 0.009) were associated with higher clinical stage. On multivariate analysis, lymphovascular invasion (P = 0.003), tumor size (P = 0.005), percentage of embryonal carcinoma (P = 0.005), stromal rete testis invasion (P = 0.008) remained significant. A tumor size of 6 cm and an embryonal carcinoma percentage of 70% were the significant cut-off values. We conclude that in addition to lymphovascular invasion, stromal rete testis invasion, tumor size, and embryonal carcinoma percentage are strong predictors of metastatic disease at presentation and their inclusion should be considered in any future TNM revision. Further, our results support the changes in the AJCC TNM eighth edition as invasion of the epididymis and hilar soft tissue were both univariately significant.

In 2016, the World Health Organization classification system of testicular tumors included the new entity prepubertal-type teratoma based on its morphological and molecular profile, and the realization that these tumors may occur in postpubertal men. For treatment and prognostic purposes, it is important to distinguish prepubertal-type teratoma from the usual postpubertal-type teratoma, because the former is benign unlike the latter. The distinction may be challenging. In this study, we investigated clinical, morphological, and molecular criteria for distinguishing prepubertal-type teratoma from postpubertal-type teratoma in a prospective series of pure testicular teratomas. All cases of pure teratoma in postpubertal men assessed at Barts Health NHS Trust or in consultation since the introduction of routine investigation of chromosome 12p status in 2010 were reviewed. Morphological features suggestive of prepubertal-type teratoma were observed in 14 out of 35 cases. All underwent molecular testing and none displayed 12p amplification. Mean tumor size was 16 mm (range 7-28 mm). None had associated germ cell neoplasia in situ or significant atrophy. Four incorporated a well-differentiated neuroendocrine tumor, 1-2 mm in size. Of the ten patients with follow-up information, none have recurred or metastasized. Twenty-one of the 35 cases were diagnosed as postpubertal-type teratoma, mean tumor size 40 mm (range 6-90 mm). One case underwent molecular testing: a tumor of pure skeletal muscle differentiation and possessed 12p amplification. Three cases presented with clinical metastases. Eight cases contained immature areas, ten cases had associated germ cell neoplasia in situ, and 17 cases had severe atrophy of the parenchyma. One case with neither germ cell neoplasia in situ nor atrophy showed necrosis. We conclude that both morphological and molecular features are of help in differentiating prepubertal-type teratoma from postpubertal-type teratoma. In nearly all postpubertal-type teratomas, molecular testing was unnecessary, and merely confirmed the morphological impression in the prepubertal-type teratomas. Our study confirmed the high incidence of well-differentiated neuroendocrine tumors in the prepubertal-type.