Longstanding clinical information and more recent ploidy and genetic studies support that the distinction of mature and immature teratoma is not important. It is clear that both mature and immature teratomas in postpubertal patients, like other examples of non-seminomatous germ cell tumors of the testis, are hypotriploid and have complex genetic abnormalities, with the consistent amplification of the short arm of chromosome 12, often in the form of an isochromosome, i(12p).^1-3  It is also clear that teratomas in postpubertal patients, whether mature or immature, are associated with metastases. The metastatic frequency in several referral series was 22-43%, probably higher than would be seen in a consecutive series because of referral bias.^4-6  The metastases in such cases may be any form of germ cell tumor, teratomatous or non-teratomatous. Additionally, teratomas in postpubertal patients are consistently associated with intratubular germ cell neoplasia of the unclassified type (IGCNU) (so-called "carcinoma-in-situ"),⁷  and frequently have cytologic atypia of their elements, reflecting this abnormal genotype. On the other hand, teratomas in prepubertal patients, whether mature or immature (which is rare), have a diploid DNA content and a normal genetic composition as shown by either karyotyping or comparative genomic hybridization (CGH) studies.^8-10  Furthermore, no testicular teratoma in a prepubertal patient, whether mature or immature, has metastasized.^11;12  Also, in contrast to the postpubertal examples, the teratomas in prepubertal patients do not have associated IGCNU,⁷  although some germ cells may appear enlarged and slightly atypical, features that had been interpreted as "reactive."¹³  Their elements do not show the cytologic atypia that is common in the postpubertal cases.

WHO '03 recognizes two benign forms of teratoma in postpubertal patients that should be classified separately, dermoid and epidermoid cysts. (Epidermoid cysts, arguably, may have a pathogenesis other than teratomatous, although the occasional occurrence of loss of heterozygosity in a minority of cases supports their neoplastic nature and is evidence against origin from mesothelial metaplasia.)¹⁴  These are benign lesions,¹⁵  with the absence of IGCNU an important criterion for their diagnosis.^7,16  Dermoids, as in the ovary, may have grossly evident hair and always have pilosebaceous units oriented to a squamous epithelial-lined surface in a skin-like fashion. A variety of non-cutaneous elements may also be seen, including cartilage and glands lined by ciliated or goblet-cell containing epithelium.¹⁷  All elements lack atypia and there is commonly an associated lipogranulomatous reaction.

Current models of histogenesis reflect these observations (see figure).

Postpubertal teratomas derive as a differentiation phenomenon from an invasive germ cell tumor, probably most commonly embryonal carcinoma, which originates from IGCNU. Prepubertal teratomas and epidermoid and dermoid cysts derive from benign germ cells.

In summary, then, teratomas in postpubertal patients, with the important exceptions of the separately categorized dermoid and epidermoid cysts, are malignant, whether they are mature or immature. In contrast, teratomas in prepubertal patients are benign, whether they are mature or immature. This understanding is reflected in the recent WHO classification.

A minor change in WHO '03 is the placement of polyembryoma into the mixed germ cell tumor category rather than its separate classification. This reflects the common recognition that this entity represents a distinctive arrangement of two germ cell tumor components, embryonal carcinoma and yolk sac tumor. A similar argument applies to "diffuse embryoma."

As far as the staging of testicular tumors is concerned, there are no changes in AJCC-TNM '02 compared to AJCC-TNM '97. However, some points deserve emphasis or clarification. Extension of the primary tumor outside of the testis usually occurs through the testicular hilum rather than by penetration of the tunica albuginea and tunica vaginalis.¹⁸  Involvement of the epididymis is still considered pT1. AJCC-TNM '02 is ambiguous with respect to the significance of extratesticular extension into the paratesticular soft tissue beyond the epididymis but which does not penetrate the tunica vaginalis or involve the spermatic cord. I, and several other pathologists with a special interest in testicular tumors, stage such cases as pT2, but a strict interpretation of AJCC-TNM '02 would permit their staging as pT1 as well. Vascular space invasion is a criterion for a pT2 tumor, but it is important not to misinterpret the common "floating" tumor cells within lymphovascular spaces secondary to knife implantation as vascular invasion. This artifact is usually associated with "buttered" tumor cells on tissue surfaces and lacks the more cohesive appearance of intravascular tumor emboli, which may have associated fibrin.¹⁹  It is also important not to mistake intratubular tumor for intravascular tumor. Intratubular tumor may have residual Sertoli cells, lacks clear-cut endothelium, has non-branching contours and relatively uniform tubular diameters and often has comedo-type necrosis, in contrast to the features of intravascular tumor. Spermatic cord involvement is a criterion for a pT3 tumor, but the involvement must be as an invasive tumor and not limited to intravascular tumor within the cord vessels. Additionally, a unique aspect to the staging of testicular tumors is the utilization of serum tumor markers in helping to define the stage groupings. For instance, patients with stage IS disease have serum marker elevation in the absence of known nodal or other metastatic disease.

References

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