Gonadal
germ cell tumors continue to be the cause of diverse, diagnostically challenging issues for the pathologist, and their correct resolution often has major important therapeutic and prognostic implications. They are academically interesting because of the biological diversity exhibited in the two gonads and variation in frequency of certain
neoplasms. The most dramatic examples of the latter are the frequency of
dermoid cyst in the ovary compared to the testis and the reverse pertaining to
embryonal carcinoma. Within the
teratoma group, there is strong evidence that ovarian and prepubertal testicular
teratomas are derived from benign germ cells, a pathogenesis that likely applies also to the rare
dermoid cysts and uncommon
epidermoid cysts of the testis. In contrast, postpubertal testicular
teratomas derive from malignant germ cells, specifically representing differentiation within a preexistent nonteratomatous
cancer. As expected, given the foregoing,
teratomas in boys are clinically benign, whereas in postpubertal males they are malignant, independent of their degree of immaturity. On the other hand, immaturity is an important finding in ovarian
teratomas, irrespective of age, although its significance in children has recently been challenged. It is usually recognized on the basis of embryonic-appearing neuroepithelium, which shows mitotic activity and apoptosis in contrast to differentiated neuroepithelial tissues, which may occur in mature ovarian
teratomas. Rarely it is based on the presence of cellular, mitotically active glial tissue. Fetal-type tissues alone are not sufficient for a diagnosis of
immature teratoma. Further differences between the teratomatous
tumors in the two gonads are the relative frequency of monodermal
teratomas in the ovary in contrast to the testis, where only one subset,
carcinoids, is seen with any frequency. When uncommon somatic-type
malignancies (usually
squamous cell carcinoma) occur in mature cystic
teratomas of the ovary, this is a de novo form of malignant transformation; similar
tumors in the testis, a very rare event, represent overgrowth of teratomatous elements that originated from malignant, nonteratomatous
germ cell tumors and, therefore, had previously undergone malignant transformation.
Germinomas may have several unusual features in each gonad; these include microcystic arrangements that suggest
yolk sac tumor, tubular patterns that mimic
Sertoli cell tumor, apparent increased cytological atypia that causes concern for
embryonal carcinoma, and prominent syncytiotrophoblast giant cells that suggest
choriocarcinoma. Awareness of these variants, good technical preparations, the retained typical cytological features of
germinoma cells, and the judicious use of tailored panels of immunohistochemical stains resolve these dilemmas in virtually all instances. Two aspects of
germinomas are unique to the testis. Firstly, intertubular growth of small
seminomas may cause them to be overlooked. Secondly, the distinctive spermatocytic
seminoma occurs only in the testis. A newly recognized aspect of this
tumor is the propensity for some to be relatively monomorphic, making them
apt to be mistaken for usual
seminoma or
embryonal carcinoma, although the characteristic polymorphic appearance in some foci, absence of intratubular germ cell
neoplasia, unclassified type, and immunohistochemical stains should prevent this error. Cytoplasmic membrane immunoreactivity for
placental alkaline phosphatase and CD117, with usual negativity for AE1/AE3 cytokeratins, is helpful in the diagnosis of
germinoma. The recently described marker, OCT3/4, a nuclear
transcription factor, is especially helpful in the differential of
germinoma and
embryonal carcinoma with other
neoplasms.
Yolk sac tumor continues to be confused occasionally with clear cell
carcinoma of the ovary. Glandular ('endometrioid-like')
yolk sac tumors mimic
endometrioid carcinomas; predominant or pure hepatoid
yolk sac tumors cause concern for metastatic
hepatocellular carcinoma or, in the ovary, primary hepatoid
carcinoma, and solid patterns, especially in limited samplings, may be misinterpreted as
germinoma. The usually younger age of patients with
yolk sac tumors helps with the differential considerations with the nongerm cell
tumors, as do other clinical and microscopic features and selected immunohistochemical stains.
Choriocarcinoma is rare in both gonads, and those in the ovary must be distinguished from metastatic
tumors of placental origin. Syncytiotrophoblast cells alone, admixed with other forms of
germ cell tumor, still are confused with
choriocarcinoma, but this phenomenon, which is much more frequent than
choriocarcinoma, lacks the plexiform arrangement of different trophoblast cell types that typifies the latter. Mixed
germ cell tumors (which may show almost any combination of components) are common in the testis but rare in the ovary. A separately categorized, rare form of mixed
germ cell tumor seen in both gonads is the polyembryoma. It is perhaps the most photogenic of all gonadal
germ cell tumors and is also intriguing because of its distinctive, organized arrangement of
yolk sac tumor and
embryonal carcinoma elements and recapitulation of very early embryonic development, even to the extent of having in its fundamental unit, the embryoid body, a miniature yolk sac, and amniotic cavity. These
tumors, which are constituted by innumerable embryoid bodies, almost always contain teratomatous glands in minor amounts, and one way of viewing the polyembryoma is to consider it the most immature form of
teratoma. Embryoid bodies are also common as a minor component of many mixed
germ cell tumors, particularly in the testis, and the diffuse embryoma is another variant that has a particular arrangement of
yolk sac tumor and
embryonal carcinoma elements. Regression of gonadal
germ cell tumors is a phenomenon restricted to the testis, for unknown reasons. These so-called 'burnt-out'
germ cell tumors can be recognized by a distinctive constellation of findings, including sometimes minor foci of residual recognizable germ cell
neoplasia, a well-defined zone of
scarring (often having residual ghost tubules), associated lymphoplasmacytic infiltrate, intratubular calcification and, in about 50%, of in situ germ cell
neoplasia.