British Association of

Urological Pathology

British Association of Urological Pathology



In two recent papers Ulbright and colleagues have described some unusual morphologic manifestations of Leydig cell tumors. The first of these contributions recorded cystic spaces, usually small, but sometimes large (Fig. 3), resulting in confusion with various neoplasms such as yolk sac tumor (4). It is hard to think of a better example of the importance of thorough sampling in evaluating gonadal tumors because when this results in other slides showing typical Leydig cell tumor, mere awareness of the phenomenon will enable the correct interpretation to be made. Particularly in cases with unusual morphology staining for inhibin may be helpful, as it may in cases of sex cord tumors of other types such as Sertoli cell tumors, granulosa cell tumors and those in the unclassified group.

The second series contained 12 tumors with adipose differentiation, eight with spindle cells and three with calcification and ossification (34). These features had only rarely been described previously. The adipose differentiation is important in that it is also a feature of some cases of the testicular tumor of the adrenal genital syndrome and accordingly does not reliably facilitate the differential diagnosis of these two entities. A spindle cell pattern, if prominent, may obscure the underlying diagnosis of Leydig cell tumor and bring other entities such as sex cord-stromal tumor, unclassified, or even testicular sarcoma into the differential diagnosis but thorough sectioning and awareness of the phenomenon usually resolves the problem. Calcification can potentially erroneously suggest the diagnosis of a large cell calcifying Sertoli cell tumor but the latter entity shows unequivocal tubular differentiation. Ossification is only a pathologic curio. None of these unusual features, including spindle cell, appears to have prognostic importance.


In our study of 60 Sertoli cell tumors, not otherwise specified (42), the two morphologic findings which we found most noteworthy in the sense that they had not been emphasized in the prior literature were the presence in many cases of a prominent diffuse growth with rather limited evidence of the tubular component that enables the diagnosis to be rendered with confidence, and in addition, the presence in some instances of cells with copious eosinophilic cytoplasm bringing the differential diagnosis of a Leydig cell tumor into consideration.

A subsequent paper on malignant Sertoli cell tumors (18) further emphasized the problem the above noted diffuse pattern may cause. First of all, not surprisingly, a diffuse growth is particularly likely to be seen in malignant tumors because of the limited differentiation seen in such cases. The 13 cases in this category were usually initially misdiagnosed as seminoma, usually of the classic type but occasionally of the spermatocytic type. In many of them the correct diagnosis was only made retrospectively after failure of the patient to respond to therapy usually successful in cases of seminoma. The problems on microscopic examination were related primarily to the diffuse growth but were compounded by other features common in seminoma: a nested pattern, cells with clear cytoplasm that was positive for glycogen in 3 of 4 tumors tested, prominent nucleoli (5 cases) and lymphoid infiltrate (10 cases). Focal tubular differentiation was crucial diagnostically but was often limited in amount. Other helpful findings were nuclei that were smaller and less pleomorphic than those of seminomas and immunohistochemical staining for inhibin and negative staining for placental-like alkaline phosphatase. As expected the testis adjacent to the tumor did not show any intratubular germ cell neoplasm.

An unusual phenomenon associated with an occasional Sertoli cell tumor and for that matter sex cord stromal tumors of the testis of other types arises when these often slowly growing tumors incorporate non-neoplastic germ cells within them resulting in a mimicry of true mixed germ cell-sex cord stromal tumors. We recently reported 10 cases of this type (35). Although the majority of the tumors were in the unclassified sex cord stromal category I will not be discussing such tumors because of time constraints and consider it briefly at this juncture. The admixed germ cells were usually at the periphery and in clusters but occasionally were in the center of the neoplasm or more diffusely distributed. None of the entrapped germ cells stained with markers for neoplastic germ cells. In our experience, this peculiar phenomenon of entrapment of germ cells within a sex cord tumor is more common than the exceptionally rare mixed germ cell sex cord-stromal tumor unclassified.


Granulosa cell tumors of both adult and juvenile types as seen so much more commonly in the ovary may be seen in the testis. The most interesting and potentially crucial issues are associated with the juvenile form so only a few remarks on it are made here. The distinctive tendency for the tumor to occur in the first six months of life is important to remember. On microscopic examination some neoplasms have conspicuous follicles and should be a relatively straightforward diagnosis but others can have only limited follicular differentiation and a solid-to-nested pattern which can be much more problematic (Fig. 4). In some cases the fluid that is typically present in the follicles may be present in an ill-defined manner in the background in foci without an overt follicular pattern and this may separate the tumor cells and impart a vague resemblance to the reticular pattern of yolk sac tumor. The immature nuclei of the juvenile granulosa cell tumor may further heighten resemblance to yolk sac tumor. Although routine light microscopic differences should enable the differential to be made there is a role for immunohistochemistry in this differential should it be deemed necessary. Finally, in some juvenile granulosa cell tumors the cells do not have the appreciable cytoplasm that is generally present and I have even seen confusion with small cell malignant tumors such as rhabdomyosarcoma. Of course, a basic principle of testicular tumor pathology, namely where the tumor is centered, can be helpful because most rhabdomyosarcomas are paratesticular albeit that they may secondarily involve the testis.