What's New in the Classification and Staging of Testicular Tumors?
Thomas M. Ulbright
Indiana University School of Medicine
In the 2003 version of the classification of testicular tumors that is soon to be published by the
World Health Organization (WHO), the most significant change from prior editions (WHO '98) relates to
teratomas. Whereas previously testicular teratomas were placed into three major categories (mature,
immature and "with malignant transformation"), WHO '03 condenses the classification into two categories:
teratoma and teratoma with somatic-type malignancy (or possibly "non-germ cell malignancy") (with
specification of the type of malignancy). The distinction of mature and immature teratoma is not
considered important, for reasons discussed below, which allows this compression. The term "teratoma
with malignant transformation" is discarded because it wrongly implies that teratoma lacking such
"malignant transformation" is benign, which is clearly not the case.
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
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
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.
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- Sesterhenn IA , Mesonero C , Davis CJ , Mostofi FK . Testicular teratomas in adults . Histopathology
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- Manivel JC , Reinberg Y , Niehans GA , Fraley EE . Intratubular germ cell neoplasia in testicular
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- Silver SA , Wiley JM , Perlman EJ . DNA ploidy analysis of pediatric germ cell tumors . Mod Pathol
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- Grady RW , Ross JH , Kay R . Epidemiological features of testicular teratoma in a prepubertal
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- Harms D , Jšnig U . Immature teratomas of childhood. Report of 21 cases. Pathol Res Pract 1985; 179
- Hawkins EP , Hicks MJ . Solid tumors and germ cell tumors induce nonneoplastic germ cell
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- Younger C , Gu J , Ulbright TM , Cheville JC , Billings SD , Cummings OW , Zhang S , Eble JN , Cheng
L . Loss of heterozygosity in epidermoid cysts of the testis . Mod Pathol 2001; 14 : 130A .
- Price EB, Jr. Epidermoid cysts of the testis: a clinical and pathologic analysis of 69 cases from
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- Dieckmann KP , Loy V . Epidermoid cyst of the testis: a review of clinical and histogenetic
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- Ulbright TM , Srigley JR . Dermoid cyst of the testis: a study of five postpubertal cases, including
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- Dry SM , Renshaw AA . Extratesticular extension of germ cell tumors preferentially occurs at the
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- Nazeer T , Ro JY , Kee KH , Ayala AG . Spermatic cord contamination in testicular cancer. Mod Pathol
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