Spermatocytic seminoma is an uncommon neoplasm unique to the testis with clinicopathologic features distinctive from classic seminoma, and is not considered a variant of the latter. It was first recognized and described by Masson ("le seminome spermatocytaire") in 1946. [1, 2, 3]
See an example of a spermatocytic seminoma depicted in the histologic image shown below.
Spermatocytic seminoma has an annual incidence of approximately 0.2 per 100 000, comprising no more than 2% of all testicular germ cell tumors (TGCTs), with no clear rise during recent decades.  Less than 400 cases have been reported in the literature since the first description. A contemporary population-based study has shown that spermatocytic seminomas represent about 1% of all seminomas, with an increase in incidence over the past decades.  In a recent series from Pakistan, there were 16 spermatocytic seminomas and 486 classic seminomas in a 21-year span. 
Patients with spermatocytic seminoma are usually older than patients with other testicular germ cell tumors, with most cases presenting on the sixth decade. However, age at diagnosis ranges from 19-92 years (mean, 53.5 y); therefore, spermatocytic seminoma should be considered in the differential diagnosis of testicular germ cell tumors presenting in young adults. 
Unlike other testicular tumors, spermatocytic seminoma does not appear to be linked to cryptorchidism and is not associated with intratubular germ cell neoplasia, unclassified type (IGCNU), or other testicular germ cell tumor subtypes.  One study made an attempt to link human spermatogonial stem cells as the cell of origin for this tumor,  evidence that was reinforced by the expression of OCT2, SSX, and SAGE1, which point to a spermatogonia as a cell of origin in a different study.  A immunohistochemical and molecular study supports that these tumors are likely to originate in a cell farther along the developmental pathway than those that give rise to other germ cell tumors. 
The primary tumor site is limited to the testis and, unlike classic seminoma, spermatocytic seminoma has never been reported as primary at extragonadal sites. Bilateral involvement occurs in less than 5% of cases and is usually asynchronous. [11, 12, 13] They rarely involve the rete testis and may compress the epididymis without invading it.
Clinical Features and Imaging
Most spermatocytic seminomas present with painless testicular enlargement, which can be referred to several years before the diagnosis. Spermatocytic seminomas are not associated with any serum marker elevation. 
Spermatocytic seminomas are usually multinodular, with a cut surface that varies from gray-white and fleshy to tan and gelatinous. Hemorrhage and necrosis may be present as well as extratesticular extension. The size varies from 1.0 to 20 cm, with more than 70% measuring 3-8 cm. Microcysts are common. Necrosis and hemorrhage are rare, and if present, these features may suggest associated sarcoma. 
Nodules of diffuse sheets of cells in spermatocytic seminoma are usually interspersed by edema. If extensive, the edema can give rise to a nested, pseudoglandular or trabecular pattern. Fibrous septa, clear cytoplasm and associated granulomatous reaction, present of classic seminoma, are virtually lacking in spermatocytic seminoma. Likewise, lymphoid infiltrate is scant to absent, and usually limited to a perivascular distribution at the periphery of the tumor. See the images below.
The most distinctive feature of spermatocytic seminoma is cellular variation. Cells with uniformly round nuclei but with variation in diameter (6-100 µm) are distributed in 3 distinctive populations: small lymphocytelike cells (6-8 µm) with smudged chromatin and slightly more cytoplasm than a lymphocyte; intermediate-sized cells (15-20 µm), the most common cell type; and large cells (50-100 µm), that may be mono- or multinucleated. The chromatin is dense in small cells and filamentous in the intermediate and large ones, with a "spireme" appearance, reminiscent of primary spermatocytes, hence the name. The mitotic rate is often high and apoptosis is prominent. The cytoplasm is eosinophilic to amphophilic and lacks glycogen (periodic acid Schiff [PAS] negative). See the following images.
The controversial and rare "anaplastic" variants of spermatocytic seminoma consist of a relatively monomorphic population of intermediate-sized cells with only foci of typical spermatocytic seminoma elsewhere. [15, 16, 17] Spermatocytic seminomas may also present in combination with sarcoma, in which the sarcomatous component, consisting of poorly differentiated spindle cells, is intermingled with the spermatocytic seminoma cells.  One recent report described a case of spermatocytic seminoma and undifferentiated sarcoma, with the sarcomatous component recurring and metastasizing to both lungs within a year of diagnosis. 
Although spermatocytic seminoma is not associated with IGCNU, intratubular spread is a common finding.  In fact, secondary nodules are thought to evolve from invasive cells in foci of intratubular spermatocytic seminoma. The tubules are distended by a polymorphous population of cells that lack the characteristic features of IGCNU.
Fine-needle aspiration cytology findings can be diagnostic if the typical triple-cell population is sampled, with a preponderance of medium-sized cells with visible nucleoli. The background should be clean, in contrast to the "tigroid" substance seen in classic seminoma. Absence of lymphocytes can also aid the diagnosis. 
Table 1. Clinicopathologic Features of Spermatocytic Seminoma Versus Seminoma (Open Table in a new window)
|Mean age, y||55||40|
|Proportion of all TGCTs||2%||Up to 50%|
|Other types of GCT||No||Yes|
|Site of presentation||Testis||Testis + midline sites|
|Nuclear pleomorphism||Yes (3 populations)||No (nuclear monotony)|
|Lymphoid reaction||Absent to scant||Prominent|
|Glycogen||Absent to scant||Abundant|
|PLAP staining||Absent to scant||Prominent|
|Modified from Sternberg's Diagnostic Surgical Pathology, 4th ed, 2004.  GCT = germ cell tumors; IGCNU = intratubular germ cell neoplasia, unclassified; PLAP = placental alkaline phosphatase; TGCT = testicular germ cell tumors.|
Spermatocytic seminoma is negative for markers such as placental alkaline phosphatase (PLAP), OCT3/4, AE1/AE3, and CD30, which are usually positive in embryonal carcinomas. Other negative markers include S-100, vimentin, actin, desmin, alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), leukocyte common antigen (LCA) and cytokeratins, although CAM5. 2 may show focal cytoplasmic positivity. 
Immunostaining for c-kit is positive in 100% of spermatocytic seminomas, although this finding is not useful in the distinction from classic seminoma because it is positive in both. Positive specific markers for spermatocytic seminoma include antibodies directed against synovial sarcoma on the X chromosome (SSX) mainly found in spermatogonia,  xeroderma pigmentosum type A protein (XPA) which is expressed in pachytenespermatocytes, and synaptonemal complex protein 1 (SCP1), a marker for cells undergoing meiosis.  Spermatocytic seminomas have been reportedly positive for OCT2 and SSX2-4 markers, which may suggest a spermatogonia as their cell of origin.  More recently, positivity for three antibodies has been described to be highly sensitive, but not entirely specific, for spermatocytic seminoma: nuclear protein in testis (NUT), GAGE7, and NY-ESO-1. 
Although classic seminomas originate from an embryonic germ cell, spermatocytic seminomas are likely to originate in a cell farther along the developmental pathway capable of differentiating toward the primary pachytene-spermatocyte stage of maturation. Because of the distinctive meiotic-type chromatin in some cells, it has been proposed that spermatocytic seminomas develop from meiotic cells.
Although haploid DNA and lectin-binding studies have failed to demonstrate advanced spermatogenic differentiation,  stage-specific markers for male germ cell development are positive in spermatocytic seminomas but not on other testicular germ cell tumors.  Similarly, proteins expressed in gonocytes and spermatogonia are consistently present in spermatocytic seminoma.
In contrast, antigens expressed in embryonic germ cells but not in the normal adult testis are usually undetectable, with the exception of p53 protein, which has been demonstrated in 80% of cases.  Furthermore, the genomic imprinting in spermatocytic seminoma has a paternal pattern in contrast to other testicular germ cell tumors, which generally show an erased pattern of imprinting, supporting the idea of a more differentiated cell of origin in spermatocytic seminoma. 
Although classic seminomas show characteristically overrepresentation of the 12p chromosome, it appears that the most common abnormality in spermatocytic seminoma is gains in chromosome 9.  Based on the region of amplification and the associated expression defined on 9p, DMRT1 (a male-specific transcriptional regulator) was identified as a likely candidate gene for involvement in the development of spermatocytic seminomas. [3, 28]
Tumor Spread and Staging
Despite nuclear pleomorphism and the alarming microscopic appearance, spermatocytic seminomas have a benign clinical course, with only 2 reports of metastasis in the literature if there is no sarcomatous component. [29, 30, 31] However, if associated with sarcoma, the sarcomatous component is likely to progress either to local recurrence or hematogenic metastasis, lung being the preferred site. [3, 30, 31, 18] Metastatic disease at the time of presentation or histological diagnosis has been reported in at least six cases of spermatocytic seminoma with sarcoma association, with two cases developing metastatic disease months or years after orchidectomy.  There has been one recent report with an association of spermatocytic seminoma with lymphoma. 
The image below depicts spread to the testicular parenchyma.
Prognosis and Predictive Factors
Unless complicated by sarcoma, spermatocytic seminomas follow a benign course and orchiectomy alone is the preferred treatment.  Therefore, and also limited by the small number of cases in most series, prognostic markers have been secondary in the disease appraisal and management. One recent series with a 6-year median follow-up did not show any recurrence in cases without sarcoma. 
It has been hypothesized, however, that apoptosis may play a role in the indolent behavior of spermatocytic seminomas in an analogy to indolent behavior in other tumor systems (notably CD30-positive cutaneous lymphoma, another neoplasm where phenotype and behavior do not match).  Significantly greater numbers of apoptotic cells and activated caspase-3-positive cells were found in spermatocytic seminoma compared with usual seminoma. Furthermore, apoptotic parameters were decreased in sarcomatous transformation of spermatocytic seminoma.