Case 5 -

Seminoma with Intertubular Growth Pedro Oliveira MD Dept. Of Pathology Instituto Portugês de Oncologia Lisbon, Portugal

Clinical History: A 31-year-old male presented with a right side spermatocele. An ultrasound evaluation of the scrotal contents done prior to surgery showed a well-defined area near the hilus (12 mm) on the left side. During excision of the spermatocele surgical evaluation of both testes was performed. As no gross abnormality was present bilateral biopsies were done. A subsequent radical left orchidectomy was later performed. Case 5 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 5 - Slide 2 Click to view with ImageScope Click to view with a Web-Based Viewer Pathological Findings: The distributed images representing the biopsy specimen of the left testis showed an intertubular growth of isolated neoplastic cells with the typical cytological features of seminoma occasionally in scattered aggregates producing slightly expansion of the intertubular space. Some dispersed lymphocytes were present as well as intratubular germ cell neoplasia of the unclassified type (IGCNU). The typical immunophenotype with PLAP+ and c-kit+ was present and highlighted the neoplastic cells from the surrounding normal tissue. In the orchidectomy specimen a typical small nodule of seminoma was present in addition to the intertubular component. Some lymphocytic aggregates and atrophy and tubular sclerosis were also present. No evidence of vascular invasion or extension to the paratesticular components was observed. Diagnosis: Seminoma with intertubular growth Discussion: Seminoma is the most common germ cell tumor of the testis. It is easily recognized by the presence of relatively uniform cells with clear cytoplasm, well defined cell borders with central nuclei with one or more prominent nucleoli and an intermingled lymphoid infiltrate. The tumor generally grows in monotonous sheets of neoplastic cells occasionally exhibiting some nodularity with delicate fibrous septa. Necrosis, calcification, syncytiotrophoblast cells as well as granulomatous reaction are additional histological findings in this tumor [1]. Sometimes other unusual growth patterns are present in either pure form or more commonly combined in different proportions to the above typical or classical pattern: tubular, microcystic, pseudoglandular, cribriform, intratubular and intertubular patterns have been described [1]. The present case depicts: the intertubular pattern of growth. Although intertubular seminoma cells (IST) are often observed at the periphery of the tumor mass in the typical presentation, pure or predominantly interstitial growth is very uncommon and only recently its clinical and morphological features have been described in a paper by Henley et al in 2004 describing a series of 12 cases [2]. The most striking clinical feature of this unusual type of seminoma is the absence of a tumor mass in the testis. Most cases were discovered either for an unrelated testicular condition such as infertility or when a metastasis of seminoma was discovered. Furthermore, sonographic structural abnormalities of the testis are often absent or inconspicuous. These features make it difficult for the urologist to identify this peculiar form of seminoma. The same can be said for the pathologist! In biopsies, like the present case, the neoplastic cells can be very inconspicuous and subtle, a finding which added to an absence of distortion of the normal testicular structure can be very tricky. Helpful features like the presence of a lymphocytic infiltrate, clusters of Leydig cells, and atrophic, hyalinized seminiferous tubules as well as IGCNU are not always present. Immunocytochemistry easily highlights the neoplastic cells either using PLAP or c-kit [1, 2] and should be performed in problematic cases. What are the differential diagnoses to be considered? First and foremost very few germ cell tumors have a pure or predominant intertubular growth in order to enter in the differential diagnosis with intertubular seminoma. Henley describes a case of placental site trophoblastic tumor as presenting a striking intertubular growth [3];however the cytological features are very distinct from the typical seminoma cells. The only germ cell neoplasm in our view that should be included in the differential is IGCNU when the intratubular cells are identified but the pathologist misses the infiltrative intertubular component! A closer inspection of the slides as well as careful attention to the morphological clues described above allow identification of the neoplastic cells. Immunohistochemistry can clarify suspicious cases. An intertubular growth pattern in the testis is more consistently associated with hematopoietic tumors (lymphoma, plasmacytoma and extramedullary myeloid tumors) or more rarely with metastatic tumors. Are the cytological features of seminoma sufficient enough to separate intertubular seminoma from either an hematopoietic or metastatic tumor? Some would say so, nevertheless it is our opinion that routine stains should always be supplemented with immunohistochemisty especially in cases without an obvious IGCNU component since the treatment and prognosis of the differential entities vary considerably. Is there any relevance to intertubular seminoma other than the recognition of the difficulties in clinical and pathological identification? Browne et al [3] have recently addressed the prognostic importance of the intertubular growth of seminoma associated with the typical pattern. They point out that the intertubular extension at the periphery of the principal tumor mass should be taken into consideration when "surveillance only" is considered in clinical stage I seminoma. Since a tumor greater than 4 cm in size and rete testis involvement are the strongest features predicting relapse in this group of patients [5], the evaluation of size can change considerably when the intertubular component is added. They also showed that intertubular seminoma is strongly associated with rete testis involvement further emphasizing the importance of evaluating the intertubular component. References: Ulbright TM, Amin MB, Young RH. Tumors of the Testis, Adnexa, Spermatic cord and Scrotum (Atlas of Tumor Pathology, III series, vol 25), Armed Forces Institute of Pathology, Washington 1999 Henley JD, Young RH, Wade CL, Ulbright TM. Seminomas with exclusive intertubular growth. A report of 12 clinically and grossly inconspicuous tumors. Am J Surg Pathol (2004) 28, 1163-1168 Browne T, Richie JP, Gilligan TD, Rubin MA. Intertubular growth in pure seminomas: associations with poor prognostic parameters. Hum Pathol (2005) 36, 640-645 Ulbright TM, Young RH, Scully RE. Throphoblastic tumors of the testis other than classic choriocarcinoma. "Monophasic" choriocarcinoma and placental site trophoblastic tumor: a report of two cases. Am J Surg Pathol (1997) 21, 282-288 Warde P, Specht L, Horwich A, et al. Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol (2002) 20, 4448-4452