358 Article

Rambam Maimonides Medical Journal
Open Access
CLINICAL RESEARCH IN ONCOLOGY
Anaplastic Variant of Classical

Seminoma of the Testis: Northern
Israel Oncology Center Experience and
Brief Review of Literature
Moshe E. Stein, M.D.1*, Jamal Zidan, M.D.2, Tomer Charas, M.D.1, Karen
Drumea, M.D.1, and Rahamim Ben-Yosef, M.D.1
Northern Israel Oncology Center, Rambam Health Care Campus, and Faculty of Medicine, TechnionIsrael Institute of Technology, Haifa, Israel; and 2Institute of Oncology, Ziv Medical Center, Safed, Israel
1
ABSTRACT
Objectives: There are only sporadic reports on the clinical behavior and appropriate treatment of
anaplastic seminoma. This retrospective study summarizes our experience with the anaplastic variant of
classical (typical) seminoma.
Methods: Between 1986 and 2006, seven anaplastic seminoma patients were staged and treated at the
Northern Israel Oncology Center. Staging procedures included meticulous physical and neurological
examinations, complete blood count, full biochemistry profile, specific tumor markers, testicular
ultrasound, and other radiological measures. All patients underwent inguinal orchiectomy and were staged
properly. Six patients had stage I disease, and one patient had stage IIA disease. Patients were irradiated
with doses ranging from 2,500 to 3,000 cGy, and the stage IIA patient received an additional 1,000 cGy
boost to radiographically involved lymph nodes.
Abbreviations: AFP, alpha fetoprotein; AS, anaplastic seminoma; B-HCG, beta-subunit of human chorionic
gonadotropin; CS, classical (typical) seminoma; CT, whole-body computerized scan; HPF, high-powered field; LDH,
lactate dehydrogenase; MSKCC, Memorial SloanKettering Cancer Center; NIOC, Northern Israel Oncology Center.
Citation: Stein ME, Zidan J, Charas T, Drumea K, Ben-Yosef R. Anaplastic Variant of Classical Seminoma of the Testis:
Northern Israel Oncology Center Experience and Brief Review of Literature. Rambam Maimonides Med J 2014;5
(1):e0006. doi:10.5041/RMMJ.10140
Copyright: 2014 Stein ME, et al. This is an open-access article. All its content, except where otherwise noted, is
distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Conflict of interest: No potential conflict of interest relevant to this article was reported.
* To whom correspondence should be addressed. E-mail: [email protected]
Rambam Maimonides Med J | www.rmmj.org.il
January 2014 Volume 5 Issue 1 e0006
Anaplastic (Undifferentiated) Seminoma
Results: After a mean follow-up of 11 years, six patients are alive with no evidence of disease. One patient
died due to an unknown, non-oncological, cause, unrelated to his previous testicular tumor, while in
complete remission.
Conclusions: Despite the low patient numbers and the retrospective nature of our study, it can be
concluded that radiotherapy treatment for early-stage anaplastic seminoma patients might achieve the same
excellent survival as for classical seminoma. However, the general consensus achieved through large-scale
studies suggests that active surveillance should be offered to all stage I seminoma patients, regardless of the
pathologic variant.
KEY WORDS: Anaplastic seminoma, early stage, good prognosis, radiotherapy
INTRODUCTION
At the present time, testicular seminomas are
commonly categorized into classical seminoma (CS),
and into the spermatocytic and anaplastic variants
of CS. Mostofi1 established the diagnosis of
anaplastic seminoma (AS) in tumors with overall
morphologic features of seminoma but with more
than three mitotic figures per high-powered field
(HPF), cellular irregularity, no fibrovascular septae,
few lymphocytes, focal necrosis, and pleomorphic
cells with non-clear cytoplasm. On the other hand,
Von Hochstetter2 suggested that, if mitotic activity
continues to be used in separating AS from CS, the
critical threshold should be elevated to six mitoses
per HPF. According to these criteria, AS constitutes
5%15% of testicular seminomas.3
gonadotropin (B-HCG), lactate dehydrogenase

(LDH)), and whole-body computerized (CT) scan.
Follow-up was provided through regular follow-up
visits and a search of the Interior Ministrys
electronic data.
There are conflicting reports about the clinical

behavior of AS. While Kademian et al.4 and Mostofi
and Price5 demonstrated an aggressive clinical
pattern, other authors6,7 demonstrated no difference
in clinical behavior between AS and CS and
suggested that treatment should be the same, stage
for stage. There are very few studies and limited
information about AS in recent years. The goal of
our study was a retrospective screening of seven AS
patients staged and treated with radiotherapy postorchiectomy at the Northern Israel Oncology Center
(NIOC) in the years 19862006.
Staging resulted in six stage I (disease confined

to testis) and one stage IIA (para-aortic lymphadenopathy 2 cm in size) patients. Initially, radiotherapy was applied with 68 megavoltage photons
following 2-dimensional planning with anatomic
bony landmarks and posterior/anterior fields. Since
1990, 3-D conformal CT-based planning was implemented.8 Four stage IA patients were irradiated with
the hockey stick method (para-aortic lymph nodes
and ipsilateral iliac lymph nodes) and three patients
with the inverted-Y method (para-aortic and
bilateral pelvic lymph nodes), with a total dose
ranging between 2,500 and 3,000 cGy, daily
fractions of 125200 cGy, five times weekly. The
stage IIA patient was additionally boosted to the
radiographically demonstrable para-aortic tumor
bulk with 1,000 cGy (daily fraction of 125 cGy). Two
patients received additional radiotherapy to the
inguinal area, due to adverse factors which might
predict relapse (one patient: perineural and lymphogenic invasion, spermatic cord involvement; one
patient: rete testis invasion). Boost was given with 6
megavoltage photons and CO-60 to a total dose of
2,500 cGy and 125 cGy daily fractions, respectively.
PATIENTS AND METHODS
RESULTS
From 1971 to 2010, 112 stage I and 26 IIA seminoma

patients were referred to the NIOC for meticulous
post-orchiectomy staging and radiation therapy.
Seven patients demonstrated the Mostofi microscopic criteria for AS.1 All patients underwent
clinical examination, full hematological and biochemistry profile, specific tumor markers (alpha
fetoprotein (AFP), beta-subunit of human chorionic
Mean age of patients was 33 years (range, 2743

years). Three were Jews and four were Arabs. Only
one patient was not born in Israel (Russian-born).
An etiological factor (cryptorchidism) was evaluated
in one patient. The tumor was confined to the right
side in four patients. Symptoms included testicular
enlargement and/or mass, pain in three patients,
and a hydrocele in one patient. Mean duration of

symptoms was 3 months (range, 18 months). With
a mean follow-up of 11 years (range, 224 years)
calculated from surgical procedure to last follow-up,
five patients are alive with no evidence of disease,
chronic severe side effects, or second primary. One
patient was lost to follow-up, and one died due to an
unknown cause unrelated to his primary disease 12
years after diagnosis.
DISCUSSION
Between 5% and 15% of all testicular seminomas are
histologically classified as AS.3 However, due to the
low number of AS patients mentioned in scientific
studies and the retrospective nature of these studies,
it is difficult to determine whether the anaplastic
differentiation predicts bad prognosis, like other
solid tumors with anaplastic biology.3 Kademian et
al.,4 in their 1977 study, and Bobba et al.,9 in their
1988 study, demonstrated a worse prognosis and
higher relapse rate compared to CS. Percarpio et al.,7
who summarized the treatment results of 77 AS
patients in three large medical centers and after a
follow-up of 28 years, found the same excellent
survival rates in AS and CS patients in early stage
following orchiectomy and radiation therapy. They
concluded that the treatment decision in AS patients
should be based on stage and generally accepted
adverse factors like size, lympho-vascular invasion,
and rete testis involvement. Cockburn et al.3 came to
the same decision (25 patients), as did Maier and
Sulak6 (39 patients).
therapy, only high-risk factors, such as tumor size

larger than 4 cm, rete testis involvement, and
vascular invasion, should be treated with radiation
therapy (total dose 2025 Gy) to the para-aortic
field alone, omitting the pelvic fields. Radiotherapy
planning should be 3-D conformal CT-based or
intensity-modulated radiotherapy, aiming to reduce
the dose to active bone marrow and radio-sensitive
abdominal organs, hence reducing potential late
toxicity and second malignancies.
CONCLUSION
Treatment of anaplastic seminoma should be the
same as for classical seminoma, stage for stage.
Currently, surveillance policy should be
implemented for all stage I seminoma, regardless of
the pathologic variant.
REFERENCES
1.
Mostofi FK. Testicular tumors: epidemiologic,

etiologic and pathologic features. Cancer 1973;32:
1186201. Full Text
2.
Von Hochstetter AR. Mitotic count in seminomas - an

unreliable criterion for distinguishing between
classical and anaplastic types. Virchows Arch A
Pathol Anat 1981;390:639.
3.
Cockburn AG, Vugrin D, Batata M, Hajdu S,

Whitmore WF. Poorly differentiated (anaplastic)
seminoma of the testis. Cancer 1984;53:19914. Full
Text
Hence, the sub-classification of seminoma into

well-differentiated and undifferentiated for purposes of treatment and prognosis may be doubted
on the basis of the Memorial SloanKettering
Cancer Center (MSKCC) experience.3 Ultrastructural
studies and electron microscopic appearance2,10,11
have failed to reveal significant differences between
AS and CS. Moreover, the poor prognosis of AS in
the past could be related to understaging in the preCT era and misdiagnosis of aggressive testicular
lymphoma and embryonal carcinoma based on light
microscopy
alone
without
histochemistry
studies.2,3,12,13
4.
Kademian M, Bosch A, Caldwell WL, Jaeschke W.

Anaplastic seminoma. Cancer 1977;40:30826. Full
Text
5.
Mostofi FK, Price EB. Tumors of the Male Genital

System. In: Atlas of Tumor Pathology, 2nd series,
fasc.8. Washington DC: Armed Forces Institute of
Pathology (AFIP); 1973:323.
6.
Maier JG, Sulak MH. Radiation therapy in malignant

testis tumors. Part 1: Seminoma. Cancer 1973;32:
121218. Full Text
7.
Percarpio B, Clements JC, Mcleod DG, Sorgen SD,

Cardinale FS. Anaplastic seminoma: an analysis of 77
patients. Cancer 1979;43:251013. Full Text
Summarizing our and world-wide accumulating

experience and current policy for stage I seminoma,
as emphasized by Schmoll et al.,14 Albers et al.,15 and
de Wit and Bosl,16 it is agreed that standard management has shifted largely to active surveillance or a
single cycle of carboplatin with area under the curve
(AUC 7) for low-risk patients. Concerning radiation
8.
Wilder RB, Buyyounouski MK, Efstathiou JA, Beard

CJ. Critical review: radiotherapy treatment planning
for testicular seminoma. Int J Radiat Oncol Biol Phys
2012;83:44552. Full Text
9.
Bobba VS, Mittal BB, Hoover SV, Kepka A. Classical

and anaplastic seminoma: difference in survival.
Radiology 1988;167:84952.

10. Janssen M, Johnston WH. Anaplastic seminoma of
the testis: ultrastructural analysis of three cases.
Cancer 1978;41:53844. Full Text
11. Motzer RJ, Agarwal N, Beard C, et al. Testicular
cancer. J Natl Compr Canc Netw 2012;10:50235.
12. Kamba T, Kamoto T, Okubo K, et al. Outcome of
different post-orchiectomy management for stage I
seminoma: Japanese multi-institutional study including 425 patients. Int J Urol 2010;17:9808. Full Text
13. Warde P, Gospodarowicz M. Evolving concepts in
stage I seminoma. BJU Int 2009;104:135761. Full
Text
14. Schmoll HJ, Jordan K, Huddart R, et al.; ESMO

Guidelines Working Group. Testicular seminoma:
ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up. Ann Oncol 2010;21(Suppl
5):v1406. Full Text
15. Albers P, Albrecht W, Algaba F, et al.; European
Association of Urology. EAU guidelines on testicular
cancer: 2011 update. Eur Urol 2011;60:30419. Full
Text
16. De Wit R, Bosl GJ. Optimal management of clinical
stage I testis cancer: one size does not fit all. J Clin
Oncol 2013;31:34779. Full Text

358 Article

Uploaded by

Copyright:

Available Formats

358 Article

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

358 Article

Uploaded by

Copyright:

Available Formats

Rambam Maimonides Medical Journal

Anaplastic Variant of Classical

Rambam Maimonides Med J | www.rmmj.org.il

January 2014 Volume 5 Issue 1 e0006

Anaplastic (Undifferentiated) Seminoma

gonadotropin (B-HCG), lactate dehydrogenase

There are conflicting reports about the clinical

Staging resulted in six stage I (disease confined

PATIENTS AND METHODS

From 1971 to 2010, 112 stage I and 26 IIA seminoma

Mean age of patients was 33 years (range, 2743

Rambam Maimonides Medical Journal

January 2014 Volume 5 Issue 1 e0006

Anaplastic (Undifferentiated) Seminoma

therapy, only high-risk factors, such as tumor size

Mostofi FK. Testicular tumors: epidemiologic,

Von Hochstetter AR. Mitotic count in seminomas - an

Cockburn AG, Vugrin D, Batata M, Hajdu S,

Hence, the sub-classification of seminoma into

Kademian M, Bosch A, Caldwell WL, Jaeschke W.

Mostofi FK, Price EB. Tumors of the Male Genital

Maier JG, Sulak MH. Radiation therapy in malignant

Percarpio B, Clements JC, Mcleod DG, Sorgen SD,

Summarizing our and world-wide accumulating

Wilder RB, Buyyounouski MK, Efstathiou JA, Beard

Bobba VS, Mittal BB, Hoover SV, Kepka A. Classical

Rambam Maimonides Medical Journal

January 2014 Volume 5 Issue 1 e0006

Anaplastic (Undifferentiated) Seminoma

Rambam Maimonides Medical Journal

14. Schmoll HJ, Jordan K, Huddart R, et al.; ESMO

January 2014 Volume 5 Issue 1 e0006

You might also like