Beneficial value of testicular sperm extraction AgarCyto in addition to the standard testicular biopsy for diagnosis of testicular germ cell tumors in nonobstructive azoospermia

Because germ cell neoplasia in situ is heterogeneously distributed in the testis, the AgarCyto made of the testicular sperm extraction cell suspension can diagnose a (pre-)malignancy even when the standard testicular biopsy is negative in nonobstructive azoospermia.

Marie-Louise Hessel, M.D., Liliana Ramos, Ph.D., Kathleen W.M. D’Hauwers, M.D., Ph.D., Didi D.M. Braat, M.D., Ph.D., Christina A. Hulsbergen-van de Kaa, M.D., Ph.D.

Volume 105, Issue 2, Pages 308-314


To study whether immunohistochemical detection of germ cell neoplasia in situ (GCNIS) in AgarCytos, made of the remnants of the testicular sperm extraction (TESE) specimen, is equally accurate as in a standard testicular biopsy.

Prospective cohort study performed between January 2013 and May 2014.

Department of Reproductive Medicine of a Dutch University Hospital.

All men with nonobstructive azoospermia (n = 197) undergoing a urological work-up followed by a unilateral or bilateral TESE for fertility treatment were consecutively included.

An AgarCyto was made of the remnants of these TESE biopsies. Simultaneously a standard testicular biopsy was performed. For all cases a routine hematoxylin-eosin (H & E) staining was performed as well as immunohistochemistry (PLAP and OCT3/4) to detect GCNIS.

Main Outcome Measure(s):
The presence or absence of GCNIS in the TESE-AgarCyto and standard testicular biopsy.

Six men (3.0%) were diagnosed with a germ cell (pre)malignancy by immunohistochemistry. No cases were encountered in which the TESE-AgarCyto was negative, whereas the standard testicular biopsy was positive for GCNIS. In one case the TESE-AgarCyto detected a premalignancy that was missed by standard testicular biopsy. Unfortunately a standard testicular biopsy was not available for direct comparison in 50% of the GCNIS-positive patients due to various reasons.

Because GCNIS is heterogeneously distributed in the testis, the TESE-AgarCyto can diagnose GCNIS even when the standard testicular biopsy is negative. Direct comparison of accuracy, however, is not reliable due to the low prevalence of GCNIS and the lack of a standard biopsy when an orchidectomy was performed simultaneously with TESE.

  • AgarCytos if proven to be accurate on larger scale studies, may potentially improve long term patient care in the male infertility population. As presented in this journal by Hansen et al, males with SA abnormalities have increased risk for testicular cancer. Male infertility is a potential barometer for future malignancies. If we are performing surgery for an azoospermic male to extract sperm, testing should be performed on a small sample of tissue to ensure that malignancy is or is not present given the increased risk.

  • Jason M. Franasiak

    Congratulations on an interesting article. Is there data in other settings comparing the addition of AgarCytos to standard testicular biopsy in terms of outcomes data? Do patients who have findings of GCNIS with AgarCytos that do not have a similar finding on standard pathology assessment have the same long term outcomes?

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