Assessment of isochromosome 12p supports that pagetoid involvement of the rete testis represents spread of germ cell neoplasia in-situ.

Authors

Harini Venkatraman Ravisankar, Sounak Gupta, Carrie Brandt, Ryan Knudson, Patricia Greipp, Jennifer B Gordetsky, Giovanna Giannico, Muhammad T Idrees, Thomas M Ulbright, Andres M Acosta

Published in

Human pathology. Pages 106240. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Pagetoid involvement of the rete testis (RT) in seminoma is widely interpreted as spread of germ cell neoplasia in situ (GCNIS) rather than true invasion; however, this concept is based largely on morphologic observations. Assessment of isochromosome 12p [i(12p)], a hallmark of invasive germ cell tumors that is absent in GCNIS, was used to determine the nature of pagetoid RT involvement.
We retrospectively identified orchiectomy specimens with pure seminoma and pagetoid RT involvement from institutional archives. Isochromosome 12p status was assessed on formalin-fixed, paraffin-embedded tissues using fluorescence in situ hybridization (FISH) with a dual-color PKP2/D12Z3 probe. Pagetoid RT involvement, invasive seminoma, and intratubular seminoma (ITS) components were analyzed separately when present.
Sixteen tumors were included, with successful FISH analysis in 15 (94%). Pagetoid RT involvement was evaluable in 14 cases and demonstrated i(12p) in only 1 (∼7%), while the remaining 13 were negative. In contrast, invasive seminoma showed i(12p) in 5/14 cases (∼36%). All seminoma components negative for i(12p) showed polysomy 12, suggesting that these are mutually exclusive alterations. Cases with discordant results contained i(12p)-positive seminoma and i(12p)-negative pagetoid RT involvement. Intratubular seminoma (ITS) was present in 6 tumors, being positive for i(12p) in 2 (∼33%).
The absence of i(12p) in pagetoid RT involvement supports its interpretation as spread of GCNIS rather than invasive tumor. Rare detection of i(12p) in RT involvement suggest that, occasionally, this lesion may represent retrograde invasion by seminoma or, more likely, in-situ progression of GCNIS.

PMID:
42628849
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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