Longer formalin fixation improved histologic quality and reduced artifacts in testicular germ cell tumors, particularly seminomas, according to a retrospective analysis of 121 orchiectomy specimens.
Tumor displacement artifact (TDA) and pseudo–lymphovascular invasion (LVI) were significantly more common in seminomas compared with in mixed germ cell tumors. TDA was observed in 68% of seminomas and 45% of mixed tumors, while pseudo-LVI was present in 53% and 19%, respectively.
TDA occurs when tumor cells are unintentionally displaced during specimen handling, often as a result of inadequate fixation. This can mimic true LVI and lead to staging errors. Pseudo-LVI—the appearance of tumor cells within vascular spaces without true invasion—can contribute to misdiagnosis and overtreatment.
“Testicular germ cell tumors, particularly seminomas and larger tumors, are highly susceptible to tumor displacement artifact (TDA) and pseudo–lymphovascular invasion,” said lead study author Reem O Ahmed, BS, of the Department of Pathology at The Ohio State University Wexner Medical Center, and colleagues.
Seminomas are more histologically fragile and prone to smearing during gross sectioning, the study found. Larger tumor size was directly associated with higher artifact rates. In seminomas with TDA, the mean diameter was 5.1 cm vs 3.8 cm without artifact (P = .04). Similar trends were observed in mixed germ cell tumors (5.4 cm vs 3.4 cm, P = .01).
Fixation duration was a key factor. In seminomas, TDA decreased from 82% with no fixation to 50% with more than one night of fixation (P = .05). Although a reduction in pseudo-LVI was also seen (64% vs 39%), it didn't reach statistical significance (P = .12).
Longer fixation also correlated with tumor size. Among seminomas fixed for more than one night, those with TDA were significantly larger compared with those without (6.8 cm vs 3.0 cm, P = .01). This suggested that deeper tissue penetration from prolonged fixation may be particularly beneficial for larger specimens.
Sectioning technique also impacted artifact rates. When grossing was performed by pathology residents rather than assistants, a higher percentage of slides showed TDA (58% vs 41%, P = .04), underscoring the role of operator technique and experience.
True LVI was more frequently observed in mixed germ cell tumors (36%) compared with in seminomas (9%) (P < .001). Within mixed tumors, the presence of ≥ 25% embryonal carcinoma was strongly associated with true LVI (56% vs 12%, P < .001), whereas tumors with ≥ 25% teratoma showed lower LVI rates (21% vs 48%, P = .03).
The researchers recommended a minimum of 2 nights of formalin fixation and the use of larger containers to achieve a formalin-to-tissue volume ratio of at least 15:1. These practices aim to reduce artifacts, enhance histologic clarity, and improve staging accuracy.
The authors disclosed no conflicts of interest.
