We read with interest the review by Vimercati et al. [1] of the scientific literature
on malignant mesothelioma of the tunica vaginalis testis (MMTVT). The authors reviewed
case series and case reports, and primarily focused their discussion on diagnostic
and prognostic characteristics of MMTVT and options for MMTVT treatment. The authors
also briefly discussed the potential etiologic role of asbestos exposure in MMTVT
development, and declared, “[T]he only causal factor so far ascertained is asbestos
exposure, and exposure to different asbestos-containing materials is the only well-documented
risk factor, as stated by IARC [International Agency for Research on Cancer].” In
this context, the authors referenced our recent review of the epidemiologic literature
on mesothelioma of the pericardium and MMTVT [2], stating, “Nevertheless, there are
authors [2] who do not agree with the absence, until today, of analytical case-control
epidemiologic studies to test this relationship.”
In response to this statement, we note several points. In our systematic literature
review and complementary analysis of U.S. registry-based incidence rates of MMTVT
[2], we assessed relevant epidemiologic findings regarding the potential etiologic
role of asbestos exposure in MMTVT development. We acknowledged the lack of analytical
epidemiologic studies, including case-control studies, to test this hypothesis but
pointed to several lines of scientific evidence that support our conclusion that the
available epidemiologic literature does not support an association, let alone a causal
association, between inhaled asbestos exposure and the risk of developing MMTVT. First,
in large occupational cohorts with heavy workplace exposures to asbestos, no cases
of MMTVT have been reported (e.g., [3]). Second, registry-based incidence rates of
MMTVT in the U.S. do not show temporal or geographical trends that would correspond
with trends in commercial asbestos use, with due consideration of latency, nor do
they reflect incidence rates of pleural malignant mesothelioma, for which asbestos
historically played an etiologic role in a substantial fraction of male cases [2,
4]. Third, the incidence of extra-pleural mesothelioma, including MMTVT, in a recent
study using the National Mesothelioma Register in Italy does not demonstrate an exposure-response
relationship, as MMTVT cases were not reported in some of the highest-risk industries
(e.g., asbestos cement, national defense, shipbuilding, and railway industries) [5].
If inhaled asbestos caused MMTVT, the highest risk of MMTVT would be expected in industries
with the highest exposure; no such exposure-response relationship is reported (see
Mezei et al. [2] for the details of this argument). Interestingly, Vimercati et al.
[1] did not reference their Italian colleagues in their article. We also note that
case reports and case series are not epidemiologic studies; they cannot establish
associations, let alone causal relationships, between exposure and disease. Nevertheless,
we found that a substantial proportion of MMTVT cases reported in the published literature
did not have documented asbestos exposure [2].
Vimercati et al. [1] also referenced the most recent IARC monograph (2012) on the
carcinogenic risks of asbestos [6] in support of their view that asbestos is an established
cause of MMTVT. The IARC monograph (2012) does not contain a single mention of MMTVT
(or of mesothelioma of the pericardium) either in the main text or in the reference
list. Thus, the IARC monograph (2012) does not and cannot conclude that asbestos causes
these rare extra-pleural forms of malignant mesothelioma. While an earlier version
of the IARC monograph (1987) concerning asbestos mentions MMTVT and pericardial mesothelioma
[7], the three references cited in a single sentence are case reports.
In addition, contrary to the opinion expressed by Vimercati et al. [1], there is considerable
evidence that in addition to asbestos and some other fibers such as erionite, ionizing
radiation increases the risk of malignant mesothelioma (e.g., [8]).
Finally, the current paradigm of carcinogenesis as a process of mutation accumulation
implies that all cancers, including malignant mesothelioma can and do occur spontaneously
without exposure to any external agents (e.g., [9, 10]).
In summary, we conclude that the available epidemiology provides no evidence that
inhaled asbestos exposure is a risk factor for the development of MMTVT. Vimercati
et al. [1] provide no evidence to the contrary. We look forward to the results of
the forthcoming Italian case-control study mentioned by the authors.