Proliferative lesions in the male reproductive system of F344 rats and B6C3F1 mice: incidence and classification

Our plain-English summary of Proliferative lesions in the male reproductive system of F344 rats and B6C3F1 mice: incidence and classification, by K. Mitsumori, M.R. Elwell (Environmental Health Perspectives, 1988).

The study

• Authors: K. Mitsumori, M.R. Elwell
• Journal: Environmental Health Perspectives
• Published: 1988;77:11-21
• Type of article: Review
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The incidences of all primary neoplasms in the testes and accessory reproductive organs of 51,230 male Fischer 344 (F344) rats and 46,752 male B6C3F1 mice were obtained from the pathology data base of more than 300 long-term toxicity/carcinogenicity studies performed for the National Toxicology Program. The overall incidence of reproductive system neoplasms in male F344 rats was 81.5%. The most common neoplasms were interstitial cell adenoma of the testis (76.6%), adenoma/carcinoma of the preputial glands (2.9%), mesothelioma of the tunica vaginalis (1.5%), and adenoma of the prostate gland (0.3%). The combined incidence (0.1%) of 59 other rare neoplasms consisted of 18 different types that occurred with a frequency of 4 or less. In contrast to the rats, male B6C3F1 mice had a low overall incidence (0.6%) of neoplasms in reproductive organs. The most common neoplasm was the interstitial cell adenoma (0.4%). Thirty additional types of neoplasms were identified. Each of these uncommon neoplasms occurred at a frequency of 12 or less with an overall combined incidence of 0.2%. Morphological features are described for neoplasms in the rat and mouse, and criteria are presented for differentiation of testicular interstitial cell adenoma, prostatic adenoma, and mesothelioma from hyperplastic changes.

In plain English

This article reviewed the pathology database of more than 300 long-term toxicity/carcinogenicity studies run by the U.S. National Toxicology Program (NTP). The authors counted all primary tumors of the testis and accessory sex organs in 51,230 male F344 rats and 46,752 male B6C3F1 mice, treated and control, and re-examined selected slides. Studies in which treatment increased these tumors were left out. The article did not study asbestos or any named substance. In the rats, 81.5% had a reproductive-system tumor, mostly interstitial cell adenoma of the testis (76.6%). Mesothelioma of the tunica vaginalis (the lining around the testis) was recorded in 754 rats (1.5%). Among rats in the historical control data from the 60 most recent NTP studies, it occurred in 51 of 3427 (1.4%). In the mice, 0.6% had such tumors, and no mesothelioma was listed. The authors thought two sarcomas of the tunica vaginalis in mice might be of mesothelial origin. They set out criteria for telling mesothelioma, testicular interstitial cell adenoma and prostatic adenoma apart from hyperplasia (non-cancerous overgrowth). They concluded that the distinction is often not clear-cut.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of a pathology database (National Toxicology Program long-term rodent studies), with microscopic re-examination of selected cases
• Who was studied: 51,230 male Fischer 344 (F344) rats and 46,752 male B6C3F1 mice from more than 300 NTP long-term toxicity/carcinogenicity studies
• Exposure: No specific exposure was studied. The animals were treated and control animals from NTP long-term toxicity/carcinogenicity studies, and the tumors were described as spontaneous. Studies with a treatment-related increase in mesothelioma or preputial gland tumors were excluded. Asbestos is not mentioned.
• Main results:
  • In male F344 rats, the overall incidence of reproductive system neoplasms was 81.5% (41,742 of 51,230 rats).
  • In male F344 rats, the most common tumor was interstitial cell adenoma of the testis (76.6%).
  • In male F344 rats, mesothelioma of the tunica vaginalis had an incidence of 1.5% (754 rats), and prostate adenoma had an incidence of 0.3% (158 rats).
  • In historical control data from the 60 most recent NTP studies, mesothelioma of the tunica vaginalis occurred in 51 of 3427 rats (1.4%).
  • In historical control data from the 60 most recent NTP studies, prostatic adenoma occurred in 26 of 3262 rats (0.8%). All 10 prostatic adenocarcinomas in the rats came from the dorsolateral lobe.
  • In male B6C3F1 mice, the overall incidence of reproductive organ neoplasms was 0.6% (283 of 46,752 mice). The most common was interstitial cell adenoma (0.4%, 169 mice).
  • In the mice, no mesothelioma was listed; two sarcomas of the tunica vaginalis were found, which the authors said might be of mesothelial cell origin.
  • Under the NTP criteria, focal thickening or a single papillary projection of mesothelial cells, without stratification or stromal proliferation, is called mesothelial hyperplasia. Complex papillary growth with stromal proliferation is called mesothelioma.
• The authors' conclusion: The authors concluded that in F344 rats, interstitial cell adenoma is the most common male reproductive tumor; preputial gland tumors, mesothelioma and prostate adenoma are relatively common; and other primary tumors are extremely rare. For lesions of the testicular interstitial cells, mesothelium and prostate, there is often no clear-cut distinction between hyperplasia and neoplasia. In B6C3F1 mice, apart from the well-differentiated interstitial cell tumor of the testis, spontaneous male reproductive tumors are extremely rare.
• Limitations the authors state:
  • The lower incidence of interstitial cell adenoma in the database than the estimated true incidence was probably related to early deaths of 20 to 40% of rats before the end of 2-year studies.
  • Slides for 26 of the 59 rare rat tumors were not available for re-examination, because of ongoing reviews or missing slides.
  • Slides for 14 of the 114 other mouse tumors were not available for re-examination.
  • The authors said further studies using immunohistochemistry and electron microscopy may be needed to determine the cell origin of the rare tumors.

Topics

Medical terms in this study, explained in our Lexicon: Neoplasm, Pathology, Interstitial, Carcinoma, Mesothelioma, Tunica Vaginalis.

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