This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Markovits, J. E. Articles by Sahota, P. S. Search for Related Content PubMed PubMed Citation Articles by Markovits, J. E. Articles by Sahota, P. S.

Granular Cell Lesions in the Distal Female Reproductive Tract of Aged Sprague-Dawley Rats

Novartis Pharmaceuticals Corporation, East Hanover, NJ

During the review of a rat carcinogenicity study, a spectrum of granular cell lesions was recognized in the distal female reproductive tract. To verify the diagnoses, cell populations of nine granular cell alterations of the cervix or vagina were characterized immunohistochemically and four were evaluated ultrastructurally. Immunoreactivity was demonstrated in 8/9 cases with S100 protein, 6/9 cases with neuron-specific enolase, and 7/9 cases with Leu-7. Granular cells were negative for smooth muscle–specific actin and calretinin. The immunohistochemical profile of these lesions was similar to that previously reported in other species, including humans. Ultrastructurally, as expected many lysosomal bodies were present in the cytoplasm of granular cells in all specimens evaluated. Based on the detailed evaluation of a series of lesions, we adopted the following diagnostic criteria and nomenclature for the granular cell changes of the female reproductive tract of rats. Granular cell aggregates were non-space-occupying lesions composed of clusters of typical granular cells. Benign granular cell tumors were space occupying lesions that typically contained prominent interstitial collagen and were either discrete masses or were difficult to discern from the surrounding tissues. Some benign tumors also contained foci of spindle cells with decreased granularity. Malignant tumors exhibited pleomorphism and an increased nucleus:cytoplasm ratio morphologically but had the same biologic behavior as the benign tumors. We applied these diagnostic criteria during the review of controls from 9 carcinogenicity studies. Up to 23% of control females in those carcinogenicity studies had granular cell lesions that could be classified into one of the three categories. Granular cell lesions appear to be common in the cervix/vagina of the Sprague-Dawley rat, and tumors may develop from granular cell aggregates.

Key words: Cervix; granular cell; immunohistochemistry; rat; ultrastructure; vagina.

Request reprints from Dr. J. E. Markovits, Novartis Pharmaceuticals, 59 Rt. 10, East Hanover, NJ 07936 (USA). E-mail: judit.markovits{at}pharma.novartis.com.

This article has been cited by other articles:

				A. C. Veit, J. T. Painter, R. A. Miller, J. F. Hardisty, and D. Dixon Characterization of Uterine Granular Cell Tumors in B6C3F1 Mice: A Histomorphologic, Immunohistochemical, and Ultrastructural Study Vet. Pathol., September 1, 2008; 45(5): 654 - 662. [Abstract] [Full Text] [PDF]

				A. R. Irizarry-Rovira, A. M. Lennox, and J. A. Ramos-Vara Granular Cell Tumor in the Testis of a Rabbit: Cytologic, Histologic, Immunohistochemical, and Electron Microscopic Characterization Vet. Pathol., January 1, 2008; 45(1): 73 - 77. [Abstract] [Full Text] [PDF]

				J. E. Markovits and P. S. Sahota Aromatase Inhibitors Prevent Spontaneous Granular Cell Tumors in the Distal Female Reproductive Tract of Sprague-Dawley Rats Toxicol Pathol, November 1, 2000; 28(6): 799 - 801. [Abstract] [PDF]