Endocrine System

Thyroid Gland - C Cell Hyperplasia

Narrative
Comment:
C-cell hyperplasia is a common finding in chronic rat studies and can be diffuse (Figure 1 and Figure 2), focal (Figure 3 and Figure 4), or multifocal. C-cell hyperplasia is distinguished from C-cell adenoma based on the size of any given focal proliferation. The generally accepted criteria for C-cell hyperplasia is a focal C-cell cluster less than five average follicular diameters or similarly small-sized clusters of C cells scattered in interfollicular spaces. In contrast to C-cell adenomas, C-cell hyperplasia is not associated with significant compression of adjacent parenchyma. C-cell hyperplasias may contain individual trapped follicles (Figure 1 and Figure 2). C-cell hyperplasia generally consists of round to polyhedral cells with abundant eosinophilic cytoplasm (Figure 2); in some cases there is a higher than typical nuclear-to-cytoplasmic ratio (Figure 4).
Recommendations:
C-cell hyperplasia should be diagnosed when present, given a severity grade. If bilateral it should be indicated in the diagnosis with a severity grade based on the more severely affected thyroid gland.
References:

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Abstract: http://www.sciencedirect.com/science/book/9780123302151

Capen CC, Martin SL. 1989. The effects of xenobiotics on the structure and function of thyroid follicular and C-cells. Toxicol Pathol 17:266-293.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/2675279

Chandra S, Hoenerhoff MJ, Peterson R. 2013. Endocrine glands. In: Toxicologic Pathology: Nonclinical Safety Assessment (Sahota PS, Popp JA, Hardisty JF, Gopinath G, eds). CRC Press, Boca Raton, FL, 655-716.

Abstract: http://www.crcpress.com/product/isbn/9781439872109

Collins WT, Capen CC, Kasza L, Carter C, Dailey RE. 1977. Effect of polychlorinated biphenyl (PCB) on the thyroid gland of rats. Ultrastructural and biochemical investigations. Am J Pathol 89:119-136.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/199066

Greaves P. 2007. Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation, 3rd ed. Academic Press, Amsterdam, 819-839.

Abstract: http://www.sciencedirect.com/science/book/9780444527714

Hardisty JF, Boorman GA. 1990. Thyroid gland. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 519–536.

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  • Image of C cell hyperplasia in the thyroid gland from a female F344/N rat in a chronic study

    Thyroid gland, C cell - Hyperplasia in a treated female F344 rat from a chronic study. Aggregates and small nests of C cells have replaced follicles in this thyroid gland.

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<p>Thyroid gland, C cell - Hyperplasia in a treated female F344 rat from a chronic study. Aggregates and small nests of C cells have replaced follicles in this thyroid gland.</p>

Thyroid gland, C cell - Hyperplasia in a treated female F344 rat from a chronic study. Aggregates and small nests of C cells have replaced follicles in this thyroid gland.
<p>Thyroid gland, C cell - Hyperplasia in a treated female F344 rat from a chronic study. Higher magnification of Figure 1 shows the contiguous nests of C cells surrounding small follicles.</p>

Thyroid gland, C cell - Hyperplasia in a treated female F344 rat from a chronic study. Higher magnification of Figure 1 shows the contiguous nests of C cells surrounding small follicles.
<p>Thyroid gland, C cell - Hyperplasia in a control male F344 rat from a chronic study. A focal proliferation of C cells is present in this thyroid gland (arrow).</p>

Thyroid gland, C cell - Hyperplasia in a control male F344 rat from a chronic study. A focal proliferation of C cells is present in this thyroid gland (arrow).
<p>Thyroid gland, C cell - Hyperplasia in a control male F344 rat from a chronic study. Higher magnification of Figure 3 shows illustrates the high nuclear-to-cytoplasmic ratio in this focal proliferation of C cells.</p>

Thyroid gland, C cell - Hyperplasia in a control male F344 rat from a chronic study. Higher magnification of Figure 3 shows illustrates the high nuclear-to-cytoplasmic ratio in this focal proliferation of C cells.

Authors

Robert R. Maronpot, DVM, MS, MPH, DACVP, DABT, FIATP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Amy Brix, DVM, PhD, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

Thomas J. Rosol, DVM, PhD, DACVP
Professor of Veterinary Biosciences
Senior Advisor, Life Sciences, Technology Commercialization and Knowledge Transfer
The Ohio State University
Columbus, OH

Susan A. Elmore, MS, DVM, DACVP, DABT, FIATP
Staff Scientist, NTP Pathologist
NTP Pathology Group
National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC