Special Senses System

Harderian Gland - Pigment

Narrative

Comment:

Lipids are the primary secretory products of the rodent Harderian gland, but porphyrin pigment is also synthesized and secreted. Porphyrin pigment occurs as golden to dark brown amorphous clumps or laminated concretions in the alveolar lumens (Figure 1 and Figure 2). Porphyrin secretion increases with age, and excessive production results in "red tears" (chromodacyorrhea). Incidentally occurring porphyrin deposits are generally more prominent in the Harderian glands of female rats and mice. Increased porphyrin secretion can also be a treatment-related effect following administration of various chemical agents.

Recommendations:

Since porphyrin pigment is a normal finding in rodent Harderian glands, pigment should be diagnosed and assigned a severity grade only if there are treatment-related differences in incidence and/or severity. It should also be diagnosed if the pathologists feels the pigment is composed of something other than porphyrin (e.g., hemosiderin or lipofuscin). Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, it is recommended that a diagnosis of pigment (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or related to some other disease process and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether or not secondary deposits of pigment are prominent enough to warrant a separate diagnosis.

References:

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Abstract: https://www.ncbi.nlm.nih.gov/pubmed/12170635

Botts S, Jokinen M, Gaillard ET, Elwell MR, Mann PC. 1999. Salivary, Harderian, and lacrimal glands. In: Pathology of the Mouse: Reference and Atlas (Maronpot RR, Boorman GA, Gaul BW, eds). Cache River Press, Vienna, IL, 49-79.

Abstract: http://www.cacheriverpress.com/books/pathmouse.htm

Brownscheidle CM, Niewenhuis RJ. 1978. Ultrastructure of the Harderian gland in male albino rats. Anat Rec 190:735-754.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/637321

Chieffi G, Chieffi Baccani G, Di Matteo L, D’Istria M, Minucci S, Varriale B. 1996. Cell biology of the Harderian gland. Int Rev Cytol 168:1-180.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/8843648

Djeridane Y. 1994. The Harderian gland and its excretory duct in the Wistar rat. A histological and ultrastructural study. J Anat 184:553-566.

Abstract: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1259964/

Greaves P. 2007. Nervous system and special sense organs. In: Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation, 3rd ed. Academic Press, San Diego, CA, 861-933.

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

Iwai H, Tagawa Y, Hayasaka I, Hayasaka I, Yanai T, Masegi T. 2000. Effects of atropine sulfate on rat Harderian glands: Correlation between morphological changes and porphyrin levels. J Toxicol Sci 25:151-159.

Abstract: http://europepmc.org/abstract/MED/10987121

Krinke GJ, Schaetti PR, Krinke A. 1996. Nonneoplastic and neoplastic changes in the Harderian and lacrimal glands. In: Pathobiology of the Aging Mouse, Vol 2 (Mohr U, Dungworth DL, Capen CC, Carlton WW, Sundberg JP, Ward JM, eds). International Life Sciences Institute Press, Washington, DC, 139-152.

Payne AP. 1994. The Harderian gland: A tercentennial review. J Anat 185:1-49.

Abstract: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1166813/

Percy DH, Wojcinski ZW, Schunk MK. 1989. Sequential changes in the Harderian and exorbital lacrimal glands in Wistar rats infected with sialodacryoadenitis virus. Vet Pathol 26:238–245.

Full Text: http://vet.sagepub.com/content/26/3/238.full.pdf

Sakai T. 1981. The mammalian Harderian gland: Morphology, biochemistry, function, and phylogeny. Arch Histol Jpn 44:299-333.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/7030263

Seely JC. 1987. The Harderian gland. Lab Anim 16:33-39.

Watanabe M. 1980. An autoradiographic, biochemical, and morphological study of the Harderian gland of the mouse. J Morphol 163:349-365.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/6990006

Williams DL. 2002. Ocular disease in rats: A review. Vet Ophthalmol 5:183-192.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/12236869

Yoshitomi K, Boorman GA. 1990. Eye and associated glands. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, CA, 239-260.

Abstract: https://www.ncbi.nlm.nih.gov/nlmcatalog/9002563

All Images

Harderian gland - Pigment in a female F344/N rat from a subchronic study. There are golden to dark brown amorphous clumps or laminated concretions of pigment (likely porphyrin) in the acinar lumens (arrow).

Harderian gland - Pigment in a female F344/N rat from a subchronic study (higher magnification of Figure 1). This higher magnification image shows the intra-acinar pigment in greater detail.

Authors and Reviewers

Author

Margarita M. Gruebbel, DVM, PhD, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

Ruth E. Hurley, DVM, PHD, DACVP
Senior Veterinary Pathologist
Huntingdon Life Sciences
North Brunswick, NJ

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