Lesions in the Larynx of Wistar RccHan: WIST Rats

Abstract

Specific regions in the rat larynx exhibit cellular changes in response to inhaled xenobiotics. These regions include the base of the epiglottis, ventral pouch, and medial surfaces of the vocal processes of the arytenoid cartilages. 1 , 2 In order to collect information on the usefulness of trimming techniques, the influence of different vehicles, the impact of different application routes in toxicity studies, and differences between induced vs. spontaneous lesions, the data obtained from a large number of inhalation and non-inhalation studies performed in Wistar RCCHan(TM): Wist rats at Harlan Laboratories Ltd Switzerland, all evaluated or reviewed by the same pathologist, were compiled for a detailed review. The value of different trimming techniques was deemed to be greatest for transverse and sagittolongitudinal section techniques, as compared to horizontolongitudinally section techniques. The comparison of lesions encountered in control rats of inhalation studies treated with different vehicles did not reveal differences in the type, distribution pattern, incidence and/or severity of spontaneous lesions. The types of lesions were also independent of different application routes in non-inhalation studies compared to inhalation studies. The pattern of spontaneous lesions in the rodent larynx was determined by degenerative and inflammatory lesions starting most often in the submucosal glands by desiccated secretion followed by mineralization and local inflammation or were induced by impacted foreign bodies. Squamous metaplasia was recorded in the respiratory epithelium overlaying the ventral gland as a spontaneous lesion in male Wistar rats from inhalation studies with a maxim of 20.0% in an inhalation oncogenicity study. Induced metaplastic changes recorded in the larynx were reversible. Other induced lesions in inhalation studies consisted of submucosal edema, necrosis, inflammation and/or granuloma. Induced lesions in non-inhalation studies were found to be exclusively related to reflux laryngitis or food impaction. It is concluded, that in rodents induced lesions of the larynx differ in type, distribution pattern, severity and incidence from spontaneous lesions.

Keywords: Wistar RccHanTM: WIST; induced laryngeal lesions; spontaneous laryngeal lesions.

Fig. 1

Diagram on possible and published sections plans of the rat larynx. 1–7: transversal sections according to Sagartz. I–III: transversal sections according to RITA. H: horizontolongitudinal section. S: sagittolongitudinal section.

Fig. 2

Foreign body granuloma with multinuclear giant cells protruding into laryngeal lumen, probably induced by hair. Level 2. HE, lens × 100.

Fig. 3

Foreign body granuloma and related chronic active inflammation of the ventral diverticulum. Level 4. HE, lens × 100.

Fig. 4

Desiccated secretion in dilated duct of submucosal sero-mucinous glands partially mineralized. Level 2. HE, lens × 40.

Fig. 5

Acute inflammation of submucosa and submucosal glandular ducts. Note mineralizations in dilated duct of sero-mucinous glands. Level 2. HE, lens × 40.

Fig. 6

Chronic active inflammation of submucosa and submucosal sero-mucinous glands. Level 2. HE, lens × 40.

Fig. 7

Subacute inflammation of submucosa. Scattered inflammatory cells characterized by granulocytes, plasma cells and lymphocytes. Level 2. HE, lens × 100.

Fig. 8

Subacute inflammation of submucosal and mucosa along with hyperplasia of respiratory epithelium. Level 2. HE, lens × 40.

Fig. 9

Squamoid epithelium is a normal variant of respiratory epithelium overlaying the ventral gland. Level 6. HE, lens × 40.

Fig. 10

Induced focal dilation of submucosal sero-mucinous glands. Level 2. HE, lens × 20.

Fig. 11

Induced submucosal edema. Level 3. HE, lens × 10.

Fig. 12

Induced submucosal subacute inflammation. Level 3. HE, lens × 10.

Fig. 13

Induced submucosal subacute inflammation. Partial loss of cilia from respiratory epithelium. Level 3. HE, lens × 100.

Fig. 14

Induced submucosal chronic active inflammation. Squamous metaplasia with focal hyperplasia and keratinization at arytenoid projections. Level 3. HE, lens × 20.

Fig. 15

Induced necrosis of respiratory epithelium. Level 2. HE, lens × 20.

Fig. 16

Induced extensive necrosis of submucosal and mucosa. Level 2. HE, lens × 10.

Fig. 17

Squamous metaplasia along with submucosal inflammation and mucosal necrosis. Level 3. HE, lens × 20.

Fig. 18

Squamous metaplasia with keratinization. Submucosal inflammatory infiltrate. Level 6. HE, lens × 100.

Fig. 19

Squamous metaplasia and focal hyperplasia. Submucosal inflammatory infiltrate. Horizontolongitudinal section. HE, lens × 100.

Fig. 20

Reflux laryngitis. Mucosal necrosis and inflammatory infiltrate and secretion. Horizontolongitudinal section. HE, lens × 10.

Fig. 21

Spontaneous adenomatoid lesion in control female Fischer 344 rat f (46 weeks at age). HE, lens × 20.

Fig. 22

Spontaneous adenomatoid lesion in control female Fischer 344 rat f (46 weeks at age). HE, lens × 40.