Nasal Squamous Cell Carcinoma and Renal Amyloidosis in a Mexican Wolf
Lucia Garcia-Camacho and Ignacio Rangel-Rodriguez
Department of Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA (Garcia-Camacho) and Universidad Nacional Autónoma de México, FES-Cuautitlán, Deparmento de Ciencias Biológicas, Estado de México, México (Garcia-Camacho, Rangel-Rodriguez)
Key Words: Mexican wolf, Canis lupus baileyi, Nose, Squamous cell carcinoma, Kidney, Amyloidosis
Abstract: A nasal squamous cell carcinoma and renal amyloidosis are described in a Mexican wolf. Presumably, the squamous cell carcinoma caused general antigenic stimulation of the immune system and secondary amyloid deposition within the glomeruli. Potassium permanganate digestion was inconclusive in distinguishing secondary type amyloidosis from primary and familial types of amyloidosis.
Introduction
The Mexican wolf (Canis lupus baileyi) represents the southern and smallest subspecies of gray wolf once confined to arid areas of southern Arizona, New Mexico, and Texas, extending into central Mexico. Extermination campaigns have greatly depleted the population, modifying its natural range of distribution. Since 1976 a protection law was passed, when only a few wolves seems to be present in wild small areas of northern Mexico. The Mexican wolf recovery team was instituted to preserve, reproduce and reintroduce to the wild this subspecies. The San Juan de Aragon zoo has been one of the most successful in achieving reproduction of its captive population, composed of certified and San Juan de Aragon lineages . Recently, the latter lineage wolves have been certified, opening the possibility of breaking out the inbreeding to generate a more stable population.
Case History
A 12-year-old, certified lineage, male Mexican wolf was housed at the San Juan de Aragon Zoo in Mexico City. The wolf suddenly lost weight and became anorexic after developing an ulcerative, rapidly-growing skin mass that eroded the bone of the nasal turbinates and protruded into the palate (Fig. 1). The diagnosis of nasal squamous carcinoma was made from cytologic aspirates and core biopsy samples. The cytologic aspirates were stained with Papanicolaou stain. Keratinized squamous cells were a distinct orange-red color (Figs. 2 & 3). The wolf lost his social status, which basically means he was rejected and attacked by other members of the pack. Because of the wolf’s poor social conditions and marked tumor-associated cachexia, he was humanely euthanatized. Subsequently, a complete necropsy examination was performed.
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| Fig. 1. Mexican wolf. A squamous cell carcinoma is present over the dorsum of the nasal bridge. |
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| Fig. 2. Mexican wolf, cytologic aspirate, Papanicolaou stain. Keratinized squamous cells are red-orange, while nonkeratinized squamous cells are blue-green. |
Fig. 3. Mexican wolf, cytologic aspirate, Papanicolaou stain. Increased magnification showing red-orange color of a cornified squamous cell. Noncornified squamous cells are blue-green. |
Gross Necropsy Lesions
The infiltrative skin mass totally effaced the normal nasal turbinate architecture and protruded into the palate. The kidneys appeared enlarged and pale with a "lumpy-bumpy" surface. When incised, the renal cortex bulged and had a granular appearance. Other significant lesions were not observed at necropsy. Specimens of representative organs and tissue were collected, preserved in 10% neutral-buffered Formalin solution, and submitted for histologic examination.
Histology
In sections of kidney, most glomeruli were enlarged and had a segmental increase in mesangial cells with variable amounts of homogenous, pale, eosinophilic material within the subendothelial spaces (Fig. 4). Occasional individual sclerotic glomeruli were seen. Fibrin was observed within some capillary loops. The renal tubules were distended with homogeneous eosinophilic material and were lined by a flattened to hyperplastic epithelium. Widespread tubular regeneration was observed throughout the kidney sections. The renal interstitium had a mild to moderate, multifocal, lymphoplasmacytic infiltrate with mild fibrosis. Sections of lymph nodes were markedly hyperplastic with diffuse plasma cell proliferation. The small intestine had a diffuse lymphocytic plasmacytic infiltrate within the lamina propria.
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| Fig. 4. Mexican wolf, kidney, hematoxylin and eosin stain. Notice increased eosinophilic mesangial matrix within the glomerulus. |
Special Stains
Fraser Lendrum stain confirmed the presence of fibrin within some capillaries of the glomerular tufts. Foci of collagen deposition were present in scattered sclerotic glomerular as observed with Masson’s trichrome stain. Glomerular deposits of amyloid were readily demonstrated with Congo red staining. Amyloid deposits appeared orange-red when viewed under tungsten illumination, but exhibited bright green birefringence in polarized light (Fig. 5). Congophilia was still present following potassium permanganate digestion for 30, 60, and 75 minutes, as well as following digestion overnight. Potassium permanganate digestion was repeated three times, but in the last assay the control specimen also resisted digestion, making interpretation the test inconclusive in distinguishing primary and secondary amyloidosis.
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| Fig. 5. Mexican wolf, kidney, Congo red stain viewed under polarized light. Congo red-stained glomerular deposits of amyloid are birefringent and appear yellow-green under polarized light. |
Electron Microscopy
Segmental thickening of glomerular basement membrane was observed due to accumulation of a granular to fibrillar material compatible with amyloid (Figs. 6 & 7). The characteristic amyloid fibrils could not be appreciated because of formalin fixation artifacts.
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| Fig. 6. Mexican wolf, kidney, electron micrograph, uranyl acetate and lead citrate stain. The glomerular basement membrane is thickened by amyloid deposition. |
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| Fig. 7. Mexican wolf, kidney, electron micrograph, uranyl acetate and lead citrate stain. Increased magnification shows the granular to fibrillar appearance of amyloid. |
Discussion
The histologic diagnoses in this Mexican wolf were: 1) Squamous carcinoma with invasion of the nasal turbinates and palate and 2) diffuse segmental renal amyloidosis with mesangial proliferation, glomerulosclerosis, fibrin deposition, and mild lymphoplasmacytic interstitial nephritis.
Systemic amyloidosis can be classified as primary, secondary, or familial. Secondary amyloidosis is observed most commonly in animals and has been described as a reaction to diverse inflammatory stimuli. Secondary amyloid deposits usually are sensitive to potassium permanganate digestion. Primary amyloidosis is less frequently observed. In this condition, the deposition of amyloid is the result of plasma cell dyscrasia, including both lymphoid and plasma cell neoplasms. The familial type of amyloidosis has not been described in animals, but is related to accumulation of prealbumin-related proteins. In theory, potassium permanganate digestion will degrade deposits of secondary amyloid, but deposits of amyloid in primary and familial amyloidosis resist digestion.
Amyloidosis in this wolf probably could be classified as secondary type. The aggressive squamous cell carcinoma may have evoked generalized chronic antigenic stimulation, as was observed in the sections of lymph node and intestine. However, the lack of sensitivity to permanganate digestion and massive accumulations of plasma cells in lymph nodes and intestines might also suggest primary amyloidosis. The familial type of amyloidosis is unlikely because it has not been documented in animals. However, clinical follow-up of the offspring must be done to exclude this possibility. Interestingly, a nasal squamous cell carcinoma also has been diagnosed in a son of this wolf. The neoplasm in the live wolf is being treated by radiotherapy, but biopsies have not been performed to confirm or exclude the presence of amyloidosis.
Selected references
1. Cohen, A.S. , and Connors, L.E. (1987). The pathogenesis and biochemistry of amyloidosis. J Pathol 151:1-10.
2. Cheville N.F. (1994) Ultrastructural Pathology: An introduction to interpretation. Iowa State University Press, Ames, Iowa, USA. pp.304-312.
3. DiBartola S.P. (1995). Renal amyloidosis. In Canine and Feline Nephrology and Urology, edited by Osborne C.A. and Finco D.R. Lea and Febiger, USA. pp 400-415.
4.Tashima, T. , Kitamoto, T. , and Tateishi, J. (1986) Histochemical classification of systemic amyloid fibril proteins. Arch Pathol Lab Med 110:885-888.
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