AFIP Wednesday Slide Conference - No. 12
December 2, 1998

Conference Moderator: Dr. Bruce H. Williams, Diplomate, ACVP
Department of Telepathology
Armed Forces Institute of Pathology
Washington, DC 20307
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Case I - 98-8397 (AFIP 2648048)
Signalment: One-year-old, spayed female, Siberian Husky, canine.
History: This dog had a history of a stick lodged in the mouth six months prior to biopsy. The dog was presented with approximately five, variably-sized, raised, ulcerated, ovoid masses in the oral cavity measuring 1 to 5 centimeters in diameter. A single "granulomatous" mass was excised from the frenulum of the tongue for histopathology.
Gross Pathology: A formalin-fixed, 1.5 x 3.5 centimeter, raised, ulcerated lingual mass was submitted for histopathology.

Contributor's Diagnosis and Comments: Tongue, frenulum (per contributor): Severe, chronic, multifocal to coalescing eosinophilic granuloma with collagen degeneration and rare intralesional bacteria.
The mass is consistent with a canine eosinophilic granuloma, a rare syndrome characterized by oral or cutaneous lesions. The most common clinical presentation is focal disease of the oral cavity. Although there is a marked breed predilection for the Siberian Husky, typically in males less than three years of age, lingual eosinophilic granulomas have been reported in a Bull Mastiff and a mixed-breed dog. Plaque-like lesions typically develop on the lateral or ventral surface of the tongue in Siberian Huskies. Palatal lesions have been reported in several breeds. While the exact cause is not known, the striking breed predilection suggests possible hereditary factors. Proposed mechanisms include trauma, insect bites and foreign bodies. In this case, the dog had a history of a stick foreign body lodged in the mouth six months prior to biopsy. Complete excision is not recommended as deformities may result, and the lesions respond readily to glucocorticoids.
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Case 12-1. Oral mucosa with extensive ulceration (except for lower right corner) & multifocal areas of liquefactive necrosis surrounded by both suppurative and granulomatous inflammation.
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Case 12-1. Oral mucosa. Necrotic foci are centered on an eosinophilic coagulum composed of necrotic cells and denatured protein which forms picket fense-like radial projections (Splendore-Hoeppli phenomenon). This material is surrounded by myriad eosinophils, fewer neutrophils, and more distant accumulations of epithelioid macrophages.
AFIP Diagnosis: Oral mucosa (per contributor): Stomatitis, proliferative, eosinophilic and granulomatous, focally extensive, severe, with collagen degeneration and ulceration, Siberian Husky, canine.
Conference Note: This pedunculated to polypoid lesion is covered by an extensively ulcerated stratified squamous nonkeratinizing epithelium. Within the mass, there are multifocal to coalescing nodular aggregates of eosinophils and macrophages that palisade around degenerate, fragmented, and sometimes hyalinized, bundles of collagen. Lymphocytes and plasma cells surround the eosinophilic granulomatous nodules, and immature fibrous connective tissue forms the peripheral boundaries of these inflammatory foci.
As noted by the contributor, canine eosinophilic granuloma may have various causes but a common histopathologic presentation. Lesions are grossly and histologically similar to those in the cat. The disease most commonly presents as single to multiple ulcerated lesions in the oral cavity, often on the lateral or ventral surfaces of the tongue or on the soft palate. The cutaneous form occurs less frequently and is characterized by multiple papules, nodules, and plaques primarily on the ventral abdomen, flanks and prepuce. Rarely, solitary lesions in the external ear canal may occur.
The etiology of canine eosinophilic granuloma is unknown, but hereditary and/or hypersensitivity mechanisms are proposed based upon breed predilection and response to glucocorticoid therapy. While the syndrome has been reported in several breeds, male Siberian huskies are classically described as the most predisposed, especially to the oral form of the disease. Recently, two separate reports from the United States and Europe describe oral eosinophilic granulomas in several Cavalier King Charles spaniels; affected animals were relatively young (four years or less), and most were male. Thus, Cavalier King Charles spaniels may also be predisposed to the oral form of canine eosinophilic granuloma.

Contributor: University of Illinois - Laboratories of Veterinary Diagnosis, 2001 South Lincoln, Urbana, IL 61802.
1. Madewell BR, Stannard AA, Pulley LT, Nelson VG: Oral eosinophilic granuloma in Siberian husky dogs. J Amer Vet Med Assoc 177:701-703, 1980.
2. Potter KA, Tucker RD, Carpenter JL: Oral eosinophilic granuloma of Siberian huskies. J Amer Anim Hosp Assoc 16:595-600, 1980.
3. Walsh KM: Oral eosinophilic granuloma in two dogs. J Amer Vet Med Assoc 183:323-324, 1983.
4. Scott DW: Cutaneous eosinophilic granulomas with collagen degeneration in the dog. J Amer Anim Hosp Assoc 19:529-532, 1983.
5. Gross TL, Ihrke PJ, Walder EJ: Nodular and diffuse diseases of the dermis with prominent eosinophils or plasma cells. In: Veterinary Dermatopathology, pp. 218-220, Mosby-Year Book, St. Louis, MO, Year Book, 1992.
6. Bredal BP, et al.: Oral eosinophilic granuloma in three Cavalier King Charles spaniels. J Small Anim Pract 37:499-504, 1996.
7. Yager JA, Scott DW: The skin and appendages. In: Pathology of Domestic Animals, Jubb KVF, Kennedy PC, Palmer N, eds., 4th ed., volume 1, pp. 699-702, Academic Press, San Diego, CA, 1993.
Case II - 93W 9960-4 or 93W 9896-3 (AFIP 2642052)
Signalment: One-year-old, female, Siberian polecat x black-footed ferret hybrid (Mustela eversmanni x M. nigripes).
History: Hybrid ferrets consumed laboratory mice experimentally infected with Yersinia pestis to determine susceptibility of ferrets to oral plague. This work was associated with the recovery program for the endangered black-foo-ted ferret. Most hybrid ferrets were febrile (temperatures >40 C) and anorectic by two days post consumption of a single in-fected mouse. They became depressed, and after a clinical course of 3 to 7 days, became moribund and were euth-anized.
Gross Pathology: This ferret was in excellent body condition (856 g). The mandibular and retropharyngeal lymph nodes were great-ly enlarged, hemorrhagic, and necrotic. Associated soft tissues were slightly edematous. The lungs were edematous and mottled. There was increased clear fluid in the thoracic cavity which contained a few fibrin strands. The gastro-intestinal tract was empty except for black tarry feces in the distal colon.

Laboratory Results: Impression smears of lung, liver, spleen, and lymph nodes were positive for Y. pestis by direct fluorescent anti-body tests. Yersinia pestis was cultured from pooled tissues and lymph nodes. No antibodies against Y. pestis were detected in serum.
Contributor's Diagnosis and Comments: Retropharyngeal lymph node: Lymphadenitis, necrotizing and suppurative, diffuse, severe, with hemorrhage, edema, vasculitis, thrombosis, and numerous coccobacilli (Yersinia pestis), Siberian polecat x black-footed ferret.
The typical lesions of plague in susceptible species are necrotizing and hemorrhagic lymphadenitis (bubo forma-tion), septicemia, and pulmonary edema and hemorrhage associated with vascular damage. The lesions in cervical lymph nodes reflect entry of the bacteria through the oropharyngeal mucosa to the regional nodes with subsequent proliferation of bacteria and septicemia. If exposure to plague is by flea bite, buboes develop at regional lymph nodes, typically inguinal and axillary. Gram-negative coccobacilli are present in large numbers in the nodes and ves-sel lumina. Disseminated intravascular coagulation and endotoxic shock occur in highly susceptible individuals.
Carnivores, with the exception of Felidae, have been thought to be relatively resistant to developing clinical plagu-e; most rodents are highly susceptible. However, a single case in a black-footed ferret demonstrated that at least some members of the genus Mustela are susceptible to fatal infection. Subsequent studies demonstrated that hy-brid ferrets (used as surrogates for black-footed ferrets) are highly susceptible to plague by oral or parenteral routes of exposure. This is important in the recovery program for the black-footed ferret, because sylvatic plague is com-mon throughout much of the west and is particularly common in prairie dogs, the primary prey of black-footed ferrets.
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Case 12-2. Lymph node. Extensive necrosis and inflammation with focal areas of hemorrhage.
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Case 12-2. Lymph node. Multifocally within zones suppuration and necrosis, are multiple large colonies of bacteria.
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Case 12-2. Perinodal fat. Brown & Brehn staining reveals that bacterial colonies are composed of short reddish-blue (Gram negative) rods.
AFIP Diagnosis: Lymph node: Lymphadenitis, necrotizing, suppurative, diffuse, severe, with numerous bacilli, Siberian polecat x black-footed ferret (Mustela eversmanni x M. nigripes), mustelid.
Note: Necrosis, suppurative inflammation and hemorrhage are present within the surrounding perinodal tissues in some sections.
Conference Note: Yersinia pestis is a nonmotile, non-spore forming, facultative anaerobic, gram-negative, bipolar coccobacillus of the family Enterobacteriaceae and is the cause of the human disease known as "plague". The organism exists on every continent except Australia, and is found most often in cool, semiarid climates. While the organism is sensitive to dessication, it can survive several weeks to months in organic material such as infected carcasses.
Wild rodents, such as prairie dogs and ground squirrels, serve as reservoirs for infection of humans and domestic animals. The wild rodent population serves as the source of infection through chronic bacteremia; transmission of Y. pestis to susceptible hosts, including humans, occurs through flea bites, by contact of the organism with mucous membranes (ingestion) or broken skin, or by inhalation of droplets from animals with pneumonic plague.
Flea bites are the most common mode of transmission among wild rodents and to humans. After fleas ingest blood from an infected host, Y. pestis multiples in the insect's gut and produces coagulase. Coagulase causes coagulation of ingested blood at subsequent feedings, obstructing the flea gastrointestinal tract. Obstruction of the gut causes regurgitation of bacteria into the wound of the next mammalian host.
Once the organism enters the mammalian host, the initial pathogenesis of infection depends upon whether infection occurs through a flea bite or through the mucous membranes or broken skin. After a flea bite, the organisms are phagocytized by neutrophils and macrophages. In neutrophils, the organism is destroyed, but in mononuclear cells the organism not only survives but multiplies. Multiplication of Y. pestis within host cells depends upon the presence of a virulence plasmid or pathogenicity island called Yop. Yop encodes a type III secretion apparatus and numerous proteins that disrupt normal host cell signal transduction pathways, including a serine-threonine kinase and a protein tyrosine phosphatase3. Infected macrophages travel to regional lymph nodes where the organism ruptures the infected phagocytic cells, replicates, and eventually causes lymphadenitis, lymphoid necrosis, and abscess formation (buboes). Initial replication in macrophages results in the production of a capsular envelope, rendering the organism resistant to further phagocytosis. Y. pestis makes a plasmid-encoded protease that activates plasminogen and cleaves complement C3 at a specific site. This secreted protease is essential for spread of the bacteria from the local site of inoculation into the bloodstream; mutant bacteria lacking this protease are much less virulent.
In contrast to flea inoculation, organisms that are ingested or inhaled from contaminated tissue or fluids by susceptible hosts have already acquired the phagocytic-resistant capsule from the previous host's macrophages, and thus the organism spreads more rapidly resulting in a shorter incubation time. The oral route of transmission is most common in cats, ferrets, and other carnivores predatory on rodents. The presence of a bacterial capsule at the time of exposure, coupled with higher numbers of organisms received from ingested infected rodents, are likely the key reasons which make susceptible mammalian carnivores vulnerable to oral routes of transmission, but refractory to percutaneous inoculation by fleas.
In fatal cases of plague, bacteria overwhelm lymph nodes, and organisms become distributed throughout the host via the lymphatic channels or bloodstream. During bacteremia organisms may become disseminated to the eye, liver, kidney, spleen, brain, and lung. Yersinia pestis contains endotoxins that may result in edema, septic shock, and disseminated intravascular coagulation.
Contributor: Wyoming State Veterinary Laboratory, 1174 Snowy Range Road, Laramie, Wyoming 82070.
1. Williams ES, Thorne ET, Quan TJ, Anderson SL: Experimental infection of domestic ferrets (Mus-tela putorius furo) and Siberian polecats (Mustela eversmanni) with Yersinia pestis. J Wildl Dis 27:441-445, 1991.
2. Williams, ES, Mills K, Kwiatkowski DR, Thorne ET, Boerger-Fields A: Plague in a black-footed fer-ret (Mustela nigripes). J Wildl Dis 30:581-585, 1994.
3. Sameulson J: Infectious diseases. In: Robbins Pathologic Basis of Disease, Cotran RS, Kumar V, Collins T, eds., 6th ed., pp. 387-388 and 356, WB Saunders, Philadelphia, PA, 1999.
4. Macy DW: Plague. In: Infectious Diseases of the Dog and Cat, Greene CE, ed., 2nd ed., pp. 295-300, 1998.
Case III - 98-1252 (AFIP 2644339)
Signalment: Seven-year-old, spayed female, Domestic Longhair, feline.
History: A bulging iris was noted in the right eye of this cat at the time of its yearly vaccination. The owner had noted the change approximately one month prior, and stated that the change had progressed. There was no apparent discomfort to the animal.
Case 12-3. Eye. As described below.
Gross Pathology: An irregularly shaped, pale tan mass measuring approximately 0.75 cm in diameter was present within the globe and extended caudally from the iris.
Contributor's Diagnosis and Comments: Eye: Iridociliary adenocarcinoma.
A partially encapsulated, highly cellular mass consisting of cuboidal to polygonal cells arranged in loose cords, packets, and occasional rosettes is adherent to the posterior aspect of the iris and to the ciliary body. The neoplasm infiltrates the base of the iris and extends into the filtration angle. Irregularly shaped, dilated channels are present in some areas, and the mass is supported by a fine fibrovascular stroma. Cells within the mass have large, round to oval, occasionally indented nuclei, 1-2 nucleoli, finely stippled chromatin, small to moderate amount of foamy, eosinophilic cytoplasm, and variably-distinct to indistinct cell margins. A few cells have large, irregularly shaped nuclei, and the mitotic rate varies from 0-3 per high-powered field. Some scleral vessels adjacent to the neoplasm contain thrombi and seemingly have "infiltrates" of cells (may not be visible in all sections); the cells are dissimilar to those within the neoplasm and may, in fact, represent a reaction to thrombosis or other negative vascular events.
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Case 12-3. Eye. A monomorphic mass replaces the iris.
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Case 12-3. Ocular tumor. Sheets of pleomorphic polygonal cells occasionally palisade around a central lumen (pseudorosette formation).
AFIP Diagnosis: Eye: Ciliary body adenocarcinoma, Domestic Longhair, feline.
Note: some sections contain minimal cataractous change.
Conference Note: This neoplasm was studied in consultation with the Department of Ophthalmic Pathology. Conference participants agreed with the contributor's diagnosis. An expansile, infiltrative, densely cellular neoplasm has effaced the ciliary body and is composed of polygonal cells arranged in packets, nests, tubular structures, and pseudorosettes, supported by a fine fibrovascular stroma. Neoplastic cells have significant atypia, with occasional bizarre cells. The mitotic rate is high. Scattered within the tumor are entrapped melanophages which contain moderate amounts of brown-black granular to globular pigment.
Immunohistochemical studies performed at the AFIP demonstrate that the tumor is multifocally positive for both keratin and vimentin, and negative for S-100 protein. The PAS reaction demonstrates that neoplastic cells align along a PAS-positive basement membrane, supporting the diagnosis of ciliary body adenocarcinoma.
Primary tumors of the globe are occasionally encountered in dogs and cats. Melanocytic neoplasms are most frequently reported, while those originating from the ciliary body epithelium are the second most commonly encountered. Ciliary body neoplasms arise from mature ciliary body epithelium, which is of neuroectodermal origin. Medulloblastomas and retinoblastomas are primary ocular tumors that arise from embryonic neuroectoderm.
Tumors of the ciliary body may be pigmented or nonpigmented, depending upon whether the neoplastic cell population arises from the inner nonpigmented or outer pigmented layer of the ciliary epithelium; nonpigmented tumors are more common than pigmented tumors. Tumors of nonpigmented epithelium tend to produce thick basement membranes, while tumors of the pigmented epithelium tend to form solid darkly pigmented masses. Ciliary body adenomas are more common than adenocarcinomas in both dogs and cats. Adenomas tend to grow endophytically, while adenocarcinomas are more likely to invade adjacent tissues. Metastasis is rare in dogs and cats with ciliary body adenocarcinoma, but may occur in advanced stages of disease. In humans, ciliary body tumors are rare, and adenomas occur more frequently than adenocarcinomas. There are few convincing reports of metastatic disease.

Differential diagnosis discussed by participants included melanoma and metastatic carcinoma. The Department of Ophthalmic Pathology considers the PAS reaction the most important laboratory procedure for differentiation of ciliary body adenocarcinoma from melanoma. Ciliary body adenocarcinomas are characterized by PAS-positive basement membranes, while melanomas are not.
Contributor: Department of Pathology, College of Veterinary Medicine, The University of Tennessee, PO Box 1071, Knoxville, TN 37901.
1. Wilcock BP: The eye. In: Pathology of Domestic Animals, Jubb KVF, Kennedy PC, Palmer N, eds., 4th ed., volume 1, pp. 519-520, Academic Press, San Diego, CA, 1993.
2. Peiffer Jr RL: Ciliary body epithelial tumours in the dog and cat: A report of thirteen cases. J Small Anim Pract 24:347-370, 1983.
3. Dubielzig RR: Ocular neoplasia in small animals. In: Small Animal Ophthalmology, Vet Clin N Amer 20(3):837-848, 1990.
4. Bellhorn RW: Ciliary adenocarcinoma in the dog. J Amer Vet Med Assoc 159:1124-1128, 1971.
5. Gionfriddo JR, et al.: Ocular manifestations of a metastatic pulmonary adenocarcinoma in a cat. J Amer Vet Med Assoc 197:372-374, 1990.
6. Shields JA, et al.: Acquired neoplasms of the nonpigmented ciliary epithelium. Ophthalmology 103:2007-2016, 1996.
International Veterinary Pathology Slide Bank:
Laser disc frame # 7926, 9395, 9451, 9456, 16852-53, 16928.
Case IV - Unlabeled 8x10 EM photo (print) (AFIP 2648170)
Signalment: Male, Fischer 344 rat.
History: This control rat was given a cyclodextrin vehicle.
Histopathologic Findings:
Kidney, hematoxylin and eosin stained sections.
Multifocally, proximal renal tubules have swollen and vacuolated epithelial cells. Affected epithelial cells contain variably-sized, intracytoplasmic, eosinophilic, granular deposits and low numbers of eosinophilic, hyaline droplets and crystals.
Contributor's Diagnosis and Comments: Kidney, proximal tubules: Renal tubular degeneration with intralysosomal amorphous material and crystals (alpha 2m globulin).
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Case 12-4. Kidney. The cytoplasm of many proximal tubules is rarified, somewhat foamy, and often contains globular to to polygon shaped eosinophilic inclusions.
Transmission Electron Micrograph, 1540X. Kidney, proximal tubules. The electron micrograph illustrates portions of four proximal tubules lined by tall cuboidal epithelial cells with a brush border, oval nuclei with dispersed chromatin and 1-2 small nucleoli, and abundant mitochondria, many arrayed perpendicularly to the basement membrane. The epithelial cells are swollen, vacuolated, and have numerous, intracytoplasmic osmiophilic amorphous deposits (secondary lysosomal contents) surrounded by an electron-lucent space and a single membrane (fused lysosomes) and large, rectangular, rhomboid or irregular to needle-like crystalline intralysosomal deposits (alpha 2m globulin). Interspersed between the proximal tubules (lower left) are small spindle cells with oval nuclei (mesangial cells).
This case is an example of two lesions, both lysosomal. The crystalline deposits are due to deposition of alpha 2m globulin, while the fused or coalesced secondary lysosomes distended with amorphous material are consistent with a lysosomal storage disorder.
Alpha 2m globulin deposits may be globular, rectangular, rhomboid or irregular in shape. Alpha 2m globulin is produced in large quantities in the liver of male rats, and accumulates as hyaline droplets in the renal tubular epithelium. Numerous chemicals can disrupt the metabolism of alpha 2m globulin, resulting in an exacerbation of protein deposition and more rapid development of nephropathy due to tubular degeneration and necrosis.
The other lysosomal alterations are consistent with a lysosomal storage disorder, in this case due to cyclodextrin administration. Cyclodextrins are widely used in oral, topical and parenteral pharmaceutical preparations to increase solubility and form stable complexes that result in enhanced drug delivery. Toxicity with these compounds varies with the specific type of cyclodextrin. Renal lesions, specifically proximal tubular degeneration and necrosis, are associated with methylated cyclodextrins, particularly TM-beta-cyclodextrins. Although the exact mechanism for the tubular lesion is unknown, these compounds disrupt phagosomal-lysosomal fusion. Although acicular microcrystals have been reported with some cyclodextrins, their origin and significance have not been determined. In the case presented here, crystals were consistent with alpha 2m globulin.

AFIP Diagnosis: Kidney, proximal convoluted tubular epithelium: Degeneration, multifocal, moderate to severe, with cytoplasmic vacuolation, variably electron-dense acicular crystals, and electron-dense rhomboidal and globular bodies, Fischer 344 rat, rodent.
Conference participants generally agreed with the following description of the submitted electron micrograph:
Kidney, proximal convoluted tubule: There are portions of at least three tubular structures, each lined by contiguous cuboidal to rectangular cells aligned along a prominent basement membrane. Along the luminal border of these cells are lush microvilli. The cells have irregularly oval nuclei which contain abundant euchromatin and peripherally clumped heterochromatin. One nucleus has two small nucleoli. The cytoplasm contains abundant, closely packed, elongate mitochondria that are often arranged perpendicularly to the basement membrane. There is a moderate amount of rough endoplasmic reticulum within the cytosol. Multifocally near the cell apices there are few pinocytotic vesicles. Interposed between adjacent tubular basement membranes are a few small cells with scant cytoplasm and oval to angular nuclei (fibroblasts or other interstitial cells).
Multifocally within the cytoplasm of the tubular epithelial cells there is an accumulation of numerous irregularly shaped, variably-sized, electron-lucent vacuoles that often coalesce (enlarged lysosomes). Superimposed within these vacuolated areas are numerous smaller, intensely electron-dense, variably-sized granules. Within most tubular epithelial cells in the vacuolated areas there are few electron-dense crystals that vary from thin spicules with sharply pointed ends, to large hexagonal or rhomboidal crystalline structures. The enlarged lysosomes containing the previously described material displace mitochondria and nuclei peripherally.
Conference Note: This case was reviewed in consultation with Dr. David Fritz, consultant to the Department of Veterinary Pathology for ultrastructural studies.
Case 12-4. Electron micrographs
Many of the tubular epithelial cells in the central tubule at the center of the photo are swollen and expanded more laterally than apically due to the vacuolated inclusions. Residual cellular organelles are peripheralized and compartmentalized. The compartmentalized mitochondria have lost proper orientation and are no longer aligned perpendicular to the basement membrane. In the epithelial cell in the center of the photo, the lateral cell boundaries are markedly widened, and the nucleus is compressed and flattened against the cell base (see cell labeled "4" at AFIP website). Because these ultrastructural changes probably alter normal cellular function, the morphologic diagnosis of "cellular degeneration" is appropriate.
Extensive intracytoplasmic vacuolation is present in the tubular epithelium. Determining the nature of these vacuoles is difficult due to the low magnification of the electron micrograph, but there is evidence that the vacuoles represent enlarged and giant lysosomes. First, of the various organelles that can become dilated in renal tubular epithelial cells, only the lysosome regularly contains material of varying size, shape, and density. The material within many of these vacuolated structures appears to be multiple lysosomes within one unit membrane. In one or two vacuoles, the individual lysosomal membranes disappear, forming one large vacuole (see center bottom tubular epithelial cell in photo, or refer to AFIP website with cell labeled "1"). Second, several vacuoles contain homogenous, medium electron-dense material suggestive of lysosomal contents (see cell labeled "2" on AFIP website). Normally, lysosomal contents are very electron-dense when tissue is fixed in 1% glutaraldehyde; however, the contributor does not mention method of tissue fixation in this case, and the preservation of lysosomal material may have been altered by an alternative fixative.

The globular to rhomboidal, electron-dense, intracytoplasmic bodies present in the tubular epithelial cells are consistent with the alpha 2m globulin hyaline inclusions seen in rat hyaline droplet nephropathy. However, the intracytoplasmic acicular (needle-like) crystals observed in this case are not characteristic of rat hyaline nephropathy, but rather are more consistent with the microcrystals observed in cyclodextrin-induced nephrosis in the male rat. The renal toxicity of cyclodextrins is manifested ultrastructurally as increased vacuoles within the apical cytoplasm of the proximal tubular epithelial cells, with the eventual formation of giant lysosomes, and the presence of acicular microcrystals within the lysosomal matrix. Cyclodextrins are known to form complexes with several cellular compounds, including lipids, cholesterol, and lipoproteins. The acicular crystals may represent cyclodextrin complexed to alpha 2m globulin in renal tubular epithelium.
Contributor: Lilly Research Laboratories, PO Box 708, Greenfield, IN 46140.
1. Alden CL, Frith CH: Urinary system. In: Handbook of Toxicology, Haschek WM, Rousseaux CG, eds., pp. 316-388, Academic Press Inc., San Diego, CA, 1991.
2. Thompson DO: Cyclodextrins-enabling excipients: Their present and future use in pharmaceuticals. In: Critical Reviews in Therapeutic Drug Carrier Systems, Bruck SD ed., 14(1):1-104, Begell House Inc., New York, 1997.
3. Frank DW, Gray JE, Weaver RN: Cyclodextrin nephrosis in the rat. Am J Comp Path 83:367-382, 1976.
4. Haschek WM, Rousseaux CG: The kidney. In: Fundementals of Toxicologic Pathology, pp. 173-177, Academic Press, San Diego, CA, 1998.
Ed Stevens, DVM
Captain, United States Army
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615
* The American Veterinary Medical Association and the American College of Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The C.L. Davis Foundation also provides substantial support for the Registry.

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