Results
AFIP Wednesday Slide Conference - No. 26


30 April 1997
 
Conference Moderator: Dr. Charles G. McLeod, Jr.
Diplomate, ACVP
Antech Diagnostics
8831 Satyr Hill Road
Carney, MD 21234
 
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Case I - 95E 9853-3 (AFIP 2550323)

 
Signalment: 18-year-old, thoroughbred gelding, horse.
 
History: This horse suffered recurrent, prolonged, severe episodes of dyspnea that were unresponsive to medical treatment. Euthanasia was performed during a dyspneic episode.
 
Gross Pathology: The lungs were pink, spongy, and normally collapsed, with the exception of mild firmness and darkening of a cranial portion of the left lung. The diaphragm was diffusely thickened (hypertrophy). The carcass was in good flesh.
 
Laboratory Results: None.
 
Contributor's Diagnoses and Comments: 1. Bronchiolitis and bronchitis, diffuse, chronic, moderate, nonsuppurative, with mild goblet cell metaplasia (all slides).
2. Bronchiolitis and bronchitis, diffuse, chronic, moderate, nonsuppurative, with moderate goblet cell metaplasia and mucopurulent exudate (95E9853-3).
 
Etiology: Presumptive respiratory hypersensitivity
 
The clinical signs and histological lesions in this horse are indicative of the syndrome know variably as heaves, chronic obstructive pulmonary disease, broken wind, chronic bronchiolitis-emphysema complex, and chronic bronchitis/bronchiolitis. Heaves occurs more commonly in stabled horses as compared to pastured horses. Moving acutely affected horses from stables to pasture is often an effective treatment. The condition is believed to be caused by hypersensitivity to inhaled allergens; molds and hay dust have both been implicated.
Emphysema is often not observed in "heavy" horses. Horses with severe, prolonged clinical signs may develop an easily observed "heave line" which represents the thickened edge of hypertrophic external abdominal oblique muscles, caused by forced expiratory efforts. The horse in this case had severe, recurrent clinical signs, but little evidence of gross lesions, other than apparent hypertrophy of the diaphragmatic muscle.
 
AFIP Diagnosis: Lung: Bronchiolitis and bronchitis, lymphoplasmacytic, diffuse, moderate, with airway epithelial hyperplasia, diffuse congestion, and multifocal alveolar edema, thoroughbred, horse, equine.
 
Conference Note: Conference participants agreed with the contributor's diagnoses. The most consistent finding in horses with clinical signs of chronic obstructive pulmonary disease is a generalized chronic bronchiolitis. Emphysema is less common. Constant features of the chronic bronchiolitis are epithelial hyperplasia, goblet cell metaplasia, peribronchiolar fibrosis, and infiltration by lymphocytes and plasma cells. Lumina of bronchioles are narrowed by accumulation of exudate and peribronchiolar fibrosis. Mucus is usually a major component of the exudate. The presence of eosinophils is quite variable ranging from very few to numerous. There are usually increased numbers of mast cells around bronchioles. Neutrophils are less common than eosinophils but sometimes the lesion has the appearance of a mucopurulent bronchiolitis.
 
Contributor: Wyoming State Veterinary Laboratory, 1174 Snowy Range Rd., Laramie, WY 82070.
 
References:
1. Jubb KVF, Kennedy PC, Palmer N: Pathology of Domestic Animals, 4th ed., vol 2, pp. 582-583, Academic Press, 1993.
2. Rooney JR, Robertson JL (eds): Equine Pathology. Iowa State University Press, pp. 46-50, 1996.
3. Smith BP (editor): Large Animal Internal Medicine. Mosby, St. Louis, pp. 533-536, 1990.
 
International Veterinary Pathology Slide Bank:
Laser disc frame #2628, 9575, 15543, 15580-3.
 
 

Case II - HB1787 (AFIP 2554540), 1 photo

 
Signalment: Japanese Cat, female, adult.
 
History: The tumorous mass had been recognized in the perianal area and gradually increased in size with ulceration of the surface. The mass was initially excised in December 1994, and thereafter recurrence of the tumor has taken place two times. The cat harboring the tumor is still alive.
 
Gross Pathology: The primary tumor measured 5 x 5 x 6 cm and had an irregular ulcerated surface. Cut surface of the tumorous mass was grayish-white and revealed fibrous septa which divided the tumor into lobules.
 
Laboratory Results: None.
 
Contributor's Diagnosis and Comments: Carcinoma of the anal sac- associated sebaceous gland.
The tumorous mass was composed of lobules of basaloid and sebaceous cells separated by fibrovascular septa. The neoplastic cells were polyhedral or angular with vesiculate nuclei and brightly eosinophilic granular cytoplasm. Occasionally, the tumor cells showed definite cytoplasmic vacuoles. Frequently, there was squamous differentiation towards the center of the neoplastic lobules. In some lobules, there was intermingling of basaloid cells with the sebaceous cells. The morphology of the present tumor is likened to that of canine hepatoid tumor. It is worth mentioning that cats have no perianal (hepatoid) gland which is a peculiar anatomical structure of dog. Accordingly, based upon the morphologic features, we suppose that the origin of the present tumor is the anal sac-associated sebaceous gland. The contribution of the sweat gland, the other glandular structure associated with the anal sac, was eliminated as the histologic criteria of the present tumor are different from that of apocrine carcinoma. There is no previous report of a similar case of perianal tumor in cat. Yager and Wilcock (1994) mentioned that they have seen only one case of feline perianal carcinoma which they reclassified as a perianal adenoma.
 
AFIP Diagnosis: Haired skin, perianal area: Carcinoma, sebaceous, Japanese cat, feline.
 
Conference Note: The conference participants agreed that the histologic findings are diagnostic of sebaceous carcinoma. The exact origin is not evident in the sections examined.
Sebaceous carcinomas are infrequent in dogs and rare in cats. These lesions are locally infiltrative, solitary, poorly circumscribed tumors made up of pleomorphic cells, a proportion of which have evidence of sebaceous differentiation. Lobule formation is often present but is not a prominent feature. Neoplastic cells are often pleomorphic with marked anisocytosis and anisokaryosis; mitoses can be numerous. All neoplastic cells seem to make an attempt at forming a sebaceous cell. In contrast, basal cell tumors with sebaceous differentiation (also known as sebaceous epitheliomas) have a preponderance of basal cells with variable amounts of orderly and often complete sebaceous differentiation. The sebaceous carcinoma lacks these two distinct and mature cell populations.
 
Contributor: Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060, Japan.
 
References:
1. Dellman HD: Textbook of Veterinary Histology. Lea and Febiger, Philadelphia, pp. 825-313, 1993.
2. Goldschmidt MH, Shofer FS: Skin Tumors of the Dog and Cat. Pergamon Press, pp 66-75, 1992..
3. Greer MB, Calhound ML: Anal sac of the cat (Felis domesticus). Am J Vet Res 27:773-781, 1996.
4. Gross TL, Ihrke PJ, Walder EJ: Veterinary Dermatopathology. A macroscopic and microscopic evaluation of canine and feline skin disease. Mosby-Year Book, pp. 381-384, 1992.
5. Pully, TL, Stannard AA: Tumors of the skin and soft tissues. In: Tumors of the Domestic Animals, Moulton, JE (ed), Univ. of California Press, pp 23-87, 1990.
6. Scott DH, Miller WH, Griffin CE: Small Animal Dermatology. Saunders WB Company, pp. 956-989, 1995.
7. Yager JA, Wilcock BP: Surgical Pathology of the Dog and Cat. Mosby-Year Book pp. 257-270, 1994.
International Veterinary Pathology Slide Bank: None.
 
 

Case III - 96-7927-5 (AFIP 2551386)

 
Signalment: 10.5-year-old, female, spayed, Domestic Shorthair cat.
 
History: Diagnosed with diabetes one year ago. Controlled with insulin. Six weeks ago became anorectic. Inflammatory bowel disease was diagnosed. A gastric tube was placed for feeding.
The cat had a distended abdomen when presented to the referring veterinarian several weeks later. 60ml of fluid was removed from the abdomen. Feline infectious peritonitis was diagnosed. After presentation to the teaching hospital, ultrasound showed an enlarged liver. 75ml of fluid was removed from the abdomen on the day prior to death; 120 ml was removed on the day of death. Respiratory difficulties and an absence of gastric emptying were noted.
 
Gross Pathology:
Multiple neoplastic masses in liver.
Sessile mass on colonic wall constricting lumen.
Multiple mesenteric implants of neoplastic tissue.
Ascites.
Laboratory Results: None.
 
Contributor's Diagnosis and Comments: Liver, cholangiocellular carcinoma with biliary hyperplasia, rupture and inspissation with transcoelomic metastasis.
All sections of liver have multiple areas of poorly demarcated glandular proliferations. Many of these have areas of necrosis centrally. The cells in these areas replace hepatic parenchyma and consist of a tall cuboidal epithelium forming glands and tubules. Bile ducts are prominent in all sections and have multiple extensions (biliary proliferation) of short tubules into the adjacent hepatic parenchyma. There are many larger bile ducts with an eosinophilic inspissated material in their lumina. Some of these secretions are partially covered by a biliary epithelium. In some areas, the bile ducts are ruptured and biliary epithelium extends into the adjacent hepatic parenchyma. Occasional glands and cysts contain eosinophilic material with variable numbers of neutrophils. Adjacent remaining hepatocytes have marked centrilobular vacuolization and atrophy with dilated sinusoidal spaces filled with erythrocytes. There is mild fibrosis of the centrilobular vein. There is also hemosiderin laden macrophages scattered throughout the interlobular zone.
Cholangiocellular carcinoma can spread by transcoelomic metastasis as noted in this case. The ascites noted in this case would be consistent with the widespread liver involvement. Metastatic sites included colonic wall, mesentery, omentum, diaphragm, and abdominal body wall. There was no evidence of lung involvement. The metastatic sites had a marked desmoplastic response which was contributory to the constriction of the colon associated with the mass on the colonic wall.
 
AFIP Diagnosis: Liver: Adenocarcinoma, Domestic Shorthair, feline.
 
Conference Note: Although the histopathologic findings are compatible with cholangiocellular carcinoma, there are no pathognomonic features of this neoplasm. Thus, metastatic adenocarcinoma from such sites as pancreas, gastrointestinal tract, lung, extrahepatic bile duct and gallbladder must be reliably excluded to reach a conclusive diagnosis of cholangiocellular carcinoma.
Cholangiocellular carcinomas are unusual in that they are very frequently multiple or diffuse, suggesting that the cause acts at multiple sites or that there is extensive intrahepatic spread. Metastasis to the regional lymph nodes is common. In the cat, there is a tendency of this neoplasm to invade Glisson's capsule and implant on the peritoneum. In humans and some carnivores, chronic infection with opisthorchid liver flukes (Opisthorchis viverrini and Clonorchis sinensis) has been associated with bile duct carcinomas.
Grossly, cholangiocellular tumors can usually be distinguished from hepatocellular tumors by their multiplicity, firmness, whitish color and the typical umbilication of those that involve the capsule.
Microscopically, cholangiocellular carcinomas produce ductules and acini, and sometimes papillary formations. The cells are cuboidal or columnar, with a moderate amount of clear or slightly granular cytoplasm. The tubules do not contain bile, but in well-differentiated specimens may contain mucin. A desmoplastic reaction and vascular invasion are common. Vascular invasion was particularly prominent in the present case.
 
Contributor: University of Illinois, Department of Pathobiology, College of Veterinary Medicine, Urbana, Illinois 61801.
 
References:
1. Feldman BF, Strafuss AC, Gabbert N: Bile duct carcinoma in the cat: Three case reports. Feline Pract Jan:33-39, 1976.
2. Lawrence HJ, Erb HN, Harvey HJ: Nonlymphomatous hepatobiliary masses in cats: 41 cases (1972 to 1991). Vet Surg 23:365-368, 1994.
3. Moore FM: Tumors of the liver and biliary system. In: Diseases of the Cats (J Holtzworth, ed). Saunders, 1987. Pg 500-504.
4. Patnaik AK: A morphologic and immunocytochemical study of hepatic neoplasms in cats. Vet Pathol 29:405-415, 1992.
5. Postorino NC: Hepatic tumors. In: Clinical Veterinary Oncology (SJ Winthrow & E.G. MacEwen, eds), Lippincott, pp. 196-200, 1989.
6. Jubb KVF, Kennedy PC, Palmer N (eds): Pathology of Domestic Animals, 4th ed., vol 2, Academic Press, pp. 405-406, 1993.
 
International Veterinary Pathology Slide Bank:
Laser disc frame #692, 693, 694, 1054, 6457, 6458, 12789, 12790, 12791.
 

Case IV - A96121098 (AFIP 2550447)

Signalment: An adult female black buck antelope (Antelope cervicapra).

 
History: Pregnant female discovered near death, died during C-section.
 
Gross Pathology: The liver is swollen with rounded margins and diffusely dark red. There are fibrous adhesions between the liver and diaphragm.
 
Laboratory Results: No significant bacterial pathogens cultured. Fecal floatation revealed strongylid eggs.
 
Contributor's Diagnosis and Comments: Deposition, amyloid, hepatic sinusoids, rumen submucosa, and spleen.
Amyloid deposits were also detected in the renal medullary interstitium. Oxidation with potassium permanganate abolished the congophilia and green birefringence indicating the deposits were of AA-type. Systemic reactive amyloidosis is observed in a variety of domestic and exotic animals. Amyloid-A (AA) is derived from an acute phase reactant protein designated serum amyloid A produced mainly by the liver. Serum amyloid A is elevated in inflammatory conditions and may have an antiinflammatory function. Systemic reactive amyloidosis is often associated with chronic inflammatory disease. In this case, except for the fibrous adhesions between liver and diaphragm, lesions suggesting chronic inflammatory disease were lacking. Deposition of amyloid is a multistep process requiring elevated levels of serum amyloid A, generation of a tissue factor termed amyloid enhancing factor that may serve as a focal point for fibrillization and lastly, heparan sulphate proteoglycan may be involved in the resistance of amyloid to proteolysis.
 
AFIP Diagnosis: 1. Liver: Amyloidosis, diffuse, severe, with hepatocellular atrophy and loss, blackbuck antelope (Antelope cervicapra), bovid.
2. Liver: Hepatitis, portal, lymphoplasmacytic, diffuse, mild.
3. Spleen, red pulp: Amyloidosis, diffuse, severe.
4. Spleen: Hemosiderosis, diffuse, moderate.
 
Conference Note: Amyloid is a pathologic extracellular proteinaceous substance deposited between cells in multiple tissues and organs in various clinical and subclinical diseases. The term amyloidosis encompasses a group of diseases sharing in common the deposition of similar appearing extracellular proteins. Amyloid proteins are predominantly AL (amyloid light chains) associated with plasma cell dyscrasias or AA (amyloid-associated protein) deposited secondary to chronic inflammation. The characteristic appearance and staining reaction of amyloid are due to the conformation of the constituent polypeptides into cross- -pleated sheets ( -fibrilloses) on x-ray crystallographic analysis.
The clinicopathologic classification of amyloidosis is determined by tissue distribution of the deposits and the presence or absence of predisposing disease.
Systemic or generalized amyloidosis is subdivided into primary (in association immunocyte abnormalities) and secondary (when associated with chronic inflammation). In localized amyloidosis, deposits are restricted to a single organ or tissue in the body and are usually associated with aggregates of lymphocytes and plasma cells.

Amyloidosis consists of about 90% fibril proteins and 10% glycoprotein (P component). AL (amyloid light chain) is derived from plasma cells, contains immunoglobulin light chains and is the predominant deposit in primary amyloidosis. It is associated with multiple myeloma and is composed of homogeneous light chains of the ( -VI type) and type or their N-terminal fragments ( -Bence Jones protein, amyloid fibril protein in multiple myeloma), or both. AA (amyloid-associated) proteins are derived from large protein precursors in the serum (SAA-serum amyloid associated) that are produced in the liver in response to interleukin-1, and perhaps other cytokines, and are associated with the HDL3 subclass of lipoproteins. SAA is an acute-phase protein associated with inflammatory reactions. AA proteins have been isolated in vitro from the digestion of delipidated SAA by monocytic serine proteases (u-PA, urokinase-type plasminogen activator-macrophages and granulocytes). This is the predominant deposit in secondary amyloidosis.
Recent studies have revealed several other proteins in amyloid deposits:
1. Transthyretin: A serum protein that binds and transports thyroxine and retinol. A mutant form of transthyretin and its fragment are isolated in familial amyloid polyneuropathies (Familial Mediterranean fever) and amyloidosis associated with aging (Alzheimer's disease) in humans.
2. 2 Microglobulin: component of the MHC class 1 molecule has recently been isolated in amyloidosis that complicates long term hemodialysis.
3. 2 Amyloid protein (A 4 protein) constitutes the core of cerebral amyloid plaques as well as the deposits found in the walls of cerebral vessels in Alzheimer's disease.
4. IAAP (islet amyloid polypeptide): major component of human and feline pancreatic islet amyloid and of amyloid in human pancreatic endocrine tumors, occurs in normal pancreatic cells of numerous species, is located in the outer lucent zone and dense core of the cell secretory vesicle in the cat and man, respectively, and is probably co-secreted with insulin. It inhibits basal and insulin-stimulated glycogen synthesis in skeletal muscle and is believed to play a role in the insulin resistance seen in type 2 diabetes mellitus in man.
5. AEF (Amyloid-enhancing factor): a glycoprotein that appears to alter the metabolism of SAA and may be essential for the deposition of AA amyloid in experimental models. Note that additional elements must be required for the deposition of amyloid in tissue since SAA when reacted to IL-1 in the presence of AEF does not give rise to amyloid.
6. GAG's (sulfated glycosaminoglycans) have been reported in several forms of amyloid deposits.
7. In addition to those proteins already described, amyloid deposits derived from hormone precursors (pro-calcitonin, proinsulin, medullary carcinoma of the thyroid) and keratin have been reported.
8. P Component (AP), also synthesized in the liver, is structurally similar to C-reactive protein and is associated with all forms of amyloidosis.
 
The pathogenesis of amyloidosis is unknown. Current evidence suggests that amyloid proteins are derived by partial degradation (monocyte-associated serine esterases, u-PA) of parent proteins. On the other hand, in some cases, there is an increase in the level of serum precursors (i.e. Ig light chains, SAA, 2-microglobulin) that appear to be structurally normal. In others (transthyretin), a genetic abnormality results in the production of a chemically abnormal precursor protein. Additionally, the conversion of these soluble precursors to their insoluble form (amyloid) involves the action of proteolytic enzymes or some other form of processing. In absence of conclusive evidence, both quantitative and qualitative changes in the precursor proteins, coupled with defective proteolysis, are implicated by recent research findings. Progressive accumulation of these proteins between cells produces pressure atrophy, degeneration, necrosis and loss of adjacent cells.
 
Contributor: Texas Veterinary Medical Diagnostic Laboratory, P. O. Box 3200, Amarillo, TX 79116-3200.
 
References:
1. Husby G: Classification of amyloidosis, Bailliers Clin Rheumatol 8(3):503-511, 1994.
2. Kisilivesky R, et al: A critical analysis of postulated pathogenic mechanisms in amyloidogenesis. Crit Rev Clin Lab Sci 29(1):59-82, 1992.
3. Linke RP, et al: Immunohistochemical identification of generalized AA- amyloidosis in a mountain gazelle (Gazella gazella). Vet Pathol 23:63-67, 1986.
4. Rideout BA, et al: Renal medullary amyloidosis in Dorcas gazelles. Vet Pathol 26:129-135, 1989.
5. Yakar S, et al: The molecular basis of reactive amyloidosis. Sem Arthritis Rheumatism 24(4):255-261, 1995.
6. Inoue S, et al: Effect of polyvinylsulphonate on murine AA amyloid: A high resolution ultrastructural study. Lab Invest 74(6):1081-1090, 1996.
7. Cheville, Norman, F. Cell Pathology, Iowa State University Press, 2nd edition, pp. 173-79, 1983.
8. Maxie MG: The urinary system. In: Pathology of Domestic Animals, eds. Jubb KVF, Kennedy PC, Palmer N, Academic Press Inc., 4th edition Vol 2, pp 484-486, 1993.
9. Obrien, T.D. et al Islet Amyloid polypeptide and Calcitonin Gene-related Peptide Immunoreactivity in Amyloid and Tumor Cells of Canine Pancreatic Endocrine Tumors. Vet. Path. 27:194-198,1990.
10. Robbins SL, Cotran RS, Kumar V (eds): Pathologic Basis of DiseasePhiladelphia, Pa.. W.B. Saunders Company, 2nd edition, pp. 210-220; 1989.
 
International Veterinary Pathology Slide Bank:
Laser disc frame #4725, 5400, 9218, 9253.
Lance Batey
Captain, VC, USA
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615
Internet: Batey@email.afip.osd.mil
 
* 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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