CASE I EX2930 (AFIP 2741283)
Signalment:12-year-old, male, Labrador retriever dog
History: Slow-growing, pedunculated mass on lower lip that had developed over a period of four months. Mass was surgically removed as it had started to ulcerate. Mass has not reappeared since resection six months ago.
Gross Pathology: Pedunculated mass approximately 1.5 x 2.0 cm on lower lip, composed of firm tissue covered by red ulcerated surface.
Laboratory Results: No laboratory investigations undertaken.
Contributors Diagnosis and Comment:
The mass is composed of a subcutaneous infiltration of mononuclear cells with a variety of morphologies covered by an ulcerated epithelial surface. Some cells resemble lymphocytes with dense round basophilic nuclei and little cytoplasm. This cell type is most common in the stalk of the mass. Most cells have a larger more open nucleus surrounded by eosinophilic faintly vacuolated cytoplasm and resemble histiocytes. In addition, there are very large cells composed of similar cytoplasm but which have large abnormally shaped nuclei. These nuclei were often eccentrically placed and had a crescentic form. Some of these cells appeared to be multinucleated but this was interpreted as plane of section effect due to their very abnormal shape. Beneath the ulcerated area there is also an acute inflammatory infiltrate and mild hemorrhage. Despite the abnormal cell morphology there are few mitotic figures. Apoptotic nuclei are more common than mitoses but are not a prominent feature.
There is scant fibrous tissue stroma, occasional blood vessels and scattered striated muscle fibers surrounded by the abnormal cells towards the base of the mass. Crush artifact is evident in the stalk of the mass.
Diagnosis: Cutaneous histiocytoma.
Differential diagnoses considered: mast cell tumor, plasmacytoma.
Despite the bizarre looking nature of some cells, these neoplasms behave as benign growths; spontaneous regression would have been expected if resection had not been undertaken. The presence of lymphocytes in the tumor is expected and is probably indicative of an immune reaction being mounted against the neoplastic cells.
AFIP Diagnosis: Lip: Plasmacytoma, Labrador retriever, canine.
Conference Comment: Differentiating plasmacytoma and histiocytoma is occasionally a difficult task. Cutaneous plasma cell tumors have been called atypical histiocytomas. They also have been misdiagnosed as Merkel cell tumor. Immunohistochemical demonstration of immunoglobulin within the neoplastic cells has clarified the histogenesis. Cutaneous plasmacytomas are relatively common and typically occur in middle-aged or older dogs with a predilection for feet, ear canal and the area around the mouth. Histologically, these tumors are expansile, unencapsulated, but well-demarcated, spherical masses composed of sheets of pleomorphic round cells that are often divided into nests and cords by a fine fibrovascular stroma. The neoplastic cells have indistinct borders with moderate amounts of eosinophilic to lightly basophilic cytoplasm. There is often moderate anisokaryosis with frequent multinucleation. The mitotic rate is variable. Nuclei are occasionally indented or crescentic and frequently retain a perinuclear halo (hof) that represents the Golgi zone. Cells recognizable as typical plasma cells, frequently with prominent Russell bodies, often can be found near the periphery. Deposits of amyloid are occasionally found within the neoplasm. Plasmacytomas are generally benign. If incompletely excised, they may recur locally. Rare instances of metastasis have been reported.
Contributor: Sanofi-Syntheolab, P.O. Box 3026, 9 Great Valley Parkway; Malvern, PA 19355
References: 1. Platz SJ, Breuer W, Pfleghaar S, Minkus G, Hermanns W: Prognostic value of histopathological grading in canine extramedullary plasmacytomas. Vet Pathol 36:23-27, 1999
2. Yager JA, Scott DW: The skin and appendages. In: Pathology of Domestic Animals, ed. Jubb KVF, Kennedy PC, Palmer N, 4th ed., vol. 1, pp. 729-731. Academic Press, New York, NY, 1993
CASE II 10772-99 (AFIP 2737425)
Signalment: 2.5-year-old, spayed female, domestic shorthair cat, feline.
History: A mass was excised from the tailhead area, recurred, and was excised again 4 months later. The cat was euthanized shortly after the second biopsy due to the locally invasive nature of the lesion. The first specimen was used for the case study but the recurring mass was identical.
Gross Pathology: None given.
Laboratory Results: 2+ Actinomyces viscosus and 1+ alpha-hemolytic Streptococcus spp. were isolated from the tissue.
Contributors Diagnosis and Comment: Pyogranulomatous cellulitis and myositis with multiple condensed bacterial colonies (sulfur granules) consisting of short, slender and beaded, gram-positive bacilli.
The chronic inflammation extends through the subcutis. The bacterial colonies are condensed into basophilic to amphophilic, irregular ring and serpiginous forms within loose aggregates of neutrophils. Occasionally, bacteria are rimmed by scant, irregular, eosinophilic, club-shaped structures (Splendore-Hoeppli). Histiocytes, huge multinucleated giant cells, and some fibroplasia surround the bacteria.
Actinomycosis is more commonly manifested as pyothorax in hunting dogs, often as a mixed infection with other bacteria. We see it most frequently in bloodhounds. Dogs may also have cervicofacial, subcutaneous, abdominal, and retroperitoneal actinomycosis. Actinomycosis in cats is usually restricted to bite wounds and pyothorax. A. viscosus is a facultative anaerobe whereas some Actinomyces species are obligate anaerobes. Nocardia is aerobic.
Other bacteria that form sulfur granules include Staphylococcus aureus (botryomycosis), Actinobacillus spp., and Streptomyces spp.
AFIP Diagnosis: Haired skin: Dermatitis and panniculitis, pyogranulomatous, diffuse, severe, with ulceration, hemorrhage, and colonies of filamentous bacilli (sulfur granules), domestic shorthair cat, feline.
Conference Comment: Actinomyces spp. are opportunistic pathogens that require disruption of mucosal barriers for infection and whose pathogenicity is greatly increased in mixed infections with other commensal organisms from the oral cavity or intestinal tract. Actinomyces fimbriae bind to specific cell surface receptors on other bacteria, creating a bacterial complex that inhibits neutrophil phagocytosis and bactericidal activity. The characteristic granulomatous lesion is due to actinomycotic induction of neutrophil chemotaxis, macrophage activation, and stimulation of B-lymphocyte hyperplasia. Proteolytic enzymes released from the inflammatory cells cause destruction of connective tissue, resulting in cellulitis as the infection extends along normal tissue planes.
Subcutaneous actinomycotic infections in cats are usually the result of fight wounds and can present as malodorous, draining abscesses with characteristic dense, bacterial aggregates (sulfur granules). The organisms are gram-positive, non-acid-fast, filamentous bacilli.
Contributor: Arkansas Livestock and Poultry Commission, #1 Natural Resources Drive, Little Rock, AR 72205
References: 1. Edwards DF: Actinomycosis and nocardiosis, In: Infectious Diseases of the Dog and Cat, ed. Greene CE, 2nd ed., pp. 303-307. WB Saunders, Philadelphia, PA, 1998
2. Migaki G, Voelker FA, JW Sagartz: Fungal diseases. In: Pathology of Domestic Animals, ed. Benirschke K, Garner FM, Jones TC, pp. 1577-1580. Springer-Verlag, New York, NY, 1978
CASE III 99-155 (AFIP 2742255)
Signalment: 1-year-old, spayed female, domestic shorthair cat, Felis domesticus, feline.
History: Presented two weeks prior to necropsy with a 3-day history of lethargy and inappetence. The cat was mildly febrile but the main clinical sign was caudal abdominal swelling, thickening and tenderness, progressing to pain upon palpation.
Gross Pathology: The caudal to mid-ventral mammary tissue and subcutaneous fat were firmer than normal, opaque and diffusely speckled orange/brown. The abdominal and mesenteric fat was similarly affected and there were multiple areas of transparent, orange, gelatinous material between the body wall and the subcutaneous fat. The peritoneal cavity contained 250 ml of cloudy, amber fluid.
Laboratory Results: Serum biochemistry demonstrated a mildly elevated anion gap, a mildly elevated lactate and a moderately elevated creatine kinase.
Contributors Diagnosis and Comment: Steatitis, severe, diffuse, chronic-active, necrosuppurative with granulation tissue and intrahistiocytic ceroid, ventral abdominal subcutis and intra-abdominal fat, domestic shorthair, Felis domesticus, feline.
Steatitis, also known as pansteatitis, panniculitis or yellow fat disease, is a nutritional disorder which affects cats, swine, mink and fish-eating birds and which has been experimentally induced in rats and chickens by feeding a diet high in unsaturated fatty acids and deficient in vitamin E. The disease is seen rarely now in cats, since it was recognized that a diet of oily fish, especially red tuna, was the cause in most cases.
The high level of unsaturated fatty acids results in peroxidation of fatty acids with generation of free radicals in the relative absence of the natural antioxidant, vitamin E. This cell damage results in the deposition of ceroid pigment, a variant of lipofuscin, derived mostly from cell membranes. The lesions in this cat are typical, with adipocyte necrosis and multifocal clusters of necrotic and viable neutrophils.
Ceroid pigment is present as brown/gray globules, mostly within the cytoplasm of macrophages. Ceroid pigment stains acid-fast with Ziehl-Neelsen. Although none were seen in this case, multinucleated giant cells can be a feature. It is also interesting to note that from the few cases reported in the literature, elevated enzymes suggestive of muscle damage, including creatine kinase, have been documented, as in this case. Some authors have speculated that this may reflect skeletal muscle damage, similar to that associated with vitamin E deficiency in other species.
According to the history provided to us, this cat had been fed a proprietary canned cat food that was tuna-based. It was euthanized mainly due to financial constraints. Anecdotally, several other cats on the same commercial diet had been presented to our nutritionist with clinical symptoms indicative of steatitis. It is interesting to note that there have been rare reports of feline steatitis in which the diet was based on white fish and even one case where liver, chicken and beef, with only a very small amount of fish, was fed. In another report, the authors were unable to confirm the exact nature of the diet eaten by the cat.
AFIP Diagnosis: Haired skin and subcutis: Panniculitis, necrotizing, suppurative and histiocytic, diffuse, moderate, with focal intrahistiocytic yellow pigment, domestic shorthair cat, feline.
Conference Comment: Pansteatitis in cats presents clinically with discomfort and pain on handling, fever, decreased appetite, and lethargy. Mortality varies in the published literature. With removal of suspect foods from the diet, forced feeding, and administration of vitamin E and corticosteroids, full recovery is possible. However, cats left untreated or diagnosed late in the course of the disease often die. Grossly, the subcutaneous fat is firm, nodular, and yellow to brown due to ceroid pigment deposition. Histologically, the characteristic feature is fat necrosis with pyogranulomatous panniculitis.
Contributor: University of Pennsylvania School of Veterinary Medicine, Department of Pathobiology, 3800 Spruce Street, Philadelphia, PA 19104
1. Koutinas AF, Miller WH, Kritsepi M, Lekkas S: Pansteatitis (steatitis, yellow fat disease) in the cat: A review and report of four spontaneous cases. Vet Derm 3:101-106, 1993
2. Nichols DK, Campbell VL, Montali RJ: Pansteatitis in great blue herons. J Amer Vet Med Assoc 189:1110-1112, 1986
3. Tidholm A, Karlsson I, Wallius B: Feline Pansteatitis: A report of five cases. Acta Vet Scand 37:213-217, 1996.
CASE IV H99-2875 (AFIP 2737304)
Signalment: 12-year-old, castrated male, domestic shorthair cat, Felis cattus.
History: The cat was referred to Exclusively Dermatology for a multifocal, nodular and ulcerative dermatopathy of 3-4 weeks duration. The cat had been anorexic for 6 days and was systemically unwell and pyrexic (400C).
Gross Pathology: None given.
Laboratory Results: CBC: Severe lymphopenia
Biochemistry: Hypercalcemia, hypercholesterolemia, hyperglycemia, pre-renal azotemia, myopathy.
PCR for feline calicivirus, Chlamydia sp. & Neospora caninum: Negative
PCR for Toxoplasma gondii & feline herpesvirus-1: Positive
Witness Ô antibody detection kit (Agen) for feline immunodeficiency virus: Positive
Contributors Diagnosis and Comment: The submission was a 6mm skin biopsy of haired skin. There was mild, irregular epidermal hyperplasia accompanied by moderate, diffuse, spongiosis and multifocal epidermal necrosis. Multifocal intra-epidermal pustules were associated with multifocal, subepidermal vesicle and pustule formation. There was diffuse superficial dermal degeneration and necrosis associated with a moderate, perivascular to diffuse, mixed, predominately neutrophilic and plasmacytic, dermatitis and panniculitis. Extensive vascular degeneration and necrosis was evident within the dermis and there was pyogranulomatous thrombosis of deep dermo-hypodermal venules. Scattered throughout the dermis and hypodermis there were individual and aggregated intra-
and extracellular protozoal zoites measuring between 1-2 um diameter and 2-6 um length.
Morphologic Diagnosis: Severe, acute, diffuse, dermal vascular necrosis and hypodermal thrombosis with a subacute, diffuse, necrotizing, mixed neutrophilic and plasmacytic dermatitis containing intracytoplasmic and extracellular protozoal zoites: Toxoplasma gondii.
Cutaneous disease is an uncommon manifestation of clinical toxoplasmosis in both humans and cats. A review of 100 cases of clinical toxoplasmosis in cats identified only two cats with cutaneous toxoplasmosis. The reported incidence of cutaneous manifestations of toxoplasmosis in humans is also <10%. Toxoplasmosis in cats is usually characterized clinically by fever, dyspnea, polypnea, anorexia, lethargy and abdominal discomfort. The histological changes described in feline cutaneous toxoplasmosis are a toxoplasmic vasculitis and associated infarction.
Acute toxoplasmosis in humans is usually characterized by isolated, asymptomatic lymphadenopathy without a rash. Cutaneous manifestations of toxoplasmosis are variable with maculopapular, nodular, purpuric, papulopustular, lichenoid, vegetative or erythema-multiforme-like lesions described. Histologically, varied combinations of vasculitis, perivasculitis, necrosis, periadnexal inflammation, and rare granulomas have been described.
As in this case, persistent fever is a frequent finding with feline toxoplasmosis. The significance of the positive serological test for FIV with concurrent clinical toxoplasmosis is controversial. Lappin et al (1996 and 1992) found there was no difference between FIV-naive and FIV-infected cats in terms of clinical illness and duration of oocyst shedding following primary exposure with T. gondii. However, the parenteral administration of T. gondii to FIV-infected cats will induce severe, generalized toxoplasmosis, whereas FIV-negative cats only developed a mild transient disease. Non-congenital toxoplasmosis in humans occurs most commonly in immunocompromised patients suffering from either a neoplastic disorder, collagen vascular disease, organ allograft transplant, or HIV.
Felidae are the definitive hosts of T. gondii. Humans and animals become infected mainly by ingesting bradyzoites from infected meat or by sporulated oocysts from cat feces. The sexual cycle of T. gondii only occurs in the intestine of cats. Ingestion of sporulated oocysts or bradyzoites by humans and animals, including cats, will result in local multiplication in the intestine and lymph nodes before dissemination of tachyzoites to other organs and tissues where they may continue to reproduce asexually or encyst as bradyzoites.
AFIP Diagnosis: Haired skin: Dermatitis, necrotizing, subacute, diffuse, severe, with epidermal hyperplasia, sub-basilar clefts, epidermal degeneration and necrosis, and numerous intracellular and extracellular tachyzoites, domestic shorthair cat, feline.
Conference Comment: The contributor provided an excellent summary for this case. Retrospective studies show that the incidence of feline cutaneous toxoplasmosis is low. Research in humans, cats and other species shows that immunosuppression can profoundly influence the severity and clinical expression of infection with Toxoplasma.
Contributor: Murdoch University, Division of Veterinary and Biomedical Science, South Street, Western Australia 6150
References: 1. Dubey JP, Carpenter JL: Histologically confirmed clinical toxoplasmosis in cats: 100 cases (1952-1990). J Amer Vet Med Assoc 203:1556-1566, 1993
2. Davidson MG, Rottman JB, English RV, Lappin MR, Tompkins MB: Feline immunodeficiency virus predisposes cats to acute generalized toxoplasmosis. Am J Pathol 143:1486-1497, 1993
3. Lappin MR, Gasper PW, Rose BJ, Powell CC: Effect of primary phase feline immunodeficiency virus infection on cats with chronic toxoplasmosis. Vet Immunol Immunopathol 35:121-132, 1992
4. Lappin MR, George JW, Pedersen NC, Barlough JE, Murphy CJ, Morse LS: Primary and secondary Toxoplasma gondii infection in normal and feline immunodeficiency virus-infected cats. J Parasitol 82:733-742, 1996
5. Leyva WH, Santa Cruz DJ: Cutaneous toxoplasmosis. J Am Acad Dermatol 14:600-605, 1986
6. Mawhorter SD, Effron D, Blinkhorn R, Spagnuolo PJ: Cutaneous manifestations of toxoplasmosis. Clin Infect Dis 14:1084-1088, 1992
7. Muller N, Zimmerman V, Hentrich B, Gottstein B: Diagnosis of Neospora caninum and Toxoplasma gondii infection by PCR and DNA hybridization immunoassay. J Clin Microbiol 34:2850-2852, 1996
8. Pujol-Rique M, Derouin F, Garcia-Quintanilla A, Valls ME, Miro JM, Jimenez de Anta MT: Design of a one-tube hemi-nested PCR for detection of Toxoplasma gondii and comparison of three DNA purification methods. J Med Microbiol 48:857-862, 1999
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