Immunohistochemical characterization of canine hyperplastic hepatic lesions and hepatocellular and biliary neoplasms with monoclonal antibody hepatocyte paraffin 1 and a monoclonal antibody to cytokeratin 7.

Immunostaining with monoclonal antibody (MoAb) hepatocyte paraffin 1 (Hep Par 1) and an MoAb to cytokeratin 7 (CK7) was performed on 105 formalin-fixed, paraffin-embedded canine hyperplastic and neoplastic hepatic lesions. Hep Par 1 was detected in 12/12 hyperplastic nodules, 17/17 hepatocellular adenomas, and 37/40 hepatocellular carcinomas. The staining was disseminated, granular, and cytoplasmic. This antibody did not react with normal or neoplastic biliary epithelium. Other hepatic tumors or tumors metastatic to the liver did not bind Hep Par 1 except one metastatic intestinal carcinoma. MoAb to CK 7 stained all hyperplastic biliary epithelium and benign cholangiocellular tumors (5/5) and 14/18 cholangiocellular carcinomas. One hepatocellular carcinoma had cells positive for both Hep Par 1 and CK 7. Liver was the only normal tissue tested that reacted with MoAb Hep Par 1. Only five nonhepatic tumors (one adrenocortical carcinoma, one interstitial cell tumor of the testis, one melanoma, and two salivary adenocarcinomas) of 277 tumors tested had focal/multifocal staining for Hep Par 1. Prolonged fixation did not alter the staining with Hep Par 1. We conclude that Hep Par 1 is a specific and sensitive marker for canine hepatocellular tumors and allows distinction between hepatocellular and biliary neoplasms.     

Feline paraneoplastic alopecia

A 14-year-old neutered female cat was presented for a second opinion regarding hair loss, anorexia, and lethargy. Examination revealed alopecia of the ventral chest, abdomen, axilla, and groin. The footpads were encrusted. The liver was enlarged and nodular. Investigation revealed an enlarged liver with multiple nodules, and small and atrophic hair follicles. Paraneoplastic alopecia due to hepatocellular carcinoma was diagnosed and subsequently confirmed postmortem.     

A case of feline paraneoplastic alopecia with secondary Malossezia-associated dermatitis

A 13-year-old neutered female domestic shorthaired cat had progressive ventral abdominal alopecia attributed initially to hyperthyroidism. Corrective treatment by unilateral thyroidectomy did not, however, resolve the dermatosis and the alopecia progressed to involve the whole ventral trunk, the lower limbs and the head. Pruritus of the lower limbs was a prominent feature and was associated with the finding of Malassezia on cytology; Malassezia -associated dermatitis was diagnosed. Resolution of pruritus was seen after treatment with oral ketoconazole and a cleansing shampoo to eliminate the yeast, but severe polyphagia, small intestinal diarrhoea and polydipsia developed subsequently and the cat was euthanased. Necropsy revealed an exocrine pancreatic adenocarcinoma with hepatic metastases. The pancreatic, hepatic and dermatologlcal lesions were found to be typical of feline paraneoplastic alopecia (FPA). Malassezia -associated dermatitis can be associated with pruritus in cats with FPA.     

Resolution of paraneoplastic alopecia following surgical removal of a pancreatic carcinoma in a cat

A 13-year-old female neutered domestic longhaired cat was presented with a five-month history of progressive weight loss and bilaterally symmetrical alopecia of the ventrum, limbs and perineum. The alopecic skin had a shiny appearance and hair in the non-alopecic areas was easily epilated. Fine needle aspirate cytology of a palpable cranial abdominal mass revealed it to be of epithelial or glandular origin. A pancreatic mass was excised by left pancreatectomy during exploratory laparotomy, and histopathology and skin biopsies confirmed a diagnosis of pancreatic carcinoma with concurrent paraneoplastic alopecia. No evidence of metastases was found on liver and lymph node biopsies. At re-examination 10 weeks after surgery, the hair had fully regrown. Skin signs recurred after 18 weeks and metastatic spread of the tumour was confirmed on postmortem examination. This case confirms that paraneoplastic alopecia associated with internal malignancies is a potentially reversible process if the internal neoplasm is excised.     

Multiple endocrine neoplasia type-I-like syndrome in two cats

Multiple endocrine neoplasia (MEN) embodies a group of diseases in human patients and domestic animals that are characterized by hyperplasia or neoplasia, or both, of two or more endocrine tissues. The MEN-1 syndrome is associated with menin gene mutations that induce various combinations of parathyroid, pituitary, and pancreatic endocrine tumors in humans. Two male, Domestic Shorthair cats developed symmetric alopecia, insulin-resistant diabetes mellitus, and pituitary-dependent hyperadrenocorticism at 12 and 13 years of age. Examination of skin biopsy specimens revealed atrophic dermatosis associated with hyperadrenocorticism. In one cat, cutaneous lesions consistent with paraneoplastic alopecia associated with pancreatic adenocarcinoma also were evident. Multiple invasive pancreatic beta cell carcinomas, pituitary corticotroph adenomas, and thyroid C-cell and parathyroid chief cell hyperplasia were diagnosed on the basis of results of gross, histologic, and immunohistochemical findings in both cats. Pancreatic exocrine adenocarcinoma was diagnosed in both cats. One cat also had hepatocellular carcinoma. Exons 1-8 of the feline menin gene were sequenced and were found to bear 93% homology with the human gene sequence, and the corresponding amino acid sequences shared 98% homology. Purification of total RNA and amplification of cDNA from lesional tissues to document mutations in the feline menin gene sequence were unsuccessful. The combination of lesions observed was consistent with the diagnosis of MEN-1-like syndrome in both cats.     

Paraneoplastic alopecia associated with internal malignancies in the cat

Abstract A paraneoplastic alopecia associated with internal malignancy is reported in four cats. Acute, bilaterally symmetrical, ventral glistening alopecia, weight loss and lethargy were present in all cats. Skin biopsy specimens exhibited severe follicular and adnexal atrophy with follicular miniaturization, minimal inflammation and, in many cases, absence of stratum corneum. At the time of díagnosis, three cats had a metastatic pancreatic adenocarcinoma and one had a bile duct carcinoma. This report confirms, and expands upon the previous report of a syndrome associating ventral alopecia and metastatic visceral carcinomas in cats. Résumé— Une alopécie paranéoplasique associée à une tumeur interne maligne est observée sur 4 chats. Les symptômes sont caractérisés par une alopécie symétrique et bilatérale sur le ventre avec un aspect brillant et lisse, un amaigrissement, une lethargic Les lésions histopathologiques sont caractérisées par une atrophie folliculaire et annexielle avec des petits follicules pileux, une inflammation dermique discréte et dans beaucoup de cas, une absence du stratum corneum. Trois chats présentent un adénocarcinome pancréatique métastasé et un chat un cholangiocarcinome. Ces cas confirment l'existence d'un syndrome associant une alopécie ventrale et des carcinomes viscéraux métastatiques chez le chat. [Pascal-Tenorio, A., Olivry, T., Gross, T. L., Atlee, B. A., Ihrke, P. J. Paraneoplastic alopecia associated with internal malignancies in the cat. (Alopécie paranéoplasique associée à des tumeurs malignes internes chez le chat.) Veterinary Dermatology 1997; 8 : 47–52.] Resumen Se describe en cuatro gatos una alopecia paraneoplasica asociada a procesos malignos internos. Todos los gatos presentaban una alopecia bilateral, simétrica, ventral, de aspecto brillante, pérdida de peso y letargia. Las biopsias cutáneas mostraron atrofia folicular y adnexal marcada, miniaturización de foliculos, inflamación minima y, en muchos casos, ausencia del estrato córneo. En el momento del díagnóstico, tres de los gatos tenian un adenocarcinoma metastático y uno tenia un carcinoma de conducto biliar. Este articulo confirma y amplia un informe previo sobre el sindrome de alopecia ventral y carcinomas viscerales metastáticos en gatos. [Pascal-Tenorio, A., Olivry, T., Gross, T. L., Atlee, B. A., Ihrke, P. J. Paraneoplastic alopecia associated with internal malignancies in the cat. (Alopecia paraneoplasica asociada a procesos malignos internos en el gato.) Veterinary Dermatology 1997; 8 : 47–52.] Zusammenfassung— Es wird über eine paraneoplastische Alopezie in Verbindung mit inneren malignen Prozessen bei vier Katzen berichtet. Bei alien Katzen traten eine akute bilateral symmetrische ventrale Alopezie, Gewichtsverlust und Lethargie auf. Die Hautbiopsien zeigten eine schwere follikuläre und adnexale Atrophie mit follikulärer Miniaturisation, geringer Entzündung und in vielen Fallen ein Fehlen des Stratum corneum. Zum Zeitpunkt der Diagnose litten drei Katzen an einem metastasierenden Adenokarzinom des Pankreas und eine Katze an einem Gallengangskarzinom. Dieser Bericht erhärtet und erweitert den früheren Bericht über ein Syndrom, das ventrale Alopezie in Verbindung mit metastasierenden Eingeweidekarzinomen bei der Katze beschreibt. (Paraneoplastische Alopezie in Verbindung mit inneren malignen Prozessen bei der Katze.) Veterinary Dermatology 1997; 8 : 47–52.]     

Food hypersensitivity in a cat

Food hypersensitivity was diagnosed in a 4-year-old Siamese cat. Clinical signs included intense erythema, with alopecia, excoriations, erosions, and crusts involving the ventral portion of the abdomen, inguinal region, medial aspect of each thigh, and cranial and lateral aspects of all 4 limbs. The cat was intensely pruritic. Histologically, there was cutaneous mast cell hyperplasia and diffuse infiltration of eosinophils in the dermis. Blood eosinophilia also was found. Clinical signs resolved after exclusive feeding of a hypoallergenic diet.     

Feline lymphangiosarcoma--definitive identification using a lymphatic vascular marker

Abstract   Three cases of feline exudative dermatitis associated with lymphangiosarcoma are described. The animals, an 11-year-old, neutered male and two 10-year-old, neutered female short hair European cats, presented with a 2-month history of transparent liquid oozing from the skin of the groin and caudal abdomen. On physical examination the neutered male cat and one of the females were slightly depressed and showed loss of weight. Skin lesions were similar in all cats and characterized by the presence of alopecia and moist dermatitis in the ventral abdomen, groin and inner thigh. The hair at the periphery appeared matted by the fluid. In all three cases, histopathological examination of skin biopsies from the abdomen identified poorly defined neoplasia involving dermis and subcutis, characterized by proliferation of spindle cells aligned along pre-existing collagen bundles. The dissection of collagen bundles gave rise to irregular shaped anastomosing, often blind-ending vascular channels and trabeculae. Vascular spaces were mostly optically empty. These histological features were strongly suggestive of lymphangiosarcoma. Neoplastic cells were positive for the blood vascular marker Von Willebrand factor, and a lymphatic vascular marker LYVE-1 (Lymphatic Vessel Endothelial receptor – 1), demonstrating the mixed vascular origin of the tumour. Ultrastructural findings confirmed the final diagnosis of lymphangiosarcoma.     

Feline paraneoplastic syndrome associated with thymoma

CASE HISTORY: A 6-year-old, spayed, female, domestic short-haired cat presented with severe erythroderma and scaling skin. She showed disturbed gait and mild behavioural changes. CLINICAL FINDINGS: The cat had a generalised, erythematous, scurfy dermatitis with marked, multifocal crusting and skin thickening. The skin was painful and contracted, which appeared to prevent normal freedom of movement. DIAGNOSIS: The cat was suspected to have a paraneoplastic syndrome. A mediastinal mass was located and histologically confirmed as thymoma. The cat was diagnosed with a thymoma- associated cutaneous paraneoplastic syndrome. CLINICAL RELEVANCE: This is a rare condition with few reports in the literature. The skin changes, both grossly and histologically, were considered to be different from those described in cases of paraneoplastic dermatosis associated with pancreatic neoplasia. The clinical presentation was characteristic and more cases may occur in practice than are recognised. In this case, as in previous reports, the tumour was grossly resectable, which could lead to cure of the clinical condition.     

Progesterone secreting adrenal mass in a cat with clinical signs of hyperadrenocorticism

A 7-year-old 7-kg (16-lb) neutered male Himalayan cat had nonpruritic progressive alopecia of 9 months' duration. The cat had hyperglycemia and glucosuria. Physical examination revealed complete alopecia along the abdomen, inguinal area, medial and caudal areas of the thighs, ventral area of the thorax, and axilla. Clinical signs were consistent with endocrine-induced alopecia and hyperadrenocorticism, however, results of diagnostic tests (ACTH stimulation and low-dose dexamethasone suppression) were not supportive of hyperadrenocorticism. Abdominal ultrasonography revealed a mass cranial to the left kidney. Blood samples were obtained before and after ACTH stimulation to measure sex hormone concentrations. Analysis revealed markedly high blood progesterone concentrations before and after ACTH stimulation. An adrenalectomy was performed and histologic examination of the mass revealed a well-differentiated adrenocortical carcinoma. The right adrenal gland could not be viewed during surgery and was assumed to be atrophic. Following surgery, the hyperglycemia and glucosuria resolved. Within 4 months of surgery, the hyperprogesteronemia had resolved, and at 12 months the cat's coat quality appeared normal. Findings suggest that cats with signs of hyperadrenocorticism should be evaluated not only for abnormal cortisol concentrations, but also for sex hormone abnormalities.     

Retrospective study: the presence of Malassezia in feline skin biopsies. A clinicopathological study

Malassezia spp. dermatitis, a rare disorder in cats, has previously been associated with immune suppression and internal malignancies. This study evaluates the presence and importance of Malassezia spp. in feline biopsy specimens submitted for histopathological examination. Five hundred and fifty haematoxylin and eosin-stained skin biopsy specimens received for histopathological examination between January 1999 and November 2000 were reviewed. Fifteen (2.7%) submissions contained Malassezia organisms in the stratum corneum of the epidermis or follicular infundibulum. Eleven of 15 cats presented with an acute onset of multifocal to generalized skin lesions. All 11 cats were euthanized or died within 2 months of the onset of clinical signs. Seven cats had dermatopathological changes and clinical signs supportive of paraneoplastic alopecia, and three cats had an interface dermatitis suggestive of erythema multiforme or thymoma-associated dermatosis. Histopathological changes were nonspecific in one cat that was euthanized 2 weeks following onset of severe pruritus and alopecia. In three cats, Malassezia spp. were found in localized sites (two chin, one footpads) and appeared inconsequential to their overall health status. One cat had Malassezia spp. in association with cutaneous demodicosis. These findings suggest that Malassezia yeast in dermatopathological specimens from multifocal or generalized lesions should prompt a thorough clinical work-up for internal neoplasia.     

Parathyroid adenocarcinoma in a nephropathic Persian cat

This report describes an uncommon clinical case of cystic parathyroid adenocarcinoma. A 17-year-old male Persian cat was presented for evaluation of a ventral cervical mass. The cat was inappetent and showed weight loss, polydipsia and vomiting. Serum biochemistry and urinalysis revealed moderate hypercalcaemia, a mild increase of creatinine, isosthenuria and proteinuria. Sodium dodecyl sulphate-agarose gel electrophoresis showed a mixed tubular proteinuric pattern, in accordance with histological examination that revealed interstitial nephritis and glomerulonephritis. Diagnosis of parathyroid carcinoma was based on histopathological findings.     

Feline paraneoplastic syndrome associated with thymoma

CASE HISTORY: A 6-year-old, spayed, female, domestic short-haired cat presented with severe erythroderma and scaling skin. She showed disturbed gait and mild behavioural changes.

CLINICAL FINDINGS: The cat had a generalised, erythematous, scurfy dermatitis with marked, multifocal crusting and skin thickening. The skin was painful and contracted, which appeared to prevent normal freedom of movement.

DIAGNOSIS: The cat was suspected to have a paraneoplastic syndrome. A mediastinal mass was located and histologically confirmed as thymoma. The cat was diagnosed with a thymoma-associated cutaneous paraneoplastic syndrome.

CLINICAL RELEVANCE: This is a rare condition with few reports in the literature. The skin changes, both grossly and histologically, were considered to be different from those described in cases of paraneoplastic dermatosis associated with pancreatic neoplasia. The clinical presentation was characteristic and more cases may occur in practice than are recognised. In this case, as in previous reports, the tumour was grossly resectable, which could lead to cure of the clinical condition.     

Anti‐isthmus autoimmunity in a novel feline acquired alopecia resembling pseudopelade of humans*

Pseudopelade is a primary scarring (cicatricial) alopecia of humans characterized by lymphocyte‐rich inflammation centred around the hair follicle isthmus. Lymphocyte folliculotropism is associated with isthmus apoptosis and, ultimately, follicular destruction and dermal fibrosis. In a cat, an acquired alopecia was diagnosed as pseudopelade based on the following criteria: (i) an adult‐onset, patchy to diffuse nonpruritic hair loss; (ii) an early folliculo‐destructive phase in which lymphocytes and dendritic cells accumulated in and around the follicular isthmus; and (iii) a late stage in which the lower segments of hair follicles underwent atrophy and were replaced by fibrosing tracts. Additionally, immunological investigations characterized the cytotoxic phenotype of isthmotropic lymphocytes and demonstrated the presence of circulating IgG autoantibodies specific for multiple follicular antigens. Altogether, the results of the present study suggest an immune‐mediated pathogenesis for this case of feline pseudopelade, similarly to that causing alopecia areata in humans and other mammalian species.     

Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature

Cutaneous paraneoplastic syndromes are a group of noncancerous dermatoses associated with internal malignancy. Their recognition can facilitate detection and timely treatment of underlying cancer. More than 30 such disorders have been identified in the human scientific literature, whereas only a few are described in veterinary medicine. This may reflect a lower incidence in animals than in people or may be the result of failure to recognize an association between certain skin lesions and neoplasia. Establishing a relationship between a cutaneous disorder and neoplasia can be difficult unless the skin lesions are rare and almost always associated with a particular tumour type, as is the case for most recognized veterinary paraneoplastic dermatoses. Among these are feline paraneoplastic alopecia, feline thymoma-associated exfoliative dermatitis, nodular dermatofibrosis, feminization syndrome associated with testicular tumours, superficial necrolytic dermatitis and paraneoplastic pemphigus. The aetiology of most cutaneous paraneoplastic syndromes has remained elusive in both people and animals.     

Hypospadias in a Himalayan cat

A one-year-old male Himalayan cat was presented with a history of chronic cystitis. Physical examination revealed that the cat had hypospadias. It was postulated that the abnormal urethral opening on the ventral aspect of the penis permitted faecal contamination of the preputial area and gave rise to the ascending infection. The hypospadias was surgically corrected and a complete recovery was achieved.     

Dermatosis and associated systemic signs in a cat with thymoma and recently treated with an imidacloprid preparation

A cat was presented with acute-onset exfoliative erythroderma and gross and histopathological lesions of erythema multiforme. Marked cardiovascular abnormalities including heart failure occurred concurrently and a dermatogenic enteropathy was also seen. Medical treatment resolved the dermatopathy and enteropathy but the heart failure progressed. A drug reaction was initially suspected to be the underlying cause with no neoplasia being detected, but repeat radiographs subsequently revealed a thymoma which had not been visible on the initial radiographs. The dermatopathy may have been a paraneoplastic disease associated with thymoma and, possibly, exacerbated by a drug reaction to imidacloprid. The cardiovascular and gastroenterological diseases were thought to be systemic effects associated with the exfoliative erythroderma. The thymoma was surgically removed but the cat subsequently died from heart failure.     

Growth hormone responsive dermatosis in three dogs

Growth hormone responsive dermatosis was diagnosed in three dogs. Each dog showed truncal hair loss, and two animals also had alopecia of the ventral neck, tail and thighs. The diagnosis in two cases was made by eliminating other causes of hormonal alopecia and demonstrating little increase in plasma growth hormone concentration after the intravenous administration of xylazine. All three dogs responded favourably to the subcutaneous administration of recombinant human somatotropin.     

Growth hormone responsive dermatosis in three dogs

Growth hormone responsive dermatosis was diagnosed in three dogs. Each dog showed truncal hair loss, and two animals also had alopecia of the ventral neck, tail and thighs. The diagnosis in two cases was made by eliminating other causes of hormonal alopecia and demonstrating little increase in plasma growth hormone concentration after the intravenous administration of xylazine. All three dogs responded favourably to the subcutaneous administration of recombinant human somatotropin.