Joint Pathology Center Veterinary Pathology Services WEDNESDAY SLIDE CONFERENCE 2013-2014 Conference 13 29 January 2014 CASE I: AVC C3670-13 (JPC 4032590). for 10-12 days and then stopped eating. Most recently, the dog developed diarrhea, non- Signalment: 10-year-old male castrated Shetland regenerative anemia and glucosuria. An Sheepdog (Canis familiaris). abdominal ultrasound revealed a severe and diffuse mottled appearance of the liver with a History: This dog was diagnosed with honeycomb pattern. Liver aspirates were taken dermatomyositis as a puppy; it had footpad for cytology assessment and the footpads were lesions characterized by hyperkeratosis, erythema, biopsied. The animal continued to deteriorate and scaling and crusting. The dog was treated first was euthanized at the owner’s request. The with novalexin and then prednisone; he did well veterinarian obtained permission to perform a postmortem examination. The liver was diffusely nodular; the rest of the abdominal viscera were unremarkable. Samples of liver and skin were submitted for histopathology. Gross Pathology: Two punch skin biopsies (0.7 cm in greatest diameter) with ulcerated surfaces and two fragments of liver (3.5 cm and 2.5 cm in their largest dimension) were submitted for histopathology. The liver samples had a nodular, irregular, capsular surface. Laboratory Results: Parameter Value Reference Interval Albumin 23 G/L 24-55 1-1. Haired skin, dog: This section of skin is covered by a thick parakeratotic serocellular crust (extending down into hair follicles), ALP 1632 U/L 20-150 with marked acanthosis and hyperplasia of basal epithelium. (HE 0.63X) 1 WSC 2013-2014 ALT 442 U/L 10-118 Glucose 9.2 mmol/L 3.3-6.1 WBC 19.1 x 103/ 6.0-17.0 mm3 segmented 94% lymphocytes 3% monocytes 2% bands 1% RBC 4.12 x 106/ 5.50-8.50 mm3 urine glucose 3+ 1-2. Haired skin, dog: Superficial necrolytic dermatitis exhibits what is known as the “red, white and blue sign”, with superficial hyperkeratosis Liver cytology performed approximately one (red arrow), marked spongiosis of the stratum spinosum (black arrow), week before euthanasia revealed cholestasis, low and marked hyperplasia of the basal layer (blue arrow). (HE 42X) numbers of attenuated and rarefied hepatocytes and possible neutrophilic inflammation. and covered with many layers of parakeratotic keratin admixed with multifocal dense aggregates Histopathologic Description: Two samples of necrotic cell debris and hemorrhage. There are taken from the edges of the metatarsal pad and foci of erosion with multiple foci of epidermal including the adjacent haired skin are examined. neutrophilic and lymphocytic infiltration. The epidermis is markedly, irregularly acanthotic Keratinocytes in the stratum spinosum are 1-3. Liver, dog: This section of liver contains numerous regenerative nodules of hepatocytes, which are easily seen against the pallor of remaining glycogen-distended hepatocytes. (HE 0.63X) 2 WSC 2013-2014 The liver sections s h o w e x t e n s i v e , interconnecting areas of parenchymal c o l l a p s e a n d h e p a t o c e l l u l a r vacuolation, usually s u r r o u n d i n g a n d isolating variably s i z e d n o d u l e s o f hepatocytes (nodular regeneration). The v a c u o l a t e d hepatocytes are often markedly enlarged with large amounts of clear to occasionally granular cytoplasm and peripheralized dense nuclei. The areas of vacuolar change also contain multifocal clusters of bile ducts and scant bundles of fibrous tissue. Small collections of band a n d s e g m e n t e d neutrophils (consistent 1-4. Liver, dog: Hepatocytes are swollen up to 5 times normal with numerous coalescing clear vacuoles (glycogen) surrounded by pale pink cytoplasmic strands (“spider cells”). Throughout the section there is marked ductular with extramedullary reaction (arrows). (HE 400X) myelopoiesis) and small numbers of markedly vacuolated, swollen and pale plasma cells and lipid-laden macrophages (intracellular edema) with plump nuclei. The infiltrate the portal spaces in these areas. Small stratum basale is markedly hyperplastic with aggregates of pigment (ceroid and/or iron)-laden numerous mitotic figures and increased nuclear to macrophages are often seen within the nodules of cytoplasmic ratio (in general, giving the epidermis parenchymal cells (pigment granulomas); scant a "red, white and blue" layered appearance). neutrophils and plasma cells also infiltrate these Occasional apoptotic bodies and migrating nodules. leukocytes are noted within the epidermis. Numerous bacterial colonies and 7 x 2 micron, Contributor’s Morphologic Diagnosis: 1. PAS positive, budding yeast (consistent with Haired skin, bilateral, metatarsal areas: Laminar Malassezia sp.) are present within the surface epidermal edema, degeneration and necrosis, keratin (not present in all slides). Multiple hair severe, with marked basal cell hyperplasia, follicles are dilated and filled with fragmented parakeratotic hyperkeratosis (ie. superficial keratin. Perifollicular, periadnexal and necrolytic dermatitis), and pustules/neutrophilic perivascular infiltrates of lymphocytes, plasma crusts containing bacterial colonies and budding cells, macrophages and neutrophils, often yeast (Malassezia sp.). associated with fibrous tissue, are present within 2. Liver: Hepatocellular vacuolar change the dermis. In rare instances, the infiltrates (vacuolar hepatopathy), severe, diffuse, with appear to invade the dermoepidermal junction. parenchymal collapse, moderate bile duct Gram staining of bacterial colonies reveals gram proliferation and nodular regeneration. positive cocci and gram negative rods. 3 WSC 2013-2014 mucocutaneous junctions, ears, periorbital region, and distal portions of the extremities. Probably the most common clinical dermatologic lesion is hyperkeratosis and deep fissuring of the footpads. Secondary skin infections with bacteria, yeasts, and dermatophytes are common. Pruritus and signs of pain are often apparent.2-4,9 Anorexia, weight loss and lethargy may also be present.3,4,9 Circulating liver enzyme activities are frequently high and plasma amino acid concentrations are severely low.2,7 Results of a study of 36 dogs with histologically confirmed SND indicated that older small-breed dogs (including Shetland Sheepdogs) were primarily affected. The median age was 10 years, and 27 (75%) dogs were male.7 Superficial necrolytic dermatitis has also been 1-5. Liver, dog: Scattered throughout the section are aggregates of 4 6 macrophages contain lipid and lipofuscin, resulting from rupture of reported in cats and captive black rhinoceroses. hepatocytes (lipogranulomas). (HE 400X) In skin sections, the histopathologic finding of Contributor’s Comment: The parakeratosis with crusting, hydropic histomorphologic appearance of the skin and liver degeneration of keratinocytes in the stratum samples are consistent with hepatocutaneous spinosum, and hyperplasia of the basal cell layer, syndrome (also called superficial necrolytic imparts the characteristic red, white, and blue dermatitis, metabolic epidermal necrosis, and appearance (referred to by some as the “French necrolytic erythema) with secondary pyoderma flag”) that is diagnostic for the disease.2 Livers of and cutaneous yeast infection. dogs with hepatocutaneous syndrome are grossly nodular. Histologically, there is severe Hepatocutaneous syndrome is a rare necrotizing vacuolation of hepatocytes, with parenchymal skin disorder of dogs that is most often associated collapse and condensation of the reticulin fiber with metabolic hepatic disease (often idiopathic network accompanied by nodular regeneration.8 vacuolar hepatopathy),2,8 although it has also been This combination of liver features has been described in diabetes mellitus, glucagon-secreting confused with hepatic cirrhosis by many authors. tumors (glucagonomas)2-4,9 and prolonged Ultrasonographic evaluation of the liver of phenobarbital administration.5 It is thought that affected dogs reveals an almost pathognomonic hepatic dysfunction may result in “honeycomb” pattern or Swiss cheese-like hypoaminoacidema, preventing essential amino appearance consisting of a hyperechoic network acids from reaching the skin, leading to surrounding hypoechoic areas of parenchyma.2,3 nutritional deprivation and subsequent necrosis. The underlying cause of these hepatic changes is The proposed pathogenesis involves increased often undetermined; however, they have been hepatic catabolism of amino acids (from increased suggested to support an underlying metabolic, gluconeogenesis),2,7 elevated glucagon levels (due hormonal, or toxic cause.3 The cause for the to decreased hepatic metabolism or glucagon– hepatopathy in this dog was not determined. secreting tumors), or disturbance of zinc metabolism (possibly a result of malabsorption).4,9 Hepatocutaneous syndrome in dogs often has a A report of superficial necrolytic dermatitis poor prognosis, and survival times are often less (SND) in dogs receiving phenobarbital suggested than one year. Treatment generally includes that drug induction of hepatic microsomal parenteral and oral administration of amino acids, enzymes may result in excessive utilization of zinc, and essential fatty acids.7 If the disease is amino acids by the liver leading to deficiency.5 caused by a glucagon-secreting pancreatic neoplasm, surgical removal of the neoplasm can Affected animals typically develop alopecia, lead to resolution of skin lesions.2 erythema, crusting, exudation, and ulceration of the skin. The lesions are generally distributed