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Cutaneous mastocytosis (CM) is a rare condition in young dogs characterized by multicentric cutaneous proliferation of neoplastic mast cells. Clinical data from 8 dogs that met inclusion criteria (age of onset less than 1.5 years, greater than 3 lesions) were obtained via a standardized survey. Biopsy samples were classified by the Kiupel/Patnaik grading systems and analyzed for c-KIT mutations. The median age of onset was 6 months (range: 2-17 months). Dogs had 5 to more than 50 lesions characterized as nodules, plaques, and papules. Seven dogs were pruritic. Clinical staging in 2 dogs did not reveal visceral involvement. No dogs had systemic illnesses at diagnosis. Histologically, CM was similar to cutaneous mast cell tumor (cMCT). Two dogs had neoplasms classified as high-grade/grade II while 6 dogs had low-grade/grade II neoplasms. No dogs had mutations in c-KIT exons 8 and 11. Treatment included antihistamines (8/8), corticosteroids (7/8), lokivetmab (3/8), and toceranib (1/8). Six dogs were alive with lesions at the end of the study with a median follow-up time of 898 days, while 2 dogs were euthanized. In dogs with high-grade/grade II neoplasms, one continued to develop lesions at 1922 days post-diagnosis, while the other dog was euthanized at 56 days post-diagnosis. One dog was euthanized 621 days post-diagnosis due to rupture of a neoplasm. CM occurs in young dogs and is histologically indistinguishable from cMCT. Current histologic grading systems did not apply uniformly to the dogs of the study and further studies are needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Allergic dermatoses are common in people and domestic animals. Resultant lesions are routinely biopsied and submitted for histological examination to confirm a diagnosis or rule out diseases with overlapping or atypical clinical features. Diagnostic pathologists and clinicians are often faced with the difficult task of determining whether an allergic reaction pattern is present on both the microscopic and macroscopic levels and correlating histopathologic findings with clinical and historical data to achieve a precise clinical diagnosis. The bulk of the current veterinary literature on allergic dermatoses focuses on atopic dermatitis in dogs, distantly followed by cats, horses, and other animals. The objectives of this review are to demonstrate the key histopathologic and clinical diagnostic features of the various allergy-mediated reaction patterns, and to provide diagnosticians with a practical guide for clinicopathological correlations. Current concepts in the pathophysiology of immediate hypersensitivity reactions, with a focus on atopic dermatitis, are discussed. Points of potential histopathologic overlap between the "classic" allergic reaction pattern and less common inflammatory, predominately eosinophilic, conditions that may mimic this pattern will be discussed with the goal of highlighting the critical need for collaboration between pathologists and clinicians in furthering patient care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.O.M. provides consultation services and has received research support from Stallergenes Greer Laboratories, North Carolina, USA.

Canine cutaneous epitheliotropic T-cell lymphoma is a neoplasm with heterogeneous clinical and histopathological presentations. Survival times and responses to therapy are variable, and indicators to predict outcomes are lacking. Clinical and histopathological parameters from 176 archival cases from the University of Pennsylvania and University of Bern (2012-2018) were investigated for associations with clinical outcomes. Histopathological evaluation used digitized whole slide images and QuPath software. Cases included 107 female and 69 male dogs from 48 breeds, with a mean age of 10.4 years. Most common clinical signs were erythema ( n = 131), crusting ( n = 108), and scaling ( n = 102). Affected sites were haired skin ( n = 159), lip ( n = 74), nasal planum ( n = 49), and paw pads ( n = 48). The median survival time (MST) was 95 days (1-850). Dogs had 4.26-fold and 2.82-fold longer MST when treated with chemotherapy and prednisone, respectively, than when receiving supportive care. Haired skin involvement (hazard ratio [HR]: 2.039, 95% confidence interval [CI]: 1.180-3.523), erosions/ulcers (HR: 1.871, 95% CI: 1.373-2.548), nodules (HR: 1.496, 95% CI: 1.056-2.118), and crusting (HR: 1.454, 95% CI: 1.061-1.994) were clinical parameters predicting poor outcomes, whereas complete posttherapeutic clinical remission (HR: 0.469, 95% CI: 0.324-0.680) and a stable disease (HR: 0.323, 95% CI: 0.229-0.456) were associated with longer survival. Histopathological features associated with the increased risk of death were extensive infiltration of the panniculus (HR: 2.865, 95% CI: 1.565-4.809), mitotic count ≥7/high-power field (HR: 3.027, 95% CI: 2.065-4.439), cell diameter ≥10.0 µm (HR: 2.078, 95% CI: 1.281-3.372), and nuclear diameter ≥8.3 µm (HR: 3.787, 95% CI: 1.647-8.707).

Palisading granulomatous dermatitis and panniculitis is recognized in various cutaneous inflammatory lesions secondary to presumed collagen damage. Cutaneous nodules with a palisading arrangement of histiocytes surrounding foci of collagen degeneration have been clinically termed palisading granuloma in dogs. Study aims were to characterize the cellular infiltrate of canine palisading granuloma and document salient clinical features. Inclusion criteria were met for 36 dogs and encompassed nodular dermal and subcutaneous histiocyte-predominant cellular infiltrates targeting and enveloping collagen fibers/necrotic foci with palisading configurations. Infectious causes were ruled out via standard histochemical stains and/or clinical data. Medical records were reviewed for signalment, clinical features, treatment, outcome, and comorbidities. Immunohistochemistry (IBA1, CD204, E-cadherin) and Masson's trichrome stain were used to assess histiocytic populations and dermal collagen, respectively. The histiocytes had moderate or strong immunolabeling for IBA1 and CD204 in 36/36 dogs (100%) and mild positive immunolabeling for E-cadherin in 3/36 dogs (8%). Alteration of collagen was graded as moderate or strong in 32/36 dogs (89%) and mild in 3/36 dogs (8%). Large breeds predominated with 30/36 dogs (83%) being ≥23 kg. Focal nodules were identified in 31/36 dogs (86%). The head/face were involved in 19/36 dogs (53%) and the extremities in 18/36 dogs (50%). Lesions from the 5/36 dogs (14%) with multiple nodules contained prominent eosinophilic infiltrates. Following excision, there was no evidence of recurrence. In conclusion, palisading granulomas are a distinct, non-neoplastic, histiocyte-predominant inflammatory condition in dogs associated with altered dermal collagen and favorable prognosis.

A minority of patients with nonsyndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in NIPAL4 (ICHTHYIN). This protein plays a role in epidermal lipid metabolism, although the mechanism is unknown. The study describes a moderate form of ARCI in an extended pedigree of American Bulldogs that is linked to the gene encoding ichthyin. The gross phenotype was manifest as a disheveled pelage shortly after birth, generalized scaling, and adherent brown scale with erythema of the abdominal skin. Pedigree analysis indicated an autosomal recessive mode of inheritance. Ultrastructurally, the epidermis showed discontinuous lipid bilayers, unprocessed lipid within corneocytes, and abnormal lamellar bodies. Linkage analysis, performed by choosing simple sequence repeat markers and single-nucleotide polymorphisms near genes known to cause ACRI, revealed an association with NIPAL4. NIPAL4 was identified and sequenced using standard methods. No mutation was identified within the gene, but affected dogs had a SINE element 5' upstream of exon 1 in a highly conserved region. Of 545 DNA samples from American Bulldogs, 32 dogs (17 females, 15 males) were homozygous for the polymerase chain reaction fragment. All affected dogs were homozygous, with parents heterozygous for the insertion. Immunolabeling revealed an absence of ichthyin in the epidermis. This is the first description of ARCI associated with decreased expression of NIPAL4 in nonhuman species., (© The Author(s) 2014.)

A scaling disorder specific to Golden Retriever dogs has been recognized by both dermatologists and pathologists, but to date has not been well characterized. At the University of Pennsylvania's Laboratory of Toxicology and Pathology, 46 cases of ichthyosis were diagnosed histologically in Golden Retriever dogs from January 2004 to January 2007. A total of 22 dogs had skin lesions documented at younger than 1 year of age; 3 dogs between 1 and 2 years of age; 13 dogs developed lesions at older than 2 years; and the time of onset was unknown for 8 dogs. A total of 25 dogs were female, and 21 were male. All dogs had strikingly similar histopathologic changes that consisted of mild to moderate laminar orthokeratotic hyperkeratosis with an absence of epidermal hyperplasia and dermal inflammation. Ultrastructural analysis using a ruthenium tetroxide fixation method was performed on punch biopsy samples from 5 dogs and compared with 2 control dogs (1 clinically and histologically normal sibling of an affected dog and 1 Cairn Terrier). All affected dogs had retained and convoluted membranes with crystalline structures in the stratum corneum. Scattered keratinocytes in the granular cell layer had prominent, clear, membrane-bound, cytoplasmic vacuoles. Pedigree analysis of 14 dogs was compatible with autosomal recessive inheritance, but incomplete dominance could not be ruled out. This unique hyperkeratotic/scaling disorder in Golden Retrievers has distinctive clinical, histologic, and ultrastructural features, which are consistent with a primary cornification defect.

Over a 16-year period, 190 tumors and tumorlike lesions from 179 pet rabbits were submitted for histopathologic examination. A total of 23 different tumor types and 1 tumorlike lesion were diagnosed. The most common diagnoses were trichoblastoma, collagenous hamartoma, and Shope fibroma. Viral-induced tumors were Shope fibroma (19) and Shope papilloma (2). Common nonviral epithelial tumors included trichoblastoma (59), squamous cell carcinoma (5), squamous papilloma (4), trichoepithelioma (3), and apocrine carcinoma (3). Common mesenchymal tumors were lipoma (10), liposarcoma (3), myxosarcoma (9), malignant peripheral nerve sheath tumor (8), fibrosarcoma (7), and leiomyosarcoma (4). Malignant melanoma was diagnosed in 8 rabbits. Collagenous hamartomas were diagnosed in 26 rabbits. Mesenchymal proliferations occurred significantly more often in male rabbits than in females. Collagenous hamartomas and myxosarcomas occurred exclusively in male animals, and 3 rabbits had multiple collagenous hamartomas. Immunohistochemistry was applied in cases in which a definite diagnosis could not be reached on hematoxylin and eosin slides. Follow-up information was received in 19 cases. Carcinomas recurred (2 of 3) or metastasized (1 of 3), whereas sarcomas frequently recurred (7 of 12). One malignant melanoma (1 of 3) and one poorly differentiated round cell neoplasm recurred (1 of 1). This is the first comprehensive retrospective analysis on skin neoplasia in pet rabbits.