Proliferative, lymphocytic, infundibular mural folliculitis and dermatitis with prominent follicular apoptosis and parakeratotic casts in a Labrador retriever: Clinical, histopathological and dermoscopic features and co-morbidities.

Proliferative, lymphocytic, infundibular mural folliculitis and dermatitis have been reported in six female Labrador retrievers from North America. This is the first report of the disease outside North America, describing the clinical and histopathological diagnosis and dermoscopic aspect of the verrucous plaques, treatment and co-morbidities in a female Labrador retriever dog.

La folliculite et la dermatite murale infundibulaire proliférative, lymphocytaire ont été rapportées chez six Labrador retrievers femelles d'Amérique du Nord. Il s'agit du premier rapport de cette affection en dehors de l'Amérique du Nord, décrivant le diagnostic clinique et histopathologique, l'aspect dermatoscopique des plaques verruqueuses, le traitement et les comorbidités chez une femelle Labrador retriever.

A foliculite e dermatite mural linfocítica infundibular proliferativa tem sido relatada em seis cadelas Labrador retriever da América do Norte. Este é o primeiro relato da doença fora da América do Norte, descrevendo o diagnóstico clínico e histopatológico e o aspecto dermoscópico de placas verrucosas, tratamento de comorbidades em uma cadela Labrador retriever.

Se ha publicado la descripción de una foliculitis y dermatitis mural infundibular, linfocítica y proliferativa en seis hembras de Labrador Retriever de América del Norte. Este es el primer informe de la enfermedad fuera de América del Norte, que describe el diagnóstico clínico e histopatológico y el aspecto dermatoscópico de las placas verrugosas, el tratamiento y las comorbilidades en una perra Labrador Retriever.

Dermoscopic findings and comparison of usefulness of longitudinal versus transversal sections in the histological diagnosis of alopecia X.

BACKGROUND: A combination of dermoscopic and histological findings may provide useful information for the diagnosis of hair follicle diseases. However, there are no studies on dermoscopic-histopathological correlations in dogs affected by alopecia X, and comparison of longitudinal versus transversal sectioning of skin biopsy specimens in the assessment of this hair loss disorder has not been thoroughly investigated. HYPOTHESIS/OBJECTIVES: The aim of this study was to correlate dermoscopic and histological features using both longitudinal and transversal sectioning of skin biopsy samples to gain additional information for the diagnosis of alopecia X. ANIMALS: Nineteen Pomeranian dogs affected by alopecia X and five healthy Pomeranians as controls. MATERIALS AND METHODS: Dermoscopic-histological correlation was performed within the diseased group, whereas histological comparisons against controls. The demographic and clinical characteristics also were related to the histological findings. RESULTS: The dermoscopic findings revealed scattered, thinned, short hairs mixed with amorphous keratoseborrhoeic-like material (follicular plugging), perifollicular and intrafollicular scaling, and hyperpigmentation varying from pinpoint black spots to a diffuse texture. Dermoscopic findings correlated with histological findings for selected qualitative and quantitative findings. The usefulness of transversal sections was demonstrated in accurately determining the hair follicular density and counts, growth arrest phases and in identifying mineralisation of hair follicle basement membrane when compared to the longitudinal. Conversely, no correlations between histological findings and demographic and clinical characteristics were detected. CONCLUSIONS AND CLINICAL RELEVANCE: These data provide evidence of the usefulness of dermoscopic evaluation as an accessory diagnostic tool and of transversal sections of skin biopsies as complementary to the diagnosis of alopecia X.

Subcutaneous panniculitis-like T-cell lymphoma: Morphological, immunophenotypical and clonality assessment in six cats.

BACKGROUND: Primary cutaneous lymphoma represents 0.2%-3% of all feline lymphomas, with nonepitheliotropic lymphomas being the most common. In humans and dogs, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a primary nonepitheliotropic lymphoma with a T-cell phenotype developing in the subcutis and often mimicking inflammation. OBJECTIVE: The aim of this report is to describe pathological, phenotypical and clonal features of SPTCL in cats. ANIMALS: Six cats with SPTCL were included in this study. MATERIALS AND METHODS: Skin biopsies were formalin-fixed, routinely processed and stained. Histological and immunohistochemical investigation for anti-CD18, CD204, CD79a, CD20, CD3, FeLVp27and FeLVgp70 and clonality assessment were performed. RESULTS: Four male and two female domestic shorthair cats, mean age 11.2 years, developed SPTCL in the abdominal (three), inguinal (two) and thoracic (one) regions. Variably pleomorphic neoplastic lymphoid cells were present in the panniculus in percentages, expanding the septa (six of six) and extending into fat lobules in one of six cats. Tumours were associated with elevated numbers of neutrophils (five of six), lesser macrophages (six of six) and variable necrosis (six of six). Neoplastic cells expressed CD3+ (six of six), with clonal T-cell receptor rearrangement detected in five of six cats. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first description of SPTCL in cats. Lesions can be confused with panniculitis, leading to delay in diagnosis and therapy. Awareness of this neoplastic disease is relevant to avoid misdiagnoses and to gain greater knowledge about the disease in cats.

Splenic stromal sarcomas in dogs: Outcome and clinicopathological prognostic factors in 32 cases.

Due to the low frequency and the changes in diagnostic techniques and terminology during the last few years, only little clinical information is available on splenic stromal sarcoma (SSS). This multi-institutional study aimed at gathering clinical cases of SSS in dogs and investigates their clinical behaviour, as well as analyse possible clinicopathological prognostic factors, including the use of adjuvant therapy. Dogs with a histologically confirmed SSS that underwent splenectomy were retrospectively included. To be included in the study, either FFPE tissue blocks or multiple tissue sections had to be available for histopathologic and immunohistochemical revision. Clinical and pathological variables, along with adjuvant therapy data, were collected. Cumulative incidence of metastatic disease was analysed through univariate and bivariate analyses. The impact of adjuvant chemotherapy on metastasis incidence and survival was assessed, considering an estimated propensity score. A total of 32 dogs were included. Among them, 22 developed metastases with an incidence of 37.5%, 59.38%, and 65.94% at 6, 12, and 24 months, respectively. Univariate analysis identified mitotic count, total scoring, and necrosis as prognostic factors. In bivariate analysis, mitotic count remained prognostic. The administration of adjuvant chemotherapy did not have an impact on metastasis incidence or survival time. The study found that dogs with SSSs are at high risk of metastasis, although a small subgroup may experience longer survival after splenectomy. Mitotic count was the only variable having a reliable prognostic impact. Adjuvant chemotherapy did not appear to decrease the incidence of metastasis or prolong survival in these dogs.

Dermoscopic features of benign sebaceous proliferations in dogs: Description, assessment and inter-observer agreement.

BACKGROUND: Dermoscopy is a useful, noninvasive technique also used to assess sebaceous lesions in humans. Sebaceous hyperplasia, sebaceous adenoma and sebaceous epithelioma are common cutaneous lesions in dogs; however, their dermoscopic features have not been investigated. HYPOTHESIS/OBJECTIVES: The objectives of this study are to describe the dermoscopic features of canine sebaceous lesions and to assess the interobserver agreement on dermoscopic parameters. ANIMALS: Thirty-four lesions excised from 17 client-owned dogs, histologically confirmed as sebaceous proliferations, were included in this study. MATERIALS AND METHODS: Sebaceous lesions were evaluated in vivo at ×10 magnification with a handheld dermoscope. Each dermoscopic image was assessed independently by two ECVD board-certified veterinary referral clinicians and an ECVD resident. RESULTS: Thirty sebaceous hyperplasias, two sebaceous adenomas and two sebaceous epitheliomas were included. Dermoscopically, most lesions (91%) had single or multiple, well-defined, white-yellowish structures composed of grouped ovoid areas (clods). Irregular linear and, less commonly, arborising vessels were detected at the periphery of the yellow lobular-like structures in 93% of sebaceous hyperplasias and in 50% of neoplastic lesions. Erosions were seen in 6% of sebaceous hyperplasias and 50% of neoplastic lesions. Good interobserver agreement was found for white/yellowish clods (k = 0.75), yellow scales (k = 0.83), brown/grey dots (k = 0.80), erosions (k = 0.82) and red/brownish scales/crusts (k = 0.75). There was moderate agreement for fissures (k = 0.48) and vascular pattern (k = 0.51-0.53). CONCLUSIONS AND CLINICAL RELEVANCE: Dermoscopy represents a useful technique to assess sebaceous gland proliferations in dogs, as it is in humans.

Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats.

Obesity is an epidemic condition linked to cardiovascular disease severity and mortality. Fat localization and type represent cardiovascular risk estimators. Importantly, visceral fat secretes adipokines known to promote low-grade inflammation that, in turn, modulate its secretome and cardiac metabolism. In this regard, IL-33 regulates the functions of various immune cells through ST2 binding and-following its role as an immune sensor to infection and stress-is involved in the pro-fibrotic remodeling of the myocardium. Here we further investigated the IL-33/ST2 effects on cardiac remodeling in obesity, focusing on molecular pathways linking adipose-derived IL-33 to the development of fibrosis or hypertrophy. We analyzed the Zucker Fatty rat model, and we developed in vitro models to mimic the adipose and myocardial relationship. We demonstrated a dysregulation of IL-33/ST2 signaling in both adipose and cardiac tissue, where they affected Epac proteins and myocardial gene expression, linked to pro-fibrotic signatures. In Zucker rats, pro-fibrotic effects were counteracted by ghrelin-induced IL-33 secretion, whose release influenced transcription factor expression and ST2 isoforms balance regulation. Finally, the effect of IL-33 signaling is dependent on several factors, such as cell types' origin and the balancing of ST2 isoforms. Noteworthy, it is reasonable to state that considering IL-33 to have a unique protective role should be considered over-simplistic.

Primary intranasal perivascular wall tumors in 2 cats.

Perivascular wall tumors (PWTs) are common well-known canine mesenchymal tumors. The term PWT has not yet been applied to cats; only 2 cases of feline soft tissue hemangiopericytomas (HEPs) are available. In human medicine, sinonasal HEP-like tumor/glomangiopericytoma (SHPCL/GP) and intranasal solitary fibrous tumor (SFT) are well-known mesenchymal tumors with staghorn vasculature and low malignant potential; however, these entities have not been described in small animals. We describe here the pathologic and immunohistochemical features of 2 cases of feline intranasal mesenchymal tumors consistent with PWTs and resembling human SHPCL/GP (case 1), and human intranasal SFT (case 2). Both cats developed intranasal, unilateral, polypoid, expansile neoplasms with a mostly patternless growth of spindle cells, minimal stroma, and prominent staghorn vessels. The stroma was PAS negative, which excludes a glomus tumor. Immunohistochemistry identified diffuse vimentin and PDGFRß expression. Case 1 was α-SMA positive (as is human SHPCL/GP); case 2 was negative (as is human intranasal SFT). Both tumors were incompletely excised, leading to recurrence in case 1. Case 2 was lost to follow up. To our knowledge, intranasal PWTs have not been reported previously in cats. The frequency of the lesions is not known, but awareness of these entities may assist in their recognition and better characterization in the future.

Identification of Histopathological Criteria for the Diagnosis of Canine Cutaneous Progressive Angiomatosis.

The term angiomatosis is used to denote a group of well-known to poorly characterized proliferative vascular entities. In animals, cutaneous progressive angiomatosis (CPA) is a disorder with variable prognosis related to the extension and depth of infiltration of the surrounding tissues by vessels. CPA may share some microscopical features with other vascular proliferations such as low-grade well-differentiated capillaritic hemangiosarcoma (HS), making the diagnosis not always straightforward, especially in small biopsies. The aim of this study is to retrospectively assess the most common diagnostic microscopical features of CPA in dogs. In this work, 11 histopathological criteria were analyzed on 31 CPA and 11 primary cutaneous HS in dogs. Features significantly associated with CPA included: lobular growth, interposition of connective tissue and adnexa between the vascular proliferation, presence of nerve fibers, and a mixed vascular proliferative component. Absence of plump/prominent endothelial cells, lack of atypia, and lack of mitoses were also significant factors differentiating CPA from HS. Additional distinctive findings in CPA, although with no statistical association to CPA diagnosis, were vascular shunting, absence of necrosis, and endothelial cell piling up. In conclusion, the combined use of different microscopical clues allowed for the distinction of CPA from HS and was considered useful for the diagnosis of CPA.

Detection of Leishmania spp. in Chronic Dermatitis: Retrospective Study in Exposed Horse Populations.

Leishmania infantum is a protozoan causing human zoonotic visceral leishmaniasis (ZVL) and visceral-cutaneous canine leishmaniosis (CanL) in the Mediterranean Basin. L. infantum is able to infect a large number of wild and domestic species, including cats, dogs, and horses. Since the 1990s, clinical cases of equine leishmaniasis (EL), typically characterized by cutaneous forms, have been increasingly diagnosed worldwide. The aim of the present study was to evaluate the presence of clinical forms of EL in CanL-endemic areas in Italy, where exposure of equine populations was ascertained from recent serological surveys. For this purpose, formalin-fixed and paraffin-embedded skin biopsies of 47 horses presenting chronic dermatitis compatible with EL were retrospectively selected for the study and subjected to conventional and q-PCR. A singular positivity for L. infantum was found; BLAST analysis of sequence amplicons revealed a 99-100% homology with L. infantum sequences. The histological examination revealed a nodular lymphoplasmacytic and histiocytic infiltrate; immunohistochemistry showed rare macrophages containing numerous positive amastigotes. The present retrospective study reports, for the first time, a case of a cutaneous lesion by L. infantum occurring in an Italian horse. Pathological and healthy skin samples should be investigated on a larger scale to provide information on the potential clinical impact of EL in the practice, and to define the role of horses in epidemiological ZVL and CanL scenarios.

A Wide-Proteome Analysis to Identify Molecular Pathways Involved in Kidney Response to High-Fat Diet in Mice.

The etiopathogenesis of obesity-related chronic kidney disease (CKD) is still scarcely understood. To this aim, we assessed the effect of high-fat diet (HF) on molecular pathways leading to organ damage, steatosis, and fibrosis. Six-week-old male C57BL/6N mice were fed HF diet or normal chow for 20 weeks. Kidneys were collected for genomic, proteomic, histological studies, and lipid quantification. The main findings were as follows: (1) HF diet activated specific pathways leading to fibrosis and increased fatty acid metabolism; (2) HF diet promoted a metabolic shift of lipid metabolism from peroxisomes to mitochondria; (3) no signs of lipid accumulation and/or fibrosis were observed, histologically; (4) the early signs of kidney damage seemed to be related to changes in membrane protein expression; (5) the proto-oncogene MYC was one of the upstream transcriptional regulators of changes occurring in protein expression. These results demonstrated the potential usefulness of specific selected molecules as early markers of renal injury in HF, while histomorphological changes become visible later in obesity-related CDK. The integration of these information with data from biological fluids could help the identification of biomarkers useful for the early detection and prevention of tissue damage in clinical practice.

Extravascular papillary endothelial hyperplasia mimicking soft tissue sarcoma in 2 cats: a potential diagnostic pitfall.

Papillary endothelial hyperplasia (PEH) is a rare soft tissue lesion arising from excessive reactive endothelial cell proliferation described in humans, dogs, and horses. PEH is considered a diagnostic challenge in humans, in which it is frequently misdiagnosed as angiosarcoma. We describe here PEH that developed at injection sites in 2 cats that were initially misdiagnosed as feline injection-site sarcoma by cytology and as subcutaneous angiosarcoma by histopathology. Morphologic features included sharp demarcation from surrounding tissues, and a layered microscopic architecture with an outer fibrous capsule from which emerged fibrovascular stalks covered by a monolayer of factor VIII-related antigen and CD31-positive flat-to-plump endothelial cells. Both lesions had a cystic core containing abundant erythrocytes and fibrin. PEH lesions did not recur in either case. Immunohistochemistry for α-smooth muscle actin and desmin demonstrated that the capsule was devoid of smooth muscle cells, excluding an intravascular origin. PEH in these cats was hypothesized to have developed extravascularly following trauma related to injection. We wish to provide awareness of PEH in domestic cats and of the risk of misdiagnoses leading to overtreatment.

Mucocutaneous and cutaneous generalized candidiasis in a thymectomized dog.

Cutaneous candidiasis is usually related to immunosuppressive diseases and/or therapies as predisposing factors. In humans, chronic mucocutaneous candidiasis (CMC) is observed with thymoma and thymectomy. In this case report we describe the clinical and pathological findings, laboratory analysis, treatment, and follow-up of a thymectomized dog with cutaneous and mucocutaneous generalized candidiasis.

Nerve Fiber Immunohistochemical Panel Discriminates between Nerve Sheath and Perivascular Wall Tumors.

Benign and malignant nerve sheath tumors (NST) pose a major challenge in routine diagnostic anatomic pathology because of shared histomorphological features with other soft-tissue tumors (STT). As a result, NST are often diagnosed as STT, a broad category that encompasses various entities including perivascular wall tumors (PWT) and that represents approximately 15% of all skin tumors in dogs. Immunohistochemistry (IHC) can assist the identification of histologic subtypes of STT. This IHC pilot study applies various markers largely expressed by peripheral nerves to twelve benign and six malignant NST and determines the intratumoral protein expression of laminin, periaxin-1, Sox-10 and S-100 in the NST subtypes. Furthermore, this study assesses the usefulness of peripheral nerve markers applied to diagnostic work cases and demonstrates the relevance of laminin expression patterns, periaxin-1 and Sox-10 in assisting the differentiation of NST from other STT, in particular from PWT.

Canine smooth muscle tumors: A clinicopathological study.

Canine smooth muscle tumors (SMTs) commonly develop in the alimentary and female genital tracts and less frequently in soft tissue. The definition of histological criteria of malignancy is less detailed for SMTs in dogs than in humans. This study evaluated the clinicopathologic features of canine SMTs and compared the veterinary and human medical criteria of malignancy. A total of 105 canine SMTs were evaluated histologically and classified according to both veterinary and human criteria. The Ki67 labeling index was assessed in all SMTs. Estrogen receptor (ER) and progesterone receptor (PR) expression was evaluated for soft tissue SMTs. Follow-up data were available in 25 cases. SMTs were diagnosed in the female genital tract (42%), alimentary tract (22%), and soft tissue (20%). Soft tissue SMTs frequently arose in the perigenital area, pelvic cavity, and retroperitoneum. A subset of soft tissue SMTs expressed ER and/or PR, resembling the gynecologic type of soft tissue SMT in humans. SMTs were less frequently malignant when assessed with human criteria than with veterinary criteria, better reflecting their benign behavior, especially in the genital tract where human criteria tolerate a higher mitotic count for leiomyoma. Decreased differentiation was correlated with increased proliferation, necrosis, and reduced desmin expression. Mitotic count, Ki67 labeling index, and necrosis were correlated with metastases and tumor-related death. Further prognostic studies are warranted to confirm the better performance of the human criteria when assessing SMT malignancy, especially genital cases, to confirm their usefulness in ER/PR-expressing soft tissue SMTs, and to better define the most useful prognostic parameters for canine SMTs.

Performance of lymph node cytopathology in diagnosis and characterization of lymphoma in dogs.

BACKGROUND: Cytopathology is a minimally invasive and convenient diagnostic procedure, often used as a substitute for histopathology to diagnose and characterize lymphoma in dogs. OBJECTIVES: Assess the diagnostic performance of cytopathology in diagnosing lymphoma and its histopathological subtypes in dogs. ANIMALS: One-hundred and sixty-one lymph node samples from 139 dogs with enlarged peripheral lymph nodes. METHODS: Based only on cytopathology, 6 examiners independently provided the following interpretations on each sample: (a) lymphoma vs nonlymphoma; (b) grade and phenotype; and (c) World Health Organization (WHO) histopathological subtype. Histopathology and immunohistochemistry (IHC) findings were used as reference standards to evaluate diagnostic performance of cytopathology. Clinical, clinicopathologic, and imaging data also were considered in the definitive diagnosis. RESULTS: Classification accuracy for lymphoma consistently was >80% for all examiners, whereas it was >60% for low grade T-cell lymphomas, >30% for high grade B-cell lymphomas, >20% for high grade T-cell lymphomas, and <40% for low grade B-cell lymphomas. Interobserver agreement evaluated by kappa scores was 0.55 and 0.32 for identification of lymphoma cases, and of grade plus immunophenotype, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Cytopathology may result in accurate diagnosis of lymphoma, but accuracy decreases when further characterization is needed. Cytopathology represents a fundamental aid in identifying lymphoma and can be used as a screening test to predict grade and phenotype. However, these results must be confirmed using other ancillary techniques, including flow cytometry, histopathology, and immunohistochemistry (IHC).

Causes of Death in Stray Cat Colonies of Milan: A Five-Year Report.

The presence of cats in urban environments has a long history. In Italy, stray cats are protected by national and regional laws, and programs of neutering and reintroduction to colonies are ongoing. Colony cats have been widely studied from a behavioral perspective, while surveys regarding their causes of death are limited, although they may provide relevant information related to public health and cat welfare. This retrospective study provides pathological descriptions and statistical analyses of the causes of death of 186 cats from 100 colonies in the city of Milan. Inflammatory processes represent the primary cause of death (37.7%) and include common feline infectious diseases such as feline panleukopenia (67.5%), particularly in kittens, and feline infectious peritonitis (32.5%), most common in adult cats. Trauma was found to be a common cause of death of young/adult cats (14%) with a generally good body condition, while severe parasitosis was less represented (2.6%). The death of old cats was statistically associated with organ failure (24.7%), particularly renal failure, and tumors (11.8%). Knowledge of the most common causes of death of colony cats could make an important contribution to the health monitoring of these cats and sanitary control of their habitats and provide information on possible related emerging animal welfare concerns.

Surgical Margins in Canine Cutaneous Soft-Tissue Sarcomas: A Dichotomous Classification System Does Not Accurately Predict the Risk of Local Recurrence.

Adjuvant treatments are recommended in dogs with incompletely excised cutaneous soft-tissue sarcoma (STS) to reduce the risk of local recurrence (LR), although guidelines are lacking on how to manage clean but close margins (CbCM). This retrospective study investigates the impact of CbCM on LR of canine STS. Ninety-eight surgically excised canine STS at first presentation were included. Tissue samples were routinely trimmed and analyzed. Cumulative incidence of LR was estimated for each category of margins (tumor-free, infiltrated, CbCM), and included CbCM in the tumor-free and infiltrated category, respectively. The prognostic impact on LR was then adjusted for relevant prognostic factors. Cumulative incidence of LR at three years differed significantly between the three categories (p = 0.016), and was estimated to be 42% with infiltrated margins, 23% with CbCM, 7% with tumor-free margins. Both when CbCM were grouped with infiltrated margins (p = 0.033; HR = 5.05), and when CbCM were grouped with tumor-free margins (p = 0.011; HR = 3.13), a significant difference between groups was found. STS excised with infiltrated margins had the greatest risk of LR. The rate of LR with CbCm was greater than recurrence rate of tumor-free margins. The category CbCM may be considered as a separate prognostic category.

International Guidelines for Veterinary Tumor Pathology: A Call to Action.

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as "living documents" on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.