Teat sinus and duct adenomatous hyperplasia in dogs.

Seventeen lesions diagnosed as teat sinus and duct adenomatous hyperplasia were identified in 10 dogs. All of the dogs were small breeds. Six were spayed female and 4 were male, 3 castrated and 1 intact. In 5 cases, the lesions involved multiple teats. They were pink to black, flattened to round, and sometimes crusted. Histologically, the lesions were usually pigmented (16/17), plaque-like to nodular masses composed of polygonal cells arranged in anastomosing trabeculae and bilayered ducts and/or cysts, with a fibrous to mucinous (Alcian blue-positive) stroma and squamous cysts (12/17). Scattered epithelial cells contained single, discrete, clear cytoplasmic vacuoles. Atypia was mild, and the mitotic count per 2.37 mm2 varied from 0 to 15 (average 2.7). Immunohistochemistry was performed on 14 of the lesions from 8 dogs. Epithelial cells were 100% panCK+ and included basally located CK14+/CK5_6+/p63+/calponin- cells and nonbasal CK19+/CK7+ cells. Cells manifesting squamous differentiation were usually panCK+/CK14+/CK5_6+/CK19-/CK7-/p63±/calponin-. In addition to fibroblasts, vimentin positivity was found in disseminated, round to stellate stromal and intraepithelial cells that often had black, granular, cytoplasmic pigment (consistent with dendritic/phagocytic cells and/or melanocytes). Of the 8 dogs for which clinical follow-up information was available, all were still alive and well, with no significant teat changes, development of mammary lesions or other masses 4 to 22 months (median 12.5) after biopsy. The histologic, immunohistochemical, and clinical findings were consistent with teat duct and sinus adenomatous hyperplasia. This is an uncommon, benign proliferative lesion that can involve multiple teats of female and male, small breed dogs.

Modeling molecular development of breast cancer in canine mammary tumors.

Understanding the changes in diverse molecular pathways underlying the development of breast tumors is critical for improving diagnosis, treatment, and drug development. Here, we used RNA-profiling of canine mammary tumors (CMTs) coupled with a robust analysis framework to model molecular changes in human breast cancer. Our study leveraged a key advantage of the canine model, the frequent presence of multiple naturally occurring tumors at diagnosis, thus providing samples spanning normal tissue and benign and malignant tumors from each patient. We showed human breast cancer signals, at both expression and mutation level, are evident in CMTs. Profiling multiple tumors per patient enabled by the CMT model allowed us to resolve statistically robust transcription patterns and biological pathways specific to malignant tumors versus those arising in benign tumors or shared with normal tissues. We showed that multiple histological samples per patient is necessary to effectively capture these progression-related signatures, and that carcinoma-specific signatures are predictive of survival for human breast cancer patients. To catalyze and support similar analyses and use of the CMT model by other biomedical researchers, we provide FREYA, a robust data processing pipeline and statistical analyses framework.

Biphasic Feline Mammary Carcinomas Including Carcinoma and Malignant Myoepithelioma.

Feline mammary tumors are usually malignant and aggressive carcinomas. Most cases are simple monophasic carcinomas (1 epithelial population), and additional phenotyping is usually not needed. In this study, we describe 10 malignant mammary tumors from 9 female cats that had unusual histomorphology: they appeared biphasic, with 2 distinct cell populations. Initially, they were morphologically diagnosed as either carcinosarcoma (1/10) or malignant pleomorphic tumor (9/10) of the mammary gland, as the latter did not match any previously described histological subtype. Immunohistochemistry (IHC) was performed for pancytokeratin, cytokeratins 8 and 18, cytokeratin 14, cytokeratins 5 and 6, vimentin, p63, calponin, alpha-smooth muscle actin, Ki-67, ERBB2, estrogen receptor alpha, and progesterone receptor. In 7 of 10 cases, the biphasic nature was confirmed and, on the basis of the IHC results, they were classified as carcinoma and malignant myoepithelioma (4/10), ductal carcinoma (1/10), and carcinosarcoma (2/10). The other 3 of 10 cases were monophasic based on IHC. In the cases of carcinoma and malignant myoepithelioma, the malignant myoepithelial cells were 100% positive for vimentin (4/4) and variably positive for p63, calponin, and cytokeratins (4/4). These findings show that, although rare, biphasic mammary carcinomas do occur in cats. In dogs and humans, tumors composed of malignant epithelial and myoepithelial cells have a less aggressive behavior than certain simple carcinomas, and therefore, their identification might also be clinically significant in the cat.

The estrogen effect; clinical and histopathological evidence of dichotomous influences in dogs with spontaneous mammary carcinomas.

The purpose of this study was to investigate the associations and explore the relationships between hormonal factors (serum estrogen, estrogen receptors and ovariohysterectomy) and other clinical/histological prognostic factors and their impact on outcome in dogs with mammary carcinomas. Data from two separate prospective studies on dogs with spontaneous mammary carcinomas were used for this research. All dogs underwent standardized diagnostic testing, staging, surgery and follow-up examinations. Serum estrogen was analyzed by competitive enzyme immunoassay or radioimmunoassay, and tumor estrogen receptor (ER) expression was analyzed by immunohistochemistry. A total of 159 dogs were included; 130 were spayed and 29 remained. High serum estrogen was associated with an overall longer time to metastasis (p = 0.021). When stratifying based on spay group, the effect was only significant in spayed dogs, (p = 0.019). Positive tumor ER expression was also associated with a longer time to metastasis (p = 0.025), but similar to above, only in dogs that were spayed (p = 0.049). Further subgroup analysis revealed that high serum estrogen was significantly associated with improved survival in dogs with ER positive tumors, but only in spayed dogs (p = 0.0052). Interestingly, the effect of spaying was the opposite in dogs with ER negative tumors; here, intact dogs with high serum estrogen but ER negative tumors had a significantly longer time to metastasis (p = 0.036). Low serum estrogen was associated with increased risk for the development of non-mammary tumors in the post-operative period (p = 0.012). These results highlight the dual effect of estrogen in cancer: Estrogen acts as a pro-carcinogen in ER positive mammary tumors, but a may have a protective effect in ER negative tumors, potentially via non-receptor mechanisms. The latter is supported by the decreased risk for non-mammary tumors in dogs with high serum estrogen, and explains the increased incidence of certain non-mammary tumors in in dogs spayed at an early age.

Developing and testing prognostic bio-scoring systems for canine mammary gland carcinomas.

Canine mammary carcinomas (CMC) represent a range of histolopathological subtypes with diverse biological behaviours. Several individual factors, including stage, grade, subtypes and presence of invasion, predict outcome. Less is known how these factors interact and impact prognosis. The purpose of this work was to develop and test comprehensive bio-scoring systems in CMCs. Clinical and histopathological data from 127 dogs with MCs treated through two prospective studies were obtained. All dogs underwent standardized pre-surgical staging, treatments and regular follow-up visits. All tumours were evaluated, classified and graded according to published guidelines. Time to primary metastasis was the main endpoint in this study. Two bio-scoring systems were developed: The multivariate scoring (MVS) was based on traditional statistical analysis where only factors significant in the multivariate analysis (tumour size and grade) were kept for the final model. The refined flexible scoring (RFS) system was based on results from subgroup analysis, which guided the development of a flexible system. Progressive worsening prognosis was observed with increasing bio-scores in both systems. MVS: Median primary metastasis-free survival (TTM1 days) was not reached in dogs with bio-scores 0 to 5, 10, 15 and 648, 149, 317, in MVS groups 25, 30, 40, respectively. Similarly, TTM1 was not reached in dogs with RFS 0, 1, 2 and 374, 407 and 149, in dogs with bio-scores 3, 4, 5, respectively. However, a more distinct separation between dogs with high risk vs low risk for metastasis was observed with RFS, suggesting superior overall prognostication regarding the risk for metastasis.

Array Comparative Genomic Hybridization Analysis Reveals Significantly Enriched Pathways in Canine Oral Melanoma.

Human Mucosal Melanoma (hMM) is an aggressive neoplasm of neuroectodermal origin with distinctive features from the more common cutaneous form of malignant melanoma (cMM). At the molecular level, hMMs are characterized by large chromosomal aberrations rather than single-nucleotide mutations, typically observed in cMM. Given the scarcity of available cases, there have been many attempts to establish a reliable animal model. In pet dogs, Canine Oral Melanoma (COM) is the most common malignant tumor of the oral cavity, sharing clinical and histological aspects with hMM. To improve the knowledge about COM's genomic DNA alterations, in the present work, formalin-fixed, paraffin-embedded (FFPE) samples of COM from different European archives were collected to set up an array Comparative Genomic Hybridization (aCGH) analysis to estimate recurrent Copy Number Aberrations (CNAs). DNA was extracted in parallel from tumor and healthy fractions and 19 specimens were successfully submitted to labeling and competitive hybridization. Data were statistically analyzed through GISTIC2.0 and a pathway-enrichment analysis was performed with ClueGO. Recurrent gained regions were detected, affecting chromosomes CFA 10, 13 and 30, while lost regions involved chromosomes CFA 10, 11, 22, and 30. In particular, CFA 13 showed a whole-chromosome gain in 37% of the samples, while CFA 22 showed a whole-chromosome loss in 25%. A distinctive sigmoidal trend was observed in CFA 10 and 30 in 25 and 30% of the samples, respectively. Comparative analysis revealed that COM and hMM share common chromosomal changes in 32 regions. MAPK- and PI3K-related genes were the most frequently involved, while pathway analysis revealed statistically significant perturbation of cancer-related biological processes such as immune response, drug metabolism, melanocytes homeostasis, and neo-angiogenesis. The latter is a new evidence of a significant involvement of neovascularization-related pathways in COMs and can provide the rationale for future application in anti-cancer targeted therapies.

Prognostic Significance of Canine Mammary Tumor Histologic Subtypes: An Observational Cohort Study of 229 Cases.

Histopathology is considered the gold standard diagnostic method for canine mammary tumors. In 2011, a new histologic classification for canine mammary tumors was proposed. The present study was a 2-year prospective study that validated the 2011 classification as an independent prognostic indicator with multivariate analysis in a population of 229 female dogs, identifying subtype-specific median survival times (MST) and local recurrence/distant metastasis rates. Dogs with benign tumors and carcinoma arising in benign mixed tumors all had an excellent prognosis. Dogs with complex carcinoma and simple tubular carcinoma also experienced prolonged survival. Those with simple tubulopapillary carcinoma, intraductal papillary carcinoma, and carcinoma and malignant myoepithelioma had a more than 10-fold higher risk of tumor-related death. The prognosis was even worse for adenosquamous carcinoma (MST = 18 months), comedocarcinoma (MST = 14 months), and solid carcinoma (MST = 8 months). The most unfavorable outcome was for anaplastic carcinoma (MST = 3 months) and carcinosarcoma (MST = 3 months), which also had the highest metastatic rates (89% and 100%, respectively). Adenosquamous carcinoma exhibited the highest local recurrence rate (50%). In the same canine population, the tumor diameter was recognized as a strong predictor of local recurrence/distant metastasis and an independent prognosticator of survival in the multivariate analysis. Excision margins were predictive only of local recurrence, whereas lymphatic invasion and histologic grade were predictive of local recurrence/distant metastasis and survival, although only in univariate analyses. In conclusion, this study validated the 2011 classification scheme and provided information to be used in the clinical setting and as the basis for future prognostic studies.

Congenital infiltrative lipomas and retroperitoneal perirenal lipomas in a calf.

BACKGROUND: Congenital lipocytic tumours have rarely been reported in cattle. Lipomas are benign tumours, but infiltrative lipomas have significant health implications due to their aggressive infiltrative growth pattern. CASE PRESENTATION: A calf was born with skeletal malformations and soft tissue proliferations, primarily on the external thoracic wall. The calf was euthanized for welfare reasons and submitted for post mortem examination. Necropsy, histopathology and post mortem computed tomography scanning revealed two types of lipocytic tumours. Widespread infiltrative lipomas were present in the muscles and connective tissues along the vertebral column and diffusely invaded the external soft tissues of the right thoracic wall. The neoplastic lipocytes had invaded intervertebral spaces thus causing congenital vertebral malformations, and further invaded the vertebral canal and the bone marrow of coccygeal vertebrae. Periosteal localization of the tumour was associated with costal hyperostosis. Two large retroperitoneal lipomas enclosed the kidneys and occupied much of the abdominal space. CONCLUSION: The development of congenital bone malformation in this calf illustrates the severe consequences of the infiltrative and aggressive growth of infiltrative lipomas during foetal development. The congenital retroperitoneal lipomas occupied a large part of abdominal cavity, but did not invade the adjacent tissues. Due to their large size, perirenal lipomas should be considered in calves with distended abdomen, even in cases without other signs of tumours.

Converting fluid-based cytologic specimens to histologic specimens for immunohistochemistry.

BACKGROUND: Cavitary effusions are often evaluated cytologically to determine if there is an underlying neoplastic cause. Differentiation of neoplastic epithelial from mesothelial populations within effusions can be difficult using routine cytology. In addition, cytology alone cannot provide information on the immunophenotype of round cell populations. Gel foam techniques can be used to convert effusions into cell blocks for immunohistochemical (IHC) staining which can then be used to differentiate mesothelial from epithelial cell populations, and also allow immunophenotyping of round cell populations within effusions. OBJECTIVES: The aim of this study was to evaluate a gel foam cell block technique for converting potential neoplastic cells in cavitary effusions into cell blocks to characterize these further by IHC. RESULTS: Thirteen canine and 7 feline samples with cohesive cell populations were evaluated using gel foam cell blocks and IHC. Samples evaluated by routine cytology were categorized as (1) epithelial cells, (2) cohesive cell population without cytologic distinction between mesothelial and epithelial cells, and (3) mesothelial cells with signs of atypia. Antibody-mediated staining of vimentin and cytokeratin of the effusion cell blocks yielded further classification of cohesive cell populations. In addition, a total of 4 effusions with malignant round cells were evaluated; they were immunophenotyped as either B- or T-cell lymphoma. CONCLUSION: The use of cytokeratin and vimentin IHC on gel foam cell blocks from cavitary effusions provided robust staining and allowed characterization of cohesive cells as mesothelial or epithelial and immunophenotyping of lymphoid cell populations. In addition, this method is cost and time effective.

Triple-negative vimentin-positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer.

BACKGROUND: Human breast cancer is a heterogeneous disease classified by molecular subtyping into luminal A, luminal B, HER2-overexpressing, basal-like, claudin-low and normal-breast like. The routinely applied and standardized immunohistochemical-based surrogates of this classification group together the last three entities as triple-negative breast cancer (TNBCs) that show the most diverse and complex heterogeneity and represent a therapeutic challenge. In the present work 156 feline mammary lesions consisting of feline mammary carcinomas (FMCs), benign neoplasms, and hyperplastic/dysplastic tissues were evaluated histologically and by immunohistochemistry for expression of basal and luminal cytokeratins (CK), vimentin, alpha-smooth muscle actin, calponin, estrogen receptor (ER) alpha (a), and progesterone receptor (PR). Thirty-seven FMCs with 27 matched non-neoplastic controls were also investigated for gene expression of ERa, ER beta, PR, and HER2. RESULTS: A large group of hormone receptors (HRs)-negative aggressive carcinomas - that did not overexpress HER2 - could be distinguished from the less aggressive (10.8%) and benign (8%) HRs + tumors, that showed bilineage (luminal and myoepithelial) differentiation. Immunohistochemical evaluations of cytoplasmic filaments indicated that HRs- FMCs are vimentin+, CK14+, and CK5_6+ carcinomas that may resemble the TNBCs (basal like/claudin low) described in women. The identification of luminal and myoepithelial progenitors within the mammary ductal system suggested potential cells/sites of origin of these tumors. A diffuse and never previously described CKs/vimentin luminal cell co-expression was detected in the non-neoplastic ducts, indicating a potential bilineage progenitor. CONCLUSIONS: These results indicate and potentially explain the high incidence of triple-negative, vimentin + aggressive tumors in cats that may used to elucidate some of the challenging features of TNBCs in women.

Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection.

One of the hallmarks of adaptive immunity is the development of a long-term pathogen specific memory response. While persistent memory T cells certainly impact the immune response during a secondary challenge, their role in unrelated infections is less clear. To address this issue, we utilized lymphocytic choriomeningitis virus (LCMV) and Listeria monocytogenes immune mice to investigate whether bystander memory T cells influence Leishmania major infection. Despite similar parasite burdens, LCMV and Listeria immune mice exhibited a significant increase in leishmanial lesion size compared to mice infected with L. major alone. This increased lesion size was due to a severe inflammatory response, consisting not only of monocytes and neutrophils, but also significantly more CD8 T cells. Many of the CD8 T cells were LCMV specific and expressed gzmB and NKG2D, but unexpectedly expressed very little IFN-γ. Moreover, if CD8 T cells were depleted in LCMV immune mice prior to challenge with L. major, the increase in lesion size was lost. Strikingly, treating with NKG2D blocking antibodies abrogated the increased immunopathology observed in LCMV immune mice, showing that NKG2D engagement on LCMV specific memory CD8 T cells was required for the observed phenotype. These results indicate that bystander memory CD8 T cells can participate in an unrelated immune response and induce immunopathology through an NKG2D dependent mechanism without providing increased protection.

Scrotal tumors in dogs: a retrospective study of 676 cases (1986-2010).

The objective of this study was to determine common tumor types that occur on the canine scrotum in relation to other cutaneous locations and to identify potential risk factors for specific scrotal tumor development. A retrospective study was conducted and the database of pathology reports from the Surgical Pathology Service of the Department of Pathology and Toxicology, School of Veterinary Medicine, University of Pennsylvania from 1986 to 2010 was searched for canine neoplastic scrotal and non-scrotal cutaneous lesions. Neoplastic lesions were evaluated based on diagnosis, breed, age, and number and location of tumors (scrotal versus non-scrotal cutaneous). Mast cell tumor, melanocytoma, malignant melanoma, vascular hamartoma, hemangiosarcoma, hemangioma, and cutaneous histiocytoma were the most common tumor types identified on the canine scrotum. Breed predispositions and mean age at diagnosis were identified for each tumor type and should be considered when planning surgical excision of a canine scrotal tumor.

Tumeurs scrotales chez les chiens : étude rétrospective de 676 cas (1986­2010). Cette étude avait pour objectif de déterminer les types communs de tumeurs qui se produisent sur le scrotum canin par rapport à d'autres endroits cutanés et d'identifier les facteurs de risque potentiels pour le développement de tumeurs scrotales spécifiques. Une étude rétrospective a été réalisée et une recherche a été effectuée dans la base de données des rapports de pathologie du Service de pathologie chirurgicale du Département de pathologie et de toxicologie de l'École de médecine vétérinaire de l'Université de la Pennsylvanie de 1986 à 2010 pour les lésions scrotales néoplasiques et les lésions cutanées non scrotales canines. Les lésions néoplasiques ont été évaluées en fonction du diagnostic, de la race, de l'âge ainsi que du nombre et de l'emplacement des tumeurs (scrotales par opposition à cutanées non scrotales). Les tumeurs à mastocytes, les mélanocytomes, les mélanomes malins, les hamartomes vasculaires, les hémangiosarcomes, les hémangiomes et les histiocytomes cutanés étaient les types les plus communs de tumeurs identifiées sur le scrotum canin. Les prédispositions des races et l'âge moyen lors du diagnostic ont été identifiés pour chaque type de tumeur et devraient être considérés lors de la planification de l'excision chirurgicale d'une tumeur scrotale canine.(Traduit par Isabelle Vallières).

Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model.

Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis.

Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While current therapeutics focus on augmenting protective immune responses, identifying therapeutics that reduce infection-induced immunopathology are clearly warranted. Despite the apparent protective role for murine CD8⁺ T cells following infection with the intracellular parasite Leishmania, CD8⁺ T cells have been paradoxically linked to immunopathological responses in human cutaneous leishmaniasis. Transcriptome analysis of lesions from Leishmania braziliensis patients revealed that genes associated with the cytolytic pathway are highly expressed and CD8⁺ T cells from lesions exhibited a cytolytic phenotype. To determine if CD8⁺ T cells play a causal role in disease, we turned to a murine model. These studies revealed that disease progression and metastasis in L. braziliensis infected mice was independent of parasite burden and was instead directly associated with the presence of CD8⁺ T cells. In mice with severe pathology, we visualized CD8⁺ T cell degranulation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8⁺ T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8⁺ T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis.

Osteomyelitis of the coxofemoral joint due to Mycobacterium species in a feline renal transplant recipient.

A 4-year-old castrated male Russian Blue cat was evaluated for acute right hind limb lameness 18 months after receiving a renal transplant. Radiographs showed a subluxated right femoral head and lysis of the acetabulum and femoral neck. A femoral head and neck ostectomy was performed on the right coxofemoral joint. Histologic evaluation of the right femoral head revealed lesions indicative of a chronic, granulomatous osteomyelitis and periostitis associated with an intralesional Mycobacterium species. However, the cat's clinical condition declined despite treatment and the owner elected humane euthanasia. All renal transplant recipients receive immunosuppressive therapy to prevent allograft rejection. The non-tuberculous mycobacterial infection of the coxofemoral joint was thought to develop secondary to long-term immunosuppressive treatment. This report illustrates the need to consider these rare opportunistic infections even many months to years following renal transplantation. Early awareness, stringent immunosuppressive drug monitoring and targeted treatment once a diagnosis has been made may be important in the successful management and prevention of mycobacterial infections in this population of patients.

Malignant peripheral nerve sheath tumor in a cat with nodal and pulmonary metastases.

Peripheral nerve sheath tumors in domestic cats are infrequently reported and are often locally invasive. An 11-year-old Domestic Shorthair cat was originally diagnosed with a right maxillary benign peripheral nerve sheath tumor at incisional biopsy. At necropsy, the neoplasm had features of malignancy including metastases to the regional lymph nodes and lung. Histologically, the neoplasm contained 2 distinct regions: spindle cells arranged in dense interwoven bundles with Antoni A areas and Verocay bodies and Antoni B regions with loosely arranged spindle cells separated by a mucinous matrix. Immunohistochemically, the neoplastic cells in the primary mass and right mandibular lymph node were strongly positive for vimentin, S-100, and glial fibrillar acidic protein. The neoplastic cells within the lung were strongly positive for vimentin and weakly positive for S-100 and glial fibrillar acidic protein.

Herpesvirus dermatitis in two cats without facial lesions.

BACKGROUND: Cats with feline herpesvirus (FeHV-1)-associated dermatitis typically present with ulcerative lesions on the rostral muzzle and nasal planum. This report describes FeHV-1 dermatitis in the flank region, in the absence of facial lesions. HYPOTHESIS/OBJECTIVES: Clinicians should be aware of this unusual manifestation of FeHV-1 dermatitis to prevent potential misdiagnosis. ANIMALS: A 12-year-old male castrated Bengal cat and a 3-year-old male castrated Siamese cat with plaques and ulcers in the flank region are described. METHODS: Formalin-fixed biopsy samples were obtained from lesional skin. Histopathology and FeHV-1 immunohistochemistry were performed. RESULTS: Each sample had epidermal and follicular necrosis with a dense dermal infiltrate of eosinophils. Few to moderate numbers of intranuclear inclusion bodies were present in keratinocytes. The presence of FeHV-1 in the lesions was confirmed with immunohistochemistry. CONCLUSIONS AND CLINICAL IMPORTANCE: Feline herpesvirus-associated dermatitis should not be ruled out based on the location of the lesion, because a correct diagnosis is imperative for proper treatment. Future studies to assess the cause of lesions at this unusual site are warranted.

Fibrosarcoma arising at the site of a retained surgical sponge in a cat.

An 8-year-old female spayed domestic shorthair cat had an abdominal mass palpated as an incidental finding on physical examination. Cytologic findings in ultrasound-guided fine-needle aspirates of the mass were most compatible with a sarcoma, with abundant mineralized material and mixed inflammation. The mass was removed surgically and on gross examination was white-tan, firm, associated with the mesentery, and when transected contained a gauze sponge in its center. On histopathologic examination, an area of central necrosis with mineralization and numerous refractile fibers consistent with sponge material was surrounded by dense fibrous connective tissue (gossypiboma). Within the connective tissue was a population of highly pleomorphic spindle cells consistent with a fibrosarcoma. Immunohistochemically, most neoplastic cells stained strongly positive for vimentin and a low number of cells were positive for smooth muscle actin. The results were consistent with a fibrosarcoma arising at the site of a retained surgical sponge. At a follow-up visit 2 months postoperatively, ultrasonographic and cytologic evidence of metastasis was found in the spleen and mesentery. To our knowledge, this is the first report of malignant transformation at the site of a retained surgical sponge in a cat and the first report of a fibrosarcoma arising within a gossypiboma in a domestic animal.

Heterozygosity for hypoxia inducible factor 1alpha decreases the incidence of thymic lymphomas in a p53 mutant mouse model.

Hypoxia inducible factors (HIF) are critical mediators of the cellular response to decreased oxygen tension and are overexpressed in a number of tumors. Although HIF1alpha and HIF2alpha share a high degree of sequence homology, recent work has shown that the two alpha subunits can have contrasting and tissue-specific effects on tumor growth. To directly compare the role of each HIFalpha subunit in spontaneous tumorigenesis, we bred a mouse model of expanded HIF2alpha expression and Hif1alpha(+/-) mice to homozygotes for the R270H mutation in p53. Here, we report that p53(R270H/R270H) mice, which have not been previously described, develop a unique tumor spectrum relative to p53(R270H/-) mice, including a high incidence of thymic lymphomas. Heterozygosity for Hif1alpha significantly reduced the incidence of thymic lymphomas observed in this model. Moreover, reduced Hif1alpha levels correlated with decreased stabilization of activated Notch1 and expression of the Notch target genes, Dtx1 and Nrarp. These observations uncover a novel role for HIF1alpha in Notch pathway activation during T-cell lymphomagenesis.