Histological and immunohistochemical features of cutaneous mast cell tumor in six captive four-toed hedgehogs (Atelerix albiventris)

This report described the histopathological and immunohistochemical features of cutaneous mast cell tumor (MCT) in six hedgehogs. The hedgehogs presented single cutaneous mass with ulcer and crusting. Histologically, the neoplastic lesions were characterized by the proliferation of well-differentiated mast cells (3 cases), and atypical mast cells (3 cases) with one atypical histiocytic morphology. Immunohistochemically, tumor cells were positive for KIT and mast cell tryptase, and were negative for Iba-1. In well-differentiated MCT, all patients were clinically improved and survived more than 365 days after surgical excision, whereas an atypical histiocytic MCT showed aggressive behavior with re-recurrence, and the animal died 115 days after surgery. These findings suggest that, compatible with other animals, well-differentiated MCT has a better prognosis in hedgehogs.     

Cutaneous papilloma and multicentric squamous cell carcinoma in four-toed hedgehogs (Atelerix albiventris)

Skin lesions possibly caused by Papillomavirus infections in two four-toed hedgehogs are described. In case 1, there was a papillary mass on the right hind limb. Histologically, the mass was consistent with a viral papilloma. In the other case, multifocal papillary masses with erosions and ulcers were found throughout the body, mainly on the extremities. Histology showed continuative lesions composed of acanthosis, Bowenoid in situ carcinoma, and squamous cell carcinoma, with abrupt transitions between the lesions. In both cases, keratinocytes in the granular layer infrequently had features of koilocytes and intranuclear inclusion bodies, and immunohistochemical staining was positive for anti-human papillomavirus antibody. To the best of the authors’ knowledge, this is the first pathological documentation of possibly papillomavirus-associated skin lesions in four-toed hedgehogs.     

Ovarian mixed germ-cell tumor comprising mature teratoma and embryonal carcinoma in a four-toed hedgehog (Atelerix albiventris)

This report describes the clinical and histopathological characteristics of a rare mixed germ-cell tumor comprising teratoma and embryonal carcinoma in the left ovary of a 10-month-old four-toed hedgehog, with chief complaints of loss of appetite and lethargy. Laparotomy revealed a swollen left ovary with small disseminated peritoneal nodules, and bilateral ovariohysterectomy was performed. The left ovary had a mature teratoma with well-differentiated fat, bone, cartilage, salivary gland, trachea, keratin cyst, and nervous tissues, and an embryonal carcinoma consisting of poorly-differentiated epithelial cells arranged in tubular, alveolar, or solid patterns. Immunohistochemically, the embryonal carcinoma cells were positive for placental alkaline phosphatase and c-KIT. This is the first case of mature teratoma with embryonal carcinoma in the ovary of a hedgehog.     

Necropsy and histopathologic findings in 14 African hedgehogs (Atelerix albiventris): a retrospective study.

From fiscal years 1992 through 1996, 14 African hedgehog (Atelerix albiventris) cases were submitted to the Animal Disease Diagnostic Laboratory at Purdue University. The most common diagnoses were splenic extramedullary hematopoiesis (91%), hepatic lipidosis (50%), renal disease (50%), and neoplastic disease (29%). Other less frequent necropsy findings were myocarditis (21%), colitis (14%), bacterial septicemia (14%), and pneumonia (14%). The data indicate that splenic extramedullary hematopoiesis, hepatic lipidosis, renal disease, and neoplasms are frequent postmortem findings in hedgehogs.     

Granulosa cell tumor in 8 African pygmy hedgehogs (Atelerix albiventris)

A retrospective study involving eight African pygmy hedgehogs histopathologically diagnosed with granulosa cell tumors was conducted. The age at onset was 2.2–4.5 years, with a median age of 3.6 years. The most common clinical signs were hematuria and abdominal distension, which were observed in >50% cases. Exploratory laparotomy was performed in all cases, and ovariohysterectomy or excision of the abdominal mass was performed. Patients with only hematuria survived for >250 days after surgery, whereas those with initial ascites showed recurrence of ascites or tumor growth and survived for approximately 130 days after surgery. Intraperitoneal injection of carboplatin was performed in three recurrent cases. In one of these three cases, the tumor mass disappeared. Hence, carboplatin can be considered a potential antineoplastic drug for the treatment of granulosa cell tumors.     

Evaluation of supraglottic airway device use during inhalation anesthesia in healthy African pygmy hedgehogs (Atelerix albiventris)

ObjectiveTo evaluate a supraglottic airway device (SGAD) designed for rabbits in African pygmy hedgehogs (Atelerix albiventris) during inhalation anesthesia.Study designProspective, randomized, blinded experimental study.AnimalsA total of 12 adult African pygmy hedgehogs (seven male, five female).MethodsHedgehogs were placed in a chamber and anesthesia was induced using isoflurane in oxygen. Oropharyngeal endoscopy was performed and video recorded. The SGAD (v-gel R1) was inserted and connected to a Mapleson D circuit. Capnography, pulse oximetry and physiologic variables were measured during anesthesia, and lung inflation was tested at 10 and 20 cmH₂O. With the SGAD temporarily disconnected, anesthetized hedgehogs were randomly positioned into right and left lateral, dorsal and sternal recumbency to evaluate the effect of a change in body position on SGAD placement. Oropharyngeal endoscopy was repeated at the end of anesthesia, and recovery time was recorded. Pre- and post-SGAD placement endoscopy videos were retrospectively reviewed and scored for gross trauma.ResultsThe median [interquartile range (IQR)] time to successful SGAD placement was 38 (16–68) seconds. The time to SGAD placement decreased as the study progressed. SGAD required repositioning in six hedgehogs, median 2.5 (IQR, 1–3.5) adjustments each, to successfully perform lung inflation or maintain capnography readings. Lung inflation at 10 cmH₂O was successfully performed without leakage in nine animals, and in the other three animals after adjusting the SGAD at 1–2 time points. Inflation at 20 cmH₂O was rarely achieved without an air leak. Changes in heart and respiratory rates during anesthesia were not clinically relevant. Median endoscopic scores were 0 (no lesions) for both pre-and postplacement.Conclusions and clinical relevanceThe SGAD was relatively quickly and easily placed, permitted lung inflation and caused no significant oropharyngeal damage. The SGAD is a practical option for airway management in African pygmy hedgehogs.     

Histiocytic sarcoma of macrophage origin in a cat: case report with a literature review of feline histiocytic malignancies and comparison with canine hemophagocytic histiocytic sarcoma

Mild nonregenerative anemia was detected in a 9-year-old neutered male domestic shorthair cat during a routine examination. Bone marrow core biopsy revealed erythroid hyperplasia; however, a specific cause was not identified. Over the next 8 months the anemia progressed, eventually becoming mildly regenerative, and moderate thrombocytopenia developed. On ultrasonographic examination, marked splenomegaly, mild hepatomegaly, and abdominal lymphadenopathy were found. Cytologic evaluation of splenic aspirates revealed increased numbers of mildly to moderately pleomorphic histiocytes that frequently had phagocytosed RBCs, leukocytes, and occasionally platelets. Histopathologic examination of the spleen and liver revealed effacement of splenic architecture by a histiocytic sarcoma (HS), and neoplastic histiocytes in hepatic sinusoids. A second bone marrow aspirate revealed neoplastic infiltration by similar cells. The histiocytes in all tissues were mildly to moderately pleomorphic and markedly erythrophagocytic. The immunophenotype of histiocytes in the spleen was CD1c(-)/CD11b(+)/CD18(+)/MHC-II(+), supporting a macrophage cell lineage. The clinical, pathologic, and immunophenotypic findings in this cat were similar to those in hemophagocytic HSs in dogs. To our knowledge, this is the first report of a HS of purported macrophage phenotype in a cat.     

A retrospective study (2006-2020) of cytology and biopsy findings in pet rabbits (Oryctolagus cuniculus), ferrets (Mustela putorius furo) and four-toed hedgehogs (Atelerix albiventris) seen at an exotic animal clinic in Tokyo,Japan

Background: Rabbits, ferrets, and four-toed hedgehogs are popular exotic pets, but comprehensive epidemiological studies in these animals have been rarely conducted. The present study aims to clarify the incidence of neoplastic and non-neoplastic diseases in pet rabbits, ferrets and four-toed hedgehogs in Japan. Methods: We histologically/cytologically investigated 1098 samples from 883 rabbits, 812 samples from 521 ferrets and 561 samples from 468 four-toed hedgehogs that were collected at Miwa Exotic Animal Hospital and submitted to the Laboratory of Veterinary Pathology, The University of Tokyo between 2006 and 2020. The examinations of necropsy samples were not included in the present study. Results: Of the 1098 samples from diseased rabbits, 721 (65.7%) were diagnosed as neoplastic and 377 (34.3%) were as non-neoplastic. Uterine adenocarcinoma (21.1%), cutaneous soft tissue sarcoma (15.1%) and mammary gland adenocarcinoma (8.2%) were the most commonly encountered neoplasms. Endometrial hyperplasia (35.8%), testicular atrophy (4.2%) and uterine adenomyosis (3.7%) were the most common non-neoplastic lesions in rabbits. Of the 812 samples from diseased ferrets, 487 (60.0%) were diagnosed as neoplastic and 325 (40.0%) were as non-neoplastic. Adrenocortical tumor (23.2%), lymphoma (19.3%) and pancreatic islet cell tumor (11.5%) were the most commonly encountered neoplasms. Extramedullary hematopoiesis in the spleen (10.5%), lymph node hyperplasia (7.7%) and cholangiohepatitis (4.6%) were the most common non-neoplastic lesions in ferrets. Of the 561 samples from diseased hedgehogs, 338 (60.2%) were diagnosed as neoplastic and 223 (39.8%) were as non-neoplastic. Endometrial stromal tumor and endometrial mixed tumor (23.7%), oral squamous cell carcinoma (13.0%) and cutaneous soft tissue sarcoma (11.5%) were the most commonly encountered neoplasms. Gingivitis/stomatitis (39.5%), endometrial hyperplasia (18.8%) and dermatitis (6.7%) were the most common non-neoplastic lesions in hedgehogs. Conclusions and clinical relevance: Information obtained from the present study will provide a useful reference for veterinarians working with these exotic animals. Based on the literature search, this is the largest-scale retrospective study on disease incidence in hedgehogs.     

Epirubicin in the treatment of canine histiocytic sarcoma: sequential,alternating and rescue chemotherapy

The aims of this study were to report treatment outcomes for dogs with histiocytic sarcoma (HS) treated with both lomustine and epirubicin, and to report response rates to epirubicin as a rescue therapy in dogs previously treated with lomustine. Medical records of dogs with a diagnosis of HS that were treated with both lomustine and epirubicin were retrospectively evaluated. Of 29 dogs receiving epirubicin alternating with, or subsequent to lomustine treatment, including in a rescue setting, response to epirubicin could be assessed in 20 with an overall response rate (ORR) of 29% and biological response rate (BRR) of 71%. Median time to progression (TTP) in 12 of these 20 dogs in which it was assessable was 69 days (range: 40‐125 days). For dogs treated in the rescue setting epirubicin specific ORR was 19% and BRR 63%. Median TTP in the 9 of these 16 dogs in which it was assessable was 62 days (range: 40‐125 days). Median survival time for all dogs treated with both epirubicin and lomustine was 185 days (range: 27‐500 days). Some dogs with HS respond to epirubicin and dogs treated with combinations of epirubicin and lomustine have modestly improved survival times compared with single agent studies, and similar to dogs with HS treated with alternating lomustine and doxorubicin. Single agent epirubicin is also a valid short term rescue therapy for canine HS.     

Subcutaneous tiletamine-zolazepam immobilization and effect of flumazenil reversal in African pygmy hedgehogs (Atelerix albiventris)

African pygmy hedgehogs (Atelerix albiventris) are popular zoological companion animals that routinely require chemical immobilization for veterinary care. The objective of this randomized, blinded, cross-over study was to evaluate the efficacy of low and high dosages of subcutaneous (SC) tiletamine-zolazepam for sedation and the efficacy of flumazenil for recovery in African pygmy hedgehogs. Twelve adult hedgehogs (7 males, 5 females) were administered tiletamine-zolazepam at 10 mg/kg (T10) or 30 mg/kg (T30) SC. Physiologic variables, reflexes and behaviors were monitored to evaluate quality of immobilization. Forty-five minutes after tiletamine-zolazepam injection, hedgehogs were administered flumazenil or an equivalent volume of saline SC. Baseline daily food intake was measured and then recorded daily for 6 days following sedation trials. Median (interquartile range [IQR]) time to onset of first effects for T10 and T30 was 2.9 minutes (2.5–5.3 minutes) and 2 minutes (1.4–2.9 minutes), respectively. Eighty-three percent of T10 and 100% of T30 hedgehogs lost righting reflex. The median (IQR) duration righting reflex was lost for T10 was 32.5 minutes (23.8–37.5 minutes) and it was lost for 47.5 minutes (36.25–63.75 minutes) for T30. Jaw tone was reduced in the majority of animals for both dosages but never lost. Heart and respiratory rate for both treatments remained within normal limits. Hedgehogs became rapidly hypothermic after induction. Flumazenil administration did not have a statistically significant effect on recovery time, but mean recovery times were 18 minutes faster for T10 hedgehogs administered flumazenil. There were no statistically significant differences in food intake within or between dosages of tiletamine-zolazepam at any time point for hedgehogs administered saline or flumazenil; however, mean food intake over the 6 days following T10 administration was 16 g/kg more for hedgehogs administered flumazenil. SC tiletamine-zolazepam at 10 and 30 mg/kg produces dose-dependent heavy sedation to light anesthesia in hedgehogs. Subjectively, while both dosages provided a sufficient depth of immobilization to permit a physical examination and noninvasive procedures like blood collection or diagnostic imaging, some jaw tone was maintained precluding endotracheal intubation. T30 provided a deeper level of immobilization than T10 but longer recovery times. Flumazenil administration did not have a statistically significant effect on recovery but recovery times were noticeably faster following SC flumazenil in hedgehogs sedated with T10. For hedgehogs immobilized with T10, mean food intake was greater when flumazenil was administered. Tiletamine-zolazepam provides an injectable option for immobilization of hedgehogs.     

Cancer‐testis antigens in canine histiocytic sarcoma and other malignancies

Cancer‐testis antigens (CTAs) are a category of self proteins aberrantly expressed in diverse malignancies, mostly solid tumours, due to epigenetic de‐repression. Normally expressed only in fetal or gametogenic tissues, CTAs are tantalizing immunotherapy targets, since autoimmunity risks appear minimal. Few prevalent CTAs have been identified in human hematologic cancers, and just two in their veterinary counterparts. We sought to discover new CTAs in canine hematologic cancers such as histiocytic sarcoma (HS) and lymphoma to foster immunotherapy development. To accomplish this, the ligandome binding the dog leukocyte antigen (DLA)‐88*508:01 class I allele overexpressed in an HS line was searched by mass spectrometry to identify possible CTA‐derived peptides, which could serve as CD8+ T‐cell epitopes. Twenty‐two peptides mapped to 5 human CTAs and 12 additional proteins with CTA characteristics. Expression of five promising candidates was then evaluated in tumour and normal tissue by quantitative and end‐point RT‐PCR. The ortholog of an established CTA, IGF2BP3, had unexpectedly high expression in peripheral blood mononuclear cells (PBMCs). Four other testis‐enhanced proteins were also assessed. AKR1E2, SPECC1 and TPX2 were expressed variably in HS and T‐cell lymphoma biopsies, but also at high levels in critical tissues, including kidney, brain and marrow, diminishing their utility. A more tissue‐restricted candidate, NT5C1B, was detected in T‐cell lymphomas, but also at low levels in some normal dog tissues. These results illustrate the feasibility of discovering canine CTAs by a reverse approach, proceeding from identification of MHC class I‐presented peptides to a comparative RNA expression survey of tumours and normal tissues.     

Evaluation of the drug sensitivity and expression of 16 drug resistance-related genes in canine histiocytic sarcoma cell lines

Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocytic cell lineages. This disease is characterized by poor response to chemotherapy and short survival time. Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS. The objectives of this study were to examine the drug sensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expression levels of 16 genes related to drug resistance in 4 canine HS cell lines established from dogs with disseminated HS were determined and compared to 2 canine lymphoma cell lines (B-cell and T-cell). These 4 canine HS cell lines showed sensitivities toward microtubule inhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canine B-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used in this study did not have enough function to efflux its substrate. Sensitivities to melphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower in the 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in this study using cultured cell lines could prove helpful in the developing of advanced and effective chemotherapies for treating dogs that are suffering from HS.     

Successful use of prednisolone and radiation therapy in a dog with intracranial histiocytic sarcoma

The ideal treatment for intracranial histiocytic sarcoma (HS) remains unclear. Herein, we report a case of intracranial HS that was successfully treated using prednisolone and radiation therapy. The patient was a 9-year-old spayed female Pembroke Welsh Corgi that presented with epileptic seizures. Magnetic resonance imaging revealed a contrast-enhancing mass adjacent to the right piriform lobe. Prednisolone administration (1 mg/kg/day) decreased the lesion size. Additional palliative radiation therapy (total dose, 37 Gy) resulted in complete disappearance of the lesion. However, on day 164, the dog’s neurological signs deteriorated, and she was euthanized. Necropsy revealed an intracranial metastasis of HS via the cerebrospinal fluid without any extracranial metastasis. Nonetheless, combined prednisolone and radiation therapy might be effective in treating intracranial HS.     

Clinical outcome,PDGFRβ and KIT expression in feline histiocytic disorders: a multicentre study

Information about histiocytic disease in cats is limited. The aim of this study was to document clinical findings and outcome in feline histiocytic disorders, and characterize the expression of PDGFRβ and KIT in order to identify potential treatment targets. Morphologically diagnosed feline histiocytic tumours were reviewed and characterized by immunohistochemistry (IHC). Five cases of feline progressive histiocytosis (FPH), eight histiocytic sarcomas (HS) and two haemophagocytic histiocytic sarcomas (HaeHS) were confirmed. PDGFRβ was variably positive in most histiocytic cases, while KIT was negative in all. Clinical presentation, treatment and outcome were also evaluated. Partial responses were recorded in measurable disease with tyrosine kinase inhibitors and lomustine, and radiotherapy achieved long‐term control in some cases. Survival times were shortest in HaeHS and disseminated disease. PDGFRβ, but not KIT, may represent a therapeutic target in feline histiocytic disorders but more studies are needed to investigate other potential treatment targets.     

Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target EPHA2

Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS.     

Prevalence,number and morphological types of multinucleated histiocytic giant cells in equine inflammatory dermatoses: A retrospective light microscopic study of skin‐biopsy specimens from 362 horses

Reasons for performing study: Multinucleated histiocytic giant cells (MHGC) are seen frequently in skin‐biopsy specimens from horses with inflammatory dermatoses. However, the prevalence, number and morphological types of these cells have not been reported. Objective: To determine the prevalence, number and morphological types of MHGC in equine inflammatory dermatoses, and the association of these cells with specific conditions. Methods: Skin‐biopsy specimens from 335 horses with inflammatory dermatoses and from 27 horses with normal skin were evaluated for the prevalence, number and morphological types of MHGC. Results: The prevalence and number of MHGC were greater in granulomatous dermatoses than in nongranulomatous dermatoses. Infectious and noninfectious dermatoses were not different in terms of prevalence or morphological types of MHGC. Foreign‐body MHGC were the predominant type in almost all cases. MHGC were not seen in normal skin. Conclusions: MHGC are seen in a wide variety of equine inflammatory dermatoses, especially those that are granulomatous. Number and morphological types of MHGC are of no apparent diagnostic significance. Potential relevance: MHGC are frequently present in a wide variety of inflammatory dermatoses in the horse. Because the prevalence, number and morphological types of MHGC are of minimal diagnostic significance, special stains and tissue cultures are necessary to confirm specific diagnoses.