Cutaneous Histiocytosis in an Eastern Gray Squirrel (Sciurus carolinensis).

A free-ranging Eastern gray squirrel (Sciurus carolinensis) was presented for ulcerated cutaneous masses at the base of both pinnae in July 2021. Diagnosis of cutaneous histiocytosis was achieved by histologic and immunohistochemical examination of one excised mass and supported by spontaneous resolution of the contralateral mass before the squirrel's release.

Feline progressive histiocytosis: a retrospective investigation of 26 cases and preliminary study of Ki67 as a prognostic marker.

Feline progressive histiocytosis (FPH) is an uncommon and infrequently reported cutaneous histiocytic proliferative disorder, whose clinical presentation is solitary or multiple cutaneous nodules and papules, with late-course internal metastasis. We describe herein the clinical, epidemiologic, histologic, and immunohistochemical features of this entity, and document the outcome of FPH based on a retrospective study of 26 cases. Female and male cats were affected equally. Lesions were evident either as solitary (16 of 26 cases) or multiple (10 of 26 cases) nonpruritic and alopecic nodules or plaques, preferentially located on the legs and extremities (73%). Follow-up was complete for 19 cats, and ranged from 41 to 1,449 d. Nine died of FPH with a median overall survival of 96 d (range: 41-238 d). The disease recurred in 14 cats after surgical excision of the nodules, and the median disease-free survival was 175 d (range: 21-1,449 d). Five of the 26 cats were alive at the end of the study, and 4 had no progression of the disease. Histologically, lesions were characterized by poorly circumscribed, unencapsulated histiocytic infiltration of dermis and subcutis. Epitheliotropism was observed in 11 (42%) cats. Atypical histiocytes diffusely and consistently expressed MHC II, CD18, and Iba1. Statistically significant higher E-cadherin expression was observed in epitheliotropic cases compared to non-epitheliotropic cases. A negative correlation between overall survival and proliferation index was evident, thus suggesting Ki67 as a promising prognostic marker.

Atypical Histiocytosis in Red Squirrels (Sciurus vulgaris).

Four red squirrels (Sciurus vulgaris) were subjected to necropsy examination over a 3-year period as part of a broader surveillance study. The squirrels presented with cutaneous, subcutaneous and/or internal swellings and nodules that consisted microscopically of sheets of atypical round cells and multinucleated giant cells. There was moderate anisokaryosis with rare mitoses. Nuclei ranged from oval to indented or C-shaped and some were bizarre, twisted or multilobulated. Many giant cells also had a bizarre morphology, with anisokaryosis within individual cells. Giant cell nuclei were often multilobulated, ring-shaped or segmented. Affected internal organs varied depending on the squirrel, but included lymph node, kidney, intestinal tract and lungs. Representative lesions from each of the four squirrels were negative for acid-fast organisms. Formalin-fixed tissues from all four squirrels and ethanol-fixed tissue from one animal were negative for Mycobacterium by polymerase chain reaction. Immunohistochemically, the majority of mononuclear and multinucleated giant cells in all four squirrels strongly expressed vimentin and class II molecules of the major histocompatibility complex. Otherwise, the atypical mononuclear and multinucleated cells were negative for CD3, Pax-5, Mac387, CD18 and E-cadherin. Based on the combination of cellular morphology, arrangement and immunophenotype, a novel form of atypical histiocytosis is considered most likely in these squirrels, although the exact origin and triggering factors remain uncertain.

Multiple Histiocytic Foam Cell Nodules in the Tongue of Miniature Dachshund Dogs.

Miniature dachshund dogs are a common breed in Japan and are known to be predisposed to granulomatous diseases. Here we report the pathologic features of multiple lingual nodules in 7 miniature dachshunds. Seven dogs had multiple nodules of variable sizes mainly on the ventral and lateral surface of the tongue. In addition, 1 dog also had masses on the left oral mucosa. Three cases had recurrence after surgical resection. Histologically, the lingual nodules were composed of aggregates of foam cells with clear vacuolated cytoplasm that were negative for oil red O, PAS, and alcian blue. They stained positively for CD204 (macrophage scavenger receptor) and MHC class II and negatively for Iba-1, E-cadherin, adipophilin, cytokeratins, S-100, and nestin. These findings indicate that the multiple lingual nodules in miniature dachshunds are an unusual, unique lesion consisting of macrophage-derived foam cells, which does not correspond to canine lingual diseases reported to date.

A review of histiocytic diseases of dogs and cats.

Histiocytic proliferative disorders are commonly observed in dogs and less often cats. Histiocytic disorders occur in most of the dendritic cell (DC) lineages. Canine cutaneous histiocytoma originates from Langerhans cells (LCs) indicated by expression of CD1a, CD11c/CD18, and E-cadherin. When histiocytomas occur as multiple lesions in skin with optional metastasis to lymph nodes and internal organs, the disease resembles cutaneous Langerhans cell histiocytosis of humans. Langerhans cell disorders do not occur in feline skin. Feline pulmonary LCH has been recognized as a cause of respiratory failure due to diffuse pulmonary infiltration by histiocytes, which express CD18 and E-cadherin and contain Birbeck's granules. In dogs and cats, histiocytic sarcomas (HS) arise from interstitial DCs that occur in most tissues of the body. Histiocytic sarcomas begin as localized lesions, which rapidly disseminate to many organs. Primary sites include spleen, lung, skin, brain (meninges), lymph node, bone marrow, and synovial tissues of limbs. An indolent form of localized HS, progressive histiocytosis, originates in the skin of cats. Hemophagocytic HS originates in splenic red pulp and bone marrow macrophages in dogs and cats. In dogs, histiocytes in hemophagocytic HS express CD11d/CD18, which is a leuko-integrin highly expressed by macrophages in splenic red pulp and bone marrow. Canine reactive histiocytic diseases, systemic histiocytosis (SH) and cutaneous histiocytosis, are complex inflammatory diseases with underlying immune dysregulation. The lesions are dominated by activated interstitial DCs and lymphocytes, which invade vessel walls and extend as vasocentric infiltrates in skin, lymph nodes, and internal organs (SH).

Multicentric histiocytosis related to avian leukosis virus subgroup J (ALV-J)-infection in meat-type local chickens.

Gross lesions characterized by swollen livers and spleens accompanied by diffuse white miliary spots, which resembled those of Marek's disease, were detected in two flocks of local meat-type chickens at a Japanese poultry processing plant in June and August 2010. The microscopic examinations revealed proliferative foci consisting of spindle or polymorphic cells in the interstitium of livers, splenic follicles and the interstitium of kidneys. These cells were positive immunohistochemically with Iba1 antibody, indicating they were histiocytic cells. Some of them contained antigens of avian leukosis virus (ALV) by immunohistochemistry,and the env gene of ALV subgroup J was detected from the spleens by polymerase chain reaction (PCR). Phylogenetic analysis of the PCR product indicated that the env gene might be descended from the American ADOL-7501 strain of ALV-J. These results suggest that the swollen livers and spleens of the meat-type chickens may come from histiocytic proliferation caused by ALV-J infection.

Diagnostic exercise: Multiple skin nodules in a cat.

A 10-year-old, neutered, male, domestic short-haired cat had numerous, small, firm, round, red, nonpruritic, nonpainful, dermal nodules 5-16 mm in diameter that ruptured within 48 hours of their appearance and subsequently crusted over. The masses were located in all regions of the body. One mass was excised from the dorsal right carpus and examined histologically, and 2 masses from the interscapular region were cultured for bacteria. The excised dermal mass from the carpus effaced normal dermal architecture, pressed tightly against the epidermis, and was composed of tightly packed round to polyhedral cells that extended to the deep margins of the sections. The overlying epidermis was extensively ulcerated and vesiculated with intraepidermal nests of cells identical to those in the dermis. There was marked anisokaryosis in the deeper regions of the mass with numerous multinucleated cells and cells with giant bizarre nuclei. The histological appearance and CD18 immunocytochemical staining of this mass are consistent with a diagnosis of feline progressive epitheliotropic dendritic cell histiocytosis.

Reactive histiocytosis of the orbit and posterior segment in a dog.

We present a case of reactive histiocytic disease involving the orbit, optic nerve, retina, and choroid in a Border Collie dog initially presenting for vision loss. Long-term partial return of vision has been achieved with systemic immunosuppression. Anterior segment and ocular surface manifestations of reactive histiocytic disease in dogs are relatively common. Posterior segment and orbital involvement, however, are minimally documented in the existing literature. To the authors' knowledge, this is the first report of disease confined to the orbit and posterior segment as well as the first report of vision loss as a presenting complaint for reactive histiocytic disease. Clinical, magnetic resonance imaging, cytologic, and histopathologic findings are reviewed.

Multifocal cutaneous histiocytic sarcoma in a young dog and review of histiocytic cell immunophenotyping.

A 9-month-old male Great Dane had progressive generalized nodular dermatopathy for several months. There were > 100 raised, alopecic, firm, painful nodules throughout the skin. Aspirates from several lesions yielded moderate numbers of irregularly round or polygonal to spindle-shaped cells with mild to moderate anisocytosis and few inflammatory cells, and the cytologic interpretation was proliferation of mesenchymal or histiocytic cells. On histopathologic examination, nodules were composed of densely packed sheets of round to spindle-shaped cells with mild anisokaryosis and low mitotic activity. Multifocal histiocytic sarcoma with a spindle-cell pattern was diagnosed based on morphologic features and intense expression of CD18. Additional immunophenotypic analysis on frozen sections of tissue confirmed the diagnosis of histiocytic sarcoma; expression of CD18, CD45, CD1a, CD11b, and CD11c, limited expression of Thy-1 (CD90) and CD80, and lack of expression of CD4, CD11d, and CD86 indicated that the cells were likely interstitial dendritic cells; a review of reactive and neoplastic dendritic cells is provided. Based on staging, internal organs were not affected. Sequential treatment with lomustine and doxorubicin failed to prevent progression of the cutaneous lesions, and the dog died 3 months after initial diagnosis. At necropsy, a focus of neoplastic cells was present in one lymph node, but except for skin other organs were not involved. The clinical presentation of histiocytic sarcoma may be unusual, and neoplastic cells may lack overt features of malignancy on cytologic and histopathologic examination. In some instances, immunophenotyping is required to differentiate histiocytic sarcoma from other histiocytic disorders.

Slowly progressive lymphohistiocytic meningoencephalomyelitis in 21 adult cats presenting with peculiar neurological signs.

Twenty-one cats presented with a history of slowly progressive neurological signs characterised by a stiff extended tail, behavioural changes, and spastic and ataxic gait. All cats had outdoor access and lived in the same geographical rural area in north-east Scotland. Histological findings were consistent with lymphohistiocytic meningoencephalomyelitis. Immunohistochemistry ruled out 15 pathogens and showed a significant expression of the interferon-inducible Mx protein, suggesting an as yet unidentified infective or environmental immunogenic trigger as the possible causative agent. The late age at onset (mean 9 years), the very slow progression of clinical signs (mean 11 months) and the peculiar clinical presentation (particularly the posture of the tail) have not been reported previously in cats with lymphohistiocytic meningoencephalomyelitis.

Sublingual reactive histiocytosis in a dog.

Lingual lesions are relatively uncommon in dogs and are mostly represented by neoplasms and glossitis secondary to trauma or infections. Reactive histiocytosis is an uncommon, poorly understood, reactive disorder characterized by proliferation of activated, interstitial, dendritic, antigen-presenting cells associated with lymphocytes and neutrophils with a specific angiocentric orientation and occasional angioinvasion and angiodestruction. Clinically, the disease has a waxing and waning behavior with possible response to treatment and regression, or progression to multiple lesions and internal organ involvement. This case report describes an unusual sublingual presentation of reactive histiocytosis in a Miniature Pinscher dog. The diagnosis was obtained by clinical and histopathological exclusion of other causes, detection of the characteristic microscopic growth pattern, and by immunocytochemistry. Histiocytic cells were vimentin, CD18, CD11c, and CD1c positive consistent with a dendritic cell origin. Anti-BCG stain (Bacillus Calmette and Guerin) was negative for etiological agents. The dog was treated with oral administration of tetracycline and niacinamide during an 8-month period. There was no indication of recurrence of the sublingual mass 2-years following treatment.

[Reactive and neoplastic histiocytic diseases in the dog]. / Reaktive und neoplastische histiozytäre erkrankungen beim hund.

There are different histiocytic diseases in dogs that are characterized by the proliferation of histiocytic cells (macrophages and myeloid dendritic cells). Histiocytic diseases can be devided into neoplastic (cutaneous histiocytoma complex, histiocytic sarcoma, dendritic cell leukaemia) and reactive forms (reactive histiocytosis, haemophagocytic syndrome). All subtypes of the cutaneous histiocytoma complex (cutaneous histiocytoma, metastatic histiocytoma and Langerhans' cell histiocytosis) are of Langerhans' cell origin. Histiocytoma, which is a solitary tumour of the skin in young dogs, shows spontaneous regression in most cases. Occasionally, metastasis to lymph nodes can be seen (metastatic histiocytoma). Only one dog with Langerhans' cell histiocytosis has been described and was euthanized. Histiocytic sarcoma, which arises from myeloid dendritic cells, can be classified as localised histiocytic sarcoma or disseminated histiocytic sarcoma. Another form of histiocytic sarcoma - haemophagocytic histiocytic sarcoma - is derived from macrophages. Histiocytic sarcoma displays a very aggressive clinical course and has a poor prognosis. Breed predispositions have been reported for the disseminated and haemophagocytic form of histiocytic sarcoma in Bernese mountain dogs, Rottweilers and varoiusretrievers. In contrast, reactive histiocytosis (cutaneous and systemic forms) develops by reactive proliferation of interstitial dendritic cells. In systemic histiocytosis, breed predilections are similar to histiocytic sarcoma. Haemophagocytic syndrome develops as a consequence of proliferation of activated macrophages in different tissues. Prognosis in general is moderate to poor and depends on the origin of the underlying disease process.

Association of West Nile virus with lymphohistiocytic proliferative cutaneous lesions in American alligators (Alligator mississippiensis) detected by RT-PCR.

West Nile virus (WNV) is known to affect captive populations of alligators and, in some instances, cause significant mortalities. Alligators have been shown to amplify the virus, serve as a reservoir host, and even represent a source of infection for humans. This study describes a cutaneous manifestation of WNV in captive-reared American alligators (Alligator mississippiensis), previously described as lymphohistiocytic proliferative syndrome of alligators (LPSA), based on the findings of gross examination, histopathologic evaluation, WNV antibody testing, and WNV reverse transcriptase polymerase chain reaction (RT-PCR). Forty alligators with LPSA and 41 controls were examined. There was a significant difference (P = 0.01(-21)) in the WNV serostatus between the treatment group (100%) and the control group (0%, 95% CI: 0-7.3%). In the treatment group, 97.5% (39/40) (95% CI: 92.7-102.3%) of the LPSA skin lesions were positive for WNV via RT-PCR. Of the skin sections within the treatment group that had no LPSA lesions, 7.5% (3/40) (95% CI: 0-15.7%) were positive for WNV. In the control group, all of the skin samples were negative for WNV (41/41) (0%; 95% CI: 0-7.3%). The LPSA skin lesions were significantly more likely to be WNV positive by RT-PCR when compared to control animals (P = 0.07(-20)) and normal skin sections from affected animals (P = 0.08(-16)). There was no significant difference in the WNV RT-PCR results between control animals and normal skin sections from affected animals (P = 0.24). These findings suggest that LPSA is a cutaneous manifestation of WNV in alligators.

Canine histiocytic diseases.

Canine histiocytic diseases are an emerging spectrum of diseases characterized by proliferations of histiocytic cells. Nonneoplastic histiocytic disease (reactive histiocytosis, comprising cutaneous and systemic histiocytosis) is uncommon. Neoplastic histiocytic diseases include cutaneous histiocytoma, which is a benign histiocytic tumor, and localized and disseminated histiocytic sarcoma (previously known as malignant histiocytosis), which are malignant diseases. The differentiation of histiocytic diseases can be challenging. This article outlines the characteristics of each disease entity and details the clinicopathologic, histologic, immunohistochemical, prognostic, and therapeutic differences among them.

Cutaneous reactive histiocytosis in dogs: a retrospective evaluation of 32 cases.

Thirty-two cases of canine cutaneous histiocytosis were retrospectively evaluated. Median age at onset was 4 years. Lesions included nodules and plaques affecting the head/face, trunk and limbs, and erythema, swelling and depigmentation of the nasal planum/nares. Systemic involvement was not ruled out in all cases. All dogs had complete resolution of dermatological lesions after initial treatment (median 45 days). Initial treatment included prednisone +/- antibiotics (12 of 32 dogs), prednisone and tetracycline/niacinamide (four of 32), prednisone and azathioprine (three of 32), tetracycline/niacinamide +/- vitamin E/essential fatty acids (six of 32), antibiotics +/- antihistamines (three of 32), cyclosporine and ketoconazole (one of 32), topical therapy (two of 32), and no treatment (one of 32). Seventeen dogs received maintenance therapy which consisted of tetracycline/niacinamide +/- vitamin E/essential fatty acids (12 of 17), cyclosporine/ketoconazole (two to three times a week) (two of 17), azathioprine daily (one of 17), prednisone/azathioprine (two times a week) (one of 17), and prednisone daily (one of 17). Median follow up was 25 months. Nine dogs had a recurrence of cutaneous histiocytosis (median days to recurrence 130 days), with seven of nine having more than one recurrence. At study completion, six dogs were deceased (no lesions at the time of death) and 26 of 32 were alive with no lesions. Ten of 26 dogs were on maintenance treatment (eight tetracycline/niacinamide, one azathioprine, one vitamin E). Previous dermatological disease and season had no detectable influence on recurrence. Recurrence was significantly more likely in dogs with nasal planum/nares lesions than dogs without these lesions. Tetracycline/niacinamide was an effective treatment option for dogs in this study population.

Nódulos fibro-histiocíticos no baço de uma cadela: relato de caso / Splenic fibroistiocytic nodules in a bitch: case report

Descreve-se a ocorrência de múltiplos nódulos fibro-histiocíticos no baço de uma cadela Rottweiler, de sete anos. O diagnóstico foi feito por histopatologia e confirmado por imunoistoquímica positiva para ED1, CD18, vimentina e lisozima. O animal foi sacrificado três meses após o diagnóstico, por severo agravamento dos sinais clínicos.

Multiple fibrohistiocytic nodules in the spleen of a 7-year-old female Rottweiler were reported. The diagnosis was made by histology and immunohistochemistry; cells were positive for ED1, CD18, vimentin and lysozyme. The dog was euthanatized three months after the tumor was diagnosed, due to severe clinical signs.

Plasma vascular endothelial growth factor (VEGF) measured in seventy dogs with spontaneously occurring tumours.

BACKGROUND: Vascular endothelial growth factor (VEGF) acts specifically on endothelial cells mediating tumour neovascularisation and initiating tumour growth and metastasis. In humans, high VEGF levels are correlated with poorer prognosis but in dogs minimal information on plasma VEGF is available. Therefore, we analysed plasma VEGF in a variety of spontaneous canine tumours. MATERIALS AND METHODS: Plasma from seventy dogs with various spontaneous tumours was taken prior to radiation therapy. A human VEGF ELISA was used for analysis. RESULTS: Mean plasma VEGF was 7.2+/-7.8 pg/ml. Mean plasma VEGF level varied among different tumour types with the highest level in oral melanomas (12.4 pg/ml). In patients with sarcomas of soft tissue or bone origin, plasma VEGF levels increased significantly with decreasing haemoglobin concentration (p =0.013). CONCLUSION: Canine plasma VEGF levels depend on tumour histology, with higher levels found in more aggressive tumours. The negative correlation between plasma VEGF and haemoglobin (hb) is most probably due to tissue hypoxia seen in anaemic animals.

Flow cytometric evaluation of hemophagocytic disorders in canine.

BACKGROUND: Hemophagocytic macrophages in canine bone marrow are observed in malignant histiocytosis as well as benign hemophagocytic histiocytosis. Cytomorphologic evaluation alone may be inadequate to consistently differentiate between benign and malignant forms of hemophagocytic disorders. OBJECTIVE: The purpose of this study was to evaluate the ability of flow cytometry and immunophenotyping to differentiate between benign and malignant types of hemophagocytic disorders in dogs. METHODS: Blood smears and bone marrow differential cell counts were evaluated for 10 dogs with hemophagocytic disorders. Bone marrow samples were labeled with monoclonal antibodies to CD18, MCH class-II, Thy-1, CD14, CD3, and CD21. Using flow cytometry, forward-angle versus side-angle light scatter plots were analyzed and immunophenotypes were determined. RESULTS: Scatter plots from 3 dogs with a necropsy diagnosis of malignant histiocytosis revealed 2 atypical cell clusters. One cluster contained cells of similar size or larger than immature myeloid cells and metamyelocytes. Cells in the other cluster were highly granular, with granularity similar to or greater than that of metamyelocytes. In bone marrow from dogs with malignant histiocytosis that was labeled with anti-CD14 antibody, macrophages represented 29-48% of nucleated cells. Seven dogs had a clinical or histopathologic diagnosis of benign hemophagocytic syndrome. Three of the dogs had normal cell distribution in scatter plots. Two dogs had 2 abnormal cell clusters: 1 within the immature myeloid and metamyelocyte gates and the other with granularity similar to or greater than that of metamyelocytes. The remaining 2 dogs had an atypical cell population, mostly within the immature myeloid gate. For dogs with benign hemophagocytic syndromes, 6-17% of cells in the bone marrow were CD14 positive. CONCLUSIONS: The cellular distribution in scatter plots and the total number of macrophages in bone marrow may be useful in differentiating malignant histiocytosis from benign hemophagocytic syndromes in dogs.

Detection of Akabane viral antigens in spontaneous lymphohistiocytic encephalomyelitis in cattle.

A 5-month-old Japanese black bull calf and twenty-seven 1-27-day-old calves exhibiting neurological signs between August and October 1998 were examined. The bull calf exhibited rapid breathing, fever, hypersensitivity, and ataxia and was euthanized 4 days after the onset of symptoms. The 27 calves primarily exhibited ataxia, and 15 had arthrogryposis. Histological examination of the bull calf revealed perivascular infiltraction by mononuclear cells, diffuse to multifocal gliosis, and neuronal necrosis in the brain and spinal cord. Multiple malacic foci were found in the midbrain in 5 cases. In contrast, in the 15 calves necropsied in October, there were fewer inflammatory changes, but there was neuronal cell loss in the ventral horn and a decrease in myelinated axons in the lateral and ventral funiculi. Immunohistochemical examination using a rabbit antiserum against Akabane virus strain OBE-1 revealed a large amount of viral antigen in the degenerating neurons and glial cells of the bull calf, mainly in the spinal gray matter. Small amounts of viral antigen in swollen axons and a few glial cells were found in 5 of 27 calves. Thirteen of the 27 calves had high neutralization antibody titers against the Akabane virus, whereas there was no significant antibody titer in most of the calves necropsied during August. The present study revealed that viral antigen detection was very useful for the diagnosis of Akabane diseases in the 5-month-old bull calf that was suspected to be infected postnatally, while it had limited usefulness in the other young calves.

Cutaneous T cell lymphoma mimicking cutaneous histiocytosis: differentiation by flow cytometry.

A two-year-old, neutered female cross-bred labrador had multiple cutaneous nodules, biopsies of which revealed pathological changes consistent with cutaneous histiocytosis. During a period of one month the dog developed multicentric lymphadenopathy, a retrobulbar mass and masses within the quadriceps and cervical muscles. Fine needle aspiration cytology of the cutaneous nodules and lymph nodes and histological examination of the cutaneous nodules and muscle masses suggested the presence of lymphoblastic lymphoma. A definitive diagnosis of CD8+ T cell lymphoma was achieved by immunophenotyping the tumour cells by flow cytometry.