VETcpd - Oncology Peer Reviewed

Andrea Mosca DVM MRCVS Senior Clinical Training Canine histiocytoma, or Scholar (Oncology) Andrea graduated histiocytic sarcoma; what happens from the University of Milan in 2014. when go wrong? Shortly after, he moved to the Histiocytic diseases are a group of conditions that are commonly observed in UK and worked dogs and rarely in cats. They can be grouped as non-neoplastic and neoplastic, in a busy first malignant and non-malignant. Gathering pertinent information regarding diagnosis, opinion 24-hour prognosis and treatment can be challenging but is important, as treatment and hospital in North outcome vary widely depending on the final diagnosis. West London. He completed a one-year rotating Key words: Histiocytes, histiocytoma, histiocytosis, histiocytic sarcoma Internship at Dick White Referrals. After that, he worked as an Oncology Clinician at the University of Glasgow Introduction non-epitheliotropic lymphoma and in November 2017, Andrea started The term has been used to (neCTCL) can be very readily confused his residency in medical oncology at the generically describe cells of with cutaneous histiocytosis and University of Cambridge. or lineage which include immunophenotyping is often needed to Langerhans cells and interstitial confirm the diagnosis. Simon Tappin MA VetMB dendritic cells. Systemic histiocytosis is a diffuse and CertSAM DipECVIM-CA FRCVS • Langerhans cells reside within the basal proliferative disease of histiocytes. It Simon graduated layers of the skin, alimentary, respiratory mainly affects the cutaneous epithelium from the University and reproductive tract epithelium and are and ocular and nasal mucosa but can of Cambridge and specialised presenting cells. also lead to a generalised enlargement of after two years • Interstitial dendritic cells arise in the peripheral lymph nodes. It mainly in practice under affects young to middle aged dogs, with took a residency perivascular locations throughout the those between two and eight years most at the University body, with the exception of the brain commonly affected. The disease was of Bristol in Small tissue, although they may be found in the originally described in Bernese Mountain Animal Medicine meninges and choroid plexus. Dogs and polygenetic inheritance has and Intensive Care, Classification of histiocytic disease where he gained his European Diploma been documented (Padgett et al. 1995). depends on the origin and type of abnormal Systemic histiocytosis has been observed in Small Animal Medicine. He is histiocytes (Table 1). currently head of internal medicine and less commonly in other breeds such as the Rottweiler, Labrador Retriever, Basset a director of the internship program Non Neoplastic: Cutaneous at Dick White Referrals. Simon is an Hound and Irish Wolfhound (Affolter external advisor to Pet Blood Bank UK. and Systemic Histiocytosis and Moore 2000a). Overall, systemic E: [email protected] Cutaneous and systemic histiocytosis are histiocytosis is a rare disease and cutaneous reactive inflammatory histiocytic diseases. histiocytosis is far more common. The pathogenesis of both cutaneous and systemic histiocytosis is not known Neoplastic Non-malignant: and pathology is dominated by activated Histiocytoma and Cutaneous dermal interstitial dendritic cells and T cells, which frequently infiltrate the walls Histiocytosis of dermal vessels creating a lympho- Cutaneous histiocytomas originate histiocytic vasculitis, suggesting immune in cells that manifest Langerhans cells dysregulation. This is supported by a typi- differentiation. Histiocytomas typically cally good response to immunosuppressive occur as solitary lesions, which usually treatment, however as yet, the triggers for undergo spontaneous regression (Figure the disease are not understood. 1). They can occur in dogs of all ages but are more likely in young dogs (50% occur Cutaneous histiocytosis is an in dogs less than two years of age). inflammatory lympho-histiocytic proliferative disorder that primarily Multiple histiocytomas (i.e. cutaneous involves skin and subcutis. It is most Langerhans Cell Histiocytosis) occur in less commonly reported in middle-aged to than 1% of cases and are more common SUBSCRIBE TO VETCPD JOURNAL older dogs, but no clear breed or sex in Shar Peis. The existence of multiple predispositions are defined. The disease histiocytomas, at the same or distant sites Call us on 01225 445561 may spread to involve the local lymph is uncommon, however occasionally this or visit www.vetcpd.co.uk nodes, which are part of the cutaneous occurs and leads to extensive involvement . Inflamed cutaneous of the skin. This is classified as cutaneous

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Langerhans Cell Histiocytosis (cLCH) which can be limited to the skin or go Table 1: Classification of canine histiocytic disease on to become a multi-system disease. This spectrum is also well documented in man. DISEASE ORIGIN Non Neoplastic Cutaneous and Activated interstitial Neoplastic Malignant: systemic histiocytosis dendritic cells Histiocytic Sarcoma Complex Histiocytic sarcoma (HS) can be generally Neoplastic Cutaneous histiocytoma and Epithelial dendritic cells: divided into localised or disseminated Non-malignant cutaneous Langerhans cell Langerhans cells histiocytic sarcomas. histiocytosis Localised histiocytic sarcoma develops Neoplastic Histiocytic sarcoma complex Interdigitating dendritic cells in from a single site, or, once the lesion Malignant lymphoid tissues, perivascular spreads beyond the local draining interstitial dendritic cells in lymph node, the disease is considered a other involved tissues, and disseminated canine histiocytic sarcoma. This was first described as of Bernese Mountain Dogs (Moore and Affolter 2005). Rottweilers, A Golden Retrievers, Flat-Coated Retrievers, and Miniature Schnauzers are also predisposed to histiocytic sarcoma complex diseases (Lenz et al. 2017). Disseminated histiocytic sarcoma is an aggressive disease characterised by the presence of multiple neoplastic masses in several organ systems. Primary sites are spleen, lung and (Figure 2). Secondary lesions may be B observed in lymph nodes and liver, and subsequently any other organs can be affected. The cellular origin of canine histiocytic sarcomas is largely unknown, however cancer cells are most often derived from cells with the phenotypic profile of interstitial dendritic cells and macrophages. Figure 2: Right lateral thoracic radiograph of a six year old male neutered Flat Coat Retriever There are several presentations of Figure 1: A 3-year-old Welsh Springer Spaniel presented with dysponea, revealing multiple histiocytic sarcomas that deserve separate with a small histiocytoma under the left eye (A) mass lesions in the dorsocaudal lung fields. additional description because of particular this received no treatment and had resolved at Fine needle aspirates of these confirmed the clinical or clinicopathological associations a recheck three months later (B) presence of a histiocytic sarcoma that are often crucial to successful diagnosis: Hemophagocytic histiocytic sarcoma: Dogs with hemophagocytic histio- Peri-articular histiocytic sarcoma (Craig et al. 2002). Invasion of bone cytic sarcomas usually have a moderate to (PAHS) is a localised form of histiocytic can occur with advanced disease. Since marked, regenerative, haemolytic anaemia sarcoma, which occurs on the limbs. The skeletal lesions are observed in disseminated and thrombocytopenia. They often have lesions originate either within the joints histiocytic sarcoma in the same sites as mild hyperbilirubinemia without jaundice (intra-articular) and/or adjacent to the (localised) articular histiocytic sarcoma, it at initial presentation. Most dogs have joints (periarticular) of the appendicular is important to determine if the skeletal hypoalbuminemia and often hypocholes- skeleton. Peri-articular histiocytic sarcoma involvement is subsequent to a soft tissue terolaemia. This clinical picture is often is the most common tumour affecting mass originating near the synovial tissues confused with immune-mediated haemo- the joints of dogs. The stifle and elbow (Schultz et al. 2007). lytic anaemia and thrombocytopenia (Evans joint are most commonly affected, and Histiocytic sarcoma can affect the syndrome) despite a negative Coombs test lesions may occur in the coxo-femoral central nervous system (CNS) (this is because cellular destruction is cell joint and carpus. Prior joint disease (most and is most commonly found in the mediated rather than through antibody commonly cranial cruciate ligament leptomeninges. They can either occur at production). Dogs with hemophagocytic rupture) is associated with increased a primary site or secondary to metastasis histiocytic sarcomas have diffuse spleno- risk of periarticular histiocytic sarcoma of disseminated histiocytic sarcoma. In a megaly, and usually lack overt masses in in dogs in the tumour-affected joint case series of CNS histiocytic sarcoma, metastatic sites such as the liver and lungs. (Manor et al. 2017). More than half of Pembroke Welsh Corgis and Retrievers Hemophagocytic histiocytic sarcomas arise the dogs reported with peri-articular were over-represented (Mariani et al. from splenic red pulp macrophages. histiocytic sarcoma were Rottweilers 2015). The CNS lesions most commonly

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