Histiocytoma is a common, benign, cutaneous neoplasm in dogs. Histiocytomas usually occur as solitary lesions, which spontaneously regress, and seldom recur. They can occur in dogs of all ages, but are more likely in dogs under three years of histiocytoma images age. Epidermal invasion by cells of histiocytoma frequently occurs and intra-epidermal nests of histiocytes resemble Pautrier’s aggregates, characteristically found in epidermotropic lymphoma (Mycosis Fungoides or MF). Epidermal invasion in histiocytoma, or presence of simultaneous multiple histiocytomas, especially in aged dogs, can appear similar to MF or non-epidermotropic cutaneous lymphoma (NECL).
Multiple histiocytomas may look like cutaneous histiocytosis, although morphologically histiocytomas are consistently epidermotropic and commonly epidermally invasive, these are not features of cutaneous histiocytosis. Delayed regression of multiple histiocytomas can occur and lesions can histiocytoma images persist for up to 10 months.   Metastatic histiocytoma Edit
Recently, several cases of histiocytoma were observed in which histiocytes had histiocytoma images migrated to draining lymph nodes and completely obliterated them. Pathologists diagnosed histiocytic sarcoma in these instances and prognosis was histiocytoma images reported as poor. In 3 instances regression of these lesions occurred spontaneously within histiocytoma images 3–4 weeks. In other instances the metastatic lesions of histiocytoma failed to histiocytoma images regress and dogs were euthanized. The disease course in these cases extended over several months. Spread beyond lymph nodes to lung has also been observed histiocytoma images in some of these cases. These complications are rare.   Langerhans cell histiocytosis Edit
The presence of multiple histiocytomas is now a well recognized histiocytoma images syndrome. However, there is yet another presentation in which widespread cutaneous lesions histiocytoma images histologically identical to histiocytoma are observed. Clinically, the lesions are almost confluent in affected regions. Rapid internal spread is observed and the affected animals have histiocytoma images all been euthanized. There is one published account of such a case, and we have data on 3 dogs with what appears histiocytoma images to be an identical syndrome.  Immunophenotypic studies Edit
Immunohistochemistry (IHC) is best performed on frozen sections of tumor (not formalin fixed material!). Histiocytoma is readily distinguished from other histiocytic disorders and cutaneous histiocytoma images lymphoma with the aid of IHC. Our work has clearly shown that histiocytomas have the phenotype histiocytoma images of epidermal Langerhans cells. They express CD1a, CD1b, CD1c, MHC class II, CD11c, and E-cadherin. Amongst leukocytes, E-cadherin expression is unique to Langerhans cells. Langerhans cells utilize E-cadherin to localize in the epidermis via homotypic interaction with histiocytoma images E-cadherin expressed by keratinocytes. Histiocytomas lack expression of CD4 and Thy-1, which are consistently expressed by histiocytes in cutaneous and systemic histiocytoma images histiocytosis. Hence cutaneous histiocytoma is a localized epidermal Langerhans cell tumor, and the rare examples of systemic spread of histiocytoma are histiocytoma images best characterized as Langerhans cell histiocytosis (LCH) similar to that observed in humans.  
Systemic Histiocytosis (SH) was originally recognized in closely related Bernese Mountain Dogs. SH is a generalized histiocytic proliferative disease with a marked histiocytoma images tendency to involve skin, ocular and nasal mucosa, and peripheral lymph nodes. The disease predominately affects young to middle aged male dogs histiocytoma images (2–8 years), although cases in females have been observed. SH has been observed in other breeds less commonly (e.g. Irish Wolfhounds, Basset Hounds and others). Clinical signs vary with the severity and extent of the histiocytoma images disease and include anorexia, marked weight loss, stertorous respiration and conjunctivitis with marked chemosis. Multiple cutaneous nodules may be distributed over the entire body, but are especially prevalent in the scrotum, nasal apex, nasal planum and eyelids. Peripheral lymph nodes are often palpably enlarged. The disease course may be punctuated by remissions and relapses, which may occur spontaneously especially early in the disease course. In severe disease, lesions become persistent and do not respond to immunosuppressive doses histiocytoma images of corticosteroids.  
Cutaneous histiocytosis (CH) is a histiocytic proliferative disorder that primarily involves skin and histiocytoma images s ubcutis and does not extend beyond the local draining histiocytoma images lymph nodes. CH occurs in a number of breeds. Evidence of spread beyond the skin would invoke the diagnosis histiocytoma images of SH, a closely related disorder. Lymphadenopathy has not been emphasized in published reports, and has only been documented in a small number of histiocytoma images our cases. The lesions occur as multiple cutaneous and subcutaneous nodules up histiocytoma images to 4 cm diameter. They may disappear spontaneously, or regress and appear at new sites simultaneously. Topographically lesions may be found on the face, ears, nose, neck, trunk, extremities (including foot pads), perineum and scrotum.  
SH has proven to be a difficult and frustrating condition histiocytoma images to treat. Consequently, many of the early cases were euthanized. Originally we treated dogs with Thymosin (derived from bovine thymus) because of reports of its effectiveness in human LCH cases. Some dogs appeared to respond to this, but not consistently. The original rationale for using thymosin was that SH was histiocytoma images likely an immunoregulatory disorder and not cancer. In the majority of instances corticosteroid treatment is ineffective, although in some instances of CH (about 10% of cases), steroid administration is very effective in controlling lesions so steroids histiocytoma images are worth trying in this disease given the expense of histiocytoma images the alternatives. More recently we have had success with immuno-suppressive doses of Cyclosporin A or Leflunomide. These drugs are potent inhibitors of T cell activation and histiocytoma images their ability to abrogate clinical disease gives further support for histiocytoma images SH and CH being disorders of immune regulation. Treatment with these drugs is exorbitantly expensive and may be histiocytoma images needed for life in dogs with continuously active disease, which usually is the case in advanced SH. It is preferable not to invoke such powerful immuno-suppressive therapy in most cases of CH in which spontaneous histiocytoma images regression of lesions or episodic disease activation is more likely histiocytoma images to occur.  
The lesions of SH in most tissues consist of perivascular histiocytoma images infiltrates of large histiocytes and variable populations of lymphocytes, neutrophils and eosinophils. The histiocytes frequently invade vessel walls and this may lead histiocytoma images to vascular compromise and infarction of surrounding tissues. The widespread distribution of lesions of SH is only fully histiocytoma images appreciated at necropsy. Histiocytic lesions have been observed in skin, lung, liver, bone marrow, spleen, peripheral and visceral lymph nodes, kidneys, testes, orbital tissues, nasal mucosa and others.
In skin, the lesions of SH and CH are virtually identical – they consist of perivascular histiocytic infiltrates containing lymphocytes and other histiocytoma images inflammatory cells in variable proportions (neutrophils, plasma cells, and occasionally eosinophils). The lesions usually involve the deep dermis and subcutis. Involvement of the superficial dermis is inconsistent and epidermotropism of histiocytoma images the histiocytes is not observed. In CH the lesions are limited to the skin and histiocytoma images draining lymph nodes.  
The histiocytic sarcoma (HS) complex encompasses a number of distinctive clinical entities which will histiocytoma images be described below. Some definitions are in order, and reflect the preferred nomenclature of the writing group of histiocytoma images the Histiocyte Society. Histiocytic neoplasia which originates at a single site is called histiocytoma images histiocytic sarcoma. This form of histiocytic sarcoma, which is often encountered on the extremities, has the best prognosis if treated early by surgical excision histiocytoma images or by amputation of a limb. When spread to distant sites beyond the local lymph node histiocytoma images occurs, the disease is then termed disseminated histiocytic sarcoma; this is more likely to occur unnoticed when primary lesions histiocytoma images occur in cryptic sites (e.g. spleen, lung, and bone marrow). This latter form of HS is most like malignant histiocytosis histiocytoma images (MH). MH is an aggressive, histiocytic neoplasm which arises in multiple sites simultaneously. Most lesions previously defined as MH are probably more correctly histiocytoma images termed disseminated HS. The occurrence of true MH is difficult to establish because histiocytoma images the lesions often occur in cryptic sites, and the existence of histiocytic neoplasia is only recognized after histiocytoma images clinical signs have appeared and disease progression is advanced. HS and MH are capable of widespread metastasis, hence in time the 2 syndromes merge clinically and it histiocytoma images is not always possible to differentiate true multicentric origin (MH) from widespread metastasis of disseminated HS. Also, it is never possible to know exactly how long the histiocytoma images disease process has been operative. Hence, the perception is that both disseminated HS and MH follow histiocytoma images a rapid clinical progression despite therapeutic intervention. This is certainly true once clinical signs are apparent, but the subclinical period is of unknown duration. 
The HS complex of diseases is best recognized in the histiocytoma images Bernese Mountain Dog in which a familial association is apparent. Other breeds are predisposed to HS complex diseases and include histiocytoma images Rottweilers, Golden Retrievers, and Flat-coated Retrievers. Although HS complex is not limited to just these breeds histiocytoma images and can occur sporadically in any breed. Primary lesions of HS occur in spleen, lymph node, lung, bone marrow, skin and subcutis especially of extremities. Secondary sites are widespread, but consistently include liver and lung (with splenic primary), and hilar lymph node (with lung primary). Clinical signs include anorexia, weight loss, and lethargy. Other signs depend on the organs involved and are a histiocytoma images consequence of destructive mass formation. Accordingly, pulmonary symptoms such as cough and dyspnea have been seen. CNS involvement (primary or secondary) can lead to seizures, incoordination and paralysis. Regenerative and non-regenerative anemia have been consistently documented in hemophagocytic HS. Lameness is often observed in periarticular HS.  
Localized HS affecting skin and subcutis have been cured by histiocytoma images early surgical excision. In the case of periarticular HS which occurs in the histiocytoma images subsynovial tissues of the extremities, amputation of the affected limb is enforced by the inoperable histiocytoma images nature of the primary lesion which ensnares structures vital to histiocytoma images limb function. Disseminated HS (including MH) is not readily treated surgically, since even in the splenic form, early metastasis to the liver has often occurred. Response to chemotherapy has been at best brief, and the disease progresses rapidly (weeks to months) to death or euthanasia.  
Gross appearance. Lesions of HS are typically destructive mass lesions with a histiocytoma images uniform, smooth cut surface and are white/cream to tan in color. Lesions have a soft consistency and may contain discolored areas histiocytoma images (typically yellow) which indicate area of necrosis, which can be extensive. Lesions can be solitary or multiple within an organ (especially spleen). Periarticular HS has a distinctive appearance: it occurs as multiple tan nodules located in the subsynovium. These lesions may encircle the affected joint. Hemophagocytic HS does not initially form mass lesions in the histiocytoma images primary sites (spleen and bone marrow). Typically, diffuse splenomegaly is observed; the cut surface is dark red and the consistency is histiocytoma images firm. The liver is usually bile stained (jaundice) and disruption of the lobular pattern due to metastasis is histiocytoma images observed – marked liver involvement can occur before destructive masses are noticeable.  
MH and HS lesions express leukocyte surface molecules characteristic of histiocytoma images DC (CD1, CD11c and MHC II). Diffuse expression of E cadherin, Thy-1 and CD4 has not been observed in HS or histiocytoma images MH in skin or other sites; this together with cytomorphology assists in the distinction of MH histiocytoma images and HS from histiocytoma and reactive histiocytosis (such as cutaneous and systemic histiocytosis). In histiocytoma, the phenotype is quite similar to that of HS except histiocytoma images for the expression of E-cadherin which occurs in histiocytoma especially in the cellular infiltrate histiocytoma images immediately adjacent to the epidermis. In reactive histiocytosis, infiltration and proliferation of activated interstitial (dermal) DC which consistently express CD4 and Thy-1 occurs. In hemophagocytic HS, histiocytes express CD11d instead of CD11c, and MHC II. Expression of CD1 molecules is uniformly low or occasionally moderate histiocytoma images but with a patchy distribution. This phenotype is consistent with macrophage differentiation rather than DC histiocytoma images differentiation in which abundant expression of CD1 and CD11c is histiocytoma images expected.
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