Page 816 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

794 PART IV Specific Malignancies in the Small Animal Patient

not regress in about half of cases and dogs are euthanized due to time. In 32 dogs with complete resolution of their lesions, 17 were
complications related to extensive ulcerated skin lesions. Attempts maintained on a variety of medications including 12 with tetracy-
cline/niacinamide either alone (n = 7) or in various combinations
to treat diffuse cutaneous LCH are rarely reported, but there is
VetBooks.ir one report of a complete but temporary response to lomustine with safflower oil, essential fatty, or vitamin E. 518 Other main-
In addition,
tenance therapies included cyclosporine/ketoconazole, azathio-
(CCNU) in a dog with diffuse cutaneous LCH.
515
there is one report of a complete response to griseofulvin treat- prine alone, prednisone and azathioprine, or prednisone alone.
ment in an 8-month-old puppy with diffuse cutaneous LCH. 516 Immunosuppressive agents such as leflunomide and cyclosporine
Dogs with solitary lesions, but with metastasis to an LN, may have A/ketoconazole and azathioprine may demonstrate efficacy in ste-
a better prognosis. A study reported on eight dogs with a solitary roid refractory cases.
cutaneous histiocytoma and LN metastasis treated with surgery SH is similar to cutaneous histiocytosis in its IHC staining
alone. Outcomes were excellent, with most alive 1 to 4 years after pattern and cell of origin, the activated interstitial DC. The dis-
diagnosis. 517 Cases of diffuse LCH with rapid progression to LN tinguishing feature is involvement of nonskin organs. The Ber-
and internal organ involvement appear to have a poorer prognosis nese mountain dog (BMD), Rottweiler, golden retriever, and
in the authors’ experience. Irish wolfhound are overrepresented and the disease appears to
be familial in the BMD. 479,509,520–524 Dermal lesions manifest in
Reactive Histiocytosis the skin with similar site predilection as CHS; however, other sites
including the subcutis, eyes, nasal epithelium, LNs, bone mar-
The reactive histiocytosis can be separated into CH and SH. Cuta- row, spleen, liver, lung, or mucous membranes are also affected.
neous histiocytosis represents a benign, diffuse aggregation of his- Clinical signs vary depending on the affected tissue and severity
tiocytes that grows rapidly into infiltrating nodules, plaques, and of disease; however, depression, anorexia, weight loss, conjunctivi-
crusts within the skin and subcutaneous tissue. 478,479,481,509,518,519 tis, and harsh respiration are common. Clinicopathologic features
This disease tends to occur in younger dogs; however, one study of SH are varied; however, anemia, monocytosis, and lymphope-
noted a range of 2 to 11 years. A breed predisposition has yet to be nia are consistently reported, and hypercalcemia is occasionally
identified; however, in one study, golden retrievers, great Danes, reported. 479,509,520–524
and Bouvier des Flanders were more common. 519 One study sug- Lesions may have a waxing and waning presentation, but gen-
gested a male predilection; however, in a second larger study, no erally do not spontaneously resolve. Corticosteroids alone appear
sex predilection was identified. 479,519 Forty-four percent of dogs ineffective in controlling this disease in the long term. 479,508,516
in one study had a previous history of dermatologic disease, with The use of azathioprine, cyclosporine A, or leflunomide has
allergic dermatitis being most common. The median duration of yielded longterm control in some cases. Some have suggested a
time from appearance of lesions to diagnosis via biopsy in this significant role of T cells in this disease via inappropriate DC and
study was 1.75 months (range 0–30 months). 519 T-cell interactions due to abnormal regulation of accessory ligands
CH is limited to the skin and subcutis, but can be multifocal. on both cell types. 479,481 The clinical course of this disease is often
The head, pinnae, limbs, and scrotum are the commonly reported prolonged but rarely results in death. Generally, there are episodes
sites. 479,518,519 Lesions may also be found on the nasal planum of response to therapy followed by recrudescence, and many dogs
and within nasal mucosa, the gross appearance of which has been are euthanized as a result of repeated relapses or failure to respond
described as a “clown nose.” In one study, 10 of 32 dogs had nasal to therapy. 479,509,520–524
planum/nares involvement, which presented as swelling, erythema,
depigmentation, and stertorous respiration. 519 Histologically, lesions
contain a pleocellular histiocytic infiltrate, often perivascular within Histiocytic Sarcoma
the dermis and subcutaneous tissue. Lymphoid infiltrates and some Genetics and Biologic Behavior
neutrophils are common and vascular invasion may be present. These
histiocytic cells express CD1a, CD1b, CD1c, CD11c, MHC class II HS was first reported in the dog in the late 1970s and a predis-
molecules, Thy-1 and CD4 but are negative for E-cadherin. 478,479,481 position in BMDs was discovered in 1986. 525,526 HS has since
The expression of Thy-1 and CD4 aids in identification of cell of ori- been identified in many breeds, and flat-coated retrievers (FCR),
gin, which appears to be the activated interstitial DC. Rottweilers, and miniature schnauzers also appear to be overrepre-
CH usually follows a benign course and responds to immu- sented. 525–527 In Japan, the Pembroke Welsh Corgi also appears to
nosuppressive therapy, although spontaneous regressions have be overrepresented. 528 Dogs are commonly middle aged or older,
also been reported. Local therapies are not often successful, as but HS has been reported in dogs as young as 3 years of age.
lesions typically recur in other locations. Systemic corticosteroids Genetic and epidemiologic studies in the BMD have revealed
are usually the firstline therapy and partial responses are seen in clues about the etiology of HS. A Swiss inheritance study found
the majority of dogs. 479,509,518,519 Many dogs require continuous the genetic predisposition for HS in BMD to be so widespread
therapy to prevent recurrence. In one study of 32 dogs, all had within the breed that selective breeding was deemed impossi-
complete resolution of lesions within a median of 45 days (range, ble. 529 One genetic study evaluating copy number aberrations in
10–162 days) from initial therapy. 518 In this study, initial therapy the BMD and FCR found deletions of the tumor suppressor genes
included prednisone alone or in combination with antibiotics (n CDKN2A/B, RB1, and PTEN. 530 In a genome-wide association
= 12), prednisone with tetracycline/doxycycline and niacinamide study, a haplotype spanning MTAP and part of CDKN2A was
(n = 4), prednisone and azathioprine (n = 3), and tetracycline/ found in 96% of BMD with HS. 531 A gain-of-function muta-
niacinamide either alone or in combination with vitamin E and tion in PTPN11 was recently identified in canine HS, and 37%
essential fatty acids (n = 6). Of the 19 dogs receiving prednisone, of BMDs with HS studied had the mutation compared with 9%
daily dosages ranged from 0.5 mg/kg to 2 mg/kg. 518 of HS in other dog breeds. 532 Two studies have also found a cor-
Longterm maintenance therapies may be warranted to prevent relation between prior joint disease and risk of periarticular HS
recurrence; however, affected dogs may have a prolonged survival (PAHS) in the BMD. 533,534