Cutaneous lymphosarcoma
From Felipedia
Cutaneous lymphosarcoma/lymphoma is a skin disease of cats which tends to occur in older animals with the mean age of 11 years. In several studies, all cats tested for FeLV were negative. Cutaneous lymphosarcoma is usually categorized as either epitheliotropic (epidermotropic), which tends to be of T-cell origin, or nonepitheliotropic, which tends to be of ß-cell, or sometimes null cell, origin.
Epitheliotropic cutaneous lymphosarcoma can be categorized as three forms: mycosis fungoides, Sezary syndrome, or pagetoid reticulosis. Of these, mycosis fungoides is the most common type of epitheliotropic lymphosarcoma diagnosed in dogs and cats.
Mycosis fungoides is a nonleukemic variant of cutaneous lymphosarcoma that occurs occasionally in dogs but rarely in cats. It is characterized histologically by epitheliotropic atypical lymphocytes, minimal spongiosis, and Pautrier's microabcesses (a discrete accumulation of neoplastic cells in the epidermis), which are characteristic histologic features of mycosis fungoides.
Sezary syndrome or Sezary-like disease has been reported in cats. It is characterized by the presence of cutaneous lymphosarcoma (generalized, exfoliative erythroderma, and lymphadenopmegaly) plus a leukemia. Pruritis is common. Histologic evaluation of skin lesions is consistent with that of mycosis fungoides, and the circulating neoplastic lymphocytes are large cells with convoluted, hyperchromatic nuclei and a high nuclear:cytoplasmic ratio that are known as Sezary cells.
Pagetoid reticulosis can resemble mycosis fungoides and Sezary syndrome histologically, because a monomorphous population of neoplastic lymphoid cells infiltrates the epidermis. Clinically, it appears to take a relatively benign course as a solitary plaque of chronic duration. Histologic examination of the ß-cell nonepitheliotropic form of cutaneous lymphosarcoma reveals lymphocytes located deeper in the dermis, with sparing of the papillary dermis and epidermis. The malignant lymphocytes are characterized as well-differentiated, poorly differentiated, undifferentiated, or large cell. Since T-cell lymphosarcoma can also appear as a nonepitheliotropic form, the lack of epidermal infiltration by lymphocytes is not by itself a useful criterion in defining ß-cell or T-cell forms of this disorder. Immunohistochemistry plus routine histologic assessment can be used to distinguish B-cell from T-cell lymphosarcoma. Clinical lesions are usually discrete solitary or multifocal nodules, sometimes with acute onset and rapid progression.
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Clinical signs
Cutaneous lymphosarcoma is characterized by infiltration of any area of the skin by neoplastic lymphocytes. It can occur as the primary form of lymphosarcoma, or it may be disseminated from or to other areas. It may occur as single or multifocal lesions on the skin. Cutaneous lymphosarcoma can affect any skin surface, but it often will exhibit mucocutaneous and oral cavity involvement. Cutaneous lesions can progress through various forms:
- Patch Stage (uncommon)
- Plaque Stage (solitary or multiple erythematous plaques)
- Tumor Stage (solitary intradermal mass, multiple tumor nodules)
- Erythematous Lesions (accompanied by alopecia and extensive epidermal scaling)
- Ulcerative Lesions (usually circular, extend through the dermis into the subcutis)
- Papillomatous Lesions (rare)
- Lymph Node Involvement (often develop a hypercalcemia)
- Sezary-like disease (crculating neoplastic lymphocytes are large cells with a convoluted nucleus and a high nucleus to cytoplasmic ratio)
It is easy to misdiagnose cutaneous lymphosarcoma because of its variable clinical presentation, and it may mimic many other skin diseases. Animals may present for a second opinion after many months of therapy in which antibiotics, dips, and steroids were not successful in eradicating a misdiagnosed problem. In one study of cutaneous lymphosarcoma, 64% (14/22) of dogs presented with a history of chronic skin conditions. The various manifestations of cutaneous lymphosarcoma have been misdiagnosed as endocrine alopecia, seborrhea, atopic dermatitis, pododermatitis, or pyoderma. In cats, differential diagnosis should also include dermatophytosis, allergic dermatitis, eosinophilic plaque, autoimmune disease, drug eruptions, and external parasites (especially Cheyletiella).
General clinical signs include nodules, plaques, pustules, ulcers, erythroderma, depigmentation, or exfoliative dermatitis. The size of involved areas ranges from small (few millimeters) to large nodules or plaques (centimeters in diameter). Small animals initially may present with lesions of coalescing, erythematous patches with alopecia and scale on the head and face, that progress to the trunk. This form then progresses to circular then irregular erythemic plaques, some with central ulceration and dry crusts on mucocutaneous junctions. The plaque form is more common in cats than in dogs. Pruritis is variable with the patch and plaque forms, but cats tend to be more pruritic than dogs and may show more self-trauma and ulceration. Both the patch and plaque forms can regress and reappear at a later date or progress rapidly to a more aggressive form.
Variably sized, painless nodules (solitary or multiple) can appear as firm, elevated, dark red, shiny, scaly, or ulcerated lesions with serous exudate oozing onto the skin surface. This exudate tends to trap keratin and form a crust on top of the nodule. If the crust is removed, the skin underneath may be hemorrhagic and hyperemic. The combination of ulcerative skin and crust can lead to areas of matted hair with a foul odor. Less pruritis is usually seen with this stage than with previous stages, although secondary bacterial infection' can cause pruritis. Progression to lymph nodes or other organs can occur.
Beale and Bolon reported that 80% of 26 dogs with the epitheliotropic cutaneous lymphosarcoma had erythema at presentation, with nodules in 57% of dogs and plaques and scales in 62% of dogs. Mucosal lesions were present in more than one-third of the dogs. There was a trend for those dogs with epitheliotropic cutaneous lymphosarcoma to survive longer after diagnosis than dogs with nonepitheliotropic lymphosarcoma. Of the dogs with epitheliotropic cutaneous lymphosarcoma, those that received treatment lived 334 days, while those without treatment lived 79 days. Of the dogs with nonepitheliotrophic cutaneous lymphosarcoma, those that received treatment lived 173 days, and those without treatment lived 40 days.
In a retrospective study of nine cats with cutaneous lymphosarcoma, five had solitary masses, four had multiple or diffuse lesions, and one was classified as mycosis fungoides. In one study of 72 dogs, only 8 of the dogs had solitary involvement, and 14 dogs had diffuse involvement. Overall, the progression of disease in cats appears similar to that in dogs (patch, plaque, then nodular). However, unlike in dogs, standard chemotherapy may not as readily alter the progression of the disease.
Hematologic changes associated with cutaneous lymphosarcoma are varied and include anemia, lymphopenia, lymphocytosis, neutrophilia and leukemia. Hepatic and renal changes may be noted. Hypercalcemia is rare but tends to occur when only the skin is affected (no lymph node or solid organ metastasis). A monoclonal gammopathy (IgG) was reported in one dog with cutaneous lymphosarcoma.
Diagnosis and staging
The diagnosis of cutaneous lymphosarcoma is dependent on biopsy. Although a diagnosis of cutaneous lymphosarcoma may be established with a fineneedle aspiration cytology, histopathology is advised in order to fully characterize the nature of the tumor. With the availability and use of immunohistochemis try for cell markers, every effort should be made to identify the tumor as T or B cell origin. Staging for cutaneous lymphosarcoma is the same as for other forms of lymphosarcoma.
Histology:
- Exocytosis of neoplastic cells into the epidermis may be diffuse or multifocal
- Formation of Pautrier microabscesses
- Involvement of adnexal structures
- Invasion of the external root sheath of the hair follicles
- Apocrine glands are frequently affected
- Sebaceous glands are infrequently infiltrated by neoplastic lymphoid cells
- Dermis shows neoplastic lymphoid infiltration
- Replacement of dermal collagen by tumor cells
- Extension into the panniculus adiposus
Cutaneous lymphosarcoma need to be distinguished in a differential diagnosis with cutaneous haemangiosarcoma.
Treatment
Treatment of cutaneous lymphosarcoma is often frustrating. Many treatments must be considered palliative, but some relief from clinical signs can be be offered. For example, regular bathing with sulfur-based shampoos may increase patient comfort and appearance, but has no effect on the primary disease. Prednisone can be used to successfully control persistent pruritis (doses ranging from 0.15-1.8 mg/kg every 24-48 hrs), but may have no appreciable effect on survival.
Radiation therapy has been used for solitary or multifocal lesions. One dog with mycosis fungoides was reported responsive to orthovoltage radiation. Palliative radiation therapy of dogs with mycosis fungoides can be rewarding, and ulcerated lesions may heal and regress.
Surgery has been effective as primary therapy in some dogs. In a report of 22 dogs with cutaneous lymphosarcoma, 8 dogs had solitary lesions and 7 of these were treated by surgical excision. Of these dogs treated by surgery, 4 were considered cured.
Caciolo, et al, however, reported a different outcome in a case study of nine cats. Five of the cats had solitary masses, and four had local excision. One cat was lost to follow up, but three had local reccurrence of lymphosarcoma within 1 month of surgery.
Numerous drugs and combinations of drugs (cyclosporine; mechlorethamine; cyclophosphamide and vincristine; doxorubicin, vincristine and prednisone; and chlorambucil and prednisone) have been used to treat cutaneous lymphosarcoma in small animals with varying success. The use of topical nitrogen mustard (mechlorethamine) was reported effective in some dogs, but it has a high incidence of allergic and irritant contact sensitization (dermatitis) in people exposed to it. Cats treated with nitrogen mustard tend to have significant bone marrow suppression and GI upset. Treatment of epitheliotropic cutaneous lymphosarcoma with chemotherapy usually results in slowing the progression or minimal regression of disease. However, one dog treated with Dacarbazine (DTIC) at a dose of 1000 mg/m2 intravenously over 2 hours every 3 weeks for 3 total treatments had a complete remission without significant side effects. Prior to the third chemotherapy, surgical removal of two resistant dermal nodules was performed, and the dog remained disease free for >1 year.
The best survival times for cutaneous lymphosarcoma are usually the result of treatment with combination chemotherapy protocols, especially if doxorubicin is a part of the protocol. Remission of 46 days was reported in one dog with epitheliotropic cutaneous lymphosarcoma treated with chlorambucil and prednisone, while a remission of 304 days was reported for another dog treated with doxorubicin, vincristine, and prednisone.
Retinoids have also recently been added to the choices available to veterinarians for treating cutaneous lymphosarcoma. The exact method of action of retinoids on neoplastic cells is unknown. Since retinoids are a vitamin A analog and vitamin A helps to regulate growth and differentiation of cells, retinoids may act by regulating epithelial differentiation and reversing malignant differentiation. White, et al, used retinoids to treat 14 dogs with cutaneous lymphosarcoma. Clinical remission, defined as >50% reduction of erythema, scaling and/or pruritis for at least 4 months after therapy initiation, was observed in 43% of the dogs treated with retinoids. Twelve dogs were treated with isotretinoin and 2 with etretinate. Of the 12 dogs with epitheliotropic lymphosarcoma treated with isotretinoin, 4 responded for between 152 and 395 days. One of the dogs responded to etretinate for 456 days, while one dog with nonepitheliotropic disease responded to isotretinoin for 535 days. For all dogs with epitheliotropic lymphosarcoma, the mean remission/ survival was 328 days. The study authors recommended a dose of 3 to 4 mg/kg of isotretinoin daily for treatment of cutaneous lymphosarcoma.
Side effects in dogs treated with isotretinoin included panting and salivation, mild dry cough, corneal lipid deposits, and high serum triglyceride value. Side effects in dogs treated with etretinate included abdominal alopecia. Adverse effects did not correlate with the dose given and occurred sporadically. Most abnormalities were transient and reversible upon cessation of therapy. Other infrequent, adverse side effects reported for retinoids include keratoconjunctivitis sicca, swollen tongue, polydipsia, signs of joint pain, pruritis, hyperlipidemia, hyperactivity, ear pruritis, erythema of the feet and mucocutaneous junctions, lethargy or anorexia with vomiting, and teratogenesis.
Of three cats with epitheliotropic lymphosarcoma treated with isotretinoin (10 mg daily), all had a good clinical response and showed a reduction of erythema and scaling, and there was abundant new hair growth. Complete remission was not achieved, but good quality of life was maintained for 182 to 547 days. In a separate study of three cats with epitheliotropic lymphosarcoma treated with 1 mg/ kg of isotretinoin every 12 to 24 hours, some improvement of clinical signs was seen (increased hair, less scale and erythema). All of the cats "felt" better, but no complete responses were seen. Survival ranged from 182 to 547 days. Diarrhea was noted in one of three cats treated with isotretinoin. Other side effects noted in cats given isotretinoin include periocular edema, periocular crusting, epiphora, and blepharospasm. Like in dogs, side effects in cats are sporadic.
References
1. Max's House
