Lymphomatoid Papulosis

Etiology

The etiology of lymphomatoid papulosis is unknown. A viral etiology has been suggested. However, studies searching for an etiologic role for Epstein-Barr virus and other herpesviruses have been consistently negative. The mechanisms involved in the spontaneous regression of skin lesions have not yet been identified. Interactions between CD30 and its ligand (CD30L) may contribute to apoptosis of the neoplastic T cells and the subsequent regression of the skin lesions, but the exact mechanism is as yet unknown.[2]

Epidemiology

Lymphomatoid papulosis accounts for about 12% of cutaneous lymphomas. It may occur at any age but, on average, earlier than CD30+ anaplastic large-cell lymphomas. It is less exceptional in children. In large series, the mean age of onset varies between 35 and 45 years. The male-to-female ratio is approximately 1 to 5.

Histopathology

The cutaneous biopsy reveals a dense dermal lymphocyte infiltrate of evocative triangular morphology with an epidermal base seen at low magnification. The composition of the infiltrate is variable and correlates with the age of the lesion. The epidermis is frequently ulcerated. Several histologic types of lymphomatoid papulosis have been described. According to the number of lymphocytes expressing CD30 and according to their size, we distinguish type A papulosis in which the CD30 cells are numerous, type B very close to the mycosis fungoides with no or few CD30+ cells and epidermotropism, and finally, type C, with large CD30+ lymphocyte plaques. Other rare forms have been reported: forms expressing markers of cytotoxicity, CD8, TIA1, granzyme B,[3] forms with angiotropism,[4] and strictly follicular forms mainly affecting the scalp.[5] Different types, in particular types A and B, can be observed in the same patient, not only from one lesion to another but also within the same lesion. The vital prognosis and the risk of association with a second hemopathy do not seem to vary from one histological form to another.

History and Physical

The classic clinical presentation is characterized by a red-brown papulonodular eruption that may become hemorrhagic and necrotic. These lesions regress within 2 to 12 weeks, leaving hypopigmented, hyperpigmented, or characteristic atrophic (varioliform) scars.[1] The coexistence of different age elements is common. Recurrence is the rule with complete remissions of variable duration. Mucosal lesions, particularly oral, are possible but exceptional.[6] The lesions vary in number from one individual to another and from one recurrence to another. Lesions may be localized, sometimes clustered within rather well-defined areas, or generalized. All areas of the skin may be affected with a predilection for the trunk and limbs. The eruption is generally asymptomatic.

Evaluation

Skin biopsy is required to confirm the diagnosis and exclude other closely mimicking diseases. Histologically A, B, or C subtypes can be identified. Once the diagnosis of lymphomatoid papulosis is confirmed, no complimentary assessments are needed. The blood count in the search for circulating atypical cells is useless. Complete blood count with biochemistry and lactate dehydrogenase are done as baseline tests. The potentially associated hematological diseases being, almost exclusively, cutaneous lymphomas, only attentive clinical examination of the skin is necessary. No imaging studies are indicated unless there is a concern for secondary lymphoma.

Treatment / Management

As it is a rare and clinically polymorphic pathology, no controlled prospective therapeutic study could be conducted to validate a certain treatment. The treatments are only suspensive and poorly efficient. In patients with relatively few non-scarring lesions, therapeutic abstention can be considered. Disabling or cosmetically disturbing forms can be attenuated or controlled with weekly doses of 5 to 20 mg of methotrexate. Used orally, subcutaneously, or intramuscularly, methotrexate is the systemic treatment of choice for lymphomatoid papulosis, regardless of histological type.[7][8] Starting with low doses (7.5 to 10 mg per week) and then increased in increments of 2.5 or 5 mg until remission of the disease is obtained. Doses higher than 25 mg per week are rarely needed. Once the remission is obtained, the dosage is gradually tapered until the lowest effective dose, or until discontinuation. In their recent publication on their experience with methotrexate in lymphomatoid papulosis, the Dutch cutaneous lymphoma group reported 90% of good to very good results, but less than one-third of patients were able to discontinue treatment following complete and sustainable remission.[8] Phototherapy can also be offered. Psoralen + ultraviolet A (PUVA) therapy has been proposed for more than 30 years to treat lymphomatoid papulosis. The disappearance of the lesions is often obtained after about fifteen sessions, but recurrences are frequent. The local chemotherapies (solution or gel of mechlorethamine), bexarotene, interferon, are sometimes used as therapeutic alternatives. When larger skin tumors develop in the course of lymphomatoid papulosis, surgical excision or radiotherapy can be proposed if spontaneous resolution does not occur after a period of 4 to 12 weeks.

The treatment of the child's papulosis poses difficulties because of the particular therapeutic risk of phototherapy at this age and the fear of using methotrexate in pediatrics. Most authors recommend therapeutic abstention or the use of very strong topical corticosteroids on papules at the initial inflammatory stages. The risk of scarring of the lesions may lead to general treatment, and ultraviolet B (UVB) phototherapy will be preferred, although its results in children are inconsistent.[9](B2)

Because of the potential risk for developing a systemic lymphoma, long-term follow-up is required in all patients with lymphomatoid papulosis.

Differential Diagnosis

The chronic nature of the disease and spontaneous regression of each elementary lesion leaving a scar, are so characteristic of lymphomatoid papulosis that differential diagnoses are rarely raised. However, the pauci-lesional form is frequently misinterpreted as:

• Insect bites
• Prurigo
• Lichenoid pityriasis
• Folliculitis
• Scabies

Histologically, the distinction may be impossible between lymphomatoid papulosis type B and mycosis fungoides, or between lymphomatoid papulosis type C and CD30 anaplastic large cell lymphoma. The diagnosis is then based on the anatomoclinical confrontation privileging the clinical aspect. The distinction between mycosis fungoides of early-stage associated with lymphomatoid papulosis (good prognosis) and a transformed mycosis fungoides of nodular evolution (poor prognosis) is important and sometimes difficult. It is based on anamnesis and anatomoclinical expertise.

Prognosis

Patients affected with lymphomatoid papulosis are at risk of developing another hematological disorder, mainly mycosis fungoides, erythrodermic T-cell lymphoma, Hodgkin disease, or large-cell CD30+ lymphoma. The hematological malignancy may precede, follow, or be concomitant with the appearance of lymphomatoid papulosis. This risk varies from 2% to 15% after 5 years of evolution, but it increases with the duration of the disease. Older age and especially the presence of a T-cell clone in the papulosis lesions are significant risk factors for the occurrence of a second haemopathy.[10] The impact on the quality of life can be important, because of the chronic course of the disease and the possible localization in visible skin areas. Regardless of the risk of secondary disease, the prognosis of lymphomatous papulosis is excellent with a 10-year disease-specific survival of almost 100%.[11]

Complications

Lymphomatoid papulosis patients are at an increased risk of developing secondary malignancies and these include:

• Mycosis fungoides
• Erythrodermic T cell lymphoma
• Hodgkin disease
• Large cell CD30+ lymphoma