Lymphomatoids papulose C86.6

Indolent (low-malignant), CD30-positive, particularly benign lymphoproliferative disease with a recurrent course over many years, characterized by single or multiple, painless, papulo-nodular or ulcerative papules and nodules with spontaneous healing, but also months, possibly even years of latency.

Note: Some authors consider the clinical picture to be benign!

Prevalence 0.1/100,000 population/year. Worldwide incidence. Predominantly in members of Caucasian ethnic groups, accounting for about 18% of CTCL.

Unknown. Viral genesis? There is an increased association with atopic disease in adolescent patients. Detectable mutation in SDC1, COL4A1, and laminin-5 genes may be associated with tumor recurrence or progression to higher-grade lymphoma (Wang TT et al. 2017).

V.a. adults; age: 7-83 years, mean age: 39 years (Xiong J et al. 2015); in a larger study of 20 patients, the mean age was 28.6 years (Wang TT et al. 2017). Very rarely, the disease is also encountered in children and adolescents.

f:m=2.3:1 (according to other sources: 1:1).

Trunk>Extremities>Face and eyelids. Rarely affected is the oral cavity.

Mostly multiple, more rarely only single (rarely more than 5, disseminated occurrence is possible, but the exception), red to red-brown or brown-purple, soft-elastic, painless, surface-smooth flat, red papules forming within a few days (eruption phase). These develop (surprisingly quickly) into red always painless nodules (up to 2 cm Ø) with an initially smooth surface.

Regularly, under initial hemorrhagic crust formation, a torpid disintegration of the central nodule areas occurs. This leads to a change in morphology! In this phase of development, the only clinical impression is an ulcer of varying depth (which cannot be explained to the examiner), which is usually hardly painful. Danger of secondary infection (pyoderma). Healing with formation of a less spectacular, hyper(hypo)pigmented scar.

After 3-8 weeks spontaneous regression with formation of scaly crusts.

Type A: Dense, diffuse, mixed-cell infiltrate extending into the subcutis, consisting of pleomorphic and anaplastic lymphoid cells as well as numerous eosinophilic and neutrophilic granulocytes, histiocytes and small lymphocytes. Numerous mitoses.

Type B: Ribbon-like dermal epidermotropic infiltrate of small to medium-sized lymphoid cells with chromatin-dense cerebriform nuclei.

Type C: Dense, diffuse infiltrate of large anaplastic cells extending into the subcutis. Few eosinophilic or neutrophilic granulocytes, histiocytes and small lymphocytes. Numerous mitoses (by far the most common type- Wang TT et al. 2017).

Type D: Dense, diffuse infiltrate of small to medium-sized CD8+ and CD30+ lymphocytes extending into the subcutis. Significant epidermotropy.

Type E (angioinvasive type): Dense, angiocentric and angioinvasive, mixed-cell infiltrate of medium-sized pleomorphic and anaplastic lymphoid cells extending into the subcutis. Evidence of necrosis and ulcer formation. Furthermore eosinophilic granulocytes.

Type F: Small intraepidermal lymphocytes next to larger pleoorphic dermal lymphocytes with a characteristic folliculotropic distribution.

Immunohistology: Tumor cells are positive for CD3 (80-90%), CD4 (80-90%), CD8 (50% of cases), CD25. In type A and C, the anaplastic, large cells express CD30 (see CD classification below). T-cell receptor gene rearrangement: Only in isolated cases evidence of monoclonality of the T-cell infiltrates. CD20 is only very rarely expressed, ALK1 is not expressed.

Lymphoma, cutaneous T-cell lymphoma, large cell, CD30-positive: Mostly solitary larger nodules; rarely grouped nodules or nodules with a tendency to ulceration. Spontaneous regressions and recurrences are possible (in up to 25% of patients).

Pityriasis lichenoides chronica: Very polymorphic clinical picture; initially small (usually < 0.5 cm), calotte-shaped, reddened, rough, superficially dull or reflective papules covered by a fine scale. Alignment along the tension lines of the skin. Typical: formation of a compact, oblate, covering, centrally adherent scale. The disease causes no symptoms apart from mild to moderate itching. Histology is generally diagnostic.

Chronic prurigo: Mostly colorful clinical picture with efflorescences of varying acuity "from fresh to scarred healed". Typical is a localized, unpleasant, stinging itching, which is responded to by an equally circumscribed and typical scratching reaction (spooning); the itching then abruptly stops. Histology reliably rules out the diagnosis of "lymphomatoid papulosis".

Remember! It is not the "disturbing efflorescences" but the agonizing itching that leads to the doctor!

Pseudolymphomas: the clinical picture is variable; mostly surface-stable, non-ulcerated, less symptomatic papules. Histology: mostly mixed, mature cell, B- and T-cell pattern. No CD30+ infiltrate.

Insect bites: Mostly itchy "artificial" looking, urticarial papules and plaques. Mostly short history. Difficult to differentiate in persistent arthropod reactions. Histology: as in pseudolymphoma.

Syphilis: history; histology and serology are diagnostic.

Eosinophilic ulcer of the oral mucosa: this DD can only be clarified histologically.

40-60% of patients develop another lymphoproliferative disease. Here, the rate of mycosis fungoides is particularly high (78% on average). Patients with lymphomatoid papulosis type A are preferentially affected (> 90%). Mycosis fungoides may parallel or precede lymphomatoid papulosis (30-40%) (60-70%).

Other lymphoproliferative disorders that may occur together with or following lymphomatoid papulosis include large cell anaplastic lymphoma (12%). Occasionally, the occurrence of Hodgkin's disease has been reported.

The therapy depends primarily on the clinical manifestation of the disease. None of the available therapies influence the natural course of the disease. All therapeutic modalities should be used with the aim of controlling the disease rather than curing it.

Localized bare infestation:

• Prompt proactive local therapy with medium-strength topical glucocorticoids, if necessary under occlusion (glucocorticoids class II and III) such as 0.1% betamethasone lotio(R030), 0.1% triamcinolone cream(R259) or intralesional administration of triamcinolone (e.g. Volon A diluted 1:1 with LA such as scandicain).
• Successful in individual case reports: topical chloromethine gel, gradual, initially twice weekly, later daily application (Dege T et al. 2024)

Alternative for multifocal spread:

• Phototherapy with PUVA therapy or PUVA bath therapy, possibly also in combination with retinoids such as acitretin (neotigason) 0.5 mg/kg bw/day as RePUVA therapy.
• If there is no response, combination of phototherapy with methotrexate (low dose of 20 mg/week).
• Alternatively: Bexarotene in the prescribed dosage.
• Six-monthly check-ups, including repeated skin biopsies, are necessary in order to detect any transition to an aggressive cutaneous T-cell lymphoma in good time!

Mostly well, recurrent blanched course for years, with absence of manifestations for months or years.

Limitation of life expectancy only by associated lymphomas (in up to 20% of patients other lymphomas develop in the course of years: mycosis fungoides, immunoblastic or large cell anaplastic lymphoma, Hodgkin's disease). The mortality rate is about 8%.

For patients who develop lymphomatoid papulosis in childhood, the probability of developing non-Hodgkin's lymphoma is 200 times higher than in the normal population.

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