Lymphomatoids papuloseC86.6

Low-malignant, CD30-positive, particularly benign T-cell lymphoma (?) with recurrent course over many years, characterized by single or multiple, painless, papulo-nodular or ulcerative skin lesions with spontaneous healing and latency for months, possibly even years.

Remark: Some authors consider the clinical picture as 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, composed of pleomorphic and anaplastic lymphoid cells and numerous eosinophilic and neutrophilic granulocytes, histiocytes, and small lymphocytes. Numerous mitoses.

Type B: Band-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. Marked 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 ulceration. Furthermore, eosinophilic granulocytes.

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

• Lymphoma, cutaneous T-cell lymphoma, large cell, CD30-positive: Mostly solitary larger nodule; rarely grouped nodules or nodules with 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), dome-shaped, reddened, dermal, superficially dull or mirror-like 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 discomfort except for mild to moderate itching. Histology is usually diagnostic.
• Prurigo simplex subacuta: Mostly variegated clinical picture with efflorescences of different acuity "from fresh to healed with scarring". Typical is a punctual, unpleasant stinging itching, which is answered with an equally circumscribed and typical scratching reaction (spooning); afterwards, the itching abruptly stops. Histology excludes the diagnosis "lymphomatoid papulosis".

  Notice.

  Not the "disturbing efflorescences", but the tormenting itching leads to the physician!
• Pseudolymphomas: the clinical picture is variable; mostly surface-stable, non-ulcerated, little symptomatic papules. Histology: usually variegated, mature cell, B- and T-cell pattern. No CD30+ infiltrate.
• Insect bites: Mostly pruritic "articular" urticarial papules and plaques. Usually 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.

• In this respect, a prompt proactive local therapy with medium-strong 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 1:1 diluted with LA such as scandicain) is recommended in case of localized, land infestation.
• Alternatively for multifocal spread:
• Phototherapy with PUVA therapy or PUVA bath therapy, possibly also in combination with retinoids like acitretin (neotigason) 0.5 mg/kg bw/day as RePUVA therapy.
• In case of non-response also combination of phototherapy with methotrexate (low dose of 20 mg/week).
• Alternatively: Bexarotene in the given dosage.
• Six-monthly check-ups and repeated skin biopsies are necessary in order to detect any transition to aggressive cutaneous T-cell lymphoma in 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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