Tuesday, 26 October 2010

Lymphomatoid papulosis

Lymphomatoid (resembling lymphoma) papulosis represents part of a spectrum of primary cutaneous CD30+ lymphoproliferative disorders. Primary cutaneous CD30+ lymphoproliferative disorders consist of a spectrum of conditions; lymphomatoid papulosis and CD30+ large cell lymphomas which are defined on the basis of clinical and pathologic features. Where a distinction cannot be made, patients are designated as ‘borderline cases’.

The CD30 marker was originally identified as a marker on Reed–Sternberg (RS) cells in Hodgkin’s disease. The classical RS cells are multinucleate, nucleoli are large and prominent. If two nuclei are present, one appears to be the mirror image of the other, and this gives an “owl’s-eye” appearance. In the skin, primary CD30+ lymphoproliferative disorders are invariably of T-cell origin (some biopsies may not show a T-cell receptor clonal pattern though). The nodal CD30+ lymphomas can be derived from B, T or null cells.

Identical T‐ cell clones can be detected in skin biopsies from patients with both mycosis fungoides (MF) and lymphomatoid papulosis. Studies using laser captured CD30+ cells and sequencing of T-cell receptor genes have shown contradictory findings. The pathophysiology of the disease remains to be clarified.

The term lymphomatoid papulosis was first used in 1968 by
Macaulay to describe a ‘self-healing rhythmical paradoxical papular eruption, histopathologically malignant but clinically benign’. Since then, there has been continued discussion as to whether lymphomatoid papulosis is a malignant, a premalignant or a benign condition. Long-term follow-up is necessary in all cases because of the risk of progression to a bona fide lymphoma such as a primary cutaneous CD30+ large cell lymphoma, MF (patients more commonly have coexistent MF) or Hodgkin’s disease in less than 5% of cases. Similarly, some patients develop lymphomatoid papulosis‐ like lesions with a preceding history of Hodgkin disease and patients with pre‐existing MF may subseqently develop lesions indistinguishable from those of lymphomatoid papulosis. There appear to be no currently available clinical or pathological prognostic markers to indicate whether such progression is likely. There is debate whether these patients actually have lymphoma from the start, which is low grade and may regress, or whether benign disease actually transforms into lymphoma. The prognosis in patients with both MF and lymphomatoid papulosis appears to be excellent.

Affected patients have recurrent crops of asymptomatic papular or papulonecrotic or nodular lesions
predominantly affecting the trunk, although any body site can be involved. The red–brown papules and nodules develop central haemorrhage, necrosis and crusting, and subsequently spontaneously disappear. Healing may leave atrophic (varioliform) scars. Characteristically, skin lesions in different stages of evolution coexist. The disease is chronic and recurrent (waxes and wanes or comes and goes). The cycle recurs every few months, with no obvious initiating factor. The lesions generally occur first in adult life and may recur in crops for up to 40 years or more. Over time, every individual skin lesion will resolve and there may eventually be a persistent remission. Angioinvasive and follicular variants of lymphomatoid papulosis have been described

It has been suggested that
interactions between CD30 and its ligand (CD30L) may contribute to apoptosis of the neoplastic T cells and the subsequent regression of the skin lesions.

It should be noted that
in general cutaneous lymphomas that are CD30+ ab initio are associated with a good prognosis.

Because of the clinical similarities between
lymphomatoid papulosis and pityriasis lichenoides et varioliformis acuta, a relationship between the two conditions was initially suggested. Clonal T-cell populations have been demonstrated in skin biopsies of both conditions. Pityriasis lichenoides et varioliformis acuta occurs more often in younger patients, is generally short-lived, does not develop nodular lesions, is more vesicular and less necrotic, and progression to a malignant lymphoma is exceedingly rare, if it occurs at all. CD30 is generally negative and if CD30+ atypical lymphocytes are found they are few and invariably CD8+ while the presence of CD30+ atypical lymphocytes (usually CD4+ but occasionally CD8+) is the hallmark of lymphomatoid papulosis as will be discussed below. It should also be noted that small recurrent lymphomatoid papulosis lesions can be misdiagnosed as folliculitis or arthropod bites for years. 

The histopathology of lymphomatoid papulosis in part correlates with the age of the sampled skin lesion. The features are a relative lack of epidermotropism and Pautrier microabscesses, but the presence in the dermis of a mixed infiltrate composed of atypical lymphocytes with large nuclei and frequent abnormal mitoses, eosinophils, neutrophils, extravasated red cells and large histiocytic cells. Some of these cells may show marked cytological atypia. The epidermis may be ulcerated and the infiltrate may extend deeply into the reticular dermis. True vasculitis is rarely seen.

Lymphomatoid papulosis can be divided on histopathological grounds
into A, B, C and D subgroups.

In the
A subgroup, lesions show non-epidermotropic infiltrate with large "Reed-Sternberg like cells" (CD30+), interspersed in an extensive inflammatory infiltrate of lymphocytes, eosinophils, neutrophils, and extravasated red blood corpuscles.

In the
B subgroup, lesions show lymphocytic infiltrates showing early infiltration of the basal and parabasal layers of the epidermis. These smaller atypical T lymphocytes are with convoluted (cerebriform) nuclei similar to those seen in mycosis fungoides and are CD30-. This subgroup might present with clinical lesions resembling pityriasis lichenoides et varioliformis acuta causing confusion.

In the
C subgroup, lesions show a monotonous population of large CD30+ lymphocytes with an overall pattern suggestive of primary cutaneous CD30+ large cell lymphoma.

In the
D subgroup, atypical CD30+ lymphoid cells express CD8 with a cytotoxic phenotype.

Many cases, however, have all types of lesions coexisting simultaneously.

There is
no evidence that intensive combination chemotherapy alters beneficially the course of lymphomatoid papulosis, and indeed there are individual case reports suggesting that high-dose intensive chemotherapy may cause transition to a more aggressive disorder!

Skin‐directed therapy options include narrow‐band UVB therapy and topical or intralesional steroids. Radiotherapy may be tried.

In the case
of cosmetically disturbing lesions (e.g. scarring or many papulonodules), low-dose oral methotrexate (5-20 mg/week) appears to be the most effective systemic therapy
for reducing the number of skin lesions. There are reports of a beneficial effect with oral dapsone too. 

This page was last updated in July 2018.  

1 comment:

  1. Note that:

    1) The papulonodules of lymphomatoid papulosis may leave transient hypopigmented or hyperpigmented macules and atrophic (varioliform) scars.

    2) Lymphomatoid papulosis B subgroup CD30 sometimes shows just small banal-appearing lymphocytes, extravasated red blood corpuscles, often with red blood corpuscles in the epidermis might also be seen.

    3) In general, cutaneous lymphomas that are CD30+ ab initio are associated with a good prognosis. In mycosis fungoides (MF), the situation in which tumour cells acquire CD30 expression, during the course of disease (i.e. in pre-existing CD30-MF), is generally regarded by some to be associated with a poor prognosis. Though others see any prognostic significance remains unclear.


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Main Works of Reference List (The first eight are my top favourites)

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  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
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