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.

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, mycosis fungoides or Hodgkin’s disease in less than 5% of cases. 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.

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.

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 (A and C subgroups, 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.

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

In the A subgroup, lesions show non-epidermotropic infiltrate with 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 atypical T lymphocytes are with convoluted (cerebriform) nuclei similar to those seen in mycosis fungoides and are CD30-.

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
.

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 CD30+ lymphoproliferative disorder! In the case of cosmetically disturbing lesions (e.g. scarring or many papulonodules), low-dose oral methotrexate (5-20 mg/week) is the most effective therapy
for reducing the number of skin lesions. 

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 can be divided on histopathological grounds into types A, B and C subgroups:

    A subgroup CD30+ [Reed–Sternberg (RS) cells]


    B subgroup CD30- [atypical CD30- lymphocytes, sometimes with cerebriform nuclei, but sometimes just small banal-appearing lymphocytes, these lymphocytic infiltrates, show early infiltration of the basal and parabasal layers of the epidermis - extravasated red blood corpuscles, often with red blood corpuscles in the epidermis].


    C subgroup CD30+ [striking large atypical cells; a monotonous population of large CD30+ lymphocytes with an overall pattern suggestive of primary cutaneous CD30+ large cell lymphoma].


    3) The CD30 marker was originally identified as a marker on RS cells in Hodgkin’s disease, but has subsequently been found on a variety of both T and B lymphocytes. 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.

    4) 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 associated with a poor prognosis.

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

  • British National Formulary
  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
  • Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health
  • Oxford Handbook of Medical Dermatology
  • Rook's Textbook of Dermatology
  • Simple Skin Surgery
  • Weedon's Skin Pathology
  • A Concise Atlas of Dermatopathology (P Mckee)
  • Ackerman's Resolving Quandaries in Dermatology, Pathology and Dermatopathology
  • Andrews' Diseases of the Skin
  • Andrology (Nieschlag E FRCP, Behre M and Nieschlag S)
  • Bailey and Love's Short Practice of Surgery
  • Davidson's Essentials of Medicine
  • Davidson's Principles and Practice of Medicine
  • Fitzpatrick's Colour Atlas and Synopsis of Clinical Dermatology (Klaus Wolff FRCP and Richard Allen Johnson)
  • Fitzpatrick’s Dermatology in General Medicine
  • Ganong's Review of Medical Physiology
  • Gray's Anatomy
  • Hamilton Bailey's Demonstrations of Physical Signs in Clinical Surgery
  • Hutchison's Clinical Methods
  • Lever's Histopathology of the Skin
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  • Macleod's Clinical Examination
  • Martindale: The Complete Drug Reference
  • Oxford Handbook of Clinical Examination and Practical Skills
  • Oxford Textbook of Medicine
  • Practical Dermatopathology (R Rapini)
  • Sexually Transmitted Diseases (Holmes K et al)
  • Statistics in Clinical Practice (D Coggon FRCP)
  • Stockley's Drug Interactions
  • Treatment of Skin Disease: Comprehensive Therapeutic Strategies
  • Yen & Jaffe's Reproductive Endocrinology