Contents
Primary cutaneous lymphomas are malignant growths of T, B and NK cells, limited to the skin at the time of diagnosis. In some cases, after many years and in the advanced stages of the disease, neoplastic cells may appear in the marrow and peripheral blood, or the internal organs may be affected.
Primary cutaneous lymphomas – causes
The cause of primary cutaneous lymphomas is not fully understood. The pathogenesis takes into account the influence of environmental factors, although the influence of UV rays, X-rays, tobacco smoke, alcohol and drugs on the development of skin lesions has not been proven. The thesis about the relationship between lymphomas and the Epstein-Barr virus (the genome of this virus was detected in individual cases of lymphoma) was also rejected. However, the role of HTLV-1 retrovirus in the pathogenesis of adult T-cell lymphoma has been confirmed in many cases. The following factors are also considered in the etiology of lymphomas: allergic and toxic, acting on the immune system and triggering the excessive activity of certain cytokines (IL-4, IL-5, IL-10, INF).
Classification of primary cutaneous lymphomas
The classification of cutaneous lymphomas is difficult due to the variability of clinical symptoms and the not always clear histological picture. The Kiel classification adopted in Europe and modified in 2005 by WHO-EORTC (European Organization for Research and Treatment of Cancer) distinguishes the following primary cutaneous lymphomas:
- cutaneous T cell lymphoma (CTCL): mycosis fungoides, Sezary’s syndrome, pagetoid retina, lymphomatoid papulosis;
- Cutaneous B-cell lymphoma (CBCL): less malignant lymphoma (immunocytoma, centrocytic lymphoma), more malignant lymphoma (centroblastic lymphoma, lymphoma
Find out how sneaky lymphoma can be
Mycosis fungoides
(Fig. 25.1 and 25.2)
Mycosis fungoides is a lymphoma of the small, brain-like T cells. It arises from peripheral T cells and is characterized by:
- chronic course,
- skin lesions,
- sometimes involvement of lymph nodes and internal organs (gastrointestinal tract, lungs, liver, spleen, CNS).
Mycosis fungoides is the most common cutaneous lymphoma, accounting for approximately 50% of all primary cutaneous lymphomas (CTLC). The disease affects 0,5-1: 100 people. The disease occurs mainly in adults, much more often in men over 000, especially those exposed to the chronic effects of adverse chemical factors of industrial origin.
The reasons
In the pathogenesis of mycosis fungoides, the following are taken into account:
- HTLV retrovirus infection,
- persistent contact hypersensitivity reactions,
- stimulation of the immune system.
DIG. 25.1. Mycosis fungoides.
DIG. 25.2. Mycosis fungoides.
Location of the mycosis fungoides
The mycosis fungoides are most often located on the chest, abdomen, buttocks, iliac regions, in the medial superficial proximal part of the limbs, and not on the mucous membranes.
symptoms
Symptoms of this ailment are very diverse, there are several stages of the granuloma, depending on the severity:
1st introductory period (praemycoticum stage) – may last for many years, skin lesions are not very characteristic, there are erythematous, erythematous-exfoliating foci, eczema-like lesions, psoriasis, plaque psoriasis or vascular atrophy of the skin. The foci are single or numerous, round, oval, amoebic, and may grow slowly. Vesicular or pustular eruptions are rarely observed. Often, patients experience hair loss in the area of the lesions. The changes are accompanied by intense itching;
2nd infiltrative period (infiltrative stage) – within erythematous changes or on clinically unchanged skin, flat, reddish-brown and reddish-brown infiltrates are formed, spreading peripherally, clearly demarcated from the surrounding area. The changes are accompanied by very intense itching. The enlargement of the lymph nodes in this period is the result of reactive processes (lymphadenitis dermathogenes);
3rd lumpy period (tumoriforme stage) – within or independently of the infiltrates, lofty, domed, soft, bluish-red tumors appear, prone to disintegrating and ulcerating. Lumpy changes in the face lead to thickening of its features (facies leonina). During this period, patients report malaise and weight loss. The simultaneous occurrence of symptoms of all stages of the disease in the same patient is characteristic. Atypical varieties of mycosis fungoides are also described:
- hives variety,
- bullous,
- exclusively lumpy,
- pustular,
- hyperkeratotic,
- hyperpigmentation,
- hypopigmentation, which occurs mainly in people with dark skin.
Mycosis fungoides has a chronic course and the initial period may last from several to several dozen years. Infiltrative and nodular changes develop very slowly, and less frequently tumors appear in the early stages of the disease. Sometimes the changes do not progress for many years, sometimes they regress periodically – spontaneously or under the influence of sunlight. Internal organs such as the liver, spleen, lungs or gastrointestinal tract – may be affected later in the disease. Lymph nodes – initially they show only reactive changes, in the nodular period their enlargement may be associated with the formation of high-grade lymphoma. The general condition of patients with granuloma is good in the initial and infiltrative periods, while in the later stages of the disease it depends on the extent to which internal organs are involved.
Diagnostics
Sometimes atypical lymphocytes are revealed in the peripheral blood. Routine laboratory tests allow the assessment of possible organ changes. In the early stage of the disease, the histological picture includes the deep layers of the dermis and sometimes the subcutaneous tissue.
Sezary’s team
Sezary’s syndrome is primary cutaneous lymphoma (type T), which is characterized by a generalized lymphadenopathy, the presence of atypical lymphocytes called Sezary cells (in the lymph nodes, skin and blood). The disease usually occurs after the age of 60, more often in men.
symptoms
The skin lesions are initially non-specific, such as eczema or chronic inflammation of the skin. Gradually, the skin of the whole body becomes inflamed – erythroderma. The skin becomes thickened and reddened (l’homme rouge – red man), leaving islets of healthy skin. After some time, the skin becomes brown discoloration.
These changes are accompanied by a very intense itching. It is also characteristic:
- facial skin involvement,
- hyperkeratosis of the hands and feet,
- generalized alopecia,
- nail changes.
Lymph nodes are enlarged, initially the changes are reactive, later in the disease they depend on a large number of atypical T cells. The course of the disease is slow, many years. Due to the decrease in the number of normal lymphocytes in the peripheral blood, skin infections and systemic infections often occur, which worsen the general condition and are sometimes the cause of death of patients.
Diagnosis
Cellular infiltration contains a large number of atypical lymphocytes with brain-shaped nuclei, the so-called Sezary cells. In the skin, lymph nodes and blood, so-called Sezary cells – atypical lymphocytes whose nuclei have folded surfaces that resemble the ganglia of the brain. Differentiation should take into account erythroderma in the course of other diseases, especially drug reactions and the early period of mycosis fungoides.
Pagetoid retina
Pagetoid reticulosis Worringer-Kolopp is a type T lymphoma with a chronic and relatively benign course. The disease is very rare, regardless of age, more often in men. Most often it attacks separate parts of the limbs, less often the lesions are disseminated.
symptoms
There are lamellar, erythematous-exfoliating foci on the skin, quite clearly demarcated from the surrounding area. In the localized form (Worringer-Kolopp type), they mainly include the lower limbs, in the disseminated form (Ketron-Goodman type), the progressive course and the possibility of mycosis fungoides development are characteristic.
Diagnostics
There are no Sezary cells in the peripheral blood. A characteristic feature of the infiltration are large lymphocytic cells with hyperchromatic, irregular nuclei. The epidermis shows acanthosis and parakeratosis. The dermis has perivascular infiltrates containing small lymphocytes and histiocytes.
Lymphomatoid papulosis
(Fig. 25.3)
Lymphomatoid papulosis is a chronic, recurrent papulo-nodular dermatosis, sometimes self-limiting, with histopathological features of malignant lymphoma. The disease occurs in both children and the elderly, most often between 30 and 40 years of age. The disease is more common in men.
Reasons: The cause of the development of the lesions is unknown so far, approximately 10-20% of cases are transformed into typical lymphoma.
Symptoms
In most cases, there are numerous small lumps and nodules with the presence of scales, crusts and hemorrhagic lesions. Eruptions resolve spontaneously, leaving pockmarked scars. At the same time, erythema spots (eczema-like foci) and individual tumors may appear.
During the infiltration period, there is extensive infiltration of lymphocytes, histiocytes, plasmocytes and eosinophils that penetrate the epidermis (epidermotropism), forming clusters of lymphoid cells, called Pautrier microcells. There is also the so-called mycosis fungoides cells, also called Sezary or Lutzner cells. These are cells that are larger than others and contain a large nucleus with a folded surface similar to the gyrus of the brain. In the nodular period, cellular infiltrates are more abundant, covering the deep layers of the dermis and sometimes the subcutaneous tissue.
RYC. 25.3. Lymphomatoid papulosis.
Cutaneous B-cell lymphoma (CBCL)
They make up about 20% of all primary cutaneous lymphomas. The diagnosis is made on the basis of the clinical picture and immunohistochemical tests, which confirm the involvement of B lymphocytes. WHO-EORTC classification distinguishes between benign and malignant lymphomas. In some cases, there is an association with Sjögren’s syndrome, Hashimoto’s thyroiditis, Helicobacter pylori and Borrelia burgdorferi infections.
symptoms
Changes occur on:
- skin,
- mucous membranes,
- sometimes on the lymph nodes,
- internal organs.
Eruptions are usually erythematous, infiltrative, papular and nodular changes, ulceration is rare. The course of the disease and the prognosis depend on the type of cells forming the infiltrates and on the coexistence of nodal and organ changes.
Diagnostics
The diagnosis of cutaneous lymphomas should include:
- interview,
- clinical symptoms,
- histological examination,
- immunohistochemical test – testing of CD antigens on the cell surface, PCR technique (polymerase chain reaction) allows to recognize whether a neoplastic growth has occurred,
- electron microscopy reveals the presence of Sezary cells, Lutzner cells and mycosis fungoides.
Treatment
Treatment is given depending on the type and period of development of the lymphoma local or systemic. Topical treatment is only used in mild forms of cutaneous lymphoma.
Topical treatment includes potent corticosteroids, nitrogranulogen, carmustine, bexarotene. Phototherapy is recommended – UVB, UVA, PUVA, radiotherapy and photodynamic therapy.
In the advanced stages, the following are used:
- systemic therapy (monotherapy or combination therapy),
- extracorporeal photophoresis (ECP), prednisolone, methotrexate, cyclophosphamide, doxorubicin, vincristine, bleomycin.
Good results were also seen with the use of interferon alpha, monoclonal antibodies and vaccines. The selection of therapy should take into account:
- the nature of the changes (some resolve spontaneously, but recur),
- general condition of patients,
- concomitant diseases and drugs used in connection with them,
- numerous side effects associated with chemotherapy.
LITERATURE:
1. Trautinger F. i wsp.: EORTC consensus recomendation for the treatment of mycosis fungoides, Sezary syndrom, Eur J Cancer 2006, 42, 1014-1030.
2. Burg G. , Kempf W., Drummer R.: Diagnostic signs of cutaneous lymphomas, JEADV 2001, 15, 358- -359.
3. Kotz E.A., Anderson D., Th ierst B.H.: Cutaneous T-cell lymphoma, JEADV 2003, 17, 132-134.
4. Sokołowska-Wojdyło M., Roszkiewicz J .: Primary cutaneous lymphomas, Czelej Publishing House 2008.
5. Kim Y.H. i wsp.: Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrom. Clinical prognostic factors and risk for disease progression, Arch Dermatol 2003, 139, 857-866.
Source: A. Kaszuba, Z. Adamski: “Dermatology. Practitioner Guide “; Czelej Publishing House