Lymphoma
Lymphoma is a type of malignant skin cancer in which cells originate from lymphocytes. Are rare (tumors about 3 cases for 1 million people per year), with numerous clinical and cellular forms. Most often, injuries are increasingly slow, confused with other skin diseases and treated only in the years after the onset.
Lymphomas occur after malignant lymphocyte degeneration, key role cells in immunity. They are mainly located in the main lymphoid organs, they produce (thymus, bone marrow), but is found in other tissues such as lymph nodes, spleen, tonsils, blood and skin. When the cancer develops from the lymphocytes located in the skin (not metastase here from another organ), called lymphoma. The two main types of lymphocytes (B and T) have different roles in immunity. From these cells can turn many cancers, with clinical prognosis, behavioral and a different treatment. Most lymphomas are skin T cells, especially because of a condition called fungoides fungus. B-lymphoma cells account for less than 1/3 of cutaneous lymphomas.
Due to their extreme variability histological cutaneous lymphomas have different ways of expression. Most often, the skin appears one or more patches or patches, rough surface cells, dry exfoliate with slow growth. The appearance can be very similar to those of eczema or psoriasis. However, the appearance of lymphoma can sometimes underline the lesion, nodular, with loss of substance (wet lesions), which can be infected and do not heal spontaneously. There are few types of tumor lesions can become important, aggressive, can affect the lymph nodes and other organs and the chance healing is low.
The correct diagnosis of skin lesion involves biopsy (removal of a piece of leather) and microscopic analysis of the cells, structure, biochemically and immunologically.
The treatment depends on the type of lymphoma cancer and is not always indicated. Sometimes the attitude and bdquo, careful monitoring is the best option. When recommended, treatment may include a topical, topical (creams with steroids, chemotherapeutic agents, UV Light, radiation) and/or a systemic approach (chemotherapy, immunotherapy).
The prognosis depends on the type of tumor and the timing of diagnosis and treatment and ndash; For example, Mycosis fungoides an early diagnosis does not alter survival in 10 years, while the one in stage IV offers survival of 20% after 10 years. [1, 2, 3]
Causes and risk factors
Lymphoma occurs when the immune cells called malignant degenerate lymphocytes after many mutations accumulate in the genetic code. They allow to multiply excessively and survive longer than normal cells, perpetuating genetic defects as many cell generations. There are two main types of lymphoma, grouped by the appearance of cells:
Hodgkin's lymphoma, which has the skin of Reed-Sternberg cell markers and tests may have, among other places
NHL, which includes all other primary malignant tumors of the other lymphatic system, including skin
The term bdquo, the names of degeneration of skin malignant leather cells. When lymphoma starts elsewhere in the body and spreads to the skin later, it is considered lymphoma.
There are no known causes of the onset of mutations in intracellular this type of cancer, but has defined several factors that increase the risk of lymphoma: decreased immunity and ndash; People with an immune deficiency (AIDS, people grafted with chronic immunosuppressive therapy) usually develops lymphoma
Infections and ndash; In addition to HIV in some parts of the world, bacteria of the genus Borrelia infection may increase the risk of developing this type of tumor. In addition, B-cell skin infection occurs most often in the presence of Epstein-Barr virus, hepatitis C virus and human herpes virus 8.
Constitutional and ndash factors; Overall, cutaneous lymphomas occur more frequently in men after the fifth decade of life. Moreover, blacks seem to be more affected than others. A
Classification of cutaneous lymphomas
There are two main types of lymphocytes, with different roles in immunity: B lymphocytes u0026 ndash; Provide humoral immunity by the production of antibodies directed against pathogenic micro-organisms
Ndash u0026 T lymphocytes; Tissues involved in immunity by specific recognition of certain subjects (and bdquo cells, memory), the manufacture of compounds called cytokines, the role of other inflammatory cells to call from the site of infection; These lymphocytes have complex roles, including the stimulator or inhibitory effect cell on other immune
From these two types of cells develop two large skin classes. In addition, they can be classified according to their microscopic appearance of markers expressed by malignant cells. The classification used worldwide is carried out by the World Health Organization and the European Organisation for the research and Treatment of cancer (abbreviated in English, who-EORTC).
Cell Skin T lymphoma
Mycosis fungoides u0026 ndash; Equal to about 50% of all cutaneous lymphomas. The cells involved are able to leave the skin by the lymph vessels, making it a systemic syndrome.
Sezary u0026 ndash Syndrome; Fungoides syndrome pseudo-fungal, but sezary defined by the presence of specific cells, significant damage to the skin and part of the rapid evolution.
Primary cutaneous lymphoma, large cell anaplastic
Lymphomatoid Papulosis
Subcutaneous panniculitis type T-cell lymphoma
Primary cutaneous lymphoma, T lymphocytes, without precision of u0026 ndash; A group containing several types of T-cell lymphomas that do not meet the criteria for the other categories.
B of Cutaneous lymphocytes
Primary cutaneous lymphoma, B lymphocytes, central-follicular zone u0026 ndash; The most common type of B-cell lymphoma
Primary cutaneous lymphomas, B cells, marginal area of u0026 ndash; related to Borrelia infection; Slow growth.
Primary cutaneous lymphoma, large diffuse B lymphocytes (typically legs)
Primary cutaneous lymphoma, large diffuse B lymphocytes (the other) [1]
Signs and symptoms
Most of the non-specific cutaneous lymphomas of the manifestations, the main sign is the appearance of one or more lesions on the skin that can be: Macules (stains) u0026 ndash; Color changes (erythema u0026 ndash, red, violet)
Tiles-changing the relief areas of the skin, sometimes the texture or color (glossy, smooth or rough)
Ndash u0026 papules; Limited projections having a small diameter
Size or growth
Erosions or ulcers (superficial loss of the substance, which is deep, causing damage and bdquo; wet)
Descuamaţie Zone
Sometimes a single lesion is present, sometimes can present several types of lesions on a particular area or several regions are affected by the skin.
Lesions may be asymptomatic or may be accompanied by: pain
Elegance
Itching
Some lymphomas may have characteristic symptoms, but not necessary: confluent erythematous plaques, intensely itchy; Lymphadenopathy u0026 ndash; Mycosis Fungoides
Toxic, which is a exfoliative dermatitis (generalized inflammation and Descuamaţie called u0026 bdquo, Red man syndrome) u0026 ndash; Sezary's syndrome
Papules with random distribution, appearance and healing and spontaneous ndash; Papulomatoză papulosis
Rarely, cutaneous lymphomas may be accompanied by systemic symptoms: fever
Weight loss
Anorexia
Asthenia [1, 3, 4]
Diagnosis
Clinical
Because of the variability in the onset and evolution of lesions, clinical diagnosis of lymphoma is often impossible. Some skin characteristics may have evolved. Overall, T-lymphoma progresses slowly, over several years, is sometimes preceded by precancerous lesions, in which the stage of a definitive diagnosis can be reached.
The Mycosis fungoides, which is the main form of lymphoma is often preceded by a para-frequent non-specific dermatitis, without pain, onset of psoriasis, a large plaque. They can advance years to reach the fungoides of classical fungal stage, stains, plaques and tumors. As a general rule, plaques are intense itching, and can progress towards a tumor prone to ulceration. Lymphadenopathy may be present. Fungal fungoides evolution may be sudden and may occur at any stage of several plaques and/or tumors, and depigmentation ulcers.
Sezary syndrome is diagnosed according to the presence Eritrodermiei (confluent erythematous plates, itching, diffuse, on almost the entire surface of the skin), as well as typical cell leukemia (diagnostic laboratory).
Primary large-cell cutaneous lymphoma, anaplastic in the form of multiple skin tumours of different sizes. Most often affects men after the 5th decade of life, but may be present in children. Non-skin lesions diffuse outward evolve slowly.
Lymphomatoid Papulosis is located the spectre of benign tumors of the skin, which takes place slowly without diffusion outside the skin. Begins with several papules that can ulcerate central and heal spontaneously for a long time (months to several years). It is more common around the age of 45 years.
Lymphoma of panniculitis subcutaneous type T lymphocytes is very rare and is manifested by the appearance of subcutaneous nodules, slow growth, especially in the lower limbs.
Unlike T-cell cutaneous lymphoma, B lymphocytes tend to evolve rapidly within a few weeks without being preceded by other skin lesions.
B-cell lymphoma of the primary cutaneous lymphoma of the marginal zone represents about 10% of the skin. It shows that one or more of the papules, erythematous plaques or nodules, painful, particularly affecting the trunk and limbs.
B-cell lymphoma, follicular Central zone has a similar appearance, but occurs more often in the head and neck. However, these demonstrations are not binding and specific.
Primary cutaneous lymphoma, diffuse to large cells B, occurs most often in the legs, in the form of large pieces. In full evolution, with diffusion to the lymph nodes and other organs. [3, 4, 5] paraclinically
Skin biopsy
In order to obtain an accurate diagnosis of lymphoma, there is a need for a thorough examination of the cells in skin lesions by various methods. They are obtained by biopsy of the suspected lesion, applying clinical situations of appropriate technique: biopsy scraping and ndash; In the case of superficial lesions can be useful segments obtained by scraping long, about 1 cm. It is a useful technique for the diagnosis of Mycosis fungoides first when they can not be practiced other types of biopsies.
u0026 ndash incisional biopsy; The removal of a small part of a larger size of the lesion, including the subcutaneous tissue.
excisional biopsy u0026 ndash; Completes surgical ablation of the therapeutic safety injury margin, depending on clinical suspicion and subsequent confirmation of diagnosis.
Fragments of skin tissue produced are then subjected to various processes (cutting, tightening formalin gel, paraffin wax, dye, etc.) and used for additional testing.
Microscopy microscopic analysis of fixed and coloured tissues can distinguish between malignant and benige lesions, as well as tumour cells of lymphoid origin. The distinction between the two major types of cutaneous lymphoma is based on the organization of malignant cells: B lymphocytes in lymphoma cells tend to arrange spherical agglomerated, non-epidermotrofice
T lymphocytes in discoid lymphoma cells are arranged horizontally and oriented epidermotrofic
Mycosis fungoides histological aspect is in the initial non-specific, inflammatory phases, but it can be revealed that the lesions are progressing. The characteristic results include: u0026 Bdquo lymphocyte infiltration, the band in the upper dermis
Épidermotropisme
Hyperchromatic nucleus lymphocytes with cérébriforme appearance
Microabcess Pautrier u0026 ndash; Clusters of mononuclear cells with atypical surrounded by a clear halo
Sezary syndrome is a very similar histology; Epidermotropismul may be absent, let alone infiltration have mycosis fungoides varied as.
Lesions of B-cell cutaneous lymphoma may be characteristic for inclusion in a subtype.
Immunohistochemistry immunohistochemical Studies show the presence of some specific markers of lymphocyte subtypes. These are proteins expressed by lymphocytes normally suffering a few changes when degenerating malignant cells. The presence of a large number of a particular type of immunohistochemical markers show these cells, of monoclonal origin (derived from a bdquo u0026, with the same parent cell markers). The molecules can be analyzed: T cell lymphoma: CD2, CD3, CD4, CD5, CD7, CD8, CD30, CD45RO, CD56
B cell lymphoma: CD5, CD10, CD19, CD20, CD21, CD23, CD30, CD43, CD79a
Depending on the presence/absence of these markers, cancer can be put into a sub. However, some types of cutaneous immunohistochemical markers may be inconclusive (e.g., the appearance of Fundoides fungoides).
Other tests in the presence of a lymphadenopathy, a biopsy is recommended to practice the lymph nodes affected. Routine biopsy is not recommended when there is no sign of clinical involvement.
Globular counts are indicated for the diagnosis of Sezary syndrome. In this case, the number of lymphocytes is increased in the peripheral blood and the sezary cells are present in large numbers. Microscopically, these lymphocytes with atypical characteristics, with the nucleus cérébriforme with a morphology similar to tissues and blood and sizes (small, less than 12 u0026 micro; m, large or very large, more than 14 u0026 micro; m).
In addition, due to the potential of skin to affect other organs, instruction of liver function (ALT), uric acid, LDH. HIV testing may be indicated Borrelia or HTLV when they are suspected involvement of these micro-organisms.
Imaging of studies (ultrasound, X-ray, abdominal CT-pelvic lymph nodes of affected persons) shows the involvement of other organs.
The staging of cutaneous lymphomas
Staging of cancer is a standard assessment of the evolution of its role in the treatment and prognosis. If cutaneous lymphomas, fungal fungoides except and sezary syndrome, a knowledge classification commonly admitted not long ago and therefore not yet all its practical implications. This system uses T, N, M, which takes into account the dilation of the skin of the tumor (T), the involvement of the regional lymph nodes (N) and the presence of metastases in other organs (M). It was developed by the International Society for lymphomas with cutaneous EORTC.
T
T1: Solitary lesion
T1A: Maximum diameter solitary lesion
T1B: Solitary lesion maximum diameter u0026 gt; 5 cm
T2: Multiple lesions confined to one area of the body or two zones of continuity
T2A: All events can be included in a circular area of a diameter
T2B: All events can be included in a circular area with a diameter between 15 and 30 cm
T2C: All events can be included in a circular area with a diameter u0026 gt; 30 cm
T3: Generalized Skin lesions
T3A: Multiple wounds affecting two areas of the body that are not in continuity
T3B: Multiple wounds, affecting three or more parts of the body
N N0: No clinical or laboratory evidence of lymph nodes with a disability N1:1 affected lymph nodes that drains an area that is or was present lymphoma N2: affected two or more lymph nodes that drain the region of the Skin with current or former lymphoma or deterioration of a lymph node that drains an area where lymphoma has never been present N3: lymph nodes alteration of the ball (mediastinal of pulmonary hilurilor, and iliac Paraortici)
M M0: No evidence of damage to other organs or M1 tissues is present in the spread of the tumor outside the lymph nodes or skin
Mycosis Fungoides and Sezary syndrome receive separate intermediate storage, including criteria T, N, M, and in addition B (the presence of cancer cells in the blood)
T Q1: Patches, papules or plates and affecting u0026 lt; 10% of the body surface T2: patches, papules or plates and affecting u0026 gt; 10% of body surface T3: At least one lesion has a diameter greater than or equal to 1 cm Q4: lesions covering at least 80% of the body surface
N N0: The lymph nodes are not enlarged by N1: the lymph nodes increase in volume, but is almost normal histology N2: The lymph nodes reached, the intermediate degree of histopathological damage N3: lymph nodes Lymphatics affected, high quality histological damage NX: Clinically affected lymph nodes, but are not evaluated histopathological
M M0: No metastases of the external lymph nodes M1 are metastases in other organs or tissues
B B0: Less than 5% of circulating lymphocytes cells are sezary B1: less than 5% of cells are circulating lymphocytes sezary B2: In the blood are at least 1,000 cells/sezary and micro; L
In this classification, the group of subcategories T, N, M, B lymphoma Step provides: Step IA T1, N0, M0, B0/B1
Step IB T2, N0, M0, B0/B1
Step IIA T1/T2, N1/N2 M0, B0/B1
Step IIB T3, N0-N2 M0, B0/B1
Step IIIA: T4, N0-N2 M0, B0
Step IIIB: T4, N0-N2 M0, B1
Step IVA1 According to any T, N0-N2 M0, B2
Step IVa2 all T, N3, M0, all B
Stage IVB any T, any N, M1, whatever B [1, 6]
Treatment
The treatment of cutaneous lymphomas includes several variations, depending on the type and subtype of the tumor, the stage where the patient's health status and his preference. Overall, this treatment can be classified in local and systemic therapies.
Local treatments
Topical drug formulations are among the most common skin lymphoma treatment tools, especially in the early stages. They may be in the form of a gel, ointment or solution, and may contain: chemotherapeutic agents (nitrogen mustard, carmustine) u0026 ndash; of treatment Mycosis Fungoides first line with role T1 or T2 or adjuvant, as well as other therapies. The main side effects are contact dermatitis and telangiectasia for treatment.
u0026 Ndash Corticosteroids; Mycosis Fungoides used for treatment (step T1 to T2 Plus) and as a second line of treatment of B lymphocyte cutaneous lymphomas
Retinoids (bexarotene) u0026 ndash; Modify the structure of the DNA of cancer cells; Useful Peter T-skin lymphomas by stages IA-IIA, refractory to other treatments
Immunotherapy (imiquimod) u0026 ndash; Improves the immune response to the lesion site
Sometimes, medications can be administered by subcutaneous means (injection) to pierce the site of the lesion. They can be administered in this way for the treatment of B-cell lymphomas: Interferon alpha
Corticosteroids
Rituximab
Phototherapy uses the ability of ultraviolet rays to kill cancer cells. Using special lamps, high intensity UVA and UVB light rays are intended for tumor lesion. PUVA is a combination of phototherapy with UVA and Psoralen, a drug that is concentrated on lesions and is activated when exposed to UVA radiation, destroying cancer cells. The best results are obtained if the Mycosis fungoides in the early stages.
Radiotherapy uses a high intensity, targeted at the affected area. If cutaneous lymphomas with superficial lesions can be used electron beam radiation. This type of radiation does not penetrate deeply, which reduces the risk of lesions of the underlying organs. It is particularly suitable for T-cell lymphomas; Sezary syndrome, can radiate the entire surface of the skin. Radiotherapy is the classic first line treatment and B lymphocytes in solitary lymphoma lesion.
Surgical excision of the lesion may be more frequently given in B-cell lymphomas is often accompanied by another local or systemic therapy.
Systemic therapies
Systemic chemotherapy is given in cutaneous lymphomas that are too advanced locally, do not respond to treatment or have spread to other parts of the body. Medications that can be used include: gemcitabine
Doxorubicin
Methotrexate
Chlorambucil
Cyclophosphamide
Chioterapia with systemic side effects and common mains: hair loss, nausea, vomiting, predisposition to infection and bleeding.
Retinoids, they can be administered via systemic, oral bexarotene is indicated for treatment of refractory T cell lymphoma to treatment.
Biological therapies that target tumor cells more specifically, are indicated in refractory T-lymphoma to other treatments. The following active substances: Vorinostat
Romidepsine
Bortezomib
Donileukin Diftitox
Rituximab
Although rarely used for the healing of cutaneous lymphomas, stem cell transplantation can be used to allow the patient a higher dose of chemotherapy. [1, 3, 4, 5] Prognosis
The main factors determining the prognosis of a patient with lymphoma are: at the time of diagnosis
Involving other areas outside the skin
The presence of systemic symptoms
Increase in LDH
The induction of clinical remission
The Mycosis fungoides diagnosed and treated at the AI stage does not change the patient's life expectancy. Stage IV, life expectancy after 10 years is 20%. Sezary syndrome, patients have a median survival of 2-4 years. There is little data on B-cell cutaneous lymphomas, which, but usually a good prognosis, given the diagnosis and the rapid treatment of wounds.
0 comments:
Post a Comment