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Cutaneous B lymphomas: Dia-Gnostic and support
Summary
Primitive cutaneous B lymphomas (LBCP) are manifested by skin lesions without evidence of an overskin injury at the time of diagnosis. This paper summarizes the clinical and histopathological characteristics of the three main types of LBCP: primitive cutaneous b lymphoma of the marginal zone, Centrofolliculaire primitive cutaneous b lymphoma, and primary large cell cutaneous B lymphoma, Lower member type. It describes the elements of the initial balance sheet, indispensable to differentiate a LBCP from a systemic B lymphoma with secondary cutaneous impairment and ends with the treatment, local, little aggressive, indolent forms, and the polychemotherapy of the forms Intermediate.
Introduction
Primitive cutaneous B lymphomas (LBCP) are by definition limited to the skin at the time of diagnosis. In Europe, they account for 23 – 28% of all primary cutaneous lymphomas. 1 – 3 Most remain localized to the skin during their evolution and require low-aggressive treatments. It is essential to distinguish them from systemic B lymphomas with secondary cutaneous impairment, since prognosis and management differ considerably.
According to the WHO/EORTC (European Organisation for the research and treatment of cancers) Classification of 2005, LBCP are distinguished from indolent and intermediate evolution (table 1). 1 indolent forms include the primitive cutaneous B-lymphoma of The marginal Zone (LBCPZM) and Centrofolliculaire cutaneous B lymphoma (LBCPCF). Intermediate-Prognosis cutaneous b lymphomas are mainly represented by the lower-limb (LBCPGCMI) Large-cell cutaneous B-type lymphoma. The rare cases of large-cell B lymphomas, classified as "other", including B intravascular lymphomas (table 1), will not be treated here.
Table 1.
Cutaneous B lymphomas According to the WHO-EORTC 2005 classification
EORTC: European Organisation for the research and treatment of cancers.
Clinical features
Primitive cutaneous B lymphoma of the marginal Zone (LBCPZM)
It is in the form of diaper-nodules erythematosus, preferentially located at the trunk (46%) and upper limbs (17%). Lesions are generally unique but can be multiple, grouped, or multifocal (Figure 1a). 4 The average age is 55 years 4 and men are twice as affected as women. Some cases are reported in children. Immunocytomes and Plasmacytomas, formerly considered as full-fledged entities, are currently classified as variants of the LBCPZM.
Figure 1.
Clinical presentation of cutaneous B-lymphomas
A. Cutaneous B-lymphoma of the marginal zone in a patient aged 73 years, manifested by several infiltrated erythematous plates of different sizes on the trunk. B. Centrofolliculaire cutaneous B-lymphoma in a 58-year-old male, in the form of a erythematous tumor of the mandible with several satellite diaper-nodules. C. Large cell skin B lymphoma, lower limb type, in a 82-year-old patient, characterized by multiple purplish and infiltrated plates of the left leg.
Differential diagnosis includes insect bites, pseudo-lymphomas, other skin tumours such as basal carcinomas 5 or multiple myeloma in case of plasma-rich lesions.
The five-year survival rate is 98 to 100%. 4.6 Spontaneous resolution of lesions occurs occasionally, sometimes leaving a anétodermique scar. The secondary release of the skin is rare. Skin recurrences after treatment are common, especially in multifocal forms, but do not alter the prognosis. Association with Borrélienne infection has been observed in some endemic areas of Europe.
Centrofolliculaire Primitive cutaneous B lymphoma
It is manifested by single or grouped papules, érythémato-purplish plaques or nodules. Multifocal lesions are found in a minority of patients. The lesions are mainly located on the head and neck as well as the trunk (Figure 1b). On the trunk, we draw attention to the centrifugal extension variant, formerly known as Reticulohistiocytoma of the dorsum or Crosti lymphoma. The average age at the time of diagnosis is 60 years. Differential diagnosis includes insect bites, pseudo-lymphomas, or other skin tumours (basal carcinoma, Merkel's tumor). In some cases, LBCPCF located in the face can mimic acne or rosacea in the form of papules or diaper-pustules of the face. 7
The five-year survival rate is > 95%. 6 in the absence of treatment, the lesions grow gradually, but they can remain stable or even regress spontaneously in rare cases. Release to Undermal sites occurs in 5-10% of cases. The presence of multifocal lesions does not seem to aggravate the prognosis. On the other hand, the exceptional location of the legs is a factor of poor prognosis, coupled with a five-year survival rate of 41%. 6.8 In some cases, LBCPCF can progress rapidly and turn into large-cell B-lymphoma. Do not hesitate to redo skin biopsies if the clinical behaviour changes. Recurrences after treatment are frequent (46.5%). However, these recurrences are usually limited to the skin and do not affect the prognosis.
Primary large cell cutaneous B lymphoma, lower limb type
This type of lymphoma is found in red, brown or bluish papules, plaques or tumors, sometimes ulcerated, on one or both legs (Figure 1c). In 10-15% of cases, lesions are located on another part of the body. It affects women and older subjects more often (median age of 76 years). It typically produces tumors that increase faster in size than indolent LBCP and are more often multiple than unique during diagnosis. In the case of ulceration, the LBCPGCMI may be taken for venous ulcer.
The prognosis is less favorable than for other types of cutaneous B-lymphoma, with a five-year survival rate between 50 and 73% according to studies. 4, 6, 9 fewer complete remissions are observed after treatment, a greater number of recurrences and an extension More frequent. 9 The main factor of poor prognosis is the location to the legs, followed by the presence of multiple lesions (stage T). 10
The main characteristics of the different LBCP are summarized in table 2.
Table 2.
Comparison of the different types of primary cutaneous B lymphoma
LBCPZM: Primitive cutaneous B lymphoma of the marginal zone; LBCPCF: Centrofolliculaire primitive cutaneous B lymphoma; LBCPGCMI: Primitive skin B lymphoma with large cells, lower limb type.
Histology and Molecular Biology
In histology, small and medium-sized cells with notched nuclei (centrocytes) and plasma on the periphery of a dense infiltration of small reactive lymphocytes are characteristic of LBCPZM. of large enchoché nucleus cells, centroblasts, accompanied by centrocytes in a diffuse or dense nodular infiltration of small reactive lymphocytes, spoke in favor of a LBCPCF. When large cells predominate in this infiltration, it can be difficult to distinguish the LBCPCF from large cells of the LBCPGCMI. LBCPGCMI is present with a diffuse infiltration mainly of centroblasts and immunoblasts (large round-core cells). These infiltrates are found in the dermis or even the hypodermis. The epidermis is not touched.
In Immunohistochemistry, the markers CD20 and CD79a, Bcl-6 and CD10, Bcl-2, MUM1/IRF4, and FOXP1 are used. The LBCPZM is BCL-2 + and BCL-6-and CD10-. In LBCPCF, follicular centre cells generally express BCL-6 and CD10 but are most often negative for BCL-2. The Positivity of Bcl-2 in a LBCPCF is highly suggestive of the tumoral nature of infiltration and speaks against a reaction infiltration. The immunohistochemistry in case of LBCPGCMI highlights a profile B (CD20 +, CD79a +) of type "activated": Bcl-2 +, Mum-1/IRF4 + and FoxP1 +, and a high proliferation rate (MiB +).
The tumoral nature of the infiltration must be confirmed by the analysis of the rearrangement of the immunoglobulin heavy chain genes on a fresh or fixed-formaldehyde biopsy. Translocations, T (14; 18), for example, are generally absent in LBCP.
Assessment and Staging
History and Clinical Examination
In the examination, the presence of B symptoms: asthenia, weight loss and nocturnal sweating, the notion of tick bites, or the presence of other pseudo-lymphoma etiology, such as drug taking, bites of arthropods or injections at injury sites. The clinical examination specifies the number, topography and extension of skin lesions, the presence of adenopathies and a Hepato-splenomegaly.
Skin biopsy
A wide skin biopsy at the scalpel, up to the hypodermis, is indispensable for analyzing the architecture of lymphocytic infiltration, practicing a targeted immunohistochemistry and searching for a clonality.
Blood balance
It contains a complete blood formula, a hepatic workup, a dosage of LDH and β2-Microglobulin and a immunofixation. In endemic European regions, borrélienne infection should be investigated by serology (and/or PCR in the skin), since it may be implicated in the pathogenesis of certain LBCPZM. A clonal population circulating through flow cytometry and PCR will also be searched. 11,12
Imaging
Systemic lymphoma should be excluded by imaging (CT-Scan or PET-ct thoraco-abdominal-pelvic and cervical in case of skin lesions of the head or neck). Any lymphadenopathy > 1.5 cm, highlighted during this examination, must be biopsied.
Marrow biopsy puncture
The indication to a marrow biopsy should be discussed cases in case. Only 2% of a collective of 80 patients with LBCPZM had a bone marrow injury. This low percentage makes it reasonably possible to stay the marrow biopsy in the case of indolent evolution of the lymphoma. It's different for the LBCPCF. Indeed, a recent study has shown that the presence of a medullary injury significantly aggravates the prognosis. 13 in the LBCPGCMI, the presence of a medullary injury does not usually alter the therapeutic choice. It is therefore not formally recommended in elderly and polymorbid patients, but should be discussed in the younger patients.
Followed
The follow-up is essentially clinical, due to a consultation every three to six months for two to three years and then depending on the evolution. Radiological testing is only necessary for LBCGCMI, for which the risk of extending is important, even after complete remission. There is no consensus regarding the type of imaging or the pace of controls. 11
TNM Classification
The TNM classification for cutaneous lymphomas is descriptive and allows for a grouping in stages according to the extension. 14 by definition, LBCP are limited to the skin and are therefore classified N0M0 (table 3).
Table 3.
Staging EORTC/ISCL non MF/SS cutaneous lymphomas
MF/SS: mycosis fungoides/sezary syndrome; EORTC: European Organisation for cancer Research and treatment; ISCL: International Society for cutaneous lymphomas.
Treatments
The choice of treatment is based on the recommendations of the French group for the study of cutaneous lymphomas and EORTC. In the absence of a prospective and comparative study, a consensus of experts, based on a review of literature and clinical experience, was established. 11,12 the extent, size and location of lesions should be taken into account when selecting Treatment.
In the case of cutaneous lymphomas indolent pauci-injury, radiotherapy (30 Gy and irradiation margins of 1-1.5 cm) is the treatment of choice. It results in a complete remission in 100% of cases. Recurrences on unirradiated sites are nonetheless frequent. 8 Depending on location, a surgical resection can be discussed. A monoclonal antibody, the anti-CD20 or rituximab, has been used in intralesional by some first-line centres successfully. 15 in the presence of a small tumor mass, simple monitoring is acceptable. In the case of multiple evolutionary lesions or high tumour mass, systemic treatment should be proposed (rituximab IV, chlorambucil). 16 polychimiothérapies are very seldom indicated in the LBCPZM. In the LBCPCF, they are restricted to the few progressive forms that escape the other treatments, to cases with an overskin progression, or to the extended forms localized to the lower limbs.
In case of LBCPZM, if the search for a borrélienne infection is positive, antibiotic therapy may be proposed at first intention. However, there is little data available in the literature, the results of which are also contradictory. 17
For LBCPGCMI, R-CHOP type chemotherapy (rituximab, cyclophosphamide, Luxurambicine and vincristine) ± radiotherapy is the treatment of choice. This treatment will nevertheless be adapted to the patient's age and commorbidités. In patients with commorbidités who contraindicate this type of treatment, radiotherapy or rituximab alone may be considered.
Conclusion
We currently know that most LBCP are favorable prognosis and require low-aggressive treatments. It is important to note the importance of the initial evaluation of the LBCP to define the type, to rule out an outskin impairment and to determine the management. It will be in most cases multidisciplinary, including dermatologist, radiologist, Radiotherapist and Oncohématologue with the collaboration of the doctor treating the patient.
Practical Implications
> cutaneous B lymphomas are most of the time favorable prognosis
> histopathological examination and immunomarquages make it possible to distinguish indolent forms from cutaneous B lymphomas to large cells, which are less good prognosis
An extension balance should be carried out at the time of diagnosis, in order to differentiate a primitively cutaneous B lymphoma from a systemic lymphoma with secondary skin impairment
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