Atypical presentation of Centrofolliculaire B lymphoma
Summary
Follicular B lymphoma is an indolent lymphoma that is manifested by fluctuating asymptomatic adenopathies. It can sometimes be in the form of skin lesions. In this case, it is essential to distinguish a secondary localization of the systemic follicular lymphoma from a primitively cutaneous B-lymphoma. The Immunophénotypique study and the extension balance allow to make a difference. In this paper, we report the first described case of systemic follicular B lymphoma with secondary cutaneous impairment that manifested in the form of mimicking-Rosaceae facial skin lesions.
Introduction
Follicular lymphoma (LF) is the second most common lymphoma among non-Hodgkin lymphomas. In Europe, its incidence is estimated at 2.18 cases for 100 000 people/year. 1 incidence increases with age. The median age at the time of diagnosis is 60 years.
The LF develops from the B cells of the germ center. In most cases, the translocation T (14; 18), which causes an overexpression of the Bcl-2 protein, a member of the protein family that blocks apoptosis, is found.
It is an indolent lymphoma, which is initially manifested by asymptomatic adenopathies. A medullary injury is present in 70% of cases, but the invasion of other organs is not usual. 2
In this paper, we report the case of a patient with systemic follicular B lymphoma with a secondary cutaneous impairment initially manifested in the form of facial papules, clinically suggestive of rosacea.
Observation
Mr. C. 87 years old, is known for hypertension treated with anticalcium, obesity, monoclonal IgM kappa Gammapathie (MGUS) and unpaired sleep apnea syndrome. It presents, in February 2011, erythematous papules, without epidermal impairment, confluent in plaques, fixed and not itchy of the two cheeks and the lobe of the right ear. Pustules and Telangiectasia are not found (Figures 1a and B).
Figure 1.
Clinical Review
Infiltrated erythematous papules, confluent in plaques, fixed and not itchy on both cheeks and the lobe of the right ear. (Polyclinic of Dermatology, HUG).
In front of these lesions, we evoke as a differential diagnosis an infiltration granulomatous (rosacea granulomatous or sarcoidosis), a lymphocytic infiltration (lymphoma, or pseudolymphome) or an inflammatory pathology of type Lupus or polymorphic lucite.
A skin biopsy is performed. A histological examination is found in lymphocytic infiltration with cytonuclear atypies and the formation of germ centres (figures 2 and 3). The Immunophénotypique study showed positivity of B (CD20 +) phenotype markers (Figure 4), a marker of Bcl-6 in Follicular centre cells (Figure 5), and diffuse positivity for Bcl-2 (Figure 6). This histological image and immunohistochemical profile are compatible with Centrofolliculaire cutaneous B lymphoma, nevertheless the positivity of Bcl-2 is unusual.
Figure 2.
Skin Histology
Under a atrophic epidermis, a dense cellular infiltration is found in the superficial, medium and deep dermis.
Figure 3.
Skin Histology
Cell ranges consisting mainly of lymphocytes showing cytonuclear atypies with formation of germ centers.
Figure 4.
Staining
Cells predominantly of B phenotype (CD20 +).
Figure 5.
Staining
BCL-6 marking in follicular centre cells as well as some positive cells for the kappa and Delta light chains of immunoglobulins within these lymphoid foci.
Figure 6.
Staining
Positivé Diffuse for Bcl-2.
We therefore perform an extension balance including a CT and a marrow biopsy (PBM). The Cervico-thoraco-abdominal scanner shows multiple adenopathies mesenteric and metastasis, not accessible to a puncture.
The PBM shows a trilinear marrow with a small CD20 + and CD79 + lymphocyte cluster, which suspects a probable medullary localization of Centrofolliculaire lymphoma (Figures 7a and B). There is not enough material for the immunomarquages. Flow cytometry on blood and medullary aspiration are negative.
Figure 7.
Marrow biopsy puncture
Presence of tumour cells in the bone marrow, including atypical B lymphocyte infiltration (CD20 + and CD79 +).
However, a molecular biology examination in the skin shows a translocation t (14; 18) between the BCL-2 genes and the immunoglobulin heavy chain (IgH) (Figure 8).
Figure 8.
Molecular biology
Translocation T (14; 18) involving the BCL-2 genes and the heavy chain Ig (IGH) detected by FISH. FISH: Fluorescence in situ hybridization.
The diffuse expression of Bcl-2, the presence of T (14; 18) translocation, a probable ganglionic attack, and a spinal impairment orient us in our case to a systemic LF with secondary cutaneous impairment.
From a therapeutic standpoint, given the comorbidities and advanced age of the patient, we introduce a cycle of four rituximab infusions of 375 mg/m2 1 x/week for one month, with favorable clinical evolution.
One year after remission, a recurrence was observed in the form of cutaneous nodules of the right temple and an infiltration of the right thoracic wall, which was objective for the CT. The histology of the right thoracic wall puncture confirms the recurrence of this grade II follicular lymphoma. Despite the introduction of a second cycle of four infusions of rituximab, followed by a maintenance treatment every three months, the evolution is unfavourable.
The patient then benefits from radiation therapy on the temple and the right chest wall which consists of 20 Gy administered in five fractions of four Gy.
Six months later, the patient shows up with a decrease in his general condition. A scanner shows a right Intraparotidienne lymphadenopathy, a Rétrotrachéale mass, and a lytic lesion of the head of the left humerus. The cytoponction of the parotid nodule shows an image compatible with known follicular lymphoma, but the puncture of the lytic lesion of the head of the humerus evokes a transformation in diffuse B lymphoma to large cells.
Discussion
In most cases, systemic LF is initially manifested by adenopathies, which may be accompanied by a medullary injury. In our case, the patient had concomitant secondary skin damage, which allowed the diagnosis to be made. Clinical and histological presentation could have been compatible with Centrofolliculaire cutaneous B lymphoma (LBCCF). Nevertheless, the positivity of Bcl-2 and the presence of translocation T (14; 18) have directed us to secondary lesions. Systemic LF and LBCCF should be considered as two different entities, given the phenotypic differences. In addition, LBCCF have a better rate of response to treatment as well as better prognosis, and therefore do not require heavy chemotherapy-type treatments in the majority of cases. 3 The expression of Bcl-2 in a cutaneous LF should therefore induce us to Look for a systemic LF with secondary cutaneous impairment by a full extension balance. 4
In our case, the disease was manifested by very atypical skin lesions, clinically suggestive of rosacea.
Lesions of primary or secondary cutaneous follicular B lymphoma are usually characterized by infiltrated erythematosus nodules distributed asymmetrically on the cephalic end, less often on the trunk. Diseases lymphoproliferative B mimicking rosacea or rhinophyma are extremely rare. There are only twenty cases described in the literature. This was a LBCCF in five cases, 5.6 of a LBC in the marginal zone in ten cases 5.7 – 10 and a chronic lymphoid leukemia 5,11 – 13 in five cases. To our knowledge, no case of systemic LF, having this type of presentation, has been previously described. Of the twenty cases described in the literature, four had pre-existing rosacea that appeared in the form of a facial flush, erythema, and cheek telangiectasia. 5.9 The appearance of papules and Rhinophyma in these cases was attributed to The progression of rosacea.
Most patients had benefited from a treatment of rosacea (antibiotics, topical treatments), with an unfavourable evolution, motivating a skin biopsy.
The average time between the initial presentation and the diagnosis was from a few months to ten years.
According to the authors, it can be assumed that chronic antigenic stimulation caused by organisms, such as the Demode (genus of mites of the Demodicidae family), results in the development of lymphoma, as for Helicobacter pylori in the Gastric lymphoma. The localization of lymphoma at the facial level may also correspond to a isomorphic phenomenon on sites of pre-existing rosacea. 5
Conclusion
Skin damage to B lymphomas may mimic rosacea or rhinophyma. The diagnosis is often late. Therefore, do not hesitate to do a biopsy in front of rosacea-type lesions that do not evolve favourably after treatment with systemic or topical antibiotics. Once the diagnosis is made, it is important to distinguish a centrofolliculaire cutaneous B lymphoma from a secondary cutaneous localization of systemic follicular B lymphoma, a staging comprising a scanner, a bone marrow biopsy, and a Immunophénotypique Study (search for the expression of Bcl-2 and translocation T (14; 18)).
Practical Implications
> biopsy should be performed in front of any rosacea not evolving favourably under systemic or local antibiotic treatment
> It is important to distinguish Centrofolliculaire cutaneous B lymphoma from follicular b lymphoma with secondary cutaneous impairment, since the prognosis and treatment will be different
In the case of Centrofolliculaire B lymphoma, the positivity of the Bcl-2 expression to the immunomarquages should refer to systemic lymphoma and induce a complete extension balance
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