On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.6 Rio de Janeiro Nov./Dec. 2004
Cutaneous B-cell lymphoma: a case report*
Mariana de Gusmão NunesI; Ana Paula Soares de Moura PierroII; Maria Fernanda Villela CoutinhoIII; José Carlos Oliveira de MoraisIV; Sueli Coelho da Silva CarneiroV; David Rubem AzulayVI
IStudying for masters degree of Dermatology
IIMD Trainee Dermatology of Dermatology Service, HUCFF/UFRJ
IIIMD Specialist Dermatology at UFRJ
IVAdjunct Professor, Department of Pathology, FM/UFRJ
VProfessor, Post-Graduation Program in Dermatology, FM/UFRJ; Adjunct Professor of Dermatology, FCM/UERJ; Physician, Dermatology Service, HUCFF/UFRJ
VIAssistant Professor of Dermatology, FM/ UFRJ; M.D. Dermatology Service, HUCFF/UFRJ; Titular Professor of Dermatology, PUC; Adjunct Professor of Dermatology, FTESM
Cutaneous lymphomas are classified as either type B cell or T cell lymphoma, the former type being less frequent. Cutaneous B cell lymphoma (CBCL) may be primary or secondary. The latter has a more aggressive natural history with a worse prognostic. In this paper, the authors present a secondary CBCL case with a three-year evolution, indolent course, without involvement of other organs beside the skin and with optimal response to chemotherapeutic treatment. The distinction between primary and secondary CBCL is very difficult to determine insofar as they are clinically and histopathologically indistinguishable. It is always necessary to investigate whether internal organs have been affected prior to defining the prognosis.
Key words: lymphoma, B-Cell; skin manifestations; prognosis.
Lymphoma is a malign neoplasia resulting from the proliferation of cells from the lymphoid system, which has a varying potential for organic aggression. Lymphocytic leukemias, plasmocytomas, Hodgkin's lymphoma and non Hodgkin's lymphomas stem from this lymphoid lineage.
The non Hodgkin's lymphomas comprise a neoplasia group derived from lymphocyte clones in their different evolutive stages. They may originate primarily in the lymph nodes (nodal lymphomas) or in lymphoid tissue connected to mucouses, skin or other structures (extranodal lymphomas).1
Cutaneous lymphomas are classified according to their cellular origin in T-cell lymphomas or B-cell lymphomas.2 Their average frequency is 0.3/100,000 inhabitants yearly, with 65% T-cell, 25% B-cell and 10% true histiocytic lymphomas or rare cell types.2,3 From the dermatological point of view, B-cell types are characterized by only a few lesions that are usually nodules or infiltrations, and are relatively fast growing. As opposed to T-cell types, they do not show pruritus.
From the histopathological point of view, B-cell types are monomorphic (small and large cells), and the infiltrate is separated from the epidermis by the so-called Unna collagen strip; whereas T-cell types are epidermotropic.4 In order to differentiate them, monoclonal antibodies are currently used. The expression of CD3, CD4, CD8, CD43 or CD45 confirms their T-cell character. And the expression of CD20, mainly, and CD19, CD23 and CD79, in addition to CD5, CD10, CD32 or CD38, confirms the B-cell character.3
B-cell cutaneous lymphoma (BCCL) may be considered primary or secondary. The primary type is the one with a cutaneous presentation but with no evidence of extracutaneous lesions at the moment of the diagnosis, or up to six months thereafter.5-9 In spite of being identical in morphological appearance, they have different clinical behaviors. The primary type has a more indolent natural history than the secondary one. It has a good prognosis, local relapses in 25% to 68% of cases, and rare extracutaneous dissemination. A patient's average survival rate over five years varies from 89% to 96%.10
A 46-year-old Afro-Brazilian man, born and living in Rio de Janeiro city, Rio de Janeiro state, and unemployed (he used to be a delivery man), sought assistance at the Dermatology Service of the Hospital Universitário Clementino Fraga Filho (HUCFF) in December 2000, complaining of a skin tumor. He reported having a history of small papules that appeared in the thoracic region three years prior. The latter associated with an insect sting that had occurred on the same spot 15 years earlier. It progressed as the lesion increased in size, turning into nodules. Approximately a year ago, the tumor grew to 8 cm in size. The patient referred to high-intensity pain at the localization and to an increased volume in the left axilla, which was also painful. He ended up seeking out another service at which draining and curettage of the lesion were done, without any improvement. He was referred to this hospital, where he was interned for 17 days for a diagnostic investigation.
The physical examination revealed a nodular lesion approximately 8 cm in diameter, with a hardened consistency. Adhering to the deep planes, the lesion had a smooth, multilobulated surface and ulceration on its lower part. It was localized on the right anterior thoracic region. There were even small skin-colored papules close to the lesion (Figure 1). An increase in volume was also observed in the left axillary region, which corresponded to a painful lymphadenomegaly. It had a hardened surface, adhered to the deep planes, and was roughly 4 cm in diameter (Figure 2). The rest of the physical examination was normal.
The diagnostic hypotheses were dermatofibrosarcoma protuberans, a tumor of the annex, spinocellular carcinoma and cutaneous lymphoma.
The laboratory investigation revealed a normal hemogram; VDRL, anti-HIV and anti-HTLV-2 were negative; the X-ray of the thorax was without alteration, and abdominal USG without visceromegalies or lymphadenomegalies. Computerized tomography of the thorax showed the lesion to be expansive and, by means of contrast, with irregular impregnation, localized in the skin and the subcutaneous tissue of the right anterior thoracic wall, and without a defined cleavage plane with the large pectoral muscle; left axilla lymphadenopathy and reactional lymph node on the right. There was an absence of pulmonary or mediastinal affection (Figure 3).
The histopathologic examination of the lesion showed dense infiltrate in the superficial and deep dermis, separated from the epidermis by a collagen strip (Figure 4). The infiltrate consisted of mononuclear cells with large nuclei, evident nucleoli and sparse cytoplasm, intermixed with reactional lymphocytes (Figure 5). The immunohistochemistry was positive for CD20 in large cells and CD3 in small ones. This confirmed the diagnosis of cutaneous large B-cell lymphoma (Figure 6). Bone marrow aspirate and biopsy were normal.
The Hematologic Service instituted chemotherapeutic treatment in combination with CHOP regimen (cyclophosphamide, adriamycin, vimentin and prednisone). Six cycles were programmed at three-week intervals between them. The patient progressed with excellent response to treatment, a reduction of the size of the cutaneous lesion after the first cycle and complete regression of the cutaneous and axillary lesions after the fourth cycle. On the other hand, the patient considered himself cured. Due to this, as well as the intensity of the side effects, he refused to continue the treatment and complete the programmed number of cycles-despite the medical staff's clarifications on the need to complete it.
B-cell lymphomas are more frequent in the lymph nodes than T-cell lymphomas. Regarding the skin, the former occur in the exact opposite way. It is now known that the skin acts like an immunologic effector organ. Moreover, it presents a resident T-lymphocytic population in the dermis similar to the lymphoid tissue associated with mucouses. This being the case, there is no doubt about the primary cutaneous origin of either epidermotropic T-cell lymphomas or non epidermotropic ones. On the other hand, there is a lot of debate about the cutaneous origin of some lymphomatous B cell processes. These may be real primary skin processes, or dermal lymphomatous infiltrations from the nodal or visceral neoplasias that were not diagnosed. There is even a debate on whether BCCL may possibly stem from persistent benign lymphocytic infiltrations of the skin, such as pseudolymphomas.1 The only thing known for sure is that primary BCCL has a better prognosis with respect to rare extracutaneous dissemination.
At the time of diagnosis, the patient showed an increase of the left axillary lymph node in addition to the cutaneous lesion. At the time, there was speculation on whether the adenomegaly would be reactive or tumoral. But the clinical aspects led to considering them as tumoral, which thereby classified BCCL as secondary. There was no affection of the other lymph node sites, not even of the internal organ or bone marrow despite three years of progression that had nonetheless evidenced an indolent course. On the other hand, the affection showed good prognosis and an excellent response to the treatment instituted. For treatment of BCCL CD 20-positive having low response rate to conventional therapies, the Food and Drug Administration approved the use of rituximab in 1998, a monoclonal antiCD20 antibody.11 The latter links up to molecule CD20 so as to trigger the cellular lysis process. In the three cases described in the literature in which this monoclonal antibody was used, there was an excellent initial response, with a subsequent relapse of BCLL CD20-negative.11,12,13 Given the low rate of side effects and its initial effectiveness, rituximab showed itself to be a promising treatment. It remains to be evaluated whether dose and administration variations, in addition to combinations with other agents, might prevent the selectivity of CD20-negative which had led to the relapse.
Still, the link the patient made to an insect sting that had occurred on the same localization several years earlier must not be forgotten. The sting may have transmitted a carcinogenic factor and progressed into a pseudolymphoma. Some authors report the finding of Borrelia burgdorferi in BCCL lesions and question whether it has a possible etiopathogenic role.14,15 To examine this finding, they emphasize the need to perform PCR and lesion cultures, in addition to serology. They also report the possibility of using oral doxycycline or parenteral cephalosporin as a treatment of the disease in its initial stage in an attempt to stimulate lesion regression.
The authors conclude that differentiating between the primary or secondary cutaneous origins of BCCL is very difficult indeed, since they are clinically and histopathologically indistinguishable. It has become extremely important to examine extracutaneous afflictions in these patients. Furthermore, in the patients' presence, it must always be possible to perform a biopsy for confirmation. The staging will contribute to an assessment of the prognosis and to the choice of therapy to be adopted.
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Mariana de Gusmão Nunes
Rua Alice, 278 / 402 - Laranjeiras
22241-020 Rio de Janeiro RJ
Tel./Fax: (21) 2558-0914 / 2556-2442
Received on May 02, 2002
Approved by the Consultive Council and accepted for publication on November 29, 2002
* Work performed at the Dermatology Service, Hospital Universitário Clementino Fraga Filho (HUCFF) and the Universidade Federal do Rio de Janeiro (UFRJ).