Primary diffuse large B-cell lymphoma of the oral cavity

Linfoma difuso de grandes células B primário de boca

RELATO DE CASO CASE REPORT

Primary diffuse large B-cell lymphoma of the oral cavity

Linfoma difuso de grandes células B primário de boca

Bruno Correia Jham^I,II; Eliza Carla Barroso Duarte^I; Anacélia Mendes Fernandes^I; Aline Cristina Batista Rodrigues Johann^I; Maria Cássia Ferreira Aguiar^III; Ricardo Santiago Gomez^III; Ricardo Alves Mesquita^III

^IGraduate student at the Department of Oral Surgery, Oral Medicine, and Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG)

^IIGraduate student at the Department of Diagnostic Sciences and Pathology, University of Maryland Dental School

^IIIProfessor at the Department of Oral Surgery, Oral Medicine, and Oral Pathology, School of Dentistry, UFMG

^{Mailing address}

ABSTRACT

Lymphomas arising within the oral cavity account for only 3.5% of all oral malignancies. Diffuse large B-cell lymphoma is a non-Hodgkin lymphoma subtype characterized by diffuse proliferation of large neoplastic B lymphoid cells. This paper reports a case of diffuse large B-cell lymphoma affecting the oral cavity of a Brazilian woman, along with its clinical, microscopical, immunohistochemical, and molecular features.

Key words: Diffuse large B-cell lymphoma, Non-Hodgkin lymphoma, Oral cancer

RESUMO

Linfomas correspondem a 3,5% de todos os casos de lesões malignas de boca. O linfoma difuso de grandes células B é um subtipo de linfoma não-Hodgkin caracterizado pela proliferação difusa de células linfóides B. Este artigo relata um caso de linfoma difuso de grandes células B localizado na cavidade bucal de uma mulher brasileira, incluindo os achados clínicos, microscópicos, imuno-histoquímicos e moleculares.

Unitermos: Linfoma difuso de grandes células B, Linfoma não-Hodgkin, Câncer bucal

Background

Diffuse large B-cell lymphoma (DLBCL) is a non-Hodgkin lymphoma (NHL) subtype characterized by diffuse proliferation of large neoplastic B lymphoid cells with nuclear size equal to or exceeding normal macrophage nuclei, or more than twice the size of a normal lymphocyte⁽⁷⁾.

Affected patients are usually in their seventh decade of life, and the clinical aspect is typically a rapidly enlarging, often symptomatic mass⁽⁷⁾. The most commonly affected site of NHL of the oral cavity and maxillofacial region is the Waldeyer’s ring: tonsils, nasopharynx, base of the tongue, and palatine tonsil⁽⁸⁾. Currently, the treatment of DLBCL consists of radiotherapy, chemotherapy or both. Importantly, DLBCL may be cured in a significant percentage of patients, depending on the initial characteristics of the tumor and the host⁽¹⁾.

Here we report a case of primary DLBCL affecting the oral cavity of a Brazilian woman, along with clinical, microscopic, immunohistochemical, and molecular features.

Case report

A 62-year-old black woman was seen at the oral pathology clinic of Universidade Federal de Minas Gerais (UFMG) complaining of a painless lesion in her mouth that had been increasing in size for the past six months. Extra-oral examination revealed asymmetry and swelling of the right side of the face (Figure 1A). Intra-oral exam showed a soft mass on the right side of the palate, containing two 3-cm eroded areas (Figure 1B). Computed tomography revealed destruction of the maxilla and zygomatic bone and invasion of soft tissue on the right side (Figure 1C), as well as invasion of the nasal cavity and maxillary sinus of the opposite side. There were no signs of the disease elsewhere in the body. Clinical diagnoses were mucoepidermoid carcinoma or maxillary sinus carcinoma. An incisional biopsy was performed, with histology showing neoplastic sheets of lymphoid cells with a solid growth pattern. Individually, cells showed scarce cytoplasm and large nucleus (Figure 1D). Sections were submitted to immunohistochemical evaluation, and the malignant cells were immunopositive for LCA and CD20 (Figure 1E). AE1/AE3, CD3, CD10, CD45RO, and S-100 were immunonegative. Following extraction of the genomic DNA, heavy immunoglobulin gene rearrangement (IgH) analysis was performed^{(3, 6, 10)}. The obtained DNA showed a discrete and homogeneous band on electrophoresis (Figure 1F, line 3). Final diagnosis was diffuse large B-cell lymphoma. The treatment consisted of dexamethasone, cyclophosphamide, vincristine, etoposide, carboplatin, adriamycin, and iphosphamide. Initially, the patient showed significant clinical improvement (Figures 1G and 1H). However, after being submitted to five cycles of chemotherapy, she unfortunately passed away.

Discussion

Clinical, microscopic, immunohistochemical and molecular features of the reported case confirm the diagnosis of primary DLBCL of the oral cavity. Following squamous cell carcinoma, lymphomas are the second most common neoplasm of the head and neck⁽⁸⁾. Nevertheless, the etiology of DLBCL remains unknown. They may originate de novo or represent progression from a less aggressive lymphoma, such as follicular lymphoma or small lymphocytic lymphoma. Underlying immunodeficiency is a significant risk factor, and DLBCL in the setting of immunodeficiency is more often Epstein-Barr virus-positive than sporadic DLBCL^{(3, 7)}. In accordance to the analysis of global gene expression employing DNA microarrays, DLBCL was broadly divided into normal germinal center B-cells (GC-like DLBCL) or activated peripheral blood B-cells (ABC-like DLBCL). Cytogenetically, GC-like lymphomas present t(14;18)(q32;q21) translocations involving the BCL-2 gene and the amplification of the c-rel locus on chromosome 2p. In this tumor subtype, oncogenesis is related to BCL-6 expression. In contrast, ABC-like tumors demonstrate trisomy 3, gains of 3q and 18q21-q22, and losses of 6 q21-22; in this case, oncogenesis is associated with expression of NF-kB target genes resulting from a constitutive activity of inhibitor kappa B (IkB) kinase⁽¹¹⁾.

Lymphomas arising within the oral cavity, such as in our case, account for only 3.5% of all oral malignancies. In the oral cavity, lymphomas usually present as an extranodal, soft-elastic, asymptomatic lesion⁽⁴⁾. One study reviewed forty cases of oral lymphomas and verified that in 66% of the cases, the lesion arose from soft tissues, and 77% of these were seen in the upper jaw⁽¹⁴⁾. Likewise, our patient showed a soft, asymptomatic lesion on the upper jaw. The lesion was mainly located in the palate; however, it was clinically difficult to precisely determine its limits and to define whether or not it extended into maxillary alveolar ridge.

The diagnosis of oral lymphomas may be challenging because frequently there is a low index of clinical suspicion, leading to misdiagnosis and/or delayed treatment. For instance, in a superficial biopsy specimen, superimposed inflammatory changes can result in a lymphoma being mistaken for a reactive or infectious process⁽¹²⁾. Thus, biopsies should be carefully performed to obtain adequate specimens. On the other hand, recent advances have made it possible to investigate lymphomas for the expression of a wide range of antigens in fixed tissues. Although standard hematoxylin- and eosin-stained sections still provide the basis for all lymphoma diagnosis, immunophenotyping (IP) is by far the most common ancillary technique used today. IP is useful both for distinguishing benign from malignant processes as well as for accurate subclassification with high sensibility and specificity. In addition, IP allows diagnosis on small biopsies that would have previously been deemed inadequate for diagnosis⁽⁵⁾. Furthermore, detection of IgH at the DNA level by use of polymerase chain reaction (PCR) to assess monoclonality has become a routine technique in the initial diagnosis of lymphoproliferative disorders. Clonality assays are useful for distinguishing reactive or benign lymph nodes from neoplastic lymphoid infiltrates in most cases. In addition, the inclusion of T-cell antigen receptors in the assessment of lymphomas results in a significant increase in the sensitivity of clonality detection⁽⁹⁾. Furthermore, microarrays are powerful tools for discovery and hypothesis generation, allowing researchers to obtain an unbiased survey of gene expression in lymphoma samples. However, their direct clinical application for individualized diagnosis has been questioned⁽¹¹⁾. In the reported case, immunohistochemistry and IgH analysis were essential for diagnosis and classification.

NHLs are usually staged according to the Ann Harbor system, being classified into four stages depending on the extent of disease⁽⁸⁾. Patients who are in stage I on admission have a better prognosis than those in stages II to IV, with 5-year overall survival rates ranging from 26% to 73%^{(12, 13)}. Unfortunately, oral cancer patients frequently take too long to seek care, what results in more difficult treatment and worse prognosis, as occurred in the reported case. This most likely occurs due to lack of information⁽²⁾. Therefore, a major requirement to increase lymphoma survival rates is providing more information on oral cancer to the population. Also, the addition of rituximab to combination chemotherapy in the treatment regimen has increased the proportion of cured patients⁽¹²⁾.

In our case report of primary DLBCL of the oral cavity we concluded that efforts should be made to diagnose this disease as rapidly as possible, since prognosis is directly related to disease staging on the patient’s admission. Both health professionals and patients should be aware of the signs and symptoms of oral lymphomas so that mortality and morbidity rates can be reduced.

Primeira submissão em 12/02/07

Última submissão em 11/06/07

Aceito para publicação em 19/06/07

Publicado em 20/10/07

This work was conducted in the Department of Oral Surgery, Oral Medicine, and Oral Pathology, School of Dentistry, UFMG. The study was sponsored by Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG CDS895/05) and by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 484974/2006-8). M.C.F. Aguiar, R.S. Gomez and R.A. Mesquita are fellow researchers of CNPq. B.C. Jham gratefully acknowledges CNPq-Brazil doctorate scholarship (201590/2006-9).

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Publication Dates

• Publication in this collection
  06 Dec 2007
• Date of issue
  Oct 2007

History

• Accepted
  19 June 2007
• Reviewed
  11 June 2007
• Received
  12 Feb 2007