Journal of Oral and Maxillofacial Pathology

CASE REPORT - LYMPHOPROLIFERATIVE DISORDERS
Year
: 2019  |  Volume : 23  |  Issue : 4  |  Page : 17--22

Physical torment: A predisposition for diffuse B-cell lymphoma


HK Puneeth1, S Ravi Raja Kumar2, Anuradha Ananthaneni1, Ananth Nag Jakkula3,  
1 Department of Oral Pathology and Microbiology, Saint Joseph Dental College, Eluru, Andhra Pradesh, India
2 Department of Oral and Maxillofacial Surgery, Saint Joseph Dental College, Eluru, Andhra Pradesh, India
3 Department of Oral and Maxillofacial Surgery, GSL Dental College, Rajahmundry, Andhra Pradesh, India

Correspondence Address:
H K Puneeth
Department of Oral Pathology and Microbiology, Saint Joseph Dental College, Eluru, Andhra Pradesh
India

Abstract

Lymphomas of the oral cavity are rare and represent only 3%–5% of all lymphomas. Diffuse large B-cell lymphomas (DLBCLs) are a heterogeneous group of tumor and the most common type of all non-Hodgkin's lymphomas (NHLs). They mostly arise from soft tissue as asymptomatic swelling and involvement of jaw bones is infrequent. We present a case of a 23-year-old patient who developed DLBCL in oral cavity region 4 months after blunt trauma. The patient lacked other physical symptoms at the time of presentation. Histopathology, bone marrow and immunohistochemistry revealed DLBCL. After chemotherapy of eight cycles, swelling was totally reduced and no relapse observed in 10 months' follow-up period. Thus, the present report represents an example of possible rapport between trauma and unresolved soft-tissue swelling which may be caused by NHLs.



How to cite this article:
Puneeth H K, Kumar SR, Ananthaneni A, Jakkula AN. Physical torment: A predisposition for diffuse B-cell lymphoma.J Oral Maxillofac Pathol 2019;23:17-22


How to cite this URL:
Puneeth H K, Kumar SR, Ananthaneni A, Jakkula AN. Physical torment: A predisposition for diffuse B-cell lymphoma. J Oral Maxillofac Pathol [serial online] 2019 [cited 2019 May 24 ];23:17-22
Available from: http://www.jomfp.in/text.asp?2019/23/4/17/252736


Full Text



 Introduction



Lymphomas constitute a group of neoplastic proliferation process of the lymphocytes and their precursor cells, mainly affecting lymph nodes, spleen and other nonhematopoietic tissues. Lymphoma, a cancer of lymphoid tissue is the second-most common neoplasm after squamous cell carcinoma in head and neck region.[1],[2] They are classified as Hodgkin's and non-Hodgkin's lymphoma (NHL). Extranodal NHL in the oral cavity is considered to be pretty uncommon.[3] Diffuse large B-cell lymphoma (DLBCL) is the most common variant of non-Hodgkin's intermediate-grade lymphomas, and affect mainly lymph nodes and the lymphatic organs, but they also frequently involve extranodal sites.[4] In the area of head and neck, they are located mainly in salivary glands, eyeballs, nasopharynx, maxillary sinus, vestibule, palate and lips.[5] PUBMED search revealed about seven cases of malignant lymphoma reported after a history of previous trauma, among those five were reported in head and neck region.[2],[6],[7],[8],[9] These lymphomas manifested 1–2 months after blunt trauma to the occipital region, cheek, forehead, periorbital and eye.

This article reports a case of trauma-induced primary DLBCL in the left maxillary vestibule in a 23-year-old male patient.

 Case Report



A male patient aged 23-year-old reported to the oral surgery department with a chief complaint of swelling in the left middle third of face since 4 months. History revealed a traumatic incident at the site of swelling 4 months back where he was hit by a hard object. Extraoral examination revealed asymmetrical face with dome-shaped swelling on the left side [Figure 1]a extending superior-inferiorly 0.5 cm below inferior-orbital ridge to 0.5 cm above the corner of mouth and anterior-posteriorly from left lateral wall of nose to 1 cm anterior to tragus. The skin over the swelling appeared normal with no secondary changes. On palpation, the lesion was tender; firm in consistency with local rise in temperature, left submandibular lymph nodes were enlarged, tender and unfixed. Intraoral examination revealed vestibular obliteration extending from 13 to 16 [Figure 1]b.{Figure 1}

Orthopantomogram and occlusal radiographs were unremarkable, whereas magnetic resonance imaging showed altered signal intensity collection in left buccal space between left temporalis and buccinator muscle with inferior tracking to submandibular space and spiral computed tomography (CT) showed soft-tissue swelling in the left anterior maxillary region [Figure 2].{Figure 2}

An incisional biopsy was advised under local anesthesia. On histopathological examination, the hematoxylin and eosin (H&E) stained tissue section showed diffuse proliferation of atypical round cells in loose connective tissue stroma. These large populations of anaplastic round cell showed cleaved and multilobulated cells resembled centrocytes, cells with peripheral margination of chromatin and prominent 2–3 nuclei resembled centroblasts, and few cells resembled immunoblast. The tumor cells are seen infiltrating the striated muscle [Figure 3] and [Figure 4]. Even the fine-needle aspiration cytology of submandibular lymph node showed similar cytological features [Figure 5]a and [Figure 5]b. Based on these features of large cell lymphoma was suspected and further investigation was carried out. Immunohistochemistry showed pancytokeratin negative ruling out epithelial origin, CD20 showed positivity [Figure 6]a, BCL-2 positivity [Figure 6]b and proliferation index with Ki-67 <70% [Figure 6]c. Correlating the clinical, histopathological and immunohistological features, a final diagnosis of diffuse large B-cell lymphoma (BCL) was given.{Figure 3}{Figure 4}{Figure 5}{Figure 6}

The patient was referred to cancer institute where chest X-ray, ultrasound of abdomen, bone scan and bone marrow biopsy did not reveal any abnormality and confirmed the lesion to be localized. The patient was sent to medical oncologist for chemotherapy. He was given rituximab 500 mg (MABTAS 500 mg), cyclophosphamide 1200 mg (Cycloxan), doxorubicin 50 mg (Zubidox 50 mg) and onvinc-1 twice weekly for a total of eight cycles. Following the chemotherapy, the swelling was completely resolved. Postoperative CT scan of the neck and brain showed normal impression.

 Discussion



Lymphoma classification is controversial, many changes have been proposed from decades. However, the new classification is based on morphological and immunological features, and the current premise is focused on genetic and molecular studies.[10] Lymphomas are of two major categories: Hodgkin's lymphoma (HL) and NHL, disparity between these two can only be recognized under the microscope. Reed–Sternberg cells, multinucleated giant cells characteristic of HL histopathologically and other neoplasms of lymphoid system are referred to as NHL which are derived from B-lymphocyte predominantly.[11]

NHLS of the oral cavity exist as primary or secondary to extension from Waldeyer's ring. These are rare and accounting for 3%–5% of the lymphomas. The most common type of NHL of oral cavity is DLBCL. Outside the Waldeyer's ring, the hard palate and maxillary vestibule appears to be involved frequently. These lesions are symptomatic and presents as rapidly enlarging mass.[12]

Etiology of primary DLBCLs of oral cavity is unknown apart from being diagnosed in HIV patients. Epstein–Barr virus, HIV virus, radioactive contaminations and hybrid genes resulting from translocation are some of the etiological factors for NHL. Trauma as a predisposing has always been a subject of debate.[6],[8] Prolonged or repeated inflammation caused by trauma may induce cellular atypia leading to carcinogenesis,[12] similar to that of the present case.

In the 19th century, German pathologist Virchow suggested the causal link between cancer and inflammation. Many molecular players are involved in cancer-related inflammation, which includes nuclear factor kappa-B (NF-κβ), signal transducer activator of transcription-3 and primary inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, 23 and tumor necrosis factor-alpha.[12] NF-κβ is a key orchestrator on innate immunity and inflammation, and few studies have demonstrated that NF-κβ may act as a mechanistic link between inflammation and cancer, but the individual role of NF-κβ activity in the development of malignancy in inflammation still remains unclear. In multiple types of hematologic malignancies, NF-κβ is rendered constitutively active through chromosomal rearrangements and overexpression of NF-κβ subunits, mutations in upstream regulators or through enhanced proteasomal activity.[12],[13] Another explanation for the development of a lymphoma is that circulating lymphoma cells may lodge and accumulate at the site of the trauma.[9]

Few cases have been reported in Japanese patients, under the term pyothorax-associated lymphoma. Moreover, DLBCL features are also seen in other chronic inflammatory conditions such as metallic implants in bone and joints, chronic osteomyelitis and use of metallic mesh implant, thus in 2008 the “World Health Organization classification of tumors of hematopoietic and lymphoid tissue” categorized DLBCL associated with chronic inflammation as distinct entity [Table 1].[2],[5]{Table 1}

Lymphomas are round cell lesions which can be diagnosed by H&E stain, but modern hematology relies on immunophenotyping for subtyping and also to distinguish between benign and malignant diseases. DLBCL can be subclassified depending on cytomorphology, gene expression profiles and based on prognosis [Table 2].[3]{Table 2}

DLBCLs express CD45 and pan-B-cell antigens (CD19, CD20 and CD79), but some cases lack the expression of one or more of this antigens. CD20 is expressed on B cells from the mature precursor B cells until the pre-plasma cell stage of differentiation, thus a specific marker for B-cell lineage and most DLBCL show diffuse positivity.[14] In normal B-cell differentiation, the B cells go through the pregerminal center (GC), GC and post-GC stages, where [Table 3] represents the expression of specific antibody and prognosis in each stage.[5]{Table 3}

Even, T-cell marker (CD5 and CD3) have been expressed in DLBCL and may have prognostic significance which is associated with more aggressive clinical course and poor outcome. Lately, few cases of large BCL showed expression of CD3 and B-lineage markers. The proposed mechanism for expression of T-cell marker is due to depression of genetic material, the transformation of progenitor cell before the divergence of B lymphocyte pathway, neoplastic expansion of normal B cells that express T-cell antigen.[15]

DLBCL comprises a heterogeneous group of tumor due to discrepancy in immunophenotyping. More than 25% of DLBCL have a translocation t(14;18) and most of them show bcl-2 with or without a translocation.[16]

Cytogenetic studies of NHL have instituted that chromosomal alterations affecting band 3q27 are relatively frequent in DLBCL (10%–20%). These alterations mainly involve reciprocal translocations between 3q27 and various other chromosome partners, including the sites of the immunoglobulin (Ig) genes (14q32, 2p12 and 22q11), and non-Ig genes (8q24, 11q13 and 5q31). Molecular cloning of the 3q27 chromosome breakpoints by several groups revealed the bcl-6 gene. At the molecular level, the bcl-6 gene rearrangement was found at a high frequency in DLBCL (30%–40%), as well as in FL at a lower frequency (5%–10%). Normally, bcl-6 is required for GC formation, antigen-specific antibody response and Th2-mediated cytokines. Both bcl-2 and bcl-6 have a pro-apoptotic effect thus inhibiting cell growth and initiating cell cycle progression.[17],[18]

DLBCL may show more than one gene rearrangement, which referred as “double” (BCL6+/MYC+) or “triple hit” (BCL2+/MYC+/BCL6+) lymphomas. The MYC translocation is characteristic of Burkitt lymphomas (BLs) but can be seen in other NHLs, including DLBCL and so-called double-hit lymphomas that have both BCL2 and MYC translocations.[19]

The differential diagnosis includes nonhematolymphoid malignancies where tumor cells show cohesive growth, cytoplasm often eosinophilic rather than amphophilic or basophilic and expression of specific immunohistochemical (IHC) markers (e.g., cytokeratin for squamous cell carcinoma, HMB 45, S-100 for melanoma). Nonreactive neoplastic process shows aggregates of bland lymphocytes without atypical features. BLs are more common in younger age groups, shows starry sky appearance, tumor cells show fine chromatin and cytoplasm shows vacuoles. IHC shows BCL2 protein negative, Ki-67: ~100% and translocation of MYC gene. Anaplastic plasmacytoma may have a history of multiple myeloma, tumor cells are smaller and CD 20−, CD138+. Histiocytic sarcoma shows often larger cells with abundant cytoplasm and shows positive macrophage lineage marker (e.g., CD68+ and CD20−).[19],[20]

Recent molecular studies evidenced that chromosomal abnormalities play an important role in the pathogenesis of the disease and its subclassification is important to guide the treatment.[4] The current treatment of DLBCL usually begins with multi-agent chemotherapy; typically, CHOP (cyclophosphamide, hydroxydoxorubicin, oncovin and prednisone) which involve three cycles.[4],[11] Early stage disease requires either chemotherapy alone or a combination of chemotherapy and radiotherapy, but bone marrow transplantation considered if remission is not maintained. The role of surgery is markedly limited in the treatment of DLBCL.[11] Newer treatment includes the use of proteasome inhibitors which targets NF-κβ pathways which is required by B-cell type DLBCL, small molecule inhibitors of signal transduction pathways and agents like lenalidomide, which modulate the cytokines and tumor microenvironment.[19] Even the same line of treatment is followed for DLBCL associated with chronic inflammation. The prognosis of NHLs depends on clinical staging, where Stage I have a better prognosis than those in Stages II to IV, with 5-year overall survival rates ranging from 26% to 73%.[21] DLBCL associated with chronic inflammation shows good prognosis with no relapse with 6 months to 5 years' follow-up. The present case showed total reduction in swelling with no relapse after 10 months of follow-up.

 Conclusion



The occurrence of primary DLBCL in oral cavity is very rare, but the connection between trauma and tumor development in our patients remains obscure, but our cases may represent an example of a trauma-induced lymphoma in the oral cavity. It is very essential for the clinician to be aware of this type of aggressive lesion, which aid in early diagnosis to improve the life expectancy of these patients. The diagnosis of these lesions is challenging due to their nonspecific nature of presenting symptoms, so proper clinical evaluation, histology as well as IHC evaluation of biopsy specimen may aid in early diagnosis and effective management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Bugshan A, Kassolis J, Basile J. Primary diffuse large B-cell lymphoma of the mandible: Case report and review of the literature. Case Rep Oncol 2015;8:451-5.
2Bach Okholm-Hansen A, Brorson S. Unexpected finding of T-cell lymphoma in a previously healthy 16-year-old patient after a thorax trauma: A case report. J Med Case Rep 2014;8:371.
3Patil AV, Deshpande RB, Kandalgaonkar SM, Gabhane MH. Diffuse large B-cell lymphoma (extranodal) of maxillary buccal vestibule. J Oral Maxillofac Pathol 2015;19:270.
4Bortoluzzi MC, Jonas Dantas B, Karen C, Salum FG, Antonia Figueiredo M. Diffuse large B-cell lymphoma of the oral cavity. Rev Cubana Estomatol 2010;47:341-6.
5Sahoo SR, Misra SR, Mishra L, Mishra S. Primary diffuse large B-cell lymphoma in the anterior hard palate: A rare case report with review of literature. J Oral Maxillofac Pathol 2014;18:102-6.
6Atoini F, Ouarssani A, Hachimi MA, Aitlhou F, Guenoun FZ, Elmejereb C, et al. Diffuse large B-cell lymphoma presenting as large anterior chest wall mass involving pleura and lung: A possible result of post-traumatic chronic inflammation. Thorac Cancer 2012;3:79-83.
7Soylu M, Ozcan AA, Okay O, Sasmaz I, Tanyeli A. Non-hodgkin lymphoma presenting with uveitis occurring after blunt trauma. Pediatr Hematol Oncol 2005;22:53-7.
8Kriwalsky MS, Schroers R, Stricker I, Hollstein S, Kunkel M. Periorbital non-hodgkin's lymphoma after blunt trauma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:e56-9.
9Morioka T, Tashima T, Nishio S, Nishie E, Fukui M, Okamura T, et al. Malignant lymphoma of the scalp at the site of a previous blunt trauma: Report of two cases. Surg Neurol 1994;42:117-20.
10Wolvius EB, van der Valk P, van der Wal JE, van Diest PJ, Huijgens PC, van der Waal I, et al. Primary extranodal non-Hodgkin lymphoma of the oral cavity. An analysis of 34 cases. Eur J Cancer B Oral Oncol 1994;30B: 121-5.
11Bhattacharyya I, Chehal HK, Cohen DM, Al-Quran SZ. Primary diffuse large B-cell lymphoma of the oral cavity: Germinal center classification. Head Neck Pathol 2010;4:181-91.
12Del Prete A, Allavena P, Santoro G, Fumarulo R, Corsi MM, Mantovani A, et al. Molecular pathways in cancer-related inflammation. Biochem Med (Zagreb) 2011;21:264-75.
13Ditsworth D, Zong WX. NF-kappaB: Key mediator of inflammation-associated cancer. Cancer Biol Ther 2004;3:1214-6.
14de Leval L, Harris NL. Variability in immunophenotype in diffuse large B-cell lymphoma and its clinical relevance. Histopathology 2003;43:509-28.
15Kumar MS, Gannepalli A, Chandragiri A, Amarnath K. Diffuse large B-cell lymphoma of maxilla – A case report of late relapse. J Clin Diagn Res 2016;10:ZD12-4.
16Mittal M, Puri A, Nangia R, Sachdeva A. Follicular lymphoma transforming into anaplastic diffuse large B-cell lymphoma of oral cavity: A case report with review of literature. J Oral Maxillofac Pathol 2015;19:379-84.
17Niu H. The proto-oncogene BCL-6 in normal and malignant B cell development. Hematol Oncol 2002;20:155-66.
18Berglund M, Thunberg U, Amini RM, Book M, Roos G, Erlanson M, et al. Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis. Mod Pathol 2005;18:1113-20.
19Said JW. Aggressive B-cell lymphomas: How many categories do we need? Mod Pathol 2013;26 Suppl 1:S42-56.
20Alexander Chan CL, John Chan KC. Hematolymphoid lesions of the head and neck. In: Barnes L, editor. Surgical Pathology of the Head and Neck. 3rd ed. USA: Informa Healthcare; 2009. p. 1044.
21Jham Correia B, Duarte BC, Fernandes AM, Rodrigues Johann AC, Ferreria Aguiar MC, Santiago Gomez R, et al. Primary diffuse large B cell lymphoma of the oral cavity. J Bras Patol Med Lab 2007;43:369-72.