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 Table of Contents  
CASE REPORT
Year : 2016  |  Volume : 2  |  Issue : 1  |  Page : 42-45

Centroblastic Variant of Non-Hodgkin's Lymphoma of Mandible: A Rare Case Report


Department of Oral and Maxillofacial Pathology, Royal Dental College, Palakkad, Kerala, India

Date of Web Publication27-Jun-2016

Correspondence Address:
Anuradha E Sunil
Department of Oral and Maxillofacial Pathology, Royal Dental College, Iron Hills, Chalissery, Palakkad, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2393-8692.184738

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  Abstract 

Non-Hodgkin's lymphoma (NHL) is the most common lymphoma that presents in extranodal areas without lymphoid tissue. It occurs in <5% of cases in the jaws and the maxilla are more commonly involved than mandible. The most common symptom is that of a nonpathognomic swelling mimicking odontogenic pathology with a mobile tooth. The lesion usually gets aggravated after extraction and presents as a painful nonhealing socket with symptoms of paresthesia. Diffuse large B-cell lymphoma is the most common subtype and has a better prognosis and overall survival in patients. The treatment of NHL is by a combination of chemotherapy and radiotherapy. We present a rare case report of occurrence of NHL in the least preferred site of mandible with nonhealing socket following extraction of mobile tooth, diagnosed on histopathology and confirmed by immunohistochemistry.

Keywords: Centroblastic diffuse large B-cell lymphoma, diffuse large B-cell lymphoma, intraosseous lymphoma, non-Hodgkin′s lymphoma


How to cite this article:
Sunil AE, Anila Namboodiripad P C, Mukunda A, Kadar N, Jassim K A. Centroblastic Variant of Non-Hodgkin's Lymphoma of Mandible: A Rare Case Report. Indian J Oral Health Res 2016;2:42-5

How to cite this URL:
Sunil AE, Anila Namboodiripad P C, Mukunda A, Kadar N, Jassim K A. Centroblastic Variant of Non-Hodgkin's Lymphoma of Mandible: A Rare Case Report. Indian J Oral Health Res [serial online] 2016 [cited 2019 Jun 15];2:42-5. Available from: http://www.ijohr.org/text.asp?2016/2/1/42/184738


  Introduction Top


Lymphomas are a heterogeneous group of malignancies arising from lymphoreticular system. They range clinically from indolent to highly aggressive and fatal neoplasm and are of two types: Hodgkin's lymphoma (HL) (10%) and non-HL (NHL) (90%). [1],[2],[3] NHL of B-cell origin is more common and occurs commonly in the extranodal sites.

Diffuse large B-cell lymphoma (DLCBL) is a subtype of NHL constituting about 30% and rarely occurs in the mandible 8% whereas isolated types constitute 0.6% only making mandible a rare site of presentation for DLCBL. Parker and Jackson in 1939 first proposed the term "primary reticular cell sarcoma of bone" for extranodal lymphomas arising at a primary site in bone. However, the term "primary lymphoma of bone" was introduced by Ivins and Dahlin in 1963. [4] Coley in 1950 suggested the criteria for diagnosis of primary lymphoma of bone, later modified by WHO as:

  • Lymphoma presenting in a single osseous site
  • Histological confirmation
  • No evidence of disease elsewhere for at least 6 months after diagnosis. [1]

  Case report Top


A 50-year-old male presented with a painful swelling in the left lower 3 rd of the face [Figure 1]. History revealed extraction of mobile 34, 35, and 36, 2 months earlier with nonhealing tooth sockets and fever, anorexia, swelling, and paresthesia of the left lower lip. The lesion did not respond to three cycles of broad spectrum antibiotics and anti-inflammatory medication. Intraoral examination revealed a bony hard swelling in relation to the nonhealing sockets. Orthopantomogram revealed diffuse, ill-defined osteolytic areas with enlargement of mandibular canal and mental foramen [Figure 2]. Whole-body scan did not reveal any deposits elsewhere in the body. Excisional biopsy was done under general anesthesia and histopathology showed diffuse infiltrates of medium to large size atypical lymphoid cells with scant to moderate cytoplasm, hyperchromatic to vesicular nuclei, few with prominent nucleoli [Figure 3]. Nuclei were hyperchromatic, moderately pleomorphic and mitotically active with irregular nuclear membrane. Prominent nucleoli with foci of necrosis were present. Based on the above findings, a diagnosis of large cell NHL was established. Immunohistochemistry (IHC) staining revealed that the atypical lymphoid cells were positive for CD20, MIB1, BCl-2, and BCl-6 [Figure 4] and [Figure 5] and negative for Epstein-Barr virus-Latent membrane protein, CD10, CD138, and CD3. Based on the above findings, a diagnosis of DLBCL-centroblastic variant was established. The patient was referred to an oncologist for chemotherapy and radiotherapy and is currently responding well to the treatment.
Figure 1: Extraoral photograph showing a diffuse swelling in the left body of the mandible

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Figure 2: Orthopantomogram shows a diffuse osteolytic lesion with enlargement of mandibular canal

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Figure 3: Showing diffuse infiltrates of medium to large size lymphoid cells with hyperchromatic to vesicular nuclei, scant cytoplasm and prominent nucleoli, (H and E, ×400)

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Figure 4: Immunohistochemistry with CD20 displaying diffuse cytoplasmic and membrane positivity for these lymphoid cells. Nuclei are negative

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Figure 5: Immunohistochemistry with MIB1 displaying high proliferation index ~80%, (staining nuclei)

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  Discussion Top


NHLs are heterogeneous malignancies of lymphoid system that vary in clinical behavior, morphologic appearance, immunologic, and molecular phenotype. They originate in lymph nodes, extranodal sites, and even in sites without lymphoid tissue. [2],[3] NHL's etiology is unknown; however, patients with immunosuppression as in HIV have an increased risk to develop NHL. [2]

The peak incidence of occurrences is 40-80 years and rare in children and young adults. [1],[4] Males are more commonly affected than females in the ratio of 3:2. [5] Extranodal lesions arise in nearly any site or organ, but gastrointestinal tract is the most common (25-30%), followed by head and neck area (11-13%). [6] Here, Waldeyer's ring is commonly involved and 2.5% of cases occur in the oral and paraoral areas. [2] Oral lesions of soft tissues appear as a painless local mass with superficial ulceration without any unique findings. [7]

NHL rarely occurs in the jaw bones (<5%) and is more frequent in the maxilla than the mandible with palate and gingiva involved in 70% of cases. [7],[8] Posterior region is preferred over anterior as reported by Rinaggio et al. [4],[8] Paresthesia of inferior alveolar nerve is a common finding in 20%. [1] The radiographic findings of NHL's are not pathognomonic showing features of nonspecific osteolysis. However, few cases have also shown diffuse enlargement of the mandibular canal. [9] The clinical and radiological features of NHL are nonspecific, and hence, the diagnosis in jaw bone is often delayed. The diagnosis is usually established with the help of histopathology and IHC. [1]

Commonly used histological classification for NHLs is the 1982 International Working Formulation, which divides NHL into three prognostic groups such as low, intermediate, and high grade. Revised European-American Lymphoma (REAL) in 1994 classifies lymphomas according to clinical and pathological behavior as low grade/indolent, intermediate grade/aggressive, or high grade/very aggressive; WHO IV edition classification gives the subtypes of DLBCL [Table 1]. [4],[10]
Table 1: Diffuse large B-cell lymphoma subtypes according to the IV edition of the WHO classification of tumors of the hemopoietic and lymphoid tissues


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DLBCL is the most common type of NHL (40%) in adults. [4] Although REAL and WHO classifications are based on genetics and immunophenotype, the diagnosis of DLBCL is still mainly based on morphology showing large B-cell with nuclear size equal to or exceeding macrophage nuclei with a diffuse growth pattern. [11]

It is an aggressive tumor which can arise in almost any part of the body. The first sign typically is observation of a rapidly growing mass infiltrating tissues or obstructing organs. It may be associated with fever, weight loss, night sweats, etc. It may arise as a primary tumor de novo or as a result of progression and transformation of a less aggressive lymphoma of a lower grade such as lymphocytic, follicular, or marginal lymphoma. [4],[10] The chromosomal abnormality is mapped to 3q27 in DLBCL. [12]

The common variants of DLBCL defined by Keil and WHO IV edition classification are as follows: [1],[4],[13]

  1. Centroblastic variant is the most common subtype and is comprised predominant population of medium to large lymphoid cells with scant to moderate amphophilic cytoplasm, round to oval 2-4 membrane-bound nuclei and vesicular chromatin. Immunoblasts present are always <90% of the cells in the tumor. A variant seen in centroblastic form is centroblast with multilobulated nuclei. These are commonly seen histopathological features in primary lymphoma of the bone and in other extranodal sites
  2. Immunoblastic variant has >90% of immunoblastic large cells with more abundant cytoplasm, large nuclei, vesicular chromatin, and single large centrally placed nucleoli. These cells can sometimes demonstrate plasmacytoid differentiation
  3. Anaplastic variant shows large to very large cells with pleomorphic nuclei that may, in part, resemble tumor cells of the anaplastic large cell lymphoma or even Reed-Sternberg cells. [11],[13]
Centroblastic lymphoma is the most common subtype with better prognosis (and overall survival) when compared with immunoblastic and anaplastic variants. [4],[10]

The treatment of NHL depends on histological classification and clinical staging of the tumor. It is usually a combination of surgery and chemotherapy-radiotherapy. Localized (stage I and stage II) low-grade extranodal lymphomas in the head and neck are treated primarily with radiation therapy whereas localized intermediate grade lymphomas are treated with radiation and chemotherapy. High-grade and advanced stage NHLs are treated with aggressive chemotherapy regimen. [4] It is noted that prognosis is excellent with survival rate of 95%. [1],[14]

The prognosis and clinical outcome of NHL depend on its histological subtype, stage, presence of symptoms, primary site, size, age of patient, type of treatment, and association with immunosuppression. [2],[15] Periodic recall is must to rule out recurrences and dissemination.


  Conclusion Top


Diagnosis of NHL in the jaw bones is challenging as there is low index of clinical suspicion, and malignant tumor may mimic common oral and dental pathological conditions. Hence, NHLs should be included in differential diagnosis in all cases of nonhealing sockets and periodontal diseases without favoring etiology. Early and prompt diagnosis favors treatment, prognosis, and survival and eliminates dissemination and advanced treatment options.

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 Top

1.
Dinakar J, Priya L, Reddy S. Primary non-Hodgkin's lymphoma of the mandible. J Oral Maxillofac Pathol 2010;14:73-6.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
Walter C, Ziebart T, Sagheb K, Rahimi-Nedjat RK, Manz A, Hess G. Malignant lymphomas in the head and neck region - A retrospective, single-center study over 41 years. Int J Med Sci 2015;12:141-5.  Back to cited text no. 2
    
3.
Shaik MA, Waghray S, Kaleem SM, Morrthy S, Shaheen N. Primary extranodal B-cell lymphoma. Int J Exp Dent Sci 2012;1:30-3.  Back to cited text no. 3
    
4.
Nayak PB, Desai D, Pandit S, Rai N. Centroblastic variant of diffuse large B-cell lymphoma: Case report and review of literature. J Oral Maxillofac Pathol 2013;17:261-5.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
5.
Kini R, Saha A, Naik V. Diffuse large B-cell lymphoma of mandible: A case report. Med Oral Patol Oral Cir Bucal 2009;14:e421-4.  Back to cited text no. 5
    
6.
Hanna E, Wanamaker J, Adelstein D, Tubbs R, Lavertu P. Extranodal lymphomas of the head and neck. A 20-year experience. Arch Otolaryngol Head Neck Surg 1997;123:1318-23.  Back to cited text no. 6
    
7.
Agrawal MG, Agrawal SM, Kambalimath DH. Non-Hodgkins lymphoma of maxilla: A rare entity. Natl J Maxillofac Surg 2011;2:210-3.  Back to cited text no. 7
[PUBMED]  Medknow Journal  
8.
Rinaggio J, Aguirre A, Zeid M, Hatton MN. Swelling of the nasolabial area. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;89:669-73.  Back to cited text no. 8
    
9.
Buric N, Jovanovic G, Radovanovic Z, Buric M, Tijanic M. Radiographic enlargement of mandibular canal as first feature of non-Hodgkin's lymphoma. Dentomaxillofac Radiol 2010;39:383-8.  Back to cited text no. 9
    
10.
Piccaluga PP, Bacci F, Sabatlini E, Rossi M, Gazzola A, Sapienza MR, et al. Large cell non-Hodgkins lymphoma: What is new in the WHO classification? Hematol Meet Rep 2009;3:43-5.  Back to cited text no. 10
    
11.
Gurbuxani S, Anastasi J, Hyjek E. Diffuse large B-cell lymphoma - More than a diffuse collection of large B cells: An entity in search of a meaningful classification. Arch Pathol Lab Med 2009;133:1121-34.  Back to cited text no. 11
    
12.
Chen CY, Yao M, Tang JL, Tsay W, Wang CC, Chou WC, et al. Chromosomal abnormalities of 200 Chinese patients with non-Hodgkin's lymphoma in Taiwan: With special reference to T-cell lymphoma. Ann Oncol 2004;15:1091-6.  Back to cited text no. 12
    
13.
Engelhard M, Brittinger G, Huhn D, Gerhartz HH, Meusers P, Siegert W, et al. Subclassification of diffuse large B-cell lymphomas according to the Kiel classification: Distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor. Blood 1997;89:2291-7.  Back to cited text no. 13
    
14.
Beal K, Allen L, Yahalom J. Primary bone lymphoma: Treatment results and prognostic factors with long-term follow-up of 82 patients. Cancer 2006;106:2652-6.  Back to cited text no. 14
    
15.
Panduric DG, Kuna T, Katanec D. Pain after tooth extraction masking primary extranodal non-Hodgkin's lymphoma of the oral cavity. Acta Stomatol Croat 2007;41:366-74.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
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