Diffuse large B-cell lymphoma (extranodal) of maxillary buccal vestibule.

Lymphomas are the group of neoplasms originating from lymphoreticular system mainly from lymph nodes, among them up to 40% of non-Hodgkin's lymphomas present extra nodally. In oral cavity, lymphomas are least common and account for 3-5% of all malignancies, presenting mainly in older age groups with male predominance. According to Revised European-American Lymphoma classification, among B-cell and T-cell subtypes of non-Hodgkin's lymphomas, diffuse large B-cell lymphoma (DLBCL) is the most common, characterized by diffuse proliferation of large neoplastic B lymphoid cells. Here we present a case report of DLBCL affecting oral cavity involving left buccal vestibule and extending onto the palate, along with its clinical, histopathologic and immunohistochemical features.

INTRODUCTION

The diverse group of neoplasms affecting lymphoreticular system is known as lymphomas. These are the malignant neoplasms mainly affecting lymph nodes, spleen and other nonhematopoietic tissues. They are divided into Hodgkin's and non-Hodgkin's subtypes and are of B-cell or T-cell origin. The majority of Hodgkin's lymphomas presents as a nodal disease involving mainly cervical and axillary nodes.[12]

Among the 40% non-Hodgkin's lymphomas presenting extranodally, gastrointestinal tract, Waldeyer's ring, spleen, salivary gland are the most common sites of occurrence and are rarely seen in the oral cavity. It may arise from preexisting low-grade lymphomas or as a de novo neoplasms.[34] In the paraoral and primarily oral lymphomas, diffuse large B-cell lymphomas (DLBCL) are most common and is show a male predominance. The most common sites of involvement intraorally are palate, buccal mucosa and tongue with the prevalence of only 3–5%.[45]

CASE REPORT

A 79-year-old male patient reported to the Department of Oral Pathology and Microbiology with a chief complaint of pain and swelling on the upper left buccal mucosa since 1-month. The swelling was insidious and gradually increased in size. The patient also reported reduced sensation on cheek mucosa of the left side.

Extraorally, facial asymmetry was noticed with diffuse swelling on the left sided cheek region, approximately 3 cm × 2 cm in size, irregular in shape, vertically extending from inferior border of zygomatic arch up to 1–2 cm above corner of mouth and was extending from ala of nose up to tragus of the ear mediolaterally. The swelling was firm and nontender on palpation with normal appearing overlying skin. The swelling was not fixed to the underlying structures. On intraoral examination, the swelling was diffuse, soft and roughly oval in shape [Figure 1]. The color of the overlying mucosa was normal as that of the surrounding mucosa. The swelling was situated in maxillary buccal vestibule extending anteroposteriorly from 26 to 28 region and mediolaterally from buccal mucosa of left side obliterating the vestibule, crossing the alveolar ridge and extending onto palatal mucosa. The swelling was approximately 4 cm × 2 cm in size and was of smooth surface texture. On palpation, the swelling was tender and not fixed to underlying structures.

Figure 1

Clinical image shows diffuse, roughly oval shape swelling situated in maxillary buccal vestibule

Radiologically, on Waters view haziness was noticed in the left maxillary sinus region as compared to the right side, extending from superior border up to inferior border of sinus vertically and extending from medial to the lateral border of sinus mediolaterally [Figure 2].

Figure 2

Radiographic images shows haziness in left maxillary sinus region

An incisional biopsy was advised from buccal mucosa of left side under local anesthesia after routine blood investigations, which were within the normal limits. Human immunodeficiency virus (HIV) Tridot screening test was also negative.

On histopathological examination, the hematoxylin and eosin stained tissue section showed diffuse, monotonous proliferation of round cells, in the form of sheets within the loose fibrillar connective tissue stroma [Figure 3]. These cells were having large nuclei with a small amount of cytoplasm resembling lymphoid cells. It also revealed the presence of cells with large nuclei showing prominent nucleoli arranged at the periphery, exhibiting condensation and vesiculation of chromatin with cellular and nuclear pleomorphism. These cells resembled centroblasts [Figure 4] and immunoblastic cells [Figure 5]. The adjacent minor salivary gland tissue with mucous acini showed infiltration of these cells, disturbing the normal architecture.

Figure 3

Histopathological image shows diffuse monotonous proliferation of round cells in the form of sheets within a loose fibrillar stroma (H&E stain, ×100)

Figure 4

Histopathological image shows round centroblastic cells with large nuclei (H&E stain, ×400)

Figure 5

Histopathological image shows round immunoblastic cells (H&E stain, ×400)

Overall histopathological features suggest the diagnosis of atypical lymphoproliferative lesion. For confirmation, further immunohistochemical evaluation was done.

On immunohistochemical analysis, CD45 (leukocyte common antigen) [Figure 6] positivity distinguished malignant lymphomas from other non-lymphoid neoplasms, strong positivity for CD20 (B-cell marker) [Figure 7] and weak expression of CD3 (T-cell) marker suggests the B-cell origin of the lesion and Ki-67 (proliferation marker) positivity indicates the proliferative potential of the lesion. Thus, the overall histopathological and immunohistochemical findings were suggestive of DLBCL.

Figure 6

Immunohistochemical image shows strong positivity for CD45 (IHC stain, ×100)

Figure 7

Immunohistochemical image shows strong positivity for CD20 (IHC stain, ×100)

DISCUSSION

In head and neck region, lymphomas are the second most common neoplasms. Among 40% extranodal non-Hodgkin's lymphomas majority of cases are of B-cell origin.[4] B-cell lymphomas are classified as precursor B-cell neoplasm and peripheral B-cell neoplasm. According to Revised European-American Lymphoma classification of non-Hodgkin's lymphomas, DLBCL is a peripheral B-cell neoplasm.[67] World Health Organization in 2008 further categorized aggressive B-cell lymphomas as:

DLBCL not otherwise specified

DLBCL associated with chronic inflammation

Large B-cell lymphoma arising in human herpes virus (HHV)-8 associated Castelman's disease

B-cell lymphoma unclassifiable and

Burkitt's lymphoma.[8]

The Kiel classification subdivided large B-cell lymphomas by pure morphology into centroblastic and immunoblastic lymphomas. The working formulation, on the other hand, subdivided large B-cell lymphomas according to their biological behavior into an intermediate-grade (large cleaved and large noncleaved) and a high-grade (immunoblastic) category.[91011]

Among DLBCLs, DLBCL not otherwise specified is the most common subtype and it accounts for up to 20–30% cases seen in elderly, above 70 years of age.[10] It is characterized by large neoplastic B lymphocytes diffusely proliferating, with nuclei larger than or equal to normal macrophage nuclei in size, or more than twice the size of normal lymphocyte and are seen arising de novo.[910] Various studies have shown that DLBCLs shows an average age of presentation that is above 50–55 years with a male predominance.[12] The present case was also reported in elderly (79-year-old) male patient.

Gastrointestinal tract, thyroid, bone, skin and lungs are the most frequent extranodal sites[8] and in orofacial region Waldeyer's ring, salivary gland, tonsils, nasopharynx, base of the tongue are frequently involved.[6] Intraorally it shows maxillary predominance (77%) and the majority of cases are reported on the palate.[13] This is in accordance with the present case which was also reported in maxillary vestibular region and extended towards the palate.

Histopathologically, the pattern of invasion in lymph nodes or extranodal sites is diffuse, with frequent peripheral tissue involvement. Malignant cells show variants such as centroblastic, immunoblastic or anaplastic cell types. The plasmablastic form is another morphologic variant but is more commonly associated with Epstein-Barr virus or anaplastic lymphoma kinase positive B-cell lymphomas.[10] In the present case, there was a presence of diffuse involvement of mucosa and infiltration of adjacent minor salivary glands, main cell types seen in this case were centroblastic and immunoblastic variants showing cells with larger nuclei and prominent nucleoli, chromatin condensation and pleomorphism.

Differential diagnosis includes – reactive non-neoplastic processes in which aggregates of lymphocytes are evident but they did not show atypical features. In case of Burkitt's lymphoma the cells are of homogeneous size and shape giving starry sky appearance due to presence of macrophages which were absent in this case. In plasmablastic lymphomas predominantly plasma cells were evident showing cartwheel-shaped nuclei. Classic Hodgkin's lymphoma is predominantly the disease of lymph nodes and rarely affects oral cavity showing Reed–Sternberg cells as a classic feature which were not evident in this case. Other malignancies such as liposarcoma, round cell type show sheets of poorly differentiated round cells with finely vacuolated or granular cytoplasm and cells may appear epitheloid or pericytoid type. Carcinomas of poorly differentiated type show atypical round cells with eosinophilic cytoplasm, but centroblastic and immunoblastic cells are not seen. Thus, after excluding all these possibilities and the presence of centroblastic and immunoblastic cells a diagnosis of DLBCL was suggested.

The beginning IHC panel includes CD20, CD3, CD45 and if alteration of B-cell areas are seen then antibodies against CD5, CD10, CD23, CD43, BCL2, BCL6 protein, etc., would be useful.[1415] Previous studies have done an immunohistochemical analysis of leukocyte common antigen (LCA), CD20, CD5 to confirm the diagnosis.[1012] Here, in the present case Ki-67 (proliferative marker), CD45 (common leukocyte antigen), CD20 (B-cell marker) analysis were done, which showed strong positivity. CD3 (T-cell marker) was weakly positive in this case. Thus, these findings confirm the diagnosis of extranodal large B-cell lymphoma.

DLBCL represents intermediate and high-grade lymphomas. It can be best treated by surgical excision with adjuvant radiotherapy if the lesion is localized; chemotherapy is the treatment of choice in case of diffuse and aggressive lesions. No significant difference in prognosis has been found between the three major groups: Centroblastic, immunoblastic and anaplastic. In diffuse cases and HIV patients, the prognosis is worse than that in follicular, nodal and HIV-negative cases.

CONCLUSION

The diagnosis of these lesions is challenging due to their resemblance to inflammatory and benign lesions, chances of misdiagnosis are more and the treatment is prolonged. Hence, the clinicians must consider it as a possible differential diagnosis since the lesions are aggressive and efforts should be taken to diagnose these lesions as early as possible as they demonstrate fatal outcomes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.