Fine-needle aspiration diagnosis of extranodal non-Hodgkin's lymphoma of the tongue.

Primary non-Hodgkin's lymphoma (NHL) of the oral region is rare. Oral manifestation is present in 3-5% of cases of NHL and oral lesions are rarely the initial manifestations. We describe primary NHL, diffuse, mixed, small and large cell type in a 50-year-old female, who presented with mass lesion primarily involving the base of the tongue; initially diagnosed by fine needle aspiration cytology and later confirmed by histopathology and immunohistochemistry. Pertinent literature is being reviewed.

Introduction

Non-Hodgkin's lymphoma (NHL) commonly affects the lymph nodes. About 25% of NHL are of extranodal (EN) origin. NHL presenting initially with oral symptoms is fairly uncommon, and primary NHL of the tongue is a relatively rare entity.[1]

Here, we present a case of EN lymphoma of the base of the tongue that was diagnosed initially by fine needle aspiration cytology (FNAC) and later confirmed by histopathology and immunohistochemistry (IHC) study. As there are no characteristic clinical features, these cases may be easily misdiagnosed clinically. FNAC along with immunophenotyping and molecular studies has gained acceptance in many centres as initial diagnostic tool in diagnosis of lymphomas.[2]

Case Report

A 50-year-old female patient presented with history of slowly growing swelling in throat since six months. She had no other symptoms like fever, weight loss, night sweats and pain. Local examination revealed 4.5×3.5 cm firm, nodular mass in the tongue base on left side. Mucosa covering the swelling was smooth [Figure 1a], mobile and non-tender, did not bleed on touch. Tonsil was free from the swelling. Other parts of oral cavity, oropharynx and neck were normal. Systemic examination including respiratory, cardiovascular, abdominal and central nervous system were normal. There was no organomegaly and lymphadenopathy. Hematological investigations including bone marrow were normal. Human immunodeficiency virus was non-reactive. Chest radiograph and abdominal computed tomography scan were normal. With the above findings, a clinical diagnosis of benign salivary gland tumor was made. FNAC done yielded highly, showing abundant discrete, monomorphic, round to oval immature lymphoid cells with deep blue scanty cytoplasm [Figure 1b]. The nuclear margin was irregular with occasional indistinct nucleoli and fine chromatin. Background showed lymphoglandular bodies, histiocytes and occasional plasma cells. Based on the cytological features, a diagnosis of primary NHL was made. Biopsy consisted of multiple bits with areas of hemorrhage which was formalin-fixed and paraffin-embedded. The histopathological section study showed hyperplastic stratified squamous epithelium overlying inflammatory granulation tissue with diffuse dense small and large neoplastic cellular infiltrate. The cells were round to oval with large prominent nuclei with scanty deep blue cytoplasm. The nuclear chromatin was fine with occasional mitotic figures. Necrosis and hemorrhage were observed. On IHC the tumor cells were positive for CD19, CD20 [Figure 2] and negative for CD3. A final diagnosis of EN, primary NHL B-cell diffuse, mixed small and large cell type was made.

Figure 1

(a) Photograph showing mass in the left tongue base (arrow); (b) Smear showing discrete lymphoid tumor cells in hemorrhagic background (H and E, ×400)

Figure 2

Section showing stratified squamous epithelium, sub-epithelium shows monomorphic population of lymphoid cells (H and E, ×100). Inset photograph showing tumor cells positive for CD20 (IHC, CD20, ×400)

Discussion

About 20 to 30% of the NHL arise from EN sites. Although lymphomas represent the third most common group of malignant lesions of the oral region, following squamous cell carcinoma and salivary gland neoplasm, their incidence is only 3–5% of which NHL of the tongue is extremely rare.[3]

Primary involvement of the tongue by NHL is rare. Wolvius et al.[1] noted only one case of NHL of the tongue in 34 primary oral EN NHL. Similarly, Tauboul et al.[1] reported just one case of NHL of the tongue in 35 cases of head and neck NHL. Das et al.[1] described two cases of FNAC of NHL in oral cavity among 45 oral and pharyngeal lesions. Haidar et al.[3] found 7 cases of NHL of the tongue among 94 patients with EN NHL of the head and neck region. Slootweg et al.,[3] Fukuda et al.[3] and Economopoulos et al.[3] on the other hand, found no tongue involvement, respectively, in 20, 15 and 52 patients with EN NHL of the head and neck. Khan et al,[4] studied 77 cases of EN NHL by FNAC, out of which only 3 cases were in the oral cavity mainly involving the tonsil and one from the palate; there was no tongue involvement in his study. Jovanovic et al,[5] described another case of primary NHL of base of the tongue in a 58-year-old patient presenting with growth in the throat which was of B-cell origin diagnosed by biopsy and not by FNAC. The common symptoms of primary NHL of the tongue are local swelling or ulcer and pain. As there are no characteristic clinical features, these cases may be easily misdiagnosed clinically. Our patient also presented with slowly growing swelling in the oral cavity clinically misdiagnosed as benign salivary gland tumor. So FNAC is very helpful in the early diagnosis of these cases for planning the management.[1]

The differential diagnosis of discrete immature round cells with scanty deep blue cytoplasm at this site are alveolar rhabdomyosarcoma, acute monocytic leukemic deposits, peripheral neuroectodermal tumors (PNET) and small cell carcinoma of the tongue. However discrete cells with scanty cytoplasm and lymphoglandular bodies in the background indicated a possibility of lymphoid origin of these cells. Alveolar rhabdomyosarcoma was excluded by absence of large pleomorphic tadpole shaped tumor cells with eosinophilic cytoplasm and these cells are positive for the vimentin and desmin. Absence of nuclear molding, prominent nucleoli and pseudorosette excludes PNET, which is positive for neuron-specific enolase. An acute leukemic deposit in the tongue is difficult to diagnose by morphology alone, but peripheral blood and bone marrow along with the cytochemistry may be helpful in the diagnosis. Small cell carcinoma shows dispersed cells with bare nuclei, teardrop and smeared cells in the background. The cells show nuclear molding, coarse nuclear chromatin and nucleoli.[16]

Little is known about the etiological factors for primary lymphoma of the oral region. Few cases of oral lymphoma have been reported in association with the acquired immunodeficiency syndrome.[3] There are documented studies of virally induced lymphomas in animals; however, the search for oncogenic viruses has failed to document this in human NHL. Another hypothesis suggested that lymphomas develop as a result of imbalanced immunoregulation, however in the great majority of malignant lymphomas, there is no overt immunologic abnormality. Malignant lymphomas are thought to arise in the oral cavity from components of the lymphoreticular system in the oral submucosa, usually Waldeyer's ring, which is the area encompassed by the nasopharynx, the tonsil and the base of the tongue. They are also thought to arise transiently from lymphoreticular cells of the peripheral blood circulation.[7]

Head and neck NHL including oral lesion are of B-cell origin and diffuse large cell is the most common type. Wide excision followed by chemotherapy and radiotherapy is the treatment of choice for the oral NHL. The prognosis of the NHL is related to the stage of the tumor, the aggressiveness of the malignant cell type and the response to treatment.[3]

Conclusion

Although oral lymphoma of the tongue is very uncommon, it should always be considered in differential diagnosis of various benign and malignant lesions in this region because treatment and prognosis of this condition is different.