NON HODGKIN'S LYMPHOMA - A GROSTESQUE PRESENTATION.
Non Hodgkin's lymphomas are heterogonous group of malignancies of lymphoid system, 40 Percent arising from extra nodal sites. Peculiar features include waxing and waning painless lymphadenopa- thy, swelling of extranodal, endoretiular organs and intraoral swellings. Majority of them are predominantly of B cell lineage. Thorough clinical, biochemical, histopathological, radiological and immunohistochemical evaluation aids in accurate diagnosis and management. A case of terminal stage Non Hodgkin's Large B cell Lymphoma in a 60yr old female patient involving extranodal sites is reported and discussed.
Key Words: Non Hodgkin's Lymphoma, CD20, B cell Lymphoma
Lymphomas are malignant neoplasms of Lymphoreticular cells. They have been traditionally divided into Hodgkin's and Non-Hodgkin's lymphoma.1 Non-Hodgkin's lymphomas are further segregated into B-cell and T-cell type based on cell origin, where the former depict approx 90 Percent and latter approx 10 Percent of all cases. Non Hodgkin's Lymphoma in contrast to Hodgkin's usually manifests outside the lymphoid system involving skin, abdomen, lungs, CNS and oral cavity with 0.1 Percent to 5 Percent incidence in oral cavity.2 It is the third most common neoplasm of oral cavity and maxillofacial region with most common intraoral sites being palate and tonsil.3 More aggressive B cell lym- phomas present with large abdominal or mediastenal mass.4
A 60 year old female reported with multiple pain- less swellings on both sides of neck and face since one year (fig 1). Initially a small swelling was noted in the right lateral neck region about a year ago which was followed by similar swellings noticed bilaterally in front and back region of neck, around ears and in the underarm region of upper extremities and in groin region which enlarged to present size with no second- ary changes.
Within 4 months duration, a swelling over left palatal roof was noted intraorally which gradually increased in size. It was not associated with pain or secondary changes but had caused difficulty in speech and chewing. No history of dysphagia or parasthesia was noted but history of recurrent fever, weight loss and night sweats since 6months was present. She also had history of multiple prior consultations with im- proper treatments and follow-ups. Her medical and family histories were non contributory.
On general physical examination patient had a lean built, was underweight, undernourished and cachexic. Generalized lymphadenopathy involving sub- mandibular (fig 2), submental (fig 3), preauricular, post auricular, cervical, supra clavicular, occipital (fig 4), axillary (fig 5) and inguinal groups were noted bilaterally with an average size of 8x10cms, non- tender with no secondary changes.
On extra oral examination gross facial asymmetry was noted on right side involving the parotid and submandibular region causing elevation of ear lobe (fig 6). The swelling was diffuse and lobulated with no secondary changes, no rise in local temperature, non- tender and was firm in consistency. All the regional groups of lymph nodes in head and neck namely preauricular, submandibular, submental, superficial cervical, supraclavicular and occipital groups were enlarged and palpable bilaterally with no secondary changes. They approximately had an average size of about 3x4 cms with occipital lymph nodes being the smallest, about 2 x 2 cm. All the groups of lymph nodes were non-tender, matted and firm in consistency.
On intraoral examination a well defined solitary lobulated swelling was seen in the left side of the palatal region measuring about 6x4cm extending from marginal gingiva of 21,22 up to distal aspect of 28 antero-posteriorly and medio-laterally from midline of palate to the free gingival margin of 24 to 28 region. Surface was smooth with two areas of shallow ulcer- ations seen measuring approx 1.5cms with sloping edges, surrounded by erythematous areas. On palpa- tion it was tender, soft to firm in consistency (Fig 7). A well defined lobular swelling was also noticed on the tonsillar area.
The thorough clinical examination indicated to- wards a lesion arising from lymph nodes. Hence, the provisional diagnosis of Non Hodgkin's Lymphoma with clinical staging IV B (Ann Arbor staging) was considered as multiple extra nodal site involvement was seen. Hodgkin's lymphomas, Lymphoblastic leu- kemia, AIDS associated persistent generalized lym- phadenopathy with intraoral neoplasm were enlisted in differentials.
Except raised ESR (110mm/hr) other hematologi- cal investigations were normal. Blood glucose levels, serum urea and creatinine levels were estimated to be in normal range. Liver and renal function tests showed no abnormalities. She was seronegative for HIV and HbsAg.
Abdominal ultrasonography (fig 8) revealed mul- tiple non homogenous lesions of varied size and pelvis suggestive of generalized lymphadenopathy and grade 1 renal parenchymal disease along with moderate splenomegaly. MRI of head and neck region was per- formed in order to assess the various soft tissue in- volvement, T1and T2 sequences showed involvement of both superficial and deep lobes of right parotid and partial involvement of left parotid glands. Bilateral submandibular salivary glands were also involved and enlarged to greater extent; maxilla revealed an exten- sive lesion involving the whole left side of palate and also left buccal cortical plate resorption i.r.t 24,25,26,27 with extension of lesion in left vestibule. Extensive enlargement of head and neck lymph nodes, Level 1-6 was noted along with pharyngeal tonsil causing par- tial obstruction of oropharynx due to elevation of posterior pharyngeal wall.
(fig 9A,B,C,D) Fine needle aspiration cytology of right upper cervical lymph node showed increased cellularity of medium and large lymphocytes having scanty cyto- plasm and was suggestive of Non- Hodgkin's lym- phoma intermediate grade mixed cellularity type. Bi- opsy of palatal lesion showed sheets of large lympho- cytes intermixed with large amount of inflammatory cells. (fig 10) The diagnosis was validated as CD20 marker was positive on immunohistochemistry. (fig 11) Final diagnosis of Non Hodgkin's Lymphoma of diffuse large B-cell type was rendered. Patient was referred to cancer institute where 8 cycles of chemo- therapy regimen constituting of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was planned. The treatment was incomplete as the patient didn't survive after 4 cycles of chemotherapy.
Lymphomas are the diverse and complex group of neoplasms affecting lymphoreticular system5 and are classified based on cell lineage by 'The Revised Euro- pean American lymphoma' (REAL/WHO) system as : B cell malignancy ,T cell/natural killer malignancy and Hodgkin's lymphoma.6,7 Hodgkin's lymphoma often presents as nodal disease whereas Non-Hodgkin's may also have an extranodal presentation.1,6 The exact etiology of lymphomas is unknown however genetic predisposition, immunodeficiency state like HIV, re- cipients under transplantation and chromosomal trans- location has been implicated.8
In 2001 Urquhae et al reported a review of 235 cases of head and neck with mean age of 67 years.9
Various studies imply that it is more common among middle age and elderly (40-80 yrs) with more male predliction and ratio being 3:2.1 HIV positive patients are 60 times more perlious than general population and around 3 Percent of HIV infected people develop lympho- mas.1 In our case patient was 60yrs old and seronega- tive for HIV.
B cell Lymphoma are the most common among Non Hodgkin's lymphomas5 which often present with initial symptoms like painless swelling of lymph nodes, Intraoral boggy swellings, ulcerations along with as- sociated systemic symptoms like fever, night sweats, weight loss etc:7 Based on associated systemic symp- toms NHL patients are further classified as "A" (No symptoms) or "B" (Constitutional symptoms), where "B" constitute systemic signs and symptoms which include fever of unknown origin ,weight loss, drench- ing night sweats, visceral pain and malaise.10 About 40 Percent of the new cases are associated with systemic signs and symptoms.3 In our case painless lymphaden- opathy on both sides of neck and face with fever, malaise, weight loss and night sweats were present, hence classified as "B" type.
Intraoral Soft tissue lymphomas usually are mis- diagnosed on preliminary examination. A painless lymph node enlargement with submucosal lesion in the junction between hard and soft palate are highly suspicious of Non Hodgkin's Lymphoma.7
Clinically and radiographically the manifestation may be similar to squamous cell carcinoma, odontoge- nic tumor or cyst.7 Spencer et al reviewed 40 cases out of which 11 cases were sited in palate or maxilla with bone involvement. Eisenbud et al reported 45 Percent occur- rence in bone in his review of 31 cases where Vanderwaal et al reported only a third of their 40 cases in bone. Clinically they may appear as ulceration or mass.9 Radiographically a well defined radiolucency with bony erosion and lack of cortex, may be observed. In the present case both clinical and radiographic involvement was noted. Radiological studies have proven that large extra osseous soft tissue masses with minimal cortical destruction can be observed on plain radiographs.11 However computed tomography and magnetic resonance imaging helps in visualizing fur- ther changes in case of large lesions with extensive bone destruction.
More aggressive B-cell lymphomas present with large abdominal or mediastenal masses.4 In our case multiple homogenous lesions of varied size could be seen in the abdomen.The diagnosis is usually based on histopathological findings and advanced investiga- tions like immunohistochemistry and the attributed markers for B cell lymphoma include CD 20, CD79a, MB2, CD30.6,12 Spencer et al reviewed 40cases where Pan B cell markers (CD20, CD79a) established B cell lineage in 39 cases.9 In our case immunohistochemis- try was positive for CD20 marker and was suggestive of B cell lymphoma.
Various treatment modalities of Non-Hodgkin's Lymphoma include radiotherapy, chemotherapy and surgery in various combinations.1 However standard modality has been chemotherapy and the regimen includes cyclophosphamide, doxorubicin, oncovin and predinsilone(CHOP).4 Radiotherapy in the range of 2400-5600cGy (35-40Gy) delivered in 180cGy daily fractions has proven successful in early cases.8 Radio immunotherapy has been employed as a new therapy for relapse cases. Yttrium90, Iodine131, ibritumomab tiuxetan are the currently used radioimmunoconjugates.4
Chemotherapy (CHOP) was administered to the present case, however treatment was incomplete after 4 cycles as the patient did not survive.
The prognosis of disease is usually good with estimated 5yr survival rate in 30 Percent cases after therapy.1
Survival is excellent in localized diseases, where as less favorable in disseminated cases.14.The response of patient population to aggressive chemotherapy in the absence of immunosupression has high efficacy with 65 Percent to85 Percent experiencing a complete survival response and 50-75 Percent attaining long term survival.1,13 Patients older than 60, with stages 3 and 4 and severe extranodal places of involvement will have an unfavorable prog- nosis as in our case.
The main purpose of this article was to report and focus on the grotesque manifestations of Non Hodgkin's Lymphoma. Awareness and scrupulous knowledge of dentist is essential in such cases for prompt diagnosis and immaculate treatment, all of which will enhance the probability of existence.
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7 Velez I, Hogge M. Primary Maxillofacial Large B-Cell Lym- phoma in Immunocompetent patients: Report of 5cases. Case Reports in Radiology 2011;doi:10.1155/2011/108023.
8 MahimaVG, Patil K, Prasannasrinivas D. Primary Non- Hodgkin's Lymphoma of Mandible. Salud I Ciencia 2012; 19(2):176-80.
9 Kemp S, Gallagher G, Kabani S, Noonan V, Hara OC. Oral non- Hodgkins Lymphoma: A review of the literature and World Health Organization classification with reference to 40 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105(2): 194-201.
10 Mawardi H, Cutler C, Treister N. Medical management update: Non - Hodgkin's Lymphoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107: 19-33.
11 Edeiken- Monroe B, Edeiken J, Kim EE. Radiologic concepts of Lymphoma of bone. Radiol Clin North America 1990; 28: 841.
12 Patil K, Mahima VG, Srikanth HS. Extranodal Non-Hodgkin's Lymphoma of the gingiva in an HIV seropositive patient. Indian journal of sexually transmitted diseases and AIDS. 2010; 31(2):112-15.
13 Nur FL, Sanz S DE, Silverman S, Miranda C, Regezi JA.Intraoral Non-Hodgkin's Lymphoma in seven patients with Acquired immunodeficiency syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996; 82: 173-78.
14 Kini R, Saha A, Naik V. Diffuse large B cell lymphoma of mandible: A case report. OralMed Oral pathol Oral cir Bucal.2009; 14: 421-24.
1 Professor and HOD of Oral Medicine and Radiology, Sri Sai College of Dental Surgery, Opposite to Shivasagar lake, Kothrepally, Vikarabad-501101, Andhra Pradesh, India
2 Assisstant Professor, Department of Oral Medicine and Radiology, Dr Sudha and Nageswararao Siddhartha Institute of Dental Sciences, Chinaoutpalli, Gannavaram Mandalam, Krishna Dis- trict, Andhra Pradesh - 521286
3 Assisstant Professor Department of Oral Medicine and Radiology, Dr Sudha and Nageswararao Siddhartha Institute of Dental Sci- ences, Chinaoutpalli, Gannavaram Mandalam, Krishna District, Andhra Pradesh - 521 286
4 Assisstant Professor, Department of Oral Medicine and Radiol- ogy, Dr.Sudha and Nageswararao Siddhartha Institute of Dental Sciences, Chinaoutpalli, Gannavaram Mandalam, Krishna Dis- trict, Andhra Pradesh - 521 286 Received for Publication: December 21, 2012 Accepted: March 10, 2013
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|Publication:||Pakistan Oral and Dental Journal|
|Date:||Apr 30, 2013|
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