Journal of the Scientific Society

CASE REPORT
Year
: 2014  |  Volume : 41  |  Issue : 3  |  Page : 183--185

A case of tonsillar anaplastic large cell lymphoma-anaplastic lymphoma kinase negative: An unusual site of involvement with review of literature


Umesh Das1, Vishwanath Sathyanarayanan1, KC Lakshmaiah1, Rekha V Kumar2,  
1 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
2 Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Correspondence Address:
Umesh Das
No. 5, OPD Block, Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru - 560 029, Karnataka
India

Abstract

We present this unusual case of the clinical importance of a 50-year-old male patient who presented with foreign body sensation in the throat and halitosis of 20 days duration. On examination, there were no palpable lymph nodes and oral cavity revealed an ulcero proliferative growth over the right tonsil. Computed tomography of the paranasal sinuses and neck revealed a heterogeneously enhancing mass involving the right tonsil measuring 3.8 cm × 3 cm. Biopsy of the tonsillar mass was suggestive of anaplastic large cell lymphoma (ALCL) with neoplastic large cells positive for CD30, epithelial membrane antigen and CD3 and negative for Tdt, CD56, anaplastic lymphoma kinase (ALK) and cytokeratin. A diagnosis of ALK negative ALCL Stage IA was made and the patient was started on chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks. He received six cycles of chemotherapy followed by 33 gray involved region radiotherapy and reassessment showed total regression of the tonsillar lesion. The patient is in complete remission and now under follow-up for the last 2 years



How to cite this article:
Das U, Sathyanarayanan V, Lakshmaiah K C, Kumar RV. A case of tonsillar anaplastic large cell lymphoma-anaplastic lymphoma kinase negative: An unusual site of involvement with review of literature.J Sci Soc 2014;41:183-185


How to cite this URL:
Das U, Sathyanarayanan V, Lakshmaiah K C, Kumar RV. A case of tonsillar anaplastic large cell lymphoma-anaplastic lymphoma kinase negative: An unusual site of involvement with review of literature. J Sci Soc [serial online] 2014 [cited 2020 Jun 2 ];41:183-185
Available from: http://www.jscisociety.com/text.asp?2014/41/3/183/141218


Full Text

 Introduction



In 1985, Harald Stein and Karl Lennert with colleagues identified an unique large cell lymphoma with anaplastic cytology, an unusual sinus growth pattern, and strong expression of the antigen Ki-1. [1] Subsequently, Ki-1 was identified as an activation antigen (now designated CD30) and a member of the tumor necrosis factor receptor family. Foss HD et al reported in 1996 that majority of such type of lymphoma produced cytotoxic material like ganzyme B and peforin [2] Currently, three distinct T cell anaplastic lymphomas (ALK + ALCL, ALK− ALCL, and primary cutaneous [C-ALCL]) are described in the 2008 World Health Organization (WHO) classification. [3] Although ALK + ALCL and C-ALCL are well characterized, diagnostic pitfalls remain. In particular, recognition of ALCL with variant histology is difficult, and distinction of C-ALCL from lymphomatoid papulosis and from systemic ALCL may be challenging. In addition, ALK is not unique to ALCL and has been detected in inflammatory myofibroblastic tumors, carcinoma lung and hereditary neuroblastoma. Despite considerable progress, questions remain regarding the biology of the ALK + and ALK− groups and their relationship to one another. Here we present an unusual case of tonsillar ALK− anaplastic large cell lymphoma.

 CASE REPORT



A 50-year-old male patient presented with foreign body sensation in the throat and halitosis of 20 days duration. There was no history of loss of weight or anorexia or dysphagia. He also gave a history of chronic ethanol consumption. On examination, the patient was moderately built and nourished. He had an Eastern cooperative oncology group performance status of one. There was no evidence of pallor and enlarged lymph nodes. Examination of the oral cavity revealed an ulcero proliferative growth over the right tonsil 3 cm × 2 cm, which was not bleeding on touch. Examination of the heart, lungs, and abdomen were unremarkable. On evaluation, his complete blood count, comprehensive metabolic panel including random blood sugar, serum electrolytes, renal functions, serum lactate dehydrogenase (LDH), and liver function tests were within the reference range. Chest X-ray was normal and X-ray soft tissue neck revealed a lobular swelling in the region of the oropharynx and upper end of hypopharnyx. Biopsy of the tonsillar mass was suggestive of anaplastic large cell lymphoma (ALCL) of the tonsil with large cells positive for CD30, epithelial membrane antigen (EMA), and CD3 and negative for Tdt, CD56, anaplastic lymphoma kinase (ALK) and cytokeratin (CK) [Figure 1] and [Figure 2]. Bone marrow aspiration did not show marrow infiltration with lymphoma cells. Echocardiogram showed mild aortic regurgitation. Computed tomography (CT) of the para nasal sinuses and neck revealed a heterogeneously enhancing mass involving the right tonsil measuring 3.8 cm × 3 cm [Figure 3]. CT of the chest and abdomen was unremarkable. A diagnosis of ALK negative ALCL Stage IA was made and the patient was started on chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weekly. Our patient received six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen followed by 33 gray involved region radiotherapy. After chemotherapy and radiotherapy the patient was in complete remission and the patient is under follow-up for the last 2 years.{Figure 1}{Figure 2}{Figure 3}

 DISCUSSION



In 1985, Harald Stein and Karl Lennert identified a unique large cell lymphoma with anaplastic cytology and expressing antigen Ki-1 (now designated CD30). [1] ALCL ALK + , ALK− ALCL and primary cutaneous (C-ALCL) were included in the 2008 World Health Organization classification. [3] ALCL-ALK− lymphoma comprises of 2-3% of non-Hodgkin lymphoma (NHL) and 12% of T-cell NHL. It is a CD30 + peripheral T-cell neoplasm that cannot be differentiated from ALCL-ALK + on histopathology, but is devoid of ALK protein. Among all systemic ALCLs, ALK− accounts for 15-50% of cases. [4] Chronic antigenic stimulation as in psoriasis and celiac disease play a role in the pathogenesis of T-cell ALCL. [5] Though, infections like Ebstein barr virus (EBV) was suggested to play a role, a recent study by Herling et al. showed no immunohistochemical evidence of EBV-latent membrane protein Type 1. [6] ALCL is also associated with breast implants and described in people working in the fertilizer industry. It affects older adults with the preponderance for males. [7] The median age at diagnosis is 55-60 years. Our case report was described in a 50-year-old male, which is consistent with the literature review. Which is in sharp contrast to the ALK + -ALCL, which involves the 20-30 years age group. Nearly, half involve lymph node at diagnosis and extranodal involvement is seen in only 15-20% (skin, liver, lung, pancreas, breast, and gastrointestinal tract) unlike in ALK + where 60% have an extranodal involvement (bone, soft tissue, bone marrow, and spleen). [4] Majority present with advanced stage with B symptoms tough our patient had a Stage IA at presentation. Primary central nervous system (CNS) ALCL has also been reported in case series in both ALK + and ALK− , [8] prognosis was worse than in other systemic extranodal ALCL and mortality was higher than in other CNS lymphomas. Tonsil is rarely involved and has been described previously in a study done by Foss et al. in 1996. Our case is probably one of the few cases of ALCL with tonsillar involvement reported so far. ALCL is associated with a high International Prognostic Index score, high LDH serum levels, and an aggressive course. [9] Most show clonal rearrangement of TCR genes t(6;7) (p25.3;q32.3) can also be seen in ALCL-ALK− . On histopathological examination, the neoplastic cells of ALCL-ALK + and ALCL-ALK− are quite similar. Other conditions like peripheral T-cell lymphoma-not otherwise specified and classical Hodgkin lymphoma should also be considered.

Immunophenotyping shows PAX5 in most cases of Hodgkins, which is absent in ALCL-ALK− . Homogenous strong staining for CD30 is a feature of ALCL-ALK− . Immunophenotyping in our case showed large cells positive for CD30, EMA, and CD3 and large cells negative for Tdt, CD56, ALK, and CK. [9] The treatment of ALCL-ALK is in the lines of T-cell lymphomas as it is uncommon, has a wide spectrum of clinical presentation, and there is no randomized trial until date. CHOP is the most commonly used regimen to treat systemic ALCL. Doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone chemotherapy followed by a consolidation therapy with high-dose methotrexate, ifosfamide, etoposide, asparaginase, and cytosine-arabinoside, or methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone have also been tried with good results. In a German high-grade aggressive NHL study, 320 patients were studied with peripheral T-cell lymphoma from seven Phase II and III trials, total, 113 cases of ALCL-ALK− were included, which were treated with CHOP, CHOP plus etoposide (CHOEP) or intensified CHOEP (high-CHOEP14/21 or mega-CHOEP). The 3-year event-free survival and overall survival were 46% and 62%, respectively, in patients with ALCL-ALK− . [10] Our patient received six cycles of CHOP regimen and a reassessment after six cycles of chemotherapy showed total regression of tonsillar lesion. There are no Phase III trials whether tansplantation upfront or at first remission, or during relapse would be beneficial. Pralatrexate, brentuximab vedotin, combinations of bortezomib with gemcitabine or vorinostat and single-agent lenalidomide are being tried in peripheral T-cell lymphomas and ALCL. [9]

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