Anaplastic lymphoma kinase positive variant of anaplastic large cell

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Case Report

Anaplastic lymphoma kinase positive variant of anaplastic large cell lymphoma: A rare entity Venkata Satya Ramesh Thummala, Sreenidhi Banda, Vinay Kumar Reddy Kundoor, Kotya Naik Maloth Department of Oral Medicine and Radiology, Mamata Dental College and Hospital, Khammam, Telangana, India

ABSTRACT Anaplastic large cell lymphoma (ALCL) is a distinct clinicopathological entity of non-Hodgkin’s lymphoma, which has been included as a T-cell neoplasm in the World Health Organization classification, with peculiar features such as painless lymphadenopathy, swelling of extranodal and endoreticular organs, intraoral swellings, and characteristic hallmark cells (eccentric, kidney-shaped, or horseshoe-shaped nuclei) and cluster of differentiation 30 (CD30) positivity. Thorough clinical, biochemical, immunohistochemical, histopathological, and radiological evaluation aids in accurate diagnosis and management of the disease. Here, we report a case of anaplastic lymphoma kinase positive variant of ALCL in a 13-year-old boy.

Key words: Anaplastic lymphoma kinase positive, B-cell lineage, CD30 positive, lymphoma, non-Hodgkin’s lymphoma, Reed–Sternberg cells

A

Introduction

naplastic lymphoma kinase positive variant (ALK+) of anaplastic large cell lymphoma (ALCL) usually affects children and young adults. ALCL positive for the anaplastic lymphoma kinase (ALK) protein involves both lymph nodes and extranodal sites. Extranodal sites commonly involve the skin (26%), bone (14%), soft tissues (15%), lungs (11%), and liver (8%). Intraoral involvement was found to be rare.[1] The manifestations of non-Hodgkin’s lymphoma (NHL), unlike Hodgkin’s lymphoma, occur outside the lymphoid system involving the skin, abdomen, lungs, and central nervous system (CNS), with only 0.1-5% incidence in the oral cavity.[2] ALCL is a distinct clinicopathological entity of NHL which has been included as a T-cell Access this article online Quick Response Code: Website: www.jiaomr.in DOI: 10.4103/0972-1363.155640

neoplasm in the World Health Organization (WHO) classification. ALCLs constitute 10-15% of all childhood lymphomas.[3] ALCL has evolved into a distinct molecular pathology over the past three decades from different pathological entities like sarcoma, metastatic carcinoma, and histiocytosis.

Case Report A 13-year-old boy reported to the department with a chief complaint of swelling on the upper right side of the face since 1 month [Figure 1]. Initially, the patient noticed a small asymptomatic swelling on the right side of the face, which gradually progressed to the present size. Patient gave a history of generalized constitutional symptoms of malaise, high fever, and headache since 1 week, which were relieved temporarily on medication. His medical history was non-contributory. On general physical examination, patient had a lean built and was underweight and undernourished. Cervical lymphadenopathy involving bilateral submandibular (2 × 2 cm in size) and right post-auricular (5 × 4 cm in size) lymph nodes was noted, which were non-tender, firm in consistency, and freely mobile. On intraoral examination, a well-defined solitary lobulated swelling

Address for correspondence: Dr. Kotya Naik Maloth, Department of Oral Medicine and Radiology, Mamata Dental College and Hospital, Giriprasad Nagar, Khammam - 507 002, Telangana, India. E-mail: [email protected] Received: 25-02-2015 Accepted: 17-04-2015 Published: 22-04-2015 432

Journal of Indian Academy of Oral Medicine & Radiology | Oct-Dec 2014 | Vol 26 | Issue 4

[Downloaded free from http://www.jiaomr.in on Wednesday, September 28, 2016, IP: 95.49.95.63] Thummala VS et al.: ALK+ ALCL

was seen on the right side of the maxilla involving the alveolar ridge with obliteration of the buccal vestibule and palatal rugae in relation to 14, 15, 16, and 53; it was roughly oval in shape, measuring approximately 4 × 5 cm, with rough and ulcerated overlying mucosa [Figure 2]. On palpation, it was soft to firm in consistency, tender, and slightly compressible with mobility of the adjacent teeth. Based on the history and clinical examination, a provisional diagnosis of lymphoma with a differential diagnosis of Ewing’s sarcoma and Langerhans cell disease was made. Routine hematological investigations were performed, which were non-contributory. Orthopantomograph (OPG) revealed a well-defined radiolucency with bone loss in relation to impacted 13 [Figure 3]. Fine needle aspiration cytology (FNAC) revealed prominent large pleomorphic lymphocytes with abundant, vacuolated cytoplasm containing typical horseshoeshaped multilobulated nucleus. Some cells showed cribriform nuclei with inconspicuous nucleoli. The smear also showed multinucleated and binucleated Reed–Sternberg like cells in a background of neutrophils and RBCs [Figure 4]. Incisional biopsy revealed an ulcerated hyperplastic stratified squamous epithelium

with an infiltrating connective tissue showing large atypical cells with abundant amphophilic vacuolated cytoplasm. The nucleus was horseshoe shaped with perinuclear eosinophilia. Numerous mitotic figures, Reed–Sternberg like cells, along with multinucleated bizarre cells were also seen [Figure 5], suggestive of ALCL. Immunohistochemical analysis was performed which revealed ALK positivity: Intense cytoplasmic and membranous positivity in larger lymphocytes and negativity for smaller lymphocytes [Figure 6]; and cluster of differentiation 30 (CD30) positivity: Intensely positive for larger lymphocytes and negative for smaller lymphocytes [Figure 7]. Based on the immunohistochemical analysis, it was confirmed as ALK+ ALCL.

Discussion Lymphomas are a diverse and complex group of neoplasms of the lymphoreticular system. The “Revised European American Lymphoma” (REAL/WHO) system has classified lymphomas as B-cell malignancy, T-cell/

Figure 2: Intraoral view of the upper jaw showing the swelling with overlying ulcerative lesion

Figure 1: Profile photograph

Figure 3: OPG revealing well-defined radiolucency with bone loss in relation to impacted 13

Figure 4: FNAC revealing pleomorphic lymphocytes with horseshoeshaped multilobulated nucleus


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and were considered as a single disease entity in the 3rd edition of the WHO classification of hematopoietic neoplasms. In most of the cases, the cells express cytotoxic granule-associated proteins and are CD30 positive.[6] However, in the 4th edition of the classification, ALK+ ALCL is a distinct entity and ALK− ALCL is a provisional entity.[7]

Figure 5: Histopathological view revealing abnormal cells infiltrating the connective tissue

Figure 6: Immunohistochemical analysis showing ALK positivity

Figure 7: Immunohistochemical analysis showing CD30 positivity

natural killer malignancy, and Hodgkin’s lymphoma, based on the cell lineage.[4,5] The ALK+ and ALK− ALCLs were defined as lymphomas consisting of lymphoid cells that are usually large with abundant cytoplasm and pleomorphic, often with horseshoe-shaped nuclei, 434

In 1982, Stein et al. first described the ALK+ variant of ALCL.[8] They originally described it as a peripheral T-cell lymphoma (PTCL) consisting usually of large neoplastic cells with abundant cytoplasm and pleomorphism, often with horseshoe-shaped nuclei. There is a translocation involving the ALK gene with expression of ALK protein and CD30, [8] as noted in the present case. About 3% of the adult NHL and 10-15% of the childhood lymphomas constitute ALK+ ALCL,[8] with a male predominance (M:F = 1.5:1). At the time of presentation, ALK+ ALCL patients will usually be in the advanced stage of the disease (65% of cases in stage III-IV) with systemic symptoms (in 75% patients), especially fever. Sixty percent of the cases show extranodal involvement, mostly in the soft tissue and bone,[8] as was seen in the present case. The peculiar histopathological features of ALCL include neoplastic cells with abundant basophilic cytoplasm that appears gray-blue in hematoxylin and eosin stained sections with a prominent Golgi zone, surrounded by the lobes of the lobulated nucleus (horseshoe or kidney shaped). The cells with these features were referred to as “hallmark cells” of ALCL by Delsol. [6] The histopathological features were consistent with the present case. T-cell lymphomas have a poorer prognosis compared to ALK+ ALCL.[9] A tumor response with 60% of patients remaining relapse-free for 5 years has been achieved in approximately 90% of patients with ALK+ ALCL treated with anthracycline-based chemotherapy. An independent predictor of survival in ALCLs is the ALK protein expression. An overall 5-year survival rate of 71% and 15% has been noted in ALK+ ALCL and ALK− ALCL, respectively.[10] The standard firstline treatment for ALK+ ALCL on type C basis, which is associated with an overall response rate of 90%, is CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).[11] ALK+ ALCL patients show significantly better outcome compared to patients with ALK− ALCL, with this strategy.[8]

Conclusion The main purpose of this article was to report and focus on ALCL, a rare condition. Awareness and thorough knowledge of dentists is essential in such cases to make a prompt diagnosis and provide immaculate treatment for a better prognosis.



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10. Piva R, Agnelli L, Pellegrino E, Todoerti K, Grosso V, Tamagno I, et al. Gene expression profiling uncovers molecular classifiers for the recognition of anaplastic large-cell lymphoma within peripheral T-cell neoplasms. J Clin Oncol 2010;28:1583-90. 11. Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, et al.; International Peripheral T-Cell Lymphoma Project. ALK− anaplastic large cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: Report from the International Peripheral T-cell Lymphoma Project. Blood 2008;111:5496-504. How to cite this article: Thummala VR, Banda S, Kundoor VR, Maloth KN. Anaplastic lymphoma kinase positive variant of anaplastic large cell lymphoma: A rare entity. J Indian Acad Oral Med Radiol 2014;26:432-5. Source of Support: Nil, Conflict of Interest: None declared.


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