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Year : 2014  |  Volume : 26  |  Issue : 4  |  Page : 432-435

Anaplastic lymphoma kinase positive variant of anaplastic large cell lymphoma: A rare entity

Department of Oral Medicine and Radiology, Mamata Dental College and Hospital, Khammam, Telangana, India

Date of Submission22-Feb-2015
Date of Acceptance17-Apr-2015
Date of Web Publication22-Apr-2015

Correspondence Address:
Kotya Naik Maloth
Department of Oral Medicine and Radiology, Mamata Dental College and Hospital, Giriprasad Nagar, Khammam - 507 002, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-1363.155640

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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.

Keywords: Anaplastic lymphoma kinase positive, B-cell lineage, CD30 positive, lymphoma, non-Hodgkin′s lymphoma, Reed-Sternberg cells

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

How to cite this URL:
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 [serial online] 2014 [cited 2023 Jan 28];26:432-5. Available from: http://www.jiaomr.in/text.asp?2014/26/4/432/155640

   Introduction Top

Anaplastic 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 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 Top

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 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.
Figure 1: Profi le photograph

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

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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 horseshoe-shaped 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.
Figure 3: OPG revealing well-defi ned radiolucency with bone loss in relation to impacted 13

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Figure 4: FNAC revealing pleomorphic lymphocytes with horseshoeshaped multilobulated nucleus

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Figure 5: Histopathological view revealing abnormal cells infi ltrating the connective tissue

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Figure 6: Immunohistochemical analysis showing ALK positivity

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Figure 7: Immunohistochemical analysis showing CD30 positivity

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   Discussion Top

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/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, and were considered as a single disease entity in the 3 rd 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 4 th edition of the classification, ALK+ ALCL is a distinct entity and ALK− ALCL is a provisional entity. [7]

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 first-line 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 Top

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.

   References Top

Agrawal MG, Agrawal SM, Kambalimath DH. Non Hodgkins lymphoma of maxilla: A rare entity. Natl J Maxillofac Surg 2011;2:210-13.  Back to cited text no. 1
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Fukuda Y, Ishida T, Fujimoto M, Ueda T, Aozasa K. Malignant lymphoma of oral cavity: Clinicopathologic analysis of 20 cases. J Oral Pathol 1987;16:8-12.  Back to cited text no. 2
Bakshi NA, Ross CW, Finn WG, Valder R, Ruiz R, Koujok K, et al. ALK-positive anaplastic large cell lymphoma with primary bone involvement in children. Am J Clin Pathol 2006;125:57-63  Back to cited text no. 3
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J. Lymphoma classification - From controversy to consensus: The R.E.A.L. and WHO classification of lymphoid neoplasms. Ann Oncol 2000;11(Suppl 1):3-10.  Back to cited text no. 4
Velez I, Hogge M. Primary maxillofacial large B-cell lymphoma in immunocompetent patients: Report of 5 cases. Case Rep Radiol 2011;2011:108023.  Back to cited text no. 5
Delsol G, Ralfkiaer E, Stein H, Wright D, Jaffe ES. Anaplastic large cell lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization Classification of Tumors Pathology and Genetics: Tumors of Hematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001. p. 230-5.  Back to cited text no. 6
Delsol G, Jaffe ES, Falini B. Anaplastic large cell lymphoma (ALCL), ALK-positive. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. 4 th ed. Lyon: International Agency for Research on Cancer; 2008. p. 312-6.  Back to cited text no. 7
Ferreri AJ, Govi S, Pileri SA, Savage KJ. Anaplastic large cell lymphoma, ALK-positive. Crit Rev Oncol Hematol 2012;83:293-302.  Back to cited text no. 8
Armitage JO, Vose JM, Weisenburger DD. Towards understanding the peripheral T-cell lymphomas. Ann Oncol 2004;15:1447-9.  Back to cited text no. 9
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.  Back to cited text no. 10
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.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]


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