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 Table of Contents  
Year : 2016  |  Volume : 7  |  Issue : 1  |  Page : 114-117  

Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate as first clinical manifestation of acquired immune deficiency syndrome

1 Department of Oral Pathology, Post Graduate Institute of Dental Sciences, Rohtak, Haryana, India
2 Department of General Pathology, Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
3 Department of Oral Pathology, Dr. Harvansh Singh Judge Institute of Dental Sciences and Hospital, Chandigarh, Punjab, India

Date of Web Publication22-Feb-2016

Correspondence Address:
Anjali Narwal
Department of Oral Pathology, Post Graduate Institute of Dental Sciences, Rohtak, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-237X.177115

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Anaplastic large cell lymphoma (ALCL) is an uncommon disease, accounting for <5% of all cases of non-Hodgkin's lymphoma. We report a case of 48-year-old male who presented a clinically benign swelling in the right anterior palatal region since last 2 months. Radiographic evaluation showed no bone loss in palatal area. Histological and radiological examination was in favor of a peripheral reactive lesion like pyogenic granuloma or a benign salivary gland tumor. Immunohistochemistry confirmed the diagnosis of anaplastic lymphoma kinase-negative (ALK(−)) ALCL. Further laboratory tests ELISA for human immunodeficiency virus (HIV) and CD4 cell count was done which showed positivity for HIV. To the best of our knowledge, it is the first case of ALK(−) ALCL in the hard palate presenting as the first clinical manifestation of acquired immune deficiency syndrome.

Keywords: Anaplastic, anaplastic lymphoma kinase, lymphoma

How to cite this article:
Narwal A, Yadav AB, Prakash S, Gupta S. Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate as first clinical manifestation of acquired immune deficiency syndrome. Contemp Clin Dent 2016;7:114-7

How to cite this URL:
Narwal A, Yadav AB, Prakash S, Gupta S. Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate as first clinical manifestation of acquired immune deficiency syndrome. Contemp Clin Dent [serial online] 2016 [cited 2020 Jul 8];7:114-7. Available from:

   Introduction Top

Infection with human immunodeficiency virus (HIV) predisposes individuals to the development of neoplasms. There are currently four acquired immune deficiency syndrome (AIDS)-defining malignancies: Kaposi's sarcoma, non-Hodgkin lymphoma (NHL) of high-grade pathologic type and B-cell or unknown immunologic phenotype, primary central nervous system lymphoma, and invasive cervical carcinoma.[1] NHLs appear in 3% of HIV-seropositive patients.[2]

Mature T-cell and natural killer (NK) cell neoplasms make up only 12% of NHL cases worldwide. Within this heterogeneous category of NHL, anaplastic large cell lymphoma (ALCL) is listed Revised European-American Classification of Lymphoid Neoplasms (REAL) as an independent entity in the REAL.[3]

ALCL is a rare subtype of T-cell lymphoma that can involve mucocutaneous sites, primarily or secondarily, as part of the systemic disease. ALCL is usually comprised of large atypical cells with abundant cytoplasm, pleomorphism, and often having kidney shaped nuclei.[4] In almost all reported cases of ALCL, tumor cells are CD30+ and in most cases they express the cytotoxic granule-associated protein (perforin). A significant percentage of ALCL harbors the t (2;5)(p23;q35) translocation. Based on the expression of resulting gene product: Anaplastic lymphoma kinase (ALK) ALCL is divided into ALK(+) and ALK(−) categories.[5]

This paper presents an unusual case of palatal ALCL, which mimicked a benign neoplasm clinically but was found to be the first clinical manifestation of AIDS in this patient.

   Case Report Top

A 48-year-old male presented with a rapidly enlarging swelling in the right anterior palatal mucosa measuring 5.6 cm × 4.5 cm with white coating, moderately painful, and bled upon touching [Figure 1]. This swelling was present since last 2 months and growing exponentially. He had visited a local dentist with this swelling for which antibiotics and analgesics were prescribed for few days but did not get any relief.
Figure 1: Intraoral anterior palatal swelling

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The patient was a nonsmoker, and his medical history did not reveal other relevant information. The extraoral examination did not show any facial asymmetry and cervical lymphadenopathy. Results of laboratory testing showed hemoglobin, hematocrit, white blood cell, and platelet counts within normal range. On intraoral examination, the swelling had not crossed the midline and appeared to be pedunculated, afebrile, nonfluctuant. Teeth associated with the swelling, i.e., all premolars and molars on the right side of the upper jaw were noncarious, nontender, and nonmobile. The swelling did not have an ulcerated surface and palpation revealed a soft consistency. The first impression of the lesion suggested clinical characteristics of benignancy suggesting pyogenic granuloma, peripheral giant cell granuloma, peripheral ossifying fibroma, and even pleomorphic adenoma as differential diagnosis. Radiographic investigations were noncontributory as they showed mild bone loss which is usually seen in relation to reactive hyperplastic lesions.

An incisional biopsy of the lesion was submitted for pathologic examination. Histopathologic sections revealed an atypical lymphocytic infiltrate consisting of large, lymphoid cells with pleomorphic nuclei, numerous atypical mitoses, and infiltrative pattern of tumor cells. These atypical round tumor cells showed vesicular nuclei having cleaved appearance with the presence of 2 or more nucleoli [Figure 2]. Neither peripheral capsule nor Reed–Sternberg cells were seen. Immunohistochemical (IHC) studies were performed with appropriate positive and negative controls on the incisional processed tissue. IHC analysis using streptavidin-biotin protocol was performed with antibodies: CKAE1/AE3, CD3, CD5, CD15, CD20, CD30, CD56, CD68, CD99, leukocyte common antigen (LCA), epithelial membrane antigen (EMA), synaptophysin, HMB-45, S-100, MPO, MUM1, and p80NPM/ALK. Tumor cells showed strong positivity with CD30 and LCA, and EMA positivity was seen only in 50% of tumor cells [Figure 3]. Negative stain was identified for CK, CD3, CD5, CD15, CD20, CD56, CD68, CD99, synaptophysin, HMB 45, S-100, MUM1, MPO, and p80NPM/ALK.
Figure 2: (a) Sheet of atypical round tumor cells with vesicular nuclei (H and E, ×10). (b) Tumor cell with cleaved nuclei (arrow head) and mitotic figure (arrow) (H and E, ×40)

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Figure 3: Tumor cells positive for (a) CD30, membrane and cytoplasm (IHC, ×10), (b) leukocyte common antigen, membrane (IHC, ×10), (c) epithelial membrane antigen, membrane and cytoplasm (IHC, ×10)

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The patient was referred to Oncology Department where further laboratory and imaging tests were performed. ELISA tests for HIV and hepatitis B and C were done. Serology of the patient came out to be strongly positive for HIV based on ELISA, negative for hepatitis B and C. Further evaluation of his seropositivity by Western blot confirmed ELISA results of HIV. CD4 cell count had dropped down to 120. Full body scan to rule out the presence of any other malignancy associated with AIDS was performed. No associated malignancy or metastasis was detected on imaging. There were also no associated lymphadenopathies.

R-EPOCH infusion chemotherapy was started for the patient in the Oncology Department with one cycle every 3 weeks for a total of six courses. HAART therapy (efavirenz + tenofovir + emtricitabine) was also initiated orally. Despite consecutive follow-up, unfortunately, the patient did not cooperate and after three cycles of chemotherapy, the patient was lost. However, it was observed during a follow-up period of chemotherapy that the swelling had decreased in size. Although, even after incisional biopsy the swelling had reduced but the remarkable reduction in size was seen after chemotherapy.

   Discussion Top

ALCL was first described as a clinical entity by Stein et al.[6] ALCL is subdivided according to the IHC features in precursor T-cells or null cells, in 60% and 25% of cases, respectively. ALCL shows positivity with CD30, EMA, LCA, Ki67, CD3, CD45, perforin, and granzyme B. Some ALCLs show positivity with ALK whereas few do not show any expression. The clinicopathologic features of ALK carrying ALCLs were first investigated by Shiota and Mori [7] and found that ALK(+) is a distinct entity clinically and pathogenetically and should be differentiated from ALK(−) tumors. WHO classification currently considers two ALCL types – ALK(−) and ALK(+). The tumors that show a positive reaction for ALK have greater cell proliferation and show relatively better prognosis.[8] On the other hand, cases of ALK(−) ALCL show inaccurate behavior with relatively unfavorable prognosis.[9] The present case did not express ALK; hence, it was considered ALK(–) ALCL. In addition, the tumor did not show expression of NK or T-cells therefore, it was also considered as null cell lymphoma. ALK(−) ALCL normally occurs in adults (40–65 years) with male prevalence, as seen in our male patient of 48 years of age.

All persons infected with HIV, whether or not they undergo seroconversion illness and pass through a phase of symptomless infection (clinical latency) which may last up to several years. In the present case, he showed positivity for HIV antibody but had no other symptoms except the palatal swelling. He also did not have any lymphadenopathy. The period of clinical latency does not mean microbiological latency as virus multiplication goes on throughout. CD4 T-cell count decreases steadily from over 1000/µl to about 500 or less. When the count falls to 200 or less, clinical AIDS sets in. In a healthy HIV negative person, normal CD4 T-cell count ranges from 460 to 1600 whereas in our patient it had dropped to 120 with no other acute infections and lymphadenopathy. Clinical AIDS with CD4 T-cell count dropped from 200 to 120 in the absence of acute illness made it an interesting case to be reported.

A search of the literature in the PubMed identified only 11 prior cases of CD30+ ALCL involving oral cavity. Of the 11 reported cases, all were of T-cell type except for one case with null cell type. Based on clinical cases found in the review of literature [Table 1],[10] there is a slight male prediction (female: male, 1:1.5), and the patients presented at a mean age of 53.4 years old. Most of the reported cases were located in the gingiva (five cases), followed by the palate (three cases), tongue (two cases), retromolar trigone (two cases), lip (two cases), the floor of mouth (one case), and buccal mucosa (one case). The main radiographic findings were bone resorption, and the main diagnostic hypothesis was a nonspecific infection. To the best of our knowledge, the present case is the first palatal ALCL, which mimicked clinically as a benign tumor and was the first clinical manifestation of AIDS. None of the ALCL cases of palate reported in literature showed serological positivity to HIV. Out of all cases reported in literature only 14% were ALK(−) in the oral cavity. Currently, there is only one case reported by Notani et al., which showed ALK expression in ALCL involving oral cavity.[11]
Table 1: Synopsis of clinicopathological and anaplastic lymphoma kinase profile of oral anaplastic large cell lymphoma reported in PubMed literature

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The differential diagnosis of ALCL includes Hodgkin lymphoma (HL) and other forms of CD30(+) T- or B-cell lymphoma with anaplastic morphology and undifferentiated carcinoma or other malignancies. HL lacks LCA expression which was positive in the present case. Other peripheral T-cell lymphomas show limited CD30 expression and lack hallmark cells which were seen in the present case. Undifferentiated carcinomas and melanoma can be identified using cytokeratin and melanoma markers which were negative for the present case.

Interestingly, the present case of ALK(−) ALCL appears to be the first case reported in the palate of HIV-seropositive patient with ALCL being the first clinical manifestation of AIDS. In our patient, it was the null cell type of lymphoma which did not show any positivity with CD3 and CD20 and happens to be the first such case.

   Conclusion Top

ALCL is a systemic malignant disease characterized by extranodal type which rarely occurs in the oral cavity as the first manifestation of acquired immunodeficiency syndrome. Hence, it is important to have accurate, clinical including HIV investigation, histological and IHC analysis of oral lesions to establish a correct diagnosis of such lesions which appear clinically benign.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Sandler AS, Kaplan LD. Diagnosis and management of systemic non-Hodgkin's lymphoma in HIV disease. Hematol Oncol Clin North Am 1996;10:1111-24.  Back to cited text no. 1
Beral V, Peterman T, Berkelman R, Jaffe H. AIDS-associated non-Hodgkin lymphoma. Lancet 1991;337:805-9.  Back to cited text no. 2
Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 1994;84:1361-92.  Back to cited text no. 3
O'leary H, Savage KJ. The spectrum of peripheral T-cell lymphomas. Curr Opin Hematol 2009;16:292-8.  Back to cited text no. 4
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC; 2008.  Back to cited text no. 5
Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: Evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 1985;66:848-58.  Back to cited text no. 6
Shiota M, Mori S. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: A distinct clinicopathologic entity. Leukemia 1997;11 Suppl 3:538-40.  Back to cited text no. 7
Ten Berge RL, Oudejans JJ, Ossenkoppele GJ, Meijer CJ. ALK-negative systemic anaplastic large cell lymphoma: Differential diagnostic and prognostic aspects – A review. J Pathol 2003;200:4-15.  Back to cited text no. 8
Campo E, Chott A, Kinney MC, Leoncini L, Meijer CJ, Papadimitriou CS, et al. Update on extranodal lymphomas. Conclusions of the Workshop held by the EAHP and the SH in Thessaloniki, Greece. Histopathology 2006;48:481-504.  Back to cited text no. 9
Rozza-de-Menezes RE, Jeronimo Ferreira S, Lenzi Capella D, Schwartz S, Willrich AH, de Noronha L, et al. Gingival anaplastic large-cell lymphoma mimicking hyperplastic benignancy as the first clinical manifestation of AIDS: A case report and review of the literature. Case Rep Dent 2013;2013:852932.  Back to cited text no. 10
Notani K, Shindoh M, Takami T, Yamazaki Y, Ohgo T, Fukuda H. Anaplastic large cell lymphoma (ALCL) in the oral mucosa with repeating recurrence and spontaneous regression of ulceration: Report of a case. Oral Med Radiol 2002;7:79-82.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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