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Year : 2014  |  Volume : 57  |  Issue : 1  |  Page : 157-158
Anaplastic lymphoma kinase (ALK) positive diffuse large B cell lymphoma in a 20 year old: A rare entity

1 Department of Pathology and Lab Medicine, Medanta-The Medicity Hospital, Gurgaon, Haryana, India
2 Institute of Medical Oncology and Hematology, Medanta-The Medicity Hospital, Gurgaon, Haryana, India

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Date of Web Publication17-Apr-2014

How to cite this article:
Sachdev R, Goel S, Gupta S, Sood N. Anaplastic lymphoma kinase (ALK) positive diffuse large B cell lymphoma in a 20 year old: A rare entity. Indian J Pathol Microbiol 2014;57:157-8

How to cite this URL:
Sachdev R, Goel S, Gupta S, Sood N. Anaplastic lymphoma kinase (ALK) positive diffuse large B cell lymphoma in a 20 year old: A rare entity. Indian J Pathol Microbiol [serial online] 2014 [cited 2022 Aug 16];57:157-8. Available from: https://www.ijpmonline.org/text.asp?2014/57/1/157/130937


A 20-year-old gentleman presented with a short history of fever and bone pains since 2 weeks. Peripheral smear showed a leukoerythroblastic blood picture with 2.0 percent blasts, hemoglobin 9.0 g/dL, total leukocyte count 6500 cells/cu mm and platelet count of 1,50,000/cu mm. Viral and dengue serology, blood cultures and malarial parasite were negative. Bone marrow aspirate and biopsy was advised in view of leukoerythroblastic picture, persistent fever and bone tenderness.

Bone marrow smears were hemodilute, but showed few large cells with high Nucleo cytoplasmic ratios, prominent macronucleoli and basophilic cytoplasm. The trephine showed total replacement of marrow elements by sheets of large, atypical and blastoid cells [Figure 1]. Flow cytometry was inconclusive, due to hemodilute nature of the sample.
Figure 1: (a) Peripheral smears showing a blast and nucleated red blood cells, leucoerythroblastic blood picture, (b) Bone marrow aspirate smear showing atypical cells with blastic morphology. (c and d) H and E section of bone marrow trephine (×10 and ×40 respectively)

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The differentials considered were acute leukemia, high grade lymphoma, melanoma, poorly differentiated carcinoma and sarcoma. A screening panel immunohistochemistry (IHC) with cytokeratin (CK, AE 1 and AE2, Biogenix), Vimentin (V9, Dako), CD45(2B11 + PD7/26, Dako) and HMB 45 (HMB 45, Dako) was put. Cells were positive for CD45 and Vimentin, negative for CK and HMB 45. A preliminary diagnosis of high grade lymphoma/leukemia was thus made.

An IHC panel of CD20 (L26, Dako), CD3 (IS 503, Dako), CD19 (LE-CD19, Dako), CD10 (56 C6, Dako), MPO (IR511, Dako), CD30 (Ber H2, Dako), CD15 (Carb 3, Dako), TdT (IS 001, Dako), CD34 (QBEnd 10, Dako), CD68 (PGM1, Dako) and CD56 (123C3, Dako) was put initially. The results unexpectedly came negative for all these markers. The next round of markers included CD138(MI 15, Dako), CD117 (YR145, Dako) and CD68 (PGM1, Dako). The atypical cells showed strong positivity for CD138 and heterogeneous CD117 expression. We thought of plasmablastic lymphoma (PL) in view of CD138 positivity and ordered anaplastic lymphoma kinase (ALK) (8A9, Dako) and PAX 5 (ZP007, Biogenix) to exclude possibility of ALK positive diffuse large B cell lymphoma (DLBCL).

Meanwhile, whole body positron emission tomography scan was done, which showed extensive, widespread nodal involvement involving cervical, mediastinal and retroperitoneal nodes with deposits in the liver and kidney.

IHC results for ALK showed a restricted, granular cytoplasmic positivity with negative PAX 5 expression [Figure 2]. A final diagnosis of ALK positive DLBCL was made and patient was started on CHOP regimen.
Figure 2: (a) CD45 immunohistochemistry (IHC) showing heterogeneous expression in atypical cells, (b) CD117 IHC with positivity in atypical cells, (c) CD138 staining in atypical cells (×40X), (d) Anaplastic lymphoma kinase IHC showing a restricted, granular, cytoplasmic staining

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ALK positive DLBCL are very rare with only 40 cases in the literature. [1] The median age is 36 years with a male: female ratio of 3:1. Common presentation is with nodal/mediastinal masses and is usually in advanced stage. The diagnosis is rendered difficult with negativity of conventional stains associated with B lymphoid lineage (CD20, CD19, PAX 5 and CD79a). The common differentials with strong CD138 positivity include ALK positive DLBCL, PL, primary effusion lymphoma (PEL) and Plasmablastic Myeloma (PM). ALK staining helps to differentiate between PL and ALK positive DLBCL. Lack of CD56 staining, absence of bony lesions and young age excluded PM. PELs present mainly with effusions and lack light chain staining. Our case had CD117 staining in addition.

These lymphomas usually lack the characteristic t(2;5) translocation but rather harbor t(2;17) translocation. [1] The overall median survival is 11 months. They are usually insensitive to rituximab owing to negative CD20.

Diagnosis of this rare entity requires awareness, high index of suspicion and a broad and extensive battery of IHC markers to arrive at a diagnosis and enable prompt institution of chemotherapy.

   References Top

1.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008.  Back to cited text no. 1

Correspondence Address:
Ritesh Sachdev
A 803, Plot Number 7A, Navrattan Apartments, Sector 23, Dwarka, New Delhi - 110 077
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.130937

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