Document Type : Original Research


Dept. of Pathology, Kerman University of Medical Sciences, Kerman, Iran


  Background and Objectives: Classic Hodgkin lymphoma (CHL), anaplastic large cell lymphoma (ALCL) and some cases of diffuse large B cell lymphoma (DLBCL) have overlapping morphologic features. Since they all represent distinct clinico-pathologic entities, we explored the differential diagnostic impact of immunophenotyping to discriminate between them. Materials and Methods: We included 61 cases diagnosed as CHL, ALCL, and anaplastic variant of DLBCL. We reviewed morphologic microscopic findings by conventional staining and immunohistochemistry (IHC) with antibodies against PAX-5, CD30, CD15, CD45, EMA, ALK-1, and LMP-1. Results: Fifty cases corresponded to CHL (81.97%), 4 cases to ALCL (6.56%), and 4 cases to DLBCL (6.56%) excluding 3 cases, which remained unclassifiable (4.92%). PAX-5 was expressed in 94% of CHL and 100% of DLBCL cases. LMP-1 was expressed in 52% of CHL and 25% of DLBCL cases. EMA was invariably expressed in all 4 cases of ALK+ALCL. It was expressed in 4/50 cases (8%) of CHL and in 2/4 cases (50%) of DLBCL. CD45 was expressed in all cases of ALCL and DLBCL but also in 3/50 cases (6%) of CHL. Conclusion: The differentiation between ALCL and CHL based on EMA and CD45 is not reliable. Utilization of PAX-5 in combination with other markers such as CD15 and LMP-1 is recommended. CD20 and PAX-5 are not too helpful in the differentiation of CHL and DLBCL, while CD15 and CD79a were found to be quite useful discriminative markers for this purpose.  


  1. Tabrizchee H, Masoomian M, Ahani F, Zare M. The pattern of malignant Tumors in Kerman province. Med J Islam Rep Iran 1998;12(1):19-23.
  2. Hashemi-Bahremani M, Parwaresch MR, Tabrizchi H, Gupta RK, Raffii MR. Lymphomas in Iran. Arch Iran Med 2007;10(3):343-8.
  3. Mohagheghi MA, Mosavi-Jarrahi A, Malekzadeh R, Parkin M. Cancer incidence in Tehran metropolis: the first report from the Tehran Population-based Cancer Registry, 1998-2001. Arch Iran Med 2009;12(1):15-23.
  4. Marafioti T, Hummel M, Foss HD, Laumen H, Korbjuhn P, Anagnostopoulos I, et al.. Hodgkin and reed-sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription. Blood 2000;95(4):1443-50.
  5. Jaffe E, Lee H, Harald S. WHO classification of tumor of haematopoietic and lymphoid tissues. ed. Lyon: IARCpress; 2001.
  6. Pileri SA, Ascani S, Leoncini L, Sabattini E, Zinzani PL, Piccaluga PP, et al. Hodgkin's lymphoma: the pathologist's viewpoint. J Clin Pathol 2002;55(3):162-76.
  7. Liu Y, Zhuang H, Liao X, Luo X, Luo D, Cai X. [Immunophenotype and differential diagnosis of Hodgkin's lymphoma]. Zhonghua Xue Ye Xue Za Zhi 2002;23(10):524-7.
  8. Higgins RA, Blankenship JE, Kinney MC. Application of immunohistochemistry in the diagnosis of non-Hodgkin and Hodgkin lymphoma. Arch Pathol Lab Med 2008;132(3):441-61.
  9. Tamaru J, Tokuhira M, Nittsu N, Nakamura S, Ichinohasama R, Suzuki R, et al. Hodgkin-like anaplastic large cell lymphoma (previously designated in the REAL classification) has same immunophenotypic features to classical Hodgkin lymphoma. Leuk Lymphoma 2007;48(6):1127-38.
  10. Willenbrock K, Kuppers R, Renne C, Brune V, Eckerle S, Weidmann E, et al. Common features and differences in the transcriptome of large cell anaplastic lymphoma and classical Hodgkin's lymphoma. Haematologica 2006;91(5):596-604.
  11. Vassallo J, Lamant L, Brugieres L, Gaillard F, Campo E, Brousset P, et al. ALK-positive anaplastic large cell lymphoma mimicking nodular sclerosis Hodgkin's lymphoma: report of 10 cases. Am J Surg Pathol 2006;30(2):223-9.
  12. Ganjei-Azar P, Nadji M. Color Atlas of Immunohistochemistry in diagnostic cytology. New York: Springer; 2007.
  13. Key m. Immunohistochemical staining methods. 4th ed. California: Dako; 2006.
  14. Medeiros LJ, Elenitoba-Johnson KS. Anaplastic Large Cell Lymphoma. Am J Clin Pathol 2007;127(5):707-22.
  15. Stein H, Foss HD, Durkop H, Marafioti T, Delsol G, Pulford K, et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood 2000;96(12):3681-95.
  16. Herling M, Rassidakis GZ, Viviani S, Bonfante V, Giardini R, Gianni M, et al. Anaplastic lymphoma kinase (ALK) is not expressed in Hodgkin's disease: results with ALK-11 antibody in 327 untreated patients. Leuk Lymphoma 2001;42(5):969-79.
  17. Bruno L, Schaniel C, Rolink A. Plasticity of Pax-5(-/-) pre-B I cells. Cells Tissues Organs 2002;171(1):38-43.
  18. Herling M, Rassidakis GZ, Jones D, Schmitt-Graeff A, Sarris AH, Medeiros LJ. Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria. Hum Pathol 2004;35(4):455-9.
  19. McCune RC, Syrbu SI, Vasef MA. Expression profiling of transcription factors Pax-5, Oct-1, Oct-2, BOB.1, and PU.1 in Hodgkin's and non-Hodgkin's lymphomas: a comparative study using high throughput tissue microarrays. Mod Pathol 2006;19(7):1010-8.
  20. Jensen KC, Higgins JP, Montgomery K, Kaygusuz G, van de RM, Natkunam Y. The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant neoplasms. Mod Pathol 2007;20(8):871-7.
  21. Carotta S, Holmes ML, Pridans C, Nutt SL. Pax5 maintains cellular identity by repressing gene expression throughout B cell differentiation. Cell Cycle 2006 ;5(21):2452-6.
  22. Li D, Li GD, Liu WP, Li FY, Zhang WY, Liao DY. [Expression of B cell-specific activator protein in lymphomas]. Zhonghua Bing Li Xue Za Zhi 2005;34(6):345-7.
  23. Foss HD, Marafioti T, Stein H. [The many faces of anaplastic large cell lymphoma]. Pathologe 2000;21(2):124-36.
  24. Browne P, Petrosyan K, Hernandez A, Chan JA. The B-cell transcription factors BSAP, Oct-2, and BOB.1 and the pan-B-cell markers CD20, CD22, and CD79a are useful in the differential diagnosis of classic Hodgkin lymphoma. Am J Clin Pathol 2003;120(5):767-77.