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Aberrant expression of T-cell marker CD7 in HIV negative intestinal plasmablastic lymphoma
Pathology (- 2016) -(-), pp. 1e2
CORRESPONDENCE Aberrant expression of T-cell marker CD7 in HIV negative intestinal plasmablastic lymphoma Sir, Plasmablastic lymphoma (PBL) is considered a rare, aggressive subtype of large B-cell lymphoma (LBCL), commonly EpsteineBarr virus (EBV) infected, developing probably from terminally differentiated, active B-cells in the transition from immunoblasts to plasma cells. PBL has a high
incidence in human immunodeficiency virus (HIV) positive or iatrogenically immunosuppressed adult males with mostly intraoral localisation, but also in other extranodal sites, and there have been cases reported in immunocompetent elderly patients.1,2 Herein, a case of PBL of the small intestine with exceptional immunophenotypic characteristics in a HIV negative, EBV negative patient is presented. A 77-year-old male without clinical or laboratory evidence of immunodeficiency and with a history of Billroth II surgery almost 30 years previously presented an ulcer in the anastomotic abducent loop of the jejunum. The partial enterectomy specimen showed an ulcerative, intramural, tumorous, whitish
(A) Intestinal wall infiltrated by neoplastic cells presenting (B) morphological characteristics of plasmablasts and immunoreactivity to (C) MUM1, (D) CD7, (E) CD43 and (F) EMA antigens. A, H&E, low power; B, H&E, high power; CeF, IHC, medium power.
Fig. 1
Print ISSN 0031-3025/Online ISSN 1465-3931 Ó 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Iliadis A, et al., Aberrant expression of T-cell marker CD7 in HIV negative intestinal plasmablastic lymphoma, Pathology (2016), http://dx.doi.org/10.1016/j.pathol.2016.07.014
2
Pathology (2016), -(-), -
CORRESPONDENCE
lesion measuring 4 cm in diameter. Haematoxylin and eosin (H&E) sections revealed sizeable tumour cells in a diffuse growth pattern (Fig. 1A), with moderate amount of cytoplasm, round to ovoid, often irregular, multiform or multilobulated nuclei with prominent nucleoli and occasional binucleate or multinucleate cell forms (Fig. 1B). The following immunohistochemistry (IHC) phenotype was observed: CD138þ, MUM1þ (Fig. 1C), CD7þ (Fig. 1D), CD43þ (Fig. 1E), EMAþ (Fig. 1F), CD30þ, p53þ, vimentinþ, CD38/þ, CD45/þ, perforin/þ, CD31/þ, CD20, CD45RA, CD79a, PAX5, IgG, IgM, IgA, k, l, CD45RO, CD2, CD3, CD4, CD5, CD8, CD56, ALK1, LMP1, CD21, CD23, CCND1, CD10, BCL2, TIA1, granzymeB. The Ki-67/MIB1 proliferation index was >90%, while EBER in situ hybridisation staining proved negative. Molecular analysis for IGH and TCR gene rearrangements demonstrated B-cell clonality. It is not unusual for some B-cell lymphomas to aberrantly coexpress one or more T-cell markers, such as CD5, CD7, CD2, CD43, CD4, and/or CD8 rarely, a phenomenon maybe indicating anomalous activation of silent or repressed T-cell differentiation genes. Immunohistochemical examination with additional cell lineage specific markers and molecular analysis for antigen receptor gene rearrangements are necessary for accurate cell lineage identification in such cases. To the best of our knowledge there are very few cases of PBL with aberrant T-cell marker positivity (CD3, CD4, CD3/CD4, CD5, CD43) in the English medical literature.3e9 Two cases, the fourth reported by Wang et al.4 and one by Podder et al.,8 seem to resemble this reported case, inasmuch as they also are EBER and express CD43 (but not CD7). Although CD43 has been found to be positive in a small percentage of cases,10 this one is unique. Apart from the rare localisation and immunocompetent patient status, it shows a diffuse, intense positivity and co-expression of two T-cell associated antigens, namely CD7, which has never been reported before, and CD43, highlighting the continually expanding range of morphological, immunophenotypic and clinical characteristics of those B-cell lymphomas with T-cell marker aberrant expression, since lineage ambiguity and heterotropic expression of T-cell antigens in terminally differentiated B-cell lymphomas are more common in EBV-infected and/or immunocompromised patients.5,6 As PBLs lack typical expression of B-cell antigens, knowledge of such features will help avoid misclassification.7 Another point being raised currently, is that such cases reinforce the notion that PBL is a distinct nonHodgkin lymphoma entity, which cannot simply be classified under LBCLs, and it demands modification of the WHO classification.8 Regarding CD7/LEU-9, the earliest T-cell associated antigen expressed on lymphocytes, the monoclonal antibody used here (clone NCL-CD7-272; Novocastra, UK), recognises a portion of the extracellular domain of the human CD7 molecule, a single-domain Ig superfamily molecule expressed on human T and NK cells, as well as on cells in the early stages of T-, B-, and myeloid cell differentiation,11 and it stained the membrane of the neoplastic cells in this case. Concerning CD43/SPN, an integral membrane protein typically expressed at high levels on most leukocytes, the monoclonal antibody used here (clone DF-T1; Dako, Denmark) offered also a membranous staining pattern of the
neoplastic cells. Notably, CD43 is expressed, apart from Tcells, on human bone marrow B-cell precursors and plasma cells, while interestingly the CD43 positive proposed murinecounterpart human B1 cells may actually possess a functional pre-plasmablast phenotype.12 It is also mentioned in the literature that plasmablastic/plasmacytic lesions, including PBL, may exhibit immunoreactivity to CD31,13,14 as observed in this case, raising differential diagnostic problems involving poorly differentiated epithelioid vascular neoplasms, such as haemangioendothelioma, in the case that the right panel of antibodies is not used. Conclusively, in order to avoid a misdiagnosis, it is worth bearing in mind that PBL may morphologically and immunohistochemically masquerade as a CD30 positive anaplastic large cell lymphoma (ALCL) or a poorly differentiated epithelioid vascular neoplasm. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose. Alexandros Iliadis Triantafyllia Koletsa Ioannis Kostopoulos Department of Pathology, Faculty of Medicine, Aristotle University, Thessaloniki, Greece Contact Triantafyllia Koletsa, MD. E-mail: [email protected] 1. Stein H, Harris NL, Campo E. Plasmablastic lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC Press, 2008; 256e7. 2. Rafaniello Raviele P, Pruneri G, Maiorano E. Plasmablastic lymphoma: a review. Oral Dis 2009; 15: 38e45. 3. Tzankov A, Brunhuber T, Gschwendtner A, et al. Incidental oral plasmablastic lymphoma with aberrant expression of CD4 in an elderly HIV-negative patient: how a gingival polyp can cause confusion. Histopathology 2005; 46: 348e50. 4. Wang J, Chen C, Lau S, et al. CD3-positive large B-cell lymphoma. Am J Surg Pathol 2009; 33: 505e12. 5. Suzuki Y, Yoshida T, Nakamura N, et al. CD3- and CD4-positive plasmablastic lymphoma: a literature review of Japanese plasmablastic lymphoma cases. Intern Med 2010; 49: 1801e5. 6. Sun J, Medeiros LJ, Lin P, et al. Plasmablastic lymphoma involving the penis: a previously unreported location of a case with aberrant CD3 expression. Pathology 2011; 43: 54e7. 7. Oliveira JL, Grogg KL, Macon WR, et al. Clinicopathologic features of B-Cell lineage neoplasms with aberrant expression of CD3: a study of 21 cases. Am J Surg Pathol 2012; 36: 1364e70. 8. Podder S, Khetan P, Sivamurthy S, et al. Rare presentation of orbital plasmablastic lymphoma with oral cavity involvement in an HIVnegative patient. BMJ Case Rep 2015 Sep 16: 2015. 9. Liu M, Liu B, Liu B, et al. Human immunodeficiency virus-negative plasmablastic lymphoma: a comprehensive analysis of 114 cases. Oncol Rep 2015; 33: 1615e20. 10. Loghavi S, Alayed K, Aladily TN, et al. Stage, age, and EBV status impact outcomes of plasmablastic lymphoma patients: a clinicopathologic analysis of 61 patients. J Hematol Oncol 2015; 8: 65. 11. Sempowski GD, Lee DM, Kaufman RE, et al. Structure and function of the CD7 molecule. Crit Rev Immunol 1999; 19: 331e48. 12. Covens K, Verbinnen B, Geukens N, et al. Characterization of proposed human B-1 cells reveals pre-plasmablast phenotype. Blood 2013; 121: 5176e83. 13. Plocharczyk E, Wakely Jr PE. CD31 expression in plasmacytic/plasmablastic lesions. Ann Diagn Pathol 2013; 17: 498e501. 14. Vaubell JI, Sing Y, Ramburan A, et al. Pediatric plasmablastic lymphoma: a clinicopathologic study. Int J Surg Pathol 2014; 22: 607e16.
DOI: http://dx.doi.org/10.1016/j.pathol.2016.07.014
Please cite this article in press as: Iliadis A, et al., Aberrant expression of T-cell marker CD7 in HIV negative intestinal plasmablastic lymphoma, Pathology (2016), http://dx.doi.org/10.1016/j.pathol.2016.07.014
CORRESPONDENCE Aberrant expression of T-cell marker CD7 in HIV negative intestinal plasmablastic lymphoma Sir, Plasmablastic lymphoma (PBL) is considered a rare, aggressive subtype of large B-cell lymphoma (LBCL), commonly EpsteineBarr virus (EBV) infected, developing probably from terminally differentiated, active B-cells in the transition from immunoblasts to plasma cells. PBL has a high
incidence in human immunodeficiency virus (HIV) positive or iatrogenically immunosuppressed adult males with mostly intraoral localisation, but also in other extranodal sites, and there have been cases reported in immunocompetent elderly patients.1,2 Herein, a case of PBL of the small intestine with exceptional immunophenotypic characteristics in a HIV negative, EBV negative patient is presented. A 77-year-old male without clinical or laboratory evidence of immunodeficiency and with a history of Billroth II surgery almost 30 years previously presented an ulcer in the anastomotic abducent loop of the jejunum. The partial enterectomy specimen showed an ulcerative, intramural, tumorous, whitish
(A) Intestinal wall infiltrated by neoplastic cells presenting (B) morphological characteristics of plasmablasts and immunoreactivity to (C) MUM1, (D) CD7, (E) CD43 and (F) EMA antigens. A, H&E, low power; B, H&E, high power; CeF, IHC, medium power.
Fig. 1
Print ISSN 0031-3025/Online ISSN 1465-3931 Ó 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Iliadis A, et al., Aberrant expression of T-cell marker CD7 in HIV negative intestinal plasmablastic lymphoma, Pathology (2016), http://dx.doi.org/10.1016/j.pathol.2016.07.014
2
Pathology (2016), -(-), -
CORRESPONDENCE
lesion measuring 4 cm in diameter. Haematoxylin and eosin (H&E) sections revealed sizeable tumour cells in a diffuse growth pattern (Fig. 1A), with moderate amount of cytoplasm, round to ovoid, often irregular, multiform or multilobulated nuclei with prominent nucleoli and occasional binucleate or multinucleate cell forms (Fig. 1B). The following immunohistochemistry (IHC) phenotype was observed: CD138þ, MUM1þ (Fig. 1C), CD7þ (Fig. 1D), CD43þ (Fig. 1E), EMAþ (Fig. 1F), CD30þ, p53þ, vimentinþ, CD38/þ, CD45/þ, perforin/þ, CD31/þ, CD20, CD45RA, CD79a, PAX5, IgG, IgM, IgA, k, l, CD45RO, CD2, CD3, CD4, CD5, CD8, CD56, ALK1, LMP1, CD21, CD23, CCND1, CD10, BCL2, TIA1, granzymeB. The Ki-67/MIB1 proliferation index was >90%, while EBER in situ hybridisation staining proved negative. Molecular analysis for IGH and TCR gene rearrangements demonstrated B-cell clonality. It is not unusual for some B-cell lymphomas to aberrantly coexpress one or more T-cell markers, such as CD5, CD7, CD2, CD43, CD4, and/or CD8 rarely, a phenomenon maybe indicating anomalous activation of silent or repressed T-cell differentiation genes. Immunohistochemical examination with additional cell lineage specific markers and molecular analysis for antigen receptor gene rearrangements are necessary for accurate cell lineage identification in such cases. To the best of our knowledge there are very few cases of PBL with aberrant T-cell marker positivity (CD3, CD4, CD3/CD4, CD5, CD43) in the English medical literature.3e9 Two cases, the fourth reported by Wang et al.4 and one by Podder et al.,8 seem to resemble this reported case, inasmuch as they also are EBER and express CD43 (but not CD7). Although CD43 has been found to be positive in a small percentage of cases,10 this one is unique. Apart from the rare localisation and immunocompetent patient status, it shows a diffuse, intense positivity and co-expression of two T-cell associated antigens, namely CD7, which has never been reported before, and CD43, highlighting the continually expanding range of morphological, immunophenotypic and clinical characteristics of those B-cell lymphomas with T-cell marker aberrant expression, since lineage ambiguity and heterotropic expression of T-cell antigens in terminally differentiated B-cell lymphomas are more common in EBV-infected and/or immunocompromised patients.5,6 As PBLs lack typical expression of B-cell antigens, knowledge of such features will help avoid misclassification.7 Another point being raised currently, is that such cases reinforce the notion that PBL is a distinct nonHodgkin lymphoma entity, which cannot simply be classified under LBCLs, and it demands modification of the WHO classification.8 Regarding CD7/LEU-9, the earliest T-cell associated antigen expressed on lymphocytes, the monoclonal antibody used here (clone NCL-CD7-272; Novocastra, UK), recognises a portion of the extracellular domain of the human CD7 molecule, a single-domain Ig superfamily molecule expressed on human T and NK cells, as well as on cells in the early stages of T-, B-, and myeloid cell differentiation,11 and it stained the membrane of the neoplastic cells in this case. Concerning CD43/SPN, an integral membrane protein typically expressed at high levels on most leukocytes, the monoclonal antibody used here (clone DF-T1; Dako, Denmark) offered also a membranous staining pattern of the
neoplastic cells. Notably, CD43 is expressed, apart from Tcells, on human bone marrow B-cell precursors and plasma cells, while interestingly the CD43 positive proposed murinecounterpart human B1 cells may actually possess a functional pre-plasmablast phenotype.12 It is also mentioned in the literature that plasmablastic/plasmacytic lesions, including PBL, may exhibit immunoreactivity to CD31,13,14 as observed in this case, raising differential diagnostic problems involving poorly differentiated epithelioid vascular neoplasms, such as haemangioendothelioma, in the case that the right panel of antibodies is not used. Conclusively, in order to avoid a misdiagnosis, it is worth bearing in mind that PBL may morphologically and immunohistochemically masquerade as a CD30 positive anaplastic large cell lymphoma (ALCL) or a poorly differentiated epithelioid vascular neoplasm. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose. Alexandros Iliadis Triantafyllia Koletsa Ioannis Kostopoulos Department of Pathology, Faculty of Medicine, Aristotle University, Thessaloniki, Greece Contact Triantafyllia Koletsa, MD. E-mail: [email protected] 1. Stein H, Harris NL, Campo E. Plasmablastic lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC Press, 2008; 256e7. 2. Rafaniello Raviele P, Pruneri G, Maiorano E. Plasmablastic lymphoma: a review. Oral Dis 2009; 15: 38e45. 3. Tzankov A, Brunhuber T, Gschwendtner A, et al. Incidental oral plasmablastic lymphoma with aberrant expression of CD4 in an elderly HIV-negative patient: how a gingival polyp can cause confusion. Histopathology 2005; 46: 348e50. 4. Wang J, Chen C, Lau S, et al. CD3-positive large B-cell lymphoma. Am J Surg Pathol 2009; 33: 505e12. 5. Suzuki Y, Yoshida T, Nakamura N, et al. CD3- and CD4-positive plasmablastic lymphoma: a literature review of Japanese plasmablastic lymphoma cases. Intern Med 2010; 49: 1801e5. 6. Sun J, Medeiros LJ, Lin P, et al. Plasmablastic lymphoma involving the penis: a previously unreported location of a case with aberrant CD3 expression. Pathology 2011; 43: 54e7. 7. Oliveira JL, Grogg KL, Macon WR, et al. Clinicopathologic features of B-Cell lineage neoplasms with aberrant expression of CD3: a study of 21 cases. Am J Surg Pathol 2012; 36: 1364e70. 8. Podder S, Khetan P, Sivamurthy S, et al. Rare presentation of orbital plasmablastic lymphoma with oral cavity involvement in an HIVnegative patient. BMJ Case Rep 2015 Sep 16: 2015. 9. Liu M, Liu B, Liu B, et al. Human immunodeficiency virus-negative plasmablastic lymphoma: a comprehensive analysis of 114 cases. Oncol Rep 2015; 33: 1615e20. 10. Loghavi S, Alayed K, Aladily TN, et al. Stage, age, and EBV status impact outcomes of plasmablastic lymphoma patients: a clinicopathologic analysis of 61 patients. J Hematol Oncol 2015; 8: 65. 11. Sempowski GD, Lee DM, Kaufman RE, et al. Structure and function of the CD7 molecule. Crit Rev Immunol 1999; 19: 331e48. 12. Covens K, Verbinnen B, Geukens N, et al. Characterization of proposed human B-1 cells reveals pre-plasmablast phenotype. Blood 2013; 121: 5176e83. 13. Plocharczyk E, Wakely Jr PE. CD31 expression in plasmacytic/plasmablastic lesions. Ann Diagn Pathol 2013; 17: 498e501. 14. Vaubell JI, Sing Y, Ramburan A, et al. Pediatric plasmablastic lymphoma: a clinicopathologic study. Int J Surg Pathol 2014; 22: 607e16.
DOI: http://dx.doi.org/10.1016/j.pathol.2016.07.014
Please cite this article in press as: Iliadis A, et al., Aberrant expression of T-cell marker CD7 in HIV negative intestinal plasmablastic lymphoma, Pathology (2016), http://dx.doi.org/10.1016/j.pathol.2016.07.014