Chronic Lymphocytic Leukemia Transdifferentiates into Neuroendocrine Carcinoma: A Case Report of a New Phenomenon

Diana Diana Castro, MD, Liqun Zhang, MD, Subhadra Nandula, PhD, Jin Choe, MD, Donghong Cai, MD, PhD


Richter’s Transformation of chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma or Hodgkin lymphoma (both are B-cell origin) are well described in literature. Recently, transformation of CLL into histiocytic/dendritic/Langerhans cell sarcoma (all are myeloid origin), dubbed as “transdifferentiation”, has also been reported. The mechanisms behind this phenomenon are not clear. Here we report the discovery of the first case of CLL evolving into a neuroendocrine carcinoma (NEC). A patient with long history of CLL developed a rectal mass and a liver mass. Biopsies confirmed rectal poorly differentiated NEC compositing with CLL, and liver metastatic NEC. FISH for CLL panel revealed trisomy 12 in both CLL and NEC.  B-cell heavy chain rearrangement study on blood sample (pure CLL) and liver metastatic NEC (pure NEC, no contamination from CLL) revealed that these two tumors shared similar monoclonal peaks. Therefore, the patient’s CLL and NEC were clonally related, and likely the NEC was transdifferentiated from CLL. This is the first case of transdifferentiation of CLL into carcinoma.

[N A J Med Sci. 2016;9(3):123-126.   DOI:  10.7156/najms.2016.0903123]


chronic lymphocytic leukemia, neuroendocrine carcinoma, transdifferentiation


Hallek M, Cheson BD, Catovsky D. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008;111:5446-5456.

Lortholary P, Boiron M, Ripault P. chronic lymphoid leukemia secondarily associated with a malignant reticulopathy: Richter's syndrome. Nouv Rev Fr Hematol. 1964;4:621-644.

Molica S. A systematic review on Richter syndrome: what is the published evidence? Leuk Lymphoma. 2010;51:415-421.

Tsimberidou AM, O'Brien S, Kantarjian HM. Hodgkin transformation of chronic lymphocytic leukemia: the M. D. Anderson Cancer Center experience. Cancer. 2006;107:1294-1302.

Bockorny B, Codreanu I Dasanu CA. Hodgkin lymphoma as Richter transformation in chronic lymphocytic leukaemia: a retrospective analysis of world literature. Br J Haematol. 2012;156:50-66.

Michelis FV, Kourti G, Skertsou M. Richter transformation of chronic lymphocytic leukemia into composite diffuse large B-cell and Hodgkin lymphoma. Leuk Lymphoma. 2012;145:43-49.

Feldman AL, Arber DA, Pittaluga S, Martinez A, Burke JS, Raffeld M. Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: Evidence for transdifferentiation of the follicular lymphoma clone. Blood. 2008;111:5433-5439.

Fraser CR, Wang W, Gomez M, Zhang T, Mathew S, Furman RR. Transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma to interdigitating dendritic cell sarcoma: Evidence for transdifferentiation of the lymphoma clone. Am J Clin Pathol. 2009;132:928-939.

Shao H, Xi L, Raffeld M, Feldman AL, Ketterling RP, Knudson R. Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: A study of seven cases. Mod Pathol. 2011;24:1421-1432.

Wang E, Hutchinson CB, Huang Q, Sebastian S, Rehder C, Kanaly A. Histiocytic sarcoma arising in indolent small b-cell lymphoma: Report of two cases with molecular/genetic evidence suggestive of a 'transdifferentiation' during the clonal evolution. Leuk Lymphoma. 2010;51:802-812.

Zhang D, McGuirk J, Ganguly S, Persons DL. Histiocytic/dendritic cell sarcoma arising from follicular lymphoma involving the bone: A case report and review of literature. Int J Hematol. 2009;89:529-532.

Baer MR, Krantz SB, Cousar JB, Glick AD, Collins RD. Malignant histiocytoses developing in patients with b-cell lymphomas. Report of two cases. Cancer. 1986;57:2175-2184.

Vasef MA, Zaatari GS, Chan WC, Sun NC, Weiss LM, Brynes RK. Dendritic cell tumors associated with low-grade b-cell malignancies. Report of three cases. Am J Clin Pathol. 1995;104:696-701.

Richter MN. Generalized reticular cell sarcoma of lymph nodes associated with lymphatic leukemia. Am J Pathol. 1928;4:285-292.

Mao Z, Quintanilla-Martinez L, Raffeld M, et al. IgVH mutational status and clonality analysis of Richter's transformation: diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 different pathways of disease evolution. Am J Surg Pathol. 2007;31:1605-1614.

Rossi D, Spina V, Deambrogi C, et al. The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation. Blood. 2011;117:3391-3401.

Xie H, Ye M, Feng R, Graf T. Stepwise reprogramming of b cells into macrophages. Cell 2004;117:663-676.

Cobaleda C, Jochum W, Busslinger M. Conversion of mature b cells into t cells by dedifferentiation to uncommitted progenitors. Nature. 2007;449:473-477.

Carotta S, Nutt SL. Losing B cell identity. Bioessays 2008;30:203-207.

Jain P, O'Brien S. Richter's transformation in chronic lymphocytic leukemia. Oncology. 2012;26(12):1146-1152.

Langerak A. Groenen P, Bruggemann M, et al. EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations. Leukemia 2012;26:2159-2171.


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