Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases

Abstract

Histiocytic and interdigitating dendritic cell sarcomas are rare tumors originating from bone marrow-derived myeloid stem cells. Recent studies have shown evidence of cross-lineage transdifferentiation of B cells in follicular lymphoma to histiocytic and dendritic cell sarcomas. In this study, we report the morphologic, molecular and cytogenetic analysis of seven cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) associated with histiocytic and dendritic cell sarcomas. All seven patients were elderly males (median age 71 years). The B-cell neoplasms preceded the development of the histiocytic and dendritic cell sarcomas in six of seven patients, and one patient had both tumors diagnosed at the same time. The tumors included four interdigitating dendritic cell sarcomas: one Langerhans cell sarcoma, one histiocytic sarcoma and one immature neoplasm with evidence of histiocytic origin. Laser-capture microdissection and PCR analysis showed identical clonal immunoglobulin gene rearrangements in the two phenotypically distinct components in all cases. There was a preferential usage of IGHV4-39 by the V-D-J gene rearrangement. By fluorescence in situ hybridization (FISH) analysis, two cases showed deletion 17p in both components, whereas four cases had normal cytogenetic findings by FISH in the CLL/SLL cells, but acquired cytogenetic abnormalities in the corresponding histiocytic and dendritic tumors. Chromosome 17p abnormalities were the most common cytogenetic abnormality detected in the sarcomas, seen in five of six cases studied. Compared with the CLL/SLL cells, the histiocytic/dendritic cells were largely negative for PAX5, but showed strong expression of PU.1 and variable and weak expression of CEBPβ. Our study provides evidence for transdifferentiation of CLL/SLL B cells to tumors of dendritic and less often histiocytic lineage, and suggests that secondary genetic events may play a role in this phenomenon.

Figure 1

CLL/SLL and synchronous interdigitating dendritic cell sarcoma, case 3. (a) Cervical lymph node showed islands and cords of the dendritic cell neoplasm sharply segregated from areas of CLL/SLL. Magnification ×200. (b) The dendritic cells had abundant eosinophilic cytoplasm, lobulated and indented nuclei, vesicular chromatin, and variably prominent nucleoli. Some cells showed highly polylobated nuclei. The CLL/SLL cells were small with round nuclei, coarse chromatin and scant cytoplasm. Magnification ×400. (c) The dendritic cells were strongly positive for S100, and partially positive for CD68. (d) They showed strong staining for PU.1 and weak and partial staining for CEBPβ, but were negative for PAX5. The CLL/SLL cells were strongly positive for PAX5 and negative for PU.1 and CEBPβ. (e) The CLL/SLL and dendritic cells showed identical clonal peaks by PCR of the IGK@ gene (IGK tube A PCR reaction). (f) Both the CLL/SLL and dendritic cell tumor showed deletion of chromosome17p by using the FISH probe for p53 (17p13). A control probe for chromosome 17 centromere (D17Z1) showed no loss of chromosome 17.

Figure 2

CLL/SLL and synchronous Langerhans cell sarcoma, case 2. (a) An axillary lymph node was effaced by interconnecting sheets and clusters of CLL/SLL cells admixed with large clusters of atypical Langerhans cells. Magnification ×100. The Langerhans cells were large with round to oval indented nuclei, vesicular chromatin, and distinct nucleoli (inset, magnification ×400). (b) The CLL/SLL cells were positive for PAX5, CD5 and CD23. The Langerhans cells showed partial positivity for CD5, and were negative for PAX5 and CD23. (c) The Langerhans cells were positive for S100, CD1a and Langerin. (d) They showed strong staining for PU.1 and weak and partial staining for CEBPβ, but were negative for PAX5. The CLL/SLL cells were positive for PAX5 and PU.1, and negative for CEBPβ. (e) The CLL/SLL and Langerhans cells showed identical clonal peaks following IGH@ FRIII PCR, upper panel). Sequencing of IGH@ gene rearrangements (lower panel) showed complete sequence identity between that of the CLL/SLL and the Langerhans cells. The asterisks indicate identical DNA sequence. The solid lines indicate corresponding V, D and J genes. The DNA sequences between the solid lines are V-D and D–J junctional sequences. (f) The Langerhans cells showed aneusomy of chromosome17p by using the FISH probe for p53 (17p13), and the chromosome 17 centromere (D17Z1) probe showed duplication of chromosome 17 in LCS. The CLL/SLL cells showed no abnormalities in chromosome 17.

Figure 3

CLL/SLL and synchronous histiocytic sarcoma, case 7 (a) An axillary lymph node was mostly effaced by sheets of CLL/SLL cells with a focal nodule composed of atypical histiocytic cells. Magnification ×40. (b) The histiocytic sarcoma cells were very large with round nuclei, vesicular chromatin, prominent central nucleoli, and voluminous pink cytoplasm. Some cells showed emperipolesis. Magnification ×100. (c) The CLL/SLL cells were positive for CD79a, CD5 and CD23. The histiocytic sarcoma cells were strongly positive for CD163. (d) They were partially positive for S100 and showed strong staining for PU.1 and CEBPβ. They were negative for PAX5. (e) The CLL/SLL and histiocytic sarcoma cells showed identical clonal peaks following IGH@ FRIII PCR, upper panel). Sequencing of the IGH@ gene rearrangements (lower panel) showed complete sequence identity between that of CLL/SLL and the histiocytic sarcoma cells. The asterisks indicate identical DNA sequence. The solid lines indicate corresponding V, D and J genes. The DNA sequences between the solid lines are V-D and D–J junctional sequences. (f) Both the CLL/SLL and IDCS showed deletion of chromosome17p by using the FISH probe for p53 (17p13). A control probe for chromosome 17 centromere (D17Z1) showed no loss of chromosome 17. In addition, the histiocytic sarcoma showed deletion of chromosome13q by using the FISH probe D13S319 (13q14.3). The CLL/SLL cells showed no abnormality in chromosome 13.