High frequency of clonal IG and T-cell receptor gene rearrangements in histiocytic and dendritic cell neoplasms.

The 2008 World Health Organization (WHO) diagnostic criteria of histiocytic and dendritic cell neoplasms from hematopoietic and lymphoid tissues no longer required the absence of clonal B-cell/T-cell receptor gene rearrangements. It is true that the clonal B-cell/T-cell receptor gene rearrangements have been identified in rare cases of histiocytic and dendritic cell neoplasms, such as those with or following lymphoma/leukemia or in some sporadic histiocytic/dendritic cell sarcomas, but the clonal features of such group of tumor are still not clear. Here we investigated the clonal status of 33 samples including Langerhans cell histiocytosis (LCH), Langerhans cell sarcoma (LCS), follicular dendritic cell sarcoma (FDCS), interdigitating dendritic cell sarcoma (IDCS) and histiocytic sarcoma (HS). Among them, twenty-eight cases were sporadic without current or past lymphoma/leukemia. Three cases were found with a past history of T-cell lymphoma, one case was followed by extraosseous plasmacytoma, and one case was found with diffuse large B-cell lymphoma (DLBCL). Our results showed that there was a high frequency of clonal IG and T-cell receptor gene rearrangements in these cases. Notably, 4 cases of LCH and 2 cases of FDCS showed both B and T cell receptor gene rearrangements concurrently. One case of FDCS synchronous with DLBCL showed identical clonal IGH in both tumor populations and clonal TCRß in FDCS alone. No matter if the presence of clonal receptor gene rearrangements was associated with the tumor origin or tumorigenesis, it might serve as a novel tumor marker for developing target therapy.

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

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 CEBPß. 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.

Interdigitating dendritic cell sarcoma following adult liver transplantation: case report and literature review.

Interdigitating dendritic cell sarcoma is an extremely rare neoplasm derived from professional antigen presenting cells. We report an unusual case of such a tumor occurring in a 61-year-old woman who had undergone orthotopic liver transplantation for stage IVA2 primary hepatocellular carcinoma with a raised preoperative α-fetoprotein level, followed by tacrolimus-based immunosuppressive therapy. During her subsequent management, the tacrolimus blood levels ranged from 7.9 ng/mL to 16.1 ng/mL. Physical examination revealed bilateral neck and left axillary lymphadenopathy. No evidence of either chronic hepatitis B virus or Epstein-Barr virus could be detected in serum. An excisional biopsy of a right neck lymph node was performed. Microscopically, the normal architecture was diffusely effaced by a proliferation of spindled to ovoid cells arrayed in a fascicular, ill-defined whorled pattern and small lymphocytes were admixed in varying numbers with the tumor cells. Immunohistochemical studies showed that the tumor cells were positive for S100 protein, vimentin and CD68. Based on these findings, the case was diagnosed as an interdigitating dendritic cell sarcoma. The patient unfortunately had no response to 2 cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), and died of wide spread disease 6 months after the original biopsy. We propose that tacrolimus-based immunosuppression was associated with the development of interdigitating dendritic cell sarcoma after liver transplantation in this case.

Differential immunophenotypic analysis of dendritic cell tumours.

AIMS: The phenotypic and biological characteristics of dendritic cell (DC) tumours have not been fully elucidated. The aim of this study was to compare the immunophenotypic characteristics of DC-related markers and cell-cycle-associated markers among DC tumours and finally to utilise them for differential diagnosis of DC tumours. METHODS: Tissue sections from 28 patients with DC tumours were immunohistochemically examined using DC-related and cell-cycle-associated markers. RESULTS: The Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS) samples were positive for S-100 protein, CD1a, Langerin, fascin, DEC-205 and DC-SIGN. Interdigitating dendritic cell sarcoma (IDCS) was positive for S-100 protein and fascin and negative for Langerin. In addition, two IDCS samples were positive for CD1a, DEC-205 and DC-SIGN. The labelling indices of Ki-67, cyclin A, cyclin B1 and acetylated histone H3 on the LCS and IDCS specimens were significantly higher than those on the LCH specimens. The expression of p53 was also significantly higher in the LCS specimens than in the LCH specimens. The numbers of infiltrating CD123(+) and FOXP3(+) cells were also significantly higher in the LCS samples than in the LCH and IDCS samples. Follicular dendritic cell sarcoma was distinguished from other DC tumours by the lack of DC-SIGN, Langerin and DCE-205. CONCLUSIONS: These results suggest that Langerin can be used to distinguish LCS from IDCS, and DC-SIGN and DEC-205 can be used to identify DC tumour cells. The frequency of cell-cycle-associated markers can be used for the differential diagnosis of malignant and benign DC tumours.