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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 CEBP β . 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.

Langerhans cell sarcoma is a rare and aggressive high grade hematopoietic neoplasm with a dismal prognosis. It has a unique morphological and immunotypic profile with a CD1a/ langerin/S100 + phenotype. T cell lineage markers except for CD4 in Langerhans cell sarcoma have not been documented previously. We report a case of 86 year-old male of Caucasian descent who presented with an enlarging right neck mass over 2 months with an underlying unknown cause of anemia. Computed tomography scan of the neck, chest and abdomen revealed generalized lymphadenopathy and mild splenomegaly suspicious for lymphoma. Diagnostic core biopsy performed on right neck mass revealed a possible T cell lymphoma with expression of T cell lineage specific marker CD3 but conclusive diagnosis could not be made due to insufficient core biopsy sample. Further excisional biopsy performed on a left inguinal node showed a hematopoietic neoplasm with features of Langerhans cell sarcoma with a focal cytoplasmic CD3 expression in 30-40% of the tumor cells. PCR for T cell receptor (TCR) gene rearrangement failed to demonstrate a clonal gene rearrangement in the tumor cells arguing against a T cell lineage transdifferentiation, suggesting an aberrant CD3 expression. To the best of our knowledge, this case represents the first report of Langerhans cell sarcoma with an aberrant cytoplasmic CD3 expression. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2065486371761991

Objective To study the clinico-pathological characteristics of Langerhans cell sarcoma (LCS) which involving epidermis. Methods A case of primary multifocal LCS was analyzed in histopathology and immunophenotype. Results A 41-year-old man with multifocal cutaneous LCS involving the inguina and waist was reported. Clinical and pathology data were available. Neoplastic cells with markedly malignant cytological features were observed. Tumor cells exhibited irregular shape with abundant and eosinophilic red staining cytoplasm; large, irregular-shaped, showing lobulated or dented nucleus and some cells with a longitudinal nuclear groove and prominent nucleoli. The tumor cells expressed CD1a, Langerin (CD207), S-100 protein, CD68 and vimentin, and did not express pan-T or B cell markers and epithelial markers. The patient died less than 1 year after diagnosis due to local recurrence and metastasis to the lung, despite the administration of local radiation and chemotherapy. Conclusions LCS is a tumor with markedly malignant cytological features that originates from Langerhans cells. Primary multifocal neoplasms involving epidermis is even rare. Accurate diagnosis is based on the histopathological and immunohistochemical of the tumor cells. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1182345104754765.

Langerhans cell sarcoma (LCS) typically presents as cytologic atypia and clinical aggressiveness and may involve multiple organs during the progression of the disease. Primary skin LCS without any extra-cutaneous site association is extremely rare and only a few such cases have been described in the literature. We present a case of unusual primary LCS in skin occurring in a middle-aged male patient. Physical examination revealed a large ulcerated cutaneous lesion and a smaller nodular lesion were located in the skin of the extensor side of his right knee. There was no regional lymph node or any other extra-cutaneous organ involvement. Histologically, typical large and pleomorphological tumor cells with epithelioid appearance and significantly malignant cytological features were observed to infiltrate in dermis and subcutaneous tissue. By immunohistochemistry, the tumor cells were positive for CD1a, S-100 protein and largerin strongly and diffusely. However, these cells were negative for CD3, CD20, CD21, pan-cytokeratin, HMB-45, Melan-A, and MPO. A diagnosis of primary cutaneous LCS was made. The patient received systemic chemotherapy of CHOP regimen, and was on a regular follow-up period for 12 months. There was no sign of relapse of tumor or any other extra-cutaneous organ involvement by whole body positron emission tomography/computed tomography (PET/CT) study. Because LCS is a high-grade malignancy with poor prognosis, it suggests that strict histological analysis and thorough radiographic examination are necessary for accurately diagnosing this tumor even if cutaneous involvement presented only. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/6527428618381393

AimsThe 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.MethodsTissue sections from 28 patients with DC tumours were immunohistochemically examined using DC-related and cell-cycle-associated markers.ResultsThe 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.ConclusionsThese 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.

Background Transformation of follicular lymphoma most typically occurs as diffuse large B-cell lymphoma, however other forms of transformation such as classic Hodgkin lymphoma and lymphoblastic transformation can occur. Secondary malignant histiocytosis also represents a rare form of transformation, which is thought to occur due to a process of transdifferentiation whereby the lymphoma cells exhibit lineage plasticity and lose all evidence of B-cell phenotype and instead acquire the phenotype of a histiocytic neoplasm. Little is known about the underlying genetic alterations that occur during this unusual process. Comparative genetic analysis of pre- and post-transformation/transdifferentiation would be one tool by which we could better understand how this phenomenon occurs. Case presentation Here we report the clinical, immunophenotypic and genetic features of a rare case of secondary malignant histiocytosis, Langerhans cell-type (Langerhans cell sarcoma) arising from a previous low grade follicular lymphoma. FISH analysis confirmed the presence of IgH/BCL2 rearrangement in both the low grade follicular lymphoma (FL) and transformed Langerhans cells sarcoma (LCS) samples, demonstrating a clonal relationship. Comparative whole exome sequencing was then performed, which identified a KRAS p.G13D mutation in the LCS that was not present in the FL. Conclusions This report highlights genetic alterations, in particular an acquired somatic KRAS mutation, that may occur during transdifferentiation, with additional significance of KRAS mutation as a possible therapeutic target in cases which otherwise would have limited treatment options.

A 57-year-old man became aware of left supraclavicular lymph node swelling, which was subsequently diagnosed as Langerhans cell sarcoma, based on a positive immunophenotype for CD1a, S-100 protein, and langerin, and histologically bizarre pleomorphism. The tumor became leukemic 3 months later. Despite intensive chemotherapy, he died of disease progression 7 months after the initial diagnosis. Tumor cells in the leukemic phase expressed CD5, CD7, CD13, CD33, CD34, CD68, and CD123. These findings suggested leukemic transformation from Langerhans cell sarcoma. Leukemic transformation may be a clinical manifestation of advanced Langerhans cell sarcoma, and should be differentiated from acute myelogenous leukemia.

We describe the rare case of a 53-year-old woman with systemic involvement of Langerhans cell sarcoma (LCS) who had undergone living-related liver transplantation. We chose the CHOP regimen as first-line chemotherapy, and clinical improvement of LCS was obtained. Intensive care was necessary due to the systemic involvement of LCS and severe infectious diseases. After the third cycle of CHOP therapy, however, disease progression was observed, and we administrated a modified ESHAP regimen (etoposide, carboplatin, cytarabine, methylprednisolone) as second-line therapy. A marked response was obtained after four cycles of this combination chemotherapy. Modified ESHAP may be a very effective combination chemotherapy regimen for LCS.