• ICC
• Langerhans
• dendritic cell
• histiocytosis

• MDM2
• chemokine
• lymphoplasmacytic lymphoma
• well‐differentiated liposarcoma

• Humans
• Male
• Middle Aged
• Waldenstrom Macroglobulinemia/pathology
• Waldenstrom Macroglobulinemia/genetics
• Waldenstrom Macroglobulinemia/diagnosis
• Liposarcoma/pathology
• Liposarcoma/genetics
• Liposarcoma/surgery
• Liposarcoma/diagnosis
• Chemokines/metabolism
• Chemokines/genetics
• Carcinogenesis/genetics

• JP23K14496 Kakenhi
• Kakenhi

• Chronic lymphocytic leukemia
• Histiocytic sarcoma
• Histiocytic/dendritic cell sarcoma
• Interdigitating dendritic cell sarcoma
• Small lymphocytic leukemia
• Transdifferentiation
• Transformation

• Humans
• Positron Emission Tomography Computed Tomography
• Leukemia/diagnostic imaging
• Fluorodeoxyglucose F18

• Chronic lymphocytic leukemia
• Clonal evolution
• Richter's transformation

• Immunohistochemistry
• Interdigitating dendritic cell sarcoma
• Skin

• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis
• Hematologic Neoplasms/genetics
• Leukocytes
• Dendritic Cells
• Skin Neoplasms

• CAR-T cell therapy
• antibody-drug conjugates
• cell line models
• diffuse large B-cell lymphoma
• monoclonal antibodies

• 805038/STIMUNO/ERC-2018- STG European Research Council

Lineage switch between myeloid and lymphoid in acute leukemia is well established as a mechanism for leukemic cells to escape chemotherapy. Cross-lineage transformation is also recognized in some solid tumors on targeted therapy, such as adenocarcinomas of the lung and prostate that transforms to neuroendocrine carcinoma on targeted therapy. Now lineage plasticity is increasingly recognized in mature lymphomas, such as small B-cell lymphomas transforming to histiocytic/dendritic cell sarcoma. However, there is no report of aggressive mature B-cell lymphoma switching from one histologic category to another upon targeted therapy. We report here a case of high-grade B-cell lymphoma with MYC and BCL6 rearrangements relapsing as a high-grade plasmablastic neoplasm with MYC and BCL6 rearrangements after R-CHOP and R-EPOCH therapy. Being aware of this rare scenario will help improve our understanding of the underlying mechanisms of therapeutic resistance and progression of lymphoma.

Langerhans cell sarcoma (LCS) is a rare malignancy with poor prognosis. LCS and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) can occur in the same diseased tissues, such as lymph nodes or skin.

A 48-year-old female Han Chinese patient was admitted for generalized lymph node enlargement for 6 years and abdominal distension for 1 wk. She was diagnosed with small B-cell lymphoma (stage IV)/CLL (Benet stage B) and received chemotherapy. She started oral ibrutinib in February 2019. She was hospitalized on June 11, 2019, and a 1.5 cm × 1.5 cm dark-red nodule with ulceration scalp lesion was found. Biopsy revealed LCS but without CLL/SLL. She was diagnosed with CLL/SLL (Binet stage C, Rai stage IV) accompanied by secondary histiocytic sarcomas and skin LCS and received cyclophosphamide, doxorubicin, vincristine, dexamethasone, and etoposide but developed severe cytopenia. She ultimately refused treatments and discharged spontaneously. She died on September 12, 2019. The literature review showed that in patients with CLL/SLL, skin lesions of LCS are accompanied by CLL/SLL. This patient was different from the previously reported cases of skin LCS in patients with CLL/SLL.

In this patient, the skin lesion of LCS showed no concomitant CLL/SLL.

• Skin
• Langerhans cell sarcomas
• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Ibrutinib
• Case report

• Chronic lymphocytic leukaemia
• Genetics
• Ibrutinib
• Richter's transformation
• TP53 disruption
• Venetoclax

• B cell lymphoblastic lymphoma
• KRAS
• NRAS
• case report
• myeloid sarcoma

• Erdheim-Chester disease
• Langerhans cell sarcoma
• Langerhans-cell histiocytosis
• histiocytic sarcoma
• histiocytosis
• indeterminate cell histiocytosis
• leukaemia
• lymphoma
• malignant histiocytic disorders
• non-Langerhans-cell histiocytosis

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/genetics
• Erdheim-Chester Disease/genetics
• Erdheim-Chester Disease/pathology
• Erdheim-Chester Disease/therapy
• Fatal Outcome
• GTP Phosphohydrolases/genetics
• Genetic Predisposition to Disease
• Histiocytic Sarcoma/genetics
• Histiocytic Sarcoma/pathology
• Histiocytic Sarcoma/therapy
• Humans
• Leukemia, Myeloid, Acute/genetics
• Leukemia, Myeloid, Acute/pathology
• Leukemia, Myeloid, Acute/therapy
• Leukemia, Myelomonocytic, Chronic/genetics
• Leukemia, Myelomonocytic, Chronic/pathology
• Leukemia, Myelomonocytic, Chronic/therapy
• Male
• Membrane Proteins/genetics
• Middle Aged
• Mutation
• Phenotype
• Proto-Oncogene Proteins p21(ras)/genetics
• Retrospective Studies
• Treatment Outcome

• cancer models
• sarcoma
• cancer

• Cell Culture Techniques/methods
• Cell Line, Tumor
• Chromosomal Instability
• DEAD Box Protein 58/genetics
• DEAD Box Protein 58/metabolism
• Dendritic Cells/cytology
• Dendritic Cells/metabolism
• Histocompatibility Antigens Class I/metabolism
• Histocompatibility Antigens Class II/metabolism
• Humans
• Immunophenotyping
• In Situ Hybridization, Fluorescence
• Karyotype
• Male
• Middle Aged
• Phagocytosis
• Receptors, Immunologic/genetics
• Receptors, Immunologic/metabolism
• S100 Proteins/metabolism
• Sarcoma/genetics
• Sarcoma/metabolism
• Toll-Like Receptor 3/genetics
• Toll-Like Receptor 3/metabolism
• Toll-Like Receptor 4/genetics
• Toll-Like Receptor 4/metabolism
• Toll-Like Receptor 9/genetics
• Toll-Like Receptor 9/metabolism
• Vimentin/metabolism

• Projekt DEAL

• Classic Hodgkin lymphoma
• EBV
• LEF1
• Richter syndrome

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/metabolism
• Child
• Female
• Hodgkin Disease/metabolism
• Hodgkin Disease/pathology
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell/complications
• Leukemia, Lymphocytic, Chronic, B-Cell/pathology
• Lymphoid Enhancer-Binding Factor 1/biosynthesis
• Male
• Middle Aged
• Young Adult

• Langerhans cell sarcoma
• Transdifferentiation
• chronic lymphocytic leukemia
• histiocytic sarcoma

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries with an incidence of 3-5 cases per 100,000 persons. Most patients follow an indolent clinical course with eventual progression and need for therapy. In contrast, T-prolymphocytic leukemia (T-PLL) is a rare type of T-cell leukemia with most patients having an aggressive clinical course and a dismal prognosis. Therapies are limited for T-PLL patients and there is a high relapse rate. Morphologically, the cells of CLL and T-PLL can show overlapping features. Here, we report the case of a 61-year-old man who presented with a clinically indolent CLL and T-PLL, initially diagnosed solely and followed as CLL, despite the presence of an associated but unrecognized aberrant T-cell population in blood. After 2 years, the T-PLL component became more apparent with cutaneous and hematologic manifestations and the diagnosis was confirmed by immunophenotypic and cytogenetic analysis. Fluorescence in situ hybridization demonstrated an ATM deletion in both CLL and T-PLL components. Retrospective testing demonstrated that composite CLL and T-PLL were both present in skin and lymph nodes as well as in blood and bone marrow since initial presentation. This case is also unique because it highlights that a subset of T-PLL patients can present with clinically indolent disease. The concomitant detection of ATM mutation in CLL and T-PLL components raises the possibility of a common pathogenic mechanism.

• Richter's syndrome
• Richter's transformation
• management
• novel agents

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.

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.

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.

The online version of this article (10.1186/s13000-018-0758-0) contains supplementary material, which is available to authorized users.

• Follicular lymphoma
• KRAS
• Langerhans cell sarcoma
• Transdifferentiation

• Células dendríticas
• Dendritic cells
• Histiocitosis
• Histiocytosis
• Immunohistochemistry
• Inmunohistoquímica
• Molecular
• Pathology
• Patología

• Dendritic Cells
• Histiocytes
• Humans
• Soft Tissue Neoplasms/pathology

• Clinicopathologic features
• Interdigitating dendritic cell
• Sarcoma

Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated B lymphocytes with molecular heterogeneity. Although therapy-related myeloid neoplasms are common in plasma cell myeloma patients after chemotherapy, transdifferentiation of plasma cell myeloma into myeloid neoplasms has not been reported in literature. Here we report a very rare case of myeloid neoplasm transformed from plasma cell myeloma.

A 60-year-old man with a history of plasma cell myeloma with IGH-MAF gene rearrangement and RAS/RAF mutations developed multiple soft tissue lesions one year following melphalan-based chemotherapy and autologous stem cell transplant. Morphological and immunohistochemical characterization of the extramedullary disease demonstrated that the tumor cells were derived from the monocyte-macrophage lineage. Next generation sequencing (NGS) studies detected similar clonal aberrations in the diagnostic plasma cell population and post-therapy neoplastic cells, including IGH-MAF rearrangement, multiple genetic mutations in RAS signaling pathway proteins, and loss of tumor suppressor genes. Molecular genetic analysis also revealed unique genomic alterations in the transformed tumor cells, including gain of NF1 and loss of TRAF3.

To our knowledge, this is the first case of myeloid sarcoma transdifferentiated from plasma cell neoplasm. Our findings in this unique case suggest clonal evolution of plasma cell myeloma to myeloma neoplasm and the potential roles of abnormal RAS/RAF signaling pathway in lineage switch or transdifferentiation.

• Clonal evolution
• Molecular profiling
• Myeloid sarcoma
• Next generation sequencing
• Plasma cell myeloma
• RAS/RAF signaling pathway
• Transdifferentiation

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 TCRβ 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.

• Langerhans cell histiocytosis
• Langerhans cell sarcoma
• Pathology Section
• follicular dendritic cell sarcoma
• histiocytic sarcoma
• interdigitating dendritic cell sarcoma

• epithelioid angiomyolipoma
• kidney
• medical imaging
• pathology,

• Adult
• Angiomyolipoma/diagnostic imaging
• Angiomyolipoma/pathology
• Female
• Humans
• Kidney/pathology
• Kidney Neoplasms/diagnostic imaging
• Kidney Neoplasms/pathology

Human soft-tissue sarcomas (STS) are rare mesenchymal tumors with a 5-year survival rate of 50%, highlighting the need for further STS research. Research has been hampered by limited human sarcoma cell line availability and the large number of STS subtypes, making development of STS cell lines and animal models representative of the diverse human STS subtypes critical. Pigs represent ideal human disease models due to their similar size, anatomy, metabolism, and genetics compared to humans. The Oncopig encodes inducible KRAS^G12D and TP53^R167H transgenes, allowing for STS modeling in a spatial and temporal manner. This study utilized Oncopig STS cell line (fibroblast) and tumor (leiomyosarcoma) RNA-seq data to compare Oncopig and human STS expression profiles. Altered expression of 3,360 and 7,652 genes was identified in Oncopig STS cell lines and leiomyosarcomas, respectively. Transcriptional hallmarks of human STS were observed in Oncopig STS, including altered TP53 signaling, Wnt signaling activation, and evidence of epigenetic reprogramming. Furthermore, master regulators of Oncopig STS expression were identified, including FOSL1, which was previously identified as a potential human STS therapeutic target. These results demonstrate the Oncopig STS model’s ability to mimic human STS transcriptional profiles, providing a valuable resource for sarcoma research and cell line development.

• interdigitating dendritic cell sarcoma
• medical imaging
• pathology
• sigmoid colon mesentery

• Colon, Sigmoid/diagnostic imaging
• Colon, Sigmoid/pathology
• Colon, Sigmoid/surgery
• Dendritic Cell Sarcoma, Interdigitating/diagnostic imaging
• Dendritic Cell Sarcoma, Interdigitating/pathology
• Dendritic Cell Sarcoma, Interdigitating/surgery
• Diagnosis, Differential
• Humans
• Male
• Mesentery/diagnostic imaging
• Mesentery/pathology
• Mesentery/surgery
• Middle Aged
• Sigmoid Neoplasms/diagnostic imaging
• Sigmoid Neoplasms/pathology
• Sigmoid Neoplasms/surgery

• Interdigitating dendritic cell sarcoma

• 18FDG- PET-CT, 18fluorodeoxyglucose-positron emission tomography-computed tomography
• ALK, anaplastic lymphoma kinase
• ATP, adenosine triphosphate
• B-RAF
• BCL2, B-cell lymphoma 2
• CD, cluster of differentiation
• CT, computed tomography
• CTCAE, common terminology criteria for adverse events
• ECG, electrocardiogram
• ECOG, eastern cooperative oncology group
• EMA, ephitelial membrane antigen
• H3Ac, acetylated histone H3
• HLA, human leukocyte antigen
• Ig, immunoglobulin
• IgH, heavy immunoglobulin
• MHC, Major Histocompatibility Complex
• MRI, magnetic resonance imaging
• NSE, neuron specific enolase
• PS, performance status
• QTc, corrected QT interval
• SUV, standardized uptake value
• TCR, t cell receptor
• TIM, T cell immunoglobulin mucin
• Vemurafenib
• WHO, world health organization
• differential diagnosis
• interdigitating dendritic cell sarcoma

Canine histiocytic malignancies (HM) are aggressive tumors that occur with particularly high frequency in certain breeds including Bernese mountain dogs and flat-coated retrievers. Robust diagnosis of HM commonly utilizes immunohistochemical stains that are broadly ineffective on formalin-fixed tissues; thus the diagnosis is often one of exclusion. Clinical outcomes are generally poor, with frequent metastasis and therapeutic failure lowering overall survival at time of diagnosis to an average of less than two months in the majority of published work. The limited understanding of the molecular mechanisms underlying HM has hindered the development of more effective diagnostic modalities and the identification of therapeutic targets. A potential avenue exists for advancing clinical management of canine cancers through extrapolation from a close counterpart in human medicine. Historically, HM have been compared to the rare and understudied subset of human cancers involving the dendritic lineage, such as dendritic cell sarcoma or Langerhans cell sarcoma. Recent data have now thrown into question the cellular origin of HM, suggesting that the disease may originate from the macrophage lineage. This review summarizes existing knowledge of HM from the clinical, histologic and molecular perspectives, and highlights avenues for future research that may aid the development of novel diagnostic and therapeutic approaches. In turn, a more advanced appreciation of the mechanisms underlying HM should clarify their cellular origin and identify appropriate opportunities for synergistic extrapolation between related canine and human cancers.

• cancer
• dendritic
• disseminated
• macrophage
• sarcoma

• breast
• fibroblastic reticular cells
• immunohistochemistry

• Array comparative genomic hybridization
• GeneScan
• Langerhans cell sarcoma
• Marginal zone lymphoma
• Trans-differentiation