RESUMO
Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.
Assuntos
Antígeno B7-H1/metabolismo , Sarcoma de Células Dendríticas Foliculares , Sarcoma Histiocítico , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Sarcoma de Células Dendríticas Foliculares/imunologia , Sarcoma de Células Dendríticas Foliculares/metabolismo , Sarcoma de Células Dendríticas Foliculares/patologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Feminino , Histiócitos/metabolismo , Histiócitos/patologia , Sarcoma Histiocítico/imunologia , Sarcoma Histiocítico/metabolismo , Sarcoma Histiocítico/patologia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização in Situ Fluorescente , Japão , Sarcoma de Células de Langerhans/imunologia , Sarcoma de Células de Langerhans/metabolismo , Sarcoma de Células de Langerhans/patologia , Linfoma Folicular/imunologia , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T/metabolismoRESUMO
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.
Assuntos
Biomarcadores Tumorais/genética , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T , Genes de Cadeia Pesada de Imunoglobulina , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T , Genes Codificadores da Cadeia gama de Receptores de Linfócitos T , Transtornos Histiocíticos Malignos/genética , Histiocitose de Células de Langerhans/genética , Cadeias kappa de Imunoglobulina/genética , Adolescente , Adulto , Idoso , Criança , Sarcoma de Células Dendríticas Foliculares/genética , Sarcoma de Células Dendríticas Foliculares/imunologia , Sarcoma de Células Dendríticas Foliculares/patologia , Sarcoma de Células Dendríticas Interdigitantes/genética , Sarcoma de Células Dendríticas Interdigitantes/imunologia , Sarcoma de Células Dendríticas Interdigitantes/patologia , Feminino , Predisposição Genética para Doença , Transtornos Histiocíticos Malignos/imunologia , Transtornos Histiocíticos Malignos/patologia , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/imunologia , Sarcoma Histiocítico/patologia , Histiocitose de Células de Langerhans/imunologia , Histiocitose de Células de Langerhans/patologia , Humanos , Sarcoma de Células de Langerhans/genética , Sarcoma de Células de Langerhans/imunologia , Sarcoma de Células de Langerhans/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto JovemRESUMO
The concept of unidirectional differentiation of the haematopoietic stem cell has been challenged after recent findings that human B cell progenitors and even mature B cells can be reprogrammed into histiocytic/dendritic cells by altering expression of lineage-associated transcription factors. The conversion of mature B cell lymphomas to Langerhans cell neoplasms is not well documented. Three previous reports have described clonally related follicular lymphoma and Langerhans cell tumours, whereas no case has been published of clonally related marginal zone lymphoma and Langerhans cell sarcoma. We describe the case of a 77-year-old patient who developed a Langerhans cell sarcoma and 6 years later a nodal marginal zone lymphoma. Mutation status examination showed 100 % gene identity to the germline sequence, suggesting direct trans-differentiation or dedifferentiation of the nodal marginal zone lymphoma to the Langerhans cell sarcoma rather than a common progenitor. We found inactivation of paired box 5 (PAX-5) in the lymphoma cells by methylation, along with duplication of part of the long arm of chromosomes 16 and 17 in the sarcoma cells. The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells. On the other hand, chromosomal imbalances might have activated genes involved in myeloid lineage maturation, transcription activation and oncogenesis. We hypothesize that this occurred because of previous therapies for nodal marginal zone lymphoma. Better understanding of this phenomenon may help in unravelling the molecular interplay between transcription factors during haematopoietic lineage commitment and may expand the spectrum of clonally related mature B cell neoplasms and Langerhans cell tumours.
Assuntos
Linfócitos B/patologia , Plasticidade Celular , Sarcoma de Células de Langerhans/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Idoso , Metilação de DNA , Humanos , Imunofenotipagem , Sarcoma de Células de Langerhans/genética , Sarcoma de Células de Langerhans/imunologia , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/imunologia , Masculino , Fator de Transcrição PAX5/genéticaRESUMO
Langerhans cell sarcoma (LCS) is a rare but potentially life-threatening neoplastic condition. The diagnosis of LCS requires morphological and immunophenotypic characterization to distinguish it from other epithelioid-appearing malignancies. Four cases of LCS were encountered in the consultative practices of 2 of the authors. The patients ranged in age from 54 to 88 years of age. In 2 of the cases the patients had a history of acute myelogenous leukemia with eruptions occurring after initiation of decitabine. One patient died within 3 months of presenting with the skin eruption, whereas the other patient is in remission. In the other 2 patients, there was no antecedent history; the presentation was in the context of a solitary nodule. One patient declined treatment and died of disseminated metastatic disease. The other patient had complete excision with no evidence of recurrent or metastatic disease. In all cases, the biopsies showed a sheet-like growth of large atypical epithelioid cells. Phenotypic studies revealed positivity for CD4, CD1a, and S100 in all and variable staining for langerin, lysozyme, CD83, CD31, and CD14. Cutaneous LCS represents a terminally differentiated myeloid tumor with a variable but potentially aggressive clinical course. It may be related to a common stem cell defect given the association with acute leukemia. The morphology ranges from atypical appearing Langerhans cell to a high-grade large cell epithelioid malignancy mimicking amelanotic nodular melanoma.
Assuntos
Sarcoma de Células de Langerhans/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/análogos & derivados , Azacitidina/uso terapêutico , Biomarcadores Tumorais/análise , Decitabina , Humanos , Imunofenotipagem , Sarcoma de Células de Langerhans/imunologia , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/imunologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Cutâneas/imunologiaRESUMO
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.
Assuntos
Biomarcadores Tumorais/análise , Complexo CD3/análise , Neoplasias Hematológicas/imunologia , Sarcoma de Células de Langerhans/imunologia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biópsia , Evolução Fatal , Rearranjo Gênico do Linfócito T/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Sarcoma de Células de Langerhans/genética , Sarcoma de Células de Langerhans/patologia , Sarcoma de Células de Langerhans/terapia , Masculino , Cuidados Paliativos , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios XRESUMO
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.
Assuntos
Epiderme/patologia , Sarcoma de Células de Langerhans/patologia , Células de Langerhans/patologia , Neoplasias Cutâneas/patologia , Adulto , Biomarcadores Tumorais/análise , Biópsia , Epiderme/química , Epiderme/imunologia , Evolução Fatal , Humanos , Imunofenotipagem , Sarcoma de Células de Langerhans/imunologia , Sarcoma de Células de Langerhans/terapia , Células de Langerhans/química , Células de Langerhans/imunologia , Neoplasias Pulmonares/secundário , Masculino , Recidiva Local de Neoplasia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Transdiferenciação Celular , Sarcoma de Células Dendríticas Interdigitantes , Sarcoma Histiocítico , Sarcoma de Células de Langerhans , Leucemia Linfocítica Crônica de Células B , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Biomarcadores Tumorais/análise , Proteína beta Intensificadora de Ligação a CCAAT/análise , Aberrações Cromossômicas , Cromossomos Humanos Par 17 , Sarcoma de Células Dendríticas Interdigitantes/genética , Sarcoma de Células Dendríticas Interdigitantes/imunologia , Sarcoma de Células Dendríticas Interdigitantes/patologia , Rearranjo Gênico do Linfócito B , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/imunologia , Sarcoma Histiocítico/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Sarcoma de Células de Langerhans/genética , Sarcoma de Células de Langerhans/imunologia , Sarcoma de Células de Langerhans/patologia , Microdissecção e Captura a Laser , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Maryland , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fator de Transcrição PAX5/análise , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/análise , Transativadores/análise , Recombinação V(D)JRESUMO
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.
Assuntos
Biomarcadores Tumorais/metabolismo , Sarcoma de Células Dendríticas Interdigitantes/diagnóstico , Histiocitose de Células de Langerhans/diagnóstico , Sarcoma de Células de Langerhans/diagnóstico , Adolescente , Adulto , Idoso , Proteínas de Ciclo Celular/metabolismo , Criança , Sarcoma de Células Dendríticas Interdigitantes/imunologia , Células Dendríticas/imunologia , Diagnóstico Diferencial , Feminino , Fatores de Transcrição Forkhead/análise , Histiocitose de Células de Langerhans/imunologia , Histonas/metabolismo , Humanos , Imunofenotipagem , Subunidade alfa de Receptor de Interleucina-3/análise , Sarcoma de Células de Langerhans/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto JovemRESUMO
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.