RESUMO
Shwachman Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome (IBMFS) characterized by neutropenia, exocrine pancreatic dysfunction, and cancer predisposition. Patients are at risk for myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) but, unlike other IBMFS, there have been no reported cases of solid tumors. We report a novel case of a solid tumor in a patient with SDS and biallelic mutations in the Shwachman Bodian Diamond Syndrome gene (SBDS). Whether the development of breast cancer in this patient is due to SDS or an isolated case due to unknown factors requires further study.
Assuntos
Alelos , Doenças da Medula Óssea/genética , Neoplasias da Mama/genética , Insuficiência Pancreática Exócrina/genética , Lipomatose/genética , Mutação , Proteínas/genética , Adulto , Doenças da Medula Óssea/complicações , Insuficiência Pancreática Exócrina/complicações , Feminino , Humanos , Lipomatose/complicações , Síndrome de Shwachman-DiamondRESUMO
Transient myeloproliferative disorder (TMD) in newborns with Down syndrome (DS) has been well described. We report 4 newborns, 2 with DS and 2 without DS, who developed TMD. One newborn with DS developed multiorgan failure and died despite treatment with low-dose cytarabine. In 3 newborns, the TMD resolved spontaneously. Two of these patients, 1 with and 1 without DS developed leukemia on subsequent follow-up and were treated successfully. We reviewed the clinical and laboratory data on 14 non-DS infants with TMD reported in the literature. According to limited data, these patients are more likely to develop leukemia than DS patients, however their outcome is better.
Assuntos
Síndrome de Down/complicações , Transtornos Mieloproliferativos/complicações , Aberrações Cromossômicas , Síndrome de Down/genética , Síndrome de Down/patologia , Evolução Fatal , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologiaRESUMO
INTRODUCTION: Therapeutic options for multiple myeloma (MM) are growing, yet clinical outcomes remain heterogeneous. Cytogenetic analysis and disease staging are mainstays of risk stratification, but data suggest a complex interplay between numerous abnormalities. Myeloma cell proliferation is a metric shown to predict outcomes, but available methods are not feasible in clinical practice. PATIENTS AND METHODS: Multiplex immunohistochemistry (mIHC), using multiple immunostains simultaneously, is universally available for clinical use. We tested mIHC as a method to calculate a plasma cell proliferation index (PCPI). By mIHC, marrow trephine core biopsy samples were costained for CD138, a plasma cell-specific marker, and Ki-67. Myeloma cells (CD138+) were counted as proliferating if coexpressing Ki-67. Retrospective analysis was performed on 151 newly diagnosed, treatment-naive patients divided into 2 groups on the basis of myeloma cell proliferation: low (PCPI ≤ 5%, n = 87), and high (PCPI > 5%, n = 64). RESULTS: Median overall survival (OS) was not reached versus 78.9 months (P = .0434) for the low versus high PCPI groups. Multivariate analysis showed that only high-risk cytogenetics (hazard ratio [HR] = 2.02; P = .023), International Staging System (ISS) stage > I (HR = 2.30; P = .014), and PCPI > 5% (HR = 1.70; P = .041) had independent effects on OS. Twenty-three (36%) of the 64 patients with low-risk disease (ISS stage 1, without high-risk cytogenetics) were uniquely reidentified as high risk by PCPI. CONCLUSION: PCPI is a practical method that predicts OS in newly diagnosed myeloma and facilitates broader use of MM cell proliferation for risk stratification.
Assuntos
Proliferação de Células , Imuno-Histoquímica/métodos , Mieloma Múltiplo/patologia , Plasmócitos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Feminino , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/biossíntese , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Mieloma Múltiplo/metabolismo , Plasmócitos/metabolismo , Estudos Retrospectivos , Fatores de Risco , Sindecana-1/biossínteseAssuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 19/genética , Sarcoma Mieloide/genética , Translocação Genética , Neoplasias do Colo do Útero/genética , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Pessoa de Meia-Idade , Proteína de Leucina Linfoide-Mieloide/genéticaRESUMO
Immunohistochemical detection of DNA mismatch repair proteins and polymerase chain reaction detection of microsatellite instability have enhanced the recognition of mismatch repair-deficient neoplasms in patients with Lynch syndrome and, consequently, led to the identification of tumors that have not been included in the currently known Lynch syndrome tumor spectrum. Here, we report 4 such unusual tumors. Three of the 4, a peritoneal mesothelioma, a pancreatic acinar cell carcinoma, and a pancreatic well-differentiated neuroendocrine tumor, represented tumor types that, to the best of our knowledge, have not been previously reported in Lynch syndrome. The fourth tumor was an adrenocortical carcinoma, which has rarely been reported previously in Lynch syndrome. Three of our 4 patients carried a pathogenic germ-line mutation in a mismatch repair gene. The unusual tumor in each of the 3 patients showed loss of the mismatch repair protein corresponding to the mutation. The fourth patient did not have mutation information but had a history of colonic and endometrial carcinomas; both lacked MSH2 and MSH6 proteins. Interestingly, none of the 4 unusual tumors revealed microsatellite instability on polymerase chain reaction testing, whereas an appendiceal carcinoma from 1 of the study patients who was tested simultaneously did. The recognition of such tumors expands the repertoire of usable test samples for the workup of high-risk families. As yet, however, there are no data to support the inclusion of these tumors into general screening guidelines for detecting Lynch syndrome, nor are there data to warrant surveillance for these tumors in patients with Lynch syndrome.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA/genética , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Feminino , Mutação em Linhagem Germinativa , Humanos , Masculino , Mesotelioma/genética , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologiaRESUMO
Synovial sarcoma (SS) of the head and neck region are rare, accounting for less than 10% of all head and neck soft tissue sarcomas. A limited number of SS have been reported in the parapharyngeal space and these reports have all been based on histological examination of resection material. The diagnosis of monophasic SS on cytology is extremely difficult. We report the first case where a SS was correctly diagnosed on a fine needle aspirate by cytology with the assistance of immunocytochemistry and fluorescence in situ hybridization. We will emphasize the importance of ancillary techniques, such as immunocytochemistry and cytogenetic/molecular pathology, in avoiding diagnostic pitfalls and correctly diagnosing monophasic SS on cytologic material. We will propose an algorithmic approach to accurately diagnose parapharyngeal spindle cell neoplasms with the use of appropriate ancillary studies in conjunction to morphological features.
Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Sarcoma Sinovial/patologia , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina , Citodiagnóstico , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Proteínas de Fusão Oncogênica/genética , Patologia Molecular , Sarcoma Sinovial/genética , Adulto JovemRESUMO
Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We present the first report of a case of FL that transformed to plasmablastic lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/ BCL2 translocation was retained in the PBL, which also acquired c-myc gene rearrangement. Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone. Our study of this unusual case expands the histologic spectrum of FL transformation and increases our understanding of the pathogenetic mechanisms of transformation of indolent lymphomas to aggressive lymphomas.