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BACKGROUND: Castleman disease (CD) comprises a group of rare and heterogeneous haematological disorders, including unicentric (UCD) and multicentric (MCD) forms, the latter further subdivided into HHV8-MCD, POEMS-MCD and idiopathic-MCD (iMCD). However, according to the Castleman Disease Collaborative Network guidelines, the diagnosis of CD can only be achieved through collaboration between clinicians and pathologists. METHODS: We applied these clinical and pathological criteria and implement with clonality testing to a retrospective cohort of 48 adult and paediatric Italian patients diagnosed with reactive lymphadenitis with CD-like histological features. RESULTS: We confirmed the diagnosis of CD in 60% (29/48) of the cases, including 12 (41%) UCD and 17 (59%; five HHV8-MCD, three POEMS-MCD and nine iMCD) MCD. Of the remaining 19 cases (40%) with multiple lymphadenopathy, 5 (26%) were classified as autoimmune diseases, 1 (5%) as autoimmune lymphoproliferative disorder, 1 (5%) as IgG4-related disease, 11 (83%) as reactive lymphadenitis and 1 (5%) as nodal marginal zone lymphoma. CONCLUSIONS: Our study emphasizes the importance of the multidisciplinary approach to reactive lymphadenitis with CD-like features in order to achieve a definitive diagnosis and choose the appropriate treatment.
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Hiperplasia do Linfonodo Gigante , Linfadenite , Linfadenopatia , Linfoma de Zona Marginal Tipo Células B , Adulto , Humanos , Criança , Hiperplasia do Linfonodo Gigante/diagnóstico , Estudos RetrospectivosAssuntos
Adipócitos/patologia , Angiomioma/diagnóstico , Obstrução Nasal/diagnóstico , Neoplasias Nasais/diagnóstico , Neoplasias dos Seios Paranasais/diagnóstico , Angiomioma/complicações , Angiomioma/patologia , Diferenciação Celular , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Obstrução Nasal/etiologia , Neoplasias Nasais/complicações , Neoplasias Nasais/patologia , Neoplasias dos Seios Paranasais/complicações , Neoplasias dos Seios Paranasais/patologiaRESUMO
OBJECTIVES: The discovery of tyrosine kinase inhibitors (TKI) has remarkably improved the clinical course of patients with non-small cell lung cancer driven by Epidermal Growth Factor Receptor (EGFR) mutations. However, virtually in all cases, the disease resurfaces in a TKI-resistant form that is mainly linked to an acquired EGFR-T790M mutation, a MET amplification, or small cell lung cancer (SCLC) transformation. Third-generation TKIs are able to block tumor growth through an irreversible binding to the T790M-mutated receptor. Such new treatments require the diagnostic analysis of new pathologic tissue or a liquid biopsy to detect the presence of the T790M mutation. MATERIALS AND METHODS: Pre-TKI and post-TKI biopsies from 27 patients with an activating EGFR mutation were collected and analyzed for EGFR-T790M mutation, MET amplification, and SCLC transformation. RESULTS: The T790M mutation was found in 16 patients (59%) whereas MET gene amplification was found in 2 (10.5%) of 19 evaluated cases. The histologic transformation from adenocarcinoma (ADC) to SCLC was identified in 3 patients (11%). In one of them reversal from SCLC back to adenocarcinoma was observed. One patient had the T790M mutation concordantly detected in 2 synchronous lesions whereas another patient showed T790M positivity only in one of 2 specimens. In 4 patients longitudinal biopsies revealed T790M gains and losses not always according to biological expectations. CONCLUSIONS: Intrapatient molecular or histologic heterogeneity may be frequently found during routine treatment of non-small cell lung cancer patients. This biological aspect may have profound repercussions on subsequent therapeutic decisions, and therefore requires in-depth investigation.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Fatores Etários , Idoso , Biópsia por Agulha Fina , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Humanos , Itália , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Análise de Sobrevida , Resultado do TratamentoRESUMO
In the last few years, immunotherapy has become part of everyday clinical practice for the treatment of many solid tumors including metastatic non-small-cell lung cancer. These drugs, however, can yield a specific toxicity profile that consists of immune-related adverse events (irAEs). Hepatotoxicity is one of irAEs and occurs in about 1-3% of cases and may be manifested by the presence of increate levels of liver enzymes (aspartate aminotransferase, alanine aminotransferase) and/or biliary stasis evidence; in these cases, a differential diagnosis with other hepatic diseases must be considered. We present the case of a 73-year-old man who presented with an alteration in liver function during treatment with pembrolizumab (anti-programmed death 1 monoclonal antibody) for a stage IV nonsquamous non-small-cell lung cancer, which was initially mistaken for drug-induced irAEs hepatic toxicity.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Hepatopatias/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Diagnóstico Diferencial , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Hepatopatias/etiologia , Hepatopatias/patologia , Neoplasias Pulmonares/patologia , Masculino , PrognósticoRESUMO
BACKGROUND: Severe skin rash is listed among important side effects of EGFR tyrosine kinase inhibitors. Polydatin (PD), a glycosylated polyphenol, is endowed with anti-inflammatory activity in human epidermal keratinocytes. OBJECTIVE: This study evaluated the effect of topical application of a moisturizer containing PD to prevent skin rash in patients with mutated non-small cell lung cancer (NSCLC) treated with afatinib. MATERIALS AND METHODS: Eligible NSCLC patients with metastatic disease were treated with first-line afatinib 40 mg/die. One day before starting systemic therapy, all patients received topical administration of a 1.5% PD-based cream b.i.d. every day until the end of afatinib treatment. RESULTS: Out of 34 treated patients, the incidence of skin rash (all grades) was 41.2% and grade 2 rash was 20.6%, and grade 3 rash was not observed in any of the patients. None of the patients discontinued therapy for toxicity. The mean duration of treatment was 6.4 months, calculated from the time treatment was started to the date treatment was stopped. CONCLUSION: The results showed that a PD-based cream can reduce the incidence of grade ≥2 skin toxicities in patients treated with afatinib. Clinical study registration number: Prot. No. 130/CE Lazio 1 Italy.
RESUMO
OBJECTIVES: Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA). MATERIALS AND METHODS: We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRß, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases. RESULTS: When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas) contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD (P<0.001, P<0.001, and P<0.001) growth factors, and their receptors VEGFR1 (P=0.002), VEGFR2 (P=0.013), and VEGFR3 (P=0.041). No differences were observed in terms of PDGFRß expression. CONCLUSIONS: According to our data, it is possible to hypothesize the existence of multiple paracrine and/or autocrine loops in TET, particularly in the high-risk ones, involved in TET growth and progression. Anti-angiogenic agents, directed to inhibit these loops, are therefore to be considered as potential tools in advanced TET therapy.
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Neoplasias Epiteliais e Glandulares/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Neoplasias do Timo/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores , Criança , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Estudos Retrospectivos , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/mortalidade , Neoplasias do Timo/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Adulto JovemRESUMO
BACKGROUND: Granulomatous peritonitis may indicate a number of infectious, malignant, and idiopathic inflammatory conditions. It is a very rare postoperative complication, which is thought to reflect a delayed cellmediated response to cornstarch from surgical glove powder in susceptible individuals. This mechanism, however, is much more likely to occur with open abdominal surgery when compared with the laparoscopic technique. METHODS: We report a case of sterile granulomatous peritonitis in an 80-y-old female after a laparoscopic cholecystectomy. Management was conservative, and no relapse was observed after over 1-y of follow-up. DISCUSSION: We propose that peritoneal exposure to bile acids during the laparoscopic removal of the gallbladder was the trigger of granulomatous peritonitis in this patient. Severe complications, such as peritoneal adhesions, intestinal obstruction, and fistula formation, were observed, but no fatalities were reported. CONCLUSION: We should be aware of this rare cause of peritonitis in the surgical setting.
Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Colelitíase/cirurgia , Peritonite/etiologia , Complicações Pós-Operatórias , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Peritonite/diagnósticoRESUMO
AIM: To evaluate if indolent B cell-non Hodgkin's lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies. METHODS: A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared. RESULTS: Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related B-NHL treated with only antiviral therapy, achieved a complete response of their onco-haematological disease (55%). Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response (54%). CONCLUSION: HCV genotypes and duration of HCV infection differed between B-NHL subtypes. Indolent lymphomas can be managed with antiviral treatment, while DLBCL is not affected by the HCV infection.
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Myeloid sarcoma (MS, previously named granulocytic sarcoma or chloroma) is a rare extramedullary tumour of immature myeloid cells. It can be present before, concurrently with, or after the diagnosis of acute myeloid leukemia. MS is extremely uncommon in acute promyelocytic leukemia (APL). In the case described here, MS was the sole site of APL relapse and the cause of spinal cord compression. The patient presented with neurologic symptoms due to a paravertebral mass of MS after 7 years of complete remission. He was treated with excision of the mass followed by local radiotherapy. Systemic treatment was also given with combined arsenic trioxide and all-trans retinoic acid and the patient was able to achieve a second prolonged clinical and molecular remission.
RESUMO
BACKGROUND: We sought to evaluate factors influencing long-term survival in 19 patients with primary neuroendocrine tumours of the thymus. METHODS: From January 1990 to December 2004, 19 patients (14 males, 5 females; mean age 48.6 years) were surgically treated for a primary neuroendocrine tumour of the thymus. RESULTS: All patients underwent radical R0 thymomectomy and were followed up for a total of 1,459 months (median: 69 months; range: 8-180). Nine patients had associated paraneoplastic syndrome. No operative mortality occurred. Two patients underwent re-do surgery because of local recurrence, respectively, 25 and 35 months after surgery. Five patients died of disease, respectively, 51, 70, 95, 131 and 153 months after surgery. One patient died of myocardial infarction with no evidence of disease. Thirteen patients are alive, of which 10 are free from disease and three with disease. The overall 5-year and 10-year actuarial survival rates were 91.6% and 69.8%, respectively (median survival: 153 months). The 10-year survival was evaluated according to histology (typical carcinoid 100%; atypical carcinoid: 66.6%; large cell neuroendocrine tumours: 0%), Masaoka staging (stage I: 100%; stage II: 50%; stage III: 66.6%; stage IV: 0%), presence of paraneoplastic syndrome (no: 87.5%; yes: 0%) and postoperative radiotherapy (yes: 40%; no: 83.3%). CONCLUSIONS: The prognosis of primary neuroendocrine tumours of the thymus is related to the grading of the neoplasm, the presence of a paraneoplastic syndrome and to the Masaoka staging but not to the postoperative radiotherapy.
Assuntos
Tumores Neuroendócrinos/cirurgia , Neoplasias do Timo/cirurgia , Adulto , Idoso , Tumor Carcinoide/complicações , Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/patologia , Síndromes Paraneoplásicas/etiologia , Prognóstico , Reoperação , Neoplasias do Timo/complicações , Neoplasias do Timo/patologia , Resultado do TratamentoAssuntos
Infecções Oculares Bacterianas , Linfoma de Zona Marginal Tipo Células B/microbiologia , Neoplasias Orbitárias/microbiologia , Psitacose/microbiologia , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Chlamydophila psittaci/isolamento & purificação , Infecções Oculares Virais , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/virologia , Neoplasias Orbitárias/tratamento farmacológico , Neoplasias Orbitárias/virologia , Psitacose/tratamento farmacológicoRESUMO
Chemokine and chemokine receptors expressed by normal and neoplastic lymphocytes play a key role in cell recruitment into skin and lymph nodes. The aim of this study was to get further insights into the role of chemokines in pathogenesis and progression of cutaneous T-cell lymphoma (CTCL) with particular regard to Sézary Syndrome (SS), a CTCL variant with blood involvement. Here, we show that functional CXCL13 homeostatic chemokine is strongly up-regulated in SS cells, well-detectable in skin lesions and lymph nodes, and measurable at high concentration in plasma of SS patients, at different levels during disease progression. Furthermore, we show that the addition of CXCL13 to CCL19 or to CCL21, the selective CCR7 agonists responsible for lymph node homing, strongly enhances the migration of CCR7+ SS cells. We also show that neutralization of the CCR7 receptor strongly impairs CCL19/21-induced chemotaxis of SS cells both in the absence or presence of CXCL13. Additional experiments performed to investigate the survival, adhesion, and metalloproteases secretion indicate that CXCL13 combined with CCL19 and CCL21 mainly affects the chemotaxis of SS cells. Our findings suggest that this newly described CXCL13 expression in SS represents a new pathogenetic mechanism of diagnostic significance.
Assuntos
Movimento Celular/fisiologia , Quimiocina CCL19/fisiologia , Quimiocina CCL21/fisiologia , Quimiocina CXCL13/biossíntese , Síndrome de Sézary/metabolismo , Idoso , Estudos de Casos e Controles , Adesão Celular , Linhagem Celular , Quimiotaxia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Síndrome de Sézary/patologiaAssuntos
Hepatomegalia/etiologia , Hipercalcemia/etiologia , Fígado/patologia , Linfoma Difuso de Grandes Células B/complicações , Esplenomegalia/etiologia , Idoso , Biópsia , Carcinoma Papilar/complicações , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/cirurgia , Confusão/etiologia , Diagnóstico Diferencial , Evolução Fatal , Hepatite C Crônica/complicações , Hepatomegalia/patologia , Humanos , Hiperparatireoidismo/diagnóstico , Nefropatias/diagnóstico , Letargia/etiologia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Neoplasias Primárias Múltiplas/complicações , Neoplasias Primárias Múltiplas/diagnóstico , Osteólise/diagnóstico , Esplenectomia , Esplenomegalia/patologia , Esplenomegalia/cirurgia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
Sézary syndrome (SS) is a rare form of cutaneous T-cell lymphoma (CTCL) characterized by a distinct metastatic pattern mainly involving blood and skin. Chemokines and their receptors play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors including non-Hodgkin T-cell lymphomas (NHLs). Here we report that SS cells express a functionally active CXCR4 and that its ligand SDF-1 is abundantly produced in the skin, which represents the main destination of SS cell spreading. SDF-1 is normally inactivated by proteolytic cleavage by the CD26/dipeptidylpeptidase IV (DPPIV). The lack of CD26 from the cell surface is a hallmark of circulating SS cells. We also show that the CD26(-) phenotype is maintained also in skin-infiltrating neoplastic T lymphocytes and that SS-affected individuals exhibit a reduced activity of plasma soluble CD26. Finally, we observe that the addition of soluble CD26 reduces the migratory response of SS cells to SDF-1 whereas the inhibition of the CD26 peptidase activity in Hut78, a CD26(+) CTCL cell line, enhances the SDF-1-induced migration of these cells. Our findings suggest that the SDF-1-CXCR4 axis could play an important role in skin homing of SS through the regulatory activity of CD26.
Assuntos
Adenosina Desaminase/metabolismo , Quimiocinas CXC/farmacologia , Dipeptidil Peptidase 4/metabolismo , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Glicoproteínas/metabolismo , Receptores CXCR4/metabolismo , Síndrome de Sézary/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Quimiocina CXCL12 , Quimiocinas CXC/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Metástase Neoplásica , Síndrome de Sézary/patologia , Pele/metabolismo , Pele/patologia , Linfócitos T/metabolismo , Linfócitos T/patologiaRESUMO
A new transperineal ultrasound-guided prostate rebiopsy method is described. The method is performed using a fixed grid approach similar to the method that has been in use for some time for brachytherapy i n prostate cancer. The method adopts special cylindrical cutting needles to take cores of varying lengths and was found to be more time consuming (this is the main reason it is mostly used for rebiopsies). It nevertheless allowed more accurate ard systematic mapping of the prostate gland than the standard method of taking multiple biopsies by sector. Sending in each biopsy fragment for separate histological examination based on grid coordinates allowed the Anatomical Pathology laboratory to build up an ideal topographic reconstruction of the disease lesions detected. The approach offers the advantages of a repeatable biopsy plan that can be compared with previous biopsies, more accurate spatial localisation of diseased tissue and accurate information on distribution within the gland. The benefits are multifold and all extremely interesting both for the diagnosis and subsequent choice, evaluation and administration of therapeutic treatment--and also for the dynamic study of evolving cell changes and cell structure anomalies detectable in the prostate gland.
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Biópsia por Agulha/métodos , Braquiterapia , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Biópsia por Agulha/instrumentação , Desenho de Equipamento , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Ultrassonografia/instrumentaçãoRESUMO
Primary cardiac lymphomas (PCLs), involving solely heart and/or pericardium at presentation, are rare events. They are frequently recognized at autopsy and generally carry a poor prognosis due either to a delay in the diagnosis or to infiltration of heart structures. We report here on two patients with large B-cell PCL. One is a 52-year-old man who presented with multiple cardiac tumors infiltrating mainly the right atrium and the inter-atrial septum. Diagnosis was established by ultrasound-assisted transesophageal biopsy of the intra-atrial multilobated tumor mass. He was treated with Rituximab-implemented high-dose sequential (R-HDS) chemotherapy followed by autologous peripheral blood stem cell transplantation, attaining complete response. He had no evidence of disease 24 months from onset. The second patient was a 70-year-old woman who presented with pericardial tamponade and low-output cardiac failure. Despite prompt pericadiocentesis and chemotherapy with cyclophosphamide and vincristine, she died 2 weeks later. Postmortem examination revealed large B-cell lymphoma proliferation confined to the heart. Whether primitive heart localizations represent an independent prognostic factor, and what specific measures should be adopted in patients with this rare presentation is the subject of the present report and review of the literature.
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Neoplasias Cardíacas/diagnóstico , Imunocompetência , Linfoma de Células B/diagnóstico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Eletrocardiografia , Feminino , Neoplasias Cardíacas/terapia , Humanos , Linfoma de Células B/terapia , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Rituximab , Transplante Autólogo , Resultado do TratamentoRESUMO
Nodal tumor-forming accumulations of plasmacytoid monocytes/interferon-producing cells (PMs/IPCs) have been described in patients with myeloproliferative disorders. Here we report a series of 9 additional cases of such association. The patients were predominantly adult (median, 62 years), males (male/female ratio, 7:2), who presented with chronic myelomonocytic leukemia (4 cases), acute myeloid leukemia (1), acute monocytic leukemia (2), unclassifiable chronic myeloproliferative (1), or myeloproliferative/myelodysplastic disease (1). The prognosis was poor (median survival, 24 months) and related to progression of the underlying myeloid neoplasm. We found that in addition to lymph nodes, PMs/IPCs accumulated to bone marrow (8 cases) and skin (4 cases). Immunohistochemical markers typically expressed by PMs/IPCs (CD68, CLA/HECA452, CD123) were found in all cases and shown useful to identify cells with variations from classic morphology. In addition, PMs/IPCs expressed the interferon-alpha (IFN-alpha) inducible protein MxA, the B-cell oncogene TCL1, and granzyme B. The biologic and clinical significance of the association between PMs/IPCs and myeloid disorders remains not clarified. Using fluorescence in situ hybridization analysis in a case known to harbor monosomy 7 in the myeloid leukemia, we demonstrated that PMs/IPCs share the same chromosomal abnormality, thus indicating that they are clonal, neoplastic in nature, and closely related to the associated myeloid tumor. Recently, a novel CD56+ hematologic neoplasm has been reported and retained to stem from PMs/IPCs. The majority of PMs/IPCs in the present series failed to express CD56, thus indicating that variants of PMs/IPCs neoplasms exist, which might represent parts of a spectrum.
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Interferons/metabolismo , Leucemia/patologia , Linfonodos/patologia , Monócitos/patologia , Transtornos Mieloproliferativos/patologia , Plasmócitos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Medula Óssea/metabolismo , Medula Óssea/patologia , Células Clonais , DNA de Neoplasias/análise , Feminino , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Interfase , Leucemia/metabolismo , Linfonodos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Transtornos Mieloproliferativos/metabolismo , Plasmócitos/metabolismo , Pele/metabolismo , Pele/patologiaRESUMO
Plasmacytomas of the testis are rare neoplasias; they may occur as isolated tumors or in concomitance with generalized multiple myeloma. We report the case of a 77-year-old man with previous clinical evidence of multiple myeloma involving skin, ribs, and lungs, and initially treated with surgery, radiotherapy, and chemotherapy attaining partial response. Fourteen months after the onset, the patient presented with left testicular enlargement due to plasmacytoma. Immunohistochemical stains showed monoclonal cytoplasmic IgA-lambda in tumour cells; serum M component showed the same immunoglobulin. Following radiotherapy the tumour mass disappeared. Nonetheless, 2 months later while on chemotherapy, disease recurred with progressive increase of skeletal lesions. The patient is currently alive with disease progression 22 months after onset. On the basis of a review of the literature, the clinical significance of testicular myeloma localization is discussed.
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Plasmocitoma/patologia , Neoplasias Testiculares/patologia , Idoso , Terapia Combinada , Progressão da Doença , Humanos , Imunoglobulina A , Cadeias lambda de Imunoglobulina , Masculino , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Plasmocitoma/imunologia , Plasmocitoma/terapia , Neoplasias Testiculares/imunologia , Neoplasias Testiculares/terapiaRESUMO
Overexpression of the TCL1 oncogene has been shown to play a causative role in T cell leukemias of humans and mice. The characterization of Tcl1-deficient mice in these studies indicates an important developmental role for Tcl1 in early embryogenesis. In wild-type embryos, Tcl1 is abundant in the first three mitotic cycles, during which it shuttles between nuclei and the embryo cortical regions in a cell-cycle-dependent fashion. The absence of this protein in early embryogenesis results in reduced fertility of female mice. The present studies elucidate the mechanism responsible for the reduced female fertility through analysis of the oogenesis stages and early embryo development in Tcl1-deficient mice. Even though Tcl1(-/-) females display normal oogenesis and rates of oocyte maturation/ovulation and fertilization, the lack of maternally derived Tcl1 impairs the embryo's ability to undergo normal cleavage and develop to the morula stage, especially under in vitro culture conditions. Beyond this crisis point, differentiative traits of zygotic genome activation and embryo compaction can take place normally. In contrast with this unanticipated role in early embryogenesis, we observed an overexpression of TCL1 in human seminomas. This finding suggests that TCL1 dysregulation could contribute to the development of this germinal cell cancer as well as lymphoid malignancies.