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1.
Acta Haematol ; 146(4): 331-337, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37068478

RESUMO

The concomitant presence of Castleman disease (CD) with other hematological pathology is an event described in the literature with increasing frequency, able to modify the diagnostic and curative approach in such patients. Very few studies in the literature describe the association of CD with concomitant neoplastic diseases; the most frequent are Kaposi's sarcomas (especially in HIV and human herpes virus-8-positive patients) and lymphoproliferative disorders, such as lymphomas. Instead, since the association with plasma cell diseases such as multiple myeloma and plasmacytoma is infrequent, there is a lack of literature. This manuscript aimed to revise the literature by describing a rare case of CD and plasmacytoma and attempting to explain the underlying triggering mechanisms.


Assuntos
Hiperplasia do Linfonodo Gigante , Doenças Hematológicas , Plasmocitoma , Humanos , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/patologia , Plasmocitoma/complicações , Plasmocitoma/diagnóstico , Doenças Hematológicas/complicações , Doenças Hematológicas/diagnóstico
2.
Chemotherapy ; 64(2): 110-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31533095

RESUMO

Patients who experience extramedullary relapses (EMR) of multiple myeloma (MM) have an adverse prognosis, also in this era of novel agents like proteasome inhibitors and immunomodulatory drugs. We describe the case of an MM patient with EMR at 2 different sites after allogeneic stem cell transplantation. EMR was refractory to bortezomib, anthracycline, and bendamustine, but the patient achieved long-term complete remission (4 years) with pomalidomide and dexamethasone. This supports the hypothesis that this could be due to the graft-versus-myeloma effect during therapy enhanced by pomalidomide.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Recidiva , Indução de Remissão , Talidomida/uso terapêutico , Transplante Homólogo
3.
Hematol Oncol ; 36(1): 269-275, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28509339

RESUMO

An accurate histological diagnosis may distinguish essential thrombocythaemia (ET) from early primary myelofibrosis (early-PMF), which is associated with worse outcome. Outcome of ET is also negatively affected by the presence of the JAK2V617F mutation. To investigate the impact of JAK2V617F mutation burden and histology on outcome, we collected 475 WHO-diagnosed ET (69.2%) or early-PMF JAK2V617F -positive patients followed in 4 Italian haematology centers. JAK2V617F allele burden was ≤50% in 90% and 87% of ET and early-PMF patients, respectively (P = .34). During follow-up, 32 (9.7%) ET and 18 (12.3%) early-PMF patients experienced 59 thrombotic events, and 27 patients (5.6%) and 6 (1.2%) patients evolved to myelofibrosis and acute leukemia, respectively. At last contact, 28 (5.8%) patients had died. In early-PMF compared to ET, the 10-year mortality rates (6.7% and 4.3%, P = .73), leukemic transformation rates (1.4% and 1.2%, P = .45), and thrombosis rates (16.7% and 12.2%, P = .12) were comparable. Only progression to overt myelofibrosis at 10 years was significantly worse (11.4% and 1.5%, P = .004). In multivariate analysis, a higher (>50%) JAK2V617F burden was significantly correlated with fibrotic progression and histology. Considering JAK2V617F -positive disease, a higher (>50%) JAK2V617F burden and histological classification are independent prognostic risk factors for disease progression. These findings reinforce the need for standardized detection of this mutation.


Assuntos
Janus Quinase 2/genética , Mielofibrose Primária/enzimologia , Trombocitemia Essencial/enzimologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Mielofibrose Primária/genética , Mielofibrose Primária/mortalidade , Mielofibrose Primária/patologia , Análise de Sobrevida , Trombocitemia Essencial/genética , Trombocitemia Essencial/mortalidade , Trombocitemia Essencial/patologia , Resultado do Tratamento , Adulto Jovem
4.
J Surg Case Rep ; 2024(2): rjae073, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38370604

RESUMO

Castleman disease is a rare and benign disorder, characterized by enlarged lymph nodes and angiofollicular lymphoid hyperplasia. We report a case of a 57-year-old male, who was admitted to our surgical department because of a retroperitoneal nodular mass measuring about 4 cm in maximum diameter, incidentally discovered on a radiologic exam performed for the onset of vague abdominal pain with posterior irradiation. The patient was subdue to laparoscopic removal of the mass and no intra- and post-operative complications were recorded. Histologic diagnosis of hyaline-vascular variant of the Castleman disease was confirmed. Only two cases have been found in the literature reporting the paraduodenal unicentric Castleman disease localization like our case. Although rare, the Castleman disease must be considered in the differential diagnosis among all the lymph nodes diseases, for avoiding improper therapies.

5.
J Cancer Res Clin Oncol ; 149(12): 10465-10471, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37278829

RESUMO

PURPOSE: Oral Squamous Cell Carcinoma (OSCC) is characterized by a high aggressiveness and a tendency to metastasize. The management of the neck in cT1-2N0 patients c follows three strategies: watchful waiting, elective neck dissection (END) or sentinel lymph node biopsy (SLNB). The aim was to assess the viability of intraoperative frozen sections of the nodes of cT1-2N0 to spot occult metastases as an alternative to SLNB, performing a modified radical neck dissection (MRND) in intraoperatively positive patients. METHODS: The patients were treated at the Maxillo-Facial Surgery Unit of Policlinico San Marco of Catania between 2020 and 2022. END was performed in all patients, including frozen section examination of at least one clinically suspicious node per level. In case of positivity after frozen section examination, neck dissection was extended to levels IV and V. RESULTS: All frozen sections were compared with a definitive test after paraffin inclusion. During surgery, 70 END were performed, and 210 nodes were analyzed with frozen sections. Among the 70 END, 52 were negative after frozen Sects. (156 negative nodes), and surgery was ended. Five of the 52 negative ENDs resulted in pN + after paraffin inclusion (9.6%), which underwent postoperative adjuvant treatment. The sensibility of our END + frozen section method was 75%, while the specificity of our test was 94%. The negative predictive value was 90,4%. CONCLUSIONS: Elective neck dissection + intraoperative frozen section could be an alternative to SLNB to spot occult nodal metastases in cT1-2N0 OSCC due to the opportunity to perform a one-step diagnostic/therapeutic procedure.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Esvaziamento Cervical/métodos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Secções Congeladas , Parafina , Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/cirurgia , Linfonodos/patologia , Estadiamento de Neoplasias
6.
Clin Case Rep ; 11(7): e7134, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37469366

RESUMO

Aggressive SM + AML has limited therapeutic options. Even a strong combination of decitabine-venetoclax-midostaurin has a transient effect on AML and a mitigated effect on SM. Larger series are required to identify the best therapeutic strategy.

7.
J Clin Med ; 12(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36675507

RESUMO

Ruxolitinib is a JAK1/2 inhibitor that has revolutionized the approach to myelofibrosis. On the one side, this drug can rapidly improve the symptoms related to the hematological disease; on the other side, the inhibition of JAK1/2 can lead to immunosuppression which may increase the risk of infections, due to a change in the cytokine balance in favor of anti-inflammatory cytokines, to direct inhibition of immune cells, and to the suppression in the production of specific antibodies. In this patient setting, much is known about possible viral and bacterial infections, while little is reported in the literature concerning parasitic infections, specifically leishmaniasis. Leishmania is a parasitic infection that can cause serious problems in immunosuppressed patients. The parasite can invade the bloodstream and cause a wide range of symptoms, including fever, weight loss, and anemia. In severe cases, it can lead to multi-organ failure and, rapidly, death. Early diagnosis and prompt treatment are essential especially for these patients, unable to respond adequately. In this case and the following review of the existing literature, the cytokine kinetics and the production of specific anti-Leishmania antibodies represent characteristic aspects capable of providing a more in-depth understanding of the mechanisms underlying these complex clinical cases in an immunocompromised patient.

8.
Clin Case Rep ; 9(9): e03817, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34589219

RESUMO

In CMML, neoplastic monocytes can be distinguished based on their immunophenotype. Supportive care myeloid growth factors in concomitant extranodal non-Hodgkin Lymphoma are safe.

9.
Leuk Res Rep ; 14: 100227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204611

RESUMO

In CD34+ cells mobilization of patients with multiple myeloma (MM), the use of Cyclophosphamide (CTX) at a dose of 2 g/m2 has low efficacy although also lower toxicity. The suboptimal mobilizing effect of low-dose CTX, however, may be overcome by plerixafor (PLX) on demand. We conducted a prospective multicenter study in 138 patients with MM to evaluate CTX 2 g/m2 in association with granulocyte-colony stimulating factor (G-CSF) and on-demand PLX. We compared results with a historical group of MM patients (n = 138) mobilized using CTX at a dose of 4 g/m2. CD34+ cells greater than 2 × 106/kg in max three aphereses were harvested in 98.6% of patients in the on-demand PLX study group while in 84.0% in the historical group, (p = 0.0001). In the on-demand-PLX study group, a successful harvest greater than 5 × 106/kg in max three aphereses was observed in 85.5% of patients versus 62.3% of patients in the historical control group, (p=0.0001). In the on-demand-PLX study group, 4.3% (6/138) of patients had febrile complications. Salvage mobilization in the on-demand PLX study group was 1.4%. In conclusions, on-demand PLX + CTX 2 g/m2 + G-CSF 10 µg/kg has higher efficacy and lower toxicity compared with CTX 4 g/m2 + G-CSF. An analysis of costs is presented.

12.
Oncotarget ; 7(41): 67333-67346, 2016 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-27637084

RESUMO

PURPOSE: Neutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL. EXPERIMENTAL DESIGN: First, N-HL function was evaluated in vitro, showing increased arginase (Arg-1) expression and activity compared to healthy subjects. Second, we measured serum level of Arg-1 (s-Arg-1) by ELISA in two independent, training (N = 40) and validation (N = 78) sets. RESULTS: s-Arg-1 was higher in patients with advanced stage (p = 0.045), B-symptoms (p = 0.0048) and a positive FDG-PET scan after two cycles of chemotherapy (PET-2, p = 0.012). Baseline levels of s-Arg-1 > 200 ng/mL resulted in 92% sensitivity and 56% specificity to predict a positive PET-2.Patients showing s-Arg-1 levels > 200 ng/mL had a shorter progression free survival (PFS). In multivariate analysis, PET-2 and s-Arg-1 at diagnosis were the only statistically significant prognostic variables related to PFS (respectively p = 0.0004 and p = 0.012).Moving from PET-2 status and s-Arg-1 level we constructed a prognostic score to predict long-term treatment outcome: low s-Arg-1 and negative PET-2 scan (score 0, N = 63), with a 3-Y PFS of 89.5%; either positive PET-2 or high s-Arg-1 (score 1, N = 46) with 3-Y PFS of 67.6%, and both positive markers (score 2, N = 9) with a 3-Y PFS of 37% (p = 0.0004). CONCLUSIONS: We conclude that N-HL are immunosuppressive through increased Arg-1 expression, a novel potential biomarker for HL prognosis.


Assuntos
Antineoplásicos/uso terapêutico , Arginase/sangue , Biomarcadores Tumorais/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/enzimologia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/imunologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Neutrófilos/imunologia , Prognóstico , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
13.
Br J Pharmacol ; 136(8): 1185-93, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12163352

RESUMO

1 We investigated the effects of prolonged exposure to copper (Cu(2+)) on vascular functioning of isolated rat aorta. 2 Aortic rings were exposed to CuSO(4) (3-24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu(2+). 3 Exposure to 2 micro M Cu(2+) in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 micro M PE by 30% (P<0.05) and impaired the relaxant response to 3 micro M ACh or 1 micro M A23187 (ACh, from 65.7+/-7.1 to 6.2+/-1.1%, n=8; A23187, from 74.6+/-8.2 to 12.0+/-0.8%, n=6; P<0.01 for both). Cu(2+) exposure did not affect the relaxant response to NO-donors. 4 Impairment of vasorelaxation appeared 3 h after incubation with 2 micro M Cu(2+) and required 12 h to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mM tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2+/-6.4%, n=10, P<0.01 vs Cu(2+) alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. 5 Twenty-four hour-exposure to 2 micro M Cu(2+) did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8+/-1.1 to 18.9+/-2.9 ng mg(-1) wet weight, n=8; P<0.01. 6 Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations of Cu(2+) impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions. British Journal of Pharmacology (2002) 136, 1185-1193


Assuntos
Sulfato de Cobre/farmacologia , Endotélio Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/fisiologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Humanos , Hidroliases/metabolismo , Técnicas In Vitro , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III , Fenilefrina/farmacologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Veias Umbilicais/metabolismo , Vasoconstritores/farmacologia
14.
Crit Rev Oncol Hematol ; 81(3): 207-23, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21511492

RESUMO

Breast cancer is a clinically heterogeneous and complex disease that can affect differently individuals with seemingly identical clinicopathologic parameters. This heterogeneity is strictly linked to individuals and tumors genetic variability. Currently, the development of high-throughput technologies are proving novel tools to tackle this complexity. By DNA microarray technology, genomic analysis has been used successfully for breast carcinomas stratification into molecular subgroups with relevant implications for clinical outcomes, and detection of prognostic/treatment predictive signatures. Indeed, DNA microarray has rapidly improved becoming a powerful diagnostic tool. Information derived from these assays allows clinicians to estimate the risk for distant recurrence, and predict accurately which patients are likely to benefit from adjuvant therapy. This review will describe the state-of-the-art of genomic analysis in breast cancer and introduce the clinicians to a genomic approach to cancer management, illustrating how it can help in defying a better diagnosis, prognosis and therapeutic treatment.


Assuntos
Neoplasias da Mama/genética , Variação Genética , Estudo de Associação Genômica Ampla/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Feminino , Humanos
15.
Hum Pathol ; 42(2): 254-68, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21106223

RESUMO

Reduced-intensity conditioning regimens have reshaped the clinical presentation of graft-versus-host disease after hematopoietic stem cell transplants. However, histopathologic features of graft-versus-host disease following reduced-intensity conditioning regimens have not been fully characterized. In a series of 112 biopsies (skin, n = 60; gastrointestinal [GI] tract, n = 44; liver, n = 8), we described the morphologic profile of graft-versus-host disease following reduced-intensity conditioning and investigated whether histopathologic changes of graft-versus-host disease following reduced-intensity conditioning have a diagnostic and/or prognostic value. Forty-four patients (49.5%) experienced acute graft-versus-host disease, 2 (2.2%) late-onset acute graft-versus-host disease (grade I, n = 13; grade II-IV, n = 33), 24 (27.0%) chronic graft-versus-host disease (de novo n = 12, progressive n = 12) and 19 (21.3%) overlap syndrome. In the skin, we observed: (i) phase-nonspecific changes, such as acute graft-versus-host disease features in chronic graft-versus-host disease patients (n = 4/24; 16.6%), (ii) subtle alterations such as superficial fibrosis in widened dermal papillae (n = 8), in acute graft-versus-host disease/late-onset graft-versus-host disease (n = 6/46; 13.0%) or chronic graft-versus-host disease (n = 2/24, 8.3%) patients, and (iii) features of chronic and acute graft-versus-host disease coexisting in the same specimen in overlap syndrome (n = 3/19; 15.7%). In the GI tract, we did not demonstrate peculiar features differing from those commonly observed in the myeloablative setting. By univariate analysis, a reduced overall survival was associated with graft-versus-host disease type (chronic graft-versus-host disease P = .006, acute graft-versus-host disease P = .03), older age (P = .04), and histopathologic diagnosis of "consistent with" + definite graft-versus-host disease (P = .02). Histopathologic diagnosis retained an independent prognostic value by multivariate analysis (P = .01). The present study indicates that pathologists should be aware of the peculiar morphologic changes of cutaneous graft-versus-host disease following reduced-intensity conditioning and further recommends histopathology in the diagnostic workup of graft-versus-host disease in patients undergoing reduced-intensity conditioning regimen.


Assuntos
Transplante de Medula Óssea/patologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Adulto , Idoso , Transplante de Medula Óssea/imunologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
17.
Leuk Res ; 33(9): 1212-6, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19230971

RESUMO

Chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL) share many features and their differential diagnosis may be challenging, especially when a leukemic picture alone is present. Monoclonal antibody panels are often useful, with CD23 being the most reliable. However, MCL diagnosis should be confirmed by immunohistochemical cyclin D1 detection, sometimes with equivocal or even negative results. Other cytofluorimetric, cytogenetics or molecular techniques are reliable but not widely available. B-CLL leukemic cells express CD200, a membrane glycoprotein belonging to the immunoglobulin superfamily. We investigated its expression on fresh neoplastic cells of 93 patients with a CD5+ lymphoproliferative disease (79 selected B-CLL and 14 MCL in leukemic phase). Although these data cannot be generalized, all B-CLL samples we examined were positive, with CD200 present on the vast majority of the cells while, in MCL patients, CD200 was expressed by a small minority of CD5+ cells in three subjects and totally absent in the remaining 11. We then examined CD200 expression on paraffin-embedded lymphoid tissues and bone marrow (BM) trephine biopsies from 23 B-CLL and 44 MCL patients. Again, all B-CLL cells were CD200+ both in lymph nodes and in BM while all MCL cells were negative. Adding CD200 in routine panels could be of diagnostic utility in excluding MCL diagnosis.


Assuntos
Antígenos CD/metabolismo , Leucemia Linfocítica Crônica de Células B/diagnóstico , Linfoma de Célula do Manto/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/imunologia , Linfoma de Célula do Manto/imunologia , Masculino , Pessoa de Meia-Idade
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