Thrombopoietin receptor agonists increase splenic regulatory T-cell numbers in immune thrombocytopenia.

Thrombopoietin receptor agonists (TPO-RA) are a valid therapy for immune thrombocytopenia (ITP), due to megakaryocyte stimulation and (poorly characterised) immune-modulatory effects. The spleen is pivotal in the pathogenesis of ITP, yet little is known on its immune microenvironment and on effects of TPO-RA on this organ. To address these topics, we analysed 35 spleens removed for primary refractory ITP. Pre-splenectomy TPO-RA administration correlated with increased splenic regulatory T cells (Tregs), type 2 T-helper cells and histiocyte density and with reduced red pulp sinusoids. Surgical outcome was not associated with TPO-RA administration, other pre-splenectomy therapies and/or Treg density. In conclusion, TPO-RA affect the splenic microenvironment, but this has no impact on splenectomy outcome.

Intraoperative examination (IOE) in pediatric extracranial tumors.

BACKGROUND AND OBJECTIVES: Intraoperative evaluation of surgical specimens by frozen sections (IOE) is required to distinguish benign and malignant lesions, assess surgical margins, and determine sample adequacy of biopsies. In the last years, it has been used also for therapeutic decisions, particularly in children, who may need other ancillary procedures, in case of malignancies. Our purpose was the evaluation of diagnostic accuracy, limits, and different role of IOE in pediatric pathology. PATIENTS AND METHODS: From 1990 to 2001, 416 IOEs were performed in 341 children, affected by lymph node pathology, soft tissue tumors, neuroblastic tumors, gonadal germ cell, and stromal tumors, hepatic lesions, renal tumors, and others; the technique was also used to assess surgical margins during major surgeries. IOEs were obtained from Tru-cut biopsies (<1 cm(3)), wide biopsies (>1 cm(3)), or from the whole lesions, and the subsequent final diagnoses were classified as conordant, discordant, and deferred. RESULTS: Three hundred seventy cases (88.9%) were concordant, 10 (2.4%) discordant, and 36 (8.6%) deferred. The disagreement was found in two small lymph node samples, three soft tissue tumors, one hepatoblastoma, one metastasis, and three surgical margins. The deferred diagnoses were related to lymph node and soft tissue lesions. CONCLUSIONS: IOE in pediatric oncology may integrate the diagnostic process and supports the therapeutic guidelines of different tumors. In our study, the diagnostic concordance was satisfactory. A rational use of the technique and the awareness of its limits are, however, prerequisites to avoid the risk of overtreatment.

Pancreatoblastoma in an adult patient. A case report.

CONTEXT: Preoperative diagnosis of a pancreatoblastoma in adults is challenging because of its rarity. Furthermore, difficulties increase since pancreatoblastomas share radiological findings similar to those found in other masses of the pancreas. CASE REPORT: A 36-year-old woman was studied with ultrasonography and CT for a mass of the pancreatic head causing obstructive jaundice. Diagnosis of pancreatoblastoma was obtained with histology and immunohistochemistry of the resected specimen. CONCLUSION: We reviewed the radiological findings of pancreatoblastomas and possible radiological criteria of differentiation from other pancreatic tumors. A pancreatoblastoma should be considered in the differential diagnosis of a pancreatic mass presenting atypical radiological features.

Three cases of pancreatic serous cystadenoma and endocrine tumour.

AIMS: To report three cases of serous cystadenoma and endocrine tumour in the same pancreas, to review the literature and to evaluate the clinicopathological features of the tumours. CASES: Three women (71, 57 and 31 years old) were admitted to hospital, two for diseases unrelated to the pancreas and the third for increasing obstructive jaundice in von Hippel-Lindau disease. Preoperative examination showed two distinct lesions in the first patient and only cystic lesions in the other two. RESULTS: Histological examination of the pancreas showed one serous oligocystic adenoma associated with a benign, well-differentiated endocrine tumour, one serous oligocystic adenoma associated with an endocrine microadenoma, and a von Hippel-Lindau-related cystic neoplasm with a well-differentiated endocrine carcinoma. CONCLUSIONS: Serous cystadenoma associated with endocrine tumour shows some clinicopathological differences with respect to the two tumours considered separately, and with respect to von Hippel-Lindau-related cases, although there is no convincing evidence at present to justify considering this association as a separate entity.

HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma.

In this study, we tested whether polymorphisms in human leukocyte antigen G (HLA-G) were associated with event-free survival (EFS) in pediatric Hodgkin's lymphoma (HL). We evaluated the association of HLA-G 3'-UTR polymorphisms with EFS in 113 pediatric HL patients treated using the AIEOP LH-2004 protocol. Patients with the +3027-C/A genotype (rs17179101, UTR-7 haplotype) showed lower EFS than those with the +3027-C/C genotype (HR= 3.23, 95%CI: 0.99-10.54, P=0.012). Female patients and systemic B symptomatic patients with the HLA-G +3027 polymorphism showed lower EFS. Multivariate analysis showed that the +3027-A polymorphism (HR 3.17, 95%CI 1.16-8.66, P=0.025) was an independent prognostic factor. Immunohistochemical analysis showed that HL cells from patients with the +3027-C/A genotype did not express HLA-G. Moreover, HLA-G +3027 polymorphism improved EFS prediction when added to the algorithm for therapeutic group classification of pediatric HL patients. Our findings suggest HLA-G +3027 polymorphism is a prognostic marker in pediatric HL patients undergoing treatment according to LH-2004 protocol.

STAT3 pathway is activated in ALK-positive large B-cell lymphoma carrying SQSTM1-ALK rearrangement and provides a possible therapeutic target.

ALK-positive large B-cell lymphomas usually harbor clathrin (CLTC)-ALK rearrangement or, more rarely, nucleophosmin (NPM)-ALK fusion gene. Here we report a large B-cell lymphoma with a peculiar pattern of diffuse and cytoplasmic immunohistochemical staining and carrying sequestosome 1 (SQSTM1)-ALK rearrangement, identified by reverse transcription polymerase chain reaction analysis and Rapid Amplification of cDNA Ends analysis and confirmed by fluorescence in situ hybridization with specific dual-color fusion probes. The gene fusion product and the transcription factor STAT3 are both phosphorylated, and thereby the pathogenetic mechanism of this case shows important analogies with that of NPM-ALK and CLTC-ALK lymphomas, in which STAT3 plays a central role in the lymphomagenesis. Consequently, STAT3 inhibition provides a possible therapeutic target also for lymphomas with SQSTM1-ALK variant translocation.