Proliferative fasciitis (PF) is a pseudosarcomatous proliferation which typically occurs in the subcutaneous tissue and fascia. Although patients are characteristically middle‐aged people, ...occasionally PF can arise in children. Histologically, PF is characterized by a proliferation of large ganglion‐like and spindle‐shaped cells which, especially in childhood, may exhibit high mitotic activity, but no atypical mitoses. We report a case of PF in the dermis of a 13‐year‐old boy. This is the first case of PF primarily arising in the dermis. Apart from the unusual site, another intriguing finding was the presence of rare atypical mitoses, a feature which has not been previously emphasized in PF. Awareness that PF may occur in the dermis, exhibiting occasional atypical mitoses, is crucial to avoid a misdiagnosis of malignancy.
Magro G, Michal M, Alaggio R, Amore ED. Intradermal proliferative fasciitis in childhood: a potential diagnostic pitfall.
Hemolytic uremic syndrome (HUS) can be triggered by Shiga toxin producing Escherichia coli (STEC) infection or it can be defined as atypical HUS (aHUS) if it is related to uncontrolled complement ...activation. aHUS is characterized by a high incidence of recurrence after kidney transplantation, and it can also occur de novo in transplant recipients. Eculizumab is used both to prevent and to treat aHUS following kidney transplantation. In this paper, we report our centre experience and we present 4 cases of HUS in patients who underwent kidney transplantation.
This is a single-center experience about HUS development in transplanted patients.
Patient 1 with end-stage renal disease (ESRD) due to STEC-HUS undergoing kidney transplantation without prophylactic therapy with eculizumab. Patient 2 with HUS secondary to an episode of diarrhea at 8 years old. After a slow progression to ESRD, she underwent kidney transplantation and she received prophylactic therapy with eculizumab due to the presence of anti-complement factor H antibodies. Patient 3 underwent pre-emptive living donor ABO-incompatible kidney transplantation and developed HUS secondary to antibody-mediated rejection. Patient 4 developed de novo HUS 16 years after kidney transplantation without a known cause.
The correct diagnosis of HUS and the identification of the complement component alterations in case of aHUS are important parameters required to predict the risk of post-transplant recurrence of the disease. In the cases we reported, eculizumab has been found to be effective both to prevent and to treat aHUS following kidney transplantation.
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.
Abstract 949
Diffuse large B cell lymphoma (DLBCL) has a highly variable outcome, and individual risk assessment is largely based on clinical features. Gene expression profiling (GEP) stratifies ...patients into those with germinal center B-cell (GCB) and activated B-cell subtype (ABC) subtype with different prognoses. These groups have been shown to predict prognosis in patients treated with CHOP or R-CHOP. Conversely, the role of other recognized prognostic markers, such as BCL2 gene abnormalities or Bcl2 expression has been questioned in the new therapeutic era.
Materials and Methods: In 438 patients treated with R-CHOP for de novo DLBCL, we analyzed the tumors by immunohistochemistry for Bcl2 protein expression and by interphase fluorescence in situ hybridization (FISH) for BCL2 translocation and other abnormalities. All cases were successfully studied by GEP. The cutoff for Bcl2 protein expression, 60%, used as prognostic factor was determined using receiver operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were assessed.
The t(14;18)(q32;q21) was detected in 82 cases (18.7%) and BCL2 gains occurred in 63 cases (14.3%). Both t(14;18) and BCL2 gains strongly correlated with higher levels of Bcl2 protein expression (p<0.0001 for both). Presence of t(14;18) was associated with the GCB subtype (p<0.0001), whereas BCL2 gains were associated with the ABC subtype (p=0.004). BCL2 gains were not predictive of PFS in any patients’ subgroups. Conversely, within the GCB subtype, patients with the t(14;18) displayed a significantly worse outcome compared to GCB patients without t(14;18) with a 5-year PFS of 45% vs 68%, respectively (p<0.0001). Outcome of patients with DLBCL associated with t(14;18) was similar to patients with the ABC subtype (45% vs 48%, p=0.30, Figure 1). No impact of the t(14;18) and BCL2 gains was observed on patients with ABC-DLBCL. Using immunohistochemistry, patients with Bcl2 positive (>60%) tumors had significantly inferior PFS in the GCB subgroup (p=0.03), but not in the ABC subgroup (p=0.54). Multivariate analysis revealed that the presence of the t(14;18), but not Bcl2 protein expression, was independent of the International Prognostic Index in predicting outcome of our patients.
Patients with the GCB subtype and t(14;18) exhibit a significantly worse prognosis than patients without t(14;18) when treated with R-CHOP. The assessment of t(14;18) by FISH approach not only functions as a valuable prognosticator for individual risk estimation in GCB-DLBCL patients in addition to the established parameters, but also provides valuable result for therapeutic intervention. Display omitted
No relevant conflicts of interest to declare.
Summary Pediatric adrenocortical tumors are neoplasms that only rarely occur in pediatric patients. Their clinical behavior is often unpredictable, and the histologic criteria of malignancy used in ...adults are not always useful in children. The aim of this study was to validate the prognostic value of the pathologic criteria of Wieneke et al and to evaluate the potential prognostic expression of matrix metalloproteinase 2 and human leucocyte-associated antigen (HLA) class II antigens in a series of 20 pediatric patients affected by adrenocortical tumors, who were enrolled in the Italian Pediatric Rare Tumor (TREP) Study between 2000 and 2007. The age range was 0 to 17.5 years (mean, 7.28 years) with a male-female ratio of 1:2. The mean follow-up was 64.4 months. The histologic diagnoses were reviewed, and the cases were classified using the criteria for malignancy proposed by Wieneke et al. The immunohistochemical expression of matrix metalloproteinase 2 and HLA class II antigens was scored by semiquantitative analysis and compared with the clinicopathologic parameters and outcome. Based on the scoring system of Wieneke et al, 7 tumors were classified as malignant; 12 tumors, as benign; and only 1 tumor, with “unpredictable behavior.” In all cases, the clinical behavior was consistent with the pathologic criteria of Wieneke et al. Notably, areas of regressive myxoid changes, not included among the criteria of Wieneke et al, were observed in all but 1 case of malignant tumors and only in 2 cases of benign tumors. Matrix metalloproteinase 2 was focally to diffusely expressed in all malignant and in most benign tumors. HLA class II antigens immunoreactivity was absent in all benign tumors and restricted to rare isolated cells in most malignant tumors. Our findings confirm that the pathologic scoring system of Wieneke et al is a simple and reproducible diagnostic tool to predict prognosis in pediatric adrenocortical tumors. Unlike in their adult counterpart, the expression of matrix metalloproteinase 2 or the loss of HLA class II antigens does not discriminate between benign and malignant tumors in children. Although pediatric adrenocortical tumors seem to be similar histologically to their adult counterparts, it is likely that they have distinctive molecular features.
The European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) was established 25 years ago with the goal to facilitate clinical trials and research collaborations in the field both within ...Europe and worldwide. Since its inception, much progress has been made whereby major improvements in outcomes have been achieved. In this Review, we describe the different diagnostic entities of non-Hodgkin lymphoma in children and young adults describing key features of each entity and outlining clinical achievements made in the context of the EICNHL framework. Furthermore, we provide an overview of advances in biopathology with an emphasis on the role of biological studies and how they have shaped available treatments. Finally, for each entity, we describe future goals, upcoming clinical trials, and highlight areas of research that require our focus going forward.
Six cases of intestinal ganglioneuromatosis (GN) included in this study reveal the occurrence of two morphologic patterns. Transmural GN was characterized by neural hyperplasia in all layers of the ...bowel wall with predominant involvement of the myenteric plexus. It was found in three patients affected by multiple endocrine neoplasia IIb. Mucosal GN, having predominant involvement of the mucosa without concomitant hyperplasia of the myenteric plexus, was associated with von Recklinghausen's disease, adenocarcinoma of the colon, and multiple adenomas with megacolon in one case each. Clinicopathologic correlations and review of the literature suggest that mucosal GN might represent a distinct entity with a lower morbidity rate than the transmural variant. Immunohistochemical stains reveal considerable heterogeneity. S-100 protein, neuron-specific enolase, and synapto-physin immunostaining followed the distribution of the nervous hyperplasia in the different intestinal layers as identified morphologically and allowed precise determination of the proliferating cells. Increased reactivity for vasoactive intestinal polypeptide, opioid peptides leu-enkephalin and met-enkephalin, and substance P was present in all cases with transmural involvement; mucosal GN showed normal reactivity for opioid peptides and focal increased staining for substance P (one case) and vasoactive intestinal polypeptide (two cases) in the lamina propria. Mild increased immunoreactivity for tyrosine hydroxylase was present in the myenteric plexus of four out of four cases. Histochemical determination of acetylcholinesterase, performed in one case of transmural type, demonstrated hyperplasia of parasympathetic fibers and neurons. Electron microscopic study of another case suggested the presence of several neurotransmitters. These results indicate that the physiopathology of GN is related to a complex hyperplasia of several peptidergic, cholinergic, and probably adrenergic nerve fibers instead of a selective overgrowth of one type of nerve fiber.
Malignant peripheral nerve sheath tumors (MPNSTs) are distinguished from a control group of typical benign schwannomas and neurofibromas on the basis of a set of quantitatively evaluated parameters, ...i.e., the cell density; the number of mitoses and apoptotic bodies; the nuclear area and shape; the number and absolute and relative areas of silver-staining nucleolar organizer regions; necrosis; and angiogenesis. Only the extent of tumor necrosis, the mitotic rate, and the parameters related to silver-staining nucleolar organizer regions discriminate between less aggressive MPNSTs (disease-free patients after 4 years of follow-up) and more aggressive MPNSTs (with recurrences or metastases during the first 4 years of follow-up).
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