IgG4-related disease with multiorgan involvement: a case-based review.

IgG4-related disease (IgG4-RD) is an immune-mediated multi-organ inflammatory disorder caused by tissue infiltration of lymphocytes with IgG4-secreting plasma cells. Herein, we discuss a case of a patient with IgG4-RD who had involvement of multiple organs: the kidneys, lymph nodes, bone marrow (biopsy performed), lungs, liver, and small intestine (imaging abnormalities). Although several case reports and series of IgG4-RD involving different organ involvement are in the literature, our patient has extensive simultaneous multi-organ involvement. We utilized the four domains (serologic, pathologic, radiologic, and pathologic) as discussed in the new 2019 ACR/EULAR classification criteria to provide a useful framework in considering an alternative tool for IgG4-RD in multi-organ involvement, where biopsy is more invasive and not always accessible. We highlight the findings of each organ involved that increase the likelihood that the patient has IgG4-RD. In our patient, the IgG4-RD classification criteria was fulfilled with total points adding up to 48. Our case meets the classification criteria for IgG4-RD, since at least one organ is involved to meet entry criteria (biopsy proven), no exclusion criteria are present, and the total points are ≥ 20. When such extensive involvement of IgG4-RD occurs, early diagnosis and treatment are recommended to avoid irreversible organ damage and better outcomes.

A Rare, Yet Treatable Pancreatic Tumor: Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma.

BACKGROUND Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of B-cell neoplasm that can have diverse presentations. When it involves the pancreas (i.e., pancreatic lymphoma), it can mimic metastatic pancreatic adenocarcinoma. Pancreatic lymphoma and adenocarcinoma often have similar clinical, laboratory, and radiographic features making the distinction challenging without pathological tissue examination. The differentiation of these 2 entities is important as the prognosis of pancreatic lymphoma is certainly more favorable with a chance of cure with chemoimmunotherapy. CASE REPORT We present an unusual case of EBV-positive DLBCL involving the pancreas that was initially believed to be metastatic pancreatic adenocarcinoma. The patient was treated with chemoimmunotherapy and had a remarkable response. This is the first known case of EBV-positive DLBCL involving the pancreas that was successfully treated with chemoimmunotherapy. CONCLUSIONS EBV-positive DLBCL can have diverse presentations, including a pancreatic mass with multi-organ involvement, which mimics metastatic pancreatic adenocarcinoma. The prognosis of EBV-positive DLBCL is thought to be worse than that of EBV-negative tumors. However, it remains certainly superior to that of its adenocarcinoma counterpart with conventional chemoimmunotherapy.

Carpal Tunnel Injections: A Novel Approach Based on Wrist Width.

INTRODUCTION: Carpal tunnel steroid injections (CTIs) have the potential risk of damaging underlying critical structures, including the median nerve (MN), radial artery (RA), and ulnar neurovascular bundle (UB). The purpose of this study was to analyze the safety of a volar radial (VR) and volar ulnar (VU) CTI, using standardized anatomical "safe zones." MATERIALS AND METHODS: This study was performed on 87 cadaveric arms using a percentage of the total wrist width as a guide for placement of a VR (30 and 33% of total wrist width) and VU (60 and 66% of total wrist width) injection. RESULTS: Our results demonstrate a wide range of anatomic variations in the location of these critical neurovascular structures near the carpal canal, indicating that using superficial landmarks alone for CTIs may result in an increased risk of iatrogenic injury to these critical structures. DISCUSSION: We propose a technique using a percentage of total wrist width as a guide for CTIs. Both VR (30% of wrist width) and VU (60% of wrist width) CTIs offer relatively safe and reliable CTI locations to the carpal canal. LEVEL OF EVIDENCE: Not applicable/cadaveric study.

The diagnosis of adult-onset haemophagocytic lymphohistiocytosis: lessons learned from a review of 29 cases of bone marrow haemophagocytosis in two large academic institutions.

AIMS: Haemophagocytic lymphohistiocytosis (HLH) is divided into paediatric (primary) and adult (secondary) types. While paediatric-HLH has been extensively characterised, similar studies in adults are limited. This study aims to evaluate the significance of the HLH diagnostic criteria as well as other clinical parameters in adults with bone marrow evidence of haemophagocytosis. METHODS: We conducted a 10-year retrospective search of the pathology archives of two institutions for cases with bone marrow haemophagocytosis. We included those cases that fulfilled the currently established HLH diagnostic criteria. For the 29 cases that met inclusion criteria, we assessed clinical features, co-morbidities, therapy and clinical outcome. The effect of 19 clinical variables on mortality outcomes was assessed using logistic and hazard regression analyses. RESULTS: Of cases for which an aetiology could be identified, infectious diseases were the most common association (14 of 19, 74%). Fever and elevated ferritin were the most frequently available criteria used to establish HLH. The overall mortality rate was 61% despite HLH-specific therapy, which had been initiated in 48% of the cases. The remaining cases were treated with supportive therapy and antibiotics. The most statistically significant marker of mortality was an elevated absolute neutrophil count (ANC), a feature not typical of HLH. CONCLUSIONS: Since elevated ANC correlates with poor outcomes in sepsis, and not HLH, we postulate that many of the patients fulfilling HLH diagnostic criteria in this study likely had sepsis/systemic inflammatory response syndrome rather than HLH. Our results highlight the need to define HLH diagnostic criteria specific to the adult population.

Differential expression of ribosomal proteins in myelodysplastic syndromes.

Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond-Blackfan anaemia, Shwachman-Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency of RPS14 in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS. Furthermore, differences in the effects of these expression alterations among myeloid, erythroid and megakaryocyte lineages have not been well elucidated. We examined the expression of several proteins related to ribosomal biogenesis in bone marrow biopsy specimens from patients with MDS (5q minus patients excluded) and controls with no known myeloid disease. Specifically, we found that there is overexpression of RPS24, DKC1 and SBDS in MDS. This overexpression is in contrast to the haploinsufficiency identified in the congenital bone marrow failure syndromes and in acquired 5q minus MDS. Potential mechanisms for these differences and aetiology for these findings in MDS are discussed.

Diagnostic microRNAs in myelodysplastic syndrome.

OBJECTIVE: The myelodysplastic syndromes (MDS) are aging-associated disorders characterized by ineffective maturation of hematopoietic elements, which are often diagnostically challenging. This study identifies microRNAs (miRNA) and miRNA targets that might represent diagnostic markers for MDS. MATERIALS AND METHODS: This study utilized a total of 42 MDS samples and 45 controls. A discovery set of 20 frozen bone marrow mononuclear cell samples (10 MDS, 10 controls) was profiled on a custom Agilent miRNA microarray. Classifier miRNAs were validated in a separate set of 49 paraffin-embedded particle preparations by real-time polymerase chain reaction (24 MDS, 25 controls). Target prediction analysis was compared to a de novo transcriptional profile of MDS derived from the Microarray Innovations in Leukemia study. c-Myb and Sufu were further investigated by immunohistochemical stains on a set of 26 paraffin-embedded samples. RESULTS: We identified 13 miRNAs of interest from the discovery set, 8 of which proved statistically significant on real-time polymerase chain reaction verification. These eight miRNAs were then examined in an independent real-time polymerase chain reaction validation set. Notably, hsa-miR-378, hsa-miR-632, and hsa-miR-636 demonstrated particularly high discrimination between MDS and normal controls. Target prediction identified potential targets of miRNA regulation that correspond to many of the genes that characterize MDS. Immunohistochemical staining performed on a third validation set confirmed that c-Myb and Sufu are differentially expressed in MDS. CONCLUSIONS: Our data utilize both discovery and validation sets and two complementary platforms to identify miRNAs associated with MDS. We have analyzed predicted targets and identified c-Myb and Sufu as potential diagnostic markers of MDS.