A case of reactive granulomatous dermatitis associated with neonatal lupus erythematosus

Neonatal lupus erythematosus (NLE) is an uncommon disorder affecting approximately one out of 20 000 live births in the United States. Common manifestations of NLE include cutaneous eruptions and cardiac involvement. The typical rash of NLE most closely resembles the rash of subacute cutaneous lupus erythematosus both clinically and histopathologically. We present a case of reactive granulomatous dermatitis (RGD) associated with NLE in a 3-month-old male in whom the initial histopathology and immunohistochemistry were concerning for hematologic malignancy. RGD is a unifying term used to describe cutaneous granulomatous eruptions that occur in response to a variety of stimuli, including autoimmune connective tissue diseases. Our case demonstrates the range of histopathological findings that may be present in the setting of NLE

Aurora-A and Polo-Like Kinases are Important Diagnostic and Therapeutic Markers in Hodgkin Lymphoma and Mimics

Background: Aurora-A (AA) and Polo-like kinases (PLK) are mitotic kinases that regulate the G2/M phase of the cell cycle. It has been demonstrated that AA acts as an upstream regulator of PLK, mediating its phosphorylation in the presence of a cofactor named Bora. PLK is activated by AA to promote checkpoint recovery in mitosis. AA and PLK are implicated in the tumorigenesis of solid tumors, and, recently, in B- and T-cell non Hodgkin lymphomas (NHL). They play a key role in tumor proliferation and disease progression in highly aggressive B-cell NHL. They also serve as indicators of disease activity and are thus attractive potential therapeutic targets. Expression of AA and/or PLK has not yet been assessed in Classic Hodgkin Lymphoma (CHL) and its mimics. This study assesses AA and PLK expression in different CHL types, such as nodular sclerosis type, mixed cellularity type, and lymphocyte rich type, and their mimics: nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal B-cell lymphoma (PMBL).Design:We assessed 27 CHL cases, 16 NLPHL cases, and 8 PMBL cases for AA and PLK expression by immunohistochemistry. CHL cases included the following: 8 mixed cellularity CHL, 1 lymphocyte rich CHL, and 18 nodular sclerosis CHL. A mouse monoclonal AA-antibody (1:1000 dilution, Abcam, UK) and a PLK-antibody (1:500 dilution, Cell Signaling Technologies, USA) were used. Each case was semi-quantitatively graded for percentage of positive cells (\u3c50% vs. \u3e50%), for staining intensity (1-3+), and for localization (nuclear vs. cytoplasmic). Immunohistochemical analysis was performed independently by 2 pathologists (KMH and KVI). Statistical analysis was performed using Fisher\u27s exact test.Results:AA was expressed in 100% of CHL and NLPHL cases. AA stained predominantly cytoplasm of tumor cells in both NLPHL and CHL. PLK was expressed in 100% of NLPHL and 96% of CHL cases (1 mixed cellularity type CHL did not stain for PLK). PLK showed both nuclear and cytoplasmic staining for both NLPHL and CHL. In contrast, only 37% of PMBL cases were positive for AA and PLK (Table 1). In the CHL group, cases with more than 50% of tumor cells expressing PLK tended to present with higher stage and extranodal disease. In the NLPHL group, PLK correlated with higher stage (III-IV) disease at presentation (p=0.044). No statistically significant differences were found in either intensity or localization of AA or PLK within or between NLPHL and CHL cohorts.Aurora-A PositiveAurora-A NegativePLK PositivePLK NegativeClassic Hodgkin Lymphoma270261Nodular Lymphocyte Predominant Hodgkin Lymphoma160160Primary Mediastinal B-cell Lymphoma3535Table 1. AA and PLK positivity in CHL, NLPHL, and PMBL.AA was expressed in CHL but not PMBL (p=0.0002)PLK was expressed in CHL but not PMBL (p=0.0009)AA was expressed in NLPHL but not PMBL (p=0.0013)PLK was expressed in NLPHL but not PMBL (p=0.0013). Conclusion: AA and PLK are commonly expressed in CHL and NLPHL but not in PMBL. Thus, they are useful markers in the distinction of CHL or NLPHL from PMBL. PLK is a useful marker for the prognostication of NLPHL. AA and PLK are attractive potential therapeutic targets in the treatment of CHL and NLPHL. Additional studies are underway to characterize an array of hematopoietic lesions known to overlap with CHL.https://scholarlycommons.henryford.com/merf2019clinres/1027/thumbnail.jp

De novo CD5+ diffuse large B-cell lymphoma: Adverse outcomes with and without stem cell transplantation in a large, multicenter, rituximab treated cohort: CD5 positivity affects DLBCL outcome

De novo CD5+ diffuse large B-cell lymphomas (DLBCL) are a distinct subgroup of DLBCL with poor prognosis. However the role of rituximab-containing therapy and salvage stem cell transplantation in this patients’ population remain to be defined. We retrospectively reviewed clinical features and outcomes of 102 patients with de novo CD5+ DLBCL treated with rituximab-containing therapy at 9 different institutions. By Hans’ criteria, 64 patients had activated B-cell (ABC) subtype, 24 germinal center B-cell (GCB) subtype, and 14 were not evaluated. No patients had a myc translocation. Eighty-three patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), 7 with rituximab, etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone (R-EPOCH) and 6 with R-CHOP with methotrexate, 3 g/m2. The overall response rate to frontline therapy was 85%. The 3-year progression free survival (PFS) and overall survival (OS) for all patients were 40% and 65%, respectively. The 3-year PFS for ABC- and GCB-subtypes was 34% and 45%, respectively. The 3-year OS for ABC- and GCB-subtypes was 62% and 67%, respectively. The median time to second treatment failure was 3 months and 1 month for ABC- and GCB-subtypes, respectively. Twenty of 28 (71%) transplanted patients with autologous, allogeneic, or both, relapsed. This study confirms the poor prognosis of de novo CD5+ DLBCL in a large multi-center cohort despite initial rituximab-containing chemotherapy and suggests that stem cell transplantation fails to salvage the majority of these patients. Approaches to prevent recurrence and/or novel therapies for relapsed disease are needed for this subgroup of DLBCL patients

Review Article - Tissue microarrays: Potential in the Indian subcontinent

Tissue microarrays (TMAs) are a means of combining hundreds of specimens of tissue on to a single slide for analysis simultaneously. The evolution of this technology to validate the results of cDNA microarrays has impacted tremendously in accurately identifying prognostic indicators significant in determining survival demographics for patients. TMAs can be generated from archival paraffin blocks, combined with sophisticated image analysis software for reading TMA immunohistochemistry, and a staggering amount of useful information can be generated in terms of the biomarkers useful in predicting patient outcome. There is a wide range of uses for the TMA technology including profiling of specific proteins in cancerous tissues and non-cancerous tissues. Given the wide variety of tissue resources available in India, investment in a dedicated TMA facility will be of immense use in the research arena in India. This review article discusses the basics of TMA construction, design, the software available for the analysis of this technology and its relevance to Indian scientists. A potential workflow structure for setting up a TMA facility is also included

Review Article - Tissue microarrays: Potential in the Indian subcontinent

Tissue microarrays (TMAs) are a means of combining hundreds of specimens of tissue on to a single slide for analysis simultaneously. The evolution of this technology to validate the results of cDNA microarrays has impacted tremendously in accurately identifying prognostic indicators significant in determining survival demographics for patients. TMAs can be generated from archival paraffin blocks, combined with sophisticated image analysis software for reading TMA immunohistochemistry, and a staggering amount of useful information can be generated in terms of the biomarkers useful in predicting patient outcome. There is a wide range of uses for the TMA technology including profiling of specific proteins in cancerous tissues and non-cancerous tissues. Given the wide variety of tissue resources available in India, investment in a dedicated TMA facility will be of immense use in the research arena in India. This review article discusses the basics of TMA construction, design, the software available for the analysis of this technology and its relevance to Indian scientists. A potential workflow structure for setting up a TMA facility is also included

Current status of prognostication in classical Hodgkin lymphoma

Classical Hodgkin lymphoma (cHL) is characterized by a paucity of neoplastic Hodgkin/Reed Sternberg (HRS) cells within a complex cellular milieu that is rendered immunologically incapable of reacting against CD30(+)HRS cells due to a plethora of immune escape mechanisms initiated by the neoplastic cells. Accounting for 25% of all lymphomas and nearly 95% of all Hodgkin lymphomas, patients with cHL are typically young adults. Besides traditional prognostic factors, such as the International Prognostic Index (IPI), newer imaging and ancillary biomarkers (CD68, Galectin-1 and plasma microRNA) have shown promise. Furthermore, the evolution of gene expression profiling (GEP) in recent years has enabled the development of several practically feasible GEP-based predictors with prognostic relevance. This review discusses the current status of clinical prognostication in cHL, the critical role of histological evaluation in light of several mimicking entities, and the relevance of tissue as well as serum biomarkers pertaining to immune escape mechanisms and recent GEP studies

A case of dual-mechanism immune-related anaemia in a patient with metastatic melanoma treated with nivolumab and ipilimumab

BackgroundThe combination of the immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab is a mainstay of treatment for selected patients with metastatic melanoma. This combination also results in more frequent immune-related adverse events (irAEs) than either ICI alone. These irAEs can be severe and their pathogenesis is poorly understood.Case presentationWe report a case of a woman with metastatic melanoma, treated with combined ipilimumab and nivolumab, who developed severe anaemia. While initial workup revealed autoimmune haemolytic anaemia, the anaemia persisted despite corticosteroids and paradoxical reticulocytopenia was observed. Bone marrow biopsy demonstrated a CD8+ T cell-mediated destruction of the red cell precursors implying concurrent pure red cell aplasia. Both processes resolved after the addition of cyclosporine A.ConclusionsThis report describes a rare case of two concurrent mechanisms of haematological irAE in a patient treated with combined ICI therapy. Successful treatment resulted only after the second underlying mechanism of toxicity was uncovered. Prompt recognition of these unusual presentations of rare irAEs is now key to effective irAE management