Ellen McPhail - Academia.edu (original) (raw)

Papers by Ellen McPhail

Journal of Clinical Pathology, Sep 1, 2009

This report describes an unusual case of cyclin D1 expression by an otherwise typical follicular ... more This report describes an unusual case of cyclin D1 expression by an otherwise typical follicular lymphoma, of low histological grade. BCL2-IGH and CCND1-IGH fusions were identified by interphase fluorescence in situ hybridisation.

Retinal Cases & Brief Reports, Feb 3, 2022

Purpose: The purpose of this study was to describe an exceedingly rare presentation of secondary ... more Purpose: The purpose of this study was to describe an exceedingly rare presentation of secondary vitreoretinal involvement by the uncommon entity “indolent T-cell lymphoproliferative disorder of the gastrointestinal tract” and illustrate the utility of fluorescence in situ hybridization for diagnosis. Methods: This is a case report. Results: A 57-year-old woman with presumed iritis on chronic topical prednisolone acetate presented with increased vitreous opacities in the right eye. She had a history of biopsy-confirmed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract involving the stomach and duodenum, JAK2-rearrangement positive, controlled on maintenance oral methotrexate. Vitreous biopsy was unremarkable with small CD3-positive and CD4-positive and CD20-negative lymphocytes, along with histiocytes and fibroblasts. Immunostains showed CD4 positivity, and fluorescence in situ hybridization revealed a JAK2 gene rearrangement, consistent with the patient's previously diagnosed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Intravitreal methotrexate injections were started in the right eye. MRI of the brain and lumbar puncture with cytology, MYD88, IL10, and flow cytometry performed at the time of right eye vitreoretinal lymphoma diagnosis revealed no evidence of central nervous system lymphoma, but subsequent bone marrow biopsy demonstrated 5% involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, JAK2-rearrangement positive, with a lung nodule on PET computed tomography. She returned 4 months later with fatigue, night sweats, and blurry vision in the left eye with vitreous and anterior chamber cellular infiltration and retinal vasculitis. Conclusion: T-cell vitreoretinal lymphoma is rare, and diagnosis can be challenging. Despite inconclusive cytology in this case, interphase fluorescence in situ hybridization detected a JAK2 gene rearrangement, which confirmed the involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and prompted appropriate treatment and workup for recurrent systemic or central nervous system lymphoma.

Frontiers in Oncology, Jul 20, 2023

Blood, Dec 2, 2016

Background: B-cell lymphomas with a MYC/8q24 rearrangement coupled with translocations involving ... more Background: B-cell lymphomas with a MYC/8q24 rearrangement coupled with translocations involving BCL2 and/or BCL6, often referred to as double hit or triple hit (DH/TH) lymphomas, typically have an aggressive clinical course. A new WHO subtype, "high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements", has been established for this entity (Swerdlow et al. Blood; 127: 2375-2390, 2016). Herein we report the treatment and outcomes of DH/TH patients at our institution. Materials and Methods: Cases were identified through the Mayo Clinic Lymphoma Database, University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), and the Mayo Clinic Cytogenetics Laboratory. Interphase FISH was performed clinically on either paraffin sections of the tissue specimens or on smears of the bone marrow aspirate specimens using break-apart probes for MYC and BCL6, dual fusion probes for IGH/MYC, IGL/MYC, and IGK/MYC, and either a BCL2 break-apart probe or an IGH/BCL2 dual fusion probe. Consensus pathology re-review was performed to define morphology as diffuse large B-cell lymphoma (DLBCL) vs. high-grade B-cell lymphoma (HGBCL). Patients with de-novo DH/TH or diagnosis of DH/TH at the time of transformation of a previously diagnosed low-grade lymphoma and who were treated with anthracycline-based chemotherapy were included in this analysis. Patients with DH/TH first identified at the time of recurrent aggressive B-cell lymphoma were excluded. Overall survival (OS) was defined as time from DH/TH diagnosis to death from any cause. EFS12 was defined as event-free status 12 months from diagnosis of DH/TH. Results: Clinical outcome analysis was performed on 71 patients (Table 1). The median age was 61 years (range 29-82). 60 patients had de-novo DH/TH and 11 patients had transformation of a previously diagnosed low-grade lymphoma. In 65 cases in which there was consensus morphology on pathology re-review, there were 39 (60%) with HGBCL morphology and 26 (40%) with DLBCL morphology. At a median follow-up of 21 months (range 1-87), the event free survival at 12 months was 43%, and the median overall survival (OS) was 22 months (95% CI: 13-NA). The OS at 5 years was 48% (95% CI: 36%-63%). Patients with DH/TH at transformation of previously diagnosed low-grade lymphoma had a very poor outcome (median OS=10.8 months, EFS12 = 10%), which was inferior to patients with de-novo DH/TH (P=0.0069). When compared to all other therapies, patients treated with R-CODOX-M/IVAC had better EFS12 (p=0.03) with a trend in improved OS (p=0.08) though this may be confounded by patient selection bias as these patients were significantly younger (p=0.0001) than patients treated with other anthracycline based regimens (table 1). Conclusion: In "high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements", induction failure occurs early. Although transformation to DH/TH from previously diagnosed low-grade lymphoma is associated with a particularly poor outcome, the overall survival for the entire cohort at 5 years was 48%, suggesting long-term cures in a subset of patients. Treatment with R-CODOX-M/IVAC may result in superior outcomes in patients less than 60 years of age. Table 1 Table 1. Figure Figure. Disclosures Ansell: BMS, Seattle Genetics, Merck, Celldex and Affimed: Research Funding. Nowakowski:Celgene: Research Funding; Morphosys: Research Funding; Bayer: Consultancy, Research Funding.

Mayo Clinic Proceedings, May 1, 2021

Kidney International, Feb 1, 2022

Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of a... more Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of amyloid A originating from serum amyloid A proteins with the kidneys being the most commonly and earliest affected organ. Previously described amyloid A amyloidosis is linked to increased production and deposition of serum amyloid A proteins secondary to inflammatory conditions arising from infectious, metabolic, or genetic causes. Here we describe a family with primary amyloid A amyloidosis due to a chr11:18287683 T>C (human genome version19) mutation in the SAA1 promoter linked to the amyloidogenic SAA1.1 haplotype. This condition leads to a doubling of the basal SAA1 promoter activity and sustained elevation of serum amyloid A levels that segregated in an autosomal dominant pattern in 12 genetically affected and in none of six genetically unaffected relatives, yielding a statistically significant logarithm of odds (LOD) score over 5. Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed specifically of the SAA1.1 isoform. Tocilizumab (a monoclonal antibody against the interleukin-6 receptor) had a beneficial effect when prescribed early in the disease course. Idiopathic forms represent a significant and increasing proportion (15-20%) of all diagnosed cases of amyloid A amyloidosis. Thus, genetic screening of the SAA1 promoter should be pursued in individuals with amyloid A amyloidosis and no systemic inflammation, especially if there is a positive family history.

American Journal of Clinical Pathology, May 18, 2023

Objectives There is a paucity of data on penile amyloidosis. We aimed to assess the frequency of ... more Objectives There is a paucity of data on penile amyloidosis. We aimed to assess the frequency of different amyloid types in surgical specimens from the penis involved by amyloidosis and correlate relevant clinicopathologic parameters with proteomic findings. Methods Since 2008, our reference laboratory has performed liquid chromatography/tandem mass spectrometry (LC-MS/MS) for amyloid typing. The institutional pathology archive and reference laboratory database were queried to retrospectively identify all penile surgical pathology specimens with LC-MS/MS results between January 1, 2008, and November 23, 2022. Archived H&E-stained and Congo red–stained sections were re-reviewed. Results Twelve cases of penile amyloidosis were identified, which represented 0.35% (n = 3,456) of penile surgical specimens. AL-type amyloid was most frequent (n = 7), followed by keratin-type amyloid (n = 3) and ATTR (transthyretin)–type amyloid (n = 2). AL-type amyloid cases often showed diffuse dermal/lamina propria deposition, whereas all keratin-type amyloid cases were localized to the superficial dermis. Two cases with keratin-type amyloid had concomitant cutaneous findings (penile intraepithelial neoplasia and condyloma). Conclusions This series, the largest to date, demonstrates that penile amyloidosis has a heterogeneous proteomic landscape. To the best of our knowledge, this is the first study describing ATTR (transthyretin)–type penile amyloid.

American Journal of Clinical Pathology, Oct 1, 2021

Human Pathology, Mar 1, 2022

LEF1 (lymphocyte enhancer binding factor 1) and SOX11 (SRY-Box 11) are highly sensitive and speci... more LEF1 (lymphocyte enhancer binding factor 1) and SOX11 (SRY-Box 11) are highly sensitive and specific for chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/ SLL) and mantle cell lymphoma (MCL) including the cyclin D1-negative subtype, respectively. We assessed the utility of these markers in a large cohort of small B cell lymphomas (SBCLs) on varied sample types. Immunohistochemistry (IHC) was performed for LEF1 and SOX11 on 354 SBCLs (129 CLL/ SLL, 33 MCL, 142 marginal zone lymphomas (MZL): nodal MZL (NMZL)-40, extranodal MZL (ENMZL)-28, splenic MZL (SMZL)-74 cases and 50 lymphoplasmacytic lymphomas/ Waldenstrom macroglobulinemias (LPL/ WM). 98% of CLL/ SLLs were LEF1 positive. SOX11 showed good sensitivity (82%) and excellent specificity for MCL (99%), with only 2 of 142 MZLs (both SMZLs) showing SOX11 expression. The low sensitivity for SOX11 was on account of inclusion of 4 non-nodal cases. All 50 LPL/ WM were negative for both LEF1 and SOX11. The expression of SOX11 and LEF1 was not always mutually exclusive, as 2 confirmed MCLs expressed both markers. LEF1 and SOX11 have excellent utility as diagnostic markers especially for atypical CD5-positive SBCLs.

Neurology Genetics, Aug 14, 2019

American Journal of Clinical Pathology, Jan 21, 2016

Mayo Clinic Proceedings, Jun 1, 2021

Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder leading to progressi... more Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder leading to progressive and life-threatening organ failure. The heart and the kidneys are the most commonly involved organs, but almost any organ can be involved. Because of the nonspecific presentation, diagnosis delay is common, and many patients are diagnosed with advanced organ failure. In the era of effective therapies and improved outcomes for patients with AL amyloidosis, the importance of early recognition is further enhanced as the ability to reverse organ dysfunction is limited in those with a profound organ failure. As AL amyloidosis is an uncommon disorder and given patients' frailty and high early death rate, management of this complex condition is challenging. The treatment of AL amyloidosis is based on various anti-plasma cell therapies. These therapies are borrowed and customized from the treatment of multiple myeloma, a more common disorder. However, a growing number of phase 2/3 studies dedicated to the AL amyloidosis population are being performed, making treatment decisions more evidence-based. Supportive care is an integral part of management of AL amyloidosis because of the inherent organ dysfunction, limiting the delivery of effective therapy. This extensive review brings an updated summary on the management of AL amyloidosis, sectioned into the 3 pillars for survival improvement: early disease recognition, anti-plasma cell therapy, and supportive care.

Haematologica, Dec 6, 2018

Mayo Clinic Proceedings, Sep 1, 2020

Human Pathology, Jul 1, 2022

Lymphoid enhancer-binding factor 1 (LEF1) is a transcription factor involved in T-cell maturation... more Lymphoid enhancer-binding factor 1 (LEF1) is a transcription factor involved in T-cell maturation and is usually absent in mature B-cells. Previous studies have shown aberrant LEF1 expression as a sensitive and specific marker in chronic lymphocytic leukemia/small lymphocytic lymphoma. Our primary aims were i) to analyze LEF1 expression in classic Hodgkin lymphomas (CHL) including de novo and Richter syndrome (RS), and to assess if LEF1 can be a surrogate marker to assess clonal relationship in RS, and ii) to compare LEF1 expression in CHL and Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). We included 117 patients: 24 CHL-RS, 66 CHL-de novo and 27 NLPHL. There was no significant difference in LEF1 expression between CHL-RS and CHL-de novo (79.2% vs 87.9%, P = 0.299), or in type I and type II CHL-RS (75% vs 81.3%, P = 1.000). However, CHL showed a significantly higher LEF1 expression compared to NLPHL (85.6% vs 44.4%, P<0.0001). As the Wnt/β-catenin pathway directly regulates LEF1 expression in a β-catenin-dependent way, β-catenin expression was assessed in 76 cases and all were negative. Additionally, no association between EBV-positivity and LEF1-expression was detected. Overall, our findings show high LEF1 expression in CHL, regardless of RS or de novo, indicating LEF1 cannot be utilized as a surrogate marker to suggest clonal relationship in RS. Compared with CHL, LEF1 expression is significantly less common in NLPHL, further attesting that they are biologically distinct entities. The absent β-catenin expression suggests LEF1 expression is independent of Wnt/β-catenin signaling pathway in Hodgkin lymphomas.

Hematological Oncology, Mar 21, 2023

Kidney International, Oct 1, 2022

Kidney International Reports, Apr 1, 2021