Gastrointestinal amyloidosis: an often unexpected finding with systemic implications.

The gastrointestinal (GI) tract is a common site of amyloidosis, but the incidence, clinicopathologic features, and systemic implications of different types of GI amyloidosis are not well understood. GI amyloid specimens (N = 2511) typed using a proteomics-based method between 2008 and 2021 were identified. Clinical and morphologic features were reviewed in a subset of cases.

Proteomic Identification and Clinicopathologic Characterization of Splenic Amyloidosis.

The spleen is a commonly encountered specimen in surgical pathology. However, little is known about the incidence, morphologic pattern, and clinical features of spleens involved by amyloidosis. We retrospectively identified 69 spleen amyloid cases typed using a proteomics-based method between 2008 and 2020.

Aberrant expression of lymphoid enhancer-binding factor 1 in Hodgkin lymphoma.

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 (CHLs), 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).

Bone marrow amyloid: a comprehensive analysis of 1,469 samples, including amyloid type, clinical features, and morphologic distribution.

Background: Bone marrow biopsy is common in patients suspected of having systemic AL amyloidosis. However, little is known about the incidence, morphology and clinical phenotype of non-AL amyloid types in bone marrow.

Methods: We retrospectively identified  = 1469 bone marrow amyloid biopsies typed using a proteomics-based method between 2008-2020.

Chronic lymphocytic leukemia (CLL) with Reed-Sternberg-like cells vs Classic Hodgkin lymphoma transformation of CLL: does this distinction matter?

The distinction between chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed-Sternberg cells (CLL-HRS; background milieu with a paucity of inflammatory cells) and overt transformation to classic Hodgkin lymphoma (CLL-HL; mixed inflammatory background) is incompletely understood. This retrospective study examined the clinicopathologic features of CLL-HRS (n = 15) and CLL-HL (n = 31) patients seen over the past three decades from a single institution. The phenotypic features of Reed-Sternberg cells in both groups were similar, including expression of CD30, CD15, and PAX5, as well as EBV status.

Somatostatin-derived amyloidosis: a novel type of amyloidosis associated with well-differentiated somatostatin-producing neuroendocrine tumours.

Objective: To report the clinicopathologic and proteomic characteristics of a novel form of amyloidosis derived from the precursor protein somatostatin.

Materials And Methods: Cases were identified by searching the Mayo Clinic amyloid liquid chromatography and tandem mass spectrometry (LC-MS/MS) typing database from 1 January 2008 to 1 September 2020 for specimens with the amyloid signature proteins and abundant somatostatin, in the absence of other amyloid precursor proteins. All available medical records and pathologic materials were examined.

Association between spinal stenosis and wild-type ATTR amyloidosis.

Age-related cardiac amyloidosis results from deposits of wild-type tranthyretin amyloid (ATTRwt) in cardiac tissue. ATTR may play a role in carpal tunnel syndrome (CTS) and in spinal stenosis (SS), indicating or presaging systemic amyloidosis. We investigated consecutive patients undergoing surgery for SS for ATTR deposition in the resected ligamentum flavum (LF) and concomitant risk of cardiac amyloidosis.

Non-cardiac biopsy sites with high frequency of transthyretin amyloidosis.

Aims: Cardiac scintigraphy, a non-invasive technique for diagnosing ATTR cardiac amyloidosis, lacks specificity in patients with concomitant monoclonal gammopathy (up to 40% of cases). For these patients, amyloid type is often established by endomyocardial biopsy (EMB), which has clinical risk. This study aimed to investigate the frequency of ATTR in amyloid-positive tendon/synovium, urinary bladder, and prostate biopsies, sites for which prior biopsy specimens might exist for patients suspected of having cardiac amyloidosis, and, when available, determine the amyloid type concordance rate with other anatomic sites and provide clinical data regarding subsequent development of cardiac amyloidosis.

Striking Association of Lymphoid Enhancing Factor (LEF1) Overexpression and DUSP22 Rearrangements in Anaplastic Large Cell Lymphoma.

Anaplastic large cell lymphomas (ALCLs) are broadly classified into ALK-positive and ALK-negative. ALK-negative ALCL is composed of DUSP22-rearranged, TP63-rearranged, and triple-negative cases. While lymphoid enhancer-binding factor (LEF1) plays a crucial role in T-cell maturation, limited data exist on its expression in T-cell lymphomas, including ALCL.

The novel form of amyloidosis derived from EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) preferentially affects the lower gastrointestinal tract of elderly females.

Aims: To characterise the clinicopathological features of amyloidosis due to EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1), a newly described amyloid type.

Methods And Results: We identified cases by searching the Mayo Clinic amyloid liquid chromatography and tandem mass spectrometry typing database for specimens with the universal amyloid signature proteins, abundant EFEMP1 spectra and absence of other specific amyloid precursor proteins. We also developed an immunohistochemical stain for EFEMP1 applicable to formalin-fixed tissue sections and performed electron microscopy in one case.

Analysis and impact of a multidisciplinary lymphoma virtual tumor board.

The aim is to prospectively evaluate the impact of a multidisciplinary lymphoma virtual tumor board. The utility of multi-site interactive lymphoma-specific tumor boards has not been reported. The Mayo Clinic Lymphoma Tumor Board is a component of the International Mayo Clinic Care Network (MCCN).

Systemic amyloidosis from A (AA) to T (ATTR): a review.

Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. There are over 15 types of systemic amyloidosis, each caused by a different precursor protein which promotes amyloid formation and tissue deposition. Amyloidosis can be acquired or hereditary and can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin and soft tissues.

Amyloid Typing by Mass Spectrometry in Clinical Practice: a Comprehensive Review of 16,175 Samples.

Objective: To map the occurrence of amyloid types in a large clinical cohort using mass spectrometry-based shotgun proteomics, an unbiased method that unambiguously identifies all amyloid types in a single assay.

Methods: A mass spectrometry-based shotgun proteomics assay was implemented in a central reference laboratory. We documented our experience of typing 16,175 amyloidosis specimens over an 11-year period from January 1, 2008, to December 31, 2018.

High level MYC amplification in B-cell lymphomas: is it a marker of aggressive disease?

While MYC translocations in B-cell lymphoma (BCL) have been extensively studied, the significance of MYC amplification (MYC amp) is poorly understood. This study characterizes BCL showing MYC amp, defined as uncountable FISH signals. Retrospective analysis of all BCL FISH for MYC aberrations performed at our institution (1/2010-2/2018) identified 44/9715 (0.

Amyloidosis in surgically resected atrial appendages: a study of 345 consecutive cases with clinical implications.

Histomorphologic parameters of atrial appendages removed during the Cox-Maze procedure have been shown to correlate with recurrence of atrial fibrillation. While amyloid deposition has been noted within atrial appendages, the incidence and significance remains incompletely understood. More accurate amyloid typing methodologies and targeted pharmacotherapeutics have recently been developed, prompting pathologists to provide more detailed information about the type of amyloid identified in such samples.

First Report of Bilateral External Auditory Canal Cochlin Aggregates ("Cochlinomas") with Multifocal Amyloid-Like Deposits, Associated with Sensorineural Hearing Loss and a Novel Genetic Variant in COCH Encoding Cochlin.

Pathogenic variants in COCH, encoding cochlin, cause DFNA9 deafness disorder with characteristic histopathologic findings of cochlin deposits in the inner and middle ears. Here, we present the first case of deafness associated with bilateral external auditory canal (EAC) cochlin deposits, previously unreported evidence suggestive of cochlin-derived amyloid formation, and a novel COCH variant. A 54-year-old woman presented with progressive sensorineural hearing loss and bilateral EAC narrowing by subcutaneous thickening.

The sensitivity and specificity of the routine kidney biopsy immunofluorescence panel are inferior to diagnosing renal immunoglobulin-derived amyloidosis by mass spectrometry.

Immunoglobulin light chain amyloidosis is the most frequent type of renal amyloidosis in the United States, accounting for 81% of cases. Accurate typing is crucial for early diagnosis and treatment of immunoglobulin-derived amyloidosis and to avoid treating other amyloidoses with potentially toxic chemotherapy. Immunofluorescence is the first step to type renal immunoglobulin-derived amyloidosis but the performance characteristics of this method are largely unknown.

Serum levels of DNAJB9 are elevated in fibrillary glomerulonephritis patients.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease. Kidney biopsy is required to establish the diagnosis. Recent studies have identified abundant glomerular deposition of DNAJB9 as a unique histological marker of FGN.

Paraneoplastic Cast Nephropathy Associated With Pancreatic Mixed Acinar-Neuroendocrine Carcinoma: A Case Report.

Acute kidney injury is common in patients with cancer and may result from sepsis, obstruction, radiotherapy, chemotherapeutic agents, and nonsteroidal anti-inflammatory drugs. Rare reports of acute kidney injury due to cast nephropathy in patients with pancreatic acinar cell carcinoma have been described, but a pathogenetic link between cast nephropathy and carcinoma was not established. We report a patient with pancreatic mixed acinar-neuroendocrine carcinoma who developed severe acute kidney injury.

Incidence of AL Amyloidosis in Olmsted County, Minnesota, 1990 through 2015.

Objective: To determine the incidence of immunoglobulin light chain amyloidosis (AL amyloidosis) in a strictly defined geographic area from 1990 through 2015.

Patients And Methods: We searched a computerized database for the records of all Olmsted County, Minnesota, residents with a diagnosis of AL amyloidosis from January 1, 1990, through December 31, 2015. In addition, records of all residents with a mention of amyloidosis were obtained from the Rochester Epidemiology Project, which contains the medical records of Mayo Clinic and Olmsted Medical Group.

Follicular Dendritic Cell Sarcoma With Indolent T-Lymphoblastic Proliferation Is Associated With Paraneoplastic Autoimmune Multiorgan Syndrome.

Nonclonal expansions of immature T cells outside of the thymus, termed indolent T-lymphoblastic proliferation (iT-LBP), have been identified in rare lymphoproliferative disorders. We report that iT-LBP is a frequent finding in cases of follicular dendritic cell sarcoma (FDCS), and shows an association with paraneoplastic autoimmune multiorgan syndrome (PAMS). We studied 31 cases of FDCS by paraffin immunohistochemistry using antibodies to CD21, CD23, CD35, clusterin, CXCL13, podoplanin, CD3, CD4, CD8, CD20, CD1a, and TdT.

Apolipoprotein CII Amyloidosis Associated With p.Lys41Thr Mutation.

Introduction: Apolipoprotein CII amyloidosis (AApoCII) is a rare form of amyloidosis. Here, we report a novel mutation associated with AApoCII amyloidosis in 5 patients and describe their clinical, renal biopsy, and mass spectrometry findings.

Methods: Five patients with renal AApoCII p.