Preoperative Identification of Medullary Thyroid Carcinoma (MTC): Clinical Validation of the Afirma MTC RNA-Sequencing Classifier.

Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III-VI). In this study we report the development and clinical performance of this MTC classifier.

Malignant teratoma of the thyroid: A difficult diagnosis by fine-needle aspiration.

Primary thyroid teratomas are rare, usually benign, and typically occur in children. We report the unusual occurrence of a malignant thyroid teratoma in a young man. Initial ultrasound and CT studies revealed an 8.

Identification of Hürthle cell cancers: solving a clinical challenge with genomic sequencing and a trio of machine learning algorithms.

Background: Identification of Hürthle cell cancers by non-operative fine-needle aspiration biopsy (FNAB) of thyroid nodules is challenging. Resultingly, non-cancerous Hürthle lesions were conventionally distinguished from Hürthle cell cancers by histopathological examination of tissue following surgical resection. Reliance on histopathological evaluation requires patients to undergo surgery to obtain a diagnosis despite most being non-cancerous.

Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules.

Importance: Use of next-generation sequencing of RNA and machine learning algorithms can classify the risk of malignancy in cytologically indeterminate thyroid nodules to limit unnecessary diagnostic surgery.

Objective: To measure the performance of a genomic sequencing classifier for cytologically indeterminate thyroid nodules.

Design, Setting, And Participants: A blinded validation study was conducted on a set of cytologically indeterminate thyroid nodules collected by fine-needle aspiration biopsy between June 2009 and December 2010 from 49 academic and community centers in the United States.

Pharyngoesophageal diverticula simulating thyroid nodules: An unusual occurrence with unique features.

Pharyngoesophageal diverticula (PED) of the Zenker's and Killian-Jamieson types arise in close proximity to the thyroid gland, and may rarely be confused with a thyroid nodule on ultrasonography. In this brief report, we detail the cytologic, clinical, and radiologic findings of three PED that were thought to be thyroid nodules, and were subjected to fine-needle aspiration (FNA). The patients were females with an age range of 51-64 years.

Identification of parathyroid tissue in thyroid fine-needle aspiration: A combined approach using cytology, immunohistochemical, and molecular methods.

Objectives: Parathyroid (PT) lesions can be difficult to recognize in thyroid fine needle aspirations (FNAs), and when not identified correctly, PT cells may be mistaken for potentially abnormal thyroid cells. We therefore studied the utility of combining cytology, immunohistochemistry, and a molecular classifier to identify PT cells in thyroid FNAs.

Methods: Thyroid FNAs were received in CytoLyt, and were evaluated initially using The Bethesda System for Reporting Thyroid Cytology (TBSRTC).

Analytical Performance of a Gene Expression Classifier for Medullary Thyroid Carcinoma.

Background: The aim of this study was to demonstrate the analytical validity of an RNA classifier for medullary thyroid carcinoma (MTC).

Methods: Fresh-frozen tissue specimens were obtained from commercial sources, and MTC diagnoses were confirmed by histopathology review. De-identified patient fine-needle aspiration biopsies (FNABs) and whole blood from normal donors were obtained.

The utility of cellient cell blocks in low-cellularity thyroid fine needle aspiration biopsies.

Background: Low cellularity can be problematic in thyroid fine needle aspiration (FNA) biopsies. The Cellient cell block (CB) system has been reported to improve cell recovery compared to traditional methods. Therefore, we studied the utility of Cellient CBs in the evaluation of thyroid FNAs, with an emphasis on low-cellularity specimens.

A Genomic Alternative to Identify Medullary Thyroid Cancer Preoperatively in Thyroid Nodules with Indeterminate Cytology.

Background: The use of calcitonin screening for the rare medullary thyroid cancer (MTC) is controversial due to questions of efficacy, accuracy, and cost-effectiveness. This study reports the results of a large prospective validation using a machine-trained algorithm (MTC Classifier) to preoperatively identify MTC in fine-needle aspiration biopsies in lieu of calcitonin measurements.

Methods: Cytology analysis on a prospective consecutive series of 50,430 thyroid nodule biopsies yielded a total of 7815 indeterminate (Bethesda categories III/IV) cases, which were tested with the MTC classifier.

Extramedullary hematopoiesis involving the thyroid: Fine-needle aspiration features and literature review.

Introduction: The thyroid has rarely been documented as a site of extramedullary hematopoiesis (EMH). We report the largest series to date, with nine cases of EMH, and compare our findings with previous reports of thyroid EMH.

Materials And Methods: Thyroid nodule fine-needle aspirations (FNAs) were collected over a 4-year period.

Primary central nervous system lymphomas: a 30-year experience at a single institution.

Primary central nervous system lymphoma (PCNSL) is a rare disease that has been increasing in frequency. Clinical, histologic, and immunohistochemical data from 64 cases of PCNSL seen at Duke University Medical Center since 1968 were reviewed and tumors were classified using the REAL classification system. Thirty-two patients were male and 32 were female, with a mean age of 57.

Post transplant CD8+ gammadelta T-cell lymphoma associated with human herpes virus-6 infection.

Gammadelta T-cell lymphoma is a rare T-cell lymphoproliferative disorder that has been reported in both immunocompetent and immunocompromised persons. This report describes a forty eight year old patient who developed gammadelta T-cell lymphoma four years after undergoing living-related kidney transplantation. The lymphoma expressed CD2, CD3, CD7, CD8 and CD56, and the gammadelta T-cell receptor and did not express CD5, CD4 and the alphabeta T-cell receptor.

Myelodysplastic syndrome occurring after autologous bone marrow transplantation for lymphoma. Morphologic features.

Clonal karyotypic abnormalities characteristic of myelodysplastic syndrome (MDS) occur in up to 18% of patients who undergo autologous bone marrow transplantation (auto-BMT) for the treatment of lymphoma. Morphologic changes are often subtle and may not meet the French-American-British Cooperative Group criteria for MDS. We retrospectively assessed dysplastic changes in peripheral blood and bone marrow specimens obtained before and after transplantation from nine patients and correlated them with karyotype and survival.

Neural cell adhesion molecule (CD56)-positive acute myelogenous leukemia and myelodysplastic and myeloproliferative syndromes.

The CD56 antigen is normally expressed on natural-killer cells but has additionally been shown to be present on a variety of hematologic malignancies, including a subset of acute myelogenous leukemia (AML). There is disagreement, however, about its prognostic significance and its association with specific cytogenetic abnormalities. All clinical samples from June 1994, through September 1995, with increased myeloblasts were analyzed by multiparameter flow cytometry for anomalous expression of CD56.

Kaposi's-sarcoma-associated herpesvirus is detected in peripheral blood mononuclear cells of HIV-infected homosexuals more often than in heterosexuals.

Purpose: The Kaposi's-sarcoma-associated herpesvirus is thought likely to play an important part in the pathogenesis of Kaposi's sarcoma, which is the most common tumor in AIDS patients. To determine whether peripheral blood is also infected by the virus, we prospectively tested mononuclear cells from HIV-infected individuals, both with and without Kaposi's sarcoma.

Patients And Methods: Thirty-three patients with AIDS were studied.

Craniocerebral plasmacytoma: MR features.

We report the MR imaging findings in two patients with solitary craniocerebral plasmacytoma, a benign plasma cell tumor that can arise from the skull, the dura, or, rarely, the brain. In both patients, the lesion was extraaxial and nearly isointense with gray matter on T2-weighted MR images, and diffusely enhanced after administration of contrast material, bearing some similarities to meningioma. A diagnosis of solitary craniocerebral plasmacytoma should be considered when a mass with these imaging features is seen, because total excision may not be necessary for this radiosensitive tumor.

Predictive value of intraoperative biopsies and liver function tests for preservation injury in orthotopic liver transplantation.

Eighty liver allografts were studied to determine the predictive value of intraoperative biopsies and postoperative liver function tests for the development of preservation injury (PI). Peak transaminase (aspartate transaminase [AST] and alanine transaminase [ALT]) and prothrombin time (PT) values achieved by each patient during postoperative days (POD) 1 through 7 were determined. PI in day 0 preperfusion biopsies (0Pre) (obtained immediately before implantation) and postperfusion biopsies (0Post) (obtained immediately after revascularization) was categorized by histological criteria as present or absent.

Detection of Kaposi's sarcoma-associated herpesvirus-like DNA sequence in angiosarcoma.

The partial DNA sequence of a putative new herpesvirus has recently been isolated from almost all cases of Kaposi's sarcoma (KS), from a small subset of AIDS-related lymphomas, and from a high proportion of multicentric Castleman's disease. The presence of this KS-associated herpesvirus, which is also known as human herpes virus 8 (KSHV/ HHV8), has not been reported in vascular tumors other than KS. We therefore examined a series of vascular neoplasms of both endothelial and pericyte derivation using polymerase chain reaction to detect a 233-hp segment of the viral DNA.

Myelodysplasia and acute myeloid leukemia occurring after autologous bone marrow transplantation for lymphoma.

Secondary hematopoietic disease manifesting as acute myeloid leukemia, myelodysplastic syndrome or clonal karyotypic abnormalities, has been recently recognized as a relatively frequent and potentially serious complication of autologous bone marrow transplantation for both Hodgkin's disease and non-Hodgkin's lymphoma. The available evidence suggests the disease results primarily from repeated exposure of the host stem cells to therapeutic agents before the time of transplant, but a conspiratory role for the transplantation procedure itself cannot be entirely excluded. Strategies to decrease the incidence of secondary hematopoietic disease include earlier stem cell harvest and/or transplantation, and the performance of screening karyotypic studies on the bone marrow prior to autologous grafting.

Detection of myeloperoxidase gene expression in minimally differentiated acute myelogenous leukemia (AML-M0) using in situ hybridization.

Acute leukemias containing > 3% myeloperoxidase (MPO)-positive blast cells, as detected cytochemically, are considered to be myelogenous in origin, regardless of the immunophenotypic markers expressed. Conversely, acute leukemias that express only myeloid antigens are also considered to be acute myelogenous leukemia (AML), even in the absence of MPO. These MPO-negative AMLs, designated AML-M0 in the FAB classification, currently require either immunophenotypic or electron microscopic studies for identification.

Trisomy 11: an association with stem/progenitor cell immunophenotype.

The clinicopathological features and the prognostic significance of acute myeloid leukaemia (AML) with trisomy 11 are currently unknown. In this study we describe 15 adult AML cases with trisomy 11. Trisomy 11 was the sole chromosomal anomaly in eight cases; the remaining seven cases were characterized by +11 in association with other karyotypic aberrations.

Expression of interleukin-1 receptor antagonist protein in malignant lymphomas. An immunohistochemical study.

Objective: Interleukin-1 (IL-1) receptor antagonist (IL-1ra) is a naturally occurring modulator of IL-1 that functions by competitively binding to IL-1 receptors without producing biologic effects. Interleukin-1 is believed to be a mediator involved in production of constitutional symptoms in patients with malignant lymphoma. Because we know of no study regarding IL-1ra expression in lymphomas, we tried to demonstrate the presence of IL-1ra in lymphomas using immunohistochemistry.

Detection of trisomy 8 by fluorescence in situ hybridization on bone marrow smears from patients with subtle myelodysplastic changes.

Trisomy 8 is the most common hyperdiploid numerical chromosomal abnormality that is found in myelodysplastic syndromes (MDSs). We explored the utility of combining fluorescence in situ hybridization interphase cytogenetics with routine morphologic analysis to characterize cases for which signs and symptoms were suggestive of MDS in which dysplastic changes were insufficient for a definitive diagnosis. Hybridization with a chromosome 8-specific centromeric probe was performed on bone marrow smears that were obtained from four patients with cytogenetically documented trisomy 8 and hematopoietic cell atypia that was suggestive but not diagnostic of MDS.

Clonal karyotypic hematopoietic cell abnormalities occurring after autologous bone marrow transplantation for Hodgkin's disease and non-Hodgkin's lymphoma.

Over a 6-year period, 275 patients were treated with autologous bone marrow transplantation (auto-BMT) for advanced-stage malignant lymphoma. After BMT, clonal chromosomal abnormalities were detected in hematopoietic cells from 10 patients. All 10 had morphologically and cytogenetically normal BMs at the time of stem cell harvest.