Heterogeneity of monosomy 3 in fine needle aspiration biopsy of choroidal melanoma.

PurposeTo report on the heterogeneity of monosomy 3 in a fine needle aspiration biopsy obtained transsclerally from choroidal melanoma for prognosis.MethodsAll clinical records for patients who had been diagnosed with choroidal melanoma and underwent iodine-125 plaque brachytherapy with intraoperative transscleral fine needle aspiration biopsy from January 2005 to August 20, 2011, and who had a positive result for monosomy 3 according to fluorescence in situ hybridization as reported by clinical cytogenetics testing were collected. Patient age and sex, total number of cells evaluated and number of cells positive for monosomy 3, tumor size, and metastatic outcome were recorded for each patient.ResultsA positive result for monosomy 3 was reported in 93 patients who underwent transscleral fine needle aspiration biopsy. Two patients were lost to follow-up immediately post-operatively, and the remaining 91 patients were included in this study. The mean number of cells evaluated in the biopsy was 273 (range 28 to 520). The mean percentage of cells positive for monosomy 3 was 62.9% (range 4.7%-100%). The mean tumor height was 5.91 mm (range 1.99 to 10.85 mm). Larger tumors were associated with a higher percentage of cells positive for monosomy 3. During the average follow-up interval of 28.9 months (range 3-76 months), choroidal melanoma metastasis developed in 18 (20%) patients. Patients whose tumors had 1%-33% of cells positive for monosomy 3 had a significantly lower risk of metastasis-related death compared to patients whose tumors harbored a higher percentage of monosomy 3 (p = 0.04).ConclusionsCytogenetic heterogeneity of fluorescent in situ hybridization for monosomy 3 exists in a biopsy sample. Larger tumors were more likely to have a higher percentage of monosomy 3 positive cells in the sample. Furthermore, patients whose tumors had more than 33% of cells positive for monosomy 3 had a poorer prognosis than patients whose tumors had lower percentages of monosomy 3

An unusual initial presentation of mantle cell lymphoma arising from the lymphoid stroma of warthin tumor.

BackgroundWarthin tumors presenting concomitantly with a lymphoma is vanishingly rare with only 15 reported cases in English literature. Herein, we report an unusual initial presentation of a mantle cell lymphoma involving the lymphoid stroma of a Warthin tumor.Case presentationA seventy-seven year old otherwise healthy gentleman with a 50-pack year smoking history presents with a slowly enlarging left cheek mass. CT scan of the neck demonstrated a left parotid gland tumor measuring 3.4 cm in greatest dimension. He underwent a left superficial parotidectomy, with subsequent histopathologic examination revealing a Warthin tumor with extensive expansion of the lymphoid stroma. Flow cytometric, immunohistochemical, and cytogenetic studies of the stromal component of the tumor confirmed the presence of a mantle cell lymphoma. Clinical staging demonstrated stage IVa disease, and was considered to be at low to intermediate risk due to the slow growth of the parotid lesion. The patient is undergoing close follow up with repeat PET-CT scans at six months.ConclusionTo the best of our knowledge, this is the first well documented collision tumor between mantle cell lymphoma and a Warthin tumor. This case also brings to light the significance of thorough evaluation of the lymphoid component of Warthin tumor

Functional and radiological outcome in surgically managed posterior wall and column fractures of acetabulum

Background: The incidence of acetabular fractures has increased following road traffic accidents. The aim of the study is to evaluate functional and radiological outcome in surgically managed posterior wall and column fractures of acetabulum.Methods: This is a prospective study done at Nizam’s Institute of Medical Sciences, Hyderabad between May 2018 and May 2020. The sample size is 20 patients between the age group 18-60 years who presented to the hospital with closed posterior wall and/or column fractures of acetabulum with or without posterior dislocation of hip joint. Functional outcome is assessed by using the modified Merle D’ Aubigne Postel clinical grading system, radiological outcome by Matta et al and perioperative complication are assessed by retrospectively analyzing medical records and radiographics examination.Results: Functional outcome according to Merle D’ Aubigne and Postel score 16 patients (75%) showed good, 3 patients (20%) showed fair, 1 patient (5%) showed poor outcome. Radiological outcome according to Matta criteria, 16 patients (75%) showed excellent quality of joint reduction, 4 patients (25%) showed good quality of reduction of joint. There was significant correlation between anatomic reduction of the joint surface and functional outcome of the patient in our study (p value <0.05).Conclusions: Accurate joint reduction is of utmost importance in reduction of posterior wall or column fractures of acetabulum as posterior wall is the weight bearing zone. Functional outcome depends on fracture type, associated injuries, selection of patient, time between injury and surgery and postoperative rehabilitation

Clinical Utility of Microarrays: Current Status, Existing Challenges and Future Outlook

Microarray-based clinical tests have become powerful tools in the diagnosis and treatment of diseases. In contrast to traditional DNA-based tests that largely focus on single genes associated with rare conditions, microarray-based tests are ideal for the study of diseases with underlying complex genetic causes. Several microarray based tests have been translated into clinical practice such as MammaPrint and AmpliChip CYP450. Additional cancer-related microarray-based tests are either in the process of FDA review or under active development, including Tissue of Tumor Origin and AmpliChip p53. All diagnostic microarray testing is ordered by physicians and tested by a Clinical Laboratories Improvement Amendment-certified (CLIA) reference laboratory. Recently, companies offering consumer based microarray testing have emerged. Individuals can order tests online and service providers deliver the results directly to the clients via a password-protected secure website. Navigenics, 23andMe and deCODE Genetics represent pioneering companies in this field. Although the progress of these microarray-based tests is extremely encouraging with the potential to revolutionize the recognition and treatment of common diseases, these tests are still in their infancy and face technical, clinical and marketing challenges. In this article, we review microarray-based tests which are currently approved or under review by the FDA, as well as the consumer-based testing. We also provide a summary of the challenges and strategic solutions in the development and clinical use of the microarray-based tests. Finally, we present a brief outlook for the future of microarray-based clinical applications

The Progress on Genetic Analysis of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world, but is one of the most common cancers in Southeast Asia. Both genetic and environmental factors contribute to the tumorigenesis of NPC, most notably the consumption of certain salted food items and Epstein-Barr virus infection. This review will focus on the current progress of the genetic analysis of NPC (genetic susceptibilities and somatic alterations). We will review the current advances in genomic technologies and their shaping of the future direction of NPC research

Myelodysplastic/Myeloproliferative Neoplasms

Myeloid malignancies exemplified by acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs) are all characterized by abnormal proliferation of stem cells. AML is characterized by proliferation of myeloid blasts that ultimately perturb normal bone marrow (BM) function and suppress hematopoiesis. The hallmarks of MDS are cytopenias (anemia, leukopenia, or thrombocytopenia), impaired differentiation in one or more of myeloid cell lines, and ineffective hematopoiesis (Tiu et al. 2011a). MPNs manifest with proliferation of one or more cell lines in the BM with accompanying BM fibrosis and extramedullary hematopoiesis (Fig. 1). When features of both MDS and MPN coexist in the same patient, the disease is called MDS/MPN overlap neoplasms. The recognition that some MDS patients have overlapping MPN features led to the coining of the term MDS/MPN overlap. This group was first described in 1997 at the clinical advisory meeting of the World Health Organization (WHO) (Harris et al. 1999) and later adapted in the 2001 WHO classification (Harris et al. 2001). As in the case of MDS and MPNs, MDS/MPN patients are also at risk for AML evolution. Within this overlapping class, four different disease entities were classified: Juvenile myelomonocytic leukemia (JMML), chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (BCR-ABL1 negative) (aCML), and MDS/MPN-unclassifiable (MDS/MPN-U), which also included the provisional disease category, refractory anemia with ring sideroblast associated with marked thrombocytosis (RARS-T). Of note, each of these disease entities has a defined natural history, influenced by a variety of factors such as BM blast counts, presence of concomitant diseases (e.g., systemic mastocytosis with associated clonal hematologic non-mast cell lineage disease [SM-AHNMD]), and different cytogenetic and epigenetic/molecular profile which may explain the clinicopathologic diversity of these diseases

Extranodal Marginal Zone Lymphoma Presenting within the Meckel Diverticulum as Diverticulitis: A Case Report

Meckel diverticulum is the most common congenital defect of the gastrointestinal tract. It can be asymptomatic or mimic appendicitis and may be complicated by bleeding, diverticulitis, obstruction, and, rarely, neoplasia. We report the first case of extranodal marginal zone lymphoma occupying a Meckel diverticulum. A 44-year-old man with history of colonic diverticulitis presented to the emergency department for evaluation of acute abdominal pain. Radiography showed enteric obstruction, prompting diagnostic laparoscopy. Above the level of mid-ileum an intact Meckel diverticulum was identified. Microscopy showed extensive infiltration of sheets of small lymphocytes with abundant cytoplasm (monocytoid B-cells) prominently in submucosa and focally transmural involving serosal adipose tissue with multiple reactive germinal centers. The immunostains showed positivity for CD20, BCL-2, and CD43 (weak) and negativity for CD3, CD5, BCL-1, CD10, and BCL-6 in monocytoid B-cells. Fluorescence in situ hybridization studies revealed API2-MALT1 fusion signals consistent with t(11;18)(q21;q21), which confirmed the diagnosis of extranodal marginal zone lymphoma, also known as mucosa associated lymphoid tissue lymphoma

One in Four Individuals of African-American Ancestry Harbors a 5.5kb Deletion at chromosome 11q13.1

Cloning and sequencing of 5.5kb deletion at chromosome 11q13.1 from the HeLa cells, tumorigenic hybrids and two fibroblast cell lines has revealed homologous recombination between AluSx and AluY resulting in the deletion of intervening sequences. Long-range PCR of the 5.5kb sequence in 494 normal lymphocyte samples showed heterozygous deletion in 28.3% of African- American ancestry samples but only in 4.8% of Caucasian samples (p<0.0001). This observation is strengthened by the copy number variation (CNV) data of the HapMap samples which showed that this deletion occurs in 27% of YRI (Yoruba – West African) population but none in non- African populations. The HapMap analysis further identified strong linkage disequilibrium between 5 single nucleotide polymorphisms and the 5.5kb deletion in the people of African ancestry. Computational analysis of 175kb sequence surrounding the deletion site revealed enhanced flexibility, low thermodynamic stability, high repetitiveness, and stable stem-loop/ hairpin secondary structures that are hallmarks of common fragile sites