Pediatric-Type Follicular Lymphoma With A Prolonged Clinical Course And Unusual Mutational Profile

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S111-S112
Author(s):  
J Muldoon ◽  
A Phelan ◽  
Y Kitagawa ◽  
M Czader
Keyword(s):  
Follicular Lymphoma ◽  
Molecular Genetic ◽  
Lymphoid Cells ◽  
Pcr Analysis ◽  
Genetic Profile ◽  
Long Duration ◽  
Mass Size ◽  
History Of ◽  
Follicular Lymphomas ◽  
Over Time

Abstract Casestudy: Pediatric-type follicular lymphoma is crucial to differentiate from other subtypes of follicular lymphomas since it carries an excellent prognosis and generally does not require radio- or chemotherapy. We present a 22-year-old male with an 8-year history of a left submandibular mass. Interval imaging studies showed no change in the mass size over time and no other sites of involvement. The patient underwent excision of the mass. Histologic sections showed effacement of nodal architecture with expansile follicles composed of medium sized to large lymphoid cells with blastoid features. Follicles showed abundant tingible body macrophages. Polarization was not seen. Neoplastic follicles were positive for CD20, PAX5, BCL6, CD10, and FOXP1, and negative for BCL2. PD1 positive cells were localized peripherally in the follicles. Clonality was confirmed by flow cytometry (kappa restricted CD10 positive B-cells in a polyclonal background) and by IGH PCR analysis (clonal peaks in FR1 and FR2). Molecular genetic testing showed the following mutations: TNFRSF14 W12* (VAF 14.8%), MAP2K1 F53V (5.7%), EZH2 Y646N (6.9%), ARID1A R1461* (7.1%). BCL2 rearrangement was not detected. MAP2K1 and TNFRSF1 are frequently reported in pediatric-type follicular lymphoma, however in the majority of cases they do not occur together. EZH2 mutation does not typically occur in pediatric-type follicular lymphoma, and is more common in classic adult- onset follicular lymphomas. Despite typical morphologic and clinical features, this patient showed a more complex genetic profile and EZH2 mutation, unusual findings in pediatric-type follicular lymphoma. It is conceivable that a higher genetic complexity has been acquired over time and is related to the long duration of the disease.

Primary Colorectal Follicular Lymphoma in 3 Dogs

2019 ◽  
Vol 56 (3) ◽  
pp. 404-408
Author(s):  
Michael A. Richardson ◽  
Tuddow Thaiwong ◽  
Matti Kiupel
Keyword(s):  
Follicular Lymphoma ◽  
Clinical Signs ◽  
Case Series ◽  
Lymphoid Hyperplasia ◽  
Lymphoid Cells ◽  
Rectal Mass ◽  
Atypical Lymphoid Hyperplasia ◽  
Polymerase Chain ◽  
Multicentric Lymphoma ◽  
Follicular Lymphomas

Primary colorectal follicular lymphomas are rare indolent lymphoid neoplasms in humans that have not been reported in dogs. We describe 3 cases of primary colorectal follicular lymphoma in dogs with histologic and immunohistochemical features similar to their human counterpart. Initial clinical signs in all dogs included tenesmus, hematochezia, and a palpable rectal mass. Two dogs were castrated males and 1 an intact female, between 9 months and 2 years of age, and of varied breeds. All 3 cases of colorectal follicular lymphoma were characterized by proliferation of follicular germinal centers with no polarity or mantle zone and were composed of centrocytes admixed with fewer centroblasts. By immunohistochemistry, lymphoid cells expressed CD20, BCL2, and BCL6 and lacked expression of CD3, CD5, and cyclin D1. Polymerase chain reaction for rearrangements of the immunoglobulin heavy chain confirmed a monoclonal population in all cases. In 2 of the 3 cases, a solitary nodular colorectal mass was excised and appeared curative; however, the third case had multiple colorectal masses and the animal developed multicentric lymphoma. This case series immunohistochemically characterizes and distinguishes colorectal follicular lymphoma from atypical lymphoid hyperplasia.

Simultaneous Phenotypically Distinct but Clonally Identical Mucosa-Associated Lymphoid Tissue and Follicular Lymphoma in a Patient With Sjögren’s Syndrome

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2247-2251 ◽  
Author(s):  
Antonella Aiello ◽  
Ming-Qing Du ◽  
Tim C. Diss ◽  
Huai-Zheng Peng ◽  
Francesco Pezzella ◽  
...  
Keyword(s):  
Lymph Node ◽  
Parotid Gland ◽  
Follicular Lymphoma ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Molecular Genetic ◽  
Pcr Amplification ◽  
Pcr Analysis ◽  
Chain Gene ◽  
Low Grade

A 44-year-old woman with a 12-year history of Sjögren’s syndrome (SS) developed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the parotid gland. Two years later, she presented with generalized lymphadenopathy and hepatosplenomegaly and a follicular lymphoma was diagnosed. To investigate the relationship of the two histologically distinct lymphomas, we re-examined their histology and immunophenotype and studied the lymphomatous tissue from the parotid, cervical lymph node, and spleen using molecular genetic methods. Histologic and immunophenotypic studies confirmed the previous diagnoses and also identified a previously unnoticed focus of follicular lymphoma in the second parotid gland biopsy. Polymerase chain reaction (PCR) amplification of the rearranged Ig heavy-chain gene showed the same sized dominant product in the MALT lymphoma and the follicular lymphoma. Similarly, PCR analysis of the t(14:18) translocation yielded an identical sized band from both MALT and follicular lymphoma. Cloning and sequencing of the Ig PCR products showed an identical CDR3 sequence from each lesion, indicating a common clonal lineage. The follicular lymphoma of the parotid gland lymph node and the follicular lymphoma of the spleen showed an identical mutation signature to that of the salivary gland MALT lymphoma. We propose that follicular lymphoma in the parotid gland lymph node may have resulted from colonization of lymphoid follicles by MALT lymphoma cells, following which the tumor cells were induced to express a follicular lymphoma phenotype, due to Bcl-2 overexpression caused by t(14;18), leading to a change in clinical behavior resulting in rapid widespread dissemination of disease. These observations suggest that the distinct phenotypes of low-grade B-cell lymphomas may be the consequence of interplay between genetic and local microenvironmental factors.

scholarly journals Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

2020 ◽  
Author(s):  
Intisar Al Alawi ◽  
Elisa Molinari ◽  
Issa Al Salmi ◽  
Fatma Al Rahbi ◽  
Adhra Al Mawali ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Clinical Diagnosis ◽  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Pcr Analysis ◽  
Genetic Profile ◽  
Polycystic Kidney ◽  
Genetic Characteristics

Abstract Background There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients.Methods We studied patients with a clinical diagnosis of ARPKD ( n =40) and their relatives [parents ( n =24) and unaffected siblings ( n =10)] from 32 apparently unrelated families, who were referred to the National Genetic Centre in Oman between January 2015 and December 2018. Genetic analysis of PKHD1 was performed through next generation sequencing (NGS) and Sanger sequencing.Results A clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years). Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly. 24 patients had documented chronic kidney disease. 24 out of the 32 families had a family history suggesting an autosomal recessive pattern of inherited kidney disease, and there was known consanguinity in 21 families (66%). A molecular genetic diagnosis with biallelic PKHD1 mutations was confirmed in 38 patients from 30 different families, giving a detection rate of 94%. Two unrelated patients remained genetically unsolved. In all of the solved cases, only four different PKHD1 missense pathogenic variants were identified: c.107C>T, p.(Thr36Met); c.406A>G, p.(Thr136Ala); c.4870C>T, p.(Arg1624Trp) and c.9370C>T, p.(His3124Tyr) located in exons 3, 6, 32 and 58, respectively. The c.406A>G, p.(Thr136Ala) missense mutation was detected homozygously in one family and heterozygously with a c.107C>T, p.(Thr36Met) allele in 5 other families. Overall, the most commonly detected pathogenic allele was c.107C>T; (Thr36Met), which was seen in 24 families.Conclusion Molecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The four PKHD1 missense variants identified suggest there may be common founder alleles in the Omani population. Cost effective targeted PCR analysis of these specific alleles can be a useful diagnostic tool for future cases of suspected ARPKD in Oman.

scholarly journals Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

2020 ◽  
Author(s):  
Intisar Al Alawi ◽  
Elisa Molinari ◽  
Issa Al Salmi ◽  
Fatma Al Rahbi ◽  
Adhra Al Mawali ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Clinical Diagnosis ◽  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Pcr Analysis ◽  
Genetic Profile ◽  
Polycystic Kidney ◽  
Genetic Characteristics

Abstract Background: There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients. Methods: We studied patients with a clinical diagnosis of ARPKD (n=40) and their relatives (parents (n=24) and unaffected siblings (n=10)) from 32 apparently unrelated families, who were referred to the National Genetic Centre in Oman between January 2015 and December 2018. Genetic analysis of PKHD1 if not previously known was performed using targeted exon PCR of known disease alleles and Sanger sequencing. Results: A clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years). Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly. 24 patients had documented chronic kidney disease (median age 3 years). 24 out of the 32 families had a family history suggesting an autosomal recessive pattern of inherited kidney disease, and there was known consanguinity in 21 families (66%). A molecular genetic diagnosis with biallelic PKHD1 mutations was known in 18 patients and newly identified in 20 other patients, totalling 38 patients from 30 different families. Two unrelated patients remained genetically unsolved. The different PKHD1 missense pathogenic variants were: c.107C>T, p.(Thr36Met); c.406A>G, p.(Thr136Ala); c.4870C>T, p.(Arg1624Trp) and c.9370C>T, p.(His3124Tyr) located in exons 3, 6, 32 and 58, respectively. The c.406A>G, p.(Thr136Ala) missense mutation was detected homozygously in one family and heterozygously with a c.107C>T, p.(Thr36Met) allele in 5 other families. Overall, the most commonly detected pathogenic allele was c.107C>T; (Thr36Met), which was seen in 24 families. Conclusions: Molecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The limited number of PKHD1 missense variants identified in ARPKD cases suggests these may be common founder alleles in the Omani population. Cost effective targeted PCR analysis of these specific alleles can be a useful diagnostic tool for future cases of suspected ARPKD in Oman.

scholarly journals Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

2020 ◽  
Author(s):  
Intisar Al Alawi ◽  
Elisa Molinari ◽  
Issa Al Salmi ◽  
Fatma Al Rahbi ◽  
Adhra Al Mawali ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Clinical Diagnosis ◽  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Pcr Analysis ◽  
Genetic Profile ◽  
Polycystic Kidney ◽  
Genetic Characteristics

Abstract Introduction There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients. Methods We studied patients with a clinical diagnosis of ARPKD ( n =40) and their relatives [parents ( n =24) and unaffected siblings ( n =10)] from 32 apparently unrelated families, who were referred to the National Genetic Centre in Oman between January 2015 and December 2018. Genetic analysis of PKHD1 was performed through next generation sequencing (NGS) and Sanger sequencing. Results A clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years). Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly. 24 patients had documented chronic kidney disease. 24 out of the 32 families had a family history suggesting an autosomal recessive pattern of inherited kidney disease, and there was known consanguinity in 21 families (66%). A molecular genetic diagnosis with biallelic PKHD1 mutations was confirmed in 38 patients from 30 different families, giving a detection rate of 94%. Two unrelated patients remained genetically unsolved. In all of the solved cases, only four different PKHD1 missense pathogenic variants were identified: c.107C>T, p.(Thr36Met); c.406A>G, p.(Thr136Ala); c.4870C>T, p.(Arg1624Trp) and c.9370C>T, p.(His3124Tyr) located in exons 3, 6, 32 and 58, respectively. The c.406A>G, p.(Thr136Ala) missense mutation was detected homozygously in one family and heterozygously with a c.107C>T, p.(Thr36Met) allele in 5 other families. Overall, the most commonly detected pathogenic allele was c.107C>T; (Thr36Met), which was seen in 24 families. Conclusion Molecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The four PKHD1 missense variants identified suggest there may be common founder alleles in the Omani population. Cost effective targeted PCR analysis of these specific alleles can be a useful diagnostic tool for future cases of suspected ARPKD in Oman.

Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive

Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 1149-1154 ◽  
Author(s):  
Anneke G. Bosga-Bouwer ◽  
Gustaaf W. van Imhoff ◽  
Ronald Boonstra ◽  
Anneke van der Veen ◽  
Eugenia Haralambieva ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Germinal Center ◽  
Blot Hybridization ◽  
Molecular Genetic ◽  
Southern Blot Hybridization ◽  
Distinct Subgroup ◽  
Group I ◽  
Follicular Lymphomas ◽  
Center Cell

Abstract Chromosomal translocations involving t(14;18)(q32;q21) and the chromosome 3q27 region are common in B-cell non-Hodgkin lymphoma of germinal center cell origin. Grade 3B follicular lymphoma (FL), consisting almost exclusively of centroblasts, is a distinct subgroup of follicular lymphomas that has more in common clinically with the aggressive diffuse large B-cell lymphomas than with their indolent FL grade 1 and 2 counterparts. We studied the cytogenetic and molecular genetic aberrations by classic cytogenetics, polymerase chain reaction, Southern blot hybridization, and fluorescence in situ hybridization, with special emphasis on t(14;18), affecting bcl-2, and 3q27 rearrangement, affecting bcl-6, in 32 cases of FL grade 3B. Three distinctive subgroups were identified based upon the existence of breakpoint 3q27, a translocation t(14;18), or the absence of both. Group I involved a t(14;18) and no 3q27 aberrations (n = 13); group II was without a t(14;18) and without 3q27 aberrations (n = 9), but had other cytogenetic aberrations; and group III was without a t(14;18) but with aberrations involving 3q27 (n = 10). None of the FL grade 3B cases harbored both a t(14;18) and 3q27 aberration. These results, in particular the finding of a mutual exclusiveness of bcl-2 and bcl-6 rearrangement, indicate at least 3 different pathways of oncogenesis in FL grade 3B. FL grade 3B with bcl-2 rearrangement probably is part of the same entity as the other follicular lymphomas (1, 2, 3A), whereas the cases with 3q27 abnormalities or other unrelated translocations are more closely related to the majority of diffuse large-cell lymphomas of germinal center cell origin.

The Path of Standard Albanian Language Formation

2018 ◽  
Vol 5 (2) ◽  
pp. 106-115
Author(s):  
Sindorela Doli Kryeziu
Keyword(s):  
Single Unit ◽  
Cultural Factors ◽  
Language History ◽  
Whole Process ◽  
History Of ◽  
Social And Cultural Factors ◽  
Cultural Body ◽  
Over Time ◽  
Language Literature

Abstract In our paper we will talk about the whole process of standardization of the Albanian language, where it has gone through a long historical route, for almost a century.When talking about standard Albanian language history and according to Albanian language literature, it is often thought that the Albanian language was standardized in the Albanian Language Orthography Congress, held in Tirana in 1972, or after the publication of the Orthographic Rules (which was a project at that time) of 1967 and the decisions of the Linguistic Conference, a conference of great importance that took place in Pristina, in 1968. All of these have influenced chronologically during a very difficult historical journey, until the standardization of the Albanian language.Considering a slightly wider and more complex view than what is often presented in Albanian language literature, we will try to describe the path (history) of the standard Albanian formation under the influence of many historical, political, social and cultural factors that are known in the history of the Albanian people. These factors have contributed to the formation of a common state, which would have, over time, a common standard language.It is fair to think that "all activity in the development of writing and the Albanian language, in the field of standardization and linguistic planning, should be seen as a single unit of Albanian culture, of course with frequent manifestations of specific polycentric organization, either because of divisions within the cultural body itself, or because of the external imposition"(Rexhep Ismajli," In Language and for Language ", Dukagjini, Peja, 1998, pp. 15-18.)

PREDICTIVE VALUE OF THE DYNAMIC DETERMINATION OF CIRCULATING TUMOR DNA ON PFS IN PATIENTS WITH EGFR MUTATED NSCLC, WITH OSIMERTINIB THERAPY

2020 ◽  
Vol 66 (2) ◽  
pp. 135-142
Author(s):  
Fedor Moiseenko ◽  
Mariya Stepanova ◽  
Nikita Volkov ◽  
Albina Zhabina ◽  
A. Myslik ◽  
...  
Keyword(s):  
Predictive Value ◽  
Molecular Genetic ◽  
Predictive Marker ◽  
Circulating Tumor Dna ◽  
Qualitative Assessment ◽  
Genetic Profile ◽  
T790m Mutation ◽  
Rare Mutations ◽  
Effect Of Therapy ◽  
Pcr Method

Aim: study of the predictive value of determining ctDNA during treatment with osimertinib in patients with NSCLC with EGFR mutation. Methods: The study included patients with metastatic EG-FR-associated NSCLC, in whom, with progression against the background of 1st - 2nd generation TKIs, the T790M mutation was detected. Patients received osimertinib therapy 80 mg/ day, daily, until progression. Before treatment, and then every 2 months, whole blood was taken to conduct a qualitative assessment of ctDNA in dynamics by the RT-PCR method. Results: From 2016 to 2019 in St. Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncology), 22 patients were identified T790M associated progression of EGFR NSCLC. 81.9% (18/22) are women, 18.1% (4/22) are men. The average age is 61.2 years (50-75). 1/22 had smoking experience for more than 30 years. The molecular genetic profile in 16 is represented by ex19del, 5 L858R, 1 -a combination of rare mutations G719S+S768I. The effect of therapy was evaluated in 20/22 patients. PR and SD were registered in 9/20 (45%) and 10/20 (50%) patients, respectively. Median PFS - 16.7 months (cI 95%, 11,4-22,0). In 12/22 patients was observed the disappearance of ctDNA T790M after 2 months of osimertinib therapy. PFS is 18,9 months (95% CI, 14,8-19,7), in patients with no mutation detected in the second month of treatment compared with the group of patients in which the ctDNA was determined (PFS 8.0 months) (CI 95%, 4,2-11,8) (p=0.015). Correlation analysis did not reveal any clinical factors associated with the disappearance of ctDNA. Conclusions: The disappearance of ctDNA in plasma after 2 months of treatment with osimertinib is associated with an increase in PFS and can be considered as a predictive marker in patients with metastatic NSCLC EGFR T790M.

Gene mutation and drug resistance of M. tuberculosis in the patients followed up in the city of Moscow

2020 ◽  
Vol 97 (12) ◽  
pp. 34-44
Author(s):  
M. A. Krasnova ◽  
E. M. Belilovsky ◽  
S. E. Borisov ◽  
A. A. Khakhalina ◽  
Yu. D. Mikhaylova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Statistical Significance ◽  
Molecular Genetic ◽  
Previous Treatment ◽  
Repeated Treatment ◽  
Phenotypic Resistance ◽  
Therapy Regimen ◽  
Treatment History ◽  
History Of ◽  
Relationship Of

The article describes a retrospective study of the results of microbiological and molecular genetic tests of 685 M. tuberculosis cultures isolated from 685 adult tuberculosis patients registered for dispensary follow-up in Moscow in 2014.The following was identified during the study: phenotypic drug resistance (FDR) of MTB to rifampicin, isoniazid, fluoroquinolones, kanamycin, amikacin, and capreomycin in groups of patients with different treatment history; the frequency of FDR to the above anti-tuberculosis drugs in strains with mutations being drug resistance markers; the frequency of various mutations in case of FDR of mycobacteria in the patients from different groups; the relationship of FDR or the presence of a particular mutation with various characteristics of the patients and their treatment history.The history of previous treatment was determined as statistical significance to provide the greatest influence on the spread of drug resistant MTB: patients undergoing repeated treatment had FDR more often and also a much more pronounced variety of mutations being markers of FDR to certain anti-tuberculosis drugs.The results of the study showed that the detection of genetic mutations in MBT associated with FDR was a reliable tool for predicting phenotypic resistance and should be used as the main method for selecting anti-tuberculosis drugs when compiling the etiotropic therapy regimen.

Transocean and the History of Tax Inversions

2018 ◽  
Vol 34 (1) ◽  
pp. 1-12
Author(s):  
Susan M. Albring ◽  
Randal J. Elder ◽  
Mitchell A. Franklin
Keyword(s):  
Multinational Corporations ◽  
Economic Impacts ◽  
Income Taxes ◽  
Tax Rates ◽  
Corporate Tax ◽  
Corporate Income Taxes ◽  
History Of ◽  
Jobs Act ◽  
The U.S ◽  
Over Time

ABSTRACT The first tax inversion in 1983 was followed by small waves of subsequent inversion activity, including two inversions completed by Transocean. Significant media and political attention focused on transactions made by U.S. multinational corporations that were primarily designed to reduce U.S. corporate income taxes. As a result, the U.S. government took several actions to limit inversion activity. The Tax Cuts and Jobs Act of 2017 (TCJA) significantly lowered U.S. corporate tax rates and one expected impact of TCJA is a reduction of inversion activity. Students use the Transocean inversions to understand the reasons why companies complete a tax inversion and how the U.S. tax code affects inversion activity. Students also learn about the structure of inversion transactions and how they have changed over time as the U.S. government attempted to limit them. Students also assess the tax and economic impacts of inversion transactions to evaluate tax policy.

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