We herein present an overview of the upcoming 5
edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms ...will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4
edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5
edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.
The hematoxylin–eosin (H&E) stain has stood the test of time as the standard stain for histologic examination of human tissues. This simple dye combination is capable of highlighting the fine ...structures of cells and tissues. Most cellular organelles and extracellular matrix are eosinophilic, while the nucleus, rough endoplasmic reticulum, and ribosomes are basophilic. This review discusses the spectrum, intensity, and texture of colors observed in H&E-stained slides to illustrate their value in surgical pathology diagnosis. Changes in color of the nuclei occur in the presence of nuclear pseudoinclusions (such as papillary thyroid carcinoma) or inclusions (such as viral infection, surfactant, immunoglobulin, and biotin). The color of the cytoplasm of spindly cells can provide clues to their nature, such as basophilic (fibroblast), eosinophilic (smooth muscle and others), and amphophilic (myofibroblast). Eosinophilic globules have diagnostic value for sclerosing polycystic adenosis of salivary gland, low-grade B-cell lymphoma, solid pseudopapillary tumor of pancreas, and inclusion body fibromatosis. Eosinophilic granules are characteristic of granular cells (lysosome-rich), oncocytic cells (mitochondria-rich), and cells with secretory products (including neuroendocrine cells). Eosinophilic crystals can be diagnostic of lymphoma/plasmacytoma and crystal-storing histiocytosis. Basophilic granules or inclusions are diagnostic of acinic cell carcinoma and malakoplakia (Michaelis–Gutmann bodies). Yellow or brown inclusions are characteristic of hyalinizing trabecular adenoma of thyroid (yellow bodies), brown bowel syndrome, and malignant melanoma. Extracellular eosinophilic deposits can be produced by many conditions, but amyloid and monoclonal immunoglobulin deposition disease are important considerations. Extracellular basophilic deposits may be seen in small cell carcinoma and systemic lupus erythematosus, but they differ in that the former is blue (nuclear material) while the latter is purple (nuclear material plus immunoglobulin).
This overview of the 4th edition of the World Health Organization (WHO) Classification of thymic tumors has two aims. First, to comprehensively list the established and new tumor entities and ...variants that are described in the new WHO Classification of thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and mediastinum; second, to highlight major differences in the new WHO Classification that result from the progress that has been made since the 3rd edition in 2004 at immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria for type A, AB, B1–B3 thymomas and thymic squamous cell carcinoma are given, and it is hoped that these criteria will improve the reproducibility of the classification and its clinical relevance. The clinical perspective of the classification has been strengthened by involving experts from radiology, thoracic surgery, and oncology; by incorporating state-of-the-art positron emission tomography/computed tomography images; and by depicting prototypic cytological specimens. This makes the thymus section of the new WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool for pathologists, cytologists, and clinicians alike. The impact of the new WHO Classification on therapeutic decisions is exemplified in this overview for thymic epithelial tumors and mediastinal lymphomas, and future perspectives and challenges are discussed.
Abstract
Background and Objectives
Meditation and mind–body exercises are suggested to delay decline or enhance cognitive capabilities in older adults. However, their effectiveness remains uncertain. ...This study assessed the effectiveness of meditation and mind–body exercises to improve cognition in elderly people aged 60 years or above. Moderator variables were also explored.
Research Design and Methods
A databases search (MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library, Web of Science, CNKI, and Wangfang) was conducted from the first available date to January 10, 2018. Inclusion criteria include (a) human older adults aged 60 years or above, (b) meditation, Tai Chi, Qigong, or yoga intervention, (c) intervention should be structured, (d) inclusion of a control group, (e) at least one outcome measure of cognition was measured at baseline and post-training, and (f) peer-reviewed journal articles in English or Chinese.
Results
Forty-one studies (N = 3,551) were included in the meta-analysis. In general, meditation and mind–body exercises improve cognition in the elderly people (SMD = 0.34, 95% CI: 0.19 to 0.48), but the cognition-enhancing effects depend on the type of exercise. In addition, cognitive performance is only improved when the length of intervention is longer than 12 weeks, exercise frequency is 3–7 times/week, or duration of an exercise session is 45–60 min/session.
Discussion and Implications
This study suggests that meditation and mind–body exercises are effective to improve cognition of older adults aged 60 years or above, and exercise parameters should be considered for intervention planning.
...the accessibility of the neck structures to fine needle aspirations and direct or computed tomographic-guided core biopsies allows for effective and initial pathologic assessment diagnostic tools ...11-15. ...the terms ameloblastic carcinoma and odontogenic sarcomas were retained, whereas all other descriptive terms including primary, differentiated, and malignant were omitted. Pathology and genetics of head and neck tumours, 3rd ed., 2005, IARC Press, Lyon 3 S. Fleskens, P. Slootweg, Grading systems in head and neck dysplasias: their prognostic value, weakness and utility, Head Neck Oncol, Vol. 1, 2009, 11 4 N Gale, R. Blagus, S.K. Mofty, Evaluation of new grading system for laryngeal squamous intraepithelial lesions-a proposed useful classification, Histopathology, Vol. 65, 2014, 456-464 5 A.J. Kimple, G.K. Austin, R.N. Shah, Polymorphous low grade adenocarcinoma: a case series and determination of recurrence laryngoscope, Vol. 124, 2014, 2714-2719 6 T.D. Patel, A. Vazquez, E. Marchiano, R.C. Park, S. Barendas, J.A. Eloy, Polymorphous low grade carcinoma of the head and neck: a population-based study of 460 cases, Laryngoscope, Vol. 125, 2016, 1644-1649 7 K.K. Ang, J. Harris, R. Wheeler, Human papillomavirus and survival of patients with oropharyngeal cancer, N Engl J Med, Vol. 363, 2010, 24-35 8 A.K. Chaturvedi, E.A. Engels, R.M. Pfeiffer, Human papillomavirus and rising oropharyngeal cancer incidence in the United States, J Clin Oncol, Vol. 29, 2011, 4294-4301 9 M.L. Gillison, Q. Zhang, R. Jordan, Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer, J Clin Oncol, Vol. 30, 2012, 2102-2111 10 M. Lechner, G.M. Frampton, T. Fenton, Genome Med, Vol. 5, 2013, 49 11 A Ferlito, G Bertino, A Rinaldo, G.M. Mannara, K.O. Deneng, A review of heterotopia and associated salivary glands neoplasms of the head and neck, J Laryngol Otol, Vol. 113, 1999, 299-303 13 J Golledge, H Ellis, The etiology of lateral cervical (branchial) cysts: past and present theories, J Laryngol Otol, Vol. 108, 1994, 653-659 14 J.K. La Plante, N.S. Person, G.L. Hedlund, Radiol Clin N Am, Vol. 53, 2015, 181-196 15 C. Garu, L.V. Johansen, J. Jacobsen, P. Gertsen, E. Andersen, B.B. Jensen, Cervical lymph node metastasis from unknown primary tumors. Suppl. 22, 2014, 6057 18 H. Haack, L.A. Johnson, C.J. Fry, Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody, Am J Surg Pathol, Vol. 33, 2009, 984-991 19 S.C. Huang, B.A. Ghossin, J.A. Bishop, Novel PAX3- NCOA1 fusion in biphenotypic sinonasal sarcoma with focal rhabdomyoblastic differentiation, Am J Surg Pathol, Vol. 40, 2016, 51-59 20 J.T. Lewis, A.M. Oliveria, A.G. Nascimento, Low-grade sino-nasal sarcoma with neural and myogenic features: a clinic-pathologic analysis of 28 cases, Am J Surg Pathol, Vol. 36, 2012, 517-525 21 J.S. Reis-Filho, R. Natrajan, R. Valcheva, Histopathology, Vol. 52, 2008, 840-846 22 A Kalova, T Vancek, R Sima, Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity, Am J Surg Pathol, Vol. 34, 2010, 599-608 23 T. Nagao, T.A. Gaffey, D.W. Vischer, Invasive micropapillary salivary duct carcinoma: a distinct histologic variant with biologic significance, Am J Surg Pathol, Vol. 28, 2004, 319-326 24 D Bell, M.E. Kupferman, M.D. Williams, A Rashid, A.K. El-Naggar, Primary colonic-type adenocarcinoma of the base of tongue: a previously unreported phenotype, Hum Pathol, Vol. 40, 2009, 1798-1802 25 A.M. Gillenwater, H. Fatani, A.K. El-Naggar, Primary intestinal-like adenocarcinoma of major salivary glands: 2 instances of previously undocumented phenotype, Head Neck, Vol. 35, 2013, E234-E236 26 R.H. Spiro, A.G. Huvas, E.W. Strong, Adenocarcinoma of salivary origin.
Metaplastic thymomas are rare biphasic thymic tumors that are characteristically well-circumscribed, confined to the thymus, and follow a benign to indolent clinical course. Their relationship to ...other thymic neoplasms remains unclear, and their molecular characteristics have not been defined. We report for the first time recurrent translocation events in metaplastic thymomas involving the Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) genes. Eight metaplastic thymomas were retrieved from two institutions' archives over a 21-year period. Paraffin-embedded material from all cases underwent targeted DNA-based hybrid capture next-generation sequencing. Cases showing no somatic alterations subsequently underwent targeted RNA sequencing. Allele-specific real-time polymerase chain reaction was performed to detect GTF2I c.74146970T>A (p.L424H) mutations. All cases showed characteristic histologic features of metaplastic thymoma and demonstrated no local recurrence or distant metastatic disease at 1-22 years of follow-up. Six of eight cases were successfully sequenced, all showing YAP1-MAML2 fusions; in four cases the fusions were detected by DNA sequencing and in two cases by RNA sequencing. Two distinct products were identified: 5' YAP1 exon 1 fused to 3' MAML2 exons 2-5 or 5' YAP1 exons 1-5 fused to 3' MAML2 exons 2-5. All cases underwent allele-specific real-time polymerase chain reaction and demonstrated no GTF2I L424H mutations. Metaplastic thymoma is a distinct, clinically indolent thymic epithelial neoplasm characterized by YAP1-MAML2 fusion and lacking the GTF2I mutations found in Type A and AB thymomas.
EBV inflammatory follicular dendritic cell (FDC) sarcoma is an indolent malignant neoplasm of spindled FDCs with a rich lymphoplasmacytic infiltrate and a consistent association with Epstein-Barr ...virus (EBV). It occurs exclusively in the liver and spleen, with the exception of a few colonic examples. In this study, we report 9 extrahepatosplenic cases, including 4 occurring in previously undescribed sites, but all apparently anatomically related to the aerodigestive tract. The cases included 5 gastrointestinal tumors all presenting as colonic pedunculated polyps, 2 presenting as mesocolon mass, and 2 involving the palatine or nasopharyngeal tonsils. One patient with a colonic tumor was complicated by paraneoplastic pemphigus. The patients had a median age of 58 years, with female predominance (female:male=7:2). A favorable outcome was observed in 7 patients. Histologically, EBV inflammatory FDC sarcomas arising from these anatomic sites were similar to their hepatosplenic counterparts. Spindled to oval neoplastic cells with ill-defined cell borders were dispersed or formed loose whorled fascicles in a dense lymphoplasmacytic background. They had vesicular nuclei with distinct nucleoli and typically exhibited a range of nuclear atypia in the same case. The neoplastic cells showed variable expression of FDC markers and were labeled for Epstein-Barr virus–encoded RNA on in situ hybridization. These 9 cases thus broaden the clinicopathologic scenarios of EBV inflammatory FDC sarcoma. Recognition of the potential existence of this tumor type in extrahepatosplenic sites permits a correct diagnosis to be made.
Enteropathy-associated T-cell lymphoma (EATL), an uncommon lymphoma of intestinal intraepithelial T lymphocytes, occurs with a higher frequency in northern Europe due to association with celiac ...disease. Data on the occurrence of EATL in the Asian population, among whom celiac disease is very rare, are conflicting. This study aimed to characterize EATL encountered in the Chinese population in Hong Kong. Eighteen cases were identified, all fulfilling the criteria of type II rather than classical EATL. The patients, including 13 men and 5 women, had a median age of 62 years. Most presented with small bowel perforation, and there was no history of malabsorption. The clinical course was aggressive, with 14 of 16 patients dying of progressive disease or complications, usually within 1 year. The histologic features were practically identical in all cases. The central zone of the tumor showed ulceration with or without perforation and was characterized by monotonous transmural infiltration of the bowel by small-sized or medium-sized lymphoma cells with few admixed inflammatory cells and no coagulative necrosis. The peripheral zone featured lateral spread of lymphoma cells in the mucosa, accompanied by variable involvement of the submucosa and muscularis. In all cases, there was an intraepithelial lymphocytosis zone contiguous or discontinuous with the peripheral zone, which was characterized by infiltration of the intestinal epithelium by nonatypical small lymphocytes, and not accompanied by other histologic changes of enteropathy. The most common phenotype of the lymphoma cells was CD3+, CD5-, CD4-, CD8+, CD56+, TIA1+, CD30-, and Epstein-Barr virus, and 2 cases showed aberrant expression of CD20. A remarkable finding was that 14 (78%) cases expressed γδ T-cell receptor, and only 6 (33%) expressed αβ T-cell receptor (with 3 cases coexpressing both T-cell receptors and 1 case expressing neither). The immunophenotype of the intraepithelial lymphocytes was either discordant (particularly with respect to CD8 and CD56 expressions) or concordant with the lymphoma cells of the corresponding cases. Thus, this study shows that EATL occurring in the Chinese population is exclusively of type II. In contrast to several studies, intraepithelial lymphocytosis can be consistently demonstrated and this component seems to represent a precursor lesion of EATL rather than a manifestation of celiac disease. In view of the differences in epidemiology and clinicopathologic features, we believe it is justified to separate out type II EATL from the EATL category as a distinct form of lymphoma, for which we propose the designation "monomorphic intestinal T-cell lymphoma."
Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell ...lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy.
Aims Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct ...BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD). Methods and results We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 × 106 cells/0.1 mL, n = 9), high dose (2 × 106 cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 ± 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 ± 182 s in controls and 393 ± 136 s in BM-treated patients, and changed after 6 months to 383 ± 223s and 464 ± 196 s BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11–0.74, P = 0.014. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4–10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02–0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation. Conclusion Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.
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