scholarly journals Classification of lymphoid neoplasms: the microscope as a tool for disease discovery

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4384-4399 ◽  
Author(s):  
Elaine S. Jaffe ◽  
Nancy Lee Harris ◽  
Harald Stein ◽  
Peter G. Isaacson

AbstractIn the past 50 years, we have witnessed explosive growth in the understanding of normal and neoplastic lymphoid cells. B-cell, T-cell, and natural killer (NK)–cell neoplasms in many respects recapitulate normal stages of lymphoid cell differentiation and function, so that they can be to some extent classified according to the corresponding normal stage. Likewise, the molecular mechanisms involved the pathogenesis of lymphomas and lymphoid leukemias are often based on the physiology of the lymphoid cells, capitalizing on deregulated normal physiology by harnessing the promoters of genes essential for lymphocyte function. The clinical manifestations of lymphomas likewise reflect the normal function of lymphoid cells in vivo. The multiparameter approach to classification adopted by the World Health Organization (WHO) classification has been validated in international studies as being highly reproducible, and enhancing the interpretation of clinical and translational studies. In addition, accurate and precise classification of disease entities facilitates the discovery of the molecular basis of lymphoid neoplasms in the basic science laboratory.

2020 ◽  
Vol 5 (53) ◽  
pp. eaay4218
Author(s):  
Dejene M. Tufa ◽  
Ashley M. Yingst ◽  
George Devon Trahan ◽  
Tyler Shank ◽  
Dallas Jones ◽  
...  

Innate lymphoid cells (ILCs) develop from common lymphoid progenitors (CLPs), which further differentiate into the common ILC progenitor (CILP) that can give rise to both ILCs and natural killer (NK) cells. Murine ILC intermediates have recently been characterized, but the human counterparts and their developmental trajectories have not yet been identified, largely due to the lack of homologous surface receptors in both organisms. Here, we show that human CILPs (CD34+CD117+α4β7+Lin−) acquire CD48 and CD52, which define NK progenitors (NKPs) and ILC precursors (ILCPs). Two distinct NK cell subsets were generated in vitro from CD34+CD117+α4β7+Lin−CD48−CD52+ and CD34+CD117+α4β7+Lin−CD48+CD52+ NKPs, respectively. Independent of NKPs, ILCPs exist in the CD34+CD117+α4β7+Lin−CD48+CD52+ subset and give rise to ILC1s, ILC2s, and NCR+ ILC3s, whereas CD34+CD117+α4β7+Lin−CD48+CD52− ILCPs give rise to a distinct subset of ILC3s that have lymphoid tissue inducer (LTi)–like properties. In addition, CD48-expressing CD34+CD117+α4β7+Lin− precursors give rise to tissue-associated ILCs in vivo. We also observed that the interaction of 2B4 with CD48 induced differentiation of ILC2s, and together, these findings show that expression of CD48 by human ILCPs modulates ILC differentiation.


2019 ◽  
Vol 60 (1-2) ◽  
pp. 53-62
Author(s):  
Feifei Du ◽  
Yongzhi Wang ◽  
Zhiyi Ding ◽  
Matthias W. Laschke ◽  
Henrik Thorlacius

Background: Polyphosphates (PolyPs) have been reported to exert pro-inflammatory effects. However, the molecular mechanisms regulating PolyP-provoked tissue accumulation of leukocytes are not known. The aim of the present investigation was to determine the role of specific adhesion molecules in PolyP-mediated leukocyte recruitment. Methods: PolyPs and TNF-α were intrascrotally administered, and anti-P-selectin, anti-E-selectin, anti-P-selectin glycoprotein ligand-1 (PSGL-1), anti-membrane-activated complex-1 (Mac-1), anti-lymphocyte function antigen-1 (LFA-1), and neutrophil depletion antibodies were injected intravenously or intraperitoneally. Intravital microscopy of the mouse cremaster microcirculation was used to examine leukocyte-endothelium interactions and recruitment in vivo. Results: Intrascrotal injection of PolyPs increased leukocyte accumulation. Depletion of neutrophils abolished PolyP-induced leukocyte-endothelium interactions, indicating that neutrophils were the main leukocyte subtype responding to PolyP challenge. Immunoneutralization of P-selectin and PSGL-1 abolished PolyP-provoked neutrophil rolling, adhesion, and emigration. Moreover, immunoneutralization of Mac-1 and LFA-1 had no impact on neutrophil rolling but markedly reduced neutrophil adhesion and emigration evoked by PolyPs. Conclusion: These results suggest that P-selectin and PSGL-1 exert important roles in PolyP-induced inflammatory cell recruitment by mediating neutrophil rolling. In addition, our data show that Mac-1 and LFA-1 are necessary for supporting PolyP-triggered firm adhesion of neutrophils to microvascular endothelium. These novel findings define specific molecules as potential targets for pharmacological intervention in PolyP-dependent inflammatory diseases.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2334-2334
Author(s):  
Isabel Barao-Silvestre ◽  
Doug Redelman ◽  
Erik Ames ◽  
Jonathan Weiss ◽  
Kai Sun ◽  
...  

Abstract Natural Killer (NK) cells are lymphocytes of the innate immune system that are able to kill a variety of tumors and pathogen-infected cells without prior sensitization. NK cells are the first lymphoid cells to repopulate following bone marrow transplantation (BMT). The present study shows that murine NK cells developing in vivo after BMT are phenotypically and functionally distinguishable from mature adult NK cells. Using a congeneic BMT mouse model (CD45.1/H-2b → C57BL/6, CD45.2/H-2b) we demonstrated here that donor derived BM-NK progenitors (CD122+NK1.1-CD3-)were present in the BM and periphery (spleen), at day 14 after BMT, and developed into NK cells expressing high levels of CD122, NKG2D, CD94, DX5 and CD43. However, surface expression of Ly49 inhibitory receptors was altered with Ly49C/I being under-expressed (9.8 %± 3.2 %), and Ly49G2 being highly expressed (62 %± 3.1 %) when compared to NK cells from non-transplanted adult mice (Ly49C/I, 43.1 %± 7.6 % and Ly49G2, 44.3 %± 13.5 %). At 28 days after BMT, there was a normalization with regard to Ly49 phenotype. The developing NK cells manifested functional deficits compared to non-transplanted adult NK, even when stimulated in vitro with Interleukin (IL)-2, as evidenced by decreased interferongamma (IFN-g) production and cytolytic activity. In order to examine the effects of major histocompatibility complex (MHC) molecules on NK development independently of allelic variation of Ly49s, we performed syngeneic BMT using B10D2 mice (H-2d). We observed the same pattern of Ly49s expression during NK development demonstrating that the acquisition of these receptors early after BMT is not determined by the MHC haplotype. Because IL-15 plays a crucial role in NK cell development, we administrated human (h) IL-15, via hydrodynamic injection of the respective gene, at day 11 after BMT, to accelerate NK maturation. This method resulted in a high but transient production of hIL-15 (736 ± 41 pg/ml) in the serum for up to 2 weeks. A subsequent but temporary increase in the numbers of donor derived NK cells (3 fold) occurred within 72 hours, in both BM and periphery, following hIL-15 gene delivery. Despite these augmenting effects, the developing NK cells still exhibited poor functionality compared to non-transplanted adult mice. These studies describe the possibility of NK development in the spleen, and indicate that normal surface expression of Ly49C/I and Ly49G2 early after BMT is time dependent, but MHC independent. Moreover, administration of hIL-15 is not sufficient to induce NK functional maturation early after BMT despite increased NK numbers.


2021 ◽  
Vol 118 (28) ◽  
pp. e2101169118
Author(s):  
Uriel Y. Moreno-Nieves ◽  
Joshua K. Tay ◽  
Saumyaa Saumyaa ◽  
Nina B. Horowitz ◽  
June Ho Shin ◽  
...  

Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a+CD103+ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.


2020 ◽  
Vol 8 (12) ◽  
Author(s):  
Vanessa Einsfeld ◽  
Ana Claudia Ramos ◽  
Beatriz Barbosa ◽  
Alberto Zen ◽  
Grasieli de Oliveira Ramos ◽  
...  

Introdução: Quando estamos frente às lesões potencialmente malignas, torna-se imprescindível o acompanhamento rigoroso dessas lesões, pois são lesões frequentes e com risco de transformação maligna consideravelmente relevante, a leucoplasia e a queilite actínica, são as lesões mais comuns encontradas na cavidade bucal. Objetivo: relatar um caso de lesão potencialmente maligna em mucosa labial. Relato de caso: Paciente sexo masculino compareceu à clínica de Diagnóstico VI da Universidade do Oeste de Santa Catarina, com a presença de lesão branca em lábio inferior, o mesmo já se encontrava em acompanhamento há seis anos, com diagnóstico prévio de queilite actínica sem atipia celular (duas biópsias prévias). Aposentado, trabalhava anteriormente como agricultor, ex-fumante e ex-etilista. Clinicamente observava-se lesão esbranquiçada, com aspecto verruciforme, localizada em lábio inferior, medindo 2 cm no maior diâmetro. Além disso, o lábio encontrava-se endurecido, com aspecto roliço. Duas hipóteses de diagnóstico foram levantadas: queilite actínica associada a leucoplasia e carcinoma verrucoso. O paciente foi submetido à nova biópsia incisional. No laudo constatou-se tratar de queilite actínica com displasia epitelial leve e o tratamento proposto foi o uso de protetor labial FPS30, além de acompanhamento clínico semestral. Conclusão: O acompanhamento desse caso clínico foi possível observar alteração no perfil citológico, onde nas primeiras biópsias não era possível observar atipia celular e na biópsia mais recente foi observado uma displasia epitelial leve, portanto o acompanhamento das lesões potencialmente malignas é fundamental para prevenir sua transformação maligna, e uma nova biópsia deve ser realizada sempre que for observada alteração no aspecto clínico da lesão.Descritores: Leucoplasia; Queilite; Biópsia; Lábio.ReferênciasPindborg JJ, Reichart PA, Smith CJ, Van der Waal I. World Health Organization International histological classification of tumours. Histological typing of câncer and precancer of the oral mucosa. Berlin: Springer; 1997.Marley JJ, Linden GJ, Cowan CG, Lamey PJ, Warnakulasuriya KAAS, Scully C. Management of potentially malignant oral mucosa lesions by consultant UK oral and maxillofacial surgeons.  Br J Oral Maxillofac Surg. 1996;34(1):28-36.Neville BW, Dam DD, Allen CM, Chi AC . Patologia oral e maxilofacial. 3. ed. Rio de Janeiro; 2016.Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. 2007;36(10):575-80.Gupta PC, Murti PR, Bhonsle RB, Mehta FS, Pindborg JJ. Effect of cessation of tobacco use on the incidence of oral mucosal lesions in a 10-yr follow-up study of 12.212 users. Oral Dis. 1995;1(1):54-8.Maito FDM. Avaliação da expressão do PCNA no epitélio lingual de camundongos submetidos à ingestão e aplicação tópica de álcool a 40 GL [dissertação]. Porto Alegre: Faculdade de Odontologia – UFRGS;2001.Markopoulos A, Albanidou-Farmaki E, Kayavis I. Actinic cheilitis: clinical and pathologic characteristics in 65 cases. Oral Dis. 2004;10(4):212-16.Cintra JS, Torres SCM, Silva MBF, Manhães Júnior LRC, Silva Filho JP, Junqueira JLC. Queilite Actínica: estudo epidemiológico entre trabalhadores rurais no município de Paracaia– SP. Ver Assoc Paul Cir Dent. 2013;67(2):118-21.Greespan D, Jordan RCK. The white lesions that kills – aneuploide dysplastic oral leukoplakia. N Engl J Med. 2004;350(14):1382-84.Bánóczy J. Follow-up studies in oral leukoplakia. J Maxillofac Surg. 1977;5(1):69-75.Huber MA. White oral lesions, actinic cheilitis, and leukoplakia: confusions in terminology and definition: facts and controversies. Clin Dermatol. 2010;28(3):262-68.Reibel J. Prognosis of oral pre-malignant lesions: significance of clinical, histopathological and molecular biological characateristics. Crit Rev Oral Biol Med. 2003;14(1):47-62.Scheifele C, Reichart PA, Oral leukoplakia in manifest squamous epithelial carcinoma. A clinical prospective study of 101 patients, Mund Kiefer Gesichtschir. 1998;2(6):326-30.Schepman K, der Meij E, Smeele L, der Waal I. Concomitant leukoplakia in patients with oral squamous cell carcinoma. Oral Dis. 1999;5(3):206-9.Kaugars GE, Pillion T, Svirsky JA, Page DG, Burns JC, Abbey LM. Actinic cheilitis: a review of 152 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88(2):181-86.Abreu MAMA, Silva OMP, Pimentel DRN, Hirata CHW, Weckx LLM, Alchorne MMA et al. Actinic cheilitis adjacent to squamous carcinoma of the lips as an indicator of prognosis. Braz J Otorhinolaryngol. 2006;72(6):767-71.Patrício JFC. Evolução das lesões pré-malignas orais: orientações para os médicos dentistas [dissertação]. Porto: Universidade do Porto; 2011.Shah AY, Doherty SD, Rosen T. Actinic cheilitis: a treatment review. Int J Dermatol. 2010; 49(11):1225-34.Pimenta FJ, Cordeiro GT, Pimenta LGGS, Viana MB, Lopes J, Gomez MV et al.  Molecular alterations in the tumor suppressor gene WWOX in oral Leukoplakias. Oral Oncol. 2008;44(8):753-58Paulo LFB, Rosa RR, Rocha MA, Durighetto Junior AF. Incidência e prevalência das lesões brancas associadas ao tabagismo atendidos no ambulatório da Unidade de Diagnóstico Estomatológico da Universidade Federal de Uberlândia no período de 1997 a 2008. Horizonte Cientifico. 2011;2:1-20.Gandolfo S, Pentenero M, Broccoletti R, Pagano M, Carrozzo M, Scully C. Toluidine blue uptake in potentially malignant oral lesions in vivo: clinical and histological assessment. Oral Oncol. 2006;42(1):89-95.Mashberg A, Samit A. Early diagnosis of asympomatic oral and oropharyngeal squamous cancers. CA Cancer J Clin. 1995;45(6):328-51.Mendes SF, Ramos GO, Rivero ERC, Modolo F, Grando LJ, Meurer MI. Techniques for precancerous lesion diagnosis. J Oncol. 2011. ID 326094.Dib LL, Kowalski LP, Curi MM. Lesões cancerizáveis de boca. In: Kowaski LP, Anelli A, Salvajoli JV, Lopes LF. Manual de condutas diagnosticas e terapêuticas em oncologia. 2.ed. São Paulo: Âmbito Editores; 2002.


2021 ◽  
pp. 306-311
Author(s):  
Iulia Gîvan ◽  
George Ciulei ◽  
Angela Cozma ◽  
Mădălina Indre ◽  
Vlad Țâru ◽  
...  

Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence and prognosis remain controversial in the literature. Regarding the presentation, there are no differences from other breast carcinomas and clinical syndromes related to hormone production are extremely rare. Refinement of the classification of neuroendocrine neoplasms of the breast is needed in order to improve the reproducibility of their diagnostic criteria and to define their clinical significance. This article presents the case of a 44-year-old female patient diagnosed with invasive breast carcinoma with neuroendocrine features, according to the 2012 World Health Organization (WHO) definition, with focus on presentation, clinical manifestations, diagnostic approach and differential diagnosis.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3719
Author(s):  
Mieszko Lachota ◽  
Marianna Vincenti ◽  
Magdalena Winiarska ◽  
Kjetil Boye ◽  
Radosław Zagożdżon ◽  
...  

Natural killer (NK) cells are innate lymphoid cells with potent antitumor activity. One of the most NK cell cytotoxicity-sensitive tumor types is sarcoma, an aggressive mesenchyme-derived neoplasm. While a combination of radical surgery and radio- and chemotherapy can successfully control local disease, patients with advanced sarcomas remain refractory to current treatment regimens, calling for novel therapeutic strategies. There is accumulating evidence for NK cell-mediated immunosurveillance of sarcoma cells during all stages of the disease, highlighting the potential of using NK cells as a therapeutic tool. However, sarcomas display multiple immunoevasion mechanisms that can suppress NK cell function leading to an uncontrolled tumor outgrowth. Here, we review the current evidence for NK cells’ role in immune surveillance of sarcoma during disease initiation, promotion, progression, and metastasis, as well as the molecular mechanisms behind sarcoma-mediated NK cell suppression. Further, we apply this basic understanding of NK–sarcoma crosstalk in order to identify and summarize the most promising candidates for NK cell-based sarcoma immunotherapy.


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