Modern Classification Systems Research Articles

Burnout: a useful diagnosis?

In psychiatry, burnout is a relevant phenomenon. A large number of individuals is feeling overburdened at work. In contrast to mental disorders, the term 'burnout' is not perceived as stigmatizing, making it therefore easier for afflicted persons to seek help. The term 'burnout syndrome' was mentioned 1974 for the first time in scientific literature. Today, there is a range of partially contradictory definitions and explanations for burnout and the burnout syndrome, respectively. In most studies, burnout is assessed by the Maslach Burnout Inventory, which is neither useful for determining the degree of pathology nor for distinguishing burnout from mental disorders such as depression. It is expected that the burnout syndrome will not be used in modern diagnostic classification systems, because of its unclear definition and conceptual contradictions. On these grounds, it appears reasonable to define burnout as long-term professional overload and a noteworthy risk factor for physical diseases and mental disorders.

(ii) Thoracolumbar spinal fractures: review of anatomy, biomechanics, classification and treatment

Abstract The management of thoracolumbar spine fractures remains a controversial issue. There is disagreement both as to how to describe these injuries and how to manage them. No ideal classification system, accepted by the world of spinal surgery, exists and such systems are under on-going development. While the majority of these injuries can be managed conservatively, new surgical techniques have been developed alongside the evolution of diagnostic tools classification systems. This article aims to revise important concepts that may help surgeons in training to understand spinal injuries and the modern approach to the management of thoracolumbar trauma. We describe relevant thoracolumbar spine anatomy and biomechanics followed by a discussion of historical and modern classification systems, and the treatment methods available to surgeons.

The Construction of Military Documents Electronic Lexicon

Based on the classification system of modern Chinese words classification system and characteristics of military documents field, the military document words are classified and descripted with morphology, syntax, complex feature, semantic and reference. And a military documents electronic lexicon prototype is designed. This lexicon can meet the requirement of military document intelligent processing well proved by application of military documents electronic lexicon.

The dystonias: Past, present, and future

It has been just over 100 years since the term “dystonia” was coined by Oppenheim.1 Since then, there has been enormous progress. The first major meeting on dystonia was the International Dystonia Symposium in 1974 in New York, sponsored by the Dystonia Medical Research Foundation. It was at this meeting that Fahn and Eldridge proposed the first widely used definition and classification system for all dystonias. It also was at this meeting that Marsden proposed considering the focal dystonias as formes fruste of generalized dystonia, several families were described pointing to a genetic basis, and Sagawa presented his patients with dopa responsive dystonia outside of Japan. The proceedings were published in 1976 as volume 14 of Advances in Neurology. These symposia continued every few years, with proceedings of each meeting published in subsequent volumes of Advances in Neurology. The 5th International Dystonia Symposium was held in 2011 in Barcelona, under the joint sponsorship of the Dystonia Medical Research Foundation and The European Dystonia Federation. However, the progress became too much for a single meeting held every few years, and additional meetings were organized to address specific topics in dystonia including genetics, cell biology, anatomy, physiology and animal models. Other meetings focussed on experimental therapeutics or treatment, with the 2nd International Congress on Treatment of Dystonia occurring this year in Hannover, Germany. The termination of the Advances in Neurology series combined with interest in reaching the widest possible audience, led to this Special Theme Issue on Dystonia. The purpose of this issue is to review some of the recent progress. It is not meant to serve as a comprehensive review of all research in dystonia. Instead, it focuses on current views and evolving concepts, the most challenging unanswered questions in dystonia research, and research priorities for the future. The article by Albanese and colleagues2 summarizes the evolving clinical definitions and subtyping of dystonia, with a proposal for a modern definition and classification system that accommodates what has been learned since the proposal of Fahn and Eldridge. Bressmann and Saunders-Pullman3 describe the history of the concept of “primary” dystonias, which are labelled “isolated” dystonia syndromes in the new classification system. Frucht4 describes a practical approach for diagnosis of dystonia in the clinic, and Fung and colleagues5 provide comprehensive list of the myriads of syndromes where dystonia is mixed with other clinical features, together with a useful strategy based on syndromic patterns to aid in diagnosis. These more general articles are supplemented by articles on topics of particular importance such as the similarities and differences among adult-onset focal dystonias,6 specific problems in children with dystonia,7 and psychiatric comorbidities.8 Scientific progress also has increased dramatically in recent years, with four new genes for isolated dystonia syndromes being described in the past year alone.9 The identification of these and other genes means that it is now possible to begin to identify common molecular and cellular pathways in dystonia.10 Our understanding of the pathogenesis of dystonia has evolved from a focus on the basal ganglia to a broader network model that includes other regions.11 Specific physiological defects have emerged as potential endophenotypic traits that predispose individuals to develop dystonia.12 With this new perspective, we now are in a position to examine Marsden’s original proposal that generalized and focal dystonias are related,6 and understand familial clustering. The article by Oleas and colleagues13 outlines the sometimes unexpected lessons we can learn from mouse models that have been genetically engineered as models of specific human dystonias, while the article by Wilson and colleagues describes insights that can be gained by exploiting phenotypic animal models that have a motor syndrome that fits clinical definitions of dystonia.14 The Special Theme Issue on Dystonia concludes with a focus on current treatments, their limitations, and ideas for experimental therapeutics.15, 16 Currently, most of our treatments are empirically driven. However, the dramatic advances in our understanding of the pathogenesis of dystonia means that we now can begin to develop more targeted therapeutics. Many of the articles in this issue raise more questions than answers, so clearly there is a lot more work to do.

Unconscious relational traumatic memory and its relevance to ‘everyday’ clinical psychiatry

The aim of this paper is to demonstrate the relevance of the concept of unconscious relational traumatic memory to 'everyday' clinical psychiatry. One clinical vignette and concepts from the Conversational Model of Psychotherapy are used to consider the potential relevance of this type of memory. The influence of modern classification systems and the dominance of the paradigm of 'biological psychiatry' over the last 30 years have together led to an emphasis on diagnosis and treatment by symptom cluster. This perspective may overlook both the patient's current psycho-social context and their personal history. An understanding of unconscious relational traumatic memory may assist in both the conceptualisation and the treatment of many patients, particularly those adults who have been abused in childhood, where the link between the early experiences and the late manifestations are frequently lost.

Epilepsy informatics and an ontology-driven infrastructure for large database research and patient care in epilepsy.

The epilepsy community increasingly recognizes the need for a modern classification system that can also be easily integrated with effective informatics tools. The 2010 reports by the United States President's Council of Advisors on Science and Technology (PCAST) identified informatics as a critical resource to improve quality of patient care, drive clinical research, and reduce the cost of health services. An effective informatics infrastructure for epilepsy, which is underpinned by a formal knowledge model or ontology, can leverage an ever increasing amount of multimodal data to improve (1) clinical decision support, (2) access to information for patients and their families, (3) easier data sharing, and (4) accelerate secondary use of clinical data. Modeling the recommendations of the International League Against Epilepsy (ILAE) classification system in the form of an epilepsy domain ontology is essential for consistent use of terminology in a variety of applications, including electronic health records systems and clinical applications. In this review, we discuss the data management issues in epilepsy and explore the benefits of an ontology-driven informatics infrastructure and its role in adoption of a "data-driven" paradigm in epilepsy research.

What is Normal? The Impact of Psychiatric Classification on Mental Health Practice and Research

Psychiatry is a rather quite young medical discipline, psychiatry evolved into its present form at the beginning of the nineteenth century (1). From its beginning there has been a discussion about the classification of mental disorders. The modern classification systems originated during the middle of the last century. In 1949 a section on mental disorders was added to the International Classification of Diseases (ICD) of the World Health Organization (WHO). The first Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association was published in 1952 and listed 106 mental disorders (2). The 1960s saw persistent attacks on the field of psychiatry from so-called anti-psychiatrists [e.g., (3)]. During that time these opponents assumed that the main purpose of psychiatric classification was to discipline maladjusted individuals. This “Zeitgeist” was best expressed in the movie “One Flew over the Cuckoo’s Nest,” which portrayed a repressive psychiatric system intent on enforcing “normal” behavior through electroshocks. Despite all of the social criticism, psychiatric professionals continued to elaborate on the original classification system, resulting in a second and third version of the DSM. These revisions were accompanied by a continuous increase in the number of mental disorders. For example, DSM-III contained 265 diagnostic categories while DSM-IV, introduced in 1994, listed 297 psychiatric disorders. Accordingly, revisions of the ICD were published. In 2013, the most recent edition, DSM-5, was released. Prior to this, fierce debate about the conceptual issues of psychiatric classification spilled over into the public media worldwide. Previous revisions that had followed the period of antipsychiatry [including those by ICD, a competing classification system of the WHO] mostly went unchallenged or were discussed only within academic circles of experts. Although current criticism has been widespread, one person in particular has given a face to the voice of those critics. Allen Francis, Professor Emeritus of Psychiatry at Duke University, is the former chairman of the taskforce that revised DSM-III, resulting in DSM-IV. Even if his critique was very much influenced by the predicted impact of those revisions on the U.S. mental health care system, he turned the knife in a wound of psychiatry, i.e., challenging the concept of psychiatric classification. Notably, he argued that lowering the threshold for psychiatric diagnoses would lead to an undue increase in the number of persons labeled in such a way, with corresponding consequences not only to them but also to the health care system itself (4).

Low flow vascular malformation of the buccal mucosa treated conservatively by sclerotherapy (3% sodium tetradecyl sulfate)

Vascular anomalies constitute some of the most difficult diagnostic and therapeutic enigmas in the head and neck region. It is of paramount importance that a modern classification system is established to differentiate vascular lesions from vascular malformations. Vascular malformations are usually congenital and venous anomalies usually expand because of hormonal changes such as puberty, pregnancy, or secondary to trauma. Here, we report a case which was diagnosed as low flow vascular malformation of buccal mucosa involving the lower lip and subsequently treated with 3% sodium tetra decyl sulfate. This paper provides overall understanding regarding the presentation and management of small vascular lesions in the orofacial region. Percutaneous sodium tetradecyl sulfate when used either alone or as adjunct to surgery is a safe, effective, and inexpensive agent in the treatment of venous malformations. However, proper case selection, evaluation, and careful planning are necessary to reduce the unwarranted risks and complications.

Axial Spine Injuries in the Current Conflicts in Iraq and Afghanistan

The burden of injury to the axial skeleton has been substantial relative to the conflicts in Iraq and Afghanistan.A coordinated treatment algorithm is required that begins with the first encounter on the battlefield and continues through treatment at a facility in the continental United States. Translation of these spinal trauma classification systems to the battlefield requires that issues of expediency,operational limitations and restrictions, and personnel be addressed.Current staffing of far-forward echelons in theater may not include a spine-trained orthopaedic surgeon, neurosurgeon, or musculoskeletal specialist.The classification systems and treatment algorithms being used today were formed in the context of a civilian trauma setting. The ready availability of advanced medical imaging, sterile operating room theaters, and specialty-specific intensive care units in these civilian hospitals may make modern spinal trauma classification systems less applicable to a far-forward battlefield setting. However, efforts must be made to adapt current knowledge in the pursuit of a theater-specific, relevant pathway or philosophy of care for the spine-injured warrior, with implementation as far forward as feasible to ensure the best possible clinical outcome.

A comparison of modern diamond classifications

Modern classification systems of diamonds are compared. The common principles of functioning and main features of classification systems are considered in order to improve and modernize them. Possible methods for improving modern diamond classification systems are discussed.

Reception of Kraepelin's ideas 1900–1960

Kraepelin's system of mental diseases has contributed substantially to the foundation of modern psychiatric diagnosis in the DSM-IV and ICD-10. Considering Kraepelin's influence in the creation of these diagnostic tools, the question arises as to how Kraepelin's contemporaries and successors reacted to his nosology. Historical libraries and archives in Munich, Berlin and Paris were searched for European and American psychiatric literature using the keywords 'Kraepelin', 'dichotomy' and 'manic-depressive disorder'. Literature from 1900 to 1960 was examined and compared to the current literature regarding Kraepelin's impact on modern classification systems. The sixth edition of Kraepelin's 'Lehrbuch' (1899) presented the dichotomy in its entirety and led to three different periods of critical comment on dichotomy and methodology between 1900 and 1960. But on the whole, Kraepelin's system was quickly and completely adopted in clinical diagnosis. The publications appearing on and following Kraepelin's centenary in 1956 represent his work as generally being the foundation of modern psychiatry. The neo-Kraepelinian movement, beginning in the late 1960s, developed more differentiated views of Kraepelin's scientific background and methodology. Notwithstanding all the criticism of Kraepelin's dichotomy, it remains more than ever the basis of psychiatric diagnosis. The criticism today shows parallels to the statements made during Kraepelin's era, mainly concerning the issue of diagnostic overlapping of the two disease entities, manic-depressive disorder and schizophrenia, and includes the question of syndromatology.

Timing of referral impacts surgical outcomes in patients undergoing repair of bile duct injuries

Bile duct injury (BDI) after laparoscopic cholecystectomy (LC) remains a significant surgical challenge. Despite claims to the contrary, the incidence of bile duct injury has remained elevated since the introduction of LC. Several issues regarding the surgical management of BDI are controversial, including: (i) identification of the surgeon and centre most capable of managing the injury, (ii) timing of surgical repair, (iii) incidence and significance of associated vascular injury and (iv) identification of patient factors which significantly impact outcome after repair. Variability in timing of referral of BDI to tertiary centres has been noted in the literature. The impact of timing of referral upon post-operative outcomes after definitive surgery has yet to be clearly investigated. We report our experience with 44 patients who required reconstructive surgery after BDI. In contrast to the many studies available in the literature, patients in the current study were classified according to a modern injury classification system. Additionally, we examined the impact of delayed referral to our centre on short- and long-term outcomes after surgical repair of BDI.

A Comment on the Zonal, Intrazonal, and Azonal Concepts and Serpentine Soils

Some prominent ecologists have stated that serpentine soils (soils with ultramafic parent materials) are azonal. Actually, only a small percentage of the serpentine soils are azonal. In order to rectify the inappropriate characterization of serpentine soils as azonal, it is helpful to review the origin and application of the zonal, intrazonal, and azonal terms in soil classification. A soil classification system based on the zonal, intrazonal, and azonal concepts was first developed by Sibirtzev in Russia (Glinka 1914). These concepts were subsequently utilized in the USA (Marbut 1927). Then they were abandoned in the precursor to the present Soil Taxonomy of the USDA (Soil Survey Staff 1960), because the zonal concepts are too ‘‘arbitrary’’ to apply objectively and consistently (Kellogg 1963). Zonal soils are those that reflect the influence of the regional climate. Very shallow soils and soils in recent alluvium, volcanic ash, eolian sand, or loess that lack significant pedological development are azonal soils. They are those rudimentary soils that in similar deposits are similar in all climatic regions (or zones), ignoring vegetative differences. Intrazonal soils are those that reflect the influence of local conditions such as poor soil drainage that make the soils different from the ‘‘normal’’ zonal soils. A major problem with these concepts is deciding what is normal. Is it a 10,000 yr old soil in glacial drift or is it a 100,000 yr old soil on basalt, granite, or serpentinized peridotite? The decision might depend on the common lithology in a region, but the soils in a region with predominantly one of these parent materials (for example, granite) might be quite different from the soils in a climatically similar region with different parent materials (for example, basalt). In fact, well drained and developed serpentine soils (those other than Entisols) might be considered zonal soils in a region where the lithology is predominantly ultramafic rocks. Most serpentine soils in the botanical California Region are Alfisols, Mollisols, and Inceptisols (Alexander et al. 2007). Only Entisols might definitely be called azonal soils, and Entisols occupy only about 0.8% of the serpentine area in the Region (Alexander 2004). Therefore most of the serpentine soils are either zonal or intrazonal, depending upon how one applies these concepts. Those who consider ultramafic rocks to be unusual components of the continental crust would assume that most serpentine soils are intrazonal. The zonal-intrazonal-azonal concepts are very useful, even though they are insufficiently definitive to use in a modern system of soil classification. The zonal and intrazonal concepts can be applied to plant associations as well as to soils. Zonal plant associations may be common on zonal soils and intrazonal plant associations may be common on intrazonal soils. The azonal concept, however, is not easily applied to plant communities. Perhaps the plant associations that conform most closely to the azonal concept are those in early stages of succession. Some plant species, such as Bryum argenteum Hedwig and Achillea millefolium L., have the azonal characteristics of being widespread across many climatic zones, but the azonal concept may not be applicable to plant associations. LITERATURE CITED

S55-03 Cultural and economic factors in European psychiatry guidance

Europe can hardly be considered as homogeneous. There are gross historical, climatological, cultural, developmental, religious, political and economic differences that render generalizations inappropriate and European “globalization” a mission impossible (and, by and large, undesirable).Psychiatry is no exception to the above and in the historical evolution of our discipline, psychiatric practice has varied. Because this evolution has followed a different course and has occurred at a different pace in the various parts of Europe, the present situation reflects all these developmental stages, thus rendering homogeneity questionable.In spite of these differences, however, there is a degree of consensus regarding the basic requirements for the practice of our discipline and the desired competencies of its practitioners. The development of a common language through the modern classification systems, the organizations of specialist psychiatrists (e.g. the UEMS) the WPA and the European Psychiatric Associations have played a useful role in the harmonization of psychiatric practices and are expected to play a more useful role in the future.In conclusion, what is required (and what can be realistically achieved) is consensus on some basic clinical, research, administrative and teaching requirements, in association with agreement on the basic ethical principles of our profession and, basically, the beneficence and non maleficence principles. European Psychiatry Guidance should involve these basic requirements that can be achieved by all European countries.

Teaching Taxonomy: How Many Kingdoms?

A group of high school students sit in the school hallway cramming for a biology quiz. The bell rings; the students shove notes and textbooks into their bags and rush off to class. The quiz is on biological classification. Depending on the textbook, the teachers, and the state curriculum, these students learned to classify all live beings into three, or five, or six major groups, called either or domains. Taxonomy, the identification, naming, and classification of living things, is an indispensable unit in any biology curriculum and indeed, an integral part of biological science. Taxonomy catalogues life's diversity and is an essential tool for communication. But it is more than that. Scientists endeavor to construct phylogenies, diagrams that, like family trees, show relationships among organisms through ancestral lineages. Thus modern classification systems are hypotheses about the genetic relationships among species and the evolutionary history of life. Taxonomy is an especially dynamic field today. New molecular data, primarily DNA sequences, are available for an ever-increasing number of organisms. It appears that, as Emile Zuckerkandl and Linus Pauling predicted in 1965, molecules really are documents of evolutionary history. DNA sequences offer a way to quantify genetic similarity. Because DNA is universal, sequence data shed new light on evolutionary relationships, not only within esoteric groups of microbes but across the entire realm of life. The goal of a unified phylogeny appears within reach. New Science, Old Standards Where new data and interpretations outpace curricula, science teachers enjoy exciting opportunities to share cuttingedge research with students. But frustrating dilemmas arise: How should new information be incorporated into the framework of existing educational standards and materials? The committees that write state and national standards, authors of textbooks, and curriculum developers must also make decisions about how best to handle new developments. The National Science Education Standards address taxonomy for grades 9-12 as follows: Biological classifications are based on how organisms are related. Organisms are classified into a hierarchy of groups and subgroups based on similarities which reflect their evolutionary relationships. Species is the most fundamental unit of classification. National Research Council, 1996 This standard describes the fundamental principles of biological classification without mentioning specific taxonomic systems. Many teachers, however, also answer to state or local standards. Since 1996, I've observed several revisions in my state's standards, the Massachusetts Curriculum Frameworks, which reflect the inherent difficulty in mandating what students should know in fields where methodologies and interpretations are controversial. Massachusetts has continually revised the expectations for student learning in biological classification, especially with regard to the number and kind of major categories of life. Presented below are the 2001 and 2006 high school life science learning standards for this topic. In 2001, students were expected to be able to how the taxonomic system classifies living things into domains (eubacteria, archaebacteria, and eukaryotes) and kingdoms (animals, plants, fungi, etc.). The standard includes an additional note: There is an ongoing scientific debate about the number of kingdoms and which organisms should be included in each. The following websites provide more information: Brave New Biosphere--whyfiles.org/022critters/phylogeny. html and The Tree of Life Project Root Page--phylogeny. arizona.edu/tree/life.html. As of 2006, Massachusetts students are required to use cellular evidence (e.g., cell structure, cell number, cell reproduction) and modes of nutrition to describe the six kingdoms (Archaebacteria, Eubacteria, Protista, Fungi, Plantae, Animalia). …

Auditory hallucinations in schizophrenia – Outcry of a diseased brain?

Schizophrenia, with a lifetime prevalence of one percent, is one of the most common mental diseases. Regarding the typology and definition, hallucinations of different qualities (auditory, visual, tactile, olfactory and gustatory) represent a so-called core symptom according to the modern classification systems ICD-10 and DSM-IV. However, under functional imaging evaluation (MEG) of a neuronal correlate of the disease, truly asymmetric relationships were found. While the notable neurophysiological finding was a general slowing of delta-theta activity within the temporal lobe, an increase in beta activity was found within the same zone during auditory hallucinations, which raises the question of whether this might be an intermittent compensation mechanism of the brain, also in the sense of a self-healing function. This might lead one to speculate whether the supposed core symptom of the disease, auditory hallucination, is not in fact a possible resistance mechanism. If this hypothesis blurts out any measure of truth, the usual therapeutic algorithm will have to be re-evaluated.

The Concept of Psychosis: Historical and Phenomenological Aspects

The historical development of the concept of psychosis and its increasing differentiation from the neuroses up to the modern classification systems, Diagnostic and Statistical Manual of Mental Disorders and International Statistical Classification of Diseases, is initially presented. In portraying this development, the struggle surrounding the clinical relevance of concepts on the one hand and their reliability and validity on the other are reflected. Thus far, diagnostic reliability has primarily been improved by focusing on externally observable symptoms in connection with expression and behavior. The identification of disease-specific symptoms, however, is principally achieved through the differential description of subjective experience. How this experience is to be explored and assessed remains for the most part unclear. With reference to its founder Karl Jaspers, the phenomenological method is presented as the decisive instrument for the assessment of experience. It is shown that a return to the legacy of phenomenology and a reformulation of the long-standing question concerning the specific symptoms of the schizophrenic psychosis are currently in progress. The revival of historical knowledge and a focus on direct clinical phenomena continue to provide inspiration for further advancement in modern psychiatry.

Taking into account the temperament factor: clinical and therapeutic implications

Temperament, although an ancient concept, seems to go far beyond modern classification systems and utilizes a wealth of valuable information including personal and family history as well as ‘non-typical’ symptoms. Thus, it succeeds to define both the specific features of the individual mood episode as well as the long term outcome of the disease, and particularly the response to treatment and overall outcome. The assessment of the temperament is not typically utilized when the therapist designs the treatment strategy. The usual practice is to prescribe antidepressants for depressive episodes and antipsychotics for psychotic symptoms; specific antiepileptics and lithium can be used as mood stablilizers. According to this practice, the ‘classic’ clinical pictures are easier to recognize and to treat, and most agents preferably treat with higher rates of success specific clinical entities, for example lithium is more useful for bipolar patients with euphoric mania and antidepressants as monotherapy for unipolar melancholic depression. However, today, the majority of patients do not fall into these ‘classic’ categories and the assessment of the temperament can reveal a number of clues highly predicting response to a specific treatment as well as the manifestation of a number of problematic effects of pharmacotherapy like agitation, induction of mixed states, rapid cycling and suicidality and even weight gain. Moreover, the knowledge of the temperament can guide the design of the therapeutic strategy with informed and careful simultaneous use of multiple agents. This strategy among others should include some but not all second generation antipsychotics aiming not to sedate, but to the fast acute treatment and prophylaxis from excessive hyperthymic or overt manic behaviours as well as suicide. from International Society on Brain and Behaviour: 3rd International Congress on Brain and Behaviour Thessaloniki, Greece. 28 November – 2 December 2007

Peripheral T-Cell Lymphomas: An Historical Perspective

Peripheral T-cell lymphomas (PTCL) remain largely unexplored due to disease rarity and biological heterogeneity as well as relatively recent recognition in modern classification systems. Before 1970, classifications of non-Hodgkin’s lymphomas (NHL) were based on morphology. The discovery of distinct T-, B- and natural killer (NK)–cell lineages led to two immunologically based classification systems proposed in 1974: the European Kiel and the North American Lukes-Collins. In 1982, the Working Formulation (WF), based on clinical and morphologic criteria, was developed in the United States. The updated Kiel classification separated B- and Tcell lymphomas but still failed to address some disease types. The addition of molecular genetic features/criteria and increasing immunophenotypic subclassification allowed for more diagnostic standardization and reproducibility. The International Lymphoma Study Group (ILSG) integrated morphologic, phenotypic, molecular and clinical information in the 1994 REAL (Revised European American Lymphoma) classification. The T-cell lymphomas were grouped into “precursor” neoplasms versus “peripheral” or post-thymic T-cell and NK neoplasms, the so-called “PTCLs.” The World Health Organization (WHO) subsequently made the following modifications: PTCLs were subdivided into predominantly leukemic, extranodal and nodal types; cutaneous and systemic anaplastic large cell lymphomas (ALCL) were separated; terminology was updated for some diseases; and subcutaneous panniculitis-type and hepatosplenic γδ T-cell lymphomas were recognized as distinct entities. Almost a decade later, the recently published fourth edition of the WHO classification has refined the classification further, including defining ALK-negative ALCL as a provisional entity, confining subcutaneous panniculitislike T-cell lymphoma to cases with an αβ phenotype and combining the γδ cases with primary cutaneous γδ PTCL. Two other provisional categories have been established under the category of primary cutaneous peripheral T-cell lymphomas: primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma and CD8-positive cytotoxic T-cell lymphoma. Several important advances in the pathobiology of PTCL have been made. Unlike mature B-cell lymphomas, there are virtually no recurrent translocations characterizing the PTCLs. The one exception is a proportion of ALCL cases in which a non-random t(2;5)(p23;q35) translocation produces a novel fusion protein composed of the nucleophosmin (NPM) and anaplastic lymphoma (ALK) coding regions. The use of more detailed cytogenetic analysis with comparative genomic hybridization and gene expression profiling now provide evidence for recurrent genetic changes in other PTCL subtypes. Several PTCL subtypes have viral associations that may be involved in disease pathogenesis. In 1982, HTLV1 was found to be the etiologic agent of adult T-cell leukemia and lymphoma. In 1988, T-cell lymphomas were described in patients with chronic Epstein-Barr virus (EBV) infections, and EBV was subsequently found to be associated with extranodal NK/T-cell lymphoma, nasal type and angioimmunoblastic T-cell lymphoma. With the development of molecular techniques in the 1990s, the importance of the γδ T-cell receptor rearrangement and impact on prognosis is apparent. For example, in the updated WHO classification primary cutaneous γδ T-cell lymphoma is recognized by an aggressive course and considered a new provisional entity. Although significant progress has been made in defining specific disease categories within the diverse group of PTCLs and establishing the prognostic significance, advances in therapy have been much slower. In the last several years, attention has turned to testing new chemotherapy combinations, targeted agents and high-dose chemotherapy approaches specifically in PTCL. The hope for the future is that treatment can be tailored better for PTCL and outcomes will more approximate what is observed in aggressive B-cell NHL.

Prognosis and Primary Therapy in Peripheral T-Cell Lymphomas

Peripheral NK/T-cell neoplasms are an uncommon group of diseases that show distinct racial and geographic variation. The prognostic significance of the T-cell phenotype has been clearly defined in recent studies by using modern lymphoma classification systems. However, within this heterogenous group of neoplasms, some have a more favorable prognosis, such as ALK-positive anaplastic large-cell leukemia (ALCL) and primary cutaneous ALCL, and some have ultimately fatal courses with standard chemotherapy programs (e.g., hepatosplenic gammadelta T-cell lymphomas). Further, unlike the benefits observed with CHOP chemotherapy in the treatment of diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphomas (PTCL), other than ALK-positive ALCL, are relatively chemoresistant to this regimen. Given disease rarity and biological heterogeneity, advances in diagnosis, prognosis and treatment have lagged behind DLBCL. Recently, however, studies are emerging that focus specifically on PTCLs with the ultimate goal of better understanding disease biology and developing more effective therapies.