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Born as orthodox catholic in 1700 in Leyden, Gerard van Swieten was orphaned as a child in 1712. He studied medicine under Herman Boerhaave in Leyden from 1720, recording the lectures of his mentor and publishing them after his death. Following his graduation in 1715, van Swieten practiced medicine and pharmacy in Leyden, giving private lectures to students in both fields. Van Swieten became known as a brilliant doctor, and it was expected that he might succeed to Boerhaave’s position after his death in 1738; however, his catholic faith was an obstacle for the protestant State University. These very beliefs, however, contributed to his instatement as the personal physician of the Austrian Empress Maria Theresia (1717–1780) in October 1744. In the summer of 1745 he was appointed physician to Maria Theresa in Vienna by Franz I. and at the same time appointed prefect of the court library. In addition to taking care of the library, other tasks he received from Maria Theresia included reformation of the medical faculty, improving the quality of Vienna’s clinics and promoting healthcare in the empire. Van Swieten is seen as one of the founders of the so-called First Wiener Medical School (Erste Wiener Medizinische Schule) in 1745, and was at the founding of the first modern clinic in 1754. Van Swieten died June 18, 1772.

Descriptions of endometriosis in 18th century monographs and manuscripts are rare and the recorded macroscopic features of endometriosis seldom support this attribution to the described cases. Recently, we became aware of an anonymous German autopsy report from the 18th century. After transcription, the manuscript was assessed by pathologists with historical expertise. This revealed that the patient died because of a malignant tumor, most probably of a gynecological origin. Furthermore, the described ovarian pathologic findings strongly support the diagnosis endometriotic ovarian cyst. Like Giovanni Battista Morgagni (1668–1772) in his landmark publication De Sedibus et Causis Morborum per Anatomen Indagatis (1761), the author correlated the pathological findings at autopsy with the symptoms of the patient. The identity of the patient could, with high probability, be established as being the Countess of Reitzenstein, the wife of a Prussian general major in the army of Friedrich the Great: Karl Erdmann von Reitzenstein (1722–1789).

The purpose of medical autopsy has changed to issues of quality assurance today. In addition, autopsies are considered valuable in medical education, e.g., delivering cases for problem-based learning for students. Many studies underscore the need for autopsies also in the era of technical progress emphasizing the continuing discrepancies between antemortem and post mortem diagnoses. Despite these important tasks, we face a decline of autopsy for several reasons with complex interactions. The role of all persons involved in this decline is evaluated and suggestions for changes are proposed. Last but not least, the future of the autopsy is in the hands of pathology itself.

IntroductionCurrently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient’s prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered prognostically unfavourable, many treatment guidelines recommend adjuvant systemic treatment for all young patients. Patients cured by locoregional treatment alone are, therefore, overtreated. Lack of prognosticators for young breast cancer patients represents an unmet medical need and has led to the initiation of the PAtients with bReAst cancer DIaGnosed preMenopausally (PARADIGM) initiative. Our aim is to reduce overtreatment of women diagnosed with breast cancer aged≤40 years.Methods and analysisAll young, adjuvant systemic treatment naive breast cancer patients, who had no prior malignancy and were diagnosed between 1989 and 2000, were identified using the population based Netherlands Cancer Registry (n=3525). Archival tumour tissues were retrieved through linkage with the Dutch nationwide pathology registry. Tissue slides will be digitalised and placed on an online image database platform for clinicopathological revision by an international team of breast pathologists. Immunohistochemical subtype will be assessed using tissue microarrays. Tumour RNA will be isolated and subjected to next-generation sequencing. Differences in gene expression found between patients with a favourable and those with a less favourable prognosis will be used to establish a prognostic classifier, using the triple negative patients as proof of principle.Ethics and disseminationObservational data from the Netherlands Cancer Registry and left over archival patient material are used. Therefore, the Dutch law on Research Involving Human Subjects Act (WMO) is not applicable. The PARADIGM study received a ‘non-WMO’ declaration from the Medical Ethics Committee of the Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, waiving individual patient consent. All data and material used are stored in a coded way. Study results will be presented at international (breast cancer) conferences and published in peer-reviewed, open-access journals.

An important indication for bone marrow investigation is the presence of bone marrow failure, which manifests itself as (pan)cytopenia. The causes of cytopenia are varied and differ considerably between childhood and adulthood. In the paediatric age group inherited bone marrow failure syndromes are important causes of bone marrow failure, but they play only a minor role in later life. This review gives a comprehensive overview of bone marrow failure disorders in children and adults. We classified the causes of bone marrow failure according to the main presenting haematological abnormality, i.e. anaemia, neutropenia, thrombocytopenia or pancytopenia. The following red cell disorders are discussed: red cell aplasia, sideroblastic anaemia, congenital dyserythropoietic anaemia, haemolytic anaemia, paroxysmal nocturnal haemoglobinuria, iron deficiency anaemia, anaemia of chronic disease and megaloblastic anaemia. The neutropenias occur in the context of Shwachman-Diamond syndrome (SDS), severe congenital neutropenia, cyclic neutropenia, immune-related neutropenia and non-immune neutropenia. In addition, the following causes of thrombocytopenia are discussed: congenital amegakaryocytic thrombocytopenia, thrombocytopenia with absent radii, immune-related thrombocytopenia and non-immune thrombocytopenia. Finally, we pay attention to the following pancytopenic disorders: Fanconi anaemia, dyskeratosis congenita, aplastic anaemia, myelodysplastic syndromes and human immunodeficiency virus (HIV) infection.

With the free movement of people in the European Union, medical mobility has increased significantly. This is notably the case for disciplines for which shortage of well-trained staff has occurred. Pathology is among those specialties and effectively the discipline is confronted with a striking increase in mobility among trainees and qualified specialists. The presumption underlying unlimited mobility is that the competencies of the medical specialists in the European countries are more or less equal, including significant similarities in the postgraduate training programs. In order to assess whether reality corresponds with this presumption, we conducted a survey of the content and practice requirements of the curricula in the EU and affiliated countries. The results indicate a striking heterogeneity in the training program content and practice requirements. To name a few elements: duration of the training program varied between 4 and 6 years; the number of autopsies required varied between none at all and 300; the number of biopsies required varied between none at all and 15,000. We conclude that harmonization of training outcomes in Europe is a goal that needs to be pursued. This will be difficult to reach through harmonization of training programs, as these are co-determined by political, cultural, and administrative factors, difficult to influence. Harmonization might be attained by defining the general and specific competencies at the end of training and subsequent testing them through a test to which all trainees in Europe are subjected.

A new variant of the HLA-A*010101 allele designated as HLA-A*0111N, previously known as HLA-A*010101var, was identified in a patient requiring a stem-cell transplantation. The patient was typed by serologic methods as HLA-A2 homozygous and by sequence-based typing (SBT) as A*010101,020601. Flow-cytometric (FCM) analysis with 11 human monoclonal antibodies (mAbs) for the A1 molecule confirmed lack of any cell membrane expression of the A*0111N allele. One-dimensional isoelectric focusing (1D-IEF) of total cell lysate from the patient’s cells revealed no cell surface and cytoplasmic A1 protein expression, whereas the HLA-A2 molecule was identified by both FCM analysis and 1D-IEF. DNA sequence analysis showed the presence of a synonymous substitution from G to T at position 597 in codon 175. RNA SBT revealed a deletion of 24 bp in exon 3, position 596 through 619, encoding codons 175 through 182 of the HLA-A*0111N allele. The synonymous substitution introduced a new splice site, resulting in an efficient splicing, because no classical A1 protein could be detected in the patient. This alternative splicing prevented the translation into a correct and stable class I molecule expression on the cell surface.

Neural network-based screening (NNS) of cervical smears can be performed as a so-called "hybrid screening method," in which parts of the cases are additionally studied by light microscope, and it can also be used as "pure" NNS, in which the cytological diagnosis is based only on the digital images, generated by the NNS system. A random enriched sample of 985 cases, in a previous study diagnosed by hybrid NNS, was drawn to be screened by pure NNS. This study population comprised 192 women with (pre)neoplasia of the cervix, and 793 negative cases. With pure NNS, more cases were recognized as severely abnormal; with hybrid NNS, more cases were cytologically diagnosed as low-grade. For a threshold value > or = HSIL (high-grade squamous intraepithelial lesions), the areas under the receiver operating characteristic (ROC) curves (AUC) were 81% (95% CI, 75-88%) for pure NNS vs. 78% (95% CI, 75-81%) for hybrid NNS. For low-grade squamous intraepithelial lesions (LSIL), the AUC was significantly higher for hybrid NNS (81%; 95% CI, 77-85%) than for pure NNS (75%; 95% CI, 70-80%). Pure NNS provides optimized prediction of HSIL cases or negative outcome. For the detection of LSIL, light microscopy has additional value.

In cryostat sections of 84 head and neck squamous cell carcinomas (HNSCC) HLA class I and beta 2m expression was analysed using monomorphic and locus specific monoclonal antibodies. Loss of expression was heterogeneous and none of the tumours tested showed a total loss of HLA class I and/or beta 2m when analysed with W6/32, which recognises HLA class I determinants and anti-beta 2m MoAbs. Weak HLA class I and beta 2m expression was found in 9 tumours (11%) and heterogeneous expression was found in 2 tumours (2%). When analysed with locus-specific antibodies (HCA2 and HC10, anti-HLA-A and anti-HLA-B/C, respectively) 37 tumours (44%) showed a loss, weak or heterogeneous expression of one or both loci. Tumours showing a down-regulated HLA class I expression were analysed for mutations in either allele of the beta 2m gene by sequencing based mutation analysis (SBMA). Exon 1 and exons 2 and 3 were amplified separately by PCR using M13-tailed intron-specific primers. PCR products were sequenced in two directions. In none of the tumours mutations in the beta 2m gene were detected. In 59% of the tumours with down-regulated HLA class I expression, lost or down-regulated TAP 1 expression was found when analysed with anti-TAP 1 antibodies. This indicates an important role for TAP in down-regulation of HLA class I expression in HNSCC.

ABSTRACT: Sequencing Based Typing (SBT) is a generic approach for the identification of HLA-A polymorphism. This approach includes the high resolution typing of the HLA-A broad reacting groups, HLA-A subtypes and will identify new alleles directly. The SBT approach described here uses a locus specific amplification of DNA from exon 1 to exon 5. The resulting 2,022 bp PCR product serves as a template for the subsequent sequencing reactions. Amplification is followed by direct sequencing of exons 2, 3 and 4 in both orientations with fluorescently labeled primers to define all polymorphic positions leading to a high resolution typing result. In this study the sequence of exons 2 and 3 of a panel of 49 cell lines was determined. In addition, the exon 4 region of 35 cell lines was also sequenced to evaluate the exon 4 polymorphism. The HLA-A type of most of the cells could be identified by sequencing only exons 2 and 3. However, the sequence of exon 4 was required to discriminate A∗0201 from A∗0209 and A∗0207 from A∗0215N. In this panel, an identical new “HLA-A∗0103” was identified in two Caucasian samples.

Background The only realistic way to improve harmonisation of European pathology training is to define the generally accepted competencies and to test them periodically during the training programme (progress test). The European Association of Pathology Chairs and Program Directors therefore decided to implement an annual on-line test using virtual slides in addition to static jpeg images and theoretical MCQ’s. The EU supported this endeavour as EUROPALS (EUROpean Pathology Assessement & Learning System). Methods To address the challenges of large scale digital testing EUROPALS teamed up with i-Path Diagnostics Ltd, a company specialising in utilisation of virtual slides in histology/pathology education and examination. Specific examination software was used in the test system. Results In the first 2 years we provided at five occasions progress tests, including 2 proctored tests, attracting hundreds of participants. The accessibility varied from suboptimal to good and improved with each subsequent test. It was influenced both by the hosting server capacity and the internet bandwidth at the user’s location. Conclusion On-line testing using virtual slides is possible but requires a good collaboration between the provider and the user. Both should be aware of the requirements and threads of large scale testing with hundreds of simultaneous users.

Dear Editor, To say that autopsy rates are declining is like kicking an open door. For more than three decades, hundreds of articles have been written to discuss this phenomenon [6]. No matter the background of the authors, clinicians and pathologists alike regret this decline and are of the opinion that this situation should be reversed in order to assure high quality medical practice [3–5, 7, 9]. However, all these papers have not had the desired effect of reversing this process. It appears that these papers served mainly to benefit the curriculum vitae of the respective authors and their list of citations. In strong contrast with this supposed lack of interest is the fact that a PubMed search for the term “autopsy” over the years 2000–2006 shows more than 10,000 links, indicating that the autopsy is still an important technique to study (mechanisms of) disease. The reasons for this decline are well known and extensively described [3]. Relatives now are more hesitant than in the past and refuse approval for an autopsy more frequently; or, perhaps, we should say that relatives in the past were as hesitant as relatives are at present but were less likely to contradict the then-well-known (and almighty) doctor. This independence has to be accepted as a fact, there is no reason to believe that this tide will change. Clinicians share some of the blame. Today, they are, perhaps, less persistent and even less interested in pursuing an autopsy because contacts with recently bereaved families are difficult, and many clinicians believe that modern imaging techniques supply them with enough critical information. Moreover, in today’s specialty and clinic orientated practice, the clinicians have less personal contacts with the patient and the relatives, and the chance that a patient dies in the presence of his own doctor is not what it was in the past. This situation will not change in the near future. Therefore, this looser relationship has to be accepted as a fait accompli, and no drastic changes can be foreseen that will influence the autopsy numbers in this respect. Finally, the various ‘medical authorities’ are also not very helpful. Requirements for specified numbers of autopsies for certification of hospitals and for residency training programmes were abolished long ago, often followed by the withdrawal of funding to perform autopsies. So what are we left with? Do we have to accept the situation as it is, or is there something that we, as pathologists, can do? It is strange that pathologists, although we must share responsibility for the waning of the autopsy, often are left in the shadow. Sometimes, long delays in the reporting of autopsy findings is mentioned as a cause of clinical dissatisfaction, but the professional competence of pathologists is almost never an issue. Yet a lot can be gained here. What are the facts? Many pathologists are not interested in autopsies and/or see them as a burden. Many pathologists lack sufficient clinicopathological background to adequately answer the questions of their clinical colleagues. Reports are often so delayed that the critical features of the case have been lost from memory, and interest therefore, is low. Reports often do not contain the relevant answers. In some occasions, the reported results are evidently wrong. Let us examine these facts one by one. Many pathologists are not interested in autopsies There is nothing wrong with the fact that some, or even many, pathologists have little direct interest. We accept that we have among our colleagues dermatopathologists, GI pathologists, etc. But for some reason, there is a widely held perception that every pathologist should be able to perform, or at least supervise, autopsies “to equally share the burden”, as is often said. This is a very strange and illogical perception. Nobody expects a general pathologist to diagnose a difficult myeloproliferative disorder or an unusual neurodegenerative disease or recognize a Sanderson’s polster, when they see one. But we nevertheless expect him/her to perform with aplomb an autopsy on a complicated intensive care unit (ICU) patient with multiorgan disease. The same problem is also seen at resident level. The UK already offers pathology training programmes without autopsy training. At a recent course for first year pathology residents in the Netherlands, I asked the 25 residents how many of them would choose such a training if offered. Five answered positively and six indicated that they would prefer never to do autopsies as a pathologist. Worse is the situation when pathologists openly put the value of autopsies up for debate. Unfortunately, this happens with increasing frequency. Many pathologists lack sufficient pathophysiological knowledge Performing autopsies not only requires a solid basis in the field of general pathology but also in the common problems of clinical medicine and in basic anatomy and physiology. The pathophysiology of the circulatory, respiratory and renal system, in addition to that of the clotting system, should be well known. Familiarity with ICU complications and their treatment is mandatory for adequate interpretation of what may be encountered in many autopsy cases. Also, the interpretation of the pathology of shock versus post mortem changes requires special training. We cannot expect that every pathologist has the time and interest to keep his competencies updated in such a broad and complex field, certainly if he/she, with the declining autopsy rates, will only occasionally be responsible for an autopsy. Reports are often delayed The fact that autopsies are often reported after many weeks or even months (and sometimes not at all) is well known and constitutes a complaint in various articles discussing autopsy decline. The responsible clinician has, in the meantime, often moved to another rotation or has forgotten the details of the disease history and has also sent the final report about the patient to the GP of the patient; thus, the case is ‘closed’ in his/her mind. This type of disconnect certainly is a source for irritation and will contribute to reluctance in asking another autopsy approval. Many autopsy reports do not contain relevant answers to the questions raised during life. It must be said that the autopsy request forms often contain marginal and/or incomplete information [2]. However, the questions raised should be answered and in an epilogue the morphological findings should be interpreted in the clinical context and vice versa. Only then the patient’s file can be closed with confidence. In some instances, the reports provide wrong information These types of errors can be due to misinterpretation of findings, often because of lack of detailed knowledge of the clinical course leading up to death, coupled with lack of insight in pathophysiological phenomena or due to hurry or even neglect [2]. The circumstances surrounding Dr. Shipman’s cases are a good example of this situation, where deaths were reported as cardiac events without sufficient evidence for such a diagnosis [8]. Similar situations might happen everywhere. This type of publicity, certainly when combined with tissue retrieval problems, will most certainly influence the attitude towards autopsies of the general public and medical professionals. These facts taken together raise real concern as to the contribution of ‘Pathology’ and pathologists in the decline in autopsy rates and, in effect, cry out for another approach by our profession to the performance of autopsies. Moreover, we cannot close our eyes to such new approaches as limited autopsies, CT and MRI procedures followed by needle biopsies and so on [1, 3]. Certainly, in the light of the declining autopsy rates, where it is difficult to acquire sufficient experience in performing, interpreting and reporting autopsies, it is necessary that the pathologists who perform autopsies are enthusiastic, interested, competent and respected for their knowledge in this field. Only then are they good sparring partners for the clinicians and good teachers for our residents. The only way to achieve this goal is to accept Clinical Autopsy Pathology as a recognised subspecialty within our profession, in the same way as other subspecialties. A period of additional training in intensive care medicine would be desirable—to learn the language of the intensive care unit which, because of the critical condition of many ICU patients, is the source of a significant number of autopsies and certainly the most complicated ones. Or possibly, there is even a case for incorporating a year of clinical experience in Medicine and Surgery into the training of a Clinical Autopsy Pathologist, an experience that surely contributed to the high level of competence that many of our illustrious predecessors displayed in autopsy pathology. Of course, there should be room for subspecialists who will usually perform their own autopsies, e.g. paediatric pathologists and neuropathologists. In conclusion, the decline in autopsy rates is a progressive one. It is time for us, the pathologists, to finally do something constructive other than to weep and wail. We have to bring our best men and women in the frontline and respect their work as highly as any other recognised subspecialty. It is that or the end of the autopsy. What if our attempts do not work, and the decline continues? In that case, we have already anticipated some of the measures that must be adopted anyway. There is no way to escape the future; it is coming. But we can reshape it by acting now. I, therefore, sincerely hope that this letter will not prove to be just an addition to my list of publications.

In this issue Lehr et al. describe the compulsory examination used by the Swiss Society of Pathology to assess senior residents, and thereby assure the professional competence of its future qualified members [1]. With this examination, Switzerland is, with Britain, one of the few European countries with a comprehensive examination (lasting several days) that tests the full range of theoretical and practical competencies required of a medical specialist-pathologist. There is considerable variation across Europe in the way that the final competencies of pathology trainees are assessed [2]. The reason for this variation is the fact that European countries are all entirely autonomous with regard to training, licensing and the issuing of specialty diplomas in postgraduate medical education. For example, in pathology six countries do not require any form of testing at all at the end of specialty training. In the remaining 26 there is considerable heterogeneity of testing [2], with autopsy competency tested in 11, gross specimen examination and sampling in 9 and cytology in 18. No exact data about the duration of these examinations are known. Harmonization of training and the assessment of its effectiveness in producing competent specialists has proven to be very difficult because very few countries are willing to give up their autonomy to decide on the competencies of their medical specialists, to be acquired during residency training. This is in stark contrast to many countries where obligatory specialty examinations, sometimes with considerable failure rates, are the norm. Examples include the North American specialty boards and the examinations of the British Royal Colleges [3, 4]. For the Royal College of Pathologists, examinations are one of the principal benchmarks by which trainees are judged to have reached professional competence. The British examinations are still copied in one form or another by their old colonies (e.g. Australia, Canada, many African countries). When one of us (JGvdT) was an external examiner in Zimbabwe in the 90’s it was much more difficult to become a pathologist there (or indeed a specialist in any medical discipline) than in the Netherlands and many other European countries. The same applies e.g. to Tanzania where, to progress further in the specialty, residents have to pass a general pathology examination already after 6 months of training. To tackle this diversity in training and testing in 1997 the European Board of Pathology (EBP) of the European Union of Medical Specialists (UEMS), introduced an annual voluntary examination for senior pathology residents, based upon a similar examination successfully introduced by the European Board of Urology. Although introduction of the examination was supported by a large majority of the members of EBP, due to the lack of any consequence of failing, and poor support by senior pathologists, the test never really got off the ground and is currently taken by only a handful of people, mainly those from outside the EU hoping to increase their prospect of finding work as pathologist in Europe. The only exception is Malta where since 2011 the UEMS examinations are officially recognized for all medical specialisms. With support of a grant from the EU, the European Association of Pathology Chairs and Program Directors (EAPCP) developed a voluntary progress test (EUROPALS) [5], comparable to the American RISE (Resident In Service Examination). The latter test is given for all medical specialties in the USA and is for pathology a good outcome predictor for the American Board Examination [6]. This EUROPALS test had a high participation rate and is now, thanks to the support of the European Society of Pathology being developed as an official progress test, not only for residents but also for specialised pathologists and subspecialists. The relevant question here of course is why trainee medical specialists, including in pathology, in so many countries in Europe are not thoroughly tested at the end of their training. This is relevant in view of the results of the American and British examinations, showing that a proportion of advanced residents do not have the core competencies, as defined by senior members of the profession, considered necessary for practicing safely. As there is no suggestion that the training in the UK or USA is substandard, the question is relevant whether introduction of similar assessments across Europe would demonstrate lacunar competencies in some of the examined residents. That is not to suggest that trainees across Europe might be less competent than their North American or UK homologues, merely that as the experience in the e.g. USA and UK indicates, assessment stimulates learning. Creating a knowledgeable, thoughtful and competent pool of specialists is surely the fundamental goal of any postgraduate medical training programme.

“History is the essence of innumerable biographies.” Thomas Carlyle; 1795–1881 The History of Medicine is a flourishing field of interest and research, with an extensive literature and several notable books, including some in the “popular” press. Interest in the History of Pathology per se is far less evident. While admitting to bias, we are of the opinion that Pathology receives short shrift in general medical histories, an opinion that we believe is shared by many colleagues. Certainly there are many pathologists who are interested in specific historical aspects of their profession. However, there are few national or international societies concerning the history of pathology. Until recently, there was no such group in Europe, a deficiency now being remedied by the formation of a History of Pathology Working Group of the European Society of Pathology. The History of Pathology Society in America has a longer record, sponsoring a 2-h “companion meeting” at the annual United States and Canada Academy of Pathology (USCAP) meeting, but it is far from active during the remainder of the year. “Unknown Unloved” is probably the best way to describe the present situation. The “Companion Meeting” at the USCAP in 2008, in Denver, CO, USA, was advertised under the billing of “Famous Europeans who shaped Pathology.” It drew an audience exceeding the meeting room capacity. The positive reactions of that audience stimulated subsequent initiatives to organize History of Pathology Symposia at the International Academy of Pathology Congress in Athens in 2008 and at the European Society of Pathology Congress of 2009. Both were well attended, providing food for thought and encouragement for the notion of soliciting a series of papers in this area or a small book, or as it turns out, both. Previous books have been few. Most enduring among these was the comprehensive A History of Pathology written by Esmond R. Long. Initially, published in 1928, a second updated Dover edition appeared in 1964. Contact with the present owners of Dover publications revealed no interest for a new edition. Fortunately Virchows Archiv was of a different opinion. The Editors have committed ample space over the next 2 years for a series of articles about the different aspects of our history. At the end of the series, the manuscripts will be combined into a book. We are very grateful to Professors H. Hofler, Editor-in-Chief, and F.T. Bosman, managing editor of Virchows Archiv, for their enthusiastic support of this project. Although the different topics will cover the time span from antiquity to the present, the papers will not be published in chronologic order. However, because each paper is designed to stand alone, this should cause no problems. The first paper in the series appears in this issue of Virchows Archiv and provides an overview of the whole period, highlighting some of the key historical moments that have determined the shape of current pathology practice. Forthcoming articles will deal with particular historical periods (e.g., the Antiquities, the Roman influence, the Arab influence), with groups of important scientists (e.g., famous anatomists—you use their names daily), or with remarkable individuals, who made special contributions, and were in many ways “early pathologists.” In addition, there will be selected articles on the history of various technical and educational aspects, such as microscopy, stains and staining methods and on the founding of museums. The twentieth century will mainly be illustrated through the history of classifications of diseases. We fully realize that it is absolutely impossible adequately to cover, or even mention, everyone who has made contributions in the field, neither is it possible to cover every discovery of significance. A coinciding relevant event is the production of an Encyclopedia of Pathology, to be published in 2012, also by Springer Verlag. This encyclopedia has a subsection on the History of Pathology and will carry more than 150 entries on historical persons and events. Both projects will be closely integrated. We hope that these publications in Virchows Archiv, and also in the Encyclopedia, will raise the level of interest in the fascinating history of our specialty and will lead to more research and critical thought concerning what we do as pathologists and why and how we do it. Guest Editors

Pathology without frontiers Pathology in Europe is still mainly directed at a national level by the national pathology societies. The main goal of these societies is to guarantee an optimum practice of the specialty, both professionally and economically, in their own country. The interest or involvement in the same aspects of the specialty in other countries was and is very limited, taking the long history of European unification into consideration. The main international organisation that binds anatomic pathologists in Europe is the European Society of Pathology. This Society is the main organiser of international European congresses that are held biannually (with a smaller intercongress in between). Moreover, it adds also to postgraduate education by its European School of Pathology and by EuroCellPath. The latter organisation addresses mainly the molecular aspects of pathology. Through these activities, the European Society of Pathology contributes to augmentation of knowledge in Europe in its widest geographical sense. However, it does not play an active role in the process of harmonisation of training and practice in Europe. With the Treaty of Rome in 1957, a free exchange of diplomas, including the medical ones, in the then European Economic Community (EEC) was realised. In 1958, representatives of the medical specialist organisations of the six involved countries convened to discuss the consequences of the free movement of doctors that could result from this decision. Europe at that time had a great diversity in specialties with only partial overlap in different countries. They, therefore, founded the European Union of Medical Specialists (UEMS) and tackled a number of problems such as manpower planning, subspecialisation, marking out of specialities, the quality of the specialty training and the consequences of free movement of medical specialists. In 1962 the UEMS founded within its organisation specialist sections for the most important specialties practised at …

Objective : To assess the accuracy of large-core needle biopsy in evaluating palpable and nonpalpable breast lesions. Methods and patients : Stereotaxic and ultrasound (US) guided core biopsies were performed in 103 breast lesions in 97 patients. Subsequently, all patients underwent surgery. All specimens (core biopsy and surgical) underwent radiography for evaluation of microcalcifications. The histopathologic findings of the core biopsies and the surgical specimens were correlated. Results : Core biopsies and surgery findings were concordant in 100% of the 27 palpable lesions and in 89% of the 76 nonpalpable lesions. One case of malignancy, ductal carcinoma in situ (DCIS), was not diagnosed by core biopsy. In 102 (99%) of the 103 breast lesions, a correct choice for additional diagnostic procedure or definitive treatment could have been made upon histopathologic findings of core biopsy. Conclusion : Stereotaxic and ultrasound-guided core biopsy are safe, reliable and less traumatic than excisional biopsy. Special attention is necessary when atypical ductal hyperplasia (ADH) or DCIS without invasive carcinoma is found. Radiography of the biopsy specimens for detection of microcalcifications is essential.

The occurrence and characteristics of intracellular immunoglobulin inclusions in non-Hodgkin’s lymphomas are described. Lymphoma cells from three patients with immunoblastic sarcoma contained classic cytoplasmic, periodic acid-Schiff (PAS)-positive Russell bodies. Immunoperoxidase staining revealed monoclonal IgG ( k ) in two cases and a polyclonal pattern in the third case, where the tumor evolved from a reactive lesion. Unusual cytoplasmic inclusions were observed in the neoplastic cells of two patients with follicular center cell lymphoma. In one case large globular structures lacking a distinct limiting membrane were seen, while the cells of the other patient contained “signet-ring-like” vacuoles filled with microvesicles. Both were PAS-negative and showed monoclonal immunoglobulin staining. In two other cases PAS-positive intranuclear inclusions consisting of monoclonal immunoglobulin IgM(κ) could be demonstrated. The possible significance of these findings in B-lymphocyte derived neoplasms is discussed.

The occurrence of two different histologic types of lymphoma in one organ, or in two different organs at the same time, or during the course of the disease, forms an intriguing biologic phenomenon. This report describes an immunohistologic study of ten such cases; seven consisting of two different non-Hodgkin’s lymphomas, together with three cases in which Hodgkin’s disease was one of the components. The findings in the non-Hodgkin’s lymphoma group are in keeping with emerging immunologic and physiologic concepts: i.e. , the different component parts appear to represent different maturation stages of the neoplastic B lymphocyte. The cases in which Hodgkin’s disease and a non-Hodgkin’s lymphoma were observed showed a surprising similarity between the malignant cells of both tumors when studied with immunoperoxidase technics for anti-light-chain and anti-heavy-chain antibodies. These observations may serve to resurrect an old belief in the common origin of certain of the non-Hodgkin’s lymphomas, and possibly also of Hodgkin’s disease. It is concluded from this study that true composite lymphomas are extremely rare and that the majority of the cases described as such are better considered as different morphologic expressions of a single malignant cell type—the lymphocyte.

Objective To assess the difference in costs between PAPNET-assisted and conventional microscopy of cervical smears when used as a primary screening tool. Study design We performed time measurements of the initial screening of smears by four cytotechnologists in one laboratory. Time was measured in 816 conventionally screened smears and in 614 smears with PAPNET-assisted screening. Data were collected on the components of initial screening, clerical activities and other activities in the total work time of cytotechnologists in the routine situation and on resource requirements for both techniques. Results PAPNET saved an average of 22% on initial screening time per smear. Due to costs of processing and additional equipment, the costs of PAPNET-assisted screening were estimated to be $2.85 (and at least $1.79) higher per smear than conventional microscopy. The difference in costs is sensitive to the rate of time saving, the possibility of saving on quality control procedures and the component of the initial screening time in the total work time of cytotechnologists. Conclusion Although PAPNET is time saving as compared with conventional microscopy, the associated reduction in personnel costs is outweighed by the costs of scanning the slides and additional equipment. This conclusion holds under a variety of assumptions. Using PAPNET instead of conventional microscopy as a primary screening tool will make cervical cancer screening less cost-effective unless the costs of PAPNET are considerably reduced and its sensitivity and/or specificity are considerably improved.