Perspectives on Low-grade Sarcomas: The Extraordinary Contributions of Sharon W. Weiss, MD.

Soft-tissue pathology encompasses a wide spectrum of neoplasms that represent some of the most challenging and problematic tumors in surgical pathology. Owing to the intensive work of dedicated pathologists, this once esoteric field has become increasingly well defined. In this review, Dr Sharon Weiss' monumental contributions to low-grade sarcomas, including low-grade fibromyxoid sarcoma/so-called hyalinizing spindle cell tumor, atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma, epithelioid hemangioendothelioma, and dermatofibrosarcoma protuberans with fibrosarcomatous transformation will be discussed.

Contributions of Dr. Louis "Pepper" Dehner to the art of cutaneous pathology, the first pediatric dermatopathologist.

Dr. Louis "Pepper" Dehner has been one of the most influential surgical pathologists of the last century. Authoring more than 450 publications, he is the premier modern pediatric pathologist. Perhaps, an area that he is less recognized and in which we would like to describe his contributions, is his role as a creator of the art of pediatric dermatopathology. Dr. Dehner has had at least 50 major publications describing, discovering, and orienting the discipline in the fields of fibrohistiocytic disorders of childhood, vascular tumors, and histiocytosis among many others. Dr. Dehner has clearly manifested that while many similarities between adult and pediatric surgical pathology exist, "children get different diseases." It is because of his mindful analysis and translation of the clinico-pathologic and biologic correlative between specific entities and advances in the field he has made that we are honored to describe some of his contributions to this particular area.

All things rhabdoid and SMARC: An enigmatic exploration with Dr. Louis P. Dehner.

Over the past several decades, our understanding of malignant rhabdoid tumors (MRT) and the central nervous system equivalent atypical teratoid/rhabdoid tumor (ATRT) has undergone considerable refinement, particularly in terms of genetic characterization. MRT (both renal and extra-renal) and ATRT share phenotypic similarities and a common genetic signature, that being inactivating alterations of the SWI/SNF complex component SMARCB1 (or rarely SMARCA4). Unfortunately, a wide array of tumors bears significantly overlapping phenotypic characteristics to MRT/ATRT, posing a formidable diagnostic challenge. Likewise, the list of tumors bearing SMARC-related alterations has grown at a dizzying pace, and the original assumption that SMARCB1 alterations were unique to MRT/ATRT has been essentially negated. It should come as no surprise that Dr. Louis P. Dehner, no stranger to enigmatic lesions, participated significantly in this pathologic controversy, and the circuitous journey of entity discovery and clarification. This review aims to (1) summarize our current knowledge of MRT and ATRT with an emphasis on genetic characterization, (2) present insight into so-called "composite rhabdoid tumors" (CRTs), and (3) and provide an updated account of others tumors bearing SMARC alterations.

Pathology of the liver in children: Where would I (we) be without "Pepper"?

A tribute to Pepper's lasting contributions to Hepatopathology.

Pulmonary and pleural pathology: Contributions of Dr. Louis "Pepper" Dehner.

Dr. Louis Dehner is an internationally renowned surgical pathologist who has published multiple textbooks and has authored or co-authored nearly 400 original articles in the medical literature. While many think of him as a pediatric pathologist, he has contributed to the literature across virtually the entire breadth of surgical pathology, and the lung and pleura is no exception. This review will highlight Dr. Dehner׳s contributions to the pulmonary and pleural pathology literature in the areas of infectious disease, medical lung disease and transplant pathology, and a number of neoplasms of the lung and pleura, with the remainder of this manuscript dedicated to the still evolving story of the pleuropulmonary blastoma as the signature contribution of his long and distinguished career.

Diagnostic immunohistochemistry through Rosai-coloured glasses.

Over the past three decades, Immunohistochemistry has materially changed the practice of diagnostic surgical pathology. Foundational observations in this field were critical to a reasoned assessment of both the risks and opportunities that immunohistochemistry afforded the surgical pathologist, and our current practice draws heavily on those early assessments. As we collectively look to and acknowledge those who recognized the value of this technique and who helped guide its development as a companion to (not a replacement for) histomorphologic evaluation, we are drawn to those whose mastery of detail and ability to draw common patterns from seemingly unrelated phenomena helped define the diagnostic power of immunohistochemistry. The focus of this review is on one individual, Dr. Juan Rosai, whose contributions transcend the simple linkage of molecular observations to morphology, recognizing novel patterns in both form and color (the latter often the lovely shades of diaminobenzidine), seemingly viewing our diagnostic world at times through an entirely different lens. By looking at Dr. Rosai's early work in this field, reviewing a selection of his seminal observations, particularly in the Immunohistochemistry of thyroid and thymic neoplasia, revisiting how his special insight is often guided by the work of the early masters of morphology, and how his mentorship of others has helped shaped academic surgical pathology practice, perhaps we can get a glimpse through that lens.

A note from history: landmarks in history of cancer, part 4.

In the second half of the 19th century, most cancer patients were cared for by surgeons who exerted ascesis and limited their operations to 1 or 2 specific areas. To assist surgeons and other physicians in caring for their patients, pathologists described newly discovered entities, refined the microscopic classification of tumors, and introduced the grading of cancers. The discoveries of Rontgen and the Curies revolutionized the diagnosis and treatment of cancers. The search for the cause of cancers extended to infectious organisms, chemicals, and radioactive materials. The 50 years covered in this review formed the groundwork for the coordinated, specialized care of cancer patients at institutions dedicated to render the most promising treatment.

Aldred Scott Warthin: Ann Arbor's Erudite, Outspoken, and Academically Transformative Early 20th Century Pathologist.

CONTEXT.­: Aldred Scott Warthin, MD, PhD, was professor of pathology and director of the pathological laboratory at the University of Michigan during the first third of the 20th century. OBJECTIVE.­: To explore the life and accomplishments of Dr. Warthin and his impact on academic anatomic and clinical pathology. DESIGN.­: Available primary and secondary historic sources were reviewed. RESULTS.­: After studying music, biology, and botany, Warthin attended medical school at the University of Michigan, graduating in 1891; he remained in Ann Arbor for 40 years, almost single-handedly transforming a rundown department into a top academic department. He was a dedicated teacher who produced 2 important pathology textbooks. His research interests were diverse. In 1913, he published one of the first papers unambiguously documenting heritability of cancers; subsequent research on one of his cancer families resulted in the description of Lynch Syndrome. He published extensively in the fields of surgical pathology and experimental pathology. He was a recognized expert on syphilis and pathology of aging. CONCLUSIONS.­: Warthin's name is eponymously associated with Warthin-Finkeldey giant cells in measles, Warthin's tumor of the parotid, and Warthin-Starry stain for the diagnosis of syphilis as well as Warthin's sign in the clinical diagnosis of pericarditis.

Short history of the autopsy: part II. From the second half of the 16th century to contemporary times.

We present the second part of our review concerning the history of autopsy. During the development of medicine the role of autopsy was obviously changing. Concurrently with the progress in the anatomical knowledge, the anatomists observed and noted both single anomalies and repetitive changes which correlated with symptoms in living patients. This is how anatomopathology came into being. We present the most famous people engaged in autopsy comprehension. We discuss main trends and ideas influencing the phenomenon of autopsy in the analyzed period: from sporadic public dissections, through theatra anatomica, introduction of autopsy to the hospital medicine and separation of anatomopathology as a medical speciality. The golden age of autopsy was the 19th century and the first half of the 20th century, with a consecutive decline in frequency. Nevertheless, despite the progress in diagnostics in vivo, it seems that autopsy will keep its important place in medicine according to the old motto "Mortui vivos docent" (the dead teach the living).

Albert C. Broders, tumor grading, and the origin of the long road to personalized cancer care.

The roots of precision cancer therapy began at the Mayo Clinic in 1914 when surgical pathologist Albert C. Broders began collecting data showing that cancers of the same histologic type behaved differently. In March 1920, based upon 6 years of clinical follow-up, Broders published his first paper, utilizing data from over 500 cases of squamous cell carcinoma of the lip that he had blindly divided into four histologic grades based upon degree of differentiation, showing that numerical tumor "grading" allowed him to predict patient prognosis. Before this, surgeons had no scientific way to evaluate prognosis. Broders then replicated his work using other types of tumors at other body sites, as did several Mayo Fellows and pathologists at other institutions. Cuthbert Dukes in London, England not only replicated Broders' findings with rectal adenocarcinomas, he also used the same data to develop the first tumor "staging" methodology by focusing upon depth of local invasion and presence or absence of lymph node metastases. Soon, tumor grading, tumor staging, or the combination of both represented state-of-the-art prognostic techniques for scientific cancer care. This brief historical vignette celebrates the 100th anniversary of Broders' first paper, which is the starting point for the long road to personalized cancer care.

Emmanuil Kondoleon: pioneer in surgical treatment for lymphedema.

Our era is characterized by the rapid improvements in treatment in all areas of medicine. But we should not forget those pioneers who, with their medical actions and inspiration, changed the course of their era and left their mark on medical history. One of those is the Greek surgeon Emmanuil Kondoleon (1879-1940). His brilliant scientific personality, numerous teaching activities, and his notable publications made him a distinguished Professor of Surgical Pathology. At the beginning of the 20th century, when very little was known about lymphedema and especially its treatment, Emmanuil Kondoleon arrived on the scene with his own original technique that led the surgical treatment of lymphedema for more than 50 years. Made famous as Kondoleon's procedure, his technique included wide excision of the fascia and concomitant partial excision of the hypertrophic tissue. Such important personalities as Kondoleon set great examples in medical history and inspire future young generations of physicians.

Historical development of the renal histopathology services in Malaysia.

Western-style medicine was introduced to Malaya by the Portuguese, Dutch and British between the 1500s and 1800s. Although the earliest pathology laboratories were developed within hospitals towards the end of the 19th Century, histopathology emerged much later than the biochemistry and bacteriology services. The University Departments of Pathology were the pioneers of the renal histopathology diagnostic services. The Department of Pathology, University of Malaya (UM) received its first renal biopsy on 19 May 1968. Hospital Universiti Kebangsaan Malaysia (HUKM) and Hospital Universiti Sains Malaysia (HUSM) started their services in 1979 and 1987 respectively. It is notable that the early services in these University centres caterred for both the university hospitals and the Ministry of Health (MOH) until the mid-1990s when MOH began to develop its own services, pivoted on renal pathologists trained through Fellowship programmes. Currently, key centres in the MOH are Kuala Lumpur Hospital, Sultanah Aminah Hospital Johor Bahru and Malacca Hospital. With the inclusion of renal biopsy interpretation in the Master of Pathology programmes, basic renal histopathology services became widely available throughout the country from 2000. This subsequently filtered out to the private sector as more histopathologists embraced private practice. There is now active continuing professional development in renal histopathology through clinicopathological dicussions, seminars and workshops. Renal research on amyloid nephropathy, minimal change disease, IgA nephropathy, fibrillary glomerulonephritis, lupus nephritis and microwave technology have provided an insight into the patterns of renal pathology and changing criteria for biopsy. More recently, there has been increasing involvement of renal teams in clinical trials, particularly for lupus nephritis and renal transplant modulation.

Surgical pathology in the 20th century at the Mount Sinai Hospital, New York.

How did the education of surgical pathology, and pathology in general, differ at Mount Sinai? Passing the examination of the American Board of Pathology was never the focus of the department. Learning criteria or quoting references was de-emphasized, but mastery of macroscopic pathology was required, supported in both word and action by two brilliant surgical pathologists, Otani and Kaneko, and by two extraordinary medical pathologists, Klemperer and Popper. Meticulous microscopy emphasized pattern rather than reliance on lists of discrete features. Otani developed a regular "problem case" meeting for a community of pathologists, made up of alumni and other interested pathologists, as well as active department members. These monthly sessions provided the highest level of "continuing medical education." Otani and Kaneko unequivocally believed in learning from cases, and Mount Sinai residents were fortunate both in the one-to-one teaching and in the wealth of material, in all systems, that came to surgical pathology. Outstanding pathologists who came from Mount Sinai settled throughout the country and provided the highest level of diagnoses, but, with the exception of Bernard Wagner, Emanuel Rubin, Fiorenzo Paronetto, Richard Horowitz, Michael Gerber, Marc Rosenblum, Bruce Wenig, Jaishree Jagirdar, Swan Thung, Cesar Moran, Hideko Kamino, Philip LeBoit, Alberto Marchevsky, and others, there were relatively few academic leaders. Otani and Kaneko did not have national reputations. Klemperer, although world renowned, was relatively unassuming, and his disciples numbered almost as many nonpathologists as pathologists. Popper did establish a major center for liver pathology, with students coming from around the world, but did not particularly promote general surgical pathology. Can the Mount Sinai approach still be applied? The decline in the numbers of autopsies performed, the demands for rapid turnaround time, the de-emphasis of gross pathology as newer technologies (eg, immunohistochemistry, cytogenetics, molecular pathology) gain place, the increasing tendency to select investigators, including basic scientists, as teaching department chairs and the financial constraints requiring increasing use of nonphysician workers all speak to the relegation of the Otani-Kaneko era to history. Is this a loss to Pathology? It is certainly a style of practice that has been lost. However, there is no reason to bemoan the state of Pathology in the beginning years of the 21st century. Pathology practice is outstanding at many medical centers throughout the world, including at Mount Sinai under the very able and creative leadership of Alan Schiller, who has presided over great enhancements of the department in both anatomic and clinical pathology, including significant advances in the study of diseases by molecular methods. Surgical Pathology at Mount Sinai has been led by James Strauchen, a renowned hematopathologist recruited by Schiller's predecessor, Jerome Kleinerman, and is currently directed by Ira Bleiweiss, a student of Kaneko. Other techniques and technologies have, to a degree, compensated for some of the changes since the Otani-Kaneko years and it is almost certain that advances in molecular pathology will allow for increasing sophistication in establishing diagnoses, and likely even grading and staging, probably even on blood, rather than tissue, samples. The science of Pathology will advance, as the art declines. Those who learned at Mount Sinai during the Otani-Kaneko years will, however, very likely tell you that they were privileged to have learned Pathology there and, especially, to have learned a distinct philosophy of Pathology under the guidance of caring, thoughtful, and especially gifted pathologists.

The Giemsa stain: its history and applications.

Gustav Giemsa was born in Germany in 1867, worked mainly as a chemist, and died in 1948. The staining method, which carries his name, was designed primarily for the demonstration of parasites in malaria, but it was also employed in histology because of the high-quality staining of the chromatin and the nuclear membrane, the metachromasia of some cellular components, and the different qualities of cytoplasmic staining depending on the cell type. The use of methylene azure and its mixture with methylene blue to form an eosinate made stable the stain and its results. Giemsa's stain is regarded as the world's standard diagnostic technique for malaria's plasmodium, and it is also the basic stain for classifying lymphomas in the Kiel classification.

The American College of Surgeons, Minimum Standards for Hospitals, and the Provision of High-Quality Laboratory Services.

CONTEXT: - The first major project of the American College of Surgeons (Chicago, Illinois), founded in 1913, was implementing Minimum Standards for Hospitals. The 1918 standard (1) established medical staff organizations in hospitals; (2) restricted membership to licensed practitioners in good standing; (3) mandated that the medical staff work with hospital administration to develop and adopt regulations and policies governing their professional work; (4) required standardized, accessible medical records; and (5) required availability of diagnostic and therapeutic facilities. One hundred years ago, these were radical expectations. OBJECTIVES: - To describe the origin, "marketing," and voluntary adoption of the 1918 standards, and to describe how the evolution of those standards profoundly affected laboratory medicine after 1926. DESIGN: - Available primary and secondary historical sources were reviewed. RESULTS: - The college had no legal mandate, so it used a highly consultative approach, funded by its membership and the Carnegie Foundation (New York, New York), to establish the Minimum Standards, followed by a nonthreatening mechanism to determine which hospitals met them. Simultaneously, the college educated the public to fuel their expectations. Compliance by more than 100-bed hospitals in the United States and Canada, although entirely voluntary, rose from negligible when first implemented in 1918 to more than 90% in only a few years. From 1922 to 1926, the American Society for Clinical Pathology (Chicago, Illinois) worked creatively with the college to establish Minimum Standards for "adequate" laboratory services. CONCLUSIONS: - The birth and implementation of this program exemplifies how a consultative approach with full engagement of grassroots stakeholders facilitated a voluntary, rapid, sweeping North America-wide change-management process. This program eventually evolved into the Joint Commission (Oakbrook Terrace, Illinois).