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.

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.

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).

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.

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.

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.

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.

Q-Probes studies in anatomic pathology: quality improvement through targeted benchmarking.

CONTEXT: The Q-Probes program is a peer-comparison quality assurance service offered by the College of American Pathologists that was created in 1989. OBJECTIVE: To establish national benchmarks around a specific quality metric at a specific point in time in anatomic pathology (AP). DESIGN: Q-Probes are based on a voluntary subscription for an individual study. Hospital-based laboratories in the United States, Canada, and 16 other countries have participated. Approximately one-third of all Q-Probes studies address AP metrics. Each Q-Probes study has a primary quality indicator and additional minor indicators. RESULTS: There have been 52 AP Q-Probes studies addressing process-, outcome-, and structure-related quality assurance issues. These Q-Probes studies often represented the first standardized national benchmark for specific metrics in the disciplines of cytopathology, surgical pathology, and autopsy pathology, and as such have been cited more than 1700 times in peer-reviewed literature. The AP Q-Probes studies that have been repeated over time demonstrate improvement in laboratory performance across an international spectrum. CONCLUSIONS: The Q-Probes program has produced important national benchmarks in AP, addressing preanalytic, analytic, and postanalytic factors in the disciplines of cytopathology, surgical pathology, and autopsy pathology. Q-Probes study data have been published, cited, and used in the creation of laboratory accreditation standards and other national guidelines.

Albert C. Broders' paradigm shifts involving the prognostication and definition of cancer.

CONTEXT: In the 19th and early 20th centuries, cancer was defined by the demonstration of invasion and metastases, based upon gross findings at surgery or autopsy. Although histopathologic examination of tumors became possible with greater and greater resolution over time, the definition of cancer remained the same. Tumors with features suggesting the biological "potential" to invade and metastasize were not cancers until they had achieved their potential. Prognostication based upon histopathologic analyses of tumor biopsies and resection specimens was not possible, as the concepts of tumor grading and staging did not exist until the 1920s and 1930s, respectively. OBJECTIVE: To examine the history of tumor grading and the concept of "carcinoma in situ" and to explore the role of Albert C. Broders, MD, and others in these discoveries. DESIGN: To address these topics, standard historiographic methods were used to examine available primary and secondary historical sources. RESULTS: Early in his career, Broders described tumor grading, showing for the first time that histopathologic findings could independently predict prognosis. This discovery quickly begat tumor staging and eventually the whole predictive biomarker field. Later in his career, Broders described carcinoma in situ, thereby changing the very definition of cancer. CONCLUSION: Historians recognize that science progresses through a series of paradigm shifts. Most clinician-scientists, even those at the very top of their fields, never make a discovery so dramatic that it changes their field forever. In the 1920s and 1930s, Albert C. Broders published 2 observations that forever changed cancer diagnosis, prognostication, and treatment.