The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease.

Mammals have two specialized vascular circulatory systems: the blood vasculature and the lymphatic vasculature. The lymphatic vasculature is a unidirectional conduit that returns filtered interstitial arterial fluid and tissue metabolites to the blood circulation. It also plays major roles in immune cell trafficking and lipid absorption. As we discuss in this review, the molecular characterization of lymphatic vascular development and our understanding of this vasculature's role in pathophysiological conditions has greatly improved in recent years, changing conventional views about the roles of the lymphatic vasculature in health and disease. Morphological or functional defects in the lymphatic vasculature have now been uncovered in several pathological conditions. We propose that subtle asymptomatic alterations in lymphatic vascular function could underlie the variability seen in the body's response to a wide range of human diseases.

The mystery of the thymus gland.

The thymus is the last organ in the human body to have its mechanisms fully understood, having had its function fully delineated more than 50 years ago (Miller , Tissue Antigens 63:509-517). Prior to this, the thymus gland has had an interesting history with theories having included a role in fetal growth and development before becoming more sinisterly, a cause of sudden infant death in the late 19th century known as status lymphaticus (Paltauf , Wien Klin Wochenschr 2:877-881). Until Miller (, Lancet 278:748-749) eventually proved its primarily immunological role, the history of this mysterious gland has closely mirrored the history of medicine itself, troubling the minds of pathologists such as Virchow (, Ueber die Chlorose und die damit zusammenhängenden Anomalien im Gefässapparate, insbesondere über "Endocarditis puerperalis," vorgetragen in der Sitzung der Berliner Geburtshülflichen Gesellschaft vom 12) and Grawitz (, Deut Med Wochenschr 22:429-431), surgeons such as Astley Cooper (, The Anatomy of the Thymus Gland) and Keynes (1953, Ann R Coll Surg 12:88), and eminent medical epidemiologists such as Greenwood and Woods [, J Hyg (Lond) 26:305-326]. This article will hopefully be of interest therefore to both clinician and historian alike. Clin. Anat. 29:679-684, 2016. © 2016 Wiley Periodicals, Inc.

Sarcoidosis: a Critical Review of History and Milestones.

Sarcoidosis is a chronic systemic disease of unknown origin and uncertain prognosis that most commonly affects young adults, and frequently presents with bilateral hilar lymphadenopathy, pulmonary infiltrates and ocular and skin lesions. The diagnosis is established when characteristic clinical-radiological features are supported by compatible histopathology of epithelioid cell granulomas, following exclusion of known causes of granulomatous inflammation. Indeed, sarcoidosis belongs to a large family of disorders that share granuloma formation as common denominator. Since its first description by Jonathan Hutchinson in 1869, sarcoidosis has generated enormous interest and considerable controversy. In Hutchinson's day, it was considered a dermatological condition, which gradually evolved into a multisystem disorder associated in the majority of cases with respiratory abnormalities. With time, it has also become clear that sarcoidosis occurs throughout the world, affecting individuals of both genders and all races, although its prevalence varies widely across ethnic and racial groups. In recent years, advances in different disciplines, particularly biochemistry, genetics, immunology and molecular biology, have improved dramatically our understanding of the disease. Yet, the critical questions regarding who gets sarcoidosis and whether it has an infectious origin remain unanswered. Sarcoidosis has a distinguished medical history that covers the last 150 years. Right from the time of seminal contributions by Hutchinson, Besnier and Boeck medical discussion on sarcoidosis has always been animated and to a certain extent emotional. Such discussions will inevitable continue until the true cause of the disease has been found, hopefully in the near future.

[Lymphatic system and lymphoscintigraphy].

Starting from Hippocrates era, the lymphatic system has been an interesting area of study for its anatomy, physiology, pathophysiology and imaging. The present review describes the history of the lymphatic system and lymphoscintigraphy. Lymphoscintigraphy comprises a simple, non-invasive imaging method of the lymphatic system and the sentinel lymph node or nodes. Additionally the intra-operative gamma-probe detection and the blue dye technique are also presented. The nuclear methods have been incorporated in the algorithm of the diagnostic approach and the therapeutic treatment of cutaneous melanoma and breast cancer, while further experience is warranted in other solid malignancies.

Toxoplasmosis: A history of clinical observations.

It has been 100 years since Toxoplasma gondii was initially described in Tunis by Nicolle and Manceaux (1908) in the tissues of the gundi (Ctenodoactylus gundi) and in Brazil by Splendore (1908) in the tissues of a rabbit. Toxoplasma gondii is a ubiquitous, Apicomplexan parasite of warm-blooded animals that can cause several clinical syndromes including encephalitis, chorioretinitis, congenital infection and neonatal mortality. Fifteen years after the description of T. gondii by Nicolle and Manceaux a fatal case of toxoplasmosis in a child was reported by Janku. In 1939 Wolf, Cowen and Paige were the first to conclusively identify T. gondii as a cause of human disease. This review examines the clinical manifestations of infection with T. gondii and the history of the discovery of these manifestations.

"Experiments of Nature" and the New Era of Immunology: an historical perspective.

This review of the events leading to the New Era of Immunology focuses on the important leads provided by the Experiments of Nature. Not only did they provide the path that led to our present knowledge of the ontogeny of the immune system, but also to an entirely new perspective of lymphocytic malignancies. The power of taking clinical clues to the laboratory to conduct experiments not otherwise envisioned and then returning with that information to impact the clinical problem that motivated the studies is elaborated. Finally, the ongoing utility of this approach is emphasized.

History: Frederic Woringer (1903-1964) and Woringer-Kolopp disease.

The two most famous dermatologic eponyms born in Strasbourg are Pautrier microabscess and Woringer-Kolopp disease. Frederic Woringer (1903-1964) was one of Pautrier's students, who had been in charge of the Laboratoire d'Histopathologie Cutanée in Strasbourg from 1930 until his death. He achieved a brilliant career in the field of dermatopathology and was very active during the great period between World War I and II. His name is linked to a rare disease, pagetoid reticulosis, which he actually misunderstood, as he was at first convinced that the characteristic intraepidermal changes were due to Paget cells. In this article, we show for the first time the original correspondence between Kolopp (who sent the case to Strasbourg) and Woringer, including discussion with masters such as Pautrier and Civatte. Civatte suggested that these mysterious intraepidermal cells might have common morphologic features with the recently described Sezary cells. After the first publication of pagetoid reticulosis, it took almost 40 years to establish a clear link with mycosis fungoides. It was Braun Falco who named the disease after Woringer and Kolopp in 1974. Woringer would certainly be surprised to know that his name is still world famous, thanks to a rare disease he was the first to extensively describe in 1939, a few days before the declaration of war.

The history of surgery of the thymus gland.

The history of surgery of the thymus gland is presented through highlights and landmark publications ranging from prehistoric times to the present day. The evolution of surgical techniques includes transcervical and transthoracic thymectomy along with other techniques such as current thoracoscopic VATS procedures. The significance of myasthenia gravis, autoimmunity, thymic oncology, adjuvant developments, and speculation on the future is discussed.