Carl Weigert's pioneer definition of heart infarction as myocardial, coagulative necrosis due to obstruction of atherosclerotic coronary arteries in 1880, overshadowed by subsequent, secondary publications in the field.

In 1880, a German Jewish Professor of Pathology, Carl Weigert (1845-1904) first defined heart infarction as myocardial, coagulative necrosis ("Coagulationsnekrose") due to obliteration of atherosclerotic coronary arteries thanks, at least, partially to his great diligence in vascular staining methods. Histochemical techniques made his name eponymic as Weigert's Hematoxylin or Weigert's and Van Gieson's elastic stains are still used in routine practice to visualize, e.g., the framework of vessels. However, his discovery has been overshadowed by far more frequently cited in recent decades, subsequent but secondary, 214-page-long book dated on 1896 and titled "L'infarctus du myocarde et ses conséquences - ruptures, plaques fibreuses, anévrismes du coeur", in which René Marie repeated Carl Weigert's words that dead cardiomyocytes lost their cellular nuclei. Weigert introduced the term "die Infarcte des Herzmuskels", in 1880, in his paper titled "Über die pathologischen Gerinnungsvorgänge", in Virchows Archiv. According to Weigert, occlusions were caused by white thrombi ("weissen Thromben") on the ground of atheromatous changes of the coronary arteries. In following manner, he gave macroscopic description of heart infarction: "If a blood supply is very roughly (German: brüsk), completely cut off in individual parts of the heart muscle, yellowish dry masses are formed that resemble coagulated fibrin". "If examined microscopically, one usually does not find any fibrinous material exudate, but often a delusively normal tissue (sometimes you can even see cross striation of the muscle fibers): but all muscle fibers (...) are anucleate". Paradoxically, coronary thrombosis was also a cause of Carl Weigert's death.

Heritage of Leopold Auerbach in the field of morphology of nervous system.

Leopold Auerbach (April 27, 1828-September 30, 1897) belongs to world famous figures in medicine, who were born, spent most of their lifetimes and died in Wroclaw (Breslau). Auerbach reported for the first time in literature about existence of plexus myentericus (plexus Auerbachi) including ganglion cells between circular and longitudinal layers of tunica muscularis propria in intestinal wall, in 1862. With his publication on muscular hypertrophy, dated on 1871, he provided ground for another eponym: "Friedreich-Auerbach disease", that refers to facial hemihypertrophy. He was raised in Jewish family, which lived for generations in Wroclaw. His elaborative scientific work was his struggle for human dignity and safe social status, which was shared with many other members of the community at the time of Jewish emancipation thorough the whole XIXth century in Germany. The great value of Leopold Auerbach for the Wroclaw University - his Alma Mater -, which was founded by an Austrian Emperor Leopold I, is even metaphorically coded by the fact, that "AL" are not only initials for Academia Leopoldina but also curiously for the name and surname of this brilliant scientist, who led rather a calm and unspectacular life. This paper is the last one from the series of our biographical papers, in which we focused on his output in the field of vascular system, morphology of invertebrates and - in only short one page-long note until now - on the topic of nervous system, so we decided to present a full text report on the latter but the most famous area of his activity.

Review on significance of GDNF, PTCH1 and RNF213 in chromophobe renal cell carcinoma illustrated by the case of 71-years-old man.

Here we review the role of GDNF, PTCH1, RNF213 illustrated by a case of renal cell carcinoma, chromophobe type (pT2a 8th pTNM edition) of the left kidney of 71-year-old man. Status of potential hotspots in 409 tumor genes were studied by means of next generation sequencing (NGS) technology (IonTorrent - Thermo Fisher Scientific, USA) using Ion AmpliSeq™ Comprehensive Cancer Panel. Next-generation sequencing (NGS) revealed mutations of GDNF (NM_001190468: c. 328C>T, p.R110W, allelic frequency 46%), PTCH1 (NM_001083607:c. 2969C

Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression.

BACKGROUND: Despite effective prevention and screening methods, the incidence and mortality rates associated with colorectal cancer (CRC) are still high. Insulin receptor substrate 1 (IRS-1), a signaling molecule involved in cell proliferation, survival and metabolic responses has been implicated in carcinogenic processes in various cellular and animal models. However, the role of IRS-1 in CRC biology and its value as a clinical CRC biomarker has not been well defined. AIM: To evaluate if and how IRS-1 expression and its associations with the apoptotic and proliferation tumor markers, Bax, Bcl-xL and Ki-67 are related to clinicopathological features in human CRC. METHODS: The expression of IRS-1, Bax, Bcl-xL and Ki-67 proteins was assessed in tissue samples obtained from 127 patients with primary CRC using immunohistochemical methods. The assays were performed using specific antibodies against IRS-1, Bax, Bcl-xL, Ki-67. The associations between the expression of IRS-1, Bax, Bcl-xL, Ki-67 were analyzed in relation to clinicopathological parameters, i.e., patient age, sex, primary localization of tumor, histopathological type, grading, staging and lymph node spread. Correlations between variables were examined by Spearman rank correlation test and Fisher exact test with a level of significance at P < 0.05. RESULTS: Immunohistochemical analysis of 127 CRC tissue samples revealed weak cytoplasmatic staining for IRS-1 in 66 CRC sections and strong cytoplasmatic staining in 61 cases. IRS-1 expression at any level in primary CRC was associated with tumor grade (69% in moderately differentiated tumors, G2 vs 31% in poorly differentiated tumors, G3) and with histological type (81.9% in adenocarcinoma vs 18.1% in adenocarcinoma with mucosal component cases). Strong IRS-1 positivity was observed more frequently in adenocarcinoma cases (95.1%) and in moderately differentiated tumors (85.2%). We also found statistically significant correlations between expression of IRS-1 and both Bax and Bcl-xL in all CRC cases examined. The relationships between studied proteins were related to clinicopathological parameters of CRC. No significant correlation between the expression of IRS-1 and proliferation marker Ki-67, excluding early stage tumors, where the correlation was positive and on a high level (P = 0.043, r = 0.723). CONCLUSION: This study suggests that IRS-1 is co-expressed with both pro- and antiapoptotic markers and all these proteins are more prevalent in more differentiated CRC than in poorly differentiated CRC.

Leopold Auerbach's achievements in the field of vascular system.

The scientific activity of Leopold Auerbach (1828-1897) was associated with Wroclaw (Brelsau) medical school, which was renowned for brilliant descriptors of cardiovascular system, whose world-famous achievements became eponymous in history of medicine. Such terms as plexus myentericus Auerbach and Friedreich-Auerbach disease are still used worldwide. Little is known about the fact that the vascular system was at least as important in his scientific impact as neuromuscular field. Actually, one could realize that ganglion cells, which were previously discovered in cardiac location, were identified by Auerbach at interface between circular and longitudinal layer of intestinal tunica muscularis proporia. Consequently, Auerbach focused closely on vessels after examination of neural and muscular components of selected parts of gastrointestinal tract. Namely, he noticed that tightly grouped cells that formed vessels in the process of vasculogenesis and angiogenesis to constitute the lining of capillaries, possessed nuclei.

Analysis of mutations of PARP1, RNF213, PAX8, KMT2C, MTRR in malignant mesothelioma of testicular tunica vaginalis testis.

Molecular next gene sequencing was used to evaluate mutations in 409 common mutated cancer-related genes in malignant mesothelioma of tunica vaginalis testis (MMTVT) of 81-year-old man. Multifocal papillary-solid areas contained necrosis among highly cellular fields with multiple mitoses. It was positive for WT1, CKAE1/AE3, calretinin, CK7 with negativity for CK5, PSA, TTF-1. Following mutations were revealed in PARP1 (NM_001618: c.2285TG, p.K135R), MTRR (NM_024010: c.147A>G, p.I49M) and two sorts of mutations in structure of KMT2C gene (NM_170606: c.2447_2448insA (c.2447dupA), p.Y816fs and NM_170606: c.1042G>A, p.D348N) for the first time in MMTVT.

Review of Potential Significance of Mutations of ADAMTS20, NF1 and PKHD1 Detected Using Next Generation Sequencing (NGS) in Dermal Fibrosarcoma Arising in Dermatofibrosarcoma Protuberans.

We examined a status of fibrosarcoma arising in dermatofibrosarcoma protuberans of 64-year-old male patient. A dermal, solid, grayish-yellow, desmin-negative trichrome-bluish tumor measured 1.5 cm in diameter pT1a (edition 8 pTNM). It was composed of spindle cells. It was consistent with dermatofibrosarcoma protuberans (ICD-O3: 8832/3) in areas of low mitotic activity, low atypia and sustained CD34 positivity. CD34-negative texture with high mitotic index and atypia was consistent with the high grade sarcoma apparently of fibrous origin, given category of poorly differentiated fibrosarcoma. The high grade component was graded (G3) and scored according to French Federation of Cancer Centers Sarcoma Group (FNCLCC): total score of 6 points: tumor differentiation: 3 points + Mitotic count: 3 points (up to 26 mitoses/ 10HPF in high-grade fields), + no necrosis: 0 points. In low grade sarcomatous component ADAMTS20 (NM_025003: c.1661C>T, p.P554L) NF1 (NM_001042492: c. 2173G>T, p.E725X) and PKHD1 (NM_138694: c. 11074C>T, p.R3692X) were revealed with following allelic frequencies: 25%, 27% and 17%. In high grade component allelic frequencies of the same mentioned mutations were 30%, 30% and 14% respectively. In the light of our findings, none of detected mutations can be regarded as a mutation that would definitely induce phenotype of high malignancy, because ADAMTS20, NF1 and PKHD1 mutations were detected both in high grade sarcoma and in low grade areas of dermatofibrosarcoma protuberans. It also points that these mutations appeared on early stages of tumor development.

Leopold Auerbach's heritage in the field of morphology and embryology with special emphasis on gametogenesis of invertebrates.

Plexus myentericus Auerbachi and Friedreich-Auerbach disease are widely used eponyms that are associated with eminent morphologist Leopold Auerbach (1828-1897), whose life is relatively little known due to limited access to his German-written XIX century biographies and lack of English biographical papers about him in world literature. Hereby we focused on hardly known achievements of Leopold Auerbach in the field of gametogenesis and embryology of invertebrates. Auerbach did not only confirm unicellularity of amoebas, which was previously discovered. He described cleavage of fertilized eggs of Ascaris nigrovenosa and Strongylus auricularis. Moreover, his accurate descriptions on germination of Paracentrotus lividus inspired a recognized German zoologist Oscar Hertwig (1849-1922). Auerbach also profoundly studied an encystation of Oxytricha pellionella on morphological grounds. His descriptions referred to karyokinesis as well as oogenesis and spermatogenesis to discover conjugations of spermatozoa in pairs in the epididymis of a beetle, Dytiscus marginalis. He also distinguished two types of spermatozoa of Paludina vivipara: the hairlike-shaped (German: haarförmigen) and the worm-shaped (wurmförmigen) ones of these fresh water (river) snails. His studies on germination (including cell division during cleavage of nematodes) inspired the others, e.g., Oscar Hertwig, and following generations to conclude that "Auerbach deserves the credit for having provided the first scientific foundation for modern teaching on fertilization" according to professor of anatomy Gustav Born (1851-1900) at Breslau University.

Basal Cell Carcinoma among Cutaneous Tumours in "Caricature," Painted by Bartolomeo Passerotti (1529-1592).

A fine and fair depiction of basal cell carcinoma is documented with great fidelity in "Caricature" by Bartolomeo Passerotti (1529-1592). The cancer is pearly white and contains an elevated centre with a sharp and somewhat depressed outline due to ulceration of the lesion. The painting is of essential didactic worth for practicing medical doctors. In addition, the masterpiece contains images of the brown elevated lesions that could turn out to be verrucous melanocytic nevi or pigmented seborrheic keratoses, but it cannot be excluded that these nodules are also basal cell carcinomas covered by a brownish crust. It is standard that microscopic verification is required for all these tumours. However, a pearly white irregular tumour is the most characteristic macroscopic presentation of basal cell carcinoma.

Bridging neighboring civilizations at academic grounds: a story of Zygmunt Albert - Rector illustrissimus ac magnificus Academiae Medicae Wratislaviensis - a pathologist who visualized gamma-glutamyl transpeptidase.

The life stories can constitute more than simple biographies to remain great lessons of honesty, grit and steadfastness in keeping standards of medical science within a strong moral fiber and flexible wiseness in hard terms like in case of Zygmunt Albert (1908-2001). This eminent pathologist histochemically visualized tissue distribution of gamma-glutamyl transpeptidase in liver and other organs under various conditions. He was also deeply involved in experimental pathology of liver, particularly in his comprehensive studies on chrysoidin-induced hepatoma that should bear eponymic name Albert's hepatoma. As he had both German and Polish roots, he became an eminent personage that wisely and consequently bridged neighboring civilizations in hard terms of escalation of hate in prewar times, during World War II and in postwar period. After he meticulously recorded Nazi crimes in Lvov, he appealed for justice in case of Nazi massive murders of Lvov Professors. He obtained his Associate Professorship in Anatomical Pathology in Lvov (Lemberg) and was one of rebuilders of Medical Faculty in postwar Wroclaw (Breslau) to serve as the first Rector Magnificus of Medical Academy of Wroclaw.

Heritage of Stanislaw Ciechanowski (1869-1945)-Discoverer of pathogenesis of prostatic hyperplasia-passionis insignia signis fulgent mirificis .

BACKGROUND: Prostatic enlargement was first correctly recognized as a prostatic hyperplasia by professor of anatomic pathology, Stanislaw Ciechanowski (1869-1945) in Cracow on contrary to Parisian urologist Jean Casimir Félix Guyon's concepts of progressing atherosclerosis as a morphological cause of prostatic overgrowth and mechanical insufficiency of lower urinary tract. METHODS: Primary resources were analyzed about Stanislaw Ciechanowski mainly from depositories of the Section of Special Collection, Stanislaw Konopka Main Medical Library Warsaw and Polish bibliograhy of Estreichers at Jagiellonian University. RESULTS: Professor of anatomic pathology, Stanislaw Ciechanowski (1869-1945) was the first to state that chronic inflammation induced overgrowth of parenchymatous and stromal prostate components in course of benign prostatic hyperplasia. Ciechanowski preformed also pioneer and notable studies in the mechanisms of carcinogenesis and classification of cancer in Poland. As one of the major Polish medical editors and a father of Polish modern medical language he was also very prolific author in the field of congenital pathology, sclerosis of pulmonary arteries, endemic goiter, intestinal emphysema, etc. Due to magnitude of autopsies, he preformed, Stanislaw Ciechanowski was a perfect candidate to complete the first edition of several volumes of main Polish handbook on anatomy of a human body after tragic death of professor Adam Bochenek. CONCLUSIONS: Ciechanowski gained such a high authority, that his opinion was found crucial in prewar Poland in the field of medical publications, but his world-famous achievement was scientific explanation of prostate overgrowth as inflammation induced hyperplasia.

Review on Retinal Gliosis Illustrated with a Series of Massive Glioses and Focal Nodular Gliosis Cases in Regard to Potential Pitfalls of Ocular Reactive Tumor-like Lesions of this Type.

This paper presents a review on retinal gliosis illustrated by series of three cases of patients (a 39-year-old man and a 35-year-old woman with massive retinal gliosis (MRG) and a 51-year-old man with truly focal nodular gliosis of retina) with intraocular tumor-like masses and loss of vision, who recently suffered from painful inflammation of eyeball and who classically had a history of remote ocular trauma, onset of blindness early in lifetime or gradual but progressive loss of sight. The diagnosis of this pathological entity is given for the lesions that are composed of GFAP strongly positive, elongated, fusiform cells consistent with fibrillary astrocytes. As illustrated in cases from our pathological practice, PAS gave positive patchy disseminated reaction in form of cellular densely purplish granules in minority of cells representing glycogen storing. This feature could be consistent with PAS-positive Müller cells that also constitute retinal gliosis as one of cellular components of normal retina that is induced to reactive proliferation. Thus, the paper presents histological background and differential diagnosis of the entity.

Protection of Children's Human Rights and Health: A Legacy of Julian Kramsztyk, Janusz Korczak, and Ludwik Rajchman.

Tutor of generations of Warsaw medical doctors, Julian Kramsztyk (1851-1926) was son of Rabbi Izaak Kramsztyk, Polish patriot and fighter for independent Poland. Julian Kramsztyk graduated in medicine from Warsaw University in 1873 to soon work as a supervisor of the Internal Diseases Department of Bersohns and Baumans Children's Hospital from 1878 to 1910, and despite of refusing professorship from Imperial Warsaw University, he worked as a lecturer of pediatric disorders from 1880 with strong association of his medical practice with scientific and editorial tasks as well as engaging in charity. This article focuses on selective retrieval of biographical data of social and scientific achievements of followers of Julian Kramsztyk: his student, pioneer of children human rights, and pioneer of healthy patterns of nutrition of children, pediatrician Janusz Korczak (Henryk Goldszmit; 1878 or 1879-1942); and a skilled bacteriologist and a brilliant epidemiologist who was a prominent activist of the League of Nations (later United Nations Organization), cofounder of the UNICEF (United Nations Children's Emergency Fund), and the first chairman of the Organization from 1946 to 1950, which was primarily dedicated to "provide emergency food and health care to children in postwar time," Ludwik Rajchman (1881-1965). Janusz Korczak works laid foundation for international recognition of children rights to health, respect, education, privacy, and all the other human rights to be included in the United Nations Convention on the Rights of the Child (UNCRC). In 1989, nutrition and vaccination issues were the main medical interests of these medical doctors and still remain major fields of UNICEF actions.

Heritage of Stanislaw Ostrowski - the only one medical doctor who became state Polish President - Patriae Semper Fidelis.

AIM: Our purpose was to write a biography of Stanislaw Ostrowski that would address in the first place the medical aspect of his professional life, with a comprehensive approach of others fields of his activity. METHODS: We essentially grounded the paper on primary resources that were papers authored by Ostrowski including his scientific publications, memories, speeches as well as contemporaneous official documents that referred to Ostrowski. Second resources were also used to double check some data from primary resources and to place the biography of Stanislaw Ostrowski in a proper background with special care to social, professional and political context. In this study, second resources comprised papers, that were prepared after the death of Stanislaw Ostrowski. RESULTS: Stanislaw Ostrowski, MD was a meticulous military medical doctor with an academic engagement at the King John Casimir University of Lvov. In addition, he was an excellent organizer, who soon got involved in politics to serve the local community with essential projects in public health particularly anti-tuberculosis campaigns in Lvov district. His quiet and proficient nature made him an ideal statesman with incredible skills to reconcile social, national and political enemies. Ostrowski was elected a member of parliament three times. He also held the position of President of the city of Lvov until World War Two. During the war, he was imprisoned and deported to Siberia, Soviet Union, in years 1939-1941. Subsequently he fought against Nazi Germans in the Polish II Corps. Ostrowski survived the war providing medical service in the various military units. Afterwards, he ran his medical practice in the UK. Stanislaw Ostrowski was the only dermatologist who became a state president. He held an office of state president of the Polish Republic on exile in London. DISCUSSION AND CONCLUSION: His life is not a simple story, but a great lesson that provides clear guidelines how to find a stable ground for lifetime being a medical doctor in the turbulent times of the 20th century even during wartime.

Malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like tumor of the gastrointestinal tract) of the small intestine in a 12-year-old boy.

The aim of this paper is a clinical and anatomopathological demonstration of a malignant lesion, a gastrointestinal neuroectodermal tumor (GNET), as an exceedingly rare cause of ileus in the pediatric population. Specifically, we present the case of a 12-year-old boy who showed dramatic weight loss, hypochromic anemia, fever, dehydration, exaggerated granulation of the terminal ileum, and mechanical ileus due to the obstruction by an intramural tumor of the small intestine. A 50cm-long part of the small intestine with pathological stricture was surgically removed, sampled and routinely fixed and stained with hematoxylin and eosin. The additional immunostains that were preformed were: PAS, S-100, HMB-45, NSE, LCA, CK AE1 / AE3, desmin, SMA, vimentin, CD99, NSE, synaptophysin, WT-1, calretinin, and DOG-1. Moreover, fluorescent in situ hybridization (FISH) with the EWSR1 Break Apart FISH Probe was applied. The neoplasm was composed of nests and alveolar patterns of frankly malignant clear cells with immunoreactivity to S-100, vimentin, and CD 99. The FISH technique detected chromosomal breaking at 22q12. The tumor metastasized to both the mesenteric lymph nodes and a number of hepatic segments. With several chemotherapy protocols, repeat laparotomies, and liver thermal ablations, the patient had a 1.5-year-long survival from the moment of diagnosis. The diagnosis of this malignancy requires both histopathological evaluation and molecular analysis, and the follow-up is based on careful clinical imaging of the neoplastic spread in order to apply proper surgical and oncological treatments. In conclusion, the clinical course of GNET was highly aggressive.

Jakub Chlebowski, Rector Magnificus Exultus - A Distinguished Professor of Internal Medicine in Postwar North-East Poland.

Jakub Chlebowski (Jakub Frydman) (1905-1969) was a distinguished professor of internal medicine and skillful organizer of health care system in Bialystok region in the North east Poland. He graduated medicine in 1929 and worked at local university in prewar Vilnius. During World War Two, arrested by the Soviets and exiled to Siberian work camps he managed to return to Poland with Kosciuszko Division of Polish Army. Then, he continued to serve as a military and university medical doctor in Cracow and Lodz, finally to take over position of director of Internal Diseases Department in 1951 in Bialystok, holding an office of rector magnificus of Medical University of Bialystok from 1959 to 1962. Chlebowski trained generations of internal medicine specialists, who later became eminent representatives of emerging branches of internal medicine as distinct subspecialties in the field of cardiology, endocrinology and gastroenterology in Bialystok. In course of anti-Semitic campaign during March Events in 1968, he was disposed from the post of director of the university hospital department. Constantly harassed, he immigrated with the family to Israel to die in public traffic accident in 1969. Jakub Frydman, who survived not only hunger of food, but also metaphorical "hunger of humanity" during World War Two, turned out to be as good and useful as daily bread for Polish community after wartime. He was so devoted in this action, that he even changed his surname into Chlebowski (Polish: Chleb=English: Bread). In this way, due to similar experience and experience-shaped mentality, Chlebowski could be counted among medical authorities of the time, the individuals with such a high moral standard as Janusz Korczak (1878 or 1879-1942) or Julian Kramsztyk (1851-1926).

Comparison of E-cadherin with STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different ER-alpha immunoprofile.

E-cadherin is a factor of good prognosis in endometrioid adenocarcinomas, while STAT3 is an oncogenic driver of carcinogenesis. E-cadherin, Bak, Bcl-xL and STAT3 were immunohistochemically detected in 78 human endometrioid adenocarcinomas. E-cadherin correlated with STAT3 (p <. 001, r = 0.537) as well as Bak (p = .005, r = 0.314) and Bcl-xL (p = .002, r = 0.340) in the whole study group. In G2 tumors, E-cadherin associated with Bak (p = .021, r = 0.319), Bcl-xL (p = .026, r = 0.309) and STAT3 (p <.001, r = 0.513) but not in G3 adenocarcinomas. E-cadherin correlated with Bak and Bcl-xL in both G1- and estrogen receptor (ER)-negative tumors with significant relation of E-cadherin and STAT3 in G1- and ER-negative tumors. Antigrowth synergy of expression was preserved for antiapoptotic Bak and proliferation-suppressing E-cadherin in IA adenocarcinomas (p = .031, r = 0.342) with no significance between Bak and E-cadherin or STAT3 and emerging correlation between E-cadherin and Bcl-xL in IB + II tumors instead (p = .003, r = 0.472). E-cadherin correlated with Bak and Bcl-xL in ER-positive adenocarcinomas (p = .002, r = 0.382 and p <.001, r = 0.439, respectively) but not in ER-negative tumors. In conclusion, expression deregulation of studied proteins is reflected in selective loss of correlation between suppressors of tumor growth (E-cadherin and Bak) presumably due to progressing impairment of growth-inhibitory properties of clone of neoplastic cells within higher staging and poorer differentiation.