Collision tumors of the thyroid. A special clinical and pathological entity

Thyroid collision tumors are rare entities that designate two histologically and morphologically distinct tumors that occur simultaneously or as metastases from other organs within the thyroid. Medullary and papillary carcinoma co-occurrence is the most frequent. Several theories tried to explain the pathogenic mechanisms underlining collision tumors, including the theory which assumes that one tumor predisposes the other, stem cell theory, and random effect theory, but their combination better explains the origin of these tumors. Hypotheses about common genetic behavior responsible for the pathogenesis have also been suggested, such as the involvement of germline mutation of RET (Rearranged during Transfection) proto-oncogene in medullary thyroid carcinoma and papillary thyroid carcinoma coexistence, but there is controversy on this topic. Management of thyroid collision tumors is challenging owing to the presence of two distinct tumors with different biological aggressiveness, treatments options, and prognosis, and needs to be individualized.

Anton Vitalievich Nemilov: A Versatile Talent

The article is dedicated to the outstanding Russian histologist Professor Anton Vitalievich Nemilov, who, being a student of St. Petersburg Imperial University, was one of the first students of Alexander Stanislavovich Dogel, the world-famous Russian scientist, the founder of neurohistology. Having so far shown a bright talent of a researcher and experimenter in his student years, Anton Vitalievich was invited to prepare for a professorship at the university and over and above met expectations based on him. He significantly contributed to the development of neurohistology, histophysiology, including histophysiology of the reproductive system. Anton Vitalievich did a lot for development of endocrinology, which he studied in a general biological but not in a purely medical aspect; this was new and valuable for that period. Finally, he made his contribution to the development of cell theory. A talented teacher, an excellent lecturer, an author of a number of brilliant textbooks, a consummate popularizer of science, an active public figure – Anton Vitalievich demonstrated so many diverse talents during his life, which was not really long, that their combination in one person seems simply unbelievable. His life was in full swing, he was full of creative plans, but the Great Patriotic War prevented their implementation. It started when Anton Vitalievich was 62 years old. Professor A.V. Nemilov wanted to continue research at his native Leningrad University, refused to be evacuated, and remained in the besieged city. With his peculiar enthusiasm, Anton Vitalievich joined defense work, angrily denounced fascism in his articles and radio speeches. However, hunger and cold of the blockade undermined his strength, and he died of exhaustion on February 2, 1942. He was under 63 years old. The article dedicated to Anton Vitalievich Nemilov presents milestones of his life and work, his contribution to science, his professional and personal traits. The paper also highlights his participation in the fight against fascism and tragic death during the blockade of Leningrad.

Stem Cell Theory of Cancer: Origin of Tumor Heterogeneity and Plasticity

In many respects, heterogeneity is one of the most striking revelations and common manifestations of a stem cell origin of cancer. We observe heterogeneity in myriad mixed tumors including testicular, lung, and breast cancers. We recognize heterogeneity in diverse tumor subtypes in prostate and kidney cancers. From this perspective, we illustrate that one of the main stem-ness characteristics, i.e., the ability to differentiate into diverse and multiple lineages, is central to tumor heterogeneity. We postulate that cancer subtypes can be meaningless and useless without a proper theory about cancer’s stem cell versus genetic origin and nature. We propose a unified theory of cancer in which the same genetic abnormalities, epigenetic defects, and microenvironmental aberrations cause different effects and lead to different outcomes in a progenitor stem cell versus a mature progeny cell. We need to recognize that an all-encompassing genetic theory of cancer may be incomplete and obsolete. A stem cell theory of cancer provides greater universality, interconnectivity, and utility. Although genetic defects are pivotal, cellular context is paramount. When it concerns tumor heterogeneity, perhaps we need to revisit the conventional wisdom of precision medicine and revise our current practice of targeted therapy in cancer care.

Hepar uterinum

The means of fetal nutrition has been debated for over two millennia, with the controversy of oral versus parenteral nutrition already in the Corpus Hippocraticum. In 1587, Aranzio rejected connections between maternal and fetal blood vessels, and coined the term hepar uterinum for the placenta. From the 16th to 18th century, fervent debate focused on the type and extent of connection between maternal and fetal vessels. But up to the middle of the 19th century, an important nutritive function was attributed to amniotic fluid. When with the discovery of oxygen the placenta’s respiratory function became understood, its nutritional function fell from grace. Most scientists realized reluctantly that the organ had numerous functions. As late as the 19th century, the advent of microscopy allowed cell theory to develop, and analytical chemistry furthered the understanding of the transport of nutrients across the placenta. The identification of the syncytiotrophoblast made passive diffusion unlikely. Radioisotopes, molecular biology, and the fluid mosaic model of the cell membrane revealed active transport mechanisms for nearly all macronutrients.

Stem Cell Theory of Cancer: Implications of a Viral Etiology in Certain Malignancies

In 1911, Peyton Rous (Nobel Prize winner in 1966) demonstrated that a virus (i.e., RSV) caused cancer in chickens. In 1976, Bishop and Varmus (Nobel Prize winners in 1989) showed that the cellular origin of retroviral oncogenes was actually normal cellular genes (i.e., proto-oncogenes). In this article, we revisit the role viruses play in the genetic origin of cancer. We review a link between viruses or cancer and autoimmunity in an alternative stem cell origin of cancer. We propose that a virus is more likely to cause cancer when it infects a progenitor stem-like cell rather than a progeny differentiated cell. We postulate that both known (e.g., HBV and HPV) and novel viruses (e.g., SARS-CoV-2) pose an imminent threat in the emergence of chronic viral diseases as well as virally induced malignancies. Knowing the origin of cancer has profound implications on our current conception and perception of cancer. It affects our conduct in cancer research and our delivery of cancer care. It would be ironic if viruses turn out to be a useful tool and an ideal means in our quest to verify a genetic versus stem cell origin of cancer. When it pertains, oncology recapitulates ontology; viral (or genetic) content may be king, but cellular (or stem-like) context is key.