Germ Cell Tumor 生殖细胞瘤

choi

曾鼎 and 刘璐, 百亿保健帝国权健，和它阴影下的中国家庭. 丁香医生, Dec 25, 2018.
(a) 微信: https://mp.weixin.qq.com/s/J5XA3K5PcOEsgs6czE0nlg
(b) Web: https://dxy.com/column/21773


PDQ Pediatric Treatment Editorial Board, Childhood Extracranial Germ Cell Tumors Treatment (PDQ®). In PDQ Cancer Information Summaries. PDQ, Dec 13, 2018 ("health professional version")
https://www.ncbi.nlm.nih.gov/books/NBK65877/

Note:
(a) "Most childhood extragonadal GCTs arise in midline sites (ie, head and neck, sacrococcygeal, mediastinal, and retroperitoneal); the midline location may represent aberrant embryonic migration of the primordial germ cells."

Heed the word "aberrant": Normally (all) "primordial germ cells (PGC)” and its progeny (germ cells), in embryology 胚胎学 (of all animals, from worms to humans), migrate to the "gonadal ridge;" together they form the future gonads. When aberrant migration of germ cells occurs, they later form extragonadal germ cell tumor (GCT), which seems invariably in the midline (from inside the brain down to tip of spine) -- of course gonadal GCT (in a testis or ovary) are not in the midline. As of the present: In humans (as well as mice), how PGC makes normal migration is unknown; in ALL animals, why and how aberrant migration of PGC occurs are unknown.
(i) normal development of PGC (and therefore, sex differentiation).
(A) Nikolic A et al, Primordial Germ Cells: Current Knowledge and Perspectives. Stem Cell International, 2016: 1-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655300/

Quote (citations omitted):

"Germ cells undergo two significantly different developmental phases. The first phase occurs during early embryogenesis, when primordial germ cells (PGCs) are formed and actively migrate to the gonadal ridge. In the second phase, the germ cells receive appropriate signals from their environment and initiate one of two distinct programs of controlled cell division, meiosis, and differentiation-oogenesis or spermatogenesis, to form gametes. The molecular basis of both processes and early germ cell development is very well understood in two species, Drosophila 果蝇 and Caenorhabditis elegans [a worm of 1 mm in length], where systematic genetic reviews have identified many of the genes required in this process. PGCs in humans have not been intensely investigated because of the technical and ethical obstacles to obtaining such cells from early embryos. The greater part of our knowledge of mammalian PGC specification has been obtained from studies using early mouse embryos"  (The review then talked about what genes were involved in PGC migration and development in Drosophila and C elegans, but you need not know these.)

"In contrast to D melanogaster and zebrafish, little is known about PGC migration and initiation of that process in mice.

(B) Naturally it is difficult to imagine what the first part of quotation in (a)(i)(A) means. Graphics will help.

Rey R et al, Sexual Differentiation. In EndoText (an e-book), last updated June 12, 2016.
https://www.ncbi.nlm.nih.gov/books/NBK279001/
, where Figure 1 was about "(A) 4-week embryo" and "(B) 5-week embryo." The author neglected to say what animal it was. Well, it is human. Mouse (especially the one we use in labs) gestation lasts 20 days. Caption of the figure listed limited number of genes that were involved. Again you need not know more.

In both (A) and (B), the embryo itself was colored brown. (A) showed the lateral view of the embryo (placed horizontally, with head at the left), whereas (B) the oblique view 9of an embryo placed vertically whose bottom half only was sketched).
(C) Richardson BE and  Lehmann R, Mechanisms Guiding Primordial Germ Cell Migration: Strategies from Different Organisms. Nature Reviews Molecular Cell Biology ("Nature Reviews" has many topics; this is in molecular and cell biology), 11: 37-49 (2010).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521894/
("The study of how cells migrate is highly relevant to our understanding of both normal and pathological processes. * * * In many animals the primordial germ cells (PGCs), precursors to sperm and eggs, arise far from the somatic cells of the developing gonad (somatic gonadal precursors (SGPs)) and therefore have to actively migrate across the embryo to reach their site of function. This process provides a useful model system for the study of cell migration within the context of a developing organism. PGC migration must be finely regulated as it follows a complex path through a variety of developing tissues. In addition to the obvious effect of disrupted PGC migration on fertility, aberrant movement to ectopic sites in the body is one mechanism that could account for the incidence of extragonadal germ cell tumours in humans. Most of our understanding of PGC migration comes from the model genetic organisms Drosophila melanogaster, zebrafish and mice. * * * The general events of PGC migration in model organisms have been well characterized (discussed below; FIG 1). Although there are important differences in the specification and migration of PGCs in these organisms, there are also several shared principles emerging")

The "neural tube" (colored blue) in FIG 1 is the precursor of central nervous system (brain and spinal cord).

In both (a)(i) (B) and ©, you can see that germ cells (undifferentiated; can be developed into either male or female cells) migrate caudally (toward the tail). Thus it is impossible to know (for anybody in the world) that these cells might be possibly migrate to brain, neck or mediastinum (the space between lungs, above heart and below neck) -- but germ cell tumors in these latter locations are extremely rare. See next.
(ii) Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®). undated (health professional version)
https://www.cancer.gov/types/bra ... -cell-treatment-pdq
(read the section "Anatomy" and view the accompanying figure)
(A) "The pineal gland [松果腺] produces melatonin * * * a hormone which modulates sleep patterns in both circadian and seasonal cycles. The shape of the gland resembles a pine cone from which it derived its name."  en.wikipedia.org for "pineal gland."
(B) melatonin
https://www.etymonline.com/word/melatonin
("it changes the skin color of certain reptiles and amphibians")

In terms of chemical structure, melatonin and melanin 黑色素 are from different categories.

choi

(d)
(i) Germ cell tumor -- wherever its location: extragonadal or gonadal -- may be either benign or malignant.
(ii) Naturally pathology determines (under microscope) what a tumor is.

Germ Cell Tumors (GCTs) General Features. American Urological Association (AUA), undated
https://www.auanet.org/education ... rs-general-features
("Either pure (60%) or mixed (40%; >2 histology) tumors")

This page talks about GCTs in ADULTS (Urology 泌尿学 is about men).

choi

(b) PDQ Table 1 showed peak age to be diagnosed with extracranial germ cell tumor is 15-19 years old.

(c) More quotations from PDQ Pediatric Treatment Editorial Board, Childhood Extracranial Germ Cell Tumors Treatment (PDQ®):

"There are few data about the potential genetic or environmental factors associated with childhood extragonadal extracranial GCTs. * * * Tumor markers 肿瘤标志物 [which are proteins in the blood stream that are present with certain cancers] [:] Yolk sac tumors [a subset of germ cell tumors] produce alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG) is produced by all choriocarcinomas and by some germinomas (seminomas and dysgerminomas) and embryonal carcinomas, resulting in elevated serum levels of these substances. Most children with malignant GCTs will have a component of yolk sac tumor and have elevations of AFP levels, which are serially monitored during treatment to help assess response to therapy." (citation omitted). * * * The [normal] fetal liver produces AFP [the production decreases and then shuts down soon after birth]."
(i)
(A) alpha-fetoprotein
https://en.wikipedia.org/wiki/Alpha-fetoprotein
("AFP is a major plasma protein produced by the yolk sac and the fetal liver during fetal development. It is thought to be the fetal analog of serum albumin")
(B) Human serum albumin 白蛋白 "is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver [after birth]. * * * Albumin transports hormones, fatty acids, and other compounds, buffers pH, and maintains oncotic pressure [ie, holding water inside blood vessels; liver disease may reduce albumin production, resulting in water seeping out of blood vessels and hence edema and ascites 腹水], among other functions."  en.wikipedia.org for "human serum albumin."
(C) in the same species, alpha-fetoprotein and serum albumin are (glyco)proteins of about the same length and molecular weight.  (The prefix "glyco-" is from Ancient Greek adjective masculine glukús sweet (taste), meaning "sugar" in science. Thus a glycoprotein is a protein with sugar attached to it through covalent bonds.)
(ii) yolk sac
(A) yolk sac. Encyclopaedia Britannica, undated
https://www.britannica.com/science/yolk-sac
is a sketch of a bird's egg. The English noun allantois is New Latin, from Ancient Greek allas sausage; allantois in a bird's egg collects waste.
(B) Unlike birds, yolk sac appears in about the sixth week after fertilization in humans. See

Papaioannou GI et al, Normal Ranges of Embryonic Length, Embryonic Heart Rate, Gestational Sac Diameter and Yolk Sac Diameter at 6–10 Weeks. Fetal Diagnosis and Therapy, 28: 207-219 (2010)
https://www.karger.com/Article/Abstract/319589
https://www.fetalmedicine.com/synced/fmf/2010_27.pdf
("To construct normal ranges for * * * yolk sac diameter (YSD) at 6–10 weeks of gestation * * * with ultrasound measurements")

The first link, provided by the publisher, is locked behind paywall.

First sentence of Introduction (at page 207) told us the time in this report was "gestational age (GA)."

Table 2 (at page 212) indicated that on gestation day 40, the 50th percentile of YSD was 12.9 mm.

"In normal pregnancy, the gestational sac appears during the 5th gestational week. The yolk sac appears 5–6 days later"  page 217.
(C) It is important to know that in humans there are two ways to describe age of pregnancy.

Obstetrics uses gestational age (GA). "Pregnancy, also known as gestation * * * Childbirth typically occurs around 40 weeks [or 280 days] from the last menstrual period (LMP). This is just over nine months * * * When measured from fertilization it is about 38 weeks."  en.wikipedia.org for pregnancy. LMP starts from day 1 of the previous menstrual cycle, which is easily recognized (the last day of menstruation is hard to tell, due to spotting or intermittent nature toward the end of menstruation).

Embryology starts counting from the moment of fertilization, which is hard to know in humans.
(D) "The mammalian ovum contains virtually no yolk." Snell GD and Steven LC, Early Embryology. In Green EL (ed), Biology of the Laboratory Mouse. McGraw-Hill, pages 205-245 (1966).
http://www.informatics.jax.org/greenbook/chapters/chapter12.shtml

Instead yolk sac is used to make (primitive) blood ("primitive hematogenesis" in biology jargon; hallmark: "production of large nucleated erythrocytes that express embryonic globins": from the Web). Later on, fetal liver takes over this function.