Extragonadal Germinal Cell Tumors

 

Primary Extragonadal Germinal Cell Tumors

          PKGhatak, MD

Primary extragonadal germinal cell tumors.

The germinal cell produces sperm or ovum. Under normal circumstances, the germinal cells are present only in the gonads (Testicles and Ovaries).

In a rare embryonic mishap, the germinal cells are present in the Pineal gland, Mediastinum and Retroperitoneal areas. Germinal cells in these locations may turn into tumors, both benign and malignant tumors.

A short review of the origin of germinal cells is essential in understanding these aberrant locations of the germinal cells.

Gonads and germinal cells have separate lines of origin. Gonads are mesodermal tissues, whereas germinal cells originate in the Yolk Sac of the developing embryo. At 5 weeks the germinal cells leave the yolk sac and migrate to the developing fetus, and travel along the Allantois behind the hindgut, behind the peritoneum and move all the way to the developing neural tube which later develops into the brain. Most of the germinal cells migrate to the genital ridge and lodge in the gonadal tissue, the rest of the germinal cells disappear.

The allantois is a narrow tube through which placental blood vessels run to and from the fetus and placenta. The fetus and extra fetal tissues (yolk sac) lie submerged in amniotic fluid in the amnion sac, the membrane of the sac is called the coelomic epithelium.

Due to developmental errors, a few germinal cells remain in the brain, mediastinum and retroperitoneal tissues. Tumors that develop at these locations are called extragonadal (non-gonadal) germinal cell tumors.

Histopathological Types.

Germ cell tumors in unusual locations may be benign or malignant. The benign tumors are called teratomas.

Teratoma.

The germ cells are endowed with the power to produce any or all cell lines and are progenitors of the Totipotent stem cells. In teratomas this characteristic is maintained, as a result, the teratomas contain hair, teeth, nails, sweat glands and other tissues. Tumors are generally multicyclic. In males, the tumor though benign by the pathological criteria but behaves like a malignant tumor. Teratomas are diverse in histology and also vary in biological behavior. In women, teratomas are benign multicyclic tumors containing hairs, teeth, nails, glands, bone and cartilage. In males, teratomas are benign looking but may behave like malignant.

Malignant germinal tumors.

The tumors are mixed cell types but one cell line dominates and is named accordingly. The usual varieties are Embryonal cell carcinoma, Choriocarcinoma. Yolk cell Carcinoma, and Seminoma.

Location of tumors.

Germinal cell tumors are midline tumors. In the brain, the usual site is the pineal gland and occasionally appears in the Pituitary gland. In the mediastinum, they are in the anterior mediastinum in between the lungs and behind the thymus gland. The abdominal site is usually in the sacrum behind the hindgut and peritoneum.

Pineal gland germinal cell tumors.

These tumors are generally malignant. Symptoms are of three categories. A growing tumor increases cerebrospinal fluid pressure and produces headaches, nausea, vomiting, and the 6^th cranial nerve palsy. Local infiltration of tumor-cerebellar dysfunction affects balance and walking. The hormone of the pineal gland is Melatonin. Disruption of melatonin production results in sleep rhythm change, and difficulty in falling asleep.

The malignant tumors secrete Chorionic gonadotropin and Alpha fetoprotein. The blood levels of these two are elevated in nearly all cases and in 1/3 of cases the CSF levels are also high. It is well known that in raised CSF pressure situation the spinal tap is contraindicated; in this circumstance, the CSF is obtained by the 4^th ventricle puncture. Blood chorionic gonadotropin is not specific for gonadal cell tumors, it is elevated in pregnancy and pregnancy related complications and in menopause. Alpha fetoprotein is also elevated in hepatic cell carcinoma and neonatal hepatitis. High chorionic gonadotropin and alpha fetoprotein in addition to an MRI of the brain suggestive of a pineal growth, in non-pregnant women, is as good as biopsy confirmed pineal germinal cell tumors.

In gonadal cell tumors of the brain, matters little, at the time of initial diagnosis, whether the tumor is benign or not. Biopsy of pineal gland tumors is reserved for tumor recurrence. At that time cell types help to direct more specific chemotherapy agents and additional surgery.

Mediastinal germinal cell tumors.

Germinal cell tumors are the second most mediastinal malignant tumors in childhood. Teratomas do not elevate blood fetoprotein and chorionic gonadotropin.

Chest x-ray detects tumors, and most patients are asymptomatic at the time of diagnosis. Biopsy of the tumor can be safely performed by the retrosternal approach. At times teratomas are detected in the thymus gland, rather than behind it.

Symptoms vary from asymptomatic to obstructive symptoms of trachea-bronchi and blood vessels of the mediastinum. Treatment is surgery, and chemotherapy and radiation are added if the tumors are malignant. In certain circumstances, chemotherapy and radiation are followed by surgery.

Ovarian germinal cell tumors are mostly benign cystic. The testicular germinal cell tumors are generally malignant seminoma and non-seminoma, appear in equal frequency. Testicular malignant tumors do not secrete chorionic gonadotropin and alpha fetoprotein.

Retroperitoneal germinal cell tumors are generally benign teratomas. And carry the best prognosis of the three locations.

Extragonadal germinal cell tumors are rare. Tumors are seen in children and young adults. Except for the sacral location, most of the tumors are either malignant or potentially malignant. Intracranial germinal cell tumors pose a diagnostic challenge but blood and CSF markers along with MRI images are virtually diagnostic.

The prognosis of sacral tumors is the best. Mediastinal seminomas have a better prognosis than Non seminomas. Overall, the 5- year survival rate is between 40 to 90 %.

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Hearing in Old Age.

 Hearing in Old Age

PKGhatak, MD

If one has passed 65 years of age, and for the first time hears someone telling he/she is short of hearing. The person feels a bit startled and annoyed. But the same person did not feel the same way when had to get a pair of reading glasses. Dealing with the deficit in hearing is different due to social stigmata. And wearing a hearing aid is a no-no.

The Latin term of old age hearing deficiency is Presbycusis. In the USA, one in three are over the age of 65 yrs. and nearly one in two over 75 yrs. has difficulty in hearing.

Persistent exposure to loud noise damages the delicate hearing organ and results in selective deafness for the frequency of sound overexposed to and once damaged it fails to grow back. In normal conversation the sound waves are like ripples on a slow flowing stream, noise in the work environment is like winds in winter storms and the noise that hits the ears in live concerts is like tsunami waves. The delicate hearing organs are not designed for mega loudspeakers and music synthesizers and the sound receptors simply wither away.

A short account of the hearing should make this clear.

The receptors of sound are called Organ of Corti. The Organ of Corti is located in the inner ear called Cochlea because of its resemblance to a snail. Inside the bony cochlea, all along the entire length, has another canal made of the membrane. Both the bony and membranous canals are filled with fluids, however, the fluid of the two canals is different in composition. The fluid of the bony canal is called Perilymph and has a high concentration of Sodium, the fluid in the membranous canal is called Endolymph which has higher Potassium levels.

Organ of Corti.

On the base layer of the membranous canal called the Basement Membrane, several groups of Hair Cells are situated on it. The hair cells are arranged in 4 layers of cells and bunched together in groups. Nerve fiber is attached to the lower pole of each hair cell. The tall hair cells have hair like projections on the top which are embedded in the top layer of the membranous canal. When the basement membrane moves up and down, the hair bends and stretches. This movement triggers the opening of pores of the hair cells and allows Sodium from the outer canal to enter the hair cells, triggering an electrical impulse that the nerve fibers carry to the hearing center in the brain.

The hair cells at the beginning of the canal respond to high frequency sounds and the hair cells on the far end of the spiral canal respond to low frequency sounds. And in between the hair cells respond to sound from high to low frequencies.

The three outer layers of hair cells receive signals from the brain and function as sound amplifiers to the outgoing impulse to the brain like transistors in radios.

The tension of the basement membrane has regional variation based on the thickness and composition of tissues. The region of the high tension area of the basement membrane vibrates to high frequency sounds and the low frequency sounds move the low tension area.

Functions of the other parts of the ear.

The outer ear, the pinna, collects sound waves, concentrates the sound waves and sends them down the ear canal. The eardrum vibrates and the vibration is transmitted to the stirrup-like tiny piece of bone attached to the inner side of the eardrum. The final of the three-piece of bone seats perfectly on the opening of the bony canal called the Oval Window and tissues around the bone make the joint airtight. Since the surface area of the oval window is 1/20th of the eardrum, the sound wave is magnified 20 times at the oval window. The waves are transmitted to the perilymph. The movement of the perilymph moves the endolymph in the membranous canal. As the endolymph moves, the basement membrane moves up and down generating nerve impulses. The 2 and 1/3 turns of the cochlea with progressive narrowing, amplify sounds further as the sound waves move to the far end of the cochlea.

Cause of hearing loss in elderly.

Like any organ, age takes its toll, but misuse and abuse accelerate the degenerative changes leading to loss of function. And in this modern age, humans are surrounded by air pollution, water pollution, light and sound pollution. The OSA regulations aim to protect the employees but the compliance is not universal and particularly true for companies with seasonal employees and mom and pop shops. And those weekend homeowners using lawnmowers, chain saws or leaf-blowers are likely to have a hearing deficit.

Genes are blamed for most maladies and so are presbycusis also. But the blame lies squarely on misuse.

The deficit due to presbycusis is detected on both ears. In an acquired illness deafness is unilateral.

The world around us.

It is interesting to survey the living world around us and note the evolution of hearing.

Plants.

Some claim plants can hear us talking to them, which makes plants grow healthier and faster. But plants have no nervous system at all. So, it is up to future scientists to find that truth.

The unicellular organism onward up to the worm:

The perception of sound in these organisms is through the surface in contact with the environment. The worms have nerve innervation of the segmental body, the nerve ends detect ground vibrations.

Insects:

The majority of insects can hear. An insect's so-called ear is an open tube, the opening of the tube is covered with overlapping cuticles. The location of sound receptors varies from one species to the other. It can be located in the abdomen, thorax, or head. Insects can hear a wide range of sounds.

Amphibians:

Salamander has primitive hearing organs inside the head and a tiny opening, one on each side admitting sound waves to the inner ear.  Frogs can hear in water and on land.

Fish:

Fish have the most elaborate hearing system. Fish have well developed inner ears on each side of the head. In addition, the lateral line of fish has nerves connected with receptors called cilia. Cilia move with the vibration of water. In some fish, the swim bladder has projections reaching the inner ears and act as sound receptors. The head of some bony fish acts as a receptor of wave movement. In some bony fish, the pectoral fine bones function as additional water vibration receptors. Fish, being underwater animals, hear only low frequency sounds.

Reptiles:

Snakes.  Snakes have no external or middle ears but have well developed internal ears. A special bone in the head connected with other bones by ligaments acts as the sound receiver. Snakes also feel ground vibrations with the body.

Lizards have the middle and inner ears but not the external ear. Ground burrowing lizards have a hearing system like snakes.

Birds:

Birds have ears, but not the pinna. The outside opening of the external canal is covered with special feathers without any burs. In vultures and condors, the external ear openings are easily visible. Songbirds have a wide range of hearing.

Mammals:

Whales and dolphins used to be land mammals, later they went back to the water. The pinna of aquatic mammals has disappeared, and the ear canals are filled with either wax or oil to prevent water entry but conduct water vibration well. Water being dense and not easily compressible, the sounds travel far and wide.

Dolphins can hear in water and out of water. In water, they hear through the vibration receptors of the lower jaw bone. When out of the water, the dolphins hear like land animals, the air enters the ears through two small openings on the side of the head. In addition, dolphins have an echolocation box on the head, a specialized receptor for ultrasonic sounds, and as the ultrasounds are received the dolphins reconstitute the ultrasound in the form of images of the prey and the immediate surroundings.

Whales:

Baleen whales (toothless) have two small external openings for the ear canal and the canal is filled with wax. The inner hearing organ is like land animals.

Toothed whales have no openings for their ears. They have a specialized structure on the lower jaw bone which acts as a receiver of sound waves. Whales can hear from very long distances but only low frequency sounds.

Land animals.

Dogs: Dog is the hearing champion among territorial mammals. A dog can move pinna in any direction by using some of the 30 muscles. A dog's hearing range is 20 to 40,000 cycles per second (Hertz); far beyond the human hearing range of 20 to 4,000 Hertz.

A look at the range of hearing of some animals.

Moth – up to 300,000 Hertz

Bullfrog - 50 – 4,000 Hertz

Owl – 200 – 12,000 Hertz

Songbird - 1000 – 8000 Hertz

Dolphin - 75 – 15,000 Hertz

Beluga whale -1000 -12,000 Hertz

Human - 64 – 23,000 Hertz

Dog - 20 – 45,000 Hertz.

The champion of hearing is the Moth.

Presbycusis comes with old age but by using ear covers in a loud noisy environment the hearing deficit can be delayed, or completely prevented.

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