Wheater's (7th ed.), Ch 9, Skin

Junqueira's (17th ed.), Ch 18, Skin

Overview:

Your attention in this work period is directed to the epithelial differentiations that serve the functions of a multifunctional organ, skin.  At the same time you should review the various tissue types that make up this organ. 

Remember:  You must derive the three dimensional morphology of the structures you are studying from essentially two dimensional tissue sections under the microscope.  Try to visualize how various profiles result from sections at different angles and levels through solid geometrical forms.

A few reminders about the most effective use of each webslide with the available tools:

1. Understand what you expect to see based on the lectures, lab manual, computer atlas (Histology Time), and textbook.
2. Survey a webslide first with the lowest objective setting and then observe it at progressively higher objective settings. 
3. Attempt to locate exemplary areas that resemble figures in your atlas or text as closely as possible.
4. Try to develop a sense of continuity of structure from whole organ to histological architecture, to cellular detail, to intracellular microstructure, to macromolecular arrangement.
5. It is often helpful to work as teams.
6. Please ask your instructor when you need assistance.

Slide Descriptions

Webslide 0058_L:  Thin Skin, human, H&E [DigitalScope]

A. Examine this slide at low power to observe major structural characteristics and variations of the epidermis.  How thick is the epidermis?  The cornified layer?

Observe the distinctive appearance of the dermis:  dense, irregular connective tissue characterized by thick dermal papillae, sections of criss-crossing collagen fiber bundles, and masses of tubular sweat glands cut in various sections.  Subtle textural differences separate the upper papillary layer from the lower reticular layer.

The separation between dermis and hypodermis is less easily made with the microscope than in the gross lab.  In the latter, skin is separated from superficial fascia at the dermis-hypodermis junction by careful dissection, taking care that the fat that characterizes hypodermis does not come away with the peeled skin.  In the slide, the spongy masses of fat mark the indistinct boundary.

B.    Observe at high power the following features.

Epidermis:

1. Appearance of typical keratinocytes.
2. Cells of the Stratum Granulosum. What do the granules represent?
3. Note the progression of cell changes from S. basale to S. granulosum.
4. The melanosomes - especially in the basal cells. Is there any particular orientation to their deposition?  What functional significance might this have?
5. Clear melanocytes and Langerhans cells.  Where are they located in the epidermis?

Dermis:

1. Dermal papillae containing capillary loops.
   1. Are there capillaries in the epidermis?
   2. What are the advantages of draping the epidermis upon dermal papillae?
2. The appearance of nerve and blood vessels.
3. Sweat glands and ducts passing toward the epidermis.
   1. How do coiled tubes appear in sections?
   2. What modifications of cell structure distinguish duct from gland?
   3. Do ducts penetrate the epidermis?

Webslide 0059_L: Lip, monkey, H&E [DigitalScope]

On this slide, two free epithelial surfaces are visible, the outermost epidermis (on the top) and the moist (mucous) surface that lines the oral cavity.  What two obvious structural modifications enable you to identify which surface is which? 
       
Note the large mass of mucous glands in the dermis under the moist epithelial surface. 

The large mass of skeletal muscle in the center line of the section is part of the sphincter-like orbicularis oris.  It serves to close the mouth and is one of the muscles of facial expression innervated by the 7th cranial nerve.  Smaller isolated patches of skeletal muscle, many longitudinally oriented, probably represent the voluntary skeletal muscle responsible for changing the shape of the lips, such as depressor labii inferioris or levator labii superioris.

Nerve bundles, especially where cut transversely, should be recognizable.  Large diameter blood vessels are also present

Webslide 0093_N: recto-anal junction, mammal, H&E [DigitalScope]

This slide contains good examples of apocrine sweat glands.

Under lowest power, locate the keratinized stratified squamous epithelium of the recto-anal junction on the far left hand side.  In this region, you will observe hair follicles with hair shafts, and associated sebaceous glands.  Deeper in the dermis, closer to the adipose tissue of the hypodermis, there are dilated glandular elements with clear lumina.  The diameter of each lumen is about 5-10 times the thickness of the surrounding epithelium.  These structures are apocrine sweat glands.

Examine the glandular epithelium at higher powers.  It is cuboidal to low columnar in structure.  Between these principal epithelial elements and the basal lamina, you will see a series of dark, flattened nuclei.  The latter are nuclei of the myoepithelial cells that act to express the apocrine secretion onto the surface of the skin.

Slide UMich 104-2: Thin skin, human, H&E [DigitalScope]

Like Webslide 0058 above, this slide features thin skin. However, this particular specimen was taken from thin skin in the region of the axilla and features excellent examples of eccrine and apocrine sweat glands. The dermal papillae are quite deep and exhibit quite obvious capillary loops. A few hair follicles and sebaceous glands can be seen. Finally, this particular specimen is from a darker-skinned individual making it very easy to see cytoplasmic melanin granules in the basal cells in contrast to the clear cytoplasm of the melanocytes. Recall that the melanocytes actually package melanin into melanosomes and rapidly secrete it in a cytocrine manner to the adjacent basal cells via numerous delicate extensions --the reason why the melanocyte cell bodies are clear is that the melanosomes are concentrated in the extensions rather than the bodies.

Slide UMich 107: Scalp, human, H&E [DigitalScope]

Underneath the thin epidermis, there are numerous circular to oblong structures with a hollow or yellow-brown center and surrounding cellular layers.  These structures are hair follicles [example] sectioned transversely or tangentially at different levels.  The keratinized component of the hair occupies the central cavity of the follicle, and appears yellow-brown when present. However, the hair often falls out during tissue processing, in which case the central cavity will appear to be occupied by just empty space. 

The surrounding layers of clear cells form the external root sheath of the hair shaft, which is a downgrowth of the epidermis. In fact, in cases where most of the epidermis is removed (such as severe abrasions or when taking skin graft), it is cells of the external root sheath that will divide and spread over the exposed surface to re-establish the epidermis.   In some sections, you may also see an internal root sheath of darker staining cells right up against the hair follicle –this is the layer of cells that actually produce the keratinized hair shaft.

Note also the presence of sebaceous glands [example] and the arrector pili muscle [example] near the hair follicle.  In most instances, you will not find complete pilosebaceous units (follicle, sebaceous gland, and arrector pili muscle) in a single section, so a bit of mental reconstruction will be required.

Slide UMich 112:  Plantar Skin, H&E [DigitalScope]

This slide is from the plantar (sole) surface of the foot similar that shown in Webslide 0065 above and offers another opportunity to study the structure of thick skin, which is very well preserved in this specimen such that it is very easy to distinguish the delicate collagen fibers of the papillary dermis from the thicker, coarse collagen fibers in the reticular dermis. Also well preserved are the eccrine sweat glands present at the interface between the fatty hypodermis and fibrous dermis. The ductal portions of the glands are darker and you can clearly see that they are lined by a stratified cuboidal epithelium. The secretory portions of the glands are also very preserved such that you can see the inner cuboidal secretory cells and the darker-staining "shell" of myoepithelial cells (the myoepthelial cells contain actin and myosin and contract in response to neural signals to propel sweat out of the glands).

Slide UCSF 180: fingertip, human, H&E [DigitalScope]

This slide features thick skin, which is so named due to the overall thickness of the epidermis. In particular, note:

• Thick (more than 20 layers) stratum corneum
• Stratum granulosum consisting of 3-4 layers of granular keratinocytes (as opposed to 1-2 layers in thin skin)
• Prominent stratum corneum
• Deep rete pegs of epidermis interlaced with correspondingly elongated dermal papillae

Also present in this slide are excellent examples of sensory mechanoreceptors:

• Meissner’s Corpuscles in the dermal papillae. Refer to relevant plates in your atlas.
• Pacinian Corpuscles in the dermis/hypodermis interface. This multilayered structure has the appearance of an onion. Why do you think that these structures would be abundant in sections of the fingertip?

Finally, this slide contains numerous excellent examples of sweat glands and ducts

II. Pathology Correlate

Basal Cell Carcinoma [DigitalScope]

Melanoma [DigitalScope]

These slides offer the opportunity to compare and contrast BASAL CELL CARCINOMA, which typically has a very low rate of metastasis and better prognosis, versus MELANOMA, which has a much higher rate of metastasis and worse outcomes.

BASAL CELL CARCINOMA

As the name implies, basal cell carcinoma is a cancer comprised primarily of epithelial cells (hence a "carcinoma") derived from the stratum basale. Upon inspection of this specimen, you should observe that the epithelium of the skin is largely intact (i.e. comprised of the normal expected layers: basale, spinosum, granulosum, and corneum), EXCEPT for the region in the center of the slide [example] where the upper layers have separated and the cells of the stratum basale have transformed into tumor cells that invade into the underlying dermis. However, what's notable is that the nests of basal cells are often fairly well encapsulated by the surrounding dermis and often show a feature known as "PALISADING" [example] whereby the basal layer of cells adopt a more columnar morphology reminescent of a picket fence or a row of stakes. The cells within these nests show features of transformed, cancerous cells such as large, euchromatic nuclei, often with multiple nucleoli, and numerous mitotic figures (i.e. cells where chromosomes can be seen in various stages of mitosis) [example] indicative of proliferation.

Fortunately, these tumors rarely metastasize and therefore are treatable via resection by "Mohs" surgery (named for Frederic Mohs, who developed the technique). The surgery is done in stages, all in one visit, while the patient waits between each stage. After a surgeon removes a layer of tissue, a pathologist examines it under a microscope in an on-site lab. If any cancer cells remain, the surgeon knows the exact area where they are and removes another layer of tissue from that precise location, while sparing as much healthy tissue as possible. The process is repeated until no cancer cells remain.

MELANOMA

Melanoma is a cancer comprised of melanocytes. The specimen slide shows multiple sections representative of what is seen at the margins (upper left section) and then more in the center of the lesion (lower right section). The section on the upper left [example] shows fairly typical features of the epidermis and dermis, although there is a bit of lymphocytic infiltration evident around blood vessels found in the dermis and the collagen fibers of the reticular dermis are quite large indicative of some degree of fibrosis likely occuring in reaction to the nearby tumor.

The next section on the slide shows so-called "Pagetoid" spread (named for Paget's disease) in which nests of melanocytes have spread "upward" into the stratum spinosum [example].

The lower sections show more of the tumor itself, which consists of nests og proliferating melanocytes that have all but obiterated the stratum basale and spinosum and extend up into the stratum ganulosum and corneum [example]. The cells of the tumor also show large, euchromatic nuclei, often with prominent nucleoli and eosinophilic cytoplasm (as opposed to the pale cytoplasm typically seen in melanocytes). Numerous mitotic figures [example] can also be found. Finally, the tumor can be seen spreading throughout the dermis and encroaching on nearby blood vessels [example], which the cells can invade and then spread to other locations in the body. As such, the rate of metastasis is much higher and the overall prognosis is much worse compared to basal cell carcinoma.

To give you an idea of what a melanoma actually looks like, here's a BRIEF VIDEO prepared by Dr. Deyrup (Director of Pathology Education) in which she reviews some of the key physical features one can see in a surgical resection specimen in our pathology collection.

EXTRA SLIDES

Webslide 0065_L: Skin, foot, human, 6 um paraffin, H&E [DigitalScope]

This slide was prepared from a piece of glutaraldehyde-fixed human plantar skin (sole of foot).  It has the following noteworthy features:
 l)    Moderately thick stratum corneum.
2)    Moderately numerous sweat glands and sweat gland ducts.
3)    Prominent stratum spinosum.