Plates 11-1 through 11-4, pp. 236-243

Ch 18, Skin, pp. 316-330

Objectives:

1. Be able to identify principal layers of the skin (epidermis, dermis and hypodermis) at the light microscope level and know the principal functions of each layer.
2. Be able to identify the layers of the epidermis in thick and thin skin and describe the major cellular events that take place in each layer in the process of keratinization.
3. Identify melanocytes and explain the process of pigment formation in the skin.
4. Be able to identify eccrine and apocrine sweat glands at the light microscope level.
5. Identify the components of the pilosebaceous apparatus and know the structural and developmental relationship between each component and the epidermis of the skin.

Slide Descriptions

The skin and its associated structures, hair, sweat glands and nails make up the integumentary system. 

I. SKIN

A. Thick skin

UMich slide 106 thick skin, sole of foot H&E [WebScope] [ImageScope]
UMich slide 112 thick skin, sole of foot H&E [WebScope] [ImageScope]

In this slide the structure of skin, especially the epidermis, is exaggerated in response to the continued stress and abrasion applied to the plantar surface of the foot.  Study the epidermis in slides 106 and 112, and identify the various strata: 

1. Stratum basale (also known as S. germinativum):  A single layer of cuboidal to columnar cells resting on and separated from the underlying dermis by a basal lamina.  Mitotic figures occur in this layer. 
2. Stratum spinosum:  Several layers in thickness.  In reduced light, the cells appear interconnected by “spinous” processes. 
3. Stratum granulosum:  A few layers of cells that are characterized by numerous, dense, basophilic granules.   These are keratohyaline and membrane coating granules.
4. Stratum corneum: Note the striking change in cellular morphology.  The cells in this layer are usually flattened with fading or absent nuclei, few cytoplasmic granules, and filled with mature keratin.   Because of differential dye penetration, the staining of the stratum corneum is variable and unpredictable.  Sectioning artifacts are common.

The principal cell type of the epidermis is termed a keratinocyte and you will see this term used as a general descriptor for the epithelial cell found in any stratified squamous epithelium.  Note the absence of blood vessels in the epidermis.  Nourishment is obtained by diffusion from capillaries in the underlying dermis. Any tubular structures seen within the epithelium [example] are actually sweat gland ducts that empty out onto the surface of the skin.

The interface of the epidermis and dermis is uneven.  A pattern of ridges and grooves on the deep surface of the epidermis fit a complementary pattern of corrugations of the underlying dermis.  The projections of the dermis are called dermal papillae and those of the epidermis, epidermal ridges (pegs), because of their appearance in vertical sections of the skin.  However, these terms are not always accurately descriptive of the three dimensional configuration of the region of interdigitation.  With low power, identify the epidermal ridges and dermal papillae. What is the function of the epidermal ridges and dermal papillae?

Note the finer arrangement of collagen fibers in the papillary dermis  [example] as opposed to the very coarse fibers of the reticular dermis [example] (so-called because the coarse type I collagen fibers in this layer form an interlacing network, or "reticulum.")  The fatty layer beneath the dermis, the subcutaneous connective tissue, is often called the hypodermis or superficial fascia.  It is this layer that allows the skin to “move”.

B. Thin Skin

Duke slide 058: thin skin, H&E [WebScope] [ImageScope]
UMich slide 104-2: thin skin, H&E [Webscope] [Imagescope]

The epidermis in thin skin is much thinner and simpler in structure.  Each stratum is thinner and the stratum granulosum may be absent. Melanocytes (derived from neural crest cells) capable of producing the pigment melanin are numerous in the deeper (toward the base) layers of the epidermis. They can be identified by the presence of an oval nucleus surrounded by a clear space and are usually found near the stratum basale as can be seen in Slide 58 [example] and 104-2 [example] .  The cells with brownish pigments are actually keratinocytes that have received melanin granules from the melanocytes by pigment donation. Scattered throughout the epithelium (but usually most abundant within the stratum spinosum) are Langerhans cells [example] These cells process and present antigens to the immune system and are recognizable by their irregularly-shaped cytolplasm and nuclei.

While the dermal papilla are not quite as pronounced compared to thick skin, the distinction between the delicate collagen fibers of the papillary dermis [example] and the coarse fibers of the reticular dermis [example] is nonetheless evident in both of these slides.

II. PERIPHERAL MECHANOSENSORY RECEPTORS

A. Meissner’s and Pacinian Corpuscles 

UCSF slide 180 finger tip H&E [WebScope] [ImageScope]

Meissner’s corpuscles [example] are touch receptors that are responsive to low-frequency stimuli and are usually associated with hairless skin of the lips and palmar and plantar surfaces, particularly those of the fingers and toes. Generally, these receptors are tapered cylinders located in the undulating connective tissue just underneath the stratified epithelium of the skin. The long axis of the cylinder is perpendicular to that of the overlying epidermis and is usually about 150 um long and is usually tucked within extensions of the underlying connective tissue dermis (called “dermal papillae”) that project into the underside of the epidermis. Within these receptors, one or two nonmyelinated endings of myelinated nerve fibers follow a spiral path through the corpuscle. The fibers are accompanied by ensheathing Schwann cells, the nuclei of which are flattened and stacked on top of each other giving the corpuscle its characteristic irregular, lamellar appearance.

Pacinian corpuscles [example] are large, ovoid structures up to 1 mm in diameter found in the dermis and hypodermis of the skin and also in the connective tissue associated with bones, joints, and internal organs. They respond primarily to pressure and vibration and are composed of a myelinated nerve ending surrounded by a capsule. The nerve enters the capsule at one pole (which might be out of the plane of section and therefore not visible) with its myelin sheath intact but then it is quickly lost. The unmyelinated portion of the axon extends toward the opposite pole from which it entered and its length is covered by flattened Schwann cell lamellae that form the inner core of the corpuscle. The remaining bulk of the capsule, or outer core, is comprised of a series of concentric, onionlike lamellae with each layer separated by an extracellular fluid similar to lymph. Each lamella is composed of flattened Schwann cells and endoneurial fibroblasts. In addition the fluid between each layer, delicate collagen fibers may be present as well as occasional capillaries. Displacement of the lamellae by pressure or vibrations effectively causes depolarization of the axon, which sends the signal to the central nervous system.

III. PILOSEBACEOUS UNITS (Hair Follicles)

UMich slide 107: Scalp, H&E [WebScope] [ImageScope]

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.

IV. SWEAT GLANDS

A. Eccrine sweat gland

UMich slide 106 [WebScope] [ImageScope] 
UMich slide 112 [WebScope] [ImageScope] 

Numerous coiled eccrine sweat glands [example] are located at the junction of dermis and hypodermis. Distinguish between the secretory portions of the gland (inner cuboidal secretory cells and outer myoepithelial cells) and the much darker-staining, stratified (two layers) cuboidal epithelial cell-lined ductal portion, which empties onto the surface of the skin.

Eccrine sweat glands are a type of merocrine gland (a gland that releases its product by exocytosis). The secretory cells of the eccrine gland are surrounded by myoepithelial cells which can contract to propel its secretions to the surface. Apocrine sweat glands (apocrine being a misnomer, they are truly a merocrine gland, not an apocrine gland) function in the same way, however, their ducts empty into hair follicles, not directly to the skin surface.

B. Apocrine glands

Duke slide 93 recto-anal junction, H&E [WebScope] [ImageScope]
UMich slide 104-2: thin skin, H&E [WebScope] [ImageScope]

Start out looking at slide 93, which is from the peri-anal region where apocrine glands may be found just under the epidermis on the left-hand side of the slide.

Look in the deep dermis or hypodermis for secretory tubules with a wide lumen [example].  The epithelium is cuboidal to columnar with distinct apical secretory granules.  What should be apparent in your section is the apical “blebbing” of the secretory cells that was responsible for histologists originally designating these cells as “apocrine” secretory cells, although we now know the cells actually secrete in a MEROCRINE manner just like eccrine sweat glands.  The “apocrine” sweat glands, present in the axillary, areolar, and anal regions, represent the second type of sweat glands.  These glands produce a viscous secretion which acquires a distinctive odor as a result of bacterial decomposition.

Since aprocrine sweat glands empty into hair follicles, the ducts are quite short, so most of what you will see are secretory portions of the glands. Similar to eccrine sweat glands, the secretory portions of apocrine sweat glands relay on the contraction of surrounding myoepithelial cells to help expel their product. These cells are evident as a squamous layer just outside the cuboidal secretory cells.

Slide 104-2 is from the axilla and actually features both eccrine and apocrine sweat glands. See if you can identify each type in this slide.

Skin Pathology Cases

UMich Slide 24 [WebScope][ImageScope]

Skin and Subcutis: Chronic Ulcer

This slide represents a non-healing scalp lesion from a 43-year-old man.

• Note under the scanning power of your microscope that the cutaneous surface is interrupted by a defect which penetrates deep into the tissue. Note, also, under the scanning power that there is a layer of exudate surfacing this defect with an underlying loose tissue and then an outer “shell” of dense fibrous tissue.

• Under the higher powers of your microscope note that the ulcer is lined by loose fibrinopurulent exudate, immediately beneath which is a zone of maturing granulation tissue (with various types of leukocytes), deep to which is a zone of relatively mature scar.

• This lesion is good example of chronic inflammation with evidence of advanced scarring as well as continued exudation. An inspection of the epidermal borders of the lesion will reveal attempted regeneration of the epithelium.

  Were this lesion finally to heal, what would be the sequence of histologic events and what would be the ultimate appearance?

  
  

UMich Slide 25 [WebScope][ImageScope]

Skin: Scar

This 27-year-old patient had a pigmented skin lesion excised which turned out to be a melanoma. 6 weeks later, another biopsy was performed at the same site to confirm complete removal of the neoplasm and absence of recurrence. As shown in the specimen, there is no remaining neoplasm, but scar tissue from initial biopsy procedure is evident.

• Under the scanning power of your microscope identify the epidermis and, at either end of the specimen some of the dermal appendages. Note that in the central portion of the specimen dermal appendages are absent and a dense connective tissue “replaces” the dermis. This is a scar. Note that the epidermis over the area of scar shows flattening of the normal rete ridge pattern seen towards the ends of the specimen. This is regenerated epidermis over the scar.

• A quick glance at UMich Slide 26 [WebScope][ImageScope] will reveal an abnormal variation on this same theme. This specimen represents a large nodule which developed in a surgical incision. You will note from the shape of the lesion that this was a “knob” projecting from the skin surface, covered with an intact (regenerated ) epidermis. This is a keloid, actually a nodule of overgrown scar tissue. Under the higher power of your scope note the peculiar coarse, glassy collagen which accounts for the bulk of the keloid. What is the clinical significance of such a lesion?

UMich Slide 178 [WebScope] [ImageScope]

History: A 35-year-old man was clearing a path in the woods. When he returned home, he noticed an intensely pruritic linear vesicular eruption on his extensor forearms. A skin biopsy was taken.

Histologic features: There is pronounced spongiosis (intercellular edema) within the epidermis resulting in intraepidermal vesicles. Exocytosis of lymphocytes (lymphocytic spongiosis) may be seen in the epidermis. There is a superficial perivascular lymphocytic infiltrate.

Based on the history, presentation, and histological findings, what do you think is the best diagnosis for this case?

1. What type (I, II, III, or IV) of allergic hypersensitivity reaction is this?

2. Does allergic contact dermatitis occur with someone's first exposure to the antigen?

UMich Slide 198 [WebScope] [ImageScope]

History: A 45-year-old woman complained of a scaly rash present for many years. On exam were multiple, well demarcated erythematous papulosquamous plaques on the elbows, arms and knees. Erythema and white scale were also present on her scalp. A skin biopsy was taken.

Histologic features: There is near confluent parakeratosis, hypogranulosis, and regular psoriasiform hyperplasia of the epidermis with slight clubbing of the rete pegs. Neutrophilic fragments can be identified in the stratum corneum and in the upper epidermis. Dilated and tortuous blood vessels are seen in the dermal papillary tips.

Based on the history, presentation, and histological findings, what do you think is the best diagnosis for this case?

UMich Slide 39 [WebScope] [ImageScope]

History: A 12-year-old boy complained of a slowly growing papule with a thickened surface on his finger. The lesion was biopsied.

Histologic features: There is hyperkeratosis, papillomatosus, and acanthosis. Within the granular cell layer, diagnostic koilocytes containing "raisin-like" nuclei are seen. Intracytoplasmic viral inclusions may also occasionally be seen.

Based on the history, presentation, and histological findings, what do you think is the best diagnosis for this case?

1. What is the cause of this condition?


2. Is it infectious? If so, how is it spread from person to person?


3. Are there any types of these lesions that are associated with an increased risk of cancer?

UMich Slide 128 [WebScope] [ImageScope]

History: A 65-year-old man complained of a slowly growing lesion on his nose. On exam, an ulcerated pearly nodule with dilated blood vessels was noted. The lesion was surgically excised and submitted to pathology for analysis.

Histologic features: There are multiple islands of neoplasia extending into the dermis demonstrating peripheral palisading and stromal retraction artifact. Connection of the neoplastic islands to the stratum basale of the epidermis is often identified.

Based on the history, presentation, and histological findings, what do you think is the best diagnosis for this case?

1. How common is this type of lesion compared to malignancies observed in humans?


2. What environmental factor predisposes to the development of this lesion?


3. In what location on the body does this type of lesion most frequently develop?


4. What is the usual biologic behavior of this type of lesion? What is its metastatic potential?

UMich Slide 123 [WebScope] [ImageScope]

History: A 30-year-old woman presented with a symmetric, uniformly pigmented, dome-shaped papule on her face. She requests its removal.

Histologic features: There is a dome-shaped, symmetric papule with multiple nests of bland nevus cells at the dermo-epidermal junction and in the dermis. Nevus cells are slightly larger in the superficial portion of the lesion and become smaller or "mature" with descent into the dermis. There is no cytologic atypia.

Based on the history, presentation, and histological findings, what do you think is the best diagnosis for this case?

1. What is the cell of origin of this lesion?


2. Can this particular type of lesion serve as a precursor to malignancy?
   
   
3. If this lesion were present from birth, very large, or present in large numbers, would this confer any greater risk of developing a malignancy?

Slide 129 [WebScope] [ImageScope]

History: A 24-year-old medical student, who used to work summers as a lifeguard, complained of a changing mole on her leg. It had begun to itch and recently darkened in color. The lesion was biopsied.

Histologic features: There are cytologically atypical melanocytes at the dermo-epidermal junction and in the dermis. Nuclei are large with occasionally prominent nucleoli. Rare mitotic figures are present. The lesion is asymmetric and poorly circumscribed.

Based on the history, presentation, and histological findings, what do you think is the best diagnosis for this case?

1. What are the risk factors for the development of this type of lesion?


2. What are some of the key factors to consider in the evaluation of this type of lesion?