The Skin and Subcutaneous Tissue
BASIC SCIENCE QUESTIONS
1. Approximately how long does it take from migration of a keratinocyte from the base layer to the time it is shed from the epidermis?
A. 10 days
B. 30 days
C. 50 days
D. 70 days
Composed primarily of keratinocytes, the epidermis is a dynamic, multilayered composite of maturing cells. From internal to external most layer, the epidermis is composed of the (a) stratum germinatum (b) stratum spinosum, (c) stratum granulosum, (d) stratum lucidum, and finally, (e) stratum corneum. Basal cells are a mitotically active, single-cell layer of the least-differentiated keratinocytes at the base of epidermal structure. As basal cells multiply, they leave the basal lamina to begin their differentiation and upward migration. In the spinous layer, keratinocytes are linked together by tonofibrils and produce keratin. As these cells drift upward, they lose their mitotic ability. With entry into the granular layer, cells accumulate keratohyalin granules. In the horny layer, keratinocytes age, lose their intercellular connections, and shed. From basal layer exit to shedding, keratinocyte transit time approximates 40 to 56 days. (See Schwartz 9th ed., p 406.)
2. What is the embryologic origin of melanocytes?
D. Neural crest
Melanocytes and other cellular components within the skin deter absorption of harmful radiation. Initially derived from precursor cells of the neural crest, melanocytes extend dendritic processes upward into epidermal tissues from their position beneath the basal cell layer. They number approximately one for every 35 keratinocytes, and produce melanin from tyrosine and cysteine. Once the pigment is packaged into melanosomes within the melanocyte cell body, these pigment molecules are transported into the epidermis via dendritic processes. As dendritic processes (apocopation) are sheared off, melanin is transferred to keratinocytes via phagocytosis. Despite differences in skin tone, the density of melanocytes is constant among individuals. It is the rate of melanin production, transfer to keratinocytes, and melanosome degradation that determine the degree of skin pigmentation. (See Schwartz 9th ed., p 406.)
3. Which of the following is the primary type of collagen present in fetal skin?
A. Type I collagen
B. Type II collagen
C. Type III collagen
D. Type IV collagen
Collagen, the main functional protein within the dermis, constitutes 70% of dermal dry weight and is responsible for its remarkable tensile strength. Tropocollagen, a collagen precursor, consists of three polypeptide chains (hydroxyproline, hydroxylysine, and glycine) wrapped in a helix. These long molecules are then cross-linked to one another to form collagen fibers. Of the seven structurally distinct collagens, the skin primarily contains type I. Fetal dermis contains mostly type III (reticulin fibers) collagen, but this only remains in the basement membrane zone and perivascular regions during postnatal development. (See Schwartz 9th ed., p 407.)
4. Which of the following is NOT a component of a mechanoreceptor in the skin (i.e., used to transmit information about mechanical forces on the skin to the central nervous system)?
A. Meissner’s corpuscles
B. Ruffini’s corpuscles
C. Pacini’s corpuscles
D. Glomus bodies
Cutaneous sensation is achieved via activation of a complicated plexus of dermal autonomic fibers synapsed to sweat glands, erector pili, and vasculature control points. These fibers also connect to corpuscular receptors that relay information from the skin back to the central nervous system. Meissner’s, Ruffini’s, and Pacini’s corpuscles transmit information on local pressure, vibration, and touch. In addition, ‘unspecialized’ free nerve endings report temperature, touch, pain, and itch sensations.
Glomus bodies are tortuous arteriovenous shunts that allow a substantial increase in superficial blood flow when stimulated to open. (See Schwartz 9th ed., p 407.)
5. A pressure of 60 mmHg can result in pressure necrosis of the skin and underlying soft tissue after
A. 20 minutes
B. 1 hour
C. 4 hours
D. 12 hours
As little as 1 hour of 60 mmHg pressure produces histologically identifiable venous thrombosis, muscle degeneration, and tissue necrosis. Although normal arteriole, capillary, and venule pressures are 32, 20, and 12 mmHg, respectively, sitting can produce pressures as high as 300 mmHg at the ischial tuberosities. Healthy individuals regularly shift their body weight, even while asleep. However, sacral pressure can build to 150 mmHg when lying on a standard hospital mattress. Patients unable to sense pain or shift their body weight, such as paraplegics or bedridden individuals, may develop prolonged elevated tissue pressures and local necrosis. Because muscle tissue is more sensitive to ischemia than skin, necrosis usually extends to a deeper area than that apparent on superficial inspection. (See Schwartz 9th ed., p 409.)
6. Which of the following radiation wavelengths is primarily responsible for the development of skin cancer after exposure to the sun?
A. UVA (400-315 nm)
B. UVB (315-290 nm)
C. UVC (290-200 nm)
D. FUV (200-122 nm)
Solar or UV radiation is the most common form of radiation exposure. The UV spectrum is divided into UVA (400 to 315 nm), UVB (315 to 290 nm), and UVC (290 to 200 nm). With regard to skin damage and development of skin cancers, significant wavelengths are in the UV spectrum. The ozone layer absorbs UVC wavelengths below 290 nm, allowing only UVA and UVB to reach the earth. UVB is responsible for the acute sunburns and for the chronic skin damage leading to malignant degeneration, although it makes up less than 5% of the solar UV radiation that hits the earth. FUV (far ultraviolet) is also absorbed by the ozone layer. (See Schwartz 9th ed., p 409.)
1. Which of the following is the best initial treatment of a burn with hydrofluoric acid?
A. Copious irrigation with water
B. Copious irrigation with a dilute solution of sodium bicarbonate
C. Application of a topical quaternary ammonium compound
D. Application of topical calcium carbonate gel
The effect of acid exposure on the skin is determined by the concentration, duration of contact, amount, and penetrability. Deep tissue coagulative injury may result, damaging nerves, blood vessels, tendons, and bone. The initial treatment should include copious skin irrigation for at least 30 minutes with either saline or water. This dilutes active acid solution and helps return the skin to normal pH. Injuries associated with hydrofluoric acid present an additional treatment challenge. Fluoride ions continue to injure underlying tissue until they are neutralized with calcium, and absorb the body’s calcium supply, which may prompt cardiac arrythmia. Topical quaternary ammonium compounds are widely used, and topical calcium carbonate gel also effectively detoxifies fluoride ions. (See Schwartz 9th ed., p 407.)
2. What is the causative agent of the lesion shown in Fig. 16-1?
A. Staphyloccocus epidermidis
B. Actinomyces israelii
C. Nocardia brasiliensis
D. Papillomavirus Type 2
Warts are epidermal growths resulting from human papillomavirus (HPV) infection. Different morphologic types have a tendency to occur at different areas of the body. The common wart (verruca vulgaris) is found on the fingers and toes and is rough and bulbous (Fig. 16-1). Plantar warts (verruca plantaris) occur on the soles and palms, and may resemble a common callus. Flat warts (verruca plana) are slightly raised and flat. This particular subtype tends to appear on the face, legs, and hands. Venereal warts (condylomata acuminata) grow in the moist areas around the vulva, anus, and scrotum.
Actinomycosis is a granulomatous suppurative bacterial disease caused by Actinomyces. In addition to Nocardia, Actinomadura, and Streptomyces, Actinomyces infections may produce deep cutaneous infections that present as nodules and spread to form draining tracts within surrounding soft tissue. Forty to 60% of the actinomycotic infections occur within the face or head. Actinomycotic infection usually results following tooth extraction, odontogenic infection, or facial trauma. Accurate diagnosis depends on careful histologic analysis, and the presence of sulfur granules within purulent specimen is pathognomonic. Penicillin and sulfonamides are typically effective against these infections. However, areas of deep-seated infection, abscess, or chronic scarring may require surgical therapy. (See Schwartz 9th ed., p 410.)
3. Which of the following is associated with pyoderma gangrenosum?
A. Monoclonal immunoglobulin A gammopathy
B. Degenerative arthritis
C. Adenocarcinoma of the colon
Pyoderma gangrenosum is a relatively uncommon destructive cutaneous lesion. Clinically, a rapidly enlarging, necrotic lesion with undermined border and surrounding erythema characterize this disease. Linked to underlying systemic disease in 50% of cases, these lesions are commonly associated with inflammatory bowel disease, rheumatoid arthritis, hematologic malignancy, and monoclonal immunoglobulin A gammopathy. Recognition of the underlying disease is of paramount importance. Management of pyoderma gangrenosum ulcerations without correction of underlying systemic disorders is fraught with complication. A majority of patients receive systemic steroids or cyclosporine. Although medical management alone may slowly result in wound healing many physicians advocate chemotherapy with aggressive wound care and skin graft coverage. (See Schwartz 9th ed., p 410.)
4. Staphylococcal scalded skin syndrome (see Fig. 16-2) is most likely to be associated with which of the following?
D. Otitis media
Staphylococcal scalded skin syndrome (SSSS) is caused by an exotoxin produced during staphylococcal infection of the nasopharynx or middle ear. Toxic epidermal necrolysis (TEN) is an immune response to certain drugs such as sulfonamides, phenytoin, barbiturates, and tetracycline. Diagnosis is made via skin biopsy. Histologic analysis of SSSS reveals a cleavage plane in the granular layer of the epidermis. In contrast, TEN results in structural defects at the dermoepidermal junction and is similar to a second-degree burn. Treatment involves fluid and electrolyte replacement, as well as wound care similar to burn therapy. Whereas those with more than 30% of total body surface area involvement are classified as TEN, patients with less than 10% of epidermal detachment are categorized as Stevens-Johnson syndrome. In Stevens-Johnson syndrome, respiratory and alimentary tract epithelial sloughing may result in intestinal malabsorption and pulmonary failure. Patients with significant soft-tissue loss should be treated in burn units with specially trained staff and critical equipment. Although corticosteroid therapy has not been efficacious, temporary coverage via cadaveric, porcine skin, or semisynthetic biologic dressings (Biobrane) allows the underlying epidermis to regenerate spontaneously. (See Schwartz 9th ed., p 411.)
5. A “sebaceous” cyst is removed from the scalp of a 48-year-old woman. Which of the following would be expected on histologic examination?
A. Presence of sebum
B. Presence of a granular layer
C. Presence of eccrine glands
D. The presence of epidermis covered by an external basal layer
Cutaneous cysts are categorized as either epidermal, dermoid, or trichilemmal. Although surgeons often refer to cutaneous cysts as sebaceous cysts because they appear to contain sebum, this is a misnomer and the substance is actually keratin. Epidermal cysts are the most common type of cutaneous cyst, and may present as a single, firm nodule anywhere on the body. Dermoid cysts are congenital lesions that result when epithelium is trapped during fetal midline closure. Although the eyebrow is the most frequent site of presentation, dermoid cysts are common anywhere from the nasal tip to the forehead. Trichilemmal (pilar) cysts, the second most common cutaneous cyst, occur more often on the scalp of females.
Histologic examination reveals several key features. Cyst walls consist of an epidermal layer oriented with the basal layer superficial, and the more mature layers deep (i.e., with the epidermis growing into the center of the cyst). The desquamated cells (keratin) collect in the center to form the cyst. Epidermal cysts have a mature epidermis complete with granular layer. Dermoid cysts demonstrate squamous epithelium, eccrine glands, and ilosebaceous units. In addition, these particular cysts may develop bone, tooth, or nerve tissue on occasion. Trichilemmal cyst walls do not contain a granular layer; however, these cysts contain a distinctive outer layer resembling the root sheath of a hair follicle (trichilemmoma). (See Schwartz 9th ed., p 411.)
6. Which of the following is indicated in the patient shown in Fig. 16-3?
A. CT of the brain
B. MRI of the sinuses
C. Ultrasound of the spleen
D. Doppler ultrasound of the femoral vessels
A capillary hemangioma (also known as a port-wine stain) present upon the midface may signify Churg-Strauss syndrome, and computed tomography of the brain is appropriate to rule out intracranial berry aneurysms. (See Schwartz 9th ed., p 412.)
7. Which of the following is the most common form of basal cell carcinoma?
B. Superficial spreading
Arising from the basal layer of the epidermis, BCC is the most common type of skin cancer. Based on gross and histologic morphology, BCC has been divided into several subtypes: nodular, superficial spreading, micronodular, infiltrative, pigmented, and morpheaform. Nodulocystic or noduloulcerative type accounts for 70% of BCC tumors. Waxy and frequently cream colored, these lesions present with rolled, pearly borders surrounding a central ulcer. Although superficial basal cell tumors commonly occur on the trunk and form a red, scaling lesion, pigmented BCC lesions are tan to black in color. Morpheaform BCC often appears as a flat, plaque-like lesion. This particular variant is considered relatively aggressive and should prompt early excision. A rare form of BCC is the basosquamous type, which contains elements of both basal cell and squamous cell cancer. These lesions may metastasize similar to squamous cell carcinoma SCC, and should be treated aggressively. (See Schwartz 9thed., p 413.)
8. A Marjolin’s ulcer arises in areas exposed to
A. External beam radiation
B. Thermal injury
Marjolin’s ulcers arise in burn scars. Squamous cell carcinoma (SCC) may arise in Marjolin’s ulcers. Along with SCCs associated with osteomyelitis and areas of previous injury, these lesions tend to be more aggressive and metastasize earlier than other SCCs. (See Schwartz 9th ed., p 414.)
9. Angiosarcoma associated with Stewart-Treves syndrome arises in areas exposed to
A. External beam radiation
B. Thermal injury
Angiosarcomas may arise spontaneously, mostly on the scalp, face, and neck. They usually appear as a bruise that spontaneously bleeds or enlarges without trauma. Tumors also may arise in areas of prior radiation therapy or in the setting of chronic lymphedema of the arm, such as after mastectomy (Stewart-Treves syndrome). The angiosarcomas that arise in these areas of chronic change occur decades later. The tumors consist of anaplastic endothelial cells surrounding vascular channels. Although total excision of early lesions can provide occasional cure, the prognosis usually is poor, with 5-year survival rates of less than 20%. Chemotherapy and radiation therapy are used for palliation. (See Schwartz 9th ed., p 418.)
10. Which type of melanoma has the best overall prognosis?
A. Superficial spreading
C. Lentigo maligna
D. Acral lentiginous
In order of decreasing frequency, the four types of melanoma are superficial spreading, nodular, lentigo maligna, and acral lentiginous. The most common type, superficial spreading, accounts for up to 70% of melanomas. These lesions occur anywhere on the skin except the hands and feet. They are typically flat and measure 1 to 2 cm in diameter at diagnosis. Before vertical extension, a prolonged radial growth phase is characteristic of these lesions. Typically of darker coloration and often raised, the nodular type accounts for 15 to 30% of melanomas. These lesions are noted for their lack of radial growth; hence, all nodular melanomas are in the vertical growth phase at diagnosis. Although considered a more aggressive lesion, the prognosis for patients with nodular-type melanomas is similar to that for a patient with a superficial spreading lesion of the same depth. Lentigo maligna accounts for 4 to 15% of melanomas, and occurs most frequently on the neck, face, and hands of the elderly. Although they tend to be quite large at diagnosis, these lesions have the best prognosis because invasive growth occurs late. Less than 5% of lentigo maligna are estimated to evolve into melanoma. Acral lentiginous melanoma is the least common subtype, and constitutes only 2 to 8% of melanomas in white populations. Although acral lentiginous melanoma among dark-skinned people is relatively rare, this type accounts for 29 to 72% of all melanomas in dark-skinned people (African Americans, Asians, and Hispanics). Acral lentiginous melanoma most frequently is encountered on the palms, soles, and subungual regions. Most common on the great toe or thumb, subungual lesions appear as blue-black discolorations of the posterior nail fold. The additional presence of pigmentation in the proximal or lateral nail folds (Hutchinson’s sign) is diagnostic of subungual melanoma. (See Schwartz 9th ed., p 415.)
11. A patient presents with a biopsy proven melanoma of the thigh which is 3 mm thick on histologic examination. At the time of excision, how wide should the margins be?
A. 1 cm
B. 2 cm
C. 3 cm
D. 4 cm
Regardless of tumor depth or extension, surgical excision is the management of choice. Lesions 1 mm or less in thickness can be treated with a 1-cm margin. For lesions 1 mm to 4 mm thick, a 2-cm margin is recommended. Lesions of greater than 4 mm may be treated with 3-cm margins. The surrounding tissue should be removed down to the fascia to remove all lymphatic channels. If the deep fascia is not involved by the tumor, removing it does not affect recurrence or survival rates, so the fascia is left intact. (See Schwartz 9th ed., pp 415-416, and Fig. 16-4.)
FIG. 16-4. The diagnosis of melanoma should be made via excisional biopsy. Based on tumor depth, appropriate margins may be planned. Indications for lymph node evaluation continue to advance as our understanding of tumor behavior improves and outcome data become available. LAD = lymphadenopathy.
12. A patient presents with a biopsy proven Merkel cell carcinoma 2 mm in diameter. At the time of excision, how wide should the margins be?
A. 1 cm
B. 2 cm
C. 3 cm
D. 4 cm
Once thought to be a variant of squamous cell carcinoma (SCC), Merkel cell carcinomas are actually of neuroepithelial differentiation. These tumors are associated with a synchronous or metasynchronous SCC 25% of the time. Due to their aggressive nature, wide local resection with 3-cm margins is recommended. Local recurrence rates are high, and distant metastases occur in one third of patients. Prophylactic regional LN dissection and adjuvant radiation therapy are recommended. Overall, the prognosis is worse than for malignant melanoma. (See Schwartz 9th ed., p 417.)
13. Which of the following chemotherapeutic agents is used in the treatment of some patients with dermatofibrosarcoma protuberans (DFSP)?
D. None of the above—DFSP is not chemosensitive
Continued study of chemotherapy efficacy on dermatofibrosarcoma protuberans (DFSP) also has produced optimistic results. Imatinib, a selective inhibitor of platelet-derived growth factor (PDGF) β-chain alpha and PDGF receptor beta protein-tyrosine kinase activity, alters the biologic effects of deregulated PDGF receptor signaling. Clinical trials have shown activity against localized and metastatic DFSP containing the t(17:22) translocation, suggesting that targeting the PDGF receptors may become a new therapeutic option for DFSP. Phase II clinical trials are under way. (See Schwartz 9th ed., p 418.)
14. Nevus sebaceous of Jadassohn is most commonly associated with
B. Squamous cell carcinoma
C. Basal cell carcinoma
Nevus sebaceous of Jadassohn is a lesion containing several cutaneous tissue elements that develops during childhood. This lesion is associated with a variety of neoplasms of the epidermis, but most commonly basal cell carcinoma (BCC). (See Schwartz 9th ed., p 418.)