For the past decade, a 29-year-old man has had waxing and waning of the lesions shown in the figure. The scalp,
lumbosacral region, and glans penis also are affected. For the past 2 years, he has had chronic arthritis in the hips and
knees. Which of the following physical findings would most likely be present in this patient?
□ (A) Guaiac-positive stool
□ (B) Friction rub
□ (C) Hyperreflexia
□ (D) Damage to the nails
□ (E) Hypertension
(D) This patient has psoriasis, a chronic skin condition with marked epithelial hyperplasia and parakeratotic scaling. Nail
changes, such as yellow-brown discoloration, pitting, dimpling, and separation of the nail plate from the nail bed
(onycholysis), affect about one third of patients. Other manifestations of psoriasis include arthritis (resembling rheumatoid
arthritis), myopathy, enteropathy, and spondylitic heart disease. Gastrointestinal mucosal involvement with hemorrhage is
not a feature of psoriasis. A friction rub from fibrinous pericarditis does not occur in psoriasis because mesothelial surfaces
are not involved. Joint laxity with hyperreflexia is a feature of Ehlers-Danlos syndrome. Renal disease and hypertension
are not typically the result of psoriasis.
An epidemiologic study is conducted to identify factors that increase the risk of skin cancer. The study documents
subjects reported to tumor registries with a diagnosis of malignant melanoma and the incidence of melanoma worldwide
over the past 25 years. Demographic information is collected. Analysis of the data is most likely to show the greatest
increase in incidence of malignant melanoma in which of the following locations?
□ (A) Edinburgh, Scotland
□ (B) Cairo, Egypt
□ (C) Brisbane, Australia
□ (D) Tahiti, French Polynesia
□ (E) Hong Kong, China
(C) The driving force behind a worldwide rise in melanoma has been increased sun exposure. The Australian population
is mainly derived from light-skinned Europeans who migrated to Australia. Indigenous, dark-skinned populations do not
have the same risk.
A 64-year-old man has noted changes in the texture and color of skin in his armpit and groin over the past 3 months. On
physical examination, there is thickened, darkly pigmented skin in the axillae and flexural areas of the neck and groin.
These areas are neither painful nor pruritic. A punch biopsy specimen of axillary skin shows undulating epidermal
acanthosis with hyperkeratosis and basal layer hyperpigmentation. Which of the following underlying diseases is most
likely to be present in this patient?
□ (A) Systemic lupus erythematosus
□ (B) Mastocytosis
□ (C) AIDS
□ (D) Colonic adenocarcinoma
□ (E) Langerhans cell histiocytosis
(D) The patient has findings typical of acanthosis nigricans, a cutaneous marker for benign and malignant neoplasms.
The skin lesions often precede signs and symptoms of associated cancers. They are believed to arise from the action of
epidermal growth-promoting factors produced by neoplasms. The rashes that develop in systemic lupus erythematosus
are the result of antigen-antibody complex deposition and often exhibit photosensitivity. Skin lesions of mastocytosis in
Robbins & Cotran Review of Pathology Pg. 524
adults often exhibit urticaria. Various skin lesions are associated with AIDS, including disseminated infections and
papulosquamous dermatoses, although not pigmented lesions. Involvement of the skin in Langerhans cell histiocytoses
typically occurs in children and produces reddish papules or nodules or erythematous scaling plaques because of the
histiocytic infiltrates in the dermis.
A 51-year-old man noticed a change in the skin lesion on the upper, outer area of his right arm, shown in the figure. The
lesion has enlarged during the past month. Physical examination yields no other remarkable findings. Which of the
following occupations is this man most likely to have had earlier in life?
□ (A) Chemist
□ (B) Lifeguard
□ (C) Miner
□ (D) Auto mechanic
□ (E) Radiation oncologist
(B) The figure shows a malignant melanoma with irregular borders and variability of pigmentation. Any change in a
pigmented lesion suggests the possibility of melanoma. Some melanomas are familial, arising from conditions such as
dysplastic nevus syndrome. Most melanomas occur sporadically, however, and are related to sun exposure, as may occur
in a lifeguard.
A 35-year-old man has had an outbreak of pruritic lesions over the extensor surfaces of the elbows and knees during the
past month. He has a history of malabsorption that requires him to eat a special diet, but he has had no previous skin
problems. On physical examination, the lesions are 0.4- to 0.7-cm vesicles. A 3-mm punch biopsy of one of the lesions
over the elbow is performed. Microscopic examination of the biopsy specimen shows accumulation of neutrophils at the
tips of dermal papillae and formation of small blisters owing to separation at the dermoepidermal junction.
Immunofluorescence studies performed on this specimen show granular deposits of IgA localized to tips of dermal papillae.
Laboratory studies show serum antigliadin antibodies. What is the most likely diagnosis?
□ (A) Bullous pemphigoid
□ (B) Contact dermatitis
□ (C) Dermatitis herpetiformis
□ (D) Discoid lupus erythematosus
□ (E) Erythema multiforme
□ (F) Impetigo
□ (G) Lichen planus
□ (H) Pemphigus vulgaris
(C) The clinical and histologic findings are typical of celiac disease with dermatitis herpetiformis. The IgA or IgG
antibodies formed against the gliadin protein in gluten that is ingested cross-react with reticulin. Reticulin is a component
of the anchoring fibrils that attach the epidermal basement membrane to the superficial dermis. This explains the
localization of the IgA to the tips of dermal papillae and the site of inflammation. A gluten-free diet may relieve the
symptoms. Bullous pemphigoid can occur in older individuals, with antibody directed at keratinocytes to produce flaccid
bullae, but there is no association with celiac disease. Contact dermatitis is most likely to be seen on the hands and
forearms. It is a type IV hypersensitivity reaction without immunoglobulin deposition and would not persist for 1 month.
Discoid lupus erythematosus is seen on sun-exposed areas and has the appearance of an erythematous rash. Erythema
multiforme is a hypersensitivity response to infections and drugs; it produces macules and papules with a red or vesicular
center, but it is probably mediated by cytotoxic lymphocytes and not by immunoglobulin deposition. Impetigo produced by
infection with staphylococci and streptococci produces pustules and crusts, mainly on the hands and face. Lichen planus
appears as violaceous papules and plaques. Pemphigus vulgaris is an autoimmune disease in which IgG deposited in
acantholytic areas forms vesicles that rupture to form erosions; it is not related to celiac disease
Over the course of 1 week, a 6-year-old boy develops 1- to 2-cm erythematous macules and 0.5- to 1-cm pustules on his
face. During the next 2 days, some of the pustules break, forming shallow erosions covered by a honey-colored crust. New
lesions form around the crust. The boy's 40-year-old uncle develops similar lesions after visiting for 1 week during the
child's illness. Removal of the crusts from the boy's face is followed by healing within 1 week. The uncle does not seek
medical care, and additional pustules form at the periphery of the crusts. Which of the following conditions most likely
explains these findings?
□ (A) Acne vulgaris
□ (B) Bullous pemphigoid
□ (C) Contact dermatitis
□ (D) Erythema multiforme
□ (E) Impetigo
□ (F) Lichen planus
□ (G) Pemphigus vulgaris
□ (H) Psoriasis
(E) Impetigo is a superficial infection of skin that produces shallow erosions. These erosions are covered with exuded
serum that dries to give the characteristic honey-colored crust. Cultures of the lesions of impetigo usually grow coagulasepositive
Staphylococcus aureus or group A β-hemolytic streptococcus. The lesions are highly infectious. Acne vulgaris is
typically seen during adolescence and produces pimples and pustules, but not crusts. Bullous pemphigoid can occur in
older individuals with antibody directed at keratinocytes to produce flaccid bullae. Contact dermatitis is most likely to be
seen on the hands and forearms. Erythema multiforme is a hypersensitivity response to infections and drugs that produces
macules and papules with a red or vesicular center. Lichen planus appears as violaceous papules and plaques.
Pemphigus vulgaris is an autoimmune disease in which IgG deposited in acantholytic areas forms vesicles that rupture to
form erosions. Psoriasis produces patches of silvery, scaling lesions.
A 50-year-old woman has been bothered by a discolored area of skin on her forehead that has not faded during the past
3 years. On physical examination, there is a 0.8-cm red, rough-surfaced lesion on the right forehead above the eyebrow. A
biopsy specimen examined microscopically shows basal cell hyperplasia. Some of the basal cells show nuclear atypia
associated with marked hyperkeratosis and parakeratosis with thinning of the epidermis. The upper dermal collagen and
elastic fibers show homogenization with elastosis. What is the most appropriate advice to give this patient?
□ (A) Reduce intake of dietary fat
□ (B) Wear a hat outdoors
□ (C) Stop taking aspirin for headaches
□ (D) Apply hydrocortisone cream to your face
□ (E) This condition is related to aging
(B) Actinic keratoses are premalignant lesions associated with sun exposure. Decreasing dietary fat is always a good
idea, but it does not have much effect on the skin of the face. Many drugs can cause acute eczematous dermatitis and
erythema multiforme. Hydrocortisone can alleviate the symptoms of many dermatologic conditions, but it cannot reverse
actinic damage. Older individuals are more likely to have actinic keratoses because of greater cumulative sun exposure,
not because of aging alone.
A 10-year-old girl is brought to the physician by her mother because multiple excoriations have appeared on the skin of
her hands over the past week. The child reports that she scratches her hands because they itch. Physical examination
shows several 0.2- to 0.6-cm linear streaks in the interdigital regions. Treatment with a topical lindane lotion resolves the
condition. Which of the following organisms is most likely responsible for these findings?
□ (A) Ixodes scapularis
□ (B) Tinea corporis
□ (C) Staphylococcus aureus
□ (D) Molluscum contagiosum
□ (E) Sarcoptes scabiei
(E) The small scabies mites burrow through the stratum corneum to produce the linear lesions, and the mites along with
their eggs and feces produce intense pruritus. Scabies is easily transmitted by contact and typically occurs in community
outbreaks. Ixodes scapularis is the tick that is the vector for Borrelia burgdorferi organisms, which cause Lyme disease
and erythema chronicum migrans. Tinea corporis is a superficial fungal infection that can produce erythema and crusting.
The erythematous macules and pustules of impetigo in children are often caused by staphylococcal and group A
streptococcal infection. Molluscum contagiosum is a poxvirus that produces a localized, firm nodule.
A 35-year-old man has noted a bump on his upper trunk for the past 6 weeks. On physical examination, there is a
solitary, 0.4-cm, flesh-colored nodule on the upper trunk. The dome-shaped lesion is umbilicated, and a curdlike material
can be expressed from the center. This material is smeared on a slide, and Giemsa stain shows many pink, homogeneous,
cytoplasmic inclusions. The lesion regresses over the next 2 months. Which of the following infectious agents most likely
produced this lesion?
□ (A) Human papillomavirus
□ (B) Staphylococcus aureus
□ (C) Molluscum contagiosum
□ (D) Histoplasma capsulatum
□ (E) Varicella-zoster virus
(C) The pink cytoplasmic inclusions, called molluscum bodies, are characteristic of this lesion. Immunocompromised
individuals may have multiple, larger lesions. The infectious agent is a poxvirus. Human papillomavirus (not a toad) is
Robbins & Cotran Review of Pathology Pg. 525
implicated in the appearance of verruca vulgaris, or the common wart. Staphylococcus aureus is implicated in the
formation of the lesions of impetigo. Disseminated fungal infections are uncommon except in immunocompromised
patients. Varicella-zoster virus causes shingles, characterized by a dermatomal distribution of clear, painful vesicles.
Many skin disorders give rise to vesicles or bullae (blisters) in the skin. The location of the bulla often aids in the
diagnosis. What disorder is most likely to produce the type of blister that is schematically illustrated in the figure?
Robbins & Cotran Review of Pathology Pg. 516
□ (A) Impetigo
□ (B) Pemphigus vulgaris
□ (C) Bullous pemphigoid
□ (D) Acute eczematous dermatitis
□ (E) Urticaria
(C) The figure shows a subepidermal bulla of bullous pemphigoid, which usually heals without scarring. Subsequent
oral lesions may appear. Most often seen in the elderly, this disease results from linear IgG deposition at the basal
cellbasement membrane attachment plaques (hemidesmosomes) containing bullous pemphigoid antigen (BPAG). In
contrast, the antibodies in pemphigus vulgaris attack the desmosomes that attach the epidermal keratinocytes. Loosening
of these junctions leads to acantholysis, and an intraepidermal blister is formed just above the basal layer (suprabasal). In
impetigo, there is infection of the superficial layer of the skin, and the blister is just under the stratum corneum
(subcorneal). Acute eczematous dermatitis has spongiotic vesicles, not bullae. In urticaria, the allergic reaction causes
increased vascular permeability in dermal capillaries. This produces superficial dermal edema, not a bulla.
A 39-year-old woman has a nodule on her back that has become larger over the past 2 months. On physical
examination, there is a 2.1-cm pigmented lesion with irregular borders and an irregular brown-to-black color. An excisional
biopsy with wide margins is performed, and microscopic examination of the biopsy specimen shows a malignant melanoma
composed of epithelioid cells that extends 2 mm down to the reticular dermis. There is a band of lymphocytes beneath the
melanoma. Which of the following statements is most appropriate to make to this patient regarding these findings?
□ (A) Your immune system will prevent metastases
□ (B) The prognosis is poor
□ (C) Other family members are at risk for this condition
□ (D) The primary site for this lesion is probably the eye
□ (E) Nevi elsewhere on your body may become malignant
(B) Extension deep into the reticular dermis indicates vertical (nodular) growth. When a melanoma exhibits a nodular
growth pattern, rather than a radial pattern, there is increased likelihood that a clone of neoplastic cells has arisen that is
more aggressive and is more likely to metastasize. Although there has been a lymphocytic response to this tumor, it is
insufficient to destroy or contain it completely. Most melanomas are sporadic, nonfamilial, and related to sun exposure.
Melanomas of the eye are much less common than melanomas of the skin. Benign skin nevi do not have a tendency to
A 39-year-old woman goes to her dentist for a routine checkup. The dentist notes that she has 0.2- to 1.5-cm scattered,
white, reticulated areas on the buccal mucosa. The woman says that these lesions have been present for 1 year. She also
has some 0.3-cm purple, pruritic papules on each elbow. A biopsy specimen of a skin lesion shows a bandlike infiltrate of
lymphocytes at the dermal-epidermal junction and degeneration of basal keratinocytes. What is the best advice to give this
patient regarding these lesions?
□ (A) A squamous cell carcinoma is likely to develop
□ (B) You may develop chronic renal disease
□ (C) A skin test for tuberculosis needs to be performed
□ (D) You should stop taking all medications
□ (E) These lesions will probably resolve over time
(E) This patient has the classic “pruritic, purple, polygonal papules” of lichen planus, with the distinctive bandlike
infiltrate of lymphocytes at the dermal-epidermal junction. The lesions of lichen planus are typically self-limited, although
the course can run for several years. Oral lesions may persist longer. There is no risk of malignancy. Although a
lymphocytic infiltrate is present, an infection or autoimmunity is not implicated. A drug eruption would not last this long.
Lesions of erythema multiforme are more likely to follow infections, drugs, autoimmune diseases, and malignancies.
A 22-year-old man and other members of his racquetball club have noticed more itching of their feet in the past 2
months. On physical examination, the man has diffuse, erythematous, scaling skin lesions between the toes of both feet.
There are no other remarkable findings. These findings are most likely the result of infection with which of the following
□ (A) Borrelia burgdorferi
□ (B) Group A β-hemolytic streptococcus
□ (C) Herpes simplex virus
□ (D) Varicella-zoster virus
□ (E) Human papillomavirus
□ (F) Molluscum contagiosum
□ (G) Propionibacterium acnes
□ (H) Sarcoptes scabiei
□ (I) Staphylococcus aureus
□ (J) Trichophyton rubrum
(J) Athlete's foot is a common disorder resulting from superficial dermatophyte infection by various fungal species,
including Trichophyton, Epidermophyton, and Microsporum. Infections that involve the foot produce the condition known
as tinea pedis. Borrelia burgdorferi causes Lyme disease, which may include a skin lesion called erythema chronicum
migrans around the original tick bite. Streptococcal and staphylococcal organisms cause impetigo, which is more common
on the face and hands. Herpetic infections first produce crops of clear vesicles, which may burst and form painful shallow
ulcers. Varicella-zoster virus is the reactivation, in adults, of childhood chickenpox in the form of vesicles in a dermatomal
distribution of the nerve in whose ganglion the virus lay dormant for years. Human papillomavirus is best known as the
cause of genital warts (condyloma acuminatum) and as a driving force behind cervical and anal squamous cell dysplasias.
Molluscum contagiosum is caused by a poxvirus and produces an umbilicated nodule. Propionibacterium acnes is a factor
in the development of acne. The little eight-legged critters known as Sarcoptes scabiei crawl around in the stratum
corneum, usually between the fingers, and cause itching, a process called scabies.
Over the past 20 years, a 75-year-old man has noticed slowly enlarging lesions, similar to those shown in the figure, on
his trunk. One of the lesions is excised, and microscopic examination shows sheets of lightly pigmented basaloid cells that
surround keratin-filled cysts. This lesion is sharply demarcated from the surrounding epidermis. What is the most likely
□ (A) Basal cell carcinoma
□ (B) Condyloma acuminatum
□ (C) Intradermal nevus
□ (D) Keratoacanthoma
□ (E) Melanoma
□ (F) Seborrheic keratosis
□ (G) Squamous cell carcinoma
□ (H) Verruca vulgaris
(F) These flat, round, pigmented, sharply demarcated lesions are benign tumors called seborrheic keratoses. They are
composed of pigmented basaloid cells. Seborrheic keratoses are common in older individuals. The lesions gradually
enlarge, but they are not painful and do not ulcerate. They mainly are a cosmetic problem. Basal cell carcinomas are
nodular, slowly enlarging lesions most common on the head and trunk and are related to sun exposure. Condylomata
acuminata, or genital warts, are caused by a sexually transmitted type of human papillomavirus; the lesions tend to be pink
to white. An intradermal nevus can produce a pigmented nodule, but microscopically it is composed of nests of small
nevus cells, and the lesions increase minimally in size over time. Keratoacanthoma may resemble squamous cell
carcinoma and grow rapidly to form an ulcerative nodule, but typically regresses in several months; squamous cell
carcinoma continues to grow. Melanomas have very atypical spindle to epithelioid cells that invade the dermis; they tend
to change in appearance over weeks to months, not years. A verruca vulgaris, or wart, also has a rough surface, but such
lesions are more common on the hands and feet, and they may regress after several years. The cells in a squamous cell
carcinoma are atypical and may invade the dermis.
A 30-year-old man is known for his large appetite. At a luncheon meeting, he notices that all the cookies contain nuts,
which the other diners have ordered knowing that he would not eat them because he would develop blotchy erythematous,
slightly edematous, pruritic plaques on his skin. These plaques would form and then fade within 2 hours. If the man eats
the cookies, which of the following sensitized cells would release a mediator that produces these skin lesions?
□ (A) Mast cell
□ (B) Neutrophil
□ (C) Natural killer cell
□ (D) CD4+ lymphocyte
□ (E) Plasma cells
(A) If the man eats the cookies, he will have “hives,” or urticaria, from an allergy to an antigen in nuts. This causes a
type I hypersensitivity reaction in which IgE antibodies are bound to the IgE receptor on mast cells. IgE-sensitized mast
cells degranulate when the antigen is encountered. Neutrophils may become attracted to this site, but they are not the
sensitized cells. Natural killer cells mediate antibody-dependent cell-mediated cytotoxicity and lyse major histocompatibility
complex class I–deficient target cells. Plasma cells secrete the IgE antibodies, but do not release the mediators for allergic
A 17-year-old girl has hundreds of skin lesions on her body that have been forming since childhood. On physical
examination, 0.4- to 1.7-cm, macular to slightly raised, plaquelike, dark brown pigmented lesions are present on sunexposed
and non–sun-exposed areas of skin. The lesions have irregular contours, and there is variability in pigmentation.
She says that her 15-year-old brother has similar lesions. Which of the following molecular changes are most likely to be
present in the DNA from this patient?
□ (A) Deletion of the von Hippel–Lindau (VHL) gene
□ (B) Mutation of the PTCH gene
□ (C) Integration of the human papillomavirus-16 (HPV-16) genome
□ (D) Deletion of the p16/INK4A (CDNK2) gene
Robbins & Cotran Review of Pathology Pg. 518
□ (E) Microsatellite instability
□ (F) Ultraviolet light–induced damage from pyrimidine dimers
(D) The clinical appearance, distribution, and occurrence in two siblings suggest that these lesions represent the
dysplastic nevus syndrome. Dysplastic nevi are precursors of malignant melanoma. The most important gene in familial
cases is cyclin-dependent kinase inhibitor 2 (CDNK2), which encodes for several tumor suppressors including p16/INK4A.
The PTCH gene is implicated in the pathogenesis of sporadic basal cell carcinomas and the familial nevoid basal cell
carcinoma syndrome. HPV-16 infection is important in the pathogenesis of squamous epithelial dysplasias and
carcinomas, particularly involving the uterine cervix. HPV-16 DNA is integrated into the host cell genome, and its protein
product inactivates host cell RB and p53 genes. The neoplasms in von Hippel–Lindau disease include renal cell
carcinoma, pheochromocytoma, and hemangioblastomas of the central nervous system. Microsatellite instability is a
manifestation of the loss of DNA mismatch repair genes, as occurs in the hereditary nonpolyposis colon carcinoma
syndrome. A defect in nucleotide excision repair is present in xeroderma pigmentosa, an autosomal recessive condition in
which sun exposure is associated with mutations in the PTCH and p53 genes
A 60-year-old man has noted the appearance of a nodule on his ear during the past month. On physical examination,
there is a 1.2-cm, flesh-colored, dome-shaped nodule on his right ear lobe. The nodule has a central keratin-filled crater
surrounded by proliferating epithelium. The lesion regresses and disappears within 1 month. What is the most appropriate
diagnosis of this lesion?
□ (A) Squamous cell carcinoma
□ (B) Basal cell carcinoma
□ (C) Seborrheic keratosis
□ (D) Actinic keratosis
□ (E) Keratoacanthoma
□ (F) Verruca vulgaris
(E) The gross and microscopic appearance is typical of keratoacanthoma. Keratoacanthomas are self-limited lesions
that often regress on their own. Lesions that do not regress should be suspected of being squamous cell carcinomas,
which typically do not regress. Basal cell carcinomas also may be raised lesions, but they also do not regress. A
seborrheic keratosis tends to be a flatter (although raised), rough-surfaced, pigmented lesion that slowly enlarges over
time. An actinic keratosis tends to be a flat, pigmented lesion that is tan to brown to red. A verruca vulgaris (wart) usually
occurs on the hands and feet, has a rough upper surface, and usually comes and goes over several years’ time
A 68-year-old man visits the physician because of a slowly enlarging nodule on his right eyelid. On physical
examination, there is a 0.3-cm pearly nodule on the upper eyelid near the lateral limbus of the right eye. The lesion is
excised, but multiple frozen sections are made during the surgery to minimize the extent of the resection and preserve the
eyelid. The microscopic appearance of the lesion is shown at low magnification in the figure. What is the most likely
□ (A) Malignant melanoma
□ (B) Dermatofibroma
□ (C) Actinic keratosis
□ (D) Nevocellular nevus
□ (E) Basal cell carcinoma
(E) Basal cell carcinomas arise as pearly papules on sun-exposed areas of the skin, particularly the face. They slowly
infiltrate surrounding tissues, gradually enlarging. Although it rarely metastasizes, a basal cell carcinoma can have serious
local effects, particularly in the area of the eye. Melanomas are usually pigmented, and they are composed of polygonal or
spindle cells that tend to grow in sheets and infiltrate to produce a grossly irregular border to the lesion. A dermatofibroma
is a benign lesion of the dermis composed of cells resembling fibroblasts. An actinic keratosis is a premalignant lesion of
the epidermis that does not invade surrounding tissue. A nevus is a small, localized, benign lesion.
A 5-year-old girl is brought to the physician by her parents for a routine health checkup. On physical examination, she
has scattered 1- to 3-mm, light brown macules on her face, trunk, and extremities. The parents state that these macules
become more numerous in the summer months, but fade over the winter. The lesions do not itch, bleed, or hurt. What is
the most likely diagnosis?
□ (A) Vitiligo
□ (B) Lentigo
□ (C) Freckle
□ (D) Nevus
Robbins & Cotran Review of Pathology Pg. 519
□ (E) Melasma
(C) Freckles are common. Individuals with a light complexion or red hair are more likely to have freckles. These lesions
may be a cosmetic problem, but they have no other significance. Areas of skin with vitiligo are depigmented. A lentigo is a
brown macule whose pigmentation is not related to sun exposure. Nevi do not wax and wane with sun exposure. Melasma
is most often a masklike area of facial hyperpigmentation associated with pregnancy.
A 19-year-old man has facial and upper back lesions that have waxed and waned for the past 6 years. On physical
examination, there are 0.3- to 0.9-cm comedones, erythematous papules, nodules, and pustules most numerous on the
lower face and posterior upper trunk. Other family members have been affected by this condition at a similar age. The
lesions worsen during a 5-day cruise to the Caribbean. Which of the following organisms is most likely to play a key role in
the pathogenesis of these lesions?
□ (A) Staphylococcus aureus
□ (B) Herpes simplex virus type 1
□ (C) Group A β-hemolytic streptococcus
□ (D) Mycobacterium leprae
□ (E) Propionibacterium acnes
(E) This man has acne vulgaris. Teenagers and young adults are affected by acne more often than other age groups,
and males are affected more often than females. Propionibacterium acnes breaks down sebaceous gland oils to produce
irritative fatty acids, and this may promote the process. The food on the cruise probably did not play a role, but stress
causes the lesions to worsen. Staphylococcus aureus and group A streptococci are implicated in the inflammatory skin
condition known as impetigo, which can include pustules and a characteristic pale yellow-brown crust. Herpes simplex
virus produces vesicular skin eruptions, most often in a perioral or genital distribution. Mycobacterium leprae causes
leprosy, which is a chronic condition that can produce focal depigmentation and areas of skin anesthesia.
21 A 53-year-old man with idiopathic dilated cardiomyopathy underwent orthotopic heart transplantation. During the next 5
years, he had two episodes of minimal cellular rejection, which were adequately treated by an increase in
immunosuppressive therapy. He has developed multiple skin lesions on the face and upper trunk over the past 6 months.
On physical examination, the lesions are similar to the lesion shown in the figure. Some of the larger lesions have
ulcerated. A biopsy specimen is most likely to identify which of the following lesions?
□ (A) Psoriasis
□ (B) Lichen planus
□ (C) Dermatofibroma
□ (D) Squamous cell carcinoma
□ (E) Erythema multiforme
(D) Risk factors for squamous cell carcinoma include ultraviolet light exposure, scarring from burn injury, irradiation, and immunosuppression. This patient was immunosuppressed to prevent graft rejection. Squamous cell carcinomas also
arise in rare disorders of DNA repair, such as xeroderma pigmentosum. Psoriasis is an inflammatory dermatosis that can
be associated with underlying arthritis, myopathy, enteropathy, or spondylitic heart disease. Lichen planus is a self-limited
inflammatory disorder that manifests as “purple, pruritic, polygonal papules,” not as elevated ulcerated lesions. A
dermatofibroma is typically solitary, firm, and dermally located. Erythema multiforme is a hypersensitivity response to
infections or drugs; the lesions have multiple forms, including papules, macules, vesicles, and bullae
A 39-year-old woman comes to her physician because she has developed vesicular skin lesions over the past week.
On physical examination, she has multiple, 0.2- to 1-cm vesicles and bullae on the skin of her scalp, in both axillae, in the
groin, and on the knees. Many lesions appear to have ruptured, and a shallow erosion with a dried crust of serum remains.
A biopsy specimen of an axillary lesion examined microscopically shows epidermal acantholysis and formation of an
intraepidermal blister. The basal cell layer is intact. Which of the following additional tests is most likely to explain the
pathogenesis of the patient's disease?
□ (A) Immunofluorescent staining of skin with anti-IgG
□ (B) Viral culture of fluid from a skin vesicle
□ (C) Determination of serum IgE level
□ (D) Cytokeratin immunohistochemical staining
□ (E) Dark-field microscopy of vesicular fluid
(A) These lesions of pemphigus vulgaris are caused by IgG autoantibodies directed at the intercellular cement
substance called desmoglein, giving a netlike appearance with immunofluorescence microscopy. The antibody deposition
disrupts intercellular bridges, causing the epidermal cells to detach from each other (acantholysis). This action causes the
formation of an intraepidermal blister. Staining with anti-IgG illuminates intercellular junctions at sites of incipient
acantholysis. Herpes simplex viral infections can produce crops of vesicles, but such a wide distribution would be unusual.
Type I hypersensitivity with urticaria does not produce an acantholytic vesicle. Keratinocytes are epithelial and are always
positive for cytokeratin. Dark-field microscopy is used almost exclusively to identify spirochetes in cases of syphilis
For the past 3 days, a 25-year-old man known to be infected with HIV has had increasing fever, cough, and dyspnea,
which has culminated in acute respiratory failure. On admission to the hospital, his temperature is 37.8°C. On physical
examination, there are no significant findings. He undergoes a bronchoalveolar lavage that yields Pneumocystis jiroveci
by direct fluorescent antigen testing. Within 1 week after initiation of therapy, he develops “target lesions” composed of
red macules with a pale, vesicular center. The 2- to 5-cm lesions are distributed symmetrically over the upper arms and
chest. Which of the following drugs is most likely to be implicated in the development of these lesions?
□ (A) Ritonavir
□ (B) Pentamidine
□ (C) Sulfamethoxazole
□ (D) Zidovudine
□ (E) Dapsone
□ (F) Adefovir
□ (G) Nevirapine
(C) The patient has erythema multiforme, a hypersensitivity response to certain infections and drugs, such as
sulfonamides and penicillin. Other inciting factors include herpes simplex virus, mycoplasmal and fungal infections,
malignant diseases, and collagen vascular diseases such as systemic lupus erythematosus. The other listed antiretroviral
drugs or antimicrobials are far less likely to cause skin reactions. Acetaminophen and dapsone are less likely to produce
erythema multiforme, but many drugs can cause skin rashes and eruptions.
A 28-year-old man has noticed slowly enlarging lesions on his hands for the past 3 years. On physical examination, the
lesions appear similar to those shown in the figure. There are no other remarkable findings. The lesions have not changed
in color, do not itch or bleed, and are not associated with pain. What is the most likely diagnosis?
□ (A) Basal cell carcinoma
□ (B) Condyloma acuminatum
□ (C) Dermatofibroma
□ (D) Intradermal nevus
□ (E) Keratoacanthoma
□ (F) Molluscum contagiosum
□ (G) Seborrheic keratosis
□ (H) Squamous cell carcinoma
□ (I) Verruca vulgaris
(I) The warts in this patient are a common problem and result from infection with one of many types of human
papillomavirus (HPV). They do not become malignant and tend to regress after several years. Basal cell carcinomas are
nodular, slowly enlarging lesions usually seen on the head and trunk and are related to sun exposure. Condylomata
acuminata, or genital warts, are caused by a type of HPV that is sexually transmitted; the lesions tend to be pink to white.
A dermatofibroma forms a subcutaneous nodule, as does an intradermal nevus. A keratoacanthoma may resemble
squamous cell carcinoma and grow rapidly to form an ulcerative nodule, but the keratoacanthoma typically regresses in
several months; squamous cell carcinoma continues to grow. Likewise, molluscum contagiosum is a self-limited condition
with a nodular appearance. Seborrheic keratoses are pale brown to dark brown, slowly enlarging lesions with a rough
surface that are most commonly found on the trunk and face of older individuals
A 32-year-old woman has noticed depigmented areas on her trunk that have waxed and waned for several months. She
says that they do not itch or bleed, and are not painful. Physical examination shows variably sized, 0.3- to 1.2-cm macules
over her upper trunk. The macules are lighter colored than the surrounding skin and have a fine, peripheral scale.
Infection with which of the following organisms is most likely to produce these findings?
□ (A) Epidermophyton species
□ (B) Herpes simplex virus
□ (C) Human papillomavirus
□ (D) Malassezia furfur
□ (E) Molluscum contagiosum
□ (F) Mycobacterium leprae
□ (G) Propionibacterium acnes
□ (H) Sarcoptes scabiei
□ (I) Staphylococcus aureus
□ (J) Streptococcus pyogenes
(D) Tinea versicolor is a common condition caused by a superficial fungal infection of Malassezia furfur. The lesions
can be lighter or darker than the surrounding skin. Epidermophyton, Trichophyton, and Microsporum genera are
dermatophytic fungi best known as the cause of athlete's foot and “jock itch.” Herpes simplex virus manifests initially with
crops of clear vesicles that may burst and form painful shallow ulcers. Human papillomavirus is best known as the cause
of genital warts (condyloma acuminatum) and as a driving force behind cervical and anal squamous cell dysplasias.
Molluscum contagiosum is caused by a poxvirus and produces an umbilicated nodule. Mycobacterium leprae is the cause
of Hansen disease, which can manifest with areas of skin anesthesia that predispose to repeated trauma.
Propionibacterium acnes is a factor in the development of acne. Sarcoptes scabiei is the cause of scabies, which appears
as pruritic reddish lesions. Staphylococcal infections may manifest as impetigo, as a complication of acne, or as wound
infections. Streptococcus pyogenes may cause impetigo, erysipelas, or scarlet fever.
After being hospitalized 1 week for treatment of an upper respiratory infection complicated by pneumonia, a 43-year-old woman develops a rash on her trunk and extremities. On physical examination, the 2- to 4-mm lesions are red,
papulovesicular, oozing, and crusted. The lesions begin to disappear after she is discharged from the hospital 1 week
later. What is the most likely pathogenesis of these lesions?
□ (A) Type I hypersensitivity
□ (B) Drug reaction
□ (C) Bacterial septicemia
□ (D) Photosensitivity
□ (E) Human papillomavirus infection
(B) The time course of this case suggests a drug reaction producing an acute erythematous dermatitis. Urticaria in
type I hypersensitivity is not as severe or as long-lasting. Sepsis rarely involves the skin in an erythematous dermatitis.
Photosensitivity may be enhanced by drugs, but ultraviolet light is the key component in light that produces
photodermatitis. Photosensitivity is not likely to be encountered with indoor lighting in the hospital room, and most
organizations do not buy light bulbs that mimic daylight, increasing the prevalence of seasonal affective disorder and
decreasing productivity by staff. Human papillomavirus infection is associated with formation of verruca vulgaris, the
A 30-year-old man with a history of Crohn disease has noted the appearance of a painful red nodule on his left lower
leg during the past week. On physical examination, his temperature is 37.3°C. There is a 0.4-cm, dark red nodule that is
very tender to palpation and has a surrounding 5-cm diameter area of paler red skin. Over the next 3 weeks, this lesion
resolves, but another develops on the opposite calf. A skin biopsy of the second lesion is done, and microscopic
examination shows a dermal mixed inflammatory infiltrate with neutrophils, round cells, and giant cells with pronounced
edema. These lesions resolve without scarring, but more lesions develop during the next year. What is the most likely
□ (A) Acne vulgaris
□ (B) Dysplastic nevus
□ (C) Erythema nodosum
□ (D) Impetigo
□ (E) Keratoacanthoma
□ (F) Molluscum contagiosum
(C) Erythema nodosum is a form of panniculitis that can be associated with infections, drug ingestion, inflammatory
bowel disease, and malignancies, but an underlying condition is not always found. The inflammation primarily involves
dermal adipose tissue. Acne vulgaris is most likely to appear on the face and upper trunk centered around hair follicles; it
often resolves with scarring. Dysplastic nevi have atypical keratinocytes without panniculitis. Impetigo is seen on the face
and hands with crusting lesions from Staphylococcus aureus and β-hemolytic streptococcal infections producing
subcorneal pustules. A keratoacanthoma is a rapidly growing ulcerative nodule that typically regresses in several months;
it resembles squamous cell carcinoma. Melanomas have very atypical spindle to epithelioid cells that invade the dermis;
they tend to change in appearance over weeks to months, not years. The lesions of molluscum contagiosum are firm
nodules that microscopically contain pink cytoplasmic inclusions, called “molluscum bodies.”
A 31-year-old man comes to his physician because of a bump on the skin of the lower abdomen that has enlarged over
the past 4 years and has become more painful in the past week. On physical examination, there is a subcutaneous,
movable, soft nodule at the belt line anteriorly that elicits pain with pressure. The overlying skin is intact. The patient
states that the nodule began hurting about 1 day after he vigorously squeezed it. The lesion is excised and does not recur.
Which of the following is the most likely diagnosis of this lesion?
□ (A) Acne vulgaris
□ (B) Epidermal inclusion cyst
□ (C) Fibroepithelial polyp
Robbins & Cotran Review of Pathology Pg. 522
□ (D) Intradermal nevus
□ (E) Trichoepithelioma
□ (F) Xanthoma
(B) The epidermal inclusion cyst is the most common form of epithelial cyst, or wen, which is a cystic structure formed
from downward growth of epithelium or expansion of a hair follicle and is lined by squamous epithelium that desquamates
keratinaceous debris in the center of the expanding cyst. Rupture of the cyst produces a local inflammatory reaction. Acne
produces comedones, most typically on the face and upper trunk of adolescents and young adults. A fibroepithelial polyp
is a skin tag that projects from the surface of the skin on a narrow pedicle. An intradermal nevus forms a pale to pigmented
nodule that tends not to change much in size. A trichoepithelioma is a form of a benign adnexal tumor, which is uncommon;
it is a subcutaneous nodule usually seen on the head, neck, and upper trunk. Xanthomas are soft, yellow nodules that may
form in the dermis from collections of lipid-laden macrophages in individuals with hyperlipidemia.
A 9-year-old girl is brought to the physician by her parents because she has been scratching a group of small bumps
on the skin of her forearm for the past month. On physical examination, there are five 0.4- to 0.9-cm, small, flat to slightly
papular, pale brown lesions on the volar surface. The lesions become more pruritic with swelling and erythema when
rubbed. A biopsy specimen of one of the lesions examined microscopically shows an upper dermal infiltrate of large cells
with abundant pink cytoplasm that stains an intense purple color with toluidine blue. Which of the following cell types is
most likely to form these lesions?
□ (A) CD4+ lymphocyte
□ (B) CD8+ lymphocyte
□ (C) Langerhans cell
□ (D) Macrophage
□ (E) Mast cell
□ (F) Melanocyte
□ (G) Merkel cell
(E) This patient has urticaria pigmentosa, a localized form of mastocytosis. The cutaneous lesions often show the
characteristic Darier sign on rubbing. Some patients may have systemic mastocytosis. Point mutations in the C-KIT
oncogene may be present. Lymphocytes, Langerhans cells, and macrophages participate in inflammatory reactions, such
as contact dermatitis. Macrophages and Langerhans cells are antigen-presenting cells. Melanocytes contain melanin
granules, which they pass on to keratinocytes to increase skin pigmentation. Merkel cells are derived from neural crest
and can form the obscure Merkel cell tumor, which resembles a small cell carcinoma
A 50-year-old man notes several small, baglike lesions that have appeared on the skin in front of his armpits over the
past 2 years. On physical examination, five small, soft papules in the anterior axillary line are covered by wrinkled skin and
attached to the skin surface by a thin pedicle. They are 0.5 to 0.8 cm in length and about 0.3 cm in diameter. One lesion
has undergone torsion and is more erythematous and painful to touch than the others. What is the most likely diagnosis?
□ (A) Fibroepithelial polyp
□ (B) Hemangioma
□ (C) Lentigo
□ (D) Melasma
□ (E) Pilar cyst
□ (F) Xanthoma
(A) A fibroepithelial polyp also is known as an acrochordon or skin tag. These common lesions are composed of a
central core of fibrovascular connective tissue covered by normal-appearing squamous epithelium. They may become
irritated, but are otherwise incidental findings. A hemangioma forms a red nodule that is composed of vascular spaces in
the upper dermis. A lentigo is a focus of melanocyte hyperplasia that produces a brown macule; in older individuals, they
are known as senile lentigines or “age spots” and are commonly found on the hands. Melasma is most often a masklike
area of facial hyperpigmentation associated with pregnancy. A pilar (trichilemmal) cyst is an epithelial cyst that forms on
the scalp. A xanthoma is a localized dermal collection of lipid-laden macrophages associated with hyperlipidemia