101 - 162

Question 1

A lichenoid infiltrate that surrounds eccrine glands is seen in:
1 Lichenoid drug rection
2 Lichen striatus
3 Lichen planus
4 Lichenoid purpura
5 Lichen planopilaris

Answer 1

Lichen striatus is an uncommon inflammatory dermatitis seen most commonly in children aged 5 to 15.

It presents unilaterally along Blaschko’s lines as raised, slightly scaly, erythematous papules, which are often pruritic. These lesions typically regress spontaneously within a year.

The histopathologic features of lichen striatus include a superficial perivascular inflammatory lymphohistiocytic infiltrate with rare plasma cells and eosinophils.

There is a focal lichenoid infiltrate in the papillary dermis with basilar vacuolar alteration and necrotic keratinocytes.

Spongiosis with exocytosis of lymphocytes can be seen in the epidermis.

A specific and distinctive feature** of lichen striatus is the presence of an **inflammatory infiltrate that surrounds hair follicles and eccrine glands.

Epidemiology

• Most commonly seen in children, although any age may be affected
• No clear racial predilection
• Possible female predilection
• Case clustering
• Seasonal variation

Presentation

• Numerous small (1- to 3-mm) skin-colored to scaly, hyperpigmented, brownish papules coalescent into linear plaques
• Arranged along lines of Blaschko (cutaneous bands of embryologic development)
• Usually unilateral, rarely may be bilateral
• Papules are flat-topped or rough-surfaced
• Distributed over extremities, particularly the leg
• Usually asymptomatic, occasionally slightly pruritic
• Some reports suggest that these lesions may koebnerize

Prognosis and treatment

• Self-limited condition, with lesions typically resolving by 1 year
• Therapeutic options include topical corticosteroids, topical retinoids, and topical calcineurin inhibitors

Histology

• Parakeratosis, mild acanthosis
• Spongiotic dermatitis
• Interface change with cytoid bodies
• Satellite cell necrosis
• Superficial dermal, perivascular

Lichen striatus. Erythematous scaly papules in a linear distribution on the thigh

Lichen striatus. Obliquely cut section. There is marked hyperkeratosis with parakeratosis, acanthosis, inflammation, and pigment incontinence

Lichen striatus. This field highlights the massive pigment incontinence.

Lichen striatus. There is a dense dermal lymphohistiocytic infiltrate

Question 2

Comma-shaped bodies are seen in:
1 Benign cephalic histiocytosis
2 Malakoplakia
3 Sarcoidosis
4 Lipoid proteinosis
5 Gaucher’s

Answer 2

Benign cephalic histiocytosis
Comma-shaped bodies and worm-shaped bodies can be seen in a variety of histiocytoses and are non-specific. The most common association is with benign cephalic histiocytosis

S-100 (-)

CD1a (-)

CD68+

Factor XIIIa +

Question 3

This tumor was excised from a verrucous yellow plaque on the scalp what is it?
1 Syringocystadenoma papilliferum
2 Eccrine acrospiroma
3 Hidradenoma Papilliferum
4 Tubular apocrine adenoma
5 Syringofibroadenoma

Answer 3

Syringocystadenoma Papilliferum: 33% arise in association with a nevus sebaceous, 10% may coexist with a BCC or trichoblastoma. A subset of cases has a deletion of 9q22 PTCH gene and 9q21 (p16). Histologically they present as surface invagination of glandular cords composed of one to two layers of cuboidal cells associated with a fibrovascular stroma with numerous plasma cells. Cystic spaces may form within which are free floating islands which are peripherally lined by cuboidal cells with an inner core composed of loose connective tissue, blood vessels and numerous plasma cells.

Fig 1 Syringocystadenoma papilliferum. Characteristic low-power morphology of a squamous epithelial border enclosing tall papillary projections with a dense infiltrate within their cores.

Fig 2 Syringocystadenoma papilliferum. The epithelium is double layered and the underlying stroma is rich in plasma cells.

Fig 3 Syringocystadenoma papilliferum. Superficially, the double-layered apocrine epithelium is replaced by squamous epithelium

Pathology

Histology

• Exophytic papillomatous lesion
• Fibrovascular core
• Papillae covered superficially by squamous epithelium
• Deeper aspect covered by a double-layered epithelium—inner tall columnar cells, outer cuboidal myoepithelial cells
• Decapitation secretion
• Ducts evident in deeper reaches
• Intense lymphocyte and plasma cell infiltrate often seen
• Background of nevus sebaceus sometimes evident

Immunopathology/special stains

• Inner layer of columnar cells positive for CEA, EMA, low-molecular-weight keratin
• Outer myoepithelial layer positive for SMA
• PAS highlights intracytoplasmic granules of inner layer

Main differential diagnoses

• Hidradenoma papilliferum
• Apocrine papillary hidradenoma

Dr Giam Yoke Chin
Senior Consultant
National Skin Centre

Introduction
Papular eruptions occurring on healthy children’s faces can be puzzling. There are many possible causes e.g. milia, comedones, molluscum contagiosum, xanthogranuloma. In 1971, Gianotti described a condition called “Benign Cephalic Histiocytosis”. This is a self-healing eruption of yellow brown papules, occurring characteristically on the face of children. As the name suggests, in this condition, benign looking histiocytes accumulate on the facial skin of children. The cause is unknown.

Clinical features
5 cases were seen from 1988 to 1993 in National Skin Centre. They include 3 Chinese, 1 Indian and 1 Malay. These children were aged three to twenty-four months, with multiple 2 to 3 mm size papules, of yellow, brown and skin colour. All occurred on the cheeks, forehead and eyelids (Fig. 1 & 2).

Two of them had extension to the trunk and limbs. Three children had the diagnosis confirmed on histology. Two declined biopsy. The children were well with no evidence of organomegaly.

Benign Cephalic Histiocytosis**: **Clinical**: Face w/ Yellow, brown papules **Histology**: Benign histiocytes. Giant cells occasionally. **Ultrastructure: Comma-shaped bodies. S-100 (-)

Histiocytosis X:** Yellow brown papules with strongly adherent scaly crusts. Scalp, trunk, mucous membrane. **Histology: Large histiocytes with kidney-shaped nuclei. Infiltrate invades the epidermis. Ultrastructure: Birbek granules. S-100 (+) Treatment: Chemo

Investigations including: full blood count, serum cholesterol, triglyceride, and liver function tests were normal. Many improved within 6 months.

Discussion
Doctors have to be aware and be familiar with this histiocytosis as it is benign and self-limiting. The eruption are flat-topped, on the face (especially upper cheeks), but
can extend to the back of ears, arms, posterior neck (Fig. 3), thighs and buttocks.

Mucous membrane, palms, soles and viscera are spared. It regresses within 6 months to leave brown macules. These heal without scarring after one to a few years. The features differentiating Benign Cephalic Histiocytosis and Histiocytosis X are summarized in Table 1.

Histology, Immunology, Electron-Microscopy
The histiocytes are benign, though some show pleomorphic nuclei; with prominent nucleoli and scanty chromatin (Fig. 4).

Older lesions may show multinucleated giant cells [4,5]. They react with OKMI and Leu M3 monoclonal antibodies. SlOO-positive cells are absent. Ultrastructurally, about 20% of the histiocytes have comma-shaped bodies in their cytoplasm. These consist of two electron dense membranes of 60A1 separated by a space of 80A’. Birbeck granules seen in Histiocytosis X are not found.

Conclusion
This is another newly described disorder of the histiocytic Syndromes in children. It is important to be aware of: this condition, to avoid over-investigation and treatment of a benign condition.

Question 4

The predominant location of the cleft in cicatricial pemphigoid is:
1 Dermal
2 Basment membrane zone
3 Basal keratinocytes
4 Supra basal
5 Subcorneal/granular

Answer 4

Basment membrane zone

Cicatricial pemphigoid is an autoimmune blistering disease that presents with ulcers, blisters and erosions of mucosal surfaces, especially the eyes and mouth. The cleft in cicatricial pemphigoid is found in the basement membrane zone/subepidermal as the antigens are usually BPAg2,laminin 5 and alpha-6-beta-4 integrin. Direct immunoflourescence is identical to that of bullous pemphigoid showing linear IgG and complement deposits in the basement membrane zone.

Pathology

Histology

• Oral lesions: • Nonspecific ulcer with chronic inflammation
• May see subepithelial cleft with mixed inflammation in lamina propria
• Cutaneous lesions: • Subepidermal blister with fibrin, edema, inflammatory cells in blister cavity
• Variable degrees of inflammation in dermis: lymphocytes and histiocytes with admixed plasma cells, eosinophils, neutrophils
• May be cell poor/free
• Dermal fibrosis in longstanding lesions

Immunopathology/special stains

• Direct immunofluorescence: • Linear IgG, C3 along basement membrane zone
• May also see IgA
• Salt-split studies: epidermal and dermal localization depending on antigen targeted
• Indirect immunofluorescence: • Low titers
• Positive in less than 1⁄3 of patients

Main differential diagnoses

• Bullous pemphigoid
• Epidermolysis bullosa acquisita
• Linear IgA disease

Fig 1 Mucosal pemphigoid. Note the intense erythema with erosion, features of desquamative gingivitis.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)

Fig 2 Mucosal pemphigoid. There is a subepidermal blister containing eosinophils and lymphocytes.

Fig 3 Mucosal pemphigoid. Note the perivascular and interstitial infiltrate of lymphocytes, histiocytes, and conspicuous eosinophils.

Fig 4 Mucosal pemphigoid. Low-power view of oral lesion.

Fig 5 Mucosal pemphigoid. High-power view of blister cavity shown in Figure 4.

Fig 6 Mucosal pemphigoid. There is perivascular and interstitial lymphohistiocytic infiltrate with occasional plasma cells.

Fig 7 Mucosal pemphigoid. Biopsy specimen of an early oral lesion showing a cell-free subepidermal cleft.

Question 5

This tumor is best visualized using PAS stains with and without diastase what is it?
1 Clear cell acanthoma
2 Seborrheic keratosis
3 Bowen’s disease
4 Tricholemmoma
5 Inverted follicular keratosis

Answer 5

Clear cell acanthoma is composed of pale staining keratinocytes that have increased glycogen content. The increased glycogen in this tumor is due to a defect in phosphorylase. Histologically the keratinocytes are mildly enlarged and pale and distinctly separated from the surrounding epidermis. The epidermis appears focally expanded by an acanthotic plate like growth that spares the follicular epithelium. Also associated with this tumor are PMNs that extend into the epidermis. There may be edema of the papillary dermal and some telangiectasis. PAS stain with and without diastase highlights the abundant glycogen.

Histology

• Overlying parakeratosis, may contain neutrophil-imbued serum crust
• Psoriasiform epidermal hyperplasia with broad rete ridges
• Area of enlarged, glycogen-rich keratinocytes with pale cytoplasm, well demarcated from adjacent normal epidermis, and sparing intraepidermal adnexal structures
• Associated neutrophilic infiltration into the lesion, occasionally forming intraepidermal collections
• Variable spongiosis
• Variable intraepidermal dendritic melanocytes
• Papillary dermal edema
• Variable, superficial, dermal neutrophil infiltrate

Immunopathology/special stains

• PAS positive
• Diastase-PAS negative

Main differential diagnoses

• Psoriasis
• Trichilemmoma
• Seborrheic keratosis with clear cell change

Fig 1 Clear cell acanthoma. There is parakeratosis, psoriasiform hyperplasia, and epidermal pallor.

Fig 2 Clear cell acanthoma. There is an intracorneal pustule. The keratinocytes have pale-staining cytoplasm. There is no atypia.

Fig 3 Clear cell acanthoma. The clear cells are strongly positive for glycogen as seen in this PAS stain.

Question 6

A skin biopsy shows numerous fibroblasts with fibrosis and thickening of the dermis. There is sparse mucin deposition and on low power the biopsy appears square. Which of the following paraproteins would you expect to find in this patient?
1 IgG lambda
2 IgA
3 IgM
4 IgG kappa
5 IgA gamma

Answer 6

IgG lambda

The description of the biopsy above is that of scleromyxedema. These patients have an associated IgG lambda paraprotein. Other IgG subtypes may occur but lambda is most common. Scleromyxedema is a subset of lichen myxedematosus (papular mucinosis). It will present with coalescent erythematous to yellow papules and plaques. The most common location is the face, but will occur in many other locations. The surrounding skin is usually sclerodermoid in appearance. (Bolognia, p648-9)

Clinical features

Epidemiology

• No gender predilection
• All races affected
• Most commonly affects those in middle age

Presentation

• Lichen myxedematosus • Discrete skin-colored to erythematous papules
• May be present in any location; limbs and trunk most common
• Typically asymptomatic
• Scleromyxedema • Discrete, waxy, skin-colored to erythematous papules
• Often begins on hands and wrists, symmetrical distribution
• Progresses to involve forearms, trunk, face
• Facial lesions characterized by linear papules that coalesce into plaques
• Results in sclerosis of the skin, contractures, tightening of skin around mouth, sclerodactyly
• May be associated with systemic involvement: esophageal, pulmonary, cardiac, neurologic
• IgG lamba gammopathy common, may evolve into multiple myeloma (rare)

Prognosis and treatment

• Lichen myxedematosus is a chronic condition
• Scleromyxedema worse prognosis, particularly if there is cardiac involvement
• Multiple myeloma rarely occurs
• Treatment is difficult: • Systemic corticosteroids, thalidomide, chemotherapy
• PUVA, photopheresis, electron-beam radiation, plasmapheresis

Pathology

Histology

• Both lichen myxedematosus and scleromyxedema show similar features
• Increased number of stellate fibroblasts in reticular dermis
• Increased dermal mucin, particularly early in the disease, which separates collagen fibers
• Dermal fibrosis and thickening is a late feature of scleromyxedema
• Mild superficial perivascular lymphocytic infiltrate
• Epidermal changes variable: atrophy to acanthosis

Immunopathology/special stains

• Mucin stains demonstrate increased dermal mucin
• Direct immunofluorescence studies may show IgG > IgM in dermis, or immediately underlying the epidermis in 1⁄3 of cases

Main differential diagnoses

• Nephrogenic systemic fibrosis
• Scleredema

Fig 1 Lichen myxedematosus. Low-power view showing separation of the dermal collagen fibers in the middle and on the left side. Toward the right, fibrosis is evident, suggesting transition to scleromyxedema.

Fig 2 Lichen myxedematosus. A light perivascular lymphocytic infiltrate is present. Increased numbers of spindled cells are seen.

Fig 3 Lichen myxedematosus. Fine, wispy strands of mucin are seen in this alcian blue preparation.

Question 7

Which of the following shows granular deposition of IgA in the dermal papillae and along the basement membrane zone on direct immunoflourescence:
1 IgA pemphigus
2 Bullous pemphigoid
3 Linear IgA dermatosis
4 Dematitis herpetiformis
5 Herpes gestationalis

Answer 7

Dematitis herpetiformis

Dermatitis herpetiformis or Duhring’s disease, presents with very pruritic vesicles symmetrically on extensor surfaces. On histology it presents as suprapapillary vesicles with mostly neutrophils and inflammatory destruction of the basement membrane zone. Direct immunoflourescence shows granular deposition of IgA in the dermal papillae and along the basement membrane zone.

Question 8

Acantholysis is not a prominent histopathologic feature of which disease?
1 Dermatitis herpetiformis
2 Darier’s disease
3 Grover’s disease
4 Pemphigus vulgaris
5 Hailey-Hailey diesease

Answer 8

Dermatitis herpetiformis is a bullous disease that on histology shows neutrophils in the dermal papillae. On direct immunoflourescence IgA is seen in a granular depostion pattern. Acantholysis is seen histologicaly in Darier’s disease, Grover’s disease, Pemphigus vulgaris, Hailey-Hailey disease and warty dyskeratoma.
Q/Q(M)-479628 Report a Problem

Question 9

The predominant cleft in dermatitis herpetiformis is:
1 Dermal
2 Basement membrane zone
3 Basal keratinocytes
4 Suprabasal
5 Subcorneal/granular

Answer 9

Basement membrane zone

Dermatitis herpetiformis or Duhring’s disease, presents with very pruritic vesicles symmetrically on extensor surfaces. On histology it presents as suprapapillary vesicles with mostly neutrophils and inflammatory destruction of the basement membrane zone. Direct immunoflourescence shows granular deposition of IgA in the dermal papillae and along the basement membrane zone. The cleft in dermatitis herpetiformis is most commonly found in the basement membrane zone/subepidermal. The antigen is transglutaminase.
Q/Q(M)-479695 Report a Problem

Question 10

Caterpillar bodies are seen in:
1 Lipoid proteinosis
2 Amyloidosis
3 Porphyria cutanea tarda
4 Mucocele
5 Dyskeratosis congenital

Answer 10

Porphyria cutanea tarda

Caterpillar bodies are thought to be type IV collagen.

Clinical features

Epidemiology

• Autosomal dominant, but majority of cases are sporadic
• Usually presents in late childhood (familial form) to early adulthood (sporadic form)
• Rare cases associated with exposure to polyhalogenated aromatic hydrocarbons
• No clear gender predilection

Presentation

• Photosensitivity, with disease flares resulting from excessive exposure to sunlight, but also potential liver insults, such as alcohol, oral contraceptives, hepatitis C virus, HIV, hemochromatosis
• Tense vesicles and bullae photodistributed classically over dorsal hands, forearms
• Often see blister remnants, crusted erosions, dyspigmentation
• Associated scarring and milia formation characteristic
• Hypertrichosis on face, usually sideburn, malar areas
• Hair (scarring alopecia) and nails (photo-onycholysis) may be affected
• Drug-induced pseudoporphyria can create similar clinical picture, although lacking hypertrichosis
• Metabolic laboratory studies show elevated urinary porphyrins

Prognosis and treatment

• Chronic, waxing–waning course, punctuated by episodes of disease flares
• Risk for hepatocellular carcinoma (hepatitis C–related?)
• Skin fragility may impair daily function, work
• Sun protection essential to management
• Therapeutic phlebotomy common first-line therapy
• Hydroxycholoroquine or chloroquine helpful
• Chelation also may be effective

Pathology

Histology

• Paucicellular subepidermal blister with festooning of dermal papillae
• Thickened papillary vessels with hyalinization
• Dermal sclerosis marked in chronic lesions (sclerodermiform)
• Solar elastosis prominent
• Identical histology in other cutaneous forms of porphyria

Immunopathology/special stains

• Direct immunofluorescence studies shows nonspecific pattern of immunoreactant (Ig, complement, laminin, and type-IV collagen) deposition around superficial dermal blood vessels, sweat glands, and along the dermal–epidermal junction
• Indirect immunofluorescence studies negative
• Thickened vessels, diastase-resistant, PAS-positive
• Intraepidermal, diastase resistant, PAS-positive “caterpillar” bodies
• Split often develops in lamina lucida but may be deep to lamina densa

Main differential diagnoses

• Pseudoporphyria
• Cell-poor/free bullous pemphigoid
• Epidermolysis bullosa congenita
• Epidermolysis bullosa acquisita
• Bullous amyloidosis

Fig 1 Porphyria cutanea tarda. Vesicles, erosions, and scarring on the dorsal hands.

Fig 2 Porphyria cutanea tarda. Scanning view of a subepidermal blister.

Fig 3 Porphyria cutanea tarda. The blister cavity is cell free. Note the festooning.

Fig 4 Porphyria cutanea tarda. The presence of erythrocytes in the lumen of the blister is a common finding.

Fig 5 Porphyria cutanea tarda. The blood vessels are thickened, and there is a background of solar elastosis.

Fig 6 Porphyria cutanea tarda. High-power view highlighting blood vessel wall hyalinization.

Fig 7 Porphyria cutanea tarda. The thickened blood vessel walls can be emphasized by direct immunofluorescence, in this example with C3. Note focal deposition along the dermal–epidermal junction as well.

Question 11

Multiple dermatofibromas are seen in:
1 Cowden’s
2 Lobomycosis
3 Incontinentia pigmenti
4 Lupus erythematosus
5 Reticulohistiocytosis

Answer 11

Multiple dermatofibromas are seen in lupus erythematosus and immunosuppression/HIV.

Question 12

This is considered to be the juvenile counterpart of DFSP:
1 Juvenile hyaline fibromatosis
2 Giant cell fibroblastoma
3 Myxofibrosarcoma
4 Myofibromatosis
5 Plexiform fibrous histiocytoma

Answer 12

Giant cell fibroblastoma

An entity called giant cell fibroblastoma is CD34-positive, is mostly seen in male children on the neck/trunk, and is thought to be a juvenile counterpart of DFSP.

Clinical features

Epidemiology

• Children, more often in boys
• Rarely in adults

Presentation

• Usually located on trunk and lower extremities
• Few- to several-centimeter plaque, nodule, or tumor

Prognosis and treatment

• Excision with wide margins is essential because recurrence is common
• Recurrence may have the histology of DFSP

Pathology

Histology

• Ill-defined infiltrative growth pattern
• Classic feature is the presence of pseudovascular spaces lined by giant cells
• Typically hypocellular with spindled and giant cells, but DFSP-like storiform areas may occur
• Mitoses are infrequent
• Some recurrences may show DFSP-like morphology
• DFSP may show areas of giant cell fibroblastoma

Immunopathology/special stains

• The majority are CD34 positive
• The lumina are negative with vascular specific endothelial markers
• CD99 positivity has also been described
• Cytogenetics: a translocation, t(17;22)(q21;q13), is seen in many cases

Main differential diagnosis

• Once the lumina are shown to be pseudovascular, there is no real differential diagnosis

Fig 1 Giant cell fibroblastoma. This view shows an admixture of spindled and multinucleate giant cells with pseudovascular spaces.

Fig 2 Giant cell fibroblastoma. Giant cells have multiple hyperchromatic nuclei.

Fig 3 Giant cell fibroblastoma. The pseudovascular spaces are focally lined by giant cells.

Question 13

Histologically, adenoma sebaceum represent which of the following lesions?
1 Neurofibromas
2 Angiofibromas
3 Collagenomas
4 Angiokeratomas
5 Smooth muscle hamartomas

Answer 13

Angiofibromas

Adenoma sebaceum, fibrous papules and pearly penile papules all have similar features histologically, presenting as angiofibromas. Features include atrophic epidermis with patchy melanocytic hyperplasia and hyperkeratosis, vertically oriented collagen, increased fibroblasts and blood vessels.
Clinical features

Epidemiology

• Affects middle-aged adults
• Commonly encountered lesion

Presentation

• Face, particularly nose
• Dome-shaped, firm, skin-colored, 2- to 3-mm telangiectatic papule
• May be clinically confused with basal cell carcinoma
• On the penis, tiny papules with similar histology may be seen—pearly penile papules
• Similar lesions, usually multiple, seen in association with tuberous sclerosis (called angiofibromas); on face also known as adenoma sebaceum; periungual lesions also known as Koenen tumors

Prognosis and treatment

• Generally no treatment is required, but the lesion is often removed when basal cell carcinoma is suspected clinically

Pathology

Histology

• Raised dermal nodule with prominent vessels and atypical spindled, stellate, or multinucleate myofibroblasts
• Collagenous stroma
• Mitotic figures are generally absent
• Melanocytic hyperplasia may be seen in the overlying epidermis
• Angiofibromas and pearly penile papules have identical histological features

Immunopathology/special stains

• Factor XIIIa positive, possibly CD34 positive
• S100-negative

Main differential diagnoses

• Dermatofibroma
• Multinucleate cell angiohistiocytoma
• Melanoma

Fig 1 Fibrous papule. Firm, dome-shaped, whitish-pink papule on the alar rim.

Fig 2 Fibrous papule. Shave biopsy showing increased vascularity and hypercellularity.

Fig 3 Fibrous papule. High-power view showing characteristic atypical myofibroblasts.

Fig 4 Fibrous papule. In this example, there is melanocytic hyperplasia in the overlying epidermis. This should not be mistaken for an atypical melanocytic proliferation or lentigo maligna.

Fig 5 Fibrous papule. The lesional cells express factor XIIIa.

Fig 6 Fibrous papule. There is focal CD34 expression.

Fig 7 Fibrous papule. S100 protein is negative in lesional cells.

Question 14

Which of the following stains is specific for melanin?
1 S-100
2 HMB-45
3 Fontana-Masson
4 MART-1
5 Melan-A

Answer 14

Fontana-Masson is a silver stain and stains melanin black. S-100, HMB 45, MART-1 (Melan-A) are melanocyte stains. S-100 also decorates Langerhans cells, acrosyringium, and neural crest-derived cells.
Q/Q(M)-478119 Report a Problem

Question 15

What are these organisms?
1 Leishmania
2 Trichosporon beigelii
3 Sporothrix schenckii
4 Penicillium marneffei
5 Histoplasmosis capsulatum

Answer 15

Leishmaniasis: Three main types: cutaneous (L tropica and mexicana), mucocutaneous (L. brasiliensis) and visceral/kala-azar (L donovani). Old world Leishmania (L tropica-major, minor and aethiopica) transmitted by Phlebotomus sandfly, new world (L mexicana, brasiliensis) transmitted by Lutzomyia sandfly. The promastigote lies in the sandfly is transmitted to humans and the amastigote infects macrophages. Macrophages become engorged with the organisms, but there is abnormal intracellular killing. Histology: Epidermis may display PEH and there is a dense dermal infiltrate consisting of foamy histiocytes, aka Leishman-Donovan bodies, with intracellular amastigotes along with epithelioid monocytes, giant cells, plasma cells and lymphocytes, variable eosinophils and PMNs. Organisms stain better with Giemsa, have a paranuclear kinetoplast and typically are located at periphery of macrophage, i.e. the Marquee sign. Can also see organism on skin slit smear. Older lesions show decreased organisms and tuberculoid granulomas may form.
Clinical features

Epidemiology

• Rare in United States
• More prevalent in South America, Central America, Mediterranean, Middle East, Africa, and Asia
• Wide age range, common in children
• Transmitted from bite of sand fly (Phlebotomus)
• Humans are an accidental host
• Different organism depending on type of leishmaniasis: • Cutaneous
• Old world (Africa, Asia, Europe): Leishmania major, L. tropica
• New world (North, Central and South America, Australia, and New Zealand): L. braziliensis, L. mexicana
• Mediterranean: L. donovani infantum
• Mucocutaneous: L. braziliensis
• Visceral: L. donovani, L. infantum

Presentation

• Cutaneous • Red papule that ulcerates with well-circumscribed, violaceous border
• Solitary or multiple lesions
• Located on face and upper limbs
• Localized lymphadenopathy
• Also known as “Baghdad boil,” “oriental sore,” “Chiclero’s ulcer”
• Mucocutaneous • Cutaneous lesion develops initially
• Mucosal lesions occur from direct extension, lymphatic or hematogenous spread
• Mucosal involvement is erosive, scarring, disfiguring
• Located on and around oral and nasal regions and may erode into cartilage; spares bone
• Hyperaccelerated immune response
• Visceral (kala-azar) • Fever
• Hepatosplenomegaly, cirrhosis
• Diarrhea
• Lymphadenopathy
• Pancytopenia
• Darkening of skin, xerosis

Prognosis and treatment

• First-line treatment: antimonials
• Other options: pentamadine, amphotericin B, ketoconazole, allopurinol, miltefosine
• Cutaneous lesions may resolve without treatment: L. brazilinesis should be treated to prevent mucocutaneous disease
• Prognosis • Cutaneous: spontaneously heals in 6 to 12 months
• Mucocutaneous: malnutrition and pneumonia most common causes of death
• Visceral: partial response to treatment; relapsing, chronic, and progressive disease

Pathology

Histology

• Acute lesions show irregular epidermal hyperplasia with ulceration
• Dense dermal infiltrate of histiocytes, lymphocytes, plasma cells
• Histiocytes contain intracellular amastigotes
• Chronic lesions may contain granulomata

Immunopathology/special stains

• Giemsa stain demonstrates intracellular organism and highlights kinetoplast

Main differential diagnoses

• Other intracellular infections • Histoplasmosis
• Granuloma inguinale
• Rhinoscleroma

Fig 1 Leishmaniasis. Low-power view of a fairly acute lesion with incipient ulceration.

Fig 2 Leishmaniasis. There is necrosis and abscess formation.

Fig 3 Leishmaniasis. There is an intense histiocytic infiltrate in the superficial dermis.

Fig 4 Leishmaniasis. Very high-power view showing amastigotes surrounded by a clear space.

Fig 5 Leishmaniasis. Low-power view of a chronic lesion showing a widespread granulomatous infiltrate.

Fig 6 Leishmaniasis. There is an admixture of plasma cells and histiocytes.

Fig 7 Leishmaniasis. High-power view of granuloma.
Fig 8 Leishmaniasis. Numerous intracellular amastigotes are seen in the superficial dermis.

Question 16

Steatocystoma multiplex is associated with:
1 Jadassohn-Lewandowsky
2 Jackson-Lawler
3 Schaufer-Brunauer
4 Zinsser-Engman-Cole
5 Touraine-Solente-Gole

Answer 16

Jackson-Lawler (Jackson-Sertoli) is known as pachyonychia congenital type 2. Multiple steatocysts can be seen in this condition.
Clinical features

Epidemiology

• May arise as a solitary lesion (steatocystoma simplex) or as multiple lesions (steatocystoma multiplex)
• Steatocystoma multiplex linked to defect in keratin 17, which is also mutated in pachyonychia congenita
• Familial form autosomal dominantly inherited
• Lesion usually arises in second and third decades of life
• No clear gender predilection
• No clear racial tendency

Presentation

• Skin-colored to translucent, smooth, 1- to 5-mm papule
• If lanced, clear fluid expressed
• Occurs in areas with sebaceous gland concentration, particularly the chest
• May exceptionally occur in conjunction with eruptive vellus hair cysts

Prognosis and treatment

• Sporadic and inherited forms benign, although lesions may rupture and incite inflammation and scarring
• Surgical excision, aspiration, and laser therapy performed

Pathology

Histology

• Dermal-based cystic lesion
• Lined by thin squamous epithelium
• Absent granular cell layer
• Mature sebaceous glands attached to wall
• Cyst lined by an eosinophilic cuticle
• Cyst lumen contains sebaceous material, keratin, and rare vellus hair fragments

Immunopathology/special stains

• Keratins 17 and 10 positive (see Eruptive Vellus Hair Cyst)

Main differential diagnoses

• Eruptive vellus hair cyst
• Epidermoid cyst
• Dermoid cyst

Fig 1 Steatocystoma. Scanning view showing a thin-walled empty cyst.

Fig 2 Steatocystoma. The stratified squamous epithelium has an inner, undulating hyaline cuticle.

Fig 3 Steatocystoma. The presence of a sebaceous gland adjacent to or in the cyst wall is a diagnostic feature.

Question 17

This was excised from the face, what is this neoplasm ?
1 Syringoma
2 Trichoadenoma
3 Basal cell carcinoma
4 Desmoplastic trichoepithelioma
5 Microcystic adenocarcinoma

Answer 17

Syringomas on the eyelids, cheeks, chests and can be eruptive and increased numbers in Down’s syndrome and a clear cell change has been associated with diabetes. Histologically this is a dermal tumor consisting of eccrine ducts, lined by two cell layers sometimes creating a tad pole appearance, there can also be small basaloid islands or strands of cells. Within the lumens of the ducts is eosinophilic material, the lumens are CEA+. The tumor is located superficially and fails to display perineural extension as is seen in MAC. The glands are associated with a fibrous sclerotic stroma, usually no (or minimal) keratin cysts or foreign body granulomas as seen in desmoplastic trichoepithelioma. Enlargement of the glandular cells more of a clear or vacuolated cytoplasm can be seen in patients with diabetes.

Clinical features

Epidemiology

• Condition of adulthood, arising at puberty
• Female predilection
• Eruptive type found in Africans, Asians, or those with Downs syndrome

Presentation

• Translucent to bluish, skin-colored, or yellowish, sometimes cystic papule, measuring a few millimeters in diameter
• Usually multiple lesions
• Most commonly arises on the face, particularly in the infraorbital region and cheek, but also may appear on the neck, chest, abdomen, axilla, penis, or vulva
• Eruptive variant often presents as brown hyperpigmented small papules on anterior trunk

Prognosis and treatment

• Benign tumor
• Surgical excision, electrosurgery, cryotherapy, laser therapy, or chemical peeling sometimes performed electively
• Clear cell syringoma associated with diabetes mellitus

Pathology

Histology

• Proliferation of small cords, strands, and tubules within the dermis, morphologically reminiscent of tadpoles
• Generally restricted to the superficial and middermis
• Tubules consist of a double layer of often flattened cuboidal cells; intracytoplasmic lumina with cuticles are generally present
• Lumina can contain amorphous, eosinophilic inspissated material
• No pleomorphism or mitotic activity
• Background sclerotic stroma
• Extension into deep dermis or subcutaneous fat and perineural infiltration absent (compare with microcystic adnexal carcinoma)
• Clear cell variant with cytoplasmic glycogen

Immunopathology/special stains

• Ductal lumina highlighted with CEA, EMA, and diastase-PAS
• Intracytoplasmic glycogen in clear cell variant highlighted with PAS

Main differential diagnoses

• Microcystic adnexal carcinoma
• Desmoplastic trichoepithelioma
• Morpheaform basal cell carcinoma

Fig 1 Syringoma. Typical low-power appearance of epithelial strands and tubules in a dense fibrous stroma.

Fig 2 Syringoma. There are well-formed tubules, some with attached attenuated epithelial strands—the so-called tadpole appearance.

Fig 3 Syringoma. The epithelial cells are uniform. Note the intracytoplasmic lumina.

Question 18

Stromelysin 3 is a negative marker for which of the following?
1 Dermatofibroma
2 Basal cell carcinoma
3 Dermatofibromasarcoma protuberans
4 Squamous cell carcinoma
5 Breast carcinoma

Answer 18

Stromelysin 3 is a negative marker which helps to distinguish dermatofibrosarcoma protuberans from dermatofibromas. Stromelysin 3 is a metalloproteinase which is expressed tissue remodeling. In a study performed by Cribier et.al. 100% of dermatofibromas stained positive Stromelysin 3 (ST3) is a member of the metalloproteinase family, which is expressed in tissue remodeling processes such as scarring, embryogenesis, or tumoral invasion.

Definition

• A low-grade malignant fibroblastic tumor of young adults characterized by a monotonous storiform growth pattern

Clinical features

Epidemiology

• Predilection for young adults

Presentation

• Slow-growing plaque that evolves into multiple nodules or protuberances (hence the name)
• Trunk and lower extremities most often affected

Prognosis and treatment

• Wide excision is recommended because there is a high risk of recurrence
• Recurrence may have the histology of giant cell fibroblastoma (see later)
• Lesion may recur with fibrosarcomatous transformation
• Fibrosarcomatous transformation (see under Histology) regarded as a poor prognostic indicator with an increased recurrence rate and significant metastatic potential
• Imatinib (Gleevec) recently FDA approved for treatment—tyrosine kinase inhibitor

Pathology

Histology

• Grenz zone often present
• Monotonous storiform growth pattern
• Tumor composed of spindled cells that are, in general, more uniform and less pleomorphic than may be seen in a dermatofibroma
• Mitoses are usually inconspicuous
• The classic picture is one of a lace-like pattern with trapped lobules of fat between spindled cells (so-called honeycomb)
• In some tumors, less classic appearances predominate: hypocellular, myxoid, and giant cell fibroblastoma–like
• Bednar tumor refers to those lesions containing pigmented dendritic cells (pigment is melanin)
• Fibrosarcomatous transformation is characterized by a typical herringbone morphology of more-closely packed spindled cells with increased mitoses
• Evaluating adequacy of excisions is problematic, because the peripheral portions may appear quite bland
• Especially in the setting of recurrences, it may be difficult to distinguish scar from hypocellular DFSP (even more problematic on frozen sections).

Immunopathology/special stains

• The majority are CD34 positive
• CD99 positivity has also been described
• Cytogenetics: a translocation, t(17;22)(q21;q13), is seen in many cases
• Pigmented cells in Bednar tumor are S100 positive

Main differential diagnoses

• Dermatofibroma
• Spindle cell melanoma
• Leiomyosarcoma
• Perineurioma

Fig 1 Dermatofibrosarcoma protuberans. Low-power view showing a diffuse spindled cell tumor.

Fig 2 Dermatofibrosarcoma protuberans. At this magnification, the classical storiform growth pattern is well demonstrated.

Fig 3 Dermatofibrosarcoma protuberans. Mitoses as seen in the center of the field are generally uncommon.

Fig 4 Dermatofibrosarcoma protuberans. Pigmented dendritic cells and melanophages characterize the Bednar tumor variant.
(Courtesy of E Calonje, MD; St John’s Institute of Dermatology, London.)

Fig 5 Dermatofibrosarcoma protuberans. This is a high-power view showing fibrosarcomatous transformation. Note the fascicular growth pattern, nuclear pleomorphism, and mitotic figure.
(Courtesy of E Calonje, MD; St John’s Institute of Dermatology, London.)

Fig 6 Dermatofibrosarcoma protuberans. Occasionally, excessive mucin deposition is a feature. Usually, more typical features are evident elsewhere in the lesion.

Fig 7 Dermatofibrosarcoma protuberans. Exceptionally smooth muscle differentiation is seen—the myoid variant.
(Courtesy of E Calonje, MD; St John’s Institute of Dermatology, London.)

Fig 8 Dermatofibrosarcoma protuberans. The tumor cells show uniform expression for CD34.

Question 19

Subcutaneous fat necrosis of the newborn has been associated with:
1 Hypocalcemia
2 Hypercalcemia
3 Hypokalemia
4 Hyperkalemia
5 Hyponatremia

Answer 19

Hypercalcemia has been noted in some cases of subcutaneous fat necrosis of the newborn.

Question 20

Eosinophilia-Myalgia syndrome is caused by:
1 Norwegian salt-petter
2 Unadultered Spanish grapeseed oil
3 Pb intoxication
4 L-Tryptophan
5 Excessive anaerobic exercise

Answer 20

L-Tryptophan

The eosinophilia myalgia syndrome is characterized by marked peripheral eosinophilia with a clinical spectrum of signs and symptoms, including generalized myalgias, pneumonitis, myocarditis, neuropathy, encephalopathy and fibrosis. Many patients progress to a clinical picture clinically indistinguishable from eosinophilic fasciitis. The disease is caused by the ingestion of certain lots of L-tryptophan.

Question 21

Which of the following immunohistochemical stains can help distinguish basal cell carcinomas and trichoepitheliomas from microcystic adnexal carcinomas?
1 Pro-collagen 1
2 CD34
3 Peanut agglutinin
4 TTF-1
5 Ber-Ep4

Answer 21

Ber-Ep4 helps distinguish between BCCs/Trichoepitheliomas and microcystic adnexal carcinomas. Morpheaform BCC and desmoplastic trichoepithelioma are Ber-Ep4 positive where as microcystic adnexal carcinomas (MAC) are Ber-Ep4 negative. Other markers that help distinguish between BCCs and trichoepitheliomas are peanut agglutinin and CD34. Peanut agglutinin is positive in BCC and negative in trichoepithelioma vs CD34 which is negative in BCC and positive in the peritumoral fibroblasts of trichoepitheliomas.

Question 22

Silver preferentially deposits in:
1 Eccrine glands
2 Apocrine glands
3 Hair follicles
4 Fat
5 Eccrine glands and apocrine glands

Type 2 minocycline pigmentation. Has what type of granules?

Type 2 minocycline pigmentation stains positive with________.

Type 3 minocycline pigmentation stains positive with ____.

Amiodarone pigmentation is found at what location and what cell is present?

Answer 22

Eccrine glands

Argyria can look like normal skin if you do not notice the silver (black) deposits in the eccrine glands in the deep dermis.

Clinical features

Epidemiology

• Exposure to a variety of medications implicated: antimalarials, chemotherapeutic agents, minocycline, psychotropic agents, heavy metals, amiodarone, azidothymidine, among others
• Wide age range (from young adults to elderly) affected, although certain agents (e.g., minocycline) generally not used in children
• Any race may be affected
• Minocycline therapy usually for more than few years duration
• Trauma may serve as risk factor in some cases (e.g., minocycline pigmentation type I)
• Sun exposure may serve as a risk factor in some cases (e.g., minocycline pigmentation type III, amiodarone)

Presentation

• Antimalarials: pretibial blue-gray (yellow for quinacrine) macular pigmentation, may also involve face, mucosae, nail bed
• Chemotherapeutic agents (e.g., bleomycin, carmustine, cyclophosphamide, daunorubicin, 5-fluorouracil): medication dependent, usually within weeks to months, may be localized or diffuse, various shades of brown-gray, can exhibit flagellate pattern, often with photosensitivity
• Minocycline: brownish-black to blue-gray macular pigmentation • Type I: blue-gray pigmentation distributed over scarred sites or at sites of previous inflammation, commonly affecting the face; involvement of acne scars typical
• Type II: blue-gray, brownish macular pigmentation, typically generalized distribution, with predilection for extremities (pretibial area typical), arising over normal skin lacking antecedent inflammation
• Type III: sun-exposed areas exhibit “muddy brown” pigmentation in symmetrical fashion
• Pigmentation may also involve teeth, nails, lips, sclerae, and internal organs (e.g., thyroid, bones, prostate, brain)
• Psychotropic agents: chlorpromazine induces purplish-gray pigmentation of face, arms, legs; tricyclics induce photodistributed blue-gray discoloration
• Heavy metals: silver (argyria) associated with localized or diffuse blue–slate gray mucocutaneous pigmentation with accentuation at photodistributed sites; gold (chrysiasis) induces photodistributed blue-gray discoloration of skin; iron from ferric subsulfate application can leave blue-gray pigmentation locally
• Amiodarone: blue-gray photodistributed pigmentation, often following photoallergic dermatitis
• Azidothymidine: bluish pigmentation of nails and brown pigmentation of skin
• Hydroxyurea: brown-gray pigmentation of nails and mucosa

Prognosis and treatment

• Pigmentation may fade slowly with discontinuation of drug
• Sun protection essential for photoexacerbated drug-induced pigmentation
• Bleaching creams and/or laser therapy may help lighten pigmentation in some cases

Immunopathology/special stains

• Masson-Fontana stain highlights melanin pigment
• Iron stains (e.g., Perl’s Prussian blue) highlight iron pigment
• Antimalarial pigmentation: Masson-Fontana positive or negative; Prussian blue negative or positive
• Chemotherapeutic agents: Masson-Fontana usually positive
• Minocycline type I: Masson-Fontana negative; Prussian blue positive
• Minocycline type II: Masson-Fontana positive; Prussian blue positive
• Minocycline type III: Masson-Fontana positive; Prussian blue negative
• Psychotropic pigmentation: Masson-Fontana positive
• Amiodarone pigmentation: lysosomal granules within macrophages highlighted by PAS stain
• Argyria: silver deposits appear white with dark field examination

Main differential diagnoses

• Postinflammatory pigmentation
• Melasma

Fig 1 Type 2 minocycline pigmentation. Note the golden-brown pigment granules.

Fig 2 Type 2 minocycline pigmentation. Perl’s Prussian blue stain is positive.

Fig 3 Type 3 minocycline pigmentation. Masson-Fontana stain is positive.

Fig 4 Amiodarone pigmentation. Perivascular pigment-rich macrophages are present.

Fig 5 High-power view showing amiodarone pigmentation.

Fig 6 Argyria. Speckled black pigmentation present along the eccrine gland basement membrane.

Question 23

The cytoplasmic granules seen in granular cell tumor are:
1 Phagolysosomes
2 Ribosomes
3 Mitochondria
4 Intermediate filaments
5 Vacuoles

Answer 23

The granules in granular cell tumor are phagolysosomes. The granularity of the granular cell layer in epidermodysplasia verruciformis may be secondary to increased ribosomes. Mitochondria fill the cells in hibernoma.
Granular Cell Tumor

Definition

• A neuroectodermal tumor characterized by S100-positive tumor cells containing lysosomal granules

Clinical features

Epidemiology

• Middle-aged to elderly adults
• Female predilection
• More common in blacks

Presentation

• Wide anatomic distribution
• Most frequently on tongue, trunk, and extremities
• 1- to 2-cm nodule
• Asymptomatic, gradually enlarges
• Other extracutaneous sites include: esophagus, small and large intestines, upper respiratory tract
• Malignant variant characterized by rapid growth, larger size, deeper lesion
• Frequently solitary, although can be multiple

Prognosis and treatment

• Excision is usually curative for benign lesions (the vast majority)
• Malignant variant rare; risk of spread to lymph nodes, lungs

Pathology

Histology

• Overlying epidermis is typically acanthotic
• May show pseudoepitheliomatous hyperplasia
• Irregular mass of cells with eosinophilic granular cytoplasm
• Uniform, small, often hyperchromatic nuclei
• Occasional mitoses may be seen
• Perineural invasion can be present and does not imply malignancy
• Criteria of malignancy include: size >5 cm, necrosis, brisk mitotic activity and pleomorphism

Immunopathology/special stains

• Diastase-PAS positive
• S100 positive
• NKI/C3, NSE, CD68, and PGP 9.5 are also positive

Main differential diagnoses

• Other granular cell tumors (e.g., granular cell leiomyoma, granular cell neurofibroma, granular cell basal cell carcinoma)
• Rhabdomyoma
• Melanocytic neoplasms

Fig 1 Granular cell tumor. Part of an ulcerated lesion showing pseudoepitheliomatous hyperplasia.

Fig 2 Granular cell tumor. The tumor cells are large with abundant eosinophilic cytoplasm and uniform vesicular nuclei.

Fig 3 Granular cell tumor. Eosinophilic, intracytoplasmic inclusions are also a common feature.

Fig 4 Granular cell tumor. Very occasional pleomorphic nuclei are sometimes seen and in the absence of other features of malignancy are of no consequence.

Fig 5 Granular cell tumor. Very occasional normal mitotic figures are sometimes present.

Fig 6 Granular cell tumor. Perineural infiltration is often seen but is of no clinical significance.

Fig 7 Granular cell tumor. There is strong and uniform S100 protein expression.

Question 24

What is this neoplasm?
1 Pilomatricoma
2 Proliferating pilar tumor
3 Trichoepithelioma
4 Basal cell carcinoma
5 Eccrine acrospiroma

Answer 24

Pilomatrixoma (Calcifying epithelioma of Malherbe): Found on the head, neck and upper extremities in the first 2 decades of life. Typically solitary but multiple pilomatricomas arise in several syndromes. Even in isolation these tumors may arise due to activating mutations in the beta-catenin gene. Histologically: This tumor consists of two major cell types plus an intermediate or transitional cell type. Initially the tumor is more cystic with the cells at the periphery of the tumor that are more basophilic with indistinct cell borders and little cytoplasm. The cells have hyperchromatic nuclei and often normal mitoses can be appreciated. Centrally there are eosinophilic “ghost or shadow” cells which are cells that have undergone terminal differentiation. These cells have more distinct borders, increased cytoplasm but only a ghost of a nucleus. Then there are cells that reside somewhere in between these two cell types. The proportion of these cells varies depending on the stage of the lesion; i.e younger lesions have more basophilic cells and appear more cystic, older lesions have a greater component of ghost cells and up to 20% of lesions on removal are completely composed of ghost cells.
Pilomatrixoma

Definition

• Benign adnexal tumor with differentiation toward the hair matrix
Clinical features

Epidemiology

• Presents in children and middle-aged adults most commonly
• Slight female predilection
• Possible predilection for whites
• Multiple lesions may be familial and can be associated with myotonic dystrophy
• Defects in beta-catenin implicated in pathogenesis

Presentation

• Firm to very hard, 2- to 3-mm to 2- to 3-cm nodule
• Often asymptomatic
• Located commonly on the head and neck, especially cheeks, but may present on the trunk and extremities
• Usually skin colored, but may exhibit bluish or vascular hue
• With stretching of the overlying skin, multifaceted angulation (“tenting”) of the skin is observed
• Multiple lesions sometimes present

Prognosis and treatment

• Benign tumor for which excision is curative
• Occasional recurrences following incomplete excision

Pathology

Histology

• Circumscribed dermal nodular proliferation arranged in cellular sheets, often with central cyst formation
• Tumor composed of two types of matrical cells: basaloid cells and ghost (shadow) cells
• Basaloid cells describe basophilic, monotonous epithelial cells
• Ghost (shadow) cells describe eosinophilic cells left with only remnant nuclear outlines
• Evolving lesions may show very brisk mitotic activity
• Calcification common and bone is not uncommon
• Areas of granulomatous inflammation with foreign-body–type giant cell reaction develop at sites of tumor degeneration

Immunopathology/special stains

• Not contributory

Main differential diagnoses

• Matrical carcinoma
• Basal cell carcinoma with matrical differentiation

Fig 1 Pilomatrixoma. Erythematous, firm nodule on the right temple of a girl.

Fig 2 Pilomatrixoma. Low-power view showing a circumscribed basophilic tumor surrounded by compressed fibrous tissue.

Fig 3 Pilomatrixoma. The basaloid cells have basophilic cytoplasm and regular oval or round vesicular nuclei with a prominent nucleolus. Note that there is brisk mitotic activity. This is a common feature and should not be taken to imply malignancy.

Fig 4 Pilomatrixoma. High-power view of typical eosinophilic anucleate “ghost” cells.

Fig 5 Pilomatrixoma. Stippled basophilic calcification is invariable in established lesions.

Fig 6 Pilomatrixoma. Many old lesions show bone formation sometimes accompanied by marrow spaces.

Fig 7 Pilomatrixoma. Scanning view of a circumscribed nodule.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)

Fig 8 Pilomatrixoma. High-power view of basaloid cells showing vesicular nuclei and mitotic activity.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)

Fig 9 Pilomatrixoma. Multinucleate giant cell are conspicuous.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)

Question 25

Which of the following lesions demonstrates a pseudo-Darier�s sign? 1 Mastocytoma 2 Spitz nevus 3 Smooth muscle hamartoma 4 Pilomatricoma 5 Bullous pemphigoid

Answer 25

Smooth muscle hamartomas are benign tumors which arise from smooth muscle of the dermis. Pseudo-Darier's sign may be elicited due to transient piloerection after rubbing. Histologically, red-orange bundles and fascicles are present with blunt-ended nuclei.

Question 26

What is the best diagnosis? 1 Keloid 2 Ochronosis 3 Lichen Nitidus 4 Compound Spitz Nevus 5 Dermatitis Herpetiformis

Answer 26

Distinguishing hypertrophic scar (HS) from keloid histopathologically is sometimes difficult because thickened hyalinized collagen (keloidal collagen), the hallmark of keloid, is not always detectable and [alpha]-smooth muscle actin ([alpha]-SMA), a differentiating marker of HS, is variably expressed in both forms of scar. Keloid Definition • Exaggerated scar tissue with characteristic hyalinization following trauma Clinical features Epidemiology * Younger individuals, including children * More common in heavily pigmented races Presentation * Raised, smooth, almost shiny nodules and plaques arising in an area of injury * Can occur anywhere, but mostly in head, neck, and shoulder region * Extends beyond the area of injury, in contrast to hypertrophic scar Prognosis and treatment * Excision, but recurrence is frequent * No tendency to regress spontaneously Pathology Histology * Characteristic feature, in the milieu of a scar, is the presence of keloidal collagen: dense, hyalinized bands of collagen * At times, multiple sections may be necessary to reveal the typical hyalinization Immunopathology/special stains • Not contributory Main differential diagnoses * Hypertrophic scar * Fibromatosis * Dermatofibroma * Note that focal keloid change can be a feature of a wide range of tumors including dermatofibroma, nodular fasciitis, desmoplastic melanoma, and even morpheaform basal cell carcinoma Fig 1 Keloid. Erythematous fibrotic plaque on the shoulder. (Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.) Fig 2 Keloid. Low-power view showing scar tissue with admixed hyalinized collagenous tissue typical of a keloid. Fig 3 Keloid. High-power view.

Question 27

Dorf balls are seen in which tumor? 1 Kaposi's sarcoma 2 Angiosarcoma 3 Tufted angioma 4 Kaposiform hemangioendothelioma 5 Dermatofibroma sarcoma protuberans

Answer 27

Dorf balls are pink amorphous globules seen in vessels in Kaposi's sarcoma. Typical histologic findings include proliferation of spindle cells, prominent slitlike vascular spaces, and extravasated red blood cells.

Question 28

Verruciform xanthoma is seen most commonly on: 1 Head and neck 2 Distal extremities 3 Oral mucosae and genital areas 4 Mucosal surfaces and trunk/proximal extremities 5 Nail bed and periungual areas

Answer 28

Verruciform xanthoma is an uncommon lesion that usually occurs on the oral mucosa of middle-aged persons or on the scrotum of middle-aged to elderly Japanese men. The most common site for verruciform xanthoma is the oral mucosa. Verruciform Xanthoma Definition • A benign lesion characterized by verrucous epidermal hyperplasia and dermal xanthomatous cells Clinical features Epidemiology * Rare lesion * Typically occurs in middle-aged adults * More common in whites * No gender predilection * Cause unknown: trauma may play causative role in oral lesions Presentation * Verrucous lesions * Typical locations include oral cavity (most common site), perioral, and perianal/genital region * Asymptomatic * Lesions that present outside perineum associated with other disorders: inflammatory linear verrucous epidermal nevus, congenital hemidysplasia with ichthyosiform erythroderma and limb defect (CHILD) syndrome, discoid lupus erythematosus Prognosis and treatment • Excision is curative Pathology Histology * Hyperkeratosis and parakeratosis * Papillomatosis, verrucous hyperplasia * Variable neutrophil infiltration * The dermal papillae contain xanthomatous cells Immunopathology/special stains • CD68 positive Main differential diagnosis • Epidermal hyperplasia may be mistaken for squamous cell carcinoma Fig 1 Verruciform xanthoma. Low-power view of the edge of a polypoid lesion. There is hyperkeratosis and acanthosis with elongation and tapering of the rete ridges. Fig 2 Verruciform xanthoma. Intraepidermal neutrophils are evident. Fig 3 Verruciform xanthoma. The dermal papillae contain a uniform population of xanthoma cells.

Question 29

The green color in chloroma is secondary to: 1 Stromelysin 2 Chloracetate 3 Fumarase 4 Myeloperoxidase 5 Alkaline phosphatase

Answer 29

Chloromas are greenish tumor grossly secondary to involvement of the skin in acute granulocytic leukemia. The green color is secondary to myeloperoxidase.

Question 30

Which of the following stains would be helpful in the diagnosis of cryptococcus? 1 Colloidal iron 2 Oil red O 3 Mucicarmine 4 Giemsa 5 Verhoeff von Gieson

Answer 30

The yeast cytoplasm of Crytococcosis stains with PAS and methanamine silver while the the capsule stains with Alcain blue and mucicarmine. Colloidal iron stains mucin; Oil red O stains fat; Giemsa stains mast cells and leishmaniasis; Verhoeff von Gieson stains elastic tissue. Cryptococcosis Definition • A systemic fungal infection Clinical features Epidemiology * Caused by Cryptococcus neoformans * The organism is found in bird droppings (pigeons) * Occurs worldwide * Occurs in immunocompromised patients, including those with HIV/AIDS Presentation * Skin is secondarily involved (very uncommonly) after primary infection in the lung * Mostly on the head and neck * Widespread papules, pustules, nodules, and ulcers * Meningitis and meningoencephalitis are common features of this infection * Primary inoculation of the skin is exceedingly rare Prognosis and treatment * Systemic antifungal therapy * Patients with meningitis fare worse Pathology Histology * Three variants: granulomatous (high host immune response), gelatinous (low host immune response), and suppurative * The organism is a 3- to 6-μm yeast surrounded by a conspicuous mucoid capsule * Narrow-based budding is characteristic * Few organisms in granulomatous form * Numerous organisms in gelatinous form; larger organisms may be seen, giving rise to a pseudoclear cell appearance; this form does not exhibit much inflammation Immunopathology/special stains * The organisms are positive with silver and PAS stains * The capsule stains with mucicarmine and alcian blue Main differential diagnoses * Histoplasmosis * It should be noted that in some infections a capsule may be absent Fig 1 Cryptococcosis. Several large umbilicated and ulcerated papules on the face of a man with HIV. Fig 2 Cryptococcosis. This case presented with multiple dermal abscesses. Fig 3 Cryptococcosis. High-power view showing a typical yeast form. The capsule is apparent. Fig 4 Cryptococcosis. Low-power view showing an intensely inflamed subcutis.

Question 31

Elastosis perforans serpiginosa is associated with all except: 1 Rothmund-Thompson 2 Scleredema 3 Ehlers-Danlos 4 Acrogeria 5 Down�s

Answer 31

Elastosis perforans serpiginosa is associated with Down�s syndrome, Ehlers-Danlos type IV, Osteogenesis imperfecta, Rothmund Thompson, Marfan�s, Werner�s, acrogeria, and penicillamine therapy. Elastosis Perforans Serpiginosa Definition • A perforating disorder of elastic fibers that may be idiopathic or associated with medications or systemic conditions Clinical features Epidemiology * Idiopathic variant may be genetically inherited * Medication-associated due to penicillamine * Associated systemic disorders include Marfan’s syndrome, Down syndrome, osteogenesis imperfecta, Ehlers-Danlos syndrome * Male predominance * Typically presents in second decade Presentation * Erythematous papules with central keratotic plug * Annular or serpiginous pattern * Commonly affects the lateral neck, may occur elsewhere * Asymptomatic or pruritic Prognosis and treatment * Often self-limited, lasting a few years * No standard effective therapy exists Pathology Histology * Acanthosis, sometimes pseudoepitheliomatous * Perforating canals containing elastotic material, keratin, and inflammatory debris (transepidermal elimination) * Dermal elastic tissue thickened and increased in amount * Variable granulomatous infiltrate Immunopathology/special stains • Elastic tissue stains highlight elastic fibers Main differential diagnosis • Other perforating disorders Fig 1 Elastosis perforans serpiginosa. Annular erythematous plaques with central clearing and scaly papules at the periphery, located on the arm. (Courtesy of L Edsall, MD, PhD; Virginia Commonwealth University, Richmond.) Fig 2 Elastosis perforans serpiginosa. Similar lesions on the neck of the same patient shown in Figure 1. (Courtesy of L Edsall, MD, PhD; Virginia Commonwealth University, Richmond.) Fig 3 Elastosis perforans serpiginosa. There is hyperkeratosis, irregular acanthosis, and a keratin-plugged epidermal invagination containing basophilic debris. Abscesses adjacent to the epidermis are evident. Fig 4 Elastosis perforans serpiginosa. High-power view of an intraepidermal abscess containing numerous eosinophilic elastic fibers. Fig 5 Elastosis perforans serpiginosa. Low-power view highlighting the elastic tissue (elastic tissue stain). Fig 6 Elastosis perforans serpiginosa. High-power view (elastic tissue stain).

Question 32

The PDGF gene has been shown to be translocated into the collagen I gene in: 1 Angiofibroma 2 Dermatofibroma 3 Dermatofibrosarcoma protuberans 4 Fibrous hamartoma of infancy 5 Solitary fibrous tumor

Answer 32

A translocation involving the PDGF gene and collagen I gene is found in dermatofibrosarcoma protuberans.

Question 33

Apocrine hidrocystoma may be associated with which of the following syndromes? 1 Downs syndrome 2 Schopf-Schulz-Passarge 3 Buschke-Ollendorf syndrome 4 Cowden's Disease 5 Osteogensis Imperfecta

Answer 33

Schopf-Schulz-Passarge is a syndrome of ectodermal dysplasia which presents with keratosis palmoplantaris with hypodontia, hypotrichosis, and cysts of the eyelids. The other answer choices have not been associated with apocrine hidrocystomas. Hidrocystoma Definition • Benign, apocrine gland–derived epithelial-lined cyst Clinical features Epidemiology * No gender predilection * No definite racial preference * Usually arises during adulthood Presentation * Translucent, sometimes bluish, dome-shaped, 2- to 3-mm to \>1-cm, soft cystic papule or nodule * Periorbital areas, particularly eyelids (Moll’s gland cyst) near medial canthus and cheek are characteristic * Also seen in other areas on head, neck, trunk, or genitalia * May be single or, less often, multiple * Can enlarge during hot weather Prognosis and treatment * Benign cyst * Electrosurgery or surgical excision sometimes used Pathology Histology * Epithelial-lined cyst within the dermis * Unilocular or multilocular * Thin, flattened cyst wall, two cell layers thick * Inner columnar type epithelium manifesting decapitation secretion and an outer myoepithelial layer * Intraluminal secretion with occasional pigment * Papillary projections sometimes evident (overlaps apocrine cystadenoma) * Occasionally seen in nevus sebaceus * Should not be confused with so-called eccrine hidrocystoma, which merely represents a cystic sweat duct (of either eccrine or apocrine derivation) (ductal hidrocystoma) * Apocrine hidrocystoma is sometimes associated with papillary epithelial hyperplasia (apocrine papillary cystadenoma) Immunopathology/special stains • Myoepithelial layer is SMA and variably S100 protein positive Main differential diagnosis • Apocrine cystadenoma Fig 1 Hidrocystoma. Multiple translucent to bluish cysts along and around the eyelid margin. Fig 2 Apocrine hidrocystoma. Low-power view of an eyelid lesion. Apocrine glands are present at the deep margin on the right side. Fig 3 Apocrine hidrocystoma. High-power view showing a double-layered epithelium. There is a hint of decapitation secretion. Fig 4 Apocrine cystadenoma. Low-power view showing marked epithelial papillary proliferation arising within a simple hidrocystoma. Fig 5 Apocrine cystadenoma. High-power view showing a double-layered epithelium and decapitation secretion. Fig 6 Ductal hidrocystoma. There is a single-layered epithelium. This entity represents a cystic duct and can be of eccrine or apocrine derivation.

Question 34

The diagnosis is: 1 Dermatofibrosarcoma 2 Nodular fasciitis 3 Angiolipoma 4 Epithelioid sarcoma 5 Liposarcoma

Answer 34

Angiolipomas are tumors of fat that are characteristically painful. Histopathologically, mature adipocytes are seen with numerous vessels. Microthrombi are often present. Angiolipoma Definition • A benign tumor of adipose tissue with increased blood vessels Clinical features Epidemiology • Young adults Presentation * Nodule, may be red or blue * Upper extremities * Generally painful * Often multiple lesions Prognosis and treatment • Excision is curative Pathology Histology * Typically encapsulated and circumscribed * Lobules of adipose tissue * Increased vascularity is present (this may be very extensive in the lesions referred to as “cellular angiolipoma”) * Mast cells may be evident * Intravascular fibrin thrombi are characteristic Immunopathology/special stains • Not contributory Main differential diagnosis • Vascular lesions such as capillary hemangioma Fig 1 Angiolipoma. Low-power view of an encapsulated tumor composed of mature adipocytes. There is an obviously increased vascularity. Fig 2 Angiolipoma. This view highlights the vascular component. Fig 3 Angiolipoma. Fibrin thrombi are a characteristic feature.

Question 35

Which of the following is true regarding S-100 Protein? 1 S-100 protein is an basic protein that binds Ca2+ and Zn2+ 2 It is not soluble in 100% ammonium sulfate at neutral pH 3 Can be detected in melanocytes and in Schwann cells 4 It is not useful in diagnosing of spindle cell melanoma & desmoplastic melanoma 5 It is not useful in diagnosing poorly differentiated cutaneous metastases

Answer 35

S-100 protein is an acidic protein that binds Ca2+ and Zn2+. At a neutral pH, it is soluble in 100% ammonium sulfate. It is useful in diagnosing both spindle cell melanomas, desmoplastic melanomas, as well as poorly differentiated cutaneous metastases. It also stains positively in neurofibromas and schwannomas.

Question 36

Which of the following sets of special immunohistochemical stains would help differentiate an atypical fibroxanthoma (AFX) from a malignant fibrous histiocytoma (MFH)? 1 CD74 and CD99 2 CD34 and Stromelysin-3 3 HMB45 and p75NPR 4 CK20 and TTF-1 5 CK20 and GCDFP-15

Answer 36

CD74 and CD99 CD74 (LN2) and CD99 help differentiate an AFX from an MFH where an AFX is CD74-,CD99+ and an MFH stains weakly from CD99 and is CD74 negative. CD34 and Stromelysin-3 differentiate dermatofibromas and DFSPs. HMB45 and p75NPR are stains helping to differentiate melanomas from desmoplastic melanomas. CK20 and TTF-1 staining differentiates a merkel cell carcinoma and metastatic small cell lung carcinoma. CK20 and GCDFP-15 staining helps distinguish primary and secondary (assoc with underlying neoplasm) Paget\'s disease. Atypical Fibrous Histiocytoma Definition • A rare variant of fibrous histiocytoma characterized by the presence of bizarre giant cells; associated with an increased recurrence rate and, exceptionally, metastases have been described. Also known as dermatofibroma with monster cells. Clinical features Epidemiology • Predominantly young adult females Presentation * Extremities, head, and neck * 1- to 2-cm papules or nodules Prognosis and treatment * Excision with a wide margin is recommended * May recur * Rare instances of metastases Pathology Histology * Similar to dermatofibroma but with very pleomorphic, atypical cells containing large nuclei and nucleoli * Proliferation may extend to the subcutaneous tissue * Mitoses, including atypical ones * Focal necrosis Immunopathology/special stains * Factor XIIIa positive * CD34 classically negative Main differential diagnosis • Atypical fibroxanthoma Fig 1 Atypical fibrous histiocytoma. Scanning view of a densely cellular tumor extending into the subcutaneous fat. Fig 2 Atypical fibrous histiocytoma. Conspicuous atypical cells with bizarre nuclei are present against a background of more typical fibrous histiocytoma. \*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\* Superficial Malignant Fibrous Histiocytoma (Superficial Pleomorphic Sarcoma—NOS) Definition • A very rare malignant tumor of the skin and subcutaneous fat; should be distinguished from myxoid malignant fibrous histiocytoma (myxofibrosarcoma) extending into the skin Clinical features Epidemiology * Elderly persons affected * Male predilection Presentation • Not specific Prognosis and treatment * Although very few cases have been documented, metastatic potential is high, and therefore a wide surgical excision is recommended * Metastasis to lung and bone Pathology Histology * Similar to atypical fibroxanthoma but extends deeply into the subcutaneous fat and adjacent structures, including muscle and bone * Necrosis is often present * Perineural infiltration and lymphovascular invasion may sometimes be present Immunopathology/special stains • A diagnosis of exclusion. At this site, pleomorphic and spindled squamous cell carcinoma, melanoma, and leiomyosarcoma should be excluded with a comprehensive immunohistochemistry panel. Main differential diagnoses * Atypical fibroxanthoma * Pleomorphic and spindled squamous carcinoma * Pleomorphic and spindled melanoma * Pleomorphic and spindled leiomyosarcoma Fig 1 Superficial malignant fibrous histiocytoma. Low-power view showing part of a spindled cell tumor extending deeply into subcutaneous fat. (Courtesy of E Calonje, MD; St John’s Institute of Dermatology, London.) Fig 2 Superficial malignant fibrous histiocytoma. There is marked pleomorphism. Diagnosis is dependent on immunohistochemistry. (Courtesy of E Calonje, MD; St John’s Institute of Dermatology, London.)

Question 37

Which of the following can be seen in dermatofibromas? 1 Hypopigmentation of the basal layer 2 Infiltration into the fat with a honeycomb pattern 3 Hypoplasia of the epidermis 4 S-100 positivity 5 Vimentin positivity

Answer 37

Dermatofibromas have characteristic features that can include collagen trapping, hyperplasia of epidermis, hyperpigmentation of basal layer, dermal spindle cells, and whorls of fibrous tissue with keloidal collagen. It stains with factor XIIIa(+) but not MAC 387 (-), S-100(-), or CD34 (-). DFSP infiltrates the fat with a honeycomb pattern.

Question 38

Which of the following is characteristic of lichen planus histopathologically? 1 Wedge-shaped parakeratosis 2 Irregular acanthosis 3 Absent interface changes 4 Parakeratosis 5 Absent granular layer

Answer 38

Irregular acanthosis Histopathology of lichen planus: Acanthosis with wedge-shaped hypergranulosis, irregular (sawtooth acanthosis), hyperkeratosis without significant parakeratosis, and basal vacuolization (interface changes).

Question 39

Which of the following regarding stains is true? 1 A Verhoeff-van Gieson stain is used to stain elastic fibers red. 2 A methanamine silver stain is used to identify bacteria. 3 A fite stain is used to identify spirochetes. 4 A Von Kossa stain is used to identify calcium. 5 A giesma stain is used to identify eosinophil granules.

Answer 39

A Von Kossa stain is used to identify calcium. Stains/Application/Result Van Gieson - Elastic fibers - Black Methanamine-silver - Fungi, parasites - Black AFB/Fite - Acid-fast bacilli - Red Von Kossa - Calcium - Black Giesma - Mast cells - Metachromatically purple

Question 40

Which marker stains melanosomes? 1 S-100 2 Mart-1/Melan-A 3 MITF 4 HMB-45 5 Fontana-Masson

Answer 40

MB-45 HMB-45 is a melanosome immunostain targeting glycoprotein. S-100 is a melanocyte immunostain, but it has low specificity also staining Langerhans cells, smooth and skeletal muscle, adipocytes, and eccrine coils. MITF is a melanocyte nuclear stain. Fontana-Masson is a melanin stain.

Question 41

What is your best diagnosis? 1 Sebaceous Glands 2 Sebaceum 3 Lichen Planus 4 Atopic Eczema 5 Angiofibroma

Answer 41

Angiofibroma Angiofibroma is a small reddish spot or bump that consists of fibrous tissue and blood vessels. They are most commonly found around the nose, cheeks, and chin, often combining to form a distinctive butterfly-shaped pattern. Previously known as adenoma sebaceum.

Question 42

Positive staining with Gross cystic disease fluid protein 15 (GCDFP-15) suggests: 1 An apocrine origin 2 An eccrine origin 3 A sebaceous origin 4 A follicular origin 5 None of these answers are correct

Answer 42

An apocrine origin Gross cystic disease fluid protein-15 (GCDFP-15) is a commonly used apocrine marker.

Question 43

Which immunohistochemical stain would be positive in eosinophilic granuloma? 1 HMB-45 2 Cytokeratin 20 3 Congo red 4 Mucin 5 CD1a

Answer 43

CD1a Eosinophilic granuloma is a form of Langerhans Cell Histocytosis (LCH), previously called Histiocytosis X. Eosinophilic granuloma is a localized, benign form which is more common in males and generally affects the bones. All forms of LCH are characterized by the infiltration of Langerhans cells on pathology, which stains for S-100, CD1a and contain cytoplasmic birbeck granules.

Question 44

The inclusions in infantile digital fibromatosis stain for trichrome and: 1 Phosphotungstic acid hematoxylin 2 Osmium tetroxide 3 Thioflavin T 4 Bodian 5 Pentahydroxy flavanol

Answer 44

Phosphotungstic acid hematoxylin Osmium tetroxide stains fat. Thioflavin T stains amyloid. The Bodian stain is for nerves. Pentahydroxy flavanol is a fluorescent stain for calcium.

Question 45

A biopsy was performed from the scalp of an elderly man what is the most likely diagnosis? 1 Metastatic renal cell carcinoma 2 Angiosarcoma 3 Carcinoid 4 Sebaceous Carcinoma 5 Clear cell hidradenoma

Answer 45

Metastatic renal cell carcinoma Clear Cell Renal Carcinoma: Metastatic lesions are commonly located on the scalp. The tumor itself is composed of cells with clear to slightly granular cytoplasm secondary to increased glycogen and lipid. The tumors typically forms abortive tubes/ducts, cords or sheets of cells. Immunohistochemical stains are + for EMA and CD10. Typically the tumor is very vascular with scant stroma associated with extravasated RBC and hemosiderin. The differential diagnosis includes clear cell hidroadenoma. This latter tumor is usually composed of a mixture of components; solid areas composed of small poroid cells often with duct formation admixed with clear cells and squamoid cells. The tumor can be solid or cystic or a combination of the two. The large cystic spaces typically contain sialomucin. The stroma is delicate fibrovascular. The tumor is + CAM 5.2, CEA, EMA, with glycogen and no lipid in the clear cells.

Question 46

All are sebaceous glands except: 1 Tyson 2 Moll 3 Wolf 4 Fordyce 5 Meibomian

Answer 46

Moll Moll's glands are modified apocrine glands located on the eyelid. Sebaceous glands in certain locations have an associated name (Tyson's on the penis, Wolf's or Meibomian on the eyelid, and Fordyce on the vermilion/oral mucosa).

Question 47

Multiple spiradenomas are seen in this syndrome: 1 Alagille 2 Brooke-Spiegler 3 Nicolau-Balus 4 Schopf's 5 Lhermitte-Duclos

Answer 47

Brooke-Spiegler Brooke-Spiegler syndrome combines multiple cylindromas and multiple trichoepitheliomas, and sometimes multiple spiradenomas can be seen as well. Alagille syndrome associates arteriohepatic dysplasia and nevus comedonicus. Nicolau-Balus' syndrome describes the constellation of multiple eruptive syringomas, milia, and atrophoderma vermiculata. Schopf's syndrome combines multiple apocrine hidrocystomas, palmar-plantar keratoderma, teeth abnormalities (hypodontia), and onychodystrophy. Lhermitte-Duclos disease may be a manifestation of Cowden's. In Lhermitte-Duclos, there is a proliferation in the cerebellum (dysplastic gangliocytoma) with macrocephaly. Eccrine Spiradenoma Definition • Benign sweat gland tumor Clinical features Epidemiology • Usually young adults • Rare cases in infancy documented • No clear gender preference • No clear racial predilection • Multiple lesions may be found in association with trichoepitheliomas and cylindromas in Brooke-Spiegler syndrome Presentation • Usually solitary, often tender or painful tumor • Skin-colored to erythematous to bluish papule or nodule • Several millimeters to 1 to 2 cm in size • Typically smooth-surfaced • Commonly located on ventral surface of the upper half of the body—on scalp, neck, trunk, and arms Prognosis and treatment • Fundamentally benign lesion • Surgical excision curative • Carcinomatous change very rare Pathology Histology • Often encapsulated and circumscribed cellular lobules of basaloid cells resembling “blue balls” filling the dermis • Dual cell population composed of polygonal cells with large, pale nuclei surrounded by a periphery of round, small cells with hyperchromatic nuclei • Small ductal lumina may be seen within the center of the lobules • No pleomorphism • Sparse or no mitotic activity • Hyaline deposits • Lymphocytic infiltrate often present (absence can be clue to possible malignant change) • Lymphedematous and telangiectatic variants • May overlap with cylindroma Immunopathology/special stains • CEA, EMA, and diastase-PAS highlight ducts • S100 positive and SMA highlights the myoepithelial cells Main differential diagnosis • Cylindroma Fig 1 Eccrine spiradenoma. Low-power view showing basaloid cellular aggregates. Telangiectasia, a common feature, is seen at the bottom right of the field. Fig 2 Eccrine spiradenoma. This view highlights the dual cell population, peripheral palisading, and ductal differentiation. Fig 3 Eccrine spiradenoma. High-power view showing ductal differentiation and diffuse lymphocytic infiltration.

Question 48

Goblet cells are seen in: 1 Cutaneous ciliated cyst 2 Endometriosis 3 Dermoid cyst 4 Bronchogenic cyst 5 Steatocystoma

Answer 48

Bronchogenic cyst Bronchogenic cysts have a pseudostratified cuboidal or columnar lining that is ciliated; goblet cells are found in the lining as well.

Question 49

What is the neoplasm in this biopsy? 1 Chondroid syringoma 2 Papillary eccrine adenoma 3 Tubular apocrine adenoma 4 Eccrine acrospiroma 5 Trichoblastoma

Answer 49

Chondroid syringoma Chondroid Syringoma: Most commonly occurs in middle age males on the head and neck. Histologically this is a well circumscribed dermal tumor composed of dilated ducts, hyaline or plasmacytoid cells (myoepithelial cells), keratinous cysts, +/- cells that show hair matricial differentiation occasionally with some areas of mature fat. All elements arise within a homogenous bluish chondromyxoid matrix (+ Type II collagen, + acid MPS stains with Alcian blue/green (stains at high and low PH) consistent with chondroitin sulfate). Focal calcification may occur. Chondroid Syringoma (Mixed Tumor) Definition • Benign sweat gland tumor associated with a chondroid matrix Clinical features Epidemiology • Adults • More often in males Presentation • Solitary firm or hard nodule • Mostly on head and neck Prognosis and treatment • Benign lesion • Excision is generally curative • Extremely rarely, malignant change may occur Pathology Histology • Circumscribed multinodular tumor with pseudocapsule • Chondroid matrix often present • Characteristic morphology is of nests of cells with eosinophilic cytoplasm, ducts, and glands • Glandular structures and ducts are lined by single- or double-layered epithelium • Cystic change is common • No pleomorphism • Mitoses rare • Plasmacytoid cells occasionally conspicuous • Squamous differentiation and keratocysts sometimes present • Follicular variant • Sebaceous differentiation is occasionally evident • Spindled cells present in the stroma • Bone formation a rare feature Immunopathology/special stains • Generally noncontributory • Inner layer is keratin, CEA, EMA, and GCDFP positive • Outer layer is S100 and SMA positive Main differential diagnosis • Malignant mixed tumor Fig 1 Chondroid syringoma. Scanning view showing a circumscribed, pseudoencapsulated, deep, dermal nodule with multiple cysts. Fig 2 Chondroid syringoma. The tumor cells have abundant eosinophilic cytoplasm and basophilic nuclei. Glandular and ductal differentiation with cystic change is evident.

Question 50

Supporting evidence for the diagnosis of mycosis fungoides is CD4+ lymphocytes with loss of CD7 as well as loss of 1 CD2 2 CD3 3 CD5 4 CD20 5 CD30

Answer 50

CD5 CD5 as well as CD7 are sometimes lost on the surface of epidermotropic T cells in mycosis fungoides. CD2, CD3, and CD5 are T cell markers. CD20 is a B cell marker. CD30 is positive in anaplastic large cell lymphoma cells, Hodgkin's lymphoma, and lymphomatoid papulosis. Reactive infiltrates can also have some CD30-positive cells.

Question 51

Which of the following is commonly seen histopathologically in pityriasis rosea? 1 Absent spongiosis 2 Full thickness necrosis 3 Exravasated erythrocytes in the subcutaneous fat 4 Lichenoid lymphocytic infiltrate 5 Focal parakeratosis

Answer 51

Focal parakeratosis Histopathological features of Pityriasis Rosea: Mild subacute spongiotic dermatitis, focal parakeratosis (corresponds to cigarette paper-like scale), perviascular lymphocytic infiltrate, hemorrhage in papillary dermis, and sometimes a few necrotic keratinocytes.

Question 52

Mantle cell lymphoma is characteristically positive for which of the following? 1 CD10 2 CD23 3 CD138 4 Bcl-1 5 bcl-6

Answer 52

Bcl-1 Bcl-1 (Cyclin D1) is a marker for mantle cell lymphoma. CD10, bcl-6, and bcl-2 are markers for follicular cell lymphoma. Bcl-2 also stains normal T cells. CD23 is a marker for CLL/SLL and is negative in mantle cell lymphoma. CD138 is a marker for plasma cells.

Question 53

Granular cell tumors will stain positive for all of the following markers except: 1 S100 2 PAS 3 PTAH 4 HMB-45 5 Neuron specific enolase

Answer 53

HMB-45 Granular cell tumors are of neural origin, with the granules representing an accumulation of lysosomes in the cytoplasm. Lesions present on the tongue in 25% of cases. The granules stain positive with periodic acid-Schiff (PAS) staining and are resistant to diastase. Being of neural origin, lesions also stain with S100 and neuron specific enolase. The cells would not react with melanocyte markers, such as HMB-45.

Question 54

The predominant location of the cleft in acropustulosis of infancy is: 1 Dermal 2 Basment mebrane zone 3 Basal keratinocytes 4 Suprabasal 5 Subcorneal/granular

Answer 54

Subcorneal/granular Acropustulosis of infancy presents as idiopathic pustules on acral skin. Diagnosis is made only after other causes of pustules have been ruled out, and it usually resolves in a few years. The cleft in acropustulosis of infancy is subcorneal/granular with neutrophils.

Question 55

A deposition of what substances leads to these deposits? 1 Homogentisic acid 2 Amyloid 3 Fungal organisms 4 Colloid 5 Tattoo

Answer 55

Homogentisic acid Ochronosis: can be either endogenous or exogenous. The endogenous form is due to an AR defect in homogentisic acid oxidase, which prevents tyrosine and phenylalanine from being degraded beyond homogentisic acid. The exogenous form of ochronosis, on the other hand, occurs from topical hydroquinone, mercury resorcinol, phenol, picric acid or benzene, or systemic quinine or chloroquine which all inhibits homogentisic oxidase and leads to a focal accumulation of homogentisic acid. Within the superficial dermis there are irregular shaped elongated yellow deposits which have been described as as bananas in the dermis that occur due to deposition of homogentisic acid on the collagen.

Question 56

Biopsy of a mucosal neuroma from a patient with MEN IIb looks histologically like a: 1 Neurilemmoma 2 Neurofibroma 3 Palisaded encapsulated neuroma 4 Traumatic neuroma 5 Neurothekeoma

Answer 56

Palisaded encapsulated neuroma Mucosal neuromas in MEN IIb often look histologically like PENs. Occasionally mucosal neuromas display thickened nerves/perineurium.

Question 57

Birt-Hogg-Dube has been associated with increased risk of renal cancer and: 1 Spontaneous pneumothorax 2 Hepatic cysts 3 Adrenal hemorrhage 4 Cirrhosis 5 Gastrointestinal polyps

Answer 57

Spontaneous pneumothorax The gene defect in Birt-Hogg-Dube is folliculin.

Question 58

Which of the following stains with Ulex europeus agglutinin I? 1 Smooth muscle 2 Eccrine glands 3 Endothelial cells 4 Macrophages 5 Melanocytes

Answer 58

Endothelial cells Ulex europeus agglutinin I is a stain which identifies endothelial cells, keratinocytes, angiosarcomes and Kaposi's sarcoma.

Question 59

62-year old female with history of acute myeloid leukemia presents with multiple edematous, erythematous papules after starting G-CSF. 1 Sweet's syndrome 2 Leukocytoclastic vasculitis 3 Bowel bypass dermatosis 4 Polymorphous light eruption 5 Erythema multiforme

Answer 59

Sweet's syndrome Sweet's syndrome, or acute febrile neutrophilic dermatoses, is often associated with AML and G-CSF. Histologically, there is marked dermal edema with a prominent infiltrate composed of neutrophils with leukocytoclasia. There is an absence of extensive vascular damage.

Question 60

What is the best diagnosis? 1 Cholesterol emboli 2 Masson's Tumor 3 Calciphylaxis 4 Leukocytoclastic vasculitis 5 Processing Artifact

Answer 60

Cholesterol emboli Cholesterol Emboli: Typically occurs after a vascular procedure but can occur spontaneously. Usually presents as livedo reticularis of distal lower extremities, associated with eosinophilia and acute renal failure. Often need multiple deeper levels on sectioning a punch biopsy to see the characteristic cholesterol clefts and fibrin thrombi in the lower dermis or subcutis.

Question 61

Which of the following stains Natural Killer Cells? 1 CD1a 2 CD11 3 CD30 4 CD56 5 CD68

Answer 61

CD56 CD56 stain Natural Killer Cells and angiocentric lymphomas.

Question 62

This biopsy was obtained from a Filipino woman who lives in Southern California, what is this organism? 1 Coccidioidomycosis 2 Rhinosporidium 3 Prototheca wickerhamii 4 Histoplasmosis capsulatum 5 Cryptococcus neoformans

Answer 62

Coccidioidomycosis Coccidioidomycosis: Found in nature in the soil of desert areas of the South West, also known as “Valley Fever”. Usually presents as a self-limited lung infection, but in less 1% of people dissemination can occur. The risk is highest in immunocompromised people, and there is a higher risk in Mexicans, Filipinos, African Americans, American Indians, and in pregnancy. Systemic illness can be associated with eosinophilia, arthritis and rarely hypercalcemia. Disseminated cutaneous lesions present as papulopustules on nasolabial fold or verrucous plaque on face. Approximately 20% of patients with pulmonary infections develop a hypersensitivity reaction to the infection resulting in erythema nodosum. Primary inoculation is rare and usually occurs in farmers and can present with a sporotrichoid pattern. Histology: Pseudoepitheliomatous hyperplasia of the epidermis overlying a suppurative granulomatous dermatitis that often contains numerous eosinophils in the inflammatory infiltrate. Within the granulomas are thin walled sporangia measuring 10-80 microns that often contain multiple endospores. The organism can usually be easily seen on H & E, but use of PAS and Congo red stains highlights the spores. The classic appearance on culture is alternating light and dark chains of organisms with a box car-like appearance.