Sec 21 Epidermal and Appendegeal Tumors Flashcards by Charlene DPA

A common feature of all premalignant keratinocyte tumors

Potential to become invasive squamous cell carcinoma

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Cutaneous neoplasms consisting of proliferations of cytologically abnormal epidermal keratinocytes that develop in response to prolonged exposure to ultraviolet

Actinic Keratosis or Solar Keratosis

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Are the initial lesion in a disease continuum that may progress to SCC

Actinic Keratosis

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Risk factors for development of Actinic keratoses

Individual susceptibility (older age, male gender, fair skin that easily burns and freckles, blond or red hair, light-colored eyes)
Cumulative ultraviolet radiation exposure Immunosuppression
Prior history of actinic keratoses or other skin cancers
Genetic syndromes (Xeroderma pigmentosum, Bloom syndrome, Rothmund-Thomson syndrome)

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The most important contributing factor in the development of AKs and SCC

Habitual exposure to UV radiation

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Play a pivotal role in the initiation of AKs and their development into SCC

Tumor suppressor gene p53

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Typical patient is an older, fair-skinned, light-eyed individual who has a history of significant sun exposure, who burns and freckles rather than tans, and who has significant solar elastosis on examination

Actinic keratosis

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Presents most commonly as a 2-6 mm erythematous, flat, rough, gritty or scaly papule; usually more easily felt than seen; most often found against a background of photodamaged skin or dermatoheliosis, with solar elastosis, dyspigmentation, yellow discoloration, ephelides and lentigos, telangiectases, and sagging skin notably prominent

Erythematous AK

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Presents as a thicker, scaly, rough papule or plaque that is skin-colored, gray–white, or erythematous; can be found on any habitually sun-exposed site on the body but has a propensity for the dorsal hands, arms, and scalp

Hypertrophic AK

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AKA cornu cutaneum; refers to a reaction pattern and not a particular lesion; a type of HAK that presents with a conical hypertrophic protuberance emanating from a skin-colored to erythematous papular base; height is at least one-half of the largest diameter

Cutaneous horn

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Pathology underlying Cutaneous horn

Actinic keratosis
Squamous cell carcinoma 
Seborrheic keratosis
Filiform verruca vulgaris
Trichilemmoma
Keratoacanthoma

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Represents confluent AKs on the lips, most often the lower lip; presents with red, scaly, chapped lips, and at times erosions or fissures may be present; complain of persistent dryness and cracking of the lips

Actinic cheilitis

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May be a marker of progression of AK to SCC

Pain

Inflammation

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Treatment: Actinic Keratosis

Lesion-targeted therapies

Liquid nitrogen cryotherapy
Curettage with or without electrosurgery
Shave excision

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Treatment: Actinic Keratosis

Topical field therapies

5-fluorouracil cream and solution
Imiquimod cream
3% diclofenac gel

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Treatment: Actinic Keratosis

Procedural field therapies

Cryopeeling
Dermabrasion 
Medium-depth chemical peel 
Deep chemical peel
Laser resurfacing 
Photodynamic therapy

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Most common destructive procedure and is typically administered with a spray device or a cotton-tipped applicator with ideal freeze time of 10-15 secs

Liquid nitrogen cryosurgery

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Cryosurgery: benefits

Ease of administration in trained hands
Lack of need for anesthetic
Lack of reliance on patient compliance

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Cryosurgery: disadvantages

Pain and discomfort
Presence of unsightly blisters and crusted wounds for a week or longer
Hypopigmentation
Scarring
Possible alopecia in treated areas

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Constitute approximately 80% of all treatments for AKs in the United States

Liquid nitrogen cryosurgery

Curettage with or without electrosurgery

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Most appropriate for patients with relatively few AKs; beneficial for treatment of lesions after biopsy and for the treatment of HAKs

Curettage with or without electrosurgery

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Involves injection of a local anesthetic followed by tangential excision of the lesion with a surgical blade; most often indicated when a clinically apparent AK is suspicious for SCC or BCC and histopathologic examination is needed

Shave excision

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Signs and symptoms that should arouse suspicion of SCC

Marked erythema
Pain
Ulceration
Bleeding
Induration
Failure to respond to prior destructive therapies

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Best used in patients with moderate to severely photodamaged skin and numerous AKs that would be too burdensome and painful to treat with the lesion-targeted therapies

Field therapies

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Extensive liquid nitrogen cryosurgery to the areas of discrete AKs as well as to the surrounding actinically damaged skin

Cryopeeling

An older technique that is quite effective in the treatment and prophylaxis of AKs but is now rarely used; causes physical destruction of the AKs with abrasion using either dry-wall sanding sheets or diamond fraises, which are powered or handheld

Dermabrasion

Medium-depth chemical peels used for AK

Jessner’s solution | 35% trichloroacetic acid (TCA)

Deep chemical peels used for AK

Phenol | High concentrations of TCA

More effective in treating thick AKs or those with appendageal epithelial atypia but are rarely used because of the potential cardiac and renal toxicity, the greater risk of scarring and infection, and the dramatic hypopigmentation that may occur postoperatively

Deep chemical peels

Two laser systems that have primarily been used for the treatment and prophylaxis of AKs; ablate the epidermis at varying depths allowing reepithelialization with adnexal keratinocytes that are less actinically damaged; effective in short-term clearing of multiple facial and scalp AK and in the long-term prevention of recurrences, and possibly the development of NMSC

``` Carbon dioxide (CO2) laser Erbium:yttrium-aluminum-garnet (er:YAG) ```

Another procedural therapy available for the treatment of multiple and diffuse AKs where topically applied ALA or MAL accumulates preferentially in the more rapidly dividing atypical cells and is converted sequentially to protoporphyrin IX, a heme precursor and photosensitizer and when exposed to a light source of the appropriate wavelength, the accumulated protoporphyrin IX generates a phototoxic reaction that destroys the treated cells

Photodynamic therapy

Single most effective means of decreasing the risk of AKs

Avoidance of UV radiation

Precancerous lesions found in association with chronic arsenicism which have the potential to develop into invasive SCC

Arsenical Keratosis

An ubiquitous element that has no color, taste, or odor which has the potential to cause characteristic acute and chronic syndromes in persons exposed to it

Arsenic

How often should regularly scheduled total-body skin examinations and general physical examinations in management of patients with chronic arsenicism and ArKs

Every 6 months

Precancerous lesions that result from long-term exposure to infrared radiation; can progress to squamous cell carcinoma (SCC)

Thermal keratosis

Precursor lesion of Thermal keratosis

Erythema ab igne

Occur in persons who are occupationally exposed to polycyclic aromatic hydrocarbons; can progress to squamous cell carcinoma (SCC); usually on the nostril rims, upper lip, or genitalia

Hydrocarbon keratosis Pitch keratoses Tar keratoses Tar warts

Hyperkeratotic papules or plaques within areas of chronic radiation dermatitis and occasionally on clinically normal skin that may arise years (56 years) after such exposure and may progress to squamous cell carcinoma common on palms, soles, and mucosal surfaces

Chronic radiation keratosis

Precancerous lesions that arise in long-standing scars from various causes

Chronic scar keratoses | Cicatrix keratoses

Malignant changes within a burn scar but can also refer to such changes in chronic ulcers or sinus tracts with sites of predilection being the extremities and overlying joints

Marjolin’s ulcer

Precancerous epithelial lesions with a viral association

``` Bowenoid papulosis (BP) Epidermodysplasia verruciformis (EV) Vulvar intraepithelial neoplasia (VIN) Anal and perianal intraepithelial neoplasia (AIN and PaIN) Penile intraepithelial neoplasia (PIN) ```

Characterized clinically by the presence of pink, reddish brown, or violaceous verrucous papules and plaques primarily on the genitalia of predisposed, usually younger, individuals, and histopathologically by the presence of SCC in situ-like changes caused by infection with HPV, particularly subtypes 16 and 18

Bowenoid papulosis (BP)

Histopathology: hyperplastic with atypia, disordered maturation, scattered mitotic figures, and dyskeratotic keratinocytes

Bowenoid papulosis (BP)

Rare inherited skin condition that arises when genetically susceptible individuals are infected with certain HPV subtypes, most notably HPV 5 and 8; present in childhood with numerous thin, pink, flat papules and plaques that resemble verruca plana; can also be widespread scaly, erythematous, or hypopigmented macules and flat papules that appear similar to tinea versicolor

Epidermodysplasia verruciformis (EV)

May occur at any age in adults can be found on any body site, including both sun-exposed and nonsun-exposed regions of the body, although it appears to have a predilection for sun-exposed surfaces such as the head and neck and for the lower legs of women, typically presents as a discrete, slowly enlarging, pink to erythematous thin plaque with well-demarcated, irregular borders and overlying scale or crust resembling a psoriatic plaque

Bowen disease

Can present as an oozing, erythematous, dermatitic plaque or as a pigmented patch or plaque

Intertriginous BD

May appear as an erythematous, scaly, thin plaque around the cuticular margin, a crusted erosion, nail discoloration, erythronychia, onycholysis, a verrucous plaque, or destruction of the nail plate

BD involving the periungual region

Can present as verrucous or polypoid papules and plaques, erythroplakia, or a velvety erythematous plaque

BD of the mucosal surfaces

Histopathology: full-thickness atypia, including in the intraepidermal portions of the adnexal structures with involvement from the stratum corneum to the basal cell layer, but BM is intact; parakeratosis, hyperkeratosis, acanthoses are present, with complete disorganization of the epidermal architecture; throughout the epidermis are numerous atypical, pleomorphic, hyperchromatic keratinocytes which may be vacuolated and have a prominent pale-staining cytoplasm, reminiscent of the cells in Paget disease; show loss of maturation and polarity; upper dermis is typically infiltrated by lymphocytes, plasma cells, and histiocytes

Bowen disease

BD that displays parakeratosis and marked acanthosis with broad, sometimes fused, epidermal rete ridges

Psoriasiform BD

BD that demonstrates a thinned epidermis, but in addition there is full-thickness atypia and lack of maturation, as well as adnexal involvement

Atrophic BD

BD that shows marked acantholysis in the epidermis

Acantholytic BD

BD that has changes of incidental epidermolytic hyperkeratosis (EHK) present

Epidermolytic BD

BD with phenomenon of intraepidermal epithelioma of Borst-Jadassohn which is nesting of the atypical cells within the epidermis

Pagetoid BD

Treatment: Bowen disease | Surgical and destructive therapies

Excision Mohs micrographic surgery Curettage with or without electrosurgery Liquid nitrogen cryosurgery

Treatment: Bowen disease | Topical therapies

5-Fluorouracil (5% cream bid for 6–16 weeks) | 5% imiquimod (daily for 16 weeks)

Treatment: Bowen disease | Nonsurgical ablative therapies

Laser ablation Radiotherapy Photodynamic therapy

HPV: Bowenoid papulosis (BP)

HPV-16,18

HPV: Epidermodysplasia verruciformis (EV)

HPV-5,8

HPV: Vulvar intraepithelial neoplasia (VIN) Anal intraepithelial neoplasia (AIN) Perianal intraepithelial neoplasia (PaIN) Penile intraepithelial neoplasia (PIN) Digital or periungual Bowen disease

HPV-16

Predominantly white lesion of the oral mucosa that cannot be rubbed off or characterized by any other definable lesion or known disease; most common precancerous lesion of the oral mucosa, with the potential to become oral SCC

Leukoplakia

Presents mostly as white, flat, uniform lesion that may have shallow cracks and a smooth, wrinkled, or corrugated surface that is consistent throughout

Homogeneous oral leukoplakia

Presents mostly as white or white and red lesion (erythroleukoplakia) that may be irregular and flat, nodular (speckled), ulcerative, or verrucous; has a higher risk of malignant transformation

Nonhomogeneous oral leukoplakia

Precancerous lesion of stratified squamous epithelium characterized by cellular atypia and loss of normal maturation and stratification short of carcinoma in situ

Epithelial dysplasia

A lesion in which the full thickness, or almost the full thickness, of squamous epithelium shows the cellular features of carcinoma without stromal invasion

Carcinoma in situ of the oral cavity

Most important risk factor for the conversion of oral leukoplakia into oral squamous cell carcinoma

Presence of epithelial dysplasia

Other risk factors for the conversion of oral leukoplakia into oral squamous cell carcinoma

``` Female gender Long duration of oral leukoplakia (OL) OL in nonsmokers Location on the floor of the mouth or tongue Size >200 mm3 Nonhomogeneous type of OL ```

A red macule or patch on a mucosal surface that cannot be categorized as any other known disease entity caused by inflammatory, vascular, or traumatic factors; can involve any mucosal surface but most commonly occurs on the oral mucosa in more than half of all cases; considered to be the most dangerous and carries the greatest risk of progressing to or harboring invasive carcinoma

Erythroplakia or Erythroplasia

Most common areas or oral erythroplakia in the oral cavity

Soft palate Floor of the mouth Buccal mucosa

Presents as a solitary, subtle, asymptomatic, erythematous macule or patch; most often <1.5 cm in its widest diameter; sharply demarcated from the surrounding pink mucosa, and surface is most often smooth and homogeneous in color; occasionally lesions of demonstrate a pebbled or stippled surface change and on palpation may have a soft and velvety feel

Erythroplakia or Erythroplasia

Predisposing factors for SCC

Precursor lesions (actinic keratosis, Bowen disease) Ultraviolet radiation exposure Ionizing radiation exposure Exposure to environmental carcinogens Immunosuppression Scars Burns or long-term heat exposure Chronic scarring or inflammatory dermatoses Human papillomavirus infection Genodermatoses (albinism, xeroderma pigmentosum, porokeratosis, epidermolysis bullosa)

Considered the predominant risk factor for SCC

UV radiation

Associated 30-fold increase in non-melanoma skin cancers, most of which are SCCs

Long term PUVA therapy

Virus recently identified in approximately 15% of cutaneous SCCs from immunocompetent patients

MCPyV polyoma virus

Disorder of DNA repair, is also characterized by early development of SCCs

Xeroderma pigmentosum

Apoptosis of keratinocytes that have sustained UV radiation-induced DNA damage, requires the p53 tumor suppressor and represents a key protective mechanism against skin cancer by removing premalignant cells that have acquired mutations

Sunburn cells

Associated with nodal metastasis in oral SCC

Bcl-2-associated athanogene 1 (BAG-1)

May present as firm, flesh-colored or erythematous, keratotic papule or plaque but may also be pigmented; may also present as an an ulcer, a smooth nodule, or a thick cutaneous horn; may also be verrucous or present as an abscess, particularly if in a periungual location; margins may be indistinct; with enlargement, there is usually increased firmness and elevation

Squamous cell carcinoma

Usually occurs in patients with a long history of cigarette smoking, tobacco chewing, or alcohol use with male predominance; most commonly evolves from lesions of erythroplakia and is usually asymptomatic; may also present as a peritonsillar abscess

Squamous cell carcinoma of oral cavity

Most common sites of oral SCC

Palate | Tongue

High risk sites of oral SCC

Floor of the mouth Ventrolateral tongue Soft palate

Begins as a roughened papule of actinic cheilitis or scaly leukoplakia, with slow progression to a tumor nodule; usually associated with persistent lip chapping with localized scale or crust, red and white blotchy atrophic vermilion zone of the lip, indistinct or “wandering” vermilion border, and small fissuring; or ulceration within an area of indurated actinic cheilitis

SCC of the lower lip

Most commonly occurs on the anterior labia majora, beginning as a small warty nodule or an erosive erythematosus plaque; may be asymptomatic but more often are associated with pruritus or bleeding

SCC of the vulva

Begins as a small pruritic verrucous lesion that becomes friable with increasing size in the genitalia

SCC of the scrotum

Usually occurs in uncircumcised males and, may account for 10% of cancers in places where genital hygiene is poor

SCC of the penis

Distinct precursor of penile SCC characterized by a velvety red plaque

Erythroplasia of Queyrat

Common precursor of SCC of the vulva

Lichen sclerosus

Typically begin decades after injury, with skin breakdown and persistent erosion; most commonly this occurs on the lower extremities at sites of chronic pyogenic or venous stasis ulcers; may be associated with increased pain, drainage, or bleeding

Scar squamous cell carcinoma

Typically presents as a large, smooth, dome-shaped, verrucous nodule with a central keratotic crater in an elderly patient on a sun-exposed site, particularly an extremity with rapid growth, up to several cm in weeks, and then gradual involution over a period of months in most cases

Keratoacanthoma

Associated neoplasms in Keratoacanthoma

``` Sebaceous neoplasms Gastrointestinal malignancies (Muir-Torre syndrome) ```

Form of SCC that encompasses several clinical entities, all characterized by slow-growing exophytic tumors with a cauliflower-like appearance that develop at sites of chronic irritation; may be clinically mistaken for giant warts

Verrucous carcinoma

Type of Verrucous carcinoma that consists of oral tumors on the buccal mucosa of elderly male tobacco chewers representing 2%–12% of all oral cancers; these tumors are most commonly found on the buccal mucosa, tongue, gingiva, and floor of the mouth

Type I - oral florid papillomatosis

Type of Verrucous carcinoma that occurs on the glans penis of young uncircumcised males, on the scrotum, on the perianal region in both sexes, and, less commonly, on the female genitalia

Type II - anogenital type

Type of Verrucous carcinoma that is a malodorous tumor often found on the plantar area in elderly men; usually involves the skin underlying the first metatarsal head and tends to form draining sinuses that are like rabbit burrows in appearance

Type III - epithelioma cuniculatum

Type of Verrucous carcinoma that occurs at other sites, including the scalp, trunk, and extremities; detection of sequences from HPV types 6, 11, 16, and 18 in epithelioma cuniculatum and type 11 sequences in oral verrucous carcinoma raises the possibility that these tumors evolve from verruca vulgaris

Type IV

May be signaled by a palpable lymph node near the site of treatment of a previous SCC; May present as large keratotic papules or nodules resembling the primary lesion; Or may be clusters of firm pink or red papules that may be keratotic centrally

Metastatic SCC

Histopathology: extension of atypical keratinocytes beyond the basement membrane and into the dermis; tumor may appear as single cells, small groups or nests of cells, or a single mass; squamous differentiation is seen as foci of keratinization in concentric rings of squamous cells called horn pearls

Squamous cell carcinoma

Histologic grading of SCC is based on

Degree of cellular differentiation

Broders’ Grading System for Squamous Cell Carcinoma

1 - <25; uniform cells, resembling mature keratinocytes, with intracellular bridges and keratin production 2 - <50 3 - <75 4 - >75; atypical cells, loss of intracellular bridges, and minimal or absent keratin production

Histopathology: SCC variant with tubular microscopic pattern and keratinocyte acantholysis

Adenoid (or pseudoglandular) SCC

Histopathology: SCC variant with keratinocytes that appear clear as a result of hydropic cytoplasmic swelling and accumulation of lipid vacuoles

Clear cell SCC

Histopathology: SCC variant with spindle-shaped atypical cells

Spindle cell SCC

Histopathology: SCC variant with characterized by concentric rings composed of keratin and large vacuoles corresponding to markedly dilated endoplasmic reticulum

Signet-ring cell SCC

Histopathology: the superficial component resembles verruca vulgaris with prominent acanthosis and papillomatosis, whereas the deeper component extends downward, displacing collagen bundles

Verrucous carcinoma

Histopathology: reveals a symmetric keratin-filled crater, with the epidermis on each side extending over to form a distinct lip

Keratoacanthoma

Diagnosis of Squamous cell carcinoma

Skin biopsy

High risk Squamous cell carcinoma

``` Diameter >2 cm Depth >4 mm and Clark level IV or V Tumor involvement of bone, muscle, nerve Location on ear, lip Tumor arising in scar Broders grade 3 or 4 Patient immunosuppression Absence of inflammatory infiltrate ```

Treatment: Squamous cell carcinoma

``` Nonexcisional ablative techniques (in situ disease only, or in special circumstances) Mohs micrographic surgery Conventional surgical excision Topical therapy (in situ disease only) Radiation therapy ```

Treatment of choice for small primary SCCs

Conventional surgical excision

Margins for excision of small primary SCCs

4 mm - for low-risk lesions or SCCs with a depth of less than 2 mm Mohs micrographic surgery - for lesions with a depth of more than 6mm or a diameter >1 cm

Indications for Mohs Micrographic Surgery

Infiltrative squamous cell carcinoma (SCC) Poorly dedined clinical margins Location on lip, ear, nail bed, nasal tip, eyelid, genitalia History of radiation at site Involvement of nerve, bone, muscle Immunosuppressed patient Recurrence of large SCC Verrucous carcinoma SCC arising from chronic scarring conditions

Can be used to treat superficially invasive to moderate-risk lesions and serves as an important adjuvant to excisional surgery in treating residual microscopic disease and providing prophylaxis against metastatic disease; may also be used as adjuvant therapy in cases in which perineural SCC was identified in surgical pathologic specimens but treatment failures occurred

Radiation therapy

Treatment: Squamous cell carcinoma (topical)

5-Fluorouracil once or twice daily for 2-4 weeks | Imiquimod 3-5 times per week for 2-4 months

May be due to enhanced interferon-γ production and effector function of T cells infiltrating the tumor

Imiquimod

Recurrence rate: Mohs micrographic surgery (Primary SCC)

3.1%

Recurrence rate: electrodesiccation and curettage (Primary SCC)

3.7%

Recurrence rate: excisional surgery (Primary SCC)

8.1%

Recurrence rate: radiation (Primary SCC)

10%

Recurrence rate: Mohs micrographic surgery (Lip SCC)

2.3%

Recurrence rate: Mohs micrographic surgery (Ear SCC)

5.3%

Most common cancer in humans and accounts for approximately 75% of all nonmelanoma skin cancers; more common in elderly; develops on sun-exposed skin of lighter skinned individuals

Basal cell carcinoma

Risk factors: Basal cell carcinoma

Ultraviolet light (UVL) exposure Light hair and eye color Northern European ancestry Inability to tan

The pivotal abnormality in all BCCs, and there is evidence that little more than this upregulation is required for BCC carcinogenesis.

Hedgehog (HH) pathway

Heritable conditions pre- disposing to the development of BCC

Nevoid basal call carcinoma syndrome or basal cell nevus syndrome (BCNS) Bazex syndrome Rombo syndrome

May develop hundreds of BCCs and may exhibit a broad nasal root, borderline intelligence, jaw cysts, palmar pits, and multiple skeletal abnormalities;occurs due to mutations in the tumor suppressor PTCH gene

Basal cell nevus syndrome

Transmitted in an X-linked dominant fashion; have multiple BCCs, follicular atrophoderma, dilated follicular ostia with ice pick scars, hypotrichosis, and hypohidrosis

Bazex syndrome

Transmitted in an autosomal dominant fashion; have vermiculate atrophoderma, milia, hypertrichosis, trichoepitheliomas, BCCs, and peripheral vasodilation; no hypohidrosis

Rombo syndrome

Presents with a friable, nonhealing lesion that bled briefly then healed completely, only to recur; usually develops on sun-exposed areas of the head and neck but can occur anywhere on the body with features include translucency, ulceration, telangiectasias, and the presence of a rolled border

Basal cell carcinoma

Most common clinical subtype of BCC which most commonly on the sun-exposed areas of the head and neck and appears as a translucent papule or nodule depending on duration; usually with telangiectasias and a rolled border; larger lesions with central necrosis are referred to by the historical term rodent ulcer

Nodular basal cell carcinoma

Subtype of BCC that exhibits increased melanization; appears as a hyperpigmented, translucent papule, which may also be eroded

Pigmented basal cell carcinoma

Subtype of BCC that occurs most commonly on the trunk and appears as an erythematous patch often well demarcated that resembles eczema that does not respond to treatment

Superficial basal cell carcinoma

An aggressive growth variant of BCC with a distinct clinical and histologic appearance; lesions may have an ivory-white appearance and may resemble a scar or a small lesion of morphea

Morpheaform (Sclerosing) basal cell carcinoma

Presents as a pink papule, usually on the lower back which may be difficult to distinguish from an acrochordon or skin tag; express androgen receptors

Fibroepithelioma of Pinkus

Seen most often with recurrent tumors located in the preauricular and malar areas; occurs most often in histologically aggressive or recurrent lesions; has been correlated with recurrent lesions, increased duration and size of lesions, and orbital invasion; may manifest as pain, paresthesias, weakness, or paralysis

Perineural invasion

Metastasis of BCC occurs only rarely, with rates varying from

0.0028 - 0.55%.

Site of predilection: BCC

Nodular and morpheaform - head and neck | Superficial - trunk

Histopathology: account for half of all BCCs and are characterized by nodules of large basophilic cells and stromal retraction; characterized by discrete nests of basaloid cells in either the papillary or reticular dermis accompanied

Nodular basal cell carcinoma

Histopathology: melanocytes are interspersed between tumor cells and contain numerous melanin granules in their cytoplasm and dendrites; tumor cells contain little melanin but numerous melanophages populate the stroma surrounding the tumor

Pigmented basal cell carcinoma

Histopathology: microscopically by buds of malignant cells extending into the dermis from the basal layer of the epidermis; peripheral layer shows palisading cells; there may be epidermal atrophy, and dermal invasion is usually minimal; there may be a chronic inflammatory infiltrate in the upper dermis

Superficial basal cell carcinoma

Histopathology: consists of strands of tumor cells embedded within a dense fibrous stroma; tumor cells are closely packed columns and, in some cases, only 1-2 cells thick enmeshed in a densely collagenized fibrous stroma; strands of tumor extend deeply into the dermis

Morpheaform (Sclerosing or Infiltrative) basal cell carcinoma

Histopathology: long strands of interwoven basiloma cells are embedded in fibrous stroma with abundant collagen.

Fibroepithelioma of Pinkus

Histopathology: shows infiltrating jagged tongues of tumor cells admixed with other areas that show squamous intercellular bridge formation and cytoplasmic keratinization

Basosquamous carcinoma

Gold standard for treating basal cell carcinoma

Excision with clear margins

Offers superior histologic analysis of tumor margins while permitting maximal conservation of tissue compared with standard excisional surgery

Mohs micrographic surgery

Treatment of choice for morpheaform, poorly delineated, incompletely removed, and otherwise high-risk primary BCCs; preferred treatment for recurrent BCC and for any BCC that occurs at a site where tissue conservation is desired; used in treating BCCs at high-risk anatomic sites, including the nasofacial junction and retroauricular sulcus

Mohs micrographic surgery

Margins needed in excision for BCC

``` <2cm - 4 mm <1 cm - 0.5-cm 1-2 cm - 0.8-cm margin >2 cm - 1.2- cm 5 mm - primary morpheaform BCC ```

One of the most frequently used treatment modalities for BCC that is operator-dependent

Curettage and Desiccation

Destructive modality that has been used in the treatment of BCC; 2 freeze-thaw cycles with a tissue temperature of −50°C (−58°F) are required to destroy BCC with a margin of clinically normal tissue destroyed

Cryosurgery

Potential serious adverse outcome with cryosurgery for BCC

Obscuring of tumor recurrence by fibrous scar tissue

A Toll-like receptor 7 agonist believed to induce interferon-α, tumor necrosis factor-α, and other cytokines to boost T helper 1 type immunity which is approved by the FDA for the topical treatment of biopsy-confirmed, small (<2 cm), primary superficial BCC

Imiquimod 5% cream

Can be consideration as a monotherapy only for superficial BCCs limited to small tumors in low-risk locations in patients who will not or cannot undergo treatment with other better-established therapies

Imiquimod 5% cream

A topically applied chemotherapeutic agent that is metabolized by dihydropyrimidine dehydrogenase, used in the treatment of actinic keratoses, has also been used to treat BCCs; generally well tolerated with a good cosmetic outcome, with the majority of patients having no pain or scarring and only mild erythema

5-Flurouracil

HHI compound, plant alkaloid, which competitively inhibits SMO protein signaling and therefore inhibiting the growth of malignant cells driven by HH activation

Cyclopamine

Involves the activation of a photosensitizing drug by visible light to produce activated oxygen species that destroy the constituent cancer cells; exogenous ALA increases intracellular production of the endogenous photosensitizer protoporphyrin type IX, which preferentially accumulates in tumor cells

Photodynamic therapy

May be useful in cases of primary BCC or as adjunct treatment for BCC when margins are positive after excision or for extensive perineural or large nerve involvement; include minimal patient discomfort and avoidance of an invasive procedure for a patient unwilling or unable to undergo surgery

Radiation therapy

Disadvantages: Radiation therapy (BCC)

Lack of histologic verification of tumor removal Prolonged treatment course Cosmetic result that may worsen over time (cutaneous atrophy and telangiectasia) Predisposition to aggressive and extensive recurrences

Rare AD disorder associated with a panoply of phenotypic abnormalities with mutations in the PATCHED1 gene residing on the long arm of chromosome 9, which plays a central role in the hedgehog signaling pathway that is essential for the establishment of normal body and limb patterning in metazoan organisms

Basal cell nevus syndrome (BCNS) or Nevoid basal cell carcinoma syndrome or Gorlin syndrome

Three abnormalities considered to be most characteristic of the Basal cell nevus syndrome:

Tumors such as medulloblastomas or BCCs Pits of the palms and soles Odontogenic cysts of the jaw

First detectable abnormality in BCNS which may be asymptomatic and therefore diagnosed only radiologically but may also may erode enough bone to cause pain, swelling, and loss of teeth

Jaw cysts

Major Criteria for BCNS

1. Basal cell carcinoma before age 20 years 2. Odontogenic keratocysts before age 15 years 3. 3 or more palmar and/or plantar pits 4. Bilamellar calcification of the falx cerebri (if younger than 20 years) 5. Fused, bifid, or markedly splayed ribs 6. First-degree relative with BCNS 7. PTCH gene mutation in normal tissue

Minor Criteria for BCNS

1. Macrocephaly determined after adjustment for height 2. Congenital malformations: cleft lip or palate, frontal bossing, “coarse face,” moderate or severe hypertelorism 3. Skeletal abnormalities: Sprengel deformity, marked pectus deformity, or marked syndactyly of the digits 4. Radiologic abnormalities: bridging of the sella turcica; rib anomalies such as bifid or splayed ribs; vertebral anomalies such as hemivertebrae, fusion, or elongation of the vertebral bodies; modeling defects of the hands and feet; or flame-shaped lucencies of the hands or feet 5. Ovarian fibroma 6. Medulloblastoma

Acquired and associated with autoimmune disease and demonstrate histologic variants of BCCs, with more hamartomatous lesions, and are characterized by palmar pits and milia

Generalized basaloid follicular hamartoma

Linked to the PTCH1 locus and thus may be due to a PTCH1 allele which demonstrate histologic variants of BCCs, with more hamartomatous lesions, and are characterized by palmar pits and milia

Multiple hereditary infundibulocystic BCC

Common epithelial tumor of the skin characterized by rapid growth, histopathologic features similar to those of cutaneous squamous cell carcinoma, and a certain tendency toward spontaneous regression; more frequent in light-skinned persons

Keratoacanthoma

Most common sites of Keratoacanthoma

Sun-exposed skin of the face, forearms, and dorsal aspects of the hands

Solitary lesion growing rapidly within a few weeks, and subsequently showing a slow involution over a period of a few months

Keratoacanthoma

In this stage, rapidly enlarging erythematous papules that grow up to a dimension of 1-2 cm or more; the lesions are symmetric and firm and show a smooth surface

Proliferative stage

In this stage, there are symmetric, firm, erythematous or skin-colored nodules with a central keratotic core where the central part can appear crateriform if the keratotic core is removed

Mature stage

In this stage, regressing lesions are characterized by a keratotic, partly necrotic nodule that becomes progressively flat upon elimination of the keratotic plug, eventually leaving a hypopigmented scar

Resolving stage

Patients with multiple keratoacanthomas should always be evaluated for

Muir-Torre syndrome

Characterized by multiple tumors growing on a localized area, usually on the face, trunk, or extremities; tumors are annular, polycyclic, or circular in morphology; area affected may reach 20 cm in diameter, and resolution may be slower than in solitary keratoacanthoma

Keratoacanthoma centrifugum marginatum

Familial form of keratoacanthoma inherited AD that affects both sexes with equal severity, characterized by the appearance of multiple, sometimes hundreds of keratoacanthomas, each with the clinicopathologic aspects of a solitary keratoacanthoma; usually develop during adolescence and early adulthood

Mulitple keratoacanthomas of Ferguson-Smith type

Keratoacanthomas may reach dimensions of several centimeters (may reach 15 cm in its diameter); show a predilection for the nose and the dorsum of the hands

Giant keratoacanthom

Variant characterized by the presence of hundreds to thousands of tiny follicular keratotic papules disseminated all over the body, with predominance on sun-exposed areas; facial involvement is usually severe, and coalescence of lesions around the eyes may cause ectropion

General eruptive keratoacanthomas of Grzybowski

Differs from the other types of keratoacanthoma by being persistent and often causing destruction of the underlying bone; tumor originates in the distal nail bed, separating the nail plate from the nail bed, and can grow rapidly causing destruction of the entire phalanx

Subungual keratoacanthoma

Keratoacanthomas described in the oral, conjunctival, nasal, and genital areas; present clinically as slowly growing crateriform lesions that tend to persist for many months or years

Keratoacanthoma of the mucosal region

Histopathology: characterized by a large central core of keratin surrounded by a well-differentiated proliferation of squamous epithelium that may resemble SCC; epidermis at both sides of the central core extends over the keratotic area in a fashion that has been described as “lipping” or “buttressing,” giving a distinct crateriform appearance; nests and strands of keratinocytes may be found apart from the main bulk of the tumor but usually do not extend lower than the level of sweat glands

Keratoacanthoma

Associated with an increased risk of Merkel cell carcinoma

Sunlight Prolonged UV exposure Photochemotherapy

Present in 80% of MCC tumors which is a small, circular, double-stranded DNA virus related to other known polyomaviruses and only one proven to integrate into a human cancer

Merkel cell polyomavirus (MCPyV)

Clinical features of Merkel cell carcinoma | at least 3

Asymptomatic (non-tender, firm, red, purple, or skin-colored papule or nodule) Expanding rapidly (significant growth noted within 1-3 months of diagnosis, but most lesions are <2 cm at time of diagnosis) Immune suppression (e.g., HIV/AIDS, chronic lymphocytic leukemia, solid organ transplant) Older than 50 years Ultraviolet-exposed site on a person with fair skin

Histopathology: small basophilic cells with scant cytoplasm, fine chromatin, and no nucleoli; numerous mitotic figures and occasional individual necrotic cells; lymphovascular invasion is a very common feature and often can be found when it is specifically searched for even in a “negative” margin

Merkel cell carcinoma

This is the most common and has uniform small cells with minimal cytoplasm, pale nuclei, and a dispersed chromatin appearance. On hematoxylin and eosin staining, the differential diagnosis for this presentation is that of the small, blue-cell tumors including melanoma and lymphoma.

Intermediate type MCC

This takes its name from small cell lung carcinoma, which is the principal differential diagnosis for this pattern. It shows irregular, hyperchromatic cells with scant cytoplasm and malignant cells that are arranged in linear patterns in ltrating stromal structures.

Small cell type MCC

The least common but perhaps most histologically distinctive type. It has a lattice-like, or network appearance, and the differential diagnosis includes metastatic carcinoid tumor.

Trabecular type MCC

The single most useful stain for MCC with “perinuclear dot” pattern

Cytokeratin 20

A cocktail of antibodies that detects multiple human cytokeratin epitopes, typically reacts with both MCC and small cell lung carcinoma

CAM 5.2

Negative in MCC and positive in small cell lung cancer and thus useful for the differential diagnosis between these two tumors

Thyroid transcription factor-1 | Cytokeratin-7

Sensitive test for detecting MCC spread to the lymph nodes

Sentinel lymph node biopsy

Defined as tumor emboli within vascular spaces and indicates a worse overall survival

Lymphovascular invasion (LVI)

Described as nodular (well-circumscribed interface between tumor and surrounding tissue) or infiltrative (rows, trabeculae, or single cells that penetrate the dermis)

Tumor growth pattern

Optimal treatment for MCC

Obtaining pathologically clear margins by surgery, typically with 1-2 cm margins

The typical doses of radiation for MCC (primary site with negative excision)

50-56 Gy given in 2-Gy fractions, five times/week over 4-6 weeks

Most significant potential side effect of Radiation therapy

Lymphedema (more common in lower extremities)

Chronic radiation skin changes

Temporary or permanent alopecia within the irradiated field Epidermal atrophy Loss of adnexal structures leading to skin or mucosal dryness Risk of subsequent secondary skin cancers in the irradiated region in patients with a life expectancy of greater than 20 years after the radiation treatment

Most commonly used chemotherapeutic regimen for MCC useful in palliation for symptomatic disease that is otherwise inoperable

Combination of etoposide and either cisplatin (perhaps more clinically effective) or carboplatin (less nephrotoxic)

5 good prognostic features in MCC

1. Primary tumor diameter ≤1 cm 2. Microscopic margins that are confidently negative following surgery 3. No lymphovascular invasion noted in the tumor 4. No profound immune suppression (HIV, chronic lymphocytic leukemia, etc.) 5. SLNB that was negative with proper immunohistochemistry studies

Rare neoplasm that affects apocrine gland-bearing skin such as the vulva, perianal region, scrotum, and penis with majority of patients in the sixth through eighth decades of life; genitals are the most commonly affected area, representing 2% of all vulvar malignancies

Extramammary Paget disease

Most common visceral malignancies associated with EMPD

Carcinomas of the rectum, bladder, urethra, cervix, and prostate

Present with a long-standing history of pruritic, erythematous, scaly, or velvety patches on the breast or in apocrine-rich areas such as the groin, perineum, or axilla

Extramammary Paget disease | Mammary Paget disease

Presents as a unilateral, erythema- tous, scaly plaque involving the nipple and/or the areola; ulceration and weeping with an eczematous appearance is frequently present; nipple erosion and discharge may occur; retraction of the nipple can be seen and usually pain, burning, and pruritus

Mammary Paget disease

Present as a well-defined, moist, erythematous, scaly, eczematous plaque; hypo- and hyperpigmentation can occur with burning and intense pruritus; lesions typically involve apocrine gland-bearing skin (i.e., genitoperineal region and axilla); most frequent site is the vulva, but perineal, scrotal, perianal, and penile skin can also be affected

Extramammary Paget disease

Histopathology: groups, clusters, or single cells within the epidermis that show nuclear enlargement with atypia, prominent nucleoli, and well-defined ample cytoplasm; intercellular bridges are absent. cells can be within all levels of the epidermis and can com-press but preserve the basal layer without junctional nest formation and can extend into the contiguous epithelium of hair follicles and sweat gland ducts; these cells have a “pagetoid” appearance; acanthosis, hyperkeratosis, and parakeratosis are often present.

Extramammary Paget disease | Mammary Paget disease

Sensitive markers for both MPD and EMPD

``` Cytokeratin 7 (CK 7) Anticytokeratin (CAM 5.2) ```

A marker for apocrine epithelium and is typically positive in primary EMPD (not associated with underlying neoplasm) but is negative in those cases of secondary EMPD with an associated malignancy

Gross cystic disease fluid protein-15 (GCDFP-15)

Regulatory gene involved in intestinal proliferation and has been suggested as a useful maker in EMPD associated with underlying colorectal tumors

CDX2

Mucin core protein (MUC) expression

MUC1 - MPD and EMPD MUC2 - secondary EMPD with an associated underlying gastrointestinal adenocarcinoma MUC5AC - primary EMPD

Most common sites of metastases of MPD/EMPD

Lymph nodes | Bone and lung

Most common benign epidermal tumor of the skin and a frequent focus of patient concern; common in middle-aged individuals; these lesions usually begin as well-circumscribed, dull, flat, tan, or brown patches that become more papular, taking on a waxy, verrucous, or stuck-on appearance with color ranging from pale white to black

Seborrheic keratosis

Classically described as a stuck-on, verrucous plaque with pseudohorn cysts; hyperkeratosis, acanthosis, and papillomatosis are hallmark pathologic findings; increased number of melanocytes may also be present, giving lesions a tan or dark brown color; usually asymptomatic but may itch

Common SK

Also known as adenoid SKs; believed a solar lentigo usually precedes this pigmented patch or papule; histologically, there are small horn cysts suspended among interwoven strands of basophilic cells

Reticulated SK

Described as verrucous, serrated, hyperkeratotic, and digitate; these lesions are commonly 1-3 mm, flat-topped, white to tan papules that adhere tightly to the skin on the lower legs; histologically, no keratinocytic vacuolar changes or viral cytopathic changes are observed, thus distinguishing them from verruca plana

Stucco keratosis

Also known as pigmented SK; benign, slow-growing SK resembles melanoma clinically, and is often located on the trunk, head, or neck of older individual; a pigmented lesion composed of nested melanocytes and keratinocytes

Melanoacanthoma

Small dark brown to black papules that are commonly found on the face of individuals of Fitzpatrick skin phototype IV or greater; histologically identical to SKs

Dermatosis papulosa nigra

Share clinical and histologic overlap with SK; rough, 1-2 mm pedunculated papules commonly located in areas of friction such as axilla, inframammary area, and neck; spontaneous regression can occur

Acrochordon or Skin tags

Histologic term used to describe intraepithelial nests of basophilic keratinocytes of varying sizes with admixed melanocytes

Clonal SK

Represent SKs that have been mechanically or chemically irritated or are involved in immunologic responses; may be from inciting trauma but can also be spontaneous inflammation; histologically, the dermis is filled with a dense inflammatory infiltrate predominantly of lymphocytes, occasionally lichenoid or neutrophil rich; swirled collections of eosinophilic keratinocytes can be seen in the epidermis; eczematous changes in or around the lesion, also known as Meyerson phenom- enon, can be seen

Irritated SK

In the context of internal malignancy with adenocarcinoma of the stomach being the most commonly associated malignancy, individuals can develop multiple, eruptive SKs also known as the

Leser-Trelat sign

Generalized term for hamartomatous proliferations of epithelium including keratinocytes, sebocytes, pilosebaceous units, eccrine glands, or apocrine glands

Epidermal nevus

Six different epidermal nevus syndromes described

1. Proteus syndrome 2. Congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome 3. Phakomatosis pigmentokeratotica 4. Sebaceous nevus 5. Becker’s nevus 6. Nevus comedonicus

Characterized by localized or diffuse, closely set, skin-colored, brown, or gray-brown verrucous papules, which may coalesce to form well-demarcated papillomatous plaques; linear configurations are common on the limbs as is distribution in Blaschko’s lines or in relaxed skin tension lines

Verrucous epidermal nevus

Extensive distribution of a verrucous epidermal nevus which take on a transverse configuration on the trunk and linear configuration on the limbs

Systemized epidermal nevus

An epidermal nevus presenting with pruritus, erythema, and scaling found most commonly on the buttocks and lower extremities

Inflammatory linear verrucous epidermal nevus (ILVEN)

Histopathology: hyperkeratosis, acanthosis, papillomatosis, and elongation of rete ridges

Epidermal nevus

Histopathology: chronic dermal inflammatory infiltrate, psoriasiform epidermal hyperplasia, and alternating bands of ortho- and parakeratosis; granular layer is absent underlying the areas of parakeratosis

Inflammatory linear verrucous epidermal nevus (ILVEN)

Differential diagnosis for Linear epidermal nevus

``` Lichen striatus Linear Darier disease Linear porokeratosis Linear lichen planus Linear psoriasis Incontinentia pigmenti ```

Presents as a linear, hairless, yellow, waxy, and verrucous plaque; can be flat at birth, becoming plaque-like under the hormonal influences of puberty. common in the scalp

Nevus sebaceous (of Jadasshon)

Most common benign tumors arising from Nevus sebaceous

Syringocystadenoma papilliferum Trichoblastoma ``` Leiomyoma Syringoma Spiradenoma Hidradenoma Keratoacanthoma ```

Very rare association of an extensive, congenital nevus sebaceous with ocular abnormalities and cerebral defects such as mental retardation or seizures

Nevus sebaceous syndrome or | Schimmelpenning-Feuerstein-Mims syndrome

Histopathology: immature sebaceous glands located high in the dermis and malformed pilosebaceous units; vellus hairs are more common than terminal hairs; epidermal acanthosis, hyperkeratosis, and pseudoepitheliomatous hyperplasia

Nevus sebaceous

Rare hamartoma of the pilosebaceous unit which presents as comedo-like dilated pores with keratinaceous plugs present in a linear, nevoid, bilateral, or zosteriform pattern which appear on the face, chest, or upper arms at birth or during childhood; an inflammatory variant also exists, with suppurative cysts and acne-like lesions

Nevus comedonicus

Association of nevus comedonicus with noncutaneous findings such as skeletal defects, cerebral abnormalities, and cataracts by the age 15 years

Nevus comedonicus syndrome

Histopathology: keratin-filled epidermal invaginations associated with atrophic sebaceous glands or follicles; epidermolytic hyperkeratosis may be seen

Nevus comedonicus

Simplest form of eccrine hamartoma, which is characterized by an increase in the number or size of eccrine coils; distributed on the trunk, arms, or legs, these lesions occur equally in men and women which may appear as an papules or normal skin

Eccrine nevus

Hamartomatous proliferations of mature apocrine glands often found within a nevus sebaceous; can be found as soft nodules or papules in the axilla or on the upper chest; histologically, the apocrine glands extend from the epidermis to the fat

Apocrine nevus

Cutaneous findings in Epidermal nevus syndrome

Epidermal nevus Hemangioma Pigmentary changes (Café-au-lait spots, hypopigmentation, Melanocytic nevi) Dermatomegaly (increase in skin thickness, warmth, and hairiness) Cutaneous malignancies (Keratoacanthoma, Basal cell carcinoma, Squamous cell carcinoma, Syringocystadenoma papilliferum, Other adnexal tumor)

Gene: Proteus syndrome

AKT1

Self-limited dermatosis most commonly affects individuals from 4 months to 15 years of age usually on the limbs in females presents with eruption characterized by the sudden onset of flat-topped, 1-3 mm, pink, tan, or hypopigmented papules in a linear configuration or Blaschkoid distribution may have an associated scale with longitudinal ridging and nail plate thinning

Lichen striatus or Blaschko linear acquired inflammatory skin eruption

Histopathology: characterized by a lichenoid, lymphocytic infiltrate involving 3-4 adjacent dermal papillae with overlying epidermal acanthosis, dyskeratosis, hyperkeratosis, and occasional parakeratosis; intraepidermal vesicles containing Langerhans cells can be seen

Lichen striatus

Tumor of epidermal origin most commonly found equally in men and women ages in the sixth to eighth decade; presents as a solitary, shiny, erythematous to brown, well-demarcated papule or nodule that blanches almost fully with pressure with surrounding collarette of scale, ranges from 5 mm to 2 cm usually found on the legs but can be located on the trunk and face which bleed with trauma

Clear cell acanthoma

Histopathology: sharply demarcated, pale-staining keratinocytes within a background of epidermal psoriasiform hyperplasia; suprapapillary plate thinning, neutrophils, and sparing of adnexal epidermis; mixed inflammatory infiltrate, papillary dermal edema, and enlarged vessels can be seen in the dermis

Clear cell acanthoma

Solitary focus of acantholytic dyskeratosis which presents as a solitary, skin-colored, umbilicated papules located on the head or neck

Warty dyskeratoma (Isolated dyskeratosis follicularis)

Histology: cup-shaped epidermal invagination with acantholysis and dyskeratosis filled with keratinaceous material

Warty dyskeratoma (Isolated dyskeratosis follicularis)

Fissured or ulcerated, usually retroauricular nodule that appears in areas of friction, as with ill-fitting eyeglasses which usually resolve after correction of ill-fitting appliance

Acanthoma fissuratum

Disease of degenerated collagen that undergoes transepithelial elimination found in adult men over the age of 50 present with a history of a suddenly appearing, skin-colored to pink papule or nodule on the ear that grew rapidly and subsequently remained quiescent (tend to be on the right helix, measuring less than 1 cm, and associated with pain which can be paroxysmal or associated with changes in ambient temperature); may have a central ulceration with an adherent hemorrhagic or scale crust

Chondrodermatitis nodularis helicis

Histopathology: hyperkeratosis and parakeratosis; ulceration may be present; degenerated collagen may be seen in the epidermis; predominantly lymphocytic infiltrate is noted in the dermis with admixed histiocytes and few neutrophils; perichondrium shows inflammation and fibrous thickening; cartilage may show hyalinization, necrosis, and, ossification

Chondrodermatitis nodularis helicis

Keratin-filled epithelial-lined cyst found most commonly in adult men and women most commonly the result of plugged pilosebaceous units but can also be caused by the traumatic implantation of epidermal cells into deeper tissues or by the proliferation of viable epidermal remnants along embryonic fusion planes which are classically skin-colored, yellow, or white dermal or subcutaneous mobile nodules with a central punctum

Epidermoid cyst

Histopathology: stratified, squamous lining with an intact granular layer containing central, eosinophilic, keratinaceous debris that can incite a foreign-body reaction of multinucleated giant cells and histiocytes when released into the dermis and surrounding tissue

Epidermoid cyst

Definitive treatment: Epidermoid cyst

Complete excision or destruction | of the cyst lining (to prevent recurrence)

Keratin-filled, epithelial-lined cysts that arise from the outer root sheath of the hair follicle, most commonly in middle-aged women presents as mobile, firm, well-circumscribed nodules located in the scalp and on the face, head, and neck

Trichilemmal cyst or Pilar cyst

Histopathology: absence of a granular layer within the cyst wall with usually eosinophilic keratin, but basophilic areas of calcification may occur in the lumen; invasion of the cyst lining into the surrounding tumor indicates malignancy

Trichilemmal cyst or Pilar cyst

Minute epidermoid cysts, lined with epidermis and filled with keratin which are thought to result from pilosebaceous or eccrine sweat duct plugging; presents as 1-2 mm, white, domed papules commonly located on the cheeks and eyelids of adults

Milia

Plaque-type, inflammatory variant of milia that is commonly located on the ear

Milia en plaque

Milia on the palate

Epstein’s pearls

Histopathology: stratified, squamous lining with an intact granular layer containing central, eosinophilic, keratinaceous debris but smaller size and occasional connection to eccrine ducts or vellus hair

Milia

Numerous, epithelial-lined, sebum-filled dermal cysts with characteristic sebaceous glands in the cyst walls which can be a sporadic or AD disorder; presents as asymptomatic, yellow or skin-colored dermal papules or cysts located most commonly on the trunk, upper arms, scrotum, or chest with expression of oily material

Steatocystoma multiplex

Histopathology: walls are composed of stratified, squamous epithelium with an absent granular layer; sebaceous glands are located in the cyst wall; there is an eosinophilic cuticle on the luminal side of this wall with keratin, oil, and hairs in the lumen

Steatocystoma multiplex

Epithelial-lined cysts containing various appendageal structures resulting from retained epithelium along embryonic fusion planes; smooth, occur in the midline, and commonly possess a deep sinus tract that connects to the epidermis; can measure between 1-4 cm, and are most commonly located on the forehead, lateral eye, or neck but can also be can be located deep in the subcutaneous tissue, intracranially, or intraorbitally

Dermoid cyst

Histopathology: stratified squamous epithelium with a variety of adnexal structures may be present; smooth muscle, pilosebaceous units, apocrine or eccrine glands, or goblet cells may also be present in the cyst walls which contain keratin and hairs

Dermoid cyst

Sequestration of 1st or 2nd branchial cleft membranes results in these cysts, sinuses, or tags which are largely sporadic usually asymptomatic often located along the angle of the mandible if arising from the 1st branchial cleft and the middle to lower third of the anterior border of the sternocleidomastoid in cases arising from the 2nd branchial cleft; may present after an upper respiratory infection as a painful mass

Branchial cleft cysts

Histopathology: cysts containing mucin are lined with epithelium containing lymphoid follicles, mucous glands, or smooth muscle with dense lymphocytic infltrate may also be seen

Branchial cleft cysts

Epithelial invaginations located in the preauricular area

Preauricular cysts or sinuses

Characterized by an increased number of normal cells in a normal arrangement

Hyperplasia

Described as an abnormal arrangement of normal tissue

Hamartoma

The treatment of choice for the majority of benign appendageal tumors

Surgical excision

Two systemic syndromes associated with sebaceous lesions

Muir-Torre syndrome | Epidermal nevus syndrome

Stage of nevus sebaceous characterized by papillomatous epithelial hyperplasia and underdeveloped hair follicles

Initial stage

Stage of nevus sebaceous which commences at puberty and is associated with remarkable sebaceous gland development, epidermal verrucous hyperplasia, and the maturation of apocrine glands; clinically, this correlates with progressive thickening and development of a pebbly verrucous surface

Second stage

Stage of nevus sebaceous which involves the development of benign and malignant neoplasms within the nevus sebaceous

Final stage

A benign enlargement of the sebaceous lobule around a follicular infundibulum common in patients with significant sun exposure in age 40 males which presents as solitary or multiple small ∼3 mm yellow or flesh-colored telangiectatic papules with a central dell on the central face

Sebaceous (gland) hyperplasia

Conditions associated with sebaceous hyperplasia

Renal transplantation Chronic immunosuppression with cyclosporine ``` Chronic renal failure Hemodialysis Corticosteroids Muir-Torre syndrome Pachydermoperiostosis X-chromosomal ectodermal dysplasia ```

Dermoscopy: yellow papule with telangiectasias and a central crater

Sebaceous (gland) hyperplasia

Histopathology: large mature sebaceous lobules clustered around discrete, often dilated, infundibula located in the upper dermis

Sebaceous (gland) hyperplasia

Benign tumors present on the head (70%) and neck of elderly individuals that serve as a marker for Muir-Torre syndrome; usually presents as a smooth, well-circumscribed, slow-growing pink, flesh-colored, or yellow papule or nodule measuring less than 0.5 cm;

Sebaceous adenoma

Histopathology: reveal multiple well-circumscribed sebaceous lobules; 2 cell populations: 1. peripheral basaloid germinative cells and 2. mature lipid-filled vacuolated sebocytes in the center of the lobule; mature sebocytes outnumber the undifferentiated germinative cells; lack atypia, necrosis, and invasive growth

Sebaceous adenoma

Most common neoplasm associated with Muir-Torre syndrome, occurring in 68% of patients where lesions tend to occur on the trunk

Sebaceous adenoma

Rare aggressive neoplasm that typically presents on the eyelids (more commonly upper) of elderly individuals (1-5.5% of all eyelid malignancies) clinically presents as a painless, slowly enlarging, subcutaneous nodule

Sebaceous carcinoma

Histopathology: characterized by asymmetric, irregular sebaceous lobules centered in the dermis; lesions are classified as well, moderately, or poorly differentiated, based on varying degrees of differentiation; tumor cells show remarkable variation in nuclear shape and size, pleomorphism, hyperchromatism, and mitotic activity and may extend into the subcutaneous fat or muscle

Sebaceous carcinoma

Four histologic patterns of Sebaceous carcinoma

Lobular Comedocarcinoma Papillary Mixed

Most common site of metastasis for Sebaceous carcinoma

Regional lymph nodes

Standard treatment for Sebaceous carcinoma

Local excision with 5-6 mm margins (Recurrence rate of 36%)

AD disorder due to inactivating germ-line mutations in the DNA mismatch repair genes MSH2, MLH1, and MSH6, leading to microsatellite instability characterized by sebaceous neoplasms, keratoacanthomas, internal malignancies, and personal or family history of this syndrome

Muir-Torre syndrome

Most common visceral malignancy in Muir-Torre syndrome

Colon cancer

Sensitive, rapid, inexpensive, convenient method for screening patients with suspected Muir-Torre syndrome

Immunohistochemical staining for mismatch repair genes

Confirms the diagnosis of Muir-Torre syndrome

Gene sequencing

Relatively common cystic lesions that present, in middle-aged or elderly individuals with slight female predilection, as solitary, smooth, translucent, flesh-colored or bluish, 1-3 mm papules on the head or neck, particularly in the periorbital region usually asyptomatic, and enlarge until a certain size is attained

Apocrine hidrocystomas

AR ectodermal dysplasia characterized chiefly by multiple eyelid apocrine hidrocystomas, palmoplantar keratoderma, hypodontia, hypotrichosis, and nail dystrophy

Schopf-Schulz-Passarge syndrome

Histopathology: a unilocular or multilocular cyst located in the dermis; epithelial lining consists of a single or double layer of cuboidal-columnar epithelium lying adjacent to an outer myoepithelial layer; decapitation secretion is notable; prominent papillations protruding into the lumen are seen in some cases

Apocrine hidrocystomas

Hamartoma consisting of a proliferation of normal appearing apocrine glands in the dermis; 2 variants: 1. pure apocrine nevus, rare, and presents as a unilateral or bilateral, soft, lobulated, dermal mass in the axilla or scalp; 2. more common variant occurs as a part of a nevus sebaceus occurring as multiple papules on the chest

Apocrine nevus

Histopathology: numerous, discrete, closely spaced tubular structures in the dermis and/ or subcutaneous fat where tubules are lined with typical apocrine glandular epithelium and contain a homogenous vacuolated pink secretion

Apocrine nevus

Rare cutaneous apocrine neoplasm that occurs primarily in women younger than 25 years of age typically presents as single or multiple firm, rubbery, smooth, mobile, painless nodules up to 2 cm in diameter; most commonly occurs in the axilla, vulva, and perianal region

Apocrine fibroadenoma

Histopathology: variably hyalinized stroma surrounding a proliferation of ductal structures with decapitation secretion

Apocrine fibroadenoma

Rare benign neoplasm of breast lactiferous ducts with peak incidence is in women in the 5th decade presents as unilateral erythematous, eroded, crusted papule on the nipple of middle-aged females with ulceration and serosanguinous discharge; usually asymptomatic, but patients may complain of irritation, burning, pain, and pruritus

Erosive adenomatosis of the nipple or florid papillomatosis

Histopathology: reveals a nonencapsulated endophytic proliferation of tubular structures in the dermis with a verrucous or ulcerated surface; tubular structures exhibit cystic dilations with discrete papillations; tubules are lined by an inner apocrine secretory epithelium and an outer myoepithelial layer; lack of atypia and necrosis

Erosive adenomatosis of the nipple or florid papillomatosis

Relatively uncommon benign neoplasm from the anogenital apocrine glands most commonly presenting in females 30-49 years of age as a small, unilateral, asymptomatic, flesh-colored nodule on the female vulva and as a subcutaneous nodule, tumor, or cyst as ectopic or nonanogenital lesions on the head and neck

Hidradenoma papilliferum

Histopathology: well-circumscribed dermal nodule which is partly solid or solid-cystic that lacks an epidermal connection; consists of an anastomosing pattern of numerous glandular structures and papillary folds; lumina are made of a double layer of cells: an inner layer of secretory cells demonstrating decapitation secretion, and an outer layer of cuboidal myoepithelial cells

Hidradenoma papilliferum

Rare benign adnexal neoplasm that presents in young adults presents as an asymptomatic, solitary, firm, pink papule or plaque measuring 1-3 cm with a small fistula draining clear, bloody, or malodorous fluid may develop, grows and becomes increasingly papillated and hyperkeratotic during puberty most commonly affects the scalp

Syringocystadenoma papilliferum

Histopathology: papillomatous epidermal invaginations lined with a double layer epithelium composed of basilar cuboidal cells and an inner columnar layer of secretory cells with plasma cell rich infiltrate is; there is typically a connection between the epithelial invagination and adjacent glands in the dermis

Syringocystadenoma papilliferum

Histopathology: epidermal invagination with papilliferous projections but characterized by asymmetry, poor circumscription, extension to the deep subcutaneous tissue, and increases in cellularity, cellular atypia, and mitoses

Syringocystadenocarcinoma papilliferum

Benign neoplasms thought to originate from apocrine glands that are more common in females and typically present in the third decade most commonly present as slow growing, pink, firm, smooth, alopecic, painful nodules ranging in size from 0.5-6 cm on the scalp; multiple lesions coalesce on the scalp forming a confluent mass called “turban tumors”

Cylindroma

AD condition due to inactivating germ-line mutations or loss of heterozygosity in the tumor suppressor gene CYLD with variable penetrance and expressivity, that present with cylindromas, trichoepitheliomas, spiradenomas, sebaceous nevi, basal cell carcinoma and milia

Brooke-Spiegler syndromec

Histopathology: characterized by dermal aggregates of large epithelial cells with abundant cytoplasm in the center and small basaloid cells in the periphery; nodules are lined by thick basement membrane-like material, and arranged in a classic jigsaw puzzle pattern

Cylindroma

A rare group of cutaneous adenocarcinomas that show apocrine differentiation most common in middle-aged to elderly males usually arises de novo which presents as an indolent, slow-growing rubbery, solid to cystic nodule or tumor ranging in size from 1.5-8 cm, color varies from red to purple, and ulceration may be present most common on the axilla followed by the anogenital skin, regions of high apocrine gland density

Apocrine adenocarcinoma

Histopathology: presents with a dermal and/or subcutaneous non-encapsulated tumor with infiltrative margins; composed of large cells with eosinophilic cytoplasm, hyperchromatic nuclei, mitotic figures, and decapitation secretion; epithelial component shows variable papillary, cribiform or trabecular, and solid patterns; signet ring cells and pagetoid spread have been reported

Apocrine adenocarcinoma

Treatment of choice: Apocrine adenocarcinoma

Wide local excision with clear margins

Common benign proliferation of eccrine glands found predominantly in middle-aged to elderly females with lesions that are typically translucent, skin-colored or blue, dome-shaped, cystic papules on the head and neck; multiple lesions clustered in the periorbital region may be a sign of ectodermal dysplasia

Eccrine hidrocystomas

Histopathology: cyst lining is a double layer of attened epithelium lacking decapitation secretion with osinophilic contents

Eccrine hidrocystomas

Rare benign eccrine hamartomas that appear in childhood and adolescence

Eccrine nevi

Classically present with a solitary, well-circumscribed, hyperhidrotic plaque with little to no epidermal change; hyperhidrotic episodes are triggered by temperature, stress, and exercise; most common location is the forearm (50%) followed by the back and trunk

Pure eccrine nevi

More common, often present at birth present with a solitary or multiple flesh-colored, red, or blue-brown nodules or plaques on the extremities, especially the legs which may be painful

Eccrine angiomatous hamartomas

Extremely rare lesions that present with nodules or plaques with hyperhidrosis

Mucinous eccrine nevi

Rare disorder of keratinization involving the intraepidermal eccrine duct or acrosyringium which presents with congenital punctuate keratoses on the hands and feet, and has been associated with deafness, developmental delay, seizures, scoliosis, anhidrosis, alopecia, onychodysplasia, and palmoplantar involvement which typically are linear and follow the lines of Blaschko

Porokeratotic eccrine ostial and dermal duct nevus

Histopathology: increase in the number or size of normal eccrine glands and also shows an increase in the number of capillaries

Eccrine nevi

Common benign neoplasms derived from intradermal eccrine duct or acrosyringium, most frequently seen in adult females with an increased frequency in Down’s syndrome (18%) present with numerous, small, firm, smooth, flesh-colored or yellowish papules on the face, especially the lower eyelids,

Syringoma

Histopathology: well-circumscribed, symmetric collections of small tadpole-shaped tubular structures in the superficial dermis; the tubules are lined by a single or double layer of bland, monomorphic, cuboidal epithelial cells

Syringoma

Histopathology: notable for abundant cytoplasm; tubular structures are surrounded by thickened collagen bundles

Clear cell syringoma

Benign eccrine tumors composed of cuticular and poroid cells similar to those seen in the eccrine acrosyringium

Eccrine poroma

Presents as a solitary hyperkeratotic plaque on the extremities of middle-aged and elderly females

Hidroacanthoma simplex

Classically present as a solitary, slow growing, flesh-colored or bright red, pruritic, painful, pedunculated papule or nodule with predilection for the sole and sides of the feet, followed by the hands, fingers, head, neck, and trunk; distinct feature is a cup-shaped shallow depression from which the tumor protrudes

Eccrine poroma

Histopathology: displays sharply demarcated aggregations of cuboidal to ovoid cells in the epidermis

Hidroacanthoma simplex

Histopathology: reveal aggregations of uniform basaloid cells that radiate from the basal layer of the epidermis into the dermis

Eccrine poromas

Histopathology: consist of several sharply circumscribed dermal nodules consisting of poroid cells with frequent ductal structures

Dermal duct tumors

Most common form of sweat gland carcinoma which presents as presents as a blue-black nodule or infiltrated plaque on the legs, feet, face, thighs, and arm characterized by rapid growth up to 10 cm, bleeding, and ulceration

Porocarcinoma

Treatment of choice: Poroma

Mohs micrographic surgery

Clinical presentation can range from solitary lesions to multiple papules, plaques, and nodules in a symmetrical and linear or nevoid pattern with most common site is the limb observed in ectodermal dysplasia (Clouston syndrome)

Eccrine syringofibroadenoma

Histopathology: multiple anastomosing cords of benign epithelial cells surrounded by a loose fibrovascular stroma; epithelial cords demonstrate ductal differentiation; occasional luminal eccrine ducts are noted within the anastomosing cords

Eccrine syringofibroadenoma

Relatively common benign adnexal tumor derived from the intradermal straight eccrine duct typically appears as a solitary, slow growing, 1-2 cm, red-brown deep-seated nodule with a slightly bluish hue, and paroxysmal pain; predilection for the ventral upper trunk

Eccrine spiradenoma

Histopathology: one or several well-circumscribed basophilic nodules in the dermis and/or subcutaneous tissue; epithelial aggregates are arranged in sheets and cords or in a trabecular pattern; 2 distinct cell populations: 1. small darkly staining basaloid cells rimming the periphery and 2. larger cells with a pale nucleus in the center of the lesion; tubular or cystic structures are noted within the epithelial aggregations; basaloid cells are often arranged in rosettes

Eccrine spiradenoma

Treatment of choice: Eccrine spiradenoma

Surgical excision with clear margins

Treatment of choice: Eccrine spiradenocarcinoma

Wide local excision

Rare benign adnexal tumor in childhood to advanced age more common in women commonly presents as a solitary, firm, flesh-colored nodule on the distal extremity with size varying from 0.5-4 cm in diameter

Papillary eccrine adenoma

Histopathology: well-circumscribed, nonencapsulated dermal nodule comprised of numerous dilated tubules surrounded by a brous stroma. The tubules are lined with an outer layer of attened epithelial cells and an inner layer of cuboidal or columnar cells with intraluminal papillary projections. The lack of atypia

Papillary eccrine adenoma

Treatment of choice: Papillary eccrine adenoma

Surgical excision with clear margins

Benign adnexal tumor which shows features of eccrine and apocrine differentiation that presents most commonly in middle-aged and elderly females presents as a slow-growing, solitary, firm, flesh-colored or red to blue, mobile, solid or cystic nodule that measures 1-2 cm in diameter most commonly located on the scalp, face, and trunk

Nodular hidradenoma or Eccrine acrospiroma

Histopathology: presents as a well-circumscribed, nonencapsulated nodular, solid, or solid-cystic lesion in the dermis and occasionally extends to the subcutaneous fat with ductal differentiation; closely packed tumor cells have a biphasic population with small dark polygonal cells and larger clear cells

Nodular hidradenoma or Eccrine acrospiroma

Treatment of choice: Nodular hidradenoma

Surgical excision with clear margins

Treatment of choice: Hidradenocarcinoma

Wide local excision of 3-5 cm

Uncommon benign appendageal tumor with ductal differentiation and a fibromyxochondroid stroma, presents with slow-growing, painless, nonspecific, firm nodules on the head and neck, especially the nose, cheeks, and upper lip size ranging from 5-30 mm

Chondroid syringoma

Histopathology: presents with a circumscribed dermal nodule with bland epithelial cells arranged in cords, ducts and tubules, embedded in a myxoid-cartilaginous stroma

Chondroid syringoma

Treatment of choice: Chondroid syringoma

Complete surgical excision

Rare highly aggressive eccrine gland tumors that present primarily in Caucasian males in their 50s present as a solitary, firm, tan or pink, rubbery nodule on the acral extremities specifically, the volar surface of the skin between the nail bed and distal interphalangeal joint

Aggressive digital papillary adenoma (ADPA) and adenocarcinoma (ADPAca)

Histopathology: multinodular dermal and/or subcutaneous proliferations of ductal and glandular structures with focal solid and cribriform zones; ductal structures exhibit cystic dilatations, in which several papillary projections are present; a fibrocollagenous stroma surrounds the epithelial components

Aggressive digital papillary adenoma (ADPA) and adenocarcinoma (ADPAca)

Rare low-grade eccrine tumor that presents in elderly males typically presents with an asymptomatic, round, elevated, reddish, ulcerated mass; most commonly occurs on the head and neck in 75% of cases, with 40% of cases on the eyelid with propensity for sudden enlargement

Mucinous eccrine carcinoma

Histopathology: well-demarcated, lobular, dermal tumor with frequent extension into the subcutaneous tissue; consists of PAS-positive, diastase-resistant multilocular pools of mucin, in which nests of bland polygonal cells are embedded

Mucinous eccrine carcinoma

Shows features of eccrine, apocrine, and follicular differentiation presents as a slow-growing, firm, indurated plaque or nodule with indistinct borders on the face, especially the upper lip which is generally asymptomatic, but numbness, burning, anesthesia, and paresthesia have been noted

Microcystic adnexal carcinoma

Histopathology: poorly circumscribed dermal tumor embedded in a desmoplastic stroma that can extend into the subcutaneous tissue and muscle; superficially, the tumor is composed of ducts, keratin horn cysts, and small cords of basaloid cells, resembling syringoma; deeper component exhibits smaller strands and cystically dilated tubules and ductal structures; there is lack of cytologic atypia; perineural invasion is common and extensive

Microcystic adnexal carcinoma

Treatment of choice: Microcystic adnexal carcinoma

Mohs micrographic surgery

Variant of trichofolliculoma or accessory tragus often apparent at birth presents as a dome-shaped, skin-colored papule or nodule from which hair protrudes; most common on the hair-bearing surfaces, including the face and periauricular region

Hair follicle nevus or Congenital vellus hamartoma

Histopathology: numerous closely packed mature vellus follicles confines to a focal well circumscribed area in the upper dermis; follicles are surrounded by a prominent sheath of perifollicular connective tissue, which in turn are surrounded by clefts; sebaceous lob- ules may be present

Hair follicle nevus or Congenital vellus hamartoma

Rare follicular neoplasm that can be congenital or develop during adulthood related to dysregulation of the PTCH signaling pathway presents depending on the variant: a solitary 2-3 mm papule, a localized plaque with alopecia, linear or blaschkoid, generalized dominantly inherited familial type, and generalized papules associated with myasthenia gravis and diffuse alopecia

Basaloid follicular hamartoma (BFH) or Benign follicular hamartoma

Histopathology: anastomosing strands of basaloid cells with numerous epidermal connections; central areas of epithelial aggregations occasionally reveal cells with a squamoid appearance

Basaloid follicular hamartoma (BFH) or Benign follicular hamartoma

Presents as a solitary, open comedo on the head and neck of elderly males which may arise in a background of cystic acne or actinic damage; lacks palpable induration

Dilated pore of Winer

Presents as solitary, open comedo lled with keratin on the upper lip

Pilar sheath acanthoma

Histopathology: reveals a single or several contiguous, markedly, dilated infundibula in upper dermis; epithelial lining reveals focal acanthosis and finger-like projections into the surrounding dermis; dilated infundibula contain cornified cells arranged in basket-weave and laminated patterns; heavy pigmentation of the epithelium can be observed

Dilated pore of Winer

Histopathology: exhibits a larger more irregular branching cystic cavity; there are multiple lobulated masses of cells radiating from the central cavity into the dermis

Pilar sheath acanthoma

An AD condition due to a mutation in folliculin, which has been linked to the mammalian target of rapamycin (mTOR) pathway; cutaneous lesions include fibrofolliculomas, trichodiscomas, fibrous papules, and acrochordons; patients have a predisposition to colonic polyposis, spontaneous pneumothorax, and renal cell carcinoma

Birt-Hogg-Dube syndrome

Histopathology: present with a dome shaped lesion with a central relatively well-differentiated hair follicle displaying a single or several contiguous, dilated, keratin-filled infundibula which are connected to several thin, focally anastomosing epithelial strands that extend in a radial fashion into the stroma; infundibula are surrounded by a distinct fibrillary collagenous or mucinous stroma with scant elastic tissue

Fibrofolliculoma

Histopathology: reveal the fine fibrillary collagenous stroma containing ectatic blood vessels; a hair follicle may be found at the margin of the lesion with stromal component

Trichodiscoma

Histopathology: presents as a dome-shaped or polypoid lesion consisting of one or more poorly formed hair follicles surrounded by a cellular stroma with numerous proliferative small blood vessels in the dermis

Fibrous papule

Benign follicular neoplasm in adults between the 4th and 6th decades which presents with a solitary, well-defined, slow-growing, brown or blue-black nodule on the head or neck, especially the scalp that can reach up to 3 cm in diameter

Trichoblastoma

Histopathology: several dermal and subcutaneous smooth-bordered collections of basaloid cells arranged in nodular, cribriform, retiform, and racemiform patterns; stroma is characteristically sclerotic or hyalinized with peripheral palisading and rudimentary follicular papillae; heavy melanin pigmentation and horn cysts can also be seen

Trichoblastoma

Small 5-8 mm, skin-colored papule on the nose, upper lips, and cheeks which can also develop on the trunk, neck, or scalp; often mistaken for basal cell carcinoma; can grow quite large to several cm

Solitary trichoepithelioma

Seen in adolescents in the setting of Brooke-Spiegler syndrome presents with numerous small, shiny, firm papules on the face with a predilection for the upper lip, nasolabial folds, and eyelids

Multiple trichoepithelioma

Histopathology: present with sharply circumscribed, symmetric, dome shaped lesions composed of aggregates of relatively monomorphic basaloid cells in the upper dermis surrounded by abundant fibrous stroma with stromal-stromal retraction; most common pattern is cribriform, but nodular, racemiform, and retiform patterns have also been observed; also exhibit peripheral palisading and papillary mesenchymal bodies

Trichoepithelioma

Rare benign adnexal neoplasm with extensive stromal sclerosis presents as a solitary, firm, skin-colored to white-gray, sclerotic annular plaque with a central depression on the upper cheek or angle of the lip of a young female, typically measures 1 cm and is asymptomatic

Desmoplastic trichoepithelioma or Sclerosing epithelial hamartoma

Histopathology: well-circumscribed lesion consisting of cords of basaloid cells that are 1-3 cells thick in the upper two-third of the dermis with small keratinous cysts and desmoplastic stroma that exhibits stromal-stromal retraction

Desmoplastic trichoepithelioma

Follicular tumor with differentiation toward the infundibular portion of the folliculosebaceous canal; presents as a solitary slow-growing, grayish nodule measuring up to 1.5 cm with most common location is the face, followed by the buttocks; can be vegetative or verrucous

Trichoadenoma

Histopathology: dome-shaped, sharply defined nodule composed of numerous round infundibulocystic structures in the dermis lined by squamous epithelium; conspicuous collagenous stroma surrounds the tumor nests

Trichoadenoma

Derived from hair matrix cells associated with activating mutations in β-catenin, a mediator in the Wnt signaling pathway, presents as a solitary, skin-colored or bluish, firm, cystic nodule on the head, neck, or proximal upper extremities which displays a “tent-sign” with many angles and surfaces apparent on skin stretch

Pilomatricoma or Calcifying epithelioma of Malherbe

Histopathology: reveals a fairly characteristic encapsulated mass of basophilic cells with minimal cytoplasm that evolve into eosinophilic shadow or ghost cells toward the center of the lesion; calcification can be prominent

Pilomatricoma

Exhibits differentiation toward the outer root sheath or trichilemmal sheath at the level of the bulb, present as a solitary, small 3-8 mm, flesh-colored, asymptomatic, keratotic papule on the face with a predilection for the nose and upper lip; can be seen arising within a nevus sebaceous

Trichilemmoma

AD condition with germ-line mutations in the tumor suppressor PTEN gene which encodes phosphatase and tensin homolog and when absent leads uninhibited phosphorylation of AKT leading to the inability to undergo apoptosis; presents with multiple trichilemmomas oral papillomas and acral palmo- plantar keratoses; increased risk for breast, thyroid, and endometrial cancer

Cowden’s syndrome

Histopathology: exo-endophytic, lobular proliferation of polygonal, pale-staining, glycogen containing squamoid cells extending from the epidermis with peripheral palisading of columnar cells, and a conspicuous PAS-positive basement membrane surrounding the lesion

Trichilemmoma

Neoplasm that demonstrates differentiation toward the follicular isthmus presents as a solitary, small, asymptomatic, thin, keratotic papule on the head or neck often misdiagnosed as a seborrheic keratosis or basal cell carcinoma

Tumor of the follicular infundibulum (TFI) or Isthmicoma

Histopathology: horizontally oriented, plate-like tumor in the upper dermis with the epithelial component showing multiple connections to the epidermis or hair follicles; epithelium exhibits a fenestrated pattern with interconnecting cords and columns with surrounding collagenous stroma

Tumor of the follicular infundibulum (TFI) or Isthmicoma

Derived from the outer root or trichilemmal sheath resents on the scalp or posterior neck of elderly patients or trunk, groin, vulva, and gluteal region; usually starts as a nodule and develops into a large, elevated, rubbery, lobulated mass that can enlarge to 10 cm and often ulcerate

Proliferating trichilemmal cyst (PTC)

Histopathology: reveals a sharply circumscribed cystic neoplasm occupying the lower dermis and subcutaneous tissue with proliferation of bland squamous cells lining nearly the whole lesion and extending within it in a radial fashion; a characteristic feature is the presence, in the center of lobules, of trichilemmal cornification

Proliferating trichilemmal cyst (PTC)