Neoplasms of the Skin and Immunodermatology



Fig. 18.1.
Steatocystoma (A, B).





Clinical



May occur in a solitary form (simplex) or as multiple lesions inherited in an autosomal dominant fashion (multiplex)

 


Microscopic



An irregular, collapsed, intradermal cyst lined by a stratified squamous epithelium with an irregular, corrugated internal cuticle. Sebaceous glands are usually evident in the duct walls, and the cyst contains proteinaceous debris but no keratin

 



Dermoid Cyst



Clinical



An embryonic closure defect that typically involves the skin lateral to the eye, the scalp, the neck, or near the mastoid process. Usually detected early in life

 


Microscopic



A unilocular dermal or subcutaneous cyst lined by stratified squamous epithelium and having hair follicles, glands, and, sometimes, smooth muscle in the cyst wall

 


Cysts Associated with Branchial Cleft Deformities



Clinical



Cystic lesions may be formed in and around the ear in association with branchial cleft deformities. These differ from the branchial cleft cyst of the neck by their location and their microscopic characteristics

 


Microscopic



May be similar to an epidermoid cyst except for their tendency to collapse and assume a multiloculated appearance. Other forms, in addition to the above, have adnexal structures and even cartilage within their walls

 


Branchial Cleft Cyst



Clinical



A developmental anomaly presenting as a cyst in the lateral aspect of the neck

 


Microscopic



A lymphoepithelial cyst characterized by a stratified squamous or a pseudostratified ciliated lining with a dense lymphocytic infiltrate with germinal centers in the wall

 


Eruptive Vellus Hair Cyst



Clinical



Small flesh-colored papules in children and young adults

 


Microscopic



An epidermoid-like cyst that contains numerous, small vellus hairs

 


Pigmented Terminal Hair Cyst



Microscopic



An epidermoid-like cyst containing numerous pigmented, terminal hairs

 


Trichilemmal (Pilar) Cyst



Clinical



Dome-shaped papules/nodules found predominantly on the scalp; may be single or multiple

 


Microscopic



A dermal or subcutaneous cyst lined by an eosinophilic stratified squamous epithelium that lacks a granular layer. The cyst contents are composed of solid, nonlaminated keratin

 


Proliferating Trichilemmal Cyst/Tumor (Fig. 18.2)



A145302_4_En_18_Fig2_HTML.jpg


Fig. 18.2.
Proliferating trichilemmal cyst/tumor (A, B).



Clinical



Multinodular scalp lesion more common in females

 


Microscopic



Well-defined, multilobular tumor with trichilemmal keratinization; dense fibrous tissue surrounds the individual lobules; cystic areas may be inconspicuous

 



Malignant forms occur but are rare

 



More marked infiltration, cytologic atypia, and mitotic activity characterize the malignant variants

 


Bronchogenic Cyst



Clinical



A developmental cyst usually found near the precordium early in life

 


Microscopic



This cystic lesion attempts to recapitulate the bronchi with a cyst lined by respiratory epithelium and a cyst wall with smooth muscle, glands, and/or cartilage

 


Thyroglossal Duct Cyst



Clinical



A developmental cyst found in the midline of the neck, near the hyoid bone

 


Microscopic



The cyst may be lined by cuboidal, columnar, or stratified squamous epithelium

 



The cyst wall contains thyroid follicles with or without skin appendages and lymphocytic inflammation

 



Smooth muscle and cartilage are absent

 


Cutaneous Ciliated Cyst



Clinical



Usually found on the lower extremities or buttocks of reproductive-aged women

 


Microscopic



Ciliated, cuboidal, to columnar lined, multiloculated cyst surrounded by fibrous tissue

 



No endometrial or fallopian tube-type stroma is evident within the cyst walls

 


Endometriosis and Endosalpingiosis



Clinical



Blue-red cysts/nodules most commonly seen in the vulvar or periumbilical regions of reproductive-aged females

 


Microscopic



Similar to the cutaneous ciliated cyst, except that the cyst wall contains endometrial/fallopian tube-type stroma with or without hemosiderin deposition

 


Hidrocystoma



Microscopic



Unilocular or multilocular cysts lined by either apocrine or eccrine epithelium



  • Apocrine: decapitation secretion (apical snouts) and a myoepithelial layer; may have papillary projections


  • Eccrine: a two-layered cuboidal epithelium with no myoepithelial layer or decapitation secretion

 


Hybrid Cyst



Microscopic



A cystic lesion combining the histologic features of more than one cyst type, usually trichilemmal and epidermoid cysts

 


Digital Mucous Cyst (Fig. 18.3)



A145302_4_En_18_Fig3_HTML.jpg


Fig. 18.3.
Digital mucous cyst.



Clinical



A fluctuant, sometimes tender, translucent nodule of the digits

 


Microscopic



Dermal mucin deposited into a cyst-like space that may or may not also contain fibroblasts and collagen

 



There is no true epidermal lining, and the cystic spaces may be multiloculated

 


Oral Mucocele



Clinical



A translucent, blue nodule usually found on the lower lip

 


Microscopic



A cystic space containing varying degrees of central mucin and lined by chronic inflammatory cells with numerous foamy histiocytes

 



There is no true epithelial lining

 



Epidermal Tumors and Proliferations



Actinic Keratosis (Senile, Solar)



Clinical



White-yellow, erythematous, and scaly patches or plaques on sun-damaged skin; some may be pigmented

 


Microscopic



While a variety of histologic types exist, all have in common epidermal dysplasia, which may also involve the hair follicles

 



Hyperplastic, atrophic, acantholytic, epidermolytic, lichenoid, pigmented, bowenoid, and clear cell categories exist and reflect additional alterations to the dysplastic epidermis (e.g., lichenoid variant = actinic keratosis with a band-like lymphocytic inflammatory infiltrate; bowenoid variant = actinic keratosis with full-thickness dysplasia = carcinoma in situ)

 


Benign Lichenoid Keratosis (Fig. 18.4) (Lichen Planus-Like Keratosis)



A145302_4_En_18_Fig4_HTML.jpg


Fig. 18.4.
Benign lichenoid keratosis.



Clinical



Solitary papule or plaque found primarily on the trunk or upper extremities

 


Microscopic



Very similar to lichen planus with a dense band-like lymphocytic infiltrate at the dermal–epidermal interface with basilar vacuolar degeneration and cytoid bodies

 



In contrast to lichen planus, eosinophils and parakeratosis may be seen

 



In contrast to a lichenoid actinic keratosis, there is no keratinocyte dysplasia

 


Seborrheic Keratosis



Clinical



Brown, elevated, and sharply demarcated lesions which occur most commonly on the face, trunk, and upper extremities

 



These benign tumors often have a “stuck-on” appearance and are more common in middle-aged and older adults

 



The sudden appearance of numerous seborrheic keratosis in association with visceral malignancy is referred to as the Leser–Trelat sign

 


Microscopic



An epidermal proliferation of bland basaloid and polygonal keratinocytes associated with prominent keratin cyst formation

 



The lesion is sharply delineated at its base and appears to grow up from the epidermis

 



Irritated forms demonstrate more endophytic growth and form numerous squamous eddies

 



Acanthotic, adenoid, clonal, pigmented, and hyperkeratotic variants exist

 


Inverted Follicular Keratosis (Fig. 18.5)



A145302_4_En_18_Fig5_HTML.jpg


Fig. 18.5.
Inverted follicular keratosis.



Microscopic



An endophytic epidermal growth with numerous squamous eddies which, like seborrheic keratosis, is sharply delineated but is centered on the hair follicles

 



Note: This entity is considered a variant of seborrheic keratosis by some experts and a viral-induced lesion by others

 


Warty Dyskeratoma (Fig. 18.6)



A145302_4_En_18_Fig6_HTML.jpg


Fig. 18.6.
Warty dyskeratoma.



Clinical



A benign, solitary, umbilicated nodule or papule on sun-exposed skin

 


Microscopic



A hair follicle-centered, endophytic squamous proliferation which is sharply delineated

 



The base of the lesion typically reveals elongated trabeculae with varying degrees of dyskeratosis that underlies broad areas of acantholytic dyskeratosis located immediately below a keratin-filled, central crater

 


Linear Epidermal Nevus



Clinical



Localized and systemic forms exist and are characterized by a linear arrangement of closely set papillomatous papules

 



The systemic form may be associated with other defects, including skeletal and central nervous system abnormalities

 


Microscopic



Both variants demonstrate epidermal papillomatosis, acanthosis, and hyperkeratosis

 



Many histologic variants exist, but, importantly, the presence of epidermolytic hyperkeratosis may be associated with systemic involvement

 


Nevus Comedonicus



Clinical



Comedo-like papules with a central keratin plug usually in a linear arrangement on the palms, soles, or other sites

 


Microscopic



Deep epidermal invaginations with laminated keratin similar to a comedo

 



Epidermolytic hyperkeratosis may be evident

 


White Sponge Nevus



Clinical



Extensive, white patches and plaques involving mucosal sites (chiefly oral but also vaginal, rectal, and esophageal) which are evident early in life and are inherited in an autosomal dominant pattern

 


Microscopic



There is acanthosis and pallor of the mucosal lining due to prominent cytoplasmic clearing (intracellular edema) of the suprabasilar keratinocytes

 



Similar changes are seen in leukoedema and pachyonychia congenita

 


Leukoedema



Clinical



Patchy white plaques and patches of the oral mucosa with an adult onset

 



These lesions remit and recur and are not inherited

 


Microscopic



Similar to white sponge nevus from which it differs by clinical grounds

 


Geographic Tongue (Lingua Geographica )



Clinical



Irregular, erythematous patches with white borders on the tongue

 


Microscopic



The erythematous areas show loss of the normal granular and horny layers, while the white areas demonstrate acanthosis with neutrophilic inflammation

 


Clear Cell Acanthoma (Fig. 18.7)



A145302_4_En_18_Fig7_HTML.jpg


Fig. 18.7.
C lear cell acanthoma (A, B).



Clinical



Solitary, slowly growing nodules or plaques with an oozing surface

 



These lesions are most common on the lower extremities

 


Microscopic



A platelike epidermal thickening by a proliferation of clear, heavily glycogenated keratinocytes

 



The tumors are sharply demarcated from the adjacent epidermis (eyeliner sign) and, characteristically, have neutrophils scattered throughout the proliferation, an important feature in separating this entity from other tumors with a platelike growth pattern

 


Large Cell Acanthoma



Clinical



Erythematous patches on sun-exposed skin

 


Microscopic



A sharply defined epidermal proliferation of enlarged, pale keratinocytes with mild dysplasia

 



Comment: these lesions are aneuploid and are best considered to be a variant of actinic keratosis

 


Squamous Cell Carcinoma In Situ (Bowen Disease )



Clinical



Erythematous, irregular, scaly patches, and plaques that may involve any skin surface as well as the mucous membranes

 



Bowen disease of the penis is often referred to as erythroplasia of Queyrat

 



Sun exposure, arsenic, and other chemicals are associated with an increased risk of development of Bowen disease

 



Approximately 5% of these lesions develop an invasive component

 


Microscopic



Epidermal acanthosis associated with full-thickness epidermal dysplasia, which may involve the adnexa

 



A dense lichenoid inflammatory infiltrate may also be present

 



Intraepidermal spread (Borst–Jadassohn phenomena) may be prominent and should be differentiated from melanoma and Paget disease

 


Bowenoid Papulosis



Clinical



Red-brown papules or plaques on the external genitalia and perineum of young adults

 



Lesions are frequently multiple, and there is a strong association with human papillomavirus (HPV) types 16 and 18 with other types occurring less frequently

 



Unlike Bowen disease, these lesions may regress and are less likely to give rise to an invasive carcinoma

 


Microscopic



Fairly discrete areas of epidermal acanthosis associated with varying degrees of epidermal dysplasia, koilocytosis, hypergranulosis, and parakeratosis

 



In situ carcinoma may be present

 


Squamous Cell Carcinoma (Fig. 18.8)



A145302_4_En_18_Fig8_HTML.jpg


Fig. 18.8.
S quamous cell carcinoma.



Clinical



Indurated, hyperkeratotic nodules which may show ulceration or verruciform changes

 



Currently, squamous cell carcinoma is the second most common cutaneous malignancy

 



The incidence is increasing

 



While most are related to sun exposure, other risk factors include fair complexion, chronic inflammation, immunosuppression, burns, HPV infection, and chemical exposure (e.g., arsenic)

 



The overall rate of metastases is approximately 5% but is >10% at mucosal sites and the ear

 


Microscopic



Atypical nests of epidermoid cells invasive into the dermis and, usually, with overlying epidermal dysplasia

 



Differentiation varies from poorly differentiated (minimal keratin production, marked nuclear pleomorphism, high mitotic rate) to well differentiated (abundant keratin pearl formation, minimal cytologic atypia, and few mitoses)

 



The presence of keratin production, intercellular desmosomes (“spines”), and overlying epidermal dysplasia are useful features in separating this tumor from other entities

 



Variants include clear cell, spindle cell, acantholytic, and verrucous tumors

 


Verrucous Carcinoma



Clinical



A variant of squamous cell carcinoma that typically appears as a large hyperkeratotic nodule

 



All cutaneous surfaces may be involved but plantar, oral (oral florid papillomatosis), and anogenital lesions are particularly common

 



These tumors frequently recur but have little metastatic potential

 


Microscopic



An endophytic and exophytic growth of well-differentiated squamous epithelium with extensive keratinization

 



The deep component shows a broad, pushing front at its advancing edge

 



If any significant nuclear dysplasia is present, a diagnosis of squamous cell carcinoma should be made

 


Keratoacanthoma



Clinical



A rapidly growing, umbilicated nodule with a central keratin plug

 



Multiple lesions may be present

 



Typically, these tumors regress over the course of a few months, but they may recur

 



These tumors are considered to be a variant of squamous cell carcinoma by some experts

 


Microscopic



A well-defined, sharply demarcated, crateriform squamous proliferation with a central keratin plug

 



The squamous epithelium frequently has a glassy appearance and lacks significant cytologic atypia

 



A lichenoid inflammatory infiltrate may be present

 



The presence of cytologic atypia, infiltrative borders, or atypical mitoses warrants a diagnosis of a squamous cell carcinoma

 


Pilar and Pilosebaceous-Derived Tumors



Dilated Pore of Winer



Clinical



Flesh-colored papule or cyst with a central keratotic plug found chiefly on the head and neck

 


Microscopic



A cone-shaped dilatation of the follicular infundibulum with a central keratin plug

 



The wall of the pore is proliferative with fingerlike projections extending into the adjacent dermis

 



No secondary hair follicles are evident within the cyst wall

 


Pilar Sheath Acanthoma



Clinical



Small nodule with a central keratin-filled pore on the upper lip

 


Microscopic



Similar in architecture to the dilated pore but with a more proliferative wall

 



The epithelium of the wall is paler than that of the dilated pore and may have some degree of peripheral palisading, suggesting abortive hair follicle development

 



No well-developed secondary hair follicles with hair formation are evident

 


Trichofolliculoma (Fig. 18.9)



A145302_4_En_18_Fig9_HTML.jpg


Fig. 18.9.
Trichofolliculoma.



Clinical



Solitary, flesh-colored nodules with a central pore from which numerous white hairs emerge

 


Microscopic



Similar to the dilated pore, a central, elongated, and dilated infundibulum is present

 



Numerous secondary hair follicles radiate peripherally from the central cavity that is filled with laminated keratin and numerous hairs

 



If sebaceous glands are evident within the secondary follicles, then a diagnosis of a sebaceous trichofolliculoma is appropriate

 


Tumor of the Follicular Infundibulum (Fig. 18.10)



A145302_4_En_18_Fig10_HTML.jpg


Fig. 18.10.
Tumor of the follicular infundibulum.



Clinical



Small, hyperkeratotic papules or plaques on the head and neck

 


Microscopic



A platelike expansion of the epidermis by interanastomosing and interweaving trabeculae of glycogenated squamous epithelium within the superficial dermis

 



The trabeculae show multiple attachments to the epidermis and to the hair follicles

 



The trabeculae may show some peripheral palisading but lack mucin deposition or stromal retraction

 



Elastic fibers are often condensed at the base of the lesion

 


Differential Diagnosis



Fibroepithelioma of Pinkus and eccrine syringofibroadenoma

 



Fibroepithelioma of Pinkus has narrow trabeculae with more pronounced basaloid differentiation, while eccrine syringofibroadenoma shows scattered eccrine ducts within its trabeculae

 


Basaloid Follicular Hamartoma



Clinical



Small, flesh-colored papules or plaques on the head and neck

 



Solitary, multifocal, and inherited variants have been described

 


Microscopic



Small, starfish- or octopus-like proliferations of basaloid cells within the dermis arranged as anastamosing trabeculae with peripheral palisading and surrounding fibrosis

 


Trichilemmoma (Fig. 18.11)



A145302_4_En_18_Fig11_HTML.jpg


Fig. 18.11.
T richilemmoma.



Clinical



Verrucous, hyperkeratotic papules usually found on the face

 



Multiple trichilemmomas occur in the autosomal dominant disorder, Cowden disease

 


Microscopic



A single lobule or, occasionally, a multilobular proliferation of round, clear (glycogen-rich) squamous cells giving a platelike thickening to the epidermis

 



There is usually a follicular accentuation to the proliferation with the pale cells growing down preexisting follicular structures

 



The lobules are surrounded by a PASD-positive basement membrane

 



A desmoplastic variant exists which, in addition to typical trichilemmoma areas, has central trabeculae surrounded by a dense, hypocellular stroma

 


Trichoadenoma (Fig. 18.12)



A145302_4_En_18_Fig12_HTML.jpg


Fig. 18.12.
Trichoadenoma.



Clinical



Yellow to flesh-colored papule on the face

 


Microscopic



Numerous keratin-filled cysts lined by a stratified squamous epithelium are evident within the dermis

 



A granular layer is present (epidermoid keratinization), and the cysts have a surrounding fibrous stroma

 



Solid trabeculae are rare

 


Trichoepithelioma



Clinical



Small flesh-colored papules on the face of young- to middle-aged adults

 



Solitary, desmoplastic, and multiple (autosomal dominant inheritance) variants exist

 


Microscopic



An admixture of keratin-filled cysts and trabeculae of basaloid cells with peripheral palisading and a surrounding fibrous stroma

 



Stromal retraction is not evident, and true hair bulb formation is rarely seen

 


Differential Diagnosis



Keratotic basal cell carcinoma is different from trichoepithelioma by having stromal retraction, mucin deposition, individual cell necrosis, and numerous mitoses

 



Microcystic adnexal carcinoma differs from desmoplastic trichoepithelioma by the presence of deeper infiltration with eccrine ducts lined by an eosinophilic cuticle. A layered appearance with cysts predominating superficially and trabeculae predominating at the deep aspect of the tumor are characteristic

 


Trichoblastoma



Clinical



A controversial entity having histologic and clinical overlap with trichoepithelioma and basal cell carcinoma

 


Microscopic



A proliferation of germinative basaloid cells arranged in nests, sheets, or trabeculae

 



Conspicuous hair bulb differentiation is seen at the edge of the nests or sheets but also as single, primitive hair follicle-like structures surrounded by a dense fibrous sheath

 



Stromal clefting and extensive mucin deposition are typically absent

 


Differential Diagnosis



Basal cell carcinoma shows stromal clefting, mucin deposition, and single cell necrosis and lacks primitive hair bulb structures

 



Trichoepithelioma has admixed keratin-filled cysts and has few to no primitive hair bulbs

 


Trichodiscoma



Clinical



A hamartomatous proliferation of the hair disk which presents as multiple flesh-colored papules on the face and also elsewhere on the body

 


Microscopic



A nodular mesenchymal proliferation surrounded by an epidermal collarette

 



Centrally there are stellate fibroblasts embedded in collagen, reticulin, and elastic fibers with abundant mucin deposition

 



Thin-walled vessels with prominent basement membranes are seen within the proliferation

 


Perifollicular Fibroma and Fibrofolliculoma



Clinical



Both occur as solitary and, more often, multiple flesh-colored papules on the face or neck

 


Microscopic



Perifollicular fibromas show a loose, concentric proliferation of fibrous tissue around normal hair follicles, while fibrofolliculomas show both a fibrous and a follicular proliferation centered on a dilated follicle

 



The epithelial component of the latter consists of epithelial trabeculae that arise from the infundibulum and are surrounded by fibrous tissue

 


Pilomatricoma (Fig. 18.13) (Calcifying Epithelioma of Malherbe)



A145302_4_En_18_Fig13_HTML.jpg


Fig. 18.13.
Pilomatricoma.



Clinical



Deep-seated, frequently calcified nodules on the head, neck, and upper extremities of children and young adults

 



These lesions may be solitary or multiple (autosomal dominant inheritance) or may be a marker of a systemic disease (Gardner syndrome)

 


Microscopic



A cystic or multinodular tumor with a biphasic epithelial growth pattern consisting of eosinophilic, ghosts, or shadow cells centrally and basophilic, basaloid cells peripherally

 



Granulomatous inflammation and calcification are frequent and may obscure the characteristic growth pattern

 


Basal Cell Carcinoma (Fig. 18.14)



A145302_4_En_18_Fig14_HTML.jpg


Fig. 18.14.
Ba sal cell carcinoma.



Clinical



Well-delineated, pearly, translucent, pink-tan papules or nodules with telangiectasia

 



Superficial, nodular/ulcerative, pigmented, diffuse, morpheaform, and fibroepitheliomatous variants exist

 



Most are found on sun-exposed skin of the elderly, but occasional cases are evident on non-sun-exposed skin

 



Basal cell carcinoma is currently the most common cutaneous malignancy, and the incidence is increasing

 



Risk of developing basal cell carcinomas is related to sun exposure and skin type

 



Multiple tumors are seen in Bazex syndrome and basal cell carcinoma nevus syndrome (Gorlin syndrome), an autosomal dominant inherited disease also having odontogenic keratocysts, palmar-plantar pits, ectopic calcification, and skeletal abnormalities

 



Basal cell carcinoma has little tendency to metastasize

 


Microscopic



A proliferation of atypical basaloid cells in nests, trabeculae, and/or cysts within the dermis but often demonstrating multifocal epidermal attachment

 



Peripheral palisading, stromal retraction, mucin deposition, single cell necrosis, and mitoses are characteristic and are useful in separating this tumor from other entities

 



Nodulocystic, metatypical (keratotic), pigmented, adenoidal, infiltrating, superficial, and morpheaform histologic variants exist, with the latter two having an increased risk of recurrence

 


Fibroepithelioma of Pinkus (Fig. 18.15)



A145302_4_En_18_Fig15_HTML.jpg


Fig. 18.15.
Fibroepithelioma of Pinkus.



Clinical



Polypoid or plaque-like lesions on the thigh or trunk

 



Considered as a premalignant lesion by many experts

 


Microscopic



Interanastomosing epithelial strands with multiple points of attachment to the epidermis and surrounded by a fibrous stroma

 



The trabeculae are thinner than the tumor of the follicular infundibulum, being two to three epithelial cells in thickness

 


Malignant Pilomatricoma



Clinical



A rare tumor occurring as tumors or nodules on the face

 


Microscopic



Similar to a benign pilomatricoma but showing areas with infiltration, mitoses, and nuclear pleomorphism

 


Nevus Sebaceous (Fig. 18.16)



A145302_4_En_18_Fig16_HTML.jpg


Fig. 18.16.
Nevus sebaceous.



Clinical



Single or multiple, yellow papules to plaques with or without verruciform features on the head and neck of infants, adolescents, and young adults

 



A linear form exists

 



Nevus sebaceous with cerebral abnormalities is referred to as the nevus sebaceous syndrome

 



Basal cell carcinoma is the most common malignancy associated with nevus sebaceous, while syringocystadenoma papilliferum is the most common benign proliferation associated with this condition

 


Microscopic



The epidermis frequently demonstrates papillomatosis or verruciform change

 



Numerous immature or abortive hair follicles are situated within the superficial dermis with a reduction in the number of mature terminal hairs

 



The sebaceous glands appear haphazardly distributed within the dermis and may appear atrophic, hyperplastic, or relatively normal in size

 



Apocrine glands are a frequent finding in the deep dermis

 


Sebaceous Hyperplasia



Clinical



Small yellow papules on the face and forehead of older adults

 


Microscopic



Enlarged, hyperplastic sebaceous glands emptying into a central hair follicle often situated in the superficial dermis

 


Sebaceous Adenoma



Clinical



Pink to yellow papules on the face and neck of older adults

 



Multiple lesions are often associated with visceral malignancy (Muir–Torre syndrome)

 


Microscopic



A multilobulated tumor often showing attachment to or emptying through the overlying epidermis

 



The lobules are composed of basaloid cells peripherally and multivacuolated cells centrally

 



By definition, the basaloid cells comprise less than 50% of cells of the individual lobules

 



Infiltration, necrosis, and frequent mitoses are absent

 


Sebaceous Epithelioma



Clinical



Similar to sebaceous adenoma

 


Microscopic



A faintly lobular tumor similar to the sebaceous adenoma

 



Basaloid cells comprise more than 50% of the cells in the individual lobules

 



While occasional mitotic figures may be seen, abundant mitotic activity, infiltration, nuclear pleomorphism, or necrosis should lead to a consideration of sebaceous carcinoma or basal cell carcinoma with sebaceous differentiation

 


Sebaceous Carcinoma (Fig. 18.17)



A145302_4_En_18_Fig17_HTML.jpg


Fig. 18.17.
Sebaceous carcinoma.



Clinical



Ulcerated or nonulcerated nodules on the head and neck region of older adults

 



The periocular region is a particularly common site where derivation from the meibomian gland occurs

 



These tumors are associated with a high metastatic potential and increased mortality (~25%)

 


Microscopic



These tumors may show irregular lobules or a diffuse infiltrating pattern

 



Attachment to the overlying epidermis may be present, and pagetoid spread is common in the periocular variants

 



These tumors show a spectrum of sebaceous differentiation varying from tumors composed predominantly of basaloid cells to tumors with numerous multivacuolated sebaceous cells

 



Infiltration, necrosis, nuclear pleomorphism, nucleoli, and mitoses are usually readily evident

 



Perineural and capillary–lymphatic space invasion may be seen

 


Immunophenotype



Cytokeratin and EMA+; S-100 protein and CEA–

 


Eccrine-Derived Tumors and Proliferations



Syringoma-Like Proliferations Associated with Alopecia



Clinical



No specific clinical findings are associated with this lesion which presents simply as alopecia of any etiology

 


Microscopic



This is a relatively rare, apparently nonneoplastic proliferation of the eccrine ducts in response to alopecia

 



The microscopic characteristic is that of the particular form of alopecia affecting the patient with the addition of a diffuse, haphazard proliferation of the eccrine ducts limited to the mid and upper dermis

 



Ducts, trabeculae, comma, and tadpole-shaped forms may all be seen

 



No nuclear pleomorphism or perineural invasion is evident, but mitotic figures may be seen

 



This proliferation may be seen throughout the scalp in cases of severe alopecia

 


Differential Diagnosis



Syringoma is usually a more localized and circumscribed eccrine proliferation and lacks the haphazard appearance of the above

 



Microcystic adnexal carcinoma and eccrine syringoid carcinoma are more infiltrative lesions that typically involve the lower dermis and the subcutis and show frequent perineural invasion

 


Eccrine Syringofibroadenoma (Fig. 18.18)



A145302_4_En_18_Fig18_HTML.jpg


Fig. 18.18.
Eccrine syringofibroadenoma.



Clinical



Single or multiple papules or nodules with a wide age range and distribution

 



The extremities are most commonly involved

 


Microscopic



Interanastomosing cords and trabeculae of epithelial cells extending into the dermis with multiple points of attachment to the epidermis

 



The cords are thin and surrounded by a fibrous stroma

 



Scattered throughout the epithelial cords are areas of eccrine duct differentiation with prominent eosinophilic cuticles

 


Differential Diagnosis



Tumor of the follicular infundibulum and fibroepithelioma of Pinkus lack eccrine differentiation

 


Syringoma (Fig. 18.19)



A145302_4_En_18_Fig19_HTML.jpg


Fig. 18.19.
Syringoma.



Clinical



Multiple flesh-colored or faintly yellow papules on the eyelids or upper face

 



Other sites may also be involved, and linear and eruptive variants occur

 



Clear cell variants may be associated with diabetes

 


Microscopic



A fairly well-circumscribed but unencapsulated neoplasm involving the mid to upper dermis composed of eccrine-derived cords and ducts

 



The cords may show characteristic tadpole-shaped forms

 



Two or more cell layers with an internal eosinophilic cuticle and varying degrees of clear cell change line the ducts

 



In general, the tumor does not infiltrate the deep dermis or subcutaneous fat, lacks mitotic activity and necrosis, and has no significant pleomorphism

 


Immunophenotype



Eccrine-derived tumors typically stain positively for the cytokeratins, EMA, and CEA, which highlights the luminal aspect of the eccrine ducts

 


Differential Diagnosis



Desmoplastic trichoepithelioma has numerous keratotic cysts and frequent calcification and lacks eccrine duct formation

 



Microcystic adnexal carcinoma is much more infiltrative and typically involves the deep dermis and subcutaneous fat

 


Chondroid Syringoma (Benign Mixed Tumor, Fig. 18.20)



A145302_4_En_18_Fig20_HTML.jpg


Fig. 18.20.
Chondroid syringoma.



Clinical



A benign, slowly growing, typically solitary tumor nodule on the head and neck; other sites may be involved

 


Microscopic



A well-circumscribed, biphasic tumor nodule located within the dermis and/or the subcutaneous fat

 



Epithelial cords, trabeculae, and ducts are embedded in an abundant myxoid, fibromyxoid, or cartilaginous matrix

 



The epithelial component lacks nuclear pleomorphism, infiltration, necrosis, and mitotic activity

 



The ducts may show eccrine and/or apocrine differentiation

 


Differential Diagnosis



Pleomorphic adenoma (benign mixed tumor of the salivary glands) should be differentiated from chondroid syringoma because of its tendency to recur and, possibly, malignant transformation

 



As these tumors are similar histologically, location and the presence of adjacent normal salivary glands are the most reliable features used to separate these entities

 


Malignant Chondroid Syringoma



Clinical



A rare, highly malignant tumor with a predilection for the distal extremities

 



These tumors frequently recur and metastasize and are associated with increased mortality

 


Microscopic



Malignant appearing, infiltrating epithelial cords, ducts, and sheets that overgrow the benign mesenchymal matrix

 



Necrosis, mitoses, and nuclear pleomorphism are present

 



An adjacent benign mixed tumor is not typically seen

 


Differential Diagnosis



Carcinosarcoma shows a malignant mesenchymal component in addition to an epithelial malignancy

 


Papillary Eccrine Adenoma



Clinical



A firm, pink to tan nodule on the distal extremities of adolescents and young adults with a female predominance

 



Blacks are more commonly affected than Whites

 


Microscopic



A fairly well-circumscribed but unencapsulated proliferation of eccrine ducts and duct-like structures within the dermis

 



The ducts are lined by a multilayered cuboidal epithelium without apical snouts

 



Micropapillary projections and transluminal bridging may be seen

 



The tumor stroma is fibrotic and frequently hyalinized. Cribriform structures, necrosis, mitotic activity, and nuclear pleomorphism are absent

 


Differential Diagnosis



Aggressive digital papillary adenoma/adenocarcinoma (see below)

 


Aggressive Digital Papillary Adenoma/Adenocarcinoma



Clinical



Asymptomatic flesh-colored nodule on the digits of middle-aged adults

 



The recurrence rate is approximately 50% for these tumors, and the overtly malignant lesions have a metastatic rate of approximately 25–40%

 


Microscopic



Generally, an unencapsulated and poorly circumscribed proliferation of eccrine ducts, tubules, cysts, and nests within the dermis and/or subcutaneous fat

 



The ducts and cystic structures are lined by a multilayered epithelium with abundant micro- and macropapillae

 



Cribriform structures are frequently identified

 



Varying degrees of nuclear pleomorphism, mitotic activity, and necrosis may be seen

 



Tumor grade correlates with metastatic potential, but all forms may metastasize

 



Note: all of these lesions are best classified as adenocarcinomas due to their propensity for recurrence

 



A histologic grade should be given as a prognostic indicator for the risk of metastases

 


Differential Diagnosis



Papillary eccrine adenoma does not show the infiltration, nuclear atypia, mitotic activity, or the cribriforming of the aggressive digital papillary adenocarcinoma

 



Nodular hidradenoma (clear cell )

 


Hidradenoma, Solid-Cystic Hidradenoma, and Eccrine Acrospiroma (Fig. 18.21)



A145302_4_En_18_Fig21_HTML.jpg


Fig. 18.21.
N odular hidradenoma (A, B).



Clinical



Solid or cystic, intradermal nodule 05–2.0 cm in diameter

 



These tumors are usually solitary but may be multiple

 



The head, neck, and extremities are most commonly involved

 



Predominates in young adults with a slight female predominance

 


Microscopic



A well-circumscribed and often pseudoencapsulated tumor composed of a single lobule or, more often, multiple lobules of eosinophilic to clear cells in the dermis

 



Cystic change may be prominent

 



Tubular structures lined by cuboidal to columnar cells with an eosinophilic cuticle are evident in most tumors and are important in proper classification

 



Foci of squamous and/or mucinous differentiation may be seen

 



While this tumor is predominantly intradermal, occasional attachments may be seen to the overlying epidermis

 



Necrosis, mitotic activity, and nuclear pleomorphism are absent or minimal in extent

 


Hidradenocarcinoma (Malignant Nodular Hidradenoma )



Clinical



Similar distribution to their benign counterparts but occurs in older individuals (>50 years of age)

 



Recurrence and metastatic rate is approximately 50%

 


Microscopic



Like the hidradenoma, this tumor is composed of eosinophilic and/or clear cells forming lobules within the dermis

 



The malignant variants, however, are asymmetrical, infiltrating, and mitotically active and demonstrate nuclear pleomorphism and/or necrosis

 


Differential Diagnosis



Clear cell squamous cell carcinoma, clear cell renal cell carcinoma, clear cell melanoma, and trichilemmal carcinoma

 



Look for tubular structures with an eosinophilic cuticle to confirm eccrine differentiation; CEA may be useful in that it highlights the luminal border of eccrine-derived structures

 


Hidroacanthoma Simplex (Intraepidermal Poroma )



Clinical



A rare, benign variant of poroma typically involving the extremities of older individuals

 


Microscopic



An intraepidermal proliferation (Borst–Jadassohn phenomenon) of round to faintly spindled cells with eosinophilic to faintly clear cytoplasm

 



Intracytoplasmic glycogen is evident on PAS staining

 



Rare eccrine ducts/tubules may be seen

 



The individual cells are remarkably uniform and lack nuclear atypia

 



The tumor cells are sharply demarcated from the squamous cells of the adjacent epidermis

 


Eccrine Poroma (Fig. 18.22)



A145302_4_En_18_Fig22_HTML.jpg


Fig. 18.22.
Eccrine poroma.



Clinical



A red to flesh-colored tumor found most frequently on the sole of the foot or hand, but other sites may be involved

 



These tumors may reach many centimeters in diameter and may be pedunculated

 



While the majority of these tumors are solitary, multiple lesions may be seen (eccrine poromatosis)

 


Microscopic



This tumor is composed of numerous cords or trabeculae of small rounded tumor cells which rain down from the epidermis into the dermis in a fairly circumscribed manner

 



The epidermal component is similar to hidroacanthoma simplex, while the dermal component often shows numerous well-formed lobules with frequently conspicuous duct formation

 



Cystic change is typically less than that seen in hidradenoma, while the degree of epidermal involvement is significantly greater

 



The tumor cells show intercellular bridges and should not be confused with squamous cells that are larger and more polygonal

 



Poromatous lesions that are entirely limited to the dermis are often called dermal duct tumors

 


Porocarcinoma (Malignant Eccrine Poroma )



Clinical



The malignant counterpart to the eccrine poroma affects similar sites but tends to occur in older individuals with a long history of progressive tumor growth

 



The recurrence and metastatic rate approaches 25%

 



Multiple cutaneous metastases are not uncommon

 


Microscopic



Like their benign counterparts, epidermal, dermal, and mixed epidermal–dermal variants are seen

 



The epidermal variants and the cutaneous metastases typically show frank pagetoidosis with scattered foci of ductal differentiation

 



The mixed variants are by far the most common and have a similar architecture to their benign counterpart; however, these tumors are infiltrative and mitotically active and demonstrate nuclear pleomorphism and occasionally perineural and capillary–lymphatic invasion

 


Cylindroma and Malignant Cylindroma (Fig. 18.23)



A145302_4_En_18_Fig23_HTML.jpg


Fig. 18.23.
Cylindroma.



Clinical



Solitary or multiple, red to purple nodules on the head, neck, or scalp

 



Multiple tumors (turban tumors) are inherited in an autosomal dominant fashion and may be associated with multiple trichoepitheliomas

 


Microscopic



Multiple, dermal-based lobules are found in the dermis and have an interlocking or “jigsaw puzzle” appearance

 



The individual lobules are surrounded by an eosinophilic basement membrane

 



Two cell types are evident within the lobules: a lymphocyte-like population of cells with hyperchromatic nuclei which predominate at the periphery of the lobules and a population of larger cells with oval, vesicular nuclei which predominate centrally

 



Hylanizing basement membrane-like material is also frequently evident within the lobules

 



Malignant variants demonstrate nuclear pleomorphism, mitotic activity, loss of the surrounding basement membrane, and infiltration of adjacent tissue

 



Malignant variants are rare and may arise in the background of multiple benign cylindromas

 


Eccrine Spiradenoma and Malignant Eccrine Spiradenoma (Fig. 18.24)



A145302_4_En_18_Fig24_HTML.jpg


Fig. 18.24.
Eccrine spiradenoma (A, B).



Clinical



Usually solitary, blue- to flesh-colored intradermal nodules on the ventral aspect of the body

 



These tumors are frequently painful Rarely, multiple tumors may be seen in a linear or zosteriform distribution

 


Microscopic



One or more basophilic tumor lobules are evident in the dermis and are usually encapsulated

 



The lobules are composed of two cell types similar to the cylindroma: a small, lymphocyte-like population and a larger cell type with oval, vesicular nuclei

 



Ductal differentiation may be conspicuous within the lobules, and pseudovascular spaces may give a hemangiomatous quality to the lesion

 



The intervening stroma often demonstrates lymphangiectasia

 



The rare malignant variants require an adjacent benign focus of typical microscopy for confident diagnosis

 



The malignant variants are characterized by infiltration, mitoses, nuclear pleomorphism, necrosis, and lymphatic invasion

 


Eccrine Duct Carcinoma



Clinical



A nodular and often ulcerated lesion of long-standing duration found most commonly on the head, neck, and extremities of older adults

 



Approximately 50% metastasize to lymph nodes or visceral sites

 


Microscopic



An infiltrating dermal tumor composed of strands, trabeculae, and tubules with varying degrees of lumen formation

 



The histologic pattern is very similar to ductal carcinoma of the breast, which should always be excluded clinically

 



There is at least some degree of nuclear pleomorphism, and nucleoli are frequently prominent

 



Mitotic figures and necrosis may also be identified

 


Syringoid Eccrine Carcinoma (Eccrine Epithelioma )



Clinical



Typically, a plaque or an ulcerated tumor of the scalp of middle-aged adults

 



This tumor is locally aggressive with frequent recurrences, but metastases are rare

 


Microscopic



A dermal-centered tumor showing extensive infiltration with the involvement of the subcutaneous fat

 



This tumor is composed of infiltrating cords and trabeculae with faint lumen formation and a dense, hyalinizing stroma

 



Unlike microcystic adnexal carcinoma, keratocysts are rarely present

 



The individual cells often have basaloid features but lack peripheral retraction

 



Nuclear pleomorphism is mild, and mitotic figures are scarce

 



Perineural invasion is frequent

 


Microcystic Adnexal Carcinoma (Fig. 18.25)



A145302_4_En_18_Fig25_HTML.jpg


Fig. 18.25.
Microcystic adnexal carcinoma (A, B).



Clinical



A flesh-colored to yellow, slowly growing firm plaque or nodule involving the head, neck, or face of older adults

 



Like syringoid eccrine carcinoma, this is a locally aggressive tumor with frequent recurrences but with no tendency to metastasize

 


Microscopic



A dermal-centered tumor showing extensive infiltration of the deep dermis and subcutaneous tissues

 



Keratocysts, trabeculae, and ductules are evident throughout the lesion, but keratocysts tend to predominate superficially while trabeculae predominate at the deeper aspect of the tumor

 



The middle of the tumor shows an admixture of all forms, giving this tumor a triphasic or trilayered look from superficial to deep

 



The individual epithelial units are frequently invested by a dense fibrous stroma, giving this tumor a sclerotic appearance

 



Perineural invasion is common, while nuclear pleomorphism and mitotic activity are rare

 


Mucinous Eccrine Carcinoma



Clinical



A flesh-colored to blue nodule on the head and neck region (particularly the eyelid) of older adults with a male predominance

 


Microscopic



A dermal-based tumor showing islands of relatively bland epithelial cells floating in pools of mucin similar to colloid carcinoma of the breast

 


Adenoid Cystic Carcinoma



General



A rare, primary cutaneous neoplasm showing a similar microscopic characteristic to its counterparts elsewhere but having a less aggressive course

 


Mucoepidermoid Carcinoma



General



A rare primary tumor of the skin showing similar histologic features to its salivary gland counterpart

 


Apocrine-Derived Tumors and Proliferations



Apocrine Nevus



Clinical



A rare lesion typically presenting as a papule in the axilla or on the scalp

 


Microscopic



An increase in the number or size of mature-appearing apocrine glands

 


Syringocystadenoma Papilliferum (Fig. 18.26)



A145302_4_En_18_Fig26_HTML.jpg


Fig. 18.26.
S yringocystadenoma papilliferum.



Clinical



Typically a solitary, verrucous to papillary lesion on the scalp, face, or neck, but other sites may be involved

 



In children, this tumor frequently arises within a nevus sebaceous

 


Microscopic



A partially cystic, dermal-centered tumor showing overlying epidermal invagination

 



The cystic space contains abundant papillary structures lined by a bilayered epithelium with apical snouts, consistent with apocrine differentiation

 



The fibrovascular cores contain abundant plasma cells

 


Hidradenoma Papilliferum



Clinical



Typically a solitary, asymptomatic nodule present in the genital region of females

 



Similar lesions have been described within the ear, nipple, and eyelid

 


Microscopic



A well-demarcated, dermal-based neoplasm showing no involvement of the overlying epidermis

 



This tumor is also frequently cystic in areas and is characterized by numerous trabeculae, epithelial fronds, and papillary structures lined by a bilayered epithelium showing apocrine differentiation (apical snouts)

 



The stroma is fibrovascular and lacks the plasma cells of syringocystadenoma papilliferum

 



Occasional cases show a more pronounced fibrous stroma with a lobular architecture akin to fibroadenoma of the breast

 



Rare cases show malignant transformation with high-grade nuclear features, frequent mitoses, necrosis, and infiltration

 


Tubular Apocrine Adenoma (Fig. 18.27)



A145302_4_En_18_Fig27_HTML.jpg


Fig. 18.27.
Tubular apocrine adenoma.



Clinical



A well-defined nodule occurring most commonly on the scalp of adults

 


Microscopic



An unencapsulated but well-demarcated proliferation of numerous ducts/glands lined by a bilayered to multilayered epithelium showing apocrine differentiation

 



Small papillary structures and occasional cribriforming may be seen and resemble proliferative lesions in the breast

 



These lesions may show some degree of nuclear atypia and mitotic activity but generally are not considered as carcinomas unless obvious infiltration of surrounding tissues is seen

 


Apocrine Carcinoma



Clinical



A rare primary tumor of the skin that typically presents as an erythematous nodule with or without ulceration in older adults

 



A variety of sites may be affected including the scalp, eye, ear, and anogenital regions among others

 



Recurrences and metastases may occur

 


Microscopic



A variety of histologic appearances may be present including cystic, papillary, sheetlike, and ductal variants

 



Infiltration of adjacent tissues is seen, and pagetoidosis may be evident

 



Nuclear pleomorphism may be mild to marked, and varying degrees of mitotic activity and necrosis may be evident

 



By definition, areas of apocrine differentiation should be identified, at least focally

 


Differential Diagnosis



Apocrine carcinoma of the breast has similar histologic and immunophenotypic characteristics and should be excluded clinically

 


Neuroendocrine-Derived Tumors



Merkel Cell Carcinoma (Fig. 18.28)



A145302_4_En_18_Fig28_HTML.jpg


Fig. 18.28.
Merkel cell carcinoma (A, B).



Clinical



An aggressive neoplasm typically presenting as a slowly growing nodule on the sun-exposed skin (head and neck region) of older adults

 



The recurrence and metastatic rate is approximately 40–50%

 


Microscopic



A variety of histologic forms may be seen and include sheetlike, ribboned, nested, trabecular, and organoid variants

 



Pseudorosettes may be prominent

 



These tumors are typically dermal based but frequently involve the subcutis and may show an intraepidermal growth pattern

 



Focal areas of squamous, eccrine, or sebaceous differentiation may be seen, and these tumors may arise in conjunction with another histologically distinct neoplasm

 



The cytologic and immunophenotypic appearance is characteristic and common to all variants

 



Cytologically, the tumor cells have very high nuclear/cytoplasmic ratios, indistinct cell borders, and hyperchromatic and finely granular nuclei with inconspicuous nucleoli and thin nuclear membranes

 



Nuclear molding and mitoses are abundant

 



Immunophenotypically, the tumor cells express low molecular weight cytokeratin (CAM 5.2) in a perinuclear dot-like pattern which may also be seen with neurofilament staining

 



Cytokeratin 20 staining is generally positive, and these tumors express a variety of neuroendocrine markers including neuron-specific enolase, chromogranin, synaptophysin, and neurofilament but are generally negative for S-100 protein and vimentin

 


Differential Diagnosis



Merkel cell carcinomas must be differentiated from a variety of other neuroendocrine tumors of either metastatic or primary origin

 



Small cell neuroendocrine carcinomas from visceral sites metastatic to skin have an essentially identical histologic appearance but have recently been reported to be cytokeratin 20 negative

 



Cutaneous neuroblastoma generally shows a filamentous background and/or focal ganglion cell differentiation and is typically cytokeratin negative (except for the olfactory variant)

 



Primitive neuroectodermal tumors/extraosseous Ewing sarcomas are usually cytokeratin negative and typically express MIC- 2

 



Soft Tissue Neoplasms and Developmental Anomalies



Adipocyte-Derived Tumors and Proliferations



Lipoma



Clinical



A sporadic or multifocal tumor of the middle aged to elderly typically involving the trunk and/or extremities

 


Microscopic



A thin encapsulated proliferation of mature adipose tissue

 



The adipose tissue may be accompanied by a wide variety of other types of mesenchymal-derived tissue: fibrous (fibrolipoma), bone (osteolipoma), cartilage (chondroid lipoma), bone marrow (myelolipoma), mucoid substances (myxoid lipoma), smooth muscle (myolipoma), and smooth muscle and vessels (angiomyolipoma)

 


Angiolipoma



Clinical



A painful, subcutaneous nodule(s) involving the upper extremities of young adults

 


Microscopic



Thin encapsulated proliferations of mature adipocytes and variably sized, thin-walled vessels

 



Microthrombi are readily identified within the vessel lumina

 



A cellular variant showing numerous small vessels with few adipocytes exists and must be differentiated from other vascular tumors that lack the proliferation of mature adipocytes

 


Spindle Cell Lipoma



Clinical



A solitary, painless, subcutaneous nodule with a predilection for the base of the neck of middle-aged to older adults

 


Microscopic



An encapsulated proliferation of mature adipocytes and bland, bipolar spindle cells embedded in a myxoid matrix with collagen fibers

 



The spindle cells may predominate and typically show bland, uniform features

 



Lipoblasts and the plexiform capillary network of myxoid liposarcoma are absent

 



Occasional cases show bizarre, multinucleated cells and merge with pleomorphic lipoma

 


Pleomorphic Lipoma



Clinical



Similar to spindle cell lipoma

 


Microscopic



Similar to spindle cell lipoma with the addition of numerous, multinucleated (floret cells) cells with hyperchromatic, peripherally situated nuclei

 


Lipoblastoma and Lipoblastomatosi s



Clinical



These are tumors of infants and young children and typically present as painless masses on the extremities in a localized (lipoblastoma) or diffuse (lipoblastomatosis) fashion

 



The latter may recur with incomplete excision

 


Microscopic



Multilobular proliferations of immature and mature adipocytes embedded in a myxoid matrix and separated by thin fibrous septae

 



The adipocytes may show a wide spectrum of differentiation from spindle cells to multivacuolated lipoblasts to mature, univacuolated adipocytes

 



These lesions tend to mature histologically with time

 


Lipofibromatous Hamartoma of Nerve



Clinical



A tumorlike condition that presents as a mass of the wrist and/or forearm

 



Typically, these patients are young children, but adult presentations also occur

 



Sensory defects, paresthesias, pain, and macrodactyly may be prominent

 



Due to the intimate association of this proliferation with nerves, surgical excision is contraindicated and may lead to permanent sensorimotor impairment

 


Microscopic



A proliferation of benign fibroadipose tissue is evident in and around nerve fibers which show secondary degeneration, atrophy, and fibrosis

 


Lipomatosis



Clinical



Multiple clinical forms exist including a diffuse variant typically involving the extremities or trunk of young children, a symmetrical variant (Madelung disease) involving the neck region of middle-aged adult males as well as visceral and pelvic variants

 


Microscopic



All are unencapsulated proliferations of mature adipose tissue involving the subcutis, skeletal muscle, and, occasionally, other structures

 


Nevus Lipomatosus Superficialis



Clinical



A hamartomatous proliferation typically presenting as multiple, polypoid papules or plaques on the buttocks, posterior trunk, or thigh of children to young adults

 


Microscopic



Small lobules of mature adipocytes are evident in the superficial and mid dermis and may be associated with keratin plugs and loss of adnexal structures

 


Hibernoma



Clinical



A slow-growing, asymptomatic mass of the chest or upper back of young to middle-aged adults

 



Other sites may also be affected

 


Microscopic



An encapsulated, multilobular tumor composed of an admixture of multivacuolated and univacuolated adipocytes and large cells with eosinophilic cytoplasm and distinct cell membranes

 


Liposarcoma



Clinical



These are rare tumors of the skin that generally present as slowly growing subcutaneous masses in older adults

 


Microscopic



The myriad of histologic types of liposarcoma are addressed in detail elsewhere

 



Generally, the liposarcomas involving the skin are of the well-differentiated (atypical lipoma) or myxoid types

 



The former have lipoma-like, sclerosing, and spindle cell variants which may recur but typically do not metastasize

 


Neural-Derived Tumors and Proliferations



Neurofibroma



Clinical



Solitary and multiple forms exist

 



The solitary variant is typically a soft, polypoid, flesh-colored tumor occurring in adults

 



The multiple or diffuse variant has a strong association with neurofibromatosis type 1 and may show extensive, cosmetically deforming lesions with a bag-of-worms appearance and feel

 



The diffuse variant is seen more frequently in childhood and adolescence

 



The diffuse variant has definite malignant potential, while the sporadic variant lacks this characteristic

 


Microscopic



A variety of histologic subtypes exist, but all are characterized by a proliferation of wavy, pointed spindle cells embedded in a variably collagenous to myxoid matrix

 



These tumors are unencapsulated but are generally well circumscribed

 



They do not infrequently incorporate dermal adnexal structures, but direct adnexal invasion is rare

 



Plexiform, diffuse, myxoid, and pacinian variants exist

 



The plexiform variant is thought to be diagnostic of neurofibromatosis, while the diffuse variant may also be associated with this disease at an increased rate

 


Special Studies



Neurofibromas are derived from nerve and, as such, demonstrate positive staining for axonal markers such as neurofilament and silver impregnation techniques

 



Similar to other neural-derived tumors, these lesions are also positive for S-100 protein, CD57, and neuron-specific enolase

 


Schwannoma (Neurilemmoma, Fig. 18.29)



A145302_4_En_18_Fig29_HTML.jpg


Fig. 18.29.
Plexiform schwannoma.



Clinical



A peripheral nerve sheath-derived tumor that generally presents as a solitary nodule/mass on the head, neck, or extremities of adults

 



Rarely, multiple tumors may be evident (schwannomatosis), and at least some of these cases are associated with neurofibromatosis type 2

 



In general, schwannomas have little, if any, malignant potential

 


Microscopic



A well-circumscribed, encapsulated tumor within the subcutis or deeper tissues

 



Occasionally, dermal involvement may be evident

 



The tumor is composed of spindle cells with wavy, pointed nuclei embedded in a collagenous and highly vascular stroma

 



Classically, cellular, Antoni A areas with palisading, Verocay bodies are admixed with paucicellular, myxoid, Antoni B areas

 



Degenerative changes are frequent findings and include hyalinization, vascular thrombosis, dystrophic mineralization, and hemorrhage

 



The ancient variants typically show some degree of nuclear pleomorphism and enlargement with a smudgy chromatin pattern

 



Plexiform variants exist and typically present in childhood or adolescence

 



These tumors are composed of multiple, cellular, Antoni A-like, encapsulated nodules that must be differentiated from plexiform neurofibroma and plexiform fibrohistiocytic tumor

 



Cellular variants are moderately to markedly cellular and may have mitotic activity. Nuclear pleomorphism and necrosis, however, are absent. Melanotic variants also exist and must be differentiated from malignant melanoma

 


Special Studies



Schwannomas are derived from the peripheral nerve sheath and, therefore, lack axonal differentiation; that is, they are neurofilament and silver staining negative

 



Schwann cells are S-100 protein positive and are generally surrounded by type IV collagen-rich basement membrane

 



Epithelial membrane antigen typically stains the capsule of schwann omas

 


Traumatic Neuroma



Clinical



Reactive, nonneoplastic proliferations of nerve in response to injury

 



Typically present as small, often painful, nodules at sites of previous injury

 


Microscopic



A well-localized but unencapsulated, haphazard proliferation of nerve fibers associated with dermal fibrosis (scar)

 


Palisaded and Encapsulated Neuroma (Solitary Circumscribed Neuroma, Fig. 18.30)



A145302_4_En_18_Fig30_HTML.jpg


Fig. 18.30.
Palisaded and encapsulated neuroma.



Clinical



Solitary, flesh-colored papule on the face of middle-aged to older adults

 


Microscopic



A nodular to multinodular, often dumbbell-shaped proliferation of spindle cells embedded in a collagenous matrix

 



These lesions are well circumscribed but only partially encapsulated

 



The superficial component generally lacks a true capsule and tends to resemble a neurofibroma, while the deep component is encapsulated and resembles a schwannoma

 



The spindle cells demonstrate wavy, pointed nuclei and lack mitotic activity

 



Contrary to its name, true nuclear palisading is rare in this lesion

 



A nerve may be evident entering the base of the lesion

 


Special Studies



Like neurofibroma, this lesion contains both axons and schwann cells and, hence, is S-100 protein and neurofilament positive

 


Granular Cell Tumor (Fig. 18.31)



A145302_4_En_18_Fig31_HTML.jpg


Fig. 18.31.
Granular cell tumor.



Clinical



Slowly growing, sometimes painful, flesh-colored nodules with a predilection for the tongue, trunk, and extremities of adults

 



While usually solitary, multiple, and familial variants exist

 


Microscopic



Irregular fascicles and/or sheets of large, round to polygonal cells with eosinophilic, granular cytoplasm

 



Cell borders are indistinct giving this tumor a syncytial appearance

 



Nuclei are generally round to ovoid, central, and monomorphic

 



Nuclear pleomorphism, mitotic activity, necrosis, and large tumor size may be associated with the rare malignant variants

 



Prominent pseudoepitheliomatous hyperplasia of the epidermis is often seen overlying this tumor and must not be mistaken for squamous cell carcinoma

 


Special Studies



While the cell of origin remains to be clarified, most authorities support a schwann cell derivation for these tumors

 



Accordingly, these tumors are usually, but not always, S-100 protein and neuron-specific enolase positive

 


Differential Diagnosis



Secondary granular cell change is not an uncommon finding in other tumor types (dermatofibroma, neurofibroma, etc.) which should be excluded prior to making the diagnosis of granular cell tumor

 



This tumor should also be differentiated from congenital epulis discussed below

 


Congenital Epulis



Clinical



A polypoid gingival lesion in newborns that may spontaneously regress

 


Microscopic



Similar to granular cell tumor, but these lesions are S-100 protein negative

 


Nerve Sheath Myxoma (NSM ) and Cellular Neurothekeoma (Fig. 18.32)



A145302_4_En_18_Fig32_HTML.jpg


Fig. 18.32.
Neurothekeoma.



Clinical



Soft, mobile, flesh-colored papules on the face or upper extremities of young adults

 



These tumors may recur with incomplete excision

 


Microscopic



NSM is a fascicular to lobular dermal tumor composed of spindle and stellate cells embedded in myxoid lobules which in turn are separated by fibrous septae

 



Cellular neurothekeoma is composed of more uniform, epithelioid cells in nests and fascicles with minimal myxoid background material

 



Mitotic activity and mild nuclear pleomorphism may be seen in both lesions

 


Special Studies



NSM is typically S-100 protein+ and is likely derived from the peripheral nerve sheath

 



Cellular neurothekeoma is S-100 protein− and its cell of origin is unclear

 



The lack of S-100 protein positivity in the cellular variants allows these lesions to be readily distinguished from most melanocytic neoplasms

 


Perineurioma



Clinical



A benign tumor of perineural origin that typically presents as a subcutaneous mass on the trunk and limbs of adults

 


Microscopic



A well-circumscribed proliferation of bland spindle cells in fascicles with whorled and storiform areas

 


Special Studies



Like perineural cells, this tumor is S-100 protein− and EMA+

 


Malignant Peripheral Nerve Sheath Tumor



General



A rare, primary cutaneous malignancy frequently associated with neurofibromatosis type 1 when primary in the skin

 



These lesions are discussed in detail in the chapter on soft tissue pathology

 


Cutaneous Meningothelial Heterotopias/Meningiomas (Fig. 18.33)



A145302_4_En_18_Fig33_HTML.jpg


Fig. 18.33.
Meningioma.



Clinical



Classic meningocele is typically a transilluminating mass along the lower spine and represents a congenital defect

 



Rudimentary meningocele is thought to be a herniation of the meninges into the superficial tissues of the scalp with a subsequent loss of its intracranial attachment

 



Cutaneous meningioma comes in three forms: type I is congenital lesion involving the head and paravertebral regions of children and is secondary to misplaced arachnoid cells during embryogenesis; type II occurs on the head and neck region of adults and is thought to be secondary to a proliferation of arachnoid cells through a cranial foramina; type III represents a metastasis or direct extension of tumor into skin from an intracranial primary lesion

 


Microscopic



Meningoceles are typically cyst-like structures lined by arachnoid cells and having surrounding dense fibrous tissue with occasional collections of meningothelial cells in whorl-like structures

 



Meningiomas are usually well-circumscribed deep dermal to subcutaneous proliferations composed of spindle cells arranged in fascicles and whorls with or without psammoma body formation

 



Nuclear pleomorphism and mitotic activity may be seen, particularly in the type III variants

 



Special studies

 



Meningothelial proliferations are usually vimentin and EMA+

 



Cytokeratin and S-100 protein may also be expressed by these tumors

 


Heterotopic Glial Tissue (Nasal Glioma)



Clinical



Flesh-colored mass on the nasal bridge of infants to young adults. Intranasal involvement may also be present

 



Radiographic studies should be performed to exclude an intracranial attachment

 


Microscopic



Nodules of benign eosinophilic, fibrillar, glial tissue within the deep dermis and subcutis

 



Rarely, neuronal cells may also be seen

 


Smooth Muscle-Derived Tumors and Proliferations



Smooth Muscle Hamartoma



Clinical



A congenital, sometimes pigmented, indurated plaque on the trunk which typically presents in infancy

 


Microscopic



A haphazard proliferation of smooth muscle fascicles in the dermis with or without basilar epidermal hyperpigmentation

 


Becker Nevus



Clinical



An acquired, organoid, hyperpigmented plaque with hypertrichosis on the back of young adults and in adolescents

 



This lesion may be associated with other congenital abnormalities

 


Microscopic



Epidermal acanthosis and basilar hyperpigmentation occasionally associated with a mild haphazard proliferation of smooth muscle fascicles within the dermis

 


Piloleiomyoma (Pilar leiomyoma, Fig. 18.34)



A145302_4_En_18_Fig34_HTML.jpg


Fig. 18.34.
Piloleiomyoma.



Clinical



Multiple, somewhat painful papules or nodules on the trunk or extremities of young adults

 



May be inherited in an autosomal dominant fashion

 


Microscopic



A fairly well-circumscribed yet irregular proliferation of smooth muscle fascicles within the dermis

 



The individual cells have elongated eosinophilic cytoplasm and cigar-shaped nuclei

 



No nuclear pleomorphism, mitotic activity, or necrosis is evident

 


Angioleiomyoma (Fig. 18.35)



A145302_4_En_18_Fig35_HTML.jpg


Fig. 18.35.
Angioleiomyoma.



Clinical



A solitary, sometimes painful nodule on the extremities of adults

 


Microscopic



A nodular, well-circumscribed proliferation of smooth muscle in fascicles admixed with numerous, variably sized vessels

 



Degenerative changes are frequent

 


Leiomyosarcoma (Fig. 18.36)



A145302_4_En_18_Fig36_HTML.jpg


Fig. 18.36.
Leiomyosar coma.



Clinical



Two clinical variants exist: a superficial or cutaneous variant and a deep or subcutaneous variant

 



The former predominates on the limbs of young adults and is likely derived from the arrector pili muscle

 



This variant may locally recur but generally does not metastasize

 



The subcutaneous variant predominates on the limbs of the elderly and has both local recurrence and metastatic potential

 


Microscopic



The cutaneous variant demonstrates an irregular, infiltrating, and haphazard proliferation of smooth muscle bundles reminiscent of piloleiomyoma

 



However, unlike piloleiomyoma, this tumor has low-grade nuclear pleomorphism, mitotic activity, and, rarely, necrosis

 



The deep or subcutaneous variant is akin to leiomyosarcomas arising elsewhere and consists of a nodular, at least focally infiltrating, proliferation of smooth muscle fibers in well-formed to ill-defined bundles with varying degrees of nuclear pleomorphism, mitotic activity, and necrosis

 


Fibrohistiocytic, Histiocytic, and Langerhans Cell-Derived Proliferations



Fibrous Histiocytoma (Dermatofibroma, Fig. 18.37)



A145302_4_En_18_Fig37_HTML.jpg


Fig. 18.37.
Dermatofibroma.



Clinical



Usually single, occasionally multiple, slightly elevated, smooth, flesh-colored to hyperpigmented nodules on the extremities or trunk of adults

 


Microscopic



Numerous subtypes have been described, but all are generally made up of a proliferation of histiocytes, fibroblasts, and collagenous tissue in varying proportions

 



The prototypical lesion (dermatofibroma) consists of a fairly well-circumscribed, unencapsulated, middermal proliferation with feathery edges, an overlying Grenz zone, and epidermal hyperplasia with basilar hyperpigmentation

 



The cellular component consists of spindled, fibroblast-like cells admixed with plump histiocytic cells in an irregular fashion

 



Storiform areas may be evident, and there may be focal extension into the subcutis

 



Chronic inflammatory cells, multinucleated giant cells, xanthomatized histiocytes, and hemosiderin-laden histiocytes are also frequently identified within these lesions

 



Important variants include atypical dermatofibroma (dermatofibroma with monster cells), aneurysmal fibrous histiocytoma, and epithelioid cell histiocytoma, all of which may be mistaken for other more aggressive entities

 



Atypical dermatofibroma is a lesion showing large, hyperchromatic, multinucleated giant cells in addition to typical dermatofibroma features and should be distinguished from atypical fibroxanthoma and malignant fibrous histiocytoma

 



Aneurysmal fibrous histiocytoma is a fibrous histiocytoma with prominent intralesional hemorrhage and cystic, pseudovascular spaces

 



This lesion should be distinguished from angiomatoid fibrous histiocytoma, a lesion of intermediate-grade malignancy occurring in the pediatric population

 



Epithelioid cell histiocytoma is composed of a polypoid well-circumscribed proliferation of angulated, epithelioid, histiocytic-appearing cells surrounded by an epidermal collarette

 



This lesion should be distinguished from melanocytic tumors, both Spitz nevus and melanoma

 


Special Studies



Most fibrous histiocytomas express FXIIIa but are negative for CD34

 



Dermatofibroma sarcoma protuberans tends to have the opposite staining pattern, but overlap and divergent staining patterns occasionally occu r

 


Angiomatoid Fibrous Histiocytoma (Fig. 18.38)



A145302_4_En_18_Fig38_HTML.jpg


Fig. 18.38.
Angiomatoid fibrous histiocytoma (A, B).



Clinical



A fairly deep-seated, usually subcutaneous, nodule or mass within the extremities of children and adolescents

 



This lesion is considered to be of borderline or intermediate malignancy and may recur and, rarely, metastasize

 


Microscopic



A circumscribed, partially cystic and lobular mass usually centered on subcutaneous tissue

 



This tumor is composed of an admixture of cystic, blood-filled pseudovascular spaces, myxoid lobules of histiocytic-appearing cells, and peripheral lymphocytic inflammation and fibrosis

 



The neoplastic cells are somewhat spindled to plump, epithelioid cells with eosinophilic to amphophilic cytoplasm and mildly pleomorphic nuclei

 



Mitotic figures may be evident

 


Special Studies



The histiocytic-appearing cells often show expression of smooth muscle actin, desmin, and CD34, suggesting to som e a myofibroblastic derivation to this tumor

 


Plexiform Fibrohistiocytic Tumor



Clinical



A slowly growing deep dermal to subcutaneous mass on the extremities of children to young adults

 



This is a tumor of intermediate malignancy that may recur and rarely metastasizes

 


Microscopic



An unencapsulated, irregular biphasic tumor consisting of short fibromatosis-like fascicles of plump spindle cells admixed with nodules of histiocytic and osteoclast-like giant cells with minimal nuclear pleomorphism

 



The admixture of nodules and fascicles gives this tumor a plexiform appearance at low power

 


Juvenile Xanthogranuloma (Fig. 18.39)



A145302_4_En_18_Fig39_HTML.jpg


Fig. 18.39.
Juvenile xanthogranuloma.



Clinical



Solitary to multiple, yellow to red papules on the head and neck region of infants are the most common presentation

 



However, adolescents and adults may also be affected, and other body sites may be involved

 



Visceral involvement may be evident with the eye being the most common extracutaneous site of involvement

 



Typically, the cutaneous lesions regress over time

 


Microscopic



Fairly well-circumscribed collection of histiocytes within the dermis admixed with Touton giant cells, xanthomatized histiocytes, and chronic inflammatory cells

 



The epidermis is spared, but periadnexal involvement is common

 



Spindle cell and inflammatory cell-rich variants exist

 


Reticulohistiocytoma and Multicentric Reticulohistiocytosis



Clinical



Solitary and multicentric variants exist

 



The former is usually a yellow to brown nodule on the upper body of adults, while the latter shows multiple lesions associated with a destructive arthritis and constitutional symptoms, also in adults

 



Occasionally, the multicentric variant is associated with visceral neoplasia

 


Microscopic



Both variants are characterized by fairly well-circumscribed proliferations of large, eosinophilic histiocytes with “glassy” cytoplasm

 



The individual cells may contain more than a single nucleus, but Touton giant cells are usually absent, and xanthomatized histiocytes are not generally present

 



Mild nuclear pleomorphism and admixed inflammation with eosinophils and lymphocytes may be evident

 


Atypical Fibroxanthoma (Fig. 18.40)



A145302_4_En_18_Fig40_HTML.jpg


Fig. 18.40.
Atypical fibroxanthoma.



Clinical



Typically a solitary, often ulcerated polypoid nodule on the sun-exposed skin (head and neck) of the elderly

 



A less common variant occurs on the trunk and extremities of young adults

 



These tumors, when limited to superficial tissues, may locally recur but have minimal metastatic potential

 


Microscopic



A nodular, often well-circumscribed, proliferation of very pleomorphic epithelioid to spindle cells with frequent mitoses, often atypical

 



These tumors are usually centered on the dermis and frequently about the dermal–epidermal junction where they stop abruptly

 



Epidermal ulceration is common, but true epidermal involvement with pagetoid spread should raise concerns about malignant melanoma or squamous cell carcinoma

 



Rarely, the tumor is composed of spindle cells in poorly defined fascicles and may be mistaken for leiomyosarcoma

 



While occasional tumors may show superficial involvement of the subcutaneous tissues, extensive subcutaneous involvement and/or prominent vascular invasion and necrosis should lead to an alternate diagnosis (e.g., malignant fibrous histiocytoma)

 


Special Studies



This tumor is a diagnosis of exclusion; therefore, S-100 protein, cytokeratin, and desmin should be negative by immunoperoxidase technique to exclude malignant melanoma, carcinoma, and leiomyosarcoma, respectively

 



Smooth muscle actin may be expressed by a subset of these tumors and is not indicative of smooth muscle differentiation (leiomyosarcoma) in the absence of desmin positiv ity

 


Malignant Fibrous Histiocytoma



General



These tumors are rarely primary cutaneous lesions and have overlapping histologic features with atypical fibroxanthoma

 



The latter tumor is often considered to be a superficial variant of malignant fibrous histiocytoma with minimal metastatic potential

 



The term malignant fibrous histiocytoma should be used for those tumors that demonstrate deep tissue involvement, vascular invasion, or extensive necrosis as detailed above

 



The histologic subtypes and clinical distribution of this tumor are detailed in the chapter on soft tissue tumor

 


Xanthomas and Xanthelasma (Fig. 18.41)



A145302_4_En_18_Fig41_HTML.jpg


Fig. 18.41.
Verruciform xanthoma.



Clinical



Numerous clinical and histologic subtypes exist, many of which are related to systemic lipid abnormalities and represent storage disorders

 



Eruptive





  • Yellow papules on the buttocks and other sites associated with type I hyperlipoproteinemia

 



Tuberous





  • Yellow papules and nodules on the extensor surfaces associated with hyperlipoproteinemia types II–IV

 

Sep 21, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Neoplasms of the Skin and Immunodermatology

Full access? Get Clinical Tree

Get Clinical Tree app for offline access