Module 14: Adnexal and Other Nonmelanocytic Neoplasms

Adnexal neoplasms are tumors arising from the skin appendages (adnexa), which include sweat glands (eccrine and apocrine), sebaceous glands, and hair follicles. They are classified by their line of differentiation:

Differentiation	Structures of Origin	Example Tumors
Eccrine	Eccrine sweat glands and ducts	Poroma, porocarcinoma, hidradenoma, syringoma, hidrocystoma
Apocrine	Apocrine glands	Syringocystadenoma papilliferum, hidradenoma (apocrine variant)
Sebaceous	Sebaceous glands	Sebaceous hyperplasia, sebaceous adenoma, sebaceoma, sebaceous carcinoma
Follicular	Hair follicle components	Pilomatricoma, trichoepithelioma, trichoblastoma, trichilemmoma, trichodiscoma, trichilemmal cyst/carcinoma

• Many adnexal tumors are benign but produce nonspecific dermoscopic findings that overlap with malignant neoplasms (BCC, melanoma, SCC).
• Dermoscopy can provide morphological information to help in diagnosis, but it is not uncommon to discover that the dermoscopic findings are nonspecific, requiring biopsy to rule out malignancy.
• Certain adnexal tumors serve as sentinel markers for hereditary syndromes (e.g., sebaceous adenoma in Muir-Torre syndrome, multiple trichoepitheliomas in Rombo syndrome).

• "White structures" (white streaks, white structureless areas, milia-like cysts) have been suggested as a dermoscopic clue favoring a follicular tumor over BCC.
• Crown vessels (nonarborizing branching vessels that surround a central structure without crossing the midline) are characteristic of sebaceous differentiation.
• Polymorphous vessels and branched vessels with rounded endings are commonly seen in eccrine/apocrine tumors.
• Blue-gray structures (dots, globules, ovoid nests) overlap between follicular tumors and BCC, requiring histopathologic confirmation.

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4.1.1 Overview

Clear cell acanthoma is a rare, benign, epithelial tumor (not technically an adnexal tumor, but discussed in this chapter as a benign nonmelanocytic lesion). It has no gender predilection and usually develops in middle-aged adults (peak incidence 50-60 years).

4.1.2 Clinical Presentation

• Morphology: Asymptomatic, erythematous, rounded papulo-nodular lesion
• Location: Usually the lower limbs
• Surface features: May reveal a peripheral epidermal collarette of scale or superimposed serous exudate

4.1.3 Histopathology

• Well-demarcated area of psoriasiform epidermal hyperplasia
• Keratinocytes have pale-staining (clear) cytoplasm
• Mild spongiosis, exocytosis of neutrophils, and thinning of the suprapapillary plates

4.1.4 Dermoscopic Features -- "String of Pearls" Pattern

The hallmark dermoscopic finding is the "string of pearls" (pearl-necklace) pattern:

• Glomerular or dotted vessels aligned and arranged in serpiginous lines, resembling a string of pearls
• This pattern is rarely seen in lesions other than CCA
• A peripheral collarette of scale may be present and may correlate with the active growth phase

Key Point: The string-of-pearls pattern -- dotted or glomerular vessels arranged in linear/serpiginous rows -- is virtually pathognomonic for CCA.

4.1.5 Treatment and Management

CCA is benign; however, if the history or the dermoscopic features are not typical, biopsy to confirm the diagnosis is the safest management strategy.

4.1.6 Differential Diagnosis

Differential	Key Distinguishing Feature
Amelanotic melanoma	Polymorphous vessels, no string-of-pearls pattern; lacks collarette
Inflamed seborrheic keratosis	Comedo-like openings, milia-like cysts, fissures
Squamous cell carcinoma	Irregular vessels, keratinization, surface scale
Basal cell carcinoma	Arborizing vessels, blue-gray structures
Psoriasis patch	Clinical context differs (widespread, bilateral); dotted vessels are diffusely distributed rather than in serpiginous lines

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Clinical Scenario

A 60-year-old woman presents with a well-circumscribed, solitary, pink-red nodule on the anterior shin. The lesion is dome-shaped and slightly pedunculated. Dermoscopy reveals dotted and glomerular vessels arranged in a characteristic serpiginous (string-of-pearls) pattern. The vessels follow a linear, snakelike arrangement across the lesion. No pigment network, blue-white veil, or white circles are present.

What is your diagnosis and key dermoscopic findings?

Clear cell acanthoma

The serpiginous vessel pattern (dotted or coiled vessels arranged in a linear snakelike configuration) is pathognomonic for clear cell acanthoma and has no differential diagnosis. Histopathologically, the dotted/glomerular vessels correspond to dilated vessels filling the tips of dermal papillae within the acanthotic epidermis composed of glycogen-rich clear keratinocytes. In the Prediction without Pigment algorithm, this pattern represents one of the four benign monomorphous vessel patterns. The absence of keratin clues or white structures further supports this diagnosis.

4.2.1 Overview

Eccrine poroma is a benign adnexal neoplasm composed of glandular ductal cells of eccrine origin. Pigmented variants account for 10-15% of poromas. Poromas can simulate both benign and malignant tumors clinically and dermoscopically.

4.2.2 Clinical Presentation

• Morphology: Asymptomatic, skin-colored to erythematous lesions; clinical presentation varies widely (sessile or pedunculated papule to large plaques and exophytic tumors)
• Location: Most frequently the trunk, followed by the limbs including acral sites (palms and soles were historically considered most common, but a multicentre IDS study showed the trunk is actually the most frequent location)
• Ulceration: May be present, especially at pressure sites

4.2.3 Histopathology

• Proliferation of small round cuboidal cells ("poroid cells") and sweat ducts
• Superficial and deep vascular proliferation combined with basaloid proliferation

4.2.4 Dermoscopic Features

Most Specific Features (low prevalence but high specificity):

• Branched vessels with rounded endings (formerly known as chalice or cherry blossom-like vessels)
• Milky-red globules
• White interlacing areas around vessels
• Yellow structureless areas

Important: None of these features are exclusive to poroma. Malignant tumors (melanoma, SCC) can also display similar structures.

Other Nonspecific but Frequently Found Features:

• Collarette of keratin/scale
• Milky-red areas
• Blood spots
• Hairpin/looped vessels
• Polymorphous vessels
• Blue/gray globules or nests

4.2.5 Four Dermoscopic Patterns of Poroma (Marchetti et al.)

Pattern	Typical Location	Key Features
Pattern 1 (most common)	Palms/soles (volar skin)	Hyperkeratotic well-demarcated border (collarette), blood spots, yellow structureless areas, milky-red globules, milky-red areas, branched vessels with rounded endings
Pattern 2	Trunk or nonvolar extremities	Polymorphous vessels, white interlacing areas around vessels, branched vessels with rounded endings
Pattern 3	Anywhere (small lesions)	Small size; branched vessels with rounded endings may be seen but often no vessels are visible; clinically simulates nodular BCC
Pattern 4	Anywhere (large lesions)	Large, sometimes pigmented; blood spots, keratin/scale, looped/hairpin vessels; resembles keratinizing tumors such as seborrheic keratosis

4.2.6 Treatment and Management

Poromas are benign, but the structures and patterns they manifest are not reliable in differentiating them from malignant tumors such as porocarcinoma. Histopathology confirmation is recommended. Several cases of malignant transformation and coexistence of poroma with porocarcinoma have been reported.

4.2.7 Differential Diagnosis

Poromas can clinically and dermoscopically simulate:

• Pyogenic granulomas
• Angiomas
• Inflamed seborrheic keratosis
• Squamous cell carcinomas
• Basal cell carcinomas
• Melanomas

Clinical Pearl: Poroma is the "great dermoscopic imitator" -- lesions suggestive of poroma should always be biopsied to confirm the diagnosis and rule out malignancy.

4.2.8 Porocarcinoma

Porocarcinoma (malignant eccrine poroma) shows:

• Polymorphous and atypical vessels (dotted, linear irregular vessels)
• Ulceration
• Yellowish scale

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Check Your Understanding

What dermoscopic features are characteristic of cylindroma?

Cylindroma typically shows a well-circumscribed pink-to-red nodule with arborizing vessels or branching linear vessels. It may also display blue-white structureless areas. When multiple, cylindromas may show a jigsaw puzzle-like arrangement (turban tumor pattern).

Key Takeaways

• Eccrine poroma characteristically shows white interlacing bands (leaf-like or flower-like white areas) with poorly visualized vessels and milky-pink globules.
• Porocarcinoma (malignant counterpart) shows polymorphous vessels, white-pink structureless areas, and irregular architecture that overlaps with other cutaneous malignancies.
• Cylindroma presents as blue-gray nodules with arborizing vessels, and the dermoscopic pattern may be indistinguishable from BCC without histology.

Sebaceous neoplasms are adnexal tumors with sebaceous differentiation that comprise a broad spectrum of histopathologic subtypes, conventionally classified from benign to malignant as: sebaceous hyperplasia -> sebaceous adenoma -> sebaceoma -> sebaceous carcinoma.

4.3.1 Sebaceous Hyperplasia

Overview

A benign neoplasm representing localized hypertrophy of the sebaceous glands.

Clinical Presentation

• Morphology: Single or multiple white to yellowish soft papules of varying size
• Location: Predominantly the face of middle-aged adults; less frequently on the chest, areolae, mouth, and genitals
• Central indentation: The center of the lesion often has a slight indentation

Histopathology

• Grouped white-yellowish nodules (hyperplastic sebaceous glands)
• Within each gland: mature sebaceous lobules/acini surround and connect a dilated central sebaceous duct

Dermoscopic Features

The three hallmark dermoscopic findings:

1. Polylobular round structures ("popcorn-like" structures) -- white to yellowish, also known as the "bonbon toffee sign"
2. Central umbilication -- corresponds to the dilated central duct
3. Crown vessels -- nonarborizing, branching vessels that extend toward the center but do not cross the midline; this vascular pattern is characteristic of (though not specific to) hyperplastic sebaceous glands

The "Cumulus Sign": The combination of crown vessels surrounding central umbilication with yellowish-white polylobular structures creates an appearance that has been likened to cumulus clouds.

Treatment and Management

No treatment is required unless for cosmetic purposes. When the lesion resembles BCC on both clinical examination and dermoscopy, biopsy is justified.

Differential Diagnosis

• BCC (most important to exclude -- arborizing vessels cross the lesion; no central yellowish lobules)
• Other sebaceous neoplasms
• Dermal nevus
• Fibrous papule
• Molluscum contagiosum
• Syringomas

4.3.2 Sebaceous Adenoma

Overview

Rare, benign neoplasms originating from sebaceous glands. They are the most common histopathologic tumor found in Muir-Torre syndrome (MTS) (reported frequency ~70%). Detection of a sebaceous adenoma should prompt evaluation for MTS.

Clinical Presentation

• Morphology: White to pink nodules
• Location: Head and neck region in midlife; in MTS, they may develop at a younger age and are often found on the torso

Histopathology

• Well-circumscribed nodular dermal proliferations of lobular aggregations of fully differentiated sebocytes with basaloid germinative cells at the periphery
• Immunohistochemistry for MSH2, MLH1, and MSH6 should be performed to rule out MTS

Dermoscopic Features

• Central indentation with a structureless ovoid white-yellow center
• Yellowish background
• Yellow comedo-like globules (without central indentation)
• Red blood crusts
• Crown vessels (radial telangiectasia, similar to sebaceous hyperplasia but often out-of-focus)

Treatment and Management

Surgical removal is the mainstay. If sebaceous adenomas are present with loss of MSH2/6/1 expression, evaluate for mismatch repair gene germline defects and familial colorectal Lynch syndrome. Genetic counseling referral is recommended if confirmed.

Differential Diagnosis

Sebaceous hyperplasia, sebaceous carcinoma, sebaceous epitheliomas, BCC, sebaceoma, and nevus sebaceous.

4.3.3 Sebaceoma

• Dermoscopic features: Homogeneous yellowish central structure with crown vessels

4.3.4 Sebaceous Carcinoma

• Dermoscopic features: Polymorphous and atypical vessels, yellowish background, ulceration

4.3.5 Sebaceous Cyst

• Dermoscopic features: White/yellow central structure, yellowish background, crown vessels

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Clinical Scenario

A 72-year-old man presents with a 4 mm yellowish papule on the nose with a central dimple. Dermoscopy reveals polylobular white-yellow structures ("popcorn-like"), a central umbilication, and crown vessels that radiate toward the center but do not cross the midline.

What is the most likely diagnosis and key dermoscopic clue distinguishing it from BCC?

Sebaceous Hyperplasia

The triad of polylobular yellowish structures (bonbon toffee sign), central umbilication, and crown vessels that do NOT cross the midline is characteristic of sebaceous hyperplasia. In BCC, arborizing vessels cross the lesion and no central yellowish lobules are present. Despite these distinguishing features, biopsy may still be warranted when the clinical-dermoscopic picture is ambiguous.

General Principles

The dermoscopic pattern of benign follicular tumors shows structures overlapping with BCC, such as:

• Linear branching vessels
• Blue-gray dots or globules

The presence of "white structures" (white streaks, white structureless areas, milia-like cysts) has been suggested as a dermoscopic clue favoring a follicular tumor over BCC.

4.4.1 Pilomatricoma

Overview

A dermal or subcutaneous tumor derived from immature hair matrix cells.

Clinical Presentation

• Location: Head, neck, and upper extremities of children and adolescents
• Morphology: Firm, solitary, sometimes partially pigmented with a gray to bluish color

Histopathology

• Early lesions: cystic, with mitotically active uniform basaloid cells covering the cystic cavity, transformed into pale eosinophilic anucleated shadow/ghost cells admixed with keratin
• Older lesions: solid, with prominent shadow cell component, keratin debris, secondary multinucleated giant cells, and dystrophic calcification

Dermoscopic Features

• Irregular yellow and/or whitish structures and streaks -- corresponding histologically to calcification
• Ulceration
• Small structureless gray-blue areas
• Reddish homogeneous areas
• Hairpin vessels and serpentine vessels
• Linear vessels at the periphery

Limitation: No dermoscopic structures are diagnostic of pilomatricoma alone. The combination of findings with the clinical context (young patient, firm subcutaneous nodule) aids diagnosis.

Treatment and Management

Simple excision for diagnosis and to prevent local persistence and growth.

Differential Diagnosis

Epidermoid or pilar cyst, calcinosis cutis, and glomus tumor.

4.4.2 Trichoepithelioma

Overview

A benign follicular tumor. The desmoplastic variant is particularly important in the differential with BCC.

Clinical Presentation

Trichoepitheliomas (including desmoplastic variant) can present as:

1. Isolated pink papule (~5 mm) on hair-bearing skin, especially sun-exposed areas of the face in young to middle-aged adults
2. Multiple small (1-5 mm) lesions in children and adolescents, usually involving the upper lip, cheeks, and paranasal region

Syndromic Association: Multiple trichoepitheliomas should prompt consideration of an autosomal dominant familial disorder such as Rombo syndrome.

Trichoepitheliomas tend to remain stable over years to decades -- an important clinical clue distinguishing them from BCC.

Histopathology

• Basaloid cells arranged in small cords and infundibulocystic structures containing keratin surrounded by fibrotic collagen

Dermoscopic Features

• Pearly white background (porcelain white or ivory in desmoplastic subtype)
• Multiple milia-like cysts
• Rosettes (polarized dermoscopy)
• In-focus arborizing vessels (fine caliber)

Critical Distinction: These features can also be seen in BCC (particularly infundibulocystic type). The key differentiating clue is often the clinical history of stability over many years, which favors trichoepithelioma over BCC.

Treatment and Management

Biopsy to confirm the diagnosis.

Differential Diagnosis

• BCC (most critical -- especially desmoplastic trichoepithelioma vs. BCC)
• Trichoblastoma
• Trichilemmoma
• Molluscum contagiosum
• Syringomas
• Milia
• Sebaceous hyperplasia

4.4.3 Trichoblastoma

Dermoscopic Features

• Blue-gray dots or globules (resembling BCC ovoid nests)
• Arborizing vessels
• White structureless areas

BCC Mimicry: Trichoblastoma shows a striking similarity with BCC. Diagnosis should always be histopathologically confirmed.

4.4.4 Trichodiscoma

Dermoscopic Features

• White globules
• Blue/gray nests
• Linear vessels

4.4.5 Trichilemmoma

Dermoscopic Features

• Keratin
• Red iris-like structures
• White halos surrounding vessels

4.4.6 Trichilemmal Cyst

Dermoscopic Features

• White/yellow central structure
• Linear branched vessels at periphery
• Structureless blue pigmentation

4.4.7 Trichilemmal Carcinoma

Dermoscopic Features

• Polymorphous and atypical vessels
• White/yellow structureless areas
• Ulceration

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Check Your Understanding

How does dermoscopy of trichoblastoma differ from that of basal cell carcinoma?

Both trichoblastoma and BCC can show arborizing vessels and blue-gray structures, making differentiation challenging. However, trichoblastoma tends to show fewer and less prominent arborizing vessels, may display elongated comma-like vessels, and often has a more symmetric, well-organized pattern compared to BCC. Definitive diagnosis often requires histopathology.

Key Takeaways

• Trichoblastoma and trichoepithelioma share dermoscopic features with BCC (arborizing vessels, blue-gray areas) but characteristically lack ulceration and large blue-gray ovoid nests.
• Desmoplastic trichoepithelioma shows ivory-white structureless areas with fine telangiectasias and must be distinguished from morpheaform BCC.
• Adnexal tumors as a group frequently mimic BCC dermoscopically; the clinical context (location, patient age, growth pattern) is essential for appropriate triage.

4.5.1 Cylindroma

Dermoscopic Features

• Unfocused arborizing vessels on a white-pink background
• Blue-gray dots or globules
• Ulceration

The combination of blue, pink, and orange hues creates a characteristic blue-pink-orange pattern.

4.5.2 Hidradenoma

Dermoscopic Features

• Homogeneous blue pattern
• Structureless white areas
• Hairpin or serpentine vessels

4.5.3 Syringoma

Dermoscopic Features

• Yellowish or brownish background
• Fine linear vessels
• Areas of hypopigmentation

4.5.4 Syringocystadenoma Papilliferum

Dermoscopic Features

• Polymorphous vessels (linear irregular, glomerular vessels)
• White halo around vessels
• Pink/white background

4.5.5 Hidrocystoma

Dermoscopic Features

• Structureless skin-colored/yellowish to bluish areas
• Linear vessels

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4.6.1 Adnexal Tumors vs. BCC

This is the single most important differential diagnostic challenge in adnexal tumor dermoscopy.

Feature	Favors Adnexal Tumor	Favors BCC
Arborizing vessels	Fine, in-focus (trichoepithelioma); unfocused (cylindroma)	Thick, well-focused, branching
Blue-gray structures	Present in trichoblastoma and follicular tumors (overlapping)	Ovoid nests, leaf-like areas, spoke-wheel areas
White structures	Prominent milia-like cysts, white structureless areas, porcelain background (follicular tumors)	Less prominent; shiny white structures (polarized)
Crown vessels	Present (sebaceous tumors); do NOT cross midline	Absent; arborizing vessels cross the lesion
Yellowish structures	Prominent (sebaceous tumors, poroma)	Absent or minimal
Clinical course	Often stable over years to decades	Progressive growth
Ulceration	Less common (except pilomatricoma)	Common in advanced BCC

4.6.2 Adnexal Tumors vs. Melanoma

Feature	Favors Adnexal Tumor	Favors Melanoma
Vascular pattern	Organized vessels (crown, cherry blossom-like, string of pearls)	Polymorphous vessels, milky-red areas, irregular dotted vessels
Pigment pattern	Absent or minimal, structureless blue-gray	Atypical network, irregular dots/globules, regression
White structures	Milia-like cysts, rosettes, white interlacing areas	Shiny white streaks (chrysalis structures)
Blue-whitish veil	Absent	May be present

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Key Takeaways

• The differential diagnosis of adnexal neoplasms frequently includes BCC, melanoma, and dermatofibroma because structural overlap is significant.
• Histopathologic confirmation is the definitive standard for adnexal tumors because no single dermoscopic feature reliably distinguishes them from other neoplasms.
• Pilomatricoma in children shows a blue-white structureless area with whitish streaks and irregular vessels, creating a unique pattern that may suggest the diagnosis before biopsy.