Benign tumors and hamartomas
Smooth Muscle Hamartoma
Definition
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A hamartomatous lesion composed of a dermal proliferation of mature smooth muscle cells growing in haphazardly arranged bundles
Clinical features
Epidemiology
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Slight male predominance
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Prevalence of 1 in about 2700 live births
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The majority of the lesions are congenital
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Familial occurrence exceptional, with autosomal-dominant inheritance reported in some families
Presentation
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Skin-colored indurated patch, plaque, follicular papules, or variably pigmented macules; occasionally associated with hypertrichosis
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Usually asymptomatic, but can be pruritic
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Stroking of the lesion can result in transient elevation of the affected area and piloerection due to smooth muscle contraction (pseudo-Darier sign)
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Induration, hyperpigmentation, and hypertrichosis diminish over time
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Unusual clinical presentations include linear, atrophic, or a morphea-like plaque
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Multiple lesions or a generalized presentation very rare
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The generalized variant occasionally part of the “Michelin-tire baby” syndrome, characterized by deep circumferential skin folds over the trunk and limbs with distinctive clinical appearance, mental retardation, and other developmental abnormalities
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Predilection for lumbosacral area and proximal extremities
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Uncommon sites include the head and neck, conjunctiva, nipple, and genital area
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Rare associated conditions include Becker nevus, congenital melanocytic nevus, and basal cell carcinoma, with the latter two conditions likely to be coincidental
Prognosis and treatment
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No treatment generally required
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Surgical excision or laser treatment usually for cosmetic reasons
Pathology
Histology
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Localized in the dermis, with occasional extension into the subcutis
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Mature smooth muscle cells, growing in haphazardly arranged bundles
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Mitotic activity absent
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Association with morphologically normal hair follicles in about 40%
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Prominent nerve fibers and collagen bundles usually present among smooth muscle bundles
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Overlying epidermis normal or displays mild hyperkeratosis, acanthosis, and hyperpigmentation of basal keratinocytes
Immunohistochemistry/special stains
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Smooth muscle actin, calponin, desmin, and h-Caldesmon positive
Main differential diagnoses
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Becker nevus
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Pilar leiomyoma (more orderly proliferation of smooth muscle bundles arranged in ramifying fascicles, intervening collagen more discrete)
Pilar Leiomyoma
Definition
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A benign smooth muscle tumor composed of interlacing fascicles of bland spindle cells displaying typical features of smooth muscle differentiation (e.g., cigar-shaped or blunt-ended nuclei and bright eosinophilic cytoplasm)
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Believed to arise from or differentiate toward the arrector pili muscle
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Lesions can be solitary or multiple and develop either as a sporadic or inherited condition
Clinical features
Epidemiology
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Most commonly develops in the second and third decades of life
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Female predominance for multiple lesions, whereas solitary tumors occur more commonly in males
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Congenital occurrence exceptional, likely overlapping with or representing a variant of congenital smooth muscle hamartoma
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A subset of pilar leiomyoma(s) occurs in the familial setting, the so-called Reed syndrome or multiple leiomyomatosis
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Autosomal-dominant mode of inheritance
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Associated with germline mutation(s) of the fumarate hydratase ( FH ) gene on chromosome 1q42.3-43 acting as a tumor suppressor gene
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Combination of multiple pilar and uterine leiomyomas, additionally complicated by development of a solitary multifocal or bilateral papillary renal cell carcinoma in roughly up to 20% of patients
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Presentation
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Firm and smooth, skin-colored, red-brown to violaceous papule(s) or nodule(s)
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Multiple lesions
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More common than solitary lesions
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Size of individual lesion usually up to 1 cm in diameter
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Often tender or painful, either spontaneously or in response to cold, pressure, or emotional stimuli
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Show predilection for extensor surface(s) of the extremities and trunk
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Distribution can be segmental, dermatomal, linear, zosteriform, or more widespread/diffuse
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Solitary lesions
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Most commonly develop on the limbs
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Tend to be larger than multiple tumors
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Frequently asymptomatic
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Rarely presentation may be with an indurated plaque
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Prognosis and treatment
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Complete surgical excision curative, but difficult to achieve in multiple tumors
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Recurrence rate as high as 50% for multiple lesions
Pathology
Histology
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Dermal-based proliferation, extension into the subcutis infrequent
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Poorly circumscribed and infiltrative, less often nodular and well circumscribed
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Interweaving/interlacing fascicles of bland spindle cells displaying typical features of smooth muscle differentiation
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Cigar-shaped or blunt-ended nuclei
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Low mitotic activity present in roughly 30% of the lesions (fewer than 1 mitosis per 10 high-power fields)
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Bright eosinophilic cytoplasm
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Histological variants
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Epithelioid
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Symplastic
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Pleomorphic cells with large, multilobated, hyperchromatic nuclei; macronucleoli; and intranuclear cytoplasmic pseudoinclusions, usually scattered among bland spindle cells
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Multinucleated giant cells not uncommon
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Mitotic activity low (usually fewer than 1 per 10 high-power fields)
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Necrosis absent
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Represents degenerative phenomenon
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Immunohistochemistry/special stains
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Positive for smooth muscle actin, desmin, calponin, and h-Caldesmon
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A small percentage of cases express keratin
Main differential diagnoses
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Cutaneous leiomyosarcoma
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Metastatic leiomyosarcoma
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Cellular dermatofibroma
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Dermatofibrosarcoma protuberans with myoid nodules
Genital Leiomyoma
Definition
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A variant of leiomyoma arising from superficial smooth muscles at genital locations, including scrotum, vulva, and nipple
Clinical features
Epidemiology
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Predilection for middle-aged adults
Presentation
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Solitary, slowly growing papule or nodule, less often a pedunculated lesion with surface ulceration
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Multiple lesions most uncommon
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Lesions can increase in size during pregnancy
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Most of the lesions are asymptomatic
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Nipple leiomyomas
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Tend to be smaller (generally less than 2 cm)
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Poorly circumscribed
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Vulvar and scrotal leiomyomas
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Size generally between 3 and 5 cm in diameter
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Well circumscribed
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Vulvar leiomyoma(s) can be associated with synchronous or metachronous development of esophageal leiomyoma(s), a condition known as esophagovulvar syndrome
Prognosis and treatment
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Complete surgical excision curative
Pathology
Histology
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Histological features essentially similar to pilar leiomyomas, including the so-called symplastic change representing a degenerative phenomenon (see corresponding section on pilar leiomyoma)
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Certain morphological features occur more commonly at genital sites (see below)
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Vulvar and scrotal leiomyomas
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More cellular than pilar leiomyomas
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Tend to be better circumscribed and more nodular but not encapsulated
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Focal or more widespread epithelioid morphology common
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Myxoid change frequent, especially during pregnancy
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Hyalinization of the stroma can be prominent
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Variably intense perivascular inflammatory cell infiltrate composed of lymphocytes, histiocytes, and eosinophils
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Immunohistochemistry/special stains/cytogenetics
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Smooth muscle actin, calponin, desmin, and h-Caldesmon positive
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Variable positivity (over 50%) for estrogen and progesterone receptors
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Androgen receptor positivity in scrotal leiomyomas
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No consistent cytogenetic change in vulvar leiomyomas, yet the data is limited
Main differential diagnoses
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Angiomyofibroblastoma
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Aggressive angiomyxoma
Angioleiomyoma
Definition
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A benign tumor composed of vascular smooth muscle cells and blood vessels
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Alternatively designated as a vascular leiomyoma or angiomyoma
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This tumor is now regarded as part of the spectrum of pericytic (perivascular) tumors that include glomus tumor and its variants, and myopericytoma and its variants
Clinical features
Epidemiology
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Slightly more common in females
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Wide age distribution from 12 to 84 years, the majority present between the fourth and sixth decades of life
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Congenital presentation exceptional
Presentation
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A solitary, slowly growing, and firm subcutaneous nodule
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Tenderness and pain, often paroxysmal, reported in up to 60% of the lesions, with the remaining lesions asymptomatic
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Size usually less than 2 cm in about 80% of the lesions
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Predilection for extremities, in particular, lower extremities (about 70%), followed by upper extremities and head and neck
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Unusual locations include intracranial site (dura) and intraosseous occurrence
Prognosis and treatment
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Complete or marginal surgical excision generally sufficient
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Recurrences exceptional, usually related to incomplete excision
Pathology
Histology
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Well-circumscribed proliferation in the subcutis, less often in the dermis
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Two main components are (1) bland smooth muscle cells and (2) blood vessels
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Smooth muscle cells
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Grow in interlacing or disorganized bundles
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Appear to originate from the vessel walls
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Perivascular concentric arrangement overlapping with myopericytoma occasionally present
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Pointed nuclei, tapering eosinophilic cytoplasm
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No cytological atypia or, when present, focal and degenerative in nature (see later)
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Mitoses generally absent or very limited in numbers
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Three subtypes of angioleiomyoma can be separated on the basis of the morphology of the vascular channels
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Solid type
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Most common type
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Closely packed bundles of spindled smooth muscle cells
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Intervening vascular channels with small slitlike lumina and thin vessel walls
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Venous type
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Intervascular smooth muscle cells blend with smooth muscle cells of the vascular walls
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Thick muscular vessel walls
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Cavernous type
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Least common type
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Small amounts of intervascular smooth muscle cells
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Intervascular smooth muscle cells difficult to separate from smooth muscles cells of the vascular walls
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Dilated vascular channels
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Histological variants
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Epithelioid
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Clear cell
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Symplastic
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Marked degenerative cellular atypia(s) and prominent nuclear pleomorphism
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Absence of mitotic activity in pleomorphic cells
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Additional histological features present in a small proportion of the cases
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Intralesional fat
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Inflammatory cell infiltrate, composed predominantly of lymphocytes with occasional formation of aggregates
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Collagen hyalinization
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Foci of calcification
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Areas of hemorrhage and/or deposition of hemosiderin pigment
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A feeding medium-sized artery
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Immunohistochemistry/special stains
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Smooth muscle actin, muscle specific actin, calponin, and h-Caldesmon positive
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Variable desmin positivity
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Negative for keratins, S100 protein, CD34, CD31, and HMB45
Genetic profile
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No consistent genetic changes have been detected
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Various gains and losses of chromosomes in about one-third of the cases
Main differential diagnoses
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Leiomyoma
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Myofibroma
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Myopericytoma (morphological and immunohistochemical overlap with angioleiomyoma)
Cutaneous Leiomyosarcoma (Atypical Intradermal Smooth Muscle Neoplasm)
Definition
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A distinctive smooth muscle tumor localized in the dermis or associated with limited extension into the superficial subcutis (generally less than 5 mm), characterized histologically by mitotic activity, cellular pleomorphism, and, much less often, tumoral necrosis
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Although such lesions have been classified as cutaneous leiomyosarcoma, they invariably follow a benign clinical course, with possible local recurrence due to incomplete/marginal excision
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Nevertheless, metastatic risk is absent when confined to dermis
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Needs to be distinguished/separated from leiomyosarcoma arising predominantly in the subcutis due to more aggressive biological behavior of the latter (see corresponding section)
Clinical features
Epidemiology
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Males predominantly affected (M:F = 2–4:1)
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Although the age distribution is wide, about 90% of the patients are older than 40 years
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Extremely rare in childhood
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Most common in the sixth decade of life
Presentation
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Solitary, slowly growing nodule or indurated plaque
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The majority appear to be asymptomatic, rare lesions painful
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Size usually less than 2 cm
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Predilection for trunk and lower extremities, followed by the head and neck and upper extremities
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Isolated examples developed in the background of traumatic injury, ionizing radiation, lupus vulgaris, smallpox and scrofuloderma scar, tattoo, nevus sebaceous, and chronic venous ulcer
Prognosis and treatment
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Status of resection margins the most important predictive factor for local recurrence(s)
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Complete wide surgical excision generally curative, with very low risk of possible local recurrence
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Recurrence rate about 20% after incomplete/marginal excision, multiple recurrences possible
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Recurrent tumors can display increased cellularity and deeper localization
Pathology
Histology
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Pure dermal-based proliferation, occasionally with very limited extension into the subcutis, generally of less than 5 mm in thickness
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Infiltrative/poorly defined (diffuse) and/or nodular growth pattern
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Intersecting fascicles of spindle cells ramifying between dermal collagen fibers
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Nuclear atypia mild to moderate, can be severe on occasion
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Nuclei cigar shaped or blunt ended with abundant eosinophilic cytoplasm
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Mitoses present, usually from 2 to 5 mitoses per 10 high-power fields, but their number can vary greatly among lesions
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Atypical mitoses not uncommon (in up to 50% of lesions)
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Eccentric perinuclear intracytoplasmic vacuoles occasionally present
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Tumoral necrosis rare (in less than 5% of the lesions), generally focal
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Multinucleated giant cells few and scattered
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A tumor-free, subepidermal grenz zone of variable thickness present in the majority of the lesions
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Additional occasional histological features
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Focal epithelioid cell morphology
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Granular cell change
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Myxoid stromal degeneration and hyalinization/sclerosis
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Multinucleated osteoclast-like giant cells
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Perivascular inflammatory cell infiltrate composed of lymphocytes and histiocytes
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Desmoplastic variant of leiomyosarcoma
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Predominance of hyalinized/sclerotic stroma over neoplastic cells
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Immunohistochemistry/special stains
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Smooth muscle actin, calponin, desmin, and h-Caldesmon positive in decreasing order of frequency
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Up to 50% display focal cytokeratin positivity
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Rare examples with focal S100 protein positivity also reported
Main differential diagnoses
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Pilar leiomyoma
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Cellular fibrous histiocytoma
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Nodular fasciitis
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Sarcomatoid carcinoma
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