Friday 31 August 2007
senile keratoses, basal cell papillomas, dermatosis papulosis nigra
Definition: Seborrheic keratoses consist of multiple benign localized neoplastic proliferations of basaloid keratinocytes, often with associated hyperkeratosis and hyperpigmentation.
These lesions are also known as basal cell papillomas, a term that describes their architecture well.
Seborrheic keratoses commonly and characteristically occur in middle-aged and elderly individuals.
Seborrheic keratoses arise spontaneously and are most concentrated on the trunk, although the extremities, head, and neck may be involved. In blacks, multiple small lesions on the face are termed dermatosis papulosis nigra.
Clinically, seborrheic keratoses (also called senile keratoses) are quite characteristic. They appear as round to oval, variably verrucous, coin-like plaques that vary in size from several millimeters to centimeters. They exhibit a uniform tan to dark-brown color and usually have a velvety to granular surface.
Individual lesions are well demarcated and may give the impression that they are "stuck on" and easily peeled off. Inspection with a magnifying lens will usually reveal small pore-like ostia impacted with keratin (a feature in differentiating these pigmented lesions from melanomas).
The term "stucco keratosis" denotes small (1-3 mm) seborrheic keratoses that characteristically occur in symmetrical distribution on the distal extremities (especially involving ankle skin).
The explosive onset of multiple seborrheic keratoses in association with internal malignancy is known as the sign of Leser-Trélat.
Recently, this rare paraneoplastic syndrome has been linked to an overproduction of alpha-transforming growth factor (alpha-TGF) by the primary malignant tumor.
Alpha-TGF binds to the epidermal growth factor receptor and thus provides a plausible explanation as to why eruptive epidermal proliferations such as seborrheic keratoses and acanthosis nigricans may accompany certain primary malignant conditions.
The cause of most seborrheic keratoses associated with advancing age (e.g., viral versus aberrant growth factors versus enhanced susceptibility to proliferative stimuli) remains to be elucidated. (AFIP)
The architecture of most seborrheic keratoses is exophytic, and lesions tend to be sharply demarcated from the adjacent epidermis.
They are composed of sheets of small cells that resemble basal cells of the normal epidermis.
Variable melanin pigmentation is present within these basaloid cells, a factor contributing to the brown coloration observed clinically.
Often exuberant keratin production occurs at the surface of seborrheic keratoses, and small keratin-filled cysts (horn cysts) and cystic keratin-filled downgrowths from the surface of the lesion into the main tumor mass (pseudo-horn cysts) are characteristic features.
Pseudo-horn cysts correlate with the keratin-filled ostia that are appreciated clinically on the surface of the lesion.
There is often a thin mantle of compacted papillary dermal collagen that abuts the lowermost epithelial elements of seborrheic keratoses.
Recognition of this feature is often helpful in differentiating seborrheic keratoses from other benign keratoses when only small curretted fragments are available for examination.
Some seborrheic keratoses have a preponderantly pedunculated architecture, and their histology merges with that of a fibroepithelial polyp.
Seborrheic keratoses have been previously divided into hyperkeratotic, adenoidal or reticulated, and acanthotic variants.
Some lesions contain striking quantities of melanin pigment, but these distinctions are not biologically significant, and their use is discouraged.
When seborrheic keratoses become inflamed, they tend to undergo squamous differentiation and become characterized by foci of "whorling" squamous cells resembling currents in a stream (eddy currents).
Such lesions, termed irritated seborrheic keratoses, are generally associated with the accumulation of variable numbers of lymphocytes and histiocytes in the superficial dermis. How these inflammatory cells (or the soluble mediators they produce) elicit squamous differentiation in a preponderantly basaloid neoplasm is an unknown biologic phenomenon.
The inflammatory stimulus of irritated seborrheic keratoses clinically is often spontaneous, is composed mainly of lymphocytes, and may represent a phenomenon analogous to that occurring in a halo nevus or regressing melanoma. Some authorities recognize two histologic patterns in irritated seborrheic keratoses.
One histologic pattern is characterized by inconspicuous squamous differentiation or eddy formation and shows a destructive lichenoid inflammatory reaction associated with individual and clustered necrotic keratinocytes within the lower epidermal layers.
This variant may result in confusion with benign lichenoid keratosis, a solitary lichen planus-like keratosis that typically affects trunk and upper extremity skin of middle-aged individuals. The other histologic pattern is a squamoid tumor, often with prominent eddies, foci of lacy acantholysis, and associated enlargement of nuclei and scattered mitotic figures.
This lesion must be differentiated from squamous cell carcinoma.
Identification of these variants as irritated seborrheic keratoses relies upon detection of residual foci of basaloid cells in the former and of characteristic eddies in the latter.
Separation of the nuclear atypia that may be seen in irritated seborrheic keratoses from the dysplasia and anaplasia of squamous cell carcinoma is assisted by recognizing that even though both show nuclear enlargement and nucleolar prominence, the reactive nuclei of irritated seborrheic keratoses have a delicate, evenly distributed chromatin pattern and a thin, uniform nuclear membrane.
The nuclei of squamous cell carcinoma, on the other hand, tend to show more coarsely aggregated chromatin and a thickened, often jagged or indented nuclear membrane. Squamous eddies may initially resemble squamous or horn "pearls" of squamous cell carcinoma, but appreciation of the characteristically laminated architecture of squamous pearls and absence of associated premature cellular keratinization or necrosis in squamous eddies facilitates their recognition.
When seborrheic keratoses involve the epithelium of hair follicles, they often proliferate in an endophytic manner and exhibit squamous differentiation in association with inflammation. Such lesions are termed inverted follicular keratoses.
Seborrheic keratoses, along with eccrine poromas, actinic keratoses, squamous cell carcinoma in situ, and occasionally, basal cell carcinoma and clear cell acanthoma, may exhibit an "intraepidermal epithelioma" pattern of growth.
This term, also known as the "Borst-Jadassohn phenomenon," connotes the discrete nesting of proliferating or neoplastic cells within the epidermis and their resultant juxtaposition with normal adjacent keratinocytes.
This is a reaction pattern not a distinctive lesion, and the term clonal seborrheic keratosis that has been previously applied to such lesions is inappropriate and even misleading, particularly in view of our emerging understanding of clonal proliferations as determined at a molecular level.
Melanoacanthoma is a rarely encountered variant of seborrheic keratosis in which numerous pigmented, dendritic benign melanocytes proliferate in association with relatively amelanotic neoplastic basaloid epithelial cells.
Differential Diagnosis. Seborrheic keratoses may be confused with epidermal nevi and with the causes of verrucous (papillary) epidermal hyperplasia.
Both epidermal nevi and nevus sebaceus generally have a characteristic clinical appearance, with onset at an earlier age than seborrheic keratoses. Often epidermal nevi have a linear configuration, and nevus sebaceus is frequently associated with alopecia.
Although both lesions may have associated mesenchymal abnormalities, and nevus sebaceus is associated with appendageal differentiation, occasional lesions may be impossible to differentiate from seborrheic keratoses based upon histologic parameters alone.
There are many causes of verrucous epidermal hyperplasia, some of which include acanthosis nigricans, sites of previous papillomavirus infection, and verrucous hyperplasia and reactive verrucous hyperplasia resulting from irritation or infection.
In general, seborrheic keratoses retain zones of basaloid differentiation, and when the entire lesion is removed and viewed at scanning magnification, tumors are sharply juxtaposed with the adjacent normal skin.
In reality, small and superficial biopsies showing verrucous, squamous, and basaloid hyperplasia frequently must be diagnosed descriptively with terms such as benign keratosis, verrucous keratosis, or verrucous (or papillary) epidermal hyperplasia.
Reliance upon clinical parameters is necessary in these instances for formulation of a definitive diagnostic assessment.
Course and Prognosis
Seborrheic keratoses demonstrate an indolent biologic course characterized by slow enlargement followed by long-term stability. They are easily treated by curettage or locally destructive measures.
The incidence of malignant degeneration is exceedingly small, although rare instances of associated basal and squamous cell carcinoma have been observed. The primary reason for treatment of seborrheic keratoses is cosmetic.