Seborrheic keratosis is a benign epidermal lesion occurring
mainly on the trunk, commonly in the interscapular area, sides of the neck, face and also on the extremities, excluding
palms and soles, usually after the age of 50 years
1. They
are sharply demarcated, brownish with a verrucous surface,
slightly raised from the surface. The lesions are coin-like,
sharply demarcated from the surrounding skin with a
stuck-on appearance
2. Rarely, they can have a targetoid
appearance
3.
The lesions are composed of basaloid cells with an admixture
of varying amount of squamoid cells. Keratin-filled
invaginations and small cysts (horn cysts) are a common
feature. Approximately one third of the lesions appear
hyperpigmented. Seborrheic keratoses show a considerable
variety of histological appearances and is usually classified into several subtypes: acanthotic, hyperkeratotic, adenoid
or reticulated, clonal, irritated, desmoplastic, inverted
follicular keratosis and melanoacanthoma. All types show
hyperkeratosis, acanthosis and papillomatosis4. Rare
changes include focal trichilemmal differentiation with
glycogen-rich cells, acantholysis with basal clear cells and
sebaceous differentiation. Very rarely, seborrheic keratosis
with pseudorosettes and adamantinoid types has also been
reported as two new histologic variants5.
The differential diagnosis of seborrheic keratosis ranges from
various benign lesions such as papilloma, senile keratosis,
keratoacanthoma and verrucous epidermal hyperplasia to
malignant lesions such as basal or squamous cell carcinoma6. Very rarely, progressive transformation to in-situ
squamous cell carcinoma (bowenoid transformation) has
been reported7.
The presence of sebaceous differentiation in seborrheic
keratosis is very rare. The differential diagnosis of such cases
include sebaceoma variant with surface changes of verruca/
seborrheic keratosis, and other tumors with sebaceous
differentiation such as trichoblastoma with sebaceous
differentiation, sebocrine adenoma (apocrine poroma with
sebaceous differentiation), superficial epithelioma with
sebaceous differentiation, low-grade sebaceous carcinoma
and basal cell carcinoma with sebaceous differentiation.
In the sebaceoma variant with surface changes of verruca/
seborrheic keratosis, there is proliferation of infundibular
keratinocytes (basaloid cells or squamous cells) associated
with hypergranulosis and tunnels of cornified cells
(thus mimicking verruca or seborrheic keratosis) with
a random admixture of sebaceous cells. In contrast
to seborrheic keratosis, sebaceoma is centered on the
upper and mid dermis, with an increased proportion of
sebaceous cells compared to the basal cells8. Recently,
the term “sebomatricoma” has been proposed as the most
appropriate term for all benign neoplasms with sebaceous
differentiation including seborrheic keratosis with
sebaceous differentiation9,10.
Rarely, sebaceoma may arise in continuity with seborrheic
keratosis wherein the lesion may be composed of two
different adjacent tumors - seborrheic keratosis with
hyperkeratosis and acanthosis with irregular proliferation
of apparently benign basaloid and squamous keratinocytes
and small horn pseudocysts and the other part composed
of sebaceoma characterised by various sized lobules with
immature sebocytes mixed with single or clustered mature
sebaceous cells11.
In trichoblastoma with sebaceous differentiation, there is
proliferation of follicular germinative cells associated with a
highly fibrotic stroma and peripheral palisading in contrast
to seborrheic keratosis. Sebocytes and sebaceous duct like
structures are observed within the basaloid aggregations8.
In contrast to seborrheic keratosis, apocrine poroma
with sebaceous differentiation (sebocrine adenoma) is a
benign cutaneous adnexal neoplasm differentiating in the
direction of sebaceous and apocrine glands. The sebaceous
differentiation is characterized by solitary instances or
clusters of sebocytes and sebaceous ducts. The apocrine
differentiation is characterized by basaloid aggregations
composed of poroid cells and cuticular cells associated with
tubular structures12.
Superficial epithelioma with sebaceous differentiation is a
rare histologically distinct benign neoplasm, occurring as
multiple or solitary lesions on the face, neck and trunk in
elderly persons. Histologically it shows superficial welldemarcated
plate like proliferation of basaloid cells with
numerous broad attachments to the overlying epidermis
with gradual merging of the tumor cells with the overlying
epidermal cells at the dermoepidermal junction. Sebaceous
cells scattered as small clusters may be seen in the lower
portion of these lobules. Within the tumor mass, few keratin
filled cystic structures lined with squamous epithelium
of epidermal or sebaceous duct. There is no peripheral
palisading of the cells nor any retraction artefact13.
Low-grade sebaceous carcinoma is composed of
cytologically neoplastic cells with large, crowded, vesicular
pleomorphic nuclei with prominent nucleoli, which is
absent in seborrheic keratosis. Rarely some cases of basal cell
carcinoma present with areas of sebaceous differentiation,
which can be differentiated from seborrheic keratosis by
the characterictic architectural pattern with peripheral
palisading and cytology of the neoplastic cells in basal cell
carcinoma8.
In the present case, there was hyperplastic stratified
squamous epithelium with acanthosis and proliferation
of uniform basaloid cells with interspersed horn and
pseudohorn cysts with deeper areas showing sebaceous
differentiation. The proportion of the sebaceous cells
are lower compared to the basaloid cells, in contrast to
sebaceoma. There was absence of peripheral palisading,
fibrotic stroma, duct-like structures or platelike proliferation
of basaloid cells. Thus a diagnosis of seborrheic keratosis
with sebaceous differentiation is arrived at.
Although seborrheic keratosis with sebaceous differentiation
is not known to present with the rare Muir-Torre syndrome,
any benign sebaceous or transitional squamosebaceous
neoplasm should be considered a possible manifestation of
this syndrome14.
Complete surgical excision is the curative method although
local destructive methods such as cryotherapy or curettage
can also be done.
Sudden onset of numerous seborrheic keratosis (termes as
Leser-Trelat sign) has been reported in most of the cases
in association with internal malignancy, most commonly
adenocarcinoma of the stomach15. Other associated
tumors include leukemia, bronchogenic carcinoma, breast
carcinoma, colorectal carcinoma, renal cell carcinoma,
transitional cell carcinoma and anaplastic ependymoma.
In contrast, occasional cases have been reported with the
Leser-Trelat sign without internal malignancy even after
extensive investigations16.
Patients with multiple seborrheic keratosis are at risk for
internal malignancy. Hence these patients need to be under
routine screening and regular follow up.
In conclusion, seborrheic keratosis is a benign epidermal
lesion characterised by hyperkeratosis, acanthosis along
with keratin-filled horn cysts and pseudohorn cysts,
and various subtypes have been reported. Sebaceous
differentiation in seborrheic keratosis, as in the present
case, is very rare. This case is reported for its rare sebaceous
differentiation and multiplicity along with the importance
of differentiating it from a variety of benign to malignant
neoplasms showing sebaceous differentiation.