ARTICLE
Cutaneous (extraocular) sebaceous carcinoma is an extremely rare tumor
that most frequently arises on the face and scalp [1-9]. The etiology
of this tumor remains unknown. Botek and Goldberg [10] reported that sebaceous
carcinoma is not associated with ultraviolet radiation exposure. We encountered,
however, two cases of sebaceous carcinoma associated with clinical and
histopathological features similar to those of actinic keratosis, which
is known to result from long-term sun exposure. These two cases suggest
that a close relationship exists between extraocular sebaceous carcinoma
and sun exposure. Furthermore, we should note that an early lesion of
extraocular sebaceous carcinoma is sometimes clinically or histopathologically
indistinguishable from actinic keratosis.
Case report
Case 1
A 75-year-old woman visited the Mihara Dermatological Clinic with a
tumor on her left temple that was first noted about 6 months previously.
She had not noticed any preexisting erythematous lesion. Dermatological
examination at that time revealed a 10 mm flat-elevated, yellowish-red
and lobulated tumor on the left temple with extensive erosion (Fig.
1). The lesion was resected and no recurrence was noted during
an 18-month follow-up period.
Histopathological examination of the resected specimen revealed intraepidermal
spread of tumor cells (Fig. 2a).
In the center of the tumor, neoplastic cells with vacuolated cytoplasm
formed lobular structures and basophilic cells surrounded them (Fig.
2b).
Neoplastic cells showed marked cellular and nuclear atypia, and atypical
nuclear divisions were also observed. Immunohistochemically, neoplastic
cells with vacuolated cytoplasm were positive for BCA-225, (CU18; Cambridge
Research Laboratories Inc.), CA15.3 (DF3; Dako corp.), Leu M1 (MMA; Becton-Dickinson)
and Thomsen-Friedreich (TF: HB-T1; Dako corp.) antigen (Fig.
3), but were negative for carcinoembryonic antigen (CEA: polyclonal
and II -7 ; Dako corp.) and gross cystic disease fluid protein-15 (GCDFP15:
D6; Cambridge Research Laboratories Inc.), and PAS staining. From these
histological, histochemical and immunohistochemical findings, we diagnosed
this lesion as a sebaceous carcinoma in situ. In the peripheral
region of the tumor, no vacuolated cells were seen and squamoid atypical
cells occupied the epidermis with parakeratosis. These findings were compatible
with actinic keratosis. Continuity of the two lesions was observed.
Case 2
An 81-year-old woman visited the Dermatological Clinic at Yamagata Prefectural
Nihon-kai Hospital with multiple erythema on her face. Some lesions were
covered with crusts, but a lesion on the left cheek was identified as
simple erythema without pruritis (Fig.
4a). Biopsy specimens were obtained from the lesions on the right
temple and left cheek. The specimen obtained from the right temple revealed
typical histopathological features of actinic keratosis. Histopathological
findings of the left cheek lesion revealed intraepidermal proliferation
of squamoid atypical cells (Fig
5a), some of which showed clear or vacuolated cytoplasm.
The lesions including those on the right temple and left cheek were
treated by cryosurgery and an occlusive dressing technique using 5-fluorouracil
cream. Then, the erythematous changes of both lesions disappeared.
The patient revisited our clinic complaining of a tumoral change on
her left cheek about 1 year after the first visit. Dermatological examination
at that time revealed a 6 x 9 mm pedunculated, red and lobulated tumor
with extensive erosion on an 8 x 10 mm flat erythema (Fig.
4b). We resected the lesion with a 5-mm margin. In the center
of the resected specimen, atypical tumor cells formed nests and invaded
the dermis (Fig. 5). Immunohistochemically,
neoplastic cells with vacuolated cytoplasm were positive for BCA-225,
CA15.3 and TF antigen, but were negative for CEA (polyclonal and monoclonal)
and GCDFP15. Some tumor cells exhibited vacuolated cytoplasm and were
positive for Sudan III staining (Fig.
6) and negative for PAS staining. From these histological, histochemical
and immunohistochemical findings, we diagnosed this lesion as sebaceous
carcinoma. On the other hand, atypical and squamoid tumor cells without
vacuolated cytoplasm occupied the epidermis in the peripheral region,
and these findings were compatible with actinic keratosis.
Discussion
Histopathologically, sebaceous carcinoma must be distinguished from
other malignant skin tumors with clear cytoplasm. In our case 1, tumor
cell nests resembled those of normal sebaceous glands. Therefore, sebaceous
differentiation of tumor cells was apparent [7]. On the other hand, our
case 2 required other methods for differentiation from bowenoid actinic
keratosis, Bowen's disease with clear cells, trichilemmal carcinoma, or
various sweat gland carcinomas. Tumor cells with clear cytoplasm in our
case, however, were positive for Sudan III staining and negative for PAS
staining. These results strongly suggest sebaceous differentiation of
tumor cells [11]. Furthermore, immunohistochemical findings of our two
cases were compatible with those of neoplastic cells with sebaceous differentiation
as already reported [11-15].
Sebaceous carcinoma of the skin, especially the extraocular type, is
an extremely rare tumor and its etiology is unknown [1-10]. It occurs
most frequently on the eyelid, an unexposed area [1, 2, 4-10]. Therefore,
Botek and Goldberg [10] reported that sebaceous carcinoma is not associated
with ultraviolet radiation exposure. On the other hand, most cases of
extraocular sebaceous carcinoma arise on sun-exposed areas as previously
reported [1, 3, 6, 11-16]. However, the face and scalp region is not only
a sun-exposed area but also an area where sebaceous glands are the most
plentiful. Many conditions that lead to sebaceous differentiation of neoplastic
cells occur in the face and scalp region. Therefore, it may not be possible
to confirm a relationship between extraocular sebaceous carcinoma and
sunlight or ultraviolet radiation exposure by the common locations of
the tumor alone.
Histopathologically, our two cases exhibited intraepidermal proliferation
of squamoid tumor cells with dermal actinic elastosis in the periphery
and invasive proliferation of the tumor cells with sebaceous differentiation
in the center of the lesions. The two lesions showed continuity.
The combination of sebaceous carcinoma and actinic keratosis may have
been accidental but neoplastic cells of actinic keratoses may differentiate
towards skin adnexa including sebocytes. Another possibility is that our
cases were merely in situ or an early stage of sebaceous carcinoma.
Most cases of in situ or early stages of sebaceous carcinoma exhibit
findings similar to those of our cases. Steffen and Ackerman [7] reported
that the smallest, most superficial, and presumably the earliest example
of extraocular sebaceous carcinoma among their cases showed aggregations
of vacuolated and non-vacuolated sebocytes with atypical nuclei in the
epidermis and infundibula. However, the histopathological findings of
that case were not similar to those of our cases. Therefore, we cannot
determine whether this possibility is correct, although we speculate that
the later explanation is more likely. More cases are required to determine
the histopathological findings of in situ or early stages of sebaceous
carcinoma.
We previously reported that the prognosis of extraocular cutaneous sebaceous
carcinoma was worse than that of cutaneous squamous cell carcinoma [11].
Certain anti-tumor drugs and radiation are ineffective for cutaneous sebaceous
carcinoma, while they are often effective for cutaneous squamous cell
carcinoma [3, 8-10]. We should note that an invasive malignant tumor arising
on lesions clinically diagnosed as actinic keratosis is not always squamous
cell carcinoma. Sebaceous carcinoma, which shows a poorer prognosis and
different biological behavior, should also be considered.
Article accepted on 20/3/00
CONCLUSION
Acknowledgement
We wish to thank Dr. Y. Hozumi for his assistance in photographic work
and Dr. S. Arai for his encouragement in preparing this manuscript.
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