Acta Dermatovenerol Croat
2012;20(1):27-29
CLINICAL ARTICLE
HMB-45 Negative Clear Cell Perivascular Epithelioid
Cell Tumor of the Skin
Teresa Pusiol1, Doriana Morichetti1, Maria Grazia Zorzi1, Surace Dario2
Institute of Anatomic Pathology; 2Institute of Ophthalmology, Rovereto Hospital,
Rovereto (TN), Italy
1
Corresponding author:
Teresa Pusiol, MD
Institute of Anatomic Pathology
Rovereto Hospital
Piazza S. Maria
38068 Rovereto (TN)
Italy
[email protected]
Received: July 4, 2011
Accepted: October 15, 2011
SUMMARY The first case of cutaneous clear cell perivascular epithelioid cell
tumor (PEComa) with negative HMB-45 marker is presented. The tumor was a
nodule 3x2 cm in size, located on the right foot in a 60-year-old man. The lesion
consisted of large irregularly shaped cells with clear cytoplasm, negative for
S-100 protein, HMB-45, Melan-A, pancytokeratin, epithelial membrane antigen
and CAM5.2. Multifocal positivity for desmin, microphthalmia transcription
factor and tyrosinase was found. The diagnosis of cutaneous PEComa of clear
cell type was made. Clear cell change is a very unusual finding in PEComa and
may pose problems in diagnostic differentiation from other clear cell cutaneous lesions that may be excluded with immunohistochemistry. In our case, the
HMB-45 negativity may be explained by extensive clear cell change. Additional studies are necessary to accept the clear cell cutaneous HMB-45 negative
PEComa as a new variant of perivascular epithelioid cell tumor.
Key words: perivascular epithelioid cell tumor, clear cell cutaneous tumor,
immunohistochemistry
INTRODUCTION
The perivascular epithelioid cell tumor (PEComa) is
a family of related mesenchymal tumors that includes
angiomyolipoma of the kidney and liver, lymphangiomyomatosis, lymphangiomyoma, and a group of
uncommon tumors that arise in soft tissue, visceral organs, skin and clear cell ‘sugar’ tumor of the lung (1-3).
Similar tumors within the spectrum of PEComa have
been reported under several different names including “clear cell myomelanocytic tumour”, “abdominopelvic sarcoma of perivascular epithelioid cells”, and
“primary extra-pulmonary sugar tumor” (4,5). Nearly
all PEComas display dual expression of melanocytic
(HMB-45, Melan A, NKIC3, microphthalmia transcription factor, tyrosinase) and smooth muscle (actin, des-
ACTA DERMATOVENEROLOGICA CROATICA
min, caldesmon, calponin) markers. The morphologic
spectrum of PEComa ranges from primary spindle cell
tumors, purely epithelioid tumors with clear, palely
eosinophilic or granular cytoplasm to PEComas with
notable pleomorphism or marked stromal sclerosis.
Clear cell change is a very unusual finding of PEComa
and may pose problems in diagnostic differentiation
from other clear cell cutaneous lesions (6). Immunohistochemistry may have a very important role in the
exact identification of the tumor, but immunohistochemical results may be variable. We report a case of
cutaneous PEComa diffusely composed by HMB-45
negative clear cells and we discuss the immunohistochemical features of the lesion.
27
Pusiol et al.
HMB-45 negative clear cell tumor
Acta Dermatovenerol Croat
2012;20(1):27-29
CASE REPORT
A 60-year-old man presented a nodule 3x2 cm in
size on the right foot that had persisted for 6 months. It
was excised and one year later, there was no evidence
of recurrence or metastatic disease. Microscopically,
the tumor consisted by a small exophytic intradermal
lesion composed of large irregularly shaped cells with
clear cytoplasm (Fig. 1). There was no evidence of epidermal origin or any junctional component. However,
the lesion had a well-formed epidermal collarette. The
neoplastic cells were of variable size and had plump
but quite uniform vesicular nuclei. The tumor cells
were negative for S-100 protein, HMB-45, Melan-A,
pancytokeratin, epithelial membrane antigen (EMA)
and CAM5.2. There was some unspecific positivity for
both CD68 and NKI-C3. Multifocal positivity for desmin (Fig. 2) as well as for microphthalmia transcription factor (MITF) was found (Fig. 3). A deep tumoral
rim was composed of epithelioid cells around small
vessels. The appearance of the lesion was suggestive
for a cutaneous PEComa for clear cell type.
Fig. 2. Immunostaining of clear cell perivascular epithelioid
cell tumor. Tumor cells staining positive for desmin (HE; X40).
PEComas are now recognized at ubiquitous anatomic locations, are most often benign and show a
marked female predominance, with a predilection
for the retroperitoneum, pelvis, uterus and abdomen (7). The extensive clear cell change of PEComa
is typical of clear cell sugar tumor. According to our
knowledge, only one cutaneous case of this tumor
has been previously reported by de Saint Aubain
Somerhausen et al. (8). In the study of ten primary
cutaneous PEComas, Liegl et al. (4) defined “clear cell
tumor” as a distinctive lesion. These authors describe
two cases with purely epithelioid morphology that
showed clear to palely eosinophilic cytoplasm. The
remaining cases with epithelioid and mixed epithelioid and spindle cell morphology showed variably
clear or granular eosinophilic cytoplasm. In our case,
the clear cell change was extensive and problems in
diagnostic differentiation from other clear cell cutaneous lesions were evident. Among melanocytic markers, HMB-45 is the most sensitive. It was expressed in
100% of primary cutaneous PEComas reported in the
literature (4). Melan-A has been reported to be positive in as many as 72% of cases and MITF was strongly
expressed in most cases reported. Desmin appears to
be the most sensitive muscle cell marker, present in
as many as 50% of lesions (4). It is evident that immunohistochemistry has a very important role in the
Fig. 1. Clear cell perivascular epithelioid cell tumor. The tumor consisted of large spindle shaped cells with clear cytoplasm. (HE; X20)
Fig. 3. Immunostaining of clear cell perivascular epithelioid
cell tumor. Focal nuclear staining for microphthalmia transcription factor was evident in neoplastic cells (HE; X40).
DISCUSSION
28
ACTA DERMATOVENEROLOGICA CROATICA
Pusiol et al.
HMB-45 negative clear cell tumor
identification of clear cell PEComas. A combination
of melanocytic markers including HMB-45, Melan A,
S-100, MITF, smooth muscle markers such as desmin,
caldesmon, calponin, and epithelial markers such as
cytokeratins and EMA are useful for the differential diagnosis. The possibility that our case might represent
a balloon cell melanoma or metastatic carcinoma was
essentially excluded by the fact that tumor cells were
negative for S-100 protein, HMB-45, Melan-A, pancytokeratin, EMA and CAM5.2. There was some unspecific positivity for both CD68 and NKI-C3. The most
important findings were multifocal positivity for desmin as well as nuclear positivity for MITF, indicating
that the appearance was diagnostic for a cutaneous
PEComa of clear cell type. The negativity of HMB-45
was surprising. Positive staining for this marker is variable. In the study of thirteen PEComas with extensive
stromal hyalinization, Hornick and Fletcher (9) report
that all tumors were positive for HMB-45 only in scattered cells. In four PEComas examined by Liegl et al.
(4), HMB-45 was positive in fewer ten 5% of tumor
cells. In our case, the HMB-45 negativity could be explained with the extensive change of clear cells that
has not been reported in the English literature on cutaneous PEComa.
CONCLUSIONS
In the identification of PEComa, MITF might have
a diagnostic value if HMB-45 results negative. However, additional studies are necessary to accept the
clear cell cutaneous PEComa with negative HMB-45
marker as a new variant of perivascular epithelioid
cell tumor.
Acknowledgment
We are grateful to Prof. Christopher D.M. Fletcher,
Professor of Pathology, Harvard Medical School, Director of Surgical Pathology, Brigham and Women’s
Hospital, Boston, Massachusetts, USA, for consultation related to the case presented.
ACTA DERMATOVENEROLOGICA CROATICA
Acta Dermatovenerol Croat
2012;20(1):27-29
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