Extrapulmonary clear cell tumour, PEComa

Definition

A tumour composed of epithelioid or spindle cells with clear or lightly eosinophilic cytoplasm and showing positivity for at least one or either HMB45 or Melan-A. Co-expression of melanocytic and myoid markers is required for morphologically atypical cases.

Epidemiology

There is a strong female predominance, even for tumours outside the female genital tract. Very few cases are associated with tuberous sclerosis¹¹.

Clinical features

Clear cell tumours are members of the family of PEComas and most commonly occur in the lung. Extrapulmonary sites include soft tissue⁸, base of skull¹¹, trachea², breast¹, heart⁵, ligamentum teres, pancreas³, rectum⁵, bladder¹¹, uterus⁴, vulva¹¹ and perineum⁵.

Macroscopic appearances

The tumour may be circumscribed or infiltrative.

Histopathology

The tumour cells are clear or lightly eosinophilic and either epithelioid or spinded. They typically grow radially around blood vessels.

Immunohistochemistry

Cam5.2	0/1(breast)1, 0/1 (pancreas)3, 0/1 (base of skull, malignant)7
AE1/3	0/1(breast)1, 0/1 (pancreas)3, 0/1 (base of skull, malignant)7, 3/23 (5-25% of cells)12
KL1	0/1 (pancreas)3
Pancytokeratin	0/1 (common bile duct)6, 0/1 (subcutis over knee, malignant)8, 0/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components)9
CK7	0/1 (base of skull, malignant)7
Desmin	0/1(breast)1, 0/1 (base of skull, malignant)7, 0/1 (subcutis over knee, malignant)8, 1/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components: spindle cell component weakly positive)9, 0/1 (uterus)10, 8/22 (>50% of cells: 3 cases, 25-50% of cells: 1 case, 5-25% of cells: 4 cases)12
Muscle-specific actin	0/1(breast)1, 0/1 (base of skull, malignant, equivocal staining of a few cells)7, 1/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components: spindle cell component moderately positive)9
SMA	0/1(breast)1, 0/1 (common bile duct)6, 1/1 (base of skull, malignant, scattered cells positive)7, 1/1 (subcutis over knee, malignant: variable, focally strong positivity)8, 1/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components: spindle cell component strongly positive)9, 0/1 (uterus)10, 20/25 (>50% of cells: 7 cases, 25-50% of cells: 5 cases, 5-25% of cells: 9 cases : positivity was greater in epithelioid than in spindle cells) 12
S-100	0/1(breast)1, 0/1 (common bile duct)6, 0/1 (base of skull, malignant)7, 0/1 (subcutis over knee, malignant)8, 0/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components)9, 0/1 (uterus)10, 8/24 (>50% of cells: 2 cases, 25-50% of cells: 3 cases, 5-25% of cells: 3 cases)12
HMB45	1/1(breast)1, 1/1 (pancreas)3, 1/1 (uterus)4, 4/4 (2 rectum, 1 heart, 1 perineum)5, 1/1 (common bile duct)6, 1/1 (base of skull, malignant, scattered cells positive)7, 1/1 (subcutis over knee, malignant: strong diffuse positivity)8, 1/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components: both components positive)9, 1/1 (uterus)10, 22/24 (>50% of cells: 9 cases, 25-50% of cells: 5 cases, 5-25% of cells: 8 cases)12
Melan-A (MART-1)	1/1(breast)1, 0/1 (common bile duct)6, 0/1 (base of skull, malignant, equivocal staining of a few cells)7, 1/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components: both components positive)9, 13/18 (>50% of cells: 1 case, 25-50% of cells: 5 cases, 5-25% of cells: 7 cases)12
Co-expression of (HBM45 or Melan-A) and SMA	20/2412
MiTF	9/18 (>50% of cells: 4 cases, 25-50% of cells: 2 cases, 5-25% of cells: 3 cases)12
TFE3	5/17 (>50% of cells: 3 cases, 25-50% of cells: 2 cases)12
NKI/C3	1/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components: both components positive)9
KBA.62	0/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components: both components negative)9
Oestrogen receptor	0/1(breast)1, 1/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components)9, 0/1 (uterus)10
Progesterone receptor	1/1(breast)1, 0/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components)9, 1/1 (uterus)10
EMA	0/1(breast)1, 0/1 (common bile duct)6, 0/1 (base of skull, malignant)7, 0/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components)9
Vimentin	0/1(breast)1, 0/1 (common bile duct)6, 0/1 (base of skull, malignant, equivocal staining of a few cells)7, 1/1 (uterus)10, 12/14 (>50% of cells: 10 cases, 25-50% of cells: 2 cases)12
NSE	0/1(breast)1, 0/1 (pancreas)3, 1/1 (common bile duct)6, 0/1 (base of skull, malignant)7
Chromogranin A	0/1(breast)1, 0/1 (pancreas)3, 0/1 (common bile duct)6, 0/1 (base of skull, malignant)7, 0/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components)9
Synaptophysin	0/1(breast)1, 0/1 (common bile duct)6, 0/1 (base of skull, malignant)7
Neu-N	0/1 (base of skull, malignant)7
CEA	0/1(breast)1, 0/1 (base of skull, malignant)7, 0/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components)9
CD10	1/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components: both components strongly positive)9
CD31	0/1(breast)1
CD34	0/1(breast)1, 0/1 (subcutis over knee, malignant)8, 0/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components)9, 0/1 (uterus)10, 0/712
CD45	0/1 (base of skull, malignant)7, 0/1 (subcutis over knee, malignant)8
CD99	1/1 (base of skull, malignant)7
CD117	1/1 (malignant rectovaginal tumour: biphasic tumour composed of spindle cell and epithelioid components)9, 1/1 (uterus)10, 1/20 ( 25-50% of cells)12
Alpha-fetoprotein	0/1 (base of skull, malignant)7
Placental alkaline phosphatase	0/1 (base of skull, malignant)7
b-HCG	0/1 (base of skull, malignant)7
p16	0/1 (uterus)10

Differential diagnosis

Site	Differential	distinguishing features
General	clear cell carcinoma, glycogen-rich	cytokeratin positive, HMB-45 negative
	clear cell carcinoma, lipid-rich	cytokeratin positive, HMB-45 negative
	metastatic melanoma	HMB-45 positive
Abdomen	GIST: PEComa may be CD117+
Kidney	renal clear cell carcinoma	cytokeratin positive, HMB-45 negative
Breast	clear cell adenomyoepithelioma	cytokeratin, actin and S-100 positive, HMB-45 negative
Breast	clear cell myoepithelioma	cytokeratin, actin and S-100 positive, HMB-45 negative
Base of skull	chordoma, chondrosarcoma, meningioma, pituitary adenoma, haemangioblastoma
Soft tissues	clear cell sarcoma of soft tissue	S-100 positive
	clear cell rhabdomyosarcoma	desmin, myogenin, myoD1 positive
	alveolar soft part sarcoma	PAS positive

Prognosis

The presence of an infiltrating margin, mitoses, necrosis and nuclear pleomorphism are associated with metastatic behaviour.

References

¹Govender, D., Sabaratnam, R.M. and Essa, A.S. Clear cell 'sugar' tumor of the breast: another extrapulmonary site and review of the literature. Am J Surg Pathol 2002;26:670-5.

²Kung, M., Landa, J.F. and Lubin, J. Benign clear cell tumor ("sugar tumor") of the trachea. Cancer 1984;54:517-9.

³Zamboni, G., Pea, M., Martignoni, G., Zancanaro, C., Faccioli, G., Gilioli, E., Pederzoli, P. and Bonetti, F. Clear cell "sugar" tumor of the pancreas. A novel member of the family of lesions characterized by the presence of perivascular epithelioid cells. Am J Surg Pathol 1996;20:722-30.

⁴Pea, M., Martignoni, G., Zamboni, G. and Bonetti, F. Perivascular epithelioid cell. Am J Surg Pathol 1996;20:1149-53.

⁵Tazelaar, H.D., Batts, K.P. and Srigley, J.R. Primary extrapulmonary sugar tumor (PEST): a report of four cases. Mod Pathol 2001;14:615-22.

⁶Sadeghi, S., H. Krigman, et al. (2004). "Perivascular epithelioid clear cell tumor of the common bile duct." Am J Surg Pathol 28(8): 1107-10.

⁷Lehman, N. L. (2004). "Malignant PEComa of the skull base." Am J Surg Pathol 28(9): 1230-2.

⁸Harris, G. C., T. A. McCulloch, et al. (2004). "Malignant perivascular epithelioid cell tumour ("PEComa") of soft tissue: a unique case." Am J Surg Pathol 28(12): 1655-8.

⁹Evert M, Wardelmann E, Nestler G, et al. Abdominopelvic perivascular epithelioid cell sarcoma (malignant PEComa) mimicking gastrointestinal stromal tumour of the rectum. Histopathology 2005; 46:115-7

¹⁰Park SH, Ro JY, Kim HS, et al. Perivascular epithelioid cell tumor of the uterus: immunohistochemical, ultrastructural and molecular study. Pathol Int 2003; 53:800-5

¹¹ Hornick JL,Fletcher CD. PEComa: what do we know so far? Histopathology 2006; 48:75-82

¹² Folpe AL, Mentzel T, Lehr HA, et al. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol 2005; 29:1558-75 [omentum or mesentery (6 cases), uterus (4 cases), pelvic soft tissues (3 cases), abdominal wall (2 cases), uterine cervix (2 cases), and vagina, retroperitoneum, thigh, falciform ligament, scalp, broad ligament, forearm, shoulder, and neck (1 case each)]

This page last revised 25.5.2006.

©SMUHT/PW Bishop