Figure 1: Cut section of a well circumscribed tumor with variegated appearance.
Figure 3: Epithelioid cells demonstrating HMB 45 immunoreactivity (HMB45; x400).
Figure 4: Epithelioid cells demonstrating smooth muscle actin immunoreactivity (SMA; x400)
Tuberous sclerosis has been associated with AML and LAM. However, only 9% of the soft tissue and gynecologic PEComas are associated with tuberous sclerosis[2,4]. The present case did not show any stigmata of tuberous sclerosis.
Morphologically, PEComas are characterized by epithelioid and spindle cells arranged around vascular channels. Admixture of both type of cells are common. Electron microscopy reveals pre-melanosomes in the tumor cells[2,3]. Immunohistochemistry aids in confirming the diagnosis. These cells are positive for melanocytic markers, namely HMB45, Melan A and MiTF and smooth muscle actin (SMA). Few cases may be positive for S-100[2,4]. This case demonstrated the characteristic histological features along with HMB45 and SMA positivity confirming the diagnosis of PEComa.
PEComas are classified into benign, of uncertain malignant potential and malignant tumors for prognostication. This is based on tumor size (>5 cm), infiltration, high nuclear grade, increased cellularity, high mitotic activity (>1 mitotic figure/50 high power fields) and tumor necrosis. Malignant PEComas have two or more of these features. Tumors of uncertain malignant potential include those with nuclear pleomorphism/multinucleate giant cells or >5 cm in size[4]. The present case was classified as PEComa of uncertain malignant potential, emphasizing the need for a long term follow up. Our patient is on periodic follow-up for the last two years and remains asymptomatic.
With regard to molecular mechanism involved in PEComas, there is activation of mammalian target of rapamycin (mTOR), a kinase causing suppression of T cell proliferation and inhibition of cell cycle progression. These processes are initiated by antigens and cytokines. The tumor suppressor genes TSC1 and TSC2, regulate the activity of mTOR. Hence, deletion of these genes causes up regulation of mTOR[3,10].
The differential diagnosis of PEComa includes clear cell sarcoma, clear cell carcinoma, conventional melanoma, epithelioid smooth muscle neoplasm, endometrial stromal sarcoma, gastrointestinal stromal tumor and paraganglioma. The morphological features, immunohistochemistry and electron microscopy aid in accurate diagnosis[3-5].
PEComas are treated by excision of the mass, salpingooophorectomy or total abdominal hysterectomy with bilateral salpingo-oopherectomy[3,6,8]. Sirolimus, an immunosuppressive agent, inhibits the activity of mTOR and is useful in the treatment of PEComa[10]. Our patient underwent mass excision. Since the mass was encircling the ureter, ureteric resection and reimplantation was necessary. No radical surgery was performed as her age and desire to conceive were major concerns.
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