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2016, Volume 32, Number 1, Page(s) 044-046
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DOI: 10.5146/tjpath.2014.01252 |
Broad Ligament Perivascular Epithelioid Cell Tumor (PEComa) of Uncertain Malignant Potential |
Mary MATHEW, Bhavna NAYAL, Lakshmi RAO, Bhawna NAGEL |
Department of Pathology, Kasturba Medical College, Manipal University, Manipal, KARNATAKA, INDIA |
Keywords: Perivascular epithelioid cell neoplasms, Broad ligament, HMB-45 protein |
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PEComas are uncommon mesenchymal tumors often involving
the pelvic organs. They have an unpredictable behavior. Accurate
diagnosis and long-term follow-up is therefore essential in these
patients. We report this case of PEComa of uncertain malignant
potential in an unusual location with excellent prognosis. |
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Perivascular epithelioid cell neoplasms / tumors (PEComas)
are tumors of mesenchymal origin characterized by
perivascular epithelioid cells with distinctive histological
and immunohistochemical features. According to the World
Health Organization (WHO), the PEComa family consists
of angiomyolipoma (AML), clear cell sugar tumor of the
lung (CCST), lymphangioleiomyomatosis (LAM), clear cell
myomelanocytic tumor (CCMMT) and unusual clear cell
tumors of the pancreas, rectum, serosa, uterus, vulva, thigh
and heart 1. These tumors can arise in various anatomic
sites including bone, falciform ligament, mesentry, uterus,
thigh and gastrointestinal tract 2. PEComas arising in the
broad ligament are extremely rare. Only seven cases have
been reported in the literature 3-9. We report a case of
PEComa involving the broad ligament in a young lady
encasing the ureter resulting in obstructive uropathy. |
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Abstract
Introduction
Case Presentation
Disscussion
References
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A 33-year-old female presented with primary infertility
and complaints of dysmenorrhea, dyschezia and dysuria
of 6 years duration. No other systemic abnormalities were
detected. Abdominopelvic ultrasound demonstrated a well-defined, hyperechoic, heterogeneous mass in the left
adnexa with multiple peripheral foci of calcification
and internal vascularity along with left sided
hydroureteronephrosis. CT abdomen and pelvis showed
a well-defined enhancing soft tissue lesion measuring
3.5x3.1x 5 cm with few specks of calcification and central
non enhancing hypodense areas in the left adnexa. Left
sided hydroureteronephrosis secondary to compression
or infiltration of the distal ureter at the level of trigone
was also noted. A clinical diagnosis of broad ligament
fibroid was entertained. The mass was excised and ureteric
reimplantation was performed. Intraoperatively, the uterus
and bilateral ovaries were normal. A highly vascular
mass measuring 5x4cm on the left side of the uterus was
noted with the left ureter traversing through the mass and
resulting in marked dilation. The excised mass was sent
for histopathological examination. Gross examination
showed a single, grey brown mass weighing 18gm and
measuring 5x4x2 cm. The cut section of the mass showed
a well circumscribed tumor with variegated appearance
and grey white friable areas (Figure 1). Microscopy
revealed nests of epithelioid tumor cells with moderate
clear cytoplasm, vesicular nuclei and prominent nucleoli
arranged around hyalinised blood vessels. In addition, occasional atypical cells with pleomorphism were noted
(Figure 2). The mitotic count was < 1/50 high power
field (hpf). There was no evidence of necrosis or vascular
invasion. The tumor cells stained positive for HMB 45
(Figure 3) and smooth muscle actin (Figure 4), and
negative for S100 and CK. A final diagnosis of perivascular
epithelioid cell tumor with uncertain malignant potential
was rendered. Biannual follow up for two years did
not show any recurrence or evidence of metastasis.
Click Here to Zoom |
Figure 1: Cut section of a well circumscribed tumor with
variegated appearance. |
Click Here to Zoom |
Figure 2: Nests of epithelioid cells with intervening blood vessels.
Inset shows focal areas with atypia and pleomorphism (H&E,
x400). |
Click Here to Zoom |
Figure 3: Epithelioid cells demonstrating HMB 45
immunoreactivity (HMB45; x400). |
Click Here to Zoom |
Figure 4: Epithelioid cells demonstrating smooth muscle actin
immunoreactivity (SMA; x400) |
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Top
Abstract
Introduction
Case Presentation
Disscussion
References
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Perivascular epithelioid cell tumors are a family of
tumors composed of epithelioid cells with abundant
clear to eosinophilic cytoplasm and immunoreactivity
to HMB45 3. Tumors classified under this family are
renal and extrarenal AML, LAM, CCST along with
extrapulmonary spindled and epithelioid tumors including
CCMMT, primary extrapulmonary sugar tumor (PEST)
and abdominopelvic sarcoma of perivascular epithelioid
cells. This classification is based on histological features
and anatomic site 2. The gynecologic tract is the most
common site of involvement, with majority of cases
reported in the uterus. PEComa arising from the broad
ligament is extremely rare. These tumors show a female
preponderance and affect middle aged individuals 4-7.
Tuberous sclerosis has been associated with AML and
LAM. However, only 9% of the soft tissue and gynecologic
PEComas are associated with tuberous sclerosis2,4. 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 cells2,3. 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-1002,4. 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 size4. 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 mTOR3,10.
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 diagnosis3-5.
PEComas are treated by excision of the mass, salpingooophorectomy
or total abdominal hysterectomy with
bilateral salpingo-oopherectomy3,6,8. Sirolimus, an
immunosuppressive agent, inhibits the activity of mTOR
and is useful in the treatment of PEComa10. 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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Abstract
Introduction
Case Presentation
Discussion
References
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1) Folpe AL. Neoplasms with perivascular epithelioid cell
differentiation (PEComas). In Fletcher CDM, Unni KK, Epstein J,
Mertens F, editors. Pathology and genetics of tumors of soft tissue
and bone. WHO Classification of Tumors. Lyon: IRAC Press;
2002. 221-2.
2) Enzinger FM, Weiss SW, Goldbum JR. Soft tissue tumors of
intermediate malignancy of uncertain type. In: Enzinger and
Weiss’s Soft Tissue Tumors. 5th ed. Philadelphia: Mosby Elsevier;
2008. 1093-160.
3) Ross C, Sharma S, Louca O, Scurr M, Hayes A, Judson I. A patient
presenting with a perivascular epithelioid cell tumor in the broad
ligament: A case report. J Med Case Rep. 2011;5:383.
4) Folpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL,Weiss
SW. 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.
5) Fukunaga M. Perivascular epithelioid cell tumor of the uterus:
Report of four cases. Int J Gynecol Pathol. 2005;24:341-6.
6) Kim HJ, Lim SJ, Choi H, Park K. Malignant clear-cell
myomelanocytic tumor of broad ligament-a case report. Virchows
Arch. 2006;448:867-70.
7) Fink D, Marsden DE, Edwards L, Camaris C, Hacker NF.
Malignant perivascular epithelioid cell tumor (PEComa) arising
in the broad ligament. Int J Gynecol Cancer. 2004;14:1036-9.
8) Rys J, Karolewski K, Pudelek J, Kruczak A, Wasilewska A,
Vogelgesang M, Kojs Z. Perivascular epithelioid tumour
(PEComa) of the falciform/broad ligament. Pol J Pathol.
2008;59:211-5.
9) Bonis RT, Dominguez TP, Calatayud FR, Jimenez EC, Piris MA,
Lopez-Lucendo NJ. Pelvic PEComa of the broad ligament with
lymph node metastasis: A case report and bibliographic review.
Arch Esp Urol. 2008;61:744-8.
10) Wagner AJ, Malinowska-Kolodzeij I, Morgan JA, Qin W, Fletcher
CD, Vena N, Ligon AH, Antonescu CR, Ramaiya NH, Demetri
GD, Kwiatkowski DJ, Maki RG. Clinical activity of mTOR
inhibition with sirolimus in malignant perivascular epithelioid
cell tumors: Targeting the pathogenic activation of mTORC1 in
tumors. J Clin Oncol. 2010;28:835-40. |
Top
Abstract
Introduction
Case Presentation
Discussion
References
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