Uterus
Other mesenchymal tumors
Perivascular epithelioid cell tumor (PEComa)
Author: Jennifer A. Bennett, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 25 February 2019
Minor changes: 9 June 2021
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: PEComa uterus[title]
Table of Contents
Definition / general | Essential features | Terminology | ICD-0 | ICD-10 | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Bennett J. Perivascular epithelioid cell tumor (PEComa). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uteruspecoma.html. Accessed December 8th, 2021.
Definition / general
- Rare mesenchymal neoplasm with myomelanocytic differentiation favored to arise from perivascular epithelioid cells
Essential features
- Best classified as a tumor of uncertain malignant potential as recurrences may occur years after initial diagnosis
- Characterized by clear to eosinophilic epithelioid or spindled cells growing in sheets, nests or cords and surrounded by delicate vasculature
- Expresses both melanoma and smooth muscle markers with variable staining intensity and distribution
- Only ~10% are associated with tuberous sclerosis complex
Terminology
- Perivascular epithelioid cell tumor (PEComa)
- Abdominopelvic sarcoma of perivascular epithelioid cells
- Primary extrapulmonary sugar tumor (PEST)
ICD-10
Epidemiology
- Only ~100 cases reported to date
- Most commonly present at 40 - 60 years (range: 9 - 80)
Sites
- Uterine corpus most common in gynecologic tract
- Rarely cervix, vagina, ovary, broad ligament
Pathophysiology
- Unknown
Etiology
- ~10% associated with tuberous sclerosis complex
Clinical features
- Generally present with nonspecific gynecologic symptoms (abnormal uterine bleeding, abdominal / pelvic pain) (Am J Surg Pathol 2018;42:1370)
- May be incidentally discovered during evaluation for adnexal mass, leiomyomas, infertility or at cesarean section
Radiology description
- No defining features to distinguish from other uterine mesenchymal neoplasms on imaging
Radiology images
Contributed by Borislav A. Alexiev, M.D.
MRI of retroperitoneal mass
Images hosted on other servers:
Sagittal T2 with heterogeneous hyperintense mass (arrows)
MRI with hyperintense mass
Prognostic factors
- 3 algorithms have been proposed for predicting behavior
- Nongynecologic specific criteria (Am J Surg Pathol 2005;29:1558)
- Benign: < 5 cm, non infiltrative, non high grade atypia, mitoses ≤ 1 / 50 high powered fields (HPFs), no necrosis, no lymphovascular invasion (LVI)
- Uncertain malignant potential: nuclear pleomorphism / multinucleated giant cells or > 5 cm
- Malignant: 2+ features (> 5 cm, non infiltrative, high grade atypia, mitoses > 1 / 50 HPFs, necrosis, LVI)
- Gynecologic specific criteria (Am J Surg Pathol 2014;38:176)
- Benign / uncertain malignant potential: < 4 features (≥ 5 cm, high grade atypia, mitoses > 1 / 50 HPFs, necrosis, LVI)
- Malignant: ≥ 4 features
- Modified gynecologic specific criteria (Am J Surg Pathol 2018;42:1370)
- Uncertain malignant potential: < 3 features (> 5 cm, high grade atypia, mitoses > 1 / 50 HPFs, necrosis, LVI)
- Malignant: ≥ 3 features
- Nongynecologic specific criteria (Am J Surg Pathol 2005;29:1558)
- Recurrences can occur years after original diagnosis
Case reports
- 44 year old woman with abnormal uterine bleeding (Diagn Pathol 2015;10:142)
- 50 year old woman with chronic abdominal pain (Rare Tumors 2012;4:e14)
- 61 year old woman with a palpable abdominal mass (Am J Case Rep 2016;17:309)
- 62 year old woman with abnormal uterine bleeding and 38 year old with adnexal mass (Eur J Med Res 2017;22:7)
- 67 year old woman with abnormal uterine bleeding (J Pathol Transl Med 2016;50:469)
Treatment
- Surgery (hysterectomy, myomectomy) is first line therapy as many are presumed leiomyomas
- Chemotherapy and radiation may be administered in patients with metastatic or recurrent disease
- mTOR inhibitors have shown variable results (Medicine (Baltimore) 2019;98:e14072, Eur J Med Res 2017;22:7, Ann Oncol 2010;21:1135)
Gross description
- Variable and resembles other mesenchymal lesions (Am J Surg Pathol 2018;42:1370)
- Typically intramural but may be polypoid
- Tan, white or gray solid mass, variable hemorrhage or necrosis
Gross images
Contributed by Borislav A. Alexiev, M.D.
Fibrous cut surface
Images hosted on other servers:
Posterior uterine mass
PEComa
Microscopic (histologic) description
- Most are myoinvasive
- Subset show permeative (tongue-like / ESS-like) growth (Am J Surg Pathol 2014;38:176, Am J Surg Pathol 2018;42:1370)
- Numerous growth patterns including sheets, nests, cords, trabeculae, pseudoalveoli and fascicles
- Epithelioid or spindled cells with clear to eosinophilic granular cytoplasm, dyshesive appearance and variable cytologic atypia and mitotic index
- Subset have dense eosinophilic (rhabdoid) or foamy cytoplasm (Am J Surg Pathol 2014;38:176, Am J Surg Pathol 2018;42:1370)
- Melanoma-like nucleoli, intranuclear pseudoinclusions, multinucleated cells, Touton giant cells and melanin pigment (rare) may be present (Am J Surg Pathol 2014;38:176, Am J Surg Pathol 2018;42:1370)
- Characterized by thin and delicate vessels but may also have thick walled (generally peripherally located) and staghorn vessels (Am J Surg Pathol 2018;42:1370)
- Radial / perivascular distribution of tumor cells often not identified
- Necrosis in ~50% and stromal hyalinization in ~80%
- Sclerosing PEComa rare in corpus (Int J Gynecol Pathol 2011;30:121, Pathol Int 2011;61:768, Am J Surg Pathol 2018;42:1370)
- TFE3 associated PEComas often epithelioid with clear cells, nested / alveolar growth, low grade atypia and rare mitoses (Am J Surg Pathol 2010;34:1395, Am J Surg Pathol 2015;39:394, Am J Surg Pathol 2018;42:1370)
- Have not been identified in tuberous sclerosis patients
- Lymphangioleiomyomatosis (LAM)-like PEComas are rare, predominantly spindled with thick walled blood vessels, cleft / slit-like spaces, low grade atypia and infrequent mitoses (Am J Surg Pathol 2018;42:1370)
- LAM-like PEComas may be present in uterus and lymph nodes (Int J Gynecol Pathol 2011;30:121)
Microscopic (histologic) images
Contributed by Jennifer Bennett, M.D.
PEComa
Infiltrative growth
Delicate vasculature
Spindled cells
Stromal hyalinization
Multinucleated giant cells
Intranuclear pseudoinclusions
Melanoma-like macronucleoli
TFE3 associated PEComa
LAM-like PEComa
HMB45
MelanA / MART-1
Desmin
Cathepsin K
Positive stains
- Cathepsin K (100%), HMB45 (98%), SMA (81%), caldesmon (75%), desmin (67%), MiTF (66%), MelanA / MART1 (58%) (Am J Surg Pathol 2014;38:176, J Clin Pathol 2015;68:418, Am J Surg Pathol 2018;42:1370)
- All of variable staining intensity and distribution
- May vary depending on cell morphology (epithelioid vs. spindled)
- TFE3 may show focal staining, but typically is non specific unless strong and diffuse (Am J Surg Pathol 2010;34:1395)
- ER and PR are variably expressed (J Clin Pathol 2015;68:418)
- TFE3 associated PEComa: HMB45 and TFE 3 (strong), MelanA / MART1 and smooth muscle markers (focal / negative)
Negative stains
- CD10 (focally positive in 27%), S100 (focally positive in 18%), pancytokeratins (focally positive in 7%), PAX8 (Am J Surg Pathol 2014;38:176, J Clin Pathol 2015;68:418)
- TFE3 associated PEComa: MelanA / MART1 and smooth muscle markers (focal / negative), MiTF negative (Am J Surg Pathol 2010;34:1395, Am J Surg Pathol 2015;39:394, Am J Surg Pathol 2015;39:813, Am J Surg Pathol 2018;42:1370)
Electron microscopy description
- May see premelanosomes and melanosomes
Molecular / cytogenetics description
- TFE3 fusions (Am J Surg Pathol 2010;34:1395, Am J Surg Pathol 2015;39:394, Am J Surg Pathol 2015;39:813, Am J Surg Pathol 2018;42:1370)
- RAD51B fusions (Am J Surg Pathol 2015;39:813, Am J Surg Pathol 2018;42:1370)
- TSC2 mutation (Am J Surg Pathol 2015;39:813) or loss of heterozygosity (J Pathol 2008;214:387)
- HTR4-ST3GAL1 fusion (Am J Surg Pathol 2015;39:813)
Differential diagnosis
- Epithelioid smooth muscle tumor (leiomyoma or leiomyosarcoma)
- Lack thin and delicate vessels, may see perinuclear vacuoles and diffuse eosinophilic cytoplasm with cytoplasmic granularity
- Typically negative or focally / weakly positive for melanocytic markers and cathepsin K (Am J Surg Pathol 2018;42:1370)
- No known association with TSC1 and TSC2 mutations or TFE3 fusions
- Poorly differentiated endometrial carcinoma
- Focal gland formation may be present
- Cytokeratin and PAX8 strongly positive, negative for myomelanocytic markers
- Malignant melanoma
- Alveolar soft part sarcoma
- Rod shaped cytoplasmic crystals (PAS+, diastase resistant), mitoses rare
- ASPSCR1-TFE3 fusion
- Placental site trophoblastic tumor
- Fibrinoid material surrounds groups of tumor cells and replaces vessel walls, endometrium may show decidual / Arias-Stella changes
- Inhibin, hPL, cytokeratin+; negative for myomelanocytic markers
Board review style question #1
- A 32 year old woman with a history of pulmonary lymphangioleiomyomatosis, seizures and angiofibromas presents with a myometrial mass. Which molecular / cytogenetic abnormality does this patient likely have?
- HTR4-ST3GAL1 fusion
- RAD51B fusion
- TFE3 fusion
- TFEB fusion
- TSC2 mutation
Board review style answer #1
Board review style question #2
- A 50 year old woman presents with a myometrial mass with lung metastases. The myometrial tumor is characterized by dyshesive epithelioid and spindled cells surrounded by a delicate vasculature. The tumor cells are strongly and diffusely positive for HMB45, desmin, SMA and caldesmon with focal melanA expression. What type of tumor does this likely represent?
- Alveolar soft part sarcoma
- Leiomyosarcoma
- Melanoma
- PEComa
- Poorly differentiated endometrial carcinoma
Board review style answer #2
