• Meta Description: Concise review of perivascular epithelioid cell tumor (PEComa) types, histology and immunohistochemistry for pathology exams.
• Author: PathologyMCQ Editorial Team
• Category: Soft tissue and gynecologic pathology
• Last Updated: March 2026
• Estimated Read Time: 10 minutes

This is a medical, educational, exam-oriented pathology review focused on diagnosis and histopathology.

At a Glance

• What this covers: Definition of perivascular epithelioid cell tumor (PEComa), classic vs TFE3 translocation vs LAM-like types, key morphology and immunohistochemistry, diagnostic tips and MCQs for revision.
• Why it matters: PEComas are rare but increasingly recognized mesenchymal tumors; accurate subtyping has implications for prognosis, genetics and potential targeted mTOR-directed therapy.
• Difficulty level: Moderate–Difficult (postgraduate pathology level)

Table of Contents

What is a perivascular epithelioid cell tumor (PEComa)?

Perivascular epithelioid cell tumor is a family of rare mesenchymal neoplasms composed of distinctive perivascular epithelioid cells that coexpress melanocytic and smooth muscle markers. These tumors typically show epithelioid to spindle cells with clear to granular eosinophilic cytoplasm arranged around blood vessels, without a known normal-cell counterpart in human tissues.

View this post on Instagram

Direct Definition: The image summarizes the three major PEComa types, listing their morphology, immunohistochemistry and representative histology.
Theory Content: Classic PEComa shows noncohesive epithelioid cells with granular cytoplasm and staghorn vessels; TFE3 translocation-associated PEComa exhibits epithelioid clear cells in a nested or alveolar pattern with low mitotic activity; LAM-like PEComa is predominantly spindle cell with thick-walled, sometimes staghorn-like blood vessels and low-grade cytologic atypia. These patterns reflect underlying molecular differences, particularly TSC1/TSC2 alterations in conventional and LAM-like lesions and TFE3 rearrangements in the translocation-associated group.

How is PEComa classified into major types?

H&E-stained sections showing perivascular epithelioid cells in PEComa. Perivascular epithelioid cell tumor is currently classified into classic PEComa, TFE3 translocation-associated PEComa and LAM-like PEComa, based on morphology, immunophenotype and molecular findings. Classic PEComa represents the conventional TSC1/TSC2-altered family, TFE3-associated lesions show MiT family translocations, and LAM-like PEComa overlaps morphologically and genetically with lymphangioleiomyomatosis.

Direct Definition: The image demonstrates classic PEComa with nests of epithelioid cells concentrically arranged around delicate vessels.
Theory Content: Recognizing the perivascular accentuation of epithelioid cells with clear or granular cytoplasm is central to diagnosing classic PEComa and separating it from clear cell sarcoma, metastatic melanoma and epithelioid smooth muscle tumors.

What are the classic PEComa histologic features?

Classic PEComa is composed of noncohesive epithelioid cells with clear to eosinophilic granular cytoplasm, often containing prominent nucleoli, multinucleated forms and rare melanin pigment. Tumor cells typically surround thin and delicate vessels but may also be associated with thick-walled, sometimes staghorn-like vascular channels, and mitotic activity is usually low.

Which patterns help distinguish classic PEComa?

H&E-stained histology of PEComa showing epithelioid cells with granular cytoplasm.
The hallmark pattern of classic perivascular epithelioid cell tumor is radial or concentric growth of epithelioid cells around a central vascular core, producing a perivascular accentuation. These tumors may show sheets, nests or trabeculae of tumor cells with abundant clear to granular cytoplasm, sometimes mimicking renal cell carcinoma or clear cell melanoma, making immunohistochemistry essential.

Direct Definition: The image shows epithelioid PEComa cells with eosinophilic granular cytoplasm arranged around small blood vessels.
Theory Content: Classic PEComa often arises in visceral organs and soft tissue, including uterus, retroperitoneum and gastrointestinal tract, and can be benign or show worrisome features such as large size, infiltrative margins, high nuclear grade or necrosis, which correlate with malignant behavior.

What defines TFE3 translocation-associated PEComa?

H&E and IHC stains of MiT family translocation renal cell carcinoma variants.
TFE3 translocation-associated PEComa is a molecularly distinct subset characterized by gene rearrangements involving the TFE3 transcription factor, resulting in strong nuclear TFE3 immunoreactivity. These tumors often occur in younger patients and tend to behave more aggressively than conventional TSC-related PEComas.

Direct Definition: The image highlights nested clear cell architecture and TFE3 positivity that typify TFE3 translocation-associated PEComa.
Theory Content: TFE3-rearranged PEComas show predominantly epithelioid clear cells in nests, sheets or alveolar structures, with delicate vasculature, higher nuclear atypia, brisk mitotic activity or necrosis; they usually lack strong smooth muscle marker expression but retain melanocytic markers.

How does TFE3-associated PEComa differ immunohistochemically?

TFE3 translocation-associated perivascular epithelioid cell tumor shows diffuse strong nuclear TFE3 staining, variable HMB45 and Melan A positivity, and often reduced or absent smooth muscle actin and desmin expression compared with classic lesions. Cathepsin K is frequently positive, aiding recognition among other clear cell neoplasms of the genitourinary and gynecologic tracts.

What is LAM-like PEComa and how does it appear?

H&E-stained section of PEComa tumor with thick-walled vessels.
LAM-like PEComa refers to PEComa lesions that closely resemble lymphangioleiomyomatosis, with predominantly spindle cells arranged around thick-walled or slit-like blood vessels, often in lung or uterine locations. These tumors share genetic alterations of the tuberous sclerosis complex genes TSC1 or TSC2 and frequently occur in association with TSC or in women of reproductive age.

Direct Definition: The image shows LAM-like PEComa morphology with fascicles of spindle cells cuffing thick-walled, sometimes staghorn, blood vessels.
Theory Content: LAM-like PEComa demonstrates smooth muscle–like spindle cells with clear to lightly eosinophilic cytoplasm, frequent perivascular growth, and cystic or cleft-like spaces; clinically, these lesions may present with pulmonary cysts, hemoptysis or uterine masses and respond to mTOR inhibition such as sirolimus due to activation of the mTOR pathway.

Which immunohistochemical markers are essential in PEComa pathology?

The diagnostic immunoprofile of perivascular epithelioid cell tumor is coexpression of melanocytic markers (HMB45, Melan A, MiTF) and smooth muscle markers (smooth muscle actin, muscle-specific actin, sometimes desmin), often with strong cathepsin K staining. Most PEComas are negative for cytokeratins and S100, which helps separate them from carcinomas and conventional melanomas.

Why is cathepsin K important in PEComa?

Cathepsin K is a lysosomal cysteine protease that shows diffuse strong cytoplasmic positivity in the majority of renal and extrarenal PEComas, often more consistently than other markers. Because many other human malignancies are cathepsin K negative, its expression has high sensitivity and specificity for PEComa within appropriate morphologic and clinical settings.

How does TFE3 staining guide PEComa subtyping?

Strong nuclear TFE3 immunoreactivity indicates a TFE3-rearranged perivascular epithelioid cell tumor, whereas most conventional TSC-related PEComas do not show TFE3 overexpression or gene fusion. Consequently, TFE3 staining helps separate TFE3-associated lesions, which often behave more aggressively, from classic or LAM-like PEComas.

How do PEComa types compare morphologically and immunohistochemically?

Classic, TFE3 translocation-associated and LAM-like perivascular epithelioid cell tumors share coexpression of melanocytic markers but differ in predominant cell shape, vascular pattern and key ancillary markers. Recognizing these patterns allows accurate categorization, prognostication and selection of appropriate molecular testing.

Morphology and immunohistochemistry of PEComa types

Feature	Classic PEComa	TFE3 translocation-associated PEComa	LAM-like PEComa
Predominant cells	Noncohesive epithelioid cells with clear to eosinophilic granular cytoplasm	Epithelioid clear cells in nests or alveolar structures	Spindle cells resembling smooth muscle, sometimes mixed epithelioid cells
Vascular pattern	Thin, delicate vessels; may show thick-walled or staghorn vessels​	Delicate vascular network separating nests; less prominent thick-walled vessels​	Thick-walled blood vessels, cleft-like or slit-like spaces, perivascular cuffs
Atypia and mitoses	Usually low-grade, rare mitoses; malignant cases show high grade, necrosis	Often higher atypia, mitoses and necrosis; more aggressive behavior	Generally low-grade atypia and infrequent mitoses
Melanocytic markers	HMB45, Melan A positive, variable intensity and distribution	HMB45/Melan A positive, often diffuse	HMB45/Melan A positive, variable intensity
Myogenic markers	Smooth muscle actin, muscle-specific actin, variably desmin positive	Often weak or negative for smooth muscle markers	Strong smooth muscle actin and other myogenic markers
Cathepsin K	Generally positive	Positive, helpful for recognition​	Positive in most cases​
TFE3	Negative or weak in most cases	Strong nuclear positivity with TFE3 gene rearrangement	Typically negative​

High – yield MCQS

Exam pearl and key takeaway

• Exam Pearl: Perivascular epithelioid cell tumor must coexpress melanocytic and smooth muscle markers, with cathepsin K and, in some cases, TFE3 serving as crucial ancillary stains.
• Key Takeaway: Accurate subtyping of classic, TFE3 translocation-associated and LAM-like PEComa integrates morphology, immunohistochemistry and molecular findings, guiding prognosis and supporting recognition of mTOR pathway–targeted treatment options.

Ready to master this topic?