PEComa, according to the World Health Organization classification, is defined as a mesenchymal tumour composed of histologically and immunohistochemically distinctive perivascular epithelioid cells.1
Although PECs were first described in 1943 by Apitz as an “abnormal myoblast” in renal angiomyolipoma (AML),8
but it was in 1992 when Bonetti et al
first described the cellular link between clear cell sugar tumour of lung (CCST), AML of the kidney, and pulmonary lymphangioleiomyomatosis (LAM).2
This association is further strengthened by the fact that all three of these entities have variable association with tuberous sclerosis complex (TSC), a group of autosomal dominant disorders caused by mutation in the TSC1
genes located on chromosomes 9q and 16p.3–5,8
In 1996, the term PEComa was coined by Zamboni et al
when they described a case of CCST in the pancreas.3,4
PEC has distinct morphologic, immunohistochemical, ultrastructural and genetic distinctive features such as an epithelioid appearance with a clear to granular cytoplasm, a round to oval, centrally located nucleus, and an inconspicuous nucleolus. PEC has mild to any atypia and a typical perivascular location. At present, PEC has no known normal counterpart. Immunohistochemically, these cells express myogenic and melanocytic markers—that is, HMB45/MelanA and alpha smooth muscle actin (ASMA).8,9
To explain the arguments regarding the term PEComa applied to all of these heterogeneous tumours such as AML, CCST and LAMS, some authors believe that they all are composed of PECs in different stages of modulation.8
Despite such doubts raised by some authors on the existence of PEComa as a distinctive tumour, at present this neoplasm is a widely accepted entity. In fact, this family of tumours, in addition to the relatively well known entities of CCST, AML and LAM, has grown to include a number of unusual visceral, intra-abdominal, soft tissue and bone tumours, such as clear cell myomelanocytic tumour of falciform ligament/ligamentum teres, abdominopelvic sarcoma of perivascular epithelioid cells, primary extrapulmonary sugar tumours, and others.3,4
Other than kidney and lung, they have also been reported in various anatomical sites such as liver, pancreas, gastrointestinal tract, bladder, prostate, uterus, ovary, vulva, vagina, pelvis, mesentery, omentum, mediastinum, retroperitoneum, nasal cavity, orbit and bones.3,4,8
Other than kidney and lung, the gynaecologic tract is the most common site of their origin.3
Interestingly, only a minority of extra renal and extra pulmonary PEComas are associated with TSC.3
Unlike our case, these tumours are mostly seen in middle aged patients (median overall age 38 years) with a striking female predominance (female to male ratio 7:1).3
Their reported presence in children has been most commonly in the form of renal AML associated with TSC.5
However, few cases of PEComas in the paediatric age group have been described in the literature in which association with TSC was not seen.6,7
Morphologically, there is variability among the members of this group of tumours, ranging from admixture of thick walled and hyalinised blood vessels, adipose tissue and spindled to plump cells in AML, to a uniform population of polygonal epithelioid cells with prominent thin walled vasculature in CCST.1–3,8
However, the common morphological feature is the presence of epithelioid to spindle shaped cells with clear to eosinophilic and granular cytoplasm intimately admixed with vessel walls,1
as seen in our case.
Immunohistochemically, tumours like PECs co-express myogenic and melanocytic markers, such as HMB45, HMSA-1, MelanA, microphthalmia transcription factor (Mitf), ASMA and, less commonly, desmin.8,9
According to a study, HMB45 is a more sensitive marker than MelanA for demonstrating melanocytic differentiation in PEComas (92% and 72%, respectively).3
S100 expression has also been seen in some cases. Rare cases expressing CD117, including the ones arising from the gastrointestinal tract (GIT), are also on record and can be potentially misdiagnosed as gastrointestinal stromal tumours (GISTS).3
Cytokeratins are negative in these tumours.1,3,8
The clinical behaviour of these tumours is usually benign, but there are many examples of malignant PEComas.3,4,10
Due to the rarity of these tumours, the criteria for malignancy are still not fully defined. However, according to WHO, PEComas displaying any combination of infiltrative growth pattern, hypercellularity, nuclear enlargement and hyperchromasia, high mitotic activity, atypical mitotic figures, and coagulative necrosis should be regarded as malignant.1
According to a study carried out by Folpe et al
which included 26 cases of extra PEComas, size >5 cm, infiltrative growth pattern, high nuclear grade, necrosis and mitotic activity of >1/50 HPF were related to aggressive biological behaviour.3
They also suggested that cases exhibiting only nuclear pleomorphism/giant cells or size >5 cm should be defined as tumours with uncertain malignant potential.3
This study is by far the largest clinicopathologic study regarding the biological behaviour of these rare tumours. While more cases with long term follow-up are needed to verify the effectiveness of this prognostic classification, it is believed that all cases of PEComa should be classified according to the criteria proposed by Folpe et al
Since our case showed hypercellularity, a mitotic index of 2–3/10 HPF and nuclear hyperchromasia, the possibility of malignant behaviour was raised.
- Although rare, PEComas, regardless of the age of the patient, should be kept in the differential diagnosis of renal or extra-renal tumours showing epithelioid clear cell morphology, provided that more common tumours have been ruled out.
- If PEComa is considered in the initial differential diagnosis, this would significantly affect the surgical management of the patient.