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PEComas (perivascular epithelioid cell tumours) are rare mesenchymal tumours, characterised by epithelioid, clear cell morphology with coexpression of melanocytic and smooth muscle markers. They are usually seen in adult females in a variety of anatomical locations, of which, kidney, lung and the gynaecologic tract are the most common. We present a case of PEComa arising from the kidney of a 12-year-old boy.
PEComas (perivascular epithelioid cell tumours) are a family of mesenchymal neoplasms which share a common histological appearance, characterised by clear or eosinophilic epithelioid but at times spindle cell morphology, with immunohistochemical expression of both melanocytic and myogenic markers and a pronounced female predilection. This morphological and immunohistochemical profile suggests that these tumours originate from distinctive perivascular epithelioid cells (PEC), a suggestion which is further supported by an observation that these tumour cells are intimately related to the blood vessel walls.1 The concept of a group of neoplasms arising from these cells was first proposed by Bonetti et al in 1992 when they described a cellular link among clear cell ‘sugar’ tumours of lung and renal angiomyolipomas and lymphangioleiomyomatosis.2 Due to the rarity of these tumours, it is difficult to predict their clinical behaviour, but there is a subset of PEComas which behave in a malignant fashion.3,4 These uncommon tumours are usually seen in middle aged woman with a median age of 38 years.3 Other than the well known clinical setting of renal angiomyolipomas with tuberous sclerosis,4,5 their presence in children is even rarer and, according to the authors’ knowledge, only a few cases have been described so far in the literature.6,7 In this article, we present a case of PEComa arising in the kidney of a 12-year-old boy with no known associated tuberous sclerosis.
A 12-year-old boy presented with acute onset of left lumbar pain and haematuria for 2 days. On examination, a firm tender mass was felt in the left lumber region, otherwise he was healthy. On further investigations, a 4×3.9 cm hypoechoic mass arising from the left kidney was noted on ultrasonography. There was no para-aortic lymphadenopathy and other abdomino-pelvic viscera including the opposite kidney were unremarkable. No computed tomography or magnetic resonance imaging was undertaken. With the clinical suspicion of malignancy, a left nephrectomy was done. Perioperatively, the mass was circumscribed and involved the lower pole of the left kidney. The specimen was sent for gross and histological evaluation.
On gross examination, the nephro-uretectomy specimen measured 9×6×2 cm and weighed 105 g, with the attached part of the ureter measuring 1.9×0.5 cm. On sectioning, a partly circumscribed grey brown solid lesion with pushing borders was visualised in the lower pole, measuring 4.6×4×4 cm (fig 1) and breaching the renal capsule. The lesion showed multiple areas of haemorrhage. The remaining renal parenchyma, renal pelvis, hilar vessels and ureter were grossly unremarkable. Representative sections from the specimen were submitted for histological assessment.
Microscopically, a cellular neoplastic lesion was identified exhibiting spindle shaped to epithelioid cells arranged in the form of short fascicles. These cells had a moderate amount of eosinophilic to clear and granular cytoplasm, with mildly pleomorphic nuclei having open chromatin and occasional prominent nucleoli (fig 2). Nuclear hyperchromasia was also noted in some areas. Mitotic count of 2–3/10 high power field (HPF) was seen. Stroma showed scattered lymphocytes and variable sized blood vessels. Special stains, periodic acid-Schiff (PAS)±diastase, highlighted cytoplasmic glycogen. With this morphology and the age of the patient, differential diagnoses of sarcomatoid renal cell carcinoma, renal rhabdoid tumour and rhabdomyosaroma were worked upon, as other relatively common tumours of this age group were ruled out on morphology alone.
A panel of immunohistochemical stains was carried out and the tumour cells were positive for vimentin and negative for cytokeratin CAM 5.2, cytokeratin AE1/AE3, and desmin antibodies. Therefore, the case was re-examined and the possibilities of renal leiomyosarcoma and PEComa were raised, so a second panel of immunohistochemical stains was ordered. This time the diagnosis was confirmed as the tumour cells were strongly positive for ASMA (alpha smooth muscle actin), HMB45 and MelanA, and were focally positive for S100 immunostain. This immunohistochemical profile together with the morphology led to the diagnosis of PEComa.
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 and TSC2 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.3 Since our case showed hypercellularity, a mitotic index of 2–3/10 HPF and nuclear hyperchromasia, the possibility of malignant behaviour was raised.
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.