Uterine leiomyosarcoma with HMB 45 positive clear cell areas W Glenn McCluggage, M.D. Royal Group of Hospitals Trust Belfast, Northern Ireland

Clinical History: A 60-year-old woman underwent hysterectomy for a fibroid uterus. Gross examination revealed a 6 cm necrotic myometrial mass. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Uterine leiomyosarcoma with HMB 45 positive clear cell areas. Commentary: Uterine leiomyosarcomas may contain a component of epithelioid or clear cells, as well as the more usual spindle cell elements. These epithelioid or clear cell areas may be minor in extent or may predominate or be the exclusive component. The presence of clear cells which are HMB 45 positive within a uterine mesenchymal neoplasm raises the possibility of a perivascular epithelioid cell tumour (PEComa). However, it has recently been shown that undoubted uterine leiomyosarcomas may contain HMB 45 positive clear cells [1, 2]. A diagnosis of uterine PEComa should not be made based solely on the presence of HMB 45 positive clear cells. The present case undoubtedly represents a uterine leiomyosarcoma since typical spindle cell areas which were positive with smooth muscle markers were present. In 1997, Bonetti et al [3] proposed a perivascular epithelioid cell (PEC) as the cell of origin of epithelioid angiomyolipoma, some variants of lymphangioleiomyomatosis, clear cell sugar tumour and more recently described neoplasms such as clear cell myomelanocytic tumour of the falciform ligament/ligamentum teres and abdominopelvic sarcoma of perivascular epithelioid cells [4, 5]. These lesions are characterised by the presence of epithelioid cells which are HMB 45 and muscle marker positive and may occur in patients with tuberous sclerosis complex. Recently it has been shown that a subset of uterine mesenchymal neoplasms are composed focally, predominantly or exclusively of clear cells that express HMB45. These neoplasms have been termed perivascular epithelioid cell tumour (PEComa) and have also been described in other organs [6, 7, 8, 9, 10]. In the seminal description of uterine PEComas, the authors admitted that these neoplasms may be part of a spectrum with uterine epithelioid smooth muscle tumours [6]. An epithelioid morphology is not uncommon in uterine leiomyosarcomas and this may be accompanied by clear cell change, the clear cells potentially being HMB 45 positive [1, 2]. Whilst the potential occurrence of uterine PEComa is acknowledged I feel more cases need to be studied before this can be recognised as a specific entity within the uterus. It is noteworthy that HMB 45 positivity has rarely been described in typical uterine leiomyomas and in normal myometrium [11]. In addition, a group of uterine mesenchymal neoplasms characterised by marked stromal hyalinisation and by epithelioid cells without clear cytoplasm has been described which were positive with HMB 45 [12]. The authors speculated whether these represented epithelioid smooth muscle tumours or belonged to the angiomyolipoma/PEComa group of neoplasms. However, it is admitted that occasionally seemingly bonafide examples of uterine PEComa have been described, including one case where ultrastructural examination revealed numerous premelanosomes [13]. It has been suggested that melan A and micropthalmia transcription factor expression is in favour of a PEComa but a recent study has shown that these markers are not uncommonly expressed in uterine smooth muscle neoplasms [14]. This study also confirmed that uterine smooth muscle neoplasms, especially epithelioid smooth muscle tumours and leiomyosarcomas, may be HMB45 positive. References Silva EG, Deavers MT, Bodurka DC, Malpica A. Uterine epithelioid leiomyosarcomas with clear cells. Reactivity with HMB-45 and the concept of PEComa. Am J Surg Pathol 2004 : 28 : 244 – 249 Hurrell DP, McCluggage WG. 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