- Email: [email protected]
Primary perivascular epithelioid cell tumour (PEComa) of the urinary bladder
746
CORRESPONDENCE
Primary perivascular epithelioid cell tumour (PEComa) of the urinary bladder Sir, Perivascular epithelioid cell tumour (PEComa) was first described by Bonetti et al. and has been subsequently defined as ‘mesenchymal tumour composed of histologically and immunohistochemically distinctive perivascular epithelioid cells’ in the latest World Health Organization (WHO) Classification of Tumours.1,2 This terminology applies to angiomyolipoma (AML), clear cell sugar tumour of the lung, lymphangioleiomyomatosis, clear cell myomelanocytic tumour of the falciform ligament/ligamentum teres, and tumours of the soft tissue and viscera with either spindled or epithelioid morphology and dual myomelanocytic differentiation. PEComa of the urinary bladder is rare with only eight cases reported in the literature.3–8 Herein another case of PEComa of the urinary bladder is described. A 42-year-old man with good past health had an incidental ultrasonography finding of a bladder mass during health screening. Computed tomography (CT) of the pelvis revealed a 6 cm contrast-enhancing tumour arising from the urinary bladder (Fig. 1A,B). Positron emission tomography (PET)-CT demonstrated a hypermetabolic urinary bladder wall mass (Fig. 1C). Flexible cystoscopy showed normal bladder mucosal surface with an extrinsic mass arising from the right lateral surface of the bladder. Transurethral resection of bladder tumour (TURBT) was performed to remove a 4 cm bulge at the right lateral wall with the overlying normal mucosa. He subsequently underwent robotic-assisted laparoscopic partial cystectomy where the post-operative course was uneventful. The partial cystectomy was an 80 60 50 mm mass with a smooth peritoneal surface of 80 70 mm on one side and raw soft tissue and muscle on another side. Its cut surface revealed a 60 50 40 mm, well-circumscribed, ovoid, tan-coloured mass with a spongy to firm consistency (Fig. 2A). Resected right pelvic lymph nodes included external iliac, internal iliac, distal iliac and obturator lymph nodes, and measured from 2 to 18 mm. On microscopy, the tumour appeared to have two growth patterns. One was composed of fascicles of spindle cells with clear to eosinophilic cytoplasm, and an elongated vesicular nucleus that may take a ‘cigar’ shape, reminiscent of smooth muscle cells. The other growth pattern displayed small organoid nests and packets of epithelioid cells, which also contained clear to eosinophilic cytoplasm (Fig. 2B). The tumour cells were generally bland and uniform, but focally exhibited atypical hyperchromatic nuclei (Fig. 2C). Mitosis
Pathology (2011), 43(7), December
was rare, with less than 1 mitotic figure per 50 high power fields (HPF). Apart from prominent hyalinised collagenous stroma, devoid of any adipose tissue, there were also striking hyalinised vessels (Fig. 2D). Tumour cells did not display any pigments or necrosis. The bulk of the tumour appeared to be subepithelial, with minimal surface erosion, but had infiltrated the full thickness of the muscularis propria of the urinary bladder. The excision was complete, but focally the perivesical soft tissue clearance was only 5 mm. The tumour cells were immunoreactive to melanocytic markers [S-100, HMB-45, micro-ophthalmia transcription factor (MiTF)], some myoid markers [smooth muscle actin (SMA) and calponin] (Fig. 3) and very focally and weakly vimentin, while other markers including other muscle markers (desmin and myogenin), transcription factor E3 (TFE3), epithelial marker (pan-cytokeratin AE1/AE3), CD34, ALK-1, neuroendocrine marker (synaptophysin) and c-kit/CD117 were not expressed. The proliferative pool as assessed by Ki-67/MIB-1 stain was clearly low, and estimated as 1%. Both the microscopic features and the immunoreactive profile supported the diagnosis of PEComa of the urinary bladder. All pelvic lymph nodes dissected were benign and reactive. PEComa of the urinary bladder is rare. Since its first description by Pan and co-workers in 2003,3 seven more cases have been reported to date. In all nine cases of urinary bladder PEComa (Table 1), including the current case, the median age at presentation was 36 years (19–48 years) with male predilection (M:F ¼ 2:1), in contrast to female predominance (M:F ¼ 1:4–7) in other non-AML PEComas.9 The clinical presentation is rather non-specific urinary symptoms, consisting of haematuria and dysuria, while a quarter of patients are asymptomatic. None of these patients show evidence of tuberous sclerosis. The tumour is generally large with average size of 5 cm (3.0–9.2 cm). The clinical behaviour of non-AML PEComas remains unclear owing to their relative rarity. Folpe et al. analysed 71 cases of non-AML PEComas of soft tissue and gynaecological origin, and have proposed a pathological classification to predict their clinical behaviours.9 The pathological parameters include size greater than 5 cm, infiltrative growth, tumour necrosis, high nuclear grade, and mitosis more than 1 per 50 HPF. PEComa is classified as ‘benign’, ‘uncertain malignant potential’ or ‘malignant’ if the tumour contains none, one, or more than one of such unfavourable parameters, respectively. However, the clinical significance of this classification applied in the urinary bladder is unknown because PEComa in this location seems to pursue an indolent clinical course. Although the clinical follow-up is limited, there is no reported case of recurrence or metastasis even in those
Fig. 1 (A,B) Contrast-enhanced computed tomography showed a 6 cm contrast-enhancing tumour over the right superolateral wall of the urinary bladder. (C) PET-CT scan demonstrated a hypermetabolic nature of the bladder mass.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
CORRESPONDENCE
747
Fig. 2 (A) Cut surface of the urinary bladder showed a 6 cm, well-circumscribed, ovoid, tan-coloured mass with a spongy to firm consistency. (B) The spindle cell component exhibited fascicular growth pattern (left lower), while epithelioid cells were arranged in small organoid packets and cords (right upper) (H&E). (C) Focal cytological atypia with nucleomegaly, moderate nuclear pleomorphism and hyperchromasia (H&E). (D) Prominent medium-to-large-sized vessels contained thick hyalinised walls (H&E).
classified as ‘malignant’ PEComa. Owing to limited experience reported, long-term regular follow-up is recommended. Recently, Nese et al. analysed 41 renal epithelioid PEComas (monotypic epithelioid AMLs) and proposed a risk stratification based on five clinical and pathological parameters,
including the association with tuberous sclerosis or concurrent AML, tumour size >7 cm, extrarenal extension/renal vein involvement, tumour necrosis, and carcinoma-like growth pattern (i.e., cohesive nests, broad alveoli, and compartmentalised sheets separated by thin vascular-rich septa).10 Renal PEComa
Fig. 3 Immunoreactivity of tumour cells to (A) HMB-45, (B) micro-ophthalmia transcription factor (MiTF), (C) smooth muscle actin (SMA), and (D) calponin.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
Pathology (2011), 43(7), December
Recent case TURBT and partial cystectomy UMP M/42 Present case
Huang et al.8
NS, not specified; TURBT, transurethral resection of bladder tumour; UMP, uncertain malignant potential.
6.0 Right lateral wall
Alive without disease at 8 months Alive without disease at 10 months Alive without disease at 21 months NS NS M/39 M/36 M/37 F/26 M/23 Weinreb et al.14 Sukov et al.7
NS Haematuria Haematuria Asymptomatic Urinary frequency and dysuria Vague urethral pain
Dome/Urachal remnant cyst Anterior wall Dome Anterior wall Left lateral wall
5.0 4.8 NS 5.0 9.2
Malignant Malignant Benign Benign UMP
Partial cystectomy TURBT Partial cystectomy and partial small bowel resection with adjuvant INF-a immunotherapy Partial cystectomy Partial cystectomy TURBT Embolisation and partial cystectomy Tumourectomy and partial cystectomy Malignant Benign Malignant 4.0 3.0 3.0 Left lateral wall Left lateral wall Posterior mid-wall F/33 F/19 M/48 Pan et al.3 Kalyanasundaram et al.4 Parfitt et al.5
Asymptomatic Haematuria Lower abdominal pain and dysuria
Treatment Classification by Folpe et al. Size (cm) Location Symptoms Sex/age Study
Summary of clinical and pathological features of PEComa of the urinary bladder Table 1
Alive without disease at 72 months NS Alive without disease at 48 months
CORRESPONDENCE
Follow-up
748
is classified as ‘low risk’, ‘intermediate risk’ or ‘high risk’ if the tumour contains 0–1, 2–3 or more than 3 of such unfavourable parameters, respectively. However, it is uncertain whether this system would extrapolate to the counterpart of the urinary bladder. The management of primary PEComa is not standardised due to the sparse number of cases. Primary excision is the main stay of treatment in localised cases, while chemotherapy, radiotherapy and immunotherapy have been reported in locally advanced or metastatic PEComas at different sites.5 Modality of surgical treatment mainly depends on the size and site of the tumour, and the involvement of adjacent structures such as bowel, ureteric orifice or spermatic cord.5,8 In our case, robotic assistance enhanced the visualisation, improved the acuity of excision and reconstruction during surgery, and obviated the need for ureteric reimplantation. Moreover, such minimally invasive surgery could minimise post-operative pain and morbidities from the wound, and reduce the length of hospitalisation. The pathological differential diagnosis of PEComa of the urinary bladder includes tumours with epithelioid and/or spindle cell components. In particular, leiomyosarcoma and metastatic malignant melanoma can be challenging for their morphological and immunohistochemical similarity shared with PEComa. PEComa shares with smooth muscle tumours the fascicular pattern of growth, the elongated spindle cells with fibrillary eosinophilic cytoplasm, and even the cigar-shape nucleus. Moreover, PEComa expresses various smooth muscle markers including SMA (84%), desmin (60%), caldesmon (33%) and rarely calponin.9 – 11 However, the epithelioid cells growing in nests and sheets, the sometimes prominent clear cytoplasm, the extensive hyalinisation of the stroma, the striking vascularity with hyalinised thick-walled vessels, and finally the expression of melanocytic markers, all set PEComa apart from smooth muscle tumours. Malignant melanoma may display spindle cells focally with short fascicular pattern, and shares with PEComa the expression of many melanocytic markers including HMB-45 (95%), MiTF (67%) and Melan-A (67%).9 – 11 Diffuse and strong immunoreactivity of S-100 and vimentin are found in most malignant melanomas (81% and 90%, respectively) and less commonly in PEComa (7% and 44%, respectively).12 The diagnostic issue can be further compounded by rare cases of pigmented PEComa.13 Malignant melanoma differs from PEComa by clinical history of primary cutaneous or mucosal malignant melanoma, the prominent nucleolus of the tumour cell, the absence of prominent hyalinised stroma and hyalinised, large, thick-walled vessels, and the lack of smooth muscle cell markers. The exclusion of other differential diagnoses is more straightforward. Sarcomatoid urothelial carcinoma, prostatic adenocarcinoma, and carcinoma of the gynaecological tract are microscopically easier to discriminate from PEComa, and in more difficult examples, tumour expression of various cytokeratins and more specific markers such as prostatic specific antigen are effective to establish the diagnosis. Paraganglioma is also rare, and may be distinctive by the cytoplasmic granularity of the tumour cells, or sometimes by the zellballen nodular growth, and reliably by the expression of neuroendocrine markers including chromogranin and synaptophysin. Finally, inflammatory myofibroblastic tumour is distinctive from the associated lymphoplasmacytic cellular infiltrate, myxoid stroma and occasional immunoreactivity to the ALK-1 marker.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
CORRESPONDENCE
PEComa of the urinary bladder is a rare tumour and more examples including long-term follow-up are needed to appraise is biological behaviour. It should be carefully differentiated from its morphological and immunohistochemical mimics. Anthony W. H. Chan* C. K. Chan{ Y. Chiu{ Sidney K. H. Yip{ Fernand M. Lai* K. F. To* Departments of *Anatomical and Cellular Pathology, and {Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
749
uncertain lineage. It occurs predominantly in males in the 5th to 7th decade, presenting as a slow growing tumour in the subcutaneous or deeper tissues of the extremities, trunk, or head and neck region,2 and rarely the retroperitoneum and mediastinum.3 Although there are reports of mediastinal metastasis,4,5 our case represents the second case originating in the mediastinum and the first histologically malignant OFMT in the mediastinum. A 50-year-old female with a 2 month history of chest wall pain, palpitations and orthopnoea was found to have a large mediastinal mass on X-ray (Fig. 1). Computed tomography (CT) revealed a large lobulated anterior mediastinal mass with internal vascularity and a 1 cm focus of calcification. It abutted the great vessels and compressed the pulmonary trunk. Further investigations with transthoracic echocardiogram and cardiac
Contact Dr A. W. H. Chan. E-mail: [email protected] 1. Bonetti F, Pea M, Martignoni G, Zamboni G. PEC and sugar. Am J Surg Pathol 1992; 16: 307–8. 2. Fletcher CD, Unni KK, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press, 2002; Neoplasms with perivascular epithelioid cell differentiation. 3. Pan CC, Yu IT, Yang AH, Chiang H. Clear cell myomelanocytic tumor of the urinary bladder. Am J Surg Pathol 2003; 27: 689–92. 4. Kalyanasundaram K, Parameswaran A, Mani R. Perivascular epithelioid tumor of urinary bladder and vagina. Ann Diagn Pathol 2005; 9: 275–8. 5. Parfitt JR, Bella AJ, Wehrli BM, Izawa JI. Primary PEComa of the bladder treated with primary excision and adjuvant interferon-alpha immunotherapy: a case report. BMC Urol 2006; 6: 20. 6. Pianezza ML, Slatnik J, Evans HJ. Clear cell myomelanocytic tumour: minimally invasive treatment of a rare bladder tumour. Can Urol Assoc J 2008; 2: 230–4. 7. Sukov WR, Cheville JC, Amin MB, Gupta R, Folpe AL. Perivascular epithelioid cell tumor (PEComa) of the urinary bladder: report of 3 cases and review of the literature. Am J Surg Pathol 2009; 33: 304–8. 8. Huang Y, Lu G, Quan J, et al. Primary perivascular epithelioid cell tumor of the bladder. Ann Diagn Pathol 2010; Oct 30: (Epub ahead of print). 9. Folpe AL, Mentzel T, Lehr HA, et al. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol 2005; 29: 1558–75. 10. Nese N, Martignoni G, Fletcher CD, et al. Pure epithelioid PEComas (socalled epithelioid angiomyolipoma) of the kidney: A clinicopathologic study of 41 cases: detailed assessment of morphology and risk stratification. Am J Surg Pathol 2011; 35: 161–76. 11. Hornick JL, Fletcher CD. Sclerosing PEComa: clinicopathologic analysis of a distinctive variant with a predilection for the retroperitoneum. Am J Surg Pathol 2008; 32: 493–501. 12. Amirsys. PathIQ ImmunoQuery. 2010 (cited May 2011). http://www.amir sys.com/portals/pathiq-immunoquery. 13. Fukunaga M, Harada T. Pigmented perivascular epithelioid cell tumor of the kidney. Arch Pathol Lab Med 2009; 133: 1981–4. 14. Weinreb I, Howarth D, Latta E, Ghazarian D, Chetty R. Perivascular epithelioid cell neoplasms (PEComas): four malignant cases expanding the histopathological spectrum and a description of a unique finding. Virchows Arch 2007; 450: 463–70.
DOI: 10.1097/PAT.0b013e32834c768b
Malignant ossifying fibromyxoid tumour: a large anterior mediastinal mass Sir, Originally described in 1989 by Enzinger et al.,1 ossifying fibromyxoid tumour (OFMT) is a rare soft tissue tumour of
Fig. 1 Chest X-ray taken before surgery, showing (A) a silhouette of a large mediastinal mass (B) which was not evident following surgery.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
CORRESPONDENCE
Primary perivascular epithelioid cell tumour (PEComa) of the urinary bladder Sir, Perivascular epithelioid cell tumour (PEComa) was first described by Bonetti et al. and has been subsequently defined as ‘mesenchymal tumour composed of histologically and immunohistochemically distinctive perivascular epithelioid cells’ in the latest World Health Organization (WHO) Classification of Tumours.1,2 This terminology applies to angiomyolipoma (AML), clear cell sugar tumour of the lung, lymphangioleiomyomatosis, clear cell myomelanocytic tumour of the falciform ligament/ligamentum teres, and tumours of the soft tissue and viscera with either spindled or epithelioid morphology and dual myomelanocytic differentiation. PEComa of the urinary bladder is rare with only eight cases reported in the literature.3–8 Herein another case of PEComa of the urinary bladder is described. A 42-year-old man with good past health had an incidental ultrasonography finding of a bladder mass during health screening. Computed tomography (CT) of the pelvis revealed a 6 cm contrast-enhancing tumour arising from the urinary bladder (Fig. 1A,B). Positron emission tomography (PET)-CT demonstrated a hypermetabolic urinary bladder wall mass (Fig. 1C). Flexible cystoscopy showed normal bladder mucosal surface with an extrinsic mass arising from the right lateral surface of the bladder. Transurethral resection of bladder tumour (TURBT) was performed to remove a 4 cm bulge at the right lateral wall with the overlying normal mucosa. He subsequently underwent robotic-assisted laparoscopic partial cystectomy where the post-operative course was uneventful. The partial cystectomy was an 80 60 50 mm mass with a smooth peritoneal surface of 80 70 mm on one side and raw soft tissue and muscle on another side. Its cut surface revealed a 60 50 40 mm, well-circumscribed, ovoid, tan-coloured mass with a spongy to firm consistency (Fig. 2A). Resected right pelvic lymph nodes included external iliac, internal iliac, distal iliac and obturator lymph nodes, and measured from 2 to 18 mm. On microscopy, the tumour appeared to have two growth patterns. One was composed of fascicles of spindle cells with clear to eosinophilic cytoplasm, and an elongated vesicular nucleus that may take a ‘cigar’ shape, reminiscent of smooth muscle cells. The other growth pattern displayed small organoid nests and packets of epithelioid cells, which also contained clear to eosinophilic cytoplasm (Fig. 2B). The tumour cells were generally bland and uniform, but focally exhibited atypical hyperchromatic nuclei (Fig. 2C). Mitosis
Pathology (2011), 43(7), December
was rare, with less than 1 mitotic figure per 50 high power fields (HPF). Apart from prominent hyalinised collagenous stroma, devoid of any adipose tissue, there were also striking hyalinised vessels (Fig. 2D). Tumour cells did not display any pigments or necrosis. The bulk of the tumour appeared to be subepithelial, with minimal surface erosion, but had infiltrated the full thickness of the muscularis propria of the urinary bladder. The excision was complete, but focally the perivesical soft tissue clearance was only 5 mm. The tumour cells were immunoreactive to melanocytic markers [S-100, HMB-45, micro-ophthalmia transcription factor (MiTF)], some myoid markers [smooth muscle actin (SMA) and calponin] (Fig. 3) and very focally and weakly vimentin, while other markers including other muscle markers (desmin and myogenin), transcription factor E3 (TFE3), epithelial marker (pan-cytokeratin AE1/AE3), CD34, ALK-1, neuroendocrine marker (synaptophysin) and c-kit/CD117 were not expressed. The proliferative pool as assessed by Ki-67/MIB-1 stain was clearly low, and estimated as 1%. Both the microscopic features and the immunoreactive profile supported the diagnosis of PEComa of the urinary bladder. All pelvic lymph nodes dissected were benign and reactive. PEComa of the urinary bladder is rare. Since its first description by Pan and co-workers in 2003,3 seven more cases have been reported to date. In all nine cases of urinary bladder PEComa (Table 1), including the current case, the median age at presentation was 36 years (19–48 years) with male predilection (M:F ¼ 2:1), in contrast to female predominance (M:F ¼ 1:4–7) in other non-AML PEComas.9 The clinical presentation is rather non-specific urinary symptoms, consisting of haematuria and dysuria, while a quarter of patients are asymptomatic. None of these patients show evidence of tuberous sclerosis. The tumour is generally large with average size of 5 cm (3.0–9.2 cm). The clinical behaviour of non-AML PEComas remains unclear owing to their relative rarity. Folpe et al. analysed 71 cases of non-AML PEComas of soft tissue and gynaecological origin, and have proposed a pathological classification to predict their clinical behaviours.9 The pathological parameters include size greater than 5 cm, infiltrative growth, tumour necrosis, high nuclear grade, and mitosis more than 1 per 50 HPF. PEComa is classified as ‘benign’, ‘uncertain malignant potential’ or ‘malignant’ if the tumour contains none, one, or more than one of such unfavourable parameters, respectively. However, the clinical significance of this classification applied in the urinary bladder is unknown because PEComa in this location seems to pursue an indolent clinical course. Although the clinical follow-up is limited, there is no reported case of recurrence or metastasis even in those
Fig. 1 (A,B) Contrast-enhanced computed tomography showed a 6 cm contrast-enhancing tumour over the right superolateral wall of the urinary bladder. (C) PET-CT scan demonstrated a hypermetabolic nature of the bladder mass.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
CORRESPONDENCE
747
Fig. 2 (A) Cut surface of the urinary bladder showed a 6 cm, well-circumscribed, ovoid, tan-coloured mass with a spongy to firm consistency. (B) The spindle cell component exhibited fascicular growth pattern (left lower), while epithelioid cells were arranged in small organoid packets and cords (right upper) (H&E). (C) Focal cytological atypia with nucleomegaly, moderate nuclear pleomorphism and hyperchromasia (H&E). (D) Prominent medium-to-large-sized vessels contained thick hyalinised walls (H&E).
classified as ‘malignant’ PEComa. Owing to limited experience reported, long-term regular follow-up is recommended. Recently, Nese et al. analysed 41 renal epithelioid PEComas (monotypic epithelioid AMLs) and proposed a risk stratification based on five clinical and pathological parameters,
including the association with tuberous sclerosis or concurrent AML, tumour size >7 cm, extrarenal extension/renal vein involvement, tumour necrosis, and carcinoma-like growth pattern (i.e., cohesive nests, broad alveoli, and compartmentalised sheets separated by thin vascular-rich septa).10 Renal PEComa
Fig. 3 Immunoreactivity of tumour cells to (A) HMB-45, (B) micro-ophthalmia transcription factor (MiTF), (C) smooth muscle actin (SMA), and (D) calponin.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
Pathology (2011), 43(7), December
Recent case TURBT and partial cystectomy UMP M/42 Present case
Huang et al.8
NS, not specified; TURBT, transurethral resection of bladder tumour; UMP, uncertain malignant potential.
6.0 Right lateral wall
Alive without disease at 8 months Alive without disease at 10 months Alive without disease at 21 months NS NS M/39 M/36 M/37 F/26 M/23 Weinreb et al.14 Sukov et al.7
NS Haematuria Haematuria Asymptomatic Urinary frequency and dysuria Vague urethral pain
Dome/Urachal remnant cyst Anterior wall Dome Anterior wall Left lateral wall
5.0 4.8 NS 5.0 9.2
Malignant Malignant Benign Benign UMP
Partial cystectomy TURBT Partial cystectomy and partial small bowel resection with adjuvant INF-a immunotherapy Partial cystectomy Partial cystectomy TURBT Embolisation and partial cystectomy Tumourectomy and partial cystectomy Malignant Benign Malignant 4.0 3.0 3.0 Left lateral wall Left lateral wall Posterior mid-wall F/33 F/19 M/48 Pan et al.3 Kalyanasundaram et al.4 Parfitt et al.5
Asymptomatic Haematuria Lower abdominal pain and dysuria
Treatment Classification by Folpe et al. Size (cm) Location Symptoms Sex/age Study
Summary of clinical and pathological features of PEComa of the urinary bladder Table 1
Alive without disease at 72 months NS Alive without disease at 48 months
CORRESPONDENCE
Follow-up
748
is classified as ‘low risk’, ‘intermediate risk’ or ‘high risk’ if the tumour contains 0–1, 2–3 or more than 3 of such unfavourable parameters, respectively. However, it is uncertain whether this system would extrapolate to the counterpart of the urinary bladder. The management of primary PEComa is not standardised due to the sparse number of cases. Primary excision is the main stay of treatment in localised cases, while chemotherapy, radiotherapy and immunotherapy have been reported in locally advanced or metastatic PEComas at different sites.5 Modality of surgical treatment mainly depends on the size and site of the tumour, and the involvement of adjacent structures such as bowel, ureteric orifice or spermatic cord.5,8 In our case, robotic assistance enhanced the visualisation, improved the acuity of excision and reconstruction during surgery, and obviated the need for ureteric reimplantation. Moreover, such minimally invasive surgery could minimise post-operative pain and morbidities from the wound, and reduce the length of hospitalisation. The pathological differential diagnosis of PEComa of the urinary bladder includes tumours with epithelioid and/or spindle cell components. In particular, leiomyosarcoma and metastatic malignant melanoma can be challenging for their morphological and immunohistochemical similarity shared with PEComa. PEComa shares with smooth muscle tumours the fascicular pattern of growth, the elongated spindle cells with fibrillary eosinophilic cytoplasm, and even the cigar-shape nucleus. Moreover, PEComa expresses various smooth muscle markers including SMA (84%), desmin (60%), caldesmon (33%) and rarely calponin.9 – 11 However, the epithelioid cells growing in nests and sheets, the sometimes prominent clear cytoplasm, the extensive hyalinisation of the stroma, the striking vascularity with hyalinised thick-walled vessels, and finally the expression of melanocytic markers, all set PEComa apart from smooth muscle tumours. Malignant melanoma may display spindle cells focally with short fascicular pattern, and shares with PEComa the expression of many melanocytic markers including HMB-45 (95%), MiTF (67%) and Melan-A (67%).9 – 11 Diffuse and strong immunoreactivity of S-100 and vimentin are found in most malignant melanomas (81% and 90%, respectively) and less commonly in PEComa (7% and 44%, respectively).12 The diagnostic issue can be further compounded by rare cases of pigmented PEComa.13 Malignant melanoma differs from PEComa by clinical history of primary cutaneous or mucosal malignant melanoma, the prominent nucleolus of the tumour cell, the absence of prominent hyalinised stroma and hyalinised, large, thick-walled vessels, and the lack of smooth muscle cell markers. The exclusion of other differential diagnoses is more straightforward. Sarcomatoid urothelial carcinoma, prostatic adenocarcinoma, and carcinoma of the gynaecological tract are microscopically easier to discriminate from PEComa, and in more difficult examples, tumour expression of various cytokeratins and more specific markers such as prostatic specific antigen are effective to establish the diagnosis. Paraganglioma is also rare, and may be distinctive by the cytoplasmic granularity of the tumour cells, or sometimes by the zellballen nodular growth, and reliably by the expression of neuroendocrine markers including chromogranin and synaptophysin. Finally, inflammatory myofibroblastic tumour is distinctive from the associated lymphoplasmacytic cellular infiltrate, myxoid stroma and occasional immunoreactivity to the ALK-1 marker.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
CORRESPONDENCE
PEComa of the urinary bladder is a rare tumour and more examples including long-term follow-up are needed to appraise is biological behaviour. It should be carefully differentiated from its morphological and immunohistochemical mimics. Anthony W. H. Chan* C. K. Chan{ Y. Chiu{ Sidney K. H. Yip{ Fernand M. Lai* K. F. To* Departments of *Anatomical and Cellular Pathology, and {Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
749
uncertain lineage. It occurs predominantly in males in the 5th to 7th decade, presenting as a slow growing tumour in the subcutaneous or deeper tissues of the extremities, trunk, or head and neck region,2 and rarely the retroperitoneum and mediastinum.3 Although there are reports of mediastinal metastasis,4,5 our case represents the second case originating in the mediastinum and the first histologically malignant OFMT in the mediastinum. A 50-year-old female with a 2 month history of chest wall pain, palpitations and orthopnoea was found to have a large mediastinal mass on X-ray (Fig. 1). Computed tomography (CT) revealed a large lobulated anterior mediastinal mass with internal vascularity and a 1 cm focus of calcification. It abutted the great vessels and compressed the pulmonary trunk. Further investigations with transthoracic echocardiogram and cardiac
Contact Dr A. W. H. Chan. E-mail: [email protected] 1. Bonetti F, Pea M, Martignoni G, Zamboni G. PEC and sugar. Am J Surg Pathol 1992; 16: 307–8. 2. Fletcher CD, Unni KK, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press, 2002; Neoplasms with perivascular epithelioid cell differentiation. 3. Pan CC, Yu IT, Yang AH, Chiang H. Clear cell myomelanocytic tumor of the urinary bladder. Am J Surg Pathol 2003; 27: 689–92. 4. Kalyanasundaram K, Parameswaran A, Mani R. Perivascular epithelioid tumor of urinary bladder and vagina. Ann Diagn Pathol 2005; 9: 275–8. 5. Parfitt JR, Bella AJ, Wehrli BM, Izawa JI. Primary PEComa of the bladder treated with primary excision and adjuvant interferon-alpha immunotherapy: a case report. BMC Urol 2006; 6: 20. 6. Pianezza ML, Slatnik J, Evans HJ. Clear cell myomelanocytic tumour: minimally invasive treatment of a rare bladder tumour. Can Urol Assoc J 2008; 2: 230–4. 7. Sukov WR, Cheville JC, Amin MB, Gupta R, Folpe AL. Perivascular epithelioid cell tumor (PEComa) of the urinary bladder: report of 3 cases and review of the literature. Am J Surg Pathol 2009; 33: 304–8. 8. Huang Y, Lu G, Quan J, et al. Primary perivascular epithelioid cell tumor of the bladder. Ann Diagn Pathol 2010; Oct 30: (Epub ahead of print). 9. Folpe AL, Mentzel T, Lehr HA, et al. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol 2005; 29: 1558–75. 10. Nese N, Martignoni G, Fletcher CD, et al. Pure epithelioid PEComas (socalled epithelioid angiomyolipoma) of the kidney: A clinicopathologic study of 41 cases: detailed assessment of morphology and risk stratification. Am J Surg Pathol 2011; 35: 161–76. 11. Hornick JL, Fletcher CD. Sclerosing PEComa: clinicopathologic analysis of a distinctive variant with a predilection for the retroperitoneum. Am J Surg Pathol 2008; 32: 493–501. 12. Amirsys. PathIQ ImmunoQuery. 2010 (cited May 2011). http://www.amir sys.com/portals/pathiq-immunoquery. 13. Fukunaga M, Harada T. Pigmented perivascular epithelioid cell tumor of the kidney. Arch Pathol Lab Med 2009; 133: 1981–4. 14. Weinreb I, Howarth D, Latta E, Ghazarian D, Chetty R. Perivascular epithelioid cell neoplasms (PEComas): four malignant cases expanding the histopathological spectrum and a description of a unique finding. Virchows Arch 2007; 450: 463–70.
DOI: 10.1097/PAT.0b013e32834c768b
Malignant ossifying fibromyxoid tumour: a large anterior mediastinal mass Sir, Originally described in 1989 by Enzinger et al.,1 ossifying fibromyxoid tumour (OFMT) is a rare soft tissue tumour of
Fig. 1 Chest X-ray taken before surgery, showing (A) a silhouette of a large mediastinal mass (B) which was not evident following surgery.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.