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Pathology International 2014; 64: 247–250
doi:10.1111/pin.12155
Letter to the Editor
Renal sclerosing perivascular epithelioid cell tumor (PEComa)/angiomyolipoma with extensive rhabdoid cell features To the Editor: Perivascular epithelioid cell (PEC) was proposed as the prototypic cell of PEComas, which has unique morphologic (smooth muscle, epithelioid, and lipid rich histology), immunohistochemical [coexpression of myogenic (smooth muscle actin) and melanocytic (HMB45) markers], ultrastructural, and genetic features, and has no known normal cellular counterpart.1 PEComas include renal and hepatic angiomyolipomas (AMLs), clear cell sugar tumor of the lung, lymphangioleiomyomatosis, and clear cell myomelanocytic tumor of the falciform ligamentum teres. Pure epithelioid PEComas (so-called epithelioid AMLs) of the kidney are related to their better known triphasic typical AML counterparts and often have disease progression.2,3 Recently, Hornick and Fletcher reported 13 sclerosing PEComas with extensive stromal hyalinization as a distinct and indolent variant of epithelioid PEComa.4 Neoplasms with rhabdoid cell features have been reported in many anatomic sites, and pediatric malignant rhabdoid tumor of the kidney represents the prototypic lesion.5 These neoplasms may exist as pure malignant renal or extrarenal rhabdoid tumors as well as composite neoplasms with rhabdoid cell features in ‘parent’ neoplasms.5 INI1 (hSNF5/ SMARCB1/BAF47) is a highly conserved factor, from yeast to humans, in an ATP-dependent chromatin-modifying complex-SWI/SNF.6 In humans, loss of INI1 expression was first described in malignant rhabdoid tumor, and since then, has been identified in several malignant neoplasms which occasionally show rhabdoid cell features.6,7 In general, INI1 loss and rhabdoid histology are associated with aggressive tumor behavior.6,7 A 51-year-old woman without any notable past or family history including tuberous sclerosis was admitted to our hospital with the chief complaint of right abdominal bloating. Abdominal computed tomography (CT) scan revealed an enhancing broad-based mass which emanated from the right kidney. The tumor measured 4.0 cm in a largest diameter. Under a diagnosis of renal cell carcinoma, right partial nephrectomy was performed for the tumor. The patient is currently alive without recurrence or metastasis of the tumor at 16 months after surgery. On gross examination, the right kidney tumor was well circumscribed, the size of which was 4.0 × 3.0 × 1.4 cm. The
tumor was surfaced by perinephric adipose tissue on one side and by kidney parenchyma on the opposite side. The cut surface of the tumor was tan-white, homogeneous and solid without evidence of hemorrhage or necrosis (Fig. 1a). Microscopically, the tumor was predominantly composed of cords, nests, and sheets of polygonal epithelioid cells with round to oval, relatively uniform nuclei and eosinophilic cytoplasm, embedded in densely sclerotic stroma (Fig. 1b). Approximately 40% of tumor cells showed rhabdoid cell features which were characterized by vesicular nuclei, occasionally prominent nucleolus, and abundant intracytoplasmic hyaline inclusions (Fig. 1c). A spindle cell component was observed in about 10% of tumor cells (Fig. 1d). Tumor cells with clear cytoplasm or significant nuclear pleomorphism were not identified. The tumor cells were frequently associated with the walls of blood vessels (Fig. 1a). A lipomatous component was not seen. Tumor necrosis and mitotic figures were absent. No perinephric fat invasion by tumor cells was observed. The background kidney had mild chronic interstitial inflammation and scattered globally sclerotic glomeruli. Immunohistochemically, the epithelioid tumor cells including those with rhabdoid cell features and spindle tumor cells showed similar immunoreactivity for the examined antibodies: diffusely positive for α−smooth muscle actin (SMA), estrogen receptor (ER), progesterone receptor (PgR), and INI1, focally immunoreactive with HMB45 (Fig. 2), and negative for PAX8. Sclerotic stroma was diffusely immunoreactive for INI1 and negative for α−SMA, ER, PgR, PAX8, and HMB45. Typically, epithelioid PEComa/AML is characterized by cohesive nests or compartmentalized/diffuse sheets of large, polygonal epithelioid tumor cells with abundant eosinophilic cytoplasm and occasional atypical nuclei, admixed with markedly pleomorphic cells with nuclear pleomorphism, hyperchromatism, and the presence of prominent nucleoli. In contrast to classic AMLs which have typical triphasic features, epithelioid PEComas/AMLs are potentially malignant lesions. In a large series of 41 pure epithelioid PEComa of the kidney, recurrence and metastasis of the tumor were seen in 17% and 49% of patients, respectively, and 33% of patients died of disease.3 Recently, Hornick and Fletcher reported 13 cases with epithelioid PEComas with extensive stromal hyalinization as a distinctive variant of ‘sclerosing PEComa’.4 Those cases showed a striking prediction for the retroperitoneum of middle-aged women, and an indolent clinical course. No case in their series involved renal parenchyma. Histologically, those tumors purely consisted of
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
248
Letter to the Editor
Figure 1 (a) Gross examination. The tumor was surfaced by perinephric adipose tissue on one side and kidney parenchyma on the opposite side. The tumor was 4 cm in greatest dimension and well circumscribed, tan-white, homogeneous, and solid. (b–d) Histologic features. (b) Epithelioid tumor cells arranged cords and nests between hyalinized stroma. Epithelioid tumor cells were frequently associated with the wall of a blood vessel (×40). (c) Rhabdoid tumor cells with vesicular nuclei, occasionally prominent nucleoli, and large intracytoplasmic hyaline globules (×400). (d) Spindle tumor cells concentrated in small areas (×200).
nests, cords, or trabeculae of relatively uniform, bland epithelioid cells embedded in dense sclerotic stroma with focal perivascular pattern. Immunohistochemically, all tumors were immunoreactive for both HMB45 and α−SMA. There have been few cases of sclerosing PEComa/AML involving kidney parenchyma; Eble et al. described two pure epithelioid AMLs with characteristic dense stromal hyalinization.8 We designated the kidney tumor of the present case as a sclerosing PEComa since its histologic and immunohistochemical findings were almost identical to those of previously reported tumors.4,8 The tumor of our case was also characterized by tumor cells with extensive rhabdoid cell features. In the kidney, although the quintessential rhabdoid neoplasm is pediatric rhabdoid tumor,5 rhabdoid tumor cells have been seen in various malignant neoplasms including medullary carcinoma of the kidney,7 conventional clear cell carcinoma,9 and malig-
nant mixed epithelial and stromal tumor of the kidney.10 Of these, loss of INI1 expression is frequently observed in renal rhabdoid tumor and medullary carcinoma of the kidney, and associated with aggressive behavior.7 In the case series of sclerosing PEComas reported by Hornick and Fletcher, one retroperitoneal tumor showed focal rhabdoid cytoplasmic inclusions, however, there was no detailed histologic/ immunohistochemical finding, figure of rhabdoid cells, or available follow-up data of this tumor.4 In their study, there was another case of pelvic sclerosing PEComa showing abrupt transition to a highly malignant morphology with marked nuclear atypia, pleomorphism, necrosis, and frequent mitoses (22/10 high-power fields), and developing metastases to lung, liver, and abdominal wall. In the present tumor, nuclear atypia, mitosis, and tumor necrosis were not observed, and the tumor has no recurrence or metastasis thus far. In addition, INI1 expression was retained in the
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Letter to the Editor
249
Figure 2 Immunohistochemical findings. (a) Epithelioid tumor cells (including those with rhabdoid cell features) showing focal immunoreactivity for HMB45. (b and c) Epithelioid tumor cells showing diffuse immunoreactivity for (b) α−smooth muscle actin and (c) estrogen receptor. (d) INI1 expression was retained in rhabdoid tumor cells. Immunoperoxidase method, original magnification ×200.
tumor cells including those with rhabdoid cell features. These findings suggest that the present patients would have a favorable clinical course, and the rhabdoid cell features of the present sclerosing PEComa/AML could be a benign morphologic change. In addition to the renal rhabdoid neoplasms mentioned above, the differential diagnoses of the present tumor may include tumors with uniform epithelioid morphology and a stromal hyalinization, such as epithelioid gastrointestinal tumor, epithelioid smooth muscle tumors, and malignant melanoma. However, according to the aforementioned characteristic clinicopathologic features, including perivascular pattern of the tumor cells and immunoreactivity for both HMB45 and α−SMA, the distinction of the current tumor from these tumors does not seem to be challenging. In summary, we have reported a case of renal sclerosing PEComa/AML with extensive rhabdoid cell features. This report suggests that the rhabdoid cell features of the present
sclerosing PEComa/AML is a benign morphologic change based on benign morphologic features and preservation of INI1 expression in tumor cells. This rare entity should be kept in mind for the differential diagnosis of renal tumors with rhabdoid components. Kosuke Miyai,1 Seema S. Mullick,1 Mukul K. Divatia,1 Steven S. Shen,1,2 Alberto G. Ayala1,2 and Jae Y. Ro1,2 1
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 2Weill Cornell Medical College of Cornell University, Houston, Texas, USA
REFERENCES 1 Bonetti F, Pea M, Martignoni G, Zamboni G. PEC and sugar. Am J Surg Pathol 1992; 16: 307–8. 2 Khan MS, Iram S, O’Brien TS et al. Renal ‘perivascular epitheloid cell-omas’. BJU Int 2006; 98: 1146–7.
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
250
Letter to the Editor
3 Nese N, Martignoni G, Fletcher CD et al. Pure epithelioid PEComas (so-called 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. 4 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. 5 Wick MR, Ritter JH, Dehner LP. Malignant rhabdoid tumors: a clinicopathologic review and conceptual discussion. Semin Diagn Pathol 1995; 12: 233–48. 6 Hollmann TJ, Hornick JL. INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol 2011; 35: 47–63.
7 Cheng JX, Tretiakova M, Gong C et al. Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Mod Pathol 2008; 21: 647–52. 8 Eble JN, Amin MB, Young RH. Epithelioid angiomyolipoma of the kidney: a report of five cases with a prominent and diagnostically confusing epithelioid smooth muscle component. Am J Surg Pathol 1997; 21: 1123–30. 9 Gzökden N, Nappi O, Swanson PE et al. Renal cell carcinoma with rhabdoid features. Am J Surg Pathol 2000; 24: 1329–38. 10 Sukov WR, Cheville JC, Lager DJ et al. Malignant mixed epithelial and stromal tumor of the kidney with rhabdoid features: report of a case including immunohistochemical, molecular genetic studies and comparison to morphologically similar renal tumors. Hum Pathol 2007; 38: 1432–7.
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Pathology International 2014; 64: 247–250
doi:10.1111/pin.12155
Letter to the Editor
Renal sclerosing perivascular epithelioid cell tumor (PEComa)/angiomyolipoma with extensive rhabdoid cell features To the Editor: Perivascular epithelioid cell (PEC) was proposed as the prototypic cell of PEComas, which has unique morphologic (smooth muscle, epithelioid, and lipid rich histology), immunohistochemical [coexpression of myogenic (smooth muscle actin) and melanocytic (HMB45) markers], ultrastructural, and genetic features, and has no known normal cellular counterpart.1 PEComas include renal and hepatic angiomyolipomas (AMLs), clear cell sugar tumor of the lung, lymphangioleiomyomatosis, and clear cell myomelanocytic tumor of the falciform ligamentum teres. Pure epithelioid PEComas (so-called epithelioid AMLs) of the kidney are related to their better known triphasic typical AML counterparts and often have disease progression.2,3 Recently, Hornick and Fletcher reported 13 sclerosing PEComas with extensive stromal hyalinization as a distinct and indolent variant of epithelioid PEComa.4 Neoplasms with rhabdoid cell features have been reported in many anatomic sites, and pediatric malignant rhabdoid tumor of the kidney represents the prototypic lesion.5 These neoplasms may exist as pure malignant renal or extrarenal rhabdoid tumors as well as composite neoplasms with rhabdoid cell features in ‘parent’ neoplasms.5 INI1 (hSNF5/ SMARCB1/BAF47) is a highly conserved factor, from yeast to humans, in an ATP-dependent chromatin-modifying complex-SWI/SNF.6 In humans, loss of INI1 expression was first described in malignant rhabdoid tumor, and since then, has been identified in several malignant neoplasms which occasionally show rhabdoid cell features.6,7 In general, INI1 loss and rhabdoid histology are associated with aggressive tumor behavior.6,7 A 51-year-old woman without any notable past or family history including tuberous sclerosis was admitted to our hospital with the chief complaint of right abdominal bloating. Abdominal computed tomography (CT) scan revealed an enhancing broad-based mass which emanated from the right kidney. The tumor measured 4.0 cm in a largest diameter. Under a diagnosis of renal cell carcinoma, right partial nephrectomy was performed for the tumor. The patient is currently alive without recurrence or metastasis of the tumor at 16 months after surgery. On gross examination, the right kidney tumor was well circumscribed, the size of which was 4.0 × 3.0 × 1.4 cm. The
tumor was surfaced by perinephric adipose tissue on one side and by kidney parenchyma on the opposite side. The cut surface of the tumor was tan-white, homogeneous and solid without evidence of hemorrhage or necrosis (Fig. 1a). Microscopically, the tumor was predominantly composed of cords, nests, and sheets of polygonal epithelioid cells with round to oval, relatively uniform nuclei and eosinophilic cytoplasm, embedded in densely sclerotic stroma (Fig. 1b). Approximately 40% of tumor cells showed rhabdoid cell features which were characterized by vesicular nuclei, occasionally prominent nucleolus, and abundant intracytoplasmic hyaline inclusions (Fig. 1c). A spindle cell component was observed in about 10% of tumor cells (Fig. 1d). Tumor cells with clear cytoplasm or significant nuclear pleomorphism were not identified. The tumor cells were frequently associated with the walls of blood vessels (Fig. 1a). A lipomatous component was not seen. Tumor necrosis and mitotic figures were absent. No perinephric fat invasion by tumor cells was observed. The background kidney had mild chronic interstitial inflammation and scattered globally sclerotic glomeruli. Immunohistochemically, the epithelioid tumor cells including those with rhabdoid cell features and spindle tumor cells showed similar immunoreactivity for the examined antibodies: diffusely positive for α−smooth muscle actin (SMA), estrogen receptor (ER), progesterone receptor (PgR), and INI1, focally immunoreactive with HMB45 (Fig. 2), and negative for PAX8. Sclerotic stroma was diffusely immunoreactive for INI1 and negative for α−SMA, ER, PgR, PAX8, and HMB45. Typically, epithelioid PEComa/AML is characterized by cohesive nests or compartmentalized/diffuse sheets of large, polygonal epithelioid tumor cells with abundant eosinophilic cytoplasm and occasional atypical nuclei, admixed with markedly pleomorphic cells with nuclear pleomorphism, hyperchromatism, and the presence of prominent nucleoli. In contrast to classic AMLs which have typical triphasic features, epithelioid PEComas/AMLs are potentially malignant lesions. In a large series of 41 pure epithelioid PEComa of the kidney, recurrence and metastasis of the tumor were seen in 17% and 49% of patients, respectively, and 33% of patients died of disease.3 Recently, Hornick and Fletcher reported 13 cases with epithelioid PEComas with extensive stromal hyalinization as a distinctive variant of ‘sclerosing PEComa’.4 Those cases showed a striking prediction for the retroperitoneum of middle-aged women, and an indolent clinical course. No case in their series involved renal parenchyma. Histologically, those tumors purely consisted of
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
248
Letter to the Editor
Figure 1 (a) Gross examination. The tumor was surfaced by perinephric adipose tissue on one side and kidney parenchyma on the opposite side. The tumor was 4 cm in greatest dimension and well circumscribed, tan-white, homogeneous, and solid. (b–d) Histologic features. (b) Epithelioid tumor cells arranged cords and nests between hyalinized stroma. Epithelioid tumor cells were frequently associated with the wall of a blood vessel (×40). (c) Rhabdoid tumor cells with vesicular nuclei, occasionally prominent nucleoli, and large intracytoplasmic hyaline globules (×400). (d) Spindle tumor cells concentrated in small areas (×200).
nests, cords, or trabeculae of relatively uniform, bland epithelioid cells embedded in dense sclerotic stroma with focal perivascular pattern. Immunohistochemically, all tumors were immunoreactive for both HMB45 and α−SMA. There have been few cases of sclerosing PEComa/AML involving kidney parenchyma; Eble et al. described two pure epithelioid AMLs with characteristic dense stromal hyalinization.8 We designated the kidney tumor of the present case as a sclerosing PEComa since its histologic and immunohistochemical findings were almost identical to those of previously reported tumors.4,8 The tumor of our case was also characterized by tumor cells with extensive rhabdoid cell features. In the kidney, although the quintessential rhabdoid neoplasm is pediatric rhabdoid tumor,5 rhabdoid tumor cells have been seen in various malignant neoplasms including medullary carcinoma of the kidney,7 conventional clear cell carcinoma,9 and malig-
nant mixed epithelial and stromal tumor of the kidney.10 Of these, loss of INI1 expression is frequently observed in renal rhabdoid tumor and medullary carcinoma of the kidney, and associated with aggressive behavior.7 In the case series of sclerosing PEComas reported by Hornick and Fletcher, one retroperitoneal tumor showed focal rhabdoid cytoplasmic inclusions, however, there was no detailed histologic/ immunohistochemical finding, figure of rhabdoid cells, or available follow-up data of this tumor.4 In their study, there was another case of pelvic sclerosing PEComa showing abrupt transition to a highly malignant morphology with marked nuclear atypia, pleomorphism, necrosis, and frequent mitoses (22/10 high-power fields), and developing metastases to lung, liver, and abdominal wall. In the present tumor, nuclear atypia, mitosis, and tumor necrosis were not observed, and the tumor has no recurrence or metastasis thus far. In addition, INI1 expression was retained in the
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Letter to the Editor
249
Figure 2 Immunohistochemical findings. (a) Epithelioid tumor cells (including those with rhabdoid cell features) showing focal immunoreactivity for HMB45. (b and c) Epithelioid tumor cells showing diffuse immunoreactivity for (b) α−smooth muscle actin and (c) estrogen receptor. (d) INI1 expression was retained in rhabdoid tumor cells. Immunoperoxidase method, original magnification ×200.
tumor cells including those with rhabdoid cell features. These findings suggest that the present patients would have a favorable clinical course, and the rhabdoid cell features of the present sclerosing PEComa/AML could be a benign morphologic change. In addition to the renal rhabdoid neoplasms mentioned above, the differential diagnoses of the present tumor may include tumors with uniform epithelioid morphology and a stromal hyalinization, such as epithelioid gastrointestinal tumor, epithelioid smooth muscle tumors, and malignant melanoma. However, according to the aforementioned characteristic clinicopathologic features, including perivascular pattern of the tumor cells and immunoreactivity for both HMB45 and α−SMA, the distinction of the current tumor from these tumors does not seem to be challenging. In summary, we have reported a case of renal sclerosing PEComa/AML with extensive rhabdoid cell features. This report suggests that the rhabdoid cell features of the present
sclerosing PEComa/AML is a benign morphologic change based on benign morphologic features and preservation of INI1 expression in tumor cells. This rare entity should be kept in mind for the differential diagnosis of renal tumors with rhabdoid components. Kosuke Miyai,1 Seema S. Mullick,1 Mukul K. Divatia,1 Steven S. Shen,1,2 Alberto G. Ayala1,2 and Jae Y. Ro1,2 1
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 2Weill Cornell Medical College of Cornell University, Houston, Texas, USA
REFERENCES 1 Bonetti F, Pea M, Martignoni G, Zamboni G. PEC and sugar. Am J Surg Pathol 1992; 16: 307–8. 2 Khan MS, Iram S, O’Brien TS et al. Renal ‘perivascular epitheloid cell-omas’. BJU Int 2006; 98: 1146–7.
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
250
Letter to the Editor
3 Nese N, Martignoni G, Fletcher CD et al. Pure epithelioid PEComas (so-called 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. 4 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. 5 Wick MR, Ritter JH, Dehner LP. Malignant rhabdoid tumors: a clinicopathologic review and conceptual discussion. Semin Diagn Pathol 1995; 12: 233–48. 6 Hollmann TJ, Hornick JL. INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol 2011; 35: 47–63.
7 Cheng JX, Tretiakova M, Gong C et al. Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Mod Pathol 2008; 21: 647–52. 8 Eble JN, Amin MB, Young RH. Epithelioid angiomyolipoma of the kidney: a report of five cases with a prominent and diagnostically confusing epithelioid smooth muscle component. Am J Surg Pathol 1997; 21: 1123–30. 9 Gzökden N, Nappi O, Swanson PE et al. Renal cell carcinoma with rhabdoid features. Am J Surg Pathol 2000; 24: 1329–38. 10 Sukov WR, Cheville JC, Lager DJ et al. Malignant mixed epithelial and stromal tumor of the kidney with rhabdoid features: report of a case including immunohistochemical, molecular genetic studies and comparison to morphologically similar renal tumors. Hum Pathol 2007; 38: 1432–7.
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
