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Perivascular epithelioid cell tumor (PEComa) presents an endometrial polyp pattern: Case report and literature review
Human Pathology: Case Reports 13 (2018) 66–68
Contents lists available at ScienceDirect
Human Pathology: Case Reports journal homepage: www.elsevier.com/locate/ehpc
Case Report
Perivascular epithelioid cell tumor (PEComa) presents an endometrial polyp pattern: Case report and literature review Xiaomei Wang, Yanbiao Fu, Baizhou Li
T
⁎
Department of Pathology, the second affiliated hospital of Zhejiang University college of medicine, Hangzhou, Zhejiang, China
A B S T R A C T
Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid cells [1, 2], which can arise in a wide array of anatomic locations, and is characterized by its myelomelanocytic phenotype and unpredictable natural history. To date, less than 80 cases of uterine PEComa have been reported in the literature [3]. Although almost all of these cases show a mural or subserosal localization. Here, we report a rare pattern of uterine PEComa which present as polypoid lesions mimicking an endometrial polyp in a 47-year-old Chinese woman.
1. Case report A 47-year-old Chinese woman with a history of breast cancer in 2016 (invasive carcinoma of no special type, grade 2) and systemic lupus erythematosus in 2013. A routine ultrasound examination in 2017 showed focal is thickened endometrium (Fig. 1A). With a clinical diagnosis of submucosal leiomyoma or endometrial polyp, a laparotomy was performed. At operation, a well-circumscribed protruding area 1.2 × 1 cm in size was found in the uterine cavity (Fig. 1B). On gross exam, the endometrial cavity contained a 1.2 × 1.0 cm polypoid lesion with a soft, grey-white cut surface. The underlying endometrium was thin and atrophic. Histologically, the lesion consisted of clusters glands, atypical cells with clear cytoplasm arrayed in hobnail pattern in the glands (Fig. 2A and B). The cells have round nuclei with smooth contours, open chromatin, and prominent nucleoli. The cells have abundant granular eosinophilic cytoplasm and some have clear cytoplasm. Infrequently, intra-nuclear inclusion body (Fig. 2C) and micro-calcification were observed. No melanin pigment was observed. There was no necrosis and no mitotic figures. No lymphatic or vascular invasion was seen. Based on these morphologic features, endometrial hyperplasia, metastastic breast carcinoma or renal cell carcinoma were favored. But the following IHC revealed the epithelioid cells were negative for epithelial markers such as AE1/AE3, Cam5.2 and CK7. GCDFP-15, GATA-3, Pax-8 and P63 were negative either. As a result all epithelial tumors such as endometrial hyperplasia, metastatic breast cancer and renal cell carcinoma were ruled out. Other markers including Desmin, P53, CD10, CD117 and napsin A were negative. However, the melanogenesis-related marker HMB45 (Fig. 2D) and MelanA were strongly positive. TFE3 was positive. Smooth muscle actin ⁎
was only focally weakly positive (Fig. 2E), and S100 protein was negative. We considered the diagnosis a melanocytic differentiate tumor. Because the glandular pattern PEComa is extremely rare, we also needed to exclude endometrial amelanotic melanoma from PEComa, but this case showed very low MIB-1 index (Fig. 2F) and focal positive SMA, and the mucosal melanoma was ruled out by this immunophenotype. The final diagnosis was an endometrial pseudoglandular PEComa. The World Health Organization [2] classification of tumors of female reproductive organs (2014) proposes the use of 7 parameters to identify those PEComas with a potentially aggressive clinical behavior. Namely, those parameters are size larger than 5 cm, have infiltrative margins, high-grade nuclear atypia, high cellularity, mitotic activity greater than 1/50 high-power fields, necrosis, and vascular invasion. This tumor size was 1.2 × 1.0 cm, well-circumscribed, no lymphatic or vascular invasion, no necrosis and no mitotic figures. In this case, the tumor does not follow either of those parameters. Therefore, we propose that the tumor was a benign endometrial PEComa. 2. Discussion The perivascular epithelioid cell (PEC) was first addressed by Bonetti et al. in 1992 [4]. Based on its morphological and immunohistochemical features. Subsequently, they further proposed that the diseases with the same phenotype, including angiomyolipoma (AML), clear cell “sugar” tumor (CCST) of the lung, and lymphangioleiomyomatosis (LAM), be a part of tumors of this entity. Then, the term PEComa, as an acronym for perivascular epithelioid cell tumor, was first introduced in 1996 by Zamboni et al. [5], who
Corresponding author. E-mail addresses: [email protected] (X. Wang), [email protected], [email protected] (B. Li).
https://doi.org/10.1016/j.ehpc.2018.04.006 Received 17 January 2018; Received in revised form 16 April 2018; Accepted 20 April 2018 2214-3300/ © 2018 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Human Pathology: Case Reports 13 (2018) 66–68
X. Wang et al.
PEComas are described as nodular or multinodular lesions with a myometrial or subserosal localization [6]. However, rarely the uterine PEComas can present as polypoid lesions mimicking an endometrial polyp. In addition, there was the very rare pseudoglandular histoarchitectural pattern which was described [4] in our case. On 2005 Folpe [7] reported the 26 cases of PEComa from soft tissue and the gynecologic tract. The morphological features of PEComas mostly showed epithelioid (N = 9), spindle cells (N = 7), or mixed epithelioid and spindle cells (N = 10) in their cases. This case was an epithelioid appearance. Nevertheless, none of the PEComas showed pseudoglandular pattern in Folpe's study. There was only one paper that reported the pseudoglandular histoarchitectural pattern in Bonetti's [8] report. The pseudoglandular appearance combined with the clear cytoplasm of the neoplastic cells results in a strong mimicry of renal clear cell carcinoma. The Pax8, a transcription factor, is a special marker for almost all clear cell RCC. For this case metastastic ccRCC is the important differentiated diagnosis. But with a negative Pax8 combined with other negative epithelial markers such as AE1/ AE3, CAM5.2 and CD10, the ccRCC was excluded. But for another kind of rare renal tumors, Xp11 translocation RCC, could express melanocytic markers such as HMB45 and Melan A. Strong nuclear TFE3 expression is a sensitive and special marker for the diagnosis of Xp11 translocation RCC. In Folpe's report, about one third (5/17) PEComas expressed TFE3. As a result, the immunophenotypic overlap could be found between PEComa and Xp11 translocation RCC. In our case the tumor cells showed diffuse weak positive staining on the nucleus for TFE3. But this patient has neither a history of RCC, nor has renal area mass at ultrasound. So Xp11 translocation RCC also could be excluded too. The uterine PEComas should be differentiated from other uterine primary tumors, such as epithelioid leiomyoma and endometrial stromal sarcoma. These tumors and PEComas can share, at least in part, some histological appearances and immunophenotype, including expression of melanocytic and smooth muscle markers. Epithelioid leiomyoma shows focal or no immunoreactivity for HMB45, with positivity for SMA and Desmin. PEComas can be difficult to differentiate from clear cell and epithelioid smooth muscle tumors [9] but these entities are negative for HMB45 [10]. Endometrial stromal sarcoma can be ruled out because there was negative staining for CD10 and positive staining of HMB45 [11]. Schoolmeester [9] reported that HMB-45 in PEComas was the most sensitive marker (16/16 positive, 100%), followed by Melan-A (14/16 positive, 88%). Muscle related markers (desmin, SMA, h-caldesmon) were expressed in the spindle cell component by most PEComas. In this case there was just focal weak positive stain for SMA, we postulate that there are no spindle cell components in this case. The very low MIB-1 proliferative index doesn't lead to the diagnosis for amelanotic melanoma or clear cell sarcoma. Though the glandular pattern and intraendometrial growth is quite uncommon for uterine PEComa, after detailed morphological and immunohistochemical differentiation, the final diagnosis is most consistent of endometrial PEComa with pseudoglandular patter and polyp appearance. Herein we have reported a rare case and have described the morphological spectrum of PEComas.
Fig. 1. A. Ultrasound showed intra-uterine echo clusters and suggested are endometrial polyp or endometrial carcinoma (among four cursors). B. Grossly, protruding lesions on the surface of endometrium mimicking an endometrial polyp (→partial tumor).
used it to describe a pancreatic tumor composed of human melanoma black 45 (HMB-45)–positive clear epithelioid cells. The latest World Health Organization classification of tumors of female reproductive [2] organs defines PEComas of the uterus as mesenchymal tumors typically containing epithelioid cells with clear to eosinophilic, granular cytoplasm demonstrating melanocytic and smooth muscle differentiation by immunohistochemistry. Since the PEComa has no distinctive clinical symptoms or signs, the diagnosis depends on pathological examination. In our case, the tumor cells were predominantly composed of epithelioid cells with eosinophilic cytoplasm and partial cells have clear cytoplasm. To date, less than 80 cases of uterine PEComa have been reported in the literature [3]. And most
67
Human Pathology: Case Reports 13 (2018) 66–68
X. Wang et al.
Fig. 2. A. Under low magnification showed the tumor was totally located in endometrium (→) and underlying endometrium between muscularis and tumor was atrophic. (original magnification ×50). B. Histologic sections showed epithelioid cells arranged in glandular architecture(original magnification ×200). C. Intranuclear inclusion body was observed (→nuclear inclusion body, original magnification ×400). D and E. The tumor cells were positive for HMB45 and focal positive for SMA (original magnification ×400). F. Tumor cells showed very low MIB-1 index (original magnification ×400).
References
[6] J.L. Liu, Y.M. Lin, M.C. Lin, et al., Perivascular epithelioid cell tumor (PEComa) of the uterus with aggressive behavior at presentation, Hematol. Oncol. Stem Cell Ther. 2 (3) (2009) 426–430. [7] A.L. Folpe, T. Mentzel, H.A. Lehr, 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. 29 (12) (2005) 1558–1575. [8] F. Bonetti, G. Martignoni, C. Colato, et al., Abdominopelvic sarcoma of perivascular epithelioid cells: report of four cases in young women, one with tuberous sclerosis, Mod. Pathol. 14 (6) (2001) 563–568. [9] J.K. Schoolmeester, B.E. Howitt, M.S. Hirsch, et al., Perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: clinicopathologic and immunohistochemical characterization of 16 cases, Am. J. Surg. Pathol. 38 (2014) 176–188. [10] M. Zamecnik, M. Michal, HMB45+ hyalinized epithelioid tumor of the uterus is linked to epithelioid leiomyoma rather than to PEC-omas, Int. J. Surg. Pathol. 9 (2001) 341–343. [11] R. Vang, R.L. Kempson, Perivascular epithelioid cell tumor (‘PEComa’) of the uterus: a subset of HMB-45 positive epithelioid mesenchymal neoplasms with uncertain relationship to pure smooth muscle tumors, Am. J. Surg. Pathol. 26 (2002) 1–13.
[1] R.J. Grimer, P.C.W. Hogendoorn, D. Vanel, Neoplasms with perivascular epithelioid cell differentiation (PEComas), in: D.M. Fletcher Christopher, A. Bridge Julia, C.W. Hogendoorn Pancras, Mertens Fredrik (Eds.), Pathology and Genetics of Tumours of Soft Tissue and Bone, Series: WHO Classification of tumours, IARC Press, Lyon, 2013, pp. 230–231. [2] E. Oliva, M.L. Carcangiu, S.G. Carinelli, et al., Mesenchymal tumors, in: R.J. Kurman, M.L. Carcangiu, C.S. Herrington, R.H. Young (Eds.), WHO Classification of Tumours of Female Reproductive Organs, 4th ed., IARC, Lyon, France, 2014, pp. 146–147. [3] A.M. Acosta, B.P. Adley, Predicting the behavior of perivascular epithelioid cell tumors of the uterine corpus, Arch. Pathol. Lab. Med. 141 (2017) 463–469. [4] F. Bonetti, M. Pea, G. Martignoni, G. Zamboni, PEC and sugar, Am. J. Surg. Pathol. 16 (1992) 307–308. [5] G. Zamboni, M. Pea, G. Martignoni, et al., Clear cell “sugar” tumor of the pancreas: a novel member of the family of lesions characterized by the presence of perivascular epithelioid cells, Am. J. Surg. Pathol. 20 (1996) 722–730.
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Contents lists available at ScienceDirect
Human Pathology: Case Reports journal homepage: www.elsevier.com/locate/ehpc
Case Report
Perivascular epithelioid cell tumor (PEComa) presents an endometrial polyp pattern: Case report and literature review Xiaomei Wang, Yanbiao Fu, Baizhou Li
T
⁎
Department of Pathology, the second affiliated hospital of Zhejiang University college of medicine, Hangzhou, Zhejiang, China
A B S T R A C T
Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid cells [1, 2], which can arise in a wide array of anatomic locations, and is characterized by its myelomelanocytic phenotype and unpredictable natural history. To date, less than 80 cases of uterine PEComa have been reported in the literature [3]. Although almost all of these cases show a mural or subserosal localization. Here, we report a rare pattern of uterine PEComa which present as polypoid lesions mimicking an endometrial polyp in a 47-year-old Chinese woman.
1. Case report A 47-year-old Chinese woman with a history of breast cancer in 2016 (invasive carcinoma of no special type, grade 2) and systemic lupus erythematosus in 2013. A routine ultrasound examination in 2017 showed focal is thickened endometrium (Fig. 1A). With a clinical diagnosis of submucosal leiomyoma or endometrial polyp, a laparotomy was performed. At operation, a well-circumscribed protruding area 1.2 × 1 cm in size was found in the uterine cavity (Fig. 1B). On gross exam, the endometrial cavity contained a 1.2 × 1.0 cm polypoid lesion with a soft, grey-white cut surface. The underlying endometrium was thin and atrophic. Histologically, the lesion consisted of clusters glands, atypical cells with clear cytoplasm arrayed in hobnail pattern in the glands (Fig. 2A and B). The cells have round nuclei with smooth contours, open chromatin, and prominent nucleoli. The cells have abundant granular eosinophilic cytoplasm and some have clear cytoplasm. Infrequently, intra-nuclear inclusion body (Fig. 2C) and micro-calcification were observed. No melanin pigment was observed. There was no necrosis and no mitotic figures. No lymphatic or vascular invasion was seen. Based on these morphologic features, endometrial hyperplasia, metastastic breast carcinoma or renal cell carcinoma were favored. But the following IHC revealed the epithelioid cells were negative for epithelial markers such as AE1/AE3, Cam5.2 and CK7. GCDFP-15, GATA-3, Pax-8 and P63 were negative either. As a result all epithelial tumors such as endometrial hyperplasia, metastatic breast cancer and renal cell carcinoma were ruled out. Other markers including Desmin, P53, CD10, CD117 and napsin A were negative. However, the melanogenesis-related marker HMB45 (Fig. 2D) and MelanA were strongly positive. TFE3 was positive. Smooth muscle actin ⁎
was only focally weakly positive (Fig. 2E), and S100 protein was negative. We considered the diagnosis a melanocytic differentiate tumor. Because the glandular pattern PEComa is extremely rare, we also needed to exclude endometrial amelanotic melanoma from PEComa, but this case showed very low MIB-1 index (Fig. 2F) and focal positive SMA, and the mucosal melanoma was ruled out by this immunophenotype. The final diagnosis was an endometrial pseudoglandular PEComa. The World Health Organization [2] classification of tumors of female reproductive organs (2014) proposes the use of 7 parameters to identify those PEComas with a potentially aggressive clinical behavior. Namely, those parameters are size larger than 5 cm, have infiltrative margins, high-grade nuclear atypia, high cellularity, mitotic activity greater than 1/50 high-power fields, necrosis, and vascular invasion. This tumor size was 1.2 × 1.0 cm, well-circumscribed, no lymphatic or vascular invasion, no necrosis and no mitotic figures. In this case, the tumor does not follow either of those parameters. Therefore, we propose that the tumor was a benign endometrial PEComa. 2. Discussion The perivascular epithelioid cell (PEC) was first addressed by Bonetti et al. in 1992 [4]. Based on its morphological and immunohistochemical features. Subsequently, they further proposed that the diseases with the same phenotype, including angiomyolipoma (AML), clear cell “sugar” tumor (CCST) of the lung, and lymphangioleiomyomatosis (LAM), be a part of tumors of this entity. Then, the term PEComa, as an acronym for perivascular epithelioid cell tumor, was first introduced in 1996 by Zamboni et al. [5], who
Corresponding author. E-mail addresses: [email protected] (X. Wang), [email protected], [email protected] (B. Li).
https://doi.org/10.1016/j.ehpc.2018.04.006 Received 17 January 2018; Received in revised form 16 April 2018; Accepted 20 April 2018 2214-3300/ © 2018 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Human Pathology: Case Reports 13 (2018) 66–68
X. Wang et al.
PEComas are described as nodular or multinodular lesions with a myometrial or subserosal localization [6]. However, rarely the uterine PEComas can present as polypoid lesions mimicking an endometrial polyp. In addition, there was the very rare pseudoglandular histoarchitectural pattern which was described [4] in our case. On 2005 Folpe [7] reported the 26 cases of PEComa from soft tissue and the gynecologic tract. The morphological features of PEComas mostly showed epithelioid (N = 9), spindle cells (N = 7), or mixed epithelioid and spindle cells (N = 10) in their cases. This case was an epithelioid appearance. Nevertheless, none of the PEComas showed pseudoglandular pattern in Folpe's study. There was only one paper that reported the pseudoglandular histoarchitectural pattern in Bonetti's [8] report. The pseudoglandular appearance combined with the clear cytoplasm of the neoplastic cells results in a strong mimicry of renal clear cell carcinoma. The Pax8, a transcription factor, is a special marker for almost all clear cell RCC. For this case metastastic ccRCC is the important differentiated diagnosis. But with a negative Pax8 combined with other negative epithelial markers such as AE1/ AE3, CAM5.2 and CD10, the ccRCC was excluded. But for another kind of rare renal tumors, Xp11 translocation RCC, could express melanocytic markers such as HMB45 and Melan A. Strong nuclear TFE3 expression is a sensitive and special marker for the diagnosis of Xp11 translocation RCC. In Folpe's report, about one third (5/17) PEComas expressed TFE3. As a result, the immunophenotypic overlap could be found between PEComa and Xp11 translocation RCC. In our case the tumor cells showed diffuse weak positive staining on the nucleus for TFE3. But this patient has neither a history of RCC, nor has renal area mass at ultrasound. So Xp11 translocation RCC also could be excluded too. The uterine PEComas should be differentiated from other uterine primary tumors, such as epithelioid leiomyoma and endometrial stromal sarcoma. These tumors and PEComas can share, at least in part, some histological appearances and immunophenotype, including expression of melanocytic and smooth muscle markers. Epithelioid leiomyoma shows focal or no immunoreactivity for HMB45, with positivity for SMA and Desmin. PEComas can be difficult to differentiate from clear cell and epithelioid smooth muscle tumors [9] but these entities are negative for HMB45 [10]. Endometrial stromal sarcoma can be ruled out because there was negative staining for CD10 and positive staining of HMB45 [11]. Schoolmeester [9] reported that HMB-45 in PEComas was the most sensitive marker (16/16 positive, 100%), followed by Melan-A (14/16 positive, 88%). Muscle related markers (desmin, SMA, h-caldesmon) were expressed in the spindle cell component by most PEComas. In this case there was just focal weak positive stain for SMA, we postulate that there are no spindle cell components in this case. The very low MIB-1 proliferative index doesn't lead to the diagnosis for amelanotic melanoma or clear cell sarcoma. Though the glandular pattern and intraendometrial growth is quite uncommon for uterine PEComa, after detailed morphological and immunohistochemical differentiation, the final diagnosis is most consistent of endometrial PEComa with pseudoglandular patter and polyp appearance. Herein we have reported a rare case and have described the morphological spectrum of PEComas.
Fig. 1. A. Ultrasound showed intra-uterine echo clusters and suggested are endometrial polyp or endometrial carcinoma (among four cursors). B. Grossly, protruding lesions on the surface of endometrium mimicking an endometrial polyp (→partial tumor).
used it to describe a pancreatic tumor composed of human melanoma black 45 (HMB-45)–positive clear epithelioid cells. The latest World Health Organization classification of tumors of female reproductive [2] organs defines PEComas of the uterus as mesenchymal tumors typically containing epithelioid cells with clear to eosinophilic, granular cytoplasm demonstrating melanocytic and smooth muscle differentiation by immunohistochemistry. Since the PEComa has no distinctive clinical symptoms or signs, the diagnosis depends on pathological examination. In our case, the tumor cells were predominantly composed of epithelioid cells with eosinophilic cytoplasm and partial cells have clear cytoplasm. To date, less than 80 cases of uterine PEComa have been reported in the literature [3]. And most
67
Human Pathology: Case Reports 13 (2018) 66–68
X. Wang et al.
Fig. 2. A. Under low magnification showed the tumor was totally located in endometrium (→) and underlying endometrium between muscularis and tumor was atrophic. (original magnification ×50). B. Histologic sections showed epithelioid cells arranged in glandular architecture(original magnification ×200). C. Intranuclear inclusion body was observed (→nuclear inclusion body, original magnification ×400). D and E. The tumor cells were positive for HMB45 and focal positive for SMA (original magnification ×400). F. Tumor cells showed very low MIB-1 index (original magnification ×400).
References
[6] J.L. Liu, Y.M. Lin, M.C. Lin, et al., Perivascular epithelioid cell tumor (PEComa) of the uterus with aggressive behavior at presentation, Hematol. Oncol. Stem Cell Ther. 2 (3) (2009) 426–430. [7] A.L. Folpe, T. Mentzel, H.A. Lehr, 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. 29 (12) (2005) 1558–1575. [8] F. Bonetti, G. Martignoni, C. Colato, et al., Abdominopelvic sarcoma of perivascular epithelioid cells: report of four cases in young women, one with tuberous sclerosis, Mod. Pathol. 14 (6) (2001) 563–568. [9] J.K. Schoolmeester, B.E. Howitt, M.S. Hirsch, et al., Perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: clinicopathologic and immunohistochemical characterization of 16 cases, Am. J. Surg. Pathol. 38 (2014) 176–188. [10] M. Zamecnik, M. Michal, HMB45+ hyalinized epithelioid tumor of the uterus is linked to epithelioid leiomyoma rather than to PEC-omas, Int. J. Surg. Pathol. 9 (2001) 341–343. [11] R. Vang, R.L. Kempson, Perivascular epithelioid cell tumor (‘PEComa’) of the uterus: a subset of HMB-45 positive epithelioid mesenchymal neoplasms with uncertain relationship to pure smooth muscle tumors, Am. J. Surg. Pathol. 26 (2002) 1–13.
[1] R.J. Grimer, P.C.W. Hogendoorn, D. Vanel, Neoplasms with perivascular epithelioid cell differentiation (PEComas), in: D.M. Fletcher Christopher, A. Bridge Julia, C.W. Hogendoorn Pancras, Mertens Fredrik (Eds.), Pathology and Genetics of Tumours of Soft Tissue and Bone, Series: WHO Classification of tumours, IARC Press, Lyon, 2013, pp. 230–231. [2] E. Oliva, M.L. Carcangiu, S.G. Carinelli, et al., Mesenchymal tumors, in: R.J. Kurman, M.L. Carcangiu, C.S. Herrington, R.H. Young (Eds.), WHO Classification of Tumours of Female Reproductive Organs, 4th ed., IARC, Lyon, France, 2014, pp. 146–147. [3] A.M. Acosta, B.P. Adley, Predicting the behavior of perivascular epithelioid cell tumors of the uterine corpus, Arch. Pathol. Lab. Med. 141 (2017) 463–469. [4] F. Bonetti, M. Pea, G. Martignoni, G. Zamboni, PEC and sugar, Am. J. Surg. Pathol. 16 (1992) 307–308. [5] G. Zamboni, M. Pea, G. Martignoni, et al., Clear cell “sugar” tumor of the pancreas: a novel member of the family of lesions characterized by the presence of perivascular epithelioid cells, Am. J. Surg. Pathol. 20 (1996) 722–730.
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