- Email: [email protected]
Mixed epithelial and stromal tumor of the kidney with endometrioid differentiation associated with pancreatic solid pseudopapillary tumor
Rev Esp Patol. 2013;46(3):172---176
Patología R E V I S TA
E S PA Ñ O L A
D E
www.elsevier.es/patologia
BRIEF REPORT
Mixed epithelial and stromal tumor of the kidney with endometrioid differentiation associated with pancreatic solid pseudopapillary tumor Vicente Sabater Marco Department of Pathology, Hospital General Universitario, Valencia, Spain Received 7 November 2012; accepted 1 December 2012 Available online 22 January 2013
KEYWORDS Endometrioid differentiation; Mixed tumor of the kidney; Adenofibroma
PALABRAS CLAVE Diferenciación endometrioide; Tumor mixto del ri˜ nón; Adenofibroma
Abstract Mixed epithelial and stromal tumor of the kidney (MESTK) is a benign cystic neoplasm. Pancreatic solid-pseudopapillary tumor (SPT) is a typically cystic carcinoma of low malignant potential. We describe a MESTK synchronous with a SPT in a female with an ovarian cystic corpus luteum. Glands showed endometrioid differentiation and the spindle cell stroma created complex leaflet-like structures similar to Müllerian adenofibroma. The SPT consisted of polygonal cells with a pseudopapillary pattern and a cystic area. Expression of estrogen and progesterone receptors in MESTK stromal cells and progesterone receptors in SPT provided a diagnostic clue, confirming the hormonal dependence in pathogenesis. Given that our MESTK is a polypoid tumor with endometrioid differentiation, the differential diagnosis with polypoid endometriosis is considered. © 2012 SEAP y SEC. Published by Elsevier España, S.L. All rights reserved.
Tumor mixto epitelial y estromal del ri˜ nón con diferenciación endometrioide asociado a un tumor sólido seudopapilar de páncreas Resumen El tumor mixto epitelial y estromal del ri˜ nón (MESTK) es una neoplasia quística benigna. El tumor sólido seudopapilar pancreático (SPT) es un carcinoma quístico de bajo potencial maligno. Este artículo describe un MESTK sincrónico con un SPT en una mujer con un cuerpo lúteo quístico ovárico. Las glándulas mostraban diferenciación endometrioide y el estroma fusocelular creaba complejas estructuras foliáceas similares a un adenofibroma mulleriano. El SPT estaba formado por células poligonales con patrón seudopapilar y un área quística. La expresión de receptores de estrógenos y progesterona en las células estromales del MESTK y de receptores de progesterona en el SPT es clave para su diagnóstico, confirmando una dependencia hormonal en la patogénesis. Dado que nuestro MESTK es polipoide y tiene diferenciación endometrioide, discutimos el diagnóstico diferencial con la endometriosis polipoide. © 2012 SEAP y SEC. Publicado por Elsevier España, S.L. Todos los derechos reservados.
E-mail address: [email protected] 1699-8855/$ – see front matter © 2012 SEAP y SEC. Published by Elsevier España, S.L. All rights reserved. http://dx.doi.org/10.1016/j.patol.2012.12.001
Mixed epithelial and stromal tumor of the kidney
173
Introduction Mixed epithelial and stromal tumor of the kidney (MESTK) is a benign cystic neoplasm composed of a mixture of epithelial and stromal elements. These tumors are characterized by the expression of estrogen and progesterone receptors in the nucleus of stromal cells, thus resembling a so-called ‘‘ovarian-like’’ stroma.1 Solid-pseudopapillary tumor of the pancreas (SPT) is a typically cystic carcinoma of low malignant potential generally occurring in young women. In these tumors, the neoplastic cells consistently express progesterone receptors.2 This article describes a synchronous MESTK with a SPT in a female with an ovarian cystic corpus luteum. This finding along with expression of estrogens and progesterone receptors in MESTK stromal cells and also progesterone receptors in SPT tumor cells confirms the hormonal dependence in the pathogenesis of both tumors. Moreover, endometrioid differentiation and Müllerian adenofibroma in MESTK are exceptional morphologic findings and it raises the differential diagnosis with polypoid endometriosis.
Case history A 44-year-old woman, with a past medical history of hypothyroidism in l-tyrosine treatment and surgery by cysts in the right ovary, experienced an episode of increasing leftsided flank pain, nausea and vomiting. Physical examination showed a palpable flank mass. She was being controlled since 2007 by a cystic mass in the left kidney and a solidcystic tumor in the pancreas. A contrast-enhanced magnetic resonance of the abdomen and pelvis revealed a multilocular cystic mass with minimal enhancement in the upper pole of the left kidney (Fig. 1A) and also, a solid and cystic lesion with a nonenhancing cystic portion in pancreatic body. She underwent distal pancreatectomy, left nephrectomy and oophorectomy. Twenty months later, the patient is alive and well.
Pathologic features The 8-cm well-circumscribed renal tumor consisted of multiple cysts of different sizes with thickened septa separating the cysts. The inner surface of the cysts was smooth and its contents were hemorrhagic (Fig. 1B). Grossly, the pancreatic body showed a multinodular tumor with solid and cystic areas measuring 4.5 cm. The cystic area was surrounded by a fibrous capsule and contained yellowish necrotic and hemorrhagic material. The left ovary showed a 3-cm cyst attached to a corpus luteum. Histopathologically, the kidney tumor bulged into the renal pelvis; it was covered by urothelium and showed a biphasic proliferation of epithelial and stromal cells (Fig. 2A). The epithelial component was composed of branched and cystic glands lined by flat to hobnail eosinophilic epithelium that sometimes formed small papillary tufts with cilia (Fig. 2B). Stromal component consisted of spindle cells with plump nuclei and scant cytoplasm. The spindle cells were condensed around the glandular component and in many foci there was hemorrhage. Vascularity was prominent and abundant thick-walled and dilated blood
Figure 1 (A) Contrast-enhanced magnetic resonance image shows a solid and cystic mass with heterogeneous enhancement of the left kidney mass. (B) Grossly, mixed epithelial and stromal tumor of the kidney appears as a well-circumscribed and strikingly cystic tumor.
vessels were observed in the stroma. In addition, there were leaflet-like structures composed of glandular and stromal elements of a different appearance; the glands were lined by endometrioid epithelium and the stroma was more cellular resembling endometrial stroma, then adopting the appearance of a Müllerian adenofibroma (Fig. 3A). Epithelial cells showed cytoplasmic staining for cytokeratin CAM 5.2, beta-catenin, E-cadherin, CD10, Bcl-2 and vimentin whereas the stromal cells showed cytoplasmic staining for Bcl-2, CD10, vimentin, desmin, smooth muscle actin (SMA) and CD34. Moreover, the stromal cell nucleus expressed estrogen and progesterone receptors (Fig. 3B). The blood capillaries were reactive for CD34 and betacatenin. S-100 protein, HMB-45, alpha-inhibin, calretinin and WT1 were negative. The pancreatic tumor was composed of polygonal cell sheets with acidophilic cytoplasm containing hyaline globules. The nuclei were round to oval and showed grooves. In other areas, the tumor cells were arranged with pseudopapillary pattern. The cystic area was surrounded by a fibrous capsule and contained coagulative necrosis, fibrin and hemorrhage. The tumor cells showed cytoplasmic staining for E-cadherin, CD10, vimentin, alpha-1-antitrypsin, CD56,
174
Figure 2 (A) Panoramic view showing the kidney tumor covered by urothelium and composed of elongated and cystic glands in a spindle cell stroma. (B) Gland lined with distinct hobnail or ciliated epithelium.
neuron specific enolase (NSE), and synaptophysin. In addition, the tumor cells showed nuclear and cytoplasmic staining with beta-catenin and nuclear staining with progesterone receptors. Cytokeratin CAM 5.2, cytokeratin 7, CD117, chromogranin and estrogen receptors were negative. The ovary showed a cystic corpus luteum composed of several layer of luteinized granulosa cells overlying theca cells.
Discussion MESTK has been described in association with idiopathic thrombocytopenic purpura3 and in patients affected by hyperparathyroidism jaw tumor syndrome.4 SPT have been described in association with familial adenomatous polyposis,5 hairy cell leukemia and papillary carcinoma of the thyroid.6 We first have reported the synchronous association of a MESTK with a SPT in a female with a cystic corpus luteum in the ovary. On microscopic examination, MESTK is defined as a tumor composed of large cysts, microcysts, glands lined by columnar, cuboidal or flattened epithelium and a spindle stromal component. Epithelial component may show endometrioid, endocervical or intestinal differentiation7,8 whereas the stromal cells
V. Sabater Marco
Figure 3 (A) Branched glands are associated with a hemorrhagic and dense spindle cell estroma creating leaflet-like structures similar to Müllerian adenofibroma. (B) In the kidney tumor, the stromal cells nuclei are strongly reactive for progesterone receptor.
may be either of luteinized ovarian-like type1 or smooth muscle type mimicking a leiomyoma.9 Endometrioid differentiation in MESTK is an unusual morphologic feature but well documented in the literature. To our knowledge only one case of Müllerian adenofibroma and adenosarcoma has been described in MESTK.7 We describe the second MESTK with endometrioid differentiation showing an architecture that closely resembled to Müllerian adenofibroma. From the immunohistochemical point of view, MESTK epithelial component expresses cytokeratin, beta-catenin, E-cadherin, Bcl-2 and vimentin while the stromal component that resembles smooth muscle expresses SMA and desmin. Strong focal brush border staining for CD10 in the epithelial component and also calretinin and alpha-inhibin expression in the stromal cells have been described.10 However, in our case, stromal cells do not express calretinin or alpha-inhibin probably because the stromal cells were of endometrial type and no ovarian-like type. Solid-pseudopapillary tumor of the pancreas (SPT) is a well-circumscribed solid neoplasia with cystic areas containing blood, necrotic debris and clusters of foamy macrophages. Histopathologically, it consists of bland epithelioid cell sheets that are arranged in a
Mixed epithelial and stromal tumor of the kidney pseudopapillary pattern. The tumor cells contain eosinophilic granules rich in alpha-1-antitrypsin and the nuclei are typically grooved. SPT expresses nonspecific markers such as vimentin, CD56, alpha-1-antitrypsin, neuron specific enolase (ENS) and synapthophysin; however, chromogranin is typically negative.11 Therefore, to confirm a SPT diagnosis the tumor cells must express other markers such as CD10, E-cadherin and beta-catenin (nuclear staining).2 Both tumors MESTK and SPT occur almost exclusively in women and also MESTK is often associated with various hyperestrogenism conditions.7,8,10,11 In addition, expression of estrogen and progesterone receptors in MESTK stromal cells9 and progesterone receptors in SPT tumor cells2 is a clue to its diagnosis. These findings not only suggest a common hormonal pathogenesis but the possibility of new therapeutic strategies in both tumors. In the current case, the presence of a cystic corpus luteum in the ovary may explain the role of steroid in the development of both tumors as well as some of its microscopic features. Cystic corpus luteum indicates the end of the luteal phase, which is characterized by secretion of estrogen and especially progesterone. In MESTK, hemorrhagic foci in endometrial-type stroma may be the result of progesterone stimulation. In SPT, coagulative necrosis and hemorrhage may represent a degenerative process due to hormonal stimulation or alteration in blood supply. MESTK is a relatively rare and distinct neoplasm that must be distinguished from other renal neoplasms. The differential diagnosis of MESTK is usually established with cystic nephroma and congenital mesoblastic nephroma. Currently, MESTK and cystic nephroma represent opposite ends of the morphologic spectrum of the same disease.9 Congenital mesoblastic nephroma is generally a solid mass composed of uniform spindle stromal cells with rare entrapped renal tubules and an infiltrative pattern at its interface with renal parenchyma. In addition, it is associated with the fusion gene ETV6-NTRK3. However, when a MESTK shows polypoid appearance and also endometrioid differentiation and Müllerian adenofibroma areas as in our case, we must include the polypoid endometriosis in the differential diagnosis. Polypoid endometriosis is a rare manifestation of endometriosis that occurs in patients with typical endometriosis in different organs and sometimes mimicking a malignant tumor. In our opinion, MESTK with endometrioid differentiation and polypoid endometriosis share some clinicopathologic characteristics. Both entities usually occur in perimenopausal women with hormonal factors in its pathogenesis. Grossly, MESTK is a tumor confined to the renal parenchyma but often bulged into the renal pelvis exhibiting a polypoid appearance, so it has been called cystic hamartoma of renal pelvis.12 Polypoid endometriosis is defined as exophytic or polypoid, tumor-like mass that is projected from a serosal or mucosal surface or from the lining of an endometriotic cyst.13 Histopathologically, MESTK and polypoid endometriosis consist of glands and stroma. The glands may exhibit a cystic hyperplasia pattern or tubal, mucinous, squamous and papillary metaplasia. The stroma may contain hemorrhage, foamy and pigmented histiocytes, fibrosis, elastosis, smooth muscle metaplasia, arterial wall thickening and decidual or myxoid areas. Immunohistochemically, in both lesions, the stromal cells
175 express vimentin, CD10,14 estrogen and progesterone receptors, SMA and desmin. Moreover, in both MESTK and polypoid endometriosis has been described endocervical and intestinal borderline mucinous tumors and leiomyomatosis.13,15 Finally, Müllerian adenofibroma is one of the main differential diagnoses of polypoid endometriosis. Considering these facts the differential diagnosis between MESTK with endometrioid differentiation and polypoid endometriosis is not easy. In this context, the clinicopathological correlation is important and useful and helpful to reach the correct diagnosis. In our case, no history of endometriosis in the patient and the absence of immunostaining for estrogen and progesterone receptors in the glandular epithelial component are two aspects that distinguish between MESTK with endometrioid differentiation and polypoid endometriosis. In summary, we first reported the synchronous association of MESTK with endometrioid differentiation and Müllerian adenofibroma with a SPT in a patient with a cystic corpus luteum in the ovary. The steroids action over hormone receptors of the MESTK and SPT tumor cells suggest a common pathogenesis. We also discuss the differential diagnosis of this MESTK with polypoid endometriosis.
Ethical disclosures Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this investigation. Confidentiality of data. The authors declare that no patient data appear in this article. Right to privacy and informed consent. The authors declare that no patient data appear in this article.
Conflict of interest The authors have no conflict of interest to declare.
Acknowledgment We thank Vicente Javier Sabater Abad for reviewing the manuscript.
References 1. Buritica C, Serrano M, Zuluaga A, Arrabal M, Regauer S, Nogales FF. Mixed epithelial and stromal tumour of the kidney with luteinised ovarian stroma. J Clin Pathol. 2007;60:98---100. 2. Serra S, Chetty R. Revision 2: an immunohistochemical approach and evaluation of solid pseudopapillary tumour of the pancreas. J Clin Pathol. 2008;61:1153---9. 3. Park HS, Kim SH, Kim SH, Paik JH, Hwang SI, Jung SI, et al. Benign mixed epithelial and stromal tumor of the kidney. Imaging findings. J Comput Assist Tomogr. 2005;29:786---9. 4. Teh BT, Farnebo F, Kristoffersson U, Sundelin B, Cardinal J, Axelson R, et al. Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21---q32 and loss of the
176
5.
6.
7.
8.
9.
10.
V. Sabater Marco wild type allele in renal hamartomas. J Clin Endocrinol Metab. 1996;81:4204---11. Ruo L, Coit DG, Brennan MF, Guillem JG. Long-term follow-up of patients with familial adenomatous polyposis undergoing pancreaticoduodenal surgery. J Gastrointest Surg. 2002;6:671---5. Acebo E, Rodilla IG, Torio B, Hernando M, García de Polavieja M, Morales D, et al. Papillary cystic tumor of the páncreas coexisting with hairy cell leukaemia. Pathology. 2000;32:216---9. Michal M, Hes O, Bisceglia M, Simpson RHW, Spagnolo DV, Parma A, et al. Mixed epithelial and stromal tumors of the kidney. A report of 22 cases. Virchows Arch. 2004;445:359---67. Yang Y, Ondrey H, Zhang L, Lu J, Lu M, Wang H, et al. Mixed epithelial and stromal tumor of the kidney with cervical and intestinal differentiation. Virchows Arch. 2005;447:669---71. Montironi R, Mazzucchelli R, Lopez-Beltran A, Martignoni G, Cheng L, Montorsi F, et al. Cystic nephroma and mixed epithelial and stromal tumour of the kidney: opposite ends of the spectrum of the same entity? Eur Urol. 2008;54:1237---46. Turbiner J, Amin MB, Humphrey PA, Srigley JR, De Leval L, Radhakrishnan A, et al. Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathologic
11.
12.
13.
14.
15.
análisis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term. Am J Surg Pathol. 2007;31:489---500. Liu X, Rauch TM, Siegal GP, Jhala N. Solid-pseudopapillary neoplasma of the páncreas: three cases with a literature review. Appl Immunohistochem Mol Morphol. 2006;14:445---53. Mensch LS, Trainer TD, Plante MK. Cystic hamartoma of the renal pelvis: a rare pathologic entity. Mod Pathol. 1999;12: 417---21. Parker RL, Dadmanesh F, Young RH, Clement PB. Polypoid endometriosis. A clinicopathologic analysis of 24 cases and a review of the literature. Am J Surg Pathol Marc. 2004;28: 285---97. Onda T, Ban S, Shimizu M. CD10 is useful in demonstrating endometrial stroma at ectopic sites and in confirming a diagnosis of endometriosis. J Clin Pathol. 2003;56:79. Chu PG, Lau SK, Weiss LM, Jiang Z. Intestinal type of mucinous borderline tumor arising from mixed epithelial and stromal tumor of kidney. Virchows Arch. 2009;455:389---94.
Patología R E V I S TA
E S PA Ñ O L A
D E
www.elsevier.es/patologia
BRIEF REPORT
Mixed epithelial and stromal tumor of the kidney with endometrioid differentiation associated with pancreatic solid pseudopapillary tumor Vicente Sabater Marco Department of Pathology, Hospital General Universitario, Valencia, Spain Received 7 November 2012; accepted 1 December 2012 Available online 22 January 2013
KEYWORDS Endometrioid differentiation; Mixed tumor of the kidney; Adenofibroma
PALABRAS CLAVE Diferenciación endometrioide; Tumor mixto del ri˜ nón; Adenofibroma
Abstract Mixed epithelial and stromal tumor of the kidney (MESTK) is a benign cystic neoplasm. Pancreatic solid-pseudopapillary tumor (SPT) is a typically cystic carcinoma of low malignant potential. We describe a MESTK synchronous with a SPT in a female with an ovarian cystic corpus luteum. Glands showed endometrioid differentiation and the spindle cell stroma created complex leaflet-like structures similar to Müllerian adenofibroma. The SPT consisted of polygonal cells with a pseudopapillary pattern and a cystic area. Expression of estrogen and progesterone receptors in MESTK stromal cells and progesterone receptors in SPT provided a diagnostic clue, confirming the hormonal dependence in pathogenesis. Given that our MESTK is a polypoid tumor with endometrioid differentiation, the differential diagnosis with polypoid endometriosis is considered. © 2012 SEAP y SEC. Published by Elsevier España, S.L. All rights reserved.
Tumor mixto epitelial y estromal del ri˜ nón con diferenciación endometrioide asociado a un tumor sólido seudopapilar de páncreas Resumen El tumor mixto epitelial y estromal del ri˜ nón (MESTK) es una neoplasia quística benigna. El tumor sólido seudopapilar pancreático (SPT) es un carcinoma quístico de bajo potencial maligno. Este artículo describe un MESTK sincrónico con un SPT en una mujer con un cuerpo lúteo quístico ovárico. Las glándulas mostraban diferenciación endometrioide y el estroma fusocelular creaba complejas estructuras foliáceas similares a un adenofibroma mulleriano. El SPT estaba formado por células poligonales con patrón seudopapilar y un área quística. La expresión de receptores de estrógenos y progesterona en las células estromales del MESTK y de receptores de progesterona en el SPT es clave para su diagnóstico, confirmando una dependencia hormonal en la patogénesis. Dado que nuestro MESTK es polipoide y tiene diferenciación endometrioide, discutimos el diagnóstico diferencial con la endometriosis polipoide. © 2012 SEAP y SEC. Publicado por Elsevier España, S.L. Todos los derechos reservados.
E-mail address: [email protected] 1699-8855/$ – see front matter © 2012 SEAP y SEC. Published by Elsevier España, S.L. All rights reserved. http://dx.doi.org/10.1016/j.patol.2012.12.001
Mixed epithelial and stromal tumor of the kidney
173
Introduction Mixed epithelial and stromal tumor of the kidney (MESTK) is a benign cystic neoplasm composed of a mixture of epithelial and stromal elements. These tumors are characterized by the expression of estrogen and progesterone receptors in the nucleus of stromal cells, thus resembling a so-called ‘‘ovarian-like’’ stroma.1 Solid-pseudopapillary tumor of the pancreas (SPT) is a typically cystic carcinoma of low malignant potential generally occurring in young women. In these tumors, the neoplastic cells consistently express progesterone receptors.2 This article describes a synchronous MESTK with a SPT in a female with an ovarian cystic corpus luteum. This finding along with expression of estrogens and progesterone receptors in MESTK stromal cells and also progesterone receptors in SPT tumor cells confirms the hormonal dependence in the pathogenesis of both tumors. Moreover, endometrioid differentiation and Müllerian adenofibroma in MESTK are exceptional morphologic findings and it raises the differential diagnosis with polypoid endometriosis.
Case history A 44-year-old woman, with a past medical history of hypothyroidism in l-tyrosine treatment and surgery by cysts in the right ovary, experienced an episode of increasing leftsided flank pain, nausea and vomiting. Physical examination showed a palpable flank mass. She was being controlled since 2007 by a cystic mass in the left kidney and a solidcystic tumor in the pancreas. A contrast-enhanced magnetic resonance of the abdomen and pelvis revealed a multilocular cystic mass with minimal enhancement in the upper pole of the left kidney (Fig. 1A) and also, a solid and cystic lesion with a nonenhancing cystic portion in pancreatic body. She underwent distal pancreatectomy, left nephrectomy and oophorectomy. Twenty months later, the patient is alive and well.
Pathologic features The 8-cm well-circumscribed renal tumor consisted of multiple cysts of different sizes with thickened septa separating the cysts. The inner surface of the cysts was smooth and its contents were hemorrhagic (Fig. 1B). Grossly, the pancreatic body showed a multinodular tumor with solid and cystic areas measuring 4.5 cm. The cystic area was surrounded by a fibrous capsule and contained yellowish necrotic and hemorrhagic material. The left ovary showed a 3-cm cyst attached to a corpus luteum. Histopathologically, the kidney tumor bulged into the renal pelvis; it was covered by urothelium and showed a biphasic proliferation of epithelial and stromal cells (Fig. 2A). The epithelial component was composed of branched and cystic glands lined by flat to hobnail eosinophilic epithelium that sometimes formed small papillary tufts with cilia (Fig. 2B). Stromal component consisted of spindle cells with plump nuclei and scant cytoplasm. The spindle cells were condensed around the glandular component and in many foci there was hemorrhage. Vascularity was prominent and abundant thick-walled and dilated blood
Figure 1 (A) Contrast-enhanced magnetic resonance image shows a solid and cystic mass with heterogeneous enhancement of the left kidney mass. (B) Grossly, mixed epithelial and stromal tumor of the kidney appears as a well-circumscribed and strikingly cystic tumor.
vessels were observed in the stroma. In addition, there were leaflet-like structures composed of glandular and stromal elements of a different appearance; the glands were lined by endometrioid epithelium and the stroma was more cellular resembling endometrial stroma, then adopting the appearance of a Müllerian adenofibroma (Fig. 3A). Epithelial cells showed cytoplasmic staining for cytokeratin CAM 5.2, beta-catenin, E-cadherin, CD10, Bcl-2 and vimentin whereas the stromal cells showed cytoplasmic staining for Bcl-2, CD10, vimentin, desmin, smooth muscle actin (SMA) and CD34. Moreover, the stromal cell nucleus expressed estrogen and progesterone receptors (Fig. 3B). The blood capillaries were reactive for CD34 and betacatenin. S-100 protein, HMB-45, alpha-inhibin, calretinin and WT1 were negative. The pancreatic tumor was composed of polygonal cell sheets with acidophilic cytoplasm containing hyaline globules. The nuclei were round to oval and showed grooves. In other areas, the tumor cells were arranged with pseudopapillary pattern. The cystic area was surrounded by a fibrous capsule and contained coagulative necrosis, fibrin and hemorrhage. The tumor cells showed cytoplasmic staining for E-cadherin, CD10, vimentin, alpha-1-antitrypsin, CD56,
174
Figure 2 (A) Panoramic view showing the kidney tumor covered by urothelium and composed of elongated and cystic glands in a spindle cell stroma. (B) Gland lined with distinct hobnail or ciliated epithelium.
neuron specific enolase (NSE), and synaptophysin. In addition, the tumor cells showed nuclear and cytoplasmic staining with beta-catenin and nuclear staining with progesterone receptors. Cytokeratin CAM 5.2, cytokeratin 7, CD117, chromogranin and estrogen receptors were negative. The ovary showed a cystic corpus luteum composed of several layer of luteinized granulosa cells overlying theca cells.
Discussion MESTK has been described in association with idiopathic thrombocytopenic purpura3 and in patients affected by hyperparathyroidism jaw tumor syndrome.4 SPT have been described in association with familial adenomatous polyposis,5 hairy cell leukemia and papillary carcinoma of the thyroid.6 We first have reported the synchronous association of a MESTK with a SPT in a female with a cystic corpus luteum in the ovary. On microscopic examination, MESTK is defined as a tumor composed of large cysts, microcysts, glands lined by columnar, cuboidal or flattened epithelium and a spindle stromal component. Epithelial component may show endometrioid, endocervical or intestinal differentiation7,8 whereas the stromal cells
V. Sabater Marco
Figure 3 (A) Branched glands are associated with a hemorrhagic and dense spindle cell estroma creating leaflet-like structures similar to Müllerian adenofibroma. (B) In the kidney tumor, the stromal cells nuclei are strongly reactive for progesterone receptor.
may be either of luteinized ovarian-like type1 or smooth muscle type mimicking a leiomyoma.9 Endometrioid differentiation in MESTK is an unusual morphologic feature but well documented in the literature. To our knowledge only one case of Müllerian adenofibroma and adenosarcoma has been described in MESTK.7 We describe the second MESTK with endometrioid differentiation showing an architecture that closely resembled to Müllerian adenofibroma. From the immunohistochemical point of view, MESTK epithelial component expresses cytokeratin, beta-catenin, E-cadherin, Bcl-2 and vimentin while the stromal component that resembles smooth muscle expresses SMA and desmin. Strong focal brush border staining for CD10 in the epithelial component and also calretinin and alpha-inhibin expression in the stromal cells have been described.10 However, in our case, stromal cells do not express calretinin or alpha-inhibin probably because the stromal cells were of endometrial type and no ovarian-like type. Solid-pseudopapillary tumor of the pancreas (SPT) is a well-circumscribed solid neoplasia with cystic areas containing blood, necrotic debris and clusters of foamy macrophages. Histopathologically, it consists of bland epithelioid cell sheets that are arranged in a
Mixed epithelial and stromal tumor of the kidney pseudopapillary pattern. The tumor cells contain eosinophilic granules rich in alpha-1-antitrypsin and the nuclei are typically grooved. SPT expresses nonspecific markers such as vimentin, CD56, alpha-1-antitrypsin, neuron specific enolase (ENS) and synapthophysin; however, chromogranin is typically negative.11 Therefore, to confirm a SPT diagnosis the tumor cells must express other markers such as CD10, E-cadherin and beta-catenin (nuclear staining).2 Both tumors MESTK and SPT occur almost exclusively in women and also MESTK is often associated with various hyperestrogenism conditions.7,8,10,11 In addition, expression of estrogen and progesterone receptors in MESTK stromal cells9 and progesterone receptors in SPT tumor cells2 is a clue to its diagnosis. These findings not only suggest a common hormonal pathogenesis but the possibility of new therapeutic strategies in both tumors. In the current case, the presence of a cystic corpus luteum in the ovary may explain the role of steroid in the development of both tumors as well as some of its microscopic features. Cystic corpus luteum indicates the end of the luteal phase, which is characterized by secretion of estrogen and especially progesterone. In MESTK, hemorrhagic foci in endometrial-type stroma may be the result of progesterone stimulation. In SPT, coagulative necrosis and hemorrhage may represent a degenerative process due to hormonal stimulation or alteration in blood supply. MESTK is a relatively rare and distinct neoplasm that must be distinguished from other renal neoplasms. The differential diagnosis of MESTK is usually established with cystic nephroma and congenital mesoblastic nephroma. Currently, MESTK and cystic nephroma represent opposite ends of the morphologic spectrum of the same disease.9 Congenital mesoblastic nephroma is generally a solid mass composed of uniform spindle stromal cells with rare entrapped renal tubules and an infiltrative pattern at its interface with renal parenchyma. In addition, it is associated with the fusion gene ETV6-NTRK3. However, when a MESTK shows polypoid appearance and also endometrioid differentiation and Müllerian adenofibroma areas as in our case, we must include the polypoid endometriosis in the differential diagnosis. Polypoid endometriosis is a rare manifestation of endometriosis that occurs in patients with typical endometriosis in different organs and sometimes mimicking a malignant tumor. In our opinion, MESTK with endometrioid differentiation and polypoid endometriosis share some clinicopathologic characteristics. Both entities usually occur in perimenopausal women with hormonal factors in its pathogenesis. Grossly, MESTK is a tumor confined to the renal parenchyma but often bulged into the renal pelvis exhibiting a polypoid appearance, so it has been called cystic hamartoma of renal pelvis.12 Polypoid endometriosis is defined as exophytic or polypoid, tumor-like mass that is projected from a serosal or mucosal surface or from the lining of an endometriotic cyst.13 Histopathologically, MESTK and polypoid endometriosis consist of glands and stroma. The glands may exhibit a cystic hyperplasia pattern or tubal, mucinous, squamous and papillary metaplasia. The stroma may contain hemorrhage, foamy and pigmented histiocytes, fibrosis, elastosis, smooth muscle metaplasia, arterial wall thickening and decidual or myxoid areas. Immunohistochemically, in both lesions, the stromal cells
175 express vimentin, CD10,14 estrogen and progesterone receptors, SMA and desmin. Moreover, in both MESTK and polypoid endometriosis has been described endocervical and intestinal borderline mucinous tumors and leiomyomatosis.13,15 Finally, Müllerian adenofibroma is one of the main differential diagnoses of polypoid endometriosis. Considering these facts the differential diagnosis between MESTK with endometrioid differentiation and polypoid endometriosis is not easy. In this context, the clinicopathological correlation is important and useful and helpful to reach the correct diagnosis. In our case, no history of endometriosis in the patient and the absence of immunostaining for estrogen and progesterone receptors in the glandular epithelial component are two aspects that distinguish between MESTK with endometrioid differentiation and polypoid endometriosis. In summary, we first reported the synchronous association of MESTK with endometrioid differentiation and Müllerian adenofibroma with a SPT in a patient with a cystic corpus luteum in the ovary. The steroids action over hormone receptors of the MESTK and SPT tumor cells suggest a common pathogenesis. We also discuss the differential diagnosis of this MESTK with polypoid endometriosis.
Ethical disclosures Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this investigation. Confidentiality of data. The authors declare that no patient data appear in this article. Right to privacy and informed consent. The authors declare that no patient data appear in this article.
Conflict of interest The authors have no conflict of interest to declare.
Acknowledgment We thank Vicente Javier Sabater Abad for reviewing the manuscript.
References 1. Buritica C, Serrano M, Zuluaga A, Arrabal M, Regauer S, Nogales FF. Mixed epithelial and stromal tumour of the kidney with luteinised ovarian stroma. J Clin Pathol. 2007;60:98---100. 2. Serra S, Chetty R. Revision 2: an immunohistochemical approach and evaluation of solid pseudopapillary tumour of the pancreas. J Clin Pathol. 2008;61:1153---9. 3. Park HS, Kim SH, Kim SH, Paik JH, Hwang SI, Jung SI, et al. Benign mixed epithelial and stromal tumor of the kidney. Imaging findings. J Comput Assist Tomogr. 2005;29:786---9. 4. Teh BT, Farnebo F, Kristoffersson U, Sundelin B, Cardinal J, Axelson R, et al. Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21---q32 and loss of the
176
5.
6.
7.
8.
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