Pathology – Research and Practice 210 (2014) 186–188
Contents lists available at ScienceDirect
Pathology – Research and Practice journal homepage: www.elsevier.com/locate/prp
Teaching Case
A huge malignant perivascular epithelioid cell tumor (PEComa) of the uterine cervix and vagina Valentina Natella a , Francesco Merolla a , Pierluigi Giampaolino b , Giuseppe Bifulco b , Pier Paolo Mainenti c , Luigi Insabato a,∗ a
Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy Department of Obstetrics and Gynecology, University of Naples Federico II, 80131 Naples, Italy c IBB-CNR, 80131 Naples, Italy b
a r t i c l e
i n f o
Article history: Received 16 April 2013 Received in revised form 2 August 2013 Accepted 15 October 2013 Keywords: PEComa Myomelanocytic tumor Uterine tumor Malignant behavior
a b s t r a c t Perivascular epithelioid cell tumors (PEComas) are a family of rare mesenchymal neoplasms, including angiomyolipoma, clear-cell “sugar” tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear-cell tumors at various other anatomic sites. These tumors are characterized by a proliferation of epithelioid cells with clear to eosinophilic cytoplasm, perivascular distribution, and coexpression of myogenic and melanocytic markers. PEComas show a female predominance, occur with some frequency in the gynecological tract, and have an unpredictable biological behavior. We report a case of a huge malignant PEComa arising from the uterine cervix and vagina. To the best of our knowledge, only 6 cases of PEComa in the cervix and 2 cases in the vagina have been reported in the literature. © 2013 Elsevier GmbH. All rights reserved.
Introduction The World Health Organization defines PEComas as “mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells” [1]. Members of the PEComa family are angiomyolipoma, clear-cell “sugar” tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear-cell tumors of other anatomical sites [2]. Yet, some authors consider “PEComa” an ambiguous term because there is no consensus on whether it should be referred only to purely epithelioid tumors or even to lesions as angiomyolipoma or lymphangioleiomyomatosis as well. Martignoni et al. believe that all these latter tumors are composed of PEC (perivascular epithelioid cells) at different stages of modulation and belong to the same family of neoplasms. Nevertheless, these authors stated that some of these neoplasms should be still indicated with their former names (i.e. AML, lymphangioleiomyomatosis) in order to simplify the communication between clinicians and pathologists [3].
∗ Corresponding author. Tel.: +39 0817463442. E-mail address: [email protected] (L. Insabato). 0344-0338/$ – see front matter © 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.prp.2013.10.003
These tumors generally occur in middle-aged women (median age, 38 years) and show a striking female predominance with an overall female-to-male ratio of 7:1 [4]. PEComas have been described in a great variety of anatomic locations and often occur in the gynecological tract, particularly in the uterus [5]. In this site, most of these tumors are benign or of uncertain malignant potential although rare malignant PEComas have been reported [6]. Here, we report a case of a huge malignant PEComa arising from the cervix and vagina, occurring in a 52-year-old woman.
Case presentation A 52-year-old, 3 para, woman presented for a second opinion because of a large mass of the uterine cervix. A prior biopsy had been performed in an outside hospital, with a diagnosis of PEComa. The paraffin block of the tissue from the previous biopsy was sent to the laboratory of Anatomic Pathology, and on the basis of the morphological and immunohistochemical profile, the diagnosis of PEComa was confirmed. The patient complained of acute pelvic pain and episodes of acute cystitis. Clinical examination revealed a large mass in her vaginal area. Serum CA-125 and CA 19-9 levels were within the normal limits. Transvaginal ultrasound showed a very vascularized cervical
V. Natella et al. / Pathology – Research and Practice 210 (2014) 186–188
187
Fig. 1. Fused F18FDG-PET/CT sagittal (a) and coronal (b) images showed a huge cervical and vaginal mass (red arrow) with high level tracer uptake (SUVmax 15). The mass dislocates behind the rectum (brown arrow), anterior the bladder (yellow arrow) and above the uterus (blue arrow) and causes bilateral hydronephrosis (green arrow). Ureteral stents were present. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
mass (12 cm × 11 cm). The patient underwent F18-FDG PET/CT to complete the local staging and to exclude distant metastases. The radiological images (Fig. 1) showed a huge cervical and vaginal mass with high level tracer uptake (SUVmax 15). The mass was dislocated behind the rectum, anterior the bladder, and above the uterus and caused bilateral hydronephrosis. The patient received 28 cycles of adjuvant radiotherapy, which was completely ineffective. She underwent a radical pelvectomy front and rear with removal of the uterus, vagina, bladder and anal canal; a neobladder and a colorectal anastomosis were performed. Grossly, a well circumscribed 12 cm × 11 cm mass was found, involving the cervix, the upper third of vagina, and compressing the bladder. Moreover, the mass partially occupied the pouch of Douglas, compressing the rectum. On cross section, the tumor showed a tan/yellow multinodular feature, with hemorrhagic changes. Histologically, the tumor was composed of large polygonal cells exhibiting focal hemorrhage and necrosis. Large, bizarre nuclei, cytoplasmic nuclear inclusions, and binucleation were occasionally found. Multifocal vascular invasion was seen. Downright, the neoplastic cells showed a definitely clear cytoplasm. A dense mixed inflammatory infiltrate and extensive hemorrhagic necrosis with focal microcalcifications were observed; mitotic activity was low (5 cm, infiltrative growth pattern, high nuclear grade, necrosis and mitotic activity >1/50 HPF with aggressive behavior
188
V. Natella et al. / Pathology – Research and Practice 210 (2014) 186–188
Fig. 2. (A) Lesion made of large epithelioid cells with large clear cytoplasm [hematoxylin-and-eosin stain (H&E), 106×]. (B) Detail of cells with large, bizarre nuclei, cytoplasmic nuclear inclusions, and binucleation (H&E, 400×, inset 630×). (C) Strong positive immunostaining of the tumor cells for HMB45 (200×). (D) Focal positive immunostaining for caldesmon (106×).
of PEComas [4]. The present case was considered to be morphologically malignant, based on its huge size (12 cm), high nuclear grade, high cellularity, moderate necrosis, and vascular invasion, however, with low mitotic rate (
Contents lists available at ScienceDirect
Pathology – Research and Practice journal homepage: www.elsevier.com/locate/prp
Teaching Case
A huge malignant perivascular epithelioid cell tumor (PEComa) of the uterine cervix and vagina Valentina Natella a , Francesco Merolla a , Pierluigi Giampaolino b , Giuseppe Bifulco b , Pier Paolo Mainenti c , Luigi Insabato a,∗ a
Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy Department of Obstetrics and Gynecology, University of Naples Federico II, 80131 Naples, Italy c IBB-CNR, 80131 Naples, Italy b
a r t i c l e
i n f o
Article history: Received 16 April 2013 Received in revised form 2 August 2013 Accepted 15 October 2013 Keywords: PEComa Myomelanocytic tumor Uterine tumor Malignant behavior
a b s t r a c t Perivascular epithelioid cell tumors (PEComas) are a family of rare mesenchymal neoplasms, including angiomyolipoma, clear-cell “sugar” tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear-cell tumors at various other anatomic sites. These tumors are characterized by a proliferation of epithelioid cells with clear to eosinophilic cytoplasm, perivascular distribution, and coexpression of myogenic and melanocytic markers. PEComas show a female predominance, occur with some frequency in the gynecological tract, and have an unpredictable biological behavior. We report a case of a huge malignant PEComa arising from the uterine cervix and vagina. To the best of our knowledge, only 6 cases of PEComa in the cervix and 2 cases in the vagina have been reported in the literature. © 2013 Elsevier GmbH. All rights reserved.
Introduction The World Health Organization defines PEComas as “mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells” [1]. Members of the PEComa family are angiomyolipoma, clear-cell “sugar” tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear-cell tumors of other anatomical sites [2]. Yet, some authors consider “PEComa” an ambiguous term because there is no consensus on whether it should be referred only to purely epithelioid tumors or even to lesions as angiomyolipoma or lymphangioleiomyomatosis as well. Martignoni et al. believe that all these latter tumors are composed of PEC (perivascular epithelioid cells) at different stages of modulation and belong to the same family of neoplasms. Nevertheless, these authors stated that some of these neoplasms should be still indicated with their former names (i.e. AML, lymphangioleiomyomatosis) in order to simplify the communication between clinicians and pathologists [3].
∗ Corresponding author. Tel.: +39 0817463442. E-mail address: [email protected] (L. Insabato). 0344-0338/$ – see front matter © 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.prp.2013.10.003
These tumors generally occur in middle-aged women (median age, 38 years) and show a striking female predominance with an overall female-to-male ratio of 7:1 [4]. PEComas have been described in a great variety of anatomic locations and often occur in the gynecological tract, particularly in the uterus [5]. In this site, most of these tumors are benign or of uncertain malignant potential although rare malignant PEComas have been reported [6]. Here, we report a case of a huge malignant PEComa arising from the cervix and vagina, occurring in a 52-year-old woman.
Case presentation A 52-year-old, 3 para, woman presented for a second opinion because of a large mass of the uterine cervix. A prior biopsy had been performed in an outside hospital, with a diagnosis of PEComa. The paraffin block of the tissue from the previous biopsy was sent to the laboratory of Anatomic Pathology, and on the basis of the morphological and immunohistochemical profile, the diagnosis of PEComa was confirmed. The patient complained of acute pelvic pain and episodes of acute cystitis. Clinical examination revealed a large mass in her vaginal area. Serum CA-125 and CA 19-9 levels were within the normal limits. Transvaginal ultrasound showed a very vascularized cervical
V. Natella et al. / Pathology – Research and Practice 210 (2014) 186–188
187
Fig. 1. Fused F18FDG-PET/CT sagittal (a) and coronal (b) images showed a huge cervical and vaginal mass (red arrow) with high level tracer uptake (SUVmax 15). The mass dislocates behind the rectum (brown arrow), anterior the bladder (yellow arrow) and above the uterus (blue arrow) and causes bilateral hydronephrosis (green arrow). Ureteral stents were present. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)
mass (12 cm × 11 cm). The patient underwent F18-FDG PET/CT to complete the local staging and to exclude distant metastases. The radiological images (Fig. 1) showed a huge cervical and vaginal mass with high level tracer uptake (SUVmax 15). The mass was dislocated behind the rectum, anterior the bladder, and above the uterus and caused bilateral hydronephrosis. The patient received 28 cycles of adjuvant radiotherapy, which was completely ineffective. She underwent a radical pelvectomy front and rear with removal of the uterus, vagina, bladder and anal canal; a neobladder and a colorectal anastomosis were performed. Grossly, a well circumscribed 12 cm × 11 cm mass was found, involving the cervix, the upper third of vagina, and compressing the bladder. Moreover, the mass partially occupied the pouch of Douglas, compressing the rectum. On cross section, the tumor showed a tan/yellow multinodular feature, with hemorrhagic changes. Histologically, the tumor was composed of large polygonal cells exhibiting focal hemorrhage and necrosis. Large, bizarre nuclei, cytoplasmic nuclear inclusions, and binucleation were occasionally found. Multifocal vascular invasion was seen. Downright, the neoplastic cells showed a definitely clear cytoplasm. A dense mixed inflammatory infiltrate and extensive hemorrhagic necrosis with focal microcalcifications were observed; mitotic activity was low (5 cm, infiltrative growth pattern, high nuclear grade, necrosis and mitotic activity >1/50 HPF with aggressive behavior
188
V. Natella et al. / Pathology – Research and Practice 210 (2014) 186–188
Fig. 2. (A) Lesion made of large epithelioid cells with large clear cytoplasm [hematoxylin-and-eosin stain (H&E), 106×]. (B) Detail of cells with large, bizarre nuclei, cytoplasmic nuclear inclusions, and binucleation (H&E, 400×, inset 630×). (C) Strong positive immunostaining of the tumor cells for HMB45 (200×). (D) Focal positive immunostaining for caldesmon (106×).
of PEComas [4]. The present case was considered to be morphologically malignant, based on its huge size (12 cm), high nuclear grade, high cellularity, moderate necrosis, and vascular invasion, however, with low mitotic rate (
