bs_bs_banner
Pathology International 2015; 65: 193–196
doi:10.1111/pin.12262
Original Article
Minute perivascular epithelioid cell (PEC) nests in the abdominal lymph nodes—a putative precursor of PEComa
Toru Nagasaka,1 Yoshiko Murakami,1 Eiichi Sasaki,1 Waki Hosoda,1 Toru Nakanishi2 and Yasushi Yatabe1 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center and 2Department of Gynecological Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
1
A perivascular epithelioid cell tumor (PEComa) is a peculiar growth defined as a mesenchymal tumor composed of histologically and immunohistochemically distinct perivascular epithelioid cells (PECs). Because neither normal counterparts nor precursor lesions of PEComa have been identified, we examined minute PEC nests, ranged from 0.8 mm to 10 mm, to investigate the possible origin of the PEComa. We examined a total of 80 677 para-aortic and pelvic lymph nodes that were systematically dissected from 1656 patients for gynecological malignancies. The identified lesions were confirmed immunohistochemically with multiple PEC markers, including smooth muscle actin, HMB45, melan-A, MiTF, ER and PgR. A total of 66 minute PEC nests were found in 21 patients (1.3% of the total population) with an average frequency of 3.1 lesions per patient. In cases of multiple involvement, 11 of 13 nests were located at the same level of multiple lymph node or on continuous levels. The lesions were preferentially distributed at the level of para-aortic and high pelvic lymph nodes. All nests were positive for actin and HMB45, whereas the other markers were positive with varying frequencies. The minute PEC nests may be associated with the possible normal counterpart of PEComas. Key words: angiomyolipoma, lymphangioleiomyomatosis, PEComa, perivascular epithelioid cell
In 2002 the World Health Organization first recognized the concept of perivascular epithelioid cell tumors (PEComas). These tumors were defined as ‘mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells’.1 The tumors comprise a family
Correspondence: Yasushi Yatabe, MD, PhD, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681 Japan. Email: yyatabe @aichi-cc.jp Received 3 December 2014. Accepted for publication 12 January 2015. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
that includes well-established angiomyolipoma (AML), clear cell ‘sugar’ tumor (CCST), lymphangioleiomyomatosis (LAM) and a number of unusual visceral, intraabdominal, soft tissue and bone tumors, which have been described under a variety of names including ‘clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres,’ ‘abdominopelvic sarcoma of perivascular epithelioid cells’ and ‘primary extrapulmonary sugar tumor.’1 All of these tumors share characteristic immunophenotypic features of both smooth muscle (smooth muscle actin and desmin) and melanocytic differentiation (HMB45, Melan-A, and microphthalmia transcription factor [MiTF]). There is a strong association between some members of the PEComa family (specifically angiomyolipoma and lymphangioleiomyomatosis) and the tuberous sclerosis complex (TSC). A high frequency of syndromic and sporadic PEComas have shown inactivation of the TSC1 or TSC2 genes.2,3 In the present study, we examined minute perivascular epithelioid cell (PEC) nests that were incidentally found in the range from 0.8 mm to 10 mm. Although the lesion has been sporadically reported in the literature as case reports,4–7 we encountered the nests rather frequently. This high frequency may be due to the use of systematic lymph node dissection for gynecological malignancies in our institute. The minute PEC nests had little clinical significance because none of the patients had suffered from TSC or had developed TSC, LAM, AML and other PEComas. Furthermore, the overall incidence, 1.3%, is much higher than that of PEComas. Highlighting the advantage of our institute, we analyzed the distribution of the minute PEC nests to investigate the possible origin of PEComas.
MATERIALS AND METHODS We retrospectively reviewed pelvic and para-aortic lymph node specimens that were resected at the time of surgery for gynecological malignancies in Aichi Cancer Center Hospital,
194
T. Nagasaka et al.
Nagoya, Japan, between 1995 and 2011. All lymph nodes were systematically collected and numbered according to their level. A total of 80 677 lymph nodes from 1656 patients were examined for the presence or absence of small PEC nests that were composed of epithelioid spindle cells with an eosinophilic cytoplasm in a fascicular fashion, cellular features that are similar to the other PEComas. When the nests were histologically identified, the lesions were immunohistochemically analyzed using the following markers: actin, desmin, HMB45, melan-A, MiTF, estrogen receptor (ER), progesterone receptor (PgR) and D2-40. Immunostaining was performed using a DAKO (Glostrup, Denmark) autostainer according to the manufacturer’s instructions. When PECs showed moderate or strong staining intensity in more than 10% of the total area, we considered the staining to be positive. Basic clinical data, including menarche age, menstrual cycle, number of gestations and associated cancer, were also obtained from patient charts. When reviewing the charts, the patient history of pulmonary LAM, another type of PEComa that includes angiomyolipoma and tuberous sclerosis complex, was of particular importance, but no patients had such clinical history. Statistical analysis The incidences of positive PEC nests according to the individual levels were assessed with a chi square test.
in Fig. 1. The sizes of the PEC nests ranged from 0.8 mm to 10 mm (average, 3.9 mm), and the nests were located in the hilum (13, 20%), both the hilum and sinus (21, 32%) and the sinus (32, 48%) but not in the cortex or the medulla (Table 1). Although a single PEC nest was found in 8 patients, 13 patients had multiple PEC nests, ranging in number from 2 to 11. Eleven of 13 multiple PEC nests were located at the same level of multiple lymph nodes or in continuous levels. No PEC nests were found in the resected tissues including uterus, ovaries and soft tissues with careful microscopic examination. The patient characteristics are summarized in Table 2. No clear association was found between the patients with and without minute PEC cell nests, according to the clinical variables examined.
Table 1 nests
Median size (mm) Location in the lymph nodes Hilum Hilum and sinus Sinus Number of nests per patients Average 1 2–5 6 or more
Table 2
RESULTS A total of 66 minute PEC nests were identified in 21 out of 1656 patients (1.3%), and representative images are shown
Figure 1 Representative image of a minute PEC nest. In the hilum of the lymph node, epithelioid spindle cells with eosinophilic cytoplasm proliferated in a fascicular fashion.
Size, location and number per patients of minute PEC 3.9 (0.8–10.0) 13 (20%) 21 (32%) 32 (48%) 3.1 8 9 4
Clinical characteristics
Median age Median menarche age Menorrhea Regular Irregular Postmenopausal Tumor site Cervix uteri Corpus uteri Ovary Peritoneum Vagina Vulva Others History PEComas Tuberous sclerosis complex
Positive for PEC nests (n = 21)
Negative for PEC nests (n = 1635)
52 13 (n = 21) 5 4 12 (n = 21) 4† 12‡ 5§ 0 0 0 0
52 13 (n = 429) 183 24 222 (n = 1635) 748 521 316 21 10 4 15
0 0
0 0
†Two patients each with squamous cell carcinoma and adenocarcinoma. ‡Eight patients with endometrioid adenocarcinoma, two with two malignant mixed müllerian tumors, one with serous adenocarcinoma, and one with undifferentiated carcinoma. §Two each for serous and clear cell carcinoma, and one with endometrioid adenocarcinoma.
© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Minute PEC nests in the lymph nodes
195
Figure 2 Distribution of the minute PEC nests. The lesions were non-randomly distributed, and para-aortic and high pelvic lymph nodes were preferentially involved.
Table 3
Actin Desmin HMB45 Melan-A MITF ER PgR TFE3
Immunohistochemical results of PEC nests
DISCUSSION
Negative
Positive
(%)
0 0 0 43 30 17 49 66
66 66 66 23 36 49 17 0
100 100 100 34.9 54.6 74.2 25.8 0
Anatomical distribution of PEC nests in pelvic cavity The pelvic lymph nodes were categorized into 13 subgroups (C1, R1 to R7, L1 to L7) to address the distribution of the minute PEC nests. Although the nests were distributed among all nodes, the para-aortic and high pelvic lymph nodes (C1, R1 and L2) were preferentially involved (Fig. 2). The preferential involvement of C1, R1 and L2 was significant according to the chi-square test, with some trends in R2 and L1.
Immunohistochemistry The immunohistological findings are summarized in Table 3 and representative images are shown in Fig. 3. Similar to other PEComas, minute PEC nests showed diffuse positive staining of smooth muscle actin, desmin and vimentin. Other characteristics of melanocytic differentiation varied according to the markers; HMB45 was positive in all lesions, whereas the expression of MiTF and MelanA was limited to 38% and 29% of PEC nests, respectively. The nuclear staining of the ER and PgR was noted focally. TFE3 was negative in all cases.
Bonetti and colleagues proposed the descriptive term ‘perivascular epithelioid cell’ (PEC) for the distinctive cell lineage found in the clear cell (‘sugar’) tumor of the lung, lymphangiomyomatosis and amgiomyolioma of the kidney. PEC is a putative cell type that is suggested to originate from the walls of vascular vessels, particularly lymphatics, because these cells are frequently intimately related to such structures.8 There is no known normal cellular counterpart to this cell type, and a precursor lesion for PEComas has not been described. In some case reports,5,6 small PEC lesions, ranging in size from 2 to 5 mm in the deep myometrium or lymph nodes, were suggested as a possible precursor of LAM. Although the authors use the term, LAM, these lesions could be equivalent to PEC nests in this study. In the present study, we examined the minute PEC nests in the pelvic and para-aortic lymph nodes in a systematic fashion. In our institute, lymph node sampling in conjunction with radical hysterectomy is a routine procedure for advanced surgically operable gynecological malignancies, and the lymph nodes removed during such procedures were systematically dissected. Thus, we suggest that the incidence and distribution of minute PEC nests was not biased, because none of the patients in this study had PEComas or tuberous sclerosis complex. The incidence of 1.3% (21 of 1656 patients) was much higher when the frequencies of PEComa-associated diseases were considered. In this study, the minute PEC nests were found most frequently in the para-aortic lymph nodes and high pelvic lymph nodes, although all examined nodes were involved. This distribution is quite similar to the sites involving PEComas, which most often arise in the retroperitoneum, abdominopelvic region and uterus.9 The tissue origins of the retroperitoneal and pelvic PEComas have been described as the soft tissue, but the current study suggests that the lymph
© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
196
T. Nagasaka et al.
Figure 3 Immunohistochemical staining of the minute PEC nest. Actin (right upper), HMB45 (left lower) and ER (right lower) were positive in the PECs in the nest.
nodes may be a source of such PEComas. This hypothesis is well exemplified by lymphangiomatosis of this tumor type, which spreads via the lymphatic channel. Actually, most minute PEC nests were localized continuously in cases of multiple involvements, and infiltration of the PEComa along the lymphatic system has been previously reported.5,7 Furthermore, Hayashi et al. showed that pelvic and retroperitoneal lymph nodes in addition to uterus were involved in all patients with pulmonary PEcoma (LAM).10 Interestingly, PEComas involving various organs, including the kidney, liver, uterus and lung, are associated in terms of a direct connection to the para-aortic or pelvic lymphatics. In summary, we examined the minute PEC nests in paraaortic and pelvic lymph nodes that were systemically dissected. The incidence was 1.3% (21 of 1656 patients), and the involvement was focused on the para-aortic and high pelvic lymph nodes. Their minimal size and distribution suggest that minute PEC nests are a potential precursor of PEComas.
ACKNOWLEDGMENT This work was supported in part by a Grant-in-Aid (1125670183) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
DISCLOSURE None declared.
REFERENCES 1 Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press, 2002. 2 Henske EP, Scheithauer BW, Short MP et al. Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. Am J Hum Genet 1996; 59: 400–6. 3 Pan CC, Chung MY, Ng KF et al. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): Genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol 2008; 214: 387–93. 4 Liang SX, Pearl M, Liu J, Hwang S, Tornos C. ‘Malignant’ uterine perivascular epithelioid cell tumor, pelvic lymph node lymphangioleiomyomatosis, and gynecological pecomatosis in a patient with tuberous sclerosis: A case report and review of the literature. Int J Gynecol Pathol 2008; 27: 86–90. 5 Clay MR, Gibson P, Lowell J, Cooper K. Microscopic uterine lymphangioleiomyomatosis perivascular epithelioid cell neoplasm: A case report with the earliest manifestation of this enigmatic neoplasm. Int J Gynecol Pathol 2011; 30: 71–5. 6 Iwasa Y, Tachibana M, Ito H et al. Extrapulmonary lymphangioleiomyomatosis in pelvic and paraaortic lymph nodes associated with uterine cancer: A report of 3 cases. Int J Gynecol Pathol 2011; 30: 470–75. 7 Yang W, Li G, Wei-qiang Z. Multifocal PEComa (PEComatosis) of the female genital tract and pelvis: A case report and review of the literature. Diagn Pathol 2012; 7: 23. 8 Bonetti F, Pea M, Martignoni G, Zamboni G. PEC and sugar. Am J Surg Pathol 1992; 16: 307–8. 9 Fletcher CDM, Bridge JA, Hogendoorm PCW et al., eds. WHO Classification of Tumours of Soft Tissue and Bone. Lynon: IARC, 2013. 10 Hayashi T, Kumasaka T, Mitani K et al. Prevalence of uterine and adnexal involvement in pulmonary lymphangioleiomyomatosis: A clinicopathologic study of 10 patients. Am J Surg Pathol 2011; 35: 1776–85.
© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Copyright of Pathology International is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Pathology International 2015; 65: 193–196
doi:10.1111/pin.12262
Original Article
Minute perivascular epithelioid cell (PEC) nests in the abdominal lymph nodes—a putative precursor of PEComa
Toru Nagasaka,1 Yoshiko Murakami,1 Eiichi Sasaki,1 Waki Hosoda,1 Toru Nakanishi2 and Yasushi Yatabe1 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center and 2Department of Gynecological Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
1
A perivascular epithelioid cell tumor (PEComa) is a peculiar growth defined as a mesenchymal tumor composed of histologically and immunohistochemically distinct perivascular epithelioid cells (PECs). Because neither normal counterparts nor precursor lesions of PEComa have been identified, we examined minute PEC nests, ranged from 0.8 mm to 10 mm, to investigate the possible origin of the PEComa. We examined a total of 80 677 para-aortic and pelvic lymph nodes that were systematically dissected from 1656 patients for gynecological malignancies. The identified lesions were confirmed immunohistochemically with multiple PEC markers, including smooth muscle actin, HMB45, melan-A, MiTF, ER and PgR. A total of 66 minute PEC nests were found in 21 patients (1.3% of the total population) with an average frequency of 3.1 lesions per patient. In cases of multiple involvement, 11 of 13 nests were located at the same level of multiple lymph node or on continuous levels. The lesions were preferentially distributed at the level of para-aortic and high pelvic lymph nodes. All nests were positive for actin and HMB45, whereas the other markers were positive with varying frequencies. The minute PEC nests may be associated with the possible normal counterpart of PEComas. Key words: angiomyolipoma, lymphangioleiomyomatosis, PEComa, perivascular epithelioid cell
In 2002 the World Health Organization first recognized the concept of perivascular epithelioid cell tumors (PEComas). These tumors were defined as ‘mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells’.1 The tumors comprise a family
Correspondence: Yasushi Yatabe, MD, PhD, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681 Japan. Email: yyatabe @aichi-cc.jp Received 3 December 2014. Accepted for publication 12 January 2015. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
that includes well-established angiomyolipoma (AML), clear cell ‘sugar’ tumor (CCST), lymphangioleiomyomatosis (LAM) and a number of unusual visceral, intraabdominal, soft tissue and bone tumors, which have been described under a variety of names including ‘clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres,’ ‘abdominopelvic sarcoma of perivascular epithelioid cells’ and ‘primary extrapulmonary sugar tumor.’1 All of these tumors share characteristic immunophenotypic features of both smooth muscle (smooth muscle actin and desmin) and melanocytic differentiation (HMB45, Melan-A, and microphthalmia transcription factor [MiTF]). There is a strong association between some members of the PEComa family (specifically angiomyolipoma and lymphangioleiomyomatosis) and the tuberous sclerosis complex (TSC). A high frequency of syndromic and sporadic PEComas have shown inactivation of the TSC1 or TSC2 genes.2,3 In the present study, we examined minute perivascular epithelioid cell (PEC) nests that were incidentally found in the range from 0.8 mm to 10 mm. Although the lesion has been sporadically reported in the literature as case reports,4–7 we encountered the nests rather frequently. This high frequency may be due to the use of systematic lymph node dissection for gynecological malignancies in our institute. The minute PEC nests had little clinical significance because none of the patients had suffered from TSC or had developed TSC, LAM, AML and other PEComas. Furthermore, the overall incidence, 1.3%, is much higher than that of PEComas. Highlighting the advantage of our institute, we analyzed the distribution of the minute PEC nests to investigate the possible origin of PEComas.
MATERIALS AND METHODS We retrospectively reviewed pelvic and para-aortic lymph node specimens that were resected at the time of surgery for gynecological malignancies in Aichi Cancer Center Hospital,
194
T. Nagasaka et al.
Nagoya, Japan, between 1995 and 2011. All lymph nodes were systematically collected and numbered according to their level. A total of 80 677 lymph nodes from 1656 patients were examined for the presence or absence of small PEC nests that were composed of epithelioid spindle cells with an eosinophilic cytoplasm in a fascicular fashion, cellular features that are similar to the other PEComas. When the nests were histologically identified, the lesions were immunohistochemically analyzed using the following markers: actin, desmin, HMB45, melan-A, MiTF, estrogen receptor (ER), progesterone receptor (PgR) and D2-40. Immunostaining was performed using a DAKO (Glostrup, Denmark) autostainer according to the manufacturer’s instructions. When PECs showed moderate or strong staining intensity in more than 10% of the total area, we considered the staining to be positive. Basic clinical data, including menarche age, menstrual cycle, number of gestations and associated cancer, were also obtained from patient charts. When reviewing the charts, the patient history of pulmonary LAM, another type of PEComa that includes angiomyolipoma and tuberous sclerosis complex, was of particular importance, but no patients had such clinical history. Statistical analysis The incidences of positive PEC nests according to the individual levels were assessed with a chi square test.
in Fig. 1. The sizes of the PEC nests ranged from 0.8 mm to 10 mm (average, 3.9 mm), and the nests were located in the hilum (13, 20%), both the hilum and sinus (21, 32%) and the sinus (32, 48%) but not in the cortex or the medulla (Table 1). Although a single PEC nest was found in 8 patients, 13 patients had multiple PEC nests, ranging in number from 2 to 11. Eleven of 13 multiple PEC nests were located at the same level of multiple lymph nodes or in continuous levels. No PEC nests were found in the resected tissues including uterus, ovaries and soft tissues with careful microscopic examination. The patient characteristics are summarized in Table 2. No clear association was found between the patients with and without minute PEC cell nests, according to the clinical variables examined.
Table 1 nests
Median size (mm) Location in the lymph nodes Hilum Hilum and sinus Sinus Number of nests per patients Average 1 2–5 6 or more
Table 2
RESULTS A total of 66 minute PEC nests were identified in 21 out of 1656 patients (1.3%), and representative images are shown
Figure 1 Representative image of a minute PEC nest. In the hilum of the lymph node, epithelioid spindle cells with eosinophilic cytoplasm proliferated in a fascicular fashion.
Size, location and number per patients of minute PEC 3.9 (0.8–10.0) 13 (20%) 21 (32%) 32 (48%) 3.1 8 9 4
Clinical characteristics
Median age Median menarche age Menorrhea Regular Irregular Postmenopausal Tumor site Cervix uteri Corpus uteri Ovary Peritoneum Vagina Vulva Others History PEComas Tuberous sclerosis complex
Positive for PEC nests (n = 21)
Negative for PEC nests (n = 1635)
52 13 (n = 21) 5 4 12 (n = 21) 4† 12‡ 5§ 0 0 0 0
52 13 (n = 429) 183 24 222 (n = 1635) 748 521 316 21 10 4 15
0 0
0 0
†Two patients each with squamous cell carcinoma and adenocarcinoma. ‡Eight patients with endometrioid adenocarcinoma, two with two malignant mixed müllerian tumors, one with serous adenocarcinoma, and one with undifferentiated carcinoma. §Two each for serous and clear cell carcinoma, and one with endometrioid adenocarcinoma.
© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Minute PEC nests in the lymph nodes
195
Figure 2 Distribution of the minute PEC nests. The lesions were non-randomly distributed, and para-aortic and high pelvic lymph nodes were preferentially involved.
Table 3
Actin Desmin HMB45 Melan-A MITF ER PgR TFE3
Immunohistochemical results of PEC nests
DISCUSSION
Negative
Positive
(%)
0 0 0 43 30 17 49 66
66 66 66 23 36 49 17 0
100 100 100 34.9 54.6 74.2 25.8 0
Anatomical distribution of PEC nests in pelvic cavity The pelvic lymph nodes were categorized into 13 subgroups (C1, R1 to R7, L1 to L7) to address the distribution of the minute PEC nests. Although the nests were distributed among all nodes, the para-aortic and high pelvic lymph nodes (C1, R1 and L2) were preferentially involved (Fig. 2). The preferential involvement of C1, R1 and L2 was significant according to the chi-square test, with some trends in R2 and L1.
Immunohistochemistry The immunohistological findings are summarized in Table 3 and representative images are shown in Fig. 3. Similar to other PEComas, minute PEC nests showed diffuse positive staining of smooth muscle actin, desmin and vimentin. Other characteristics of melanocytic differentiation varied according to the markers; HMB45 was positive in all lesions, whereas the expression of MiTF and MelanA was limited to 38% and 29% of PEC nests, respectively. The nuclear staining of the ER and PgR was noted focally. TFE3 was negative in all cases.
Bonetti and colleagues proposed the descriptive term ‘perivascular epithelioid cell’ (PEC) for the distinctive cell lineage found in the clear cell (‘sugar’) tumor of the lung, lymphangiomyomatosis and amgiomyolioma of the kidney. PEC is a putative cell type that is suggested to originate from the walls of vascular vessels, particularly lymphatics, because these cells are frequently intimately related to such structures.8 There is no known normal cellular counterpart to this cell type, and a precursor lesion for PEComas has not been described. In some case reports,5,6 small PEC lesions, ranging in size from 2 to 5 mm in the deep myometrium or lymph nodes, were suggested as a possible precursor of LAM. Although the authors use the term, LAM, these lesions could be equivalent to PEC nests in this study. In the present study, we examined the minute PEC nests in the pelvic and para-aortic lymph nodes in a systematic fashion. In our institute, lymph node sampling in conjunction with radical hysterectomy is a routine procedure for advanced surgically operable gynecological malignancies, and the lymph nodes removed during such procedures were systematically dissected. Thus, we suggest that the incidence and distribution of minute PEC nests was not biased, because none of the patients in this study had PEComas or tuberous sclerosis complex. The incidence of 1.3% (21 of 1656 patients) was much higher when the frequencies of PEComa-associated diseases were considered. In this study, the minute PEC nests were found most frequently in the para-aortic lymph nodes and high pelvic lymph nodes, although all examined nodes were involved. This distribution is quite similar to the sites involving PEComas, which most often arise in the retroperitoneum, abdominopelvic region and uterus.9 The tissue origins of the retroperitoneal and pelvic PEComas have been described as the soft tissue, but the current study suggests that the lymph
© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
196
T. Nagasaka et al.
Figure 3 Immunohistochemical staining of the minute PEC nest. Actin (right upper), HMB45 (left lower) and ER (right lower) were positive in the PECs in the nest.
nodes may be a source of such PEComas. This hypothesis is well exemplified by lymphangiomatosis of this tumor type, which spreads via the lymphatic channel. Actually, most minute PEC nests were localized continuously in cases of multiple involvements, and infiltration of the PEComa along the lymphatic system has been previously reported.5,7 Furthermore, Hayashi et al. showed that pelvic and retroperitoneal lymph nodes in addition to uterus were involved in all patients with pulmonary PEcoma (LAM).10 Interestingly, PEComas involving various organs, including the kidney, liver, uterus and lung, are associated in terms of a direct connection to the para-aortic or pelvic lymphatics. In summary, we examined the minute PEC nests in paraaortic and pelvic lymph nodes that were systemically dissected. The incidence was 1.3% (21 of 1656 patients), and the involvement was focused on the para-aortic and high pelvic lymph nodes. Their minimal size and distribution suggest that minute PEC nests are a potential precursor of PEComas.
ACKNOWLEDGMENT This work was supported in part by a Grant-in-Aid (1125670183) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
DISCLOSURE None declared.
REFERENCES 1 Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press, 2002. 2 Henske EP, Scheithauer BW, Short MP et al. Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. Am J Hum Genet 1996; 59: 400–6. 3 Pan CC, Chung MY, Ng KF et al. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): Genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol 2008; 214: 387–93. 4 Liang SX, Pearl M, Liu J, Hwang S, Tornos C. ‘Malignant’ uterine perivascular epithelioid cell tumor, pelvic lymph node lymphangioleiomyomatosis, and gynecological pecomatosis in a patient with tuberous sclerosis: A case report and review of the literature. Int J Gynecol Pathol 2008; 27: 86–90. 5 Clay MR, Gibson P, Lowell J, Cooper K. Microscopic uterine lymphangioleiomyomatosis perivascular epithelioid cell neoplasm: A case report with the earliest manifestation of this enigmatic neoplasm. Int J Gynecol Pathol 2011; 30: 71–5. 6 Iwasa Y, Tachibana M, Ito H et al. Extrapulmonary lymphangioleiomyomatosis in pelvic and paraaortic lymph nodes associated with uterine cancer: A report of 3 cases. Int J Gynecol Pathol 2011; 30: 470–75. 7 Yang W, Li G, Wei-qiang Z. Multifocal PEComa (PEComatosis) of the female genital tract and pelvis: A case report and review of the literature. Diagn Pathol 2012; 7: 23. 8 Bonetti F, Pea M, Martignoni G, Zamboni G. PEC and sugar. Am J Surg Pathol 1992; 16: 307–8. 9 Fletcher CDM, Bridge JA, Hogendoorm PCW et al., eds. WHO Classification of Tumours of Soft Tissue and Bone. Lynon: IARC, 2013. 10 Hayashi T, Kumasaka T, Mitani K et al. Prevalence of uterine and adnexal involvement in pulmonary lymphangioleiomyomatosis: A clinicopathologic study of 10 patients. Am J Surg Pathol 2011; 35: 1776–85.
© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Copyright of Pathology International is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
