Uterine cervical adenocarcinoma associated with lobular endocervical glandular hyperplasia: Radiologic pathologic correlation

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1 doi: /jog J. Obstet. Gynaecol. Res. Vol. 44, No. 2: , February 2018 Uterine cervical adenocarcinoma associated with lobular endocervical glandular hyperplasia: Radiologic pathologic correlation Ayumi Ohya 1, Shiho Asaka 2, Yasunari Fujinaga 1 and Masumi Kadoya 1 1 Department of Radiology, Shinshu University School of Medicine and 2 Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan Abstract Aim: We aimed to identify the radiologic features of uterine cervical adenocarcinoma associated with lobular endocervical glandular hyperplasia (LEGH). Methods: We retrospectively analyzed magnetic resonance (MR) images and pathologic findings of eight patients who underwent preoperative MR imaging followed by surgical resection and who were pathologically diagnosed with adenocarcinoma (except for adenocarcinoma in situ) associated with LEGH. We assessed the following MR findings: multicystic component (MC), solid component (SC), signal intensity of SC on diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) map, and radiological stage (r-stage) based on the FIGO classification. A pathologist reevaluated the pathological stage (p-stage) according to the FIGO classification. We correlated the MR findings with the pathologic features. Results: Eight patients were classified into the following three types based on the MR findings: type A, MC and SC; type B, only SC; and type C, only MC. In the five patients with type A, diffusion restriction (DR) was seen on DWI and the ADC map. In 80% of type A cases, the r-stage matched the p-stage. In the one patient with type B, DR was not seen on DWI or the ADC map, and the r-stage matched the p-stage. In the remaining type C cases, DR was not seen on DWI or the ADC map, and the r-stage was underestimated compared with the p-stage. Conclusion: On MR imaging, the most common type of adenocarcinoma with LEGH is type A; type C is difficult to diagnose as carcinoma. Key words: adenoma malignum, lobular endocervical glandular hyperplasia, magnetic resonance imaging, minimal deviation mucinous adenocarcinoma, uterine cervix. Introduction Squamous cell carcinoma is the most common type of cancer in the uterine cervix. However, adenocarcinoma currently comprises 10 25% of all cervical carcinomas, and its incidence has increased compared with three decades ago. 1 Although squamous cell carcinoma and 94% of adenocarcinomas are associated with high-risk human papillomavirus (HPV), 1 gastrictype mucinous carcinoma and minimal deviation adenocarcinoma (MDA) are reportedly unassociated with HPV infection. 2 MDA or adenoma malignum reportedly presents as a multicystic mass of the uterine cervix on magnetic resonance (MR) images. 3 5 However, lobular endocervical glandular hyperplasia (LEGH), a benign glandular lesion of the cervix, 6 was also recently reported to present as a multicystic mass (a so-called cosmos pattern) on MR images. 7 Because the pathologic features of MDA closely resemble those of LEGH, it is possible Received: June Accepted: September Correspondence: Dr Ayumi Ohya, Department of Radiology, Shinshu University School of Medicine, Asahi, Matsumoto , Japan. ayuayukick@yahoo.co.jp Japan Society of Obstetrics and Gynecology

2 MR images of adenocarcinoma with LEGH that LEGH lesions were included in previous studies of MDA and adenoma malignum. In the World Health Organization classification, MDA and adenoma malignum are synonymous and defined as extremely well-differentiated gastric-type mucinous carcinoma. 1 Gastric-type mucinous carcinoma, especially MDA, has more aggressive features including peritoneal spread and a poorer prognosis than usual types of adenocarcinoma. 8 Some reports have described adenocarcinoma in association with LEGH, 9 11 and it has been suggested that LEGH might be a precursor lesion of adenocarcinoma, especially gastric-type mucinous carcinoma. 2,12 Hence, LEGH is thought to be a precursor lesion of poorprognosis adenocarcinoma. In consideration of the precancerous potential of LEGH, Takatsu et al. 7 have recommended follow-up or simple hysterectomy as the treatment of choice. However, this is controversial; simple hysterectomy might be an overtreatment because LEGH is a benign lesion and the frequency of its malignant transformation is unclear. Therefore, before treatment, it is necessary to distinguish between LEGH and carcinoma associated with LEGH. We consider that knowledge of the radiologic features of carcinoma associated with LEGH is important to ensure an accurate and early diagnosis. To our knowledge, only a few reports have described adenocarcinoma associated with LEGH, including the radiologic findings in such patients. 7,9,10 Takatsu et al. 7 and Tsuboyama et al. 10 have reported that adenocarcinoma associated with LEGH had solid and cystic components on MR images. However, Takeuchi et al. 9 reported that endocervical adenocarcinoma associated with LEGH was seen as a multicystic lesion in the uterine cervix with hydrometra on MR images. These case reports described radiologic pathologic correlations. 9,10 In addition, one cohesive study of the radiologic and pathologic correlation of adenocarcinoma associated with LEGH has been published. 7 However, no cohesive study has described the correlation of MR findings, including the findings on diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) map, with pathologic features. Additionally, no study has described the accuracy of staging using MR imaging in adenocarcinoma with LEGH. Therefore, we investigated the detailed radiologic features of adenocarcinoma associated with LEGH and correlated the MR findings, including the findings on DWI and the ADC map, with the pathologic findings for early diagnosis of this condition on MR imaging. Methods Patient population We reviewed the pathology database of the Department of Laboratory Medicine of our institution and identified eight female patients who underwent preoperative MR imaging and were pathologically diagnosed with adenocarcinoma (except for adenocarcinoma in situ) associated with LEGH after surgical resection from January 2001 to September In all patients, the area of the adenocarcinoma was close to the area of the LEGH, and we regarded the lesions as adenocarcinoma associated with LEGH because LEGH is a potential precursor lesion of adenocarcinoma. 2 The pathologic types of carcinoma in these patients were gastric-type mucinous carcinoma and MDA (n = 6), serous carcinoma (n = 1), and usual type endocervical adenocarcinoma (n = 1). The pathologic diagnosis was based on the World Health Organization classification criteria (2014). 1 MR imaging had been performed in all patients within 1.5 months before surgery. The mean age of the patients was 59.1 years (range, years). This study was approved by the ethical committee of our institution (no. 3550). The ethical committee also granted a waiver of informed consent for use of the patients specimens and MR images because diagnostic use of the samples was completed before the study and there was no risk to the involved patients. Samples were also coded to protect patient anonymity. MR examination MR images were acquired using 3-T MR scanners (Verio and Trio; Siemens Medical Systems) in three patients and using 1.5-T MR scanners (Optima; GE Healthcare; Symphony and Avanto; Siemens Medical Systems) in five patients. We analyzed the findings of axial fat-suppressed T1-weighted imaging (T1WI), axial and sagittal T2-weighted imaging (T2WI) with or without fat suppression, axial DWI, the axial ADC map, and axial and sagittal contrast-enhanced fatsuppressed T1WI. The parameters of each sequence varied because this study was retrospective and involved a long study period. The scan parameters for each sequence are shown in Table S1. Radiologic image analysis Two experienced radiologists independently assessed the following features of the lesions on the MR images without the patients clinical information: multicystic component, solid component, signal intensity of the 2017 Japan Society of Obstetrics and Gynecology 313

3 A. Ohya et al. solid component and septa on DWI and the ADC map, and radiological stage based on the Federation Internationale de Gynecologie et de Obstetripue (FIGO) classification. When the radiologists disagreed regarding the findings, they discussed the case until they reached consensus. A cystic component was defined as a markedly hyperintense area on T2WI without enhancement on contrast-enhanced fat-suppressed T1WI. A multicystic component was defined as a close aggregation of cystic components (Fig. 1). A solid component was defined as a nodular, massive, or infiltrative area shown as a hyperintense area relative to the cervix stroma on T2WI with enhancement on contrast-enhanced T1WI (Fig. 1). The septa among the multicystic components recognized in the center of LEGH lesions were not defined as a solid component. We considered that diffusion restriction of water molecules was present within the lesion when the solid component and septa of the lesions were shown as hyperintense areas on DWI and hypointense areas on the ADC map relative to the uterine myometrium. When the presence of a carcinoma could not be identified on MR images, we considered the lesion to be stage 0. Pathologic image analysis One pathologist reevaluated and retrospectively analyzed the pathologic findings using hematoxylin eosin-stained sections to confirm the histologic type of carcinoma associated with LEGH. Pathological staging was also based on the FIGO classification. In addition, the radiologic findings of the multicystic components and solid components within the lesions were correlated with the pathologic findings by all readers. Figure 1 Definition of multicystic component and solid component in the present study. A multicystic component was defined as a close aggregation of cystic components, which presented as very hyperintense regions on T2-weighted imaging (T2WI) and hypointense regions on contrastenhanced T1-weighted imaging (T1WI). A solid component was defined as a nodular or massive area (left side) and infiltrative area (right side) with hyperintensity relative to the cervix stroma on T2WI and enhancement on contrast-enhanced T1WI. Gd, gadolinium; U, uterus Japan Society of Obstetrics and Gynecology

4 MR images of adenocarcinoma with LEGH Results MR findings of adenocarcinoma associated with LEGH and pathologic correlation The MR findings are summarized in Table 1. Multicystic components were seen on the MR images of seven of eight patients. Small cysts were present inside the lesion, and relatively large cysts were present outside the lesion; this has been referred to as the cosmos pattern (Figs 2, 4). It was thought that cystic components on MR images corresponded to relatively large cavities of the gland on the histological examination. Not all cystic components were histologically composed of LEGH. The wall of some cystic components consisted of carcinoma cells in Patients 1, 5, and 7 (Figs 2, 4). Only Patient 5 had a somewhat irregularly defined cystic component. However, all lesions had a multicystic component and showed a cosmos pattern. In Patient 8, cystic components were scattered, not closely aggregated, and most lesions were composed of a solid component on MR images (Fig. 3). Histologically, the area of LEGH was very small and most of the lesion was composed of invasive carcinoma with scattered nabothian cysts (Fig. 3). In six of the eight patients, the solid component could be detected on MR images (Table 1; Figs 2 3). Histologically, the solid components were the areas of invasive carcinoma within the lesions. In Patients 6 and 7, the solid component could not be detected on MR images (Fig. 4). In Patient 6, localized carcinoma cells within LEGH were pathologically observed. In Patient 7, localized LEGH within adenocarcinoma was pathologically observed (Fig. 4). DWI was performed in seven of the eight patients (Table 1). In four of these seven patients, diffusion restricted areas were seen (Table 1); that is, solid components were shown as hyperintense areas on DWI and hypointense areas on the ADC map (Fig. 2). In these four patients, solid components were present and the diffusion-restricted areas matched the solid components. In Patients 6, 7, and 8, no diffusionrestricted area was seen (Fig. 4). Histologically, in Patient 6, the area of carcinoma was very small. In Patient 7, extremely well-differentiated carcinoma sparsely infiltrated the cervical stroma and parametrium, and the cell density of the carcinoma part was lower than that of the four patients with solid components on MR images (Fig. 4). In Patient 8, welldifferentiated carcinoma had infiltrated the cervical stroma surrounding the cervical canal without a desmoplastic reaction, replacing the normal cervical gland (Fig. 3). Summarizing the above MR findings of adenocarcinoma associated with LEGH, the patients were classified into three types by the ratio of multicystic and solid components (Tables 1 2, Fig. 5). Type A comprised multicystic and solid components, and five of eight patients (Patients 1 5) were classified as having this type (Fig. 2). Diffusion-restricted areas were seen in all of the solid components of type A on DWI and the ADC map (Table 2). Type B comprised almost a totally solid component without diffusion-restricted areas on DWI or the ADC map, and one patient (Patient 8) was classified as having this type (Table 2, Fig. 3). Type C comprised only a multicystic component, and two patients (Patients 6 and 7) were classified as having this type (Fig. 4). No diffusion-restricted areas were seen in type C (Table 2, Fig. 4). Correlation between radiologic and pathologic stages In four of the five patients with type A and the one patient with type B, the radiologic stage matched the pathologic stage (Table 2). In Patient 5, whose radiologic stage did not match the pathologic stage, a small area of vascular invasion in the parametrium was Table 1 Magnetic resonance imaging findings Patient no. Age (years) Type Multicystic Solid DR r-stage p-stage Type of MR findings 1 50 G Yes Yes Yes 2A 2A Type A 2 64 G Yes Yes Yes 2B 2B Type A 3 62 Serous Yes Yes Yes 1B 1B Type A 4 67 U Yes Yes NE 1B 1B Type A 5 46 G Yes Yes Yes 1B 2B Type A 6 55 G Yes No No 0 1A Type C 7 54 MDA Yes No No 0 2B Type C 8 75 G No Yes No 1B 1B Type B DR, diffusional restriction; G, gastric-type mucinous carcinoma; MDA, minimal deviation adenocarcinoma; MR, magnetic resonance; NE, not evaluated; p-stage, pathological stage; r-stage, radiological stage; U, usual type endocervical adenocarcinoma Japan Society of Obstetrics and Gynecology 315

5 A. Ohya et al. Figure 2 Patient 1. Gastric-type mucinous carcinoma associated with lobular endocervical glandular hyperplasia (LEGH). This case was classified into type A based on the following magnetic resonance findings. (a,b) The lesion in the uterine cervix consists of an area of marked hyperintensity on fat-suppressed T2-weighted image and an infiltrative or nodular area of slight hyperintensity relative to the normal cervical stroma (white arrow). (c) The former area is hypointense and the latter was slightly hyperintense on gadolinium-enhanced fat-suppressed T1-weighted image (white arrow). Hence, the lesion was considered as having both multicystic and solid components. (d) On a fat-suppressed T2- weighted axial image of external os level, an infiltrative solid component is seen at the surrounding cervical cavity (arrowhead). (e) A diffusion-weighted image shows the hypointense solid component of the lesion compared with the uterine myometrium (arrowhead). (f) The apparent diffusion coefficient map shows the hypointense uterine myometrium (arrowhead). Hence, water diffusional restriction is seen in the area of the solid component. (g) Hematoxylin eosin (HE) staining shows a relatively large cavity of gland corresponding to a cystic component on MR images. Carcinoma cells lined the inside of the cystic component. (h) HE staining shows LEGH within the lesion. (i) HE staining shows invasive carcinoma in the cervical stroma; this area is comparable with the solid component on magnetic resonance images. Bar = 100 μm Japan Society of Obstetrics and Gynecology

6 MR images of adenocarcinoma with LEGH seen histologically. In the remaining patients, all of whom had type C and gastric-type mucinous carcinoma (including MDA), the radiologic stage was underestimated compared with the pathologic stage (Table 2). In particular, Patients 6 and 7 were considered to have stage 0 lesions on radiological staging. Patient 6 had a stage 1A lesion on histological staging, and the area of the adenocarcinoma was small. However, Patient 7 had stage 2B lesions on histological staging, although no parametrial invasion was identified on MR images. In Patient 7, small and sparse clumps of carcinoma cells infiltrated the parametrium without a desmoplastic reaction (Fig. 4). Discussion This is the first report of the features of uterine cervical adenocarcinoma associated with LEGH on MR imaging, including DWI and the ADC map, in a large group of patients. The MR findings of adenocarcinoma with LEGH were classified into three types (Table 2, Fig. 5). Type A was the most common type (Table 2, Fig. 2). Some case reports support our results because the lesions comprised a mixture of solid and cystic parts (i.e., type A in the present study). 7,10 In type B, the area of LEGH in the lesion was very small histologically (Fig. 3). Takatsu et al. 7 described two cases of MDA with focal LEGH seen as predominantly solid lesions. The MR findings of our type B case matched the findings of their cases. In one of seven cases reported by Takatsu et al., 7 the lesion was a focal MDA with LEGH and could be classified as type C. In one of our type C cases (Patient 6), adenocarcinoma was focally seen within LEGH. Focal MDA and adenocarcinoma may coexist in approximately 10 15% of lesions showing a cosmos pattern on MR images. 7 In general, it is difficult to detect stage 1A carcinoma on MR imaging. In our other type C case (Patient 7), the majority of the lesion was MDA, and a focal area of the lesion affected by LEGH was found histologically (Fig. 4). However, it was difficult to detect a solid component or invasion to the parametrium on MR images. Histologically, invasive carcinoma formed a glandular lesion and small nest and infiltrated both the myometrium and parametrium. These results suggest that not only focal MDA and gastric-type mucinous adenocarcinoma but also advanced cancer associated with LEGH might show a cosmos pattern without a solid component as shown in type C on MR images. Thus, we consider that cytological diagnosis, organizational diagnosis by conization, and other diagnostic techniques play a crucial role in the management of LEGH. Multicystic components were clearly revealed on MR images in seven of eight patients (type A and C). However, there are pitfalls in the use of MR images to accurately diagnose adenocarcinoma associated with LEGH. Multicystic components on MR images are usually considered a typical finding of LEGH. The present study indicates that this is not always true because some cystic components on MR images consisted of gastric-type mucinous carcinoma (Patients 1, 5, and 7). In addition, cystic components associated with tumors were identified in only 0.025% of cases of squamous cell carcinoma but occurred in 80% of cases of gastric-type mucinous carcinoma. 13 Hence, a cystic component is common in gastric-type mucinous carcinoma. Though our study indicates that multicystic components suggest the existence of LEGH, not all of the cystic components are always composed of LEGH. All solid components of type A and B on MR images corresponded to the areas of invasive carcinoma observed histologically. In previous reports, adenocarcinoma associated with LEGH had a solid part that could sometimes be detected on MR images. 7,8 The existence of solid components within the lesion is a very important radiologic finding for an accurate diagnosis of adenocarcinoma associated with LEGH. In five of six cases of type A and B, which had solid component on MR images, the radiological staging matched the pathological staging. Hence, observing the existence of a solid component within the lesion may indicate the correct diagnosis. On the other hand, Takatsu et al. 7 reported that LEGH contained small cysts or solid parts often surrounded by larger cysts in the cervical stroma (the socalled radiologic cosmos pattern ). Radiologically, the solid parts seen as septa among the multicystic or aggregated small cystic components existed in the center of the lesions, but no nodular or infiltrative solid components were seen. Thus, the solid parts of LEGH described by Takatsu et al. 7 were radiologically defined as aggregated small cystic components seen as a solid-like hyperintense area with spotty marked hyperintense areas on T2WI in our study. They were discriminable from the nodular or infiltrate solid components of the adenocarcinoma on MR images. In this sense, there were no solid components in the LEGH cases that we experienced clinically. Additionally, no 2017 Japan Society of Obstetrics and Gynecology 317

7 A. Ohya et al. Figure 3 Patient 8. Gastric-type and intestinal-type mucinous carcinoma associated with lobular endocervical glandular hyperplasia (LEGH). This case was classified into type B based on the following magnetic resonance findings. (a,b) The cervical mucosa is thick for the patient s age on sagittal and axial fat-suppressed T2-weighted imaging (FS-T2WI). FS- T2WI also shows thinning of the cervical stroma. FS-T2WI shows spotty very high intensity, which is suspected to be a cyst. (c) The mass surrounding the cervical canal like the normal cervical mucosa is slightly hyperintense on gadolinium-enhanced fat-suppressed T1-weighted imaging. (d) On diffusion-weighted imaging, the mass is shown as a slightly hyperintense area relative to the myometrium. (e) On the apparent diffusion coefficient map, the mass is shown as a hyperintense area. Hence, no diffusion restriction is seen in the lesion. (f) Hematoxylin-eosin (HE) staining shows well-differentiated invasive carcinoma in the cervical stroma. (g) HE staining shows a very small area of LEGH. Bar = 100 μm Japan Society of Obstetrics and Gynecology

8 MR images of adenocarcinoma with LEGH Figure 4 Patient 7. Minimal-deviation adenocarcinoma associated with lobular endocervical glandular hyperplasia. This case was classified into type C based on the following magnetic resonance findings. (a) Sagittal fat-suppressed T2weighted imaging (FS-T2WI) shows a multicystic lesion in the internal cervical os without a solid component. (a,b) Sagittal and axial FS-T2WI shows that the cystic component comprised internal small cystic foci and external large cystic foci. (c) Diffusion-weighted imaging shows a slightly hyperintense area relative to the myometrium within the multicystic lesion. (d) On the apparent diffusion coefficient map, no hypointense area relative to the myometrium is present within the multicystic lesion. Hence, no diffusion restriction is seen in the lesion. (e) Hematoxylin eosin staining shows variously sized cysts within the lesion. (f) Extremely well-differentiated carcinoma cells line the inside of the cystic component. (g) Extremely well-differentiated carcinoma infiltrates the parametrium without a desmoplastic reaction. Bar = 100 μm Japan Society of Obstetrics and Gynecology 319

9 A. Ohya et al. Table 2 Classified magnetic resonance findings Type Findings n DR Accuracy of r-stage A Multicystic and solid 5 4/4 4/5 B Almost solid 1 0/1 1/1 C Only cystic 2 0/2 0/2 One patient did not undergo diffusion-weighted imaging. DR, diffusional restriction; r-stage, radiological stage. reports have described LEGH with nodular or infiltrative solid components. DWI and ADC maps are valuable tools for establishing a radiological diagnosis of malignant tumors. Malignant tumors are believed to present as hyperintense areas on DWI and hypointense areas on ADC maps because of the constraint of water molecule movement within the malignant tumor tissue; this constraint of movement reflects the high cell concentration of the tumor. In the present study, diffusionrestricted areas were seen in all solid components of patients who underwent DWI (type A) but were not seen in the lesions without a solid component (type C). In Patients 6 and 7, diffusion restriction was not seen even within septa among cystic components on DWI and ADC maps. In type B (Patient 8), diffusionrestricted areas were not seen within solid components on DWI and ADC maps. The carcinoma areas in each of these cases (Patients 6 8) were gastric-type mucinous carcinoma. In Patient 6, the carcinoma area was very small and the FIGO stage of the lesion was 1A. Stage 1A carcinoma cannot be seen on MR imaging. In contrast, Patients 7 and 8 had a FIGO stage higher than 1A. In these two cases, however, the lesions comprised a glandular area of very welldifferentiated carcinoma cells compared with the other cases in our study. Tsuboyama et al. 10 reported that two components (the obvious adenocarcinoma Figure 5 Three types of adenocarcinoma with lobular endocervical glandular hyperplasia. Type A comprises a multicystic component (white area) and a nodular or infiltrative solid component (gray area). Type B comprises a solid component. Type C comprises only a multicystic component. U, uterus Japan Society of Obstetrics and Gynecology

10 MR images of adenocarcinoma with LEGH component and an MDA component) displayed much higher ADC values than usual cervical carcinoma. Castán Senar et al. 14 reported that the ADC map showed no diffusion restriction within MDA. Considering these reports, some gastric-type mucinous carcinomas might present as lesions without a diffusion-restricted area on DWI and ADC maps, although they still might be progressive lesions. We consider that a diffusion-restricted area was not seen on DWI and ADC maps because of the low cellular density of the lesions or low consistency of the mucus retained within the glands composed of carcinoma cells. In Patient 8, the combination of MR findings (i.e., the enhancement on contrast-enhanced fatsuppressed T1WI and no diffusion restriction on DWI and the ADC map) might suggest the presence of a mucinous component in the lesion, such as gastrictype mucinous carcinoma. The results of the present study indicate that DWI and ADC maps are useful techniques with which to detect the solid component within a lesion, although it is difficult to detect the malignant portion when the lesion consists of only a multicystic component and exhibits a cosmos pattern without a solid component. Additionally, diffusionrestricted areas might not be seen on DWI and ADC maps even if the lesion has the solid components of gastric-type mucinous carcinoma. A gastric-type mucinous carcinoma is considered to have a poorer prognosis than a usual type endocervical adenocarcinoma because it aggressively infiltrates the surrounding tissues and frequently exhibits peritoneal and abdominal spread. 1 MR findings in such cases should be interpreted with extreme caution. Unfortunately, we could not accurately diagnose parametrial invasion on MR images in two patients in the present study (Patients 5 and 7, who had gastrictype mucinous carcinoma and MDA, respectively). Microscopically, specifically in Patient 7, we observed small and sparse conglomerations of extremely welldifferentiated carcinoma cells infiltrating the parametrium without a desmoplastic reaction (Fig. 5). Takatsu et al. 7 described a case of MDA with LEGH that showed multiple cysts with an inner solid pattern on MR imaging, which was highly suggestive of LEGH, and a small nest of MDA was found in a peripheral area of the LEGH. These specific types of invasion might hamper accurate diagnosis on MR images. Hence, we should note the possible existence of invisible invasion (possible underdiagnosis) when attempting to diagnose a mass composed of both multicystic and solid components on MR images. There are some limitations of our study. First, this was a retrospective cohort study with a small number of patients. However, only seven cases of adenocarcinoma with LEGH were reported in a previous multicenter study. 7 Our study was a single-center study with a slightly larger number of patients than the previous study. Second, because we did not perform HPV DNA testing, we cannot rule out the possibility that the adenocarcinoma and LEGH coexisted incidentally. However, we believe that collision tumors of LEGH and adenocarcinoma unassociated with LEGH are very rare. Third, the MR imaging parameters varied. The slice thickness of MR images might influence judgment regarding multicystic components and solid components (Table S1). However, this was avoidable because of the data obtained from the long investigation period. Fourth, we did not compare MR findings between adenocarcinoma associated with LEGH and LEGH without adenocarcinoma because only a few patients underwent total hysterectomy for the treatment of LEGH. In these patients, no solid components were seen. In conclusion, the common radiologic feature of adenocarcinoma with LEGH was a mixture of multicystic and solid components. It is important that solid components, most of which present as a diffusionrestricted area, on MR images correspond to the area of invasive carcinoma histologically. We believe that MR imaging has a very important role for the accurate diagnosis of adenocarcinoma associated with LEGH. However, it should be noted that diagnosis on MR imaging has pitfalls. To avoid misdiagnosis, a comprehensive diagnosis including MR imaging, cytological examination, conization, and other techniques is recommended. Disclosure No funding was received for this study. All of the authors declare that they have no conflict of interest. References 1. Kurman RJ, Carcangiu ML, Herrington CS et al. Would Health Organization Classification of Tumors of Female Reproductive Organs. Lyon: IARC Press, Nara M, Hashi A, Mutara SI et al. Lobular endocervical glandular hyperplasia as a presumed precursor of cervical adenocarcinoma independent of human papillomavirus infection. Gynecol Oncol 2007; 106: Japan Society of Obstetrics and Gynecology 321

11 A. Ohya et al. 3. Yamashita Y, Takahashi M, Katabuchi H, Fukumatsu Y, Miyazaki K, Okamura H. Adenoma malignum: MR appearances mimicking nabothian cysts. Am J Roentgenol 1994; 162: Oguri H, Maeda N, Izumiya C et al. MRI of endocervical glandular disorders: Three cases of a deep nabothian cyst and three cases of a minimal-deviation adenocarcinoma. Magn Reson Imaging 2004; 22: Doi T, Tamashita Y, Yasunaga T et al. Adenoma malignum: MR imaging and pathologic study. Radiology 1997; 204: Nucci MR, Clement PB, Young RH. Lobular endocervical glandular hyperplasia, not otherwise specified: A clinicopathologic analysis of thirteen cases of distinctive pseudoneoplastic lesion and comparison with fourteen cases of adenoma malignum. Am J Surg Pathol 1999; 23: Takatsu A, Shiozawa T, Miyamoto T et al. Preoperative differential diagnosis of minimal deviation adenocarcinoma and lobular endocervical glandular hyperplasia of the uterine cervix: multicenter study of clinicopathology and magnetic resonance imaging findings. Int J Gynecol Obstet 2011; 21: Kojima A, Mikiami Y, Sudo T et al. Gastric morphology and immunophenotype predict poor outcome in mucinous adenocarcinoma of the uterine cervix. Am J Surg Pathol 2007; 31: Takeuchi K, Tsujino T, Sugimoto M, Yoshida S, Kitazawa S. Endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia showing rapid reaccumulation of hydrometra. Int J Gynecol Cancer 2008; 18: Tsuboyama T, Yamamoto K, Nakai G et al. A case of gastrictype adenocarcinoma of the uterine cervix associated with lobular endocervical glandular hyperplasia: Radiologicpathologic correlation. Abdom Imaging 2015; 40: Nishio S, Tsuda H, Fujiyoshi N et al. Clinicopathological significance of cervical adenocarcinoma associated with lobular endocervical glandular hyperplasia. Pathol Res Pract 2009; 205: : [Correction added on 11 December 2017 after first online publication: References 7 and 11 have been corrected.] 12. Takatsu A, Miyamoto T, Fuseya C et al. Clonality analysis suggests that STK11 gene mutations are involved in progression of lobular endocervical glandular hyperplasia (LEGH) to minimal deviation adenocarcinoma (MDA). Virchows Arch 2013; 462: Kido A, Mikami Y, Koyama T et al. Magnetic resonance appearance of gastric-type adenocarcinoma of uterine cervix in comparison with that of usual-type endocervical adenocarcinoma. Int J Gynecol Cancer 2014; 24: Castán Senar A, Paño B, Sako A, Nicolau C. Magnetic resonance imaging of adenoma malignum of the uterine cervix with pathologic correlation: A case report. Radiol Case Rep 2016; 11: Supporting information Additional Supporting Information may be found in the online version of this article at the publisher s web-site: Table S1 Magnetic resonance scan parameters for each sequence. The parameters of each sequence varied, because this study was retrospective and a long study period Japan Society of Obstetrics and Gynecology