Endocervical-type mucinous adenocarcinoma (ECA) of the uterine cervix is defined as a tumor composed of cells resembling those of the endocervical glands, but recent studies have demonstrated that a minority of ECAs displays a gastric immunophenotype. The aim of this study was to assess the significance of the gastric phenotype. Fifty-three cases of mucinous adenocarcinoma of the uterine cervix (37 FIGO stage IB, 4 stage IIA, and 12 stage IIB) were reviewed and reevaluated using a newly established morphologic criteria for distinguishing gastric type adenocarcinoma, which was defined as a tumor showing clear and/or pale eosinophilic and voluminous cytoplasm, with distinct cell borders. The results were correlated with gastric immunophenotype, determined by HIK1083 and MUC6 immunostaining, and patient outcome. Following the current World Health Organization scheme (2003), 47 tumors (89%) were classified as ECA, 1 (2%) as intestinal type, 1 (2%) as mixed endocervical and intestinal type, and 4 (8%) as minimal deviation adenocarcinoma. Twelve of 47 (26%) ECAs and all 4 minimal deviation adenocarcinomas, reclassified as gastric type using the novel criteria, were frequently positive for HIK1083 with a rate of 75% (12/16), whereas only 11% (4/37) of nongastric tumors were positive. There was no significant difference in MUC6 reactivity between gastric and nongastric type tumors (31%, 5/16 vs. 16%, 6/37; P=0.4). Patients with gastric-type adenocarcinomas had a significantly decreased 5-year disease-specific survival rate (30 vs. 77%; P<0.0001), and the gastric type morphology was related to a significant risk for disease recurrence compared with the nongastric type (P=0.001; HR, 4.5; 95% confidence interval, 1.42-14.2). HIK1083-positivity was also related to decreased 5-year disease-specific survival rate (38% vs. 74%; P<0.005). Mucinous adenocarcinoma of the uterine cervix with gastric immunophenotype can be a distinct morphologic variant showing an aggressive clinical course.

Purpose:To determine the feasibility of diffusion-weighted (DW) MRI of uterine endometrial cancer and to investigate whether the apparent diffusion coefficient (ADC) values of endometrial cancer differ from those of normal endometrium and whether they differ according to the histologic grade of the tumor. Materials and Methods:Study population included 18 consecutive females with surgically proven endometrial cancer and 12 females with pathologically confirmed normal endometrium in cervical cancer patients. Visual evaluation and ADC measurement were performed in endometrial cancer and normal endometrium.Results: All endometrial cancer and the normal endometrium appeared hyperintense on DW images. The mean ADC value (10 Ϫ3 mm 2 /second) of endometrial cancer was 0.88 Ϯ 0.16, which was significantly lower (P Ͻ 0.01) than that of normal endometrium (1.53 Ϯ 0.10). The mean ADC value for each histologic grade was 0.93 Ϯ 0.16 (G1), 0.92 Ϯ 0.13 (G2), and 0.73 Ϯ 0.09 (G3). Conclusion:The present study showed that DW imaging is feasible in demonstrating uterine endometrial cancer and ADC measurement has a potential ability to differentiate between normal and cancerous tissue of the endometrium. The ADC values of endometrial cancers of higher grade show tendency to decrease compared to those of lower grade, although estimation of histologic grade based on ADC values seems difficult because of considerable overlap.

The usefulness of diffusion-weighted (DW) magnetic resonance (MR) imaging for the diagnosis of uterine sarcomas was investigated, as well as whether DW images and quantitative measurement of apparent diffusion coefficient (ADC) values can facilitate differentiating uterine sarcomas from benign leiomyomas. MR images including DW images were obtained in 43 surgically treated patients with 58 myometrial tumors, including seven uterine sarcomas (five leiomyosarcomas and two endometrial stromal sarcomas) and 51 benign leiomyomas (43 ordinary leiomyomas, two cellular leiomyomas and six degenerated leiomyomas). Qualitative analysis of non-enhanced and postcontrast MR images and DW images and quantitative measurement of ADC values were performed for each myometrial tumor. Both uterine sarcomas and cellular leiomyomas exhibited high signal intensity on DW images, whereas ordinary leiomyomas and most degenerated leiomyomas showed low signal intensity. The mean ADC value (10(-3) mm(2)/s) of sarcomas was 1.17 +/- 0.15, which was lower than those of the normal myometrium (1.62 +/- 0.11) and degenerated leiomyomas (1.70 +/- 0.11) without any overlap; however, they were overlapped with those of ordinary leiomyomas and cellular leiomyomas. In addition to morphological features on nonenhanced and postcontrast MR sequences, DW imaging and ADC measurement may have a potential ability to differentiate uterine sarcomas from benign leiomyomas.

Gastrointestinal phenotype in cervical adenocarcinomas was examined by immunohistochemistry and correlated with morphologic features. Antibody panels included anti-MUC2, MUC6, CD10, chromogranin A (CGA) and HIK1083. In addition, expression of p16 INK4 , a cyclin-dependent kinase inhibitor which is expressed in a variety of high-risk HPV-related conditions, was studied. A total of 94 invasive adenocarcinomas including 20 minimal deviation adenocarcinomas (MDAs) and 72 adenocarcinomas in situ (AIS) were examined. MDAs were most frequently positive for HIK1083 and/or MUC6, two representative gastric markers, with a rate of 95%, followed by intestinal-type adenocarcinomas (IAs) with a rate of 85% whereas only 27% of 56 usual endocervical-type adenocarcinomas (UEAs) were positive. MUC2, a goblet cell marker, was positive in 85% and 25% of IAs and MDAs, respectively, while in only 14% of UEAs. CD10 was positive in 15% of IAs, indicating incomplete intestinal differentiation without a brush border in most of the cases. CGA-positive cells were frequently seen in MDAs and IAs with rates of 60% and 62%, respectively. Nuclear and cytoplasmic p16 INK4 positivity was identified in 93% of UEAs, whereas 30% of MDAs were positive for p16 INK4 . Results in AISs were comparable to their invasive counterparts, but morphologically usual-type AISs identified in eight cases of MDA were frequently positive for HIK1083 (75%) and MUC6 (63%), and p16 INK4 . Of note was the existence of lobular endocervical glandular hyperplasia (LEGH) with atypical features including cytologic abnormalities, and/or papillary projection, which were identified in this study in pure form (n ¼ 3) or in association with MDAs (n ¼ 6), but not in cases of other types of adenocarcinomas. These observations indicate that gastrointestinal phenotype is frequently expressed in MDAs and IAs, and there seems to be a possible link between MDA, and LEGH and morphologically usual-type AIS with gastric immunophenotype in histogenesis. Frequent absence of p16 INK4 expression in MDAs suggests a possibility that high-risk HPV does not play a crucial role in development of MDAs, in contrast to the majority of endocervical adenocarcinomas. p16 INK4 immunohisto-

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The combination of MRI, Pap smears, and gastric mucin will improve the accuracy of the preoperative diagnosis of MDA and LEGH. Patients suspected of having LEGH may need to be treated with less aggressive methods.

GAS showed aggressive behavior with ominous histopathological predictors as well as decreased survival.• GAS also showed resistance to radiotherapy.• GAS is therefore considered a distinct entity that should be distinguished from UEA. a b s t r a c tObjective. Gastric-type mucinous carcinoma (GAS) is a novel variant of mucinous carcinoma of the uterine cervix. As shown in the original Japanese group description, in recent studies, GAS represents a more aggressive disease than the usual-type endocervical adenocarcinoma (UEA). Detailed clinicopathological features of this variant remain to be elucidated in a larger series of patients.Methods. Patients were enrolled by the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group after receiving the approval of each Institutional Review Board. The study population comprised of women with stage I to II endocervical adenocarcinomas who underwent surgery between 2000 and 2009. Representative slides were evaluated by central pathological review (CPR), categorized into either GAS or UEA, and correlated with clinicopathological features and outcome.Results. Among the 393 enrolled patients with endocervical adenocarcinoma, 328 patients met the criteria for CPR and the study eligibility criteria and were included in further analysis. A total of 95 of the 328 tumors were classified as GAS. Compared with UEA, GAS was more significantly associated with bulky mass, deep stromal invasion, lymphovascular space invasion, parametrial invasion, ovarian metastasis, positive ascitic fluid cytology, j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / y g y n o pelvic lymph node metastasis, and pathological (p) T stage but was not related to the degree of histological differentiation. Disease-free survival (P b 0.0001) and overall survival (P b 0.0001) were poorer in patients with GAS than in those with UEA.Conclusions. GAS showed aggressive behavior with ominous histopathological predictors as well as decreased survival. GAS is therefore considered a distinct entity that should be distinguished from UEA.Clinical trial information. UMIN Clinical Trials Registry: UMIN000007987

Lobular endocervical glandular hyperplasia is a morphologically distinct pseudoneoplastic glandular lesion, which has unique phenotypic characteristics shared by pyloric glands of the stomach. Although most are found incidentally, some cases may show clinical and radiological features resembling those of adenoma malignum.