FSH-producing pituitary neuroendocrine tumor as a cause of ovarian hyperstimulation syndrome.

Summary: Functioning gonadotroph tumors are rare neoplasms that can cause ovarian hyperstimulation syndrome (OHSS) in women of reproductive age. Here, we present a case of a follicle-stimulating hormone (FSH)-producing pituitary neuroendocrine tumor (PitNET) with irregular menstrual cycles and OHSS in a Japanese woman. A 34-year-old woman with bilateral multi-cystic ovarian mass was referred to our hospital for ovarian surgery. The imaging feature of magnetic resonance imaging (MRI) of the ovary and elevated estradiol levels with normal FSH and low luteinizing hormone (LH) levels led us to suspect the presence of a functioning gonadotroph PitNET. MRI revealed a 19-mm pituitary tumor, and increased tracer uptake was observed in the pituitary lesion on 111In-pentetreotide scintigraphy. Transsphenoidal tumor resection resulted in the resolution of the ovarian enlargement, normalization of her menstrual cycles, and spontaneous pregnancy. Immunohistochemistry (IHC) of the resected tumor for pituitary transcription factors, including steroidogenesis factor 1 (SF1) and estrogen receptor alpha, demonstrated positive immunoreactivity, whereas IHC for pituitary-specific positive transcription factor 1 was negative, suggesting that the tumor belonged to the SF1 lineage of PitNETs (gonadotroph tumor). The tumor cells showed positive expression of FSHß, while LHß was mostly negative. Consistent with the high pituitary tumor uptake observed on 111In-pentetreotide scintigraphy, the pituitary tumor showed positive expression of somatostatin receptor 2A. Detailed clinical and histological evaluations will provide useful information to understand these rare functioning gonadotroph tumors better. Learning points: Functioning gonadotroph tumors are very rare neuroendocrine tumors of pituitary origin. Women of reproductive age presenting with bilateral multi-cystic ovarian enlargement, irregular menstrual cycles, and hyperestrogenemia under unsuppressed follicle-stimulating hormone (FSH) levels should be evaluated for FSH-producing tumor. Raising awareness of OHSS due to functioning gonadotroph tumors is crucial to prevent unnecessary ovarian surgery. Comprehensive histological analysis may provide useful information to better understand the characteristics of functioning gonadotroph tumors.

Diagnostic Value of DCE-MRI for Differentiating Malignant Adnexal Masses Compared with Contrast-enhanced-T1WI.

PURPOSE: To compare the diagnostic performance of dynamic contrast-enhanced-MR (DCE-MR) and delayed contrast-enhanced (CE)-MRI added to unenhanced MRI, including diffusion weighted image (DWI) for differentiating malignant adnexal tumors, conducting a retrospective blinded image interpretation study. METHODS: Data of 80 patients suspected of having adnexal tumors by ultrasonography between April 2008 and August 2018 were used for the study. All patients had undergone preoperative MRI and surgical resection at our institution. Four radiologists (two specialized in gynecological radiology and two non-specialized) were enrolled for blinded review of the MR images. A 3-point scale was used: 0 = benign, 1 = indeterminate, and 2 = malignant. Three imaging sets were reviewed: Set A, unenhanced MRI including DWI; Set B, Set A and delayed CE-T1WI; and Set C, Set A and DCE-MRI. Imaging criteria for benign and malignant tumors were given in earlier reports. The diagnostic performance of the three imaging sets of the four readers was calculated. Their areas under the curve (AUCs) were compared using the DeLong method. RESULTS: Accuracies of Set B were 81%-88%. Those of Set C were 81%-85%. The AUCs of Set B were 0.83 and 0.89. Those of Set C were 0.81-0.86. For two readers, Set A showed lower accuracy and AUC than Set B/Set C (less than 0.80), although those were equivalent in other readers. No significant difference in AUCs was found among the three sequence sets. Intrareader agreement was moderate to almost perfect in Sets A and B, and substantial to almost perfect in Set C. CONCLUSION: DCE-MR showed no superiority for differentiating malignant adnexal tumors from benign tumors compared to delayed CE-T1WI with conventional MR and DWI.

Mesonephric-like adenocarcinoma of the ovary in an elderly woman: A case report and a review of the literature.

Mesonephric-like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical mesonephric adenocarcinoma (MA). Here, we present a case of MLA of the ovary along with a literature review. An asymptomatic 84-year-old woman presented with a pelvic mass, detected by computerized tomography. Magnetic resonance imaging demonstrated a polycystic mass with a solid component in the left adnexal region. The solid component showed low signal intensity on T2-weighted imaging and high signal intensity on diffusion-weighted imaging. We strongly suspected an ovarian malignant tumor; therefore, surgical resection of the uterus and adnexa was performed. Macroscopically, the tumor was predominantly solid with yellowish-tan cut surface. Microscopically, it showed a tubular pattern with intraluminal colloid-like material resembling MA. The tumor cells were negative for estrogen receptor, calretinin, and CD10 and positive for PAX8 and TTF-1. These findings are consistent with those of MLA.

Diagnostic Accuracy of Magnetic Resonance Imaging for International Federation of Gynecology and Obstetrics 2018 IB to IIB Cervical Cancer Staging: Comparison Among Magnetic Resonance Sequences and Pathologies.

OBJECTIVE: This study aimed to investigate the most accurate magnetic resonance (MR) sequence for tumor detection, maximal tumor diameter, and parametrial invasion compared with histopathologic diagnoses. METHODS: Fifty-one patients with International Federation of Gynecology and Obstetrics 2018 IB1 to IIB cervical cancer underwent preoperative MR imaging and surgical resection. Two radiologists independently evaluated the tumor detection, parametrial invasion, and tumor size in each of T2-weighted image, diffusion-weighted image, and contrast-enhanced T1-weighted image. Results obtained for squamous cell carcinoma (SCC) and adenocarcinoma were also compared. RESULTS: Neither the tumor detection rate nor parametrial invasion was found to be significantly different among sequences. Tumor size assessment using MR imaging with pathology showed good correlation: r = 0.63-0.72. The adenocarcinoma size tended to be more underestimated than SCC in comparison with the pathologic specimen. CONCLUSIONS: Cervical cancer staging by MR images showed no significant difference among T2-weighted image, diffusion-weighted image, and contrast-enhanced T1-weighted image. Adenocarcinoma was prone to be measured as smaller than the pathologic specimen compared with SCC.

Diagnostic performance of preoperative MR imaging findings for differentiation of uterine leiomyoma with intraligamentous growth from subserosal leiomyoma.

PURPOSE: To evaluate the diagnostic performance of MRI findings for differentiating uterine leiomyoma with intraligamentous growth, or broad ligament fibroid, from subserosal leiomyoma. METHODS: This study included 37 patients with surgically confirmed uterine smooth muscle tumors (36 leiomyomas and one smooth muscle tumor of uncertain malignant potential) with intraligamentous growth (IL) and size-matched control of 37 patients with subserosal leiomyoma (SS). Two radiologists independently evaluated eight preoperative MRI findings: tumor shape, degeneration, attachment to uterus, ovary elevation, ureter displacement, bladder deformation, rectal displacement, and separation of round ligament (RL) and uterine artery (UA). The diagnostic values of these findings and interobserver agreement were assessed. Receiver-operating characteristic (ROC) analysis of the number of positive MRI findings for diagnosing IL was performed. Clinical outcomes including surgical method, operation time, intraoperative blood loss, perioperative complications, and postoperative hospital stay of the two groups were compared. RESULTS: Significant differences in tumor shape, attachment to uterus, ovary elevation, ureter displacement, and separation of RL and UA were found between IL and SS. Four of these findings, excluding ureter displacement, showed moderate to substantial interobserver agreement. When two or more of these four findings were positive, sensitivity, specificity, and area under the ROC curve were 91%, 77%, 0.90 in reader 1 and 82%, 89%, 0.91 in reader 2. The operation time was significantly longer for IL than for SS. CONCLUSION: Tumor shape, attachment to uterus, ovary elevation, and separation of RL and UA are useful MRI findings for differentiating intraligamentous leiomyoma from subserosal leiomyoma.

Diffusion-weighted imaging of uterine adenomyosis: Correlation with clinical backgrounds and comparison with malignant uterine tumors.

AIM: To elucidate correlation between signal intensity on diffusion-weighted images (SI-DWI) and clinical backgrounds for uterine adenomyosis and to compare SI-DWI of adenomyosis and malignant uterine tumors. METHODS: This study examined 46 adenomyosis patients diagnosed using magnetic resonance imaging and 25 patients with surgically confirmed malignant uterine myometrial tumor. First, adenomyosis cases were classified visually into high-intensity and low-intensity groups based on the SI-DWI compared with that of normal uterine myometrium. Secondly, correlation was assessed between SI-DWI of adenomyosis and patient clinical background information such as age, menopausal status, menstrual cycle and dysmenorrhea severity. Third, quantitative comparison was made of low-intensity adenomyosis (LIA), high-intensity adenomyosis (HIA) and malignant tumor groups for the signal intensity ratio (SIR) on DWI and the apparent diffusion coefficient (ADC). Their diagnostic performance was evaluated using logistic regression analysis and receiver operating characteristic (ROC) analysis. RESULTS: The 46 adenomyosis cases were classified as 26 low-intensity and 20 high-intensity cases. Significant correlation was found only for menstrual cycle phases. HIA had significantly lower SIR and higher ADC than malignant tumor. The ADC of HIA was significantly higher than that of LIA. The combination of SIR and ADC showed excellent diagnostic performance (area under ROC curve, 0.99). CONCLUSION: There is a variation in signal intensity on DWI of uterine adenomyosis and it is associated with menstrual cycle phase. Adenomyosis with high signal intensity on DWI can be differentiated from malignant lesions by its lower signal intensity on DWI and higher ADC than that found for malignant uterine tumors, however overlaps exist.

Microcystic, Elongated and Fragmented Pattern Invasion Can Adversely Influence Preoperative Staging for Low-grade Endometrial Carcinoma.

PURPOSE: To investigate the influence of microcystic, elongated and fragmented (MELF) pattern invasion on preoperative evaluation of lymph node (LN) metastasis and myometrial invasion in patients with low-grade endometrial carcinoma. METHODS: The study included 192 consecutive patients with low-grade endometrial carcinoma who underwent preoperative computed tomography (CT) and magnetic resonance imaging (MRI), followed by surgery. One hundred sixty one of 192 patients underwent LN dissection and were analyzed for LN metastasis. All patients were analyzed for myometrial invasion. Presence of enlarged LN was evaluated by using size criteria on CT. Depth of myometrial invasion was evaluated on MRI using T2-weighted imaging, diffusion-weighted imaging and contrast-enhanced T1-weighted imaging comprehensively. Sensitivity and specificity for LN metastasis and deep myometrial invasion were evaluated for MELF group and non-MELF group. The difference of sensitivity between two groups was compared using Chi-square and Fisher's exact test. RESULTS: MELF pattern invasion was identified in 43/192 patients (22%). LN metastases were observed in 18/39 patients in MELF group and 6/122 patients in non-MELF group for pelvic LN and 11/29 patients in MELF group and 4/57 patients in non-MELF group for para-aortic LN. Sensitivity for the detection of pelvic LN metastasis in MELF group was significantly lower than in non-MELF group (16.7% vs 66.7%). As for the assessment of the deep myometiral invasion, pathological deep myometrial invasion were found in 31/43 patients in MELF group and 32/149 patients in non-MELF group. Sensitivity in MELF group showed lower values than in non-MELF group (54.8% vs 78.1% for reader 1, 54.8% vs 62.5% for reader 2), although there was no statistically significant difference (P = 0.09 for reader 1 and P = 0.72 for reader 2). CONCLUSION: In case of low-grade endometrial carcinoma with MELF pattern invasion, preoperative staging by CT and MRI have a risk for underestimation.

MR findings of uterine PEComa in patients with tuberous sclerosis: report of two cases.

Tuberous sclerosis complex (TSC), a rare autosomal dominant neurocutaneous disorder, is characterized by the presence of benign congenital tumors in multiple organs. Neoplasms with perivascular epithelioid cell differentiation (PEComas), including angiomyolipoma (AML) and lymphangioleiomyomatosis (LAM), can occur in association with TSC. This report describes two cases of uterine PEComas presenting characteristic MR imaging features reflecting pathological findings. From MR images, both cases showed single or multiple large, irregularly shaped or lobulated hemorrhagic lesions within the myometrium. They differed from typical adenomyotic cysts in their large size and irregular margins. Histopathologic analysis revealed that the hemorrhage was caused by adenomyosis and tumor cells that proliferated in surrounding stroma of the hemorrhagic lesions, compatible with PEComas. Microscopic observation revealed an infiltrative growth pattern of PEComas, with small nodules formed. The tumor lesions, however, were difficult to detect on MR images. The myometrium showed normal appearance on both T1-weighted and T2-weighted images in both cases. We speculate that PEComas may infiltrate extensively into the myometrium even when the myometrium shows almost normal radiologic appearance.

Longitudinal changes in magnetic resonance imaging of malignant and borderline tumors associated with ovarian endometriotic cyst comparing with endometriotic cysts without arising malignancy.

PURPOSE: To investigate magnetic resonance (MR) findings and to detect malignant transformation of ovarian endometriotic cysts by comparing longitudinal changes in patients with ovarian malignant/borderline tumors associated with ovarian endometriotic cysts (tumor group) with those of patients with endometriotic cysts (control group). METHODS: Tumor group patients (n = 10) had ovarian malignant/borderline tumors with pathologically confirmed association with endometriosis and available prior MRI of endometriotic cysts. Control group patients (n = 40) had been diagnosed more than two times as having ovarian endometriotic cysts by MRI examination. The tumor and solid portion sizes were measured. Two radiologists independently evaluated signal intensity (SI) of the cystic portion on both T1-weighted and T2-weighted images (WI), presence of shading on T2WI, and T2 dark spot sign in both groups and evaluate longitudinal changes of those findings. RESULTS: Pathological diagnoses of the tumor group were clear cell carcinoma (n = 6), endometrioid carcinoma (n = 1), serous carcinoma (n = 1), mucinous borderline tumor (n = 1), and endometrioid borderline tumor (n = 1). Tumor size had increased significantly in the tumor group (p = .004), but not in controls. Solid portions were identified in all cases only when neoplasms were suspected. Disappearance of shading during the follow-up period was observed more in tumor group (n = 2) than in the controls (n = 0). No significant difference was found between groups in the SI on T1 and T2WI, and T2 dark spot sign for the two MR examinations. CONCLUSIONS: The MR findings suggesting malignant transformation were emergence of a solid portion and increase in cyst size. Disappearance of shading also facilitates the follow-up of endometriotic cysts.

A Predictor of Tumor Recurrence in Patients With Endometrial Carcinoma After Complete Resection of the Tumor: The Role of Pretreatment Apparent Diffusion Coefficient.

OBJECTIVES: The aim of this study was to assess the prognostic and incremental value of pretreatment apparent diffusion coefficient (ADC) values of tumors for the prediction of tumor recurrence after complete resection of the tumor in patients with endometrial cancer. METHODS: This study enrolled 210 patients with stages IA to IIIC endometrial cancer who had undergone complete resection of the tumor and pretreatment magnetic resonance imaging. The minimum and mean ADC values (ADCmin, ADCmean) of tumors and normalized ADC (nADCmin, nADCmean) were calculated from magnetic resonance imaging. The primary outcome was recurrence-free survival (RFS). Receiver operating characteristic analysis was performed to compare the diagnostic performance of ADC values of 4 types. The Kaplan-Meier method, log-rank tests, and Cox regression were used to explore associations between recurrence and the ADC values with adjustment for clinicopathological factors. RESULTS: In receiver operating characteristic curve analysis, the areas under the curve were significant for ADCmean and nADCmean predicting tumor recurrence but were not significant for ADCmin and nADCmin. Regarding univariate analysis, ADCmean and nADCmean were significantly associated with increased risk of recurrence. Multivariate analysis showed that ADCmean and nADCmean remained independently associated with shorter RFS. In the high-risk group, the RFS of patients with lower ADC values (ADCmean and nADCmean) was significantly shorter than that of patients in the higher ADC value group. CONCLUSIONS: Pretreatment tumor ADCmean and nADCmean were important imaging biomarkers for predicting recurrence in patients after complete resection of the tumor. They might improve existing risk stratification.

Solitary oropharyngeal neurofibroma: MR appearance with pathologic correlation and review of the literature.

Although neurofibroma is a common soft tissue tumor of the head and neck, neurofibroma of the oropharynx is extremely rare. Here, we report a case of neurofibroma of the palatine tonsil. Magnetic resonance imaging was useful in demonstrating the location of the tumor as well as its well-defined appearance. The present case showed a target sign; the tumor exhibited peripheral hyperintensity and central hypointensity on T2-weighted images, reflecting its characteristic zonal anatomy.