Progression Patterns in Non-Contrast-Enhancing Gliomas Support Brain Tumor Responsiveness to Surgical Lesions.

Purpose: The overall benefit of surgical treatments for patients with glioma is undisputed. We have shown preclinically that brain tumor cells form a network that is capable of detecting damage to the tumor, and repair itself. The aim of this study was to determine whether a similar mechanism might contribute to local recurrence in the clinical setting. Methods: We evaluated tumor progression patterns of 24 initially non-contrast-enhancing gliomas that were partially resected or biopsied. We measured the distance between the new contrast enhancement developing over time, and prior surgical lesioning, and evaluated tumor network changes in response to sequential resections by quantifying tumor cells and tumor networks with specific stainings against IDH1-R132H. Results: We found that new contrast enhancement appeared within the residual, non-enhancing tumor mass in 21/24 patients (87.5%). The location of new contrast enhancement within the residual tumor region was non-random; it occurred adjacent to the wall of the resection cavity in 12/21 patients (57.1%). Interestingly, the density of the glioma cell network increased in all patient tumors between initial resection or biopsy and recurrence. In line with the histological and radiological malignization, Ki67 expression increased from initial to final resections in 14/17 cases. Conclusion: The non-random distribution of glioma malignization in patients and unidirectional increase of anatomical tumor networks after surgical procedures provides evidence that surgical lesions, in the presence of residual tumor cells, can stimulate local tumor progression and tumor cell network formation. This argues for the development of intraoperative treatments increasing the benefits from surgical resection by specifically disrupting the mechanisms of local recurrence, particularly tumor cell network functionality.

Endometrial microcalcifications detected by ultrasonography: clinical associations, histopathology, and potential etiology.

Endometrial microcalcifications are uncommon, with alleged clinical implications ranging from innocuous to ominous. We reviewed the histopathologic slides from 29 patients who had endometrial echogenic foci on pelvic ultrasound and found many endometrial microcalcifications. The extent of microcalcifications in each specimen was graded on a semiquantitative scale from 0 to 3. The mean patient age was 54 years (range, 34-81 years). The specimens included endometrial biopsies, curettages, and hysterectomies. Most of the patients had presented with abnormal vaginal bleeding. Fifteen patients (51.7%) were postmenopausal, 10 (34.5%) were premenopausal, and the rest were perimenopausal. The most frequent endometrial types were atrophic (39.5%), inactive (23.3%), and proliferative (14%). Six specimens (14%) showed benign endometrial polyps. One patient had well-differentiated endometrioid carcinoma of the endometrium without myometrial invasion. Specimens from 16 patients (55.2%) had microcalcifications. The patients with calcifications were older than those without calcifications (mean age, 60 vs. 47 years, respectively; P = 0.017). The extent of microcalcifications positively correlated with the presence of endometrial polyps (P = 0.00076), postmenopausal state (P = 0.004), atrophic endometrium (P = 0.002), and hormone replacement therapy (P = 0.013). The microcalcifications were concentric or amorphous, intraglandular or stromal. They were focally associated with minute papillary epithelial projections or with degenerated endometrial glands. Follow-up was available on 26 patients (89.7%). Except for the patient with endometrioid carcinoma, none has developed uterine, adnexal, or peritoneal malignancy. In summary, endometrial microcalcifications are histologically heterogeneous and are associated with older patient age, postmenopausal state, atrophic endometrium, and endometrial polyps. Those found incidentally by means of pelvic ultrasonography, in our experience, did not portend malignancy.