Two rare cases of benign struma ovarii with malignant recurrence.

Summary: Struma ovarii is an ovarian teratoma that comprises 2-5% of all ovarian teratomas. Malignant transformation of struma ovarii occurs in less than 5% of all cases, and metastatic disease is even rarer. We report two cases initially diagnosed with benign struma ovarii that presented malignant transformation, specifically highly differentiated follicular carcinoma of the ovary (HDFCO), some years after the first diagnosis. Case 1 concerns a 37-year-old female featuring HDFCO of the right ovary with multiple metastatic foci, who was diagnosed with benign struma ovarii 14 years ago. Case 2 concerns a 26-year-old female diagnosed with HDFCO of the left ovary. This patient was initially diagnosed with benign struma ovarii 6 years ago that recurred 4 years after the diagnosis. Both patients were treated with surgery, adjunctive total thyroidectomy, and radioactive iodine (131I) therapy. Learning points: Malignant transformation of struma ovarii is very rare (<5%). Diagnosis of HDFCO without extra ovarian dissemination is difficult due to the resemblance of its histological appearance with normal thyroid tissue. There is no consensus on the postoperative treatment of malignant struma ovarii (MSO). Clinical and histological features of MSO should be assessed for the postoperative treatment decisions. TSH suppression and thyroglobulin level measurements are necessary for patient follow-up.

Nationwide Real-World Data of Microsatellite Instability and/or Mismatch Repair Deficiency in Cancer: Prevalence and Testing Patterns.

Determination of microsatellite instability (MSI)/mismatch repair (MMR) status in cancer has several clinical implications. Our aim was to integrate MSI/MMR status from patients tested in Greece to assess the prevalence of MSI-high (MSI-H)/deficient MMR (dMMR) per tumor type, testing patterns over time and concordance between MSI and MMR status. We retrospectively recorded MSI/MMR testing data of patients with diverse tumor types performed in pathology and molecular diagnostics laboratories across Greece. Overall, 18 of 22 pathology and/or molecular diagnostics laboratories accepted our invitation to participate. In the 18 laboratories located across the country, 7916 tumor samples were evaluated for MSI/MMR status. MSI/MMR testing significantly increased in patients with colorectal cancer (CRC) and other tumor types overtime (p < 0.05). The highest prevalence was reported in endometrial cancer (47 of 225 patients, 20.9%). MSI-H/dMMR was observed in most tumor types, even in low proportions. Among 904 tumors assessed both for MSI and MMR status, 21 had discordant results (overall discordance rate, 2.3%). We reported MSI-H/dMMR prevalence rates in patients with diverse cancers, while demonstrating increasing referral patterns from medical oncologists in the country overtime. The anticipated high rate of concordance between MSI and MMR status in paired analysis was confirmed.

Highly Differentiated Follicular Carcinoma of Ovarian Origin: A Systematic Review of the Literature.

(1) Background: Highly differentiated follicular carcinoma of ovarian origin (HDFCO) is an extremely uncommon neoplasm, associated with struma ovarii. There are scarce cases reported in the literature and, subsequently, no reliable conclusions on its pathophysiology, treatment, and prognosis can be drawn. The goal of this study is to enrich the literature on the topic by adding our own experience with a case, and simultaneously accumulate all cases published up to date. (2) Methods: The present review was performed in accordance with the guidelines for systematic reviews and meta-analyses (PRISMA). PubMed (1966-2022), Scopus (2004-2022), and Clinicaltrials.gov databases were screened for relevant articles published up to July 2022. (3) Results: Twenty patients with HDFCO were identified. The included patients were aged 47.15 years (range 24-74). The predominant origin was ovarian (60%) and extraperitoneal spread was confirmed in 15% of the cases. Surgical treatment varied from conservative to radical (35.3% vs. 41.2%, respectively) and the administration of supplementary therapy and thyroidectomy was not universal. Combined thyroidectomy/radioactive iodine therapy was applied in just 62.5% of the reported cases. There was one patient who demonstrated disease recurrence and lives with the disease. No disease related morbidity was reported. (4) Conclusions: HDFCO represents a low-grade malignant tumor, whose rarity does not allow for reliable conclusions. Standard treatment including complete surgical excision and supplementary treatment seems to offer a favorable prognosis in selected cases.

Could Mismatch Repair Status Serve as a Biomarker for Immunotherapy in Endometrial Carcinoma?

AIM: To study whether mismatch repair (MMR) status is related to the expression of programmed cell death-ligand 1 (PD-L1) and CD8 counts in a series of grade 3 endometrial carcinomas. MATERIALS AND METHODS: The expression of MMR protein PD-L1 and CD8+ cell count were evaluated by immunohistochemistry and related to several clinicopathological parameters. RESULTS: Among 105 endometrial carcinomas, 40% were of endometrioid and 60% of non-endometrioid histology. MMR deficiency was observed in 28.6% of cases and was related to endometrioid histology (p<0.001), positive PD-L1 expression (p=0.047) and high CD8+ cell count (p=0.022). When examined by histotype, endometrioid MMR-deficient tumors were related only to PD-L1 expression (p=0.032) but not to high CD8+ cell count (p=0.231), whereas non-endometrioid MMR-deficient carcinomas were not related to either of these markers. MMR deficiency was associated with PD-L1+/CD8high status (p=0.006), whilst MMR proficiency was associated with PD-L1-/CD8low status. In MMR-proficient tumors, high CD8+ cell infiltration alone and combined with PD-L1- status was associated with better progression-free survival (p=0.013 and p=0.04, respectively). CONCLUSION: MMR-deficient high-grade endometrioid tumors might be more likely to benefit from immunotherapy compared to other grade 3 endometrial carcinomas.

Mismatch repair status in high-grade endometrial carcinomas of endometrioid and non-endometrioid type.

PURPOSE: To evaluate mismatch repair (MMR) status in a series of high-grade endometrial carcinomas and correlate it with several clinicopathological characteristics and with survival. METHODS: One hundred and one patients with high-grade endometrial carcinoma, both of endometrioid and of non-endometrioid type were included in the study. The expression of MLH1, MSH2, MSH6 and PMS2 was evaluated by immunohistochemistry. RESULTS: In our cohort, 41 women had an endometrioid and 60 women a non-endometrioid carcinoma. Endometrioid histotype was statistically more frequent in deficient MMR (dMMR) tumors (73.3%), while non-endometrioid carcinomas in proficient (pMMR) cases (73.8%) (p<0.001). When analyzing the group of endometrioid and non-endometrioid carcinomas separately, only dMMR endometrioid cancers were found to be statistically related to deep myometrial invasion, lymph-node metastases and advanced stage (p=0.035, p=0.011 and p=0.028, respectively). Univariate and multivariate analysis revealed no relation between MMR status and progression-free survival (PFS) or overall survival (OS). Adjuvant treatment was not found to influence the course of the disease. When MMR proteins were studied separately, MLH1/PMS2 loss was related to deep myometrial invasion (p=0.019 and p=0.036, respectively) and MSH6 loss to lymph-node metastases (p=0.04). CONCLUSIONS: In our group of high-grade endometrial carcinomas, MMR deficiency was statistically more frequent in endometrioid than in non-endometrioid cancers. Furthermore, only dMMR endometrioid type grade 3 carcinomas were found to be related with features indicative of aggressive behavior. Considering some unique relation of each MMR protein with distinct clinicopathological features, the assessment of all four proteins is proposed.

Esophageal gastrointestinal stromal tumor: diagnostic complexity and management pitfalls.

Introduction. Gastrointestinal stromal tumors of the esophagus are rare. Case Presentation. This is a case of a 50-year-old male patient who was referred to our department complaining of atypical chest pain. A chest computed tomographic scan and endoscopic ultrasound revealed a submucosal esophageal tumor measuring 5 cm in its largest diameter. Suspecting a leiomyoma, we performed enucleation via right thoracotomy. The pathology report yielded a diagnosis of an esophageal gastrointestinal stromal tumor. The patient has shown no evidence of recurrence one year postoperatively. Conclusions. This report illustrates the complexity and dilemmas inherent in diagnosing and treating esophageal GISTs.

Immunohistochemical evaluation of podocalyxin expression in glomerulopathies associated with nephrotic syndrome.

It is now well established that morphological change of podocytes is closely correlated to the development of proteinuria. The aim of this study was to investigate the role of podocalyxin, a major podocyte protein, in the pathogenesis of glomerulopathies primarily associated with the nephrotic syndrome. Immunohistochemical expression of podocalyxin has been evaluated in 51 renal samples, including healthy controls, patients with podocytopathies (minimal change disease [MCD], focal segmental glomerulosclerosis [FSGS]) and membranous glomerulopathy (MG). A computerized image analysis program has been used. Statistical analysis was performed using analysis of variance and Bonferroni tests. Immunohistochemical expression of podocalyxin has been observed within the podocytes of healthy controls. In MCD, podocalyxin expression was globally reduced despite the normal appearance of the glomeruli. In FSGS, podocalyxin loss was observed in both the segmental sclerotic and the nonsclerotic areas being significantly more prominent in the former. Reduction of podocalyxin in MG was demonstrated for the first time immunohistochemically. The percentage of the stained area was statistical significantly higher in the controls than in each pathologic group. However, among pathologic groups (FSGS, MCD, MG), there was no statistically significant difference. This is one of the few studies investigating podocalyxin immunohistochemical expression in glomerulopathies associated with nephrotic syndrome. The observed reduction in podocalyxin expression suggests that it constitutes a target molecule in nephrotic syndrome pathogenesis regardless of the underlying cause.