Coexistence of Hashimoto's Thyroiditis in Differentiated Thyroid Cancer: Post-Operative Monitoring of Anti-Thyroglobulin Antibodies and Assessment of Treatment Response.

INTRODUCTION: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto's thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. METHODS: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. RESULTS: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. CONCLUSIONS: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.

Primary large B-cell lymphoma involving the cerebellopontine angle mimic acoustic schwannoma: Role of MR Spectroscopy in differential diagnosis. A case report.

Primary central nervous system (CNS) lymphoma is a very rare aggressive non-Hodgkin disease that originates in CNS (brain, leptomeninges, spinal cord, or eyes). It seems to have increased over the last two decades in both immunocompromised and immunocompetent patients. Primary large B-cell lymphoma involving the cerebellopontine angle (CPA) is extremely rare: only 15 cases of large B-cell lymphoma of the CPA have been reported worldwide; based on our knowledge, no cases studied with MR Spectroscopy. Primary large B-cell lymphoma of the CPA must be differentiated from other cerebellopontine angle diseases, such as acoustic neuroma and meningioma. An early and accurate diagnosis of this neoplasm is necessary for the best management because it is a radiosensitive and chemosensitive tumor. Herein, we report a rare case of B-cell lymphoma involving the left CPA in a 65-year-old man who presented with 3 months of hearing loss on the left, illustrated by MR and TC imaging, highlighting how the MR Spectroscopy, thanks to their greater specificity, is decisive in achieving the correct diagnosis of primary lymphoma and differentiating it from acoustic schwannoma or meningioma. Therefore, in the suspicion of a malignant heteroplastic lesion of the CPA, we suggest including Spectroscopy in the MR study protocol.

Current and emerging investigational venetoclax-based therapies in chronic lymphocytic leukemia.

Introduction: Venetoclax has emerged as a breakthrough treatment which has revolutionized the therapeutic paradigm of chronic lymphocytic leukemia (CLL). This is primarily attributed to the efficacy of venetoclax as a time-limited, chemo-free, therapy in a field dominated by targeted agents given on a continuous schedule. Furthermore, compelling clinical data support the use of venetoclax in combination with other targeted agents in the hope of preventing drug resistance due to the emergence of acquired mutations.Areas covered: This paper provides an overview of clinical results of newly approved or investigational venetoclax-based therapies for CLL. In view of current and potential roles in CLL care, the strengths and disadvantages of venetoclax-combinations are discussed. The MEDLINE database, ClinicalTrials.gov and conference proceedings were all reviewed to select the relevant literature.Expert opinion: While the advent of venetoclax-based combinations has significantly expanded the therapeutic options for patients with CLL, further research with longer follow-up is required to address remaining open questions such as (I) the role of venetoclax as fixed duration therapy(II) timing and threshold of minimal residual disease (MRD) assessment for therapy discontinuation, (III) the efficacy of novel triplet combinations with venetoclax as backbone therapy, (IV) indications for the re-initiation of therapy with venetoclax.

Sister chromatid exchange: A possible approach to characterize familial breast cancer patients.

Sister chromatid exchange (SCE) frequency is widely used as an indicator of spontaneous chromosome instability. We investigated SCE frequency in the peripheral blood lymphocytes of familial and sporadic breast cancer (BC) patients from the Apulian Caucasian Population. Eighty-one patients were enrolled: 22 with familial history and 59 sporadic patients. Eleven familial patients had an 'increased risk' of BRCA gene mutation (BRCAPro ≥ 10%) and were candidates for BRCA1 and BRCA2 mutation analysis. For these reasons, we stratified the 22 familial BC patients in two group: 'low-risk' (n=11) and 'high-risk' (n=11) patients for BRCA gene mutations. Two of these 11 'high-risk' patients (18%) had pathogenic mutations in the BRCA2 gene. The subjects were not cigarette smokers or alcohol or drug users, and had no genetic disorders or chronic diseases affecting the family. Our results showed a significant increase in SCE frequency in the familial (5.305 ± 1.088/metaphase) (P<0.0001) and the sporadic patients (3.943 ± 0.552) (P<0.0001) compared to the controls (3.197 ± 0.649). We found that the SCE frequency was always significantly higher in familial than in sporadic patients, regardless of their clinicopathological characteristics. Moreover, we observed that the frequency of SCE in BRCA2 mutation carrier patients was higher compared to patients without mutations in BRCA1/2 genes. These findings highlight an intrinsic genomic instability in familial patients, and we suggest that SCE frequency may be used as a biomarker to better characterize familial BC.

In vitro short-term test evaluation of catecholestrogens genotoxicity.

Estrogens are indicated as being the most important etiological factors for the development and progression of breast cancer. The implication of estrogen in breast cancer has been associated mostly with the estrogen receptors that mediate cell proliferation. Evidence also exists to support the hypothesis of a direct role of estrogens as tumor initiators. However, the role of estrogen genotoxicity in breast cancer is still questionable. In this study the genotoxic activity of catecholestrogens and 16alpha-hydroxy estrone has been investigated by performing Salmonella strain TA98 and TA100 Ames tests, sister chromatide exchange assays (SCE) and micronucleus assays on human peripheral lymphocytes (CBMN and ARA/CBMN). We found a lack of positive results with micronucleus assays, except for 2-hydroxy estradiol (2-OHE(2)), which shows a peculiar "bell shaped" trend of micronucleus number versus concentrations. SCE assay suggests weak genotoxic activity of all tested catechol metabolites, except 4-hydroxy estrone (4-OHE(1)), which also showed negative results by ARA/CBMN. In this open debate, our results support the hypothesis of a weak genotoxicity, not correlated with the carcinogenetic potential of estrogens.