Open Access

As Neuroendocrine Tumors (NET) often present as metastatic lesions, immunohistochemical assignment to a site of origin is one of the most important tasks in their pathological assessment. Since a fraction of NETs eludes the typical expression profiles of their primary localization, additional sensitive and specific markers are required to improve diagnostic certainty. We investigated the expression of the transcription factor Pituitary Homeobox 2 (PITX2) in a large-scale cohort of 909 NET and 248 Neuroendocrine Carcinomas (NEC) according to the Immunoreactive Score (IRS) and correlated PITX2 expression groups with general tumor groups and localization of the primary. PITX2 expression (all expression groups) was highly sensitive (98.1%) for midgut-derived NET, but not perfectly specific, as non-midgut NET (especially pulmonary/duodenal) were quite frequently weak or moderately positive. The specificity rose to 99.5% for a midgut origin of NET if only a strong PITX2 expression was considered, which was found in only 0.5% (one pancreatic/one pulmonary) of non-midgut NET. In metastases of midgut-derived NET, PITX2 was expressed in all cases (87.5% strong, 12.5% moderate), while CDX2 was negative or only weakly expressed in 31.3% of the metastases. In NEC, a fraction of cases (14%) showed a weak or moderate PITX2 expression, which was not associated with a specific tumor localization. Our study independently validates PITX2 as a very sensitive and specific immunohistochemical marker of midgut-derived NET in a very large collective of Neuroendocrine Neoplasms. Therefore, our data argue towards implementation into diagnostic panels applied for NET as a first line midgut marker.

Ferroelectricity, where electronic degrees of freedom determine the polar order—thereby enabling fast switching and phase control—is an important research field in current condensed-matter physics. Using a combination of resistance noise and dielectric spectroscopy we investigate the nature of relaxor-type electronic ferroelectricity in the organic conductor κ-(BETS)2Mn[N(CN)2]3, a system that represents a wider class of materials of correlated electron systems for which functionalities for organic spintronics recently have been discussed. The two complementary spectroscopies reveal a distinct low-frequency dynamics on different length scales, namely (i) an intrinsic relaxation that is typical for relaxor ferroelectrics which classifies the systemas a possible new multiferroic, and (ii) twolevel processes which we identify as fluctuating polar nanoregions (PNR), i.e., clusters of quantum electric dipoles that fluctuate collectively. The PNR preform above the metal insulator (MI) transition. Upon cooling through TMI, a drastic increase of the low-frequency 1/f-type fluctuations and slowing down of the charge carrier dynamics is accompanied by the onset of strong non-equilibrium dynamics indicating a glassy transition of interacting dipolar clusters. The freezing of PNR and non-equilibrium dynamics is suggested to be a common feature of organic relaxor-type electronic ferroelectrics.

Improved long-term survival rates after allogeneic hematopoietic cell transplantation (alloHCT) make family planning for young adult cancer survivors an important topic. However, treatment-related infertility risk poses challenges. To assess pregnancy and birth rates in a contemporary cohort, we conducted a national multicenter study using data from the German Transplant Registry, focusing on adult women aged 18-40 who underwent alloHCT between 2003 and 2018. Out of 2,654 transplanted women, 50 women experienced 74 pregnancies, occurring at a median of 4.7 years post-transplant. Fifty-seven of these resulted in live births (77%). The annual first birth rate among HCT recipients was 0.45% (95%CI: 0.31 - 0.59%), which is more than six times lower than in the general population. The probability of a live birth 10 years after HCT was 3.4 % (95%CI: 2.3- 4.5%). Factors associated with an increased likelihood of pregnancy were younger age at alloHCT, non-malignant transplant indications, no total-body-irradiation (TBI) or a cumulative dose of <8 Gray, and non-myeloablative/reduced-intensity conditioning. 72% of pregnancies occurred spontaneously, with assisted reproductive technologies (ART) used in the remaining cases. Preterm delivery and low birth weight were more common than in the general population. This study represents the largest dataset reporting pregnancies in a cohort of adult female alloHCT recipients. Our findings underscore a meaningful chance of pregnancy in alloHCT recipients. ART techniques are important and funding should be made available. However, the potential for spontaneous pregnancies should not be underestimated, and patients should be informed of the possibility of unexpected pregnancy despite reduced fertility. Further research is warranted to understand the impact of conditioning decisions on fertility preservation.