Classic Hodgkin lymphoma (CHL) is a well-defined neoplasm characterized by the presence of a minority of pathognomonic Hodgkin and Reed–Sternberg (HRS) cells in a reactive inflammatory background. Although genotypically of B cell origin, HRS cells exhibit a downregulated B cell program and therefore are set apart from other B cell lymphomas in the current WHO classification. However, cases with morphological and phenotypic features overlapping with CHL have been recognized, and the category of B cell lymphoma—unclassifiable—with features intermediate between diffuse large B cell lymphoma (DLBCL) and CHL, also termed grey zone lymphoma, was first introduced into the WHO classification in 2008 as provisional entity. These cases, as well as others raising a differential diagnosis of CHL can present diagnostic problems, as well as therapeutic challenges. Whereas some of these lymphomas only represent biologically unrelated morphological mimics, others, especially mediastinal grey zone lymphoma, exhibit genetic and gene expression profiles which overlap with CHL, indicating a true biological relationship. In this review, we address areas of diagnostic difficulties between CHL and other lymphoma subtypes, discuss the biological basis of true grey zone lymphoma based on recent molecular studies and delineate current concepts for the classification of these rare tumors.

Congenital Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a Mullerian-duct anomaly that is characterized by agenesis of the uterus and upper part of the vagina. Uterus remnants of varying sizes can often be found. Although a functional uterus is missing, the existence of endometriosis in this patient group has been described in the literature; however, a histopathological comparison of the characteristics of the endometrium within the uterus remnants versus endometriotic peritoneal lesions in the same patient is lacking. Moreover, the characteristics of endometriotic tissue in patients with MRKH syndrome have not been correlated with those of patients with endometriosis without Mullerian anomaly. Patients who underwent laparoscopic neovagina creation with the removal of uterus remnants and possible resection of endometriotic lesions between 2010 and 2022 at the Department of Women’s health of the University of Tuebingen were included in our study. Uterine remnants and endometriotic tissue were evaluated via histopathology and immunohistochemistry and were compared to endometriotic samples from patients without Mullerian anomaly. Endometriosis was detected in nine MRKH patients; in four patients, endometrial remnants could be sufficiently compared to endometriotic lesions. All samples exhibited increased expression of hormonal receptors. In two patients, Ki67 proliferation index was significantly increased in peritoneal endometriotic lesions compared with the endometrium of the remnants. In contrast, endometrium and endometriotic lesions of endometriosis patients did not exhibit any differences in the Ki67 proliferation index. Our results demonstrate distinctive immunohistochemical variability between uterine remnants and endometriotic lesions in patients with MRKH syndrome compared with patients with endometriosis, indicating a possible explanation model of the yet-unknown etiology of endometriosis. For confirmation, investigation of a broader patient collective is necessary.

Recent studies have revealed an association between TP53 mutations and endocrine resistance in hormone receptor-positive, HER2-negative breast cancer (HR + HER2 −BC). Aberrant p53 immunostaining (IHC) patterns may provide a surrogate marker for TP53 mutations. Building upon a ternary algorithm of aberrant staining patterns, this study evaluates the reliability of p53 IHC as screening tool for TP53 mutations in BC (NST). Furthermore, it describes the histopathological and molecular characteristics of TP53-mutated cases, along with the mutational status of PIK3CA. This study comprised 131 early-stage, node-negative BCs with available core biopsies and resection specimens. Cases were categorized as follows: HR + HER2 − (85 cases), HER2 + (21 cases) and triple negative (TN, 25 cases). Aberrant IHC staining patterns for p53 were defined as overexpression (OE), complete absence (CA) and cytoplasmic (CY). In addition, targeted sequencing of TP53 and PIK3CA genes was performed. TP53 mutations were identified in 53 of 126 cases (42.1%). Within HR + HER2 − cases, TP53 mutations were found in 17 of 80 cases (21.3%). IHC accurately predicted TP53 mutation in 96.2% of cases with a specificity of 100%. Additionally, there was a significant agreement between missense mutations and OE, as well as between truncating mutations and CA (κ 73% and 76%). CY was observed in two TN cases with truncating mutations within the nuclear localization signalling domain of p53. TP53-mutated cases exhibited higher grade, greater nuclear pleomorphism and higher Ki-67 proliferation index and were associated with the PIK3CA wild-type status (p < 0.001). p53 IHC may provide a useful screening tool for identifying TP53-mutated BC of NST.

Cancer affects the mechanical properties of tissue. Therefore, elastography techniques can be used to differentiate cancerous from healthy tissue. Due to probe size and restricted handling, most elastography techniques are not applicable in minimally invasive surgery (MIS). Established techniques such as endoscopic ultrasound elastography measure under undefined boundary conditions, making the determination of quantitative mechanical properties challenging. Water flow elastography (WaFE) has recently been introduced for application in MIS. Here, we present an improved WaFE measurement method in which the probe attaches itself to the sample with a small suction pressure. This leads to defined boundary conditions, allowing for a quantitative determination of the Young's modulus of tissue. To facilitate fast measurements, we developed a correction model for the hydrodynamic resistance and the fluid inertia of the tubing. We used WaFE for ex vivo measurements on human bladders and found a significantly larger Young's modulus for cancerous vs. healthy tissue. We determined the optimal classification threshold for the Young's modulus to be 8 kPa and found that WaFE can differentiate between cancerous and healthy tissue with a sensitivity of 0.96 and a specificity of 1. Our results underline that WaFE can be a helpful differentiating tool in MIS.