Histopathological assessment of tumour regression, nodal stage and status of resection margins determines prognosis in patients with oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy.

OBJECTIVES: In advanced oral squamous cell carcinoma (OSCC), tumour regression after neoadjuvant radiochemotherapy seems to be an important prognostic factor. In this study, we intended to compare regression grading according to two previously described regression models and to analyse the association of tumour regression and other tumour characteristics with patients' characteristics and overall survival. METHODS: The retrospective study included 63 treatment-naive patients with primary OSCC of stages II-IV, who were treated with a concomitant neoadjuvant radiochemotherapy followed by radical surgery. Assessment of histopathological features was performed, there under regression grading according to two previously described regression models. RESULTS: Both tumour regression models provided comparable results in terms of distribution of different regression grades. In univariate analysis regression gradings (P = 0.003 and P = 0.007), ypT-stage, ypN-stage and status of resection margins (P < 0.001) were significantly associated with the 5-year overall survival (OS). None of the pretreatment clinicopathological parameters showed association with histopathological tumour regression. Multivariate analysis revealed the status of resection margins and of lymph node metastasis as statistically significant features for OS (P = 0.020 and P = 0.003, respectively). CONCLUSION: Tumour regression grading, nodal stage and status of resection margins predict prognosis in patients after neoadjuvant treatment. Currently, there are no pretreatment clinicopathological parameters, which predicting good tumour response to therapy. Thus, identifying non-responding patients, which might benefit from an intensified systemic therapy, requires surgical resection and consecutive histopathological assessment. Therefore, further investigation and validation of new, especially, molecular predictors of tumour response to radiochemotherapy remains an unmet, future clinical need.

Evaluation of histological regression grading systems in the neoadjuvant therapy of rectal cancer: do they have prognostic impact?

PURPOSE: Neoadjuvant treatment options have been developed to improve survival of patients with locally advanced rectal cancer. As only patients with a major histopatholocial response benefit from this preoperative therapy, several tumor regression grading systems have been developed. However, currently no accepted comprehensive grading system for clinical use is available. Therefore, we studied the impact of four histological regression grading systems in the neoadjuvant therapy of rectal cancer. METHODS: In this retrospective study, 85 patients with locally advanced rectal cancer were included. All patients received a neoadjuvant radiochemotherapy followed by surgical resection. The histological regression grading was evaluated using four classification systems: (1) grading system by the Japanese society of colorectal cancer, (2) grading system by Junker-Müller, (3) grading system by Dworak, (4) Cologne grading system. The four classification systems were analyzed for their prognostic impact. RESULTS: The following significant correlations were detected between the four classification systems and the ypTNM categories: (1) patients with a ypT3/4 category had significantly more often a worse histopathologic response in all four grading systems (p = 0.001); (2) a ypN0 category was significantly correlated with good histopathologic response only in the Cologne grading system; (3) in the Junker-Müller and Dworak grading systems, a ypM0 category was significantly correlated with a good histopathologic response (p = 0.046; p = 0.03). However, none of the used classification systems had a prognostic impact on survival. CONCLUSIONS: Currently, none of the analyzed histological regression grading systems is effective for clinical use.

[Current aspects of liver allograft pathology]. / Aktuelle Aspekte zur Histopathologie im Rahmen der Lebertransplantation.

Liver allograft pathology continues to play an important role in the diagnosis and management of complications in the course of liver transplantation. This article summarizes important patterns of liver damage and also considers new aspects of transplant pathology from the literature. In the context of transplant rejection, late cellular rejection has aroused new interest. Histopathological changes in late rejection differ from acute cellular rejection and there seem to be similarities to de novo autoimmune hepatitis and idiopathic post-transplant hepatitis. Central perivenulitis is a typical change in late cellular rejection and should be differentiated from central toxic necrosis. Other important areas of transplant pathology include vascular and biliary changes resulting from surgical complications or as sequelae of immunosuppressive therapy. Furthermore, disease recurrence plays an important role and combined patterns of disease poses a challenge for the pathologist.

Influence of formalin fixation on tissue dimensions in palatal tonsils.

AIM: To investigate the change of tissue dimensions after formalin fixation, and to determine the optimal time of fixation. HYPOTHESIS: Formalin fixation may lead to shrinkage in tissue dimensions and may thus alter tumor stages. BACKGROUND: It is often observed in tumor surgery that the dimensions in vivo seem larger than after resection, and tissue appears to shrink further after formalin fixation. This might alter dimensions and assessment of spread of the tumor and thus lead to a lesser tumor classification and stage. In cases where the decision for adjuvant chemoradiation is based upon the stage, it may thus be of relevance for the patient to evaluate the pathologic and not the in vivo dimensions of the tumor. MATERIAL AND METHODS: In order to obtain comparable tissues, we investigated 100 palatal tonsils after cold steel dissection tonsillectomy for chronic tonsillitis. There were four time points investigated: directly after excision in the operating room and after four, 24 and 72 h of fixation in formaldehyde (4% Formaldehyde in phosphate buffer pH 7.4). The tissue was measured in the following dimensions: volume (ml), weight (g) and length, broadness and width (mm). RESULTS: The tissue size did not change significantly in dimensions except for an increase in length. The time of fixation did not influence the size. DISCUSSION: Formalin fixation does not significantly influence the tissue dimensions of palatal tonsils in comparison to direct ex vivo measurements. A minimal time of fixation of 20 h is required in order to stop all degenerative processes; however, longer fixation does not change the dimensions of the specimen. CONCLUSION: The null hypothesis has to be withdrawn that tissue dimensions are altered by formalin fixation. Thus, the histopathological measurements do not influence TNM staging.

[Epithelial downgrowth 48 years after penetrating eye trauma]. / Epithelimplantationszysten--48 Jahre nach Bulbuspenetration.

BACKGROUND: Epithelial invasion is a rare but severe complication after penetrating eye trauma or intraocular surgery. Cystic ingrowth can occur even after decades. CASUISTICS: A 53-year-old woman developed two epithelial cysts in the left eye 48 years after penetrating trauma with a dart. After primary wound closure the intraocular status remained stable for 48 years before symptoms appeared. Preoperative diagnostics (e.g. ultrasound biomicroscopy) detected the origin of the epithelial downgrowth from an intracorneal cyst. Histology confirmed the clinical suspicion of a cystic epithelial ingrowth. CONCLUSION: The latency of our case is the longest reported interval between penetrating eye trauma and appearance of epithelial ingrowth to be described in detail. Ultrasound biomicroscopy is able to detect the origin of epithelial ingrowth.

[Epithelial-mesenchymal transition of biliary epithelial cells in advanced liver fibrosis]. / Epitheliale-mesenchymale Transdifferenzierung von Gallengangsepithelzellen bei fortgeschrittener Leberfibrose.

UNLABELLED: The conversion of epithelial cells in a mesenchymal cell type is called "epithelial-mesenchymal-transition" (EMT). This process is defined by a loss of epithelial specific characteristics such as cell adhesion, polarity and a reorganization of cytoskeletal proteins. EMT has been shown to be involved in progression of cancer and in obstructive renal fibrosis. In this study we analyzed liver tissues in a bile-duct ligation model of rats and human liver biopsies with cholestatic fibrosis and chronic hepatitis c infection to determine if biliary epithelial cells undergo phenotypical and functional changes during chronic injury. METHODS: Liver tissue of rats and human patients was examined by immunohistochemistry using antibodies against epithelial and mesenchymal specific targets as well as molecules of potentially activated signaling pathways. To study contribution of biliary epithelial cells in extracellular matrix production we performed laser microdissection combined with real-time PCR. RESULTS: Bile duct ligation in rats induced a prominent biliary epithelial proliferation and a pronounced expression of vimentin was observed in biliary epithelial cells, whereas no vimentin expression was detectable in bile duct cells of sham operated rats. In human liver biopsies from patients with cholestatic fibrosis and chronic hepatitis c infection a prominent biliary expression of vimentin could be shown. Despite this, epithelial marker proteins were still detectable. Further, we observed collagen I mRNA expression in laser microdissected bile ducts. CONCLUSION: Biliary epithelial cells show cytoskeletal rearrangements during chronic liver injury towards a mesenchymal phenotype. The detection of collagen I mRNA in bile duct cells suggests that they might participate in extracellular matrix production.