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Purpose Histogram analysis can better reflect tumor heterogeneity than conventional imaging analysis. The present study analyzed possible correlations between histogram analysis parameters derived from Intravoxel-incoherent imaging (IVIM) and histopathological features in rectal cancer (RC). Methods Seventeen patients with histopathologically proven rectal adenocarcinomas were retrospectively acquired. In all cases, pelvic MRI was performed. Diffusion weighted imaging was obtained using a multi-slice single-shot echo-planar imaging sequence with b values of 0, 50, 200, 500 and 1000 s/mm2. Simplified IVIM analysis was performed using the IntelliSpace portal, version 10 and the following images were generated: f (perfusion fraction) map, D (true diffusion coefficient) map, and ADC map utilizing all b-values. Histogram based analysis of signal intensities was performed for every IVIM map using an in-house matlab tool. Histopathology was investigated using Ki 67 specimens with calculation of Ki 67-index and cellularity. CD31 stained specimens were used for calculation of microvessel density (MVD). Results There were statistically significant correlations between Ki 67 index and mode derived from ADC as well as entropy from f, r=−0.50, p=.04 and r=−0.55, p=.02, respectively. MVD correlated well with parameters derived from f. Conclusion IVIM histogram analysis parameters can reflect histopathology in RC. ADC and D values are associated with proliferation potential. Perfusion fraction f is associated with MVD.

Background Immunotherapy has become a cornerstone of the modern cancer treatment. It might be crucial to predict its expression non-invasively by imaging. The present study used diffusion-weighted imaging (DWI) quantified by whole lesion apparent diffusion coefficient (ADC) values to elucidate possible associations with programmed cell death ligand 1(PD-L1) expression in head and neck squamous cell cancer (HNSCC). Patients and methods Overall, 29 patients with primary HNSCC of different localizations were involved in the study. DWI was obtained by using a sequence with b - values of 0 and 800 s/mm2 on a 3 T MRI. ADC values were evaluated with a whole lesion measurement and a histogram approach. PD-L1 expression was estimated on bioptic samples before any form of treatment using 3 scores, tumor positive score (TPS), immune cell score (ICS), and combined positive score (CPS). Results An inverse correlation between skewness derived from ADC values and ICS was identified (r = -0.38, p = 0.04). ADCmax tended to correlate with ICS (r = -0.35, p = 0.06). Other ADC parameters did not show any association with the calculated scores. Conclusions There is a weak association between skewness derived from ADC values and PD-L1 expression in HNSCC, which might not be strong enough to predict PD-L1 expression in clinical routine. Presumably, ADC values are more influenced by complex histopathology compartments, comprising cellular and extracellular aspects of tumors than only of a single subset of tumor associated cells.

Primary vaginal carcinoma is rare. There are two pathogenetic pathways, one associated with HPV high-risk infection and another one with inactivation of p53. Vaginal Paget's disease is rare and mostly associated with vulvar disease or represents intravaginal spread of associated locoregional cancer. Diagnostic vaginal biopsies should be examined by step sections on H&E. Sentinel lymph nodes should be processed completely using ultrastaging. Morphology-based prognostic factors with good clinical evidence are tumour stage and lymph node status. Molecular markers are not currently relevant for treatment decision and prognosis.

Accurate disease classification is fundamental for the selection of the treatment approach, prognostication, selection of clinical trials and for research purposes in routine clinical practice. Extrauterine high-grade serous carcinoma (HG-SC) may arise from the ovary, the fallopian tube and rarely from the peritoneal surface epithelium. Regardless of its origin, the vast majority of patients with HG-SC share clinical symptoms, present with advanced stage disease and suffer from a poor prognosis. Recent data suggest that there is an increasing incidence of HG-SC arising from the fallopian tube. Data from the Clinical Cancer Registry of Leipzig of surgically treated non-uterine pelvic carcinomas were analyzed regarding their sites of origin. Depending on the histology, cases were separated into high-grade serous and non-high-grade serous tumors. Based on different approaches in the assessment of the site of origin, three distinct time periods were defined. The frequency of the specific sites of origin was compared to the different time periods and histologic subtypes. The majority of cases (57.9%; 279/482) were high-grade serous carcinomas, 42.1% of the cases presented with endometrioid, clear cell or mucinous histology. Overall, a 1.7-fold decrease of carcinomas with ovarian origin, paralleled by a 10.3-fold increase of tubal carcinomas was noted between 2000 and 2019. Based on the histopathological subtype, there was a 2.1-fold decrease of ovarian and a 7.1-fold increase of tubal carcinomas in patients with HG-SC. In non-high-grade serous tumors, the frequency of the different sites of origin did not change. 83.7% of tumors with non-high-grade serous histology originated from the ovary, whereas 86.8% of the carcinomas with tubal origin were of high-grade serous histology. The present and published data of non-uterine pelvic cancers may suggest an increase of tubal and decrease of ovarian carcinomas. However, there is rising morphologic and molecular evidence that non-uterine HG-SC actually arise from the fallopian tubes via its precursor STIC instead of from the ovary. This evidence has had an impact on the handling and reporting of non-uterine surgical specimens and its definition of the site assessment. In conclusion, the increasing frequency of tubal carcinomas and the associated decrease in ovarian cancer appears to be due to the reclassification of tumors previously classified as ovarian and greater emphasis on examining the resection specimens of non-uterine pelvic carcinomas.

Endometrial mesonephric-like adenocarcinoma (ML-AC) represents a recently recognized subtype of endometrial adenocarcinoma (AC) associated with a subtle immunophenotype with a characteristic KRAS-mutation. Detailed clinico-pathologic analyses and prognostic data on ML-AC are limited. We report a series of four cases with histopathological, immunohistochemical, and molecular analyses. These cases as well as the data of previously published cases were reviewed for clinico-pathologic variables and clinical follow-up information. Forty cases of ML-AC were identified. ML-AC represents about 1% of all endometrial carcinomas. Similar to other types of endometrial AC, vaginal bleeding was the leading presenting symptom, and the mean age was 60.0 years (range 31–91). More than a half of the patients presented with locally advanced disease (≥ FIGO stage II) at time of diagnosis, developed a recurrence or died of the disease within a mean follow-up period of 24.7 months (range 3–144.5 months). The most common site of distant disease was pulmonary involvement. Microscopically, ML-ACs present with mixed morphology and show a co-expression of so-called mesonephric and Mullerian markers, suggesting a Mullerian origin of the tumors. Immunostaining for PD-L1 was negative in all tested cases, using different antibodies against PD-L1. Retained staining for mismatch repair proteins on immunohistochemistry and a POLE-mutation suggest a copy number low phenotype within the molecular classification of endometrial carcinomas. Almost all cases showed a KRAS-mutation at codon 12 (mostly G12V). Uterine ML-AC represents a distinct subtype of invasive endometrial AC, associated with KRAS-mutations and characteristic immunohistochemical findings. Clinically, ML-AC may show an aggressive behavior with a high rate of recurrent disease and a substantial risk for distant metastatic disease, especially to the lungs.

Zahlreiche therapie- und prognoseorientierte Studien zum Zervixkarzinom haben eine Uberarbeitung der FIGO-Klassifikation erforderlich gemacht. Das mikroinvasive Karzinom wird allein durch die Tiefe der Stromainfiltration definiert, die flachige (horizontale) Ausdehnung ist nunmehr irrelevant. Makroinvasive Karzinome, die auf die Cervix uteri begrenzt sind, werden anhand der Tumorgrose subkategorisiert in: FIGO IB1/T1b1 – zervikale Stromainvasion >5,0 mm und ≤2 cm maximale Tumorgrose, FIGO IB2/T1b2 – Tumorgrose >2 cm und ≤4 cm, FIGO IB3/T1b3 – Tumorgrose >4 cm. Sowohl die pelvinen als auch die paraaortalen Lymphknoten werden als regionare Lymphknoten definiert. Der Befall pelviner Lymphknoten wird als FIGO IIIC1/pN1a und eine Metastasierung in paraaortale Lymphknoten mit und ohne Beteiligung pelviner Lymphknoten als FIGO IIIC2/pN1b klassifiziert. Der Nachweis einer Corpusinfiltration und eine adnexale/ovarielle Metastasierung sind nicht stagingrelevant.

Background and objectives Texture analysis derived from morphological magnetic resonance (MR) images might be associated with histopathology in tumors. The present study sought to elucidate possible associations between texture features derived from T1-and T2-weighted images with proliferation index Ki67 in soft tissue sarcomas. Methods Overall, 29 patients (n = 13, 44.8% female) with a median age of 52 years were included into this retrospective study. Several soft tissue sarcomas were investigated. Texture analysis was performed on pre-contrast T1-weighted and T2-weighted images using the free available Mazda software. Results The best correlation coefficients with Ki67 index were identified for the following parameters: T1-weighted images “45dgr_RLNonUni (p = 0.50, P = 0.006), T2-weighted images “S (4,0)SumAverg” (p = −0.45, P = 0.02). A ROC analysis was performed for Ki67-index with a threshold of 10%. The highest area under the curve (AUC) was found for the parameter “T1_WavEnHL_s-7” with an AUC of 0.90. For the threshold of Ki67 = 20% the highest AUC was identified for the parameter „T2_S (1,1)Entropy” with an AUC of 0.77. Conclusion Several texture features derived from T1-and T2-weighted images correlated with proliferation index Ki67 and might be used as valuable novel biomarkers in soft tissue sarcomas.

Objective Diffusion weighted imaging (DWI) can be quantified by apparent diffusion coefficient (ADC) and can predict tissue microstructure. The aim of the present study was to analyze possible associations between ADC histogram based parameters with different histopathological parameters in cervical squamous cell carcinoma. Materials and methods 18 female patients (age range 32–79 years) with squamous cell cervical carcinoma were retrospectively enrolled. In all cases, pelvic MRI was performed with a DWI (b-values 0 and 1000 s/mm2). Histogram analysis was performed as a whole lesion measurement. Histopathological parameters included expression of EGFR, VEGF, Hif1-alpha, Her2 and Histone 3. Spearman's correlation coefficient was used to analyze associations between investigated parameters. Results Analyze of the investigated ADC histogram parameters showed a good interreader variability, ranging from 0.705 for entropy to 0.959 for ADCmedian. EGFR expression correlated statistically significant with several histogram parameters. The highest correlation was observed for p75 (p = −0.562, P = 0.015). There were several correlations with histone 3, the highest with p25 (p = −0.610, P = 0.007). None of the ADC related parameters correlated statistically significant with expression of VEGF, Hif1-alpha and Her2. Conclusion Histogram analysis showed a good interreader agreement. ADC histogram parameters might be able to reflect expression of EGFR and histone 3 in cervical squamous cell carcinomas, but not expression of VEGF, Hif1-alpha and Her2.

Perifocal edema of brain tumors is associated with survival and neurological symptoms. Our aim was to analyze associations between perifocal edema and immunohistochemical features including proliferation potential, microvessel density, neoangiogenesis and invasiveness in brain metastasis (BM).35 patients with BM were included into the retrospective study. The tumors were localized supratentorial in 25 lesions (71.4%) and infratentorial in 10 lesions (28.6%). The following immunohistochemical features were calculated on histopathological specimens: microvessel density, proliferation index Ki 67, matrix-metallopeptidase 9 (MMP9) extracellular matrix metalloproteinase inducer (EMMPRIN) and vascular endothelial growth factor (VEGF) expression. Tumor and edema volumes were estimated semiautomatically on magnetic resonance images.There were no correlations between tumor volume and edema volume. Moreover, no correlation was identified between the investigated immunohistochemical features and tumor/edema volume. In the non-small cell lung cancer subgroup, a positive correlation between tumor volume and VEGF expression was observed (r = 0.52, P = 0.02) and edema volume correlated inversely with MMP9 expression (r = -0.53, P = 0.02).In BM, no linear associations exist between tumor volumes, edema volumes and immunohistochemical features reflecting proliferation potential, neoangiogenesis, microvessel density and MMP9 expression. However, in the subgroup of non-small cell lung cancer, there might be associations between MMP9 expression and edema volume as well as between tumor volume and angiogenesis.

BACKGROUND: Our purpose was to evaluate associations of combined 18 F-FDG-PET and MRI parameters with histopathological features in head and neck squamous cell carcinoma (HNSCC). METHODS: Overall, 22 patients with HNSCC were acquired (10 with G1/2 tumors and 12 with G3 tumors). 18 F-FDG-PET/CT and MRI was performed and maximum standardized uptake value (SUV max ), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) were estimated. Neck MRI was obtained on a 3 T scanner. Diffusion weighted imaging was performed with estimation of apparent diffusion coefficient (ADC). Perfusion parameters K trans, V e , and K ep were derived from dynamic contrast-enhanced (DCE) imaging. Different combined PET/MRI parameters were calculated as ratios: PET parameters divided by ADC or DCE MRI parameters. The following histopathological features were estimated: Ki 67, EGFR, VEGF, p53, hypoxia-inducible factor (HIF)-1α, and cell count. Spearman's correlation coefficient (p) was used for correlation analysis. P RESULTS: In overall sample, cellularity correlated with SUV max /ADC min ( P = .558, P = .007), TLG/ADC min ( P = .546, P = .009), and MTV/ADC min ( P = .468, P = .028). MTV/ K ep correlated with expression of HIF-1α ( P = .450, P = 0,047). In G1/2 tumors, SUV max /ADC min correlated with HIF-1α ( P = − .648, P = .043); MTV/ K ep ( P = −.669, P = .034) and TLG/ K ep ( P = −.644, P = .044) with Ki67. In G3 tumors, cellularity correlated with SUV max /ADC min ( P = .832, P = .001), SUV max /ADC mean ( P = .741, P = .006), and TLG/ADC min ( P = .678, P = .015). MTV/ADC min and TLG/ADC min tended to correlate with HIF-1α. CONCLUSION: Combined parameters of 18 F-FDG-PET and MRI can reflect Ki 67, tumor cellularity and expression of HIF-1α in HNSCC. Associations between parameters of 18 F-FDG-PET and MRI and histopathology depend on tumor grading.

Objective Apparent diffusion coefficient (ADC) values derived from Diffusion-weighted images are able to reflect tumor microstructure, such as cellularity, extracellular matrix or proliferation potential. This present study sought to correlate prognostic relevant histopathologic parameters with ADC values derived from a whole lesion measurement in head and neck squamous cell carcinoma (HNSCC). Materials and methods Thirty-four patients with histological proven primary HNSCC were prospectively acquired. Histogram analysis was derived from ADC maps. In all cases, expression of Hif1-alpha, VEGF, EGFR, p53, p16, Her 2 were analyzed. Results In the overall patient sample, ADCmax correlated with p53 expression (p = −0.446, p = 0.009) and ADCmode correlated with Her2-expression (p = −0.354, p = 0.047). In the p16 positive group there were several correlations. P25, P90 and entropy correlated with Hif1-alpha (p = −0.423, p = 0.05, p = −0.494, p = 0.019, p = 0.479, p = 0.024, respectively). Kurtosis correlated with P53 expression (p = −0.466, p = 0.029). For p16 negative carcinomas the following associations could be identified. Mode correlated with VEGF-expression (p = −0.657, p = 0.039). ADCmax, P75, P90, and Std correlated with p53-expression (p = −0.827, p = 0.002, p = −0.736, p = 0.01, p = −0.836, p = 0.001 and p = −0.70, p = 0.016, respectively). There were no statistically significant differences of ADC histogram parameters between p16 positive and p16 negative carcinomas. Conclusion ADC histogram values can reflect different histopathological features in HNSCC. Associations between ADC histogram analysis parameters and histopathology depend on p16 status.

Head and neck squamous cell carcinoma (HNSCC) is one of common cancers worldwide. Positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) is increasingly used for diagnosing and staging, as well as for monitoring of treatment of HNSCC. PET parameters like maximum and mean standard uptake values (SUVmax, SUVmean) can predict the behavior of HNSCC. The purpose of this study was to analyze possible associations between these PET parameters and clinically relevant histopathological features in patients with HNSCC. Overall, 22 patients, mean age, 55.2 ± 11.0 years, with different HNSCC were acquired. Low grade (G1/2) tumors were diagnosed in 10 cases (45 %) and high grade (G3) tumor in 12 (55 %) patients. In all cases, whole body PET was performed. For this study, the following specimen stainings were performed: MIB-1 staining (KI 67 expression), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, hypoxia-inducible factor (HIF)-1α, and human papilloma virus (p16 expression). All stained specimens were digitalized and analyzed by using the ImageJ software 1.48v. Spearman’s correlation coefficient (ρ) was used to analyze associations between investigated parameters. P values

OBJECT: Thyroid cancer represents the most frequent malignancy of the endocrine system with an increasing incidence worldwide. Novel imaging techniques are able to further characterize tumors and even predict histopathology features. Texture analysis is an emergent imaging technique to extract extensive data from an radiology images. The present study was therefore conducted to identify possible associations between texture analysis and histopathology parameters in thyroid cancer. METHODS: The radiological database was retrospectively reviewed for thyroid carcinoma. Overall, 13 patients (3 females, 23.1%) with a mean age of 61.6 years were identified. The MaZda program was used for texture analysis. The T1-precontrast and T2-weighted images were analyzed and overall 279 texture feature for each sequence was investigated. For every patient cell count, Ki67-index and p53 count were investigated. RESULTS: Several significant correlations between texture features and histopathology were identified. Regarding T1-weighted images, S(0;1)Sum Averg correlated the most with cell count ( r =0.82). An inverse correlations with S(5;0)AngScMom, S(5;0)DifVarnc S(5;0), DiffEntrp and GrNonZeros ( r =−0.69, −0.66, −0.69 and −0.63, respectively) was also identified. For T2-weighted images, Variance with r =0.63 was the highest coefficient, WavEnLL_S3 correlated inversely with cell count ( r =−0.57). WavEnLL_S2 derived from T1-weighted images was the highest coefficient r =−0.80, S(0;5)SumVarnc was positively with r =0.74. Regarding T2-weighted images WavEnHL_s-1 was inverse correlated with Ki67 index ( r =−0.77). S(1;0)Correlat was with r =0.75 the best correlation with Ki67 index. For T1-weighed images S(5;0)SumofSqs was the best with r =0.65 with p53 count. For T2-weighted images S(1;−1)SumEntrp was the inverse correlation with r =−0.72, whereas S(0;4)AngScMom correlated positively with r =0.63. CONCLUSIONS: MRI texture analysis derived from conventional sequences reflects histopathology features in thyroid cancer. This technique might be a novel noninvasive modality to further characterize thyroid cancer in clinical oncology.

// Alexey Surov 1 , Hans Jonas Meyer 1 , Stefan Schob 1 , Anne-Kathrin Hohn 2 , Kristina Bremicker 1 , Marc Exner 1 , Patrick Stumpp 1 , Sandra Purz 3 1 Department of Diagnostic and Interventional Radiology, University Hospital of Leipzig, 04103 Leipzig, Germany 2 Department of Pathology University Hospital of Leipzig, 04103 Leipzig, Germany 3 Department of Nuclear Medicine, University Hospital of Leipzig, 04103 Leipzig, Germany Correspondence to: Alexey Surov, email: alex.surow@medizin.uni-halle.de Keywords: uterine cervical cancer, PET, DWI, cell count, KI 67 Received: February 07, 2017 Accepted: February 27, 2017 Published: March 09, 2017 ABSTRACT The purpose of this study was to analyze associations between apparent diffusion coefficient (ADC) and standardized uptake values (SUV) values and different histopathological parameters in uterine cervical cancer. 21 patients with primary uterine cervical cancer were involved into the study. All patients underwent a whole body simultaneous 18 F-FDG PET/MRI. Mean and maximum SUV were noted (SUV mean and SUV max ). In all tumors minimal, mean, and maximal ADC values (ADC min , ADC mean , and ADC max ) were estimated. Combined parameters were calculated: SUV max /SUV mean, ADC min / ADC mean, SUV max /ADC min and SUV max /ADC mean. In all cases the diagnosis was confirmed histopathologically by tumor biopsy. Histological slices were stained by hematoxilin and eosin, MIB 1 monoclonal antibody, and p16. All histopathological images were digitalized and analyzed by using a ImageJ software 1.48v. The following parameters were estimated: cell count, proliferation index KI 67, total and average nucleic areas, epithelial and stromal areas. Spearman’s correlation coefficient was used to analyze associations between ADC and SUV values and histological parameters. P value s ≤ 0.05 were considered as statistically significant. ADC min and ADC min / ADC mean were statistically significant lower in N positive tumors. KI 67 correlated statistically significant with SUV max (r = 0.59, p = 0.005), SUV mean (0.45, p = 0.04), ADC min (r = –0.48, p = 0.03), SUV max /ADC min (r = 0.71, p = 0.001), SUV max /ADC mean (0.75, p = 0.001). SUV max correlated well with epithelial area (r = 0.71, p = 0.001) and stromal areas (r = –0.71, p = 0.001). SUV values, ADC min , SUV max /ADC min and SUV max /ADC mean correlated statistically significant with KI 67 and can be used to estimate the proliferation potential of tumors. SUV values correlated strong with epithelial area of tumor reflected metabolic active areas.

Purpose Programmed death 1 ligand (PD-L 1) plays an essential role in oncology. It might be crucial to predict its expression non-invasively by imaging. Dynamic-contrast enhanced MRI (DCE MRI) is one of the important imaging modalities in head and neck squamous cell cancer (HNSCC). The aim of the present study was to analyze possible associations between histogram analysis parameters of DCE MRI and PD-L 1 expression in HNSCC Methods Overall, 26 patients with primary HNSCC of different localizations were involved in the study. DCE MRI was obtained on a 3 T MRI and analyzed with a whole lesion measurement using a histogram approach. PD-L 1 expression was estimated on bioptic samples before any form of treatment using 3 scores (Tumor positive score (TPS), Immune cell score (ICS) and Combined positive score (CPS)). Results CPS correlated with mode derived from Ktrans (r = 0.40, p = .04). Also CPS correlated with P90 derived from Kep (r = 0.40, p = .04). ICS correlated with the maximum derived from Kep (r = 0.41, p = .03) and entropy derived from Kep (r = 0.43, p = .02). There were no associations between DCE MRI parameters and TPS. Conclusion Ktrans and Kep related histogram analysis parameters derived from DCE MRI correlated moderately with PD-L 1 expression of immune cells in HNSCC.

The handling and reporting of resected lymph nodes in gynecologic cancer follows the recommendations of the German national guidelines and the recommendations of the International Collaboration of Cancer Reporting (ICCR) and the International Society of Gynecologic Pathologists (ISGyP). The definitions of micrometastases and isolated tumor cells are in accordance with the definition of the UICC (Union Internationale Contre le Cancer) and TNM system. Both findings must be reported as part of the pathology report and final tumor classification. It is mandatory to examine all excised lymph nodes with complete processing of all nodes up to 0.3 cm and slicing of all larger nodes in 0.2-cm wide intervals with complete processing of all lamellae. The amount of the resected lymph nodes in correlation to positive nodes, the metric dimension of the largest lymph node metastasis per lymph node region, and the presence of extracapsular extension of the lymph node deposits must be part of the pathology report. The handling and cutting of sentinel lymph nodes are similar to nonsentinel nodes. Within frozen section analyses and final processing from paraffin-embedded sentinel nodes, all nodes should be examined by three-step sections with an interval of about 200 µm. In cases of negative sentinel nodes on HE staining, immunohistochemical ultrastaging should be performed.Die Aufarbeitung von Lymphonodektomiepräparaten gynäkologischer Malignome orientiert sich an den nationalen AWMF-Leitlinien und internationalen Empfehlungen. Die Definition von Mikrometastasen und isolierten Tumorzellen entspricht den Festlegungen der UICC(Union Internationale Contre le Cancer)/TNM(TNM-Klassifikation maligner Tumoren). Deren Nachweis soll im Befundbericht erwähnt werden sowie in die Tumorklassifikation einfließen. Alle übersandten Lymphknoten (LK) sollen untersucht werden mit vollständiger Einbettung aller LK bis 0,3 cm und Lamellierung aller größeren Lymphknoten parallel zu ihrer kurzen Achse in ca. 0,2 cm dicken Scheiben. Bestandteile des histologischen Befundberichtes sind: Zahl der befallenen LK im Verhältnis zur Zahl der entfernten/untersuchten LK entsprechend der Entnahmelokalisationen, metrische Ausdehnung der größten LK-Metastase, Fehlen/Nachweis einer extrakapsulären Ausbreitung. Zuschnitt und Einbettung von Sentinel-LK mit oder ohne Schnellschnittuntersuchung erfolgt in Analogie zu Nicht-Sentinel-LK mit Anfertigung von ca. 3 HE-gefärbten Stufenschnitten in einem Abstand von ca. 200 µm sowohl vom Gefrier- als auch Paraffinblock. Stellen sich die Sentinel-LK in der HE-Färbung negativ dar, soll ein immunhistochemisches Ultrastaging erfolgen.

Cervical cancer metastases to the ovary may occur with advanced tumor stage, deep cervical stromal involvement and corpus involvement. Endocervical adenocarcinoma in situ (AIS) with ovarian involvement is exceptionally rare with about twelve reported cases. Here we present a case of endocervical AIS with ovarian and pulmonary involvement 39 months after the initial diagnosis. The characteristics of that case were compared and summarized with the eleven previously published cases. The patients’ age ranged between 30 and 40 years (median 37.4 years). The time interval between the diagnosis of AIS and ovarian involvement was 26.7 months (range 2–84 months). Majority of the patients are alive without evidence of disease after a median time of 63.4 months (range 9–156 months). All reported cases were positive for high-risk HPV which was associated with strong p16 expression on immunohistochemistry. The ovarian involvement by endocervical AIS suggests the concept of a transtubal spread of the neoplastic cervical cells with or without previous colonization within the endometrium without evidence of invasive growth, suggesting a seed and soil spread of the disease. In cases with ovarian involvement by the AIS and without additional extragenital spread, the prognosis may be favorable.

Introduction: Texture analysis is an emergent imaging technique to quantify heterogeneity in radiological images. It is still unclear whether this technique is capable to reflect tumor microstructure. The present study sought to correlate histopathology parameters with texture features derived from contrast-enhanced CT images in head and neck squamous cell carcinomas (HNSCC). Materials and Methods: Twenty-eight patients with histopathological proven HNSCC were retrospectively analyzed. In every case EGFR, VEGF, Hif1-alpha, Ki67, p53 expression derived from immunhistochemical specimen were semiautomatically calculated. Furthermore, mean cell count was estimated. Texture analysis was performed on contrast-enhanced CT images as a whole lesion measurement. Spearman's correlation analysis was performed, adjusted with Benjamini-Hochberg correction for multiple tests. Results: Several texture features correlated with histopathological parameters. After correction only CT texture joint entropy and CT entropy correlation with Hif1-alpha expression remained statistically significant (ρ = -0.60 and ρ = -0.50, respectively). Conclusions: CT texture joint entropy and CT entropy were associated with Hif1-alpha expression in HNSCC and might be able to reflect hypoxic areas in this entity.

Diffusion-weighted imaging (DWI) is a functional imaging technique sensitive to microstructure in tissues. It is widely acknowledged to reflect cellularity in tumors. A small part of DWI is also sensitive to perfusion-related information and might therefore be also be able to reflect microvessel density in tumor tissues. Aim of the present study was to elucidate possible correlations between microvessel density and apparent diffusion coefficient (ADC) values in head and neck squamous cell carcinoma (HNSCC). Thirty-four patients with histologically proven primary HNSCC were included in the study. DWI was performed with a 3 T magnetic resonance imaging (MRI) (b-values 0 and 800 s/mm2) and histogram analysis was calculated with a whole lesion measurement. In every case, microvessel density was estimated with CD105-stained specimens. There were no statistically significant correlations between ADC histogram parameters and microvessel density. The calculated correlation coefficients ranged from r = -0.27, P = .13 for entropy and vessel area to r = 0.16, P = .40 for ADCmin and vessel count. Whole-lesion histogram analysis of ADC values cannot reflect microvessel density in HNSCC.

// Alexey Surov 1, 2 , Hans Jonas Meyer 2 , Anne-Kathrin Hohn 3 , Curd Behrmann 2 , Andreas Wienke 4 , Rolf Peter Spielmann 2 , Nikita Garnov 1 1 Department of Radiology, Martin Luther University Halle-Wittenberg, Halle, Germany 2 Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany 3 Department of Pathology, University of Leipzig, Leipzig, Germany 4 Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin Luther University Halle-Wittenberg, Halle, Germany Correspondence to: Alexey Surov, email: Alexey.Surov@medizin.uni-leipzig.de , Alex.surow@medizin.uni-halle.de Keywords: rectal cancer, diffusion weighted imaging, intravoxel incoherent motion, histopathology, tumor grading Received: November 11, 2016 Accepted: January 24, 2017 Published: February 27, 2017 ABSTRACT Our purpose was to correlate different intravoxel incoherent motion (IVIM), histopathological and clinical parameters in rectal cancer. 17 patients with histologically proven rectal cancer investigated on a 3.T device were included into the study. DWI was performed using a multi-slice single-shot echo-planar imaging sequence with b values of 0, 50, 200, 500 and 1000 s/mm. 2 A polygonal region of interest was drawn within the tumors on every b image. The following parameters were retrieved from IVIM: apparent diffusion coefficient (ADC), true diffusion (D), pseudo diffusion coefficient (D*), perfusion factor (f), and relative perfusion f·D*. In every case, cell count, nucleic areas, proliferation index KI 67, and microvessel density were estimated on histopathological specimens. Pearson’s correlation coefficient was used to analyze the association between the parameters. ADC correlated well with KI 67 index and D tended to correlate with cell count and KI 67. ADC and D tended to correlate with total nucleic area. The perfusion factor f correlated well with stained vessel area, total vessel area, and vessel count. D* and fD* correlated with mean vessel diameter. Distant metastasized tumors had higher D* and fD* values. IVIM parameter reflected different clinical and histopathological features in rectal cancer.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) can characterize perfusion and vascularization of tissues. DCE MRI parameters can differentiate between malignant and benign lesions and predict tumor grading. The purpose of this study was to correlate DCE MRI findings and various histopathological parameters in head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Sixteen patients with histologically proven HNSCC (11 cases primary tumors and in 5 patients with local tumor recurrence) were included in the study. DCE imaging was performed in all cases and the following parameters were estimated: K trans , V e , K ep , and iAUC. The tumor proliferation index was estimated on Ki 67 antigen stained specimens. Microvessel density parameters (stained vessel area, total vessel area, number of vessels, and mean vessel diameter) were estimated on CD31 antigen stained specimens. Spearman's non-parametric rank sum correlation coefficients were calculated between DCE and different histopathological parameters. RESULTS: The mean values of DCE perfusion parameters were as follows: K trans 0.189 ± 0.056 min −1 , K ep 0.390 ± 0.160 min −1 , V e 0.548 ± 0.119%, and iAUC 22.40 ± 12.57. Significant correlations were observed between K ep and stained vessel areas ( r = 0.51, P = .041) and total vessel areas ( r = 0.5118, P = .043); between V e and mean vessel diameter ( r = −0.59, P = .017). Cell count had a tendency to correlate with V e ( r = −0.48, P = .058). In an analysis of the primary HNSCC only, a significant inverse correlation between K trans and KI 67 was identified ( r = −0.62, P = .041). Our analysis showed significant correlations between DCE parameters and histopathological findings in HNSCC.

BACKGROUND: Thyroid carcinomas represent the most frequent endocrine malignancies. Recent studies were able to distinguish malignant from benign nodules of the thyroid gland with diffusion-weighted imaging (DWI). Although this differentiation is undoubtedly helpful, presurgical discrimination between well-differentiated and undifferentiated carcinomas would be crucial to define the optimal treatment algorithm. Therefore, the aim of this study was to investigate if readout-segmented multishot echo planar DWI is able to differentiate between differentiated and undifferentiated subtypes of thyroid carcinomas. PATIENTS AND METHODS: Fourteen patients with different types of thyroid carcinomas who received preoperative DWI were included in our study. In all lesions, apparent diffusion coefficient (ADC)min, ADCmean, ADCmax, and D were estimated on the basis of region of interest measurements after coregistration with T1-weighted, postcontrast images. All tumors were resected and analyzed histopathologically. Ki-67 index, p53 synthesis, cellularity, and total and average nucleic areas were estimated using ImageJ version 1.48. RESULTS: Analysis of variance revealed a statistically significant difference in ADCmean values between differentiated and undifferentiated thyroid carcinomas (P = .022). Spearman Rho calculation identified significant correlations between ADCmax and cell count (r = 0.541, P = .046) as well as between ADCmax and total nuclei area (r = 0.605, P = .022). CONCLUSION: DWI can distinguish between differentiated and undifferentiated thyroid carcinomas.

To analyze associations between histogram analysis parameters derived from conventional magnetic resonance imaging (MRI) and different histopathological features in head and neck squamous cell carcinoma (HNSCC). Thirty-four patients with histologically proven primary HNSCC were prospectively acquired. Histogram analysis was derived from pre-contrast T1-weighted (T1w) and T2-weighted (T2w) images. In all cases, expression of HIF-1α, VEGF, EGFR, p53, Ki67, and p16 as well as tumor cell count was analyzed. In the overall sample, inverse correlation between entropy derived from T1w images and p53 expression (p = − 0.458, P = 0.01) was found. Furthermore, p10 derived from T1w images correlated with VEGF expression (p = 0.371, P = 0.04). In the p16-positive tumors, VEGF expression correlated with several parameters derived from T1w images: mean (p = 0.481, P = 0.032), p10 (p = 0.489, P = 0.029), p25 (p = 0.475, P = 0.034), median (p = 0.468, P = 0.037), and mode (p = 0.492, P = 0.028). Several T2w parameters were associated with p53 expression: mean (p = 0.569, P = 0.007), p25 (p = 0.508, P = 0.019), p75 (p = 0.479, P = 0.028), median (p = 0.555, P = 0.009), and mode (p = 0.468, P = 0.033). Kurtosis derived from T2w images correlated with cell count (p = 0.534, P = 0.013). In p16-negative carcinomas, T2w parameters correlated with p53 expression: max (p = 0.736, P = 0.015), p90 (p = 0.687, P = 0.028), and standard deviation (p = 0.760, P = 0.011). T2w p10 (p = − 0.709, P = 0.022) and T2w p25 (p = − 0.733, P = 0.016) correlated also with HIF-1α expression. Multiple associations between histogram parameters derived from T1w and T2w images and clinically relevant histopathological features were found in HNSCC. Therefore, imaging parameters can be also used as surrogate markers for tumor cellularity, proliferation, and vascularization in HNSCC. The identified correlations differed significantly between p16-positive and p16-negative cancers.

Histogram analysis is an imaging analysis in which a whole tumor can be assessed, and every voxel of a radiological image is issued into a histogram. Thereby, statistically information about tumor can be obtained. The purpose of the study was to analyze possible relationships between histogram parameters derived from conventional MRI sequences and several histopathological features in cervical squamous cell carcinomas.A total of 18 female patients (age range 32-79 years) with squamous cell cervical carcinoma were retrospectively enrolled into the study. In all cases, pelvic MRI with a clinically protocol was performed. Histogram analysis was performed as a whole lesion measurement, calculating several percentils, minimum, mean, median, mode, maximum, kurtosis, skewness, and entropy. Histopathological parameters included expression of epidermal-growth factor (EGFR), vascular endothelial growth factor, hypoxia-inducible factor 1-alpha, Her2, and Histone 3. Spearman's correlation coefficient was used to analyze associations between investigated parameters.Several pre- and postcontrast derived T1-weighted parameters correlated inversely with EGFR expression. For precontrast T1-weighted images, the strongest correlation was found for p90 (ρ = -0.77, p = 0.004). For postcontrast T1-weighted images, the strongest correlation was observed for minimum (ρ = -0.64, p = 0.021). Several parameters derived from T2-weighted images were statistically significant different between Her2-positive and Her2 negative tumors. Skewness had the best p-value ( p = 0.004).Histogram analysis parameters of T1-weighted and T2-weighted images reflect HER2 status and EGFR expression in cervical cancer. Histogram parameters cannot predict cell count, proliferation index, or angiogenesis related histopathological features.

Functional imaging modalities like Diffusion-weighted imaging are increasingly used to predict tumor behavior like cellularity and vascularity in different tumors. Histogram analysis is an emergent imaging analysis, in which every voxel is used to obtain a histogram and therefore statistically information about tumors can be provided. The purpose of this study was to elucidate possible associations between ADC histogram parameters and several immunhistochemical features in rectal cancer. Overall, 11 patients with histologically proven rectal cancer were included into the study. There were 2 (18.18%) females and 9 males with a mean age of 67.1 years. KI 67-index, expression of p53, EGFR, VEGF, and Hif1-alpha were semiautomatically estimated. The tumors were divided into PD1-positive and PD1-negative lesions. ADC histogram analysis was performed as a whole lesion measurement using an in-house matlab application. Spearman's correlation analysis revealed a strong correlation between EGFR expression and ADCmax (p=0.72, P=0.02). None of the vascular parameters (VEGF, Hif1-alpha) correlated with ADC parameters. Kurtosis and skewness correlated inversely with p53 expression (p=-0.64, P=0.03 and p=-0.81, P=0.002, respectively). ADCmedian and ADCmode correlated with Ki67 (p=-0.62, P=0.04 and p=-0.65, P=0.03, respectively). PD1-positive tumors showed statistically significant lower ADCmax values in comparison to PD1-negative tumors, 1.93 ± 0.36 vs 2.32 ± 0.47×10-3mm2/s, p=0.04. Several associations were identified between histogram parameter derived from ADC maps and EGFR, KI 67 and p53 expression in rectal cancer. Furthermore, ADCmax was different between PD1 positive and PD1 negative tumors indicating an important role of ADC parameters for possible future treatment prediction.

Our purpose was to analyze possible associations between histogram analysis parameters of dynamic contrast-enhanced magnetic resonance imaging DCE MRI and histopathological findings like proliferation index, cell count and nucleic areas in head and neck squamous cell carcinoma (HNSCC). 30 patients (mean age 57.0 years) with primary HNSCC were included in the study. In every case, histogram analysis parameters of Ktrans, Ve, and Kep were estimated using a mathlab based software. Tumor proliferation index, cell count, and nucleic areas were estimated on Ki 67 antigen stained specimens. Spearman's non-parametric rank sum correlation coefficients were calculated between DCE and different histopathological parameters. KI 67 correlated with Ktrans min (p = -0.386, P = 0.043) and s Ktrans skewness (p = 0.382, P = 0.045), Ve min (p = -0.473, P = 0.011), Ve entropy (p = 0.424, P = 0.025), and Kep entropy (p = 0.464, P = 0.013). Cell count correlated with Ktrans kurtosis (p = 0.40, P = 0.034), Ve entropy (p = 0.475, P = 0.011). Total nucleic area correlated with Ve max (p = 0.386, P = 0.042) and Ve entropy (p = 0.411, P = 0.030). In G1/2 tumors, only Ktrans entropy correlated well with total (P =0.78, P =0.013) and average nucleic areas (p = 0.655, P = 0.006). In G3 tumors, KI 67 correlated with Ve min (p = -0.552, P = 0.022) and Ve entropy (p = 0.524, P = 0.031). Ve max correlated with total nucleic area (p = 0.483, P = 0.049). Kep max correlated with total area (p = -0.51, P = 0.037), and Kep entropy with KI 67 (p = 0.567, P = 0.018). We concluded that histogram-based parameters skewness, kurtosis and entropy of Ktrans, Ve, and Kep can be used as markers for proliferation activity, cellularity and nucleic content in HNSCC. Tumor grading influences significantly associations between perfusion and histopathological parameters.

The challenges of histopathology have been changed dramatically during the last years. The pathologist nowadays is a diagnostic oncologist. The histopathologic report is one cornerstone and within the majority of cases the basement of quality control and decision making for patients treatment. The final pathology report bases on a very accurate macroscopic description and cutting of the specimens. The quality of the histopathological report is mainly influenced by the available clinical information. So, it is necessary that the pathologist and the clinician speak the same language. This chapter describes the requirements for good clinical practice in handling and reporting of different kinds of hysterectomy specimens and gives an overview about the needs as well as for the clinicians but also for gynaecologic pathologists. Special focus was made on the requirements for optimal handlings influenced by the clinicians. The procedure colloquially known, as frozen section is one of the most important and potentially stressful tasks that the pathologist performs in practice. The advances and limitations of that technique is discussed. Detailed descriptions are given for the parameters included in the histopathology report for benign and malignant disease within hysterectomies, lymphonodectomy and omentectomy specimens.

Apparent diffusion coefficient (ADC) histogram analysis has been used to some extent in cervical cancer (CC) to distinguish between low-grade and high-grade tumors. Although this differentiation is undoubtedly helpful, it would be even more crucial in the presurgical setting to determine whether a tumor already gained the potential to metastasize via the lymphatic system. So far, no studies investigated the potential of 3T ADC histogram analysis in CC to differentiate between nodal-positive and nodal-negative entities. Therefore, the principal aim of our study was to investigate the potential of 3T ADC histogram analysis to differentiate between CC with and without lymph node metastasis. The second aim was to elucidate possible differences in ADC histogram parameters between CC with limited vs. advanced tumor stages and well-differentiated vs. undifferentiated lesions. Finally, correlations of p53 expression and Ki-67 index with ADC parameters were analyzed. Eighteen female patients (mean age 55.4 years, range 32–79 years) with histopathologically confirmed cervical squamous cell carcinoma of the uterine cervix were prospectively enrolled. Tumor stages, tumor grading, status of metastatic dissemination, Ki67-index, and p53 expression were assessed in these patients. Diffusion weighted imaging (DWI) was obtained in a 3T scanner using the following b values: b0 and b1000 s/mm2. Group comparisons using Mann-Whitney U test revealed the following findings: nodal-positive CC had statistically significant lower ADC parameters (ADCmin, ADCmean, median ADC, Mode, p10, p25, p75, and p90) in comparison to nodal-negative CC (all p

Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT.