Reporting of melanoma cell densities in the sentinel node refines outcome prediction.

INTRODUCTION: Sentinel node biopsy is a key procedure to predict prognosis in melanoma. In a prospective study we compare reporting on melanoma cell densities in cytospin preparations with semiquantitative histopathology for predicting outcome. PATIENTS AND METHODS: Sentinel nodes from 900 melanoma patients were bisected. One half of each node was disaggregated mechanically. The melanoma cell density (number of HMB45 positive cells per million lymphocytes with at least one cell showing morphological features of a melanoma cell) was recorded after examining two cytospins. For the second half the maximum diameter of metastasis was determined after haematoxylin and eosin (H&E) and immunohistological staining of three slides. RESULTS: Cytospins were positive for melanoma in 218 of 900 patients (24%). Routine pathology was positive in 111 of 900 (12%) patients. A more extensive pathological workup in cytospin-only positive patients led to a revised diagnosis (from negative to positive) in 23 of 101 patients (22.7%). We found a moderate but significant correlation between melanoma cell densities (determined in cytospins) and the maximum diameter of metastasis (determined by pathology) (rho = 0.6284, p < 0.001). At a median follow-up of 37 months (IQR 25-53 months) melanoma cell density (cytospins) (p < 0.001), thickness of melanoma (p = 0.008) and ulceration status (p = 0.026) were significant predictors for melanoma specific survival by multivariable testing and were all confirmed as key predictive factors by the random forest model. Maximum diameter of metastases, age and sex were not significant by multivariable testing (all p > 0.05). CONCLUSION: Recording melanoma cell densities by examining two cytospins accurately predicts melanoma outcome and outperforms semiquantitative histopathology.

[Cosmetic and functional results after resection of cutaneous neurofibroma in neurofibromatosis type 1 : Operation of neurofibroma improves quality of life while having moderate complications]. / Kosmetische und funktionelle Ergebnisse nach Resektion kutaner Neurofibrome bei Neurofibromatose I : Die Operation von Neurofibromen führt zu einer Verbesserung der Lebensqualität bei moderaten Komplikationen.

BACKGROUND: Neurofibromatosis type 1, also known as Recklinghausen's disease, is a neurocutaneous tumor syndrome that is genetically determined and is associated with infestation of the integument with neurofibromas (nerve sheath tumors). The occurrence of neurofibromas can be very stressful for patients and often contributes to a reduced quality of life for patients, especially if externally visible body parts are affected. The aim of this study is to show to what extent the resection of cutaneous neurofibromas can improve patients' quality of life. MATERIALS AND METHODS: For this study, we conducted a retrospective data collection via questionnaire on the quality of life before and after the surgical removal of cutaneous neurofibromas at the Department of Dermatology, University Hospital of Tübingen. An adapted dermatological quality of life index and a postoperative questionnaire on patient satisfaction were used. In addition, patient data were taken from doctor's notes, surgical reports, and outpatient documentation. A total of 30 patients with neurofibromatosis type 1 who underwent inpatient or outpatient surgery for cutaneous neurofibromas at the Tübingen dermatology hospital between 2016 and 2020 were surveyed. The survey results were statistically analyzed and represented as absolute and relative frequencies. RESULTS: Our study indicates an improved quality of life after surgery for cutaneous neurofibromas, especially regarding limitations in everyday life, self-consciousness, the choice of clothing, and leisure activities. The majority of our patients showed no new occurrence of neurofibromas in the surgical area and postoperative bleeding or wound infections were rare. CONCLUSION: In relation to the high level of satisfaction with the surgical and cosmetic results and also the positive influence on quality of life, our study indicates a favorable risk-benefit ratio for the resection of cutaneous neurofibromas in neurofibromatosis I.

Microvessel density and angiogenesis in primary hepatic malignancies: Differential expression of CD31 and VEGFR-2 in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

BACKGROUND: Microvessel density is an indicator of tumor-driven neoangiogenesis. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have distinct vascular patterns, which are also reflected in their imaging characteristics. Since a significant proportion of HCC are treated without biopsy confirmation, it is essential to discriminate HCC and ICC radiologically. The aim of our study was therefore to compare microvessel density and expression of VEGFR-2 in HCC and ICC, since these data may ultimately help us to better understand their imaging characteristics. Whereas CD31 documents vessel density, VEGFR-2 expression is an indicator of tumor-related neoangiogenesis. METHODS: CD31 and VEGFR-2 expressing microvessels were quantified on tissue microarrays of 95 resection specimens of HCC and 47 cases of ICC. Microvessel density was evaluated by counting immuno-reactive vascular structures both within the tumor and adjacent liver control tissue, respectively. Further 16 cases of ICC were immunostained for CD31 and VEGFR-2 on full sections. RESULTS: The frequency of VEGFR-2 (46.2/HPF; range 0-150) and CD31 (61.2/HPF; range 2.6-140) expressing vascular structures was significantly increased in HCC compared to adjacent liver parenchyma (VEGFR-2 33.3/HPF, range 0-87, CD31 21.4/HPF, range 0-78, both p < 0,001). ICC revealed significantly less VEGFR2-positive microvessels (15.4/HPF; range 2-77) compared to matched control tissue (42.3/HPF; range 4.6-109), whereas microvessel density with CD31 was comparable between ICC and adjacent liver (32.1/HPF; range 5.3-78 versus 28.0/HPF; range 5.3-57; p = 0.89). In ICC, the tumor-to-normal microvessel density ratio was 0.38 for VEGFR-2 and 1.24 for CD31. These ratios were nearly identical (VEGFR: 0.38; CD31: 0,97) for the 16 cases of ICC studied on whole sections, confirming the validity of the TMA approach. In contrast, ratios of VEGFR-2 and CD31 in HCC vs. adjacent liver were significantly higher (VEGFR: 2.23; CD31: 6.57). Expression of VEGFR-2 by tumor cells was not observed in any of the cases. CONCLUSIONS: HCC and ICC differ significantly in their microvessel density, confirming the hypovascular nature of ICC as compared to the hypervascularity of HCC. Of note, inverse tumor-to-normal ratios of microvascular VEGFR-2 expression between the two neoplasms indicate distinct features of neoangiogenesis. Whether these differences can be exploited for improvements in imaging of hepatic tumors and may play a role for anti-angiogenic treatment strategies requires further studies.