The presence of lymph node metastases has a considerable effect on the prognosis and therapy of patients with malignant melanomas. Therefore, the histopathological examination of what are known as sentinel lymph nodes, the first lymph nodes that metastasising cancer cells reach, is of great importance. However, the examination method has its technical limitations where very small metastases are concerned. Professor Dr. Anja Ulmer, a dermatologist at Tübingen University, has now developed a method that is not only far more sensitive than previous methods but that also enables the collection of information on the number of metastatic melanoma cells.
Melanoma is a malignant tumour of melanocytes (pigment cells) which are found predominantly in the skin and which grow uncontrollably. The number of people contracting the disease has increased almost ten-fold over the last 50 years. In Germany alone, around 15,000 people every year are diagnosed with this malignant tumour, and the number is growing. The reason for the increase in the number of melanoma cases is first of all the exposure to UV radiation, which is getting stronger. A large proportion of the world’s population are exposed – intentionally or unintentionally – to intense UV light. Fortunately, the majority of melanomas can be detected very early on. However, the risk of metastasising cannot always be completely excluded.
"The thicker the tumour, the higher the risk that the melanoma cells have already metastasised," said Prof. Dr. Anja Ulmer from the Department of Dermatology at the University Hospital of Tübingen. Metastasising preferentially occurs by way of the local lymph vessels. Once a tumour thickness exceeds one millimetre, doctors will routinely look at the sentinel lymph nodes. Numerous studies suggest that the metastases of the primary tumour settle first in the sentinel lymph nodes before they continue to the downstream lymph nodes or the blood. "The prognosis for the patient depends very much on whether the sentinel lymph nodes are affected or not," said Ulmer.
This knowledge is also essential for further therapy planning. If melanoma cells are found in the sentinel lymph nodes, the only efficient cure is the radical removal of all lymph nodes of the body area affected. "It is known that some patients with lymph node metastases can still be cured by surgically removing the metastases," said the dermatologist.
However, the accuracy of diagnosis depends very much on the histopathological preparation of the lymph nodes, which involves cutting them into thin slices. “In the case of very small metastases, cases do arise where they are not detected during the histopathological examination,” said Ulmer. This is mainly due to technical reasons. Ulmer compares this phenomenon with a worm in an apple – depending on how the apple is cut, the worm can remain undiscovered or not.In order to boost the informative value of sentinel lymph node biopsies, the scientist and her team of researchers have now developed a method that makes it possible to detect even the smallest accumulation of tumour cells. Ulmer once again uses the apple-worm example to explain the principle. “Instead of cutting the lymph node into pieces, we squeeze it through a thin sieve, rather like making apple sauce.” Squeezing the lymph node through a sieve releases melanoma and healthy cells of the lymph node from the united cell structure. They can then be examined under the microscope. Specific staining enables the researchers to discern a single tumour cell from a million normal cells.Ulmer was able to show that her immunocytological method could be used to identify metastatic melanoma cells in numerous lymph nodes which showed negative in routine histopathological examinations. “Our method seems to be a lot more sensitive than the current standard method,” said Ulmer who also sees another, far greater advantage in the fact that this method also enables researchers to make quantitative statements on the tumour load in the lymph node examined. “Our data suggest that there is a link between the number of tumour cells in the sentinel lymph nodes and the patient prognosis,” said the scientist.
Ulmer also hopes to find out whether her new method also enables treatment strategies to be deduced. “At present, there are many different schools of thought as to whether it is necessary to surgically remove all regional lymph nodes in cases where the sentinel lymph node contains only a few metastases.” Ulmer believes that the surgical removal of the lymph nodes, a process associated with many complications, is only justified if the patient has a good chance of survival. An initial answer to this exciting question might soon be found. At present, Ulmer is analysing the data from a study her team has recently carried out. However, regardless of the results she obtains, Ulmer attaches great importance to the fact that her new method is not in competition with the standard method currently used by pathologists. “It is more like a complementary examination.” The reason for this is that Ulmer’s method is not currently 100 percent reliable. “In very rare cases we do not find metastatic melanoma cells, despite the fact that they show up in histopathological biopsies.”Ulmer recently received a grant of 26,000 euros from the Ludwig Hiermaier Foundation for Applied Cancer Research. She will use the money to further optimise the new method. “In cooperation with pathologists, we want to work out a concept that combines both examination methods in order to give the patients maximum benefit, and keep the costs manageable,” said Ulmer referring to her next scientific objective.