Abstract
In pathology, tissue images are evaluated using a light microscope, relying on the expertise and experience of pathologists. There is a great need for computational methods to quantify and standardize histological observations. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of tumor cells and their microenvironment are of special interest. Here, we systematically investigated tumor cell properties and their spatial neighborhood relations by a new application of statistical analysis to whole slide images of Hodgkin lymphoma, a tumor arising in lymph nodes, and inflammation of lymph nodes called lymphadenitis. We considered properties of more than 400, 000 immunohistochemically stained, CD30-positive cells in 35 whole slide images of tissue sections from subtypes of the classical Hodgkin lymphoma, nodular sclerosis and mixed cellularity, as well as from lymphadenitis. We found that cells of specific morphology exhibited significantly favored and unfavored spatial neighborhood relations of cells in dependence of their morphology. This information is important to evaluate differences between Hodgkin lymph nodes infiltrated by tumor cells (Hodgkin lymphoma) and inflamed lymph nodes, concerning the neighborhood relations of cells and the sizes of cells. The quantification of neighborhood relations revealed new insights of relations of CD30-positive cells in different diagnosis cases. The approach is general and can easily be applied to whole slide image analysis of other tumor types.
Highlights
The lymph node is a structured organ with major compartments, such as the subcapsular sinus, B cell follicles, the T cell zone, trabecular and medullary sinuses, and blood vessels
We focus on a special type of lymph node tumor, the Hodgkin lymphoma, exploring the two main types of the classical Hodgkin lymphoma, the nodular sclerosis and the mixed cellularity, and the non-tumor case, the lymphadenitis, representing an inflammation of the lymph node
We considered more than 400, 000 cells immunohistochemically stained with CD30 in 35 whole slide images of tissue sections
Summary
The lymph node is a structured organ with major compartments, such as the subcapsular sinus, B cell follicles, the T cell zone, trabecular and medullary sinuses, and blood vessels. Many cells of different type enter the lymph node. They migrate from compartment to compartment, interact with each other and with other cells, and show a complex movement in a stromal cell network [1]. The movement of tumor cells would be of great interest to comprehend the progress of the disease. Hodgkin lymphoma (HL) is a malignant tumor disease of the lymphoid system, which originates from B-lineage cells at various stages of development [2]. In the United States, about 185, 000 people were diagnosed with HL in 2011. 1, 100 people die of HL per year in the United States, so HL is still a severe disease
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