The host inflammatory cellular reaction around the grain is variable. There are three types of tissue reaction.
Type I Tissue Reaction
In type I, there is a zone of neutrophils in the vicinity of the grain. These are sometimes found within the grain substance causing its disintegration. Some histiocytes may also be seen among the neutrophils but they are more numerous outside the neutrophil zone. Some of the histiocytes have a foamy cytoplasm and give a positive reaction for fat and stain positive for CD 68 antigen.
Capillaries, which are sometimes abundant, surround the neutrophil/ histiocytes zone and they are occasionally, surrounded by a layer of fibrin. Lymphocytes, plasma cells, fibroblasts and some macrophages are usually seen in this vascular zone. The lymphocytes and plasma cells increase in number towards the investing fibrous tissue in the periphery of the lesion.
Type II Tissue Reaction
In type II reaction, the neutrophils largely disappear and are replaced by histiocytes and multinucleated giant cells. Some of the latter contain fragments of grains or pigmented cement substance without any hyphae. The macrophages may contain a black pigment derived from the grain. At this stage the grain itself is usually small and fragmented. This type of histiocytes/giant cell reaction follows on the earlier neutrophil response, which causes fragmentation of the grain.
Type III Tissue Reaction
In the third type of reaction (Type III), the grain material has largely or completely disappeared leaving a compact epithelioid granuloma with or without langerhans giant cells. This however, is an uncommon reaction but represents spontaneous regression in some grains.
The three types of tissue reaction may be found in the same lesion. Viable grains are nearly always present in biopsy material. It is not known if spontaneous regression of all the grain ever occurs in mycetoma.
The unique feature of M. mycetomatis is the formation of a capsule around the lesion. The lesion grows by expansile growth in the tissue plains. In the bones there is usually no capsule formation, the organism usually forming cavities that are filled with the grains. This gives the bone support and may explain the rarity of pathological fractures in mycetoma.
Ultra-structurally, the hyphal elements are spherical to elongated and are embedded in grain matrix. The hyphae are septate; the cytoplasm may be densely ribosomal or disorganized. Some hyphae appear empty, being devoid of cytoplasm. Cytoplasmic organelles such as nuclei and mitochondria are not usually seen. Intra–hyphal re-growth is sometimes seen. The hyphal wall is often markedly thickened. This feature may be involved in the transformation of the fungus to the pathogenic state.
The pigmented substance surrounding the hyphae consists of amorphous electron-dense material and vesicles. The nature of the pigment is not known with certainty. Histologically it resembles melanin and it may be a fungus product. Sclerosis and melanization of the host tissue is, in some manner, responsible for the formation of the cement substance.
Ultrastructural studies of the host reaction show neutrophils adherent to the grain. The cytoplasm of the neutrophil is stretched over the grain and the neutrophils granules are concentrated in the part of the cytoplasm adjacent to the grain. This is an immune adherence, which is mediated by immunoglobulins and is an example of antibody dependent cell mediated cytotoxicity. Immunoglobulin and complement can be demonstrated in the grain.
Bones are frequently involved in advanced mycetoma of the soft tissue. Occasionally primary bone mycetoma in the absence of soft tissue involvement is seen. M. mycetomatis produces lytic lesions which are large in size, few in number and have well defined margins; this is well seen radiologically.