Overview of Histiocytic Diseases - Public Version
Histiocytes are leukocytes (white cells) that occur in tissues. Histiocytes include 2 major lineages of cells -‐ macrophages and dendritic cells -‐ they are very important in the immune system. Macrophages remove cell debris, foreign material and clear intracellular pathogens. Dendritic cells ensure that T lymphocytes respond correctly to molecules recognized as foreign (eg peptides derived from pathogens), or altered self (eg mutated peptides derived from cancer cells). So, histiocytes are integrally involved in the function of the immune system. In fact, one form of histiocytosis - the reactive form (cutaneous and systemic histiocytosis) - occurs as a result of a defect in the interaction of dendritic cells and T lymphocytes - an immuno-regulatory disorder which is amenable to treatment with immuno-suppressive drugs.
Histiocytic diseases are frustrating, because it may be diﬃcult to diﬀerentiate the reactive histiocytoses from inﬂammatory disease, in which appropriate inﬁltration and proliferation of histiocytes has occurred in response to an infectious agent (so called granulomatous, reactive inﬂammatory disease). Furthermore, we have recently recognized a syndrome called inflamed cutaneous T cell lymphoma, which mimics cutaneous reactive histiocytosis.
The clinical presentation and behavior and responsiveness to therapy vary tremendously between the various histiocytic disease syndromes observed. Canine cutaneous histiocytoma is a benign neoplasm which usually occurs as a single lesion in young dogs of all breeds, and spontaneously regresses (there are rare exceptions to this rule). Cutaneous histiocytosis (CH) presents with single or multiple lesions, which tend to wax and wane, and may even spontaneously regress. A few cases respond to corticosteroids, the remainder persist and may require more aggressive immunosuppressive therapy. Systemic histiocytosis (SH) is a familial disease of Bernese Mountain Dogs and also occurs sporadically in other breeds. SH presents with prominent skin manifestations identical to those seen in CH, but mucous membranes (ocular and nasal) and a variety of other organ systems, including lymphoid organs, lung, and bone marrow may also be involved. Although the lesions may wax and wane early in the course, SH is a progressive disease that often requires continuous immunosuppressive therapy. Histiocytic sarcoma and malignant histiocytosis (MH) occur with high incidence in Bernese Mountain Dogs, Rottweilers, Flat Coated Retrievers, Golden Retrievers and sporadically in many other breeds. Histiocytic sarcomas occur as localized lesions in spleen, lymph nodes, lung, bone marrow, skin and subcutis, brain, and periarticular tissue of large appendicular (limb) joints. Histiocytic sarcomas can also occur as multiple lesions in single organs (especially spleen), and rapidly disseminate to involve multiple organs. Hence, disseminated histiocytic sarcoma is diﬃcult to distinguish from MH, which is a multi‐system, rapidly progressive disease in which there is simultaneous involvement of multiple organs such as spleen, lymph nodes, lung, bone marrow, skin and subcutis. Response of histiocytic sarcomas and MH to chemotherapy is often brief.
It is vitally important that the correct diagnosis by pathologist experienced with the full spectrum of histiocytic disease is obtained, so that it is clear which of these histiocytic diseases has occurred in a given case. Only then can the likely outcome be predicted and appropriate treatment (if one exists) instituted. More detailed descriptions with images of the individual histiocytic diseases are available on this site. This information is targeted at clinicians and pathologists who seek to understand the ﬁner points of distinguishing the various diseases. Feel free to point your veterinarian to this site for this purpose.
Some breeds have a higher incidence of histiocytic disease. Bernese mountain dogs, Rottweilers, Flat coated retrievers, and Golden retrievers experience a high incidence of the malignant histiocytic diseases (localized and disseminated histiocytic sarcoma). Bernese mountain dogs also have a high incidence of cutaneous and systemic histiocytosis. In the case of Bernese mountain dogs, a clear familial relationship has been established for SH and histiocytic sarcoma. Shar Peis have a high incidence of cutaneous Langerhans cell histiocytosis (cLCH or multiple cutaneous histiocytomas) with or without delayed regression.