A Brief Overview of Histiocytic Disorders of Animals (January 1996)
Diane E. Brown, DVM, PhD and
Raquel Walton, VMD
To
begin, what is a histiocyte? Current
literature uses the term to include both monocyte/macrophage and Langerhans
cell/dendritic cell series. A lack of
consistent terminology in the literature and appropriate diagnostics have led
to confusion in the differentiation of histiocytic disorders. Certain disorders have, because of
cytomorphologic characteristics, been erroneously called
"histiocytic". Examples of
diseases which are not of proven histiocytic origin include cutaneous
histiocytoma, "histiocytic" lymphoma, and malignant fibrous
histiocytoma (also known as giant cell tumor of soft parts). True histiocytic disorders, i.e., malignant
histiocytosis, systemic histiocytosis, and hemophagocytic syndrome must be
differentiated from these misnamed disorders.
To add to the confusion, other disorders with similar morphologic
features can mimic malignant histiocytosis.
These include large cell anaplastic carcinoma of the lung, pulmonary
lymphomatoid granulomatosis, and granulomatous inflammation.
To
focus on the features of malignant histiocytosis; it is a rare, rapidly
progressive proliferative disorder of the mononuclear phagocyte system which
has been described in adult dogs, including Bernese Mountain dogs and other
breeds. Malignant histiocytosis is
diagnosed histiologically by the often systemic proliferation of large,
pleomorphic, single and multinucleated histiocytes with marked cellular atypia
and phagocytosis of erythrocytes and leukocytes. The lung and hilar lymph nodes are commonly
involved as well as other lymph nodes, bone marrow, liver, spleen, and central
nervous system.
Thrombocytopenia and anemia have been
associated with malignant histiocytosis.
Positive reactivity of neoplastic cells allows identification of
neoplastic cells to lysozyme and alpha-1-antitrypsin can be demonstrated by immunohistochemistry. This immunohistochemical reactivity allows
identification of neoplastic cells as histiocytic in origin and is paramount to
definitive diagnosis of the neoplasm.
Malignant
histiocytosis must be differentiated from systemic histiocytosis. Systemic histiocytosis is a familial proliferative
disorder in Bernese Mountain dogs of nonneoplastic histiocytes that is
characterized by a lengthy clinical course and consistent skin lesions. By contrast, malignant histiocytosis has a
rapidly fatal course with characteristic cytologic atypia. By cytomorphology
alone, malignant histiocytosis may be difficult to differentiate from
granulomatous inflammation, anaplastic large cell carcinoma of the lung,
lymphoma and pulmonary lymphomatoid granulomatosis. Lack of inflammatory
components and presence of features of malignancy aid differentiation of
malignant histiocytosis from granulomatous inflammation. Prominent features of large cell anaplastic
carcinoma that often differ from malignant histiocytosis include karyomegalic
cells, nuclei with large, prominent central nucleoli and rare
phagocytosis. As in lymphoma, neoplastic
histiocytic cells are discrete; however, oval to reniform nuclear morphology
and larger amounts of finely granular vacuolated cytoplasm aid differentiation
of the histiocytic cells from neoplastic lymphoid cells. Unlike pulmonary lymphomatoid granulomatosis,
malignant histiocytosis does not have an angiocentric distribution nor a marked
lymphoid component. Eosinophils can be
present with both disorders.
Immunohistochemistry may aid in
the differentiation of these disorders.
A diagnosis of malignant histiocytosis should be based on cytomorphology
and immunohistochemistry of cytology and tissue sections. Lysozyme (a histiocytic marker) aids
differentiation of malignant histiocytosis from lymphoid and epithelial
neoplasms. Pulmonary lymphomatoid
granulomatosis and histiocytic lymphoma are not immunoreactive for
lysozyme. An epithelial marker (cytokeratin)
will aid differentiation of carcinoma.
Histiocytic Disorders of Animals
Disorder Cell Lineage Species Distrib.
Neoplastic
Malignant histiocytic dog, widespread yes
histiocytosis (dendritic cells) cat incl. bone
marrow
Systemic histiocytic Bernese widespread no
histiocytosis (dendritic cells) Mtn Dog incl. skin
Cutaneous histiocytic dog skin, SQ no histiocytosis (dendritic
cells)
Hemophagocytic histiocytic dog, bone
marrow no
syndrome cat liver,
spleen
Cutaneous histiocytic? dog skin yes,
histiocytoma (dendritic cells?) regresses
"Histiocytic" lymphoid dog,cat, multifocal, yes
lymphoma horse incl. skin
Pulmonary lymphoid dog lung yes
lymphomatoid
granulomatosis
Malignant fibrous unknown dog, cat, skin, yes
histiocytoma not histiocytic? horse widespread
Large cell epithelial dog lung, yes anaplastic mets carcinoma
of the lung
Granulomatous histiocytic all focal to no
inflammation species widespread