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9.4.2.2 Hemarthrosis
True hemarthrosis, defined as hemorrhage within the synovial space, can be difficult to differenti-
ate from inadvertent blood contamination. Therefore, the clinician should communicate any dif-
ficulties encountered during sample collection or irregular amounts of blood seen during aspiration
to the laboratory. Joint fluid associated with true hemarthrosis is typically homogeneously pink/
orange/red. Cytological evaluation reveals an increased density of red blood cells, a dilute glycosa-
minoglycan background, increased hemosiderin laden and erythrophagocytic macrophages, and,
if chronic, hematoidin crystals (Figure 9.5). Erythrophagocytic macrophages are macrophages
with erythrocytes in their cytoplasm. Hemosiderin is an iron storage complex that forms within
macrophages as erythrocytes are being broken down. The pigment granules on Wrights–Giemsa
staining appear dark blue green to almost black and can vary between very fine to globular within
the cytoplasm. Special stains to identify iron (i.e. Prussian blue) can be performed to identify
hemosiderin from other pigment granules. Hematoidin crystals are breakdown products of biliru-
bin that crystalize to form diamond‐to‐rectangular‐shaped light brown‐gold refractile crystals. Of
note, macrophages are capable of phagocytizing erythrocytes post‐collection and within collection
tubes. Therefore, it is crucial to make fresh smears at the time of collection to discern in vivo from
in vitro erythrophagia. The presence of hemosiderin and hematoidin is more definitive for true
hemorrhage because they take longer to form and suggest chronicity. Possible differentials for
patients with hemarthrosis include trauma, coagulation disorders (hemophiliacs versus anticoag-
ulants), or any condition that disrupts blood supply and causes hemorrhage (i.e. neoplasia).

9.4.3 Neoplasia

All cell populations within the joint organ have the potential to become neoplastic. Diagnosis of a
neoplastic disorder can be reached by combining the clinical picture with the cytological findings.
Establishing a diagnosis based on synovial fluid analysis can be difficult; neoplastic synovial fluid is
highly variable in cellular and protein composition and can appear similar to any of the other cate-
gories described above. It is the presence of cells that display atypia and criteria of malignancy that
should alert the evaluator to consider neoplastic differentials (e.g. synovial cell sarcoma in
Figure 9.5F). Ancillary diagnostics, such as biopsy, immunocytochemistry or immunohistochemis-
try, and/or flow cytometry, are typically required to reach a definitive diagnosis, as multiple types of
sarcomas have similar morphological feature. Additionally, other tumor tissue types, such as carci-
nomas and lymphomas, have been reported to metastasize or localize to synovial tissue and fluid.

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