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144 PART II Diagnostic Procedures for the Cancer Patient
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• Fig. 7.37 Fine-needle aspirate of a transmissible venereal tumor (TVT).
• Fig. 7.36 Fine-needle aspirate of a histiocytic sarcoma. Note extreme Note the coarse chromatin and small discrete vacuoles in the cytoplasm
pleomorphism, phagocytosis, and bizarre multinucleated cell (inset). that are often referred to as a “string of pearls.” (Courtesy Dr. Robert Hall.)
T-cell–mediated immune response that likely leads to the spon- the sole warning of their malignant nature. Rarely is a definitive
taneous resolution of these tumors. Presumed histiocytomas that diagnosis of HHS made cytologically and histologic examination
do not resolve or that increase in size should undergo histologic is required; a clinical presentation of hemolytic anemia nonre-
evaluation to rule out cutaneous lymphoma or a more aggressive sponsive to immunosuppressive therapy, with or without other
histiocytic neoplasm. peripheral blood cytopenias, warrants consideration of HHS. In
the absence of defined masses, a histologic diagnosis may also be
Histiocytic Sarcomas of Dendritic and Macrophage difficult.
Lineage Differential diagnoses for these tumors depend on cytologic
Histiocytic sarcomas of dendritic and macrophage lineage are appearance. Few tumors are as pleomorphic as the round cell
malignant tumors and are variably called HS, malignant his- variant of HS; however, differential diagnoses may include
tiocytosis (MH), and hemophagocytic histiocytic sarcoma (HHS), anaplastic carcinoma and pleomorphic lymphoma. Differen-
depending on clinical presentation, cytomorphologic appear- tial diagnoses for the spindle-cell variant include a variety of
ance, and specific cell lineage (see Chapter 34, Section F). These other sarcomas. Differentials for HHS are not tumors at all,
tumors have at least three cytologic appearances. First, the tumor but include reactive macrophage proliferations secondary to
may be composed of a highly pleomorphic population of discrete other tumors or other inflammatory processes (hemophagocytic
round cells with extreme variations in N:C ratios, cell size, and syndrome).
nuclear size (Fig. 7.36). The cytoplasm is basophilic and may
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contain numerous vacuoles, thought to be lysosomes, or phago- Transmissible Venereal Tumor
cytosed erythrocytes, leukocytes, other tumor cells, or cellular Transmissible venereal tumor (TVT) is a unique transmissible
debris. Nuclei are typically round but may vary in shape and have tumor thought to be of histiocytic origin. Its morphologic appear-
indented or irregular margins. Chromatin is coarse to clumped, ance is distinctive, and cytologic evaluation can provide a defini-
and nucleoli are prominent and vary in number, size, and shape. tive diagnosis, especially when the tumor is located in typical
Multinuclearity and bizarre mitotic figures are common. Many locations, such as mucous membranes of external genitalia and
of these tumors are infiltrated by low numbers of small lympho- nasal cavity. The N:C ratio is moderate to high. The nucleus is
cytes, plasma cells, and neutrophils. The second form comprises centrally or eccentrically located and has coarse chromatin and
round, oval, and spindle cells with a more sarcoma-like appear- one or more prominent nucleoli (Fig. 7.37). The cytoplasm is
ance. Pleomorphism is less striking, but criteria of malignancy lightly basophilic and contains characteristic clear vacuoles, often
are present and warrant a cytologic interpretation of malignancy. giving a “string of pearls” appearance. Mitotic figures are frequent.
Cytoplasmic vacuolation and phagocytic behavior also are less Mature lesions may contain infiltrating small lymphocytes. When
frequent. Nuclear shape is typically round to oval or elongate. found in atypical locations, such as the torso, limbs, and lymph
These two forms are consistent with a tumor of dendritic cell nodes, TVT may be mistaken for lymphoma, HS, or amelanotic
origin. melanoma.
The third form is HHS, in which neoplastic macrophages
constitute a “wolf in sheep’s clothing” because the cells resemble Mesenchymal and Epithelial Tumors That May
phagocytic macrophages found in inflammatory lesions and sel-
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dom exhibit criteria of malignancy. The cells have moderate Appear as Discrete Round Cell Tumors
N:C ratios; vacuolated cytoplasm that frequently contains hemo- Mesenchymal and epithelial tumors that may appear as discrete
siderin or phagocytosed erythrocytes, neutrophils, or platelets; round cell tumors include amelanotic melanoma, granular cell
and round central nuclei with reticular chromatin and one to two tumor, anaplastic carcinoma, OSA, chondrosarcoma, rhabdomyo-
variably prominent nucleoli. More prominent pleomorphic fea- sarcoma, and liposarcoma. Histologic examination of the tumor
tures may be seen in a few cells. The neoplastic macrophages may and immunohistochemical evaluation may be required to ascer-
form dense sheets in spleen, liver, or bone marrow, which may be tain the lineage of these round cell imposters.