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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. 
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