Page 84 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 3 The Pathology of Neoplasia 63

as in squamous epithelium exposed to ultraviolet radiation, can research continues to identify tumor-associated and cell-specific
be a preneoplastic condition. Anaplasia is a loss of differentiation molecular alterations, tumor classifications and subclassifica-
tions are likely to change accordingly. Molecular techniques
or atypical differentiation and is a feature of many, but not all,
VetBooks.ir malignancies. (e.g., IHC, PCR, flow cytometry) ideally will keep pace with
Tumor nomenclature often denotes the histogenesis and
new findings to support diagnostic application of newly dis-
expected biologic behavior (benign or malignant) (Table 3.1). covered molecular characteristics and biomarkers. Broad
Benign tumors of both epithelial and mesenchymal origin typi- encompassing techniques for large genomic, proteomic, and
cally are associated with the suffix –oma (e.g., papilloma, adenoma, metabolomic fingerprinting of tumors are used as discovery
osteoma, fibroma). Exceptions exist, such as melanoma – which, tools to scan for alterations that define subclasses of tumor
when considered malignant based on histopathologic features, types previously unidentified by more traditional methods. The
should be classified specifically as malignant melanoma (it may identification of specific genetic mutations, varied cell surface
be referred to as melanocytoma when benign). Mesothelioma and receptor expression, altered signaling pathways, or altered cel-
lymphoma are other examples that have no benign counterparts. lular metabolic responses to these genetic modifications may
Leukemia, a malignancy of blood cells in circulation (occasionally identify unique fingerprints for a tumor; these, when combined
referred to as “liquid tumors”), also has no benign counterpart, with traditional histologic methods, could allow more accurate
although a leukemoid reaction is a nonmalignant condition that subclassification, prognostication, and personalized treatment
mimics leukemia. 2,5,8 Malignant tumors of epithelial origin are (see Chapter 8).
typically carcinomas (e.g., squamous cell carcinoma [SCC], tran-
sitional cell carcinoma [TCC]), whereas those of mesenchymal Histopathologic Features of Neoplasia
origin typically are associated with the suffix –sarcoma (e.g., osteo-
sarcoma [OSA], fibrosarcoma [FSA], leiomyosarcoma). Some Despite advances in molecular techniques and other ancillary
tumor classifications do not inherently denote biologic behavior diagnostics, light microscopy remains the standard technique for
(e.g., mast cell tumor [MCT], plasma cell tumor), and determi- tumor diagnosis. Neoplasia has certain histologic features that
nation of such often depends on assessment of specific reported distinguish it from hyperplasia or inflammation, and some fea-
histopathologic features and/or published clinical studies. tures differentiate benign from malignant neoplasia. In some cases
Therefore a knowledge of the terminology used to describe these features can be difficult to observe. Definitive diagnosis of
tumor-associated histopathologic features is critical to a true malignant versus benign, or even neoplasia versus inflammation
understanding of the pathology report. Pathologic descriptions or hyperplasia, may not always be possible. In these cases repeat
serve to communicate tumor histogenesis and histomorphologic biopsy or additional ancillary tests may be necessary to facilitate a
evidence of malignant potential (Table 3.2). A low magnifica- definitive diagnosis.
tion assessment of the tumor periphery often provides insight When inflammation is present, reactive fibroblasts and endo-
into whether a tumor might be benign (e.g., well demarcated, thelial cells (ECs) can display features similar to neoplasia how-
2
compressive) or malignant (e.g., infiltrative). The tumor architec- ever, in reactive tissue with inflammation, the fibroblasts and ECs
ture may inform histogenesis—cords, rows, nests, rafts, and acini are oriented perpendicular to one another (reactive granulation
generally indicate epithelial origin; streams and bundles suggest tissue) and the lesion is associated with substantial cellular inflam-
mesenchymal origin; and solid sheets often indicate hematopoi- mation. Epithelioid macrophages in granulomatous inflammation
etic (round cell) origin. In addition to the overall appearance of can be mistaken for tumor cells, but the pattern of tissue involve-
a mass, detailed cellular features in the pathology report may also ment and the presence of other inflammatory cells (mixed inflam-
confer malignant potential (see Table 3.2). Cellular shape is sig- mation) help rule out neoplasia. In some tumors, especially those
nificant because it indicates the cell of origin (histogenesis) and with surface ulceration or intratumoral necrosis, an extensive
weighs heavily on the diagnosis. Shape may be reported as round, amount of inflammation can obscure neoplasia. Other tumors,
polygonal, spindle, or other. The degree of cellular differentiation however, may be associated with inflammation as a defining his-
is typically noted, which refers to the phenotypical maturation topathologic feature that influences tumorigenesis (e.g., feline
and subsequent recognition of a cell; marked atypia and anapla- injection-site sarcomas [ISSs], posttraumatic ocular sarcomas). In
sia tend to reflect poor differentiation and often preclude cellular still other tumors, inflammatory infiltrates may be a recognized
identification. Monomorphic and pleomorphic describe the overall tumor-associated immune response (e.g., lymphocytic infiltrate in
cell population and refer to uniformity or variability, respectively, histiocytomas). 12
of the cell sizes and shapes and/or their respective nuclei. Anisocy- Benign tumors may be most difficult to distinguish from
tosis and anisokaryosis refer specifically to cellular and nuclear size, hyperplasia (see Table 3.2) because both have a proliferation of
respectively, and more specifically reflect the variability or range of well-differentiated cells that resembles normal tissue. Distortion
size throughout the neoplastic cell population. Karyomegalic cells or loss of normal tissue architecture occurs in benign neoplasia,
refer to those with extremely large nuclei. Additional nuclear fea- and usually the tumor grows in an expansive manner, causing
9
tures reported may include binucleated or multinucleated cells, compression of adjacent tissue. These tumors typically are well
bizarre nuclei, and/or prominent or multiple nucleoli, in addition demarcated and may have a fibrous tumor capsule. Hyperpla-
to mitotic figures. A scirrhous (also desmoplastic) response reflects sia tends to retain normal tissue orientation, does not compress
fibroblastic proliferation with collagen deposition, observed in adjacent tissue, and lacks a fibrous capsule. In general, if allowed
some malignant neoplasms, typically carcinomas. 10,11 In situ refers to grow, benign neoplasia attains a larger size than a hyperplastic
to a malignancy, usually limited to lesions of epithelial origin, that lesion. In some instances, such as sebaceous gland adenoma versus
has not yet invaded beyond the natural confines of the basement sebaceous gland hyperplasia or feline benign thyrofollicular prolif-
membrane. 2,5 erations (thyroid adenoma versus adenomatous hyperplasia), the
Neoplasia can arise from any cell type, resulting in a sig- distinction between adenoma and hyperplasia may be clinically
nificant number of different tumor types and classifications. As irrelevant. 13