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CHAPTER 7 Diagnostic Cytopathology in Clinical Oncology 131
of malignancy and suggest malignant behavior, but these features Sending Cytologic Samples to a Diagnostic
may be observed in nonneoplastic cells found in primary inflam- Laboratory
matory lesions.
VetBooks.ir population that suggest malignant behavior, with greater empha- When using a referral diagnostic laboratory, two to four unstained
Criteria of malignancy are cellular features within a single
sis placed on nuclear criteria. The more criteria observed, the smears should be sent. If a highly cellular smear has been stained
and examined by the oncologist for confirmation of sample qual-
more likely the tumor is malignant. Cellular and cytoplasmic ity and the cellularity of the remaining unstained smears is in
criteria of malignancy include variation in cell size (anisocyto- question, send the stained smear in addition to the unstained
sis), abnormal cellular arrangement (3-dimensional [3D] clus- smears. All slides should be packed in rigid slide containers to
ters instead of a monolayer), cells that are smaller or larger than prevent breakage during shipment. For shipment by commercial
their normal counterpart, variable nuclear-to-cytoplasmic (N:C) mail services, slide holders are placed in a cardboard box with suf-
ratios or N:C ratios that differ from what is expected for the cell ficient padding; padded envelopes are not recommended because
type, intensely basophilic cytoplasm (hyperchromasia), abnormal these may not provide sufficient protection. Slides should not be
vacuolation or granulation, and aberrant phagocytic activity. refrigerated before or during shipment. Exposure to formalin or
The nucleus is the most important component of the cell when formalin fumes should be avoided during the preparation and
determining the biologic behavior of a neoplasm. Nuclear crite- shipment of cytologic specimens because this will permanently
ria of malignancy include variation in nuclear size (anisokaryosis), alter staining characteristics and render the sample nondiagnos-
unusual nuclear shape, multinuclearity, variation in nuclear size tic; surgical biopsy specimens preserved in formalin should be
within the same multinucleated cell, nuclear fragments, multiple sent separately from cytologic specimens, or each type of sample
nucleoli that vary in size and shape within the same nucleus or should be sealed in separate plastic bags. If cavity fluids or mucosal
among cells, increased mitoses, and nonsymmetric mitoses (Fig. washes are submitted, include two freshly made unstained smears
7.6). When Papanicolaou stain is used, additional nuclear fea- along with the fluid (in EDTA) or wash (sealed container). Plain
tures such as irregular thickening of the nuclear membrane can tubes (red top) or sterile vials are required for specimens that may
be evaluated. Cellular gigantism (cell >10 times the diameter of be cultured. For all submitted glass slides, indicate how the slides
an erythrocyte) and the presence of macronuclei (>5 times the were prepared and whether a concentration method was used for
diameter of an erythrocyte) or macronucleoli (larger than an
erythrocyte) are particularly disturbing criteria of malignancy. cavity effusions.
In nonneoplastic cells, the chromatin pattern is finely stippled
in replicating or metabolically active cells and condensed in Interpretation of Cytologic Specimens
mature quiescent cells. Finely stippled chromatin is also com- The final interpretation of a cytologic specimen should be based
mon in rapidly proliferating neoplastic cells, and chromatin not only on the cytologic findings but also on signalment, history,
that is irregularly clumped or ropy is unusual and suggestive of clinicopathologic findings, and imaging results. This information
a neoplastic process. Some nonneoplastic cells, including meso- should be provided in a concise but complete summary to the
thelial cells, fibroblasts, and squamous epithelial cells, may have individual evaluating the sample. When submitting samples to a
criteria of malignancy when they are highly proliferative in the cytopathologist, the exact location of the lesion should be clearly
presence of inflammation. Conversely, some malignant tumors described because “thoracic mass” could indicate a mass located
such as apocrine gland tumors of the anal sac have few criteria in the skin, subcutis, body wall, mediastinum, thoracic cavity, or
of malignancy.
pulmonary parenchyma; the differential diagnoses will be differ-
ent for different locations. For clinicians who perform an initial
evaluation of the cytologic specimen, observational and interpre-
tative skills can be developed by comparing their findings with
*
*
• Fig. 7.5 Fine-needle aspirate of a mast cell tumor. Note the heteroge-
neous populations of cells, including mast cells, eosinophils (thick arrow),
fibroblasts (white arrow), and lymphocytes. Extracellular matrix (thin
arrows), likely collagen, is also present and stringy chromatin (asterisks) • Fig. 7.6 Fine-needle aspirate of a hemangiosarcoma with multiple criteria
from broken nuclei is noted. of malignancy. Inset: An atypical mitotic figure from a liposarcoma.