BRONCHIAL BIOPSIES AND THEIR PITFALLS

Endobronchial biopsy is the most commonly used procedure
for obtaining a diagnosis in non–small cell carcinomas including
squamous carcinoma and is described in detail elsewhere
in this volume. In this procedure, a small fragment of bronchial
mucosa is fixed in formalin and embedded in a block of
paraffin wax for sectioning. Diagnostic tumor tissue my not
be evenly distributed in the tissue and multiple sections of the
block may be required to obtain a definitive histological result.
Occasionally, squamous carcinomas may have an inaccessible
endobronchial component and the easiest access to diagnostic
material is through transbronchial biopsy. Here the same
considerations of sampling artifact and representation of the
tumor through all sections of the block are relevant.
Cytology Cytological specimens may be obtained through transbronchial
or transthoracic fine-needle aspiration or through expectoration
of sputum, either spontaneous or induced. Cytological
specimens are fixed in alcohol-based fixatives and typically stained
by the Papanicolaou method, which incorporates orange G dye
that produces an intense waxy red-orange staining of squamous
cell cytoplasm (Fig. 22.6). 61 Elongated single cells ( tadpole cells or
fiber cells ) are frequent. Nuclei are large, irregular shaped, and irregularly
condensed. Less differentiated tumors contain sheets of cells
with high nuclear/cytoplasmic (N/C) ratios with fewer differentiated
squamous cells. Although sheets of cells with well-defined cell
borders can be suggestive of squamous cell carcinoma, intercellular
bridges cannot be easily visualized in cytological specimens and
therefore are not a reliable criterion. The appearance of the aspirate
can vary with the technique used to sample the tumor. In squamous
cell carcinoma, for example, a sputum specimen will more
likely sample better differentiated superficial tumor cells, whereas
techniques such as bronchial brushing or fine-needle aspiration
will sample more cells from within a tumor mass that may show
more of the tumor sheets and less differentiated cells. 61
The overall sensitivity and specificity of cytological specimens
in a recent literature review of 16 studies by the Duke
University Center for Clinical Health Policy Research were
0.66 and 0.99, respectively. 62 The sensitivity of sputum specimens
is highest for squamous cell carcinoma and small cell
carcinoma (the centrally located tumors), 62,63 and is most
specific for squamous cell carcinoma. 61 The diagnostic yield is
better with larger tumors, which are centrally located, and in
patients who present with bloody sputum. 63
Differential Diagnosis A major differential diagnostic
consideration in an endobronchial biopsy is the distinction between
invasive squamous carcinoma and noninvasive squamous
lesions in the respiratory mucosa. In some cases, in situ squamous
carcinoma may exhibit considerable pleomorphism and
may be difficult to distinguish from invasive carcinoma purely
on the basis of the cytological appearances. An additional consideration
is the extension of in situ tumor into the bronchial
glands, which many mimic invasive carcinoma. Finally, the
bronchial lining may respond to many different types of injury
such as pneumonia, infarcts, and radiation or chemotherapy by
converting from mucociliary epithelium to squamous epithelium
that can mimic squamous cell carcinoma. It is therefore
important that a history of these conditions accompany requests
for pathological examination. In order to be completely
confident of a diagnosis of invasive carcinoma, unequivocal
invasion with nests of cells or single cell infiltrates eliciting a
stromal response in the underlying mucosa is required.
The diagnosis of squamous carcinoma is usually made by
conventional light microscopic examination of small biopsy or
cytology specimens. Diagnosis can be difficult or misleading
when small numbers of tumor cells are available for study and
in approximately 30% of these small specimens, distinction
of cell type cannot be made or the specimen is misdiagnosed.
This can be a critical issue since agents such as the vascular endothelial
growth factor (VEGF) blocker, bevacizimab, 64 may
cause cavitation in squamous tumors that can be life threatening
while pemetrexed may be less effective against squamous
tumors than against adenocarcinoma.