Page 517 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 24 Tumors of the Respiratory System 495

Pathology and Natural Behavior History and Clinical Signs

Carcinomas, including adenocarcinoma, SCC, and undifferenti- Although many intranasal diseases will have overlapping clinical
VetBooks.ir ated carcinoma represent nearly two-thirds of canine intranasal signs, a strong suspicion of cancer is appropriate for older animals
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with an intermittent and progressive history of unilateral (initially)
tumors. Sarcomas (usually fibrosarcoma, chondrosarcoma,
osteosarcoma, and undifferentiated sarcoma) comprise the bulk of
these
25,74
the remaining cancers. Both carcinomas and sarcomas are char- epistaxis or mucopurulent discharge (or both). The average dura-
tion of clinical signs before diagnosis is 2 to 3 months;
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acterized by progressive local invasion. The metastatic rate is gen- most commonly include epistaxis, bloody or mucopurulent nasal
erally considered low at the time of diagnosis but may be as high discharge, facial deformity due to bone erosion and subcutaneous
as 40% to 50% at the time of death, which is usually attributable extension of tumor, unwillingness to open the mouth, sneezing,
26
to the primary disease rather than metastatic lesions. The most dyspnea or stertorous breathing, exophthalmos, and ocular dis-
common sites of metastasis are the regional lymph nodes (LNs) charge as a result of mechanical obstruction of the nasolacrimal
and the lungs. 26,35,36 Less common sites include bones, kidneys, duct. 25,34,74 Differential diagnoses for animals with these clinical
liver, skin, and brain. 37–40 signs include fungal (Aspergillus sp.) or bacterial rhinitis, idio-
Rare tumors of the sinonasal region in dogs include round pathic nonspecific rhinitis (usually lymphoplasmacytic), rare nasal
cell tumors (such as lymphoma), mast cell tumor (MCT), and parasites, bleeding disorders, hypertension, foreign body, trauma,
transmissible venereal tumor. Other malignancies include hem- and developmental anomalies (e.g., cystic Rathke’s clefts). 75–77
angiosarcoma, melanoma, neuroendocrine carcinoma, nerve If facial deformity is present, the diagnosis is almost always can-
sheath tumor, neuroblastoma, fibrous histiocytoma, multilobular cer; 78–79 however, aspergillosis, sporotrichosis, and a rare, benign
osteochondrosarcoma, hamartoma, rhabdomyosarcoma, and leio- condition, angiomatous proliferation of the nasal cavity or angio-
myosarcoma. 26,41–58 The biologic behavior of these less common fibroma, also can cause facial deformity. In a retrospective study of
malignancies is not well defined, although small retrospective case 105 cases of dogs with intranasal disease, the characteristics of the
series have been reported for lymphoma, intranasal MCT, and mel- nasal discharge were evaluated to determine whether they corre-
anoma. 59–62 Benign, yet often locally invasive lesions such as polyps, lated with diagnosis. In dogs with confirmed neoplasia (n = 23),
80
fibromas, dermoid cysts, and angiofibroma can also be seen. 63,64 the median duration of discharge was 60 days. Mucoid discharge
A number of studies have attempted to elucidate possible in pure or mixed form was seen more frequently in neoplasia com-
molecular mechanisms associated with canine sinonasal tumori- pared with fungal, nonspecific rhinitis and foreign body cases.
genesis. In one study using a single polyclonal antihuman anti- When signs lasted more than 14 days, hemorrhagic discharge was
body, nuclear p53 accumulation was detected in nearly 60% of seen more commonly in dogs with neoplasia compared with those
nasal adenocarcinomas (11 of 19), which suggests that overexpres- with rhinitis or other causes. Nasal stridor was also noted more
65
sion of a mutated p53 tumor suppressor protein may play a role. often in dogs with neoplasia.
Cyclooxygenase-2 (COX-2) expression has been detected to vary- Clinical signs can be temporarily alleviated by a variety of
ing degrees in most sinonasal epithelial tumors sampled 66–69 and symptomatic treatments, including antibiotics, steroids, and non-
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in normal paratumoral respiratory epithelium and stromal tissue. steroidal antiinflammatory drugs (NSAIDs). An initial response
74
In one study, epidermal growth factor receptor (EGFR) expression to these treatments should not diminish the index of suspicion for
and vascular endothelial growth factor (VEGF) expression were neoplasia in older dogs with clinical signs consistent with cancer. 74
detected in over 50% and 90% of the 24 nasal carcinomas evalu- On rare occasions, animals with tumors involving the caudal
70
ated, respectively. All tumors expressed either EGFR or VEGF, region of the nasal cavity may have only neurologic signs (e.g.,
but there was no association between the immunoreactivity for seizures, acute blindness, behavior change, paresis, circling, and
70
each protein. To evaluate expression of receptor tyrosine kinases obtundation) caused by direct invasion of the cranial vault. 55,56,81
(RTKs) with the intent to establish a rationale for use of TK inhib- However, absence of neurologic signs does not rule out tumor exten-
itors (TKIs), VEGFR2 and platelet derived growth factor receptor sion into the cranial vault because most dogs with nasal tumors that
(PDGFR) α and β have been evaluated in 187 nasal carcinoma extend beyond the cribriform plate do not exhibit neurologic signs.
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samples. VEGFR was expressed in 84% of the samples and was
predominantly cytoplasmic-membranous, similar to what is seen Diagnosis and Staging
in high grade MCTs. PDGFRα was noted in 71% of cases and
PDGFRβ in 40%, both with weak to moderate intensity. Coex- A definitive diagnosis of sinonasal cancer requires a tissue biopsy,
pression of RTKs was common. The authors concluded that stud- even though diagnostic imaging and historic information can be
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ies evaluating clinical utility of TKIs are warranted. Expression of highly suggestive. Coagulation disorders must be ruled out before
peroxisome proliferator-activated receptor γ (PPAR-γ), a nuclear biopsy because bleeding during the procedure is to be expected.
receptor involved in glucose metabolism and fatty acid storage, The superior imaging value of CT and MRI over conven-
has also been shown in canine nasal carcinomas. The authors of tional radiographs for canine nasal disease, including neoplasia,
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that study suggested that expression patterns may differ in tumor is well documented. 27,49,75,82–88 Cross-sectional imaging provides
tissue compared with normal nasal epithelium. The role of these improved anatomic detail, which allows accurate determination
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proteins in carcinogenesis is not clear, and further investigation is of the extent of tumor (staging) and localization of nasal cavity
needed before clinical relevance can be determined. Evaluation of abnormalities (Fig. 24.4). 27,49,75,82–88 It also facilitates evaluation
the inflammatory infiltrate in 31 canine nasal carcinomas revealed of the integrity of the cribriform plate and identification of poten-
an abundance of neutrophils and macrophages, which were pres- tial tumor extension into the cranial vault. Although, in general,
ent in greater numbers than in normal canine mucosa. Plasma MRI allows for better resolution of soft tissue structures, one
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cells and T lymphocytes were also detected; however, levels did report showed no clinically relevant benefit to using MRI over
not correlate with particular tumor subtype. CT to evaluate nasal tumors that do not extend into the cranial