Bronchogenic Adenocarcinoma with Intrapulmonary Metastases
in a Domestic Shorthair Cat
Jamie Zhen
Clinical Advisor: Dr. Cheryl E. Balkman
Basic Science Advisor: Dr. Erica L. Behling-Kelly
Senior Seminar Paper
Cornell University College of Veterinary Medicine
April 30th, 2014
Key words: Pulmonary neoplasia, metastases, chronic respiratory disease
SUMMARY
Primary pulmonary tumors are very rare in cats with adenocarcinoma being the most
commonly diagnosed pulmonary neoplasia. The initial working diagnosis can be made with
thoracic radiographs. Definitive diagnosis is made with biopsy obtained either at surgery or
necropsy. Primary lung tumors can metastasize to other areas of the lungs, lymph nodes, other
internal organs, as well as unusual sites including digits, skeletal muscle, and eyes. Pulmonary
neoplasia usually carries a poor prognosis, and is worse with the presence of metastases. This
report describes a case of bronchogenic adenocarcinoma with intrapulmonary metastases in a 12
year-old male castrated domestic shorthair cat. The tumor had also metastasized to the thyroid
gland and regional lymph nodes. This patient presented to Cornell University’s Hospital for
Animals for a history of chronic coughing, weight loss, lethargy, and inappetence. This report
describes the clinical, imaging, and pathological findings in a cat diagnosed with bronchogenic
adenocarcinoma with intrapulmonary metastases.
CASE HISTORY
A 12 year-old male castrated domestic shorthair cat was presented to Cornell University's
Hospital for Animals' Internal Medicine Service for evaluation of a chronic cough that started
about 2-3 months prior. About the same time, he started displaying signs of inappetence and
lethargy. The coughing episodes were intermittent and not paroxysmal. These coughing episodes
were not always productive, but the most recent coughing episode resulted in hemoptysis. The
patient’s drinking, urination, and defecation had been normal.
The patient had a history of renal disease, which manifested after being placed under
general anesthesia for a dental procedure. The renal values had returned to normal since then.
The patient was up-to-date on rabies vaccination, but not FVRCP (feline viral rhinotracheitis,
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calicivirus, parvovirus) vaccination. He had tested negative for feline leukemia virus and feline
immunodeficiency virus about one year ago. He was not currently on any medications. The
patient lived with 6 other cats at home and they were all strictly indoors and healthy. The
patient’s diet consisted of a quarter cup of Authority dry food three times daily with some canned
wet food. The patient had no travel history.
CLINICAL FINDINGS
On presentation, the patient was quiet, alert, and responsive with a normal heart rate (210
beats per minute) and respiratory rate (30 breaths per minute). His temperature was elevated at
103.3 F. An intermittent gallop rhythm was noted on auscultation, but no heart murmurs were
heard. Increased lung sounds (harsh lung sounds) were appreciated bilaterally. A right thyroid
slip was appreciated on palpation. He had mild serous ocular and nasal discharge. Oral
examination revealed mild generalized dental tartar and halitosis. No masses, pain, or
organomegaly were appreciated on abdominal palpation. His kidneys were normal-sized and
smooth. All peripheral lymph nodes were within normal limits. The remainder of the patient's
physical exam was unremarkable.
Blood was drawn for quick assessment tests, complete blood count, chemistry panel, and
baseline T4. Quick Assessment Tests (QATS) revealed a low packed cell volume (hematocrit) of
33%. The total protein, blood glucose, and BUN were unremarkable (total protein 7.8 g/dL,
blood glucose 82 mg/dL, blood urea nitrogen [BUN] 15-26 mg/dL).
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COMPLETE BLOOD COUNT (CBC)
Result
Test
Reference Interval
Hematocrit
13% (Low)
31 - 48
MCV
64 fL (High)
40 - 52
MCHC
30 g/dL (Low)
32 - 35
Absolute Reticulocyte count
22.5 thou/uL (NORMAL)
8.5 - 60.7
WBC
432 thou/uL (High)
5.1 - 16.2
Segmented neutrophils
380 thou/uL (High)
2.3 - 11.6
Band neutrophils
38.9 thou/uL (High)
0 - 0.1
Monocytes
8.6 thou/uL (High)
0 - 0.7
Platelet count
52 thou/uL (Low)
195 - 624
Table 1. Complete blood count results.
Complete blood count revealed a severe macrocytic, hypochromic, minimally
regenerative anemia (hematocrit 13%). The discrepancy between the packed cell volume (PCV)
from the QATS with the hematocrit of this CBC was due to the large amount of white cells in the
blood that prevented appropriate sedimentation of the red blood cells, which lead to a falsely
elevated PCV.
A severe inflammatory leukogram with a left shift was observed in this patient. Mild
toxic changes were observed in the neutrophils. Severe thrombocytopenia was present, although
platelet clumps were observed in the blood smear, potentially leading to a falsely decreased
platelet count. However, increased consumption of platelets could be a cause for the
thrombocytopenia given the history of hemoptysis.
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CHEMISTRY PANEL
The chemistry panel revealed a mild hypokalemia (2.8 mEq/L, Reference range: 3.8-5.7)
likely due to the history of kidney disease and subsequent loss in urine. The hypokalemia could
also be due to the patient’s inappetence (decreased potassium intake). The patient’s AST was
mildly elevated (49 U/L, Reference range: 15-44), which could be due to skeletal muscle damage
given the evidence of muscle atrophy or due to some hepatocellular damage.
BASELINE T4
The baseline T4 or total T4 level in this patient was low (1.34 ug/dL, Reference range:
1.5-4), ruling out the possibility of hyperthyroidism as a cause for the right thyroid slip and
weight loss. The low total T4 likely suggested this patient had sick euthyroid syndrome.
URINALYSIS
The urine was minimally concentrated with a urine specific gravity of 1.029, which was
consistent with his history of acute kidney disease. The remainder of the urinalysis was
unremarkable.
RADIOGRAPHY
Figure 1. (A) Ventrodorsal and (B) lateral radiographs of
the thorax of the cat revealed diffuse, multiple variably
sized cavitary lesions with thickened walls.
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Thoracic radiographs revealed severe, numerous pulmonary air cavity lesions that were
irregularly margined and thick-walled. The lobar bronchi were normal and did not definitively
connect with the air cavity structures.
CT SCAN
Computed tomography (CT) scan of the thorax was performed to further characterize the
lesions revealed on thoracic radiographs. The CT scan revealed diffuse, variably sized, abnormal,
air-filled sacs in all of the lung lobes within the lung parenchyma. These air-filled sacs were
surrounded by thick walls and they did not communicate with the airways. The left middle lung
lobe was consolidated on the ventral aspect.
DIFFERENTIAL DIAGNOSIS
Differential diagnoses for this patient given the diffuse cavitary lung lesions with a severe
anemia and inflammatory leukogram were infectious causes and neoplasia (either primary and/or
metastatic). Infectious causes include bacterial, viral, fungal, parasitic, and protozoal in origin. In
cats, certain parasites such as Paragonimus species and foreign body infiltration may result in
cavitary lung lesions.1 Neoplasia in this patient can be primary and/or metastatic and may
include carcinomas or sarcomas as they usually metastasize to the lungs.
FURTHER DIAGNOSTIC TESTING
TRACHEAL WASH CYTOLOGY
While under anesthesia in preparation for the tracheal wash procedure, the patient
experienced a productive cough. The contents were collected and evaluated cytologically, which
revealed a highly cellular sample consisting of a large number of clusters of neoplastic cells
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(epithelial in origin) admixed with a large number of inflammatory cells (predominantly
neutrophils) in the background. The epithelial cells were pleomorphic and were predominantly
found in sheets and clusters. Marked anisocytosis and anisokaryosis were noted with
macronucleoli. Interpretation of this cytology smear was diagnostic for a carcinoma with
purulent inflammation and necrosis.
BONE MARROW CYTOLOGY EVALUATION
Due to the remarkable complete blood count where there was a severe anemia, a marked
inflammatory leukogram with a left shift and toxic changes, and a thrombocytopenia, a bone
marrow aspirate was performed to search for evidence of bone marrow disease. The bone
marrow cytology was interpreted as granulocytic hyperplasia with probable erythropoietic
hyperplasia and probable megakaryocytic hypoplasia. Given the results of this bone marrow
cytologic evaluation with the marked inflammatory leukogram, the leading differential was
paraneoplastic leukocytosis.
PROGNOSIS
Given the diagnosis of a metastatic pulmonary carcinoma with evidence of respiratory
clinical signs, this patient carried a poor prognosis. The owners elected for euthanasia and an
educational necropsy was performed.
GROSS PATHOLOGY
The necropsy revealed the presence of multiple neoplastic nodules within the pulmonary
parenchyma. Other findings included bilateral thyroid enlargement, hepatic congestion with
multifocal biliary cysts, bilateral nephrolithiasis and regional papillary necrosis, and
nematodiasis in the jejunum.
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HISTOLOGY & IMMUNOHISTOCHEMISTRY
Histologic examination of the lungs and thyroid glands revealed evidence of an
adenocarcinoma. The cellular morphology in the pulmonary and thyroid nodules were similar
and because it was uncertain if they represented two separate primary neoplasms or metastatic
disease, immunohistochemical stains were placed on both lung sections and thyroid gland
sections. Thyroglobulin, cytokeratin 7, and cytokeratin 19 stains were placed on the tissue
sections. Thyroglobulin staining is specific for neoplasms of the thyroid; cytokeratin 7 is a
general epithelial cell marker; cytokeratin 19 is an epithelial cell marker that is used for staining
bronchioles. Both the lung and thyroid sections stained negative for thyroglobulin and
cytokeratin 7, whereas they were both strongly positive staining for cytokeratin 19.
A regional lymph node revealed evidence of neoplastic cell infiltration. The
immunohistochemical studies were consistent with an anaplastic bronchogenic carcinoma with
intrapulmonary, thyroid gland, and regional lymph node metastases.
Other histologic diagnoses included bilateral severe chronic lymphoplasmacytic
pyelonephritis and unilateral nephrolithiasis with papillary necrosis; multifocal moderate
neutrophilic, histiolytic encephalitis; and focal pancreatic adenoma, which was considered
incidental.
DISCUSSION
Primary lung tumors are very rare in cats with 70-80% of these tumors being
adenocarcinomas.2 Affected animals have a mean age of 12 years (range 2-20 years) with no
recognized sex or breed predispositions.3 There seems to be no correlation between FeLV and
FIV infection with lung carcinomas in cats.4 Early signs of illness may be non-specific such as
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weight loss, weakness, lethargy, vomiting, and anorexia, and may be followed by signs
associated with respiratory disease such as dyspnea, tachypnea, nonproductive cough, and
hemoptysis, which are usually evident late in the course of disease.4,5 Early diagnosis of primary
lung tumors in cats is usually difficult given the non-specific clinical signs and non-specific
changes in routine laboratory data.4 There was one case report of hypercalcemia of malignancy
in a cat with bronchogenic adenocarcinoma.6 Our patient had a severe macrocytic, hypochromic,
minimally regenerative anemia likely due to a combination of hemorrhage with the history of
hemoptysis as well as anemia of chronic inflammation, and probable ineffective hematopoiesis.
Paraneoplastic leukocytosis was described in a cat with pulmonary squamous cell carcinoma
where the white cell count returned to normal range after surgical resection of the tumor.7 Our
patient’s severe inflammatory leukogram with a left shift was consistent with paraneoplastic
leukocytosis. Thoracic radiography may show evidence of a solitary lung tumor, pleural effusion
in about 33% of cases,5 and rarely cavitary lesions.1 The diffuse cavitary lesions seen on thoracic
radiographs of our patient is a very unusual presentation of primary lung tumors in cats. Despite
diagnostic work-up with complete blood count, chemistry panel, and imaging, definitive
diagnosis is made by histologic examination of biopsy or necropsy specimens.4,5
Metastasis of primary lung tumors can occur in other areas of the lungs, abdominal or
mediastinal lymph nodes, liver, spleen, pancreas, kidneys, eyes, skin and even skeletal muscle.2,4
Another unusual site of metastasis in cats with primary lung tumors is the digits, which is
described as the feline lung-digit syndrome.3 In fact, about 1 out of every 6 laboratory
submissions of amputated feline digits contained a metastatic lesion, usually from bronchogenic
adenocarcinomas.3 Our patient showed evidence of intrapulmonary as well as thyroid gland and
regional lymph node metastases. The prognosis for cats with primary lung tumors is generally
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poor.4 Surgical treatment for cats with moderately differentiated lung tumors resulted in a
median survival time of 698 days (range 19-1,526 days, n = 12 cats) compared to cats with
poorly differentiated lung tumors, which resulted in a median survival time of 75 days (range 13634 days, n = 9 cats).8 Negative prognostic indicators included the presence of clinical signs
(specifically dyspnea), pleural effusion, evidence of metastasis, and poorly differentiated
tumors.9 Given the diffuse cavitary lung lesions in our patient, surgical resection was not an
appropriate treatment option. Additionally, our patient had evidence of metastases and poorly
differentiated neoplasia, which were both negative prognostic indicators. Cats with primary lung
tumors that were diagnosed before the presence of clinical signs were more likely to have a lowgrade tumor and longer survival times, which is critical information to take into account when
making the decision to treat surgically in these patients.9
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REFERENCES
1. Rossi F et al. Unusual radiographic appearance of lung carcinoma in a cat. Journal of Small
Animal Practice. (2003) 44:273-276
2. Langlais LM et al. Pulmonary adenocarcinoma with metastasis to skeletal muscle in a cat.
Practitioners’ Corner. (2006) 47:1122-1123
3. Goldfinch & Argyle. Feline lung-digit syndrome: unusual metastatic patterns of primary lung
tumors in cats. Journal of Feline Medicine and Surgery. (2012) 14:202-208
4. Petterino C et al. Bronchogenic adenocarcinoma in a cat: an unusual case of metastasis to the
skin. Veterinary Clinical Pathology. (2005) 34(4):401-404
5. Kahn & McEntee. Primary lung tumors in cats: 86 cases (1979-1994). JAVMA. (1997)
211(10):1257-1260
6. Schoen K et al. Hypercalcemia of malignancy in a cat with bronchogenic adenocarcinoma.
Journal of American Animal Hospital Association. (2010) 46:265-267
7. Dole RS et al. Paraneoplastic leukocytosis with mature neutrophilia in a cat with pulmonary
squamous cell carcinoma. Journal of Feline Medicine and Surgery. (2004) 6(6):391-395
8. Kahn & McEntee. Prognosis factors for survival in cats after removal of a primary lung tumor:
21 cases (1979-1994). Veterinary Surgery. (1998) 27:307-311
9. Maritato et al. Outcome and prognostic indicators in 20 cats with surgically treated primary
lung tumors. Journal of Feline Medicine and Surgery. (2014) 16(4):1-6
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