Mucinous Pleural Effusion in a Dog with a Pulmonary Adenocarcinoma and Carcinomatosis
An 11 yr old castrated male greyhound presented to the Washington State University's Veterinary Teaching Hospital (WSU VTH) for evaluation of a 4 day history of pleural effusion. The pleural effusion had a gelatinous appearance, suggestive of mucus, and was characterized cytologically as a pyogranulomatous exudate with some features suggestive of a carcinoma. Postmortem examination identified a pulmonary mass with evidence of carcinomatosis. Pulmonary papillary adenocarcinoma with carcinomatosis was the histologic diagnosis. Abundant mucin production was present, consistent with a mucinous pulmonary adenocarcinoma. To the authors' knowledge, this is the first report of a mucinous pulmonary adenocarcinoma with mucus pleural effusion in a dog.
Introduction
Mucinous pulmonary adenocarcinomas are rarely reported in human medicine and are similar to nonpulmonary mucinous adenocarcinomas of the gastrointestinal tract, pancreas, and breast in that the neoplastic cells retain an ability to produce mucinous compounds.1 Seeding of serosal surfaces with neoplastic cells can result in mucinous effusions. Mucus-producing tumors have been rarely reported in the veterinary literature. One dog with a cardiac myxosarcoma had a mucinous pleural effusion.2 In another dog, mucinous peritoneal effusion was present with a gastric carcinoma.3 To the authors' knowledge, mucinous pulmonary adenocarcinoma has not been previously reported in dogs. The purpose of this report is to present a case of mucinous pulmonary adenocarcinoma and the associated effusion characteristics.
Case Report
An 11 yr old castrated male greyhound presented to the WSU VTH for evaluation of pleural effusion diagnosed 4 days prior to presentation. Two years prior to presentation to the WSU VTH, the dog underwent splenectomy for splenic vein thrombosis. Cardiac arrest occurred intraoperatively and the dog was revived via a diaphragmatic window and cardiac massage. Moderate mitral valve regurgitation and severe systolic dysfunction attributed to systemic inflammatory disease and dilated cardiomyopathy were observed on a postoperative echocardiogram. The patient was initially discharged with pimobendan and enalapril; however, the medications were discontinued shortly after discharge without clinical signs of progressive cardiovascular disease.
At the time of initial presentation to the referring veterinarian, the dog had been coughing, inappetent, and lethargic the previous day. Abnormal results of a complete blood cell count and serum biochemical profile included mild anemia (5.19 × 109/L; reference range, 5.5–8.5 × 109/L with a hematocrit of 36.9%; reference range, 37–55%), leukocytosis with mature neutrophilia and monocytosis (total WBC was 26.41 × 109/L; reference range, 5.5–16.9 × 109/L; neutrophils were 22.37 × 109/L; reference range, 2–12 × 109/L; and monocytes were 2.49 × 109/L; reference range, 0.3–2 × 109/L), mild hyperchloridemia (124 mmol/L; reference range, 109–122 mmol/L), hyperglycemia (8.99 mmol/L; reference range, 3.89–7.94 mmol/L), and elevated creatinine (176.80 μmol/L; reference range, 44.20–159.12μmol/L). The mild creatinine elevation with normal blood urea nitrogen was attributed to normal variation for the breed because healthy retired racing greyhounds and other dogs with increased muscle mass can have increased creatinine levels.4–6 Further, given that greyhounds commonly have higher hematocrit values than other dog breeds, the anemia was viewed as potentially more severe than suggested based on the value alone.4 The mature neutrophilia and monocytosis were consistent with chronic inflammation. The hyperchloridemia in the face of a normal Na concentration most likely represented a secretional metabolic acidosis; however, that could not be confirmed because blood gas analysis was not performed. Differential diagnoses for a secretional metabolic acidosis included gastrointestinal or renal loss of bicarbonate, dilutional acidosis, or compensation for a respiratory alkalosis.
Thoracic radiographs revealed severe, bilateral pleural effusion and a suspected soft-tissue opacity in the cranioventral thorax. Bilateral thoracocentesis was performed and 1600 mL of a viscous, gelatinous, blood-tinged fluid was removed. Thoracic radiographs following thoracocentesis revealed that a moderate amount of pleural effusion remained. The right cranial lung lobe was collapsed, with evidence of an air bronchogram, and the remaining lung fields appeared normal. Fluid analysis, including an automated cell count, protein determination via refractometry, and cytology of the effusion were suggestive of a protein-rich transudate (total protein was 29 g/L, red blood cells were 10 × 109/L, specific gravity was 1.020, and total nucleated cell count was 2.48 × 109/L) with no evidence of either neoplasia or etiologic agents.
Treatment with 11.7 mg/kg doxycycline per os (PO) q 12 hr was initiated. Two days later, when clinical signs of lethargy, hyporexia, and hind-limb weakness returned, the patient was referred to the WSU VTH for further evaluation.
At the time of referral, the patient was quiet, alert, and responsive. Body weight was 42.6 kg, temperature was 38.8°C, heart rate was 96 beats/min, and the patient was panting with increased respiratory effort. Lung sounds were absent in the ventral half of the thorax, and soft bronchovesicular sounds were heard dorsally. Bilateral jugular pulsations, synchronous with the expiratory phase of respiration, were noted. The remainder of the physical examination was unremarkable.
Bilateral thoracocentesis was performed, and 705 mL of blood-tinged, viscous fluid was removed from the chest. Fluid analysis was consistent with an exudate (specific gravity was 1.023, total protein was 33 g/L, total nucleated cell count was 40.59 × 109/L, and packed cell volume was <2%). A differential cell count of the nonneoplastic cells revealed 89% nondegenerate neutrophils, 10% large mononuclear cells consistent with macrophages, and 1% small lymphocytes. There was no evidence of “wind-rowing.” An abundant population of cohesive and individual round cells with marked anisocytosis and anisokaryosis and variable nuclear/cytoplasmic ratios was present. The cells ranged in size from 30 to 140 μm and had round, oval, or frequent bizarre multilobulated and vacuolated nuclei composed of dense, coarse, or fine granular chromatin. Large prominent nucleoli were seen in some cells. Multinucleation with severe anisokaryosis was commonly seen within the same cell population. Abundant basophilic cytoplasm with indistinct vacuoles that often peripheralized the nuclei was also observed. The high degree of cellular atypia favored a neoplastic etiology over the dysplasia that can be seen secondary to severe inflammation. High numbers of nondegenerate neutrophils were present. Moderate numbers of actively phagocytic macrophages were seen. The fluid was classified as a pyogranulomatous exudate highly suspicious for malignant neoplasia. The unusual mucoid nature of the fluid appreciated grossly added further suspicions to a neoplastic etiology because that fluid characteristic would not be expected with traditional effusion etiologies. Anaerobic, aerobic, and fungal cultures were submitted with no growth observed.
An echocardiogram, performed due to the history of cardiovascular disease, revealed an echogenic pleural effusion. A well-circumscribed, heterogeneous, soft-tissue mass near the left atrium and auricle measuring 6.5 cm × 7 cm was observed. Moderate to severe systolic dysfunction was present but was considered unchanged from the previous echocardiogram. Crystalloidsa were administered at a rate of 4 mL/kg/hr overnight providing maintenance fluids with correction of anticipated ongoing losses. Additional diagnostics, including a thoracic computed tomographic scan and either ultrasound- or computed tomographic-guided biopsies of the intrathoracic mass, were declined. Instead, treatment with palliative therapy for a presumed intrathoracic carcinoma was elected. The patient was discharged the following day with carprofenb (2.3 mg/kg PO q 12 hr) and tramadolc (3.5 mg/kg PO q 8 hr). A metronomic chemotherapeutic protocol with lomustined was prescribed (2.78 mg/m2 PO q 24 hr); however, the patient was euthanized due to poor quality of life 2 days after discharge before lomustine could be administered.
A partial necropsy was performed by the referring veterinarian. Gross pathological findings noted by the referring veterinarian included 2.5 L of blood-tinged viscous fluid in the pleural space. Irregular lobulated masses ranging in size from 0.1 to 0.5 cm were present diffusely on the pleura throughout the thoracic cavity. A large mass was present in the left middle lung lobe with multiple small masses throughout the remaining lung lobes. A mass measuring 2 cm × 1.5 cm × 1 cm was present at the heart base. The size of the mass was likely overestimated during the echocardiogram due to significant lung lobe atelectasis surrounding the mass. Samples were submitted for histopathology.
Results of histological examination of the lung, pleura, and heart base mass were similar. Moderately cellular invasive masses were composed of neoplastic epithelial cells in single to multiple layers forming papillary projections supported by a moderate amount of collagenous stroma. The neoplastic epithelial cells were small to large and cuboidal to columnar with moderate amounts of eosinophilic cytoplasm and occasional tufts of apical cilia. The nuclei were small to large and oval to irregular with vesicular chromatin, variably distinct nucleoli, and infrequent (but often irregular) mitotic figures. Abundant mucin was present within the luminal spaces formed by the papillary projections of the neoplastic cells (Figure 1). Replicate sections treated (and appropriately controlled) with Alcian blue (pH 2.5) and Mayer's mucicarmine (Figure 2) histochemical stains verified mucin within the lumina. Altogether, the findings were consistent with a mucinous pulmonary papillary adenocarcinoma with metastasis to the lungs, pleura, and heart base.
Citation: Journal of the American Animal Hospital Association 51, 5; 10.5326/JAAHA-MS-6227
Citation: Journal of the American Animal Hospital Association 51, 5; 10.5326/JAAHA-MS-6227
Discussion
The dog described in this report was diagnosed with an uncommon tumor type. The presence of a tumor was initially suggested by the presence of an unusual type of pleural effusion in conjunction with radiographic findings. The basic pathophysiologic mechanisms that result in pleural effusions include alterations in the Starling forces (i.e., either decreased colloid oncotic pressure or increased capillary hydrostatic pressure), increased vascular permeability, and reduced lymphatic drainage. Effusions with the properties of mucus are not expected when fluid accumulates secondary to one of those traditional etiologies and therefore suggest the presence of a cell or tissue type capable of secreting mucus into, or communicating with, the pleural space. Given that such cells are not normally found in the thoracic cavity and do not normally communicate with the pleural space, the fluid type strongly suggested the presence of an aberrant cell/tissue (i.e., a neoplasm) such as a mucus-secreting carcinoma. In dogs, mucoid abdominal effusions have been described in association with mucus-secreting tumors of the stomach and small intestine.3,7 Gelatinous peritoneal effusion has also been reported with mucus-producing neoplasms and secondary to gallbladder rupture unrelated to neoplastic disease.8 The study authors are not aware of any previous reports of a mucus-producing pulmonary tumor.
In the patient described herein, the initial fluid analysis was consistent with a protein-rich transudate, suggestive of etiologies related to increased hydrostatic pressure, including congestive heart failure, pulmonary hypertension, tissue inflammation, and nonexfoliative neoplasia. The second fluid sample obtained was markedly different because it was consistent with a sterile exudate with abundant epithelial-like cells displaying criteria of malignancy. Exudates result from an inflammatory response to exogenous, neoplastic, or infectious agents.9 In both instances, the gelatinous nature of the effusion was a striking fluid characteristic. Furthermore, it is important to note that the mucoid characteristics were present prior to overt cytological evidence of neoplasia.
Mucinous effusions reported in the human literature are associated with neoplasia. Most notably, pseudomyxoma peritoni (PMP) is a rare syndrome in which perforation of appendicular adenomas results in mucinous ascites. That condition is believed to develop as a result of disseminated mucous-producing neoplastic cells that adhere to serosal surfaces. Tumors of the appendix are the most common source of neoplastic cells; however, PMP has also been described in association with colorectal and ovarian tumors.10 Both spontaneous and iatrogenic extension of PMP into the thoracic cavity has been reported, resulting in pleural effusions with similar characteristics.11 A single case report of PMP has been described in a dog with an intestinal adenocarcinoma.7
Conclusion
Although rare, mucinous pleural effusions are strongly suggestive of neoplasia. The findings in this case lend support for implementing diagnostics directed at identifying the source of the neoplasia in patients with mucinous pleural effusions even in the absence of cytological evidence of neoplasia.
Histological appearance of the pulmonary mass in an 11 yr old castrated male greyhound with a mucinous pulmonary adenocarcinoma and carcinomatosis. Note the abundant mucinous material within the luminal spaces created by the papillary projections of neoplastic cells. Hematoxylin and eosin staining of formalin-fixed paraffin-embedded lung, magnification ×200
A replicate section treated with Mayer's mucicarmine histochemical stain of formalin-fixed paraffin-embedded lung verifies the identification of mucin (deep rose). Original magnification ×100.
Contributor Notes
