Abstract
Case Description—An 11-year-old neutered female domestic longhair cat was evaluated because of a 1-week history of progressive dyspnea, signs of depression, and loss of appetite. A histiocytic sarcoma had been excised from the mammary gland 6 weeks earlier.
Clinical Findings—Physical examination findings were consistent with pleural effusion, and thoracic and abdominal radiography and ultrasonography revealed pleural effusion, a thoracic mass involving the aorta and pulmonary artery, and a caudal abdominal mass that most likely represented enlarged iliac lymph nodes. Cytologic examination of the pleural fluid and fine-needle aspirates from the iliac and right popliteal lymph nodes revealed abundant cells with neoplastic characteristics of indeterminate origin. The clinical diagnosis was generalized malignant neoplasia.
Treatment and Outcome—Pleural drainage was necessary every 5 to 6 days. Exploratory thoracotomy and biopsy of the mass were recommended for better characterization of the thoracic disease. Simultaneously, palliative treatment by advancement of the omentum into the thorax was performed. A final diagnosis of disseminated histiocytic sarcoma was made, and treatment with doxorubicin was begun after surgery. During the 13 months after surgery, the cat was free from signs of respiratory tract disease and had normal activity levels with good exercise tolerance. Fifteen months after surgery, the cat's clinical condition worsened and the cat died.
Clinical Relevance—Findings suggested that thoracic omentalization may be considered for palliative treatment of cats with refractory neoplastic pleural effusion when frequent thoracocentesis is necessary and other treatments are not suitable.
An 11-year-old 4.3-kg (9.5-lb) neutered female domestic longhair cat was referred to the Cardiorespiratory Service of the Veterinary Teaching Hospital of the University of Murcia for evaluation of progressive dyspnea, exercise intolerance, tachypnea, labored breathing, signs of depression, and loss of appetite of 1 week's duration. A mammary mass had been removed 6 weeks earlier, and results of histologic examination of the mass were consistent with a diagnosis of localized histiocytic sarcoma.
On initial physical examination, the cat was alert and in good body condition (body condition score of 3 on a scale from 1 to 5). Mucous membranes were slightly pale, and the capillary refill time was < 2 seconds. Respiration was characterized by shallow breathing with increased respiratory effort and a respiratory rate of 60 breaths/min. The right popliteal lymph node appeared larger than normal. Thoracic auscultation revealed muffled heart sounds and muffled breath sounds bilaterally in the ventral aspect of the thorax. Echocardiography did not reveal any cardiac abnormalities, but thoracic ultrasonography revealed abundant anechoic pleural effusion and a structure of mixed echogenicity without well-defined outlines that was cranial to the heart and appeared to involve the aorta and pulmonary artery.
Proposed diagnostic testing to determine the underlying cause of the effusion included hematologic and serum biochemical analysis, thoracocentesis and analysis of the pleural fluid, abdominal radiography, abdominal ultrasonography, and fine-needle aspiration of the right popliteal node. Results of a CBC and serum biochemical profile were within reference limits, and results of tests for FeLV antigen and FIV antibody were negative. Ultrasonography-guided thoracocentesis was performed, and 250 mL of yellowish fluid characterized as a modified transudate was removed. Cytologic examination of the pleural fluid revealed abundant pleomorphic cells with giant nuclei and abundant nucleoli suggestive of a neoplastic origin. Abdominal radiography revealed an elongated soft tissue mass (approx 10 × 4 cm) in the caudal aspect of the abdomen that was causing ventral displacement of the colon and most likely represented enlarged iliac lymph nodes. Ultrasonographically, the iliac lymph nodes appeared well delimited with heterogeneous echogenicity. Cytologic examination of fine-needle aspirates of the iliac and right popliteal nodes revealed abundant cells with neoplastic characteristics of indeterminate origin.
The clinical diagnosis was generalized malignant neoplasia. The cat had a normal respiratory pattern and appeared more playful after the pleural fluid was removed. However, repeated thoracocentesis was necessary every 5 to 6 days during the subsequent 3 weeks. Treatment with prednisolone (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) and furosemide (1 mg/kg [0.45 mg/lb], PO, q 12 h) for 1 week did not alter the frequency with which thoracocentesis was required or the amount of fluid removed.
Because frequent thoracocentesis was needed to resolve clinical signs, exploratory thoracotomy and biopsy of the masses were recommended to allow for histologic characterization of the tumor and better characterization of the pleural disease. Simultaneously, palliative treatment by advancement of the omentum into the thorax was performed, as described for treatment of chylothorax.1,2 Briefly, a right 9th intercostal space thoracotomy and right paracostal laparotomy were performed. The thoracic cavity was filled with yellowish fluid, but once the fluid was removed, the only abnormality identified was a poorly circumscribed pale mass cranial to the heart. Exploration of the peritoneal cavity revealed enlarged, well-circumscribed, pale iliac lymph nodes. An omental pedicle was obtained and advanced into the thoracic cavity through a 1-cm defect created in the diaphragm approximately 2 cm medial and ventral to the left crus. The omentum was expanded to optimize the contact surface and sutured to the mediastinum cranial to the heart. Biopsy samples were obtained from the thoracic mass and iliac lymph nodes, and the thoracic and abdominal cavities were closed routinely.
Biopsy samples were fixed in formalin, embedded in paraffin, and sectioned at a thickness of 4 μm. Sections for histologic examination were stained with H&E. Sections for immunohistochemical analysis were stained by use of the avidin-biotin-peroxidase complex technique with antibodies against cytokeratin, vimentin, HLA DR antigen (major histocompatability complex II), CD3, CD79a, S-100 protein, λ chains, κ chains, and myeloid–histiocyte antigen (MAC 387).a Appropriate positive and negative controls were included for each antibody.
Microscopically, the neoplasm was densely cellular and unencapsulated and was composed of sheets of pleomorphic round, binucleated and multinucleated giant cells (Figure 1). Cells were characterized by an eosinophilic, finely vacuolated cytoplasm. Nuclei of the cells were pleomorphic, ranging from irregularly rounded to large and multilobulated with a euchromatic pattern. Numerous mitotic figures were observed, and some mitotic figures were atypical. The mass was highly infiltrative, and numerous metastatic cells were observed within lymphatic vessels. Histologic characteristics of the tumor cells were consistent with a diagnosis of histiocytic sarcoma, but other diagnoses that were considered included undifferentiated sarcoma, large T-cell lymphoma, plasmocytoma, and undifferentiated carcinoma. The tumor was negative for cytokeratin, CD3, CD79a, S-100 protein, MAC 387, λ chains, and κ chains and positive for vimentin and HLA DR antigen. Some lymphocytes positive for CD3 were seen scattered throughout the neoplastic cells. On the basis of these results and taking into consideration previous results of histologic examination of the mammary gland mass, the final histopathologic diagnosis was disseminated histiocytic sarcoma.
Photomicrographs of sections of a thoracic mass in a cat with neoplastic pleural effusion. A—Neoplastic cells were characterized by an eosinophilic, finely vacuolated cytoplasm (arrows). Nuclei were pleomorphic, ranging from irregularly rounded to large and multinucleated (arrowheads), with a euchromatic pattern. H&E stain; bar = 50 μm. B—Immunohistochemical staining indicated that most neoplastic cells were positive for the HLA DR antigen (arrows). Notice the intracytoplasmic immunolabeling of giant multinucleate cells (arrowhead). Bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 234, 10; 10.2460/javma.234.10.1299
The cat was discharged from the hospital 48 hours after surgery; respiratory pattern and appetite were normal at the time of discharge. Ten days after discharge from the hospital, treatment with doxorubicin (30 mg/m2, IV, q 21 ≤ for 5 doses) was begun. Chemotherapy was well tolerated, and the size of the right popliteal lymph node and abdominal and thoracic masses was substantially reduced. During the following 13 months, the cat was free from signs of respiratory tract disease and had normal activity levels and good exercise tolerance. Periodically throughout this period, the cat had mild signs of inspiratory effort when handled, mild to moderately high SUN (mean ± SD, 123.6 ± 11.7 mg/dL) and creatinine (3.1 ± 0.3 mg/dL) concentrations, and mild nonregenerative anemia (mean ± SD Hct, 24.4 ± 4.6%). Mild pleural effusion was always identified by means of ultrasonography or radiography. The cat's appetite was variable, and progressive weight loss occurred. Fourteen months after surgery, new mammary and perineal masses were detected and inspiratory effort was increased. The clinical condition of the cat quickly became worse, and the cat died a month later (15 months after surgery).
On postmortem examination, poorly circumscribed pale masses were found in the mammary gland, mesentery, mediastinum, and perineal region. A large, firm, pale mass was seen in the mediastinum. The mesenteric, mediastinal, popliteal, inguinal, and iliac lymph nodes were larger than normal and gray. A small portion of the intestinal tract and mesentery was found in the thoracic cavity. Histologic and immunohistochemical analyses of necropsy specimens confirmed the diagnosis of disseminated histiocytic sarcoma.
Discussion
Pleural effusion is the abnormal accumulation of fluid in the pleural space and may result from conditions that increase systemic and pleural capillary hydrostatic pressure (eg, congestive heart failure), decrease plasma oncotic pressure (eg, hypoalbuminemia), increase capillary permeability (eg, inflammation), or cause lymphatic obstruction or dysfunction. In addition, trauma, coagulopathies, and vessel erosion resulting from neoplasia or infection may cause hemorrhagic pleural effusion.3,4 The nature of the fluid that accumulates depends on the underlying mechanism, and pleural effusion may be a transudate or modified transudate or may be chylous, purulent, hemorrhagic, or neoplastic. In cats, mediastinal lymphoma, other types of intrathoracic neoplasia, pyothorax, cardiomyopathy, and feline infectious peritonitis have been reported as the most frequent underlying causes of pleural effusion.3
Neoplastic pleural effusion in cats is most commonly associated with tumors of the cranial mediastinum or pleura.5 The most common tumors in these areas in cats are lymphosarcoma, thymoma, and mesothelioma,6 and to the authors' knowledge, only a single case of histiocytic sarcoma affecting the mediastinum has previously been reported in cats.7 Neoplasia may cause pleural effusion by any mechanism that interferes with the formation and absorption of pleural fluid, including invasion of lymph nodes, obstruction (neoplastic embolism) or erosion of lymphatic or blood vessels, increased capillary permeability, secondary pleuritis and atelectasis, and hypoalbuminemia.4,5 Combinations of several of these mechanisms are usually responsible for pleural effusion in any individual patient as well as in the cat described in the present report. Respiratory distress, with severity depending on the amount of fluid present, is the most common clinical sign in cats with pleural effusion, although a cat with histiocytic sarcoma involving the vertebral canal and mediastinum only had neurologic signs.7
Treatment of neoplastic pleural effusions depends on the underlying disease and the patient's clinical signs.5 Surgery, chemotherapy, and radiotherapy are the most suitable options for initial treatment of tumors such as lymphoma, thymoma, and chemodectoma.5 Refractory effusions caused by tumors for which there is no successful initial treatment might be treated in a palliative manner. Intermittent thoracocentesis or placement of a thoracic drainage tube may be appropriate for short-term management. In the present case, however, additional treatment was considered necessary because repeated thoracocentesis was required every 5 to 6 days. Excision of the thoracic mass was not considered in this cat because of the close relationship between the thoracic mass and several large vessels and the presence of metastatic disease. Chemotherapy was not initially recommended because of the lack of a specific histologic diagnosis prior to surgery. An alternative palliative treatment that could have been considered in this case was placement of a pleuroperitoneal or pleurovenous shunt. In dogs, however, these shunts often malfunction and become obstructed with fibrin, with the result that thoracocentesis is still intermittently necessary and multiple surgeries may be necessary to replace or unclog shunts.4 Additionally, no information exists about their use in cats. The standard palliative treatment for neoplastic effusions in human medicine is chemical pleurodesis, which involves instilling a sclerosing agent such as tetracycline, bleomycin, or talc into the pleural cavity to create chemical pleuritis and subsequent pleurodesis.5 However, experience with pleurodesis in veterinary medicine is limited, and the procedure was not considered a suitable option in this case. For this reason, we elected to attempt thoracic omentalization as a means to control the pleural effusion.
The omentum has many properties that render it useful in a variety of veterinary surgical procedures, including treatment of prostatic abscesses, treatment of large, chronic, nonhealing wounds, vascular surgery, and gastrointestinal tract surgery.2,8 To a large extent, these properties are a result of the high density of lymphoid tissue in the omentum, which provides for efficient lymphatic drainage.8 Thoracic omentalization has previously been described for treatment of idiopathic chylothorax in a dog1 and in a cat.2 In both cases, respiratory signs associated with pleural effusion resolved for long periods (16 months and 13 months, respectively) after the procedure. The surgical technique is not complicated but requires thoracic and abdominal access.1,2 To the authors' knowledge, use of this technique for palliative treatment of neoplastic pleural effusion has not been reported. After thoracic omentalization, the volume of pleural effusion in the cat described in the present report was substantially reduced and repeated thoracocentesis was no longer necessary. During the 14 months after surgery, the cat had stable respiratory function and a good quality of life. Herniation of abdominal contents identified during necropsy probably occurred in the last month of the cat's life since it had not been observed on any of the radiographs obtained during periodic recheck examinations.
The histologic diagnosis in the present case was histiocytic sarcoma. This is a malignant neoplasm of histiocytic lineage, which comprises either monocytemacrophage or dendritic cell lineage.7 Disseminated histiocytic sarcoma is typically difficult to differentiate from malignant histiocytosis, a malignant neoplasm also of histiocytic lineage. However, malignant histiocytosis is characterized by disseminated lesions that simultaneously arise in multiple organs, including the skin, spleen, liver, lymph nodes, and bone marrow.9,10 Histiocytic sarcoma and malignant histiocytosis are rare in cats, and it is difficult to differentiate between the 2 on the basis of histologic or immunohistochemical findings. In addition, immunohistochemical determination of the exact lineage of histiocytic cells from which these neoplasms has arisen is not yet possible. However, immunohistochemical staining is a useful tool in differentiating these tumors from others with similar histopathologic appearance, such as large T-cell lymphomas, plasmocytomas, undifferentiated sarcomas, and undifferentiated carcinomas. In the present case, results of immunohistochemical staining were suggestive of a histiocytic origin of the tumor cells.7,11 Localized histiocytic sarcoma often occurs as a primary lesion involving the skin and subcutis, especially of the extremities, but other primary lesions have been described involving the spleen, lymph node, lung, bone marrow, and periarticular tissues.11,12 Localized histiocytic sarcoma is invasive, and metastasis to draining lymph nodes occurs early in the course of the disease. Metastasis is also typically quite extensive, with the condition recognized as disseminated histiocytic sarcoma once the tumor has spread to sites beyond the local lymph nodes.11–13 In animals with disseminated histiocytic sarcoma, the primary origin of the tumor is often difficult to determine.12 In the cat described in the present report, the tumor was initially detected in the mammary gland, and to the authors' knowledge, this is the first report of disseminated histiocytic sarcoma originating in the mammary gland in a cat.
The clinical course of disseminated histiocytic sarcoma is typically rapid.14,15 The effects of radiation therapy in dogs with histiocytic sarcoma have not been evaluated, although anecdotal information has been published.14 Similarly, the potential benefits of chemotherapy in dogs with histiocytic sarcoma have been largely unstudied, although reports of responses to liposomal doxorubicin, paclitaxel, lomustine, and various chemotherapy protocols have been published.14 Histiocytic sarcoma in cats resembles the condition in dogs in regard to disease progression, but the incidence appears to be markedly lower in cats.15 Results of treatment of histiocytic sarcoma in cats have not been documented since only a few cats with histiocytic sarcoma have been described in the literature and most of these were euthanatized after the diagnosis was established.7,11,16,17 In the present case, doxorubicin was selected for chemotherapy because it is considered the most effective single agent to treat soft tissue sarcomas, tolerance is usually good in cats, and the drug is not expensive.18 In this cat, adverse effects other than mild cumulative nephrotoxicosis were not seen. However, it could not be determined whether the long survival time was attributable to chemotherapy, thoracic omentalization, or both. A substantial reduction in the size of the tumors in the cat was evident after chemotherapy, and regrowth of the tumors was reasonably slow. On the other hand, mild pleural effusion was consistently seen on follow-up radiographs, suggesting that chemotherapy had not caused production of pleural fluid to stop. Thus, although chemotherapy likely slowed the course of the neoplastic process, thoracic omentalization was crucial for long-term control of the pleural effusion and associated respiratory signs.
References
- 1.↑
Williams JM, Niles JD. Use of omentum as a physiologic drain for treatment of chylothorax in a dog. Vet Surg 1999;28:61–65.
- 2.↑
Lafond E, Weirich WE, Salisbury SK. Omentalization of the thorax for treatment of idiopathic chylothorax with constrictive pleuritis in a cat. J Am Anim Hosp Assoc 2002;38:74–78.
- 3.↑
Davies C, Forrester SD. Pleural effusion in cats: 82 cases (1987–1995). J Small Anim Pract 1996;37:217–224.
- 4.↑
Sanders NA, Sleeper M. Pleural transudates and modified transudates. In: King LG, ed. Textbook of respiratory disease in dogs and cats. Missouri, Pa: WB Saunders Co, 2004;587–596.
- 5.↑
Kisseberth WC, MacEwen EG. Complications of cancer and its treatment. In: Withrow SJ, MacEwen EG, eds. Small animal clinical oncology. 2nd ed. Philadelphia: PhiladelphiaB Saunders Co, 1996;129–225.
- 6.↑
Carreras JK, Sorenmo KU. Neoplasms of the cranial mediastinum and pleura. In: King LG, ed. Textbook of respiratory disease in dogs and cats. Missouri, Pa: WB Saunders Co, 2004;587–596.
- 7.↑
Smoliga J, Schatzberg S, Peters J, et al. Myelopathy caused by histiocytic sarcoma in a cat. J Small Anim Pract 2006;46:34–38.
- 8.↑
Hosgood G. The omentum—the forgotten organ: physiology and potential surgical applications in dogs and cats. Compend Contin Educ Pract Vet 1990;12:45–50.
- 9.
Walton RM, Brown DE, Burkhard MJ, et al. Malignant histiocytosis in a domestic cat: cytomorphologic and inmunohisto-chemical features. Vet Clin Pathol 1997;26:56–60.
- 10.
Kraje AC, Patton CS, Edwards DF. Malignant histiocytosis in 3 cats. J Vet Intern Med 2001;15:252–256.
- 11.
Bell R, Philbey AW, Martineu H, et al. Dynamic tracheal collapse associated with disseminated histiocytic sarcoma in a cat. J Small Anim Pract 2006;47:461–464.
- 12.↑
Affolter VK, Moore PF. Localized and disseminated histiocytic sarcoma of dendritic cell origin in dogs. Vet Pathol 2002;39:74–83.
- 13.
Goldschmitd MH, Hendrick MJ. Tumors of the skin and soft tissues. In: Meuten DJ, ed. Tumors in domestic animals. 4th ed. Ames, Iowa: Ames, Iowaowa State University Press, 2002;109–111.
- 14.↑
Clifford CA, Skorupski KA. Histiocytic diseases. In: Withrow SJ, MacEwen EG, eds. Small animal clinical oncology. 4th ed. Philadelphia: PhiladelphiaB Saunders Co, 2007;814–823.
- 15.↑
Moore PF, Affolter VK. Canine and feline histiocytic diseases. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 6th ed. Philadelphia: PhiladelphiaB Saunders Co, 2007;779–783.
- 16.
Pinard J, Wagg CR, Girard C, et al. Histiocytic sarcoma in the tarsus of a cat. Vet Pathol 2006;43:1014–1017.
- 17.
Tanimoto T, Shirota K, Shida T, et al. Histiocytic sarcoma in a cat. Nippon Juigaku Zasshi 1988;50:291–293.
- 18.↑
Rassnick KM. Medical management of soft tissue sarcomas. Vet Clin North Am Small Anim Pract 2003;33:517–531.
Dako, Glostrup, Denmark.
