Histologic, immunohistochemical, and clinical features of 27 mammary tumors in 18 male dogs

Twenty-seven mammary tumors from 18 male (3 intact, 15 neutered) dogs were collected. The average age at diagnosis was 9.2 years (range, 2-14 years). Seven of the dogs were Cocker Spaniels. Five dogs had multiple mammary tumors. All tumors were benign. Twenty-six were simple adenomas with mixed acinar and papillary patterns. The acinar pattern was predominant in 17 cases. One adenoma was complex with a prominent myoepithelial component. The myoepithelial component of 25 of the 25 tumors was immunohistochemically positive for calponin and p63. In the cases for which relevant clinical information was available, there was no reported history of obesity, testicular tumors, or sex hormone therapy. Surgery was the only reported treatment for these tumors. Only 1 dog was reported to have developed an additional mammary tumor. None of the dogs for which case outcome was known died or was euthanatized as a result of mammary tumor. Although uncommon, mammary tumors do occur in male dogs. Although mammary tumors may be quite cellular, the presence of an intact myoepithelium, which can be demonstrated with immunohistochemistry for calponin and p63, indicates benignancy, as the clinical behavior documents.     

Hyperadrenocorticism associated with excessive sex hormone production by an adrenocortical tumor in two dogs.

An 11-year-old spayed female Labrador Retriever and a 9-year-old castrated male miniature Poodle were evaluated because of clinical signs of hyperadrenocorticism. Cortisol testing did not support a diagnosis of hypercortisolemia in either dog; however, imaging studies revealed unilateral adrenal tumors in both dogs. Serum concentrations of 17-hydroxyprogesterone, progesterone, and estradiol were high in both dogs, and androstenedione concentrations were also high in 1 dog. It is suspected that sex hormone secretion by the adrenal tumors in these dogs resulted in clinical signs of hyperadrenocorticism. Clinical signs and hormonal abnormalities resolved in the male dog after surgical resection of the tumor. There was no improvement in clinical signs after treatment with mitotane in the female dog, which died 2 months after diagnosis. Histologic evaluation confirmed the presence of adrenocortical carcinoma in both dogs.     

Histopathologic Diagnosis and Analysis of 44 Cases of Pet Dog Tumors

56 cases of suspected tumor materials from a pet hospital in Beijing were collected from 2015 to 2016, the histopathological method was used for tumor diagnosis, then the varieties of onset, sites, age and gender of tumors were statically analyzed. The results showed that among the 56 cases, 44 cases were diagnosed as tumors. There were 21 cases of benign tumor, including rianalgland adenomas, sebaceous adenoma,mast cell tumor and so on. There were 23 cases of malignant tumors, including breast cancer, squamous cell cancer, adenocarcinoma of anus and so on. The results indicated that skin, perianal and breast had a higher incidence. The tumor onset rate became higher after 7 years old. The skin tumors and breast cancer were more common in female pet dog, however, the anal gland peripheral tumor onset rate of male pet dogs was higher. This study provided a reference for the epidemiology and diagnosis of canine tumors in the future.     

44例宠物犬肿瘤病理诊断及分析

收集北京地区2015~2016年宠物医院的部分宠物犬肿瘤病例56例,采用组织病理学方法进行病理诊断,并对患病动物的品种、发生部位、年龄和性别与肿瘤发生关系进行了统计分析。结果发现,56个病例中有44例确诊为肿瘤,其中良性肿瘤21例,包括肛周腺瘤、皮脂腺瘤和肥大细胞瘤等;恶性肿瘤23例,包括乳腺癌、鳞状上皮细胞癌和肛周腺癌等。本次采集的病例中,大型犬与小型犬发病率持平,皮肤、肛周与乳腺部位肿瘤的发生率较高;7岁以后是肿瘤高发期;雌性犬皮肤和乳腺肿瘤的患病率高于雄性,雄性宠物犬肛周腺肿瘤的发生率高于雌性,肿瘤总患病率雄性与雌性持平。本研究为今后宠物犬肿瘤的流行病学及诊断提供了新的参考资料。     

Comparative immunohistochemical characterization of canine seminomas and Sertoli cell tumors

Primary testicular tumors are the most common causes of cancer in male dogs. Overall, the majority of canine patients should be cured by testicular surgery. However, tumor markers are not well-known in veterinary medicine. We sought to determine using immunohistochemistry whether the combined human testicular tumor markers (placental alkaline phosphatase, OCT3/4, CD30, alpha-fetoprotein, inhibin-alpha, vimentin, c-KIT, and desmin) are expressed in canine seminomas and Sertoli cell tumors (SCTs). We examined 35 canine testicular tumors, 20 seminomas and 15 SCTs. c-KIT was expressed markedly in canine seminomas. Both inhibin-alpha and vimentin were expressed significantly in canine SCTs. The results of this study demonstrate differences and similarities between tumor marker expression of testicular tumors in dogs and humans. All the main markers in current routine use are discussed as well as potential useful markers for benign and malignant tumors, and tumor progression.     

Surgical Treatment of Pheochromocytoma: Technique, Complications, and Results in Six Dogs

Six dogs were diagnosed with phcochromocyloma and staged according to the World Health Organization's system for tumor classification. Two dogs had benign tumors (Tl, NO, M0) and four dogs had malignant tumors (T2, NO. M 1 or T3, N0, M0). All dogs had adrenalectomy, two dogs had concurrent nephrectomy, and three dogs had concurrent resection of a tumor thrombus from the vena cava. Anesthetic complications occurred in five dogs, including wide variations in heart rate (four dogs), blood pressure (five dogs), and cardiac arrythmias (one dog). One dog died 12 hours after surgery from partial dehiscence of the suture line and hemorrhage from the vena cava, and one dog died 6 days after surgery during general anesthesia for treatment of laryngeal paralysis. Four dogs survived from 3 to 23 months (median, 15 months). One dog remained hypertensive after surgery. Benign and malignant pheochromocytomas seem to be amenable to surgical resection. © Copyright 1994 by The American College of Veterinary Surgeons     

Clinical signs associated with brain tumors in dogs: 97 cases (1992-1997).

OBJECTIVE: To determine the prevalence of various clinical signs in dogs with brain tumors. DESIGN: Retrospective study. ANIMALS: 97 dogs with brain tumors. PROCEDURE: Medical records were reviewed for signalment, tumor type and location, and clinical signs. RESULTS: 33 breeds were represented; Golden Retrievers were most commonly affected. Most dogs were older (median age, 9 years); 95% of dogs were > or = 5 years old. Seventy-six percent of dogs had tumors in the supratentorial region. Seizures were the most common clinical sign at initial examination, with lower prevalence for circling, ataxia, and head tilt. Meningioma was the most common tumor. CONCLUSIONS AND CLINICAL RELEVANCE: Brain tumors develop most often in dogs > or = 5 years old and are uncommon in dogs < 5 years old. Seizures are a common clinical sign, and a brain tumor should be considered in dogs that have their first seizure after they are 4 years old.     

Retroperitoneal sarcomas in dogs: 14 cases (1992-2002)

OBJECTIVE: To describe the clinical features, surgical and histologic findings, biological behavior, and outcome of dogs with retroperitoneal sarcomas. DESIGN: Retrospective study. ANIMALS: 14 dogs. PROCEDURES: Medical and pathology records from 1992 to 2002 of dogs with tumors originating in the retroperitoneal space were reviewed. Dogs with retroperitoneal tumors originating from the adrenal glands, kidneys, or ureters were excluded. Inclusion criteria included observation of a tumor arising from the retroperitoneal space during exploratory surgery or necropsy and histologic confirmation of tumor type. Details of clinical signs, diagnostic findings, surgical management, and outcome were determined from medical records and telephone interviews with veterinarians and owners. RESULTS: Retroperitoneal sarcoma was diagnosed in 14 dogs, 2 at necropsy and 12 during exploratory surgery. Hemangiosarcoma was the most common histologic diagnosis. Seven dogs had regional extension of the sarcoma into adjacent organs, and 4 dogs had metastatic disease. Grossly complete resection was possible in 6 dogs. Cytoreductive surgery or incisional biopsy was performed in the remaining dogs. Two dogs were treated with palliative radiation therapy (1 intraoperatively and 1 postoperatively). Three dogs received adjunctive chemotherapy, although none completed the targeted course because of development of local recurrence or metastatic disease. Local recurrence was reported in 2 of 12 dogs and metastasis in 10 of 14 dogs. Thirteen dogs died or were euthanatized as a result of the retroperitoneal sarcoma; 1 dog was alive and disease-free 410 days after surgery. Median survival time was 37.5 days. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, retroperitoneal sarcomas are aggressive tumors with a high rate of local recurrence and metastasis, and a poor survival time.     

Cytologic examination of fine‐needle aspirates from mammary gland tumors in the dog: diagnostic accuracy with comparison to histopathology and association with postoperative outcome

Background: Mammary tumors are the most common neoplasms in female dogs. Malignant tumors may carry a poor prognosis and necessitate surgery. Few data are available on the value of cytologic examination as a diagnostic or prognostic tool for mammary tumors in dogs. Objectives: The objectives of this study were to determine whether cytologic findings in fine‐needle aspirate specimens of canine mammary tumors correlate with histopathologic results and whether the cytologic diagnosis is associated with postoperative outcome. Methods: In this prospective study, fine‐needle aspirate samples were obtained from 50 mammary tumors in 50 dogs. Results of cytologic and histopathologic examination were compared, using the histologic diagnosis as the reference method. Kaplan–Meier log rank analysis was used to evaluate univariate association of the cytologic diagnosis with duration of survival, local control, and metastasis‐free interval. Results: Adequate cytologic samples were obtained in 43/50 (86%) cases. The cytologic diagnosis correlated with the histologic diagnosis for benign and malignant tumors in 40/43 (93%) and 35/43 (81%) cases, respectively. Cytologic examination had a sensitivity of 88% and a specificity of 96% for the diagnosis of malignancy. The cytologic diagnosis had significant univariate association with duration of survival (P=.016), recurrence‐free interval (P=.003), and metastasis‐free interval (P=.014). Conclusions: Cytologic examination of mammary tumors in the dog has satisfactory accuracy, sensitivity, and specificity for the diagnosis of malignancy and is associated with postoperative outcome. Further studies on the diagnostic accuracy of cytology as well as multivariate analysis of its preoperative prognostic value in mammary tumors in the dog are warranted.     

Mammary tumors in a colony of beagle dogs

In a lifetime study, female beagle dogs in a closed colony were administered 226radium and 90strontium. An unirradiated control group was included in the study. A total of 223 of 356 dogs at risk developed 1,112 mammary proliferative growths (hyperplastic nodules and neoplasms). There was no correlation between occurrence and types of lesions in radiation and control groups. The age range for first occurrence of lesions was 10.4 to 13.9 years; hyperplastic nodule and benign mixed tumor occurred 1 to 2 years earlier than other lesions. A multiplicity of growths of similar or different morphological type were common throughout the lifetime of the dog. The female beagles, collectively, developed 244 hyperplastic nodules, 78 adenomas, 694 benign mixed tumors, 78 carcinomas, 14 malignant mixed tumors, and four myoepitheliomas. Proliferations occurred with increasing frequency from the cranial to caudal mammary glands. Metastasis was found in 77% of the dogs with carcinoma. The median time from diagnosis to metastasis was 10 months, but was shorter in dogs with infiltrative carcinoma.     

Cross-Sectional Imaging Characteristics of Pituitary Adenomas, Invasive Adenomas and Adenocarcinomas in Dogs: 33 Cases (1988–2006)

Background: Pituitary tumors in dogs can be adenomas, invasive adenomas, or adenocarcinomas. In people, invasive adenomas and pituitary adenocarcinomas carry a worse prognosis than adenomas.
Hypothesis/Objective: To identify differentiating features on cross-sectional imaging in dogs with pituitary adenomas, invasive adenomas, and adenocarcinomas.
Animals: Thirty-three dogs that had computed tomography (CT) or magnetic resonance imaging (MRI) performed and a necropsy diagnosis of pituitary adenoma ( n = 20), invasive adenoma ( n = 11), or adenocarcinoma ( n = 2).
Methods: Medical records were retrospectively reviewed for signalment, history, and diagnosis. CT and MR images were reviewed for characteristics of pituitary tumors.
Results: Mean (± standard deviation) age for dogs with pituitary adenomas (10.6 ± 2.9 years) was greater than that of those with invasive adenomas (8.3 ± 2.7 years, P = .04). Eighteen out of 20 (90%) dogs with adenomas had contrast-enhancing masses. Thirteen out of 20 (65%) had homogeneous enhancement. Mean adenoma height was 1.2 ± 0.7 cm. Eight out of 20 (40%) adenomas were round and 8/20 (40%) compressed surrounding brain. Eleven out of 11 dogs (100%) with invasive adenomas had contrast-enhancing masses. Seven out of 11 (64%) masses were homogeneous. Mean invasive adenoma height was 1.8 ± 0.7 cm, which was significantly greater than adenomas ( P = .03). Mass shape varied from round to oval to irregular. Six out of 11 (55%) masses compressed surrounding brain. Clinical and imaging features were variable for 2 dogs with adenocarcinomas.
Conclusions and Clinical Relevance: Invasive adenoma should be suspected if a dog with a pituitary tumor is <7.7 years of age and has a mass >1.9 cm in vertical height. Adenocarcinomas are uncommon and metastatic lesions were not seen with imaging.     

Cytologic findings from a benign giant cell tumor of the tendon sheath in a dog

A 6‐year‐old male neutered Australian Shepherd dog was presented for evaluation of a subcutaneous mass on the plantar aspect of the proximal left metatarsus. Fine‐needle aspirate smears contained numerous plump spindle cells and large multinucleated cells amongst a considerable amount of pink extracellular matrix. Histopathologic diagnosis of the tissue obtained during initial biopsy and eventual surgical cytoreduction of the mass was a benign giant cell tumor of the tendon sheath (GCTTS). Immunohistochemically, the synovioblastic neoplastic cells were diffusely strongly positive for vimentin and S‐100, were multifocally moderately positive for cytokeratin AE1/3, and were negative for CD18, muscle‐specific actin (MSA), and melanoma‐associated antigen (mutated) 1 (MUM‐1). The dog recovered from surgery and underwent definitive radiation therapy to treat the local residual disease. Eight months later, the mass had not recurred. The diagnosis of GCTTS in this case supports previously published reports describing GCTTS as a relevant disease entity in dogs, and provides the first documentation of cytologic findings with this tumor. Further investigation is needed to correlate pathologic features with clinical behavior and response to therapy in dogs.     

The Biologic Behavior of Mast Cell Tumors in Pug Dogs

Introduction:  The purpose of this study was to quantitate the risk and to describe the behavior of mast cell tumors (MCT) in Pugs.
Methods and Materials:  Using the Veterinary Medicine Database, the frequency of MCT in Pugs was compared to the frequency in other dogs using a Chi‐square test. To describe the biologic behavior of MCT in pugs, cases with histologically confirmed diagnosis were identified through the University of Minnesota (UMN) Diagnostic Laboratory and Veterinary Medical Center. Histology was reviewed by a single pathologist. Survival analysis was performed to determine the impact of clinical and histologic data on survival.
Results:  The frequency of MCT diagnosis in Pugs was significantly increased compared to other dogs (OR = 2.28, 95% CI = 1.81–2.86). Twenty‐five purebred Pugs with a diagnosis of MCT were identified through UMN. Multiple cutaneous tumors were documented in 14 (56%) of the dogs. Most tumors were low to intermediate grade. Only three dogs have died of their disease. Sixteen are still living (median follow‐up = 660 days). The only factors predicting survival were grade, mitotic index and tumor size.
Discussion:  Our data confirms MCT predisposition in Pugs and suggests that mast cell tumors in Pugs are relatively benign, despite the presence of multiple cutaneous tumors in most cases. Multiple tumors in breeds with predisposition to MCT may indicate separate primaries rather than advanced stage disease.
This work was supported in part by NCI grants R03‐CA101030 and K08‐CA89530.     

Partial esophagectomy with single layer closure for treatment of esophageal sarcomas in 6 dogs

OBJECTIVE: To report partial esophagectomy (PE) as a treatment for esophageal sarcoma in dogs. STUDY DESIGN: Retrospective study (2000-2002). ANIMALS: Six dogs with caudal thoracic esophageal tumors. METHODS: Medical records of 6 dogs that had surgical removal of esophageal tumors were reviewed. Signalment, medical history, physical examination results, complete blood count, surgical procedure, tumor classification, postoperative treatment, and complications were retrieved. RESULTS: Esophageal masses were approached by thoracotomy and esophagotomy on the side opposite the mass, removed with 1 cm margins by full thickness excision, and the defects closed with a single layer of interrupted sutures. All dogs recovered rapidly without major complications. Tumors were fibrosarcoma (3 dogs), undifferentiated sarcoma (1), and osteosarcoma (2). Five dogs were administered doxorubicin chemotherapy after surgery. Good quality of life was observed postoperatively in 5 dogs until deterioration necessitated euthanasia; survival ranged from 2-16 months. The remaining dog was alive, 20 months after surgery. CONCLUSIONS: Partial esophagectomy and closure using 1 suture layer, was an effective, simple, and safe technique for removal of sarcomas of the distal thoracic esophagus. CLINICAL RELEVANCE: Removal of esophageal masses by partial esophagectomy can be used reliably as a method of esophageal surgery.     

Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs: 42 cases (1990-2003)

OBJECTIVE: To reexamine (via immunohistochemical techniques) canine tissue samples that had been previously classified as gastrointestinal leiomyosarcomas (GILMSs), identify and differentiate gastrointestinal stromal tumors (GISTs) from GILMSs, and compare the biological behavior and clinical course of GISTs and GILMSs in dogs. DESIGN: Retrospective case series. ANIMALS: 42 dogs. PROCEDURES: Medical records of 42 dogs for which a histologic diagnosis of GILMS was confirmed were reviewed for signalment, clinical signs, physical examination findings, results of initial diagnostic tests, surgical findings, adjunctive treatment, location of the tumor, completeness of resection, and outcome after surgery. Archived tumor tissue specimens from each dog were restained via immunohistochemical techniques to differentiate tumor types. Long-term follow-up information was obtained from the medical record or through telephone interviews with owners and referring veterinarians. RESULTS: On the basis of immunohistochemical findings, 28 of 42 tumors were reclassified as GISTs and 4 were reclassified as undifferentiated sarcomas; 10 tumors were GILMSs. In dogs, GISTs developed more frequently in the cecum and large intestine and GILMSs developed more frequently in the stomach and small intestine. Median survival times for dogs with GISTs and GILMSs were 11.6 and 7.8 months, respectively; if only dogs surviving the perioperative period were considered, median survival times were 37.4 and 7.8 months, respectively. These differences, however, were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, many previously diagnosed GILMSs should be reclassified as GISTs on the basis of results of immunohistochemical staining. The biological behavior of these tumors appears to be different.     

Expression of vascular endothelial growth factor in tumors and plasma from dogs with primary intracranial neoplasms

OBJECTIVE: To quantitatively evaluate expression of vascular endothelial growth factor (VEGF) in intracranial tumors in dogs and determine whether relationships exist between circulating and intratumoral VEGF concentrations and tumor type and grade. ANIMALS: 27 dogs with primary intracranial neoplasms and 4 unaffected control dogs. PROCEDURES: Plasma and brain tumor samples were obtained from each dog, and plasma and intratumoral concentrations of VEGF were measured by use of an ELISA. RESULTS: Dogs with meningiomas (n = 11) were significantly older than dogs with oligodendrogliomas (7) or astrocytomas (9). Measurable VEGF was detected in all tumors, and a significant negative correlation between age and intratumoral VEGF concentration was detected. Age-adjusted comparisons identified significant differences in intratumoral VEGF concentrations among all tumor types; the highest VEGF concentrations were associated with astrocytomas. Within each tumor type, increasing tumor grade was significantly associated with increasing VEGF expression. Plasma VEGF concentrations were detectable in 9 of 27 dogs; the proportion of dogs with astrocytomas and a detectable circulating VEGF concentration (7/9 dogs) was significantly higher than the proportion of dogs with meningiomas (1/11 dogs) or oligodendrogliomas (1/7 dogs) with a detectable circulating VEGF concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Overexpression of VEGF appears common in canine astrocytomas, oligodendrogliomas, and meningiomas. In the neoplasms examined, intratumoral VEGF concentrations correlated well with tumor malignancy. The VEGF expression patterns paralleled those of analogous human tumors, providing evidence that dogs are a suitable species in which to study angiogenesis and intracranial neoplasia for human application.     

犬常见肿瘤流行病学调查及组织病理学诊断

为探讨犬常见肿瘤的发病规律，试验收集哈尔滨地区2016-2017年宠物医院部分犬肿瘤病例71例，采用组织病理学方法对犬肿瘤进行病理学诊断，并对患病动物的品种、性别、年龄、发生部位和饮食情况与肿瘤发生关系进行统计分析。结果显示，71例确诊肿瘤病例中，恶性肿瘤28例，包括鳞状上皮细胞癌3例，基底细胞癌5例，乳腺癌14例，淋巴瘤2例，肾母细胞瘤、精原细胞癌、生殖细胞癌、侵袭性血管黏液瘤各1例；良性肿瘤43例，包括良性乳腺肿瘤15例，纤维瘤10例，平滑肌瘤5例，乳头状瘤和精原细胞瘤各3例，造釉细胞瘤、耵聍腺瘤、脂肪瘤、结节样增生、性索间质细胞瘤、颗粒细胞瘤、肛周腺瘤各1例。上述病例中，乳腺和皮肤是犬肿瘤的高发部位，分别占全部患犬的40.8%和34.0%；患病犬年龄1~16岁不等，平均发病年龄为9.1岁，7岁以后是肿瘤的高发期，中老年犬仍为主要发病群体，但低龄犬发病数量上升；各品种犬均可发生肿瘤，其中杂种犬发病率最高，其次是贵宾犬和京巴犬，且主要为乳腺肿瘤；饮食习惯主要以剩饭剩菜类和肉拌饭类为主，分别占患犬总数的39%和30%；部分肿瘤类型与犬的性别、是否绝育有关，如乳腺肿瘤多发生于未绝育的老年母犬。本研究结果为犬肿瘤的流行病学及诊断提供了参考依据，对犬肿瘤的预防和诊断有一定的借鉴意义。     

Hypoglycemia associated with nonislet cell tumor in 13 dogs

Hypoglycemia associated with nonislet cell tumor was found in 13 dogs. In each dog, clinical signs were related directly to adrenergic and neuroglucopenic effects of hypoglycemia and included collapsing episodes, tremors, restlessness, weakness, and grand mal seizures that were responsive to glucose administration. Eight of the dogs had hepatocellular carcinoma; surgical resection of the tumor achieved remission of clinical signs in 3 of these dogs. Other hepatic tumors associated with hypoglycemia included leiomyosarcoma and hemangiosarcoma involving solitary lobes of the liver. Nonhepatic tumors included splenic hemangiosarcoma, diffuse metastatic melanoma, and salivary gland adenocarcinoma.     

Treatment of chronic pleural effusion with pleuroperitoneal shunts in dogs: 14 cases (1985-1999).

OBJECTIVE: To describe complications and outcome associated with chronic nonseptic pleural effusion treated with pleuroperitoneal shunts in dogs. DESIGN: Retrospective study. ANIMALS: 14 dogs. PROCEDURE: Medical records at 4 veterinary schools were examined to identify dogs with chronic nonseptic pleural effusion that were treated by use of a pleuroperitoneal shunt between 1985 and 1999. Signalment, history, physical examination and laboratory findings, cause and type of pleural effusion, medical and surgical treatments, complications, and outcome were reviewed. RESULTS: 10 of 14 dogs had idiopathic chylothorax, and 4 had an identified disease. All but 1 dog with idiopathic chylothorax and 1 dog with chylothorax from a heart base tumor had unsuccessful thoracic duct ligation prior to pump placement. No intraoperative complications developed during shunt placement. Short-term complications developed in 7 of 13 dogs, necessitating shunt removal in 2 dogs and euthanasia in 1. Eight of 11 dogs with long-term follow-up developed complications; the overall mean survival time and the interval in which dogs remained free of clinical signs of pleural effusion were 27 months (range, 1 to 108 months) and 20 months (range, 0.5 to 108 months), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Pleuroperitoneal shunts can effectively palliate clinical signs associated with intractable pleural effusion in dogs. Numerous short- and long-term complications related to the shunt should be expected. Most complications can be successfully managed, but even when shunts are functional some treatments fail because of severe abdominal distension or massive pleural fluid production that overwhelms the functional capacity of the shunt.