History
A 3-year-old female intact Labrador Retriever presented to a veterinary teaching hospital for evaluation of hyporexia, apathy, dyspnea, and abdominal distension of 3 days’ duration after giving birth to stillborn pups 4 days prior. The owner also reported the appearance of cutaneous nodules 30 days before consultation. Upon physical inspection, serpiginous, diffuse nodules of rigid consistency and variable diameters (from a few millimeters to several centimeters) were observed, mainly affecting the patient’s back and abdomen. Physical examination revealed pale ocular mucosa, cyanotic oral mucosa, tachypnea, tachycardia, muffled heart sounds, hepatomegaly, and a positive fluid wave test. Furthermore, the patient presented with generalized lymphadenopathy.
Clinical and Clinicopathologic Findings
A CBC revealed severe anemia, leukocytosis (neutrophilia), and thrombocytopenia. Proteinuria was detected on urinalysis, and a serum biochemistry panel revealed hypoalbuminemia (Supplementary Table S1). Excessive collection of free fluid in the abdomen, hepatomegaly, and generalized lymphadenomegaly were observed upon ultrasonography. Echocardiography revealed alterations (transversal view of the left ventricle) consistent with pericardial and pleural effusion, which was confirmed by the presence of a large amount of fluid in the space between the heart and pericardial sac and moderate fluid in the pleural space (Figure 1).
A—M-mode cross-sectional view on echocardiogram. Pathological space is observed (arrow). B—Transverse view of the left ventricle showing nonadherence of the pericardium (arrow) to the myocardium (arrowhead). Free fluid can be found in the pleural space, outside the pericardial sac (asterisk).
Citation: Journal of the American Veterinary Medical Association 261, 8; 10.2460/javma.23.01.0042
Immediately thereafter, the patient underwent pericardiocentesis and thoracentesis, and pleural and pericardial fluids were drained. Despite treatment, the patient died between 15 and 20 minutes after treatment and was referred for necropsy followed by histopathological evaluation of organs. The major macroscopic findings included a nodule in the left ventricle, mass around the aorta (Figure 2), and fibrin in the pericardium. Furthermore, other findings included hepatomegaly, splenomegaly, and enlargement of all lymph nodes, several of which showed structural loss. Free fluid (foamy content) was observed in the pleura, pericardium, abdominal cavity, and trachea.
Visible mass (white arrow) surrounding the aorta (A). Histopathological study of the infiltrative mass indicated a neoplasm consisting of rounded cells (black arrows) in the cardiac striated musculature (black arrowhead) with basophilic and rounded nuclei and scarce eosinophilic cytoplasm (B). H&E stain; 40X magnification; bar = 40 µm.
Citation: Journal of the American Veterinary Medical Association 261, 8; 10.2460/javma.23.01.0042
Formulate differential diagnoses, then continue reading.
Histopathologic and Cytologic Findings
Abdominal, pleural, and pericardial fluid analyses were performed (Supplementary Table S2). Histopathological examination of the infiltrative mass in the heart and around the aorta marked the presence of neoplastic lymphocytes diffusely among cardiomyocytes, causing distortion of the tissue architecture. The neoplastic lymphocytes were large to moderate with scarce cytoplasm, moderate anisokaryosis, round to oval, and other beveled nuclei with very evident multiple nucleoli and sparse chromatin. The presence of 43 mitotic figures in 10 hpf was seen (Figure 2).
Neoplastic cells were located discreetly and focally in the dermis and in an accentuated and multifocal manner in the hypodermis and muscles without epitheliotropism. The characteristics of the cells were the same as those of the heart. The spleen and lymph node tissues were also affected.
Morphologic Diagnosis and Case Summary
Pericardial and abdominal exudate presented findings compatible with lymphoma.
Histopathological findings revealed excessive atypical lymphocytes in the cardiac tissue, spleen, lymph nodes, and cutaneous tissue.
Based on the patient’s history, clinical signs, complementary examinations, and necropsy findings, a diagnosis of pericardial effusion due to lymphoma was confirmed.
Differential Diagnoses
The differential diagnoses of this case include diseases that cause lymphadenomegaly, such as those of infectious origin (ehrlichiosis, leishmaniasis, and toxoplasmosis), other hematopoietic tumors (eg, leukemia, multiple myeloma, malignant or systemic histiocytosis), immune-mediated conditions (eg, lupus and pemphigus, and metastasis of other neoplasms to the lymph nodes).1 Among the differential diagnoses for pleural effusions are heart failure, hemothorax, pyothorax, and other neoplasms, such as mesothelioma and thymoma.1 The relevant nonneoplastic causes for pericardial effusions in dogs are infectious pericarditis, idiopathic pericardial effusion, intrapericardial cysts, trauma, uremia, and right congestive insufficiency. Neoplastic differentials mainly include hemangiosarcoma and chemodectoma.1,2
Clinical pathological findings compatible with cutaneous lymphoma vary from patient to patient and are often related to dermatitis with nonspecific initial presentation (erythema, scaling, alopecia, and depigmentation). This dermatitis can lead to the formation of plaques and firm nodules that may be alopecic and/or ulcerated, arcuate, serpiginous, or horseshoe shaped,1 such as that observed in the patient. Cutaneous lymphoma is easier to visualize and collect for cytopathological and histopathological examinations than cardiac lymphoma. Therefore, early cutaneous lymphoma diagnosis could have been fundamental to treatment success.
Comments
The present case was classified according to the WHO as stage V (extranodal in an organ other than the liver or spleen) and substage b (with clinical signs).2 It was not possible to identify the organ of origin, as the patient also presented with lymphoma in the skin and lymph nodes, along with the heart. Dogs with stage III lymphomas presenting clinical signs have worse prognoses for remission and survival than dogs with low-grade lymphomas. Therefore, the present case had an unfavorable prognosis.3
The patient presented with multiple severe and easily observable clinical signs, such as dyspnea, apathy, and ascites. However, the recent pregnancy history, lack of veterinary prenatal care, and recent delivery of stillborn pups may have been the clinical signs of lymphoma, resulting in a delay in seeking medical assistance by the owners. Consequently, its late diagnosis led to worsening of a condition that had an unfavorable prognosis.
The vast majority of cardiac neoplasms occur frequently in middle-aged to older dogs, except for lymphomas that often affect younger dogs.2 Therefore, since the patient was 3 years old, this report is consistent with these findings.
Hematological alterations may vary according to the lymphoma type and patient’s condition. Commonly found alterations include normocytic and neutrophilic leukocytosis, indicating secondary infection or inflammatory response.1 Cases that result in anemia, thrombocytopenia, neutropenia, and lymphocytosis, as well as atypical lymphocytes and lymphoblasts in the bloodstream, may indicate bone marrow involvement and require further investigation. Blood biochemistry may reveal altered hepatic and renal profiles, indicating that these organs may be possibly compromised.1
Typical ultrasonographic findings of lymphoma include lymphadenopathy, characterized by enlarged and hypoechoic lymph nodes, splenomegaly with multiple hypoechoic areas, hepatomegaly, intestinal wall thickening, splenic tumors, and abdominal effusion.1 Several of these findings were present in this case, including hepatomegaly, splenomegaly, lymphadenopathy, and abdominal effusion.
The patient’s diagnostic plan included blood tests, liver and kidney function tests, proteinograms, cytological and histopathological examinations of the compromised tissue, abdominal ultrasound, and echocardiography. However, other complementary tests, such as chest radiography, tomography, and myelography, could have been requested for further evaluation. In addition, immunology-based techniques, such as immunophenotyping and immunohistochemistry, would have contributed important information regarding the exact cell type involved in the neoplasm. This is an especially pertinent technique for differentiating lymphomas specifically.1,4
It is important to investigate all the differential diagnoses that occur in pericardial effusions, especially cardiac neoplasms. Literature cites an important number of tumors that can affect the heart or a part of it: hemangiosarcoma, aortic body tumors (chemodectoma and paraganglioma), ectopic thyroid carcinoma, thyroid adenoma, melanoma, mast cell tumor, blastoma, granular cell tumor, mesothelioma, myxoma, myxosarcoma, mesenchymoma, undifferentiated sarcoma of presumptive myofibroblastic origin, fibroma, fibrosarcoma, rhabdomyoma, rhabdomyosarcoma, leiomyoma, leiomyosarcoma, chondrosarcoma, osteosarcoma, paraganglioma, peripheral nerve sheath tumor, hamartoma, lipoma, valvular osteosarcoma, valvular myxosarcoma and valvular metastasis of disseminated tumors, and histiocytic sarcoma.2 However, some clinical presentations may be more common than others; for example, hemangiosarcoma, the most common type of cardiac tumor, is usually mass forming, and aortic base tumors, such as chemodectoma, are generally considered nonfunctional, benign, and of low metastatic power.2 Thus, the prognosis, treatment, and clinical presentation may vary, and the investigation of clinical, laboratory, or imaging alterations in other organs, although not always present, should be performed with parsimony.1,2 As in this case, clinical signs of skin and lymphadenopathy could be additional factors contributing to the final diagnosis.
Notably, cardiac neoplasms do not always exhibit evident clinical abnormalities.2 Furthermore, heart imaging examinations in such cases are challenging because of the risk of arrhythmias and hemorrhages during the procedure. This is relevant because of the frequent lack of evident mass formation or identifiable masses.4 Although cytological analysis must be performed when there is pericardial effusion formation, its effectiveness is questionable. Studies2,3 have demonstrated that false negatives can represent up to 74% of cardiac tumor identification, being successful mainly when the fluid hct is below 10%. However, the accuracy of cytological analysis markedly improves in lymphoma because of its high cellularity and exfoliative and less hemorrhagic nature.2,3
Finally, the high incidence of lymphoma in dogs raises doubts as to whether the heart is rarely affected because it does not have lymphoid tissue or whether primary and secondary cardiac lymphomas are underdiagnosed due to their challenging diagnosis. Therefore, we emphasize the need to include a lymphoma in the differential diagnosis of pericardial effusion in dogs.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org
Acknowledgments
Larissa Ayane do Nascimento Braz is funded by the Coordination for the Improvement of Higher Education Personnel (CAPES), Brazil (case No.: 88887.610798/2021-00).
The authors declare that there were no conflicts of interest.
The authors would like to thank the University of Franca for the support and its collaborators, especially interns Maysa Barbosa de Almeida and Professor Pamela Rodrigues Reina Moreira, PhD.
References
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Noronha NP, Bakiewicz WP, Biondi LR, Chamas PPC. Cardiac lymphoma in dogs—report of three cases with citological diagnosis. Braz J Vet Res Anim Sci. 2019;56(2):e153496. doi:10.11606/issn.1678-4456.bjvras.2019.153496
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Zhao Y, Huang S, Ma C, Zhu H, Bo J. Clinical features of cardiac lymphoma: an analysis of 37 cases. J Int Med Res. 2021;49(3):300060521999558. doi:10.1177/0300060521999558
