Abstract
Neoplasms in dogs are estimated to account for up to 83% of all canine malignancies, while canine leishmaniasis is endemic and highly incident in areas like Brazil, east Africa, and India. The worldwide incidence of both diseases may indicate the presence of these two pathologies in the same tissue sample as eventual cases. However, a relationship between leishmaniasis and malignant disorders has been postulated in human and veterinary medicine. Depending on several direct or indirect factors, leishmaniasis can affect the clinical manifestation, diagnosis, therapeutic protocols, and the outcome of various malignant disorders. In addition, the similarity of the clinical presentation of cutaneous or visceral leishmaniasis with the clinical signs observed in many tumors may lead to misdiagnosis. Clinical cases of co-localization of Leishmania parasites and tumor cells in dogs were more associated with transmissible venereal tumors than histiocytic tumors, non-histiocytic lymphoma, or squamous cell carcinoma. This chapter reviews the circumstances involving canine leishmaniasis and malignant disorders, and the current challenge that the association between them represents to misdiagnosis or tumor-promoting potential of leishmaniasis, providing an overview of dog cases.
Keywords
- Leishmania
- neoplasm
- dog
- transmissible venereal tumor
- diagnosis
1. Introduction
Neoplasms in dogs are estimated to account for up to 83% of all canine malignancies [1]. Its etiology is largely unknown and believed to be multifactorial [2], genetic [3, 4], auto-immune [5], hemoparasitic [6, 7], and viral diseases [8]. The exact mechanism by which chronic inflammatory processes induce oncogenesis is still unclear, but persistent immunosuppression [9], epigenetic events [10], and relevant association with immunosenescence [11] have all been associated with neoplasm developments.
In transmissible venereal tumor (TVT), sarcoma, small-cell lymphoma, and adrenocortical adenoma, amastigotes were observed in the macrophage’s cytoplasmic vacuoles and inside the neoplastic cells, probably in consequence of an atypical dissemination of
A relationship between leishmaniasis and malignant disorders has been postulated in human and veterinary medicine [22, 24]. Among the proposed theories, the chronic inflammation induced by
2. Histopathology, biochemical, and hematological parameters of canine leishmaniasis
The liver, spleen, and lymph nodes are the organs most affected by the disease [26], as well as the kidney and skin. In humans with visceral leishmaniasis, liver function and morphology are modified by the presence of an inflammatory process in the portal and intralobular region, locally concentrated or diffusely localized. In dogs experimentally infected by intravenous and intraperitoneal injection of amastigotes of
Parasitism caused by
In the kidney, the accumulation of immune complexes in the glomeruli can initiate glomerulonephritis and interstitial nephritis, which can lead to chronic renal failure in dogs, [34]. Santos et al. [35] evaluated histological alterations of dogs naturally infected with
In general, skin lesions in dogs are focal ulcers, with raised edges, like human lesions. Other dermatological signs are alopecia, papular, and nodular dermatitis [36]. Boechat et al. [37] verified the presence of
Canine leishmaniasis is also associated with alteration in hematological and biochemical parameters. Erythrogram of dogs seropositive for leishmaniasis shows moderate anemia, usually presented in the normocytic and normochromic form with non-regenerative character [39, 40]. This characteristic can be a consequent of the bone marrow invasion by the parasite, which induces inflammation and contributes to the reduction of erythrocyte production [41]. A thrombocytopenia is common and occurs due to vasculitis caused by immune complexes circulating blood, thrombocytopoiesis disorders, and platelet destruction [40].
Leukocyte response changes according to the stage of the disease [42]. Lymphopenia occurs due to the sequestration of cells in the spleen and lymph nodes, as well as by the destruction caused by
An unusual case of persistent pancytopenia caused by leishmaniasis in a human patient receiving immunomodulatory therapy for myeloma was recently described [47] and draws attention to possible similar cases in dogs. Pancytopenia in multiple myeloma is commonly caused by plasma cell infiltration and cytotoxic medications, however, fungal, bacterial, or viral infection, and treatment-associated myelodysplasia also warrant consideration. In regions where leishmaniasis occurs naturally, it should be also investigated, and in this case, the diagnosis of
An usual alteration associated with leishmaniasis is hyperproteinemia, caused by the activation of B lymphocytes and high production of antibodies [40]. In fact, there is a decrease in the serum albumin level, in contrast to an expressive increase in the globulin levels, causing a significant increase in the levels of total plasmatic proteins during canine leishmaniasis [43, 48]. Liver function may also be normal or with changes suggestive of liver diseases [49]. It can be detected by increased activity of liver enzymes such as alkaline phosphatase (AP) and alanine aminotransferase (ALT) [49, 50, 51].
Alterations in biochemical parameters can also be associated with leishmaniasis treatment. A case report of a tumor lysis-like syndrome during therapy of visceral leishmaniasis consisting of hyperkalemia, hyperphosphatemia, hyperuricemia, and acute renal insufficiency, soon after the initiation of liposomal amphotericin B chemotherapy for severe visceral leishmaniasis, was observed in a human patient. Allopurinol therapy and intravenous fluid administration lead to a full recovery of the metabolic parameters. Awareness of this condition by veterinarians can lead to early recognition and preventive management of patients undergoing leishmaniasis treatment [52].
3. Tumor and Leishmania infection association
The worldwide incidence of cancer and the endemicity of leishmaniasis in areas like Brazil, east Africa, and India may indicate the presence of these two pathologies in the same tissue sample as eventual cases. Both diseases display an immunological bias in the pathology, course, and outcome of the disease progression associated with an impaired host Th1 response. Therefore, the Th2 cytokine microenvironment occurring in compartmentalized organs in progressive leishmaniasis [53] may potentially promote tumor cell proliferation as well as the other way around. In addition, the similarity of the clinical presentation of cutaneous, mucosal, or visceral leishmaniasis with lesions observed in many malignant disorders may lead to misdiagnosis [54]. Clinical cases of co-localization of
The clinical identification of leishmaniasis is frequently related to skin lesions. However, most of the evidence about the association between cutaneous leishmaniasis and skin cancer is still based on case reports and other clinical observations rather than strong epidemiological observational studies [55]. An unlikely association of squamous cell carcinoma with an active cutaneous leishmaniasis was reported in an immunocompetent human patient [25], and a report of a case of basal cell carcinoma (Clark level IV) that had been developed on characteristic active lesion of mucocutaneous leishmaniasis, suggesting that carcinogenesis, in this case, was triggered by
Differential diagnosis of leishmaniasis and malignancy disorders due to similarities in clinical presentation, as well as its association, is perhaps reported for the three clinical forms of leishmaniasis: visceral, cutaneous, and mucosal. A chronic skin lesion histopathologically compatible with squamous cell carcinoma, and hence programmed for Mohs surgery, showed to be cutaneous leishmaniasis after review of the clinical and epidemiological history, and laboratory diagnosis. Treatment with miltefosine led to a complete resolution of the lesion [58]. Zambarbieri et al. [19] reported a case of
A report of visceral leishmaniasis in a human patient with a lung tumor highlights leishmaniasis as a possibility to be considered in the diagnosis of causes of fever in patients undergoing chemotherapy in an endemic area [59]. In humans, visceral leishmaniasis was also reported in association with Hodgkin’s lymphoma [60], melanoma [61], and lymphoma, the last with cases of
A mucosal lesion with a tumor-like appearance by indirect laryngoscopy, but negative in indirect immunofluorescence assay test and bone marrow aspirate examination for
Other atypical report is the co-occurrence of mucosal leishmaniasis caused by
A gingival tumor-like lesion measuring 3 cm in the longest axis was reported to be an atypical presentation of visceral leishmaniasis in a six-year-old male mongrel dog. Upon histopathological analysis, a granulomatous inflammatory infiltrate, composed of plenty of plasma cells, lymphocytes, and histiocytes filled with amastigotes, was observed in the biopsy lesion. The diagnosis was confirmed by serological and immunohistochemistry assays. This case report reinforces that clinical and pathologist veterinarians should include leishmaniasis in the differential diagnosis of tumors and other chronic diseases of oral mucosa, especially in areas where the disease is endemic [69].
The relationship between parasites and immunotherapy is controversial, especially in leishmaniasis. It is well known that the increasing use of immunosuppressant medication by antitumor therapies makes patients susceptible to a new infection or turn symptomatic those asymptomatic
4. TVT and Leishmania infection association
Canine TVT (CTVT) is a unique neoplastic entity, contagious and sexually transmitted especially those of street life and of reproductive age, and regarded as the oldest known mammalian somatic cell neoplasm in constant transmission. CTVT occurs worldwide with higher incidence in tropical areas, and has been mostly reported in dogs (
Clinical signs often consist of genital lesions which, when present, may manifest as a single or multiple mass, friable on the foreskin or vulva [76, 77, 79], serosanguineous secretion, odor foul, and areas with or without necrosis [73]. In a case reported por Duzanski et al. [79] dog’s tumor initially adhered to the adjacent tissues, and developed to a friable hyperemic mass of the cauliflower aspect. Metastasis may occur with lymphatic or visceral spread usually associated with underlying immunological impairment. In addition, TVT extragenital lesions, such as cutaneous, are common and have been reported even without primary genital lesions [71].
Atypical presentations of TVT are reported in association with
A TVT was curiously reported associated with cutaneous metastasis in a female dog with leishmaniasis reactive left prescapular lymph node and subcutaneous nodular mass, not adhered to the musculature. Other visible signs were onychogryphosis, opaque, shineless, and brittle fur, with pruritic and lichenified exfoliative dermatitis in the left scapular region, ear tips and snout, and the presence of a few quantity of brownish-colored vulvar discharge with a putrid odor were the main clinical alterations. Cells with characteristics of TVT located in the genital mucosa, observed by cytology, demonstrated the presence of amastigote forms of the protozoan
Another atypical presentation of disseminated TVT associated with leishmaniasis occurred in an 8-year-old female dog that was pluriparous. There were no external genital lesions, but TVT cells were present on the serous and endometrial surface in the histopathological examination of the uterine horns, in addition to cystic endometrial hyperplasia. The history of breeding with a stray dog indicates TVT sexual transmission, and then dissemination to the omentum, peritoneum, spleen, and liver, probably favored by immunosuppression [81].
Kegler et al. [82] made the first report describing infection of tumor cells by
Clinicopathological findings of canine TVT in leishmaniotic dogs can aid in the understanding of the biological behavior of TVT associated with leishmaniasis for future cases. In summary, TVT can harbor a large number of
5. Conclusions
The cases of tumors that mimic leishmaniasis lesions indicate the need for an adequate cytological and histopathological diagnosis. Likewise, cases of clinical presentation of leishmaniasis that resemble tumors require special attention and may be related to atypical
Acknowledgments
This research was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES (Finance Code 001), by Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (26/211.680/2021) and Fundação de Amparo à Pesquisa e Desenvolvimento Científico e Tecnológico do Maranhão (APP-12233/22). HSR (CNPq 150336/2023-3) and FA-S (CAPES 88887.363006/2019-00) are postdoctoral research fellows. KC (315225/2021-1) and ALA-S (313348/2021-9) are research productivity fellows by Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq.
References
- 1.
Vail DM, Thamm DH, Liptak JM. Hematopoietic tumors. In: Withrow and MacEwen’s Small Animal Clinical Oncology. 2019. pp. 688-772. DOI: 10.1016/B978-0-323-59496-7.00033-5. Epub 2019 Nov 22. PMCID: PMC7161413 - 2.
Thamm DH. Novel treatments for lymphoma. Veterinary Clinics of North America: Small Animal Practice. 2019; 49 (5):903-915. DOI: 10.1016/j.cvsm.2019.04.004 Epub 2019 May 29 - 3.
Aricò A, Ferraresso S, Bresolin S, Marconato L, Comazzi S, Kronnie G Te, Aresu L. Array-based comparative genomic hybridization analysis reveals chromosomal copy number aberrations associated with clinical outcome in canine diffuse large B-cell lymphoma. PLoS One. 2014; 9 (11):e111817. DOI: 10.1371/journal.pone.0111817 - 4.
Giannuzzi D, Marconato L, Elgendy R, Ferraresso S, Scarselli E, Fariselli P, et al. Longitudinal transcriptomic and genetic landscape of radiotherapy response in canine melanoma. Veterinary and Comparative Oncology. 2019; 17 :308-316. DOI: 10.1111/vco.12473 - 5.
Suárez-Bonnet A, García-González B, Ramírez GA, Peñafiel-Verdú C, Jaber JR. Pemphigus erythematosus and cutaneous epitheliotropic lymphoma in a Labrador retriever dog. Iranian Journal of Veterinary Research. 2019; 20 :221-224 - 6.
Brunker JD, Hoover JP. B-cell lymphoma in a dog with ehrlichiosis (Ehrlichia canis) and systemic histoplasmosis (Histoplasma capsulatum). Canadian Veterinary Journal. 2007; 48 :292-295 - 7.
Ferro S, Palmieri C, Cavicchioli L, Zan G De, Aresu L, Benali SL. Leishmania amastigotes in neoplastic cells of 3 nonhistiocytic canine tumors. Veterinary Pathology. 2013; 50 :749-752. DOI: 10.1177/0300985813480192 - 8.
Bandi C, Mendoza-Roldan JA, Otranto D, Alvaro A, Louzada-Flores VN, Pajoro M, et al. Leishmania tarentolae: a vaccine platform to target dendritic cells and a surrogate pathogen for next generation vaccine research in Leishmaniases and viral infections. Parasites and Vectors. 2023; 16 :1-13. DOI: 10.1186/s13071-023-05651-1 - 9.
Martins LPA, Fukasawa JT, Messias MBBF, Castanho REP, Andrade AL, Sperança MA, et al. Severe visceral leishmaniasis and COVID-19 coinfection in an immunosuppressed patient. Revista do Instituto de Medicina Tropical de São Paulo. 2022; 64 :1-5 - 10.
Ayipo YO, Ajiboye AT, Osunniran WA, Jimoh AA, Mordi MN. Epigenetic oncogenesis, biomarkers and emerging chemotherapeutics for breast cancer. Biochimica et Biophysica Acta—Gene Regulatory Mechanisms. Oct 2022; 1865 (7):194873. DOI: 10.1016/j.bbagrm.2022.194873. Epub 2022 Sep 5. PMID: 36064110 - 11.
Mancuso S, Carlisi M, Santoro M, Napolitano M, Raso S, Siragusa S. Immunosenescence and lymphomagenesis. Immunity & Ageing. 2018; 15 :1-7. DOI: 10.1186/s12979-018-0130-y - 12.
Morales-Yuste M, Martín-Sánchez J, Corpas-Lopez V. Canine leishmaniasis: Update on epidemiology, diagnosis, treatment, and prevention. Veterinary Science. 2022; 9 :1-20. DOI: 10.3390/vetsci9080387 - 13.
Corpas-López V, Merino-Espinosa G, Acedo-Sánchez C, Díaz-Sáez V, Morillas-Márquez F, Martín-Sánchez J. Hair parasite load as a new biomarker for monitoring treatment response in canine leishmaniasis. Veterinary Parasitology. 2016; 223 :20-25. DOI: 10.1016/j.vetpar.2016.04.001 - 14.
Fontes JLM, Mesquita BR, Brito R, Gomes JCS, de Melo CVB, Dos Santos WLC. Anti-Leishmania infantum antibody-producing plasma cells in the spleen in canine visceral leishmaniasis. Pathogens. 2021; 10 :1-11. DOI: 10.3390/pathogens10121635 - 15.
Koutinas AF, Koutinas CK. Pathologic mechanisms underlying the clinical findings in canine Leishmaniosis due to leishmaniainfantum/chagasi. Veterinary Pathology. 2014; 51 :527-538. DOI: 10.1177/0300985814521248 - 16.
Solano-Gallego L, Koutinas A, Miró G, Cardoso L, Pennisi MG, Ferrer L, et al. Directions for the diagnosis, clinical staging, treatment and prevention of canine Leishmaniosis. Veterinary Parasitology. 2009; 165 :1-18. DOI: 10.1016/j.vetpar.2009.05.022 - 17.
Grano FG, José JE, Melo GD, de Souza MS, Lima VMF, Machado GF. Toll-like receptors and cytokines in the brain and in spleen of dogs with visceral Leishmaniosis. Veterinary Parasitology. 2018; 253 :30-38. DOI: 10.1016/j.vetpar.2018.02.030 - 18.
Di Mattia D, De Bellis F. Leishmania spp. in perianal adenoma in a dog: A case report. Topics in Companion Animal Medicine. 2019; 34 :33-35. DOI: 10.1053/j.tcam.2018.12.004 - 19.
Zambarbieri J, Pigoli C, Caniatti M, Scarpa P. Leishmania spp. in a cutaneous histiocytoma of an old dog. Diagnostic Cytopathology. 2021; 49 :1067-1069. DOI: 10.1002/dc.24839 - 20.
Manzillo VF, Pagano A, Guglielmino R, Gradoni L, Restucci B, Oliva G. Extranodal γδ-T-cell lymphoma in a dog with leishmaniasis. Veterinary Clinical Pathology. 2008; 37 :298-301. DOI: 10.1111/j.1939-165X.2008.00048.x - 21.
Albanese F, Poli A, Millanta F, Abramo F. Primary cutaneous extragenital canine transmissible venereal tumour with Leishmania-laden neoplastic cells: A further suggestion of histiocytic origin? Veterinary Dermatology. 2002; 13 :243-246. DOI: 10.1046/j.1365-3164.2002.00301.x - 22.
Margarito JM, Ginel PJ, Molleda JM, Moreno P, Novales M, López R. Haemangiosarcoma associated with leishmaniasis in three dogs. Veterinary Record. 1994; 134 (3):66-67. DOI: 10.1136/vr.134.3.66 - 23.
Di Mattia D, Fondevila D, Abramo F, Fondati A. A retrospective histopathological, immunohistochemical and molecular study of the presence of Leishmania spp. in the skin of cats with head and neck ulcerative dermatitis. Veterinary Dermatology. 2018; 29 :212-e76. DOI: 10.1111/vde.12535 - 24.
Kopterides P, Mourtzoukou EG, Skopelitis E, Tsavaris N, Falagas ME. Aspects of the association between leishmaniasis and malignant disorders. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2007; 101 :1181-1189. DOI: 10.1016/j.trstmh.2007.08.003 - 25.
Ouattassi N, Titou A, Hammas N, et al. Squamous cell carcinoma associated with an active cutaneous leishmaniasis in immunocompetent patient: Case presentation of an unlikely association and literature—review. The Egyptian Journal of Otolaryngology. 2022; 38 :148. DOI: 10.1186/s43163-022-00335-6 - 26.
Tafuri WL, De Oliveira MR, Melo MN, Tafuri WL. Canine visceral Leishmaniosis: A remarkable histopathological picture of one case reported from Brazil. Veterinary Parasitology. 2001; 96 :203-212. DOI: 10.1016/S0304-4017(00)00436-2 - 27.
Gonzalez JL, Rollan E, Novoa C, Castano M. Structural and ultrastructural hepatic changes in experimental canine leishmaniasis. Histology and Histopathology. 1988; 3 :323-329 - 28.
Melo F, Amaral M, Oliveira P, Lima W, Andrade M, Michalick M, et al. Diffuse intralobular liver fibrosis in dogs naturally infected with Leishmania (Leishmania) chagasi. American Journal of Tropical Medicine and Hygiene. 2008; 79 :198-204. DOI: 10.4269/ajtmh.2008.79.198 - 29.
Santana CC, Vassallo J, De Freitas LAR, Oliveira GGS, Pontes-De-Carvalho LC, Dos-Santos WLC. Inflammation and structural changes of splenic lymphoid tissue in visceral leishmaniasis: A study on naturally infected dogs. Parasite Immunology. 2008; 30 :515-524. DOI: 10.1111/j.1365-3024.2008.01051.x - 30.
Rallis T, Day MJ, Saridomichelakis MN, Adamama-Moraitou KK, Papazoglou L, Fytianou A, et al. Chronic hepatitis associated with canine Leishmaniosis (Leishmania infantum): A clinicopathological study of 26 cases. Journal of Comparative Pathology. 2005; 132 :145-152. DOI: 10.1016/j.jcpa.2004.09.004 - 31.
Pinto AJW, Figueiredo MM, Ferreira RA, Caliari MV, Tafuri WL. Unusual small intestine inflammatory lesions in a dog with visceral leishmaniasis. Brazilian Journal of Veterinary Pathology. 2013; 6 :19-25 - 32.
Silva KLO, De Andrade MMC, Melo LM, Perosso J, Vasconcelos RO, Munari DP, et al. CD4+FOXP3+ cells produce IL-10 in the spleens of dogs with visceral leishmaniasis. Veterinary Parasitology. 2014; 202 :313-318. DOI: 10.1016/j.vetpar.2014.03.010 - 33.
Lima IS, Silva JS, Almeida VA, Junior FGL, Souza PAN, Larangeira DF, et al. Severe clinical presentation of visceral leishmaniasis in naturally infected dogs with disruption of the splenic white pulp. PLoS One. 2014; 9 (2):e87742. DOI: 10.1371/journal.pone.0087742 - 34.
Manna L, Gravino AE, Picillo E, Decaro N, Buonavoglia C. Leishmania DNA quantification by real-time PCR in naturally infected dogs treated with miltefosine. Annals of the New York Academy of Sciences. 2008; 1149 :358-360. DOI: 10.1196/annals.1428.018 - 35.
Santos JP d, Alves LC, Ramos RAN, Pimentel D d S, Carvalho GA d, Monteiro MFM, et al. Histological changes and immunolabeling of Leishmania infantum in kidneys and urinary bladder of dogs. Revista Brasileira de Parasitologia Veterinária. 2013; 22 :420-423. DOI: 10.1590/s1984-29612013000300017 - 36.
Saridomichelakis MN. Advances in the pathogenesis of canine leishmaniosis: Epidemiologic and diagnostic implications. Veterinary Dermatology. Oct 2009; 20 (5-6):471-489. DOI: 10.1111/j.1365-3164.2009.00823.x. PMID: 20178485 - 37.
Boechat VC, Pereira SA, Júnior AAVM, Dos Santos SA, Miranda LFC, Figueiredo FB, et al. Frequency, active infection and load of Leishmania infantum and associated histological alterations in the genital tract of male and female dogs. PLoS One. 1 Sep 2020; 15 (9):e0238188. DOI: 10.1371/journal.pone.0238188. PMID: 32870947; PMCID: PMC7462300 - 38.
Verçosa BL, Melo MN, Puerto HL, Mendonça IL, Vasconcelos AC. Apoptosis, inflammatory response and parasite load in skin of Leishmania (Leishmania) chagasi naturally infected dogs: A histomorphometric analysis. Veterinary Parasitology. 26 Oct 2012; 189 (2-4):162-170. DOI: 10.1016/j.vetpar.2012.04.035. Epub 2012 May 3. PMID: 22694833 - 39.
Almeida V, Lima I, Fraga D, Carrillo E, Moreno J, Dos-Santos WLC. Hematological changes in dogs with visceral leishmaniasis are associated with increased ifn-γ and tnf gene expression levels in the bone marrow. Microorganisms. 2021; 9 (8):1618. DOI: 10.3390/microorganisms9081618 - 40.
Medeiros CM d O, Melo ACC, Lima AKF, da Silva ING, de Oliveira LC, Silva MC. Perfil hematológico de cães com Leishmaniose visceral no município de Fortaleza, Ceará. Ciência Animal. 2008; 18 :43-50 - 41.
da Costa-Val AP, Cavalcanti RR, de Figueiredo Gontijo N, Marques Michalick MS, Alexander B, Williams P, et al. Canine visceral leishmaniasis: Relationships between clinical status, humoral immune response, haematology and Lutzomyia (Lutzomyia) longipalpis infectivity. The Veterinary Journal. 2007; 174 :636-643. DOI: 10.1016/j.tvjl.2006.11.006 - 42.
Gomez MA, Belew AT, Navas A, Rosales-Chilama M, Murillo J, Dillon LAL, et al. Early leukocyte responses in ex-vivo models of healing and non-healing human Leishmania (Viannia) panamensis infections. Frontiers in Cellular and Infection Microbiology. 2021; 11 :1-12. DOI: 10.3389/fcimb.2021.687607 - 43.
Ferreira TMV, Oliveira ATC, de Carvalho VM, Pinheiro ADN, de Carvalho Sombra TCF, Ferreira TC, et al. Leukocytes and Albumin in Canine leishmaniasis. Acta Scientiae Veterinariae. 2021; 49 :1-7. DOI: 10.22456/1679-9216.111869 - 44.
Baxarias M, Jornet-rius O, Donato G, Mateu C, Alcover MM, Pennisi MG, et al. Signalment, immunological and parasitological status and clinicopathological findings of Leishmania-seropositive apparently healthy dogs. Animals. 2023; 13 :1-19 - 45.
Nicolato RDC, De Abreu RTd, Roatt BM, Aguiar-Soares RDdO, Reis LES, et al. Clinical forms of canine visceral leishmaniasis in naturally Leishmania infantum-infected dogs and related myelogram and hemogram changes. PLoS One. 2013; 8 (12):e82947. DOI: 10.1371/journal.pone.0082947 - 46.
Amusategui I, Sainz A, Rodríguez F, Tesouro MA. Distribution and relationships between clinical and biopathological parameters in canine leishmaniasis. European Journal of Epidemiology. 2003; 18 :147-156. DOI: 10.1023/A:1023090929302 - 47.
Camilleri M, Richards H, Pomplun S, Wilson A, Checkley A, Rabin N. Leishmaniasis as an unusual cause of pancytopenia in a patient receiving immunomodulatory therapy for myeloma. British Journal of Haematology. 2020; 190 (3):305. DOI: 10.1111/bjh.16663 Epub 2020 Apr 22 - 48.
Giunchetti RC, Mayrink W, Carneiro CM, Corrêa-Oliveira R, Martins-Filho OA, Marques MJ, et al. Histopathological and immunohistochemical investigations of the hepatic compartment associated with parasitism and serum biochemical changes in canine visceral leishmaniasis. Research in Veterinary Science. 2008; 84 :269-277. DOI: 10.1016/j.rvsc.2007.04.020 - 49.
Tesfanchal B, Gebremichail G, Belay G, Gebremariam G, Teklehaimanot G, Haileslasie H, et al. Alteration of clinical chemistry parameters among visceral leishmaniasis patients in western tigrai, ethiopia, 2018/2019: A comparative cross-sectional study. Infection and Drug Resistance. 2020; 13 :3055-3062. DOI: 10.2147/IDR.S261698 - 50.
Abreu-Silva AL, Lima TB, Macedo AA, Moraes-Junior FJ, Dias EL, Batista ZS, et al. Flebotomíneos Em Uma Área Endêmica Na Ilha De São Luís. Revista Brasileira de Parasitologia Veterinária. 2008; 17 :197-203 - 51.
Kost W d O, Pereira SA, Figueiredo FB, Mendes Junior AAV, Madeira M d F, Miranda L d FC, et al. Frequency of detection and load of amastigotes in the pancreas of Leishmania infantum-seropositive dogs: clinical signs and histological changes. Parasites and Vectors. 2021; 14 :1-13. DOI: 10.1186/s13071-021-04813-3 - 52.
Liberopoulos E, Alexandridis G, Elisaf M. A tumor lysis-like syndrome during therapy of visceral leishmaniasis. Annals of Clinical & Laboratory Science. 2002; 32 (4):419-421 - 53.
Cardoso FO, Zaverucha-do-Valle T, Almeida-Souza F, Abreu-Silva AL, Calabrese KDS. Modulation of cytokines and extracellular matrix proteins expression by Leishmania Amazonensis in susceptible and resistant mice. Frontiers in Microbiology. 2020; 11 :1986. DOI: 10.3389/fmicb.2020.01986 - 54.
Schwing A, Pomares C, Majoor A, Boyer L, Marty P, Michel G. Leishmania infection: Misdiagnosis as cancer and tumor-promoting potential. Acta Tropica. 2019; 197 :104855. DOI: 10.1016/j.actatropica.2018.12.010 Epub 2018 Dec 7 - 55.
Carrillo-Larco RM, Acevedo- Rodriguez JG, Altez-Fernandez C, Ortiz-Acha K, Ugarte-Gil C. Is there an association between cutaneous leishmaniasis and skin cancer? A systematic review. Wellcome Open Research. 2019; 4 :110. DOI: 10.12688/wellcomeopenres.15367.1 - 56.
Al-Kamel MA. Basal cell carcinoma developed on an active lesion of mucocutaneous leishmaniasis: A case report from Yemen. Archives of Clinical Dermatology. 2018; 1 (1):4. DOI: 10.24983/scitemed.acd.2018.00072 - 57.
Guder S, Kelahmetoglu O. Solitary cutaneous leiomyoma mimicking leishmaniasis. Dermatologic Therapy. 2020; 33 (6):e14003. DOI: 10.1111/dth.14003 Epub 2020 Jul 27 - 58.
Prieto MD, Uribe-Restrepo AF, Arcos D, Vargas DA. Case report: Squamous cell carcinoma referred for mohs surgery found to be cutaneous leishmaniasis. The American Journal of Tropical Medicine and Hygiene. 2018; 99 (6):1537-1540. DOI: 10.4269/ajtmh.18-0243 - 59.
Claudio U, Alessandro O, Luca C, Jacopo V, Katia F. Visceral leishmaniasis in a patient with lung tumour: A case report. Tropical Doctor. 2019; 49 (2):147-149. DOI: 10.1177/004947 5519825781 Epub 2019 Feb 6 - 60.
Porto VBG, Carvalho LB, Buzo BF, Litvoc MN, Santos ACS, Rocci RA, et al. Visceral leishmaniasis caused by Leishmania (Leishmania) amazonensis associated with Hodgkin’s lymphoma. Revista Do Instituto De Medicina Tropical De São Paulo. 2022; 64 :e51. DOI: 10.1590/S1678-9946202264051 - 61.
Dunzinger A, Datinger C, Loidl A, Walcherberger B, Lengauer RA, Mehraban N, et al. Visceral hepatic leishmaniasis in a melanoma patient in FDG-PET. Current Medical Imaging. 2022; 18 (4):425-428. DOI: 10.2174/157340561 7666210714122602 - 62.
Kalmi G, Vignon-Pennamen MD, Ram-Wolff C, Battistella M, Lafaurie M, Bouaziz JD, et al. Visceral leishmaniasis in patients with lymphoma: Case reports and review of the literature. Medicine (Baltimore). 2020; 99 (45):e22787. DOI: 10.1097/MD. 000000 0000022787 - 63.
Boulvard-Chollet X, Cañete- Sánchez FM, Hernández-Pérez PM, Romero-Robles LG, Garrastachu-Zumarán P. Visceral leishmaniasis versus multiple myeloma relapse: Spleen as the main clue. Revista Española de Medicina Nuclear e Imagen Molecular (English Edition). 2022; 41 (Suppl. 1):S64-S65. DOI: 10.1016/j.remnie.2022.04.003 Epub 2022 May 12 - 64.
Cobo F, Rodríguez-Granger J, Gómez-Camarasa C, Sampedro A, Aliaga-Martínez L, Navarro JM, et al. Localized mucosal leishmaniasis caused by Leishmania infantum mimicking cancer in the rhinolaryngeal region. International Journal of Infectious Diseases. Sep 2016; 50 :54-56. DOI: 10.1016/j.ijid.2016.08.003. Epub 2016 Aug 8. PMID: 27515498 - 65.
Fikre H, Teklehaimanot E, Mohammed R, Mengistu M, Abebe B, van Griensven J, et al. Atypical mucocutaneous leishmaniasis presentation mimicking rectal cancer. Case Reports in Infectious Diseases. 2023; 2023 :2768626. DOI: 10.1155/2023/2768626 - 66.
Papakonstantinou I, Koumpis E, Fytsili E, Panteli A, Milionis H, Papoudou-Bai A, et al. Leishmaniasis mimicking multiple myeloma. International Journal of Hematology. 2022; 44 (1):44-46. DOI: 10.1111/ijlh.13667 Epub 2021 Jul 29 - 67.
Beudet H, L’Ollivier C, Bouabdallah R, Campana F, Bagonchy A, Lepidi H, et al. Co-occurrence of mucosal leishmaniasis caused by Leishmania infantum and mucosal-associated lymphoid tissue lymphoma. Travel Medicine and Infectious Disease. 2023; 52 :102519. DOI: 10.1016/j.tmaid.2022.102519 Epub 2022 Dec 15 - 68.
Chong GM, Ong DSY, de Mendonça MM, van Hellemond JJ. Painful and swollen tongue: Mucosal leishmaniasis due to Leishmania infantum. International Journal of Infectious Disease. 2021; 113 :109-112. DOI: 10.1016/j.ijid.2021.09.071 Epub 2021 Sep 29 - 69.
Honse CO, Figueiredo FB, Gremião IDF, Madeira MF, Alencar NX, Miranda LHM, et al. Atypical tumor-like mass of canine visceral leishmaniasis. Source Journal of Veterinary Science. 2015; 1 (1):1-7 - 70.
Erdogan M, Caner A, Namlıses D, Sadıqova A, Nalbantsoy A, Oltulu F, et al. Parasites and immunotherapy: Immunostimulatory effect of Leishmania spp. in cancer treatment. European Journal of Cancer. 2019; 110 :S33. DOI: 10.1016/j.ejca.2019.01.098 - 71.
Carreira VS, Ferrari HF, Langohr IM, Mackenzie C, Montezzo LC, Taira E, et al. Leishmania sp. amastigotes identification in canine transmissible venereal tumor. Case Reports in Veterinary Medicine. 2014; 14 :603852. DOI: 10.1155/2014/603852 - 72.
Ganguly B, Das U, Das AK. Canine transmissible venereal tumour: a review. Veterinary and Comparative Oncology. 2016; 14 (1):1-12. DOI: 10.1111/vco.12060 Epub 2013 Aug 25 - 73.
Strakova A, Murchison EP. The changing global distribution and prevalence of canine transmissible venereal tumour. BMC Veterinary Research. 2014; 10 :168. DOI: 10.1186/s12917-014-0168-9 - 74.
Bendas AJR, Moreto PLDN, Coxo AB, Holguin PG, Soares DDV. Intra-abdominal transmissible venereal tumor in a dog: A case report. Brazilian Journal of Veterinary Medicine. 2022; 26 (44):e001422. DOI: 10.29374/2527-2179.bjvm001422 - 75.
Nabity MB, Lees GE, Boggess MM, Yerramilli M, Obare E, Yerramilli M, et al. Symmetric dimethylarginine assay validation, stability, and evaluation as a marker for the early detection of chronic kidney disease in dogs. Journal of Veterinary Internal Medicine. 2015; 29 (4):1036-1044. DOI: 10.1111/jvim.12835 - 76.
Oliveira CM. Doenças do sistema genital e reprodutor. In: Jericó MM, Andrade Neto JP, Kogika MM, editors. Tratado de Medicina Interna de Cães e Gatos (1). Roca; 2019 - 77.
Huppes RR, Silva CG, Uscategui RAR, De Nardi AB, Souza FW, Tinucci-Costa M, et al. Tumor Venéro Transmissível (TVT): Estudo retrospectivo de 144 casos. Ars Veterinária. 2014; 30 (1):13-18. DOI: 10.15361/2175-0106.2014v30n1p13-18 - 78.
Ostrander EA, Davis BW, Ostrander GK. Transmissible tumors: Breaking the cancer paradigm. Trends in Genetics. 2016; 32 :1-15 - 79.
Duzanski ADP, Feo HB, Montoya Flórez LM, Dinau FC, Paiva BR, Brandão CVS, et al. Fibrosis in canine transmissible venereal tumor after chemotherapy with vincristine. Brazilian Journal of Veterenary Medicine. 2023; 24 :e000123. DOI: 10.29374/2527-2179.bjvm000123 - 80.
Diamantino LUS, Oliveira AP de, Andrade K dos S, Santos MW da C, Pereira ZS, Mendonça FL de. M, et al. Transmissible venereal tumor associated with cutaneous metastasis and leishmaniasis in a bitch. Acta Scientiae Veterinariae. 2021; 49 . DOI: 10.22456/1679-9216.108475 - 81.
Trevizan JT, Carreira JT, Souza NC, Carvalho IR, Gomes PB, Lima VM, et al. Disseminated transmissible venereal tumour associated with leishmaniasis in a dog. Reproduction in Domestic Animals. 2012; 47 (Suppl. 6):356-358. DOI: 10.1111/rda.12110 - 82.
Kegler K, Habierski A, Hahn K, Amarilla SP, Seehusen F, Baumgärtner W. Vaginal canine transmissible venereal tumour associated with intra-tumoural Leishmania spp. amastigotes in an asymptomatic female dog. Journal of Comparative Pathology. 2013; 149 (2-3):156-161. DOI: 10.1016/j.jcpa.2012.11.241 Epub 2013 Jan 21 - 83.
Marino G, Gaglio G, Zanghì A. Clinicopathological study of canine transmissible venereal tumour in Leishmaniotic dogs. Journal of Small Animal Practice. 2012; 53 (6):323-327. DOI: 10.1111/j.1748-5827.2012.01201.x Epub 2012 Apr 10