Clinic-Pathological Aspects of Spleen Hemophagocytic Histiocytic Sarcoma in a Dog

Thaynan Cunha Vieira, Luiz Flávio Telles, Karen Yumi Ribeiro Nakagaki, Geovanni Dantas Cassali

Abstract


Background: Histiocytes are cells that differentiate into macrophages and dendritic cell lines from bone marrow CD34+ stem cells. The hemophagocytic histiocytic sarcoma (HHS) is the only malignant neoplasm originating from macrophage lineages, being a variation of histiocytic sarcoma (HS), originated from dendritic cells. In general, the HHS shows aggressive biological behavior, due to the erythrophagocytosis characteristic of this disease and overall average survival around seven weeks, affecting mainly Bernese Mountain Dog, Rottweiler and Golden Retriever breeds. Therefore, the objective of this work is to report the case of a dog with HHS, emphasizing the clinical aspects and its diagnostic method.

Case: An 8-year-old bitch Rottweiler, was attended with history of inappetence and prostration. The complete blood count showed normochromic normocytic anemia, monocytosis and thrombocytopenia, with serum urea levels below the reference value for the specie in the biochemical examination. The abdominal ultrasound highlighted splenomegaly, with heterogeneous parenchyma and presence of a vascularized mass and an enlarged splenic vein.  Thoracic radiographic examination showed multifocal and rounded radiopaque structures in the pulmonary parenchyma, suggesting metastatic formation. Rapid serological tests for detection of the main hemoparasitosis antibodies were negative, as well as negative Coombs test. The animal was submitted to exploratory laparotomy with medial line access and posterior splenectomy. The spleen microscopic evaluation revealed neoplastic proliferation cells in mantle arrangement and solid nests areas, supported by a fine fibrovascular stroma. The cells had broad and eosinophilic cytoplasm, round nuclei and some pleomorphism, rude chromatin and evident nucleoli. It was also observed the presence of marked anisocytosis and anisocariosis, hemophagocytic activity, and 27 mitoses in 10 fields (40 x). There were atypical mitoses and necrosis and extensive hemorrhaged areas. These histopathological findings suggested a histiocytic malignant neoplasia and immunohistochemical analysis   was performed to define a better histiocytic neoplasm origin. The neoplastic cells showed positive imunostaining for CD11d and Iba1 and negative imunostaining for CD3 and CD20, as well as a proliferative index of 80%, supporting the diagnosis of HHS in the animal's spleen. The following hematological analyzes demonstrated persistence of anemia, worsening of thrombocytopenia, prolongation of activated partial thromboplastin time, hypoproteinemia with hypoalbuminemia, serum increase of creatinine, alkaline phosphatase and total bilirubin. Myelogram showed erythrocyte and granulocytic lineage hypoplasia, thrombocytic aplasia and more than 50% of macrophages in bone marrow cell population. The animal’s clinical condition worsened rapidly, after successive transfusions and administration of chemotherapy with lomustine, leading to death 14 days after the surgery.

Discussion: HHS is the most serious clinical presentation among histiocytic disorders, conferring an extremely unfavorable prognosis. In addition, the scientific literature that specifically addresses the HHS is rare, with therapeutic extrapolations being performed for the treatment of HS from dendritic cells. The racial predisposition and clinical findings, associated with hematological changes, histopathological analysis and confirmation by immunohistochemistry allowed the diagnosis of HHS, a rare and underreported neoplasm, with aggressive biological behavior and with still inefficient treatment in veterinary medicine.


Full Text:

PDF

References


Allison R.W. 2012. Laboratory Evaluation of the Liver. In: Thrall M.A., Weiser G., Allison R.W. & Campbell T.W. (Eds). Veterinary Hemathology and Clinical Chemistry. 2nd edn. Danvers: Wiley-Blackwell, pp.401-423.

Asada H., Ichii O., Tomiyasu H., Uchida K., Chambers J.K., Goto-Koshino Y., Ohno K., Kon Y. & Tsujimoto H. 2019. The intratumor heterogeneity of TP53 gene mutations in canine histiocytic sarcoma. Journal of Veterinary Medical Science. 81(3): 353-356.

Cherpinski V.A., Gonçalves A.D., Viriatto F. & Fam A.L.D. 2017. Sarcoma Histiocítico Hemofagocítico em um cão - Relato de Caso. Biociências, Biotecnologia e Saúde. 19: 148-150.

Clifford C.A., Skorupski K.A. & Moore P.F. 2020. Histiocytic Diseases. In: Vail D.M., Thamm D.H. & Liptak J.M. (Eds). Small Animal Clinical Oncology. 6th edn. St. Louis: Elsevier Inc., pp.791-810.

Hedan B., Thomas R., Motsinger-Reif A., Abadie J., Andre C., Cullen J. & Breen M. 2011. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior. BMC Cancer. 11: 201. DOI: 10.1186/1471-2407-11-201

Jark P.C. & Rodigheri S.M. 2016. Distúrbios Histiocíticos. In: Daleck C.R. & De Nardi A.B. (Eds). Oncologia em Cães e Gatos. 2.ed. Rio de Janeiro: Editora Roca, pp.661-671.

Meuten D. 2012. Laboratory Evaluation and Interpretation of the Urinary System. In: Thrall M.A., Weiser G., Allison R.W. & Campbell T.W. (Eds). Veterinary Hemathology and Clinical Chemistry. 2nd edn. Danvers: Wiley-Blackwell, pp.322-377.

Moore P.F. 2014. A Review of Histiocytic Diseases of Dogs and Cats. Veterinary Pathology. 51(1): 167-184.

Moore P.F. 2017. Canine and Feline Histiocytic Diseases. In: Meuten D.J. (Ed). Tumors in Domestic Animals. 5th edn. Ames: John Wiley & Sons Inc., pp.222-336.

Moore P.F., Affolter V.K. & Vernau W. 2006. Canine hemophagocytic histiocytic sarcoma: A proliferative disorder of CD11d+ macrophages. Veterinary Pathology. 43(5): 632-645.

Mullin C. & Clifford C.A. 2019. Histiocytic Sarcoma and Hemangiosarcoma Update. Veterinary Clinics of North America - Small Animal Practice. 49: 855-879.

De Nardi A.B., Reis Filho N.P. & Viéra R.B. 2016. Quimioterapia Antineoplásica. In: Daleck C.R. & De Nardi A.B. (Eds). Oncologia em Cães e Gatos. 2.ed. Rio de Janeiro: Roca, pp.333-378.

Picarsic J. & Ronald J. 2018. Pathology of histiocytic disorders and neoplasms and related disorders. In: Abla O. & Janke G. (Eds). Histiocytic Disorders. Cham: Springer International Publishing, pp.3-50.

Takada M., Smyth L.A., Thaiwong T., Richter M., Corner S.M., Schall P.Z., Kiupel M. & Yuzbasiyan-Gurkan V. 2019. Activating Mutations in PTPN11 and KRAS in Canine Histiocytic Sarcomas. Genes. 10(7): 505. DOI: 10.3390/genes10070505

Valli V.E.O. (Ted). 2007. Hematopoietic System. In: Maxie M.G. (Ed). Pathology of Domestic Animals. 5th edn. v.3. Philadelphia: Elsevier, pp.107-324.

Weiser G. 2012. Introdution to Leukocytes and the Leukogram. In: Thrall M.A., Weiser G., Allison R.W. & Campbell T.W. (Eds). Veterinary Hemathology and Clinical Chemistry. 2nd edn. Danvers: Wiley-Blackwell, pp.118-122.

Weiser G. 2012. Interpretation of Leukocyte Responses in Disease. In: Thrall M.A., Weiser G., Allison R.W. & Campbell T.W. (Eds). Veterinary Hemathology and Clinical Chemistry. 2nd edn. Danvers: Wiley-Blackwell, pp.127-139.

Weiss D.J. 2002. Flow cytometric evaluation of hemophagocytic disorders in canine. Veterinary Clinical Pathology. 31(1): 36-41.




DOI: https://doi.org/10.22456/1679-9216.106173

Copyright (c) 2021 Thaynan Cunha Vieira, Luiz Flávio Telles, Karen Yumi Ribeiro Nakagaki, Geovanni Dantas Cassali

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.