Open Veterinary Journal, (2026), Vol. 16(6): 3690-3697

Case Report

10.5455/OVJ.2026.v16.i6.40

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A case report of canine fibrosarcoma: Pathomorphological features and caspase-3 and HSP-70 expression in a local dog

Etriwati Etriwati^1*, Muhammad Nur Salim¹, Siti Aisyah¹, Nazaruddin Nazaruddin¹, Ummu
Balqis¹, Denny Irmawati Hasan¹, Teuku Reza Ferasyi^2,3, Owen Fernando⁴, Nuzul Fadilah Putri⁴,
Zuldya Marzona⁴, Sugito Sugito⁵ and Erwin Erwin⁵

¹Laboratory of Pathology, Faculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

²Laboratory of Veterinary Public Health, Faculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

³Center for Tropical Veterinary Studies-One Health Collaboration Center, Universitas Syiah Kuala, Banda Aceh, Indonesia

⁴Bachelor of Veterinary Medicine, Faculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

⁵Laboratory of Clinic and Surgery, Faculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

*Corresponding Author: Etriwati Etriwati. Laboratory of Pathology, Faculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia. Email: etriwati.2102 [at] usk.ac.id

Submitted: 12/12/2025 Revised: 15/05/2026 Accepted: 25/05/2026 Published: 11/06/2026

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Abstract

Background: Fibrosarcoma is a malignant fibroblast cell neoplasm often found in dogs. The occurrence is spontaneous with an unknown cause. A malignant tumor is determined by the activity of certain proteins or enzymes crucial for cell cycle control. Caspase-3 is associated with apoptotic activity, whereas heat shock protein-70 (HSP-70) is involved in tumor progression and cellular stress responses. The case reports the pathomorphological features and immunohistochemical expression of caspase-3 and HSP-70 in spontaneous fibrosarcoma in a local dog.

Case Description: This case report was based on a 15-year-old female domestic dog cadaver originating from Mata Ie Village, Darul Imarah District, Aceh Besar Regency, Aceh Province, Indonesia. The dog cadaver was necropsied according to the standard procedure for gross pathology observation. The swollen liver, kidneys, lungs, and spleen were collected to make histopathology slides with hematoxylin and eosin, Mason’s trichome, and immunohistochemistry for caspase-3 and HSP-70 staining. Gross anatomical observation revealed a massively swollen right liver lobe with firm consistency, icterus, and necrotic foci. The kidneys, lungs, and spleens were swollen with firm consistency, pale strikes, and necrotic foci. Spleen edges were swollen with a tender consistency and blackish red in color. The histopathological examination revealed many spindle-shaped fibroblast cells, necrotic cells, and angiogenesis in the liver. Spindle-shaped fibroblasts were accompanied by necrosis in the glomerulus and tubules. Spindle-shaped fibroblasts and local emphysema were found in the lungs. Spindle-forming fibroblast cells, merged red and white pulp, and trabeculae with hyperplasia were observed in the spleen. Mason’s trichome staining revealed a collagen mass in the liver, lungs, spleen, and kidneys. Caspase-3 and HSP-70 were expressed in all organ samples.

Conclusion: Based on the pathomorphological observation, fibrosarcoma in the liver, kidneys, lungs, and spleen was identified in the local dog. Caspase-3 expression was categorized as low positive with a percentage contribution of 18.18%, whereas HSP-70 expression was classified as positive with a percentage contribution of 36.19%.

Keywords: Apoptosis, Fibroblast, Fibrosarcoma, Heat shock protein, Tumors.

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Introduction

Abnormal masses that divide continuously, do not coordinate with the surrounding tissues, and do not die upon apoptosis are known as tumors or neoplasms (Brown et al., 2023). Soft tissue tumors in animals often pose diagnostic challenges due to their anatomical and histopathological features, similar to other types of tumors. Histopathological examination using hematoxylin and eosin (HE) staining is the basic method for tumor diagnosis; however, additional tests are needed to improve accuracy in certain cases. Masson’s trichrome staining helps identify collagen deposition, while caspase-3 and heat shock protein-70 (HSP-70) expression evaluation provides information on apoptosis activity and tumor cell stress response (Sha et al., 2023; Etriwati et al., 2025). Fibrosarcoma is a type of malignant tumor originating from fibrous tissue that requires accurate identification due to its invasive nature and prognostic implications.

Fibrosarcoma cases are often found in older dogs, whereas breed and sex factors have no significant effect on the incidence of fibrosarcoma. Fibrosarcoma generally has irregular and nodular shapes, without a defined border with the surrounding tissues, and no capsule in gross anatomy. The histopathology of fibrosarcoma featured many spindle-shaped pleomorphic to found fibrocytes with multiple prominent nuclei with eosinophilic cytoplasm, multiple nucleoli, and rough chromatin (Subapriya et al., 2018).

The microscopic morphology of most tumors consists of one cell type, mesenchymal or epithelial. The incidence rate of fibrosarcoma in dogs is approximately 9.60% (Gupta and Tiwari, 2009). Fibrosarcoma in the dog hepatobiliary system accounts for approximately 1% of all neoplasms (Vatnikov et al., 2020). The incidence of fibrosarcoma is closely related to radiation exposure, chemical carcinogens, infection, and trauma that cause genetic mutation.

Fibrosarcoma is a neoplasm caused by cells dividing more than normal cells or cells with low apoptosis. Liu et al. (2017) mentioned that through immunohistochemistry observation, disturbance in caspase-3 expression may increase the formation and development of tumors. Caspase-3 expression is lower in poorly differentiated cells than in moderately differentiated cells. The apoptosis level in neoplasm cases can be linked to the cell’s own response by defending through antiapoptosis expression. HSP-70 also increases the tumor incidence rate. Heat shock protein-70 is the strongest defense against apoptosis (Li et al., 2021).

Studies on tumor growth at the cellular and molecular levels provide important information on the role of HSP in tumor growth, invasion, metastasis, prognosis, and tumor therapy. The HSP is a carcinogenesis biomarker in several cancerous cell tissues and can be used to diagnose tumors (Sha et al., 2023).

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Case Details

Case history

This case report was based on a 15-year-old female domestic dog cadaver originating from Mata Ie Village, Darul Imarah District, Aceh Besar Regency, Aceh Province, Indonesia. The cadaver was necropsied at the Pathology Laboratory, Faculty of Veterinary Medicine, Universitas Syiah Kuala. According to anamnesis, before death, the dog had a decreased appetite, and for the last 2 weeks, pain around the abdomen was observed. The observation of the dog’s outer condition revealed mucous exudate in the mouth and nostrils and icteric mucous membranes. The dog cadaver was necropsied in the Pathology Laboratory, Veterinary Medicine Faculty, Universitas Syiah Kuala, Aceh, Indonesia, according to standard procedures. On gross pathology observation, the dog was diagnosed with a suspect tumor. Liver, kidneys, lungs, and spleen samples were collected and fixed in 10% buffer-neutral formalin solution. These specimens were routinely processed in paraffin block for light microscopy, and histopathological sections were produced for HE staining, Masson’s trichrome staining, and immunohistochemistry staining. Hematoxylin–eosin and Masson’s trichrome staining were performed on five fields of view at magnifications ranging from 40 to 1,000. Masson’s trichrome staining was performed using Masson’s Trichrome Goldner (with light green) kit (AP0267, Gennova Scientific, S.L, Spain). Immunohistochemical staining was performed using caspase-3 antibody (anti-caspase-3 antibody [E87] ab 32351, Abcam, 1:250 in antibody diluent) and HSP-70 antibody (anti-HSP70 antibody/BB70 ab53496, 1:250 in antibody diluent). Immunohistochemistry staining was performed according to the protocol for Mouse and Rabbit Specific HRP/DAB Detection IHC Kit (ab64264), and modification was done as performed by Aisyah et al. (2021) and Etriwati et al. (2023). The results of caspase-3 and HSP-70 immunohistochemical staining were evaluated using a binocular microscope (Olympus BX51, Olympus Corporation, Japan) and documented by CellSens Microscope Imaging Software at 400x magnification with five field-view repetitions. Quantitative analysis of the percentage contribution of immunopositive areas for caspase-3 and HSP-70 expression was performed using ImageJ software version 1.54p integrated with the IHC Profiler plugin. Immunohistochemical staining intensity was classified based on the percentage contribution of high positive, positive, low positive, or negative staining categories (Varghese et al., 2014).

Macroscopic observation revealed that the left lobe of the liver was swollen, hemorrhagic, and icteric with massive swelling, an undefined border, firm consistency, and a dry incision aspect. The kidney is swollen, anemic, and firm in consistency. Upon incision, the cortex and pelvis were pale, and the medulla was swollen and anemic in a diffuse manner. Nodular swelling, necrotic foci, and a positive floating test with firm consistency are observed in the lungs. The spleen is generally swollen, dark red in color, and has nodular swellings with firm consistency and infarcted edges (Fig. 1).

Fig. 1. The gross pathology of a fibrosarcoma in a local dog. (A) liver: massive tumor (circle) with undefined border, hyperemia, hemorrhage, and icterus; (B) kidney: anemic and swollen (arrow); (C) lungs: pulmonary emphysema, swelling (circle) with necrotic foci and; (D) spleen: swollen (a) infarct on the edges (b).

Microscopic observation with HE staining showed polygonal to spindle-shaped tumor cell morphologies with oval nuclei, pale cytoplasm with undefined cell borders, and round cells with round nuclei. The tumor cells in the liver showed angiogenesis, spindle-shaped fibroblasts with tapering nuclei and pointed ends, a fibrous nest containing fibrils, vacuoles, and hyperchromatic and eosinophilic granulocytes. Neoplastic spindle cells with nucleoli of varying sizes and a biphasic growth pattern were located with a fibrous background. Spindle cells appeared anaplastic with one large nucleus or several mitotic nuclei. Masson’s trichrome staining confirmed collagenous connective tissue (Fig. 2).

Fig. 2. The fibrosarcoma histopathology in the liver of a local dog. Spindle-shaped fibroblast cells with tapering nuclei and pointed ends, a fibrous nest filled with fibrils (FN), hyperchromatic and eosinophilic granulocytes (Gr), and vacuoles (Vc). The collagen connective tissue is stained green (D). Hematoxylin–eosin (A, B, C) and Masson’s trichrome (D) staining. Magnification 200× (A and B); 100X (C and D).

Necrotic glomeruli, tubules with intravascular coagulation, vacuoles, and desquamation of tubular epithelial cells were observed in the kidney. The tumor region showed small numbers of spindle fibroblasts with tapering nuclei and pointed ends. The lungs showed pulmonary emphysema, alveoli in tight formation as an indication of fibrosis, angiogenesis, and small numbers of spindle-shaped fibroblasts and mononuclear leukocytes (Fig. 3).

Fig. 3. Histopathology of fibrosarcoma in the kidney and lungs of a local dog. Glomerular necrosis (Nc), vacuole (Vc), fibroblasts (Fc), and emphysema (Em). Kidney (A and B) and lungs (C and D) HE staining, magnification [A, C (40×); B, D (1000×)].

The white pulp appeared to merge with the red pulp, making differentiation difficult. The spleen trabeculae were abnormal in size due to connective tissue hyperplasia, and new trabeculae were formed in several areas. In the spleen area with the tumor, the morphological features were similar to those observed in the liver and kidney tissue, which showed spindle-shaped fibroblast cells with pointed ends and angiogenesis (Fig. 4).

Fig. 4. Histopathology of fibrosarcoma in the spleen of a local dog. (A) white and red pulp are difficult to distinguish; (B) splenic trabecula with hyperplasia (Hp); (C) newly formed trabecula (Nt); (D) fibroblast cells (Fc). HE staining, magnification [A (40×); B and C (100×); D (1000×)].

Quantitative analysis of immunopositive areas demonstrated that caspase-3 expression was categorized as low positive with a percentage contribution of 18.18%, while HSP-70 expression was classified as positive with a percentage contribution of 36.19%, based on the IHC Profiler scoring system (Fig. 5).

Fig. 5. Expression of caspase-3 and HSP-70 of fibrosarcoma in the liver of a local dog (brown-stained). Immunohistochemical staining using caspase-3 antibody (anti-caspase-3 antibody [E87] ab 32351 [A] and HSP-70 antibody (anti-HSP70 antibody/BB70 ab53496 [B]. Negative control for anti-caspase-3 antibody [C] and anti-HSP70 antibody [D], magnification 400×.

Ethical approval

The research protocol was approved by the Ethics Committee of the Faculty of Veterinary Medicine, Universitas Syiah Kuala Animal Care Experiments (approval no. 435/KEPH/IX/2025).

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Discussion

The macroscopic findings of a swollen liver with a massive left lobe, nodular swelling in the spleen and lungs, and diffuse swelling of the renal medulla indicate that the tumor is malignant or cancerous. Cancer is clinically defined as a mass resulting from the irregular proliferation of somatic cells, which causes the loss of cell growth control mechanisms (Brown et al., 2023). Malignant tumors are characterized by a rapid increase in size, the tendency to invade surrounding tissue, and the ability to metastasize to other organs (Patel 2020).

The morphological features of tumor tissues were dominated by proliferation of fibroblasts, angiogenesis, and nuclear proliferation of various sizes alongside mitosis, which strengthens the assumption that the tumor was formed by malignant fibroblast tissue. According to Sebastian et al. (2021), fibrosarcoma is a malignant tumor characterized by anisocytosis (different cell sizes and shapes), anisokaryosis (different nucleus sizes and shapes), a high number of mitotic cells with multiple nuclei, many nuclei, and cytoplasm unable to absorb color well. The nucleus of a benign tumor cell is typically similar to the nucleus of its origin cell, which is defined and uniform, whereas the nucleus of a malignant tumor is undefined and not uniform, so it does not look like the origin cells. The nucleus controls cell division through nucleoproteins contained within the chromatin. Increasing nuclear chromatin caused rough and grouping features in the edge of the nucleus, making it appear hyperchromatic. Neoplastic cells are characterized by an elongated pleomorphic nucleus with a prominent nucleolus and a high mitotic rate, as well as necrosis and multifocal lymphoid aggregates (Vascellari et al., 2006).

Glomeruli showed multifocal necrosis, whereas the tubules showed intravascular coagulation, hydropic degeneration, vacuolization, and desquamation of tubular epithelial cells. The tumor area of the kidney showed low numbers of spindle-shaped fibroblasts with tapering nuclei and pointed ends. Spindle cell tumors account for only about 1% of all kidney tumors and are more aggressive than clear or granular cells (Srigley and Delahunt, 2009). Several kidney tumor cases with spindle cells have an infausta prognosis and are resistant to several forms of systemic therapy (Shuch et al., 2012). Fibrosis is the result of a chronic inflammatory reaction caused by various stimuli, such as tissue trauma, persistent infection, allergic reaction, chemicals, radiation, and autoimmune reactions (Wynn, 2008). Pulmonary fibrosis can be defined as excessive growth related to excessive deposition of the extracellular matrix component.

Generally, abnormal fibroblast cell proliferations during neoplasm can be explained as being caused by the disturbed extracellular matrix dynamics, producing metalloprotease that promotes tumor growth by stimulating vascularization (Kendall and Bostwick, 2014). New vascular growth is important because tumor cell proliferation, invasion, and metastasis are highly dependent on an adequate supply of oxygen and nutrients (Nishida et al., 2006). New blood vessels are formed through angiogenesis. It is a complex development process that includes basal membrane degradation through protease secretion, endothelial cell proliferation, migration, blood vessel tube formation, and endothelial cell differentiation. The findings of spindle neoplastic cells in the liver, lungs, kidneys, and spleen, as well as the morphological changes of the cytoplasm and nucleus in this study, are similar to those of high-malignancy tumors (Fischer et al., 2020; Lashen et al., 2022). This case described a pleomorphic cell area with many hyperchromatic nuclei, abnormal mitosis, rough chromatin tissue, and a dense chromatin black nucleus. The structures stained green during Masson’s trichrome staining are extracellular matrices with collagen and elastin as constituent elements. In fibrosarcoma, the collagen fibers are positive under Masson’s trichrome staining (Shokrpoor et al., 2023).

Immunohistochemical analysis revealed the expression of caspase-3 and HSP-70 within the tumor tissues. These findings align with previous reports indicating that caspase-3 expression is associated with apoptotic activity in canine fibrosarcoma and various other malignancies, while HSP-70 is linked to tumor progression and cellular stress responses (Porter and Jänicke, 1999; Ciocca and Calderwood, 2005). Caspase-3 activity inhibition in the liver suppresses hepatocyte death induced by Deoxyribonucleic Acid damage, subsequently triggering hepatic carcinogenesis (Shang et al., 2018). Loss of caspase-3 expression is closely related to apoptosis resistance in carcinomas (Persad et al., 2004). Such resistance leads to a critical imbalance between cell growth and cell death, ultimately stimulating oncogenesis (Obeng, 2021). HSP-70 can suppress apoptosis, which can increase tumor growth and metastasis (Li et al., 2000). Inhibiting HSP70 activity can disrupt apoptosis-related tumor cell signaling pathways (Ishaq et al., 2016).

HSP-70 immunoreactivity was specifically detected within tumor cells and exhibited a strong correlation with tumor progression-associated pathological parameters, including increased tumor size, portal vein invasion, and advanced tumor stage (Joo et al., 2025). HSP70 expression was associated with the presence of grade III tumors in canine tumor samples, and the absence of HSP70 expression correlated with longer survival (Romanucci et al., 2012). HSP expression in tumors is associated with increased cell proliferation, metastasis, poor prognosis, and chemotherapy response (Boudesco et al., 2018). HSP-70 overexpression is a characteristic of cancer with poor prognosis and can result in death (Ferretti et al., 2024). HSP-70 plays a dual role in cancer progression, as it can promote tumor growth, enhance tumor cell resistance, and suppress anticancer mechanisms (Sha et al., 2023).

In this case report, determining the main cause of the neoplasm is difficult because the dog’s medical history does not note any medical treatment, medication, or even vaccination throughout her life. Therefore, additional studies are warranted to elucidate the underlying cause of spontaneous neoplasia in this patient.

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Acknowledgments

The authors would like to express gratitude to the Rector, Universitas Syiah Kuala, and the Indonesian Government for Associate Professor Research Grant No. 207/UN11.2.1/PG.01.03/SPK/PTNBH/2024, 03 Mei 2024.

Conflict of interest

The authors declare no conflicts of interest.

Funding

None.

Authors’ contributions

The authors will declare the contributions of each author. E.W., S.A., S.S., and E.E. were responsible for the case report, observations, and data interpretation. E.W., D.I.H., O.F., N.F.P., and Z.M. prepared the histopathology slides, performed the staining procedures, and wrote the initial draft of the manuscript. E.W., N.Z., U.B., M.N.S., E.E., and T.R.F. provided supervision and performed a critical review of the manuscript. All authors have read and approved the final version of the manuscript.

Data availability

All data were provided in the manuscript.

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