Abstract
Multiple primary tumors (MPTs) are rare in dogs and challenging to diagnose when distinct lesions coexist. A 9‐year‐old mixed‐breed female presented with mammary and cutaneous masses. Imaging revealed no pulmonary metastasis but metallic foreign bodies. Histopathology identified a low‐grade intraductal carcinoma (HER2‐negative), melanosis with borderline proliferative features in an inguinal lymph node, and benign acrochordons. Immunohistochemistry confirmed S100 positivity and elevated Ki‐67 in the melanocytic component, suggesting melanocytic lesion with borderline proliferative features. Treatment included bilateral mastectomy, lymph node excision, and chemotherapy. Post‐treatment bloodwork showed mild cytopenias and biochemical changes consistent with hepatocellular stress. No recurrence or metastasis occurred within 6 months. This case highlights the role of multimodal diagnostics in distinguishing MPTs from metastasis and guiding therapy in complex geriatric oncology cases.
Keywords: breast cancer, chemotherapy, immunohistochemistry, multiple primary tumors (MPTs), veterinary oncology
1. Introduction
Multiple primary tumors (MPTs) are histologically distinct tumors that develop independently in the same patient [1]. Unlike metastatic disease, each tumor in an MPT case originates from a separate oncogenic event. MPTs can occur at the same time (synchronous) or at different times (metachronous), and they may be benign, malignant, or a combination of both [2, 3]. In dogs, MPTs are rarely reported, and their diagnosis requires a combination of clinical evaluation, imaging, histopathology, and immunophenotyping [4, 5]. In some cases, the complete diagnosis may be overlooked if only one lesion is sampled or if additional lesions are incorrectly interpreted as metastatic spread.
Mammary gland tumors are the most common neoplasms in intact female dogs. Retrospective studies report high rates of malignancy (approximately 50%) and metastasis (up to 50%), both of which significantly contribute to mortality [6–8]. Canine mammary tumors frequently occur as multicentric lesions involving multiple glands within one or both mammary chains, and therefore surgical planning often requires assessment of the entire mammary chain rather than isolated lesion excision. For this reason, radical or bilateral mastectomy is commonly indicated when multiple glands are affected, to reduce the risk of residual disease and occult intramammary spread.
In addition, hormonal influence plays a key role in the pathogenesis and progression of canine mammary tumors. Ovarian steroid hormones, particularly estrogen and progesterone, are known to contribute to tumor development and may influence tumor behavior. Consequently, ovariohysterectomy is frequently recommended at or around the time of mastectomy in intact female dogs as part of standard oncologic management, aiming to reduce endogenous hormonal stimulation and improve long‐term disease control.
An evaluation of hormone receptor status, including estrogen receptor (ER), progesterone receptor (PR), and HER2 expression, may assist in prognostication and therapeutic decision‐making [9, 10]. Early surgical resection helps prevent progression and improves outcomes.
Canine melanocytic tumors account for approximately 4% of all canine neoplasms, with variable biological behavior ranging from benign melanocytomas to malignant melanomas [11, 12]. These tumors most commonly occur in the skin, particularly in older dogs. However, the biological progression from benign to malignant forms remains unpredictable, making accurate histopathological and immunohistochemical assessment essential for diagnosis and staging [13].
Acrochordons are benign fibroepithelial tumors composed of a fibrovascular core covered by hyperplastic epidermis without cytological atypia or invasion [14, 15]. They can occur in dogs of any age but are more commonly diagnosed in dogs over 5 years old [16]. They are typically incidental findings in older dogs and are clinically relevant primarily when they occur concurrently with other neoplastic lesions, as they may complicate clinical interpretation of multifocal masses.
This case report presents a rare occurrence of synchronous MPTs in a single dog and highlights the importance of multimodal diagnostic evaluation—including imaging, histopathology, and immunohistochemistry—in distinguishing MPTs from metastatic disease and in guiding appropriate surgical and oncologic management.
2. Case Presentation
A 9‐year‐old intact female mixed‐breed dog was referred for evaluation of multiple mammary and cutaneous masses. On physical examination, two firm, mobile, nonadherent mammary gland masses were identified: one located in the left caudal abdominal mammary gland (M4) and the other in the right inguinal mammary gland (M5), each measuring approximately 2–3 cm in diameter. The right inguinal lymph node was moderately enlarged, firm, and non‐painful on palpation. In addition, two small, well‐circumscribed cutaneous masses were noted on the caudal aspect of both hind limbs.
2.1. Investigations
Thoracic radiographs revealed increased interstitial pulmonary opacity and several metallic fragments consistent with prior ballistic trauma, but no evidence of metastasis (Figure 1A–C). B‐mode ultrasonography of the mammary mass showed a hypoechoic, heterogeneous lesion with small hyperechoic foci and increased peripheral vascularity (Figure 2A,B). Mild splenomegaly and bilateral adrenal gland enlargement were observed. Echocardiography showed mild systolic dysfunction and papillary muscle bulging but did not preclude surgical management.
Figure 1.
Thoracic radiographs. (A) Right lateral view showing diffuse interstitial pulmonary pattern and multiple metallic foreign bodies suggestive of previous ballistic trauma. No pulmonary nodules are present. (B) Left lateral view showing diffuse interstitial pulmonary pattern and numerous metallic foreign bodies distributed throughout the thoracic soft tissues and lung fields, consistent with previous ballistic trauma. The cardiac silhouette and pulmonary margins appear unremarkable. No evidence of discrete pulmonary nodules or pleural effusion is observed. (C) Ventrodorsal view confirming the presence of multiple metallic fragments in the thoracic soft tissue and lung fields, without evidence of metastatic lesions or pleural effusion.
Figure 2.
B‐mode and color Doppler ultrasonographic images of the left caudal abdominal mammary gland. (A) B‐mode image showing a hypoechoic mass with heterogeneous echotexture. (B) Color Doppler image demonstrating increased peripheral vascular flow within the lesion, findings frequently associated with malignant mammary neoplasms.
Bilateral mastectomy and excision of the right inguinal lymph node and cutaneous thigh masses were performed. Postoperative recovery was uneventful.
Histopathology of the mammary mass showed low‐grade intraductal carcinoma. Microscopic examination revealed an intraductal epithelial proliferation completely occupying and distending pre‐existing ductal spaces without evidence of stromal invasion. Surgical margins were histologically clear; the nearest margin measured 1.0 cm from the lesion and the deep margin was uninvolved. Based on these findings, the pathologic staging was reported as pT1. N0. Mx, corresponding to at least clinical stage I out of V. Representative histological features of the mammary mass are shown in Figure 3.
Figure 3.
Histopathologic sections of the left mammary gland radical mastectomy specimen (H&E staining). (A) Low‐power (×40) view showing intraductal epithelial proliferation occupying and distending pre‐existing ducts without evidence of stromal invasion. (B) Higher magnification (×400) demonstrating Neoplastic cells were arranged in solid and cribriform patterns, exhibiting mild to moderate nuclear pleomorphism (nuclear atypia score 2). (C) Mitotic figures are infrequent, with a mitotic count of 2 per 10 high‐power fields. (D) Section of the surgical margin confirming absence of tumor infiltration; the closest margin measured 1 cm from the lesion.
The specimen labeled as “left inguinal lymph node” measured approximately 5 × 3 cm. The nipple skin overlying the right inguinal region exhibited increased basal melanocyte density and diffuse melanin deposition (melanosis). The submitted inguinal lymph node retained its overall architecture without effacement. Within nodal sinuses and interfollicular zones, numerous pigment‐laden macrophages (melanophages) containing coarse brown‐black melanin pigment were present (Figure 4). The final histopathological diagnosis was melanosis of the nipple skin accompanied by melanophage infiltration within a reactive inguinal lymph node. Although melanosis is generally considered a benign lesion, subsequent immunohistochemical findings (strong S100 expression and a Ki‐67 labeling index ≥ 10%) supported interpretation of the lesion as a melanocytic lesion with borderline proliferative features, rather than purely reactive pigment deposition.
Figure 4.
Histopathologic sections of the left inguinal lymph node specimen (H&E staining). (A) Low‐power (×40) view showing the lymph node architecture with preserved nodal structure and prominent accumulation of melanin pigment within sinusoidal and interfollicular areas. (B) Higher magnification (×400) highlighting numerous melanophage cells containing coarse brown‐black pigment dispersed within the nodal parenchyma. (C) Epidermis–dermis junction demonstrating proliferation of melanocytes extending into the superficial dermis overlying the lymph node. (D) Section of the overlying nipple skin with melanosis characterized by increased basal melanocyte density and diffuse melanin deposition.
Cutaneous lesions on the hind limbs were diagnosed as benign acrochordons. A histological section of the lesion is presented in Figure 5.
Figure 5.
Histopathological image of the excised acrochordon (H&E staining) showing hyperplastic epidermis and fibrocollagenous stroma with abundant vasculature, consistent with soft fibroma.
Based on the presence of histologically distinct lesions (mammary carcinoma, melanocytic lesion, and acrochordons), a diagnosis of MPTs was made.
Initial hematological evaluation revealed marked thrombocytopenia (67 × 103/μL) and mild monocytopenia. Post‐chemotherapy testing showed mild thrombocytopenia (161 × 103/μL), marked neutropenia (30%), a left shift (band cells 2%), and relative lymphocytosis (63%), suggesting bone marrow suppression. Red cell parameters remained within normal limits throughout. These findings are summarized in Table 1.
Table 1.
Comparative hematology results before and after chemotherapy with interpretation of changes.
| Parameter | Pre‐Chemotherapy | Post‐Chemotherapy | Unit | Interpretation (change) |
|---|---|---|---|---|
| HCT | 39.00 | 42.50 | % | Normal → Normal |
| HB | 13.00 | 14.20 | g/dL | Normal → Normal |
| RBC | 6.24 | 6.85 | 106/μL | Normal → Normal |
| MCV | 62.50 | 62.00 | fl | Normal → Normal |
| MCH | 20.80 | 20.70 | pg | Normal → Normal |
| MCHC | 33.30 | 33.40 | % | Normal → Normal |
| PLT | 67.00 | 161.00 | 103/μL | Marked ↓ → Mild ↓ (Thrombocytopenia improving) |
| WBC | 6.40 | 5.50 | 103/μL | Normal → Lower limit |
| Neutrophils | 66.00 | 30.00 | % | Normal → Marked ↓ (Neutropenia) |
| Band | 1.00 | 2.00 | % | Upper limit → Mild ↑ (Left shift) |
| Lymphocytes | 29.00 | 63.00 | % | Normal → Marked ↑ (Relative lymphocytosis) |
| Eosinophils | 2.00 | 2.00 | % | Lower limit → Lower limit |
| Monocytes | 2.00 | 5.00 | % | Mild ↓ → Normal |
Serum biochemistry was within or near reference intervals pre‐ and post‐chemotherapy, with mild elevations in liver enzymes (ALT, AST, ALP) and creatinine suggesting minimal hepatocellular stress without overt dysfunction. See Table 2 for detailed biochemical results.
Table 2.
Pre‐ and post‐chemotherapy serum biochemistry results and interpretation.
| Parameter | Pre‐chemotherapy | Post‐chemotherapy | Unit | Interpretation (change) |
|---|---|---|---|---|
| Total protein | 7.20 | 7.20 | g/dL | Upper limit → Upper limit |
| Albumin | 3.10 | 3.20 | g/dL | Lower limit → Normal |
| Globulin | 4.10 | 4.00 | g/dL | Normal → Normal |
| Glucose | 88.00 | 101.00 | mg/dL | Normal → Normal |
| Urea | 53.80 | 42.30 | mg/dL | Upper limit → Normal |
| BUN | 25.00 | 20.00 | mg/dL | Normal → Normal |
| Creatinine | 0.70 | 1.50 | mg/dL | Normal → Upper limit |
| AST (AGOT) | 29.10 | 55.00 | U/L | Normal → Upper limit |
| ALT (SGPT) | 89.50 | 72.70 | U/L | Upper range → Normal |
| ALP | 113.00 | 73.00 | U/L | Upper limit → Normal |
| Phosphorus (P) | 4.50 | 4.30 | mg/dL | Normal → Normal |
Immunohistochemistry was performed to further characterize both lesions. The mammary epithelial proliferation was hormone receptor‐positive (ER expression in ≥ 10% of tumor nuclei; PR expression in ≥ 5%) and negative for HER2 by standard immunostaining. The pigmented nodal and cutaneous cells were strongly immunoreactive for S100. The Ki‐67 labeling index within the melanocytic component was estimated at ≥ 10%. Cytokeratin AE1/AE3 highlighted epithelial elements but was negative in the melanocytic/pigmented population. A summary of histological and IHC findings is presented in Table 3.
Table 3.
Histopathology and IHC findings.
| Tissue | Diagnosis | ER (%) | PR (%) | HER‐2 | S100 | Ki‐67 (%) | CK AE1/AE3 |
|---|---|---|---|---|---|---|---|
| Mammary gland (left) | Malignant carcinoma | ≥ 10 | ≥ 5 | Neg | — | — | — |
| Cutaneous masses | Acrochordon (soft fibroma) | — | — | — | — | — | — |
| Inguinal lymph node | Melanocytic lesion with borderline proliferative features | — | — | — | High | ≥ 10 | Negative |
Morphology and immunophenotype support diagnosis of a low‐grade intraductal carcinoma of the mammary gland with clear surgical margins and no histologic evidence of invasion or lymphovascular spread. The pigmented cutaneous lesion and associated nodal pigment accumulation were morphologically consistent with melanosis accompanied by prominent melanophage infiltration. However, strong S100 immunoreactivity together with a Ki‐67 labeling index of ≥ 10% supported interpretation as a melanocytic lesion with borderline proliferative features, rather than purely reactive pigment deposition. Importantly, there was no histologic or immunohistochemical evidence of metastatic mammary carcinoma to the lymph node and no definitive features diagnostic of malignant melanoma were identified.
Overall pathologic assessment therefore favors synchronous, histologically distinct neoplastic processes: a low‐grade intraductal carcinoma of the mammary gland and a separate melanocytic lesion with borderline proliferative features, together with incidental benign acrochordons of the cutaneous excisions. Imaging and histopathological findings, in conjunction with immunophenotyping, were essential for distinguishing MPTs from metastatic disease. An overview of clinical and diagnostic features is provided in Table 4.
Table 4.
Clinical and diagnostic summary.
| Parameter | Finding |
|---|---|
| Age/Sex/Breed | 9‐year‐old female mixed‐breed dog |
| Tumor locations | Right inguinal and caudal abdominal mammary glands; cutaneous tumors on both pelvic limbs |
| Lymph node involvement | Right inguinal lymph node (excised; no metastatic carcinoma) |
| Imaging findings | Thoracic radiograph: pulmonary metallic foci, no metastasis; abdominal ultrasound: splenomegaly, renal calculi, adrenal enlargement |
| Echocardiogram | FS: 12%; bulged papillary muscle, stable under anesthesia |
| Bloodwork | Neutropenia, mild thrombocytopenia, lymphocytosis (63%), band cells (2%) |
2.2. Treatment
Following clinical staging and pre‐anesthetic evaluation, the patient underwent bilateral radical mastectomy with concurrent excision of the right inguinal lymph node and excision of cutaneous masses. An ovariohysterectomy was also performed during the same surgical procedure. The decision for complete mammary chain removal was based on the presence of multiple mammary masses involving different glands, increasing the likelihood of multicentric disease and occult microscopic spread within the mammary chain. A radical approach was therefore selected to ensure complete excision of affected and potentially at‐risk mammary tissue.
Ovariohysterectomy was performed as part of the oncologic surgical plan due to the well‐established hormone responsiveness of canine mammary tumors and the potential role of ovarian steroids in promoting tumor progression. Although the exact therapeutic benefit in established malignant cases remains debated, ovariohysterectomy is commonly recommended at or around the time of mastectomy to reduce endogenous hormonal stimulation and improve long‐term disease control, particularly in intact female dogs.
The right inguinal lymph node was removed for both staging and therapeutic purposes, given its enlargement on physical examination and its anatomical drainage of the affected mammary glands. Excision of cutaneous masses was performed concurrently to allow definitive histopathological classification and to rule out metastatic or synchronous neoplastic disease. The surgical procedure was well‐tolerated, with no intraoperative or immediate postoperative complications.
Although the intraductal carcinoma was low‐grade and completely excised with histologically clear margins, adjuvant chemotherapy was elected because of the multifocal mammary involvement, the presence of synchronous neoplastic lesions, and the absence of definitive evidence regarding the biological behavior of this uncommon presentation. Carboplatin was selected as an alternative to doxorubicin because the patient’s concurrent cardiac disease made anthracycline therapy undesirable. The protocol included carboplatin administered intravenously at 300 mg/m2 every 21 days for a total of five cycles. Hematological parameters were closely monitored prior to each dose. During treatment, hematological monitoring revealed transient thrombocytopenia and marked neutropenia; biochemistry remained within normal limits. No recurrence or metastasis was observed during 6 months of follow‐up.
Premedication included 0.9% NaCl (5–10 mL/kg/hour IV), Ondansetron (0.5 mg/kg IV), Pantoprazole (1 mg/kg IV), and Dexamethasone (0.1–0.2 mg/kg IV), to mitigate gastrointestinal and hypersensitivity reactions. The patient tolerated the protocol well, with no significant adverse effects observed; hematology and serum biochemistry were monitored throughout.
The dog’s clinical status remained stable, with no recurrence of mammary or cutaneous masses, and the lymph node remained static in size. At the 6‐month follow‐up, the patient was clinically well and free of any detectable neoplastic recurrence or metastasis.
2.3. Outcome And Follow‐Up
The dog was monitored clinically and through imaging every 4–6 weeks during chemotherapy and at 3 and 6 months following the final treatment. No new masses were detected, and the surgical sites healed without complications. Thoracic radiographs and abdominal ultrasound at follow‐up showed no signs of local recurrence or distant metastasis. Hematological abnormalities, including thrombocytopenia and neutropenia, resolved by the final chemotherapy cycle. The dog remained asymptomatic and maintained normal appetite, activity, and behavior throughout the monitoring period. At the 6‐month re‐evaluation, the patient was considered in clinical remission with no evidence of tumor recurrence or progression.
3. Discussion
This case highlights the rare presentation of MPTs in a single canine patient, including a low‐grade intraductal carcinoma of the mammary gland, a melanocytic lesion with borderline proliferative features characterized histologically by melanosis with melanophage infiltration, and cutaneous fibroepithelial polyps (acrochordons). Each lesion demonstrated distinct histopathological characteristics and no evidence of metastatic behavior. A diagnosis of synchronous MPTs was confirmed by integrating imaging, histopathology, and immunohistochemistry after excluding metastatic disease. To the authors’ knowledge, this is the first reported case in a dog documenting this specific combination of synchronous, histologically unrelated tumors with distinct clinical and pathological behavior.
Ductal carcinoma in situ is rarely reported in dogs, as most mammary carcinomas present at a more advanced stage with evidence of stromal invasion [17]. In this case, early detection and complete surgical excision with clear margins likely contributed to a favorable prognosis. Canine intraductal carcinomas can exhibit estrogen and progesterone receptor along with HER2 expression patterns; these markers have diagnostic and potentially therapeutic implications [18]. Hormone receptor expression (ER and PR positivity) further supported the classification of a less aggressive tumor phenotype, consistent with findings in human oncology.
The pigmented inguinal lymph node was initially concerning for malignant melanoma because of its S100 positivity. However, the absence of overt cytological atypia, the low mitotic rate, and preservation of nodal architecture favored melanosis with melanophage infiltration on histopathological examination. Nevertheless, the Ki‐67 labeling index of ≥ 10% suggested increased proliferative activity, and when interpreted together with the immunophenotypic findings, supported classification of the lesion as a melanocytic lesion with borderline proliferative features rather than purely reactive pigment deposition. No definitive histopathological or immunohistochemical evidence of malignant melanoma was identified. Although melanosis is well‐documented in humans, it is rarely described in veterinary literature and may be under‐recognized due to limited awareness or misclassification.
The presence of cutaneous acrochordons was incidental but contributed to the complexity of the presentation. These lesions are benign and have been sparsely reported in dogs, typically associated with chronic irritation or metabolic conditions.
This case underscores the critical importance of distinguishing MPTs from metastatic disease in canine oncology. Accurate diagnosis of MPTs requires a thorough diagnostic workup and careful interpretation of histopathological findings. The successful outcome in this case highlights the value of a multidisciplinary approach to diagnosis and treatment in veterinary oncology.
Author Contributions
Mohammad Reza Foroughi-Gilvaee: conceptualization, case management, data collection, manuscript drafting, and overall supervision. Nadi Maazi: clinical evaluation, diagnostic interpretation, and critical revision of the manuscript. Negin Raazi: preparation of figures, and assistance in manuscript writing. Ahad Muhammadnejad: histopathological examination, data interpretation, and critical manuscript review.
Funding
No funding was received for this manuscript.
Disclosure
All authors read and approved the final manuscript.
Ethics Statement
Ethical approval was not applicable to this case report.
Conflicts of Interest
The authors declare no conflicts of interest.
Foroughi‐Gilvaee, Mohammad Reza , Maazi, Nadi , Raazi, Negin , Muhammadnejad, Ahad , Synchronous Multiple Primary Tumors in a Dog: A Case Report, Case Reports in Veterinary Medicine, 2026, 3637175, 8 pages, 2026. 10.1155/crve/3637175
Academic Editor: Domenico Caivano
Contributor Information
Mohammad Reza Foroughi-Gilvaee, Email: emad.foroughi95@gmail.com.
Domenico Caivano, Email: domenico.caivano@unipg.it.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.