Canine multiple primary tumours: Mammary tubular carcinoma, uterine leiomyosarcoma, and facial sebaceous epithelioma (2024)

Abstract

Multiple primary malignant tumours (MPMTs) are multiple neoplasms with independent pathogenetic origins, placing great importance onthe tumorigenesis and clinical treatment. However, due tothe rare occurrence and diagnostic confusion, MPMTs have rarely been investigated inveterinary medicine. Inthis report, a10-year-old intact female Maltese dog had MPMTs, consisting oftwo malignant tumours and one benign tumour each derived from atopographically different site: tubular carcinoma inthe mammary glands, leiomyosarcomaintheuterus and sebaceous epithelioma inthe cheek. The unique combination ofMPMTs would bethefirst case inveterinary research togive insight into the diagnosis, disease characteristics, and surgical treatment.

Keywords: leiomyosarcoma, mammary gland tumour, multiple origins, primary tumours, sebaceous epithelioma

Recently, inparallel with advances incancer treatments and prolonged survival, the number ofmultiple primary malignant tumours (MPMTs) has gradually increased inhuman and veterinary medicine (Lv et al. 2017). MPMTs are defined bythe presence oftwo ormore distinct malignant tumours that have different origins, satisfying three criteria: (1)histopathological confirmation ofmalignancy ofeach tumour; (2)topographically separation and difference ofeach tumour; (3)nometastatic lesion found (Zhai et al. 2018). MPMTs are crucial ininvestigating the tumour pathogenesis, diagnostic procedures, and clinical treatment. However, due tothe rare occurrence and lack ofresearch, MPMTs have rarely been studied inveterinary medicine.

Canine mammary gland tumour (MGT) isthe most commonly diagnosed neoplasm, comprising the major proportion ofreproductive tumours infemale dogs (Kuppusamy et al. 2019). Inaddition, many retrospective studies have found that MGT has ahigh malignancy rate (approximately 50%) and ahigh metastatic potential (almost 50%)., mainly giving rise tomortality indogs (Im et al. 2014; Feliciano et al. 2023). Therefore, the early diagnosis and surgical resection are imperative, which allow the prevention oftumour progression and better prognosis.

Uterine tumours occur very rarely, less than 0.5% ofall canine tumours, usually affecting middle-aged toolder female dogs that have not been spayed (Percival et al. 2018). Leiomyoma isthe most common, accounting for 90%, while leiomyosarcoma isextremely rare, which grows slowly and possibly invades inside the abdomen (Serin et al. 2010). Insome unknown manner, both tumours are endocrine dependent and frequently associated with gynaecological diseases such asovarian follicular cysts, oestrogen-secreting tumours, endometrial hyperplasia, mammary hyperplasia, and mammary neoplasia (Pena et al. 2006; Tsioli et al. 2011). Mainly, leiomyosarcoma can induce abdominal distension, dyspnoea, and general dullness due tothe huge volume occupancy inthe abdomen.

Sebaceous epitheliomas are benign tumours and are occasionally found, accounting for 2% ofall skin tumours indogs, which occur most often onthe head, ears, and dorsum between 8and 13years ofa*ge (Goldschmidt and Hendrick 2002; Giuliano et al. 2009). The histopathological findings are characterised bymoderate lobular irregularity, and basaloid cell proliferation with few well-differentiated sebocytes surrounded byinterlobular stroma (Yoon and Par 2016).

The patient received surgical treatments onthree tumours having either cancerous ornon-cancerous lesions depending onthe mammary gland, uterus, and cheek.

The histopathological examination and morphological classification confirmed acase ofMPMTs composed oftwo concurrent primary malignant tumours with sebaceous epithelioma.

Case presentation

A10-year-old intact female Maltese dog was presented with multiple masses inthe 4^thand 5^thmammary glands and the left cheek. The masses inthe mammary gland units were firm and mobile without any significant signs inthe axillary and inguinal lymph nodes onboth sides byphysical examination. Onthe other hand, the cheek mass was soft, mobile, and measured ataround 4–5cm indiameter, causing severe pruritus and ulceration.

Laboratory tests revealed that the biochemistry and electrolytes were normal. However, the complete blood count (CBC) detected non-regenerative anaemia and severe leucocytosis along with moderate neutrophilia. Moreover, the radiography, ultrasonography, and computed tomography (CT) scans found masses inthe abdomen and cheek (Figure1). The abdominal mass was measured ataround 7cm indiameter and multilobulated between the splenic tail and urinary bladder, while the facial mass was around 4cm with anirregular margin. Inthis case, apartial mastectomy and facial tumorectomy, along with anexploratory laparotomy and ovariohysterectomy, were considered the best therapeutic option. After the surgical treatment, each collected mass was subject toahistopathological examination.

The mammary gland lesions were mainly composed ofpoorly differentiated tubular structures (Figure2). There was minimal tubular differentiation, but occasional lumens were present. Individual neoplastic cells showed moderate anisocytosis and anisokaryosis and had oval-shaped vesicular tochromatic nuclei and afairly extensive amount ofcytoplasm. The MGT was diagnosed astubular carcinoma with gradeII malignancy according tothe staging system for canine MGT (Misdorp et al. 1999).

The facial tumour lesions were mainly composed ofbasaloid reserve cells inislands ortrabeculae, which were polyhedral shaped and had scant tomoderate amphophilic cytoplasm (Figure3). The nuclei were large and vesicular and had multiple small nucleoli. There were scattered small foci ofsebaceous differentiation, characterised byclusters ofcells with lipidised cytoplasm, indicating morphological features ofabenign tumour. The immunohistochemistry (IHC) confirmed that the majority ofthe neoplastic cells were positive for pan-cytokeratin, leading toadiagnosis ofsebaceous epithelioma.

In the uterus, the endometrium had cystic endometrial hyperplasia, resulting inmoderate mucometra and endometritis. The tumour lesions mainly comprised ofspindle-shaped orpolygonalcells with abundant, wispy cytoplasm and indistinct cell borders with ahigh cellular density (Figure3). Nuclei highly varied insize and shape, some ofwhich were cigar tospindle-shaped, and others vesicular with indistinct nucleoli. Occasionally bizarre tumour cells with big nuclei were found throughout the lesions. Furthermore, numerous mitoses were observed, including atypical figures. The IHC against desmin confirmed adiagnosis ofleiomyosarcoma (data not shown).

DISCUSSION

MPMTs are defined bythe presence oftwo ormore distinct malignant tumours that have apathogenetic origin inmultiple organs, which could besynchronous ormetachronous, occurring within 6months from the diagnosis ofaprevious malignant tumour or6months after the first diagnosed tumour, respectively (Zhao et al. 2015; DeLuca et al. 2019). Previously, the histopathological examination confirmed two malignant tumours intopographically separated two organs: the tubular carcinoma ofthe mammary gland and uterine leiomyosarcoma. The tumours were not related toeach other, leading toadiagnosis ofMPMTs along with the sebaceous epithelioma ofthe cheek. However, wecould not define its tumorigenesis due toalack ofinformation about the outpatient.

In clinical oncology, the most crucial part ofapplying appropriate treatment isclassifying the tumour’s origin site and defining its stage and grade correctly. The difficulties indistinguishing between MPMTs and metastatic secondary tumours provide challenges toclinicians. Without the identification ofthe encountered tumours, the optimal treatment cannot beachieved. Inhuman medicine, MPMTs have been studied thoroughly, while there are many limitations inveterinary medicine despite the clinical importance ofMPMTs. The incidence ofMPMTs was between 0.734% and 11.7% in1104269humans (Demandante et al. 2003), and was 3% in1722 dogs (Rebhun and Thamm 2010).

Fortunately, anexploratory laparotomy helped toacquire the uterine neoplasm, resulting inthe successful tumorectomies ofthree tumors originating from three different sites. Inthe present case, nometastasis was found inthe MGTs, but the uterine leiomyosarcoma was highly suggestive ofmetastasising due tomultiple enlarged lymph nodes accordingtoanabdominal CT scan. Tothe best ofour knowledge, this isthe first case ofaunique combination ofthree independent tumours inveterinary medicine, including the mammary gland, uterus, and facial sebaceous gland. Still, wehave several limitations: (1)the lymphadenectomy ofthe metastatic lymph nodes was not available due topoor accessibility and increased burden tothe geriatric patient, leaving the exact metastatic lesion ofthe lymph nodes undefined; (2) the origin ofabdominal incidentaloma shown bythe diagnostic imaging did not correspond tothe actual tumour origin site; (3)although new strategies treating mammary cancer have been developed (Vazquez et al. 2023), wecould not apply any immunotherapy ortargeted therapy against the specific protein due tothe owner’s unwillingness.

Nonetheless, anoptimal clinical treatment was designed and performed. The patient has been doing well without any signs ofrecurrence ordistant metastasis for over two years, confirmed byperiodic physical examinations, radiography, and sonography. Furthermore, itis avery encouraging result considering that the average 1-year survival rateofpatients with mammary cancer is19% and that ofpatientswith leiomyosarcoma is75%, respectively (Rasotto et al. 2017; Cohen et al. 2003). It shows the surgical resection ofeach neoplasm tobe clinically significant when treating concurrent tumours.

Additionally, the medical imaging alone would not besufficient enough toidentify atumour’s origin and distinguish between primary and metastatic tumours. Any further studies onMPMTs should include research for the biological, clinical, pathological, and molecular characteristics, providing optimal diagnostic and therapeutic options asstudied inmammary cancer (Vazquez et al. 2023). Inthis context, webelieve the present case would contribute toestablishing astandardised diagnosis and medical procedures for MPMTs, appealing toclinicians and researchers inveterinary medicine.

Conflict of interest

The authors declare noconflict ofinterest.

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