‘Eyes are the window to the soul’…or is it the heart?

Are you looking at lymphoma or perhaps listening to it? The diagnosis of lymphoma can be challenging, reflecting the often-insidious effects of either the primary mass or secondary spread. The case report in this issue by Talbot et al. (2025) describes an unusual location for a primary lymphoma tumour, in the interventricular septum extending around the aortic valve. Significant cardiac findings were noted on auscultation; qualities of cardiac murmurs were consistent with findings attributable to an uncommonly encountered differential diagnosis of effective aortic stenosis. Though presumably not acute in onset at this location, clinical presentation was only prompted when overt signs of periocular swelling were observed by the owner. Lymphoma accounts for 1.3–2.8% of equine neoplasms (Taintor & Schleis, 2011) and T-cell rich, large B-cell lymphoma (TCRBCL) is the most common subtype (40–45% of cases) (Durham et al., 2012; Valli et al., 2016). Lymphoma associated with peri-ocular swelling (Murphy et al., 1989; Rendle et al., 2012) has also been reported; in this case, the peri-ocular swelling was an early sentinel, preceding detection of the primary cardiac infiltration. The accompanying case report also highlights pertinent nuances when interpreting cardiac findings and provides an important aide-mémoire for presentations and manifestations of TCRBCL. Lymphoma is the most common haematopoietic equine neoplasia (Muñoz et al., 2009). Lymphoma arises from lymphoid tissue that includes lymph nodes, spleen and gut-associated lymphoid tissue. In human medicine, the presence of Reed Sternberg cells, a giant cell usually derived from B lymphocytes, identified from aspiration or biopsy determines the classification of Hodgkin lymphoma. Non-Hodgkin lymphoma, however, is the most common recognised type of lymphoma in domestic animals (Taintor & Schleis, 2011) and can be classified further by immunophenotyping neoplastic lymphocytes as B cell, T cell or NK cell. Equine lymphoma is classified into one of five forms: cutaneous, multicentric, alimentary, mediastinal and solitary tumours of extranodal origin (Durham et al., 2012). Veterinary adaptation of the World Health Organization classification for human lymphoma has determined most equine lymphomas are TCRBCL and present typically as subcutaneous nodules (Durham et al., 2012). TCRLBCL is determined by presence of large neoplastic B-lymphocytes with irregular nuclei and coarse chromatin with prominent nucleoli and adjacent sheets of small, reactive T-lymphocytes (Rissi et al., 2023). TCRBCL diagnosis is confirmed by collective results from histopathology, immunohistochemistry and PCR antigen receptor arrangement can be used adjunctively (Collar et al., 2019; Rissi et al., 2023). Case reports of equine presentations of TCRBCL in scientific literature in the past 2 years describe invasive primary lesions located in the mouth, brain, retropharyngeal region and heart (de Bruijn et al., 2025; Peretti et al., 2024; Rissi et al., 2023; Talbot et al., 2025). Clinical signs of lymphoma typically develop insidiously and at presentation are non-specific and may reflect the function of the organs involved or the extent and duration of involvement. Common findings are weight loss and anorexia (Durham et al., 2012; Taintor & Schleis, 2011; Valli et al., 2016). Peri-ocular swelling was highlighted in the accompanying case report as an early indicator of disease. A variety of multicentric lymphoma-associated ocular manifestations have been recognised and include intermittent unilateral or bilateral blepharitis, chronic ocular discharge, oedematous third eyelid, unilateral exophthalmos, corneoscleral masses and chronic uveitis unresponsive to treatment (Germann et al., 2008; Murphy et al., 1989; Rebhun & Del Piero, 1998; Rendle et al., 2012; Stoppini et al., 2005). In light of the peri-ocular region being an apparent predilection site (Rebhun & Del Piero, 1998), the authors of the case report by Talbot et al. (2025) highlight that peri-ocular swelling should be considered as a potential early sign of lymphoma in horses. Cardiac lymphoma has been reported previously (Hargreaves et al., 2018; Penrose et al., 2012), the difference in presentation with the case report by Talbot et al. (2025) included markedly expanded and nodular valvular leaflets and evidence of effective aortic stenosis and suspected forward failure of the heart. Aortic stenosis was determined from echocardiography with marked thickening of the interventricular septum, aortic, mitral, tricuspid and pulmonary valves; no significant valvular regurgitation was observed. Aortic stenosis with forward failure of the heart is considered exceptionally rare in horses (Hammond et al., 2023), and the lack of left or right sided congestive heart failure is unusual. The report highlights how the pertinent cardiac murmur qualities of point of maximal intensity and radiation detected on auscultation corroborated the rare cardiac pathology. A definitive diagnosis of lymphoma can be challenging and it was not achieved pre-mortem in the accompanying case report. This case highlights that comprehensive evaluation of lymphoma cases is indicated, including but not limited to, physical examination, blood analysis, thoracic and abdominal ultrasonography/diagnostic imaging and further investigation associated with lesion location and organ involvement. Serum globulin concentrations are associated with location of lymphoma and survival times (Wensley et al., 2023). Following collective interpretation of diagnostic investigation and clinicopathological findings and as discussed in the case report, fine needle aspirate or biopsy has been reported for definitive diagnosis in up to 60% of cases antemortem (Rebhun & Bertone, 1984) but may be limited by tumour location. Understandably, the cardiac biopsy technique (Decloedt et al., 2016) was not employed in this case. The prognosis for horses with lymphoma depends on the form of lymphoma and the stage at which the horse is presented. Multi-drug chemotherapy protocols have been described for treatment of multicentric lymphoma (Luethy et al., 2019) with partial responses in multicentric cases; reported treatment is generally considered palliative. Lymphoma is the most common haematopoietic neoplasm, accounting for 1.3%–2.8% of all equine neoplasms. T-cell rich large B-cell lymphoma is the most common type of lymphoma and has a myriad of manifestations and thus presentations. Aortic stenosis and forward failure of the heart in horses are rare. Horses with acute-onset cardiac murmurs and peri-ocular swelling should have comprehensive investigation. None. No conflicts of interest have been declared. Not applicable.