A retrospective descriptive study of colorectal large or intermediate cell lymphoma in cats managed with surgical resection and/or medical management

Abstract

Objectives

The current standard-of-care treatment for feline gastrointestinal intermediate- or large-cell lymphoma is systemic chemotherapy. There is some evidence that feline lymphoma patients with a solitary gastrointestinal mass may benefit from excisional surgery followed by chemotherapy; however, most studies of feline gastrointestinal lymphoma combine various stages and anatomical sites of the disease. Studies indicating different behaviour of feline gastrointestinal lymphoma depending on its anatomical location have been published, and significantly longer survival times have been seen in canine colorectal lymphoma. The aim of the present study was therefore to describe the signalment, treatment and outcome of cats with intermediate- or large-cell lymphoma in the colorectal region.

Methods

The medical records of three veterinary hospitals were retrospectively searched for cats diagnosed with a colorectal intermediate- or large-cell lymphoma. The data were collected and subjected to a univariate analysis, and median values were calculated for each of the variables of interest. Median survival times were estimated using the Kaplan–Meier method.

Results

A total of 11 cats were included in the study, with the most common presenting signs being haematochezia, hyporexia, diarrhoea and weight loss. Different treatment strategies and their combinations were used, leading to an overall median survival time of 177 days, with a difference seen between chemotherapy only (29 days) and a combination of surgery and chemotherapy (972 days). Two cats treated with both surgery and chemotherapy were alive at more than 20 months after diagnosis.

Conclusions and relevance

This is the first study to describe specifically cases of cats with intermediate- to large-cell colorectal lymphoma. Even though the number of cases was limited because of the rarity of the disease, the data indicate multimodal treatment might be beneficial in these cases.

Keywords

Colorectal lymphoma large-cell lymphoma high-grade lymphoma gastrointestinal lymphoma

Introduction

Lymphoma, a malignant neoplasm originating from lymphocytes, is the most common tumour type of the gastrointestinal tract in cats. It can be divided histopathologically into low-grade (>80% small cell), intermediate to high-grade lymphoma (>90% intermediate/large cell) and large granular types.^1–4 Alimentary lymphoma can be diffuse or, less commonly, form solitary lesions and can be found in any part of the gastrointestinal tract. Other organs, such as the regional lymph nodes, spleen and liver, can also be affected simultaneously.^1-2 Unlike in alimentary small-cell lymphoma, cats with large-cell lymphoma often present more severe clinical signs and tend to have a significantly worse response to therapy and shorter survival times.^4–6

Only a limited number of studies have focused solely on the treatment and prognosis of gastrointestinal intermediate- or large-cell lymphomas (ILCLs).^4,7–11 Anatomical localisation was usually described in these studies; however, further conclusions of possibly different outcomes according to this feature were often hindered by a small and diversely treated population. Furthermore, ILCL of the large intestine is considered a less common type, accounting for only 5–22% of all alimentary ILCLs.^{2–8,11–13}

The standard-of-care treatment for feline ILCL is currently systemic chemotherapy.^{4,8,10–12,14–16} Isolated studies have also looked into the use of surgery or radiotherapy in cats with alimentary ILCL.^{12,13,17–19} One such study found that colorectal ILCL presents a relatively good outcome after surgical removal, compared with the same type of lymphoma in different parts of the gastrointestinal tract.¹²

The aim of the present study, therefore, was to describe cases of cats with ILCL in the colorectal region, including their signalment, treatment and outcome, using collected clinical data from three referral centres.

Materials and methods

This multi-institutional, descriptive case series included cats presented to three veterinary referral hospitals in the UK (Pride Veterinary Centre, The Royal (Dick) School of Veterinary Studies’ [R(D)SVS] Hospital for Small Animals and Queen’s Veterinary School Hospital) between 2011 and 2021. The medical records of these hospitals were retrospectively searched for cats diagnosed with colorectal ILCL. The owners signed written consent forms before enrolment. The study was approved by the Royal College of Veterinary Surgeons Ethics Review Panel (reference number 2022-008-Holenova) and R(D)SVS Veterinary Ethical Review Committee of the University of Edinburgh (reference number 104.22).

To include a case in this study, the patient had to be diagnosed by histology or cytology with an ILCL in the rectum, colon and/or ileocaecocolic junction and undergo medical (chemotherapy or corticosteroids) and/or surgical treatment. The case was excluded if there was histological or cytological evidence of lymphoma in other organs, except for disease in the local lymph nodes, or if any masses were observed in other parts of the gastrointestinal tract (stomach, small intestine) on abdominal ultrasound or CT scan. This was to ensure the lymphoma was primary to the colorectal site rather than a part of a disseminated disease. Cases were also excluded if the histological and/or cytological results or interpretation of abdominal ultrasound and/or CT scan were not available for review at the time of data collection.

The collected data consisted of patient signalment (age, sex, breed), presenting clinical signs, results of physical examination, bloodwork, including feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) status, imaging interpretation, cytological and histological results, presence of comorbidities identified during the work-up, information on the anatomic localisation of the lymphoma, type of treatment and incidence of side effects. Data regarding remission and the date of relapse and treatment at that time, as well as the date and cause of death, were also reviewed, if available.

Staging procedures consisted of haematology, serum biochemistry, retroviral testing, CT scan of the thorax and abdomen and/or abdominal ultrasound and thoracic radiographs, and cytological samples of the lymph nodes, liver and spleen, at the discretion of each clinician.

Treatment of each patient was reviewed, and the response to the treatment was assessed using the Veterinary Cooperative Oncology Group (VCOG) Response Evaluation Criteria in Solid Tumours (RECIST) where repeated abdominal imaging was performed.²⁰ Otherwise, the treatment response was based on the evolution of the presenting clinical signs, as perceived by the owners and clinicians in charge (Table 1). Progression-free survival (PFS) was then defined as the time from the date of the first treatment of lymphoma to progression documented by abdominal imaging or recurrence of clinical signs related to lymphoma, or to death.

Table 1

Criteria for treatment response evaluation²⁰

	Abdominal imaging	Clinical signs
Complete remission	Complete disappearance of the tumour and normalisation of the size of regional lymph nodes	Complete resolution of all presenting clinical signs
Partial remission	Reduction of the sum of diameters of tumour size and regional lymph nodes of at least 30%	Marked improvement of presenting clinical signs
Stable disease	Less than 30% reduction or less than 20% increase in the sum of diameters of the tumour and regional lymph nodes	Presence of stable clinical signs
Progressive disease	At least 20% increase in the sum of diameters of the tumour and regional lymph nodes; evidence of new lesions	Worsening or recurrence of the presenting clinical signs

Survival time, defined as the time from diagnosis to the time of death, was calculated for each patient with a known date of death. Death was considered related to the disease in cases where progressive disease was reported at the time or in the weeks before the event, or in the absence of other reported causes of death.

Statistical analysis

The descriptive data gained from the medical records were analysed using descriptive statistics. The Kaplan–Meier method was utilised to estimate the median survival time (MST). Cats that were lost to follow-up, or still alive at the time of data collection, were censored in the survival analysis.

Results

A total of 11 cats fulfilled the criteria and were included in this study. The case details are listed in Table 2.

Table 2

Signalment, diagnosis, staging, treatment and outcome data for 11 cats

Case number	Age (years)	Sex	Diagnostic tests	Disease localisation	Staging tests	Cytological/histological diagnosis	Treatment	Best response	Remission duration (days)	Survival time (days)
1	10	FE	AUS, histology, IHC	Colon and caecum	FNA of the RLN	Large B-cell lymphoma, mitoses 0/HPF	CS	PR	NA	>36
2	14	FN	AUS, cytology	Descending colon	FNA of the RLN, liver, spleen, TXR	Large-cell lymphoma	CS	NA	NA	NA
3	11	FN	AUS, cytology	Colon	TXR	Large-cell lymphoma	CS	NA	NA	NA
4	12	FN	AUS, cytology	Colon		Large-cell lymphoma	High-dose COP	PR	19	29
5	4	MN	AUS, cytology, histology, IHC	Descending colon	FNA of the liver, spleen,histology of the LN	Large B-cell lymphoma	S, CS	CR	23	34
6	10	FN	AUS, cytology, histology	Transverse colon	FNA of the spleen, histology of the RLN	Large-cell lymphoma	S, CHOP	CR	Ongoing	>659
7	10	MN	AUS, cytology, histology	Rectum	FNA of the spleen, RLN	Large-cell lymphoma	S, CHOP	CR	971	972
8	6	FN	AUS, CT, cytology, histology, IHC	Colon	FNA of the RLN, CT scan of the thorax	Large B-cell lymphoma	S, CHOP + COP maintenance	CR	Ongoing	>1210
9	4	FN	AUS, histology	Colon	Histology of the RLN and spleen, CT scan of the thorax	Intermediate- to large-cell lymphoma, low grade	S, high-dose COP	CR	120	177
10	7	MN	CT, histology, IHC	Rectum and colon	CT scan of the thorax	Intermediate to large B-cell lymphoma	l-asparaginase + vincristine	PR	NA	NA
11	12	MX	AUS, cytology	Colon	FNA of the RLN, liver	Intermediate- to large-cell lymphoma	High-dose COP + L	CR	76	105

AUS = abdominal ultrasound; CHOP = doxorubicin, cyclophosphamide, vincristine, prednisolone; COP = cyclophosphamide, vincristine, prednisolone; CR = complete remission; CS = corticosteroids; FE = entire female; FN = neutered female; FNA = fine needle aspiration; HPF = high power field; IHC = immunohistochemistry; L = l-asparaginase; MN = neutered male; MX = male with unknown status; NA = not available (patient lost to follow-up)/not applicable; PR = partial response; RLN = regional lymph nodes; S = surgery; TXR = thoracic radiographs

Signalment

The study group consisted of seven females (one entire, six spayed) and four males (three castrated, one of unknown status); the median age was 10 years (range 4–14). The vast majority (10/11) were domestic shorthair cats.

History and physical examination

The most frequent presenting complaints were haematochezia (8/11), hyporexia (7/11), diarrhoea and weight loss (6/11 for both). Lethargy was observed in nearly half of the cats, vomiting in three cats, and two cats each presented rectal tenesmus and prolapse; faecal incontinence was seen in one case.

Corticosteroid treatment with either a single injectable dose or short oral treatment was reported in four cases within the weeks preceding referral. Other cats received supportive treatment, such as gabapentin, probiotics, meloxicam, cobalamin, mirtazapine and maropitant, or no treatment at all.

The median body condition score in the eight cats that had this parameter reported was 3.5/9 (range 1–7), with the median weight of all cats being 4.0 kg (range 2.1–4.7). An abdominal mass or abnormally thickened colon was palpated in 6/8 cats with presence of a colic abnormality; no anomaly was reported on examination of the other two cats. A mass in the rectum was visualised in three cats that presented with a rectal prolapse. Other anomalies identified on the physical examination were heart murmur in two cats and dehydration in one cat.

Diagnosis and staging

Haematology and serum biochemistry were performed in all animals. In five cats, neutrophilic leucocytosis was observed, accompanied by monocytosis and eosinophilia in two, whereas three cats presented a mild to moderate degree of anaemia and one thrombocytopaenia (without verification on manual count). Mild azotaemia, moderate hypoalbuminaemia and moderate hyperkalaemia were each identified in one cat. Point-of-care immunoassay (SNAP FIV/FeLV Combo, IDEXX Laboratories, in one, the rest unknown) for feline retroviral infections, FeLV and FIV, was performed in three (cases 3, 5 and 7) and four cases (cases 1, 3, 5 and 7), respectively. One cat (case 5) tested positive for FeLV, while the results of the remaining tests were negative.

All animals underwent abdominal imaging (ultrasound 9/11, CT scan 1/11, both 1/11) that localised the mass and/or thickening to the colon in eight cases (7/8 mass, 1/8 diffuse thickening), to the colon and rectum in one case, to the colon and caecum in one case and to the rectum only in one case. Prominent or enlarged regional lymph nodes (colic or mesenteric) were seen in 10 cases. Enlarged or prominent lymph nodes were sampled either by fine needle aspiration or excised during surgery in 8/10 cases, and only two samples (cases 2 and 11) showed presence of lymphoma, with the remaining cases being compatible cytologically or histologically with a reactive lymphoid hyperplasia. Cytology of the liver and spleen was performed in three and five patients, respectively. The cytological sample of liver in case 11 was consistent with a neutrophilic inflammation. The remaining splenic and hepatic samples did not show evidence of lymphoma infiltration in these organs.

Two patients underwent thoracic radiography and three patients underwent a thoracic CT scan. The patients that underwent radiography of their thorax had suspected mild sternal lymphadenopathy, while that was seen in only 1/3 cats that underwent a thoracic CT scan. None of the sternal lymph nodes were sampled.

Lymphoma was diagnosed via cytological samples of the mass in eight cases, with histological confirmation after excision in five of them. Three cats had a histological diagnosis only (two surgical biopsies and one endoscopic biopsy). Further specification of the lymphoma via immunohistochemistry was performed in four cases, all showing the presence of a B-cell lymphoma. Intermediate- to large-cell lymphoma was diagnosed in three cases, with the rest being large-cell lymphoma. The grade of the tumour was not readily reported by the pathologist (two high-grade and one low-grade lymphoma). However, the observed mitoses were 0 per high-power field in one case (case 1) and above 10 in the rest of the cases where the grade was not concluded in the histology report.

Treatment

Three cats received treatment with corticosteroids only: two were treated with prednisolone (at a dosage of 2.25 and 2.5 mg/kg q24h) and one with a single intramuscular injection of methylprednisolone acetate (at a dose of 1.6 mg/kg).

Chemotherapy only was used in three cases with variable protocols, of which none were finished. The high-dose vincristine, cyclophosphamide and prednisolone (COP) protocol was administered as described in a previous publication.²¹ Case 4 developed progressive disease (suspected renal involvement) during the initial phase of the high-dose COP protocol, at which point lomustine was given. Treatment with l-asparaginase and vincristine was started in case 10, with a partial response observed, but no further treatment was administered because of financial limitations. The intended protocol in case 11 was high-dose COP; however, due to development of an eye ulcer requiring enucleation, subcutaneous injection of l-asparaginase was used following the first week of treatment and the second dose of the COP protocol was postponed by a week. At the time of progressive disease (following the third dose of the induction phase of the COP protocol), treatment was switched to lomustine and then doxorubicin.

One cat underwent surgical removal of the mass (partial colectomy), followed by a short course of prednisolone treatment at a low dose (0.5 mg/kg q24h). The other four cats received adjuvant chemotherapy after removal of the mass (partial colectomy in cases 6, 8 and 9 and submucosal resection of prolapsed mass in case 7). The protocol used in these cats was mostly vincristine, cyclophosphamide, doxorubicin and prednisolone (CHOP), which was intended to be administered as described in a previous publication.¹⁴ However, two cats received only three cycles owing to side effects and financial constraints, while one cat completed the protocol and continued with the maintenance phase of the COP protocol for an additional 6 months. The last cat received an adjuvant high-dose COP protocol, and doxorubicin followed by lomustine was administered upon disease progression.

There were no major complications associated with surgical treatment in these cases. The majority of chemotherapy side effects were gastrointestinal and haematological in nature, with persistent VCOG grade 4 alanine aminotransferase elevation in case 4 and persistent VCOG grade 2 azotaemia in case 6 seen after completion of the chemotherapy protocol.²² Anorexia was seen repeatedly in cases 6, 7 and 8 (VCOG grades 1 and 2), and neutropenia in the same cases as well as in case 9 (mostly VCOG grade 1 or 2, three episodes of VCOG grade 3 and two episodes of VCOG grade 4).

Outcome

The best reported response was a complete response in six cases, lasting 23 to at least 1210 days, including two cases still in complete remission at the time of data collection. A partial response was seen in three patients, while the response was unknown in two patients that were lost to follow-up.

The mean PFS for all patients with available data was 120 days (range 23 to >1210). Four cats died of suspected progressive disease 29–177 days after diagnosis. One cat, initially presenting with a rectal mass, was euthanased 972 days later because of an ileal mass of unknown origin associated with septic peritonitis, likely due to intestinal perforation. Four cats were lost to follow-up shortly after diagnosis, with only one being followed after discharge for another 36 days, at which time the clinical signs started to worsen, suggesting progressive disease (case 1).

For survival analysis, patients were divided into groups according to the treatment received. The four groups consisted of corticosteroid treatment (cases 1–3), surgery (case 5), chemotherapy (cases 4, 10 and 11) and surgery followed by chemotherapy (cases 6–9).

The survival data were calculated using eight cats, of which three were censored in the statistical analysis (one was lost to follow-up and two were still alive at the time of data collection). The MST of the five cats was 177 days. The cats that received both surgical and medical treatment with chemotherapy had the longest survival times (177 to >1210 days; MST 972), compared with patients treated with chemotherapy only (29–105 days; MST 29). However, the number of patients in these two groups was too small to allow meaningful statistical analysis. A larger study would be needed to evaluate the significance of the difference in survival times observed between the treatment groups in the present study.

Discussion

This is the first study to describe specifically cases of feline intermediate- or large-cell colorectal lymphoma. Considering the small number of cats tested, only B-cell lymphoma was identified. This correlates with previous studies, which showed a 67–100% prevalence of ILCL of B-cell origin in the colorectal location, as well as with a study that showed markedly higher frequency of a large B-cell lymphoma in the ileocaecocolic junction when compared with the frequency of a T-cell lymphoma.^2,4,23,24

Colorectal lymphoma has been previously described in dogs as an uncommon type of lymphoma with markedly longer survival times when compared with lymphoma in other anatomical sites.^25,26 Similar to feline colorectal lymphoma, a predominance of B-cell immunophenotype was reported. The study by Desmas et al²⁵ did not show any significant difference in survival times between chemotherapy alone and chemotherapy combined with local treatment.

Although medical management remains the gold standard for ILCL in cats, it bears a variable response in the cases of alimentary localisation, with approximately one-fifth to two-thirds of cases achieving a complete response.^8,14–16,27 MSTs in such cats are then in the approximate range of 7–15 months with different protocols; the MSTs for non-responders or partial responders have been significantly shorter (16–47 days and 83–150 days, respectively).^{7–10,15,16,27} In the present study, the survival of the single cat that was treated with chemotherapy only and reached complete remission was substantially shorter than the MST reported previously (case 11, with a survival time of 105 days). However, the best reached response of this cat was based on clinical signs and physical examination only, and the chemotherapy protocol was interrupted by an emergency surgery; therefore, it is difficult to draw conclusions in this setting.

The role of surgical resection of alimentary ILCL before chemotherapy remains unclear.^8,12,13,17 Aside from cases with suspected intestinal rupture or obstruction, surgical management may also be considered in cases with localised disease^12,13 or when intestinal perforation after chemotherapy is a major concern, although this was reported in only 17% of cats with alimentary lymphoma.²⁸ Historically, surgical resection of colorectal lymphoma resulted in an MST of 97 days, which did not differ significantly from that of cats treated with chemotherapy alone or as an adjuvant treatment.²⁹ One recent study reported similar survival times after surgery for alimentary ILCL, when cases including those that did not survive to suture removal were considered.¹² No significant difference in MST was observed between the cats receiving adjuvant chemotherapy after surgery and those who did not, although the number of cases was small.¹² Another study later showed prolonged survival (MST 417 days) in cats with alimentary ILCL that underwent both surgery and adjuvant chemotherapy.¹³

Interestingly, surgical excision was reported to lead to prolonged survival times in cats with large intestinal ILCL, with an MST of 675 days in one study;¹² however, the study group was small and the effect of adjuvant chemotherapy on these patients was not examined.¹² In the present study, only one patient was treated with surgery followed by a short course of corticosteroids alone and had a shorter survival compared with those that received adjuvant chemotherapy. More importantly, markedly prolonged survival times were observed in patients treated with both surgery and adjuvant chemotherapy (177 to >1210 days; MST 972), with two patients still alive and in remission at the time of data collection.

The present study has several limitations because of the rarity of the disease and the retrospective nature of the study. The main limitation is the small sample size and the variability in treatment types and their combinations, none of which were randomised. Another limitation is the number of patients that were lost to follow-up, further hindering the value of survival analysis of the described population. Other limitations are inherent to the retrospective and multicentric nature of the study, including the fact that cytological and histological samples were not interpreted by the same pathologist, or reviewed, and that only a small number of the histological tumour samples were assigned a tumour grade. The chemotherapy protocols also differed when chemotherapy alone was used (COP) and when it was used in an adjuvant setting (CHOP protocol, mostly). Although the superiority of one protocol over the other has not been established in cases of feline alimentary ILCL,⁸ it could have influenced the response and survival times in this population. In addition, assessment of response based solely on clinical signs and physical examination was suboptimal, leading to an overestimation of both the number of patients with complete response and the time to disease progression. Taking all these limitations into account, the results of this study should be interpreted with caution as a result of the weak level of scientific evidence. It is hoped that more insight can be gained from a larger, prospective study.

Conclusions

Although this study involved only a small number of patients and therefore provides limited evidence, it suggests that extended survival times are achievable in feline colorectal ILCL. Surgery combined with adjuvant chemotherapy may contribute to successful management in appropriately selected cases. Future research should investigate this approach in a randomised, controlled and prospective study.

Footnotes

Acknowledgements

We wish to thank Professor Tim Sparks, Waltham Petcare Science Institute, for providing statistical support for this study.

Accepted: 11 April 2025

Author note

The abstract of this study was presented at the 2024 BSAVA Congress in Manchester.

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

Linnaeus Veterinary Limited supported the costs of the open access publication charges.

Ethical approval

The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS. Although not required, where ethical approval was still obtained, it is stated in the manuscript.

Informed consent

Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers, tissues and samples) for all procedure(s) undertaken (prospective or retrospective studies). No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required

ORCID iD

Katerina Holenova

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