Standardized classification of synchronous gastrointestinal small cell lymphoma and gastrointestinal mast cell tumors in 15 cats

Abstract

Objectives

Synchronous primary tumors have been defined as two or more concurrent, yet independent tumors diagnosed within 6 months or less. The primary objective of this study was to investigate the occurrence and clinical findings in cats with synchronous gastrointestinal (GI) small cell lymphoma (SCL) and GI mast cell tumor (MCT) at two referral hospitals. A secondary objective was to classify these tumors as distinct or mixed, and if mixed, categorize them histomorphologically as collision or combined tumors based on standardized definitions informed by literature review.

Methods

The databases of the Schwarzman Animal Medical Center (AMC) and University of Veterinary Medicine in Vienna, Austria (Vetmeduni) were searched between January 2012 and December 2022 for cats with synchronous GI SCL and GI MCT. Clinical findings, treatment and outcome were abstracted from medical records. Biopsy or autopsy reports and, when available, slides and/or histopathology images indicating the presence of a synchronous GI SCL and GI MCT were reviewed by two board-certified pathologists.

Results

A total of 15 cats were diagnosed with synchronous GI SCL and GI MCT, representing 4.3% of 329 cats with GI SCL in the AMC population. This study identified 15 cats with a total of 18 synchronous tumors. Six cats had tumors classified as distinct tumors and six as combined. Three cats had both distinct and combined tumors. Survival in this group of cats was in the range of 8–1189 days.

Conclusions and relevance

This is the first report to classify synchronous tumors in cats as distinct and combined tumors. The results of this study indicate a wide range of survival times for cats with synchronous GI SCL and GI MCT, suggesting that despite the diagnosis of synchronous tumors, the outcome is similar to cats with either GI SCL or GI MCT.

Plain language summary

Fifteen cats diagnosed with intestinal small cell lymphoma and intestinal mast cell tumor at the same time

When two unrelated tumors occur within 6 months or less of one another, they are called synchronous tumors. This study investigated gastrointestinal (GI) small cell lymphoma (SCL) and GI mast cell tumor (MCT) occurring synchronously in cats. The tumors were classified as distinct if they were distant from each other and mixed if they occurred at the same site. A total of 15 cats with synchronous GI SCL and GI MCT were identified at two veterinary hospitals, Schwarzman Animal Medical Center (AMC) and University of Veterinary Medicine in Vienna, Austria. Of the 329 cats in the AMC population with GI SCL, 4.3% were also diagnosed with a GI MCT. Six cats had distinct tumors and six cats had mixed tumors. Three cats had both distinct and mixed tumors. Seven cats survived more than 30 days after surgery (range 8–1189). Cats may have more than one type of tumor at the same time and multiple intestinal biopsies are required to identify these tumors. The results of this study suggest that the outcome in cats with synchronous GI SCLs and GI MCTs is similar to those with either one of these tumors despite the diagnosis of two tumors at the same time.

Introduction

Synchronous primary tumors have been defined in the veterinary and human literature as two or more concurrent, yet independent tumors diagnosed within 6 months or less of one another.^{1 –5} Based on the human literature, metachronous tumors occur 6 months or more apart.^{2 –5} Synchronous primary tumors can be further classified as distinct, meaning physically separate from one another, or mixed. The latter denotes a tumor appearing macroscopically as one mass, but when examined microscopically, contains two or more cell types.^1,2,5 Histologic subtypes of mixed tumors have been defined in several human review papers and are based on geographic and physical interactions of the neoplastic cells and their presumed tumorigenesis.^{1,6 –8} Mixed subtypes include collision, combined colonized or biphenotypic/biphasic tumors. The differences between subtypes can be minor and difficult to distinguish. ⁸ However, a lack of consensus in their use can result in these terms being used interchangeably, which is not ideal for reproducibility and comparisons between studies.^{1,7 –9} Therefore, there is a need for well-defined histomorphologic criteria and standardized usage of terms in veterinary medicine that allow for reproducibility and comparison between studies.

In a large retrospective study of dogs with multiple distinct tumors, mast cell tumors (MCTs) were one of the most common tumor types occurring with another primary tumor. ¹⁰ Reported data from one veterinary diagnostic center identified mixed tumors encompassing MCTs and multiple other tumor types, including lymphoma. ¹ A synchronous hepatosplenic lymphoma and visceral MCT was reported in a dog; however, the diagnosis of the visceral MCT was made on cytology alone and therefore further characterization of these tumors into synchronous tumor subtype(s) was not reported.^10,11 Synchronous tumors have not been well documented in cats. A large retrospective study of 680 European shorthair cats found seven cats with multiple tumors, the most common being squamous cell carcinoma and mammary gland tumors. ¹² The authors of that study did not indicate if the tumors were distinct or mixed. A second retrospective study of feline tumors identified 2.7% of cats with multiple primary tumors; however, the location of these tumors was not specified. ¹³ Laurenson et al ¹⁴ reported 4/14 cats with gastrointestinal (GI) MCTs having synchronous GI small cell lymphoma (SCL). Those authors did not report on the histomorphologic subtype or outcome in those cats. To our knowledge, there are no studies reporting on the occurrence, histomorphologic classification and outcome of cats diagnosed with synchronous GI SCL and GI MCT, which we have observed in our clinical practice.

Lymphoma is the most common feline neoplasm, with GI SCL accounting for 36–75% of all feline alimentary lymphoma.^15,16 Lymphoma primarily affects the alimentary tract in older cats that test negative for feline leukemia virus (FeLV). ¹⁷ As GI SCL is a low-grade malignancy, treatment is less intense than for GI large cell lymphoma and long survival times are common.^{18 –20} GI MCTs affect the GI tract, spleen, liver and abdominal lymph nodes in cats.^21,22 GI MCTs represent approximately 4–5% of feline intestinal tumors.^12,13,23,24 Recent reports suggest survival times of 1–2 years can be achieved in cats with GI MCT.^21,22

The primary objective of this study was to investigate the occurrence and clinical findings in cats with synchronous GI SCL and GI MCT at two referral hospitals. A secondary objective was to classify these tumors as distinct or mixed, and if mixed, categorize them histomorphologically as collision or combined tumors based on standardized definitions informed by literature review.

Materials and methods

The medical records and autopsy database of the AMC and the surgical biopsy and autopsy database at the Vetmeduni were retrospectively searched between January 2012 and December 2022 for cats with synchronous GI SCL and GI MCT. The date of study entry for all cats was defined as the date of diagnosis with synchronous GI SCL and GI MCT by histology. The end date was defined as the date of death (natural death or death by euthanasia) or the close of data collection if still alive on 31 December 2022. Data collected from the medical records, when available, included age, sex and neuter status, clinical signs, clinicopathologic testing, chemotherapeutic/treatment protocol(s), response to therapy and survival time.

Two board-certified (American College of Veterinary Pathologists) pathologists (TAD and HD) reviewed biopsy and autopsy reports for all cases and, where available, any histopathology images or slides. GI SCL was diagnosed using routine hematoxylin and eosin staining and, in some cases, molecular clonality testing (PCR for antigen receptor T-cell gamma locus rearrangement [PARR]) or immunohistochemistry (IHC) within the stomach, small intestine and/or large intestine. GI MCT was defined as documented MCT histopathology and, in some cases, IHC. The noteworthy histomorphologic features, as well as PARR and IHC findings (when available), were reviewed by each pathologist separately and each case was classified by the definition criteria summarized in Figure 1 and study objective 2. Pathologists were blinded to each other’s results during the review process. One discordant case was resolved via consensus review and discussion. Mixed tumor subtype definitions were based on previously reported definitions in human medicine.^1,6,7 Collision tumors were defined as two or more distinct neoplastic populations that develop adjacent to one another, with no intermingling of the neoplastic cells at the border. Combined tumors were defined as two or more separate neoplastic populations that were intermingled either at the border or throughout the tumor. Distinct tumors represented two or more geographically separate tumors (ie, within separate segments of intestine).

Figure 1.

Diagram highlighting the criteria for categorization of synchronous tumors. Synchronous tumors are defined as two or more tumors diagnosed within 6 months of one another and can be classified into mixed and distinct tumors. Mixed tumors include collision, combined and biphenotypic types of synchronous tumors: (a) collision tumor with two or more distinct neoplastic populations that are juxtaposed with no intermingling at their borders; (b) combined tumors with two or more separate neoplastic populations that are adjacent and intermixed; (c) biphenotypic tumors arise from a common stem cell precursor that undergoes divergent differentiation resulting in separate population phenotypes with overlapping immunohistochemical and molecular properties; and (d) distinct tumors with two or more geographically separated tumor populations

The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) was used to assess response to treatment in patients that had abdominal imaging performed after surgery and during treatment. ²⁵ If abdominal imaging was not performed after treatment, response was assessed by the clinician based on clinical signs and categorized as complete clinical response (100% resolution of clinical signs for ⩾30 days), partial clinical response (⩾50% but <100% resolution of clinical signs for ⩾30 days) or non-responder (<50% improvement of clinical signs or response of <30 days), based on previous recommendations. ¹⁸

Results

Epidemiology

A total of 329 cats with confirmed GI SCL were identified in the AMC databases. Of the cats in the AMC population, 14 also had a synchronous GI MCT. A 15th cat with synchronous GI SCL and GI MCT was identified at the University of Veterinary Medicine in Vienna (Vetmeduni). The diagnosis of GI SCL was based on histopathology in all cats (Table 1). The cat from Vetmeduni and 4/14 cats from AMC were diagnosed with synchronous GI SCL and GI MCT at autopsy. Because there was no outcome information for the five cats diagnosed at autopsy, we report on signalment, anatomical tumor location and histological information from all 15 cats and clinical signs with treatment and outcome from 10 cats.

Table 1.

Diagnostic procedure and histopathology results by anatomic location in 15 cats with synchronous gastrointestinal (GI) small cell lymphoma (SCL) and GI mast cell tumor (MCT)

Cat	Diagnostic procedure	Small intestine	Large intestine	Liver	Abdominal lymph node	Other biopsies
1	Exploratory celiotomy R&A Full-thickness biopsies	SCL jejunum, duodenum, ileum	MCT colon	Mild lipidosis	NSF	None
2	Exploratory celiotomy R&A Full-thickness biopsies	SCL jejunum, colon	MCT colon	Chronic cholangitis, mild lipidosis	MCT Round cell infiltrate, (PARR+)	None
3	Exploratory celiotomy R&A Full-thickness biopsies	SCL jejunum MCT jejunum	Not biopsied	Not biopsied	MCT	None
4	Exploratory celiotomy R&A Full-thickness biopsies	MCT jejunum SCL jejunum	Not biopsied	Hepatic adenoma	MCT	Exocrine pancreatic hyperplasia
5	Exploratory celiotomy R&A Full-thickness biopsies	SCL jejunum (PARR+) MCT jejunum Chronic LP jejunitis	Not biopsied	Biliary cyst, LP neutrophilic periportal inflammation	Reactive hyperplasia	None
6	Exploratory celiotomy R&A Full-thickness biopsies	SCL jejunum (confirmed IHC CD3) MCT jejunum (confirmed IHC c-kit)	Not biopsied	Not biopsied	Not biopsied	None
7	Exploratory celiotomy Full-thickness biopsies	SCL jejunum MCT duodenum	Not biopsied	Mild lipidosis	MCT, eosinophilic lymphadenitis	SCL stomach
8	Exploratory celiotomy Full-thickness biopsies	SCL jejunum MCT jejunum	Not biopsied	MCT	MCT	None
9	Exploratory celiotomy Full-thickness biopsies	SCL ileum (PARR+) MCT jejunum Mild LP eosinophilic enteritis duodenum	Not biopsied	MCT	MCT	Stomach LP gastritis, possible MCT Mammary gland adenoma
10	Exploratory celiotomy Full-thickness biopsies Splenectomy	SCL jejunum MCT jejunum	Not biopsied	Not biopsied	MCT	MCT spleen
11	Autopsy	SCL duodenum, jejunum, ileum MCT jejunum	NSF	Cystadenoma	Reactive hyperplasia	Cardiomyopathy
12	Autopsy	SCL duodenum, jejunum MCT jejunum	Not biopsied	Moderate lymphocytic cholangitis	Lymphoid hyperplasia	Cardiomyopathy
13	Autopsy	SCL duodenum, jejunum MCT jejunum	LP colitis	Vacuolar hepatopathy	Lymphoid hyperplasia	Hemoabdomen
14	Autopsy	SCL segment not specified MCT duodenum, jejunum	LP colitis	LP cholangitis	Plasmacytosis	Pancreatitis
15	Autopsy	SCL segment not specified	MCT	MCT	SCL MCT	SCL pancreas

IHC = immunohistochemistry; LP = lymphoplasmacytic; NSF = no significant findings; PARR+ = PCR for antigen receptor T cell gamma locus rearrangement positive; R&A = resection anastomosis

Clinical findings

The mean age of the 15 cats at the time of diagnosis was 12.2 years (range 5–17; median 13). This study population included one intact female, five castrated male and nine spayed female domestic shorthair cats.

Clinical signs at the time of diagnosis in cats with an ante-mortem diagnosis included vomiting (n = 4), diarrhea (n = 3), weight loss (n = 2) and inappetence (n = 1). Three of these cats experienced multiple clinical signs at the time of diagnosis. Four cats experienced no clinical signs. In these four cats, identification of synchronous GI SCL and GI MCT occurred incidentally during diagnostic investigations for other diseases, including chronic kidney disease (CKD), CKD with resistant urinary tract infections, hyperthyroidism, and inguinal masses and mammary gland tumors.

Several comorbidities were identified in the 10 cats at the time of diagnosis, including pancreatitis (n = 3), hyperthyroidism (n = 3), mammary gland tumor (n = 2), diabetes (n = 1), steroid responsive enteropathy/inflammatory bowel disease (n = 1), chronic food responsive enteropathy characterized by diarrhea (n = 1), recurrent urinary tract infections (n = 1) and cutaneous basal cell carcinoma (n = 1).

Preoperative hematology and biochemical profile results were available for all 10 cats with an ante-mortem diagnosis. The most common hematologic abnormality was monocytosis (n = 4). Other abnormalities included neutrophilia (n = 2) and anemia (n = 1). The most common biochemical profile abnormality was azotemia. Based on the International Renal Interest Society (IRIS) staging system, one cat was categorized with stage 1 CKD and seven cats were categorized with stage 2 CKD. Other abnormalities included hypokalemia (n = 2) and hypochloremia (n = 1).

Histopathology

This study identified 15 cats with a total of 18 synchronous GI MCTs and GI SCLs (Figure 1; Table 2). Six cats had tumors classified as distinct tumors and six as combined tumors. Three cats had both distinct and combined tumors (Table 2). One of the cats (cat 2), with distinct GI SCL in the jejunum and GI MCT in the colon, also had a possible collision tumor of GI SCL and GI MCT in the colon. PARR confirmed the presence of a clonal population of lymphocytes in the colon but histomorphometry was inconclusive and additional tissue was not available for further analysis; therefore, a definitive diagnosis of GI SCL in the colon could not be made. Immunohistochemistry for c-kit was used to identify one cat with GI MCT.

Table 2.

Classification of synchronous gastrointestinal (GI) small cell lymphoma (SCL) and GI mast cell tumor (MCT) in 15 cats

Synchronous tumor classification *	SCL location	MCT location
Distinct (Cat 1)	Duodenum, jejunum, ileum	Colon
Distinct (Cat 7 † )	Jejunum	Duodenum
Distinct (Cat 9 ‡ )	Ileum	Jejunum
Distinct (Cat 14)	Segment not specified	Duodenum, jejunum
Distinct (Cat 15)	Segment not specified	Segment not specified
Distinct, possible collision tumor in colon (Cat 2)	Jejunum, colon	Colon
Combined (Cat 3 ‡ )	Jejunum	Jejunum
Combined (Cat 4)	Jejunum	Jejunum
Combined (Cat 5)	Jejunum	Jejunum
Combined (Cat 6)	Jejunum	Jejunum
Combined (Cat 8)	Jejumum	Jejunum
Combined (Cat 10)	Jejunum	Jejunum
Combined and distinct (Cat 11)	Jejunum, duodenum, ileum	Jejunum
Combined and distinct (Cat 12)	Jejunum, duodenum	Jejunum
Combined and distinct (Cat 13)	Jejunum, duodenum	Jejunum

^*See ‘Materials and methods’ for a description of the classification scheme

^†Diagnosis based on histology report

^‡Diagnosis based on review of histopathology images

Treatment and outcome

In total, 10 cats had an ante-mortem diagnosis of synchronous GI SCL and GI MCT. Four underwent exploratory celiotomy to obtain full-thickness GI biopsies and six cats had intestinal resection anastomosis as well as full-thickness biopsies. Three cats were humanely euthanized within 19 days postoperatively because of clinical decline and poor prognosis. One of those cats received steroid therapy.

In this group of 10 cats, survival was in the range of 8–1189 days (Table 3). Of the 10 cats with an ante-mortem diagnosis, seven survived longer than 30 days postoperatively, all of which were monitored on a regular basis by board-certified oncologists as was appropriate to their treatment protocol. One cat received no adjuvant treatment postoperatively and was still alive and well based on physical examination, laboratory evaluation and diagnostic imaging 466 days after diagnosis. Six cats received chemotherapy in addition to steroid therapy (Table 3).

Table 3.

Treatment and outcome in 10 cats diagnosed ante-mortem with synchronous gastrointestinal (GI) small cell lymphoma (SCL) and GI mast cell tumor (MCT)

	Number of cats	Days since surgery	Treatment (see key for drugs administered)	Response to treatment	Necropsy	Cause of death
Alive	3	731	1, 2	CR	N/A	N/A
		466	No treatment	CR	N/A	N/A
		742	1, 5	CR	N/A	Lost to follow-up
Dead related to GI SCL or GI MCT	2	64	1, 3	PD	Yes	MCT
		19	No treatment		No	Clinical decline postoperatively
Dead because of causes other than GI SCL or GI MCT	5	302	1, 4, 5	CR	No	Hypernatremia
		1189	1, 2, 3	PR	Yes	Urothelial carcinoma
		521	1, 2, 4	PD	Yes	Metastatic nasal carcinoma
		8	No treatment		No	Neurologic event
		18	No treatment		No	Uncontrolled diabetes

Treatment key: 1 = glucocorticoids; 2 = toceranib phosphate; 3 = vinblastine; 4 = cyclophosphamide; 5 = chlorambucil CR = complete response; N/A = not available; PD = progressive disease; PR = partial response

Response to treatment was available for all seven cats that lived longer than 30 days postoperatively. The median follow-up for the seven cats living longer than 30 days was 573 days (range 64–1189). One cat was alive and lost to follow-up at 742 days postoperatively. Table 3 summarizes the outcome in all 10 cats with an ante-mortem diagnosis.

Discussion

This study is the first to classify synchronous tumors in cats. The relatively high percentage (4.3%) of cats with synchronous GI SCLs and GI MCTs should be anticipated as GI SCL is the most common tumor identified in the GI tract. GI MCTs represent approximately 4–5% of feline intestinal tumors.^12,13,23,24 In humans, interpretation of the data surrounding synchronous tumors is complicated by different definitions of synchronous with regard to anatomic location and time between development of the first and second tumors; despite those challenges, multiple primary tumors occur in 1.3–5.8% of human cancer patients. ²⁶ We identified 18 synchronous tumors in 15 cats as some cats had both distinct and mixed tumors. Combined tumors and distinct tumors occurred with equal frequency in this group of cats, with six combined and six distinct tumors identified. In addition, one of the cats (cat 2), with distinct tumors in the jejunum and colon, also had a possible, but not confirmed, collision tumor of GI SCL and GI MCT in the colon (Table 2). Ancillary testing (PARR) of colonic samples identified a clonal population of lymphocytes in the colon. During review of the available microscopic samples from the colon, the histomorphologic features were not diagnostic for SCL. Thus, this case was designated as a possible collision tumor of the colon.

The predisposing factors for the development of synchronous tumors are unknown; however, several hypotheses have been proposed. ²⁷ Growth factors, and possibly other factors, within the tumor microenvironment may help promote growth of a second tumor within the first. Synchronous tumors may develop in response to environmental carcinogens. In cats from Italy, cutaneous squamous cell carcinoma was reported in 3/7 cats with synchronous basal cell carcinoma, unspecified sarcoma and a ceruminous gland adenoma. Those authors suggested exposure to ultraviolet light in outdoor cats as well as infection with Felis catus papillomavirus as possible environmental initiators and promotors.^12,28 Whether environmental factors play a role in synchronous GI SCL and GI MCT remains to be determined. Synchronous tumors may develop from a common progenitor cell and differentiate along divergent lines due to a common underlying driver mutation. Support for this theory is lacking in GI SCL and GI MCT; mutations common to both tumor types have not been identified. ²⁹ Both distinct and synchronous tumors can be driven by underlying genetic mutations that initiate tumorigenesis; for example, an underlying genetic cause has been identified in humans with multiple neuroendocrine neoplasia and has been speculated in small animals.^{10,30 –34}

Risk factors for multiple primary tumors in humans include genetics, viral infection, smoking, betel quid chewing, and environmental or treatment-related factors. ²⁶ We speculate the risk of synchronous tumors in cats is influenced by environmental factors, as has been suggested in humans; however, we currently lack information or evidence regarding this possibility. Finally, coincidental development of synchronous tumors may occur. This is a reasonable explanation in GI SCL and synchronous GI MCT since both are common GI tumors in cats.^13,23,24

Because synchronous tumors are uncommon, there are no standard treatment protocols. To optimize treatment, an individualized treatment strategy will be required, taking into consideration histologic grade, tumor stage, prognostic markers and genetic mutations common to both tumors.^5,35,36 Ideally, a treatment that is active against both tumors without increasing toxicity and decreasing survival can be found. In the case of the seven cats surviving longer than 30 days postoperatively and receiving treatment, the only treatment common to all seven was glucocorticoids. Glucocorticoids are frequently recommended treatments for both cancers.^18,19,22 The variety of drugs administered and small number of cats make it impossible to assess the effect of other chemotherapeutic agents administered to cats with GI SCL and GI MCT; however, the wide range of survival times in these cats with synchronous tumors mirrors the wide range of survival times in cats diagnosed with only one of these two tumors.^18,19,22 Five of the cats in this study died from causes other than synchronous GI SCL and GI MCT. This observation has been reported in studies of cats with only one of these tumors.^20,22 The wide range of survival times and death from causes other than GI SCL and GI MCT when these tumors occur synchronously suggest the prognosis is similar to that for cats with only one of these tumors, as has been suggested in a study of dogs with mixed tumors. ¹

The present study has some limitations. The retrospective nature of this study presented challenges because histopathology sections were not available for all cats. In addition, classification of the tumors from two cats were made based on the images accompanying the histopathology report. In only one was the classification based solely on the report itself. This was a cat with distinct tumors in the jejunum and duodenum where separation of collision and combined tumors would not have been required. In addition, the segments of the GI tract biopsied were not standardized and other categories of synchronous tumors may have gone unrecognized because all cats did not have comprehensive biopsies performed (GI tract, liver, spleen and lymph nodes). Because of this, the actual occurrence of synchronous GI SCL and GI MCT could be different from that calculated in this data set.

The authors recommend adoption and strict usage of standardized clear definitions for multiple primary tumors in veterinary medicine based on reports in human medicine^{2 –9} to allow for reproducibility of data and comparison between studies (summarized in Figure 1). For these purposes, synchronous tumors were defined as two or more tumors diagnosed within 6 months of one another, including in the same biopsy. Therefore, given our inclusion criteria, all tumors reported here were synchronous. Metachronous tumors represent multiple tumors where additional tumor(s) are diagnosed more than 6 months from diagnosis of the first.^{2 –5} Distinct tumors represent two or more separate tumor populations that are geographically separated (eg, within distinct and separate segments of the GI tract or within separate organs) (Figure 1d). Mixed tumors is a general term in which two or more neoplastic populations are intimately associated (either juxtaposed or intermingled) and include collision, combined, colonized and biphenotypic tumor subtypes. Mixed tumors can represent only benign processes, a combination of benign and malignant tumors, or only malignancies.^2,6 Mixed tumors typically present clinically as a single nodule or mass; however, with microscopic review, two or more neoplastic populations are seen.^2,5 Collison tumors are defined as two or more distinct neoplastic populations that are juxtaposed with no intermingling at their borders (Figure 1a).^2,6,7,9 Combined tumors represent two or more separate neoplastic populations that are adjacent and intermixed (Figures 1b and 2).^6,7 To facilitate reproducible separation between collision and combined tumor subtypes, the authors recommend strict adherence to the histomorphologic criteria for collision tumors defined by the absence of mixing between the two distinct neoplastic cell populations at their juxtaposed margins.

Figure 2.

A cat with synchronous small intestinal mast cell tumor (MCT) and small cell lymphoma (SCL) (combined tumor). (a) Subgross image shows the lighter-stained MCT in the mucosa (close to the lumen), submucosa (asterisk) and tunica muscularis (two asterisks) (hematoxylin and eosin [H&E]). (b) High magnification image showing intermingling of darker-stained, neoplastic small lymphocytes (top of image, arrow) and lighter-stained mast cells (bottom of image, asterisk) within the small intestinal lamina propria (H&E). Inset: higher magnification view of lymphocytes at the top of the image intermixed with mast cells at the bottom of the image

Conclusions

This is the first report to classify synchronous tumors in cats as either combined or distinct. Our findings support previous recommendations to biopsy multiple sites of the GI tract because disease is not uniformly distributed.^5,37,38 To further characterize synchronous tumors in veterinary patients, multi-institutional studies with larger case numbers and standardized classification criteria are needed to allow meaningful comparisons across studies.