Follow-up studies by large intestinal biopsies and necropsy in dogs with clinical signs of large bowel disease.

The results of follow-up studies in 77 dogs with clinical signs of large bowel disease are presented. In 32 dogs colonic and/or rectal biopsy follow-up studies were done, combined with necropsy in seven dogs. In 45 dogs a follow-up necropsy only was done. The time between the first and the last series of biopsies varied from three to 729 days and between the first series of biopsies and necropsy from one to 980 days. Colitis found in 45 dogs in the initial biopsies was still present in 29 cases in the follow-up biopsy studies and/or at necropsy. Eleven cases showed hystiocytic ulcerative colitis. In general, adenoma, carcinoma and lymphosarcoma were confirmed in the follow-up examination, except for one adenoma, which appeared to be a carcinoma at necropsy. In cases in which the differential diagnosis was adenoma or carcinoma, the necropsy diagnosis was always carcinoma and in cases of a differential diagnosis of lymphosarcoma and/or colitis, lymphosarcoma was always diagnosed at necropsy. Several dogs without colonic changes in the initial biopsies had other gastric or small intestinal lesions at necropsy such as gastritis and enteritis of the small intestine, or tumors, in these areas.     

Treatment of feline gastrointestinal small-cell lymphoma with chlorambucil and glucocorticoids

Gastrointestinal (GI) lymphoma is the most frequently diagnosed form of lymphoma in the cat and is categorized into two distinct forms based on the size of neoplastic lymphocytes. Treatments for both large- and small-cell GI lymphoma have been described previously; however, multiple chemotherapy protocols were used, a minimal amount of histopathological characterization was provided, and, in most studies, the majority of diagnoses were obtained via endoscopic pinch biopsies. Twenty-eight cats (24 with full-thickness intestinal biopsies) were diagnosed with small-cell GI lymphoma and treated with a combination of chlorambucil and glucocorticoids. The majority of cases were strongly CD3+, and many displayed epitheliotropism. The overall clinical response rate was 96%, with a median clinical remission duration of 786 days. Follow-up identified seven cats with relapsed disease-all of which were treated with a rescue protocol of cyclophosphamide and glucocorticoids; the response rate was 100%, and four of the 28 cats were diagnosed with a second malignancy.     

Detection of monoclonality in intestinal lymphoma with polymerase chain reaction for antigen receptor gene rearrangement analysis to differentiate from enteritis in dogs

The diagnosis of canine intestinal lymphoma by morphological examination is challenging, especially when endoscopic tissue specimens are used. The utility of detection of antigen receptor gene rearrangement by polymerase chain reaction (PARR) in canine lymphoma has been well established, but its usefulness to distinguish enteritis and intestinal lymphoma remains unclear. In this retrospective study we assessed clonality of 29 primary canine intestinal lymphoma, 14 enteritis and 15 healthy control cases by PARR analysis, using formalin‐fixed, paraffin‐embedded full‐thickness tissue specimens. We could detect monoclonal rearrangements in 22 of 29 canine intestinal lymphomas [76%; 95% confidence interval (CI) 56–90%] and polyclonal rearrangements in all of the enteritis and healthy control cases (100%; CI 88–100%). We revealed a predominance of T‐cell phenotype compared to B‐cell phenotype (85%; CI 65–96% and 15%; CI 4–35%, respectively). We showed that PARR analysis contributes to differentiation of canine intestinal lymphoma from enteritis and to phenotyping of lymphomas.     

Comparison of Histopathologic Findings in Biopsies from the Duodenum and Ileum of Dogs with Enteropathy

Background: In the investigations of dogs with chronic small intestinal diarrhea collection of ileal biopsies lengthens procedural time and has been of uncertain value.
Objectives: To evaluate whether there was agreement between histologic changes present in samples of duodenal and ileal mucosa, and hence to provide initial information in the process of determining whether collection of ileal biopsies is clinically justified.
Animals: 40 dogs with chronic small and large intestinal diarrhea from which endoscopic (in 30 cases) or surgical (in 10 cases) duodenal and ileal biopsies had been collected.
Methods: Samples were reviewed concurrently by two observers (MJD and MDW) using the scoring system developed by the World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group. Comparisons were made by kappa analysis.
Results: Microscopic pathology was observed in 30 cases. Only eight out of this 30 (27%) had the same histopathologic diagnosis in both the duodenum and the ileum. This dropped to 3 out of 30 (10%) if different disease severity was also considered as disagreement. Microscopic pathology would have been found in 60% and 80% of the 30 cases, if only duodenal or ileal biopsies respectively, had been available.
Conclusions and clinical importance: There was poor agreement between histopathological findings from duodenal versus ileal biopsies with abnormalities sometimes being more readily detected in the ileum. Routine collection of ileal plus duodenal samples appears warranted when concurrent small and large intestinal diarrhea is present.     

Aspects of the diagnosis, pathogenesis and epidemiology of canine parvovirus

Between 18 July 1980 and 2 January 1981, 188 samples (145 faeces and 43 intestinal contents) were submitted from dogs with suspected canine parvovirus (CPV) enteritis. CPV was demonstrated in 56 (30%) of these samples; the weekly rate of positive CPV identification was remarkably constant at approximately 30% even though clinical and often post-mortem findings strongly supported a diagnosis of CPV enteritis. The simplest, most sensitive and most rapid method for detection of virus was haemagglutination (HA) which was twice as sensitive as isolation of virus and 8 times as sensitive as electron microscopy (EM). Forty nine of 56 (88%) samples positive for CPV were from dogs less than 1 year old and 44 (79%) CPV-positive samples were from pups less than 6 months old; only one sample from a pup less than 2 months old (pup was 7 weeks old) was positive. An additional 68 samples (53 faeces and 15 intestinal contents) were submitted from Beagle dogs that were part of a colony of approximately 1200 dogs. Epidemiological data pinpoints the entry of CPV into the colony in November 1978 at which time most dogs including pups less than 6 months of age developed antibody to CPV without developing clinical disease. From these data an overview of some aspects of the pathogenesis and epidemiology of CPV is constructed.     

DIAGNOSTIC VALUE OF ULTRASONOGRAPHY IN DIFFERENTIATING ENTERITIS FROM INTESTINAL NEOPLASIA IN DOGS

One hundred and fifty dogs with histopathologically confirmed intestinal disease were evaluated retrospectively. Sixty-one dogs had enteritis and 89 dogs had intestinal neoplasia. Ultrasonographic findings including the thickness and distribution of the intestinal lesion, the integrity of intestinal wall layering, regional lymph node thickness, the location of the intestinal segment involved, and regional motility were evaluated. Dogs with intestinal tumor had wall thickness (1.5 cm) significantly greater than dogs with NSE lesions (0.6 cm; p < 0.001). Ninety-nine percent of dogs with intestinal tumor had loss of wall layering while 88% of dogs with NSE had normal or altered wall layering (p < 0.001). Dogs with NSE were significantly more likely to have diffuse lesion (72%) than dogs with intestinal tumor (2%; p < 0.001). Lymph node median thickness in 24/61 dogs with NSE was 1.00 cm. The median thickness of the lymph nodes in 56/89 dogs with intestinal tumors was 1.9 cm. A multivariate analysis showed that loss of wall layering alone was an excellent predictive factor in differentiating intestinal tumor from NSE. In our population, dogs with loss of intestinal wall layering were 50.9 times more likely to have a tumor than enteritis.     

Follow-up studies by peroral gastric biopsies and necropsy in vomiting dogs.

The results of follow-up studies in 139 vomiting dogs are presented. Follow-up studies were performed by biopsies in 34 dogs, by biopsies and necropsy in six dogs and by necropsy only in 99 dogs. The times between the first and the last series of biopsies varied from three to 1042 days and from one to 656 days between the first series of biopsies and necropsy. From the 55 dogs with gastritis in the first series of biopsies, 35 also showed gastritis in the following biopsies or at necropsy. These were mainly severe types of gastritis such as diffuse, hypertrophic or atrophic. Ten dogs with superficial gastritis showed no gastric changes at necropsy, two dogs had edema only and three dogs had gastric changes other than gastritis, such as multiple polyps. In general, carcinoma and lymphosarcoma were found in the biopsies as well as at necropsy, but in three cases of terminal carcinoma only gastritis had been diagnosed initially. In 35 dogs the first series of gastric biopsies showed no pathological changes, but in 22 of these dogs gastritis, ulceration, fibrosis, atrophy, gastric dilation with local necrosis, and perforation or lymphosarcoma of the submucosa were found in the second series of biopsies or at necropsy. Several dogs which did not have gastric changes at necropsy had enteritis or intestinal lymphosarcoma.     

Sandwich ELISA detection of Clostridium perfringens cells and alpha-toxin from field cases of necrotic enteritis of poultry

Sandwich ELISAs (sELISAs) for the detection of Clostridium perfringens cells and alpha-toxin were developed and used to screen intestinal samples from normal broiler chickens and from clinical cases of necrotic enteritis. The assays clearly distinguished between the two sets of samples. The sELISA absorbance values from samples obtained from the majority of healthy birds were low and those from the majority of necrotic enteritis cases were high. Together, the assays provide a suitable test for the rapid screening for the diagnosis of necrotic enteritis in poultry.     

Clinical and pathologic features of parvoviral diarrhea in pound-source dogs

From June 1980 through May 1982, 161 pound-source dogs that developed diarrhea while being used in research were evaluated to determine whether canine parvovirus (CPV) type 2 was the etiologic agent. Evaluation included notation of clinical signs, determination of serum CPV-specific immunoglobulin (Ig) M and IgG titers, virus isolation attempts, and histologic examination of tissues. Criteria for diagnosis of canine parvoviral enteritis were serum CPV-specific IgM antibodies, isolation of CPV from feces, and histologic evidence of intestinal crypt cell necrosis. Upon arrival, 67 clinically normal pound-source dogs were evaluated to determine the prevalence of fecal shedding of CPV and to determine their antibody titers to CPV. Parvovirus was not isolated from any of these dogs, although 76% had IgG antibodies and 3% had IgM antibodies. Of the 161 dogs with diarrhea, 40 (25%) had parvoviral enteritis. Of dogs with parvoviral enteritis, 71% had IgG antibodies and 68% had IgM antibodies. Canine parvovirus was isolated from 18 dogs. Serum IgG antibodies were found in 85% of dogs with diarrhea due to other causes. The geometric mean titer of IgG antibodies to CPV was not significantly different among the 3 groups. Clinical signs that appeared significantly (P less than 0.05) more often in dogs with parvoviral enteritis included bloody diarrhea, anorexia, fever (greater than or equal to 39.4 C), and leukopenia (WBC less than 6,000/mm3). Cases occurred throughout the year, without apparent seasonal variation. The duration between arrival and onset of diarrhea was significantly (P less than 0.05) shorter for dogs with parvoviral enteritis.(ABSTRACT TRUNCATED AT 250 WORDS)     

The histological appearance of large intestinal biopsies in dogs with clinical signs of large bowel disease.

Colonic and rectal forceps and excision biopsies of 355 dogs with clinical signs of large bowel disease were investigated. Five percent of the forceps biopsies were unsuitable for examination; all excision biopsies were of good quality. Forceps biopsies were obtained from one to eight sites, up to 60 cm cranial from the anus, while excision biopsies, mostly from tumors, were from the rectoanal region. Slight to severe colitis and/or proctitis was found in 192 dogs (54%). A single type of colitis was seen in 160 dogs; in 53 cases the lesions were local, in 107 cases multiple. A combination of different types of colitis was found in 32 dogs. Atrophic colitis, diffuse colitis and canine histiocytic ulcerative colitis were the most prominent findings, followed by ulcerative, superficial and eosinophilic colitis. Follicular, hypertrophic and aspecific granulomatous colitis were found in only a few cases. Tumors were diagnosed in 57 dogs (16%). Of these tumors 50 were of epithelial and seven were of mesenchymal origin. A high percentage (61%) of the epithelial tumors consisted of adenomas of the rectoanal region. In ten other dogs (3%) a differential diagnosis of lymphosarcoma or colitis had to be made. Colitis and colorectal tumors were more prevalent in Boxers, German Shepherds, Poodles, Great Danes and Spaniels. In the Boxers simple chronic colitis, as well as canine histiocytic ulcerative colitis were more frequently found, the latter especially in females. Other biopsy findings were edema, crypt cysts, hemorrhages, an increased number of intraepithelial lymphocytes and an increased or decreased number of goblet cells.     

ULTRASONOGRAPHIC AND PATHOLOGIC FEATURES OF INTESTINAL SMOOTH MUSCLE HYPERTROPHY IN FOUR CATS

The ultrasonographic findings for four cats with intestinal smooth muscle hypertrophy are described. In two cats, intestinal smooth muscle hypertrophy was associated with chronic enteritis. In the remaining two cats, intestinal smooth muscle hypertrophy affected the intestinal tract proximal to stenosis due to alimentary lymphoma and an intestinal foreign body, respectively. Moderate increased thickness of the affected intestinal wall, measuring 7-8 mm, was evident on abdominal ultrasonographic examination of all subjects. In addition, the ultrasonographic five-layered feature of the intestinal wall was maintained, and only the muscular layer appeared thickened. Abdominal ultrasound allowed a presumptive diagnosis of intestinal smooth muscle hypertrophy that was confirmed histologically in all cats.     

Detection of Mycobacterium avium subspecies paratuberculosis-specific DNA by PCR in intestinal biopsies of dogs

Background: Mycobacterium avium subspecies paratuberculosis (MAP) is the cause of paratuberculosis. MAP infections have not been reliably detected in dogs, but a reemerging debate about the link between MAP and Crohn's disease has renewed interest about the occurrence of MAP in pets.
Hypothesis: This study was undertaken to examine canine intestinal biopsies for the presence of MAP-specific DNA.
Animals: Forty-two dogs with chronic vomiting, diarrhea, or both; and 14 dogs with no gastrointestinal disease.
Methods: All dogs with signs of gastrointestinal disease had a standard work-up for chronic gastrointestinal disease. Endoscopically obtained intestinal biopsies were submitted for histopathologic and molecular investigations. Biopsies were screened for MAP-specific DNA by 3 polymerase chain reaction (PCR) methods (nested, seminested, and triplex real-time PCR). Samples from control dogs were obtained during necropsy.
Results: Histopathology of the biopsies was indicative of inflammatory bowel disease (IBD) in 17 and neoplasia in 6 dogs. Six dogs showing nonspecific changes responded to diet and were classified as having food-responsive enteropathy. In 13 dogs a final diagnosis was not established. MAP-specific DNA was detected and confirmed by sequencing in 8 dogs (19%). These dogs were diagnosed with food-responsive enteropathy (n = 3), IBD (n = 2), and open diagnosis (n = 3). MAP-specific DNA was not detected in dogs with no gastrointestinal disease.
Conclusions and clinical importance: MAP-specific DNA was detected in approximately one fifth of dogs with chronic gastrointestinal disease and might play a role as a pathogenic agent. Apart from animal welfare, the zoonotic aspect warrants further studies addressing the viability of MAP organism in canine intestinal biopsies by culture.     

Evaluation of the degree and distribution of lymphangiectasia in full-thickness canine small intestinal specimens diagnosed with lymphoplasmacytic enteritis and granulomatous lymphangitis

Intestinal lymphangiectasia (IL) is often observed in dogs with chronic small intestinal diseases. Hypoplasia of the lymphatic vessel due to decreased lymphangiogenesis, which has been suggested in human idiopathic IL, may contribute to the pathogenesis of canine IL. This study aimed to evaluate the diameter and number of lymphatic vessels in full-thickness small intestinal specimens of dogs with IL. Immunohistochemical labeling of lymphatic endothelial cell markers was performed on retrospectively retrieved full-thickness small intestinal specimens. Sixteen dogs with histologically confirmed IL were included, of which 10 had lymphoplasmacytic enteritis (LPE), and six had granulomatous lymphangitis (GL). Nine dogs that died from non-gastrointestinal disorders and with little or no abnormalities in the small intestine were used as controls. Lymphatic vessel diameters in dogs with IL were significantly increased in all layers of the small intestine, including the villus lacteal, lamina propria, submucosa, muscularis, and mesentery, compared with controls (all P<0.01). There was no significant difference in the lymphatic vessel diameters between dogs with LPE and GL (all P>0.05). There was no significant difference in the number of lymphatic vessels between dogs with IL and the controls in all layers of the small intestine (all P>0.05). This study demonstrated that IL was observed in all layers of the small intestine, including the submucosa, muscularis, and mesentery, independent of the underlying disease. Factors other than reduced lymphatic vessels would contribute to the pathogenesis of IL in dogs.     

Immunocytochemical demonstration of lymphocyte subsets and MHC class II antigen expression in synovial membranes from dogs with rheumatoid arthritis and degenerative joint disease

The study describes the distribution of canine leucocyte antigens in synovial membrane biopsies from six dogs with canine rheumatoid arthritis (CRA) and from eight dogs with osteoarthritis (OA) secondary to spontaneous rupture of the cranial cruciate ligament (CCL) (n = 5) or patellar luxation (n = 3). Synovial membranes from five dogs without evidence of joint lesions were used as control tissues. In the subsynovium of dogs with normal joints CD5+, CD4+, CD8+ and alpha beta TCR+ lymphocytes were present only in low numbers. With monoclonal antibody (mAb) to MHC class II antigen, either none or up to 20-30% of synovial lining cells were immunoreactive. Furthermore, scattered MHCII+ stromal cells were seen in the deeper subsynovial layer. In synovial membrane biopsies from dogs with CRA numerous diffusely and perivascularly distributed CD5+ lymphocytes were found in the subsynovium. CD4+ cells outnumbered CD8+ cells and were more numerous in the perivascular areas. In all the CRA cases examined, there were markedly higher numbers of alpha beta TCR+ cells compared with gamma delta TCR+ cells. With mAb to CD21, low numbers of immunoreactive lymphocytes were demonstrated. In all the CRA cases, a marked increase of MHC class II antigen expression was noted. In the majority of samples, 50% or more than 90% of the synovial lining cells were strongly MHC class II+. Throughout the subsynovial layer there were numerous MHC class II+ cells and included those with dendritic morphology and inflammatory mononuclear cells. Furthermore, marked perivascular immunoreactivity for MHC class II antigen was found. In biopsies from dogs with OA, there were markedly lower numbers of subsynovial CD5+, CD4+ and CD8+ lymphocytes. T-cells were mainly diffusely distributed. In three of the eight OA dogs examined, there was an increased percentage of synovial lining cells expressing MHC class II. The majority of OA cases had subsynovial major histocompatibility complex (MHC) class II+ cells with a dendritic morphology.     

Feline alimentary lymphoma: 1. Classification, risk factors, clinical signs and non-invasive diagnostics

PRACTICAL RELEVANCE: Alimentary lymphoma (AL) occurs commonly in cats and exists as distinct subtypes that differ in their clinical course, response to treatment and prognosis. Accurate diagnosis is important to guide appropriate treatment. CLINICAL CHALLENGES: Differentiation of low-grade alimentary lymphoma from lymphoplasmacytic enteritis can be challenging, especially where endoscopic intestinal biopsies, which sample only the mucosa and submucosa, are used. The major differentials for intermediate- and high-grade alimentary lymphoma are other neoplastic and non-neoplastic intestinal mass lesions. The diagnosis of large granular lymphocyte lymphoma requires vigilance as it may be missed with routine diagnostics. PATIENT GROUP: AL affects predominantly middle- to old-aged domestic crossbred cats (median age 10-13 years). EVIDENCE BASE: The evidence supporting this review is grade II, III and IV, derived from prospective studies, retrospective case series, reviews, extrapolation from other species, pathophysiological justification and the combined clinical experience of those working in the field.     

Clinical and pathological classification of canine intraocular lymphoma

The objectives of this retrospective study of 100 dogs with intraocular lymphoma were to describe the histomorphologic and immunohistochemical features of canine intraocular lymphoma, determine the proportion of cases with presumed solitary ocular lymphoma (PSOL) compared to multicentric disease, and assess the clinical outcomes of these patients. Selected cases from Penn Vet Diagnostic Laboratory and Comparative Ocular Pathology Lab of Wisconsin (2004–2015) were evaluated and subtyped using the WHO classification system. Peripheral T‐cell lymphoma and diffuse large B‐cell lymphoma were the two most common subtypes. Questionnaires were distributed to the referring veterinarians and veterinary ophthalmologists inquiring about clinical signs at time of enucleation, staging, patient outcome, treatment, and disease progression. Cases were categorized as PSOL if only ocular involvement was noted at the time of diagnosis based on the clinical staging criteria. The majority of cases (61%) did not have systemic involvement at the time of diagnosis, and these cases did not progress postoperatively. Median survival time (MST) was significantly higher for the presumed solitary intraocular cases: 769 vs. 103 days, hazard ratio of 0.23 (95% CI: 0.077–0.68). The subtype of lymphoma did not affect survival time. The results of this study suggest two significant points of clinical interest: the majority of dogs (61%) presented without signs of systemic involvement of lymphoma at the time of enucleation, and dogs with only ocular involvement showed no disease progression postenucleation.     

Histological examination of the intestine from dogs and cats with intussusception

Objectives : To review the histological findings in the intestine from dogs and cats with intussusception. Methods : Medical records and histopathology reports of dogs and cats with intussusception were reviewed retrospectively. Results : Fourty‐nine animals (31 dogs and 18 cats) were identified for inclusion. Tissues examined com‐prised the intussusception alone in 29 animals (16 dogs and 13 cats), and the intussusception with additional intestinal biopsies in 20 animals (15 dogs and 5 cats). Twenty‐eight of 49 (57·1%) animals, comprising 19 of 31 (61·3%) dogs and 9 of 18 cats (50%) had abnormalities detected on histological examination of tissue. Eleven of 29 (46·9%) cases where only the intussusception was submitted achieved a histological diagnosis, compared to 17 of 20 (85%) where additional biopsies were submitted (P=0·003). Cats (median age 36 months, range 2 to 174) were significantly older than dogs (median age 7·5 months, range 1 to 125 months, P=0·010) and were significantly more likely to have underlying neoplasia (5 of 9; 55·6%) compared to dogs who were more likely to have inflammatory causes (17 of 19; 89·5%, P=0·020). There was no association between histological diagnosis and location of the intussusception (P=1·000). Clinical Significance : Histological abnormalities were detected in more than half of the animals. Diagnosis of intestinal disease in animals with intussusception may be improved by submission of additional biopsy samples. Cats with intussusception are more likely to be older and have underlying neoplasia than dogs which are more likely to have inflammatory disease.     

Practical aspects of immunocytochemistry in canine lymphomas

The aim of this study was to evaluate the utility of immunocytochemistry in a standard veterinary practice and to determine the immunophenotype of tumor cells in cases of multicentric lymphoma in dogs by immunocytochemical analysis of fine-needle biopsy specimens. The study was performed on cytological samples collected from 54 dogs, in which multicentric lymphoma was recognised based on clinical data, cytology or cytology and histology, and follow-up information. Diagnosis of lymphoma was established according to the updated Kiel classification. Immunocytochemical assays were conducted using commercially available antibodies to the pan T-lymphocyte marker CD3 and B cell antigen receptor complex CD79 alpha. Among all animals examined B cell lymphoma was recognized in 42/54 (77.8%) of cases, while in the remaining 12/54 (22.2%) of dogs T cell lymphoma was recognized. In 11 animals with lymphoma recognized cytologically, in which an entire lymph node was obtained for histology, the results of routine cytology and immunocytochemistry fully corresponded with findings revealed by histology and immunohistochemistry. Immunocytochemistry can be successfully conducted in smears stored at room temperature for 24 hours without changes of staining results. It can be stated that application of standard cytopathological assessment in connection with immunocytochemistry of lymph nodes samples collected from dogs with lymphoma is a method of choice for establishing final diagnosis, and avoids the need for reexamination or collection of tissue samples for histopathology and immunohistochemistry during surgical procedures in ambiguous cases.     

Structural and functional changes of neuronal and glial components of the feline enteric nervous system in cats with chronic inflammatory and non-inflammatory diseases of the gastrointestinal tract

Immunohistochemical examinations of the enteric nervous system (ENS) were performed on biopsies of healthy cats and compared to findings in cats suffering from inflammatory bowel disease or intestinal lymphoma. In lymphocytic–plasmacytic enterocolitis all affected samples had significant reductions in glial fibrillary acidic protein and vasoactive intestinal peptide (VIP) and mostly of neuron-specific enolase (NSE) possibly reflecting alterations in enteric glial cells and neurons. In cases with eosinophilic gastroenterocolitis significantly reduced phosphorylated neurofilament (PN) expression was present suggesting a disturbance in neuronal cytoskeleton, whereas cats with fibrosing enteropathy had reduced expression of NSE, non-phosphorylated neurofilaments (NPN), PN and VIP, possibly reflecting neuronal disturbances. In cases with intestinal lymphoma only the reduction in PN and the increase in NPN were obvious suggesting direct damage or interference of neoplastic cells with enteric neurons. In conclusion, structural and functional alterations of the ENS may contribute to clinically evident signs of vomiting and/or diarrhea.