LOW GRADE ALIMENTARY LYMPHOMA IN A BENGAL CAT

Abstract

An adult cat was presented with an acute on chronic episode of lethargy, vomiting

and diarrhoea. Endoscopic biopsies of the duodenum alongside the clinical signs

and the ancillary test helped diagnose low grade alimentary lymphoma (LGAL) and

differentiate it from inflammatory bowel disease (IBD). Thoracic radiographs and the

abdominal ultrasound revealed no signs of metastasis. A chemotherapy protocol

comprised of oral administration of chlorambucil and prednisolone was started since

indolent lymphomas respond better to it. Complete blood counts showed no bone

marrow toxicity as an adverse reaction to the chemotherapy but the patient required

cobalamin supplementation prior to and after the diagnosis was made. Median

survival times of approximately 2-3 years can be expected. The cat was considered

in remission, 180 days after starting the treatment.

Introduction

Alymentary lymphoma (AL), the most common anatomical form of lymphomas in

cats, comprises a group of diseases centred on the gastrointestinal (GI) tract. Three

histological grades of AL are recognised: low (LGAL), intermediate and high (Barrs

and Beatty, 2012). Clinically these types of lymphoma are distinct entities with

different clinical presentations, therapies and outcomes. Although infection with

feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are major risk

WORD COUNT 2499

factors for the development of lymphoma, cats with GI lymphoma are usually

negative for both viruses.

Helicobacter infection may play a role in the development of feline GI lymphoma

(Gieger, 2011) as has been seen in humans with MALT gastric lymphoma (Ettinger

and others, 2017).

Chronic inflammation due to IBD may progress into intestinal lymphoma in cats,

(Roberts, 2015) as chronic antigenic stimulation in genetically predisposed patients

might stimulate transformation to malignant T-cell and progression to LGAL, (Ettinger

and others).

LGAL has been reported in cats ranging in age from 1 to 20 years (median 13

years), with most cats being middle-aged to older (Gieger, 2011).

Presenting signs include weight loss, anorexia, lethargy and diarrhoea. Vomiting is

not a consistent feature of the disease (Hayes, 2006). Abdominal palpation is often

unremarkable, but may reveal palpably thickened intestines and enlarged mesenteric

lymphnodes (Roberts, 2015).

Complete blood count (CBC) abnormalities in cats with gastrointestinal lymphoma

may include anaemia (non-regenerative anaemia of chronic disease or regenerative

anaemia secondary to intestinal blood loss) and neutrophilia (secondary to

inflammation, neoplasia and stress) whilst biochemical abnormalities may reveal

hypoalbuminemia secondary to intestinal loss. Increased liver enzymes may indicate

hepatic lymphoma or concurrent liver disease (Kiupel and others, 2011).

Hypocobalaminaemia is a frequent finding and is useful both to locate disease to the

small intestine (SI) and also identify an area for therapeutic intervention. Exocrine

pancreatic insufficiency (EPI) can have similar clinical signs and has to be ruled out

by checking serum trypsin-like immunoreactivity (TLI). If diarrhoea is a clinical sign

2
then a full faecal analysis (including Trichomonas) should be submitted (Roberts,

2015).

Differentiating IBD from LGAL in cats is a diagnostic challenge (Kiupel and others,

2011). The ultrasonographic pattern associated with LGAL has been recognised as a

diffuse thickening of the muscularis propria of the SI but this pattern is also described

with feline IBD (Daniaux and others, 2014).

Definitive diagnosis can only be achieved by histological evaluation of samples

obtained during endoscopy or exploratory coeliotomy (Roberts, 2015).

Gastro-duodenoscopy allows for collection of gastric, duodenal and jejunal intestinal

sample. Despite being a convenient and minimally invasive test (Scott and others,

2011), may be less sensitive then full thickness biopsy, unless ileoscopy is

performed as well. Surgical biopsies give the most reliable diagnosis when

neoplastic lymphocytes infiltrates intestinal muscle layer (Ettinger, 2017).

Further histological phenotyping using immunohistochemestry, flow cytometry and

assessment of T-cell clonality by polymerase chain reaction (PCR) analysis of T- and

B- cell receptor rearrangements improve the accuracy of diagnosis.

As a diffuse, indolent, metastatic disease LGAL is best treated with systemic

chemotherapy (Roberts,2015) comprised of a combination of prednisolone and

chlorambucil which is well tolerated, has good response rates, with a median survival

time of 2-3 years (Ettinger, 2017).

Several protocols have been published (Table 9) with largely similar response rates

and median survival times. A protocol involving a higher dose of chlorambucil every

two weeks has been suggested to have comparable results to the other protocols.

Potential chlorambucil side effects are vomiting, nausea, anaemia,

thrombocytopenia, leucopoenia, neurotoxicity, alopecia and poor hair re-growth.

3
Doses of glucocorticoids used vary within each study from 1mg/kg to 3mg/kg daily or

5mg/cat to 10mg/cat daily, usually weaned to 1mg/kg to 2mg/kg every other day

once in remission. Cyclophosphamide has been used as a rescue therapy, with good

responses.

Monitoring of haematology is recommended every three to four weeks initially and

then every three months once in remission. As weight loss is the predominant clinical

sign, monitoring improvement in this is often the best guide to success of treatment

(Roberts, 2015).

Dietary modifications should be considered for patients with concurrent IBD where

hypoallergenic diets should be considered.

The prevalence of hypocobalaminemia in cats with GI lymphoma was reported to be

78% in one study thus supplementation is essential (Gieger, 2011).

History

A 5 year old, male neutered, Bengal cat, presented with an acute on chronic

episode of vomiting and diarrhoea. A decrease in appetite and water intake was

noted by the owner. The cat had multiple episodes of watery diarrhoea in the past

that were not always accompanied by vomiting. Previous CBC, serum biochemistry

and faecal analysis were deemed unremarkable. The cat was dewormed every 6

months, annually vaccinated but not routinely deflead as he was strictly indoors. For

the last 8 months, the cat was fed a hypoallergenic diet, D/D venison Hills. Prior to

the event, the owner fed him a different, none specialised, cat food.

4
Clinical Examination

On presentation the cat was quiet, alert and responsive. Body score condition was

4/9 (Nestle Purina Body Condition System) and a one kilogram weight loss was

noted since the last examination. The gums were pink but tacky with a capillary refill

time of 2 seconds. The heart rate was 180 beats per minute with no murmur. No

arrhythmia was auscultated. The respiration rate was 24 breaths per minute with no

abnormal lung sounds. Abdominal palpation revealed possible thickened intestines

in the mid-cranial abdomen. No masses were felt and the patient was comfortable.

The rectal temperature was 38.9 degrees Celsius (°C). The patient had a moderate

skin tent.

Diagnostic Techniques

Differential diagnosis included: Dietary sensitivity (food poisoning/ food

intolerance/ food allergy)/ Antibiotic responsive diarrhoea/ IBD/ Pancreatitis/ EPI/

Neoplasia.

The initial diagnostic plan included a CBC ,serum biochemistry, urinalysis with

sediment, a snap test for FeLV and FIV and a snap test for feline pancreas- specific

lipase (Spec fPL®). Abdominal ultrasound and thoracic Xrays were also performed.

The haematology was mostly unremarkable (Table 1). The thrombocytopenia was

dismissed by a blood smear examination which showed thrombocyte clumps on the

feathered edge. The blood biochemistry revealed mild hypoproteinemia (Table 2).

The snap tests for FeLV/FIV were negative. Spec fPL® was considered normal.

5
A urine sample collected via cystocentesis was analysed: urine specific gravity was

1.045, pH 6, protein 1+, no traces of glucose, urobilinogen or bilirubin. Plain urine

sediment was unremarkable. Stained urine sediment (Diff-Quick® coloration) was

negative for inflammatory cells, bacteria and casts.

The abdominal ultrasound was performed by an experienced ultrasonographer and

revealed no changes in the intestinal architecture (thickness ranged between 2.3cm -

3.5 cm), no loops of dilation, no plication and no foreign bodies (Picture 1, 2, 3). Mid

abdomen showed a focal region of lympadenopathy and reactive fat (Picture 4).

The liver, gall bladder and spleen were unremarkable. The stomach was empty with

normal layering and both pancreatic limbs showed no changes. Both kidneys and

the bladder had a normal appearance. No free fluid was seen.

A faecal sample was collected and sent for analysis and culture (Table 3). The

results tested negative for the presence of parasites, giardiosis, trichomoniasis,

salmonelosis and campylobacteriosis.

Blood samples were later collected for TLI, folate and vitamin B12 levels (Table 4).

These showed low levels of cobalamin and elevated levels of folate and TLI, which

were more suggestive of dietary sensitivity or IBD.

The cat was discharged from the hospital and started on Purina feline HA (Purina®

Pro Plan®Vetrerinary Diet Feline Hypoallergenic). A short course of probiotic

(Protexin Pro-Kolin +, 3mls, p.o, b.i.d.) and antacid syrup (Zantac® 150 mg/10 ml

GlaxoSmithKline , 0.6mls, p.o., t.i.d) were prescribed.

6
Vitamin B12 (Intravit 12, 0.05% injectable solution, Norbrook®) injections were

administered weekly for 4 weeks followed by a CBC, blood biochemistry and

cobalamin levels check-up.(Table 5, 6, 7).

As the levels of vit-B12 normalised, the injections were stopped.

The owner reported the cat was doing much better but the stools were still soft. A

two week trial with metronidazole ( Metrobactin , Dechra®, 10mg/kg,p.o., b.i.d.)

showed no improvement. Weight loss was still noted.

The owner agreed to the collection of gastro-intestinal biopsies and chose

endoscopically retrieved samples over full thickness surgical biopsies after

discussing the risks, limitations and possible complications.

The cat was premedicated with buprenorphine (Buprecare, Animalcare®- 0.02mg/kg

intramuscular (i.m.)) and medetomidine (Sedator, Dechra®- 10 µg/kg i.m.). General

anaesthesia was induced with propofol (PropoFlo 28, Abbott ®- 4 mg/kg

intravenous) and maintained with Isoflurane (IsoFlo 100% w/w, Abbott®) at 2%

vaporised in oxygen.

Biopsies collected from the stomach and duodenum, using a flexible endoscope,

were sent to an external laboratory. It was not possible to sample the jejunum.

Diagnosis

The histopathology and PCR for Antigen Receptor Rearrangements tests were

compatible with LGAL (Lymphoma, T-cell, small cell, low grade, duodenum) (Tabel

8).

7
Treatment

Treatment options were discussed with the owner in regards to the frequency of

medication administration and the patient was started on the protocol of

administering prednisolone (Prednidale®, Dechra -20 mg/m2, every other day for

life) and chlorambucil (Leukeran®-GlaxoSmithKline-20 mg/m2, every other week for

life).

Progress and outcome

Monitoring of haematology was done before starting the treatment and at 1 week, 3

weeks, 2 months and 6 months after (Table 10).

No side effects of chlorambucil were seen. Polyruia, polydipsia and polyphagia were

noted but mild.

At the moment of writing, 180 days post treatment, the patient was consider in

remission as no vomiting or diarrhoea was noted and the weight was stable.

Cobalamin supplementation was restarted due to low levels.

Discussion

The diagnosis of LGAL is challenging and requires a stepwise approach and

specialised ancillary procedures. Clinical signs such as vomiting, diarrhoea, weight

loss and anorexia are seen in both LGAL and IBD. An accurate diagnosis is critical

because disease outcome and therapy depends on it (Kiupel and others 2011).

8
Ultrasonography was initially used to differentiate IBD from AL, as it can

demonstrate diffuse or focal wall thickenening, loss of wall layering and mesenteric

lymphadenopathy. A muscularis to submucosa ratio> 1 is indicative of an abnormal

bowel segment but isn’t pathognomonic for AL as it can also be caused by a foreign

body or chronic enteropathy ( Ettinger, 2017). Nevertheless, the study published by

Zwingerberger and others, revealed that 7 out of 56 cats with no small intestine

pathology (12.5 %) had thickening of the muscularis propria.

In the presented case, the challenged laid in detecting lymphoma or IBD in the

absence of any intestinal wall changes. Definitive diagnosis was reached by

obtaining samples for histopathology.

For AL, controversy still exists to the diagnostic sensitivity of endoscopically derived

biopsy versus full thickness surgical biopsies (Ettinger 2017). The advantage of

surgically obtained biopsies is that they are transmural and therefore include all of

the layers of the GI tract, allowing the pathologist to evaluate the disease process

thoroughly (Gieger, 2011). Conversely, endoscopic procedures have minimal risk of

perforation and septic peritonitis compared to surgical biopsy, is quicker, less

stressful, and less invasive to the patient (Washbau and others, 2010).

Unfortunately, comparisons of endoscopic and full-thickness biopsy methods have

shown cases of lymphoma may be misdiagnosed as IBD compared to full-thickness

samples obtained surgically (Evans and others, 2006), as histological evaluation is

often limited to the mucosa in this biopsy specimens (Willard and others, 2008). The

reason could be a suboptimal endoscopic technique which has a significant impact

on the diagnostic accuracy of the method (Evans and other, 2006). The use of

WSAVA GI Standardisation Group standard report forms, may help to ensure

complete and reliable endoscopic examinations (Washbau and others 2010).

9
Samples were obtained endoscopically from the stomach and duodenum which

could have missed a diagnosis of alimentary lymphoma, as ileal biopsies are being

recognised as potentially providing valuable information not always found in the

duodenal biopsies (Washbau and others 2010). The limitation was due to the fact

that ileocecocolic junction and the jejunum, are difficult to sample endoscopically

(Kiupel and and others 2011).

The histopathology results indicated a dense monotonous lymphocytic population

with an increased number being intraepithelial. These findings were supportive of AL

in the study by Kiupel and other, 2011. The report also revealed a mild admixture of

plasma cells and eosinophils which makes the distinction between chronic

inflammation and emergent LGAL more difficult for the pathologist.

Immunophenotyping is an important diagnostic tool to differentiatie between IBD

and LGAL when histologic changes are ambiguous (Wally and others, 2005). These

can be achieved by using imunohistochemestry (IHC) or PAAR (Moore and others,

2012).

The method chosen for this case was PARR, as a diagnosis of LGAL was best

confirmed by T-cell antigen receptor gene rearrangement analysis in a study by

Moore and others. According to the WSAVA Gastro-Intestinal Standardization

Group, more studies are required in order to prove the superiority of one test.

Definitive diagnosis of LGAL, T-cell, was achieved following PAAR and treatment

options were discussed.

LGAL is typically a slowly progressive disease, and chlorambucil, a

chemotherapeutic agent that targets slowly dividing lymphocytes, is used along with

prednisone or prednisolone (Stein and others, 2010).

10
The patient was started on a be-weekly administration of chlorambucil and daily

administration of prednisolone. Compared to other protocols, it has the advantage of

less owner and cat exposure to chemotherapy.

Another reason for choosing this regime is the complete remission (CR) percentage.

In one study of 42 cats with LGAL treated with prednisone daily and chlorambucil

every 48–72h, the CR was 56% while the administration of prednisone daily and

chlorambucil every 24h for 4 consecutive days every 3 weeks, was showed to have

a 69% CR in Fondancaro’s study and a 76% CR in Lingard’s study.

In the article published by Stein and others, the administration of chlorambucil as a

bolus beweekly and of prednisone daily, the CR was 96%.

Overall, all protocols have largely similar response rates and median survival times.

The prognosis for LGAL patients is good with a median survival time of 26 months (

Gieger, 2011).

Chemotherapy is always worth attempting in cases of feline alimentary lymphoma,

especially when the patients tolerate well the administration of the tablets and no

toxic changes are seen. Many cats will enjoy a good quality of life while owners

benefit from having their pets longer which is one of the most important aspect of

veterinary oncology.

11
 Barrs, V., Beatty, J., (2012), Feline alimentary lymphoma classification, risk

factors, clinical signs and non-invasive diagnostics, Journal of Feline Medicine

and Surgery 14, 182–190.

 Daniaux, L., Laurenson,M.P., Marks, S.L., Moore, P., Taylor, L., Chen, R.,

Zwingenberger, A., (2014), Ultrasonographic thickening of the muscularis

propria in feline small intestinal small cell T-cell lymphoma and inflammatory

bowel disease, Journal of Feline Medicine and Surgery, Vol 16 (89–98)

 Day, J., Hall, E., (2017), Diseases of the small intestine, Textbook of

Veterinary Internal Medicine vol 2, eighth edition, Ettinger, S.J., Feldman,

E.C., Cote, E., Elsevier Health Sciences 2017, pp 1560-1561.

 Evans, S.E., Bonczynski, J.J., Broussard, J.D., Han, E., Baer, K.E., (2006),

Comparison of endoscopic and full-thickness biopsy specimens for diagnosis

of inflammatory bowel disease and alimentary tract lymphoma in cats, Journal

of the American Veterinary Medical Association, 229(9), pp 1447-50.

 Gieger, T., (2011), Alimentary lymphoma in cats and dogs, The Veterinary

clinics of North America 41, 419-32.

 Hayes, A., (2006), Feline lymphoma specific disease presentation, In Practice

(2006) 28, pp 578-585.

12
 Kiupel, M., Smedley, R.C., Pfent,C., Xie Y., Xue Y., Wise, A.G., DeVaul, J.M.

and Maes, R.K., (2011), Diagnostic algorithm to differentiate lymphoma from

inflammation in feline small intestinal biopsy samples, Veterinary Pathology,

48(1), pp 212-222

 Moore,P.F., Rodrigues-Bertos, A., Kass, P.H., (2012), Feline Gastrointestinal

Lymphoma: Mucosal Architecture, Immunophenotype, and Molecular

Clonality, Journal of Veterinary Pathology, 49, pp 658-668.

 Roberts, P., Vet times (2015), Low grade alimentary lymphoma,

https://www.vettimes.co.uk/article/low-grade-alimentary-lymphoma/, accessed

May 20 2018.

 Scott ,K.D., Zoran ,D.L., Mansell ,J., Norby, B., and Willard M.D., (2011),

Utility of endoscopic biopsies of the duodenum and ileum for diagnosis of

inflammatory bowel disease and small cell lymphoma in cats, Journal of

Veterinary Internal Medicine, 25,pp 1253–1257

 Stein TJ, Pellin M, Steinberg H, (2010), Treatment of feline gastrointestinal

small-cell lymphoma with chlorambucil and glucocorticoids, Journal of

American Animal Hospital Association, 46, pp 413–417.

 Washabau, R.J., Day, M.J., Willard M.D., Hall, E.J., Jergens, A.E., Mansell,

J., Minami, T., and Bilzer, T.W., (2010), Endoscopic, biopsy, and

13
 histopathologic guidelines for the evaluation of gastrointestinal inflammation in

companion animals, Journal of Veterinary Internal Medicine, 22,pp 10-26

 Waly, N.E., Gruffydd-Jones, T.J., Stokes, C.R., Day, M.J.,(2005),

Immunohistochemical diagnosis of alimentary lymphomas and severe

intestinal inflammation in cats, Journal of comparative pathology, 133, 253-

260

 Willard, M.D., Mansell, J., Fosgate, G.T., Gualtieri, M., Olivero D Lecoindre,

P., Twedt, D.C., Collett, M.G., Day, M.J., Hall, E.J., Jergens, A.E., Simpson,

J.W., Else, R.W., Washabau, R.J.,(2008) ,Effect of sample quality on the

sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in

dogs and cats, Journal of Veterinary Internal Medicine, 22, pp 1084-9.

 Zwingenberger AL, Marks SL, Baker TW, Moore PF.(2010), Ultrasonographic

evaluation of the muscularis propria in cats with diffuse small intestinal

lymphoma or inflammatorybowel disease, Journal of Veterinary Internal

Medicine, 24, pp 289–92.

14
APPENDICES

Tabel 1

CompleteBlood Count

RBC 6.61 x10¹²/l (5-10)

HGB 9.1 g/dl (8-15)

PCV 30.16 % (24-45)

MCV 46 fl (39-55)

MCH 13.7 pg pg (12.5-17.5)

MCHC 30.1 g/dL (30-36)

PLT 250 10⁹/l (300-800)

WBC 5.7 10⁹/l (5.5-19.5)

LYM 1.5 10⁹/l (1.5-7)

MON 1 10⁹/l (0-1.5)

NEU 4 10⁹/l (2.5-14)

EOS 0 10⁹/l (0-1)

BAS 0.1 10⁹/l (0-0.2)

15
Table 2

Serum Biochemestry - Vetscan

TOTAL PROTEIN 52 g/L (54-82)

ALBUMIN 28 g/L (22-44)

GLOBULIN 24 g/L (15-57)

TOTAL BILIRUBIN 5 mmol/L (2-10)

ALT 49 U/L (20-100)

ALKP 12 U/L (10-90)

UREA 7.2 mmol/L (3.6-10.7)

CREATININE 92 umol/L (27-168)

CALCIUM 2.23 mmol/L (2-3)

PHOSPHORUS 1.01 mmol/L (1.0-2.74)

GLUCOSE 8.1 mmol/L (4.0-8.3)

AMYLASE 667 IU/L (300-1100)

SODIUM 151 mmol/L (135-155)

POTASSIUM 4.8 mmol/L (3.7-5.8)

16
Table 3

MICROBIOLOGY- Faecal Analysis

McMaster <100 Ova/Gram (none seen)

Giardia Antigen Negative

FAECAL BACTERIOLOGY

Salmonella Not isolated

Campylobacter Not isolated

E.coli Heavy, mixed growth consisting mainly of

E.coli cultured at 48 hours incubation.

Thrichomonas foetus Negative

17
Table 4

Results prior to vit B12 supplementation

Feline TLI * 230 ng/ml (35 -130 )

Folic Acid * >24.0 ng/ml ( 9.7 - 21.6)

Vitamin B12 * <150 pg/ml 290-1500

Table 5

Results after vit B 12 supplementation

Folic Acid *22.3 ng/ml ( 9.7 - 21.6)

Vitamin B12 379.0 pg/ml 290-1500

18
TABEL 6

Complete Blood Count

RBC 7.52 x10¹²/l (5-10)

HGB 12.5 g/dl (8-15)

PCV 40.4 % (24-45)

MCV 53.7 fl (39-55)

MCH 16.6 pg (12.5-17.5)

MCHC 30.9 g/dL (30-36)

PLT 320 10⁹/l (300-800)

WBC 12.17 10⁹/l (5.5-19.5)

LYM 3.77 10⁹/l (1.5-7)

MON 0.5 10⁹/l (0-1.5)

NEU 6.3 10⁹/l (2.5-14)

EOS 0 10⁹/l (0-1)

BAS 0.1 10⁹/l (0-0.2)

19
Table 7

Serum Biochemestry

TOTAL PROTEIN 62 g/L (60-80)

ALBUMIN 23 g/L (25-46)

GLOBULIN 29 g/L (25-50)

ALBUMIN/GLOBULIN 1.14 ratio (1.4-0.7)

TOTAL BILIRUBIN 3 mmol/L (0-15)

ALT 87 IU/L (15-60)

ALKP 59 IU/L (18-180)

CK 1234 IU/L (50-200)

UREA 11.7 mmol/L (3.5-12)

CREATININE 167 umol/L (88-140)

CALCIUM 2.35 mmol/L (2-3)

PHOSPHORUS 1.35 mmol/L (1.0-2.5)

GLUCOSE 6.6 mmol/L (4.0-5.3)

CHOLESTEROL 2.1 mmol/L (2.0-6.5)

AMYLASE 689 IU/L (500-2500)

LYPASE 33 IU/L (0-200)

SODIUM 151 mmol/L (135-155)

POTASSIUM 4.3 mmol/L (4.0-5.5)

CHLORIDE 118 mmol/L (115-130)

20
Table 8

Hystopathology report

Description

A. Gastric mucosa These sections of gastric mucosa extend to

the deep lamina propria. There are sparse to

moderate amounts of palely basophilic mucus

on the surface.

The sections are bordered by intact

columnar epithelium. Intraepithelial

lymphocytes are not recognised. The

subjacent lamina propria is loose collagenous

fibrous tissue within which are mildly

congested capillaries.

The stroma extends into deeper areas at 1-2

well-differentiated fibrocytes per intergland

space

and lymphocytes and plasma cells are present

at 1-2 cell per intergland space. The glands

themselves are lined by orderly and well-

differentiated chief and parietal cells, and

gland

lumens contain sparse amounts of palely

basophilic mucus.

21
 B. Small intestine The sections are bordered by intact

columnar epithelium within which are

multifocally very numerous intraepithelial

lymphocytes (too numerous to count where

aggregated). Within the villous proprial stroma

are multifocally dense sheets of round

lymphocytic cells. The nuclei of these cells are

1-1.5 times the size of adjacent erythrocytes.

Chromatin is coarsely clumped and many cells

have at least 1 small densely hyperchromatic

nucleolus. Mitoses are infrequently observed

(up to 1 per x 400 field view).

Immunohistochemical description This result indicates the presence of a clonal T

Parr PCR: Clonal T-cell Receptor lymphocyte population which has been found

Rearrangement to be more than 90% specific for the diagnosis

of lymphoma/leukaemia

Interpretation A. gastric mucosa.

B. Lymphoma, T-cell, small cell, low grade,

duodenum.

Comment Given the clinical history and histological

findings, notwithstanding the 90% specificity

of PARR, the diagnosis of lymphoma appears

the most likely differential diagnosis in

this patient

22
Tabel 9

Chlorambucil protocol

Dose Refrences Overal MST %CR DFI or CR

15mg/m2 q 24hr for Fondcaro et 17 months 69% 20.5 months

4days al,1999, 14.9 months 76% 18.9 motnhs

Lingard et al,

2009

2mg/cat q 48 hours Kiselow et al, 23 m 56% 29 months

2008

20 mg/m2 q2weeks Stein et al, 2010 Not reported 96% 25 months

MST- median survival time, DFI- disease free interval, CR- complete response

23
FIGURE 1

FIGURE 2

24
 FIGURE 3

Ultrasonography Figure 1, 2, 3

Small and large intestine showing normal layering and thickness

25
 FIGURE 4

FIGURE 5

Ultrasonography figure 4, 5

Lympadenopathy in mid abdomen

26