1. Diagnostic and Treatment
Dilemmas in NHL
Archrob Khuhapinant, M.D., Ph.D.
Board of Internal Medicine, Hematology and
Clinical Pathology
Division of Hematology, Faculty of Medicine
Siriraj Hospital, Mahidol University, Thailand
22 February, 2013

2. A 63-YO Male with Chronic Sinusitis and
Nasal Obstruction
 An elderly male has suffered from chronic
sinusitis and difficult nasal breathing for 18
months.
 Numerous visits to ENT department in many
governmental and private hospital with multiple
episodes of antibiotics and small surgical
debridement
 Multiple CT scan revealed only pansinusitis with
local destruction
 Pathological biopsies revealed only necrosis and
inflammation.

4. Important Investigations
 Hb 13.1 g/dl, WBC 8710/mm3 (N 90.8, L 6, M
3.2), platelet 272 000/mm3
 Normal renal and liver function test
 LDH 283 U/L
 HBsAg, Anti-HCV, Anti-HIV – negative
 Anti-HBc Ab – positive
 Serum galactomannan - negative

5.  Initial workup to exclude Wegener
Granulomatosis
 C-ANCA - negative
 P-ANCA – positive
 Anti-Myeloperoxidase (MPO) – negative
 Anti-Proteinase 3 – negative
 Multiple biopsy at left maxillary mucosa, right
inferior turbinate, left ethmoid, left soft palate,
right oropharynx were done

6. Tissue Biopsy
HE
CD56
Courtesy of T Pongpruttipan, MD.

7. Final Pathological Diagnosis
 Varying degree of tissue necrosis with focal
abnormal mononuclear aggregations
 Extranodal NK/T-cell lymphoma, nasal type
 CD3+, CD20-, CD56+, CD5-, TIA1+, beta F1-,
CXCL13 focal+, EBER+
 Lymphoma at right maxillary sinus, right
inferior turbinate, left soft palate
 Chronic inflammation at left ethmoid

8. Diagnosis of Sinonasal Lymphoma
 32 pts, Taichung Veterans
General Hospital, 1990-2010
 Symptoms
 Nasal obstruction
 Rhinorrhea
 Bloody
discharge/epistaxis
 Post nasal drip
 Facial swelling
 Neck mass
 Orbital symptoms
 Fever
 Weight loss
 Time to diagnosis 8.9
months
 First impression
 Benign or malignant
nasal neoplasms 20
(62.5%)
 Rhinitis or rhinosinusitis
12 (37.5%)
 Final diagnosis
 NK/T-cell lymphoma 13
(40.6%)
 PTCL 12 (37.5%)
 DLBCL 7 (21.9%)
 Success diagnosis due to
repeated biopsy, endoscopic
sinus surgery, turbinectomy,
Caldwell-Luc operation
Yen TT, et al. The diagnosis of sinonasal lymphoma: a challenge for
rhinologists. Eur Arch Otorhinolaryngol 2012;269:1463-9.

9. Diagnostic Dilemma in ENKTL
 Factors relating to
delayed diagnosis
 Insufficient specimen
size
 Massive necrosis
 Large number of
inflammatory cells
 Poor atypia
 Average time delay
12.8 months
 Poor prognostic factors
 Age >60 years
 B symptoms
 ECOG PS ≥ 2
 High LDH
 Tumor spreads to
adjacent lymph nodes
 Tumor spreads to skin
or adjacent bone
 High Ki67
 EBV DNA titer >6.1
x107
copies/ml
Yanagi H, et al. Extranodal natural killer/T-cell
lymphoma: a diagnostic dilemma. Rhinology
2012;50(3):325-31.

10. Poor Overall Survival for ENKTL
Vose J, et al. International peripheral T-cell and natural killer/T-cell lymphoma
study: pathology findings and clinical outcomes. JCO 2008;26:4124-30.

11. Outcome of ENKTL Treatment
Status N Treatment CR rate
(%)
OS Reference
New case 47 CHOP 18 5-Y
10%
Ann Oncol
2012;21:1032-40.
Relapsed/
refractory
6 SMILE 50 NA Cancer Sci
2008;99:1016-20.
Relapsed/
refractory
39 SMILE 38 NA JCO 2010;28:584s.
Relapsed/
refractory
18 LMD 56 NA Blood
2008;112:217a.
Relapsed/
refractory
15 L-asp + MTX 47 5-Y
33 %
Ann Oncol
2009;20:110-6.

12. LOGO
Wichuda Thamprasert, M.D.,
Archrob Khuhapinant,M.D.,Ph.D.
A 7-Year Retrospective Clinical Study of
Patients Diagnosed of Extranodal NK/T-cell
Lymphoma, Nasal Type in Siriraj Hospital
Division of Hematology, Faculty of Medicine,
Siriraj Hospital, Mahidol University,Thailand
Abstract book of the 41th annual conference of the Thai Society of Hematology 2012. Controversies
in Hematology. March 12-15, 2012. Bangkok, Thailand, p116.

13. Results: Baseline characteristic
Characteristic No. of patients (%)
Age
< 60 y 30 (83.3)
> 60 y 6 (16.7)
Sex
Male 20 (56)
Female 16 (44)
Primary site of tumor
Nasal cavity 22 (61.1)
Sinus 2 (5.6)
Nasopharynx/oropharynx 5 (13.9)
Intestine 2 (5.6)
skin 5 (13.9)
Type of lesion
Mass 24 (66.7)
Infiltrative 7 (19.4)
Ulcerative 5 (13.9)
Characteristic No. of patients (%)
Local invasion
Yes 16 (44.4)
No 19 (52.8)
Bone marrow involvement
Yes 2 (5.7)
No 33 (94.3)
Ann Arbor stage
I ,II 25 (69.4)
III, IV 11 (30.6)
B symptom
Yes 29 (80.6)
No 7 (19.4)
International prognostic
index
0-1 22 (61.1)
2-4 14 (38.9)

14. Characteristic No. of patients (%)
LDH Level
Normal 18 (52.9)
Elevated 16 (47.1)
Initial EBV DNA status (n=8)
< 6.1 x 107
copies/ml 8 (100)
range < 600- 233,000 copies/ml median of 2,625 copies/ml
Results: Baseline characteristic

15. Results: Treatment outcome
Firstline treatment outcome (n=31)*
Chemotherapy/RT
No. of
patients(%)
IT
Treatment outcome
CR PR SD PD Death
CHOP
with local RT 4 (12.9) 3 4 - - - -
without local RT 24 (77.4) 17 4 - 1 8 9
SMILE 1 (3.2) - 1 - - - -
CHOEP + local RT 1 (3.2) - 1 - - - -
Cisplatin/5FU 1 (3.2) - - 1 - - -
Total 31 20 10 1 1 8 9
Note * 2 patients cannot be evaluated for treatment outcome due to
ongoing treatment
CR rate 16%

16. Results: Overall survival

17. • ENKTL poorly responds to CHOP result in
CR rate only 16 % with short duration of
remission
• Local radiation combine with chemotherapy
resulted in better outcome
• Poor outcome were associated with no
local radiation, local invasion, low serum
albumin ( < 3.5 g/dL), ECOG ≥2, and
elevated serum LDH

18. Yamaguchi M, et al. JCO 2011;29:4410-16.

19. A 58-YR Female with Multiple Rectal Polyp
 A middle-aged woman has complaint of
multiple episode of lower abdominal pain and
diarrhea.
 Pharmacologic treatment or changes in
intake food characteristics were fruitless.
 She denied fever, body mass or nodules,
weight loss, malaise or fatigue.
 Stool examination and parasitic examination
were unremarkable.

20. Esophago-Gastroduodenoscopic Finding

21. Colonoscopic Finding (1)

22. Colonoscopic Finding (2)

23.  Numerous diminutive polyps at rectum
 Biospy was done
 Pathological finding
 Abnormal lymphoid infiltration, consistent with
malignant lymphoma, diffuse large B-cell
lymphoma, NOS
 Diffuse mucosal infiltration by medium and
large-sized lymphoid cells; marked with CD20,
bcl-2 and bcl-6, not marked with CD3
Colonoscopic Finding (3)

24. Important Investigations
 Hb 15 g/dl, WBC 9400/mm3 (N 56.2, L 40, M
3.1, E 0.5), platelet 231 000/mm3
 Normal renal and liver function tests
 LDH 378 U/L
 CT scan of neck, chest, whole abdomen
 No significant cervical, mediastinal,
intraabdominal lymphadenopathy. No
stomach, intestinal or colonic mass. No
ascites.

25. Bone Marrow Aspiration
 Numerous small lymphoid cells around 60%
 Very few medium-sized or large lymphoid
cells