- 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. 3. 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 4. 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 5.
Tissue Biopsy HE CD56 Courtesy of T Pongpruttipan, MD. 6. 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 7.
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. 8. 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. 9. 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. 10. 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. 11. 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. 12. 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) 13. 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 14. 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% 15.
Results: Overall survival 16. 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
17. Yamaguchi M, et al. JCO 2011;29:4410-16. 18. 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. 19. Esophago-Gastroduodenoscopic
Finding 20. Colonoscopic Finding (1) 21. Colonoscopic Finding (2)
22. 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) 23. 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. 24. Bone Marrow Aspiration Numerous small lymphoid cells
around 60% Very few medium-sized or large lymphoid cells
