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IORIGINAL ARTICLE IPrimary Non-Hodgkin's Lymphoma ofWaldeyer's

Ring-A Retrospective AnalysisRakesh Kapoor, Chander Mohan Sehgal, Rakesh Raman Sharma,

Vinod Kumar, S. Goshal, F. D. Patel, S. C. Sharma

Abstract

T\\ emy -five newly diagnosed cases ofprimary Waldeye!'s Ring (WR) Non-Hodgkin's lymphoma(NIIL) registered from 1989-99 were analysed. These comprised 5% of tota! NHL cases. The mostcommon site was tonsil (44%). followed by nasopharynx (20%), base of tongue (20%). nasal cavity(12%) and palate (4%). All the patients were staged thoroughly according to Ann Arbor staging systemand -10% patients were stage I. 36% patients stage II. 4% stage TIl and 20% stage IV. Eighty-eight percent patients were high grade at presentation and 12% were intermediate grade. Three patients abscondedwithout treatment. Patients were treated with radiotherapy alone (4/22 patients). chemotherapy withCHOP regimen alone (9/22 patients) or a combination ofboth (9/22 patients). On comparison. completeresponse was recorded in 4/4 patients treated with radiotherapy alone. 5/9 patients treated withchemotherapy alone and 7/9 patients treated with combination ofradiation and chemotherapy (p>O.05).The range offollow up period was 1-10 years with median 20 months. Overall 16/22 evaluable patientswere with no evidence ofdisease on last follow up and the primary site was the most common site offirst failure. A combined modality treatment except for stage Ia seems to be the treatment ofchoice forthis relatively (UlCOmmOn entity of Primary Waldeyer's \{jng NHL.

Key Words

Non-Hodgkin's lymphoma, Waldeyer's \{jng

Introduction

The lymphoid tissues of the nasopharynx. tonsillar

region. base of tongue. and oropharyngeal wall are

referred to as Waldeyer's Ring (WR). Clinical

in'olvement of these lymphoid tissues by malignant

I) mphomas has long been appreciated. At the Ann Arbor

Symposium in 1971. Waldeyer's Ring was acknowledged

as a discrete lymphatic site for the staging of patients

\lith lymphoma (I). Malignant lymphoma involving WR

rna) be primary. or secondary to disseminated disease.

The frequency of involvement of Waldeyer's ring by the

lymphomas varies considerably around the world. The

WR is the primary site of involvement in5% to 10% of

patients with non-Hodgkin's lymphoma (NHL) in the

United States (2-4). A higher incidence has been reponed

in European counties. probably related to the practice of

routine biopsy ofWR in all patients with NHL. to unique

referral patterns. or to the possible influence of various

etiologic or environmental factors (5.6). Most

From tbe Dep:trtmcllt of R~diotberapy.Postgraduate lnstitute of i\tedical Education and Research, Chandigarb - 160012, Il':DIA

Correspondence (0: Dr. Rakesh Kapoor. Assist'3.l1t Professor, Department of Radiotherapy. PGIMER. Challdigarh - 160012. India

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I~ mphomas of '\'R belong 10 the HI. group with

Ilodgkin's disease 1111)) being extremely rare (7,8). Tbc

treatment ofWalde\ er's Ring :\HL has e\ olwd 0\ er the

:car\ 1'1'0111 radiollll'rap: alolle {either in\-ohed field or

>.'''tended field radiation) to c!lclllothcrap) alone and

reccntl) comhineu IlHhialit: approach. rhis paper

presents the rarit) or prcsclll:Jtioll. clillicopathologi-c

bchcl\ iour and nlillpari:-,oll of rl'sponsc to \'3rious

treatment approach ..''''' ill Prim;lI") \\'aldcyer's ring HL

at PGIMLR. Chamligarh.

\1aterial & \Ietho<l\

Bl'l\\CL'1l !()Xl) Il' It)<)l). 101;\ll)l· -lHO bioI'S) pro\cl1­

Ill'\\ I) t!lagnn ....l:d ca ...."' .... or'.on-lllldgh.in... l) lllphol11a \\('n.:

registered. rhe in\ o!\ CllH.:nl or \\ aIde) ('1"" Ring. at

prcst:lltaLion \\a~ seen in 25 -fRO (SOu) cases.

/\11 the patients lln(lcn\\~nl thorough illu.:stigati\ ('

\\ork up including tissue hiopsy of speeillc sites.

laborator) ill' l..'slig:lliol1s {complete blood COllll'S.

biochemislJ: I. .\-1';\: chesl. CTscan abdomen and pt:h is

and bone marro\\ bi( lPS: as essential staging procedures.

Staging \'\US done in ac('nrd~lIlcL' \\ ith Ann Arbor staging

system (9.10) modi lied 1,,1' Waldeyer's ring as follo\\s:

stage I. iovohemcnt limited 10 WR: stage II. regional

(ccn ical) lymph npclc ill\ ()h L'lllcnt in addition to that of

\\ R: stagc III. n"d,,1 il1\ "h ement abm'e and belo\\ the

di~lphrag.lll (including ... pll..-(,l1) togdhcr \\i'th \VR

iIl\ (.\1\ l..'IllCJ1t. stage 1\'. d I ssem inated in\ o!\ ement ofonc

or llh)rl..' L''\:lra-I) mphaliL organs or tis<;lIe~ in addition to

thai of \tVR. Within each stagt.'. extension into adjacent

soft tissuC' \\a~ denolcd b) ilL". I:ach stage \\as

:=;ubdi\'idcli into A or 11 calL'gories depending Oil lhe

presence or ah"ence re"pecti\ el.: _of fever. nighl sweats.

and/or \\eight loss (10% of body \\eight). The

morphologic classi licalion into various grades was done

according to the Working Formulation (II).

Patients were treated \\ ith radiotherapy alone.

chcmolherap~ alone or combined modality depending

upon the stage. bulk of tumour and grade of disease.

External radiotherapy \\:" ckli\ered on mega \oltage

72

telethcrap~ machine to a dose of 35 G) - -10 G~ 3--1

\,"ccks 15-20 li'actions to the involved lield by t\\·o lateral

parallel opposed lields. CHOP regtmen

Ic~c1ophosphamide- 600 mg/m2 i.\ .. adriam~ein --10

mgil112 i.\·.. \incristine - I mg/m2 i.\. on lirsl da: each

and pr~dinsolone - ..to mg/m2 p.o. x 5 days) was used

as lhe first line chcl11otherap) and six such courses

were gi\ en at :3 \\cekl.: intC'IYal. COl11bin~d modalil~

approach \\ as planllcd for all patients \'\ ith stage II hand

abm e.

rhe complications n1' trl..'aIIll1.'J11 \\ere recorded

aCl:ording to \\'110 criteria Sun i\ al data and lime t(,

tirst relapse measured lrllllllhc UCHt.' orinilialln.:atll1~nl

\\'ere analysed h~ IiI'" table analysis (12). The statistical

signi ficancc \\ as ":OlllplilCd using chi square tesl.

Results

Patients characfert",,·tic,fi

\1a"imulll 17 '15 (65°/0) patients \\en: -1-0 ~ ears and

abo\ c in age (median age 5~ years). hmsi I \\as the most

CQIllI11I..H1 site (-lOtl,o) 1'0110\\ cd h.: nastlphal:' Il\. (20°01.

base of tongue (10U o). lla~al Li.l\ 1l: (12°'0) and palale

(-I%). A t initial staging. 10 25 (-10" ,,) "ra II pat ients lIer,

localized to the site ofnrigill i.t.:. ~(ag~ I a. 9'25 (360

were stage II (II a-X. II h - I). J 251~",,) \,," stagc IIlr

and 5'25 (20%) \\ere slClge I\' (I\':l - I. 1\ h - -ll, ~2~'

o~g%) \\eTC high gradt.: "(III an,J1 ~5 1i2\1 n ) \\cr

intcI1111.:diate grade. ~OI1~ llt' \ lUI" patll.:JllS \\ as nfh)\\ gra

histopath"I"g\ (I'ablc I).

Primary treatmftllt I1lOdalit)' used

Three patients absconded \\'ithout treatlllen!. Patient

with stage I a intermediate grade disease \\ere treat(\.

with radiotherapy alone (4/22 patil'nl:::'l and n::st l)fthr

patients were lreated \\ ith chl:Jl1oth~r3p~ alone \\1

CHOP regimen (9/22 patients) or a combination "fbot

ehemotherap\ and radiothcral" (1)'22 patients).

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Complications oftreatl11ellf Table I-P:ttients Characteristics

1- +- -Overall RT alone lJ. CHOP alol1B X. CHOP'" RT I

4

S

I

10

3

x

11·80 \Can.

_"Icdian .\gl' 52 .,cal's

0.3+----~---~----~---~o

0.'

0.7

0.5

0.8

0.4

Figure 1: Actuarial disease free survival

Years

Table 2-llcspousc to Treatlllent

First Line Tn'almenl

RT alone -l

eeT alone l)

ceT .... RT l)

Age

0.9

Sex\Iale

FemaleIlisiopathology

lllgh gradeIntermediate graJ.:Low grade

Stage

I a

I b

II a

lib

III a

III b

IVa

IV b

Primal) Complete Partial response No responst.:treatment response (CR) (PRl (~RI

RT alone (41 4

CIIOP alone (9) 5 2 2

ClIO? + RT (9) 7 I I

N "" 22 16 (720 0) 3(13°01 303°0)

The follo\\ up period ranged from 1-10 years (median

20 months). /\11 relapscs occurred within 2 years of

completing primary treatmcnl. The median interval to

completc response and relapsc was 14 months. O"erall

7 patients relapsed after achieving complete responsc

with 2/7 relapscs at primary site only and 5/7 at both

primary plus distant sites. So. fU'st relapses were most

commonly noticed at the primary site ofdisease. Because

of inadequate long term follow up after treatmcnt the

survival characteristics in this study are as recorded 011

lasI follow up. Failurcs werc treated with salvage

chemolherap) but none showed complete response. This

series does nol intend to address the role of second line

therapy in Waldeyer's Ring NHL. On last follow up 16/

22 patients were with no evidence of clinical or

radiological disease. In the current series, actuarial

disease free survival at 2 and 4 years is 77% and 46%

respectively (Fig. I).

Respollse. paltems offailure alld survival

Complete rcsponse was seen in 4/4 patients treated

\lith radiotherapy alone. 5/9 patients treated with

Cht:l1101hcrap) alone and 7/9 patients treated with

combined modalit). O,erall 16/22 (72%) patients

achie"ed complete remission after primary treatment. 3/

,2 (13%) achicvcd partial regression ofdiscase whereas

322 (13%) achicved no rcsponse (Table 2).

All the 22 paticnts successfully completed the planned

Ireatmenl. 4/4 patients \\ho received radiotherapy alone

had on I) gradc I - II mucositis. Gradc I - n hematological

loxicit) was seen in 6/9 patients who received

chemotherapy alone and no treatment delay was notice.d.

2/9 patients \\ho received combined modality treatment

had grade III mucositis which delaycd treatmcnt by onl)

a fe\\ days and this complication subsidcd completel)

with cOllscn-ati\ e treatment.

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Discussion

Retrospective studies are usually unsuitable for the

purpose ofcomparing different treatment regimens. 111ey

ma) alien be useful. however. to expand our knowledge

or the etiology and natural history of disease. The non­

Ilodgkin's I) mphomas of Waldcyer's ring form an

interesting clini<.:al entity. Unfortw1ately, because of their­

infrequent occurrence and the presence ofvariables such

as histologic type and stage of disease. it is difficult to

draw any lil"l11 conclusions regarding the necessity of

specilic staging procedures or the efficacy of various

treatment regimens.

In the United States. the frequency of involvement of

Waldeyer's ring in the non-Hodgkin's lymphomas has

been reported to be 5-10%. (2-4) Our observed frequency

01" 5% is compatible with the figure.

Lymphoma ofWR is primarily a disease ofadvancing

age with approximately 80% of patients being over 50

: ears of age at diagnosis. As in other studies of primary

WR lymphoma.(5.6.13-18) the tonsil was the most

common site in the cutTent series (44°,/0).

Anderson el. af. (19) found in a study of483 patients

"ith NHL that only 22% of patients had Stage l-lJ

disease. [n the current series despite essential staging

procedures majority of patients were staged I and II.'

fhe predominance of high grade lymphoma (88%.

current series) in WR has been consistently reported in

previous series (-1-6.13.15. I 7.18.20).

In a series from Italy. 19% of patients had low-grade

disease (21). A large percentage (28%) had diffuse small­

cleaved celli) mphoma. an entity rarely recognized today.

76% to 85% of patients had intennediate or high-grade

disease (22.23). In current series it was 88% high grade.

12% intermediate grade. no case oflow grade pathology.

Patients have been treated with a variety of

approachcs involving radiation with or without

chemotherapy for limited stage disease and

chcmothcrapy lor advanced disease. Local-regional

radiotherapy may yield good results in patients with early

74

(Stages I and II) disease when rigorous staging

procedures exclude systemic disease (24-26).

Radiotherapy treatment alone is associated", ith a

high rate ofrelapse. Ofpatients with stage I and II discase.

approximately half will relapse. mostly at distant sites

(27-29). Stage I patients have generally fared well. \\ ith

survival rates of60% to 83% at 5 years. Stage II patcnts

fared less well. with survival rates of about 30% (30).

Combined modality therapy may offer belter outcome

than radiotherapy alone. Outcome appeared better \\ ith

combined modality treatment. with a 5-year as nr78%

for stage I and 42% for stage Il patients (3 I).

The best evidence for the effectiveness of combined

modality therapy comes fi'OI11 a large randomized study

of 3 16 patients with stage I disease of Waldeyer's ring

(32). Patients were allocated to treatment with radiation

alone, chemotherapy alone (with a cyclophosphamide.

doxorubicin, vincristine, and prednisone [CHOP I or

CHOP like regimen for six cycle). or a combination of

chemotherapy and radiation. Complete response rates

were high in all groups (>85%). Failure free suni,al

[FFS] and as at 5 years of follow up were signi licantl)

better in the combine modality group compared \\ ith

either radiation therapy alone or chemotherapy alone

(FFS, 83% v 48% v 45%: as. 90% v 56%, 58%). The

majority ofpatients who relapsed did so in lymph nodes

or viscera below the diaphragm: only 5 of the 24 patieltls

who relapsed manifested disease above the clavicles.

Only one patient failed within the treatment volwne: this

was a patient with a rapidly progressive undifferentiated

lymphoma. Salvage of patients who relapsed was

attempted with a number ofchemotherapy combinations.

and was generally unsuccessful. with a 20% actuarial j.

year survival from the diagnosis of relapse.

Conclusion

Waldeyer's Ring NHL is a relatively rare entity in

our set-up. Treatment of patients with Waldeyer's

ring lymphomas should be made in accordance with

the histologic subtype and stage of disease. Patient,

with low grade lymphoma may be treated with

radiation therapy. Treatment for this group ot

Vol. 4 No.2. April-June 200

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patients should eonsisl of doxorubiein based therapy(CliOI') for six C) cles combined with radiotherapy to

\\'aldeyer's field.

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